CHEMICAL ENGINEERING METHODS AND TECHNOLOGY

HOMOGENEOUS CATALYSTS: TYPES, REACTIONS AND APPLICATIONS

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CHEMICAL ENGINEERING METHODS AND TECHNOLOGY

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CHEMICAL ENGINEERIN NG METHODS S AND TECHN NOLOGY

HOMOG GENEO OUS CATALY A YSTS: TYPES S, REA ACTION NS AND D APPL LICATI IONS

ANDREW W C. POE EHLER

EDITOR

Nova Scien nce Publishe ers, Inc.

N York New

Copyright 2011 by Nova Science Publishers, Inc.

All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book.

LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA

Homogeneous catalysts : types, reactions, and applications / editor, Andrew C. Poehler. p. cm. Includes index. ISBN 978-1-61324-749-5 (eBook) 1. Catalysts. I. Poehler, Andrew C. QD505.H647 2010 660'.2995--dc22 2010043903

Published by Nova Science Publishers, Inc. New York

CONTENTS
Preface Chapter 1 Metallic Nanoparticles Nanocomposites: Their Catalytic Applications Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio Recent Evolution of Oxidation Catalysis by Mo Complexes Carla D. Nunes and Pedro D. Vaz Homogeneous Catalysts Based on Bis(imino)pyridine Complexes of Iron, Cobalt, Vanadium and Chromium: The Kinetic Peculiarities of Ethylene Polymerization N.V. Semikolenova, A.A. Barabanov, L.G. Echevskaya, M.A. Matsko and V.A. Zakharov Rational Design of Chiral Ruthenium Complexes for Asymmetric Hydrogenations Ji Vclavk, Petr Kaer and Libor erven Supramolecular Gel Catalyst: Bridging Homogeneous and Heterogeneous Catalysis Jianyong Zhang and Stuart L. James Glycerol as a Sustainable Solvent for Homogeneous Catalysis Adi Wolfson, Christina Dlugy and Dorith Tavor Homogeneous Catalysis in Carbonylative Coupling Reactions Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage Synthesis, Characterization and Catalytic Stud of Oxovanadium (IV) Complexes with Tetradentate Schiff Bases A.P.A. Marques,, E.R. Dockal, Ieda Lucia Viana Rosa and F.C. Skrobot Unique Design Tools for the Synthesis and Design of Dendrimers as Supports for Recoverable Catalysts and Reagents and their Applications in Asymmetric Synthesis Ashraf A. El-Shehawy vii 1 43

Chapter 2 Chapter 3

97

Chapter 4

127

Chapter 5

155 185 205

Chapter 6 Chapter 7 Chapter 8

233

Chapter 9

247

vi Chapter 10

Contents Recent Strategies in Phase Transfer Catalysis and its Application in Organic Reactions P.A.Vivekanand and Maw-Ling Wang Hexenoic Acids and their Derivatives Preparation using Selective Homogeneous Catalysts Libor erven and Elika Leitmannov Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids C.F. Liu, A.P. Zhang, W.Y. Li, W. Lan and R.C. Sun Palladium Complexes of N-Heterocyclic Carbenes in Homogeneous Catalysis and Biomedical Applications Chandrakanta Dash and Prasenjit Ghosh Methods for Enhancing the Activity and Selectivity of Homogeneous Catalysts in the Oxidation Processes Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

325

Chapter 11

371

Chapter 12

387

Chapter 13

403

Chapter 14

463 499

Index

PREFACE
In chemistry, homogeneous catalysis is a sequence of reactions that involve a catalyst in the same phase as the reactants. Topics discussed in this book include the catalytic applications of metallic nanoparticles nanocomposites; olefin oxidation chemistry based on Mo catalysts; homogeneous catalysts based on Bis(imino) pyridine complexes of iron, cobalt, vanadium, and chromium; Ru catalysts in asymmetric hydrogenation; supramolecular gel catalysts; glycerol as a sustainable solvent for homogeneous catalysis; homogeneous catalysis in carbonylative coupling reactions and methods for enhancing the activity and selectivity of homogeneous catalysts in the oxidation process. Chapter 1 More than a simple review, this is a compilation of what has been done so far in relation to metallic nanoparticle-polymer composites with applications in catalysis reported up to now. The authors are going through all the transition metals from scandium to the noble metals to the copper group. Also, they report that, basically, the noble or platinum group metals are the metals commonly used as catalysts although some of the others have been proven to work as catalysts on different reactions. Chapter 2 For 80% of all compounds produced in chemical and pharmaceutical industry at least one catalytic step is essential during their synthesis. Catalysts speed up chemical reactions but can be recovered unchanged at the end of the reaction. They can also direct the reaction towards a specific product and allow reactions to be carried out at lower temperatures and pressures with higher selectivity towards the desired product. This is a principle that is pursued with increasing emphasis and dedication leading to far more specific and cleaner processes. Homogeneous catalysts, on the other hand are usually complexes, which consist of a metal centre surrounded by a set of organic ligands. The latter impart solubility and stability to the metal complex and can be used to tune the selectivity of a particular catalyst towards the synthesis of a particular desirable product. By varying size, shape and electronic properties of the ligands, the active site at which the substrate binds can be constrained in such a way that only one of a large number of possible products can be produced. Oxidation catalysis is a quite important transformation in both industrial and academic aspects. Within this field, catalysts, ranging from a variety of available metal centered systems, which rely on Mo are one of the most important. Traditionally, oxidation catalysts are based on metal oxides, holding M=O moieties, with the metal center lying in high oxidation state. A large number of important chemical reactions are catalyzed by MoVI complexes. Inclusively, several industrial processes such as

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Andrew C. Poehler

ammoxidation of propene to acrylonitrile, olefin epoxidation (ARCO and Halcon processes), and olefin metathesis reactions are carried out over molybdenum catalysts. Furthermore, as molybdenum is highly available to biological systems, the coordination chemistry of MoVI has stimulated considerable interest in view of its biochemical relevance, and many MoVI complexes have been studied as models of molybdoenzymes. In recent years the development of new approaches to prepare new and stable catalyst has turned to low oxidation state MoII organometallic complexes. These pre-catalysts proved to be quite adequate to the purpose by being highly active and selective in the epoxidation of olefins and in oxidation of other substrates. Additionally, such pre-catalyst complexes are more stable towards air and moisture which allows easier handling. This chapter lights up some recent advances on olefin oxidation chemistry based on Mo catalysts with special focus on the development of new approaches to achieve active catalysts. Chapter 3 The family of highly active ethylene polymerization catalysts based on the complexes of transition metals with bis(imino)pyridine ligands has been intensively studied in the last ten years. In this study the authors summarize the known data and present new kinetic results on the ethylene polymerization over homogeneous catalysts based on Fe(II), Co(II), V(III) and Cr(III) bis(imino)pyridine complexes with close ligand framework (2,6-(2,4,6R3LMeCln, where R= H, Me, i-Pr, t-Bu, L=(C6H3N=CMe)2C5H3N, M= Fe(II), Co(II), V(III), Cr(III), n=2,3). The effects of the activator nature (different samples of methylalumoxane (MAO), or aluminium trialkyls) and polymerization conditions on the activity of these complexes and the resulted PE structure (molecular weight, molecular weight distribution, content of methyl and vinyl groups) have been studied. For the first time the number of active centers and propagation rate constant for ethylene polymerization with Fe(II), Co(II), Cr(III) and V(III) bis(imino)pyridine complexes, activated with MAO and Al(i-Bu)3, have been determined using method of polymerization inhibition by radioactive carbon monoxide (14CO). The experimental data obtained in comparable conditions have shown that the catalytic properties of bis(imino)pyridine complexes ( polymerization activity, number of active centers and propagation rate constant, copolymerization reactivity, composition of optimal activator, formation of single site or multiple sites catalytic system, catalysts thermal stability and PE structure) are mainly determined by transition metal center of complex. The size of the substituents R in 2,6-positions of arene ring in the ligand L affects the number of active centers and molecular weight of PE as well. Chapter 4 Thorough optimization of reaction conditions for maximum yield is the essential prerequisite of every reaction conducted on an industrial scale. In the field of asymmetric chemistry, an additional yield requirement arises, i.e. the stereoselectivity of the reaction. The plethora of fine chemical products available on the world market indirectly demands constant improvements in the production processes and literally dictates an individual, made-to-measure solution for the best efficacy. The relentless expansion of the product range thus demands rapid but reliable tools for finding the optimal reaction conditions for a synthesis of the chiral product in question. Naturally, there is no catalyst to suit all substrates. Much like enzymes, almost every reaction requires at least a slightly modified catalyst or reaction conditions. Trial-and-error syntheses and subsequent testing of all (at first sight) potentially effective catalysts are as costly and time consuming as traditional combinatory methods, due to immense possibilities

Preface

ix

of the catalyst and substrate structures. Many of the complexes prepared by these laborious procedures finally prove ineffective when trying to utilize them in a stereoselectively catalyzed reaction. Therefore, the objective is to synthesize only those truly offering the desired behaviour. While only a few metal centres can be used effectively (namely Ru, Rh, Os, Ir), the auxiliary ligands offer infinite solutions of key changes to the structure. The rational design has become a well-known term to describe the process of fine-tuning the ligand. Although this chapter focuses on Ru catalysts, Rh complexes are also mentioned, owing to the high parallelism of these two coordination centres in the field of asymmetric hydrogenation. The term rational design comprises the practice of altering the molecular structures aided by computational modelling. Bearing in mind the structure of the chiral product, an experienced theoretical-organic chemist should be able to assemble a well-founded series of ligands offering good possibilities of achieving the desired performance in a particular situation. This process involves a competent rejection of structures with a significant potential of failure with regards to enantioselectivity. Given the vast number of possibilities, such a process would ideally be performed automatically, i.e. either by high-throughput experimentation (HTE) techniques, which have been amply reviewed [1] and are not covered within this chapter despite their rapid development in recent years, or through computational chemistry. This preliminary virtual assay is often referred to as in silico screening. Recently, high-capacity virtual ligand libraries have been created and analyzed, allowing a systematic description of existing ligands and a subsequent prediction of the properties of analogues. Computational methods on various levels of complexity are available, enabling us to refine the search results by stepwise reduction of the number of potentially successful catalysts by employing more sophisticated techniques. Nevertheless, it ought to be noted that empirical findings still maintain an inimitable and supreme role. Molecular modelling is doubtless a powerful tool but one needs to appreciate that even models of the highest accuracy are still an approximation and will never yield 100% match. Nowadays, there are thousands of ligands used in asymmetric syntheses and millions of further possibilities. Nonetheless, the reader is advised to note that this chapter concentrates on those used in asymmetric hydrogenation. Ligands used for asymmetric hydroformylation, hydrocyanation, reductive amination, allylic alkylation, hydrosilylation etc., are not covered. Occasionally, however, some of these are mentioned as explanatory references that may be applied to all ligands, including those for hydrogenation. Chapter 5 Supramolecular gels have received growing attention in recent years. They represent a novel type of soft materials which may find application in various aspects. Various organogels and metallogels offer rich possibilities for catalysis. Supramolecular gels can be used in catalysis by incorporating a catalytically active unit as part of the gelator. There are three strategies in literature: 1) catalysis by discrete gelators; 2) catalysis by coordination polymer gelators; 3) catalysis by post-modified gels. Unique new catalytic properties can arise from combining gels with catalytically active centres. Interestingly supramolecular gels show enhanced activity compared with their homogeneous analogues in a number of cases. They exhibit some combined advantages of homogeneous and heterogeneous catalysis. Chapter 6 With its promising physical and chemical properties, glycerol can be used as a sustainable solvent in many catalytic and non-catalytic organic reactions. Polar and non-

Andrew C. Poehler

toxic, glycerol is a biodegradable, recyclable liquid that is manufactured from renewable sources and that facilitates the dissolution of organic substrates, inorganic compounds, and transition metal complexes. Glycerol also enabled easy isolation of the reaction product either by extraction with glycerol immiscible solvents such as diethyl ether, ethyl acetate, and supercritical carbon dioxide or through distillation. Using glycerol as a solvent also enabled catalyst recycling, emulsion-like systems, and microwave-promoted reactions. Furthermore, in many reactions, the use of glycerol as a solvent promoted improved activities and selectivities of the reactants. In addition, in certain reactions such as the catalytic transferhydrogenation of various unsaturated organic compounds and the transesterification of alcohols, glycerol was used as both solvent and reactant. Chapter 7 Carbon monoxide is a ubiquitous molecule in organometallic chemistry and an important feedstock in multiple catalytic processes both at the laboratory and industrial levels. Palladium-catalyzed carbonylation reactions of alkenes/alkynes, aromatic halides with different nucleophiles have undergone rapid development since the pioneering work of Reppe and Heck, such that nowadays plethora of palladium catalysts and various synthetic protocols are available for the synthesis of aliphatic and aromatic carboxylic acids as well as their derivatives. The carboxylic acid and its derivatives like amides, esters, thioamides etc. and ketones prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products. The term carbonylation covers a large number of closely related reactions that all have in common that carbon monoxide is incorporated into a substrate by the addition of CO to an aryl-, benzyl- or vinylpalladium complex in presence of suitable nucleophiles. Various carbonylation reactions like alkoxycarbonylation, phenoxycarbonylation, aminocarbonylation, thiocarbonylation, carbonylative Suzuki coupling reaction, carbonylative Sonogashira coupling reaction etc. have been explored using palladium as a catalyst of choice. Palladium along with variety of ligands has been widely employed as homogeneous catalysts to affect carbonylation reactions. The scope of carbonylation reactions is also extended for the synthesis of pharmaceuticals and their important intermediates using carbonylation as the key step using homogeneous catalysis, which reveals that complex synthetic processes can be accomplished under carbonylation conditions. Herein, the authors summarize the recent developments in homogeneous catalysts and selected organic applications in this area. Chapter 8 The synthesis, characterization and catalytic study of Oxovanadium (IV) complexes and yours precursors Schiff bases [N,N-bis(salicylidene)-1,2-phenylenediamine], [N,N-bis(salicylidene)-1,3-phenylenediamine] and [N,N-bis(salicylidene)-1,3xylylenediamine] are reported. The Schiff base ligands were characterized by elemental analysis, melting points, Fourier Transformed Infra-red spectroscopy, electronic spectroscopy and 1H and 13C Nuclear Magnetic Resonance spectra. The oxovanadium (IV) complexes were characterized by elemental analysis, melting points, Fourier Transformed Infra-red spectroscopy and electronic spectroscopy. The oxidation catalytic of methyl phenyl sulfide with the complexes in solution and heterogeneisated by means of supporting on alumina was studied. The catalytic reactions were accompanied by gas chromatography; the catalytic products were characterized by 1H Nuclear Magnetic Resonance and Fourier Transformed Infra-red spectroscopy. The product of catalytic reaction, methyl phenyl sulfoxide, can be

Preface

xi

used as an intermediate in the fabrication of pharmaceuticals. The oxovanadium (IV) complex from the Schiff base [N,N-bis(salicylidene)-1,3-xylylenediamine] presents the best catalytic activity in homogeneous system probably due to its flexibility that favors the access of the substrate to active center in the catalysis. Chapter 9 The use of soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer limitations, and therefore they should lead to systems with activities similar to their monomeric analogues. Catalysis seems to be a research area in which promising applications for dendrimers may be developed. Indeed, dendritic catalysts are nanosized, and as such they are, as biomolecules, easily isolable from homogeneous reaction media by precipitation, filtration, ultrafiltration or ultracentrifugation. In particular, dendrimers have recently attracted a lot of attention, since these well-defined macromolecular structures enable the construction of precisely controlled catalyst structures. This combination of features makes dendrimers suited to close the gap between homo- and heterogeneous catalysis, or, in other words, dendrimers will combine the advantages of homo- and heterogeneous catalysis. Dendrimers have a number of potential applications, but the present chapter is specifically focus on summarizing the major concepts for their properties as well as the most pronounced advances for their applications as supports for recoverable catalysts and reagents in asymmetric synthesis. This chapter highlights some of the notable examples of the catalytic reactions using supported dendritic catalytic systems in such reactions as hydrogenation, hydroformylation, alkyation, epoxidation, dialkylzinc addition to aldehydes and imines, Heck and other Pd-catalyzed C-C bond formation. The intriguing properties of dendrimers in catalysis including activity, selectivity, stability, and recyclability will be addressed. Further key issues in this chapter relate to the deviating properties of dendrimers as compared to their linear macromolecular counterparts is considered. Chapter 10 In view of the increasing environmental and economical concerns, it is now imperative for chemists to invent as many environmentally benign catalytic reactions as possible. Successful completion of reactions involving lipophilic and hydrophilic reactants can be achieved by employing an environmentally benign technology viz., phase transfer catalysis (PTC). Some of the prominent features of the PTC include, improved reaction rates, lower reaction temperatures and the absence of expensive anhydrous or aprotic solvents. Owing to its simplicity and the low cost of most of the phase transfer catalysts, the PTC technology has found universal adoption. As a result, PTC is considered to have great potential for industrial-scale application. Nowadays, due to these salient features, it has become an important choice in organic synthesis and is widely applied in the manufacturing processes of specialty chemicals, such as drugs, pharmaceuticals, dyes, perfumes, additives for lubricants, pesticides, monomers etc. Due to ever increasing necessity of increasing the efficiency of PTC in industries, researchers incessantly invented new and novel phase transfer catalysts with more active-sites and higher efficiency. Asymmetric phase-transfer catalysis has attracted considerable attention as a convenient technique for the synthesis of chiral molecules. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been employed to achieve the goal for inducing asymmetry into product molecules. Currently, ingenious new analytical and process experimental techniques viz., ultrasound and microwave irradiation assisted PTC transformations have become immensely popular in promoting various organic reactions. Phase transfer catalysis will be of curiosity to anyone working in academia and industry that needs an up-to-date critical analysis and summary of catalysis research and applications. In view of the success and vitality of this

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Andrew C. Poehler

technique, the authors have proposed to present recent happenings in the field of PTC and to study its applications to various organic reactions. Typical applications of PTC in silent, ultrasonic and microwave conditions are described. Further, kinetics of various organic reactions catalyzed by PTC carried out under a wide range of experimental conditions will be presented. Chapter 11 Some C6 unsaturated alcohols, aldehydes and acids are widely used in perfume chemistry. The easiest method for the preparation of hexenoic acids from the point of view of selectivity and simplicity is the selective hydrogenation of easily available sorbic acid (trans,trans-hex-2,4-dienoic acid). Depending on the catalyst used different regio and stereoisomers, can be obtained in various mixtures. From hexenoic alcohols the most commonly used compounds of this type are the socalled leaf alcohols, specifically cis-hex-3-en-1-ol and trans-hex-2-en-1-ol. These compounds can be prepared by selective hydrogenation of the sorbic alcohol obtained for example from the chemical reduction of sorbic acid. Details of the preparation of these compounds by hydrogenation using heterogeneous catalysts are given elsewhere [1-4]. The major disadvantages of the use of heterogeneous catalysts in this case are the low selectivity of the process (in the case of hex-3-enoic acid derivatives there is essentially no selectivity) and the use of sorbic acid itself is impossible. Instead salts or preferably methyl or ethyl esters are used, introducing another step to the process. The use of homogeneous catalysts opened new possibilities to carry out the hydrogenations and significantly higher selectivities of formation of the desired products. As stated above hexenoic acids and alcohols have very interesting fragrant properties. The titling of the two hexenols as leaf alcohols is partly reflective of their smell their fragrance resembles that of freshly cut grass. Perfumers [5] define their fragrance a little more precisely: cis-hex-3-en-1-ol is specified by its intense smell of fresh grass, it is a component of geraniol, lavender and brandy mint oil, it is added to flower aromas (lilac for example) and it can be used in imitations of mint and different fruit mixtures. trans-Hex-2-en-1-ol has in low notes a strong fruit smell (chrysanthemum or wine), it is sweeter and more fruity than cishex-3-en-1-ol and it is often used as a component of artificial strawberry. It is also used for a refreshing orange aroma and it is a component of artificial geraniol and lavender oil. transHex-2-en-1-oic acid has a warm fruit aroma after dilution, partly herbaceous and slightly acidic. It is used as an imitation of raspberry or in many other fruit aromas that require a caramel-acid note. The fragrant properties of hexenoic aldehydes are also very interesting for the perfume industry but the simplest method of preparation (aldol condensation) was not superseded by hydrogenation due to the low stability of aldehydes. Chapter 12 Homogeneous modification of sugarcane bagasse cellulose with succinic anhydride (SA) was catalyzed with three different catalysts including iodine, Nbromosuccinimide (NBS), and 4-dimethylaminopyridine (DMAP) in a solvent system containing 1-butyl-3-methylimidazolium chloride ionic liquid ([C4mim]Cl) and dimethylsulfoxide (DMSO). The effects of the mass ratio of catalyst/SA, reaction time, and reaction temperature on the degree of substitute (DS) of cellulose were investigated. The results showed that the DS of cellulosic derivatives increased to 0.56-1.54 under the experimental conditions catalyzed with iodine, 0.92-2.31 with NBS, and 0.94-2.34 with DMAP, from 0.24 without any catalysts, indicating that these three catalysts were effective catalysts for cellulose succinoylation in ionic liquids. The possible mechanism of

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xiii

homogeneous succinoylation catalyzed with these catalysts and the actual role of these catalysts were also investigated. Fourier transform infrared and solid-state crosspolarization/magic angle spinning 13C NMR spectroscopies also provided evidence of catalyzed homogeneous succinoylation reaction. The results indicated that the reaction of hydroxyl groups at C-6, C-2, and C-3 positions in cellulose occurred. Chapter 13 The knowledge of the efficient formation of CX (X = C and N) bonds asymmetrically or otherwise is vital to contemporary organic synthesis. In this context notable is the contribution of Pd towards the development of the area. The specialty of Pd as a metal lies in its ability to efficiently construct numerous types of CX (X = C, N, O and S) bonds under ambient conditions. A key strength of Pd mediated synthesis thus lies in its chemo- and regio selectivities that facilitate the synthesis of intricate target molecules otherwise not conveniently accessible by traditional methods. Furthermore, Pd, being a late transition metal, inherently possesses important attributes like, the air and moisture stability and the functional group tolerance, which often are the key ingredients of a successful catalyst. Of late, the N-heterocyclic carbenes (NHC) have added a new chapter in the design, discovery and development of Pd catalysts, thereby generating an enormous interest in its palladium complexes in recent years. The strong -donating nature of the N-heterocyclic carbene ligand in the catalyst allows oxidative insertions of challenging substrates while the ligand topological steric demands promote the fast reductive elimination reactions, which together constitute two important steps in numerous catalysis cycles. Additionally, the strong palladiumN-heterocyclic carbene (PdNHC) interaction help stabilizes many catalytically important active species at low ligand to Pd ratios and also at high temperatures thereby broadening its scope of catalytic applicability. Apart from the CX (X = C and N) bond forming reactions, the Pd complexes of N-heterocyclic carbenes perform various other reactions like the oxidation reactions, Tsuji-Trost reaction and the polymerization reactions etc. Even extending further beyond chemical catalysis, the palladium N-heterocyclic carbene complexes exhibit promising potential in various biomedical applications like in the anticancer studies. Chapter 14 The application of metal-complex catalysis opens the possibility of regulating the relative rates of elementary stages CatO2, CatROOH, CatRO2 and in that way of controlling the rate and selectivity of processes of radical-chain oxidation [20]. By changing the ligand environment of the metal center or adding different activating compounds, it is possible to vary the yields of target products, and thus control the reaction selectivity. The catalyst performance is always accompanied by its deactivation. It should be mentioned that in its original form, a catalyst often represents only the precursor of real catalytic particles. By introducing various ligands-modifiers into reaction, it is possible to accelerate the formation of catalytically active species and prevent or hinder the processes that lead to catalyst deactivation. Understanding of the mechanisms of the additives action at the formation of catalyst active forms and mechanisms of regulation of the elementary stage of the radical-chain oxidation may apparently lead to the development of new, efficient catalytic systems and selective oxidation processes.

In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 1

METALLIC NANOPARTICLES NANOCOMPOSITES: THEIR CATALYTIC APPLICATIONS

Roco Redn*, N. G. Garca-Pea and F. Ramrez-Crescencio
Centro de Ciencias Aplicadas y Desarrollo Tecnolgico Universidad Nacional Autnoma de Mxico, Cd. Universitaria A.P. 70-186, C. P. 04510, Coyoacn, Mxico D. F., Mxico.

ABSTRACT
More than a simple review, this is a compilation of what has been done so far in relation to metallic nanoparticle-polymer composites with applications in catalysis reported up to now. We are going through all the transition metals from scandium to the noble metals to the copper group. Also, we report that, basically, the noble or platinum group metals are the metals commonly used as catalysts although some of the others have been proven to work as catalysts on different reactions.

INTRODUCTION
Nanocomposites can be defined as nanomaterials that combine one or more separate components in order to obtain the best properties of each component in which nanoparticles act as fillers in a matrix, usually a polymer matrix. In catalysis, in particular, metal nanoparticles act as catalysis centers, while the matrixes are the supports of these centers, trying to obtain materials that can have both properties as large, recoverable and reusable supports but with plenty of reaction centers, like in heterogeneous catalysis, which can be soluble obtaining the benefits of homogeneous catalysts. Since nanoparticles have high relationship superficial area/volume which gave them their different properties compaired from their macromolecular counterpart; they are so reactive
*

Corresponding Author Roco Redn, telephone +52-55/5622-8602, ext. 1154; FAX +52-55/5622-8651, E-mail: rredon@unam.mx.

Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

that it is necessary to protect them by adding extra molecules such as polymers or dendrimers and they can have either inter- or intra-molecular interactions or a combination of both (Figure 1).

Inter-molecular interactions

= Metallic NPs = Matrix molecules

Figure 1. Possible interactions in Nanocomposites.

Intra-molecular interactions (Chemical bond)

Sc-Mn groups
The first elements that we are going to address, are from the groups scandium to manganese, which basically, can produce metal oxides and usually are employed as supports of other metallic nanoparticles, thus in this part we are going to mention a few researches, that include the above mentioned metals and their applications. Titanium. No information about synthesis of Nb nanocomposites has been found during the present review. On the other hand, it is well known that titanium has been largely used as titanim oxide as catalyst support, basically for heterogeneous catalysis, and in this direction there are some researches that include gold metallic nanoparticles as catalyst centers, where the authors fount that, the high catalytic activity of SSP-Au/TiO2 1073 is attributed to the highly dispersed gold particles being modified by a strong interaction with TiO2 that induced a synergy effect in the catalysis [1], some others only report the synthesis of the nanocomposites TiO2-metallic NPs [2], or the main research is around some optic applications, like in the Murrays paper, where they report spectral features of far-infrared electromagnetic radiation absorption in anatase TiO2 nanopowders that they attribute to absorption by acoustic phonon modes of the dispersed nanoparticles [3]; as corrosion protective. A TiOx porous layer obtained by templating synthesis was used as nanostructured reservoir for an organic corrosion inhibitor. This provides active corrosion protection and self-healing ability of the coating system [4]; finally, we have found a example where titanium NPs are use in medical applications where the authors reported a increased skeletal muscle cell and osteoblast numbers on hydrothermally-treated nano-hydroxyapatite/collagen type i composites for entheses applications [5].

Metallic Nanoparticles Nanocomposites

The case of vanadium is similar to titanium, thus the reports include vanadium composite as catalyst; the case presented is a metallic Ag arrays assembled in nanoporous VSB-5 nanocrystals, where the catalytic activity of these Ag(O)-VSB-5 composites was found to be highly efficient catalysts for the syntheses of olefin aldehyde from styrene [6] and in optical applications with vanadium oxide (VO2) in a study where they reported that the optical contrast between the semiconducting and metallic phases is dramatically enhanced in the visible region, presenting size-dependent optical resonances and size-dependent transition temperatures [7a] in a study concerning the absorption and scattering of infrared radiation by vanadium dioxide nanoparticles with a metallic shell, where the authors prove that the transition of VO2 to the metallic state near (or away from) plasmon resonances leads to a decrease (or increase) in the absorption and scattering cross sections for a given wavelength [7b]; or in a material to build fiber-optic by using ion implantation to dope the VO2 nanoparticles with tungsten or titanium ions, where they demonstrated, the ability to control the characteristics of the phase transition [7c]. In the case of chromium we only found reports related to optical application with the use of aerosils modified by chromium oxide, where the optical properties of the nanocomposites demonstrates that the obtained nanocomposites can be used as passive Q switches [8]; or as an etch mask to fabricate pyramidal pits and then as a deposition mask to form the metallic pyramids [9] As in the previous elements, manganese also has been used as manganese oxide as support for gold NPs, obtaining a synergistic catalytic effect on conversion and selectivity in the case of Au/MnO2CeO2 catalysts, due to the coexistence of metallic and nonmetallic gold species within nano gold particle and the minor presence of Ce3+ species [10]; on the manufacture of new generation catalysts containing various metals (nickel, manganese, copper, palladium) deposited on a porous support such as alumina or silica gel, which in the case of asymmetric catalysts, Pd nanoparticles associated to cinchonidine as an asymmetric ligand inside silica particles have been prepared by this process for the ethyl pyruvate hydrogenation [11]; or for the production of carbon nanotubes with marine manganese nodule as a versatile catalyst, where the catalytic metal cations, originally accommodated in the mineral, moved to the outer surface, where they aggregated to metallic nanoparticles available for the growth of the nanotubes [12] and just, synthesized for future applications [13]. In the last years, yttrium has become an important constituent of various materials for technical applications [14] and a wide range of articles have been published, essentialy as Y2O3, (yttria) [15] and yttrium aluminium [16] (or iron [17]) garnet nanoparticles.The only example that we found reported related to metallic yttrium involves an AlYNiCoPd alloy achieved by the group of Louzguine-Luzgin [18]. Many of the articles about Zirconium and nanoparticles are more related with ZrO2 (zirconia) as an excellent support of other nanostructures [19]. Although, some investigations about metallic nanostructured zirconium have been informed. Bulk metallic glasses based on zirconium NPs had attracted great attention due to their elastic strain and remarkable plasticity [20]. J. B. Qiang et. at. [20] have prepared an alloy ingot with a composition Zr65Al7.5Cu27.5. Hajlaoui et. al. [21] reported an Cu50Zr50 alloy. And the group of Eckert [22] has achieved Zr62-xTixCu20All0Ni8 bulk samples (0 x 7.5). Other examples of alloys as Dutkiewiczs [23] can be found. S. P. Gubin [24] and collaboratores reported a metallic zirconium-poly(carbosilane) nanocomposites. As in the case of scandium, no information about synthesis of Niobium nanocomposites has been found during the present review. Metallic niobium particles are reported only in

Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

alloys; generally with Fe and B [25]. In addition, some investigations have been made on Nb as support of magnetic Tb nanoparticles [26]; as thin films [27] or matrix [28]. Physical techniques of synthesis were used when metallic molybdenum NPs were required. V. S. Purohit [29] has obtained NPs through microwave assisted electron cyclotron resonance (ECR) plasma induced chemical sputtering process, using hydrogen as the ionizing gas, with particle sizes of 6-7 nm. Molybdenum nanocomposites are more usual than naked or not protected NPs, due to their reactivity with environmental oxygen. Berkos group has achieved Mo nanoparticles on a TiO2 (1 1 0) surface trough molecular vapor deposition (MVD) [30]. Other studies, like Ptigny s [31], Blondeau-Patissier [32], Domenichinis [33], Pruniers [34], or Petukhovs [35] are focus on this system. L.A. Daz et. al. [36] have obtained alumina/molybdenum nanocomposites putting together -alumina powder and MoCl5 in anhydrous ethanol. Unlike physical techniques, little information about synthesis of metallic molybdenum NPs by soft chemical reduction is found. Redels group had obtained dispersions of this metal through thermal decomposition of Mo(CO)6, using ionic liquids (ILs) as stabilizers [37]. Technetium. 99mTc is widely used in radiopharmaceutical for diagnosis and therapeutic purposes [38] mainly as coordination compounds [39]. Fortunatelly, some reviews of 99mTc nanocomposites are reported [38-40], where the authors inform that these NPs have compositions based on TcxSy. Only a few reports have ben found related to lanthanum NPs, like the one from Cao et. al. [41], who informed a method for preparing graphitic carbon encapsulated lanthanum NPs. On other paper, lanthanum hydroxide nanofibers have been synthesized by Djerdj et. al. [42] Fokema and Ying [43] have synthesized La2O3 through an aqueous solution of La(NO3)3 added to an aqueous organic base and aged for 12-24 h. This oxide presented a catalytic activity for NOx reduction with methane in the presence of oxygen. Peng et. al. [44] have obtained Lanthane-doped mesoporous TiO2 nanoparticles via hydrothermal process by using cetyltrimethylammonium bromide (CTAB) as surfactant-directing agent and pore-forming agent. Mesoporous doped TiO2 nanoparticles have mean diameter of 20 nm with mean pore size of 2.2 nm and show activity on the oxidation of rhodamine. As the rest metals in these grops, hafnium has been studied as de correspondant, in this direction B. Reddy and coworkers [45] have synthesized nanocomposite oxides of CeO2HfO2, for soot oxidation. Silica-Hafnia nanocomposites have been obtained by Loureiro et. al. [46] Nanoparticles of HfO2 have been obtained through ultrasonically assisted hydrothermal decomposition of HfO(OH)2.nH2O by Meskin et. al. [47] Reactions of hafnium isopropoxide with hafnium halides at high temperature in pure TOPO (Trioctylphosphine oxide) yield nanometer-sized HfO2 nanocrystals of 5.5 nm [48]. Nano-tantalum powders have been prepared by arc-plasma method and the average diameter of the grains is 10 nm [49] the product consist of a large quantity of nanoparticles of tantalum and hexagonal TaO phase. Schulz et. al. [50] have obtained Ta2O5/SiO2 particles by flame spray pyrolysis (FSP). On other investigations, oxides of tantalum have been synthesized by thin-wire explosion [51], non-aqueous condensation of tantalum ethoxide [52], and hydrolysis of tantalum ethoxide [53]. Tantala-coated polystyrene (PS) particles were prepared by hydrolyzing tantalum ethoxide in ethanol at 28 C in the presence of functionalized PS beads (540 nm), the polymer core was removed either via chemical treatment with toluene or calcination at 650 C obtaining sub-micrometer hollow spheres of Ta2O5 [54].

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Sahoo and coworkers [55] have obtained tungsten nanoparticles by thermal decomposition of tungsten hexacarbonyl [W(CO)6] at 160 C in presence of a mixture of (1:1) surfactants, oleic acid and trioctyl phosphine oxide (TOPO) under a blanket of Ar gas. The presence of surfactant reduces the particle size and with further increase in surfactant concentration increases the particle size. Tungsten NPs [56] are obtained reproducibly by thermal or photolytic decomposition under argon from mononuclear metal carbonyl precursors M(CO)6 (M = Cr, Mo, W) suspended in the ionic liquids BMim+BF4-, BMim+OTfand BtMA+Tf2N- (BMim+ = n-butyl-methyl-imidazolium, BtMA+ = n-butyl-trimethylammonium, Tf2N = N(O2SCF3)2, OTf = O3SCF3) with a very small and uniform size of 1 to 1.5 nm in BMim+BF4- which increases with the molecular volume of the ionic liquid anion to ~100 nm in BtMA+Tf2N-. A mixture of scheelite (CaWO4) and magnesium was milled together for 100 h in a nitrogen atmosphere, after removal subproducts, 10 nm crystallites of elemental tungsten were obtained [57]. Thermal plasma process was applied by Ryu et. al. [58] to produce nanosized tungsten powder using ammonium paratungstate (APT) as the precursor. The produced tungsten powder was treated by hydrogen during which minor amounts of WO2 or WO3 were reduced to tungsten. Finally, nanosized W powder consisting of spherical particles of less than 50 nm was obtained. WO3/TiO2 composite NPs have been synthesized by dissolving W and Ti precursors in a suitable solvent and spraying into a high temperature acetylene-oxygen flame using a reactive atomizing gas, obtaining sizes from 5 to 20 nm and 10 to 50 nm. Additionally WO3/TiO2 has been successfully tested for selective catalytic reduction of NOx. [59], with good results. WO3/polyacrylonitrile nanocomposite were obtained by Wei et. al. [60] stirring WO3 nanoparticles in a commercially available polyacrylonitrile (PAN) solution. Makaryan [61] have studied the synthesis of composite polymer-based materials. Polymeric matrices chosen are the copolymer of formaldehyde and dioxalane (CFD) and the polyphenylene sulphide (PPS). Results indicate a higher hardness using amorphous nanosized tungsten fillers with a particle size less than 10 nm. Rhenium nanostructures have been synthesized by Hassel and coworkers [62]. A NiAl 1.5 at.%Re eutectic alloy was directionally solidified using a constant growth rate and temperature gradient. The selective dissolution of the NiAl matrix with a mixture of HCl:H2O2 produced rhenium fibers (diameter ~400 nm) Digestion of the NiAlRe eutectic in sulphuric acid, on the other hand, produced mainly long rhenium fibres. On the other hand, rhenium sulfide nanoparticles have been obtained by Tu et. al. [63].

FE-CU GROUPS
These are the main metals that had ben involved in catalysis since the catalysis was explored, thus we are going to try to cover the newest publications on the nanocomposites metal NPs-support molecule and their catalytic applications. In the last years, iron has become more important in catalysis, especially in within the employment of nanoparticles, thus we are going to mention some of the last papers related on nanocomposites that contain iron nanoparticles and their uses mainly on catalysis, even though there are some other applications like in magnetism or optical, which will be mention also.For example they had been used supported on carbon nanotubes in during FisherTropsch synthesis [64]; in the decomposition reaction of H2O2 by measuring the formation of gaseous O-2, using a Fe-0/Fe3O4 composite [65]. Fe/SBA-15/carbon composites were used as

Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

catalyst in the benzylation reaction of benzene with benzyl chloride [66]; as model catalyst Fe film on SiO2 during preannealing in O-2 and NH3 and during C2H2 decomposition, where the catalyst metal surface supplies sites to dissociate the hydrocarbon precursor and then guides the formation of a carbon lattice and the liftoff of a carbon cap. The Fe the active state of the catalyst is a crystalline metallic nanoparticle, while graphitic networks do not form on oxidized Fe [67a]; in the synthesis of carbon nanotubes (CNT), by using a nanocomposite of montmorillonite clay through anchoring on FeCo nanoparticles [67b] or by using Fe-doped carbon aerogels [67c]; by employing ferrocene, yielding nanofiber-supported iron oxide nanoparticles, while secondary carbon nanofibers with diameters in the range from 10 to 20 nm were subsequently grown from cyclohexane catalyzed by the sintered metallic iron nanoparticles under reducing conditions [67d]; in the case of metallic iron particles in montmorillonite matrix, to obtain a catalytic conversion of phenol oxidation of 49.5 % with a 67.4 % of selectivity to carbon dioxide and tar, where the authors propose that the iron species dispersed in clay matrix may provide the catalytic active sites and the size of iron species has an effect on selectivity [68]; as support like iron oxide with gold NPs in methanol oxidation, obtaining an enhanced oxidation with the use of this support [69]; in microwave oxidation of alcohols using supported metallic iron nanoparticles [70]. Most of the reports are related with the magnetic [71-82]; optical properties [83], as templates [84]; dissecants; in the design of permeable reactive barriers [85]; as humidity sensors [86] or only the synthesis of iron nanocomposites for future applications [87-96]. The reports that we have found for cobalt nanocomposites are some related to magnetic applications [97-99] and one more related to the synthesis for future applications [100]. The case of nickel, as in its bulk applications, there are more catalysis examples; in their use as catalysts in Sonogashira coupling reactions [101]; in methanation, with silica supported Ni NPs, where the nanoparticles were more efficient without the support [102]; in order to understand the oxidation of the nanoparticles surface when catalytic reactions take place and to understand more of the enantioselective heterogeneous catalysis, the authors made a study with nickel NPs and tartaric acid [103]; there are also some papers related to magnetic applications [104-107] and those dedicated on the nickel nanocomposite synthesis [108-113]. There are some papers dedicated to copper NPs catalysis, such is the case of the reactions to produce Hydrogen by reforming of methanol in supercritical water; in this paper the authors reported the in sittu generation and regeneration of the Cu NPs catalyst [114]; in the Ullman reaction with sonochemically derived copper powder that shows the presence of porous aggregates (50-70 nm) which contain an irregular network of small nanoparticles. The as prepared copper NPs are catalytically active toward the mentioned "Ullmann reaction"-that is, the condensation of aryl halides to an extent of 80-90 % conversion [115]; on other paper, the authors reported that copper metallic particles are formed and get anchored in the siloxane oligorner obtained during the reaction of phenylsilane and ethyleneglycol with bispyridinium, tetrachlorocopper(II). These supported metallic copper particles can catalyse the coupling reactions of silanes with alcohols [116]; Finally, the use of copper NPs, in this case deposited onto mesoporous SBA-15 support were proved in catalytic activity tests for CO oxidation, where the best performance was obtained when the catalyst was calcined at 500 C and reduced at 550 C [117]. The rest of the papers that we have found are related to other applications such as optical [128-124]; as combustion characteristics [125]; as insulators [126]; as cathode material [127]; studing their mechanical properties [128], and there are those related to the synthesis of copper nanocomposites [129-133].

Metallic Nanoparticles Nanocomposites

Ruthenium catalysis. Metallic ruthenium NPs are used in the catalytic hydrogenation of unsatured bonds. Marconi et. al. tested -Al2O3 supported metallic ruthenium nanoparticles in the catalytic hydrogenation of methyl benzoate to methyl cyclohexanoate, and 2-(4carbomethoxyphenyl)-1,3-dioxane to 2-(4-carbomethoxycyclohexyl)-1,3-dioxane [134]. For methyl benzoate, the best results were found for the Ru-TOA supported on -Al2O3 using cyclohexane as solvent, with a quantitative reaction in 8 h; and, in the case of 2-(4carbomethoxyphenyl)-1,3-dioxane, the same catalyst was reported as the most catalytically active, with a quantitative reaction in 20 h, using tetrahydrofuran (THF) as solvent. In the last case, the authors performed a modified catalytic test in solventless conditions, and lower times of reaction (15 h) were achieved, though they found less selectivity of the desired product (95%). Recently, Raspolli Galletti et. al. have developed -Al2O3 supported ruthenium(0) NPs to catalyze the hydrogenation of phenol [135]; which has shown a catalytic activity up to 88% conversion in 2 h, and a selectivity of 83% to cyclohexanone product (cyclohexanol is the only byproduct). In a previous work, they have explored the synthesis of this catalysis via polyol method assisted by microwave irradiation [136]. In this case, the best result was achieved with 81.5% conversion in 2 h, with 87% selectivity to cyclohexanone product. Chaudret group obtained ruthenium nanoparticles supported onto nanoporous alumina membranes, and tested them in the catalytic hydrogenation of 1,3-butadiene in the gas phase [137]; they have determined better activities for the nanoparticles pre-reduced and later supported due to regularity inside the pores. Quantitative conversion was achieved in 25 minutes when 5 nm particles are used. Recently, Hans group used a PVP (poly (vynilpyrrolidone)) modified silica to support ruthenium nanoparticles [138]. A Ru/silica catalyst was tested too in the hydrogenation of benzene under biphasic (ionic liquids-benzene) conditions. Quantitative conversions were achieved in almost every case with TOF up to 74900 h-1, when the silica modified PVP support is used. Boujday and collaborators have used a SBA-15-type mesoporous silica to introduce the [Ru-(C6Me6)2Mo5O18 Ru(C6Me6)(H2O)] poly-oxomolybdate by wetness impregnation, using dichloromethane as solvent, reduce under a reducing atmosphere, and finally test it in the catalytic hydrogenation of benzene [139]; with better catalytic activity at 623 K. Su and collaborators have synthesized silica, carbon coated silica, and templated mesoporous carbon supported ruthenium(0) nanoparticles [140]. When these catalysts were tested in the hydrogenation of benzene and toluene, almost quantitative conversions were achieved in almost every experiment with TOF up to 37.7 h-1, for benzene, and 9.8 h-1 for toluene. The Tsangs group used CO2 supercritical microemulsions to synthesize Ru nanoparticles [141]. These NPs were tested in the reduction of citral. Quantitative conversion is achieved when the ruthenium composite is used, with 75.5% selectivity for the citronellal (CIAL) product. In contrast, Manikandan and co-workers obtained less selectivity and a major dispersion of products, from 11% to 43% (geraniol, nerol, citronellal and citronellol, as principal products), for the hydrogenation of citral when two montmorillonite supported ruthenium catalysts were used [142]. Lius group has used the 1,1,3,3-tetramethylguanidinium trifluoroacetate ([TMG][TFA]) ionic liquid to support metallic ruthenium nanoparticles on montmorillonite (MMT) [143]. In the hydrogenation of benzene, better results were obtained in comparison with other catalysts (Ru/C and Ru/Al2O3) prepared by the authors. Quantitative yields were reported at 40 C, in 1.5 h, and a TOF of 667 h-1. In a similar synthesis, Kantam and coworkers obtained nano-crystalline magnesium oxide supported ruthenium nanoparticles,

Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

using chlorine hydroxide ionic liquid, and used them in the transfer hydrogenation of various carbonyl compounds [144]. 95% conversion of acetophenone to 1-phenylethanol (acetone as by product) was achieved in 6 h. Asedegbega-Nieto and co-workers have supported ruthenium nanoparticles onto carbon nanofibers with different topographies and used them to hydrogenate selectively 4-acetamidophenol (paracetamol) [145]. During the catalytic hydrogentation, the main product was a mixture of cis- and trans-4-acetamidocyclohexanol with conversion of 60%; the best trans-/cis- ratio (1.4) is achieved when the ruthenium nanoparticles are supported onto the platelet-like carbon nanofiber. In the same line of investigation, Takasaki and collaborators used carbon nanofibers to support ruthenium nanoparticles and used them in the partial hydrogenation of 1,1-bi-2-naphthol (BINOL) derivatives [146]. The best results were achieved for BINOL with a substrate/catalyst ratio of 1390, at 50 C, in 48 h, with a 99% yield of isolated 5,5,6,6,7,7,8,8-octahydro-1,1-bi-2naphtol (ee of >99.9%). In a previous work, this group used carbon nanofibers with different topographies as supports, and applied these catalysts in the hydrogenation of toluene [147]. There, the authors determined that the best support is the platelet-type carbon nanofiber with a quantitative conversion of toluene to methylcyclohexane with a TOF up to 14200 h-1. By their way Zhaos group, employed templated porous carbon materials to obtain supported ruthenium nanoparticles, and used them to catalyze the hydrogenation of benzene [148]. Almost quantitative conversion (99.8%) is achieved when a benzene/Ru(0) ratio of 10000 is used, in 1.0 h, at 110 C, and a TOF of 9980 h-1. Other group that has used carbon to obtain a Ru(0) catalyst, is Denicourt-Nowicki et. al. [149]; the catalysts were tested in the catalytic hydrogenation of o- m- and p-xylene. Superior results were obtained when randomly 3methyladed--cyclodextrin is used as stabilizer in the catalytic hydrogenation of m-xylene, with 30.5 h-1 TOF, and 88.6% selectivity for the cis-1,3-dimethylcyclohexane, thought better selectivity is achieved with the correspondent -cyclodextrin with o-xylene. In a recent investigation, the same group combined randomly methylated cyclodextrins and N,Ndimethyl,N-hexadecyl,N-(2-hydroxyethyl)-ammonium chloride salt to form an inclusion complex and stabilize metallic ruthenium nanoparticles, which were used in the catalytic hydrogenation of arenes [150]. The best TOF (83.3 h-1) was achieved for the hydrogenation of styrene, when -cyclodextrin is used as part of the inclusion complex, though only the alkene is reduced. When longer times are used in the catalytic reaction, the reduction of aryl group is achieved. In other work, this group developed the stabilization of Ru(0) NPs by the random methyladed cyclodextins [151]. In this investigation, the catalysts were tested in the catalytic hydrogenation of alkenes, and in every case, quantitative reactions were achieved in different times. The best results were for cyclohexene with a TOF of 34 h-1, when 3-methyladed-cyclodextrin is employed. A previous work from this group focused in the stabilization efficiency of the methylated cyclodextrins, and realized the first attempts to apply these ruthenium NPs in the catalytic hydrogenation of aryl derivatives [152]. In every case, the reaction was quantitative, with superior results for benzene with 25h-1 TOF, if the metylated-cyclodextrin is used as stabilizer. On the other hand, Sun et. al have used a series of Y zeolites (PQ-13.6, LZY-82 and a dealuminated DLZY-82) to prepare zeolite supported ruthenium NPs by ion exchange and subsequent reduction in a H2 flow [153]. These catalysts were compared with their sulfide analogous, and the authors reported lower catalytic properties, yet better selectivity toward the formation of isomerisation products. Philippot, Roucoux and Clavers group have developed an interesting oncoming to enantioselective

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catalysis [154]. In a homogeneous catalysts approach, they have used furanose derived diphosphite ligands as stabilizers. The catalyst was tested in the catalytic hydrogenation of oand m- methylanisol; in the first case, quantitative hydrogenation was achieved in pentane, at 20 C, with 100% selectivity for the cis-1-methoxy-2-methylcyclohexane product, with a TON of 98; and in the second case, quantitative conversion was fulfilled in pentane, at 20 C, 79% selectivity for selectivity for the cis-1-methoxy-3-methylcyclohexane product, with a TON of 98. In the same way, Duponts group has achieved metallic NPs in ionic liquids, they have used 1-n-butyl-3-methylimidazolium (BMI) and 1-n-decyl-3-methylimidazolium (DMI) N-bis(trifluoromethanesulfonyl)imidates (NTf2) an tetraflouroborates (BF4) ionic liquids to synthesize well dispersed metallic ruthenium nanoparticles by [Ru(COD)(2-methylallyl)2] decomposition under H2 flow at 50 C [155]. These stabilized NPs were used in the catalytic hydrogenation of arenes in biphasic conditions, and superior result were obtained for toluene when [BMI][BF4] is used as stabilizer, with a 85% of conversion to methylcyclohexane in 18 h at 75 C. In contrast, when the hydrogenation of more substituted benzenes are carried out, low conversions are achieved. By their way, Rossi et. al. used RuO2 as precursor to synthesize Ru(0) nanoparticles in ionic liquids [156]; with a quantitative conversion and a TOF of 953 h-1. A lower, but still good, TOF is achieved for toluene with 556 h-1 in the same conditions. When it comes to colloidal nanoparticles, Lu et. al. achieved PVP protected nanoparticles and used them in the catalytic hydrogenation of arenes, olefins and carbonyl compounds [157]. Quantitative conversions were achieved in every case, with superior TOFs from 1,100 h-1, for methylbenzoate, to 45,000h -1, for benzene. Finally, the hydrogenation of carbon monoxide to yield hydrocarbons (Fischer-Tropsch process) was reported by Kou and Yans group [158], where an activity up to 1.6 h-1 has been achieved for the reaction carried out in water, using NaBH4 as reducing agent. A more recent investigation is reported by Kang et. al. They have used supported ruthenium nanoparticles onto different supports to carry out the Fischer-Tropsch process [159]. The best conversion (34%) of CO is achieved for the modified carbon nanotubes supported ruthenium NPs, with 60% selectivity for C10-C20 hydrocarbons. Other colloidal ruthenium NPs were achieved by stabilization with octa(aminophenyl) silsesquioxane (OAPS). Yang and collaborators carried out the investigation [160]. The obtained NPs get poor TOFs (from 0 to 6 h-1) for the reduction of phenylaldehydes. Perticis group have used inorganic polyorganophosphazenes to support Ru(0) NPs and used them in the hydrogenation of various unsatured groups [161]. The authors said that their catalyst is soluble in organic mediums, so the cataytic tests can be carried out in biphasic or homogeneous mediums. When the catalysts were tested in the reduction of olefins, better result is achieved for the hydrogenation of -acetoamido acrylic acid with a quantitative conversion to N-acetylalanine, with 16.7 h-1 TOF, in a biphasic medium (catalyst/H2O). When tested in the hydrogenation of ketones, good results with 16.6 h-1 TOFs were achieved for the hydrogenation of ethyl pyruvate to ethyl lactate in a homogeneous medium (ethanol). On the contrary, poor results are obtained when the catalyst is employed in the reduction of aryl derivatives (3.3 h-1 TOF for p-aminomethyl-benzoic acid to 4-aminomethylcyclohexane carboxylic acid with 3 cis-/trans- ratio). Other catalytic reduction carried out by Ru(0) NPs is the hydrogenation of aromatic nitrocompounds. Recently, Pietrowski an collaborators, who studied the reduction of o-chloronitrobenzene to o-chloroaniline using magnesium fluoride supported ruthenium NPs as catalyst [162]. Zuo group prepared SnO2 supported metallic ruthenium NPs and used them to catalyze the hydrogenation of o-chloronitrobenzene [163]. When the Ru/SnO2 and Ru/PVP were tested for

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

the catalytic hydrogenation, similar values were reported: quantitative conversion with >99.9% selectivity for the desired product. Other catalytic reaction that can be seen as reduction is the catalytic ammonia decomposition. Some examples catalyzed by ruthenium NPs are found. Zheng and collaborators prepared a series of -Al2O3 supported Ru(0) NPs, to study kinetically the catalytic decomposition of NH3 [164]. With their catalysts, at 823 K, a complete decomposition of NH3 is achieved. By their way, Yin et. al. have realized studies in the catalytic decomposition of ammonia, using supported ruthenium NPs. In an article, they have synthesized a series of ZrO2 materials modified with KOH and NH4-OH (labeled as ZrO2-KOH and ZrO2-NH4OH, respectively) [165]. The ruthenium NPs were supported by incipient wetness impregnation of the support materials using ethanolic [Ru(acac)3] solution. The best conversion (58.2%) was achieved at 673 K, using the ZrO2-KOH supported ruthenium chlorine free NPs. The catalysts obtained via RuCl3 showed poor activities, proving chloride poisoning in the samples. In other work, this group supported ruthenium NPs onto CNT through the same method and modified with KOH [166]. Besides, CNT, other supports (MgO, activated carbon, ZrO2, and Al2O3) were employed to compare the catalytic activities. A quantitative conversion was achieved at 550 C, with a H2 formation rate of 33.5 mmol/(g-catal min). In a process contrary to the hydrogenation of unsatured bonds, the ruthenium NPs catalyzes the oxidation of molecules also. One of most reported processes is the partial oxidation methane. Gedankens group studied the catalytic activity of SBA-15supported ruthenium NPs in the partial oxidation of methane [167]. The maximum conversion of methane (65.4%) is achieved with a Ru loading ratio of 14 %, at 750 C with 83.5% selectivity for the CO product. Latter, this group used a similar process to synthesize a Ru/TiO2 mesoporous catalyst [168]; but in this occasion, ultrasound is used instead of microwave irradiation. Better results were achieved in this experiment, with up to 88.5% conversion of methane, with 95.5% and 95.8% selectivity to CO and H2, respectively, when the reaction is carried out at 800 C. Other work focused in this catalytic reaction is the one developed by Balint et. al. [169] The catalyst was obtained through a polyol process in presence of -Al2O3. The best result is achieved at 650 C with a 79% conversion of the methane, and 72.1% and 67.6% selectivity to CO and H2, each. In other experiment, the group studied the dependence of the formation of equilibrium RuO2 Ru at lower and higher temperatures, on the formation of completely oxidized products and CO/H2 production [170]. Concluding that higher temperatures, and consequently production of Ru(0), are necessary for a good production of CO/H2(syngas). In a previous work, this group investigated the partial reduction of methane, using NO as oxygen source [171]. The catalyst used is the same, synthesized by the same method. At 650 C, the highest selectivity is achieved with 81% and 82% for CO and H2, respectively. Other process catalyzed by ruthenium NPs is the oxidation of arenes, via a wet air oxidation. Guerrero-Ruiz and collaborators report this process [172]. The supports used were ZrO2 modified with SiO2, mesoporous high surface area graphite (HSAG), and commercial activated carbon (AC). The ruthenium NPs were loaded by impregnation of the supports with an excess of solvent (THF and ethanol) volume in a rotatory evaporator with solutions of the precursors, dried, and reduced under a H2 flow. In a comparative conversion of the arenes to CO2, the oxidation is realized in absence of catalyst, 473 K is required to obtain 90% and 100%, for aniline and phenol, respectively. When the supported catalysts were tested, up to 269 h-1 and 1232 h-1 TOFs were achieved, for aniline and phenol, respectively, with high mineralization yields,

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11

when activated carbon is used in both cases. Perkas and co-workers developed a similar method [173]. This group, supported ruthenium nanoparticles over mesoporous TiO2 (modified with dodecylamine) and ZrO2 (modified with sodium dodecyl-sulfate) with high surface area, prepared by a sonochemical method. When the catalytic oxidation of acetic acid was carried out, up to initial rate of 19.0 mol-acid/(h*mol-cat) when Ru/ZrO2 is employed; in the case of oxidation of succinic acid, up to initial rate of 30 mol-acid/(h*mol-cat), when Ru/TiO2 is used; finally, when p-coumaric acid oxidation was tested, rapidly disappeared to yield p-hydroxybenzoic and p-hydroxybenzaldehyde acids, with Ru/TiO2, which were further oxidized. Other process reported for the ruthenium NPs mediated catalysis, is the oxidation of D-glucose to D-gluconic acid. Matveevas group developed a ruthenium catalyst for this process [174]. The catalysts were prepared by impregnation of Ru(OH)Cl3 into a hypercrosslinked polystyrene (HPS) matrix. Up to 13.8x10-3 s-1 TOFs are found for this catalyst, with 99.6% selectivity for the D-gluconic acid product. Besides the decomposition of ammonia, synthesis of ammonia is carried out by ruthenium NPs. Recently, Seetharamulu et. al. have used two ruthenium alkali promoted catalysts supported onto Mg-Al hydrotalcite (HT) [175]. The highest activity is reported for the double promoted catalyst, modified with the polyol process, with more than 160 x 104 TOF; while the cesium promoted catalyst is more active at lower temperatures. Moroz group used the cesium promoted ruthenium catalyst, supported onto MgO, to also synthesize ammonia [176]. The catalyst was deposited via two successive wetness impregnation methods of acetone Ru(OH)Cl3 and ethanol Cs3CO3 solutions. Superior activities were achieved for the cesium promoted catalyst in comparison with the ruthenium catalyst. In the article, the authors try to explain these results. Recently, an investigation of catalytic decomposition of NaBH4 to produce H2 via polystyrene microspheres supported ruthenium NPs is reported by Chen and co-workers [177]. By their way, Liu and collaborators had used a LiCoO2 supported ruthenium catalyst via a microwaveassisted polyol process [178]. With 1 wt. % Ru/LiCoO2 loading, rate up to 0.05 L(H2)/(s g(catalyst)) achieved. In the same line of investigation, zkar group have prepared a Ru(0) dispersion stabilized by sodium acetate by chemical reduction with NaBH4 [179]. Up to 7.9 s-1 TOF is achieved with this catalyst. Choi et. al. reported a series of polymer supported ruthenium NPs to catalyze carbenoid transfer reactions [180]. When different diazoacetamides are tested in the intramolecular carbenoid C-H insertion, N-p-chlorobenzylN-tert-butyl--ethoxycarbonyl--diazoacetamide gave the best result, with a 98% yield of isolated product, with an exclusive production of the cis--lactam, in 1 h, when the NCPS-Ru catalyst was used. The authors report the catalytic production of -lactams by the catalytic carbenoir C-H insertion of diazoacetamides derived from amino acids, using NCPS-Ru as catalyst, too: when used the diazoacetamide prepared from L-phenylalanine, up to 90% yield was obtained for the trans--lactam. The intramolecular carbenoid N-H insertion reaction catalyzed by NCPS-Ru was examined also: allyl diazoacetates gave proline products with high cis- selectivity and in superior yields (91-96%). These substrates were tested in the catalytic cyclopropanation, too: production of cyclopropyl lactones in good yields (70%-89%) was achieved. When tested the catalytic intramolecular tandem ammonium ylide/[2,3]sigmatropic rearrangement reaction, up to 95% yields were achieved, with no [1,2]rearrangement product detected. This catalyst is active toward the intermolecular cyclopropanation of alkenes, with up to 91% yield for styrene, with 70:30 trans-/cis- ratio. In the catalytic intermolecular carbenoid N-H insertion high yields (99%-60%) were obtained by

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

a one-pot reaction of the appropriate amine and ethyl diazoacetate, even in scaling up reactions. Finally, intermolecular carbenoid C-H insertions were tried: the reaction of methyl phenyl diazoacetate with different substrates, up to 62% yield for only one product is achieved. Selective aerobic epoxidation of alkenes is catalyzed by ruthenium NPs stabilized by H5PV2Mo10O40 (POM) and supported by wet impregnation on -Al2O3; this investigation was developed by Neumans group [181]. Different alkenes were tested in the catalytic epoxidation, and the best result was achieved when cyclododecene was used, with a 66% epoxide yield. No other products beside epoxide were detected. Yu and Che group used ruthenium NPs supported on hydroxyapatite to catalyze cis-hydroxilation and oxidative cleavage of alkenes [182]. This catalyst was tested with other substrates, too, and up to 85% yield for styrene glycol was obtained, when styrene is used. Finally, when the catalytic oxidative cleavage of alkenes is carried out, up to 92% yield is obtained for the 1-methyl-1phenylethene (obtaining methylphenone). Chang group used a series of colloids to catalyze a Heck type olefination and a Suzuki coupling [183]. When the catalyst obtained was tested in the Heck olefination, up to 99% isolated yield, using iodobenzene and styrene. When a commercial available Ru/Al2O3 catalyst was tested for the Heck type and Suzuki catalysis, even better results were found. Rhodium catalysis. By far, the most common reaction catalyzed by metallic rhodium nanoparticles is the hydrogenation of unsaturated bonds. On the reduction of aromatic rings, Launays group have carried out catalytic test over styrene, anisole, toluene, m-xylene, and tetralin with a Rh(0) catalyst [184]. The best results are obtained for ethylbenzene from styrene and methoxycyclohexane from anisole with almost 100% yields. Previously, the synthesis of an other Rh(0) catalyst containing a mesoporous siliceous material, with MCM41 pore architecture, has been reported by the same group [185]. The resulting supported NPs have been used in the reduction of styrene, o-, m- and p-xylene, and phenol; obtaining ethylcyclohexane, 1,2-dimethylcyclohexane, 1,3dimethylcyclohexane, 1,4dimethylcyclohexane (with a cis- preference in every case) and cyclohexanol/cyclohexanone, respectively. A complete conversion has been reached in all cases under H2 1MPa in less than 3 h. Other silica-supported Rh(0) NPs have been achieved by Mvellec et. al. [186] During the catalytic tests, they use a series of activated aryl rings, and the best results were obtained for anisole and phenol (with 129 h-1TOFs) and styrene (127 h-1 TOF). The worst result was for Aniline (31 h-1 TOF). Barthes group has carried out catalytic hydrogenations in toluene, anisole and o-xilene, using silica supported metallic Rh(0) NPs [187]. The authors, changed a series of variables and determined the best conditions, obtaining 100% conversion for toluene and anisole, with 282 h-1 and 300 h-1 TOFS, respectively; and 94% with a TOF of 120 h-1 for o-xilene. Besides, they found and interesting cis-/trans- 92/8 ratio of the product 1,2dimethylcyclohexane. Rossis group has achieved recoverable catalyst by synthesizing Rh(0) NPs deposited over an amino modified silica-coated Fe3O4 system [188]. They carry out experiments in cyclohexene and benzene obtaining >99% conversion under all conditions and TOFs up to 7600 h-1 with cyclohexene. Carbon supported Rh(0) NPs are also used as catalyst for aryl hydrogenation. Ikeda and co-workers have achieved a Rh(0) carbon core-shell nanostructure [189]. t-butylbenzene was employed as model reaction obtaining 99% yield in 2 h, at 353 K. Other hydrogenations catalysis have been carried out over benzoic acid, 3hydrooxypyridine and byphenyl, with 85% yield for cyclohexanecarboxylic acid, 98% for 3hydroxypiperidine, and up to 97% for bycyclohexane. Sons group has achieved charcoal supported Rh(0) NPs with well defined shapes [190]. The best activities are reported for

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tetrahedral nanoparticles over anthracene, with up to 99.3% selectivity for 1,2,3,4,5,6,7,8octahydroanthracene. Other arenes have been used in hydrogenation with these NPs; TOFs of 600 h-1 have been achieved for benzene, toluene, and methyl benzoate. Among the nanostructured carbon supports, CNT are widely used in the production of metallic NPs. Recently, Wais group has reported an investigation in the synthesis of a series of multiwalled carbon nanotubes (MWCNT) supported nanoparticles [191]. One of them refers to a system of metallic Rh obtained via water-in-hexane microemulsion method and then supported over carboxylic acid functionalized nanotubes. Benzene was used as model reaction catalysis; 118.1 h-1 TOF has been achieved. In a previous article, this group used the same catalyst to hydrogenate anthracene [192]; where 76.2% conversion has been found with a 62.4% selectivity for 1,2,3,4-tetrahydroanthracene. In other investigation, Kakade et. al. have used MWCNT as support materials for Rh(0) prepared by a simple microwave treatment [193]. When toluene was used for catalytic test, TON up to 9900 with nearly 100% conversion to methyl cyclohexane has been fulfilled. Other aryl derivatives have been used to test the catalytical activity. Wais group has obtained Rh(0) NPs synthesized in a water-in-CO2 microemulsion in presence of surfactants [194]. These NPs have been used in the hydrogenation of naphthalene and phenol in supercritical CO2. In the first case, tetralin with a >96% yield has been achieved; when it comes to phenol, >92% of conversion to cyclohexanone and cyclohexane with a ratio 15:1, calculated from the NMR peaks intensities, have been fulfilled. Recently, a Rh/Al2O3 catalyst synthetized by flame spray have been accomplished by Hoxha et. al. and used in enantioselective hydrogenations tests [195]. The hydrogenation of a couple of -ketoesters, ethyl pyruvate and ethyl 3-methyl-2-oxobutyrate in the presence of quinine (QN) and cinchonidine (CD), respectively, have been achieved. The systems have shown 53% enantiomeric excess (ee) for the -hydroxiester with 56% yield in 2h and 59% ee with 100% yield, each. Other -Al2O3 supported Rh(0) NPs obtained by Metal Vapor Synthesis have been used to hydrogenate unsatured bonds by Petricis [196] and Vitullis group [197]. The hydrogenation of 4-(6-methoxy-2,-naphthyl)-3-buten-2-one and 2acetyl-5,8-dimethoxy-3,4-dihydronaphthalene have been performed with a modified supported Rh-trioctylamine (TOA); 100% and 86% selectivity, respectively, to the hydrogenation of the ,-unsatured bond have been achieved (not the carbonyl or the aromatic fragments). In other work, the same catalyst has been used in the hydrogenation of methylbenzoate and cinnamaldehyde, and silylformylation of 1-hexyne. In the hydrogenation case, 80% and 100% selectivity for the ,-unsatured bond or the aryl system have been obtained. In the silylformylation case, a quantitative reaction and 100% selectivity for the (Z)1-(Dimethylphenylsilyl)-2-formyl-1-hexene product have been accomplished. By their side, Park et. al. performed hydrogenations over anisole and benzene with a rhodium in aluminum oxyhydroxide [Rh/AlO(OH)] prepared through a sol-gel reduction [198]. The reactions were carried out at room temperature and 75C in n-hexane and solventless, respectively. They have achieved nearly quantitative reactions in every case and TOFs up to 1700h-1. In a previous work from the same group, the actual catalyst was entrapped in a bohemite matrix by gelation with water [199]. The same systems in solventless conditions achieved 1000 h-1 and 5000 h-1, respectively. On the other hand, dos Santos and Duponts group has combined IL (1-n-butyl-3 methylimidazolium tetrafluoroborate) and sol-gel method to immobilize Rh(0) NPs within a silica network [200]. They have obtained TOFs up to 54 min-1 in 22 min for 1-Decene. Other catalyst, synthesized by Cimpeanu exploits the generation and

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

entrampment of Rh(0) NPs in simple solid ammonium salts by inducing their supercritic CO2 melting to form ionic liquids, and has been used in the hydrogenation of cyclohexene and benzene [201]. TOF values for both hydrogenations have been found in the order of 104 h-1 and 102 h-1, each. When it comes to colloidal catalysts, ionic liquids are commonly used as stabilizers of many metallic NPs. Recently, Janiak group has obtained Rh(0) NPs stabilized by ionic liquids (BMim+BF-4, BMim+OTf- and BtMA+NTf-2 [BMim+ = n-butyl-methylimidazolium, BtMA+ = n-butyl-tri methyl-ammonium, OTf- = -O3SCF3, NTf-2 = N(O2SCF3)2]) through thermal decomposition of Rh6(CO)16 [202]. The tests were performed in cyclohexene and yields up to 98% are obtained in 2.5 h, 75C, and 1% metal wt. Duponts group synthesized metallic Rh(0) NPs in 1-nbutyl-3-methylimidazolium hexafluorophosphate ionic liquid ([BMI][PF6]) under H2 at 4 bar and 75C for 1 h [203]. A series of hydrogenation catalytic tests were executed to correlate the results to the Raft equation. In a previous work, this group used the same method to carry out the hydrogenation of benzene [204]. The tests were performed in three systems: BMIPF6; acetone and solventless. The best results have been found for the solventless conditions with 21 h-1 TOF. The authors, reported poor conversions in many hours due to aggregations and lost of catalytic activities of the Rh(0) NPs. Dysons group combined the PVP-Ionic liquid method to synthesize a catalyst highly active under biphasic hydrogenation of unsatured molecules [205]. They compared the catalytic activity of the Rh(0) NPs in different ionic liquids using styrene hydrogenation as model reaction, finding better catalytic activities for ionic liquids with hydroxyl groups and weakly- or non-coordinating anions. Nearly quantitative conversions for styrene, cyclopentene, 1-octyne and 1-decyne, and average turnover frequency (TOF) of at least 2000 h-1 are obtained. In a similar strategy, Kous group used poly[(N-Vinyl-2-pyrrolidone)-co-(1vinyl-3-alkylimidazolium chloride)] copolymer to stabilize metallic rhodium NPs reduced with H2 in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([BMIM][BF4]) [206]. A series of substituted aryl rings were used for the catalytic tests. The best results obtained were for benzene with 96% conversion and for phenol with a better TOF (247 h-1); although poor conversion and a 74/26 ratio for the products cyclohexanol/cyclohexanone were achieved. In a previous article, this group reported the catalytic hydrogenation in benzene with the same NPs system [207]. In this study, TOF of 250 h-1 was obtained in 16 h. Diferent bipyridine ligands were used alongside ionic liquids to obtain colloidal Rhodium NPs and later used in aromatic hydrogenation, by Roucox and co-workers [208]. With 3,3-bipyridine and 4,4-bipyridine system, 100% conversion to ethylcyclohexane has been achieved. Other aryl derivatives used were; benzene, toluene, ethylbenzene, propylbenzene, cumene, and styrene. The best results were achieved for 4,4-bipyridine in all cases. Other work from this group reports the synthesis of the same system with 2,2-bipyridine ligand and their use in hydrogenation of styrene under different conditions [209]. PVP is other capping agent used in the stabilization of colloidal NPs. Delmas et. al. have used PVP protected rhodium NPs, synthesized through a solvolysis method, to study the catalytic hydrogenation of oct-1-ene in a biphasic system [210]. They carried out kinetic studies in the temperature range 303-323 K. The rate was found to be first order with catalyst concentration, hydrogen pressure and oct-1ene concentration. Other biphasic system (water-benzene), using PVP entrapped Rh(0) NPs reduced by Cp2V, is employed by Pellegatta and collaborators [211]. For the hydrogenation of benzene, 250 h-1 TOF is achieved; benzene, deuterated benzene, phenylacetylene and styrene kinetic tests were carried out also with this system. Before their silica supported catalyst investigations, Roucouxs group developed a series of catalytic hydrogenations with

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metallic rhodium nanoparticles synthesized via chemical reduction with sodium borohydride, and stabilized only with N,N-dimethyl-N-cetyl-N-(2-hydroxiethyl)ammonium salts (HEA16X, X=Br, Cl, I, CH3SO3, BF4). In their last article, this group has obtained excellent results in a one pot hydrogenation-dehalogenation of chlorobenzenes [212]. When chlorobenzene and 4-chlorotoluene were used in the catalytic tests, 100% conversion has been achieved to cyclohexane and methylcyclohexane in 1.7 and 7.3, respectively. Other report, explores the hydrogenation of N-, O-, and S-heterocycles, as pyridine, 2-picoline, quinoline, N-methylindole, furan, benzofuran, and 1,3,5-triazine [213]. In each case, a quantitative reduction has been found, with better TOFs for furan to THF (200 h-1) and 1,3,5triazine (176 h-1). When thiophene and benzothiophene were used, no hydrogenation was fulfilled. In a previous work, the influence of the counter-ion in the surfactants, over catalytic hydrogenation of various benzene derivatives were investigated [214]. Better results were found when HEA16Cl was employed as stabilizer; and when this catalyst was used over disubstitued benzene derivatives, the cis- diastereomers are the major products (up to 99%). Aditionally, they realized catalytic studies in a biphasic system [215]. With appropriate conditions the authors, obtained TOFs of 429 h-1, 256 h-1, and 149 h-1 for anisole, toluene and p-xilene, respectively. Other reactions catalyzed by metallic rhodium NPs less reported include; hydrogenolysis or alcanolysis of different molecules and CO hydrogenation. AlemnVzquez and collaborators have used alumina supported Rh NPs in the catalytic ring opening of cyclohexane [216]. The best results were obtained with an impregnation route, with a 37% conversion in 4 h. CeO2 supported Rh(0) NPs are used in the catalytic ring opening of methylcyclobutane and hydrogenation of CO by Hayeks group [217]. For catalytic ring opening of methylcyclobutane, 5 h-1 10 h-1 TOfs were detected; for CO hydrogenation, 0.55 h-1 TOF was detected, in contrast to Rh/SiO2 were 0,15 h-1 TOF was achieved. In a previous work, the same group used this catalyst to hydrogenate CO [218]. The catalysis for the inverse CeO2/Rh thin film with a TOF of 4.70x10-2 s-1. Fukuoka et. al. achieved nanoparticles inside FSM-16 siliceous material by impregnation of the Rh salt, calcination under O2, and subsequent reduction in H2 [219]. This supported catalyst was used in the catalytic hydrogenolysis of butane and a TOF of 195h-1 has been achieved with 96% selectivity to the production of methane; 3% and 2% production of n-propane and ethane, respectively, is found. An interesting catalyst chemically reduced in presence of (R)-2,2_-bis(diphenylphosphino)-1,1_-binaphthyl ((R)-BINAP) ligand and tetraoctylammonium bromide (TOAB), and later supported on silica by impregnation was achieved Lis group [220]. These NPs were tested in the catalytic hydroformylation of styrene and vinyl acetate with a syngas flow. When compared to unsupported Rh-BINAP, homogeneous catalyst and Rh/SiO2; 92% branched selectivity and 25% ee (S-enantiomer) are achieved for the Rh-BINAP catalysts and 89% to 92% branched selectivity and 26% to 30% ee (S-enantiomer) for the Rh-BINAP/SiO2. Although, low total conversion are obtained, 5% and 6-9%, respectively. Other Rh(0) NPs used in the catalytic hydroformylation of styrene are the ones synthesized by Axet and coworkers [221]. They have obtained colloidal NPs via H2 decomposition of two organometallic precursors ([Rh(3-C3H5)3] and [Rh(-OMe)(cod)]2) in the presence of two chiral diphophite ligands. Regioselectivity up to >99% for the branched product with 40% of ee has been fulfilled. In the same line of catalytic tests, Tuchbreiter et. al. obtained poly(ethylene imine) amides (PEI) protected Rh(0) NPs [222]. The chemical reduced nanocomposite achieved >99% conversion with 88% selectivity for hydroformylation reaction. As the Rh/PEI prepared via H2 reduction showed better results, an experiment varying syngas pressure was

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

realized, where the authors found better selectivity for hydroformylation catalysis at higher pressures; although the system was not sensitive to this variable. In a previous reaction, Dupont group applied their Rh(0) NPs synthezised via imidazolium ionic liquids to hydroformylate 1-alkenes [223]. Quantitative conversions to aldehydes in 4 h were found, with 25 ratio of lineal/branched aldehydes. A catalytic related reaction is the hydrosilylation of multiple bonds. Thiot and co-workers used a polyionic gels method to synthesize Rh(0) NPs and used these composites in the catalytic hydrosilylation of acetylene [224]. The reaction proceeded with regio- and stereoselectivities to afford the (E)-1-silyl-1-alkene in 89% yield. Other investigation to hydrosilylate aromatic nitriles was carried out by Petricis group [225]. They used -Al2O3 supported and unsupported Rh(0) NPs synthesized via Metal Vapour Synthesis (MVS). The catalytic tests were realized under solventless condition and activated and deactivated aryl niriles were tested. Quantitative conversions were obtained for the unsupported nanoparticles at 100C with trimethylhydrosylane (HSiMe3), regardless the nitrile nature; when triethoxyhydrosylane is employed, lower conversions (75-80%) are achieved. The supported nanoparticles denoted sensitivity to the aryl nitrile subtitution; better conversions (80%) are obtained for benzonitrile and trimethylhydrosylane, the lower ones were achieved for the deactivated aryl nitrile. In a later paper, this group reported a catalytic sylilformylation reaction, adding trioctylamine (TOA), as stabilizer, to their catalyst. The authors report tests of a reaction in 1-hexyne, and obtained a quantitative conversion in 10 h with a 100% stereoselectivity for the (Z)-1-(Dimethylphenylsilyl)-2-formyl-1-hexene product. Longer time reactions are required to achieve the same results when the TOA unprotected catalyst is used. In other proceses, catalytic oxidation of molecules is also applied to metallic rhodium NPs. Although less information about this reaction is available. In a recent investigation, Somorjais group has reported studies of CO oxidation over rhodium NPs supported on SBA-15 [226]. Better oxidations were found for smaller NPs, with up to 1.69 s-1 TOFs. When the catalysts were calcined before use, a decrease in the turnover frequency is registered due to the formation of Rh2O3. In other report, Newton et. al. realized studies of CO oxidation using a Al2O3 supported rhodium catalyst [227]; where they found a correlation between the catalyst performance and the existence of different Rh(0), Rh(I), and Rh(III) phases. In the catalytic oxidation of alcohols, Hasik and co-workers carried out tests with composites of Rh(0) and polypyrrole (PPy) [228]. When the catalysis was carried out over isopropyl alcohol, acetone and propene were found as products in a 97.49/2.51 ratio at 370 K, 94.8/5.15 at 400 K, and 90.64/9.36 at 430 K. Acetone was also the main product, with a lesser degree of propionaldehyde and COx, when Senkan group used a Rh/TiO2 catalyst to fulfill the partial oxidation of propylene [229]. The titania supported NPs were obtained through lasser ablation. Montini et. al. achieved a Rh/CexZr1-xO2-Al2O3 composite and used it for the ethanol steam reforming [230]. The system favors the dehydrogenation of ethanol to acetaldehyde, although some acetone formation is detected. In other work, a Rh/Ce0.2Zr0.8O2Al2O3 catalyst was synthesized by the same method [231]. In this work, the authors determined that above 750 K the decomposition ethanol to H2, CO, and CO2 occurs; a clear indication that above that temperature, the water gas shift reaction is operative. Palladium catalysis. When it comes to palladium catalysis, many articles have been published in the last ten years, and it is impossible review all these investigations. But two main catalytic reactions have been reported for palladium(0) NPs: reduction of alkenes and alkynes and C-C cross coupling. In the last case, a number of excelent reviews have been published in the last years like Astrucs [232-233], who focuses mainly in the catalytic Heck

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cross coupling. Trzeciak published a fine review, where the author studied mechanistically the Heck reaction [234]. On the other hand, Joness group reviewed palladium catalysts used in the Mizoroki-Heck and Sukuki-Miyaura couplings [235]. Previous to these reviews, Farina has realized a study of high-turnover catalysts, homogeneous and heterogeneous, used in cross coupling reactions [236]. Gomez et. al. made a review where informed about C-C cross coupling and hydrogenation reactions catalyzed by palladium NPs [237-238]. A review of great interest in our group is the one realized by Jess and collaborators [239]. This report exhibits catalytic reactions carried out with dendrimer-supported palladium NPs, the type of investigation developed by our group [240]. Hydrogenation reactions. Harada et. al. used carbon black (CB), activated carbon (AC), and mesoporous carbon (CMK-3) to support palladium(0) nanoparticles, and used them in the oxidation of benzyl alcohol and C=C hydrogenation of cinnamaldehyde [241]. For the oxidation of benzyl alcohol to benzaldehyde, the maximum activity (>80%) was achieved in an hour, when CMK-3 and AC were used with a [NaOH]/[PdII] ratio of 4:1, and CB with a 8:1 [NaOH]/[PdII] ratio. When a commercial cPd/C was tested for this catalytic reaction, the catalysts prepared by the authors showed better activities in the 2-10 range of [NaOH]/[PdII] ratios. In the catalytic hydrogenation of cinnamaldehyde to 3-phenylpropionaldehyde, quantitative conversion was fulfilled when Pd/CB was used with a 4:1 [NaOH]/[PdII] ratio, in 3 h. Mastalir group has achieved palladium(0) NPs encapsulated in graphite and used them to catalyze the hydrogenation of 1butene, cis-2-pentene, and cyclohexene, and isomerization of 1-butene and cis-2-pentene [242]. When the 1-butene is tested, a quantitative conversion is achieved, with 0.086 s-1 TOF, 1.680 hydrogenation/isomerization selectivity, and 0.327 production selectivity of cis-2butene/trans-2-butene in the isomerization catalysis. For the conversion of cis-2-pentene, up to 50% was achieved, in 90 minutes, with predominance for the catalytic isomerization, with a 60% production for the trans-2-pentene, 5% for 1-pentene, and 35% for pentane. Finally, no transformation was detected for cyclohexene. CNT are used as supports to synthesize palladium(0) NPs. Tessonnier group used MWCNTs supported palladium(0) NPs for the selective hydrogenation of cinnamaldehyde into hydrocinnamaldehyde [243]. Quantitative conversions were achieved in 25 h, with 80% selectivity for the hydrocinnamaldehyde. Chun et. al. used ionic liquid modified MWCNTs to obtain palladium catalysts and test them in the hydrogenation of different olefins [244]. TOFs up to 2820 h-1 are achieved when styrene is used as substrate. In a related investigation, sepiolite clay is modified with 1,1,3,3 tetramethylguanidine trifluoroacetic acid (TMG+ TFA-), 1,1,3,3-tetramethylguanidine lactic acid (TMG+ LA-) and 1,1,3,3-tetramethylguanidine acetic acid (TMG+ AA-) ionic liquids to support palladium(0) NPs, and use them in the reduction of alkenes and in the C-C cross coupling [245]. The catalyst was synthesized by mixing an aqueous solution of H2PdCl4 and the previously modified sepiolite, dried, and reduced under H2 flow. TOF up to 10000 h-1 is achieved with quantitative conversions, when 1-hexene and styrene are employed as substrates. The use of other ILs did not change the activity. Kiwi-Minster group explored the ionic liquid-carbon nanofibers (CNF) anchored to sintered metal fibers (SMF) stabilization of palladium NPs for a posterior use in the partial hydrogenation of acetylene under continuousflow conditions [246]. Selectivity up to 85% for ethylene was achieved with a rate of 3.7x10-2 mol(gPdS)-1, at 150 C. Hou and co-workers used the 2,3-dimethyl1-[3-N,N-bis(2pyridyl)propylamido] imidazolium ([BMMDPA][PF6]) and 1-n-butyl-2,3dimethylimidazolium hexaflourophosphate ([BMMIM][PF6]) ionic liquids to synthesize some palladium(0) NPs via H2 flow [247]. Quantitative conversions were found when this NPs

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

were tested in the catalytic hydrogenation of cyclohexene to cyclohexane, styrene to ethylbenzene, and ethyl actylate to ethyl propionate at 35 C, with a 500:1 substrate/Pd ratio. No byproducts were detected in any case. Duponts group stabilized palladium(0) NPs in 1-nbutyl-3-methylimidazolium hexafluorophosphate (BMIPF6) or tetrafluoroborate (BMIBF4), via H2 reduction of Pd(acac)2 dissolved in the before mentioned ionic liquids [248]. When these dispersions are used in the partial hydrogenation of 1,3-butadiene, 99% conversion is achieved, with 72% selectivity for 1-butene. Crooks and collaborators are one of the first groups in achieving dendrimer-encapsulated NPs, especially palladium and platinum nanoparticles obtained via chemical reduction with NaBH4 of a palladium salt [249]. Part of their investigation has focused in the correlation between the generation of the dendrimer used to encapsulate and the activity in different catalytic reactions. In one investigation, this group tested dendrimer-encapsulated palladium(0) NPs in the catalytic reduction of allyl alcohols [250-251]. They have found selectivity for lineal substrates, especially with high generation dendrimers. This behavior is attributed to steric interaction between the substrates and the functional groups on the dendrimer periphery. Astruc group has achieved palladium NPs stabilized by click ferrocenyl dendrimers catalytically active in the hydrogenation of styrene [252]. In other investigation, this group used a series of dendrimers (triazolyl dendrimers, triaziolylferrocenyl dendrimers, and a PAMAM dendrimer) to encapsulate or stabilize Pd(0) NPs and used the composites to reduce styrene to ethyl benzene [253]. The best catalytic results that they obtained for a triazolyl dendrimer first generation with 27 dendronic-9-propyl units with up to 3390 h-1 TOF when methanol was used as reducing agent. Also, triazolyl dendrimer-encapsulated Pd(0) NPs were tested in the catalytic hydrogenation of allyl alcohols by Astruc group [254]. When a zero generation was used, better catalytic activities were found (8088 h-1 TOF), for the hydrogenation of allyl alcohols. Okitsu et. al. employed a sonochemical preparation to produce Al2O3 supported NPs. The sonochemical reduction was carried out in the presence of alcohol additives (methanol, ethanol, and 1-propanol). When these nanoparticles were tested in the catalytic hydrogenation of 1-hexene and trans-3-hexene, rate up to 700 mmol(Pd-g)-1min-1, for the hydrogenation of 1-hexene, with NPs reduced in 1-propanol. Bruening and co-workers synthesized -Al2O3 supported poly(acrylic acid) (PAA) and polyethyleneimine (PEI) thin films. These films are used as supports for metallic palladium nanoparticles [255]. TOF up to 3500 h-1 was achieved in the catalytic hydrogenation of 1-propen-3-ol. In a recent investigation, the catalytic reaction is tested when the catalyst loading is varied [256]. The best results were obtained with lower loadings. Metallic palladium NPs embedded in a PAA and/or PEI thin film, all supported onto alumina, were used by this group in the hydrogenation of allyl alcohols [257]. TOF up to 5880 h-1 was achieved for allyl alcohol. In a previous work from this group, the same catalyst was used in the hydrogenation of allyl alcohols [258], and TOFs up to 727 h-1 for penten-3-ol. Ebert and co-workers obtained catalytically active poly(amideimide) nanofibre mat supported palladium(0) NPs for the hydrogenation of methyl-cis-9octadecenoate (methyl oleate) [259]. When the catalytic tests were carried out, two possible products can be detected: the trans-isomer methyl-trans-9-octadecenoate (methyl elaidate) and the hydrogenation product methyl-cis-9-octadecanoate (methyl stereate). After their experiments, they conclude that the process of hydrogenation of the methyl oleate takes place via isomerization reaction. Erman and collaborators, synthesized poly(acryonitrile-co-acrylic acid) supported NPs by electrospinning the copolymer-Pd solution [260]. The Pd reduction was carried out by an hydrazine solution, before and after electrospinning. This catalyst was

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tested in the selective hydrogenation of dehydrolinalool (3,7-dimethyloct-6-ene-1-yne-3-ol, DHL), up to 11.3 reaction rate is achieved when the catalyst is synthesized when a high concentration of acrylic acid co-polymer was used and the reduction was carried out after electrospinning. Somboonthanakij and collaborators, have synthesized SiO2 supported palladium(0) NPs, via flame spray pyrolysis method, with palladium acetylacetonate and tetraethylorthosilicate (TEOS) as palladium and silicon precursors, to use them in the partial hydrogenation of 1-heptyne [261]. TOF up to 66.2 s-1 has been achieved, with 42% conversion and 93% selectivity for the 1-heptene product. In a recent investigation, this group used the same catalyst in the same reaction to compare its performance with an impregnation made catalyst. Up to 95% selectivity for 1-heptene is achieved, with a 75% conversion, when 10% loading of flame spray made catalyst is used. Obares group used a series of supported and unsupported Pd(0) NPs to catalytically hydrogenate styrene, 1,5cyclooctadiene, and 6bromo-1-hexene [262]. The n-dodecyl sulfide stabilized NPs were achieved by reducing with hydrazine hydrate and sodium hydroxide in presence of n-dodecyl sulfide, using ethanol as solvent. In other experiment, these NPs were supported over silica. The best conversions were obtained for the silica supported NPs, with quantitative conversions in the reaction of styrene to ethylbenzene; the same results were found for the reaction of 6-bromo-1-hexene to 1bromohexane; in the hydrogenation of 1,5-cyclooctadiene, quantitative conversion was found, although a 1:1 ratio is achieved in the production of 1-cyclooctene and cyclooctane. Jayaramans group modified silica with poly(ether imine) based dendritic phosphine ligands to support palladium(0) NPs [263]. When this catalyst was used in the hydrogenation of various olefins, quantitative reactions were obtained in each case, in 4 h or less, at 25 C. on the other hand, Mastalir et. al. tested MCM-41 supported palladium(0) NPs and tested in the hydrogenation of alkyne reductions [264]. The catalysts were obtained by hydrazine reduction, before and after addition of SiO2 precursor (Na2Si3O7), using tetradecyltrimethylammonium (C14TABr). TOF up to 5.56 s-1 with 8.7% conversion was achieved in the case of 1-hexyne with 100% selectivity to 1-hexene. A similar result was reached for the conversion of 3-hexyne (5.34 s-1) with 8.2% conversion and 94.5% selectivity to the trans-3-hexene product. Better results were achieved by Minsker group in the selective reduction of 1-hexyne to 1-hexene (9.2 s-1, in 85% conversion with 96.5 selectivity) [265]. In a recent experiment, this group achieved shape defined palladium NPs, by NaBH4 or ascorbid acid reduction of H2PdCl4 in presence of cetyltrimethylammonium bromide (CTAB) [266]. These NPs were used in the catalytic hydrogenation of 2-methyl-3-butyn-2-ol. The best results were achieved with the largest Pd spheres. In a previous article, the group used PdCl2(NH3)4 as metal precursor, and used the NPs in the same catalytic reaction [267]. Other report from this group sinthezised palladium(0) NPs stabilized in block-copolymer micelles and used them in the selective hydrogenation of 2-butyn-1,4-diol [268]. TOF up to 0.91 s-1 was achieved when the alumina supported catalyst was used, 94% selectivity is reached in a quantitative reaction. A gel type resin (FCN) as a result of copolymerization of glycidyl methacrylate (GMA), styrene, and ethylene glycol dimethacrylate, was used to support palladium NPs, and test them in the hydrogenation of 2-butyne-1,4-diol and phenylacetylene [269]. For the hydrogenation of 2-butyne-1,4-diol, up to 92% selectivity for the 2-butene-1,4diol product was obtained with a total of 90% conversion, although from this product, up to 50% suffers other processes like isomerization, decomposition, etc. In the reduction of phenylacetylene to styrene, the catalyst yielded 90% of total conversion, with up to 91.4% selectivity to styrene. An increase in the palladium loading did not increase the rate of

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

hydrogenation or the selectivity. Nanospheres derived from hydroxylated polyisoprene (PHI), cross-linked poly(2-cinnamoyloxyethyl methacrylated) (PCEMA), and poly(acrylic acid) (PAA), were developed by Underhill et. al. to encapsulate palladium(0) NPs and test them in the catalytic reduction of triethylallyl ammonium bromide (TEAA), vinylacetic acid (VAA), methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) [270]. The catalysis was improved when the tests were carried out at a pH=10. When it comes to colloidal systems, surfactants like cetyltrimethylammonium bromide (CTAB) were used to stabilize palladium(0) NPs. Piccolo and co-workers used this cationic surfactant to produce well defined palladium NPs in dispersion [271]. The best results were found when prism-like NPs were used in the catalytic reduction of 1,3-butadiene (0.80 s-1 TOF). A colloidal system of palladium(0) NPs were obtained by Wai and collaborators to hydrogenate 1-phenyl-1cyclohexene, methyl trans-cinnamate and trans-stilbene [272]. When this catalysis was tested in 10-(3-propenyl)anthracene, >50% conversions were detected after 9 minutes of reaction. This group combined H2SO4-HNO3 modified MWCNTs and supercritical conditions to support Pd(0) NPs [273]. The palladium reduction was carried out in supercritical CO2, with a H2 flow, in presence of the nanotubes. This catalyst was used in the hydrogenation of transstilbene; 96% conversion is achieved in 10 min of reaction. In other investigation, the group used high density polyethylene (HDPE) granules and fluoropolymer (PFA) tube to support Pd(0) NPs [274]. The deposition was the same, and quantitative monoreduction of naphthalene was achieved in 10 minutes with the HDPE supported Pd(0) NPs. Lower but good conversions were carried out in benzene and phenol in 60-50 minutes. In a previous work, this group used a water-in-CO2 microemulsion to obtain palladium NPs and use them in the reduction of a number of olefins [275]. In the catalytic hydrogenation of 4methoxycinnamic acid, trans-stilbene, maleic acid and nitrobenzene >99% conversion were detected in almost each case (>95% conversion for styrene) in 20 s to 30 min (for the reduction of nitrobenzene to aniline). By their way, Lee and co-workers used a supercritical CO2 system to synthesize mesoporous silica SBA-15 supported Pd(0) NPs to hydrogenate the 4-methoxycinnamic acid benzyl ester [276]. The catalyst was prepared by mixing palladium(II) hexfluoroacetylacetonate (Pd(hfac)2) with SBA-15 in THF, drying, and later loading the palladium(II) composite into a reactor and producing the super critic CO2. Quantitative conversion was achieved when 150 bar of CO2 was added to the hydrogenation reaction, with a 93% selectivity for the ester product. Meric et. al. also used a super critical CO2 to synthesize Pd(0) NPs, which were used in the catalytic hydrogenation of citral [277]. When the catalysis was carried out in super critic conditions; >99% conversion was achieved in less than an hour, with up to 68% selectivity for the citronellal (CIAL) product. Other work from this group reports the same catalytic system [278]. Sastry and collaborators obtained a H-Y zeolite grafted with amine groups to support Pd(0) NPs [279]. When tested in the hydrogenation of styrene, penylacetylene, and nitrobenzene, quantitative reactions were achieved in 30 min, 90 min, and 40 min, respectively, with 99.2%, 85.9%, and 100% selectivity for ethylbenzene, ethylbenzene, and aniline, each. Silver catalysis. The main catalytic reaction reported with metallic silver nanoparticles is the reduction of nitrogen compunds. Recently, Liu et. al, have immobilized PVP supported silver NPs onto halloysite nanotubes through reduction of AgNO3 by polyol process [280]. This composite was used in the reduction of 4-nitrophenol to 4-aminophenol; kinetic studies were carried out to determine the effect concentration of NaBH4. Murugadoss and co-workers

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embedded silver NPs inside a chitosan matrix [281]. Obtaining a TOF value of 1.5x10-3 s-1. Qian group carried out a similar investigation [282]. They have supported the silver NPs over a cuttlebone derived organic matrix (-chitin) by reducing via Tollens reagent and NaBH4. At 10 min, they have achieved a 71.5% conversion. By their side, Pradhan et. al. achieved colloidal silver NPs reduced with NaBH4, CO, N2H4, and ascorbic acid [283]. Faster results were found with the NaBH4 reduced NPs. In a related catalytic reaction, Rupa and collaborators have used TiO2 supported NPs to photodegradate the commercial dye Reactive Yellow-17 (RY-17) [284]. More investigations have been developed in the degradation of commercial dyes, like the one realized by Demir group, who used microfiber supported silver NPs to reduce methylene blue [285]. This nanocomposite, along with NaBH4, reached a total degradation within 11 min; although they do not report which products were obtained. An experiment was carried out in the absence of the silver NPs, and no degradation was observed. In a previous work, Kundu and co-workers used this catalytic reaction to sense low concentrations of ammonia in solution [286]. Other catalytic degradation carried out by metallic silver nanoparticles is the phenol degradation. Dais group supported silver NPs over TiO2 with a twistlike helix structure [287]. They report better photocatalytic results with the NPs obtained via chemical reduction. Again, they didnt report any possible product in the reaction. Other group of reactions commonly catalyzed by metallic silver NPs is the oxidation of molecules. Li and collaborators obtained silver NPs with well-defined shapes and used them to oxidize styrene to benzaldehyde and styrene oxide [288]. The truncated triangular silver NPs were synthesized by a solvothermal method in N,N-dimethylformamide (DMF) in the presence of PVP. The best catalytici results were obtained with cubic NPs in 12 h with 82% conversion. A 81:19 ratio for benzaldehyde was achieved. Debecker and co-workers obtained silver NPs via multiple layers surfactants and latter supported over TiO2 or V2O5/TiO2 by wet impregnation, and used them in benzene oxidation to CO2 and H2O [289]. The Ag-V2O5/TiO2 showed better conversion (100%) at 350C than the Ag-TiO2. In a recent investigation, Tian and collaborators obtained Ag/SBA-15 catalysts prepared through an in situ reduction method using hexamethylenetetramine (HMTA) and formaldehyde as reducing agents and used them in the catalytic oxidation of CO [290]. When the formaldehyde reduced catalyst was tested in the CO oxidation, no catalytic activity was detected below 150C and its maximum activity (100% conversion) was detected at 270C; while the HMTA reduced catalyst showed low activity at temperatures slightly above room temperature, although its catalytic maximum (100%) was reached at 230C. In a slightly different reaction, Kanedas group has explored the catalytic oxidation of phenylsilanes to silanols [291]. Their catalyst are hydroxyapatite (Hap) supported silver NPs. When dimethylphenylsilane was used, 99% conversion was obtained, with a 99:1 selectivity for dimethylphenylsilanol; different phenylsilanes were used, and conversions of 96% - 99% were achieved in each case. In contrast, when tris n-butylsylane and t-butyldimethylsilane were tested, no catalytic activity was found. Osmium. The reports on osmium metal nanoparticles have been focused on the synthesis, thus Wang et. al. [292] obtained an average particle size of the Os nanoclusters in a stable colloidal solution of 0.9 nm with a size distribution of 0.6 1.8 nm (:0.28). The Os nanoclusters can be separated from the reaction system as a precipitate and the precipitated can easily dissolve in many organic solvent such as acetone and THF to form stable colloidal solutions. Gyenge et. al. [293] used tetrabutylammoniumtriethylhydroborate

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

(C4H9)4N[BH(C2H5)3] as both reductant and stabilizer, obtaining a mean particle size of 2.4 nm. Os NPs are electrochemically active for BH4- oxidation. Yung and coworkers [294] have synthesized Os NPs supported on MWCNTs by vacuum pyrolysis at 573 K using [Os3CO10(NCMe)2] as precursor. The NPs prepared have a mean diameter of 1.8 nm. Osmium islands deposited on Pt (111) have been synthesized by Strbac et. al. [295] and Pacheco Santos et. al. [296], using this system for the catalytic oxidation of ethanol. Iridium. Dupont et. al. [297] have realized several studies about synthesis of nanoparticles in different ionic liquids(ILs); where, their results indicate that IL reacts with the nanoparticle surface and generate surface-bound protective species which on the one hand, is responsible to some extend for their catalytic activity, but on the other hand, explains their relatively low stability that leads to aggregation/agglomeration and eventually to the bulk metal. Reduction of [(1,5-COD)IrCl]2 by H2 in neat acetone yields 1 equivalent of H+Clfor each Ir(I) reduced to iridium(0) resulting in a highly efficient (100%), acid-assisted, high selectivity(100%) acetone hydrogenation catalyst [298]. Mvellec et. al. [299] have obtained aqueous suspensions of Ir NPs through chemical reduction of IrCl3 assisted by sonication in the presence of a surfactant: N,N-dimethyl-N-cetyl-N-(2-hydroxyethyl)ammonium chloride salt. This catalytic suspension was efficient for hydrogenation of benzenederivatives such as mono or disubstituted arenes and provides the corresponding saturated compounds. Due to the reaction is carried out in two phases; catalyst can be reused after simple decantation in a separating funnel without a significant loss of activity. Yinghuai et. al. [300] have obtained iridium NPs using a different ionic liquid as stabilizer. Ir nanoparticles (~3.5 nm) are used for borylation of benzene and catalyst is recyclable by extraction of impurities. Stowell et. al. [301] have synthesized iridium NPs in the presence of different capping ligands to hydrogenate 1-decene to decane. They found that good capping ligands appear to be poor choices for catalytic applications. So, the ligands must be strong enough binders to stabilize nanocrystals but weak enough to provide reactant access to the metal surface. RodrguezGattorno et. al. [302] have prepared iridium NPs supported on Al2O3. This catalyst was used for opening the cyclohexane ring showing better results than Rh/Al2O3. Cunha and Cruz [303] reported decreased activity for very small metal particles (1-2 nm) in the study of the hydrogenation of benzene and toluene over Ir /-Al2O3. Yang et. al. [304] have obtained Ir NPs supported on SiO2 using cinchona alkaloids and (1S,2S)-diphenylethylenediamine as chiral modifier to improve the dispersion and stability of the Ir particles. A good catalytic performance in the asymmetric hydrogenation of acetophenone in MeOH was obtained. Catalyst can be recycled by centrifugation-decantation method. Gupta et. al. [305] have used presynthesized iridium nanocrystals stabilized by weakly bound tetraoctylammonium bromide (TOAB) ligands to be infused into presynthesized mesoporous silica using CO2 and toluene to produce an active catalyst for 1-decene hydrogenation, where desorption of ligands from the adsorbed nanoparticle surface, onto the support and into the decene during reaction, will enhance metal binding to the surface and aid catalyst stability. Miyao et. al. [306] have used a reversed micelle technique to obtain hollow silica nanospheres (~35 nm) containing Ir NPs (1-2 nm) for studies in hydrogen storage. Park et. al. [307] have reported the synthesis of iridium NPs in aluminum oxyhydoxide Ir/AlO(OH). This catalyst was proved to be active for hydrogenation of various arenes and ketones under mild conditions, room temperature and even with an hydrogen balloon. Catalyst was recupered by simple filtration. Iridium-based films on Au electrode surface have been synthesized by Birss et. al. [308], sol-gel solution showed Ir NPs of 1-2 nm average size and IrOx were not detected.

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Platinum. Yang et. al. [309] have obtained platinum NPs stabilized by polyaryl ether trisacetic acid ammonium chloride dendrimer through an alcohol reduction method. Such nanoparticles are used to carry out hydrogenation of nitrobenzene derivatives with molecular hydrogen under mild conditions. The catalytic activity of the dendritic catalyst decreased with the increase of the generation of the dendrimer, this can be explained considering that larger dendrimers could limit the accessibility of the substrates into the active centers of platinum nanoparticle-cored dendrimer. Using other dendrimers as stabilizers for Pt NPs, Du et. al. [310] have carry out the hydrogenation of phenyl aldehydes to phenyl alcohol under an atmospheric pressure of H2. Huang, et. al. [311] have synthesized platinum NPs stabilized with a PAMAM G4OH dendrimer, then NPs were immobilized onto mesoporous silica SBA15. Ethylene and pyrrole hydrogenation reactions were studied, and it was found that the activity was increased to a certain temperature. This behavior is explained by a partial decomposition of dendrimer capping. In the same way, Deutsch et. al. [312] have used hydroxyl terminated PAMAM G4 dendrimers to stabilize platinum NPs obtained by reduction of Pt2+ with hydrogen. After, silica was added to a Pt-G4OH. In order to activate the catalyst, the dendrimer was removed via calcination. Lang et. al. [313] have used PAMAM G5 OH dendrimers to obtain stabilized platinum NPs that were deposited on SiO2. After removal dendrimer, toluene hydrogenation and CO oxidation were studied. Esumi et. al. [314] have used poly(propyleneimine) (PPI) dendrimers and PAMAM dendrimers to stabilize platinum NPs. They found that the average particle sizes of the metal nanoparticles are almost independent of the concentration of the dendrimer as well as the generation for both the PAMAM and the PPI dendrimers. The nanocomposites were used for reduce 4-nitrophenol to 4-aminophenol, the rate constants decrease with increasing dendrimer concentration. This decrease is attributed to the increase of the dendrimer adsorption on the metal nanoparticles. Michels et. al. [315] have obtained platinum NPs stabilized by supramolecular dendritic assemblies of -cyclodextrins and PPI dendrimers, they proposed that low generation assemblies do not provide kinetic barriers to prevent NPs aggregation into larger metal clusters. Puniredd et. al. [316] have obtained Pt NPs within a ultrathin film matrix formed by covalent layer-by-layer assembly of pyromellitic dianhydride (PMDA) and second generation PAMAM dendrimer in supercritical CO2. This film matrix is immobilized onto SiO2. Presence of nanoparticles within the dendrimer layers are important to demonstrate the charge storage effect for non-volatile memory applications while the dendrimer layers act as a host network to trap the Pt nanoparticles. Using a G6-OH PAMAM dendrimer, NaBH4 and different amounts of K2PtCl4, Ye et. al. [317] have obtained platinum NPs of different sizes and small narrow size distributions. Dendrimer encapsulated nanoparticles (DENs) are immobilized in a glassy carbon electrode and are used for oxygen reduction reaction (ORR). When the size of DENs was reduced, lower ORR activity was observed, also, the total Pt surface area decreases as the sizes of the DENs decreases. Recently Knecht et. al. [318] have reported that dendrimer complexes with Pt2+ are not fully reduced when exposed to BH4- in aqueous solutions. Platinum NPs supported over hypercrosslinked polystyrene (HPS) have been synthesized by Bykov and collaborators [319]. Modification of Pt/HPS catalyst with cinchonidine gave better results for enantioselective hydrogenation of ethylpyruvate. Marty et. al. [320] have studied the hydrogenation of isophorone at room temperature and pressure H2=2 bar with platinum NPs. Okamoto et. al. [321] have obtained a nanocomposite made of MWCNTs, poly(benzimidazole) (PBI) and Pt nanoparticles. MWCNTs are wrapped with PBI

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

and deposition of Pt nanoparticles was carried out via polyol method. The composite was used for methanol oxidation and have higher efficiency than carbon black/Pt system. Zhu et. al. [322] have obtained MWCNT/PANI composite films supporting electrodeposited Pt NPs. The composites were used for the electrochemical oxidation of formic acid. Taylor et. al. [323] have obtained Pt/SWCNTs composite in supercritical methanol. Using a surfactant (SDS) in the synthesis of Pt NPs they have obtained superior polymer electrolyte membrane (PEM) fuel cell activity. Bayrakceken et. al. [324] have obtained platinum NPs supported on the outer surface of MWCNTs by reduction of PtMe2COD using hydrogen on supercritical CO2. Song et. al. [325] have reported that generation in situ of platinum seeds and autocatalytic growth in presence of surfactants leads to two- and three-dimensional platinum nanodendrites. Changing liposomes type, sheetlike nanodendrites or foamlike nanosheets of platinum can be obtained. Luo et. al. [326] have reported crown-shaped platinum NPs using UV irradiation in the presence of G4-NH2 PAMAM dendrimers in water. Dendrimers also play a role as stabilizers for the particles. Platinum particles supported on polypyrrole (PPy) and polyaniline (PANI) have been used by Hasik et. al. [327] to catalyze the isopropyl alcohol conversion. They found that activity of PPy-based composite was higher than the exhibited by the PANI-based one. This fact was explained by the authors by the presence of different acidic centers in the polymers. Yoo et. al. [328] have synthesized platinum NPs encapsulated on Al2O3, this support provides small diameter and size distribution due to its pore dimension. Such nanostructures were used for hydrogenation of propene. Collier et. al. [329] have prepared solvent stabilized Pt NPs by the electron beam evaporation of the metal and co-condensation with the vapours of organic solvents at 77 K in a Torrovap metal atom reactor. These NPs were used for the enantioselective catalytic hydrogenation of ethyl pyruvate and shown similar results that previous supported analogous. Using a Pt/PVP colloidal solution in methanol, 298 K and hydrogen at 0.1 MPa, Liu et. al. [330] have achieved hydrodechlorination of monochlorobenzene to benzene and finally to cyclohexane with high catalytic efficiency. Using Pt PVP-protected NPs as precursor Lin et. al. [331] have obtained a Pt/PVP@MCM-41 composite (MCM-41: mobile crystalline material) which is active in the conversion of cinnamic acid in their corresponding hydrocynnamic acid. Platinum NPs embedded in polypyrrole(PPy) nanowires have been synthesized by Li et.al. [332] over a glassy carbon electrode (GCE), and were used for electrocatalytic oxygen reduction and methanol oxidation. Comparing PPy-Pt/GCE with Pt/GCE they have found that the activity and stability of the Pt nanoclusters embedded in PPy nanowires were higher than pure Pt deposited on electrode. Advantage of this system is attributed to a protection effect of the 3D structure of the composite to poisoning. Synthesis of platinum-polystyrene nanocomposite through an alcohol-reduction method has been studied by Kim et. al. [333] this method have the advantage that do not need an additional reduction agent. Wang et. al. [334] have synthesized platinum nanoparticles reducing H2PtCl6 with ethanol in presence of PVP. Modifying PVP and ethanol amounts can obtain different particle sizes. Dendrimer encapsulated platinum NPs functionalized with glutamate dehydrogenase and supported on CNT, have been employed by Tang et. al. [335] to build a multilayer biosensor of glutamate. Li et. al. [336] have used Octa(diacetic aminophenyl) silsesquioxanes (OAAPS)to stabilize Pt, Pd and Ru NPs. That have been used for hydrogenation of phenyl aldehydes. Kostelansky et. al. [337] have stabilized Pt NPs with the water-soluble phosphine ligand tris(4phosphonatophenyl)phosphine (TPPTP). The negatively charged TPPTP-Pt NPs were

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electrostatically deposited onto a glassy carbon electrode (GCE) modified on multilayers and are used for oxygen reduction reaction (ORR). Platinum-silica aerogel nanocomposites have been synthesized by a supercritical impregnation method by Yoda and collaborators [338]. Niesz et. al. [339] have obtained Pt NPs by reduction of H2PtCl6 in water with NaBH4 in the presence of the capping poly(ethylene oxide)13-poly(propylene oxide)30-poly(ethylene oxide)13 triblock copolymer at room temperature. Addition of anionic Pt salt under flowing H2 gave larger NPs. Mark et. al. [340] have proposed the use of S layers from S. acidocaldarius and D. radiodurans as a biomolecular template to order arrays of dendrimer encapsulated platinum NPs. This approached, provide regular 2D arrays. Park et. al. [341] have obtained a Pt/PPy nanocomposite by means of ultrasonic irradiation in the presence of sodium dodecyl sulfate or poly(N-vynil-2-pyrrolidone). Gold. There are numerous routes for the production of colloidal Au(0) nanoparticles, but the method described by Brust and its variation are one of the most popular synthetic schemes in the field [342]. Gold nanoparticles functionalized with carbohydrates (glyconanoparticles) have been synthesized by several groups [343]. Tang et. al. [344] have found that large citrate protected gold nanoparticles (around 17 nm) can be extracted from water into chloroform using hyperbranched polyethylenimine (HPEI) polymers, and hyperbranched polymer showed better results than its corresponding linear analog. Prignon et. al. [345] have mentioned that synthesis of dendrimers is prohibitive for many applications because of the high cost of the dendrimer synthesis although hyperbranched polymers can be easily accessible and they can effectively stabilize metal nanoparticles in organic solvents. Using a hyperbranched polymer chemically analogous to PAMAM dendrimers, they have obtained gold nanoparticles. Kumar et. al. [346] have synthesized gold NPs in the matrix of a plasticized anion-exchange membrane, where gold NPs are dispersed throughout the matrix of the membrane but excluded from the surface. Wu and coworkers [347] have developed a method in which nanocomposite with hydrophilic clay faces and hydrophobic polystyrene (PS) brushes in the edges are used to stabilize PS colloidal particles, after poly(2-vinyl pyridine) (P2VP) chains are adsorbed to the surface of these particles and then gold NPs are prepared in P2VP brushes. Ishida et.al. [348] have deposited gold NPs onto polymer beds such as poly(methyl methacrylate) (PMMA), polystyrene (PS), polyaniline (PANI), poly(vynilchloride) (PVC) and melamine-formaldehyde resin (MF). Catalytic performance of Au/polymers over oxidation of glucose with H2O2 was affected by the kinds of polymer supports and has less influence by the size of Au nanoparticles. PMMA as polymeric support of gold NPs have been used by Kuroda et. al. [349] for studying the reduction of 4nitrophenol to 4-aminophenol and it was compared with other reported supports for the same reaction.The results indicate that the structures of polymer supports play an important role in determining the catalytic activities. Oxidation of 1-phenylethanol with dioxygen in water catalyzed by microgel-stabilised gold NPs with poor results, have been developed by Biffis et. al. [350] They argue that the bad performance of the Au nanoclusters may be partially related to their large size. However, Miyamura et. al. [351] have obtained better results not only with 1-phenylethanol but with several alcohols at room temperature under atmospheric conditions. These results were obtained using gold nanoclusters stabilized with polystyrene. Using a four dendritic thiol ligands, Advincula [352] have found that average size of gold NPs increases while the sizes distributions becomes broader as the size of thiophene dendron increases. They argue that the increased steric congestion, between dendrons, leads to slower

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Roco Redn, N. G. Garca-Pea and F. Ramrez-Crescencio

reaction with the growing Au nanoparticles, resulting in the formation of larger gold clusters and broader size distribution. One-dimensional arrays of Au-dendrimer nanocomposites have been obtained by Torigoe et. al. [353] using poly(oxymethylphenylene) dendrons (PPD) of generations (G) 1-4 functionalized with a thiol group at the focal point as capping ligands. The size and shape of Au-NCDs (nanoparticles-cored dendrimers) change with the generation number of dendrons [354]. When increasing the generation number of dendrimer the size of the gold nanoparticles increases and polydispersities too. Gold nanoclusters capped by dendron thiol-terminated Frchet-type benzyl ether dendrons (G1) have been synthesized by Li et. al. [355] Size-controlled gold nanoparticles were obtained by the variation of the mole ratio of G1 to Au. The Au atoms in the G1-gold clusters were largely Au(0). Love et. al. [356] have determined that using branched ligands leads to smaller and better defined Au NPs than using an analogous nondendritic stabilizer, indicating that also, the structural nature of the dendritic branching must play a role in controlling nanoparticle growth - not just the simple steric effect of dendritic size. Shon et. al. [357] have obtained nanoparticle-cored dendrimers (NCDs) through the synthesis of monolayer-protected nanoparticles and then adding dendrons on functionalized nanoparticles by a coupling reaction. Tomalia and Huang [358] have reported Cystamine core (G13) PAMAM dendrimers reduced to their respective thiol core, functionalized dendrons using DTT. Bakshi et. al. [359] have obtained gold NPs in aqueous phase in the presence of sodium dodecylsulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) and poly(amidoamine) dendrimers (PAMAM). Krasteva and coworkers [360] have found that resistivity and vapor-sensing properties of chemiresistors made from gold nanoparticle/poly(propyleneimine) composite films depend on the size (generation) of the dendrimers. Using maltose-modified PPI dendrimers (generation 2-5), Pietsch and collaborators [361] have obtained gold NPs using NaBH4 or only dendrimer as reducing agent. For the 4th generation dendrimer (G4) the autoreduction process is much faster compared to the low generation dendrimers G2 and G3, in the case of G5 dendrimer, the reduction of metal ions is practically instantaneous. Lee et. al. [362] have reported, through a one pot synthesis, a composite made of SWNT-PANI-Au; polymerization of aniline and formation of Au nanoparticles (average size 5 nm) are simultaneously achieved in the presence of -irradiation. Using a two-phase method Rodrguez-Vzquez et. al. [363] have obtained gold clusters capped with tetrahexylammonium bromide. These clusters are stable in aqueous solution for several years. In order to functionalize gold NPs, a poly(aryl ester) dendron was used by Frein et. al. [364] They have obtained NPs in biphasic media using tetraoctylammonium bromide (TOAB), water, toluene and NaBH4 obtaining nanoparticles ordered in evenly spaced rows. The separation between the rows corresponds to 1.3 times the length of the dendron in its fully extended conformation. The average size of the nanoparticles was 1.2 0.4nm. Huang et. al. [365] have obtained gold nanorods via oxidation of spherical gold nanoparticles using NaH2PO4 in the medium of cetyltrimethylammonium bromide (CTAB). Fabrication of hydrophobic gold nanorods from hydrophilic one have been developed by Mitamura et. al. [366] DNA-based gold nanostructures have been synthesized by several groups obtaining bi- and tridimensional arrays [367]. Olefin metathesis can be achieved on the surface of gold nanoparticles [368]. Gold NPs supported over TiO2, CeO2, Al2O3 and SiO2 have been used by Zanella and collaborators [369] for the water gas shift reaction. Again, it is mentioned that nature of the support must be taken into account in order to explain the catalytic behavior of these catalysts. Mertens et. al. [370] have studied the

Metallic Nanoparticles Nanocomposites

27

catalytic oxidation of several 1,2-diols to hydroxy-carboxylates with gold nanocolloids They argue that in comparison with Pt and Pd, Au is more resistant to deactivation by chemical poisoning or overoxidation and it displays a higher intrinsic chemoselectivity. Au sols were prepared by reduction of HAuCl4 with NaBH4 in an aqueous solution of poly(vinylalcohol), obtaining gold NPs with average size of 2-4 nm, this catalyst was recovered by filtration through a membrane (polyimide, cellulose acetate, poly(dimethylsiloxane) or DESAL-5 DK) and then reutilized without significant lose of activity. Gazsi et. al. [371] have studied the synthesis of hydrogen via methanol oxidation using gold supported on CeO2, Al2O3, TiO2, MgO, activated carbon and SiO2. Dapurkar et. al. [372] have used gold NPs (less than 10 nm) supported on TiO2, MgO, Al2O3, CeO2 and C for studying the oxidation of benzylic compounds into their corresponding ketones without solvent at 1 O2 atm and T 100C. Mitsudome et. al. [373] have reported that the oxidative lactonization of diols using molecular oxygen as a primary oxidant can be catalyzed by Hydrotalcite supported gold NPs. Guan et. al. [374] have studied the ethanol dehydrogenation by gold nanoparticles supported on mesoporous sillicas and conventional sillicas obtaining different particle sizes. Maximum activity for alcohol dehydrogenation was observed at a particle size around 6 nm. Methanol oxidation over Au/TiO2 (prepared by deposition precipitation method) catalyst have been studied by Nuhu et. al. [375]. Supported gold chloride is the most active catalyst for the hydrochlorination of ethyne, the activity being correlated with the metal's high standard electrode potential was reviewed by Bond and Thompson [376]. Diao et. al. [377] have reported that gold submicroparticles (AuSMPs) dispersed on indium tin oxide (ITO) are catalytically active toward CO electrooxidation in solution. They also found that the halide ions (Cl-, Br-, I-) exhibit significant poisoning effect on the catalytic activity of AuSMPs/ITO electrodes. Oxidation of nitic oxide can be catalyzed by TiO2-Au nanocomposite film electrode as reported by Milsom et. al. [378]. Films have 3050 nm per layer and gold NPs exhibit a 20 nm average diameter. Santosh et. al. [379] have prepared a catalyst of MWNT, polyaniline (PANI) and gold nanoparticles (8-10 nm) MWNTPANI-Au, which was used to demonstrate electrocatalytic oxidation of methanol and CO. Gold NPs supported on TiO2 were used by Raptis et. al. [380] as a heterogeneous catalyst for the isomerization of epoxides to allylic alcohols in high yields and good selectivity. Au over SiO2, TiO2 and silylated materials have been synthesized by Aprile et. al. [381] and used for epoxidation of alkenes with O2, they demonstrate that intermediates of reaction involves organo-gold species.

CONCLUDING REMARKS AND FUTURE PROSPECTS

As matrices, supports, templates or protectors, polymers that are part of the composites help nanoparticles to work better as catalysts by lowering costs, by increasing their selectivity and/or reactivity, by being environmentally friendly or through a combination of these applications. Thus, the study of this kind of materials is still growing and, providing a new twist on Feynman's famous quote, it is necessary to keep in mind that there is plenty of room, not only at the bottom, but everywhere in order to find the dream catalyst, the best catalyst which is cheap, recoverable, recyclable, efficient and non-contaminant. Thus, as mentioned above, there is a promising future and still a lot of work to be done to get the best catalyst ever designed.

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Roco Redn n, N. G. Garc a-Pea and F. Ramrez-Cre escencio

ACKNO OWLEDGME ENTS

Financial support s for th his research by PAPIIT IN101308 I and d PUNTA is gratefully

ac cknowledge ed.

ABOUT THE AUTH HORS

Roco Red dn was born in Mexico City C in 1969. In 1993 she obtained her r B. Sc. In Chemistry at th C he Universida ad Nacional Autnoma A de Mxico. Obta aining her Ph h. D. in the sa ame Universit ty in 2002. During D her Ph. . D. studies, she s had the oportunity o of working w in di ifferent Chem mistry Groups aroun the Wo orld; in 1997 in i England in Essex Univer rsity and in 19 998 in Oxfor rd University with Prof. J. R. Dilworth h; in 1998 in n Spain, with Prof. Ana A Albeniz at Valladolid Unive ersity, and in USA U at Hawa aii University with Prof. Cr raig Jensen fr rom 1998 to 2001. Finally y she obtained d a Post-doct toral position in the Labo oratorio de M Materiales y Nanotecnologa a, CCADET in the Univers sidad Naciona al Autnoma de d Mxico, w where she actua ally works on the synthesis and character rization of nan nocomposites dendrimerno oble metal NP Ps and their ca atalytic applica ations.

M Metallic Nanop particles Nanocomposites

29

Nidia G. Garca G Pea was w born in Toluca, T Mexico, in 1982. She obtained d her B.Sc. de egree in chem mistry from th he Universida ad Nacional Autnoma A de Mxico in 20 008. She is cu urrently worki ing with Prof. Redn in nan nostructured materials m appli ied to catalysis, to obtain he er M.Sc. degre ee in chemistr ry. She expects to graduate in i 2010.

Fermn Ra amrez was born in Puebla a, Mxico, in n 1984 and studied s chemistry at the U Universidad Nacional Autn noma de Mx xico. His und dergraduate re esearch was done d in the gr roup of Prof. Roco R Redn concerning fr ree-solvent syn nthesis of irid dium nanoparti icles. He is cu urrently comp pleting his Ma aster thesis on interactions of o iridium nan noparticles wit th dendritic sp pecies.

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In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 2

RECENT EVOLUTION OF OXIDATION CATALYSIS BY MO COMPLEXES

Carla D. Nunes* and Pedro D. Vaz
Centro de Qumica e Bioqumica, Departamento de Qumica e Bioqumica Faculdade de Cincias da Universidade de Lisboa Ed. C8, Campo Grande, P-1749-016 Lisboa, Portugal

ABSTRACT
For 80% of all compounds produced in chemical and pharmaceutical industry at least one catalytic step is essential during their synthesis. Catalysts speed up chemical reactions but can be recovered unchanged at the end of the reaction. They can also direct the reaction towards a specific product and allow reactions to be carried out at lower temperatures and pressures with higher selectivity towards the desired product. This is a principle that is pursued with increasing emphasis and dedication leading to far more specific and cleaner processes. Homogeneous catalysts, on the other hand are usually complexes, which consist of a metal centre surrounded by a set of organic ligands. The latter impart solubility and stability to the metal complex and can be used to tune the selectivity of a particular catalyst towards the synthesis of a particular desirable product. By varying size, shape and electronic properties of the ligands, the active site at which the substrate binds can be constrained in such a way that only one of a large number of possible products can be produced. Oxidation catalysis is a quite important transformation in both industrial and academic aspects. Within this field, catalysts, ranging from a variety of available metal centered systems, which rely on Mo are one of the most important. Traditionally, oxidation catalysts are based on metal oxides, holding M=O moieties, with the metal center lying in high oxidation state. A large number of important chemical reactions are catalyzed by MoVI complexes. Inclusively, several industrial processes such as ammoxidation of propene to acrylonitrile, olefin epoxidation (ARCO and Halcon processes), and olefin metathesis reactions are carried out over molybdenum catalysts. Furthermore, as molybdenum is highly available to biological systems, the coordination
*

Corresponding author: Phone: +351 217 500 876, Fax: +351 217 500 088, E-mail: cmnunes@fc.ul.pt

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Carla D. Nunes and Pedro D. Vaz

chemistry of MoVI has stimulated considerable interest in view of its biochemical relevance, and many MoVI complexes have been studied as models of molybdoenzymes. In recent years the development of new approaches to prepare new and stable catalyst has turned to low oxidation state MoII organometallic complexes. These precatalysts proved to be quite adequate to the purpose by being highly active and selective in the epoxidation of olefins and in oxidation of other substrates. Additionally, such precatalyst complexes are more stable towards air and moisture which allows easier handling. This chapter lights up some recent advances on olefin oxidation chemistry based on Mo catalysts with special focus on the development of new approaches to achieve active catalysts.

INTRODUCTION
The significant enzymatic role of molybdenum in biochemical reactions [13] specially in the oxidation of aldehydes, purines and sulfides [4] induced chemists to use molybdenum complexes as biomimetic catalysts in the oxygenation of organic compounds [5,6]. Under such auspices, MoVI dioxo-complexes have been extremely investigated [79] particularly with respect to the catalytic role of transferase enzymes like nitrate reductase in which their active sites consist of a cis molybdenum dioxo moiety [10,11]. The ability of molybdenum to form stable complexes with oxygen-, nitrogen-, and sulfur-containing ligands led to development of molybdenum Schiff base complexes which are efficient catalysts in both homogeneous and heterogeneous reactions [1215]. The activity of such complexes varies markedly with the type of ligands and coordination sites [16]. Molybdenum-catalyzed olefin epoxidation has received interest from both academic and industrial research laboratories because epoxides are important building blocks in organic synthesis and polymer science [1720]. Although numerous procedures have been developed [21-24], there is still a need for the development of new catalysts that may uncover a more detailed understanding of oxidation pathways and inform the design of more efficient catalytic systems. Since the first example of a molybdenum oxo complex catalyzing the epoxidation of alkenes with peroxides such as organic hydroperoxides and hydrogen peroxide [25], a variety of different complexes have been developed [2641]. Despite this, molybdenum catalysts are also suitable for many other oxidation reaction types. Oxidation of alcohols to aldehydes and ketones is one of the most important transformations in organic synthesis [4244]. In particular, the oxidation of primary alcohols to aldehydes is important since they find wide applications as intermediates in fine chemicals particularly for perfume industry [4548]. Traditionally, the oxidation of alcohols is carried out using stoichiometric inorganic oxidants such as permanganate, bromate, or chromate based reagents which generates large amount of heavy metal waste [49-52]. Several transition metal-based homogeneous systems such as palladium [5364], ruthenium [6568], manganese [69,70], tungsten [71], rhenium [72], copper [73,74], and iron [75,76] have also been reported. However, mixtures of the organic substrates, products, solvents, and molecular oxygen are well known for being explosion hazards in many cases. In addition, catalytic oxidation of amines is also a major functional transformation in organic synthesis [4246]. Amongst the possible amine oxidation products (hydroxyl, nitroso, nitro, azo and azoxy), aromatic nitroso compounds are utilized extensively as chemical feedstocks for a wide range

Recent Evolution of Oxidation Catalysis by Mo Complexes

45

of useful materials such as dyes, pharmaceuticals, perfumes and plastics [47,48]. As a drawback, amine oxidation poses problems due to non-regioselectivity or over-oxidation of amines and competitive oxidation of substrates. Within this context, MoVI complexes have proved also as adequate catalysts for such transformations being explored in several works given its functional as well as structural similarity with molybdo-enzymes catalyzing a variety of oxidation reactions [7780]. Oxidation reactions using Mo complexes occur in the presence of terminal oxidants, Chart 1, such as hydrogen peroxide (H2O2), or organic hydroperoxides, such as urea hydrogen peroxide complex, tert-butyl hydroperoxide, ethylbenzene hydroperoxide, cumyl hydroperoxide and trityl hydroperoxide. Chart 1

Hydrogen peroxide 1

UreaH2O2 complex 2

tert-Butyl hydroperoxide 3

Ethylbenzene hydroperoxide 4

Cumyl hydroperoxide 5

Trityl hydroperoxide 6

From this library of peroxide oxidants it has been found in recent years that H2O2 is the least competent oxidation agent concerning olefin epoxidation. In this way olefin epoxidation reactions have centered mainly on the use of the organic hydroperoxides. When these are used, olefin epoxidation proceeds via a Lewis acid catalyzed process. This is a class of reactions known as heterolytic reactions involving a two-electron transfer process. In this process the catalytic center does not undergo a change in its oxidation state. It occurs since the electron-transfer steps involving the metal are concerted and accordingly there is no valence net change in the metal. The key role of the metal is then to activate the organic peroxide (ROOH) in such a way that an O atom from it may be transferred to the olefin.

OXIDATIONS WITH [MOVIO2]2+ COMPLEXES AS CATALYSTS

The majority of studies dealing with catalytic applications using high-oxidation state Mo complexes has traditionally relied on the use of simple complexes centered on the tetrahedral MoO2X2 (X = Cl, Br) core shown in Chart 2.
VI

46

Carla D. Nunes and Pedro D. Vaz Chart 2

7, 8 Particular interest in MoVI-oxo complexes arose in the late 1960s when ARCO and Halcon presented patents on the olefin epoxidation catalyzed by MoVI compounds in homogeneous phase [81,82]. In the following years different mechanisms were suggested to explain the reactivity of these complexes. The debate as to which of the two main proposed mechanisms is more accurate, the one favored by Mimoun et al. [83] or the one suggested by Sharpless et al. [84] has not been settled to date, despite the fact that several theoretical and mechanistic studies have been presented [85]. It has been generally agreed, however, that formation of a MoVI alkyl peroxide occurs followed by transfer of the distal oxygen atom of the alkyl peroxide rather than an oxo ligand [86]. The industrial ARCO and Halcon process employs tert-butyl hydroperoxide (tbhp) as oxidizing agent. Despite the fact that H2O2 is a more environmentally friendly oxidant (the only byproduct formed is H2O), tbhp has other advantages that still make it the preferred oxidizing agent in industrial processes [87]. A kinetic model, proposed by the groups of Khn and Gonalves [88], was built up for a homogeneous batch reactor based on a simplified mechanism involving three steps: (i) reversible coordination of tbhp to the starting MoVI complex to give a MoVI alkylperoxide; (ii) irreversible oxidation of cyclooctene to cyclooctene oxide by the species formed in step 1, with formation of the starting complex and tert-butyl alcohol; (iii) reversible coordination of tert-butyl alcohol to the starting complex. This model is consistent with the observed kinetics. The first step in this reaction mechanism was characterized in more detail by studying the kinetics of the reaction of the starting complexes with tbhp in the absence of any reductant by UV/Vis spectroscopy. Rate constants, equilibrium constants, and activation parameters were determined. All S values were negative and therefore support an associative mechanism in which a seven-coordinate intermediate is formed. The results also suggest that the first step is not always the rate-limiting step of cyclooctene epoxidation with these complexes. DFT calculations later on have confirmed such findings for such mechanism proposal [89]. This mechanism, proceeds through coordination of the hydroperoxide to the metal center, Scheme 1. Coordination proceeds by means of the distal oxygen atom of the peroxide, rather than the proximal one. The very next step is the H-atom transfer to one of the oxo ligands of the metal center. It then starts with a hydrogen transfer from the peroxide to one of the terminal Mo=O oxygen atoms and the remaining t-BuOO anion binds as a seventh ligand, forming a fivemembered ring held together by a hydrogen bond. In the second step, a concerted approach of the olefin to the MoOd (Od = distal) bond gives rise to an intermediate containing a sevenmembered MoCCOdOp(t-Bu)HOMo ring (Op = proximal). In the final step, decomposition of the intermediate leads to the starting complex, alcohol and the desired epoxide. The activation energy for the addition of the olefin (second step) is the highest one, in agreement with available kinetic studies showing that the catalyst formation is not always a

Recent Evolution of Oxidation Catalysis by Mo Complexes

47

rate-limiting step. There is also evidence that the resulting alcohol by-product (t-BuOH) can react with the starting complex, competing with t-BuOOH and hence leading to the progressive catalyst poisoning, which has been observed experimentally.

Scheme 1. Proposed reaction mechanism for t-BuOOH activation and olefin epoxidation at the NOX face of octahedral [Mo2O2X2L2] (X = Cl, Br, Me) complexes. The metal is hidden for clarity. Op and Od stand for proximal and distal O atoms in peroxide.

From the continuing research developed using such catalysts, much of the work has centered on ligand design. Many works have been devoted to exploring the chemistry of a large family of complexes of formula MoO2X2(N,N) or MoO2(N,O)2 where N,N and N,O are bidentate ligands and X = Cl, Br, alkyl [89101]. The reactivity and selectivity of such complexes is largely dictated by the bidentate ligands and recently a high asymmetric induction was achieved for the first time on this kind of systems [102]. The simpler MoO2X2 or MoO2X2L2 derivatives (L = labile ligand) have been less studied in this regard [103105]. Starting from the late 70s and early 80s decades of the XXth century, a rising interest in stable organometallic complexes arose during the development of models for reactive intermediates for the nitrogenase enzyme [106108]. For this reason, reactions of MoO2X2(bpy) (X = Cl, Br ; bpy = 2,2-bipyridine) precursors with different Grignard reagents were thoroughly explored by Schrauzer and co-workers. The first isolated compounds were of the type MoO2BrR(bpy) and being synthesized by reacting MoO2Br2 (bpy) with different organomagnesium halides in thf. Some of the MoO2BrR(bpy) complexes were isolated [R = Me [106], Et [106], CH=CH2 [107]], while others were only generated in solution [R = Pr, i-Pr, t-Bu, CH2C(CH3)3] [108]. Complexes with Me and Et react back with Br2 to yield MoO2Br2(bpy) and CH3Br or C2H5Br, respectively. A modification of the synthetic method used for MoO2BrR(bpy) afforded the preparation of several complexes of composition MoO2R2(bpy), as evidenced in Chart 3.

48

Carla D. Nunes and Pedro D. Vaz Chart 3

The first compound of this type obtained, MoO2Me2(bpy) [109], was synthesized by reacting MoO2Br2(bpy) with methylmagnesium chloride in thf. Several other complexes, namely, ethyl [112], propyl [112], butyl [112], neopentyl [110], cyclopentyl [112], cyclohexyl [112], benzyl [111], several aryl [113116], and organosilicon derivatives [117], followed in the following years using different Grignard reagents. From this set of complexes, MoO2Me2(bpy) exhibits a high thermal stability (melting point = 503 K) and is stable under air. The decomposition temperatures were found to be related to the stability of the Mo-C bond. Decomposition was observed to occur on prolonged heating under basic or acidic conditions in solution. The most temperature sensitive are those complexes with hydrogens in -position like the diethyl derivative or those where steric effects cause an additional Mo-C bond labilization, as found in the c-C6H11 derivative. In 1991 the first examples of MoO2R2L2 complexes were reported, where L2 was not bpy but 4,4-dimethyl-2,2-dipyridyl (Me2-bpy), conferring a higher solubility to the synthesized compounds [118]. The MoVI compounds MoO2R2L2 [L2 = Me2bpy; R = CH2CHMe2 (9), CH2CMe3 (10), (CH2)4CH=CH2 (11), CH2Ph (12), CH2C6H4Me-p (13), and CH2CMe2Ph (14), Chart 4, were prepared by reaction of the corresponding Grignard reagents with MoO2Br2L2, followed by aerobic oxidation of the resulting reaction mixture. Chart 4

12

10

13

11

14

The decomposition reactions of these compounds were studied in very detail by Vetter and Sen [118]. The complexes were found to decompose in solution under inert gas atmosphere at varying rates. The course or rates of the reaction were found not to be influenced by the nature of the solvent in use. As the decomposition evolves, insoluble

Recent Evolution of Oxidation Catalysis by Mo Complexes

49

molybdenum oxides are formed and in solution quantitative amounts of hydrocarbons can also be detected. Anaerobic decomposition associated with a given complex is a sensitive function of the hydrocarbyl group R. If -hydrogens are present on R, equal amounts of alkane and alkene are formed through a -hydrogen abstraction pathway. When -hydrogens are absent from R, the predominant product is the free radical R formed by Mo-R homolysis. Other complexes of the type MoO2R2L2 (R = CH3, C2H5; L = bidentate Lewis base ligand) were reported by the research groups of Gonalves, Khn, and Romo during the past decade [34,94,95,119,120]. A wide range of compounds was synthesized, bearing a variety of bidentate ligands of the type 1,4-diazabutadiene (R-dab), with different R groups, phenanthroline, and substituted bypiridines, Chart 5. Chart 5

Besides providing access to more soluble complexes, which are better amenable to reactivity and spectroscopic characterization than the modestly soluble MoO2R2(bpy) derivatives, the different stereochemical and electronic characteristics of these ligands impart distinct reactivities to the MoO2R2 core. Such complexes were obtained by alkylation of MoO2X2L2 (X = Cl, Br) with the appropriate Grignard reagent [34,94,119,120]. The catalytic properties of MoO2X2L2 (X = Cl, Br) and MoO2R2L2 [R = CH3, C2H5; L = 1,4-diazabutadiene (R-dab), with different R groups, phenanthroline, or substituted bypiridines] (Chart 5) have been recently studied in detail by several research groups [34,94,95,119,120]. The complexes were found to be active for the epoxidation of olefins using tert-butylhydroperoxide as oxidant at moderate temperatures (328 K). However, when H2O2 was employed as the oxidant, no epoxidation products could be obtained, Scheme 2. The catalytic performance of such complexes is resumed in Table 1 showing results of olefin epoxidation using both MoO2X2L2 (X = Cl, Br) and MoO2R2L2 (R = CH3, C2H5; L = N,N-bidentate ligands) complexes as catalysts.

Scheme 2. Efficient and inefficient olefin epoxidation using tbhp and H2O2, in the presence of MoVI catalysts.

50

Carla D. Nunes and Pedro D. Vaz

Table 1. Catalytic performances of catalysts based on MoO2X2L complexes (X = Cl, Br, CH3; L = bidentate Lewis base ligand) in cyclooctene epoxidation at 328 K and after 24 h reaction [94].
X Cl 15 Br 16 73 L Conversion % 89

57 17 65 18 27 19

24 20 CH3 21 35 22 92 23 35

89 24

Recent Evolution of Oxidation Catalysis by Mo Complexes

51

60 25

29 26 72 27 48 28 40 29

In most cases, the overall yield obtained after 4 h is relatively low (between 5 and 60%), but increasing greatly up to 24h reaction time. However, over a 24 h period yields proved to be strongly dependent on L and R ligand type used. Electron-attracting ligands L lead to more active compounds, rendering the electron deficient molybdenum center. Steric effects of the ligands also seem to play an important role on the catalytic activity. Ligands, which create more steric hindrance near the metal center, usually decrease the catalytic performance of complexes. Increasing both reaction time and temperature leads to a significant increase in the product yield in all examined cases. However, at ca. 363 K further increase in product yield is hampered by catalyst decomposition. This is most evident with the organometallic MoO2R2L2 (R = CH3, C2H5; L = N,N-bidentate ligands) derivatives. It is also remarkable that during the catalytic cycle loss of the R group as methane, ethane, or methanol by a potential MC bond breaking does not play an important role. The use of MoO2X0-2L1,2 (X = halogen; L = mono-, bi- or tridentate ligands) complexes have also been thoroughly studied as evidenced in Table 2. In fact variation of the coordination sphere around the metal center (0-2 halogen ligands and 1 or 2 Lewis base ligands) were found to be crucial based on the reported results. From the results shown in Table 2, it is possible to observe that terminal olefins are generally more resistance to oxidation and that the use of H2O2 does not favor the reaction. This is quite clear in the epoxidation of cyclooctene where reactions do occur to completeness in the presence of tbhp while with H2O2 they do not.

Table 2. Catalytic Performance of MoO2X0-2L1,2 (X = halogen; L = mono-, bi- or tridentate ligands) complexes in olefin epoxidation.
X L Olefin Oxidant Conversion % Epoxide sel. % Ref.

30

O2

96

121

O2 O2

86 95

85 81

tbhp 31 tbhp tbhp tbhp

73 46 100 96

100 100 100 100

122

tbhp

70

100

tbhp

96

100

tbhp

46

65

tbhp

48

68

tbhp tbhp tbhp F H2O2

40 77 45 99

100 91 100 100 123

32

Cl

33

tbhp

100

100

124

tbhp

100

59

H2O2 34

68

100

125

Table 2 (Continued).
X L Olefin Oxidant Conversion % 100 Epoxide sel. % 100 Ref.

tbhp 35 H2O2 36

126

80

100

127

tbhp 37

96

100

128

Recent Evolution of Oxidation Catalysis by Mo Complexes

55

Room temperature ionic liquids (RTILs) have also been used as alternative solvents. The catalytic properties of MoO2R2(Me-p-tolyl-dab)2 (38, 39) (R = Cl, CH3 ; Me-p-tolyl-dab = 1,4-p-tolyl-1,4-diaza-2,3-dimethyl-1,3-butadiene) were assessed for olefin epoxidation under not only the previously applied conditions (tbhp as oxidant, 328 K) but also using as alternative solvent several RTILs, Chart 6 and Table 3 [129]. Chart 6

38, 39

The authors reported that this complex presents excellent selectivity toward the epoxide formation relatively high activity under solventless conditions or with additional solvent, either chlorinated or an adequate RTIL. The application of RTILs also enabled the catalyst recycling. From several RTILs tested in recycling catalytic experiments with complex 39 the best results were observed for the system using [bmim]NTf2, as evidenced in Table 3, entry 8. When developing catalysts for a given reaction one must bear in mind not only high activity but more important, selectivity. In fact if a catalytic system is not selective then it is of no real use. In a quest for more efficient and selective catalysts some works have devoted to the development of MoVI catalysts with chiral ligands to yield enantiopure compounds. The need of enantiomerically pure chiral compounds faces a continuous rise. This is powered by the increasing number of legal regulations and health concerns as well as the need for industrial efficient processes. Enantiopure complexes are used mainly in pharmaceuticals but not limited to, as well as in other sectors such as flavor and aroma chemicals, agricultural chemicals, and specialty materials. Development of chiral active pharmaceutical ingredients (APIs), in particular, is of major relevance since it is recognized that enantiomers of a chiral compound can have dramatically different biological activities, in some case with severe adverse effects [130]. Chiral epoxidations are currently of high interest for the synthesis of non-racemic chiral intermediates in the pharmaceutical and chemical industries to generate such optically pure products [87]. Chiral epoxides, for example, are a key structural unit present in many biologically active compounds as well as in important natural products [131]. Asymmetric catalysis is a particularly elegant and efficient method to achieve the introduction of such functional groups into larger organic compounds [132]. From the results discussed above in this chapter, it was shown that non-chiral MoVI (organo)complexes could successfully yield racemic epoxides. Such results led to the belief that some chiral derivatives of these complexes might be applied equally efficiently as chiral

56

Carla D. Nunes and Pedro D. Vaz

catalysts. The application of chiral MoVI complexes in olefin epoxidations was a spin-off of the application of homogeneous MoVI catalysts in the Halcon and Arco processes [81,82]. Starting in the 70s decade of the XXth century, MoVI complexes with different types of chiral ligands, among which diisopropyltartrates, lactamides and several other hydroxyacid amides, have found application in chiral epoxidation reactions. Some examples accounted with the use of N-alkyl ephedrines [133], methyl pyrolinols and diisopropyl tartrates as ligand species [134]. Chiral ligands which were easy to make and stable in oxidation reaction conditions were also searched for. Ligands that would also allow the possibility of varying steric characteristics easily through simple substitutions, were found in the class of 2-pyridyl alcohols, which were known to be easily accessible [135,136] and from which MoO2L2 (L2 = 2-pyridyl alcoholate) type complexes that were active as catalysts for epoxidation, could be prepared. Table 3. Catalytic performance of MoO2R2(Me-p-tolyl-dab)2 (R = Cl, CH3) complexes (38, 39) for olefin epoxidation in the presence of regular solvents or RTILs [129].
R Cl Solvent / RTIL None Dichloroethane Conversion % 100 94 73 CH3 [bmim]PF6 (R = nBu) None Dichloroethane 100 100 90 [bmim]PF6 (R = nBu) [C8mim]PF6 (R = nOct) 94 Epoxide sel. % 100 100 100 100 100 100 100

96 [bmim]NTf2 (R = H) [bdmim]NTf2 (R = CH3)

100

53 14

100 100

[C5O2mim]PF6

92 [(d-h)2dmg]PF6

100

Recent Evolution of Oxidation Catalysis by Mo Complexes

57

In 1999 Bellemin-Caponnaz and others demonstrated this by applying the ligand 2[()menthol-pyridine] to such a complex [137]. A conversion of ca. 20% with an ee of 25% using 1-hexene as substrate, was obtained. In 2000, Herrmann et al. [138] made use of chiral precursors, Chart 7, to form enantiomerically pure 2-pyridinyl alcoholates which were subsequently applied as chiral ligands in MoVI complexes. Chart 7

40

41

42

The complexes were examined for their catalytic activity and good conversions, in the range of 70%, being observed. Enantioselectivities were more dependent on the ligands being found to range between 4 and 26%, with the bulkier norbornane ligands leading to the highest optical inductions. Later on, in 2001, Gonalves and coworkers [139] reported MoVI dioxo complexes holding coordinated pyridyl alcoholate ligands and used in olefin epoxidation. Mono-substituted complexes were more active than those with two chiral ligands. Another class of suitable C2-symmetric bis(oxazolines) chiral chelating ligands were developed in parallel [96] by Romo et al. for the epoxidation of trans--methylstyrene. Using tertbutylhydroperoxide (tbhp) as oxidant at 328 K, up to 86% conversion was achieved although ees were very low, lying in the range from 4 to 6%. Teruel and colleagues [92] also applied chiral oxazoline ligands attached to MoO2 cores, Chart 8, 43. In that case the oxazoline ligands were bound to the metal by a covalent MoO bond in contrast to previous reports, Chart 8, 44 [96]. Chart 8

43

44

Using styrene as substrate, toluene as solvent and tbhp as oxidant, conversions from 25 to 30% were reached within 18 h at 308 K. Selectivity was below 50% and ees were still negligible (ca. 2%). Khn and coworkers [98] also synthesized MoO2Cl2L (L = oxime), [MoO2(thf)2L] (L = cis-p-menthane-3,8-diol) and MoO2Cl(thf)L (L = 8-phenylthioneo- and

58

Carla D. Nunes and Pedro D. Vaz

isoneomenthol) complexes. Conversions were found to reach 6382% obtained with the cis-methylstyrene as substrate, tbhp as oxidizing agent and toluene as solvent (328 K). The observed ees were on an average low, with 24% in the best case using complex (45), Chart 9, at 72% conversion. Chart 9

45

The first sugar ligands were attached to [MoO2]2+ moiety by Rao and coworkers [140] in 2001, to prepare complexes of general formula MoO2L (L = sugar), Chart 10. Chart 10

46, 47

These were applied in olefin epoxidation by Khn et al. [141]. Turnover frequency (TOF) was high (13000 h-1 in the best case) when cyclooctene was the substrate although velocity of reaction slowed down with increasing time. When esterification was used to protect the OH group in the sugar ligand tridentate coordination of the ligand took place due to Lewis acid catalyzed deacetylation. In the case of cis--methylstyrene ees of up to 30% were achieved. In 2004 Herrmann published [142] further results in continuation of previous work published in 2000 [138]. A number of chiral 2-pyridinyl alcohols were used as ligands for the MoO2 core. When tbhp or cumyl hydroperoxide (chp) were used as oxidants and trans-methylstyrene as substrate, ees of up to 23% and conversions up to 58% (temperatures 323 343 K) were reached [142]. Following also their previous work [92], Teruel et al. published further research, in 2004, which made possible to explain the good activity and low enantioselectivity of the MoVI complexes with coordinated oxazoline ligands [143]. They proposed a reaction mechanism for olefin epoxidation catalyzed by a seven-coordinate molybdenum species with hemilabile ligands as it was later on confirmed by kinetic and theoretical studies [88,89], and already discussed in this chapter. In the same year, Singh and

Recent Evolution of Oxidation Catalysis by Mo Complexes

59

coworkers [144] also reported a chiral MoVI compound with bidentate oxazoline ligands, active in the epoxidation of styrene, reaching yields of up to 70%. Khn et al. used a tetradentate chiral Schiff base, see Chart 8, 44, obtaining ees up to 26% with cis-methylstyrene [145]. Gonalves and coworkers also prepared chiral 1,4-diazabutenes of the type RN=C(Ph)C(Ph)=NR; (1R,2R)-N,N-dibenzylidenecyclohexane-1,2-diamine and hexa-coordinate MoVI complexes [100]. The resulting complexes were applied as effective catalysts for epoxidation using cis- and trans--methylstyrene by tert-butylchloroperoxide. Reactions were found to proceed with high retention of configuration and high selectivity to the epoxide, only for cis--methylstyrene though. In this case high 77% ee at room temperature was obtained (at 24% conversion). Increasing the reaction temperature increased the epoxide yields but good enantiomeric excesses (ca. 65%) could only be achieved at low conversions (ca. 12%). Shi and coworkers [146] used both mono and tetradentate compounds for the asymmetric olefin epoxidation of cis-1-propenylphosphonic acid with 30% aqueous hydrogen peroxide affording (1R,2S)-()-(1,2)-epoxypropyl phosphonic acid. This reaction is strongly influenced by ligands, solvents as well as reaction temperatures. For example in a complex with a tetradentate salen ligand, Chart 11, better ees were obtained in noncoordinating solvents such as methylene chloride than in a solvent like ethanol. An ee of 69% for a MoVI complex coordinated to ligand 48 was observed at 30% conversion after 24 h reaction time. Chart 11

48

In addition to these results, a few others not discussed within the text are screened in Table 4, stressing the relevance and difficulties of assessing enantiopure epoxides. In fact, the systems presented in Table 4 using the pyridine 2-alcoholate ligands reported by Hamann [148] were found to be quite original since they relied on the use of chiral hydroperoxides instead of the use of chirality in the ligands. The outcome was the synthesis of epoxides with good ees and additionally, these being obtained from a linear terminal olefin which is usually seen as unactivated. In parallel studies some attention has been devoted, in recent years, to the use of [MoO2(acac)2] (acac = 2,4-pentanedionate) in the epoxidation of olefins as well as in sulfide oxidation using tert-butyl hydroperoxide (tbhp), cumyl hydroperoxide (chp) or trityl hydroperoxide (thp) and chiral bis-hydroxamic acid (bha) derivatives as ligands [149-151]. In olefin epoxidation experiments all oxidation products were achieved in high enantiomeric excess (ee) and, additionally it was found that an excellent regiospecificity was also achieved, Table 5.

Table 4. Chiral epoxidation of olefins with MoO2L2 complexes and organic hydroperoxides.
Complex Olefin Oxidant Conversion % Epoxide Sel. % ee % Ref.

tbhp

92

100

<5

147

49 7 36 <5 <5

AcO OAc O OOH

50 100 100 30 100 100 50 148

100

100

20

100

100

28

100

100

53

100

100

40

100

100

38

100

100

34

62

Carla D. Nunes and Pedro D. Vaz

From Table 5 it is possible to conclude that trisubstituted and terminal alkenes also provided good selectivity (entries 813). Another important aspect of such Mobha catalysts is that it selectively oxidizes the most electron rich alkene in the presence of multiple double bonds (entries 14, 15, 17). Encouraged by the selectivity observed for myrcene oxidation (Table 5, entry 16, squalene (Table 5, last entry), an important biogenetic precursor of steroids and polycyclic terpenoids, was subjected to similar reaction conditions. To delight of the authors, the Mo-bha complex in the presence of 1 equiv of chp selectively provided 2,3epoxysqualene with good enantioselectivity (69% ee). It was noteworthy since synthesis of 2,3-epoxysqualene often requires multiple steps. Asymmetric sulfide oxidation, has garnered extensive attention from the synthetic community, for the rapid preparation of enantiopure sulfoxides. Of particular value are those compounds which contain chiral sulfoxides, a structural class widely utilized in both the pharmaceutical industry and academia [152-156]. Although a number of methods for assessing high enantioselectivity during sulfide oxidation have emerged in recent years [152165], low enantioselectivity and restrictive structural requirements are still serious obstacles for such transformation [152-156]. The Yamamoto group has reported also the use of the Mo-bha system for asymmetric sulfide oxidation, according to the reaction shown in Scheme 3.

Scheme 3. Reaction conditions for asymmetric sulfide oxidation using Mo-bha catalytic system.

Table 6 evidences the most relevant achievements stressing catalysts capability to perform such transformations which are relevant in organic synthesis. Additionally in that work [150] the authors have also reported kinetic resolution for formation of sulfides to sulfones, as evidenced in Scheme 4. In this way the authors have found that the Mo-bha system selectively oxidizes a single optical isomer with resulting resolution enhancement which is sometime so difficult to achieve [150]. In a different approach, Sheikshoaie [166] has reported selective oxidation of sulfides to sulfoxides or sulfones by varying the quantity of urea hydroperoxide (uhp) used as oxidant, in the presence of a MoVI dioxo complex. In this way if uhp/sulfide ratio is 1 only sulfoxides are obtained. On the other hand if that ratio rises to 5 sulfones are selectively obtained. This is a fine example of selectivity tuning based on variation of reaction conditions.

OXIDATIONS WITH [MOVIO(O2)2]2+ COMPLEXES AS CATALYSTS

Transition metal peroxo and peroxy complexes have played for some time now an important role in the epoxidation of alkene substrates to their respective epoxide products. A variety of synthesis of peroxocomplexes of various metals are known [167169] to catalyze the oxidation of olefins, arenes, phenols, alcohols, phosphines and sulfides [170174].

Table 5. Chiral epoxidation of olefins using MoO2(acac)2 complex with bha ligands [149].
Ligand Olefin Oxidant Epoxide Yield % ee %

tbhp 51

20

28

tbhp 52 chp thp

15

42

72 27

66 96

chp 53 tbhp

82

87

92

96 (R,R)

chp

77

64 (R,S)

Table 5 (Continued).
thp 95 85 (R)

chp

84

82 (R)

O chp tbhp 95 77 85 (R) 43 (R)

Ph
chp 89 50 (R,S)

tbhp

41

81(S,S)

tbhp chp tbhp chp

47 91 13 33

33 (E/Z) 75 (R) 43 69

Recent Evolution of Oxidation Catalysis by Mo Complexes

65

Table 6. Asymmetric sulfide oxidation using MoO2(acac)2 complex with bha ligands and thp as oxidant [150].
Sulfide Reaction time / h 16 Yield / % 81 ee (%), config 79 (S)

20

75

81 (S)

19

76

75 (S)

18

81

82 (S)

24

66

62 (R)

17

82

86 (S)

19

83

72 (S)

O N OH N OH C(4-iPrPh)3

O S + : :

(PhiPr-4)3C

O O S

MoO2(acac)2 , thp, CH2Cl2 Racemic 273 K, 41 h 298 K, 24 h 45 (75% ee) 46 (68% ee) 55 54

Scheme 4. Kinetic resolution of sulfoxides during sulfoxide to sulfone oxidation.

The catalytic activity of peroxometal complexes is influenced by the type of metal atom, the number of peroxo ligands attached to the catalyst and the nature of the remaining ligands in the coordination sphere [175187]. In this regard MoVI complexes are an important class of oxidants for this type of reaction, and quite a number of studies have been conducted [22,27,188,189]. Similarly to that described previously in this chapter, much of the impetus for this research has in many ways been due to the early contributions by Mimoun et al. in 1969 [190] and the earlier development of the Arco [81] and Halcon industrial processes [82].

66

Carla D. Nunes and Pedro D. Vaz

In oxoperoxo chemistry of Mo, an important structural motif, in which two peroxo groups and a doubly bonded oxo ligand create the median MoO(O2)2 plane, is well known [191]. This core, although recognized as most stable [191] and a common motif in oxoperoxomolybdenum [192], has a high formation tendency, but is also a rather reactive species, which readily performs substrate oxidation, converting itself into a [MoO(O2)]2+ core, which gives more stable compounds than its diperoxo analogue. In such complexes, organic ligands are generally used to complete the coordination sphere. When these are less bulky, the 7-coordinate complexes obtained are of the type MoO(O2)2L (L = bidentate ligand) [177,193195]. In the case of bulkier ligands, the oxomonoperoxo core, namely, [MoO(O2)]2+ accommodates the bidentate ligands by forming oxomonoperoxo complexes of the type MoO(O2)L2 (L = bulky bidentate ligand) [193-195]. Recently, it has been shown that the MoO(O2)2 cores with bidentate ligands are useful catalysts in the epoxidation of olefins [196200]. MoVI-peroxo complexes also catalyze the oxidation of alcohols to carbonyl compounds [201] and amides to hydroxamic acids [202,203]. In addition some other achievements in oxidation of several organic substrates with varying functional groups, among which primary and secondary alcohols, as well as sulfides have also been reported [204210]. Despite enormous effort that has gone into developing these processes, far lesser progress has been made over the years in obtaining highly stereoselective versions of this reaction using oxoperoxo MoVI chiral complexes at either the stoichiometric or catalytic level. The quest for a chiral analogue of the Mimoun oxodiperoxo MoVI type complexes of general formula MoO(O2)2Ln (n = 1,2; L =H2O, dmf, hmpa, py), Chart 12, for olefin epoxidation using molecular oxygen [190], yielding chiral epoxides, is still an open challenge. In the late 1970s Schurig et al. [211] reported the preparation of an optically active MoVI-oxodiperoxo complex 55 (Chart 13) and its application in enantioselective epoxidation of trans-but-2-ene. Conversion to the trans-(1R,2R)-but-2-ene oxide was accomplished, in all cases, with an yield of 70% and ee of up to 34%. Shortly afterwards, Kagan et al. [212] reported another catalytic version of this reaction, showing its effectiveness over a range of olefins which could be enantioselectively epoxidized in the presence of only 10 mol% of 55. The highest ee obtained was only 35%, again for the epoxidation of trans-but-2-ene. The reason advanced for such result was that an enantiofacial discrimination of the olefins and kinetic resolution leading to enrichment of the enantiomers was not likely [212]. Chart 12

54

Recent Evolution of Oxidation Catalysis by Mo Complexes Chart 13

67

55

Mimoun then tested some chiral monodentate ligands noticing there was no observable asymmetric induction [213]. In attempts to study the mechanism of oxygen transfer in this epoxidation reaction by Modena and co-workers a series of reactions with chiral MoVI catalysts as chiral tools was carried out to probe its mechanism. The highlight of this work was use of complex 55 in the epoxidation of trans-oct-2-ene under the same conditions as used by Schurig et al. affording the major enantiomer with 36% ee [214]. It was also evidenced that certain chiral monodentate ligands, like, ()-menthyl-phosphoric triamide and N,N-dimethyl-()-menthylamine-N-oxide, can be used to give enantioselective epoxidations (albeit low, 79% ee) which contradicted previous findings of Mimoun [213]. Still, unfortunately, such studies were unable to provide clear-cut evidence on the oxygen transfer mechanism from the MoVI-peroxo complex. Besides reactions using complex 55, Schurig et al. [215] also prepared a set of other chiral MoVI-oxodiperoxo complexes based on a series of enantiomerically pure hydroxyamides, (S)-piperidine lactamide (pla) (56), (S)-N,N-dimethyl3-phenyllactamide (dmpla) (57), (S)-2-hydroxy-3-methylbutanoic acid piperidineamide (hmbpa) (58), (2S,3S)-2-hydroxy-3-methylpentanoic acid piperidineamide (hmppa) (59), (S)3-hydroxybutanoic acid piperidineamide (hbpa) (60), (S)-N-acetylprolinol (AcPro) (61) and (S)-N-benzoylprolinol (BzPro) (62), schematized in Chart 14. A series of stoichiometric epoxidations of prochiral, chiral racemic and chiral non-racemic olefins were used in a study using the above mentioned complexes. The best results were obtained using trans-but-2-ene with the complex derived from (S)-piperidinelactamide, MoO(O2)2pla, (49% ee) and (S)-3methylpent-1-ene with either MoO(O2)2pla (51% ee for the 2S,3S diastereomer and 49% for the 2R,3S diastereomer) or with MoO(O2)2dmla (55) (51% for the 2S,3S diastereomer and 49% for the 2R,3S diastereomer). Another relevant factor discovered was that enantioselectivity was inversely dependent on the degree of alkyl substitution present in the olefin, as reaction ee decreased in the following order: prop-1-ene > but-1-ene > 3-methylbut1-ene. Preferential formation of (R)-alkyloxiranes has been detected. The chiral hydroxyamide ligands mentioned above with a variety of structural differences were screened with an objective at gaining some insight into the influence of: (a) the size of the amide component, (b) the degree of branching of the alkyl substituents, (c) presence of an additional stereogenic centre, and (d) the type of chelate ring formed by the ligand with the metal, on the enantioselectivity of the reaction.

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Carla D. Nunes and Pedro D. Vaz Chart 14

56 pla

57 dmpla

58 hmbpa

59 hmppa

60 hbpa

61 AcPro

62 BzPro

Since then it has been established that when the steric bulk in the main chain of the ligand was increased depending on the type of amide ligand there was an increase or decrease in the ee. The chelate ring geometry formed between the ligand and the metal was also shown to affect enantioselectivity of oxirane formation, as this property increased in the following order: seven-membered chelate > six-membered chelate > five-membered chelate. It was also established that the addition of optically pure 1,2-alkanediol additives enhanced ees of the oxirane products. For instance, epoxidation of trans-but-2-ene with MoO(O2)2pla and one equivalent of (2S,3S)-butanediol yields the corresponding epoxide with 93% ee. It was suggested that a subsequent kinetic resolution of the oxirane products by a till then unknown Mo-diol catalyst would lead to this enantiomeric enrichment. It was only in 1999, a decade later, that Stirling and co-workers reported their work on the use of chiral phosphinoylalcohol complexes of MoVI for the epoxidation of a number of olefins [216]. The complexes were obtained from the reaction of chiral phosphinoyl alcohols with MoO(O2)2 being suggested that coordination to the Mo center would occur through the P=O group, according to Chart 15. Chart 15

63

64

65

66

67

68

69

70

Recent Evolution of Oxidation Catalysis by Mo Complexes

69

The resulting complexes were screened in the epoxidation of both terminal and disubstituted olefins under both stoichiometric and catalytic conditions. The ees determined were in the 239% range (see Table 7, for some selected results). In the case of complex MoO(O2)270 epoxidation of hept-1-ene was carried out under both stoichiometric and catalytic conditions, using tbhp as terminal oxidant (Table 7, entries 7 and 8). In the former, it was raised that the mechanism most likely involves a direct attack of the olefin on one of the peroxo oxygen atoms [217]. Table 7. Epoxidation of hept-1-ene with MoO(O2)2L (L = P ligands in Chart 15) complexes and tbhp, under stoichiometric and catalytic conditions [216].
Ligand 64 65 66 67 68 69 70 70
a b

Conversiona / % 72 55 77 39 47 80 35 >70b

ee / % <2 0 <2 9 23 8 3 3

All reactions carried out under stoichiometric conditions (olefin : catalyst ratio of 10); Carried out under catalytic conditions (olefin : catalyst ratio of 200).

Although ees were very low, ca. 3% in both cases, the catalytic reaction outperformed most probably based on a different mechanism. Such mechanistic proposal had been previously suggested by Thiel [218,219]. The authors ruled out a mechanism of coordination of olefin to the metal center and opted for a situation in which two or more mechanisms were at work for which predominance of a single one being determined by the actual reaction conditions used. Based on a model (Chart 15, 63) it was also suggested that both O1 and O3 should be the transferred oxygen atoms as they are proximal to the chiral ligand, and asserted that despite the environment near O1 being different to that around O2 it is the rate of oxygen transfer that dictates the degree of enantioselectivity. Chart 16

71

72

Shortly after, Yoon and co-workers reported the preparation of MoVI-oxodiperoxo complexes based on (R)-piperidinylphenylacetamide 71 and (R)-piperidinylmandelamide 72

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Carla D. Nunes and Pedro D. Vaz

(Chart 16), and the first report of a catalytic epoxidation using this type of complex when both trans- and cis--methylstyrene were transformed to the corresponding epoxides [221]. Under the conditions used, and despite moderate yields, they were able to achieve moderate to good ees (2681%). The highest ee (81%) was obtained using trans--methylstyrene and complex 72. Later on in 2004, the preparation of the first chiral MoVI-oxodiperoxo complexes 73, 74 containing N/O ligands (Chart 17) were reported [143]. Chart 17

73

74

75

Table 8. Aromatic olefin epoxidation using 2-(1-pyrazole)pyridineoxodiperoxo MoVI chiral complex 75 and tbhp [222].
Olefin Conversion / % 31 86 28 37 44 49
n.d. = not determined, due to small yield of epoxide.

ee / % 2 1 0 5 6 n.d.

Both have been tested in the catalytic epoxidation (2.5 mol% catalyst) of cyclooctene and (R)-limonene in the presence of tbhp. Epoxidation of the latter was found to be unselective and additionally ees were not reported. At the same time, a new report on the synthesis of 2(1-pyrazole)pyridineoxodiperoxo MoVI chiral complex 75 (Chart 17) has been presented, which was used in a series of stoichiometric and catalytic olefin epoxidations with tbhp [222].

Recent Evolution of Oxidation Catalysis by Mo Complexes

71

In the latter case the catalytic epoxidation reactions, led to almost no ee (Table 8). In further attempts, excess styrene was treated with the same complex being benzaldehyde the sole product. This arises from epoxide decomposition due to oxidative cleavage under the reaction conditions used. Under the same conditions an excess of cyclohexene originated the corresponding epoxide along with cyclohexane-1,2-diol. This result led to the suggestion that catalytic olefin epoxidations could be based on two possible mechanisms at work: (i) that suggested by Thiel [218,219] involving oxygen transfer from the coordinated alkylperoxide addition and (ii) direct transfer of an oxygen to the olefin from one of the peroxo oxygen atoms of complex 75 [217]. In a sequel of the work [221], it was proposed that the mechanism would involve a coordinated alkylperoxide to the MoVI species, being this the active catalytic species [89]. Continuation of this subject [223], led to the study of series of chiral pyridines and pyrazoles, Chart 18, to form chiral alkyl hydroperoxide MoVI species in situ. As in previous reports, no enantioselectivity was observed in these reactions. Chart 18

76

77

78

79

In face of these and previous results, lack of enantioselectivity was put down to the following reasons: (1) presence of other chiral or achiral MoVI peroxy or peroxo species in solution competing with the principal oxoperoxy complex (multiple catalytically active species, which had been alluded to by Mitchell and Finney [224]); (2) labile nature of the peroxy ligand, particularly at high temperature during reaction, leading to generation of a number of competing diastereomeric transition states; (3) fast on/off exchange of ligands or part of ligands from the coordination sphere of MoVI peroxy complex. In fact, weak coordination has been recently proposed by Barlan and co-workers [225] to explain the lack of success using such epoxidizing system. This as well as exchange between coordinated alkyl hydroperoxides and alkoxides has recently been demonstrated on the basis of some DFT calculations [89]. Fast on/off exchange of ligands or part of ligands mentioned above from the coordination sphere of MoVI peroxy complex could have been the reason for lack of enantioselectivity in the last system discussed above [223]. This is most probably the key reason why only poor to fair enantioselectivities are obtained using oxoperoxo MoVI catalysts in olefin epoxidation.

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Carla D. Nunes and Pedro D. Vaz Table 9. Catalytic oxidation of olefins, alcohols, amines and sulfides using [MoO(O2)2(hpeoh)] [hpeoh = o-C6H4(OH)C(CH3)=NOH] (80), H2O2 and NaHCO3 in acetonitrile [230,231].
Substrate Product Temp. / K 298 Yield 91 96 98

90 70 90 87 97 313 91 97 353 81 98 63 89 60 88
96

96 96 78

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73

Over the last decade the Thiel group have conducted exhaustive studies on this catalytic reaction using 2-(pyrazol-3-yl)pyridinyloxodiperoxo MoVI complexes in both homogenous [218,219] and in heterogeneous phases later on [226228]. One combined study by this group [229] using both NMR experiments and DFT calculations, evidenced that ligand dissociation appeared to occur. Activation energies required (89110 kJmol1 in Thiels study) for ligand dissociation are provided by high temperatures required for successful epoxidation reactions. Such findings by Thiel and co-workers identified the principle reason why the asymmetric induction is so weak in such systems. Another important reason in the case of the oxodiperoxo MoVI complexes, is that the two electrophilic oxygen atoms are disposable to the incoming nucleophilic olefin. In addition, and due to the symmetric disposition of the two peroxo groups both enantiomers of the oxirane product should be obtained. Noticeably, oxygen to olefin transfer rates are different, depending on the system, but not enough to provide high enantioselectivities. Most probably, ligand dissociation from metal is the reason why rates of oxygen transfer are not significantly different. This point had previously been mentioned by Ross [216]. To circumvent this problem and develop catalysts that can reach high eneantioselective products one must realize that: (1) stronger non-dissociating chiral ligands are to be used; (2) the rate difference of the oxygen transfer from the two peroxo ligands must be accentuated; (3) additional efforts must be spent developing and testing chiral monoperoxo complexes holding strongly coordinating chiral ligands. More recently some more works have been published concerning oxidation of a variety of substrates using MoO(O2)2 complexes with pyridine and phenol oxime derivatives as ligands [230,231] and using H2O2 as oxidant and in the presence or absence of NaHCO3 as a co-catalyst. Results are summarized in Table 9, showing that conversions are quite high across substrates. Despite no ees have been reported it should be mentioned that in most cases selectivity is quite high. In addition and according to the authors, use of NaHCO3 seems to lead to different regioselectivity as evidenced by the oxidation of cinammyl alcohol which in its presence yields the epoxide as the sole product with 70% (Table 9, entry 5). When in the absence of NaHCO3 the same substrate under similar reaction conditions leads to cinnamylaldehyde in 89% yield (Table 9, entry 14), at a different temperature though. In both cases selectivity is 100% to the respective oxidation product. At the same time the Gallindo group [232], reported the epoxidation of cyclooctene in the presence of MoO(O2)2(4-MepyO)2 and using urea hydrogen peroxide complex (uhp) as oxygen source. An additional novelty was the use of a room temperature ionic liquid (RTIL) as reaction medium, particularly [C4mim][PF6] (1-butyl-3-methyl-1H-imidazol-3-ium hexafluorophosphate). Substrate conversion was found to reach a maximum of 89%, giving the corresponding epoxide with 83% yield. Still, these works although recent, stress the demand for more robust catalysts based on the point raised above in this chapter.

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Carla D. Nunes and Pedro D. Vaz

OXIDATIONS WITH [MOII(CO)2,3]2+ COMPLEXES AS PRE-CATALYSTS

Since the starting of the XXIst century, an increasing awareness on the use of precatalysts has been observed [33,38,233]. Such pre-catalysts are simply organometallic MoII carbonyl complexes which can be oxidized to the dioxo MoVI homologues. The very first example of a complex of this family was CpMoO2Cl reported in 1963 by Cousins and Green [234], obtained by oxidation of [CpMo(CO)3]2 and CpMo(CO)2(-C3H5). The dioxo complex mentioned above was synthesized in very low yields and surprisingly as the only isolable product from air oxidation of CpMo(CO)2(-C3H5) in the presence of HCl. From the recent evolution on the use of the latter carbonyl complexes it was found that these undergo oxidative decarbonylation to yield the corresponding organometallic MoVI dioxo congeners [235]. In that work the group of Gonalves showed possible the direct use of the CpMo(CO)3Cl carbonyl complex as a precatalyst for olefin oxidation using tbhp. It was also found that under the catalytic reaction conditions the tricarbonyl complex rapidly yields CpMoO2Cl which was reported to be the active species. Comparison of the catalytic performance with the use of the dioxo complex was found to produce similar results, both complexes reaching identical performance in cyclooctene epoxidation (complete substrate conversion with 100% selectivity to the epoxide after 6h). After those results have been reported, other works concerning the direct use of MoII carbonyl complexes as precatalysts, which are then oxidized in situ to yield the active species, followed. The set of catalytic systems tested since then is resumed in Table 10, accounting not only for the catalytic system used (precatalyst complex, oxidant and olefin) but also to its achievements. From data shown in Table 10 concerning cyclooctene epoxidation it should be mentioned that the work of Abrantes et al. [236] has used microwave radiation as a convenient method to perform the heating of the catalytic tests, as compared with conventional oil bath heating. Such approach has proved quite adequate as kinetics as well as conversion and yields are superior (Table 10, entries 2, 3 and 4, 5) for both the case of cyclooctene and limonene. In the case of primary alcohol oxidation yielding the corresponding aldehydes, excellent selectivities have also been reached. The results show that the Mo acetylide complex is very efficient catalyst for accomplishing such transformation [238], with maximum selectivity. Such system can very well tolerate electron-rich as well as electron-withdrawing substituents on aromatic ring. According to the authors, the water soluble nature of the catalytically active species, an oxo-peroxo Mo acetylide moiety and formation of organic phase of the product (aldehyde) have enabled very easy and efficient recycle of this homogeneous catalyst even up to five recycles without appreciable loss in conversion and aldehyde selectivity. More recently, and derived from the above mentioned Cp complexes, a series of complexes containing the Cp ligand with ansa bridges were also prepared and its catalytic performance reported. The original idea behind the synthesis of ansa-bridged compounds was to hinder Cp-loss after possible intermediate ring slippage. Ansa-bridged derivatives have been used to introduce chirality in the system by transforming the bridging C atoms into chiral centers. However, it turned out that ansa-bridges with only two carbon atoms in the bridge are not sufficiently stable, due to considerable ring strains under oxidative conditions [239]. Introducing chirality with a chiral substituent on the Cp-ring has also been attempted.

Recent Evolution of Oxidation Catalysis by Mo Complexes Table 10. Catalytic performance in olefin or primary alcohol oxidation using CpMo(CO)3X (X = Cl, CH3, Aryl ; Cp = Cp or Cp derivatives) complexes.
Complex Cp ; X Cp ; Cl 81 Oxidant tbhp Substrate Conversion 100 Selectivity 100 Ref. 235

75

Cp ; CH3 82

tbhp

94 (mw) 86

100 100 100 100 84

236

tbhp

91 (mw) 80

CpCOProBz ; CH3 83

tbhp

100

237

Cp-CCPh ; CCPh 84

H2O2

86

92

238

87

87

90

90

60

88

65

91

72

82

70

75

82

88

82

85

In the case of the use of N-heterocyclic carbene Cp derivative ligands, reported by Royos group [240] these were not as active (Table 11, last 3 entries) as the regular ansa-Cp

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Carla D. Nunes and Pedro D. Vaz

derivatives reported by Khn. In fact only one of the catalysts, holding the most bulkier Cp derivative showed a high activity towards cyclooctene epoxidation (Tabel 11, last entry). Table 11. Catalytic activity of ansa-CpMo(CO)2X (X = CO, I) in cyclooctene epoxidation.
Complex Yield Ref.

100 85 100 86

239

100 87

100 88

100 89

25 90

25 91

240

11

92

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77

91

93

Table 12. Catalytic activity of Mo(3-C3H5)X(CO)2L complexes in olefin epoxidation.

X Cl L CH3CN 94 Conversion / % 100 Ref. 241

N
95

95

241

88 96

241

100 97 99 98 100 99 Br CH3CN 100 100

241

242

243 241

100 101 99 102 64 103 45 104

241

242

244

244

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Carla D. Nunes and Pedro D. Vaz

80 105 33 106 64 107

245

245

246

In a different though parallel perspective, related catalytic systems using Mo(3C3H5)X(CO)2Ln (X = Cl, Br; Ln = mono or bidentate lewis base ligands) complexes have also been reported in recent years [241-246]. These works screened over quite some ligands, as evidenced in Table 12. Table 13. Catalytic activity of MoX2(CO)3L complexes in cyclooctene epoxidation.
X Br L CH3CN 108 Conversion / % 100 88 109 I CH3CN 110 81 63 111 247 247 Ref. 247 247

13 112

248

9 113

248

In fact it was found that catalytic activities were very dependent on the type of ligand used. Generally the ligands used relied on N,N bidentate ligands but in some cases it was found that when the ligands hold NH moieties deactivation does occur with conversions dropping down drastically (Table 12). More recently the use of carbene ligands in these allyl complexes has been reported showing good activities using H2O2 as oxygen source [243]. Epoxide yields were found to reach almost 100 % in many cases stressing the usefulness of such association. In fact such system (Tabel 12, entry 6) was found to be more active in cyclooctene epoxidation than the Cp counterparts (Table 11, 3 last entries).

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The use of related though different complexes from the MoX2(CO)3Ln (X = Br, I; Ln = mono or bidentate Lewis base ligands) heptacoordinate halocarbonyl family were also reported to possess catalytic activity in olefin epoxidation [247,248]. These complexes were developed in pioneering work by Baker for catalytic applications other than oxidation [249]. However, such systems were found to have quite high performances, Table 13, although it was found very recently that such systems suffer from the same ligand dependency which leads in some cases to deactivation. This is true when ligands hold NH moieties as already discussed a few lines above in this chapter [248]. In fact a survey on such ligands has permitted to establish an important ligand structurecatalytic activity relationship stressing the importance of the inexistence of deactivating NH moieties. This is shown in Figure 1. Attempts at understanding the mechanistic aspects of the transformation of the MoII carbonyl precursors into their MoVI dioxo congeners by means of an oxidative decarbonylation process have been the aim of quite some works. To this concern the chemistry of CpMoO2X and CpMo(CO)3X (X = Cl, Br, CH3) complexes has by far been the mostly studied across years as compared to the other mentioned carbonyl systems based on the Mo(3-C3H5)X(CO)2Ln or the MoX2(CO)3Ln (X = Cl, Br, I; Ln = mono or bidentate Lewis base ligands) halocarbonyl families reported above in this chapter. The first records dealt mainly with the development of proper methods of preparing the CpMoO2Cl complex from CpMo(CO)3Cl. Cousins and Green were the first authors to rationalize several synthetic methods for obtaining the CpMoO2X (X = Cl, Br) complexes (Chart 19) [250-252]. One of the methods consists in the irradiation of [CpMo(CO)3]2 in a solution of the haloform of interest (either chloro- or bromoform) and with O2, which affords the desired CpMoO2X (X = Cl, Br) complexes. Chart 19

81, 114

Both derivatives showed to be stable under inert N2 atmosphere, decomposing slowly under air and rapidly in solution. As in the first method, yields were also reported to be very low. This is the result of relatively unspecific synthetic pathways, leading also to other species such as mono oxo and dimeric complexes. These difficulties have surely been the cause for a gap between these early works and the next publications dealing with Cp dioxo molybdenum complexes which have emerged in the late 1980s [253,254]. The synthesis of Cp*MoO2Cl [Cp* = 5-C5(CH3)5] was obtained by oxidation of the dimeric carbonyl complex [Cp*Mo(CO)2]2 with O2 in chloroform and subsequent treatment of this intermediary with PCl5, yielding a -oxo bridged dimer, Scheme 5. This complex exhibited good thermal stability being also able to be manipulated in dry air, along with both ease of preparation and separation from other reaction products. Such synthetic procedure was a

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Carla D. Nunes and Pedro D. Vaz

substantial improvement in comparison to its Cp counterpart previously described by Green [234]. Several other methods have emerged in the following years for the synthesis of CpMoO2Cl (Cp = Cp, Cp*) and will be briefly addressed in the following lines. The several synthetic pathways developed for Cp*MoO2Cl (58) are also summarized in Scheme 5. This scheme stresses the different synthetic routes as well as its efficiencies in both terms of reaction time and product yield. In particular irradiation of Cp*Mo(CO)3Cl in toluene under an O2 purge and UV radiation for 2 h ,yields Cp*MoO2Cl [255]. In a parallel pathway the chloride carbonyl Cp*MoCl4 precursor complex discarded the need to conduct the reaction in chlorinated solvents.

Figure 1. Ligand structurecatalytic activity relationship from MoII based complexes for cyclooctene conversion. The numbers adjacent to ligand names refer to the respective reference.

Recent Evolution of Oxidation Catalysis by Mo Complexes

81

Scheme 5. Synthetic pathways for preparation of Cp*MoO2Cl (see text for details).

This complex was found to yield Cp*MoO2Cl by reaction with aqueous NaOH in the presence or absence of air [256]. Reaction times lower than 30 min, in the absence of air (N2) led to the formation of Cp*MoOCl2. On the other hand in the presence of air Cp*MoO2Cl is obtained. In this context the former complex seems as the logical intermediate to the dioxo complex. When reaction times longer than 30 min are used the formation of the -bridged oxo dimer [Cp*MoO2]2O is obtained. Such dimeric complex is likely formed via hydrolysis of Cp*MoO2Cl generating Cp*MoO2OH, which then undergoes condensation by loss of H2O. Despite this, the base used in these reactions is not innocent on the products obtained. In fact, when Cp*MoCl4 reacts with t-BuNH2 in the presence of water and air the [Cp*MoO3] anionic trioxo complex is formed being isolated as its [t-BuNH3]+ salt. Subsequent treatment of this complex with gaseous HCl gives Cp*MoO2Cl neatly. A few other methods have since then been reported [257,258], including treatment of [Cp*Mo(CO)2]2 with 30% hydrogen peroxide and HCl [258]. A major improvement on the synthesis of (5-C5R5)MoO2Cl (R = H, CH3, CH2Ph (Bn)) complexes from their corresponding and readily available (5-C5R5)Mo(CO)3Cl precursors was reported in 2003 [259]. The desired complexes could be obtained in yields reaching 75% by stirring a CH2Cl2 solution of the carbonyl precursors with excess of tbhp for ca. 2 h (Scheme 5). Dimethyldioxirane was found to be unable to oxidatively decarbonylate to (5C5R5)MoO2Cl in contrast to other systems [260]. Comparison with previously described synthetic routes, evidences the latter method of oxidative decarbonylation of (5C5R5)Mo(CO)3Cl provides a more general route comprising different derivatives of the Cp

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Carla D. Nunes and Pedro D. Vaz

ring. All three compounds originally described in that work can be handled in air for brief periods of time, but are rather moisture sensitive in solution. (5-C5Bn5)MoO2Cl is significantly more stable than its Cp and Cp* congeners, probably due to steric bulk effect of the Cp ligand. Similarly, a striking increase in stability, even in comparison to Cp*MoO2Cl had also been previously observed with the compound (5-C5Ph4R)MoO2Br (R = 2,5dimethoxyphenyl) [261]. At the same time Poli et al. reported speciation studies of Mo complexes containing the Cp* ligand over the entire pH range in an essentially pure aqueous environment by several methods, including stopped-flow kinetic analysis, on-line electrochemical flow-cell and electrospray mass spectroscopy [262264]. Such studies revealed the existence and stability of Cp*MoO2OH and [Cp*MoO2]+ complexes as a function of pH. The authors also concluded that the inertness of the Cp*Mo bond, resists hydrolysis down to pH zero. As a consequence this blocks three coordination positions, rendering the Cp*MoVI species unable to form extended oligonuclear aggregates. Although many efforts have been devoted to the preparation of the above mentioned (5C5R5)MoO2X [R = H, CH3, CH2Ph (Bn); X = Cl, Br, CH3] many other studies dealt with the catalytic applications of these and other complexes not only in olefin epoxidation (the majority of examples) but also in the oxidation of other substrates. The catalytic activity of dioxomolybdenum complexes containing cyclopentadienyl ligands was until recently solely examined for Cp*MoO2Cl by Bergman and Trost [255]. This complex was shown to act as active catalyst for the epoxidation of several olefins (such as cyclooctene, geraniol, 1,2,4,5-tetramethylcyclohexa-1,4-diene), as long as they do not include any electron-withdrawing groups. Apart from tbhp, other alkyl hydroperoxides such as cumyl hydroperoxide and n-hexylhydroperoxide could be used as oxidants. However, when H2O2 and thp were used no catalytic reaction occurred and the oxo-peroxo complex Cp*Mo(O2)OCl was formed. When in the absence of olefins, the authors found that tbhp would react with Cp*MoO2Cl yielding also the Cp*Mo(O2)OCl complex. Catalytic reactions performed with the isolated Cp*Mo(O2)OCl did not lead to any oxidation products. Consequently this species was considered to be an unwanted side product, and being concluded that the active species cannot be a 2-coordinated peroxo complex. These results were later supported by Roesky et al. who analyzed the X-ray crystal structure of Cp*Mo(O2)OCl and also described this compound as being not active as olefin epoxidation catalyst in the presence of excess tbhp, thus confirming previous findings [265]. Apart from formation of Cp*Mo(O2)OCl, the catalyst precursor Cp*MoO2Cl seems to maintain its integrity during the catalytic reaction, showing no observable oxidation of the Cp* ligand as evidenced by 1H NMR data [255]. The effect of the alkyl peroxide used on the relative rate of the epoxidation reaction was investigated and the obtained rates were consistent with formation of an intermediate species in which the alkyl group of the peroxide moiety is intact. In this way, relative rates depend on structure of the alkyl group of peroxide and catalyst loads of 25% were used depending on substrate and reaction temperatures spanned from r.t. (room temperature) to 333 K. The study of the catalytic properties of the (5-C5R5)MoO2Cl [R = H, CH3 (Me), CH2Ph (Bn)] complexes as catalysts for the epoxidation of cyclooctene, styrene and 1-octene has been extended [259]. Reactions were conducted at 328 K using catalyst loadings of 1 mol%, with tbhp as oxidant. Influence of ring substituents on catalyst activity was studied in detail

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for cyclooctene. Both (5-C5H5)MoO2Cl and (5-C5Bn5)MoO2Cl complexes show good activity, reaching 100% conversion after 4 h reaction time. However, in a second and third catalytic run (by addition of new substrate) the complex (5-C5Bn5)MoO2Cl maintains most of its activity, while that of the Cp derivative declines strongly due to catalyst decomposition. Similarly (5-C5Me5)MoO2Cl reaches only about 60% of the activity of the other derivatives in the first run and shares the same decomposition problems observed for (5-C5H5)MoO2Cl under catalytic conditions. Due to its high stability and activity, catalytic runs were performed using a catalyst load of (5-C5Bn5)MoO2Cl as low as 0.1% under the same reaction conditions. TOFs (turnover frequencies) of 4000 h-1 were achieved, and lowering the Mo compound load to 0.01%, values of 20000 h-1 were reached. However, at these low catalyst loadings the residual amount of water present in the system gains increasing influence on the catalytic performance after some time and consequently, the catalytic activities decrease considerably after 1 h reaction time for the lowest catalyst amounts applied [259]. According to the authors, the high activity of this complex, despite its higher steric bulk, was ascribed both to its higher stability towards moisture and the lower electronic density at the Mo center, in comparison to the derivatives (5-C5Me5)MoO2Cl and (5-C5H5)MoO2Cl, due to a weaker Mo-ring bond, as reflected in 95Mo NMR and vibrational spectroscopy. Epoxidation of styrene and 1-octene was also successful using (5-C5R5)MoO2Cl [R = H, CH3, CH2Ph (Bn)], the best results being again obtained with complex containing the bulkier ligand. Ring opening of the styrene epoxide to the diol is not significant under the conditions applied; 1octene, being an unactivated, unfunctionalized olefin reacts significantly slower than the other substrates. When Gonalves first reported on the use of CpMo(CO)3Cl as a precatalyst that could be used directly for catalysis which would undergo oxidative decarbonylation in situ it was mentioned that CpMoO2Cl was the active catalyst [235]. Such statements were published based on several spectroscopic observations in which the authors proved that the oxidative decarbonylation process proceeds via the release of CO rather than CO2. This means that in the process CO ligands are not involved in any oxidation process. It should also be mentioned, however, that in a recent work an in-depth study based on kinetic data has been accomplished by the Colbran group [266]. According to the authors and, given the marked dependence of catalytic efficiency on the cyclopentadienyl substituent, no (5-C5Ar5)MoO2Cl (Ar = aryl group) complex had been screened for epoxidation catalysis. That study was motivated by the fact that the same authors had in a previous report demonstrated that (5-C5Ar5)MoO2X complexes may exhibit exceptional stability, such as the [(5-C5Ph4R)MoO2Br] (R = 2,5-dimethoxyphenyl) complex already mentioned previously in this chapter [261]. Using this latter mentioned complex it was found that the epoxidation mechanism must involve, most probably, three species, according to Scheme 6. According to the model, the initial [(5-C5Ph4R)MoO2Br] (R = 2,5-dimethoxyphenyl) complex leads to a species A which is catalytically active, though it transforms into a transient species B. This latter species is predicted to be inactive, though it converts into species C which will be the active species. By the end of the catalysis run, species C will be the only Mo-containing species present. Based on 1H NMR data, species C is formed by loss of the cyclopentadienyl moiety. According to the kinetic model, Scheme 6, species C is the active catalyst that dominates the faster phase. Recharging the catalytic system with

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cyclooctene and tbhp at this point leads to immediate catalysis consistent with species C remaining present and active at the end of the run.

Scheme 6. Mechanistic model proposed according to kinetic data (k1 k2 > 5 105 s1 ; 35kA kC = 7.3 (0.3) 105 s1 ; kB 0 s1) [266].

Two insights followed from this information. First, (perarylcyclopentadienyl) MoVI dioxo species do catalyze alkene epoxidation. Second, the Cp ligand is lost from Mo as the catalysis proceeds, leading to the in situ generation of a much more efficient catalyst. The latter finding evidenced that loss of the Cp ligand from a CpMoO2X catalyst, even if only slight, should always be considered in alkene epoxidation catalyzes, because the thus-formed Mo species C may be the most active catalyst. Although, Polis group has revealed a varied and rich aqueous chemistry in its speciation work under varying pH conditions as already mentioned in this chapter [264], indeed they have also showed that loss of the Cp* ligand may occur under certain conditions [267]. In this way presumption of complete stability for an alkylcyclopentadienyl MoVI oxo catalyst during epoxidation catalysis may be unfounded. Difficulties that have been previously encountered in reconciling kinetic data [33,94,95,101,259,268,269] with trends in parameters such as the steric bulk of the ring substituents as well as either the tendency or ability of the Cp to undergo catalysis-facilitating ring slippage was found to have its cause in loss of the alkylcyclopentadienyl ligand, even in trace amount, to afford a more active MoVI (per)oxo species. Most recently the mechanism of olefin epoxidation using CpMo(CO)3(CH3) has been clarified based on both kinetic data and DFT calculations [270,271]. According to the authors this complex has quite some differences as compared to its homologue CpMo(CO)3Cl. It was found for the former that the mechanism proceeds through a combined cycle involving two possible pathways, Scheme 7. Those works have finally shed some light on what was happens behind the scenes concerning such catalysts with Cp ligands. Of course it is now hoped that work is to be carried out to reveal how other related systems behave, either Mo(3-C3H5)X(CO)2Ln or MoX2(CO)3Ln (X = Cl, Br, I; Ln = mono or bidentate Lewis base ligands) halocarbonyl families which are also active players in such chemistry.

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Scheme 7. Overall mechanism for the oxidation of CpMo(CO)3(CH3) by tbhp and the epoxidation activities of the resulting oxidated complexes CpMoO2(CH3) and CpMoO(O2)(CH3) [270,271].

CONCLUSION
The present chapter aimed at an overview of recent literature concerning the role of Mo complexes in oxidation chemistry. Behind such interest one can find the usefulness of the industrial processes developed by ARCO and Halcon in the late 1960s [81,82]. The first complexes were developed about 50 years ago, although catalytic applications have only been exploited with more interest starting in the 80s decade of the XXth century, promoted by the mentioned industrial processes that raised the interest of the scientific community. Even though this represents a time span of 30 years to the present days it was only in the last 10-15 years or so that this chemistry has been properly explored. In fact many works devoted not only to develop catalytic applications, mainly in olefin epoxidation, but also to understand what happens behind the scenes during the catalytic cycle. Proof of this are many works which have reported on kinetics and DFT studies of the respective mechanisms, as discussed in this chapter. Although literature review was accomplished exhaustively, it certainly was not complete. Despite this, the view presented here shows the panorama of the present state of the art concerning Mo oxidation chemistry as given by three main topics discussed above, namely [MoVIO2]2+, [MoVIO(O2)]2+ and [MoII(CO)2,3]2+ (pre-)catalysts. After reading this chapter one may think that in a way all topics merge to a common end, MoVI-oxo core, and in fact they do. This is evidenced since the dioxo core may lead to oxo-peroxo and that the carbonyl precursors originate the dioxo and subsequently the oxo-peroxo (Scheme 7). Regardless of this, the fact is that imagination seems to be the limit as given by the increasing number of works dealing with several aspects. This ranges from preparing different (and more efficient) catalysts, testing new oxidants and reaction conditions or by performing oxidation reactions in substrates other than olefins. This latter aspect was clearly illustrated by some fine examples of sulfide oxidation, whose reactions in some cases were shown to be tuned so that

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asymmetric products could be obtained. Still, there is much work to do especially in the field of the organometallic derivatives whose chemistry is still in its early days. It is therefore aim of this chapter to provide the reader with a critical update on the most relevant literature that may help pointing the way ahead from this point onwards.

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In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 3

HOMOGENEOUS CATALYSTS BASED ON BIS(IMINO)PYRIDINE COMPLEXES OF IRON, COBALT, VANADIUM AND CHROMIUM: THE KINETIC PECULIARITIES OF ETHYLENE POLYMERIZATION
N.V. Semikolenova*, A.A. Barabanov, L.G. Echevskaya, M.A. Matsko and V.A. Zakharov
G.K. Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences 630090, Novosibirsk, Russian Federation

ABSTRACT
The family of highly active ethylene polymerization catalysts based on the complexes of transition metals with bis(imino)pyridine ligands has been intensively studied in the last ten years. In this study we summarize the known data and present new kinetic results on the ethylene polymerization over homogeneous catalysts based on Fe(II), Co(II), V(III) and Cr(III) bis(imino)pyridine complexes with close ligand framework (2,6-(2,4,6-R3LMeCln, where R= H, Me, i-Pr, t-Bu, L=(C6H3N=CMe)2C5H3N, M= Fe(II), Co(II), V(III), Cr(III), n=2,3). The effects of the activator nature (different samples of methylalumoxane (MAO), or aluminium trialkyls) and polymerization conditions on the activity of these complexes and the resulted PE structure (molecular weight, molecular weight distribution, content of methyl and vinyl groups) have been studied. For the first time the number of active centers and propagation rate constant for ethylene polymerization with Fe(II), Co(II), Cr(III) and V(III) bis(imino)pyridine complexes, activated with MAO and Al(i-Bu)3, have been determined using method of polymerization inhibition by radioactive carbon monoxide (14CO). The experimental data obtained in comparable conditions have shown that the catalytic properties of bis(imino)pyridine complexes ( polymerization activity, number of
* Corresponding author. Tel.:+7(383)326 95 51, E mail address: N.V.Semikolenova <nvsemiko@catalysis.ru>

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active centers and propagation rate constant, copolymerization reactivity, composition of optimal activator, formation of single site or multiple sites catalytic system, catalysts thermal stability and PE structure) are mainly determined by transition metal center of complex. The size of the substituents R in 2,6-positions of arene ring in the ligand L affects the number of active centers and molecular weight of PE as well.

Keywords: 2,6-bis bis(imino)pyridine complexes of iron (II), cobalt (II), chromium (III) and vanadium (III), ethylene polymerization, polyethylene, molecular weight distribution

1. INTRODUCTION
The olefin polymerization catalysts based on soluble well defined transition metal complexes, providing access to polymers with new or improved characteristics, is currently a subject of great academic and industrial interest. During the 80s large efforts were devoted to creation of the group 4 metallocene systems. The advances in the development of metallocene and their related half-sandwich (constrained geometry) catalysts [1] gained the insight into the nature of the activated species and the possibilities for controlling the polymeric products structure and resulted in a number of commercial processes for preparation of new polyolefinic materials. To expand the range of the produced polymers, considerable efforts have been devoted to the discovery of new families of catalysts based on the complexes of non-metallocene nature. An important advance in this direction was made by Brookhart and co-workers, who have shown that nickel and palladium complexes with bulky a-dimine ligands are capable of polymerizing ethylene to high molecular weight polymers [2]. This discovery has stimulated rapid development of new generation of post-metallocene catalysts. Advances in this field are broadly covered in a number of reviews [3-6]. At present, complexes of transition metals with polydentate nitrogen-containing ligands are considered as one of the most promising families of post-metallocene catalysts. It was reported by Brookhart [7,8] and Gibson [9,10] that 2,6-bis(imino)pyridine complexes of iron and cobalt (Scheme 1, RnLMCl2, where M=Fe(II) or Co(II), L= 2,6-bis(imino)pyridine ligand, Rn - the substituents in the arene ring of the ligand L ) when activated with methylaluminoxane (MAO) form extremely active homogeneous catalysts for ethylene polymerization to linear polyethylene (PE). This type of catalysts is easer to synthesize and they are more tolerant to polar groups than metallocenes. In the last ten years the catalysts based on bis(imino)pyridine complexes have attracted much academic and industrial interest and were intensively studied.

Scheme 1 The structure of iron and cobalt 2,6-bis(imino)pyridine complexes (M=Fe(II) or Co(II), R= Me, R1,R2,R3 = H, Me, Et, t-Bu, i-Pr)

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During further investigations it was found [11-15] that iron bis(imino)pyridine complexes can be activated with common aluminium trialkyls (AlMe3, AlEt3, Al(i-Bu)3, Al(n-Oct)3), that substantially simplifies the catalytic systems and broadens the possibilities of their use in the polymerization processes. Highly linear PE samples are obtained with iron and cobalt bis(imino)pyridine complexes. The values of molecular weight (Mw) and molecular weight distribution of the resulted PEs are governed by the substituents in phenyl rings of the ligand [5,7-10], giving the possibility to obtain polymers with different value of Mw from oligomers to high molecular weight PE. Later, it have been shown that vanadium(III) [16-18] and chromium(III) [19-21] complexes with bis(arylimino)pyridine ligands can be regarded as promising catalysts for ethylene polymerization. Commonly, in the literature the data on the catalytic properties of the systems based on bis(imino)pyridine complexes of various composition are discussed separately. Such an approach hinders the ascertainment of patterns in the catalytic properties of these systems since the catalytic activity and the molecular structure of the resulting PE are affected by the polymerization conditions (catalyst concentration, the nature and amount of the activator, polymerization temperature etc.). In this study we summarize the known data, including those obtained by ourselves [12, 22-35] and present new results on the polymerization properties of homogeneous catalysts based on Fe(II), Co(II), V(III) and Cr(III) bis(imino)pyridine complexes. A detailed study on the effect of the activator nature and the ligand composition on the catalytic behavior of bis(imino)pyridine complexes and the resulting PE structure has been undertaken. The experimental data have been obtained under comparable conditions allowing us to reveal the effect of the transition metal on the catalytic properties of the homogeneous catalysts based on bis(imino)pyridine complexes. For ethylene polymerization over Fe(II), Co(II), Cr(III) and V(III) bis(imino)pyridine complexes, activated with MAO and Al(i-Bu)3 the number of active centers and propagation rate constant have been determined using the method of polymerization inhibition by radioactive carbon monoxide (14CO). The experimental data obtained under comparable conditions have shown that the catalytic properties of bis(imino)pyridine complexes ( polymerization activity, number of active centers and propagation rate constant, copolymerization reactivity, composition of optimal activator, formation of single-site or multiple-sites catalytic system, catalysts thermal stability and PE structure) are mainly determined by transition metal center of complex. The size of the substituents R in 2,6 positions of the arene ring in the ligand L affects the number of active centers and molecular weight of PE as well.

2.1. CATALYSTS BASED ON RNLFECL2

Effect of Activator
The data on the activity of homogeneous catalytic systems composed of 2,6-Me2LFeCl2 with different activators and structure of the resulted PE are summarized in Table 1.

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Run

Activator

Yield Kg PE/ mol Fe bar 9100 11000 6800 12300 7600 12300 470

Maximum activity, Kg PE/ mol Fe bar min 500 330 430 300 250 320 20

3)

Mw, 103

Mw/ Mn

Content per 1000 3 = 2 0.8 1.0 0.7 0.6 1.2 -

4)

Content per PE molecule 3 1.2 1.0 1.5 1.4 1.1 = 2 0.9 1.2 0.5 0.6 0.9 -

1) 1) 2) 1) 2) 1) 1)

1 2 3 4 5 6 7

MAO MAO (50) MMAO AlMe3 Al(i-Bu)3 Al(n-Oct)3 Ph3C[B(C6F5)4] + Al(i-Bu)3

71 75 106 115 46 -

8.3 4.6 12.0 11.0 6.3 -

1 0.8 1.9 1.5 1.4 -

1)

Polymerization in toluene at 35 C, ethylene pressure 2 bar, for 30 min, [Fe] =1.4 10-5 mol/l, Al/Fe=500.
Polymerization in heptane, all other conditions as run 11)

2) 3) 4)

Calculated according to Figure 1 IRS data

The kinetic curves for correspondent polymerization runs are shown on Figure 1.
600 Activity, kg PE/mol Fe bar min
1

500 400 300 200 100 0 10 Time, min 20

5

4 6

30

Figure 1. Kinetic curves for ethylene polymerization over the catalysts composed of 2,6-Me2LFeCl2 and different activators: (1) MAO; (2) (50); (4) AlMe3 ; (5) Al(i-Bu)3 (6) Al(n-Oct)3.(Number on the curve corresponds to the number of the experiment in Table 1).

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All examined systems exhibited low thermal stability and virtually lost polymerization activity at temperatures above 50 C. At 35 C highly active catalytic systems providing high PE yield were formed upon activation of 2,6-Me2LFeCl2 with two different MAO samples (commercial MAO with AlMe3 content ~0.5 M and MAO sample with the reduced content of AlMe3 ( ~ 0.001 M of AlMe3, MAO(50)); MAO modified with Al(i-Bu)3 (commercial sample, MMAO) and aluminium trialkyls (AlMe3, Al(i-Bu)3 and Al(n-Oct)3 ) (Table 1). In contrast to metallocene catalysts, a borate activator was not effective for iron bis(imino)pyridine catalysits (Table 1, run 7). The examined catalysts exhibited high initial activity decreasing in the course of polymerization (Figure 1). The system stability and PE yield depend on the activator nature. The catalyst obtained upon activation of iron complex with commercial MAO exhibited very high initial activity, but the latter rapidly fell with the polymerization time (Figure 1, curve 1). The systems formed by 2,6-Me2LFeCl2 interaction with aluminium trialkyls (AlMe3, Al(n-Oct)3), provided higher PE yield (Table 1, runs 4, 6) than that obtained in presence of MAO and MMAO (Table 1, runs 1 and 3) due to the higher stability of these systems (Figure 1, curves 4, 6). The catalysts formed by interaction of iron complex with Al(i-Bu)3 and MMAO, soluble in aliphatics, show high initial activity in the polymerization in heptane medium (Table 1, runs 3 and 5). These systems were less stable than that prepared using MAO purified from AlMe3 (MAO(50)), AlMe3 and Al(n-Oct)3 (Figure 1), causing the reduced yield of PE. The obtained polyethylene samples were highly linear (about one -CH3 and vinyl terminal groups per one PE molecule) (Table 1). The values of molecular weight and polydispersity (Mw/Mn values) depend on the activator nature. Data in Table 1 and Figure 2 show that in the presence of MAO (50), PE with the lowest polydispersity was obtained (Mw/Mn=4.6, Table 1, run 2 , Figure 2, curve 2), whereas the Mw/Mn value of PE sample prepared using commercial MAO was noticeably higher (Mw/Mn=8.3, Table 1, run 1, Figure 2, curve 1).
1,0 0,8 d Wf/d log M 1 0,6 0,4 0,2 0,0 2 3 4 Log M 5 6 7 5 6 2

Figure 2. MWD of PE produced with homogeneous catalysts composed of 2,6-Me2LFeCl2 and different activators: (1) MAO; (2) (50); (5) Al(i-Bu)3 (6) Al(n-Oct)3.(Number on the curve corresponds to the number of the experiment in Table 1.) ( Wf= weight fraction, M=molecular weight.)

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Polymers prepared with the systems (2,6-Me2LFeCl2/Al(i-Bu)3) and (2,6Me2LFeCl2/AlMe3) were characterized by the highest Mw values (Table 1, runs 4, 5), whereas using Al(n-Oct)3 as activator the PE sample with the lowest molecular weight was obtained (Table 1, run 6). Broad molecular weight distribution (MWD) of the polymers formed in the presence of the catalysts composed of 2,6-Me2LFeCl2 and different activators indicate that a set of different active sites is formed in these catalytic systems, so the catalysts of this type should be regarded as multiple-site catalysts.

Effect of the Ligand Composition

Changes in the ligand environments of iron bis(imino)pyridine complexes results in changes in catalysts productivity and polymer molecular weight [5,7-10]. As it was shown in [10], in presence of MAO as activator, ketimine catalysts ( R= CH3-, Scheme1) are more productive than their aldimine analoges (R = H-, Scheme1). Modification of the aryl ring attached to the imino nitrogen atoms has the pronounced effect on the catalysts activity and the molecular weight of the produced PE [5, 7-10]. The data on the catalytic behavior of iron bis(imino)pyridine complexes Rn-LFeCl2 bearing different substituents in 2,6 position in the aryl ring of the ligand are collected in Table 2 and Fig. 3. Table 2. Effect of the substituents R on the activity of Rn-LFeCl2/MAO catalysts and molecular weight characteristics of the PE produced.
Run 1* 2 3 4 Rn 2-Me 2,6-Me2 2,6-i-Pr2 2,6-Cl2 Yield Kg PE/ mol Fe bar 12650 9100 6650 5800
3)

Maximum activity, 770 500 980 1100

Kg PE/ mol Fe bar min

Mw, 10-3 71 220 15

Mw/Mn 8.3 20.0 2.9

-5

Polymerization in toluene at 35 C, ethylene pressure 2 bar, for 30 min, [Fe] =1.4 10 MAO/Fe=500. * Only oligomers were obtained.

mol/l,

The studied catalysts showed high initial activity that fell with the polymerization time. In accordance with the previously obtained results [7,9,10], complexes with a single orthosubstituent on each aryl ring are highly active in oligomerization of ethylene to linear olefines ( Table 2, run 1). The catalysts based on iron complexes with a substituent at both ortho positions of the aryl ring in presence of MAO as activator show high activities for ethylene polymerization, producing strictly linear high-molecular weight polymer. The molecular weight of the product depends on the size of the alkyl substiuents in 2,6-position of the aryl rings ( R1, and R2, Scheme 1): with the increase of steric bulk of the substiuents the Mw values of the produced PE increase. The yield of PE decreases with the increase the substituents R1 and R2 steric bulk because of lower stability of the catalysts formed (Table 2, runs 2, 3, Fig 3).

Homogeneous Catalysts Based on Bis(imino)pyridine Complexes

4

103

0,8 d Wf/ d log[M]

0,4 3

0,0 2 3 4 Log M 5 6 7

Figure 3. MWD of PE produced with homogeneous catalysts 2,6-R2LFeCl2/MAO: R= Me (2), i-Pr (3), Cl (4) (Number on the curve corresponds to the number of the experiment in Table 2). ( Wf= weight fraction, M=molecular weight).

Catalytic system based on the iron complex bearing electron-attracting halogen substiuents [36] (2,6-Cl2LFeCl2, Table 2, run 4) was found to be less stable, than those obtained using alkyl-substituted complexes. Though the catalyst (2,6-Cl2LFeCl2/MAO) exhibited the highest initial activity, the PE yield was lower than that obtained with the complex 2,6-Me2LFeCl2. Linear PE produced with (2,6-Cl2LFeCl2 /MAO) catalyst was characterized with the lowest Mw and Mw/Mn values (Table 2, run 4 and Fig 3, curve 4). It should be mentioned, that introduction of a halogen substituent into the p-position of the aryl ring results in an increase of the catalysts activity and a decrease in PE Mw value as well [37]. The obtained results indicate, that besides steric effects, electronic properties of the substituents in the ligand of iron bis(imino)pyridine complexes have the pronounced influence upon their polymerization properties.

Characterization of the Active Species

The active intermediates of the catalysts based on iron bis(imino)pyridine complexes with different activators (MAO, AlMe3, Al(i-Bu)3, Al(n-Oct)3) have been studied by 1H , 2H NMR and EPR spectroscopy [12, 22-28, 38 ]. The authors of [38] reported that upon interaction of 2,6-Me2LFe(II)Cl2 with the excess of MAO, the intermediates containing iron in the +3 oxidation state might be formed (however, the question of how iron(II) catalyst precursors could afford iron(III) catalysts in the presence of such reducing agents as AlMe3 and MAO was not considered). Later on, by a comparative study of 2,6-Me2LFeCl2 /MAO and 2,6-Me2LFeCl3 /MAO catalysts, it was shown that the close precursors of the active centers in both catalysts are ferrous complexes containing iron in +2 oxidation state [24].

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The structure of the intermediates was determined from 1H and 2H NMR spectra. It has been reported that in conditions approaching to real polymerization, neutral heterobinuclear complexes of the type [LMe Fe(II)Cl(-R)2AlR2] or [LMe Fe(II)R(-R)2AlR2] dominate in the reaction solution in 2,6-Me2LFeCl2+AlR3 systems, whereas in 2,6-Me2LFeCl2 /MAO systems the ion pairs [LMeFe(II)(-Me)(-Cl)AlMe2]+[Me-MAO]- (at Al/Fe< 200) and [LMe Fe(II)(Me)2AlMe2]+[Me-MAO]- (at Al/Fe> 500) were the predominant species [24-27]. Activation of 2,6-i-Pr2LFeCl2 with MAO and aluminium trialkyls ( AlMe3, Al(i-Bu)3) has been studied in more details using 1H and EPR spectroscopy [28]. It was found that interaction of 2,6-i-Pr2LFe(II)Cl2 with aluminium trialkyls results in one-electron reduction of the former with formation of heterobinuclear complex of the type [LiPr(-)Fe(+)(-Me)2AlMe)2] or [LiPr(-)Fe(+)(-i-Bu)(-X)Al(i-Bu)2] (X = i-Bu or Cl), depending on the activator used (either AlMe3 or Al(i-Bu)3). The observed intermediates were relatively unstable and decayed within minutes at room temperature. At the same time, formation of new EPR active species was observed: (1) LiPrAlMe2 having signal at g = 2.003 and (2) another species with a signal at g = 2.08, presumably of the type LFeI-Alk where the modified ligand L has a singlet ground spin state and iron (I) is low-spin (S = 1/2). When AlMe3-free methylalumoxane (MAO (50)) was used as the activator, ion pairs of the type [LFeII(-Me)2AlMe2]+[MeMAO] are formed. These ion-pair intermediates are more stable and persist in solution for several hours.

Data on the Number of Active Centers and Propagation Rate Constants

The data on the number of active centers (Cp) and rate constants of propagation reactions (kP) at olefin polymerization with homogeneous catalysts are of great importance for analysis of the kinetic peculiarities of the reaction and elucidation of factors, determining the catalysts activity. Polymerization inhibition by 14CO is a well known method for the determination of the active metal-carbon bonds in the catalytic systems of different types. This method is based on 14CO insertion into the metal-polymer bond, thus causing termination of the polymerization process and formation of labeled polymer. Earlier we have used this method to evaluate CP and kP values for ethylene and propylene polymerization with Ziegler-Natta catalysts [39,40]. As it was shown in [41], carbon monoxide reacts with a Fe(II)-complex of composition 5H5(CO)2Fe(CH3) by inserting into the Fe-CH3 bond. A variety of alkyl complexes of transition metals react with carbon monoxide in the same manner. The available literature data on the reaction of carbon monoxide with a Fe(II) alkyl complexes prove feasible application of polymerization inhibition with 14CO for determination of the Fepolymer chains number (number of active centers) at polymerization over the catalysts based on bis(imino)pyridine complexes of Fe(II). Thus, we have used this method to determine the and kP values at ethylene polymerization over (2,6-Me2LFeCl2/MAO) and (2,6Me2LFeCl2/Al(i-Bu)3) catalysts [30-32]. The obtained and kP values are summarized in Table 3. The values determined at short polymerization times (pol = 1.5-2 min) were equal to 0.07 and 0.41 mol/mol Fe for 2,6Me2LFeCl2/ and 2,6-Me2LFeCl2/Al(i-Bu)3 catalysts, respectively (Table 3, runs 1 and 3). For both catalysts the CP values decrease with polymerization time. At the initial period of polymerization the reactivity of the examined catalysts (especially 2,6-Me2LFeCl2/MAO) is

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extremely high (kP = 5104 L/mols at 35C), for comparison, the kP value of the Ziegler-type catalyst TiCl4/MgCl2/AlEt3 is equal to 1.2104 L/mols at 80C [42-44]. For both catalyst 2,6Me2LFeCl2/MAO ( Table 3, runs 1 and 2) and 2,6-Me2LFeCl2/Al(i-Bu)3 (Table 3, runs 3 and 4) the kP value observed at pol = 1.5 2 min noticeably decreases as the reaction proceeds. Table 3. CP, kP and PE MWD data obtained at ethylene polymerization over the catalysts based on 2,6-Me2LFeCl2
Run
1)

Cocatalyst

min.

pol,

CP, R2), Kg PE/ mol Fe mol/mol Fe bar min

k, L/mol s

Mw 10-3

Mw/Mn

1 2 3 4
1)

MAO // Al(i-Bu)3 //

1.5 9 2 7

600 100 1700 210

0.076 0.039 0.41 0.16

49500 15000 26000 8200

44 54 39 66

6.9 7.2 7.6 7.1

Polymerization in toluene ( runs 1,2) or heptane ( runs 3,4) at 35 C, ethylene pressure 2.9 bar, [Fe] = 3-810 -6 mol/l, Al/Fe = 500; 14CO/Fe = 21; CO = 5 min. 2) Polymerization rate in the moment of 14 introduction.

Thus, deactivation of 2,6-Me2LFeCl2/ and 2,6-Me2LFeCl2/Al(i-Bu)3 catalysts with polymerization time is determined both by lowering of the active centers number and the decrease of the calculated kP value.
0,8 9 min

0,8

b)

a)
0,6 d Wf / d log M
1.5 min

0,6 d Wf / d log M

7 min 2 min

0,4

0,4

0,2

0,2

0,0 2 3 4 log M 5 6 7

0,0 2 3 4 log M 5 6 7

Figure 4. Effect of polymerization duration on the MWD of PE produced with 2,6-Me2FeCl2/MAO. (Table 3; runs 1 and 2) ( a) and 2,6-Me2FeCl2/Al(i-Bu)3 catalysts (Table 3; runs 3 and 4) (b).

The data presented above allow to suggest that active centers with different reactivity (i.e., with different kP value) are presented in both catalysts 2,6-Me2LFeCl2/ and 2,6Me2LFeCl2/Al(i-Bu)3. As polymerization proceeds, the centers with high reactivity in the

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chain propagation reaction are deactivated first. Data on the broad and bimodal MWD of PE, produced at polymerization over these catalysts (Fig.4) confirm the conclusion on the formation of active centers with different reactivity [30]. The data of Fig. 4 show that contribution of the low-molecular-weight shoulder in MWD curves decreases with the increasing of polymerization time. The detailed analysis of MWD data [32] draw us to the conclusion that at pol = 1-10 min two types of active centers are present in the studied catalysts. At the initial stage of polymerization, highly active but unstable centers produce the low molecular weight PE. The less active and more stable centers produce PE with high Mw. The ratio of different centers changes with polymerization time. As apparent from the above, the values of propagation reaction rate constants calculated for ethylene polymerization over 2,6-Me2LFeCl2/ and 2,6-Me2LFeCl2/Al(i-Bu)3 catalysts are the average values, characterizing different active centers present in the system at the time moment. We believe, that at the starting moment of polymerization (ol < 1.5 min), the proportion of highly active centers is higher and, correspondently, the values of kP should be higher then the measured average values 5-2.6104 L/mols. It should be noted that the increase in PE molecular weight with polymerization time going with simultaneous reduction of the average kP values indicate a sharp decrease in the average rate of chain transfer reactions. This lowering is faster than the decrease of the rate of chain propagation. Thus, the main peculiarities of iron bis(imino)pyridine complexes as an active component of the homogeneous ethylene polymerization catalyst are the following: 1) high activity at activation with different organoaluminium activators and especially with aluminium trialkyls; 2) formation of linear PE with high Mw and broad MWD; 3) noticeable effect of the size and the nature of the substituents at 2,6 positions of the aryl ring in the ligand of iron complex and of the organoaluminium activator on the Mw and polidispersity (Mw/Mn values) of the resulted PE; 4) formation of the multiple active sites (differing by reactivity and stability in the chain propagation and transfer reactions) in these catalysts upon interaction of RnLFeCl2 with both MAO and aluminium trialkyls and variation of the ratio of these sites in course of polymerization; 5) presence of active centers with very high kp value ( 5.0104 L/mol s, 350C), but low thermal stability; 6) strong effect of catalysts composition and polymerization duration upon the number of active centers; the measured Cp values vary in the range of 0.410.04 mol/mol Fe.

2.2 CATALYSTS BASED ON RNLCOCL2

Effect of Activators
Table 4 presents the data on the catalytic activity at ethylene polymerization of the Co(II) bis(imino)pyridine complex (2,6-Me2LCoCl2) with different activators and characteristics of the obtained PE samples. The results of Table 4 (runs 1-3) show that, when activated with the same co-catalysts, 2,6-Me2LCoCl2 exhibited noticeably lower activity than the analogous Fe(II) bis(imino)pyridine complex (Table 1, runs 1,2,4). The catalyst system 2,6-Me2LCoCl2/Al(i-Bu)3 was almost inactive (Table 4, run 4). Like the 2,6-Me2LFeCl2-based systems, catalysts with 2,6-Me2LCoCl2 as the active

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107

component were inactive at polymerization temperatures above 50C. The time-dependent polymerization activities of the catalysts based on 2,6-Me2LCoCl2 are shown in Fig. 5.

Table 4. Ethylene polymerization over the catalysts based on 2,6-Me2L Cl2

Run Activator
3) Yield Maximum Kg PE/ activity, mol Co bar Kg PE/ mol Co bar min

Mw 10-3

Mw/ Mn

4)

Content per 1000 3 = 2 15.0 16.8 16 -

Content per PE molecule 3 0.9 1.1 1.0 = 2 0.9 1.2 1.0 -

11) 21) 31)

1)

MAO MAO (50) AlMe3 Al(i-Bu)3

3100 2700 3600 20

75 100 60 10

1.5 1.9 1.6 -

1.8 1.9 1.8 -

15.0 16.0 16 -

Polymerization in toluene at 35 C, ethylene pressure 5 bar, for 30 min, [Co] =1.410-5 mol/l, Al/Co=500. 2) Polymerization in heptane, all other conditions were as in runs 1-3 3) Calculated according to Figure 3 4) 13 C NMR data
100 Activity, kg PE/ mol Co bar min 1 3 60

2)

80

40

20

0 10 Time, min 20 30

Figure 5. Kinetic curves for ethylene polymerization over the catalysts composed of 2,6-Me2LCoCl2 and different activators: (1) - MAO; (2) - (50); (3) - AlMe3. (Number on the curve corresponds to the number of the experiment in Table 4).

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As in the case of bis(imino)pyridine iron complexes, the catalysts 2,6-Me2LCoCl2 /MAO (MAO(50)) demonstrate high initial activity that fell with the increase in polymerization time. The values of the initial activity and the rate of deactivation depend on the activator composition. Similar to 2,6-Me2LFeCl2, 2,6-Me2LCoCl2 activated by MAO demonstrates high initial activity and the highest deactivation rate (Table 4, run 1, Fig. 5, curve 1). The catalyst formed by interaction of cobalt complex with AlMe3 was characterized with noticeably higher stability ( Fig. 5, curve 3). The PE samples obtained with homogeneous catalysts composed of 2,6-Me2LCoCl2 and different activators are characterized by low Mw and narrow MWD (Mw/Mn=1.8-1.9, Table 4). These polymers are extremely linear, containing one terminal CH3 and one CH=CH2 group per polymer molecule (Table 4). Thus, at interaction of 2,6-Me2LCoCl2 with different activators only one type of active center is formed, and in contrast to 2,6-Me2LFeCl2, the homogeneous catalysts based on this cobalt complex can be regarded as the single-site catalysts.

Effect of the Ligand Composition

The data about ethylene polymerization over Co bis(imino)pyridine complexes bearing different alkyl substiuents in the aryl rings of the ligand activated with MAO are presented in Table 5 and Fig. 6. Table 5. Effect of the substituents R on the activity of Rn-LCoCl2/MAO catalysts and produced PE molecular weight characteristics
Run Rn 2,6-Me2 2,4,6-Me3 2,6 -i-Pr2 2-t-Bu 2,5-t-Bu2 Yield Kg PE/ mol Co bar 2900 5800 1250 4500 6100
1)

Maximum activity,

Kg PE/ mol Co bar min 280 700 150 750 270

Mw 10-3 1.5 1.7 18 330 12002)

Mw/Mn

1 2 3 4 5

1.8 1.8 2.0 2.5 -

Polymerization in toluene at 35 C, ethylene pressure 2 bar, for 30 min ( for run 1 - 15 min) , [Co] =1.4 10 -5 mol/l, MAO/Co=500. 1) Calculated according to Figure 5 2) Mv value (intrinsic viscosity data)

The values of maximum activity and the rate of catalysts deactivation depend on the ligand composition of cobalt complexes. In comparison with 2,6-Me2LCoCl2 /MAO system, the catalyst based on 2,4,6-Me3LCoCl2 complex, bearing three Me groups in o- and ppositions of the aryl rings, demonstrates higher initial activity, causing the increased yield of PE ( Table 5, runs 1 and 2, Fig 6, curves 1 and 2). In accordance with the literature data [10, 45-47], the catalyst 2-t-Bu-LCoCl2/MAO was less stable, its high initial activity sharply fell within some minutes ( Fig. 6, curve 4), whereas the system based on 2,5-t-Bu2LCoCl2

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109

displayed quite stable kinetic curve, resulting in the highest PE yield (Table 5, run 5, Fig 6, curve 5). PE samples obtained with the catalysts RnLCoCl2/MAO were characterized with narrow MWD ( Mw/Mn=1.8-2.5) and high linearity ( one terminal -CH3 and one -CH=CH2 group per polymer molecule) ( Table 5). Introduction of the third alkyl substituent into the p- position of the aryl ring had almost no effect on the Mw and polydispersity values of PE ( Table 5, runs 1 and 2). The value of PE molecular weight noticeably increased with the increasing steric bulk of the substiuents R ( Table 5, runs 1, 3, 5). The catalyst based on 2-t-Bu-LCoCl2, bearing the only one t-Bu -group in o-position of the aryl ring, produced PE with the Mw value more than 200 times higher than that of polymer, obtained over 2,6-Me2LCoCl2 /MAO catalyst (Table 5, Runs 1 and 4). Introduction of the second t-Bu-group into the ligand results in formation of PE with extremely high molecular weight ( Mv = 1200000, Run 5). Cobalt complexes with halogen substituents are approximately an order of magnitude less active than their iron analogues and produce linear PE with very low Mw and narrow Mw/Mn ( for PE produced with 2,6-Cl2LCoCl2 at 00C Mw=370 g/mol, Mw/Mn= 1.15) [36].

Activity, kg of PE/ mol Co min bar

800

600 1 2 4 400 5

200

10 Time, min

20

30

Figure 6. Kinetic curves for ethylene polymerization over homogeneous catalysts Rn-PhLCoCl2/MAO: Rn= 2,6-Me2 (1), 2,4,6- Me3 (2), 2-t-Bu (4), 2,5-t-Bu2 (5). (Number on the curve corresponds to the number of the experiment in Table 5).

Thus, similar to the iron complexes, ligand environment in bis(imino)pyridine cobalt complexes has a great influence on theirs polymerization behavior (activity, stability and MW of the produced PE). It should be noted, that narrow MWD of all obtained PE samples indicate that independently of their ligand composition, the catalysts based on bis(imino)pyridine cobalt complexes retain their single-site character.

Characterization of the Active Species

Recently the nature of the active sites of polymerization formed upon interaction of bis(imino)pyridine cobalt complexes with MAO and aluminium trialkyls was intensively

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studied [12, 40-42]. According to results of Gibson and Gal, in the LCoIICl2/MAO system, initial cobalt(II) pre-catalyst reduction to cobalt(I) halide is followed by conversion to a cobalt(I) methyl and ultimately to a cobalt(I) cationic species. Addition of ethylene affords an ethylene adduct [LCoI(2-C2H4)]+[Me-MAO], which is considered as the immediate precursor to the active species [48-50] In contrast, our 1H and 2H NMR studies of 2,6Me2LCoIICl2/MAO system showed that cobalt(II) complex with proposed structure 2,6Me2LCoIIMe(Cl)(MAO) strongly predominates in the reaction solution at 20C for at least several hours after mixing 2,6-Me2LCoIICl2 and MAO [12 ]. The detailed 1H, 2H, and 19F NMR characterization of cobalt(II) and cobalt(I) species formed in the systems Rn-LCoIICl2/MAO, LCoIICl2/AlMe3/[CPh3][B(C6F5)4] and LCoIICl2/AlMe3 (where Rn = 2,6-Me2, 2,4,6-Me3-, 2,6-i-Pr2 and 2-t-Bu) was recently undertaken [29]. It was shown, that the ion pairs [RnLCoII(-Me)2AlMe2]+[A], [RnLCoIIMe(S)]+[A], and [RnLCoI(S)]+[A] can be observed in the catalyst systems RnLCoIICl2/MAO and RnLCoIICl2/AlMe3/[CPh3][B(C6F5)4] ([A] = [Me-MAO] or [B(C6F5)4]; S = toluene or vacancy), whereas neutral complexes RnLCoI(-Me)(-Cl)AlMe2 and RnLCoI(-Me)2AlMe2 predominate in the catalyst systems RnLCoIICl2/AlMe3. Addition of monomer (C2H4) plays the key role in formation of the direct precursors of the polymerization active centers of the catalysts based on RnLCoIICl2. In the case of RnLCoIICl2/MAO systems, addition of ethylene results in the rapid reduction of cobalt(II) to cobalt(I) and only the ion pairs of the type [RnLCoI(S)]+[A] are present in the reaction solution at 20C. In the case of RnLCoIICl2/AlMe3 systems, in the presence of ethylene the ion pair with proposed structure [RnLCoI(2-C2H4)]+[AlMe3Cl] is the major cobalt species in the reaction solution. Thus, in contrast to the catalysts based on bis(imino)pyridine complexes of iron, similar intermediates (ion pairs of cobalt(I)) are present in the systems RnLCoIICl2/MAO/C2H4 and RnLCoIICl2/AlMe3/C2H4. The obtained results can explain the close polymerization results (similar activity and PE structure) obtained with the catalyst systems formed by interaction of RnLCoCl2 complexes with MAO and AlMe3.

Data on the Number of Active Centers and Propagation Rate Constants

Data on the values of Cp and kP at ethylene polymerization with the catalysts 2,6Me2LCoCl2/MAO have been obtained by method of polymerization quenching by 14 CO [33, 34]. We have to extend this study to polymerization over the catalysts based on 2-t-BuLCoCl2 and 2,5-t-BuLCoCl2 complexes. The obtained data are summarized in Table 6. In the initial moment of polymerization over the catalyst 2,6-Me2LCoCl2/MAO the number of active centers is high ( 23% with respect to total content of cobalt complex) ( Table 6, run.1). With the increase in polymerization time form 5 to 15 min, the CP value decreases by a factor of 1.6 ( up to 0.14 mol/mol Co, Table 6, run 2). In contrast to the catalysts based on 2,6-Me2LFeCl2, the values of propagation rate constant determined for the catalyst 2,6-Me2LCoCl2/MAO ( 3.6103 L/mols at 350) were independent of the reaction time. Obviously, the reason of the catalyst 2,6-Me2LCoCl2/MAO deactivation with the increase of polymerization time is the reducing of the active centers number. It should be mentioned that the number of active centers formed in the system 2,6-Me2LCoCl2/MAO (2314% with respect to total content of cobalt complex) is noticeably higher than that formed in

Homogeneous Catalysts Based on Bis(imino)pyridine Complexes

111

2,6-Me2LFeCl2/MAO catalyst (8-4%, Table 3). The reduced polymerization activity of the catalyst 2,6-Me2LCoCl2/MAO in comparison with that of the catalyst based on iron complex is determined by lower propagation rate constants. Table 6. CP, kP and PE MWD data at ethylene polymerization over the catalysts RnLCoCl2/MAO.
Run
1)

Complex

min 2,6-Me2LCoCl2 // 2- t-BuLCoCl2 2,5-tBu2LCoCl2 2,5-tBu2LCoCl2 5 15 1 3.5

pol,

R2), Kg PE/ mol Co bar min 130 80 520 210

M CP, k, k tr , Mw mol/ L/mol s 10-3 L/mol s mol Co

Mw/Mn

1 2 3 4

0.23 0.14 0.73 0.48

3520 3570 3580 2350

90 100 0.82
-

1.9 1.8 320 -

1.7 1.8 2.7 -

53)
1)

3.5

270

0.69

3200

0.53)

3703)

2.13)

Polymerization in toluene at 35 C, ethylene pressure 2.9 bar, [Co] =5 - 1610-6 mol/l, Al/Co=500; 14 CO/Co = 13-40; CO = 5 min.. 2) Polymerization rate in the moment of 14 introduction. 3) Polymerization at 500C

The data of Table 6 show that PE samples, obtained with 2,6-Me2LCoCl2/MAO at different polymerization time (5- 15 min), are characterized by similar Mw, Mw/Mn and kP values. So, in contrast to the catalysts based on the corresponding iron complex, were a set of active centers is formed and the determined kP is an average value ( Table 3), the catalyst 2,6Me2LCoCl2/MAO contains only one type of active center and the determined kP value reflects the actual reactivity of these centers. The values of propagation rate constant determined for 2-t-BuLCoCl2 /MAO and 2,5-tBuLCoCl2/ MAO catalysts were close to that, found for 2,6-Me2LCoCl2/MAO system (Table 6, runs 3, 4). Evidently, higher activities of the systems based on t-Bu-substituted complexes in comparison with that of the catalyst 2,6-Me2LCoCl2/MAO, are accounted for higher numbers of the active centers present in these systems (0.23, 0.48 and 0.73 mol/molCo correspondingly for Me2LCoCl2 , 2-t-BuLCoCl2 and 2,5-t-Bu2 LCoCl2, Table 6) Study on the effect of the monomer pressure (1-5 bar) upon the molecular weight characteristics of the PE, produced with RnLCoCl2/MAO catalysts (Rn = 2,6-Me2-, 2,4,6-Me32-t-Bu-, 2,5-t-Bu2-), have shown that Mw and Mw/Mn values of polymers are independent of the monomer pressure. The obtained PE samples were highly linear and contain one CH3 and one CH=CH2 group per polymer chain. These results provide evidence, that the main reaction of polymer chain transfer at polymerization over these catalysts is the reaction of the

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chain transfer to monomer. On the basis of the obtained experimental data the values of chain transfer rate constants (ktrM ) were determined (Table 6). The value of ktrM depends on the steric bulk of the o-substiuents in the aryl ring of the ligand (ktrM = 90 and 0,82 L/mol s for 2,6-Me2LCoCl2 and 2-t-BuLCoCl2 correspondingly, polymerization at 350C, Table 6, runs 1 and 3). The value of ktrM for 2,5-t-Bu2 LCoCl2 based catalyst was found to be 0.5 L/mol s (polymerization at 500C). Bulky substituents at the o-position of the aryl ring of complex ligand hinder the reaction of chain transfer, and with the increase of the substituents bulk the value of ktrM decreases, thus leading to the increase in the molecular weight of the produced PE. Thus, cobalt bis(imino)pyridine complexes as ethylene polymerization catalysts are characterized by reduced activity in comparison with that of corresponding RnL2FeCl2 complexes. This low activity is determined by lower value of rate propagation constants. The catalysts formed by interaction of RnLCoCl2 with both MAO and aluminium trialkyls are single-site systems; they produce highly linear PE with narrow MWD. The bulk of the substituents at the o positions of the aryl ring in the ligand of cobalt complex greatly affects the activity and the Mw values of the PE produced. It was found that the increased activity of complexes with t-Bu-substituents is determined by an increase in the number of active centers with the same kP value. Increase of PE molecular weight is determined by strong decrease in the value of chain transfer rate constant.

2.3. CATALYSTS BASED ON RNLVCL3

Bis(imino)pyridine complexes of V(III) as active catalysts for ethylene oligomerization and polymerization were introduced by R. Schmidt et.al. [18]. In presence of MAO as activator productivities of vanadium complexes varied from 3103 to 580103 kg PE/mol V for 30 min at reaction temperature 600C and ethylene pressure 250 psig. The catalysts productivity and properties of the obtained products depend on the substituents in the aryl ring of bis(imino)pyridyl ligand : as the bulk of the alkyl substituents increases, the productivity decreases, whereas formation of solid PE increases. Products obtained with 2,6substituted complexes consisted mainly of solid polymer.

Effects of Polymerization Temperature and Activators

2,6-Et2LV(III)Cl3 was used to study the effects of polymerization temperature and activators upon the catalysts properties at ethylene polymerization. The obtained results are collected in Table 7 and Fig. 7. In contrast to the iron and cobalt-based catalysts, inactive at polymerization temperatures above 50 C, catalytic systems based on 2,6-Et2LVCl3 were highly active at 60 C (Table 7, runs 1 and 3). At 35C, 2,6-Et2LVCl3 activated with commercial MAO, was characterized by lower activity but the stable kinetic curve (Fig. 7, curve 1).

Table 7. Ethylene polymerization over the catalysts based on 2,6 Et2LVCl3

Run Activator T C

min

pol,

1)

2)

Yield

Maximum activity, Kg PE/ mol V bar min 170 350 360 260

Mw 10-3

Mw/Mn

3)

Content per 1000 3 =2 4.2 -

Kg PE/ mol V bar

Content per PE molecule 3 1.0 =2 1.0 -

1 2 3 4
1) 2)

MAO MAO MAO

4)

35 60 60 60

30 4 30 30

3300 3250 11000 6500

-5

6.7 5 12 -

2.4 2.1 4.8 -

4.2 -

MAO(20)

Polymerization in toluene at ethylene pressure 2 bar, [V] =1.4 10 mol/l, Al/V=500. Calculated according to Figure 4 3) 13 C NMR data 4) MAO sample with reduced content of AlMe3 (~ 0.01 M of AlMe3)

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400 Activity, kg PE/ mol V bar min

300

200

100

0 10 Time, min 20 30

Figure 7. Kinetic curves of ethylene polymerization over 2,6-Et2LVCl3 /MAO . (1) polymerization at 35 C; (3) polymerization at 60 . (Number on the curve corresponds to the number of the experiment in Table 7).

In polymerization runs at 60 C the catalyst 2,6-Et2-LVCl3/MAO showed high initial activity (Fig. 7, curve 3). which rapidly fell with the polymerization time. Reducing the free AlMe3 content in MAO samples (MAO(20)) used for activation of vanadium complex (Table 7, run 4) led to the decrease of the initial activity and of the PE yield. In the presence of MAO completely purified from free AlMe3 (MAO(50)) or with AlMe3 as activator, 2,6-Et2LVCl3 was inactive. PE prepared with the catalysts 2,6-Et2LVCl3 /MAO) displayed high linearity and low Mw. (Table 7). The value of PE polydispersity depends on the polymerization conditions (temperature and polymerization time). PE with narrow MWD (Mw/Mn =2.4) was obtained in polymerization run at 35 C (Table 7, run 1). Increase in the polymerization temperature up to 60 C resulted in formation of PE with narrow MWD at short polymerization time (Mw/Mn=2.1, at pol = 4min; Table 7, run 2), but with the increase in polymerization times polydispersity of PE increases (Table 7, run 3, Mw/Mn=4.8). Evidently, interaction of 2,6Et2LVCl3 with MAO at the temperature 600C generates unstable centers of the only one type. These centers are responsible for the formation of PE with low Mw and narrow MWD at the beginning of polymerization. As the polymerization proceeds, the new centers which produce PE with higher Mw are formed. As a result, Mw and Mw/Mn values of the produced PE increase with time. The nature of the active species formed upon interaction of RnLVCl3 with MAO remains unclear. The samples (2,6-Et2LVCl3 +MAO) display broad unresolved NMR and EPR spectra that hinder the assignment of the signals.

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115

Data on the Number of Active Centers and Propagation Rate Constants

The method of polymerization quenching by 14CO was applied to determine the Cp and kP values for ethylene polymerization over the catalysts 2,6-Et2LVCl3 /MAO and 2,6Me2LVCl3 /MAO at 35 and 600C. The obtained results are shown in Table 8. Table 8. CP, kP and PE MWD data at ethylene polymerization over the catalysts based on 2,6 R2LVCl3 complexes
Run.1) Complex T, C

min

pol,

R2), CP, k, Kg PE/ mol V mol L/ mol V s bar min /mol V

Mw, Mw/Mn 10-3

1 2 3 4
1)

2,6Et2LVCl3 // // 2,6Me2LVCl3

35 60 60 60

5 2 19 3

90 870 210 880

0.18 0.50 0.31 0.42

2580 16430 6380 19900

5.7 5.5 11 3.3

2.5 2.2 4.1 1.9

Polymerization in toluene at ethylene pressure 2.9 bar, [V] =14 - 21 10-6 mol/l, Al/V=500, /V = 500-700; 14CO/V = 14-22; CO = 5 min. 2) Polymerization rate in the moment of 14 introduction.

The values of Cp and kP found for 2,6-Et2LVCl3 /MAO catalyst at 350C ( Table 8, run1) are lower than those for the catalysts, based on iron and cobalt bis(imino)pyridine complexes (Tables 3 and 6), being the reason of the lower activity of 2,6-Et2LVCl3 /MAO at this temperature. With the increase in polymerization temperature up to 60oC, activity of the vanadium based catalysts noticeably increases due to the increase in both the active centers number and kP value ( Table 8, runs 1 and 2). Similar activity exhibited by the catalysts based on 2,6-Et2LVCl3 and 2,6-Me2LVCl3 is determined by formation of close number of active centers (Cp = 0.4-0.5 mol/mol V) with similar reactivity (kP = 1.6-2.0104 L/mol s) (Table 8, runs 2 and 4). The molecular weight of the polymers, obtained with vanadium bis(imino)pyridine complexes, depend on the steric bulk of the substituents in 2,6-position of the aryl rings of the ligand. MW of PE produced with 2,6-Et2LVCl3/MAO catalyst is somewhat higher than that of polymer, prepared using the system based on 2,6-Me2LVCl3 ( Table 8, runs 2 and 4 and Fig. 8, curves 1 and 3). In both cases PE with narrow MWD (Mw/Mn = 1.9 2.2) was obtained, indicating that at activation of vanadium bis(imino)pyridine complexes with MAO only one type of active centers is generated.

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2 1,2 1,0 0,8 0,6 0,4 3 0,2 0,0 1 2 3 4 log M 5 6 7 4

Figure 8. MWD of PE produced over RnLVCl3/MAO catalysts at 600C: (2) Rn = 2,6-Et2-, polymerization for 2 min; (3) Rn = 2,6-Et2-, polymerization for 19 min; (4) Rn = 2,6-Me2-, polymerization for 3 min; (Number on the curve corresponds to the number of the experiment in Table 8).

Effect of the reaction time upon the Cp and kp values at polymerization over the catalyst 2,6-Et2LVCl3/MAO was studied ( Table 8, runs 2 and 3). As polymerization proceeds from 2 to 20 min, the catalyst activity noticeably decreases. It was found that deactivation of the catalyst with polymerization time is caused by lowering of both the number of active centers and the value of propagation rate constant. PE sample obtained at longer polymerization time was characterized by the increased Mw value and broadened MWD due to formation of a high-molecular weight PE fraction ( Fig. 8, curve 2). Probably, at longer polymerization times new active centers, producing high molecular weight PE appear in the system and initially single-site catalyst 2,6Et2LVCl3/MAO should then be regarded as a multi-site one. In this case (Table 8, run 3), the determined reaction rate constant is an average value, characterizing different active centers present in the system at the time moment. Thus, vanadium bis(imino)pyridine complexes are effectively activated only with MAO Reduction of the free AlMe3 content in MAO reduces the catalytic activity of RnLVCl3/MAO system. Active centers formed by interaction of RnLVCl3with MAO demonstrate higher thermal stability in comparison with those of RnL2FeCl2 and RnLCoCl2based systems. The catalysts RnLVCl3/MAO act as a single-site systems at low polymerization temperatures (35C). At high temperature (60 C) they act as a single-site catalysts only at a short polymerization times, but as the polymerization proceeds they turn into multi-site catalysts.

2.4. Catalysts Based on RnLCrCl3

A family of chromium (III) bis(inino)pyridine complexes (RnLCrCl3, Rn= H, Me, Et, i-Pr, t-Bu) was synthesized and tested in ethylene polymerization by Esteruelas et.al [19]. It was shown that upon activation of RnLCrCl3 with MAO the catalysts highly active at the increased

d Wf / d log M

Homogeneous Catalysts Based on Bis(imino)pyridine Complexes

117

polymerization temperatures (700C) are formed. These catalysts produce highly linear polyethylene. The substituents at the o-position of the N-aryl groups affected both catalytic activity and molecular weight of the resulting PE. Complexes with two o-substituents proved to be more active catalysts than those, bearing one alkyl group in the o- position of the aryl ring. The increase of steric bulk of the substituents causes a decrease in the catalytic activity, whereas the molecular weight of the produced PE increases. The highest activities were achieved with the catalysts based on Cr(III) complex with Me substituents in both o- and pposition of the aryl ring (2,4,6-Me3LCrCl3 ).

Effect of Activators
Figure 9 (curve 1) shows the kinetic curve of the ethylene polymerization at 70C over chromium(III) bis(imino)pyridine complex (2,4,6-Me3LCrCl3) activated with MAO. In contrast to the previously described catalysts based on iron, cobalt and vanadium complexes, and in line with the results of ref. [19], at polymerization with this catalyst a long period of acceleration is observed. The effective method to form the active component of these catalysts via preliminary interaction of 2,4,6-Me3LCrCl3 with MAO solution at low molar ratio of the components (AlMAO/Cr=100-200) was suggested in ref. [19]. A thus prepared solution of the chromium complex is very stable and could be used for ethylene polymerization at 70 C in heptane with Al(i-Bu)3 as an additional co-catalyst.
400 Activity, kg PE/mol Cr bar min 2 300 6 200 1 100

0 10 20 30 Time, min 40 50 60

Figure. 9. Kinetic curves for ethylene polymerization over 2,4,6-Me3LCrCl3 at various preactivation mode and polymerization temperature: (1) - polymerization without preactivation ( polymerization at 70 C and 5 bar of C2H4 , in toluene with MAO as co-catalyst, Al/MAO=500). (2) - preactivation with MAO at 250C, MAO/Cr= 200 ( polymerization at 70 C, in heptane, at 5 bar of C2H4, with Al(i-Bu)3 , Al(i-Bu)3 /Cr=1000); (4) - preactivation with MAO (50) at 250C, MAO/Cr= 200 ( polymerization at 70 C, in heptane, at 5 bar of C2H4, with Al(i-Bu)3, Al(i-Bu)3 /Cr=1000); (6) - preactivation with MAO at 250C, MAO/Cr= 200 ( polymerization at 35 C, in heptane, at 5 bar of C2H4, with Al(i-Bu)3, Al(i-Bu)3 /Cr=1000); (Number on the curve corresponds to the number of the experiment in Table 9).

Table 9. Effect of preactivation mode on the ethylene polymerization activity of 2,4,6-Me3LCrCl3

Run.
4) 5)

Pre-activator

[Cr] mol/l

Yield Kg PE/ mol Cr bar

Maximum activity, Kg PE/ mol Cr bar min 140 330 400 360 300 260

Mw 10-3

Mw/Mn

6)

Content per 1000 3 =

2

Content per molecule 3 0.97 0.9 -

PE

=
2

11) 22) 32) 42) 52) 63)

1) 2)

MAO MAO (20) MAO (50) MMAO MAO

20.0 3.3 5.0 5.0 5.0 5.0

4740 7880 9680 9920 2870 12400

1.3 1.5 1.2 1.1

1.9 1.9 1.7 1.9

17.0 17.2 -

15.6 16.0 -

0.9 0.8 -

Polymerization in toluene at 70C, ethylene pressure 5 bar, for 60 min, co-catalyst MAO (Al/Cr=500) Polymerization in heptane at 70C, ethylene pressure 5 bar, for 30 min, co-catalyst Al(i-Bu)3 (Al(i-Bu)3/Cr =1000), 3) Polymerization at 35C, ethylene pressure 5 bar, for 30 min, co-catalyst Al(i-Bu)3 (Al(i-Bu)3/Cr=1000), 4) Molar ratio Al/Cr =200 5) Calculated according to Figure 9 6) 13 C NMR data

Homogeneous Catalysts Based on Bis(imino)pyridine Complexes

119

In the case of pre-activation of 2,4,6-Me3LCrCl3 with MAO at the molar ratio AlMAO/Cr =200, the polymerization starts immediately with high activity (Fig. 9, curve 2) providing higher PE yield in comparison with that of the system without preactivation (Table 9, runs 1 and 3). The EPR studies of the catalyst systems 2,4,6-Me3LCrCl3/activator (where activator was MAO, MMAO) have shown the appearance of EPR spectra after mixing the reagents. These spectra are characteristic of S = 3/2 chromium(III) complexes [51]. The initial signals of Cr(III) disappeared within 5-30 min, depending on the nature of the co-catalyst used. Apparently, the activation of 2,4,6-Me3LCrCl3 with MAO leads to formation of the active centers via the reduction of Cr(III) to a lower oxidation state. In accordance with that, recently synthesized bis(imino)pyridine complexes of Cr (II) [52] and complexes containing Cr in formal monovalent oxidation state [53] proved to be highly active at ethylene polymerization in the presence of MAO. Data in Table 9 and Fig. 9 show that the preactivated systems 2,4,6-Me3 LCrCl3/MAO/Al(i-Bu)3 revealed high initial activity at increased polymerization temperature (70 C ) which rapidly fell with the increase in polymerization time. Therefore the yield of PE obtained in polymerization run at 35 C for 30 min was 1.5 times higher than that, obtained in polymerization at 70 C (compare runs 2 and 6, Table 9) due to the higher stability of the catalyst at lower polymerization temperature. (Figure 9, curves 2 and 6). Catalytic systems based on 2,4,6-Me3LCrCl3, preactivated by different samples of MAO produce highly linear PE with narrow MWD (Mw/Mn = 1.71.9) and close Mw values (1.21.5103) (Table 9, runs 2-4).

Data on the Number of Active Centers and Propagation Rate Constants

Table 10 represents the data on the number of active centers and their reactivity for ethylene polymerization at 35 and 700C with 2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3 catalyst, determined using the method of polymerization quenching by 14CO. At 350C and at a short polymerization time (pol = 4 min) the number of active centers formed in the catalytic system is rather high ( 0.36 mol/mol Cr), whereas the reactivity of these centers is relatively low ( (kp= 1400 L/mol s, Table 10, run 1). The Cp value determined at the increased polymerization temperature (700C , pol= 3,5 min) was noticeably higher (Cp= 0.76 mol/mol Cr). With the increase in polymerization temperature the kP value also increases up to 3430 L/mol s (Table 10, run 2). In agreement with the literature [19,35], the catalyst 2,4,6-Me3 LCrCl3/MAO/Al(i-Bu)3 produces PE with narrow MWD, proving that only one type of active center is formed in this system. Lowering of the polymerization temperature results in a shift of the PE MWD curve to the low-molecular weight region ( Fig.10, curve 1). The increase in the PE MW at higher polymerization temperatures seems to be unusual, because it is well known that the increase in polymerization temperature leads to the decrease in molecular weight of polymers. To explain these contradictions the following considerations can be suggested. Probably, in course of polymerization on the active centers of the catalyst temporary interruption of polymer chain propagation reaction can occur (for example, due to coordination of aluminium trialkyl on the active center) with formation of so-called dormant centers. It is possible to assume that the time of dormant state of the active

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centers decreases with the increase of polymerization temperature, resulting in formation of polymer with the increased MW. Table 10. The CP, kP and PE MWD data at ethylene polymerization with the catalyst 2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3.
Run 1)

min

pol,

T, C

Rb), Kg PE/ mol Cr bar min

CP, mol/mol Cr

k , L/mol s

Mw 10-3

Mw/ Mn

1 2
1)

4 3

35 70

80 260

0.36 0.76

1410 3430

0.8 1.2

1.3 1.5

Polymerization in heptane at ethylene pressure 3 bar, [Cr] =0.5-110-6 mol/l, Al(i-Bu)3/Cr =1000, 14 CO/Cr = 17-22; CO = 5 min. 2) Polymerization rate in the moment of 14 introduction.

2,0 1

1,5 d Wf / d log M

1,0

0,5

0,0 1 2 3 log M 4 5

Figure 10. MWD of PE produced over 2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3 catalyst at different polymerization conditions: (1) 350C, 4 min; (2) 700C, 3 min; (Number on the curve corresponds to the number of experiment in Table 10).

Thus, the obtained data show that the active component of the catalysts based on 2,4,6Me3 LCrCl3 can be formed only in presence of MAO. The active centers of these systems provide high PE yield in polymerization at 70 C. Narrow MWD of PE samples obtained with the systems (2,4,6-Me3LCrCl3/MAO) /Al(i-Bu)3, evidences that interaction of 2,4,6Me3LCrCl3 with MAO produce only one type of active centers and the catalysts of this type can be regarded as single site catalysts. The number of active centers formed at the initial

Homogeneous Catalysts Based on Bis(imino)pyridine Complexes

121

moment of polymerization at 700C is high ( 0.76 mol/mol Cr), but these centers are very unstable and are rapidly deactivated with polymerization duration. The catalysts (2,4,6Me3LCrCl3/MAO)/Al(i-Bu)3 are characterized by low reactivity at propagation reaction ( the kP value is 1.4103 L/mol s at 350C )

3. ETHYLENE-1-HEXENE COPOLYMERIZATION OVER THE HOMOGENEOUS CATALYSTS BASED ON BIS(IMINO)PYRIDINE COMPLEXES

An important property of polymerization catalysts is their ability to control the molecular structure of the growing polymer by the copolymerization of ethylene with -olefins. Data on ethylene copolymerization with 1-hexene promoted by catalytic systems based on bis(imino)pyridine complexes of Fe(II), V(III) and Cr(III) are presented in Table 11. Table 11. Ethylene /1-hexene copolymerization with homogeneous catalysts based on bis(imino)pyridine complexes
Catalyst 2,6-Me2LFeCl2/Al(i-Bu)3 Al/Fe=500 2,6-Et2LVCl2/MAO MAO/V=500 2,4,6-Me3LCrCl2/MAO/Al(i-Bu)3 MAO/Cr=200 Al(i-Bu)3/Cr = 1000
3)
1) 2)

T, C 35 60

1)

[C6H12]/ [C2H4] 3.2 3.2

2)

Bu / /1000 C < 1.0 4.8

r1 >1000 200

70

2.0

2.4

400

Me2Si(Ind)2ZrCl2+ MAO

60

25

Co-monomers molar ratio in the polymerization medium Bu-branching content in the obtained polymer (13 NMR data) 3) Data of ref. [55]

The copolymerization parameter r1 was determined using the simplified copolymerization equation ([C]/[C2H4]pol = 1/r1[C]/[C2H4]react) where [C]/[C2H4]pol is the molar ratio between the units of 1-hexene and ethylene in the copolymer, and [C]/[C2H4]react is the molar ratio between the concentrations of the co-monomers in the reaction medium [54]. In comparison with the well known catalyst based on zirconocene complex [50], the r1 values found for iron, vanadium and chromium complexes were noticeably higher (Table 11). The obtained results indicate that catalytic systems based on iron, vanadium and chromium bis(imino)pyridine complexes display very low copolymerization ability.

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CONCLUSION
The data presented above on the ethylene polymerization activities at different temperatures for bis(imino)pyridine complexes with different transition metal center and the Cp and kp values together with the data on Mw and MWD of the produced polymers are summarized in Table 12. Table 12. Comparison of bis(imino)pyridine complexes as homogeneous catalysts for ethylene polymerization
Catalyst 2,6-Me2LFeCl2 (MSC) 2,6-Me2LCoCl2 (SSC) 2-t-BuLCoCl2 (SSC) 2,5-t-Bu2LCoCl2 (SSC) 2,6-Et2LVCl3 (SSC MSC) 2,4,6Me3LCrCl3 (SSC)
o

T, C 35 35 35

Rp kgPE/mol Mminbar 1700 100 130 80 520 100 210 90 870 210 80 260

Cp mol/mol M 0.410.039 0.23 0.14 0.73 0.48 0.69 0.18 0.50 0.31 0.36 0.76

kp 10-3 L/mols 49 15 3.6 3.6 2.4 3.2 2.6 16.5 6.3 1.4 3.4

Mw 10-3 44 115 1.8 320 1200 1) 370 5.7 5.5 11 0.8 1.2

Mw/Mn 4.6 12 1.8 2.7 2.1 2.5 2.2 4.1 1.3 1.7

35 50 35 60 35 70

1)

Mv value (intrinsic viscosity data)

It is evident, that the catalytic behavior of bis(imino)pyridine complexes with close composition of the bis(imino)pyridyl ligands essentially depends on the transition metal center. The catalysts based on 2,6-Me2LFeCl2 are characterized by (1) very high activity at low polymerization temperatures (35 C) with different activators (both MAO and aluminium trialkyls); (2) low thermal stability of the active sites; (3) formation of multiple active sites and transformation of the active centers in the course of polymerization, (4) formation of linear PE with high Mw and broad MWD; (5) the reduction of catalysts activity with polymerization time is caused by decrease in the number of active centers and their reactivity with polymerization duration. Interaction of 2,6-Me2LCoCl2 with different activators produces only one type of active site, characterized by (1) relatively low activity and low thermal stability; (2) PE with low Mw and narrow MWD is produced with the catalysts based on 2,6-Me2LCoCl2; (3) deactivation of the catalysts in course of polymerization is connected with the reduction of the number of active centers, whereas their reactivity remains constant; (4) the molecular weight of the produced PE is greatly affected by the size of the substituents at the o positon in the

Homogeneous Catalysts Based on Bis(imino)pyridine Complexes

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aryl ring of bis(imino)pyridyl ligand due to profound effect of these parameter on the transfer reaction constant. 2,6-Et2LVCl3 is activated only upon interaction with MAO. Thus formed catalyst is highly active within the broader temperature range (35-60 C). At low polymerization temperature (35 C), it can be regarded as a single site catalyst producing PE with narrow MWD. At higher polymerization temperatures (60 C) the polymerization kinetics for this catalyst becomes more complex: during the polymerization, the catalysts activity sharply decreases, whereas Mw and Mw/Mn values of the produced PE increase. This catalyst acts as a single site in the initial period of polymerization ( 5 min), producing PE with narrow MWD, but with the increase of polymerization time the initial active centers are deactivated ( the Cp value decreases) and new multiple active sites are formed in the system. The centers appear in course of polymerization are less active than the initial ones and produce PE with higher MW. As a result, the measured catalysts reactivity decreases whereas the Mw value of the produced PE increases and MWD broadens. Highly active catalysts based on 2,4,6-Me3LCrCl3 are formed upon interaction of chromium complex with MAO at low MAO/Cr molar ratio. Only one type of active center is formed in the systems (2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3, producing PE with low Mw and narrow MWD at polymerization temperatures at 35-700C. Thus, bis(imino)pyridine complexes of Co(II), V(III) and Cr(III) generate single site catalysts. However, in the catalysts based on RnLVCl3 in the course of polymerization simultaneously with the deactivation of the initially formed highly active centers, new active centers appear, resulting in broadening of MWD of the resulted PE. The main difference between RnLFeCl2 catalysts and the catalysts based on RnLCoCl2 , RnLVCl3 and RnLCrCl3 is formation of multiple active centers upon interaction with activators of different types: MAO or AlR3. Iron and cobalt-based systems are inactive at the temperatures higher than 50 C. The active centers of the catalysts with RnLVCl3 and RnLCrCl3 as active component are noticeably stable and these systems exhibit high initial activity at 60-70 C. Comparison of the catalytic properties of bis(imino)pyridine complexes with similar ligand framework has shown that in polymerization runs at 35 C the value of maximum activity decreases in the order 2,6-Me2LFeCl2> 2,4,6-Me3LCrCl3> 2,6-Et2LVCl3> 2,6-Me2LCoCl2, whereas the values of PE yield forms another order: 2,4,6-Me3LCrCl3 >2,6-Me2LFeCl2 >2,6-Et2LVCl3 2,6Me2LCoCl2 because of different stabilities of these catalysts (Table 12). Activity of these catalysts depends on both the number of active centers and the value of propagation rate constants. Additionally, the yield of PE depends on the stability of these centers ( the decrease in Cp values with polymerization time). The kp values are very high for the catalysts based on the iron complexes ( 50-15103 L/mol s, 350C) and rather low and similar for the complexes of Co, V and Cr (3.6-1.4103 L/mol s, 350C). The number of active centers depends on polymerization conditions ( duration, temperature, activator) and varies within a broad range (0.76 - 0.04 mol/mol M). The Mw values of PE are mainly determined by the substituents in the aryl ring of bis(imino)pyridyl ligand, however the transition metal also affects the PE molecular weight: the Mw values of PE produced at 35 C decrease in the order 2,6Me2LFeCl2 2,6-Et2LVCl3> 2,6-Me2LCoCl2 2,4,6-Me3LCrCl3.

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ACKNOWLEDGMENTS
The authors are grateful to Prof. K.P Bryliakov and Dr. I.E. Soshnikov for preparation of iron, cobalt, vanadium and chromium bis(imino)pyridine complexes, used in our study. The work was supported by the Russian Foundation for Basic Research (grant No. 07-0300311).

REFERENCES
[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] McKnight, A.L., Waymouth, R.M., Chem.Rev. 1998, 98, 2587-2598. Johnson, L.K., Killian, C.M., Brookhart, M.J., J.Am.Chem.Soc. 1995,117, 6414-6415. Britovsek, G.J., Gibson, V.C., Wass, D.F., Angew.Chem.Int.Ed.,1999, 38, 428-447. Gibson,V.C., Spitzmesser, S.K., Chem.Rev. 2003, 103, 283-315. Gibson, V.C., Redshaw, C., Solan, G.A., Chem.Rev., 2007, 107, 1745-1776. Bryliakov, K.P., Russ. Chem. Rev., 2007, 76, 253-304. Small, B.L., Brookhart, M., J.Am.Chem.Soc., 1998, 120, 7143-7144. Small B.L., Brookhart M., Bennet A.M., J. Am. Chem. Soc. 1998, 120, 4049-4050. Britovsek, G.J., Gibson, V.C., Kimberley, B.S., Maddox, P.J., McTavish, S.J., Solan, G.A., White, A.J., Williams, D.J., Chem. Commun. 1998, 849-850. Britovsek, G.J., Bruce, M., Gibson, V.C., Kimberley, B.S., Maddox, P.J., Mastroianni, S., McTavish, S.J., Redshaw, C., Solan, G.A., Strmberg, S., White, A.J.P., Williams, D.J., J. Am. Chem. Soc., 1999, 121, 8728-8740. Kumar, K.R., Sivaram, S., Macromol.Chem.Phys, 2000, 210, 1513-1520. Semikolenova, N.V., Zakharov, V.A., Talsi, E.P., Babushkin, D.E., Sobolev, A.P., Echevskaya, L.G., Khusniyarov, M.M., J. Molec. Catal. A: Chem. 2002, 182-183, 283294. Wang, Q., Yang, H., Fan, Z., Macromol. Rapid Commun., 2002, 23, 639-642. Radhakrishnan, K., Cramail, H., Deffliex, A., Franois, Ph., Momtaz, A., Macromol. Rapid Commun, 2003, 24, 251-254. Wang, Sh., Liu, D., Huang, R., Zhang, Yu., Mao, B., J.Molec.Catal. A:Chem., 2005, 245, 122-131. Reardon, D., Conan, F., Gambarotta, S., Yap G., Wang, Q., J.Am.Chem.Soc., 1999, 121, 9318-9325. Schmidt, R., Welch, M.B., Knudsen, R.D., Gottfried S., Alt, H.G., J.Molec.Catal. A:Chem., 2004, 222, 9-15. Schmidt, R., Welch, M.B., Knudsen, R.D., Gottfried, S., Alt, H.G., J.Molec.Catal. A:Chem., 2004, 222, 17-25. Esteruelas, M.A. , Lopez, A.M., Mendez, L., Olivan, M., Oate, E., Organometallics, 2003, 22, 395-406. Small, B.L., Carney, M.J., Holman, D.M., ORourke C.E., Halfen, J.A., Macromolecules, 2004, 37, 4375-4386. Nakayama, Y., Sogo, K., Yashida, H., Shiono, T., J. Polym.Sci Part A:Polym. Chem., 2005, 43, 3368-3375.

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[22] E.P. Talsi, D.E.Babyshkin, N.V. Semikolenova, V.N.Zudin, V.N.Panchenko,V.A. Zakharov, , Macromol. Chem. Phys. 202, No 10, 2046-2051(2001). [23] E.P. Talsi, D.E.Babyshkin, N.V. Semikolenova, V.N.Zudin, V.A. Zakharov, Kinetics and Catalysis, 2001, V. 42, No. 2, P. 147-153. [24] Bryliakov, K.P., Semikolenova, N.V., Zudin, V.N, Zakharov, V.A., Talsi, E.P., Cat. Commun., 2004, 5, 45-48. [25] Bryliakov, K.P., Semikolenova, N.V., Zakharov, V.A., Talsi, E.P., Organometallics, 2004, 23, 5375-5378. [26] Talzi, E.P., Bryliakov, K.P., Semikolenova, N.V., Zakharov, V.A., in New Developments in Organometallic Chemistry Research Ed. Marin A.Cato, Nova Science Publishers Inc., New York, 2006 pp. 151-191. [27] Talsi, E.P., Bryliakov, K.P., Semikolenova, N.V., Zakharov, V.A., Bochmann, M., Kinetics and Catalysis, 2007, 48, 490-504. [28] Bryliakov, K.P., Talsi, E.P., Semikolenova, N.V., Zakharov, V.A., Organometallics, 2009, 28, 3225-3232. [29] Soshnikov, I.E., Semikolenova, N.V., Bushmelev, A.N., Bryliakov, K.P., Lyakin, O.Y., Redshshaw, C., Zakharov, V.A., Talsi, E.P., Organometallics, 2009, 28, 6003-6013. [30] [30] Barabanov, A.A. Bukatov, G.D. Zakharov, V.A. N.V. Semikolenova, L.G. Echevskaja, M.A. Matsko, Macromol. Chem. Phys., 2005, 206, 2292-2298. [31] Barabanov, A.A., Bukatov, G.D., Zakharov, V.A., Semikolenova, N.V., Echevskaja, L.G., Matsko, M.A, Pol. Sci., Ser.B, 2005, 47, 349353. [32] Zakharov, V.A., Semikolenova, N.V., Mikenas, T.B., Barabanov, A.A., Bukatov, G.D., Echevskaya, L.G., Mats ko, M.A., Kinetics and Catalysis, 2006, 47, 303-309. [33] Barabanov, A.A., Semikolenova, N.V., Bukatov, G.D., Matsko, M.A., Zakharov, V.A., Polymer Science, Ser B, 2008, 50, 326-329. [34] Barabanov, A.A, Bukatov, G.D, Zakharov, V.A, Semikolenova, N.V., Echevskaja, L.G., Matsko, M.A., Macromol. Chem. Phys, 2008, 209, 25102515. [35] Semikolenova, N.V., Zakharov, V.A., Echevskaja, L.G., Matsko, M.A., Bryliakov, K.P., Talsi, E.P., Catal. Today, 2009, 144, 334-340. [36] Chen, Y., Chen, R., Qian, C., Dong, X., Sun, J., Organometallics, 2003, 22, 4312-4321. [37] Paulino I.S., Schuchardt, U., J.Molec.Catal. A:Chem., 2004, 211, 55-58. [38] Britovsek, G.J.P., Clentsmith, G.K.B., Gibson, V.C., Goodgame, D.M.L., McTavish, S.J.,Pankhurst, Q.A., Catal. Commun., 2002, 3, 207-211. [39] Bukatov, G.D., Goncharov, V.S., Zakharov, V.A., Macromol. Chem. Phys,. 1995, 196, 1751-1759. [40] Bukatov, G.D., Zakharov, V.A., Macromol. Chem. Phys., 2001, 202, 2003-2009. [41] McFarlane, K., Lee, B., Bridgewater, J., Ford, P.C., J. Organomet. Chem, 1998, 554, 49-61. [42] Chumaevskii, N.B., Zakharov, V.A., Bukatov, G.D., Kuznetzova, G.I., Yermakov, Y.I., Makromol. Chem., 1976, 177, 747-761. [43] Zakharov, V.A., Chumaevskii, N.B., Bukatov, G.D., Ermakov, Yu.I., Makromol. Chem. 1976, 177, 763-775. [44] Zakharov, V.A., Bukatov, G.D., Barabanov, A.A., Macromol. Symp., 2004, 213, 19-28. [45] Kim, I., Han, B.H., Ha, Y.S., Ha, C.S., Park. D.W., Catal. Today, 2004, 93, 281-285. [46] Kim, I., Han, B.H., Kim, J.S., Ha. C.S., Macromol. Res. 2005, 13, 2-7.

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[47] Liu, J.Y., Zheng, Y., Li, Y.G.,. Pan, L, Li, Y.S., Hu. N.H., J. Organomet. Chem., 2005, 690, 1233-1239. [48] Kooistra, T.M., Knujenburg, Q., Smits, J.M.M., Horton, A D., Budzelaar, P. H. M., Gal, A. W., Angew. Chem., Int. Ed., 2001, 40, 4719-4722. [49] Humphries,M.J.; Tellmann,K.P., Gibson, V. C.; White, A. J. P.; Williams, D. J., Organometallics, 2005, 24, 2039-2050. [50] Redshaw, C., Gibson, V. C.,. Solan, G. A Chem. Rev., 2007, 107, 1745-1776. [51] Bryliakov, K.P., Lobanova M.V., Talsi, E.P., Dalton Trans., 2002, 2263-2265. [52] Small, B.L., Carney, M.J., Holman, D.M., ORourke, C.E., Halfen, J.A., Macromolecules, 2004, 23, 4375-4386. [53] Vidyarante, I., Scott, J., Gambarotta, S., Duchateau, R., Organometallics, 2007 26, 3201-3211. [54] Zakharov, V.A., Echevskaya, L.G., Bukatov, G.D., Macromol.Chem., 1991, 192, 28652874 . [55] Kaminsky, W., Macromol.Chem.Phys., 1996, 197, 3907- 3945.

In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 4

RATIONAL DESIGN OF CHIRAL RUTHENIUM COMPLEXES FOR ASYMMETRIC HYDROGENATIONS

Ji Vclavk, Petr Kaer and Libor erven*
Department of Organic Technology, Faculty of Chemical Technology Institute of Chemical Technology Prague Technicka 5, 166 28 Prague 6, Czech Republic

INTRODUCTION
Thorough optimization of reaction conditions for maximum yield is the essential prerequisite of every reaction conducted on an industrial scale. In the field of asymmetric chemistry, an additional yield requirement arises, i.e. the stereoselectivity of the reaction. The plethora of fine chemical products available on the world market indirectly demands constant improvements in the production processes and literally dictates an individual, made-tomeasure solution for the best efficacy. The relentless expansion of the product range thus demands rapid but reliable tools for finding the optimal reaction conditions for a synthesis of the chiral product in question. Naturally, there is no catalyst to suit all substrates. Much like enzymes, almost every reaction requires at least a slightly modified catalyst or reaction conditions. Trial-and-error syntheses and subsequent testing of all (at first sight) potentially effective catalysts are as costly and time consuming as traditional combinatory methods, due to immense possibilities of the catalyst and substrate structures. Many of the complexes prepared by these laborious procedures finally prove ineffective when trying to utilize them in a stereoselectively catalyzed reaction. Therefore, the objective is to synthesize only those truly offering the desired behaviour. While only a few metal centres can be used effectively (namely Ru, Rh, Os, Ir), the auxiliary ligands offer infinite solutions of key changes to the structure. The rational design has become a well-known term to describe the process of fine-tuning the ligand. Although this chapter focuses on Ru catalysts, Rh complexes are also mentioned,
*

Corresponding author: Phone: +420 220 444 214, Fax: +420 220 444 340, E-mail: libor.cerveny@vscht.cz.

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owing to the high parallelism of these two coordination centres in the field of asymmetric hydrogenation. The term rational design comprises the practice of altering the molecular structures aided by computational modelling. Bearing in mind the structure of the chiral product, an experienced theoretical-organic chemist should be able to assemble a well-founded series of ligands offering good possibilities of achieving the desired performance in a particular situation. This process involves a competent rejection of structures with a significant potential of failure with regards to enantioselectivity. Given the vast number of possibilities, such a process would ideally be performed automatically, i.e. either by high-throughput experimentation (HTE) techniques, which have been amply reviewed [1] and are not covered within this chapter despite their rapid development in recent years, or through computational chemistry. This preliminary virtual assay is often referred to as in silico screening. Recently, high-capacity virtual ligand libraries have been created and analyzed, allowing a systematic description of existing ligands and a subsequent prediction of the properties of analogues. Computational methods on various levels of complexity are available, enabling us to refine the search results by stepwise reduction of the number of potentially successful catalysts by employing more sophisticated techniques. Nevertheless, it ought to be noted that empirical findings still maintain an inimitable and supreme role. Molecular modelling is doubtless a powerful tool but one needs to appreciate that even models of the highest accuracy are still an approximation and will never yield 100% match. Nowadays, there are thousands of ligands used in asymmetric syntheses and millions of further possibilities. Nonetheless, the reader is advised to note that this chapter concentrates on those used in asymmetric hydrogenation. Ligands used for asymmetric hydroformylation, hydrocyanation, reductive amination, allylic alkylation, hydrosilylation etc., are not covered. Occasionally, however, some of these are mentioned as explanatory references that may be applied to all ligands, including those for hydrogenation.

HISTORICALLY IMPORTANT CHIRAL LIGANDS

Phosphorus A Foundation Stone of Asymmetric Synthesis
The aim of this chapter is to outline the progression in asymmetric catalysis involving phosphorus, as this ligand class undeniably belongs to the most important compounds used for reduction of prochiral alkenes and ketones in particular. If it were not for the first phosphorus-based ligands, the branch of asymmetric synthesis might not exist to the contemporary extent at all. [2] The most important ligands, which formed the very foundation depicting the development in this field within the past decade, are presented below. The origins of successful chiral ligands date back to 1971 when Kagan and Dang introduced the bisphosphine chelate DIOP 1 [3] possessing C2 scaffold chirality. Independent of this work, Knowles et al. discovered the monophosphine CAMP ligand 2 [4] which enabled a comfortable synthetic procedure of L-DOPA, the most extensively-used drug for clinical treatment of Parkinsons disease. Knowles, well aware of this ultimate discovery, readily developed a structural analogue DIPAMP 3 [5] which was soon synthesised on an

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129

industrial scale the famous Monsanto L-DOPA synthesis. These two ligands prosper from phosphorus atom chirality and surprisingly, since their introduction, not many monodentate ligands had emerged by 2000. In 1977, Fryzuk and Bosnich prepared a very simple yet potent C2-symmetric diphosphine CHIRAPHOS 4. [6] Incorporated in a Rh complex, CHIRAPHOS proved very selective in -N-acylaminoacrylic acids hydrogenation.

O O

P PPh2 PPh2 P MeO Me P OMe

PPh2 PPh2 (R,R)-CHIRAPHOS 4

(R,R)-DIOP 1

OMe CAMP 2 (R,R)-DIPAMP 3

Figure 1. The pioneering phosphorus chiral ligands.

In 1980, a huge step forward was made by Noyori et al., [7] who presented the axially chiral BINAP ligand 5. This synthesis was successful only thanks to the persistence of the Noyori group as their discovery was preceded a 4-year search for the best procedure. [8] The introduction of this bisphosphine ligand (Figure 2) substantially extended the range of alkenes possible to hydrogenate, namely the noteworthy syntheses of naproxen, [9] -tocopherol, morphine or dextromethorphan, all of these being widely-used pharmaceuticals. Additionally, reduction of functionalized ketones afforded valuable products, in particular carbapenem [8] and levofloxacin antibiotics, to name the most significant. Selective catalytic hydrogenation of simple ketones, however, still remained unapproachable due to the lack of Ru-binding heteroatoms in the substrate structure. This only became possible after the introduction of the RuII XylBINAP-diamine and TolBINAP-diamine systems [10] (6 in Figure 2), the diamine being DPEN or DAIPEN. The true rationale behind this advancement was a path-breaking metal-ligand bifunctional mechanism [11] which did not require the substrate to bind to the Ru centre directly, and could thereby proceed without the need for the substrate to contain Ru-coordinating structures. For example, the new system allowed a convenient synthesis of a potent antidepressant (R)-fluoxetine. [8] Interestingly, BINAP is able to operate both on RhI and RuII coordination centres, yet with the opposite stereoselectivity owing to different reaction pathways. [12] In 1991, Burk [13] added BPE 7 and DuPhos 8 to the expanding ligand collection for prochiral alkene reduction using Rh catalysts. These ligands (Figure 3), belonging to the bis(phospholane) group, were the first representatives possessing the rigid phosphocyclic structure which proved to be very powerful in terms of enantioselectivity of the complex. As a result, many analogues emerged which are mentioned further in the text. The ferrocenyldiphosphine JosiPhos 9 type of ligand, developed by Togni et al., [14] demonstrated the possibility of applying various substitutions to the phosphorus atoms, thus optimizing the structure of the ligand to serve a particular substrate.

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Cl Ru P Cl NH2

P PPh2 PPh2

NH2

Ru-diamine-diphosphine (R)-BINAP 5 OMe

Cl PAr2 Ru PAr2 Cl

H2 N N H2

Cl PAr2 Ru PAr2 Cl

H2 N OMe N H2

Ar = 3,5-Me2C6H3: 6a [RuCl2{(R)-XylBINAP}{(R,R)-DPEN}] Ar = 4-Me-C6H4: 6b [RuCl2{(R)-TolBINAP}{(R,R)-DPEN}]

Ar = 3,5-Me2C6H3: 6c [RuCl2{(R)-XylBINAP}{(R)-DAIPEN}] Ar = 4-Me-C6H4: 6d [RuCl2{(R)-TolBINAP}{(R)-DAIPEN}]

Figure 2. Noyoris original BINAP ligand and Ru-BINAP/diamine complexes.

R P R P R

R P R P R

R Fe

PR2 PPh2

R = i-Bu, Ph, cyclohexyl JosiPhos 9

BPE 7

DuPhos 8

Figure 3. Bis(phospholane) and ferrocenyldiphosphine ligands.

BINOL-derived monodentate ligands [15d] (Figure 4) bring a new approach, establishing a whole new family of chiral auxiliaries whose chirality rests on the phosphorus atom rather than the ligand backbone. Although Knowles CAMP has already been discussed as an efficient monophosphine, the real boom in this area started as late as 2000! Soon after Kagan highlighted the importance of research in this area, [16] pioneering structures emerged from laboratories of Pringle, [15a] Reetz [15b] and Feringa, [15c] who introduced monophosphonites, monophosphites and monophosphoramidites, respectively (10a,b,c). Until then, it was believed that chelating ligands were needed to obtain asymmetric induction. The advantages of Rh catalysts bearing monodentate ligands comprise mainly high modularity and straightforward syntheses from cheap precursors. [17] This feature enabled de Vries et al. [18] to implement a high-throughput experimental route for finding the right catalyst. Morever, mixing these ligands together was a very interesting method yielding high enantioselectivity, since they were monodentate and more of them coordinated to the central

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atom at the same moment. Typically, so-called homocombinations occured when only one ligand was used, however one-pot usage of two different ligands (not necessarily 1:1) led to selectivity-enhancing heterocombinations. [19]

O P O R

O P O OR

O P O N

R R'

monophosphonites 10a

monophosphites 10b

monophosphoramidites 10c

Figure 4. BINOL-derived monodentate phosphorus ligands.

Although many monodentate ligands were BINOL-based, some noteworthy alternatives were available (Figure 5), as in the case of Me-SIPHOS 11 developed by Zhou [20] (2002), which was a very powerful tool for -aryl enamide asymmetric reduction. Additionally, Helmchen [21] introduced in 2002 a bulky phosphane derivative 12 capable of highly selective itaconates hydrogenation. The structure of diazaphospholidines 13 [22] manifested a great deal of creativity; a recent derivative (discussed below) performed extremely well in an acrylate reduction, regardless of the fact that this ligand was not originally intended for hydrogenation reactions.

O O

O P H

Ph N P OR N

MeSIPHOS 11

12

13

Figure 5. Non-BINOL monodentate phosphorus ligands.

Ligands Used in Asymmetric Transfer Hydrogenation

In 1995, Noyori et al. [23] disclosed the pilot catalytic system RuCl(6arene)(arenesulfonyl-diamine) 14 which initiated the development of asymmetric transfer hydrogenation (ATH) as a remarkable branch in chiral synthesis. Up to now, we have only described catalysts used for standard asymmetric hydrogenation (AH) where gaseous H2 was used as the reducing agent. ATH, utilizing organic compounds (IPA, HCOOH/TEA azeotrope) as the source of hydrogen, was yet one step closer to enzymes which naturally utilize designated hydrogenation media such as NAD(P)H or FADH2.

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14 Ar: benzene, p-cymene, mesitylene R: tolyl, 1-naphthyl, 2,4,6-(CH3)3-C6H2
NH2

NHTs

NH2 NHTs

Cl

H N H

Ru N SO2R Ph Ph

15

NHTs NH2

NH2 NHTs

R2 R1 NH OH

16a: R1 = Me, R2 = H 16b: R1 = Me, R2 = Me 16c: R1 = Me, R2 = Bn 16d: R1 = Me, R2 = CH2(C6H4)C6H5 16e: R1 = Ph, R2 = Bn

NH R1 R2 OH

17a: R1 = Me, R2 = H 17b: R1 = H, R2 = Me 17c: R1 = Ph, R2 = H 17d: R1 = H, R2 = Ph

Figure 6. Ru half-sandwich complexes and examples of their auxiliary chiral ligands.

The original catalysts were primarily Ru or Rh half-sandwich species, employing an aromatic ligand and a chelate auxiliary (Figure 6). In the case of Ru, the 6-arene is represented by benzene or its derivatives. [24] The number of options started to grow intensely with the evaluation of all utilizable chiral auxiliaries. Many of them have been tested, i.e. from the original N-sulfonylated 1,2-diphenylethylenediamines [25] (included in 14) to various diaminoindanes 15, [26] -amino alcohols 16 [27] or 2-azanorbornyl alcohols 17. [28] However, all of these performed well only in the ATH of aromatic ketones. An example of an aliphatic ketone ATH is presented further in the text. The authors were of the opinion it was beneficial to the readers to provide a concise historical review of the evolution of ligands capable of asymmetric reactions catalysis. It should by now be obvious that the pool of fundamental structures, serving nowadays as a brainstorm source, is truly voluminous. Since the reader at this point should have at least a basic knowledge of how such structures could be approached, the following text proceeds to the chiral ligand rational design.

RATIONAL DESIGN OF CHIRAL LIGANDS

Since their discovery, aforementioned ligands have been modified extensively by means of rational design. The systematic approach attempts to categorize (and individually quantify) all possible changes that can be made to the original structures. Commonly adverted sites have been the steric surroundings of the donor atoms (usually P, N, O), the backbone profile, the angle formed by the donor atoms and the central atom etc. (see Figure 7). Although these parameters influence one another to a certain extent, causing an obstacle to a systematic assay, this approach has remained a popular and promising way for a ligand enhancement, especially when followed by proper analytical methods. In the next section, relevant alterable parameters are described and real examples provided.

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Figure 7. The main features of a ligand: backbone, donor atoms (labelled D) and their substituents (R).

The ligands steric and electronic properties can be modified in several ways: 1) the backbone, 2) substitutions at the ligating sites, 3) changes contributing to the firmness of the scaffold, but not affecting the donor atoms positioning, and 4) major adjustments affecting the angle between the ligand atoms and the metal. In the following section, this is discussed in detail.

1) Substitutions on the Backbone

The main backbone framework can be extended in specific directions, thus shaping the active site cavity for the substrate. Protruding substituents are able to retain the substrate molecule in a specific position, favouring the transition state leading to the desired enantiomer. The substitution may also evoke a transfer of electron density which is further discussed in a separate section. Below, a few examples of backbone substitution are presented. A superb example of this is the improvement of BINAPO 18 by introducing ortho- aryl substituents to produce o-BINAPO 19 [29] (see Figure 8). Molecular modelling revealed [30] that most probably, the additional aromatic rings hindered the phenyl groups on phosphorus atoms (in Figure 8 displayed with arrows), which made the ligand less flexible. BINAPO, a rather ineffective ligand compared with others of its kin, was thus improved to the much more effective o-BINAPO. Monodentate ligands derived from a BINOL skelet (Figure 9) have also been subject to research in this category. Interestingly, ortho- substitution has been examined in two different versions. Reetz and co-workers introduced a number of different substituents into the position 3, but not to 3', changing its symmetry from C2 to C1 and adding a second stereogenic centre onto the phosphorus atom. This way, novel diastereomeric ligands 20a,b,c were identified, giving excellent ee values whether pure, or mixed diastereomerically. [31] By contrast, Zhang [32] inserted phosphine substituents into both 3 and 3' positions, increasing the number of P atoms in the molecule from one to three. It should be noted that these phosphinephosphoramidite ligands 21 are bidentate, with the third phosphorus atom left unbound.

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R Ph O PPh2 O PPh2 O P Ph O P Ph Ph R BINAPO 18 o-BINAPO 19 R = Me: Me-o-BINAPO R = Ph: Ph-o-BINAPO R = 3,5-Me2C6H3: Xylyl-o-BINAPO

Figure 8. BINAPO and o-BINAPO.

OR O P O N Me O R = Me, Bn, Bz 20b Me O P N OR

R = Me, Bn, Bz 20a

R O P O N Me Me

PPh2 O P O PPh2 21 N R R = Me, Et R

20c

R = Me, Ph, SPh, SiMe3, Si(Ph)3

Figure 9. Ortho- substituted BINOL ligands.

2) Substitutions on the Donor Atoms

The steric effect of the donor atom substituents is basically similar to the backbone substitution, i.e. to hold the substrate molecule in the optimal position enabling the desired enantioface differentiation. However, the residues may be electron-donating or electronwithdrawing, which naturally affects the electronic properties of the ligand; this is further analysed in a separate section. Several examples are discussed below to point out the diversity of donor atom substitutions. Phosphorus monodentate ligands 10 can bear a variety of R- groups at the donor site. Originally, these were relatively simple as Me, Et, i-Pr, Ph etc. Gradually, more special alternatives have emerged (Figure 10). The laboratories of Chan et al. [33] came up with an inventive idea introducing a ferrocenylphosphine group, thus giving birth to highly versatile phosphine-phosphinites and phosphine-phosphoramidites 22. These ligands performed outstandingly in reducing -dehydroamino acid derivatives (ees up to >99). Moreover, 22a exhibited the advantage of improved air and water stability over the original phosphinite

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which allowed much a more comfortable usage. The introduction of the ferrocenylphosphine group has also been studied by other research teams. [34] A different approach was taken by Zheng et al. who successfully applied carbohydrate substitution to the monophosphite backbone. [35] His D-Mannitol derivative ManniPhos 23, benefiting from an inexpensive facile synthetic procedure, displayed excellent enantioselectivity in reduction of various functionalized olefinic substrates. As these examples represent only a fragment of possible substitutions, a curious reader may find more in the relevant literature. [36] Alongside the BINOL-based monodentate molecules, extremely stable diazaphospholidines were reported by Gavrilov and co-workers. [37] From these multipurpose ligands, a noteworthy adamantane-1-ol derivative 24 proved to be a highly selective ligand in methyl 2-acetamidoacrylate Rh-catalysed hydrogenation, demonstrating that adamantane also possessed qualities of a valuable structural component in modular ligand design.
Ph O P O X Me PPh2 Fe Ph 22a X = -N(Me)22b X = O O O

OR

O O

O O

O P

ManniPhos 23 Ph N P O N 24

Figure 10. Innovative donor atom substitutions on monodentate phosphorus ligands.

3) Changes Towards Rigidity

BPE 7 and DuPhos 8 represent perfect examples of a backbone structural modification leading to a similar, yet more sterically-constrained product. Comparing these two structures (Figure 3), one would draw the conclusion that BPE is rather flexible within the ethylene region, whereas aromatic DuPhos is built more rigidly. Although BPE shows excellent results regarding selectivity, DuPhos performs even better on the same substrate series, [13] most probably thanks to the enhanced rigidity of the backbone. In general, structural rigidity has proven extremely good for stereoselectivity which led Zhang et al. to the development of a phosphabicyclic ligand PennPhos 25, [38] capable of highly selective reductions of simple ketones, cyclic enamides and enol acetates. Many other ligands utilizing the phosphorus chirality together with phosphacyclic structural rigidity have been introduced by this group (see Figure 11 for a few examples), [39] where BINAPINE 29 [40] belongs to the most remarkable ones.

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Me Me P Me Me (R,S,R,S)-Me-PennPhos 25 P P

HH HH P t-Bu P t-Bu TangPhos 26 P t-Bu t-Bu

DuanPhos 27

Me N P

Me P

P N Me

t-Bu t-Bu

Me

Me Me bis(azaphosphorinane) 28 BINAPINE 29

Figure 11.Zhangs phosphocyclic ligands.

Regarding ATH ligands, their structure can be reinforced using an additional covalent bonded bridge between the 6-aromate and sulfonyl group of the chiral ligand [41] (30a in Figure 12), thus preventing the aromatic ring from its rotation. As a result, there is only one, pocket-like ligand with a fairly fixed conformation. Moreover, the tether may also be directed to the other end of the diamine. These so-called reverse-tethered catalysts (30b in Figure 12) displayed a higher activity in comparison to the original non-tethered structures. [42] The last example to be mentioned (30c [43]) harnesses an improved tether structure containing a benzene ring. Furthermore, the ligand includes another six-membered ring connecting the donor atoms, which in combination with the revamped tether enables superior structural rigidity, affording distinct asymmetric induction. A wide palette of enantiopure substrates was prepared using a Rh complex containing this ligand, where cyclohexylmethyl ketone (ee 87 %) was of a particular interest given the fact it was an aliphatic substrate.

SO2 Cl Ru N H N H Ph Ph 30a
Figure 12. Tethered catalysts for ATH.

Cl H

Ru N Ph 30b

Ts Ts Ph N

Rh N H

30c

4) Major Changes to the Backbone

Changing the length or conformation of the backbone leads to a different positioning of the donor atoms towards the metal centre, which most probably dramatically affects the

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complex properties. There is no universal and exact way of measuring the steric qualities of a ligand, however, a number of approximations exist that enjoy popularity. Naturally, each of them has its own optimal area of usage based on the models they are based on. In the next section, the most familiar ones are discussed in detail (i.e. the cone angle and the natural bite angle) and other reported steric descriptors briefly described.

The Cone Angle The cone angle (Figure 13a), mostly suitable for axially symmetric monodentate phosphines, was first implemented by Tolman. [44] Its definition is based on a space-filling model of a Ni-PR3 complex, where the Ni-P distance is fixed at 2.28 . In the case of general unsymmetrical ligands PR1R2R3, three semicone angle values (i/2) were separately measured, averaged and doubled, which afforded the as well (Figure 13b). Ferguson et al. [45] complemented the concept by introducing the so-called ligand profiles for bulky phosphines, allowing another useful measure of the ligand shape all the way round. It needs to be said that every coordination centre has its own typical M-P bond length meaning that the application of the cone angle to complexes of other metals should be considered. However, the cone angle is still being used very often for its simplicity, high reputation and good agreement with factual data. Therefore it is not surprising that Tolmans extensive review [44] belongs to the most cited Chem. Rev. articles.

Figure 13. a,b) The cone angle ; c) The bite angle n; d) Comparison of and n on a chelating ligand.

There are two ways to obtain a cone angle value. From an X-ray analysis, [46] one can deduct the value with reasonable accuracy, however, a solid crystalline sample is required. Since the angles in a crystalline substance may (and usually do) differ from those in a solution, which are the conditions where the ligands actually operate, a computational

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approach is often preferred as a convenient method for finding conformations representing the true energy minima, which are more likely to exist in a solution. An example of this can be found in a recent paper by Gavrilov et al. [37]

The Bite Angle The cone angle may be used for the evaluation of chelating ligands, [47] although a different approach is preferred since the sterical description of phosphorus chelating ligands by the cone angle is not often very conclusive. Bidentate ligands are seldom round shaped and thus the cone angle is often not a precise measure. This is the reason why the natural bite angle is preferred (n in Figure 13b,c). Its definition is as follows: The natural bite angle is the preferred chelation angle determined only by ligand backbone constraints and not by metal valence angles. [48] Therefore, this concept does not depend on the selection of the transition metal. An important feature is that adjusting the bite angle, one may observe significant differences both in activity and selectivity of the catalyst. [49] It has become a very important parameter of the backbone steric properties and several real applications are presented below to highlight its significance. TunePhos 32 [50] is a textbook example of adjusting the bite angle (and smart ligand fixation as a bonus), as illustrated in Figure 14. Stemming from MeO-BIPHEP 31, Zhang et al. appended an alkanediyl bridge to this structure (C1 to C6 long), discovering direct correlation between the bridge length and the ligand natural bite angle. It has been demonstrated that every substrate favours different bite angle range. [39] Another clear and convenient way of ligand optimization was thus invented.

MeO MeO

PPh2 PPh2

( H 2C ) n
O

PPh2 PPh2

(R)-MeO-BIPHEP 31

(R)-TunePhos 32

Figure 14. Original MeO-BIPHEP. TunePhos bite angle variability.

However, the aforementioned bonus in the form of the ligand fixation is necessary to achieve the selectivity, as demonstrated in the following example. Figure 15 depicts MiniPHOS 33, [51] Bis-P* 34 [52] and substituted 1,3-bis(phosphino)propane 35, the only difference between each being the backbone length the longer the chain, the more active the catalyst obtained for dehydroamino acids reduction. Nevertheless, ligand 35 displayed very poor selectivity (14 % ee) in contrast to 33 and 34 which both showed outstanding results (99.0 and 99.9 % ee, respectively). [53] This was due to the four- or five- membered constrained chelate cycles these ligands formed with the metal. The atropisomeric structure of BINAP, BINAPO, TunePhos and others provided the necessary stabilization of the sixmembered ring formed upon complexation. Hence, the ligand backbone rigidity should not be omitted when experimenting with the bite angle, although exceptions to this exist. [54]

Rational Design of Chiral Ruthenium Complexes

t-Bu P Me P Me t-Bu t-Bu P Me P Me t-Bu t-Bu P Me 35

139
P Me t-Bu

(R,R)-MiniPhos 33

(S,S)-BisP* 34

Figure 15. MiniPHOS, Bis-P* and bis(phosphino)propane structures.

A major change to the backbone moiety, although not affecting the bite angle, could be observed in the structure of a monodentate ligand 36 derived from H8-BINOL, as displayed in Figure 16. The Rh-H8-MonoPhos catalyst offered excellent selectivity in asymmetric enamide reduction, mostly 3% higher than in the case of original MonoPhos (i.e. 10c possessing the NMe2 heelpiece). [55]

O P O N

R R'

R = R' = Me or Et R = -CH(Me)Ph, R' = H or Me R + R' = -(CH2)4-

H8-BINOL 36

Figure 16. H8-BINOL ligands.

Other Steric Descriptors In some cases, the above descriptors are less suitable for characterizing the ligand steric requirements. For this reason, further descriptors are provided in the following text, regardless of their special burden related to their empiric dependency. One theoretical approach, in particular the MESPsteric parameter, is mentioned further in the text, i.e. at the end of the electronic parameters subsection, as the method is mainly oriented towards the electronic properties and this steric parameter followed as a consequence. Koide et al. defined the pocket angle [56] for chelating phosphorus ligands as an alternative to the cone angle used preferentially for monodentate ligands. This method similarly utilizes CPK models obtained from crystallographic data. Perpendicular (||) and parallel () pocket angles were established so as to completely describe the non-conical bidentate ligand. White and co-workers introduced an interesting solid angle () concept [57] which is based on projecting the ligand atoms on the inside of a unit sphere as depicted in Figure 17. The metal is considered a light source and the solid angle is then calculated from the shadow area cast upon the sphere. In addition to the aforementioned ligand profile, White simultaneously proposed a radial profile [57b] as a plot of dependence of on the P-M distance. Radial profiles comparison has enabled further analysis of the ligand steric requirements. A recent paper by Guzei [57c] represents a good complement to this topic with some improvements included.

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Fi igure 17. The li igand projection n used for solid angle () calcu ulation.

Recently quite q popular, the S4' steric parameter wa as first introd duced by Orpe en [58] and us sed as a descr riptor by Cund dari et al. [59] For the mode el complex M-PXn, S4' can be worked ou ut easily as a difference bet tween (<M-P-X) and (< <X-P-X). Ther refore, the S4'' parameter ca an be obtained d directly from m crystallograp phic data using only the cor rresponding bo ond angles, w which makes it very user-fr riendly. Under rstandably, co omputational attempts a have e also been re eported on bo oth full DFT T and ONIOM M [60] de esignated DFT T-S4' and ON NIOM-S4', ac ccordingly (co omputational methods m are di iscussed furth her in general). .

Fi igure 18. Harve eys He8_ring (a a) and He8_wed dge (b). The par rentheses repres sent a general sp pacer or the pr resence of two monodentate m lig gands.

Figure 18 displays d an alt ternative to the e cone angle established e by Harvey and co-workers c . They introduce ed the He8_ste eric parameter r [61] which simulates s spac cial interaction ns between th he monodenta ate ligand in question q and other o ligands in cis configu uration in an octahedral co omplex. Also known as the He8_ring, a planar p He8 cyc cle of a constra ained radius (2.5 ( ) was pl laced opposite e the phospho orus atom at a fixed distanc ce of 2.28 and the whol le structure op ptimised, start ting with a pre e-optimised fr ree ligand geo ometry. The in nteraction energy (which is s in fact repres sented by the He H 8_steric des scriptor) between the ligand d and the He8 auxiliary a is al lmost exclusiv vely of a steri ic origin as th he He-P distan nce (3.383 ) exceeds the sum s of van de er Waals radii i of the two ato oms (3.2 ), which w is the re eason why ele ectronic contributions are

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almost negligible. A similar concept, called He8_wedge, has been soon afterwards developed for P,N bidentate ligands. [62] In this situation, it turned out to be more convenient to fix four He atoms (strictly speaking, every second atom of the eight-membered ring) in the ligating sites of an octahedral complex in a fixed 2.28 distance from the transition metal. The angles between He atoms were constrained at 90/180 values and the starting ligand geometry was adapted from a tetrahedral zinc complex. After setting the donor-metal distances P-M, N-M (2.28 and 2.00 where possible, or the shortest possible distances for ligands where this could not be accomplished), the metal was deleted and the resulting structure optimized. The practical usage of these parameters is further discussed in this text.

Computational Methods
Before the electronic descriptors are presented, a general outline of computational approaches is provided. Theoretical chemistry offers a variety of tools that may be utilized to obtain the descriptor values and thus molecular modelling of such systems can be carried out using molecular mechanics, semi-empirical or DFT levels of theory. Pure ab initio computing comes into question merely in the case of the simplest phosphines due to its enormous hardware requirements and employing DFT counts with reasonably small molecules and a well selected basis set. [63] Consequently, one probably chooses the level of theory according to their computational resources, the system investigated and the accuracy aspired. Nowadays, most of the ligands can be computed on the semi-empirical or even DFT level, owing to technological advances in computing centres. However, large biomolecules, representing another quickly evolving field of rational design, still have to settle for molecular mechanics or molecular dynamics. [64] An illustrative comparison of QM (MINDO/3, MNDO) and MM (MM2) was presented by Chin et al., [65] however these model phosphines were not actually real ligands used in asymmetric synthesis.

Electronic Ligand Descriptors

Having described the steric parameters of ligands, it is necessary to give an account of descriptors concerning their electronic properties. Since these can actually be applied to all structural changes, it has been described at the end of this subsection, while the account of the sterical descriptors was given more conveniently together with the backbone adjustments. Parallel to steric descriptors, there are several pioneering concepts among the electronic ones, followed by certain advanced successors. In a chronological sequence, the descriptors based on experimental work are first demonstrated, while the section is concluded with an overview of computationally accessible parameters. In his landmark work, [44] Tolman investigated a large series of PR3 ligands incorporated in a [Ni(CO)3PR3] model complex and ranked them according to CO(A1) in CH2Cl2 solution, defining the Tolmans electronic parameter (TEP) scale. A direct correlation was shown between the stretching frequency CO(A1) and electronic properties of the phosphine ligand. Electron-donating R groups increase the phosphine basicity, causing electronic enrichment of the metal and subsequent transfer of electron density into the CO s* antibonding orbital. Naturally, this weakens the CO bond and its stretching frequency decreases. On the TEP

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scale, the most basic phosphine P(t-Bu)3 was selected as a reference ligand in the Ni complex (with the A1 band of 2056.1 cm-1) and other phosphines were related to [Ni(CO)3P(t-Bu)3] through the parameter . Crabtree [66] generalized this approach and showed that, as a matter of fact, any carbonyl-containing complex may be used in the TEP scale. Tolmans system was insufficient for complexes with two cis-configured phosphine ligands/a chelating ligand, so Crabtree employed a cis-[Mo(CO)4L-L] complex to measure CO(A1) and designed a formula which enabled a conversion of these values onto the original Ni-complex based TEP scale. Therefore, every complex may possess its own scale, which can be chosen according to the ligand requirements, however an interconversion is possible between these scales. [67] The Lever electronic parameter (LEP) [68] is a useful alternative to those experimentally obtained by IR spectroscopy. Considering Mn/Mn1 redox potentials to be fully additive, Lever defined the LEP parameter as 1/6 of ERu(III)/Ru(II) potential for RuL6 in acetonitrile. Similarly to TEP, his extensive list of LEP values for over 200 ligands has also been used as a benchmark for validating theoretical methods. [73,74] Among alternative experimental ways of investigating the phosphine basicity is the usage of 13C NMR spectroscopy. Chemical shifts of carbons from CO ligands in various complexes were found to be affected by the presence of other donor ligands. Taking advantage of those central atoms which are also NMR active nuclei, coupling constants (1JPB, 1JPSe, 1JPPt, 1JPW) were studied as well. While these coupling constants were found to be related to the corresponding bond strength (and to P basicity, accordingly), the 1JPC constants did not seem to be linked to the phosphorus basicity at all. [67] Regarding the basicity, one would have obviously expected some kind of experimental pKa or pKb studies. Indeed, pKa values of conjugated acids to a series of PR3 tertiary substituted phosphines were measured e.g. by Allman and Goel, showing a fine correlation with the electronic data. [69] However, these experimental models exhibited one or more major drawbacks which provoked others to come up with improved solutions. Firstly, electronic properties of the ligand were our target, while these methods afforded only indirect results via a certain complex. Secondly, the overall electronic effects of the ligand (described by Tolmans electronic parameters) were a sum of two opposite phenomena the -donation of the phosphorus lone pair into the metals vacant orbitals, and the -backdonation from the metal to an empty orbital of the phosphorus atom (arguably * [70]). Considerable efforts have been made to isolate these two factors, revealing the complexity of this problem. Giering and co-workers proposed an appreciable concept, [71] where the phosphines were distributed into three classes: -donor/-donor, -donor and -donor/-acceptor according to correlation of EL' of Mn and Fe complexes with pKa values of the phosphines in question. Afterwards, they came up with a sophisticated quantitative analysis of ligand effects (QALE), [72] stepwise establishing three parameters describing the electronic properties of phosphines. These parameters were d (representing donor ability), p (characterizing acidity) and Ear, whose notation stemmed from its original purpose of an aryl effect description, although its role is now considered operative even in non-aryl substituted phosphines. The next focus is on theoretical investigative methods which are invaluable in the field of ligand design due to the experimental unavailability of required data and an appealing possibility to predict ligand properties. As an analogue to TEP, Crabtree reported the computed electronic parameter (CEP) [73] using frequency calculations on a DFT level of theory. Since DFT frequency jobs investigating bulkier phosphines tended to be

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computationally very demanding, Cundari and co-workers [74] devised a semi-empirical quantum mechanical approach allowing a wide range of feasible calculations. Having had a good agreement with TEP, LEP and CEP, their semi-empirical parameter SEP turned out to be a highly suitable computational option for quick in silico testing. Having followed these simple analogues to the original works of Tolman, more advanced methods were developed. The findings of Suresh and Koga, [75] who have established the convenient molecular electrostatic potential (MESP), i.e. a computational method consistently describing electronic properties of substituted phosphines (PR3), presented a handy example relevant to this topic. The MESP approach did not require any experimental background and therefore could also be used to predict the properties of new structures in silico. It was the bare ligands that were evaluated, eliminating any influences of a complex species. The key idea was finding the global minimum Vmin of MESP pertaining to the lone pair region of the phosphine ligand, which was exactly the area of interest as the lone pair electron density was connected to the phosphine basicity. Similarly to Tolmans ranking, P(t-Bu)3 showed the highest -donating power by having the lowest Vmin value. PH3 was included as well to set up a reference point of unsubstituted phosphine; if electron donating groups were present, Vmin value decreased and vice versa. Moreover, the results fairly correlated with Tolmans CO(A1) scale, pKa of PR3 conjugate acids, E of a complex formation reaction and finally H and E for an iron complex redox reaction (FeII/FeI). In 2006, a noticeable attempt was made by Suresh [76] to separate electronic and steric properties, again using the MESP computational concept. ONIOM method was used to achieve this: the surroundings of phosphorus atom (in each case bearing the hydrogen atoms, i.e. PH3) were calculated using a DFT level of theory, while the R groups were treated with molecular mechanics. In this configuration, the positioning of the link hydrogen atoms of PH3 depended on the steric requirements of the neighbouring R groups. This tampering with the phosphine bond angles affected the p-character of the lone pair, enabling the steric effect of the phosphine substitution to be observed. Evidently, the number of ligand steric and electronic descriptors is significant and only a limited selection is presented here. For this reason, the interested reader is encouraged to study cited literature for more ligand descriptors. [77]

Reaction Mechanism Analysis

This chapter would not be complete without an account of the mechanistic aspects of asymmetric catalysis. Profuse works have been dedicated to this field in order to understand the reaction mechanisms, yielding an invaluable expertise in the form of highly detailed information on the very nature of the catalytic process. In the following text, the computational analyses of the transition states (TSs) are described, and a rationale of the origin of enantioselectivity is included, albeit in a very brief form. DFT analysis of transition states (TS) is discussed as well as some computationally cheaper approaches which may partially or completely avoid costly QM calculations. The investigation of the full catalytic cycles is not covered within this text given the complexity of the problem. Describing the relative positioning of the molecules (i.e. substrate and catalyst) during TSs explains its relation to the reactions enantioselectivity. When a prochiral substrate is present in the chiral environment of the catalyst, certain options for its approach to the

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complex are more sterically and electrostatically [78] favoured than others. Every route is then followed by a more or less probable diastereomeric TS. The successful ligands used in AH and ATH are chiral rigid molecules which strive for the reaction to proceed preferentially via the favourable TSs leading to the desired enantiomer. The energy difference between the favourable and disfavourable TSs determines the reaction ee and is temperature dependent. [79] In other words, raising the temperature leads to a stereoselectivity decrease. The quadrant approach has been the most utilized one for TSs analyses. The space surrounding the catalyst is divided into four equal quadrants and the entire problem is thus more systematic. Some catalysts, like 14, are designed advantageously to fully occupy three quadrants, so as to disallow formation of TSs within these regions. In such a case, TSs may be explored computationally in detail thanks to their limited number. However, others are much more complicated, like e.g. BINAP with 68 possible TSs. [80] As the quadrant approach has already been well described, relevant literature is cited. [53,81] If only a few TSs are likely to form for structural reasons, thorough computational analysis on a DFT level is feasible on contemporary resources, as long as the molecules are not too big. Although such a quantum-mechanical approach yields very precise outcomes with respect to geometries, better methods, like MP2, should be used for energy calculations. Despite the extreme usefulness of such accurate results, these can really be obtained by investigating a rather small catalytic system. For larger molecules, alternative procedures need to be employed. The QM/MM method is the most popular way of reducing the computational resource needs, [82] dividing the entire system into sub-areas treated by different tools. The active catalytic site is thus modelled by QM methods due to higher accuracy requirements, especially regarding electronic properties, while the surroundings are treated by MM, which afford results good enough since these parts of the system are mostly sterically governed and their description by a force field is sufficient. Another possibility, developed by Norrby, [83] allows TSs analyses merely on a MM level. This method is called QM-guided MM (Q2MM) and employs custom force fields derived from previous QM calculations. An important feature of Q2MM is that these modified force fields actually allow the TSs to be calculated as energy minima, which can be accomplished with ordinary MM methods. The process of the substrate approaching the catalyst can be modelled as well, [84] revealing the differences between the four quadrants. Such an analysis may provide us with useful reasoning as to why the reaction does not take place through a TS within a certain quadrant, while in others it proceeds with high activity and/or selectivity.

CONTEMPORARY TRENDS IN CATALYST DESIGN

In an ideal world, it would be possible to predict catalyst properties for a certain stereoselective reaction entirely in silico. Even though the reality is still far from this prospect, promising attempts have recently been emerging, proposing sagacious routes for ligand computational screening by employing state-of-the-art research technology. Although these prototypes have not yet been implemented into a routine use, they will certainly facilitate the development of subtle techniques useful in ligand design.

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A successful solution requires solid foundations applicable to a broad variety of situations. Obviously, this is mostly conditional on a proper application of the knowledge obtained by investigating the ligand steric and electronic descriptors, which has already been outlined. Already the fact that such a large-scale ligand screening combines several techniques of limited accuracy (i.e. choice of descriptors, the computational level of theory) implies that the entire process is rather delicate and every component should be wellconsidered to reach the required robustness. The idea of a ligand map has been brought into play, showing that within a certain region of the map, functionally similar ligands should reside. This was already broached by Tolman [44] who plotted CO vs. and showed characteristic areas of differently substituted ligands (e.g. P(OR)3 and aliphatic PR3 only occurred in certain areas, each of their own). Then he added a third parameter (generally denoted Z), which would depend both on and CO, and obtained a 3D landscape revealing the ratio of and CO effect on Z in a slope-shaped manner. This way, Tolman was e.g. able to elegantly demonstrate that 13C NMR chemical shifts were mainly related to the electronic properties, whereas H for reactions of excess phosphorus ligands with a certain Pt complex proved to be sterically-governed. Although Tolman used corporeal models to manually 3D-plot his results, he showed an invaluable way of ligand mapping. Consequently, with a reliable set of descriptors and solid framework, more precise ligand space reference points could be established. Here, we give an account of the most recent attempts. Cundari and co-workers [59] developed Tolmans primary ideas and presented stereoelectronic phosphine maps based on MM/semi-empirical calculations. Their conclusion was that alkyl and aryl phosphines were surprisingly similar in terms of both steric and electronic properties. They identified a gap in the map pertaining to the phosphines with very low basicity, as in the case of e.g. P(t-C4F9)3, and pointed out the unusual qualities of cyclic phosphines which expanded the map to a considerable extent.

Ligand Knowledge Base

In 2006, the group of Professor Harvey [61] came up with a set of computational descriptors of monodentate phosphorus ligands which they called the ligand knowledge base (LKB). The target of this project has been an automated global ligand descriptor assemblage, capable of interpreting experimental data and, more importantly, predicting the properties of unknown species. An emphasis was put on careful selection of enough reliable descriptors and proper statistical evaluation methods in order to create a consistent infobase applicable to a variety of molecules. In other words, some descriptors needed to be excluded due to their excessive specificity, low sensitivity or difficult in silico automatization, but at the same time a sufficient number of them had to be utilized to record all important features of the ligands. Since experimental parameters were not uniformly accessible, Harveys group chose to exploit crystallographic databases by means of molecular modelling on DFT level of theory, using both supercomputers and distributed computing Grid methods. A series of 61 representative ligands was used, with the aim of including a wide range of compounds, including symmetric (PA3), asymmetric (PA2B) and several utterly exotic molecules. Given the availability of a wide range of empirical data for monodentate phosphines, a comparison of these with theoretical descriptors was made possible, showing the feasibility of the whole

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concept. Some utilized descriptors were also contextualized with similar but more often used ones to justify their applicability (for example, He8_steric was contextualized with Tolmans , which actually was not used for LKB at all). The ligands were also investigated in both free and in protonated and borane adduct forms. Their Pd complexes were also utilized to obtain information on their electronic properties. In the end, the following decriptors were used: HOMO and LUMO energies, proton affinities, adduct binding energies, NBO charges, geometry descriptors indicating the differences after complexation, and several steric parameters (He8_steric and S4' [58]). As the number of often substantially correlated descriptors was quite high, the so-called principle components (PCs) were derived from the descriptors as their linear combinations. Chemically similar ligands tended to cluster in certain regions of the PC1 vs. PC2 plots, which represented a next step after Tolmans pioneering ligand map. Although the quantitative interpretation of these maps did not prove reliable owing to PCA sensitivity to outlier values, the qualitative information obtained by this method became quite useful. Multiple linear regression (MLR) was also utilized to confirm the correlation between empiric data and calculated descriptors, thus enabling prediction of experimental parameters for unknown ligands investigated computationally. Later, Harvey et al. reported a similar concept applicable for chelating P,P- and P,N- ligands, which they called LKB-PP. [62] They used a similar selection of descriptors but applied some bidentate-related ones as the ligand bite angle or He8_wedge. This way, the first chelating ligand map was proposed. In comparison to the original monophosphine configuration, the usage of linear regression for predictive purposes turned out to be limited due to scarcity of appropriate experimental data.

Three Spaces
Inspired by quantitative structure-activity and structure-property techniques (QSAR, QSPR) commonly used for drug discovery in the pharmaceutical industry, Rothenberg et al. [85,86] showed that in silico screening of even highly extensive libraries could be accomplished without any MM or QM calculations or three-dimensional models. Of course, the simplification in the form of 2D topological descriptors did not offer very accurate results but was sufficient enough for a preliminary exploration of large ligand sets (i.e., over 105). As they pointed out, [86] even the MM level 3D calculations handled only around 100 ligands per hour, while 2D descriptors were able to analyze ca. 100,000 species per hour. This way, potentially useful areas of the ligand space could be quickly discovered and further explored by more accurate methods to actually identify (or predict) the most satisfactory molecules. Nevertheless, their most significant contribution was the development of a complex system for the construction and refinement of virtual catalyst libraries. [87,88] They specified their search to an organometallic catalyst utilising bidentate ligand, which was disassembled to the very basic building units. Consecutively, three multi-dimensional spaces A, B, C were established. Discrete space A comprised all catalyst structures to be explored; each point in the space uniquely determined a different structure; while each dimension in A pertained to a different building block (ligating, backbone and residue blocks). Space A was inherently connected to continuous space B, composed of catalyst descriptors and reaction conditions. Finally, continuous space C was defined to comprise figures of merit (TOF, TON, ee, etc.), enabling efficient catalysts identification. Spaces B and C shared a connection through

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QSAR/QSPR modelling methods and this way, one could observe the desired properties (C) related to the actual catalyst structures (A). This idea represents a major step forward since it has contrived to link the real catalyst performance properties to its structure. Developing and improving such a model is both intriguing and desirable as it can be a very powerful means of catalyst rational design, especially if accompanied by real laboratory experiments.

Simulated Evolution
Very recently, Riant et al. [89] opened another innovative way of computational searching for the best catalysts using simulated evolution. At first, a library of Noyori-type ATH catalysts was assembled and evaluated by means of HTE. Subsequently, a mother generation G0 was brought together from this library either manually or randomly, and utilizing a custom-programmed genetic algorithm, some of the best catalysts were reached evolutionarily, even when using only 10 % of the library for G0 creation. Obviously, the goal of this method is to find the majority of good catalysts in a few generations. If developed further, the simulated evolution might be another promising way of chiral catalyst design. Nonetheless, one should be vigilant in using these methods because, as was succinctly pinpointed by Rothenberg: Just because a program did not crash does not mean that the results are meaningful. [90] Correct statistical data interpretation and thorough validation of the computing models are vital for the models to be both employable and trusted.

CONCLUSION
This chapter has attempted to present a concise insight into the contemporary methods of catalyst design applicable not only to Ru complexes used in asymmetric hydrogenation but also to various other catalytic systems. In order to be able to effectively master the extensive catalyst/ligand libraries and discover new species by reliable predictive models, a robust set of yardsticks is critical to properly describe the ligands and complexes. These descriptors were presented and discussed in terms of their efficacy, reliability and applicability for in silico compound searching. Nevertheless, a cursory computational search may often prove insufficient and fallible, calling for more sophisticated methods as full scale QM calculations or reaction mechanisms analyses. Regardless of the vast availability of the tools exploiting theoretical chemistry, the genuine in silico catalyst design still remains a great challenge. Although computational methods afford an enormous assistance, practical experiments still play the decisive role. Due to an immensely rapid development in this exciting field, only the basic idea of the whole process could be presented, citing the relevant literature for further details. The toolbox for asymmetric synthesis has developed extremely within the past four decades and is still a key area of contemporary research in this field.

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ACKNOWLEDGMENT
The authors wish to acknowledge with gratitude the financial support by the Grant Agency of the Czech Republic (Grant GACR 104/09/1497) and the Ministry of Education of the Czech Republic (Grant CEZ: MSM 604 613 7301).

LIST OF ABBREVIATIONS
asymmetric hydrogenation asymmetric transfer hydrogenation 2,2'-bis(diphenylphosphino)-1,1-binaphthyl 4,4'-di(t-butyl)-4,4',5,5'-tetrahydro-3,3'-bi-3H-dinaphtho[2,1-c:1',2'e]phosphepin BINOL: 1,1'-bi-2-naphthol BIPHEP: 2,2'-bis(phosphino)-6,6'-dimethoxy-1,1'-biphenyl BisP*: (S,S)-1,2-bis(alkyl-methylphosphino) ethanes BPE: 1,2-bis(phospholano)ethane CAMP: o-anisylcyclohexylmethylphosphane CEP: computed electronic parameter CHIRAPHOS: bis(diphenylphosphino)butane CPK: Corey-Pauling-Koltun DAIPEN: 1,1-di(4-anisyl)-2-isopropylethylenediamine DFT: density functional theory DIOP: 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane DIPAMP: 1,2-bis[(o-anisyl)-(phenyl)phosphino]ethane DPEN: 1,2-diphenylethylenediamine DuanPhos: 2,2'-di(t-butyl)-2,3,2',3'-tetrahydro-1H,1'H-(1,1')biisophosphindolyl DuPHOS: 1,2-bis(phospholano)benzene ee: enantiomeric excess 5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diol H8-BINOL: HOMO: highest occupied molecular orbital HTE: high-throughput experimentation IPA: isopropyl alcohol JosiPhos: (R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine L-DOPA: levodopa; L-3,4-dihydroxyphenylalanine LEP: Lever electronic parameter LKB: ligand knowledge base LUMO: lowest unoccupied molecular orbital ManniPhos: monophosphites derived from D-Mannitol Me-SIPHOS: N-Dimethyl-[1,1'-spirobiindane-7,7'-diyl]phosphoramidite MESP: molecular electrostatic potential MINDO: modified intermediate neglect of differential overlap MiniPhos: (R,R)-1,1-bis (alkylmethylphosphino) methanes MLR: multiple linear regression MM: molecular mechanics AH: ATH: BINAP: BINAPINE:

Rational Design of Chiral Ruthenium Complexes MNDO: MP2: NBO: NMR: ONIOM: PC: PCA: PCR: PennPhos: QALE: Q2MM: QM: QSAR: QSPR: SEP: TangPhos: TEA: TEP: TOF: TolBINAP: TON: XylBINAP: modified neglect of differential overlap MllerPlesset perturbation theory of the second order natural bond orbital nuclear magnetic resonance spectroscopy our own n-layered integrated molecular orbital and molecular mechanics principal component principal component analysis principal component regression endo-2,5-dialkyl-7-phosphabicyclo[2.2.1]heptanes quantitative analysis of ligand effects QM-guided molecular mechanics quantum mechanics quantitative structure-activity relationship quantitative structure-property relationship semi-empirical electronic parameter 1,1'-di(t-butyl)-(2,2')-diphospholane triethylamine Tolman electronic parameter turnover frequency 2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl turnover number TS: transition state 2,2'-bis[di(3,5-xylyl)phosphino]-1,1'-binaphthyl

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ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 5

SUPRAMOLECULAR GEL CATALYST: BRIDGING HOMOGENEOUS AND HETEROGENEOUS CATALYSIS

Jianyong Zhanga and Stuart L. Jamesb
a) School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. b) Centre for the Theory and Application of Catalysis (CenTACat), School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, Northern Ireland BT9 5AG, UK.

ABSTRACT
Supramolecular gels have received growing attention in recent years. They represent a novel type of soft materials which may find application in various aspects. Various organogels and metallogels offer rich possibilities for catalysis. Supramolecular gels can be used in catalysis by incorporating a catalytically active unit as part of the gelator. There are three strategies in literature: 1) catalysis by discrete gelators; 2) catalysis by coordination polymer gelators; 3) catalysis by post-modified gels. Unique new catalytic properties can arise from combining gels with catalytically active centres. Interestingly supramolecular gels show enhanced activity compared with their homogeneous analogues in a number of cases. They exhibit some combined advantages of homogeneous and heterogeneous catalysis.

INTRODUCTION
Precisely what is, and what is not, a gel has proved notoriously difficult to define [1-5]. Many, but not all, consist of two continuous phases which interpenetrate on the macroscopic scale [1-10]. All of the examples discussed herein consist mainly of a liquid (e.g. water, ethanol, hydrocarbon etc.) which interpenetrates with a persistent network structure, formed by a second species, the gelator. Although such gels are mainly liquid (often > 97%), they exhibit some rheological properties like those of a solid, for example they are elastic, meaning that after deformation, up to a certain limit, the original shape is recovered [1-2]. The

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apparent contradiction between their mainly liquid constitution, but solid-like rheology, is due to the persistent character of the network, and its attraction to the liquid, which prevents the liquid constituent from flowing freely (although the molecules of the liquid continue to diffuse throughout the structure). The network structures are often made up of fibres. These propagate and interconnect, or entangle, within the liquid phase. Many supramolecular gels form reversibly. For example, heating can cause a change to a simple liquid phase (sol) and subsequent recooling can reform the gel. The temperature at which the transition occurs is the gel point (Tgel). Various classifications of gels are commonly used. Gels formed by changing the temperature are called thermotropic. Those formed by changing the concentration of the gelator are called lyotropic. When the connections within the network are strong (e.g. predominantly covalent bonds, or due to strong entanglement), this can lead to so-called strong gels. Characteristically, such gels exhibit sharp, well defined gel points. Where network connections are weak, or due to easily disrupted entanglement, this can lead to weak gels. These typically do not have sharp gel points [3-5]. Both strong and weak gels can be reversible. Gels with networks which are maintained by covalent bonds, and which are not reversible, are often termed chemical gels. Gels which have networks maintained by weaker intermolecular forces (and are normally reversible) are termed physical gels [9]. Distinction is also often drawn between gels based on aqueous phases (hydrogels) [10] and those based on organic phases (organogels) [7, 8]. The gelators themselves may be polymers, or inorganic particles [1-2]. Alternatively, small molecules can also gelate by aggregating into fibres within the liquid phase [3-10]. This type of supramolecular self-assembly can occur through solvophobic effects, hydrogen bonding, metal coordination, van der Waals attraction etc. Alongside the general development of supramolecular chemistry, the study of such small molecule gelators (often called low molecular weight gelators, or LMWGs) has increased greatly in recent years. Like protein, a gel has a primary (angstrom to nanometer scale), secondary (nano- to micrometer scale), and tertiary structure (micro- to millimeter scale) (Figure 1). The primary molecular level recognition promotes the aggregation of the gelator molecules, the aggregation forms the secondary structure, such as fibres, micelles, sheets, vesicles and so on, and finally the secondary aggregates are entangled to form the 3D tertiary structure to trap solvent [10]. Hydrogen bonding is believed to be a common driving force for aggregation of gelators in organic solvents via forming 1D hydrogen-bonded network, while in protonic environments, solvophobic effects are more important to protect from solvent. However, metal coordination is expected to play a key role in metal-containing gels. Metal coordination may be employed to form 3D matrix when a metal complex is a gelator, and normally does not disrupt the gel network when a gelator gelates metal-containing liquid. Other metalrelated interactions like metallophilic attraction are also important for the primary aggregation in gels. It is still difficult to predict whether a gel phase will form from knowledge of the molecular structures of a liquid and a potential gelator. The molecular organization within the fibres of a gel may be crystalline, and, for example, give rise to X-ray diffraction patterns [11]. The difficulty in predicting gelation is therefore related to the difficulty in predicting crystal structures, which is considerably complicated by polymorphism or supramolecular isomerisation and relies on understanding the selection of a given supramolecular molecular packing mode [12]. However, gels are potentially more complex to understand since they are

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often based on two components and the interaction between the liquid and the gelator also needs to be understood. A gel may be thought of in some ways as a failed crystal, because propagation has occurred predominantly in only one direction (if it is based on fibres) and prevented in the remaining two. Due to the difficulty in predicting gel phases, many gels are still discovered serendipitously. However, as will be seen below, certain families of gelator molecules have emerged, and to a degree, their structural features (e.g. urea-type groups etc.) may be incorporated into the design of new gelators with a degree of optimism and rationality. In this regard, it is also worth mentioning that Shinkai proposed that 1D growth of the fibres may be correlated with the molecular packing [13,14], and Dastidar has proved this point and show crystal engineering concept can be exploited to design simple LMWGs [1517].

Figure 1. The primary, secondary, and tertiary structure of a self-assembled supramolecular gel of a urea-based LMWG [10].

Supramolecular gels have been found applications in various areas due to its unique twophase structure, nonometer-size matrix, and metal centre for metal-containing gels. They have been applied in the food, cosmetic and petroleum industries, and potential applications as stimuli responsive materials [18-20], template of various metal, inorganic and organic materials [21,22], biomaterials [23] and electronic devices [23] have also been reported. The fact that many supramelecular gels form reversibly makes them of interest as responsive materials [18,24] (e.g. changing their physical state in response to physical or chemical triggers) and the presence of metal ions enriches the scope for responsiveness itself (e.g. to species which ligate or interfere with ligation [25], or by redox triggers [26]) and for signaling that response (e.g. through a change in spectroscopic, electronic or magnetic properties [27,28]). One of the interesting aspects of gels is their ability to template other structures, especially porous materials. This is achieved by polymerization, precipitation or reduction of

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precursors in the liquid phase, and subsequent dissolution or calcination to remove the gelator network. The method offers extensive possibilities for controlling the morphologies of diverse materials.

CHARACTERISATION TECHNIQUES
Various techniques can be used to gain structural information on different length scales [10]. With regard to the molecular packing within the gelator, infra-red [29,30] and NMR [31] spectroscopies can give information on the presence of hydrogen bonds, and more generally the local environments [32] and motions [33] of functional groups. Absorption and emission spectroscopies can give information on the packing (e.g. stacking) of aromatic groups, for example [34]. Information on molecular packing modes can also be obtained from analysis of wide X-ray diffraction combined with modelling [35]. In addition, comparison of the X-ray powder diffraction patterns given by a gelator in its crystalline form(s) with that from its gel can help to identify the gels molecular packing [11,36]. Small angle X-ray or neutron scattering can give information on the packing, for example, of molecular stacks within the fibres [37]. To investigate the larger scale structure, electron microscopy can be applied. Due to the need for a high vacuum, sample preparation can involve preliminary drying, but this can also cause to structural changes. Alternatively, cryoscopic-TEM and SEM can be applied in which the sample is prepared by rapidly freezing it to liquid nitrogen temperatures to preserve the original structure and imaging performed at low temperature. Rheological study [3840] of gels can give information on the number and strength of connections in the network. The temperature at which gelation occurs for thermotropic gels, Tgel, may be measured by the so-called dropping ball technique. A small ball bearing is placed on the gel, which is then heated until, at Tgel, the ball falls through the material. Spectroscopic indications of Tgel may differ from rheological determinations since the former detects association at the molecular level whereas the latter may depend on larger scale association. By placing the gel between two surfaces, and inducing oscillatory shear in the gel by movement of one surface, various parameters can be obtained including the complex modulus (G*), the storage or elastic modulus (G') and the loss modulus or (G''). G' is a measure of how much energy is stored in a material upon deformation, whereas G'' is a measure of the energy lost as heat. Generally for strong gels, which are formed from strong network connections, G'>>G''.

GEL FOR CATALYSIS

Traditional homogeneous catalysts have identical catalytic sites and clear structureactivity relations, and usually provide high reaction rate and afford high selectivity and yield. However, homogeneous catalysts have a number of drawbacks. For example, the problem of recycling of the catalyst leads to loss of expensive catalysts and to impurities in the products. To address the problems, heterogenising homogeneous catalysts by immobilisation is a trend toward developing efficient catalyst recycling systems. Various structures including silicas,

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159

zeolites and organic polymers have been developed for this purpose [41-43]. However, these methods often suffer from difficulties to retain or raise the activity and selectivity. Supramolecular gels have recently been used in catalysis as a new strategy to design catalyst recycling systems. Supramolecular gels are characteristic of finite short ranged order with periodically disordered arrangement of the building units, which are different with either amorphous polymers or crystals with infinite long ranged order with periodic arrangement of asymmetric units. The gel network has a large surface area in contact with solution. Catalytically active motifs have been incorporated in supramolecular gels because of their following advantages as catalyst [44]: Efficient and readily accessible. The gel has large specific surface area and the catalytically active units located in the gel fibres are accessible to solute molecules. Additionally the 3D porous structure of gels facilitates high molecular diffusivities, and favours transport of large molecules to and from the active sites. Easy-to-handle. Embedding the catalyst into a 3D gel network allows for its easy recovery after the reaction comparing with traditional homogeneous catalysts. The solid-like properties of gels would result in facile isolation of the catalyst by simple filtration. Well-defined objects (fibres) in the nanoscale. In contrast to conventional polymersupported heterogeneous catalysts, the structure of the catalytic sites in supramolecular gels can be controlled at a molecular level. The gels contain wellordered arrays of catalytic or binding units or stimuli responsive subunits, because supramolecular gels are formed from the ordered aggregation of small molecules through non-covalent bonds to yield elongated supramolecules that further aggregate to fibres. Dynamic supramolecular interactions may offer supramolecular gels some new properties different from those of traditional supported catalysts. Because of the reversibility of supramolecular interactions, supramolecular gelation can be easily modulated by external stimuli, such as temperature, pH, light and other chemical or physical stimuli, resulting in their potential applications in photonic, stimuli responsive, sensing, or catalytic materials, drug release, etc.. Therefore, Catalytic function of gels can be expected to be controlled by stimuli such as temperature, concentration, pH. Rapid progress of supramolecular gels provides a rich pool for active catalysts and allow for rational design and synthesis.

In general supramoelcular gel materials combine some advantages of homogeneous and heterogeneous catalysis, as well as the special features of their supramolecular nature. In addition, supramolecular gels may provide a suitable model for understanding of emergence of life and construction of cell mimetics [45]. Catalytically active centres can be incorporated into gelators directly according to their driving forces for molecular aggregation or by post-modification. Three strategies have appeared in literature: 1) gelation by discrete organo-/metallogelators; 2) gelation by coordination polymer gelators; 3) post-modification of a preformed gel with catalytically active centre (Figure 2) [44,45].

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Cat. Cat. Cat. Cat. Cat. Cat. Cat. Cat.

L L
Cat. Cat.

L
Cat.

Figure 2. Incorporation of catalytically active centre into gel networks (schematic representation): a) gelation by discrete gelators; b) gelation by coordination polymer gelators; c) post-modification of a preformed gel with catalytically active centre.

1. CATALYSIS BY DISCRETE GELATORS

1.1 Discrete Organogelator
Supramolecular organogels based on low-molecular weight gelators are formed through reversible non-covalent interactions. The gels from LMWGs are typically formed by dissolution of gelator in an appropriate hot solvent and subsequent cooling to a lower temperature. They can be readily transformed into fluids by heating and are generally thermoreversible. The dynamic nature of the system is also revealed by Escuder and Miravet that a fraction of the molecules remain in solution in equilibrium with the phase separated fibrillar material [46]. A report by Inoue et al. is among the earliest reports of organogel catalysis [47]. Using a cyclic dipeptide cyclo-(S)-Phe-(S)-His (1) as catalyst, addition of hydrogen cyanide to aldehydes were carried out as a gel at low temperature (-20 oC) when the solvent is toluene (Table 1). Interestingly the gelation of the reaction mixture makes the degree of asymmetric induction significantly increased. At -20 oC an extremely high enantioselectivity was observed for the conversion of benzaldehyde to (R)-2-hydroxyl-2-phenylacetonitrile (97% conversion with 97% ee). Following this observation, Danda found that high enantioselectivity and high conversion was obtained in the hydrocyanation of 3-phenoxybenzaldehyde to (S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (92% and 91% ee) catalysed by the cyclo-(R)-Phe-(R)-His (2) toluene gel [48]. The gelator can be recycled by extraction. The reaction mixture is thixotropic, which has an important influence on the enantioselectivity. As the viscosity of the reaction mixture is lowered, the enantioselectivity is raised, whereas the conversion was not influenced (Table 2). In these early reports, the self-assembled fibrillar structure of gels was poorly understood and the gels were considered to be completely amorphous. In an subsequent effort for enzyme mimicking, Guler and Stupp synthesised peptide amphiphile 3, which forms hydrogels at concentrations greater than 0.1 wt% and pH above 6.5, arising from self-assemble of piptide amphiphiles into nanofibres [49]. TEM revealed formation of high-aspect-ratio cylindrical nanostructures with diameters of 7 1 nm. In comparison, compounds 46 are soluble in

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water to form polydisperse spherical aggregates with diameters ca. 15-20 nm (Figure 3). The supramolecular aggregates were subjected to hydrolysis of 2,4-dinitrophenyl acetate, a model ester compound, to 2,4-dinitrophenol at 25 oC and pH 7.4. Significantly higher catalyst activity and stability was detected for the hydrogel of 3 than the others (Figure 4). The activity enhancement is due to higher density presentation of reactive sites with significant internal order on nanofibres relative to catalysts in solution and in spherical micelles. Table 1. Asymmetric addition of hydrogen cyanide to aldehydes catalysed by the cyclo(S)-Phe-(S)-His (1) gel.
O HN NH O R H O 1 N NH (2 mol %) HO R CN H

HCN (2 equiv), Toluene, -20 oC

Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Aldehyde benzaldehyde benzaldehyde(p-OMe) benzaldehyde(m-OMe) benzaldehyde(o-OMe) benzaldehyde(m-OPh) benzaldehyde(p-Me) benzaldehyde(p-NO2) benzaldehyde(m-NO2) benzaldehyde(p-CN) 2-napthaldehyde 6-methoxy-2-napthaldehyde fufural nicotin-3-aldehyde cyclohexanecarbaldehyde isovaleraldehyde hexanal pivalaldehyde

Time/h 8 10 8 10 8 10 2.5 8 8 1.5 6 8 0.5 2.5 5 8 5

Conv./% 97 57 83 45 97 78 99 100 100 61 88 60 73 96 44 90 60

ee/% 97 78 97 84 92 96 53 4 32 91 73 42 54 58 18 56 58

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Table 2. Influence of thixotropy in asymmetric addition of hydrogen cyanide to 3phenoxy-benzaldehydes catalysed by the cyclo-(R)-Phe-(R)-His (2) gel.
O HN NH CHO O HCN (2 equiv), Toluene, 6 h, 5 oC N NH NC OH H O

O 2 (2 mol %)

Entry 1 2 3 4
HN N N

Rate of stirring/rpm 150 200 250 300

Yield/% 97 97 97 97

ee/% 74 86 92 92
R

HN

H 2N O H N O HN N

H N

O N H O

H N

O N H O

H N

O N H O

H N

O N H NH2 O

N H

H2N

3, R = Palmitoyl 5, R = H R

HN

H2N O H N O

H N

O N H N O

O N O N

O N H NH2 O

N H

H2N

4, R = Palmitoyl 6, R = H

Figure 3. TEM images of 3 (A), 4 (B), 5 (C) and 6 (D) [49].

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163

Fi igure 4. Observ ved rate increase e in hydrolysis of o 2,4-dinitroph henyl acetate (H His-Omet = L-histidine m methyl ester) [49 9].

O N NH O NH N H H N H N O N H HN N NH O N NH N H O O N H O N H O

H N

H N O H N O H N O

O N H HN N O N H HN N O N H HN N

H N

O O 7a-c, n = 1, 4, 6

H N

Fi igure 5. L-proline derivatives 7a-c, 7 multiple H-bonding H interactions between n 7c, and SEM images of th he xerogels of 7c from MeNO2 and EtNO2 [50 0].

nd Escuder et al. a recently rep ported that a series s of L-pro oline derivativ ves 7a-c are Miravet an ca apable of self f-assembly int to organogels s in MeCN, ethyl e acetate or o toluene [50 0]. 7c also fo orms gels in MeNO M mages of the xerogels revealed a fibrilla ar structure, 2 and EtNO2. SEM im w which are microcrystalline as demonst trated by X-ray powder diffraction (Figure ( 5).

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Formation of aggregates through multiple H-bonding interactions is responsible for the gel formation. An acid-base indicator dye, bromothymol blue, is drawn to its blue form in the presence of the gel but remains yellow in the presence of a solution (Figure 6). Considerable basicity enhancement of L-proline secondary amine is due to proximity of L-proline groups in the gel fibres as compared to solution.

Figure 6. Evolution of bromothymol blue color during gelation of compound 7c in MeCN. The starting yellow (not basic) solution turned into a blue (basic) gel [50].

Such a basicity enhancement leads to remarkably different catalytic activity towards the aldol reaction between acetone and 4-nitrobenzaldehyde. Reactions were performed in the gel phase, by diffusion of the aldehyde through a MeCN gel containing acetone. In solution, 7a-c behave as enantioselective catalysts for the aldol reaction, whereas in the gel state, the catalytic activity of the L-proline moiety in enamine-based aldol reactions is inhibited, and they are basic catalysts inactive in the aldol reaction but active in the based-catalysed aldol racemisation (Table 3). Table 3. Results of racemisation of 4-hydroxy-4-(p-nitrophenyl)-2-butanone.
OH O CHO + O2 N O Cat., MeCN 2 weeks, -20 oC O 2N

Entry 1 2 3 4 5 6

Catalyst 7a-sol 7a-gel 7b-sol 7b-gel 7c-sol 7c-gel

[catalyst] sol/mM 6.5 6.5 2.4 2.4 2.4 2.4

[catalyst] gel/mM 5.5 9.6 9.6

Enantiomeric ratio (S:R) 1:4.0 1:2.9 1:4.0 1:1.3 1:4.0 1:1.2

Table 4. The Henry reaction of nitroalkanes and aldehydes catalysed by the 7c gel.

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165

CHO + R X NO2 Cat. (10 mol %) MeCN, 2 d

NO2 HO R + X I X II

NO2 R R +

NO2 NO2 R

X III

Entry 1 2 3 4 5 6 7 8

R Me Me H H H H H H

Reagent 4-nitrobenzaldehyde 4-nitrobenzaldehyde 4-nitrobenzaldehyde 4-nitrobenzaldehyde 4-chlorobenzaldehyde 4-chlorobenzaldehyde 4-methoxybenzaldehyde 4-methoxybenzaldehyde

T/oC 5 (gel) 25 (solution) 5 (gel) 50 (solution) 5 (gel) 50 (solution) 5 (gel) 50 (solution)

Yield 99 15 38 46 11 -

of

Yield of II + III /% 5 2 33 4 99 100

nitroaldol/%

The gel phase of 7c as active phase has been shown in the Henry nitroaldol reaction between nitroalkane and aldehyde [51]. For catalytic studies, a solution of 4nitrobenzaldehyde was left to diffuse into the gel prepared in the corresponding nitroalkane. A sharp change in catalytic activity was observed (Figure 8). Highly efficient catalytic activity for the Henry reaction was only observed in the aggregated state upon gel formation (Table 4). For example, a quantitative conversion of the aldehyde to nitroaldol was obtained in the reaction of nitroethane and 4-nitrobenzaldehyde. The results suggest that the catalytic activity of 7c can be regulated by minor temperature changes (5 and 25 oC) due to reversible sol-gel transition. The reactions also work for highly and moderately reactive aldehydes (e.g. 4-nitrobenzaldehyde and 4-chlorobenzaldehyde). Different reaction mechanisms have been proposed for the catalytic performance (Scheme 1). The reactions in the gel phase start with the deprotonation of the nitroalkane by the secondary amine of L-proline through an ionic pair type mechanism, while in solution formation of iminium intermediates may result in the nitroalkene byproducts. Miravet and Escuder et al. further designed an amphiphilic hydrogelator derived from Lproline, 8 [52]. SEM revealed a network of ribbons of less than 300 nm in width and several m in length (Figure 8). X-ray powder diffraction of the xerogel confirmed a lamellar structure bilayer with intercalation of the alkyl tails. For catalysis for the direct aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, reagents were topped on the gel dissolving in toluene and the product was obtained with quantitative yield after 24 h at 5 oC with high stereoselectivity (anti: syn 92:8, 88% ee). It is a heterogeneous catalytic system and after

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decantation of the toluene phase the catalytic hydrogel could be reused for at least three times with similar efficiency and stereoselectivity (Table 5).

Figure 7. Temperature controlled catalysis in the Henry nitroaldol reaction [51].

Scheme 1. Reaction mechanism of the Henry nitroaldol reaction [51].

Supramolecular Gel Catalyst

O NH N H O H N 8

167

Figure 8. Photographic and SEM images of the hydrogel of 8 [52].

Table 5. Direct aldol reaction catalysed by hydrogel-8.

O + 20 equip O2N CHO Hydrogel-8 (0.2 equip) Toluene-water 1 equip O OH

NO2

Entry n 1 2 3 4

Ru C

T/o 25

t/h 16 24 24 24

Yield/% >99 98 >99 >99

anti:syn 91:9 92:8 93:7 92:8

ee/% 18 88 87 90

1 3

st

5 5 5

2nd
rd

Dtz et al. reported that pyridine-bridged bisbenzimidazolium salts with long alkyl chains 1a-d efficiently gelate a variety of alcohols, MeCN, and other polar solvents [53]. TEM revealed morphologies of 250-500 nm wide and several micrometer long straight fibres, indicating a parrallel columnar packing (Figure 9). X-ray analysis, SAXS and 1H NMR studies show that supramolecular interactions including stacking between the aromatic rings, H-bonding, and van der Waals interactions between the alkyl chains are responsible for the gelation. The MeCN gels are efficient phase transfer catalysts with stirring for Nalkylation of benzimidazole, benzotriazole and imidazole (Table 6). The catalysts can be recovered after filtration and reused after regelation with MeCN.

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N + N R X-

N X+ N R

9a, R = n-C16H33, X = Br 9b, R = n-C16H33, X = I 9c, R = n-C12H25, X = I 9d, R = n-C8H17, X = I

Figure 9. TEM images of the gels of 9a-d formed from i-BuOH [53].

Table 6. Phase-transfer N-alkylation of benzimidazole, benzotriazole and imidazole catalysed by gel-9.

X Br Br

+ ArH

cat. (5 wt%), 25% NaOH MeCN, RT Ar X Ar

Entry 1 2 3 4 5 6

X N N N N N CH

Ar benzimidazole benzimidazole benzotriazole imidazole imidazole benzimidazole

Catalyst gel 9b/MeCN gel 9a/MeCN gel 9b/MeCN gel 9a/MeCN gel 9b/MeCN gel 9b/MeCN

Time/h 3 5 3 6 5 3

Yield/% 89 92 59 67 63 90

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1.2 Discrete Metallogelator

Discrete metal complexes have been recently reported to act as gelators [54,55]. Discrete metallogelators self-assemble through multiple noncovalent bonds, such as H-bonding, - stacking, solvophobic effects, electrostatic interactions and other supramolecular weak interactions. The metal-ligand interaction is only a secondary force to form 3D gel matrix in some sense, which can be understood to mainly form discrete complexes. Such gels involving weak interactions may be transformed to a fluid by external stimuli (heating, sonication etc.) to break these interactions and thus thermally reversible like their organogelator analogues. Dtz et al. reported that a palladium CNC pincer Pd(II) carbene complex bearing long alkyl substituents, 10, is a good gelator for normal organic solvents [56]. TEM revealed that larger fibres are present in xerogels from protic solvents (e.g. MeOH, AcOH), while dense networks of smaller fibres result from nonprotic solvent (e.g. DMF, DMSO, DMA, and THF) (Figure 10). Thermoreversible sol-gel transition was observed for the gels at 5060 oC. The planarity of the metal-chelating pincer ligand may allow for aggregation by intermolecular interaction, enhanced by PdPd interactions and van der Waals interactions between the alkyl chains. Promising catalytic activity of the palladium pincer carbene gel was observed in the double Michael addition of -cyanoacetate to methyl vinyl ketone with in situ prepared DMF and DMSO gels as catalyst under slow stirring (Table 7).
+ N N n-C16H33 N Pd I 10 N N n-C16H33 I-

Figure 10. TEM images of gels formed from palladium(II) pincer complex 10 [56].

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Jianyong Zhang and Stuart L. James Table 7. Double Michael addition of -cyanoacetate catalysed by gel-10.
i

+ NC O

CO2Et

Pr2NEt, cat. CH2Cl2, RT NC CO2Et

Entry 1 2 3 4

Catalyst 10-gel/DMSO (4 wt%) 10-gel/DMF (4 wt%) 10 blank

k/[10-6 s-1] 24.1 10.4 5.5 3.8

t1/2/h 7.9 18.5 35 51

You et al. examined the morphology evolution of a series of supramolecular aggregates based on dinuclear metallocyclic Pd2L2 units formed by semirigid imidazole derivatives 11a-f and Pd(OAc)2 (Scheme 2) [57]. Ligands 11a and 11b are soluble in DMSO and assemble into spherical particles with the average diameters of ca. 46 and 66 nm, respectively, revealed by dynamic light scattering DLS, AFM and TEM studies. Whereas ligands 11c-f bearing phenolic hydroxyl groups with Pd(OAc)2 at a 1:1 molar ratio form gels in DMSO, DMA, and other DMSO solvent mixtures. H-bonding among the phenolic hydroxyl groups, the anions, and the solvent molecules plays an important role in the gelation process. 3D globular networks, formed by interconnection of smaller spherical aggregates, lead to gelation as revealed by TEM (Figure 13). The gels formed by 11c-f and Pd was used to catalyse the phenylation of indole with phenylboronic acid. The 11c-Pd(II) gel afforded the product in about 50% yield, higher than those of the soluble complex and the xerogel (less than 5% yield).

N R1 R2 N

N 11a: R1 = Me, R2 = H; 11b: R1 = H, R2 = H; 11c: R1 = Cl, R2 = OH; 11d: R1 = Me, R2 = OH; 11e: R1 = t-Bu, R2 = OH; 11c-Pd(II) gel, O2 (1 atm) AcOH, RT, 10 h

N OH OH N

N 11f

H + PhB(OH)2 N H

Ph N H

Scheme 2. Phenylation of indole with phenylboronic acid catalysed by 11-Pd(II) gel.

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171

Figure 13. TEM and AFM height images of spherical aggregates of 14a-Pd (a,b,c) and 14b-Pd (d,e,f), and TEM image of the 14e-Pd xerogel obtained from DMSO [57].

2. CATALYSIS BY COORDINATION POLYMER GELATORS

Gels formed by coordination polymers, infinitely extending metal-ligand assemblies with bridging organic ligands, are of interest considering a large number of metal ions and organic ligands available [54,55]. Metal-ligand interactions are the main driving force to form the 3D gel network as coordination polymers act as gelators. Such coordination polymer gels based on metal-ligand interactions generally can not be redissolved upon heating and do not show thermoreversible gel-sol transitions. Xu et al. reported a type of polypyridine-based palladium(II) coordination polymer gels [58]. Reactions of polypridine ligands 12a and 12b with Pd(OAc)2, 12c with Pd(OAc)2 or [Pd(en)(H2O)2](NO3)2 in DMSO gave metallogels after 4 h ~ 2 months which did not flow on inversion of the vial. In the oxidation of benzyl alcohol to benzaldehyde on exposure to air, the wet gel prepared from ligand 12a exhibited the optimal result, giving a total catalytic

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turnover (72) about twice that of Pd(OAc)2, and three that of the corresponding precipitate from acetone (Scheme 3).
OH OHOH OH N N N NH N HN N N N N NH HN N 12c CHO N N

HN N N 12a N N N

12b

OH

12-Pd(II) gel (0.1 mol %) air, 90 oC, 2 h

Scheme 3. Aerobic oxidation of benzyl alcohol catalysed by the 12-Pd(II) gels.

A larger tripyridine ligand 13 was later reported by our group to form coordination polymer gels with Pd(COD)(NO3)2 in a range of mixed organic solvents (e.g. MeOH-CHCl3) [59]. The gels can be formed with a range of Pd/13 ratios from 1:1 to 1:4 during a shorter period of 2 min to 2 h. 1H NMR, FT-IR, and fluorescence spectroscopic studies showed a combination of Pd-N coordination, H-bonding, - stacking being present in the gel aggregates. SEM revealed an interesting morphology evolution of spherical assemblies to fibrous structures in the xerogels with decreasing Pd/13 ratios from 1:1 to 1:4 (Figure 11). The 13-Pd(II) gel/xerogels efficiently catalyse the Suzuki-Miyaura coupling under atmospheric conditions (Table 8, entries 14). Interestingly, the fibrous network has been shown to have higher activity than spheres in Suzuki-Miyaura coupling. The xerogel catalyst can be recovered by simple filtration for at least 5 times and reused without significant loss of activity.
N HN O 1/4 equiv Pd
2+

1 equiv Pd2+ N N N H N O N

O NH N

13

Figure 11. Morphology evolution of Pd-pyridyl gels depending on Pd/L ratio.

The gel nanofibres based on the Pd-13 gel can be supported on superparamagnetic magnetite (Fe3O4) nanoparticles by simply mixing 13, and Pd2+ in CHCl3-MeOH with a Pd/13 molar ratio of 1:1 in the presence of magnetite nanoparticles [60]. The presence of magnetite nanoparticles was unambiguously confirmed by TEM and magnetism studies (Figure 12).

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173

The superparamagnetic 13-Pd(II)-MNPs xerogel show similar activity in Suzuki-Miyaura CC coupling reactions (Table 8, entries 58). The xerogel can be magnetically isolated with a permanent magnet and reused for 5 times in the reaction of iodobenzene and phenylboronic acid. Table 8. Suzuki cross-coupling of aryl halides and phenylboronic acid catalysed by the 13-Pd(II) (1:1) gel and the 13-Pd(II)-MNPs xerogel.
R X = I, Br X + 1.5 equip B(OH)2 13-Pd(II) gel (1 mol %) 3 equip Na2CO3, MeOH, 60 oC R

Entry 1 2 3 4 5 6 7 8

X I Br Br Br I Br Br Br

R H H COMe OMe H H COMe OMe

Catalyst 13-Pd(II) gel 13-Pd(II) gel 13-Pd(II) gel 13-Pd(II) gel 13-Pd(II)-MNPs xerogel 13-Pd(II)-MNPs xerogel 13-Pd(II)-MNPs xerogel 13-Pd(II)-MNPs xerogel

Time/h 90 15 15 15 120 60 15 30
Magnetic gel

Yield/% >99 28 >99 26 >99 78 97 27

N HN O + N N N O 13 H N N Pd2+ + Fe3O4 mixed

O NH N

product substrate

a
Figure 12 (Continued).

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Jianyong Zhang and Stuart L. James

Figure 12. Magnetic gel nanofibres for organic transformation, and TEM images of the 13Pd(II) xerogels before (a,b) and after (c,d) loading of magnetite nanoparticles [60].

Uozumi et al. reported a palladium-based coordination polymer gel based on a tripodal flexible triphosphine 14 [61]. A yellow gel is obtained upon reaction of 14 with PdCl2(NCPh)2 in toluene at 100 oC for 24 hours. 31P MAS NMR of the gel showing a singlet at 20.0 ppm is consistent with complexation of palladium species and the ligands through PdP coordination bonding. The xerogel is insoluble in water and several types of organic solvents (chlorinated solvents, toluene, methanol). The xerogels catalytic ability was investigated in the Suzuki-Miyaura coupling of aryl halides with boronic acids in water. High yields of coupling products were obtained and Electron-deficient as well as electron-rich aryl iodides/bromides readily coupled with arylboron reagents bearing para-, meta-, and orthoEWG and EDG substituents to give the corresponding biaryls in 80-99% yields. The catalyst could be recycled at least four times with retention of similar activity as demonstrated in the reaction of iodobenzene with 4-tolylboronic acid (Scheme 4).
PPh2

O 6 O O O 6

O Ph2P
I + (HO)2B 1.5 equip

O 6 14

PPh2

14-Pd(II) xerogel (0.05 mol %) 3 equip Na2CO3, H2O, 3 h, 100 oC

1st use: >99% (GC yield) 2nd use: 91% (GC yield) 3rd use: 95% (GC yield) 4th use: 90% (isolated yield)

Scheme 4. Suzuki cross-coupling catalysed by the 14-Pd(II) xerogel

Supramolecular Gel Catalyst

N N

175

RO RO

15a: R = CH2OCH3, n = 1 15b: R = CH2CH3, n = 1 15c: R = n-C6H13, n = 1 15d: R = n-C6H13, n = 2

N N

Figure 13. SEM image of the 15a-Cu(I) xerogel [62].

Table 9. Huisgen 1,3-dipolar cycloaddition catalysed by the 15Cu(I) xerogels.

N3 15-Cu(I) xerogel (1 mol %) H2O, RT, air N N N R

+ R 1.2 equip

Entry 1 2 3 4 5 6 7 8 9 10

R Ph Ph Ph Ph Ph p-Tol m-Tol 2-Py TMS n-Bu

Catalyst 15aCu(I) 15bCu(I) 15cCu(I) 15cCu(I) 15dCu(I) 15cCu(I) 15cCu(I) 15cCu(I) 15cCu(I) 15cCu(I)

Time/h 18 18 18 8 18 18 18 18 18 18

Yield/% 78 73 100 97 97 95 100 100 12 8

Bian and Gao et al. investigated chiral binaphthylbisbipyridine-based copper(I) coordination polymer gels [62]. Equimolar 15a-d and Cu(MeCN)2BF4 in hot MeCN-CH2Cl2, MeCN-THF, or MeCN-dioxane (v/v, 1/1) form gels on cooling to RT. SEM revealed that the existence of nanofibres are responsive for the gelation (Figure 13). Formation of 1D coordination polymer of tetrahedral Cu(I) ions and the ligands at a ratio of 1:1 is necessary for the gelation as indicated by 1H NMR, UV-vis and CD spectroscopy. DSC analysis showed the 15a-Cu(I) gel has no endothermic transition up to 100 oC. - stacking interaction between the 1D coordination polymers was revealed by UV-vis spectroscopy. Cu(I) is significantly stabilised by the gel network with an increase of 1.20 V for the redox potential of Cu(I)/Cu(II) of 15c-Cu(I) compared to Cu(I)(2,2'-bipyridine)2. The catalytic activity of the

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15Cu(I) xerogels was explored in the Huisgen 1,3-dipolar cycloaddition (click reaction) (Table 9). The 15cCu(I) xerogel gave optimal result in the reaction of benzyl azide and phenylacetylene with quantitative conversion in water at RT. The xerogel catalyst can be easily separated from the reaction mixture, and the recovered catalyst could be used for consecutive reaction for three times without significant loss of activity.

3. CATALYSIS BY POST-MODIFIED GELS

Loading of catalytically active centres to a preformed functionalised organogel or metallogel is another strategy to produce a gel catalyst. Miravet and Escuder reported pyridine-functionalised organogels. Dipyridine ligands based on amide linkages with stereospecific attachment of isopropyl groups, 16a and 16b, efficiently gel H2O and a variety of organic solvents including toluene (Scheme 5) [63]. Intermolecular mutiple H-bonding similar with that present in 7c is the driving force for gelation. The toluene gels could be postmodified by complexation of Pd(II) ions to from Pd-N(pyridine) coordination bond for catalytic activity. A solution of Pd(OAc)2 in toluene was layered on top of the gel and was observed to diffuse into it. Evidence for incorporation of palladium into the actual fibres of the gel was obtained from TEM, since no metal shadowing was required to image these fibres (Figure 10). Metal-complexation could help reinforce H-bonding organogel fibres to obtain mechanically robust gels. The Pd(II)-immobilized gel showed catalytic activity for the oxidation of benzyl alcohol to benzaldehyde at 65 oC with a maximum yield of 50% (10 turnover numbers) after 48 h.
O N N H O 16a H N H N O O N H N N O N H O H N 16b H N O O N H N

OH

16-Pd(II) gel (5 mol %) toluene, air, 65 oC, 48 h

CHO

Scheme 5. Aerobic oxidation of benzyl alcohol catalysed by the 16-Pd(II) gels.

A very simple method for formation of a coordination polymer gel involves reaction between Fe(NO3)39H2O and the 1,3,5-benzentricarboxylic acid (H3BTC) in ethanol [64]. The gel forms within a few minutes, is stable to a range of solvents but dissolves in aqueous hydrochloric acid. The Fe3+ gel is potentially useful since it also forms in the presence of methylmethacrylate, which can be polymerised to give PMMA and the gel template removed with aqueous HCl. This leaves the organic polymer imprinted with the original gel structures. Accordingly SEM showed this PMMA to have a sponge-like structure with pores in the size range 1-10 m (Figure 15). With the gel as template, macroporous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) was fabricated to show promise in chromatographic separation of protein [65]. Recently, Kaskel et al. investigated the

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adsorption properties of the Fe(III)-carboxylate gels. Their aerogels have highly porous nature with a combination of micro- and macroporosity (total pore volume 5.62 cm3 g-1 and BET surface area 1618 m2 g-1), which are promising as catalysts or catalyst supports [66].

Figure 14. TEM images of the xerogels of 16b before modification with Pt-shadowing (A) and after modification with Pd(OAc)2 with no shadowing (B, C) [63].

Figure 15. SEM images of spongelike PMMA templated by the Fe(III)-BTC gel [64].

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H HOOC PPh2 H HOOC H HOOC 17a

CO OOH

HOOC N

H3BT TC

COOH

HOOC

N H 17b

Sc cheme 6. Bridging carboxylate e acids for meta allogels.

For catalys sis, the Fe-BT TC gel has been b modified d with differe ent functional groups to ob btain a ran nge of func ctionalised Fe-gels F based d on dicarb boxylic acid, e.g. 5di iphenylphosph hanylisophtha alic acid (17a a, Scheme 6) ) [67]. Gels could be for rmed when m mixing of the solutions of 17a and Fe( (NO3)39H2O in alcohols and a DMF. SE EM of the xe erogels reveal led globular or r block-like morphologies m o 2-10 m fo of orming an inte erconnected po orous network k (Figure 16a a,b). The pho osphine-functi ionalised gel with phospho orus donor av vailable for fu urther coordin nation has pro omising cataly ytic application ns for post-m modification w catalytical with lly active cent tres. After loa ading of Pd(II) ), the gel show wed efficient catalysis c in th he SuzukiMi iyaura crosscoupling of aryl a halides/b bromopyridine es with variou us boronic ac cids under am mbient atmosp phere (Table 10). 1 The phos sphine gel sho ows potential to act as a ne ew type of fun nctionalisable porous scaffo old, and the ge el could be eas sily recovered and reused fo or subsequent t reactions, e.g. the coupl ling of 4-bromopyridine with w 3,5-diflu uorophenylbo oronic acid.

Fi igure 16. SEM and TEM images of the Pd(II) modified 17a Fe(III) (a,b) an nd 17bFe(III) (c,d) xe erogels [67,68]. .

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Table 10. SuzukiMiyaura crosscoupling of aryl halides/bromopyridines with boronic acids catalysed by the Pd(II) modified 17Fe(III) gels.
17-Fe(III)Pd(II) gel (0.5 mol %) 3 equip Na2CO3 MeOH, 60 oC

R X = I, Br

X +

B(OH)2 1.5 equip

Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Catalyst 17a-FePd gel 17a-FePd gel 17a-FePd gel 17a-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel
N + Br PyBr R R B(OH)2

X I Br Br Br I I Br Br Br Br Cl Cl Cl Cl

R H H OMe COCH3 H H H COCH3 OCH3 OCH3 H H COCH3 COCH3

Time/h 1.0 0.5 1.0 1.0 0.5 0.5 0.25 0.5 0.5 1.0 11 0.5 1.0 3.0
N R

Yield/% 100 71 35 99 >99 >99 91 >99 72 69 46 8 14 12

17-Fe(III)Pd(II) gel (0.5 mol %) 3 equip Na2CO3 MeOH, 60 oC R

Entry 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Catalyst 17a-FePd gel 17a-FePd gel 17a-FePd gel 17a-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd xerogel

PyBr 4-bromopyridine 4-bromopyridine 3-bromopyridine 2-bromopyridine 4-bromopyridine 4-bromopyridine 3-bromopyridine 3-bromopyridine 2-bromopyridine 2-bromopyridine 4-bromopyridine 3-bromopyridine 3-bromopyridine 2-bromopyridine

R F H F F Me Me Me Me Me Me F F F F

Time/h 2.0 1.0 3.0 2.0 1.0 1.25 0.5 2.0 6.0 1.0 3.0 27 5.0 2.0

Yield/% 95 >99 71 52 >99 >99 >99 77 86 30 58 93 8 16

The coordination bond (e.g. Fe-N bond) present in metallogels has been employed to immobilise active catalysts resulting from the dynamic nature [68]. A bifunctional ligand, 51H-benzo[d]imidazole-1,3-dicarboxylic acid (17b, Scheme 6), forms coordination polymer gels with Fe3+ in DMF-H2O, DMF, and DMF-MeOH. The xerogels have an interconnected

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porous network of globular nanometer-sized particles of ca. 100 nm, as indicated by SEM and TEM (Figure 12c,d). In the gels, the hard metal ion Fe3+ strongly coordinates to carboxylate groups to form the gel network, and Fe3+ may also coordinate to the imidazole group less strongly. When Pd2+ is loaded, binding of softer Pd2+ via the imidazole N atom is more favourable resulting in cleavage of FeN(imidazole) bond and generation of new PdN bond due to their different binding ability. Compared with its homogeneous analogue, the Pd(II)modified coordination polymer gel exhibited significantly improved activity in the Suzuki Miyaura crosscoupling (e.g. coupling of phenylboronic acid and 4-bromoanisole), and could be reused for several times (Table 10).

CONCLUSION
Gels are a type of aggregates between highly ordered aggregates (crystals) and random aggregates (amorphous solid). Its particular complexity of gels has been shown in literature. The actual molecular structures of most gels are still beyond current techniques. The results of crystal engineering help understand the structure of gel network, but it is still far from the final structure. Supramolecular interactions between gelators, between liquids, and between gelator and liquid have not been fully understood yet. The rational design, especially of catalytic gelators, is still in infancy. As shown above, supramolecular gels provides an interesting, useful and increasingly important medium in which to investigate and exploit catalytic chemistry, and indeed the chemistry and physics of active catalytic centres in general. The examples described in the chapter demonstrate that unique new catalytic properties can arise from combining gels with catalytically active centres. In some cases supramolecular gels show enhanced activity compared with their homogeneous analogues, as already noted. With the ever-present need for enabling materials for current and future technological needs, one can be optimistic that further catalytic applications may follow since catalytic supramolecular gels are clearly synthetically available and they display unusual catalytic properties.

ACKNOWLEDGMENT
We gratefully acknowledges the Natural Science Foundation of China (NSFC) (Grants No. 20903121), the Specialized Research Fund for the Doctoral Program of Higher Education of China, the Fundamental Research Funds for the Central Universities, and the SRF for ROCS, SEM, for financial support.

REFERENCES
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[59] Liu, YR; He, L; Zhang, J; Wang, X; Su, CY. Evolution of spherical assemblies to fibrous networked Pd(II) gels from a pyridine-based tripodal ligand and their catalytic property. Chem. Mater., 2009, 21, 557563. [60] Liao, Y; He, L; Huang, J; Zhang, J; Zhuang, L; Shen H; Su, CY. Magnetite nanoparticle-supported coordination polymer nanofibers: synthesis and catalytic application in Suzuki-Miyaura coupling. ACS Appl. Mater. Inter., 2010, 2, 23332338. [61] Yamada, YMA; Maeda, Y; Uozumi, Y. Novel 3D coordination palladium-network complex: a recyclable catalyst for Suzuki-Miyaura reaction. Org. Lett., 2006, 8, 4259 4262. [62] He, Y; Bian, Z; Kang, C; Cheng Y; Gao, L. Chiral binaphthylbisbipyridine-based copper(I) coordination polymer gels as supramolecular catalysts. Chem. Commun., 2010, 46, 35323534. [63] Miravet, JF; Escuder, B. Chem. Commun., Pyridine-functionalised ambidextrous gelators: towards catalytic gels. 2005, 57965798. [64] Wei, Q; James, SL. A metal-organic gel used as a template for a porous organic polymer. Chem. Commun., 2005, 15551556. [65] Yin, J; Yang, G; Wang, H; Chen, Y. Macroporous polymer monoliths fabricated by using a metal-organic coordination gel template. Chem. Commun., 2007, 4614-4616. [66] Lohe, MR; Rose, M; Kaskel, S. Metal-organic framework (MOF) aerogels with high micro- and macroporosity. Chem. Commun., 2009, 6056-6058. [67] Zhang, J; Wang, X; He, L; Chen, L; Su, CY; James, SL. Metal-organic gels as functionalisable supports for catalysis. New J. Chem., 2009, 33, 10701075. [68] Huang, J; He, L; Zhang, J; Chen L; Su, CY. Dynamic functionalized metallogel: An approach to immobilized with improved activity. J. Mol. Catal. A Chem., 2010, 317, 97103.

In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 6

GLYCEROL AS A SUSTAINABLE SOLVENT FOR HOMOGENEOUS CATALYSIS

Adi Wolfson*, Christina Dlugy and Dorith Tavor
Green Processes Center, Chemical Engineering Department, Sami Shamoon College of Engineering, Bialik/Basel Sts. Beer-Sheva, 84100 Israel.

ABSTRACT
With its promising physical and chemical properties, glycerol can be used as a sustainable solvent in many catalytic and non-catalytic organic reactions. Polar and nontoxic, glycerol is a biodegradable, recyclable liquid that is manufactured from renewable sources and that facilitates the dissolution of organic substrates, inorganic compounds, and transition metal complexes. Glycerol also enabled easy isolation of the reaction product either by extraction with glycerol immiscible solvents such as diethyl ether, ethyl acetate, and supercritical carbon dioxide or through distillation. Using glycerol as a solvent also enabled catalyst recycling, emulsion-like systems, and microwave-promoted reactions. Furthermore, in many reactions, the use of glycerol as a solvent promoted improved activities and selectivities of the reactants. In addition, in certain reactions such as the catalytic transfer-hydrogenation of various unsaturated organic compounds and the transesterification of alcohols, glycerol was used as both solvent and reactant.

Keywords: Glycerol, sustainable solvent, catalysis, homogeneous catalysis, green chemistry, catalyst recycling.

1. INTRODUCTION
The need for an efficient, low energy, and clean (i.e., "greener") industrial process in which energy and waste are minimized and costs are reduced is of universal concern. Solvents are used daily in innumerable industrial processes as reaction mediums, in
*

Corresponding author. Email: adiw@sce.ac.il.

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separation procedures, and in dilutions. The chemical, physical, and biological natures of a solvent are of paramount importance in any process that involves mass, heat, or momentum transfer [1, 2]. Safety and the environment are also primary concerns in the selection of a solvent [3, 4]. As such, using a biodegradable solvent from a renewable resource such as plants is preferable. In addition, the chosen solvent should have minimal volatility and it should be chemically and physically stable, recyclable, and reusable. When a solvent is used as part of the reaction media, the solubilities of the reactants (gases, liquids, and solids) must be taken into account. The chemical composition of the solvent can also affect reaction activity and selectivity, and its physical properties may dictate the reaction conditions [5]. Organic chemistry is typically carried out in solution to dissolve reactants and/or homogeneous catalysts and usually requires large amounts of solvent [5]. Traditionally employed in the majority of chemical processes, petrochemical solvents have severe implications for the environment. Hence the search for environmentally friendly reaction mediums is of primary interest. Catalysis also plays an important role in the prevention of waste generation in organic synthesis [6-8], as it combines several transformations into single steps. In some reactions, catalysis can eliminate the need for toxic reagents. Furthermore, improving reaction selectivity in catalytic processes helps reduce the formation of byproducts and thus leads to simpler, cleaner, and more effective separation processes [9-12]. Moreover, catalytic reactions are usually performed under milder conditions resulting in lower energy consumption. Solvent characteristics also dictate the most effective separation method for product recovery [13]. The ease with which the product can be separated from the costly soluble metal catalyst for the latter to be recycled is often the determining step for large-scale implementation. A solvent with a relatively high boiling point would allow distillation of more volatile products, but when large organic products are involved, distillation is usually not applicable. In addition, the harsh conditions often present during product distillation may lead to product or catalyst decomposition. Extraction of the products using an additional solvent, which would form a two-phase (biphasic) system with the reaction solvent, is a feasible alternative. Although commonly used to recycle catalysts [11], many biphasic catalytic systems, either reaction or extraction, suffer from cross-contamination of the liquid phases, an undesired result that necessitates additional downstream separation. The ideal system for simple separations without the addition of an extraction solvent, therefore, would involve substrates that are fully or partially miscible in the reaction phase and products that are poorly miscible. When the addition of an extraction solvent is necessary, the reaction solvent should be immiscible with a variety of other solvents. Furthermore, extraction solvent selection should also be based on how it affects the environment, worker safety, and the ease of subsequent separations.

Alternative Reaction Media

Reaction solvent suitability also depends on, in addition to its solubility and environmental friendliness, whether it promotes easy product separation and catalyst recovery, i.e., whether it is a sustainable solvent. A variety of environmentally benign solvent alternatives has been proposed in the literature, including water, ionic liquids, fluorous solvents, and supercritical fluids. Water, with its ideal environmental impact, relatively low

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price, and reasonable boiling temperature, is an attractive solvent, but the negligible solubility of many organic compounds in water can cause low reaction rates [14]. Moreover, the water crisis currently facing the entire planet is liable to increase the price and decrease the availability of water for industrial applications. Water-organic biphasic systems were thus employed to solve solubility limitations and to recycle transition metal complexes (TMCs). However, reactions run in biphasic systems are usually accompanied by mass transfer limitations. Organic and catalytic reactions in mixtures of paraffin with fluorinated solvents have also been reported in the literature [15, 16]. In these systems, the reaction is single phase if performed at the reaction temperature while a temperature decrease leads to a two-phase system. Although this system enables the TMCs to be separated and recycled, they must undergo tedious modification prior to their use in the reaction. Furthermore, solvent decomposition at high temperatures may yield hazardous compounds. Recently, increasing attention has been focused on ionic liquids (ILs) as alternative green solvents due to their unique and versatile physical and chemical properties [17-20]. Ionic liquids are organic salts that are liquid near ambient conditions (Tm < 100 C). Composed of ions, they have negligible vapor pressure and thus do not contribute to airborne pollution. ILs have already been used in numerous mono- or biphasic catalytic systems in a variety of organic reactions with and without TMCs and enzymes. Separation of the products and recycling of the catalyst were accomplished by distillation or extraction with a non-miscible solvent. Nevertheless, the widespread use of ILs as reaction media has been thwarted by their considerable drawbacks. The relatively high price of most ILs will prevent them from being used as solvents in large-scale processes, even though they can be recycled and re-used. While ILs are potentially green, mainly due to their low vapor pressure, their chemical and physical properties and toxicology and safety measurements are not completely known [21, 22]. In addition, some ionic liquids have low biodegradability, and large amounts of hazardous and volatile organic solvents are utilized in their production. Supercritical and compressed fluidsespecially supercritical carbon dioxide (scCO2) represent another potential class of green solvents. Supercritical fluids are substances above their critical temperature and pressure [23-25] and represent a highly tunable solvent class. Because supercritical fluids are extremely sensitive to pressure and temperature, large changes in properties like density, viscosity, diffusivity, and thermal conductivity, to name but a few, are possible. This sensitivity allows for the precise selection of the desired properties for any given reaction with supercritical fluids, and, as such, compressed fluids represent many solvents in one compound. CO2 from non-sequestered sources represents an environmentally benign and non-toxic solvent for reaction, extraction, and material processing [26-29]. Its relatively low critical pressure and temperature (Tc=31C, Pc= 74 bar) together with its low toxicity and environmental impact and affordable price make it an even more attractive solvent candidate. Used for years for analytical or extraction purposes, scCO2 is now widely used in extraction and purification processes in the petrochemical, food, and pharmaceuticals industries [30, 31]. Supercritical fluids, especially scCO2, have also been reported as green solvents for catalysis. The reactants and catalysts with specialized ligands are in one homogeneous phase. CO2 can be miscible with reaction gases (e.g., H2, O2, CO, etc.), a characteristic that can completely eliminate common interfacial mass transfer limitations. In addition, separations can be

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achieved via changes in the temperature or pressure. However, it is often difficult or uneconomical to render reactants, products, and especially metal complex catalysts soluble in the supercritical fluid phase. Based on the above-mentioned specifications for an environmentally friendly solvent, glycerol (glycerin, 1,2,3-propanetriol), widely available and inexpensive, has a high potential of fulfilling the requirements of a green solvent. Glycerol is the main by-product from the conversion of oils and fats in oleochemical production (Figure 1) [32, 33]. In the past decade, its price has substantially decreased due to an increase in supply from the production and use of fatty acid derivatives in the food, cosmetics, and drugs industries and in biofuel synthesis, i.e., biodiesel. Indeed, the biodiesel market is growing rapidly as it is sulfur- and aromaticsfree and since it is obtained from renewable resources.
OCOR1 OCOR2 OCOR3 Triglyceride Alcohol ROCOR1 OH

Catalyst 3 ROH

+
ROCOR2

+
OH

OH

+
ROCOR3 Mixture of alkyl esters

Glycerol

Figure 1. Transesterification of triglycerides.

A non-toxic, biodegradable, and recyclable liquid that is highly inert and stable, glycerol is compatible with many other chemical materials. These qualities make it suitable for use as a humectant, plasticizer, emollient, thickener, dispersing medium, lubricant, sweetener, bodying agent, antifreeze, and processing aid. As such, glycerol has been approved for food and drug use by many government agencies (US FDA, etc.) and is used as an ingredient or processing aid in cosmetics, toiletries, personal care, drugs, and food products. In addition, glycerol derivatives such as glycerol esters are also extensively used in many industries. Glycerol also forms the raw material in chemical syntheses [34] such as the production of dendrimers and hyperbranched polyethers and polyesters [35], catalytic hydrogenolysis to propylene glycols (especially 1,3-propanediol, which is a high value chemical in the synthesis of polyesters [36, 37]), and catalytic oxidation to form various commercially important compounds such as dihydroxyacetone and glyceraldehydes [38]. Used as an energy source for microorganism fermenting systems, glycerol yielded ethanol and hydrogen [39]. However, in all applications, whether as a reactant or as an additive, glycerol is used principally as a highly refined and purified product. And as increasingly greater quantities of glycerol are generated by the biodiesel industry, economical ways of glycerol utilization must be explored to further defray the cost of biodiesel production. In this review we will explore the scope and limitation of using glycerol as a sustainable reaction medium in organic transformations.

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2. GLYCEROL AS A SUSTAINABLE REACTION MEDIUM

Glycerol's physical and chemical properties hint at its promise to be used as a green solvent. It has a very high boiling point and negligible vapor pressure, it is compatible with most organic and inorganic compounds, and it does not require special handling or storage. Like other polar organic solvents such as DMSO and DMF, glycerol dissolves inorganic salts, acids and bases, enzymes and TMCs, but it also dissolves organic compounds that are poorly miscible in water and it is non-hazardous. Hydrophobic solvents such as ethers and hydrocarbons, which are immiscible in glycerol, enable reaction products to be simply extracted. Product distillation is also feasible due to the high boiling point of glycerol. A comparison of several relevant properties of glycerol, water, ionic liquid [1-butyl, 3methylimidazolium hexafluorophosphate (BmimPF6) as a representative commercial and commonly used IL], and perfluorohexane (tetradecafluorohexane) as the representative fluorocarbon solvent are summarized in Table 1. Table 1. Properties of alternative green solvents [40]
Glycerol 290 <1 42.5 629 1.29 Yes 12600 Without/ minor H2 O 100 92.51 78.5 1 1 >90000 Minor BmimPF6a >300 <1 11.4 312 1.37 No ~1500 Without C6F14 58-60 n.a. <5 n.a 1.66 No ~5000 Tedious

NBP(C) Vapor pressure at 50C (mmHg) Dielectric constant (25C) Viscosity (cP) (30C) Density (g/mL) Biodegradability LD50 (Oral-Rat) (mg/Kg) TMCs modification
a

BmimPF6= 1-butyl-1-methylimidazolium hexafluorophospate.

In addition to the characteristics that confer upon glycerol its potential for use as a green reaction medium, it boasts additional properties that grant it superiority over alternative green solvents. First, because glycerol is produced as a by-product of the constantly expanding oilbased chemical industries, its availability is high and its price is low. In addition, the production of glycerol is a simple transesterification (Figure 1) process that is not associated with the use of a toxic reagent or the production of large amounts of toxic waste as with other green solvents. In short, its unique chemical, physical, and biological properties make glycerol an exceptionally safe solvent. Based on all the advantages outlined above, Wolfson, Dlugy, and Shotland reported several years ago for the first time about the use of glycerol as a reaction medium in both catalytic and non-catalytic organic syntheses [40]. Since then, glycerol has been successfully employed as a green solvent in a wide variety of organic reactions and synthesis methodologies, showing its versatility as a solvent for organic synthesis (Table 2). Indeed, glycerol is suitable in homogeneous and heterogeneous chemo- and bio-catalyst systems as well as in catalyst free systems, and in most of the reactions, high product yields and selectivities were achieved.

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Adi Wolfson, Christina Dlugy and Dorith Tavor Table 2. Organic reactions in glycerol

Entry Reaction Non Catalytic 1 Nucleophilic substitution 2 Reduction of carbonyls 3 aza-Michael reactions 4 Michael reactions 5 Ring opening of epoxide 6 Electrophilic activation of aldehydes 7 Wolff-Kishner reduction of benzaldehyde 8 Electro reduction of benzaldehyde Homogeneous and heterogeneous chemo-catalysts 9 Heck coupling

Catalyst Pd(OAc)2 Pd(OAc)2(TPPTS)2a PdCl2 PdCl2(TPPTS)2a PdCl2(DPPF)2b Pd/C Pd(OAc)2 Pd(OAc)2(TPPTS)2a PdCl2 PdCl2(TPPTS)2a PdCl2(DPPF)2a Pd/C KOH CeCl3*7H2O Bases Bases Pd/APc Ru(p-cumene)Cl2-dimer RuCl2(TPPTS)3a Ru/C Pd/C Raney-nickel RhCl2(TPPTS)3a Pd/C Ru-BINAP [C8Mim]NTf2d KF/Alumina Free and immobilized bakers yeast, Aspergillus terreus, Rhizopus oryzae Novozyme-435

Reference 40 40, 43 41 41 41 42 43 43 40, 44, 45

10

Suzuki coupling

44

11 12 13 14 15 16

Aldol condensation Electrophilic substitution of indoles Ring opening of epoxides Knoevenagel-type reactions , -diarylation of acrylates Transfer hydrogenation-dehydrogenation

45 46 47 47 48 50, 51

17

Hydrogenation

40, 43 43 41 52 40, 53, 54, 43, 55

18 Asymmetric reduction 19 Dimerization 20 Michael reactions Homogeneous and heterogeneous bio-catalysts 21 Asymmetric reduction

22

Trans-esterification (kinetic resolution of racemate)

40, 49

Glycerol as a Sustainable Solvent for Homogeneous Catalysis

a

191

TPPTS= tris-(3-sulfophenyl)-phosphine trisodium salt. b DPPF= [1,1'-Bis (diphenylphosphino) ferrocene). c Pd/AP= palladium nanoparticles stabilized over sugar-based surfactant. d [C8Mim]NTf2= 1-methyl-3-octyl imidazolium bis[trifluoromethylsulfonyl]amide.

Solubility of Reactants and Products in Glycerol

The key property of a reaction solvent is its solvation capability. A solvent should facilitate the combination of reactants and catalysts, and as such, it should be able to dissolve solids, liquids, and gases as required. Many organic reactions also require the dissolution of salts and organic compounds or hydrophilic and hydrophobic molecules simultaneously. On the other hand, the solubility of the reaction product in the reaction medium and the nature of the solvent also dictate separation technique. Glycerol, a polar organic solvent, can dissolve a variety of compounds, but it also facilitates the separation of many organic molecules by simple extraction with glycerol immiscible solvents. Several catalyst-free organic transformations were performed in glycerol using its ability to dissolve both organic and inorganic molecules (Table 2, entries 1-8). Table 3 summarizes the yields of several representative catalyst-free reactions in glycerol, water, or DMSO for comparison and illustrates the beneficial use of glycerol as a reaction solvent. One of the first examples of organic transformation in glycerol that exploits its ability to dissolve a non-polar organic compound and a polar ionic salt together is the nucleophilic substitution of benzyl chloride with potassium thiocyanate [40]. Similarly, the nucleophilic substitution of benzyl bromide with ammonium acetate (Figure 2a) was run in water, DMSO, or glycerol, and the reactions in both organic solvents were faster than that in water, since the solubility of benzyl bromide, which is negligible in water, was augmented in the organic solvents (Table 3, entry 1). The yield of benzyl acetate in DMSO was higher then in glycerol, but as a natural, biodegradable, green organic solvent, glycerol is preferable. Separation of product at the end of the reaction was done by extraction with diethyl ether followed by evaporation of the extracting solvent under reduced pressure [40]. It should be maintained that although the addition of extraction solvent makes the procedure "less green", when glycerol is used, less hazardous extraction solvents can be used because glycerol is immiscible with a variety hydrophobic solvents. Another example of the advantage of using glycerol (as a polar reaction medium) instead of water and DMSO was demonstrated by Gu and Jrme in the catalyst-free azo-Michael reaction between p-anisidine and n-butyl acrylate (Figure 2b; Table 3, entry 2; [41]). The reaction, which showed no product in the DMSO and only trace amounts of product in the water, yielded large amounts of product in the glycerol. The authors assumed that the different behaviors observed for water and glycerol arose from the better affinity of p-anisidine for the glycerol interface, thus inducing a faster reaction rate compared to what was observed with water. At the end of the reaction the product was removed by extraction with ethyl acetate after which the glycerol was re-used twice. The second and third reaction runs returned comparable product yields. Moreover, using crude glycerol from the transesterification of oil (Figure 1), which produced about 20% water and soap, was also tested in the same reaction and yielded similar amounts of product. Employing crude glycerol as a solvent has definite environmental and economical advantages as it does not require tedious purification after alcoholysis. In the same report, Gu and Jrme also studied the catalyst-free ring opening of styrene oxide with p-anisidine (Figure 2c; Table 3, entry 3; [41]). In this reaction, which is usually

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acid-catalyzed, the reaction in either water or glycerol proceeded successfully, even without a catalyst. Moreover, in terms of selectivity, glycerol was also shown to perform well, as the regioselectivity obtained in glycerol was higher than that for water.
Br OAc

a)

NaOAc

NaBr

NH2 O b) OMe H N O c) NH2 MeO a H N MeO b CHO d) NO2

H N O MeO O

OH

+
OMe

OH

H N

2 N H N H

Figure 2. Catalyst-free reactions in glycerol: a) Nucleophilic substitution; b) aza-Michael reaction [41]; c) Ring opening of styrene oxide [41]; d) Electrophilic activation of nitrobenzaldehyde [42].

The electrophilic activations of aromatic aldehydes were also reported to proceed better in glycerol than in water or in different organic solvents (Figure 2d; Table 3, entry 4; [42]). Again, reactions that usually include acid catalyst were run in glycerol under catalyst-free conditions. In the reaction between 4-nitrobenzaldehyde and 2-methylindole, not only was the product yield in glycerol higher than in water, but it also resulted in a glycerol insoluble solid that was easily isolated by filtration. The examples discussed above illustrate the flexibility of glycerol as a reaction solvent that facilitates both the dissolution of a range of organic and inorganic compounds and simple product separation. Furthermore, in addition to the green nature and production process of

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glycerol compared to other green alternative reaction mediums, its use as a solvent also permitted running several reactions without catalyst and yielded higher activities and selectivities. The reaction procedure in glycerol is therefore cleaner as it is more material and energy efficient. Table 3. Catalyst-free organic transformations in polar solvents Product yield (%)
Reaction Nucleophilic substitutiona aza-Michaelb,[41] Ring opening c,[41] Electrophilic activation of aldehydese, [42]
a

Water 38.1 <5 88 (a/b=76/24)d 76

DMSO 100 0 0 <5

Glycerol 60.3 82 85 (a/b=93/7)d 95

Reaction conditions: 0.8 mmol benzyl bromide, 0.88 mmol ammonium acetate, 5 ml solvent, 70 C, 1 h. b Reaction conditions: 1.0 mmol p-Anisidine, 1.0 mmol, butyl acrylate, 1 mL solvent, 100 C, 20 h. c Reaction conditions: 1.0 mmol p-Anisidine, 1.0 mmol butyl acrylate, 1 mL solvent, 100 C, 20 h. d Regioselectivity as presented in Figure 2c.e Reaction conditions: 90 C, 3 h.

Heterogenization of Metal Catalysts in Glycerol

Catalysts are required for many organic reactions to proceed. In fact, the development of environmental friendly processes often rely on catalysis, the inclusion of which may enable toxic reagents to be replaced and may improve reaction activity and selectivity. As a result, the formation of by-products can be reduced, leading to simpler, cleaner, and more effective separation processes [6-9]. Heterogeneous catalysts have the distinct advantage that they can be easily separated and re-used while homogeneous catalysts are usually very specific, active, and selective. Therefore, TMCs in biphasic systems are frequently heterogenized to combine the advantages of homogeneous and heterogeneous catalysis [11].
X

Pd catalyst, base +

a)
X=Br, I

+ Glycerol

HX

B(OH)2

b)

Pd catalyst, base
+

Glycerol X=I, Br, Cl

Figure 3. a) Heck coupling of halobenzene and activated olefin; b) Suzuki cross-coupling of halobenzene and phenylboronic acid [44].

A variety of catalytic reactions were run in glycerol using homogeneous and heterogeneous chemo- and bio-catalysts (Table 2, entries 9-22). One of the first examples of a

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catalytic reaction in glycerol was the palladium-catalyzed Heck C-C coupling reaction of iodobenzene and butyl acrylate (Figure 3a; [40]). A more intense study of the scope and limitations of C-C coupling in glycerol was reported later for both the Heck coupling of halobenzenes with various alkenes and the Suzuki cross-coupling of halobenzenes with phenylboronic acid (Figure 3a and b; [44]). Palladium salts and complexes and supported palladium catalyst were used together with organic and inorganic bases as co-catalysts (Table 4). In general, it was found that glycerol can function as an alternative green solvent for the C-C coupling reactions. Various halobenzenes can be employed and as expected, iodobenzene was the most active halobenzene. The use of palladium salts and complexes as catalysts and inorganic bases as co-catalysts yielded more products (Table 4). Table 4. Palladium-catalyzed Heck and Suzuki coupling of iodobenzene with butyl acrylate and phenylboronic acid in glycerola [44]
Entry 1 2 3 4 5 6 7 8 9 10 11
a

Catalyst PdCl2 PdCl2 Pd(OAc)2 Pd(OAc)2 PdCl2(TPPTS)2 PdCl2(TPPTS)2 Pd(OAc)2 (TPPTS)2 Pd(OAc)2 (TPPTS)2 PdCl2(DPPF)2e Pd/C Pd/C

Base Et3N Na2CO3 Et3N Na2CO3 Et3N Na2CO3 Et3N Na2CO3 Na2CO3 Et3N Na2CO3

Time (h) 4 4 4 4 4 4 4 4 4 4 4

Yield (%) Heckb 74 100 65 72 87 100 (83)d 56 100 86 40 78

Time (h) 1 1 1 1 1 1 1 1 1 1 1

Yield (%) Suzukic 76 90 81 95 83 94 66 75 82 61 88

0.5 mmol iodobenzene, 0.75 mmol butyl acrylate or phenylboronic acid, 0.01 mmol catalyst, 0.6 mmol base, 5 g glycerol, 80 C. b 4 h. c 1h. d Styrene was employed instead of butyl acrylate. eAs above, but using 20 g glycerol.

As a sustainable solvent, glycerol also enabled both solvent and catalysts to be recycled [40, 44]. The recycling of transition metal complexes of the types PdCl2(TPPTS)2 and PdCl2(DPPF)2 (DPPF= [1,1'-Bis (diphenylphosphino) ferrocene) and the supported palladium catalyst (Pd/C) in glycerol was examined in the Suzuki cross-coupling of iodobenzene and phenylboronic acid (Figure 3b; Table 5; [44]). Catalysts were recycled after the extraction of both iodobenzene and biaryl from the glycerol catalytic phase using diethyl ether. Then, equal amounts of fresh substrates and sodium carbonate were added to the glycerol, and the reactions were re-run under identical conditions. The activity of PdCl2(DPPF)2 was not reduced after each cycle while those of PdCl2(TPPTS)2 and Pd/C were (Table 5). In the case of PdCl2(TPPTS)2, the authors assumed that the reduction in its activity may have resulted from the decomposition of the complex, as the formation of palladium aggregates was observed.

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195

As previously mentioned, glycerol synthesis via alcoholysis yielded crude glycerol with alcohol, water, and soap as leftovers. Yet when glycerol is used as a reactant or as an additive, usually it must be in its highly refined and purified form. The tedious purification process may be avoidable, however, if non-purified, crude glycerol is used as the reaction medium. Therefore, crude glycerol from several oil sources and without any purification was also tested as a reaction medium in the palladium-catalyzed Heck coupling of iodobenzene and butyl acrylate using various catalysts (Figure 3a; Table 6; [44]). The reaction was compared to those in pure glycerol and in pure glycerol with the addition of methanol and water to resemble crude glycerol contaminates (Table 4). In general, although it was found that the crude glycerol yields were lower than those in pure glycerol with all the catalysts tested, they were still satisfactory. In addition, for more stable complexes, as in the case of PdCl2(TPPTS)2, the conversion in crude glycerol was close to that of the reaction in pure glycerol (Table 6, entry 3). Table 5. Catalyst recycling in the Suzuki cross-coupling of iodobenzene and phenylboronic acid in glycerola [44]
Yield (%) Pd/C 98 61 50

Catalyst /Cycle 1 2 3

PdCl2(TPPTS)2 88 55 47

PdCl2(DPPF)2b 82 80 80

a 0.5 mmol iodobenzene, 0.6 mmol phenylboronic acid, 0.6 mmol Na2CO3, 2 mol% palladium, 5 g glycerol, 80 C, 1h. b 20 g glycerol.

Table 6. Conversions of iodobenzene in the palladium-catalyzed Heck coupling of iodobenzene and butyl acrylate in crude glycerola [45]
Entry Catalyst Pure glycerol Pure glycerol+ methanolb 96.1 70.8 85.9 77.6 Pure glycerol+ waterb 97.2 71.2 86.5 77.2 Crude glycerol without the addition of KOH 58.5 41.3 76.4 39.0 Crude glycerol with the addition of KOHc 63.6 45.7 78.8 47.8

1 2 3 4
a

PdCl2 Pd(OAc)2 PdCl2(TPPT S)2 Pd/C

94.2 70.1 86.1 (73)d 75.4

Reaction conditions: 5 mL glycerol, 0.5 mmol iodobenzene, 0.6 mmol butyl acrylate, 80 C, 4 h. b Addition of 0.25 g methanol or water. c Addition of 0.5 mmol KOH. d Before the reaction, pure glycerol was mixed with methyl esters of fatty acid.

To test whether leftovers from crude glycerol synthesis caused the reduced performance, small amounts of methanol, water, or methyl esters of fatty acids were added to the pure glycerol during the reaction. It was found that while the addition of either methanol or water did not affect reaction conversions, the addition of fatty acid esters, i.e. biodiesel, to pure glycerol resulted in a lower conversion (Table 6, entry 3). The authors mentioned that since

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the palladium-catalyzed Heck coupling of halobenzene and activated olefin involved coordination of a double bond of an olefin to the catalyst, it is possible that the biodiesel and the soap traces in the crude glycerol coordinated to the catalyst and decreased its activity. Nevertheless, as crude glycerol was produced by the alcoholysis of triglyceride in the presence of KOHwhich can also serve as co-catalyst in Heck couplingthe reaction was run with and without the addition of extra KOH. Similar conversions with both reactions, revealing that the residual base from the synthesis of crude glycerol can be re-used in the Heck reaction (Table 6). Crude glycerol from several oil sources was also used as a reaction medium in the aldol condensation of n-valeraldehyde (Figure 4; Table 2, entry 11; [45]), using fresh or residual KOH from alcoholysis as a catalyst. As expected, the condensation occurred with or without the addition of excess base. The reactions run without the extra addition of fresh KOH yielded lower conversions, probably since some of the KOH was lost and deteriorated during the alcoholysis of the oil. In addition, it was found that the oil source did not affect reaction performances [45]. Finally, the glycerol and the soluble base within were also successfully recycled by extraction of the product with diethyl ether and the addition of fresh substrate.
O

KOH 800C, 2h
H

Conversion with the addition of KOH: 43% Conversion without the addition of KOH: 28%
Figure 4. Aldol condensation of n-valeraldehyde [45].

Another example of a recyclable catalytic system involving glycerol entails the use of CeCl3*7H2O in indole reactions with aliphatic and aromatic aldehydes (Figure 5; Table 2, entry 12; [46]). A variety of bis(indolyl)methanes were synthesized in good to excellent yields and the glycerol and catalyst mixture was re-used up to five times after extraction of the product with ethyl acetate without special treatment, and comparable yields were produced during each subsequent synthesis.
R 2 X NH X=H, Br R=Aliphatic, aromatic

RCHO

CeCl3*7H2O 750C, 1.5-10h X NH 70-95% yield NH X

Figure 5. Synthesis of bis(indolyl)methanes [46].

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197

Emulsion Catalytic Systems in Glycerol

The high polarity of glycerol enabled the products to be easily isolated and the catalyst to be easily recycled by extraction with hydrophobic organic solvents like ethers and esters. Yet the polarity of glycerol may also be a drawback when the reactants comprise highly hydrophobic compounds, in which case biphasic systems may develop, resulting in mass transfer limitations and lower activity. The addition of surfactant to the reaction mixture can facilitate the mixing of the two phases to produce an emulsion-like system. The catalytic hydrogenation of styrene (which has a low solubility in glycerol) using a RhCl2(TPPTS)3 catalyst was studied in glycerol with and without the addition of surfactant (Figure 6; Table 2, entry 17; [40]). The reaction without added surfactant was slower then that in methanol under similar conditions, but the addition of Pluronic, a triblock copolymer surfactant, increased the conversion by almost 40%, from 61% to 84%.

Rh(TPPTS) 3 Cl2 H2 80 0 C, 3h

Conversion without the addition of surfactant: 61% Conversion with the addition of surfactant: 84%
Figure 6. Catalytic hydrogenation of styrene [40].

Karam and co-authors also demonstrated a noteworthy emulsion catalytic system in glycerol (Table 2, entry 13; [47]) in their study of the base-catalyzed ring opening reaction of epoxides (Figure 7). Initially, several conventional solid bases were employed as catalysts, yielding full epoxide conversion after only 18 h and large amounts of by-product from the epoxide-glycerol reaction. The authors assumed that the low activity was due to the low solubility of the reactants, which have long hydrocarbon chains, in the polar glycerol catalytic phase. Employing a new family of aminopolysaccharides (APs) as surfactants and catalysts with basic characters led to a decrease in reaction time and yielded only trace amounts of byproduct from the epoxide-glycerol reaction. (Figure 7).

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OH O ( )9 ( )9 O ( )9

O ( )9

O Product ester OH ( )9 O OH OH

Glycerol ether Solid base : time=18 h, conversion=98%, selectivity (ester/ether)=80/15 Aminopolysaccharide (AP): time=3 h, conversion=98%, selectivity (ester/ether)=95/traces

Figure 7. Ring opening of epoxides [47].

The authors suggested that the use of APs allowed the organic substrates to diffuse better in the glycerol phase by creating hydrophobic environments within the glycerol. Moreover, they found that micellar catalysis in glycerol was superior to that in water as the emulsions formed in glycerol were found to be unstable. As a result, rapid phase separation at the end of the reaction allowed easy product extraction without the assistance of organic solvents. The procedure was successfully used not only in the selective ring opening of epoxides with carboxylic acids, but also in other base-catalyzed reactions in glycerol, such as Knoevenageltype reactions, Henry reactions, and Michael additions [47]. The same sugar-based surfactants (APs) were also used to stabilize palladium nanoparticles in the , -diarylation of acrylates (Figure 8; Table 2, entry 15; [48]). Typically, the , -diarylation of acrylates is performed at high temperatures in organic solvents with high boiling points, but a greener synthesis route is possible with glycerol because of its greater environmental friendliness and because the reaction temperature can be reduced when using glycerol [48]. However, the highly glycerol miscible reaction products are difficult to extract using glycerol immiscible solvents. Furthermore, distillation of the glycerol is also not a feasible option due to its high boiling point. Hence, scCO2, which was found to be soluble in glycerol (glycerol is only negligibly soluble in scCO2), was tested as an extraction solvent. It was found that at 50 C, 250 bar, and with a scCO2 flow of 40 g min1, the , -diarylated products were cleanly and selectively recovered with a molar purity of 93% while the Pd/AP remained in the glycerol phase.

O OR

Pd/AP, NH3

Ar Ar

O OR

2 Ar-I
1200C 70-90% Yield

Figure 8. , -diarylation of acrylates [48].

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Microwave-assisted Synthesis in Glycerol

As a non-volatile, highly polar organic solvent, glycerol is also applicable in microwavepromoted reactions. Based on the ability of the solvent to absorb microwave energy and convert it into heat, microwave heating is a more efficient and energy saving alternative to conventional heating [56, 57]. Polar solvents, especially those with hydroxyl substitution are very attractive solvents for this purpose due to their high dielectric constants and high boiling points. Hence, glycerol seems to be an excellent candidate for microwave-assisted reactions. In addition, non-volatile up to very high temperatures, glycerol is superior to water and other organic solvents typically used for this purpose. The first example of a microwave promoted organic transformation in glycerol was the Wolff-Kishner reduction of benzaldehyde to toluene (Figure 9; Table 2, entry 7; [43]). The reaction, which was carried out in a domestic microwave at lower temperatures than under conventional heating, was much faster, and it yielded full conversion and selectivity to toluene. In addition, microwave-promoted heating was also reported to enhance C-C coupling reactions [58]. Therefore, the Suzuki C-C cross coupling reaction in glycerol was also performed under microwave irradiation in a domestic microwave (Table 7). The results illustrated in Table 7 confirmed the assumption that glycerol can be used successfully as a solvent in microwave-assisted reactions.
NH2 H O
+

N H2NNH2
+

KOH

Yield=100% Selectivity=100%
Figure 9. Microwave-promoted Wolff-Kishner reduction of benzaldehyde to toluene in glycerol [43].

Glycerol as Reactant and Solvent

In the above-mentioned reactions, glycerol was used as a sustainable solvent, where it enabled the dissolution of both reactants and catalysts, enhanced reaction activities and selectivities, facilitated easy separation of the products and recycling of the catalysts, and supported more efficient heating. In addition to being a solvent, glycerol can also function as a reactant. One example of such a system is the lipase catalyzed kinetic resolution of an ester racemate in glycerol, for which the glycerol functioned as both solvent and resolving agent (Table 2, entry 22; [40, 49]). In another example, glycerol was used simultaneously as solvent and hydrogen donor in the catalytic transfer-hydrogenation of various unsaturated organic compounds while oxidizing to dihydroxyacetone (Figure 10; Table 2, entry 16; [50, 51]). The reduction of unsaturated compounds in glycerol, previously studied in the presence of metal hydrides as stoichiometric reductants (Table 2, entry 2; [40, 43]), yielded large amounts of waste that had

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to be neutralized, thus making the reduction procedure less environmental friendly and less attractive. Table 7. Microwave-promoted Suzuki cross-coupling of iodobenzene and phenylboronic acid in glycerola [44]
Entry 1 2 3
a

Heating oil bath microwave microwave

Time (min) 60 5 10

Conversion (%) 94 15 61

Reaction conditions: 0.5 mmol iodobenzene, 0.6 mmol phenylboronic acid, 0.6 mmol Na2CO3, 2 mol% palladium, 5 g glycerol, 80 C, 4h.

Alternatively, the catalytic hydrogenation of several organic molecules (Table 2, entry 17; [40, 43]) as well as the enantioselective hydrogenation of ethyl acetoacetate over RuBINAP in glycerol (Table 2, entry 18; [43]) were limited most likely by the low solubility of molecular hydrogen in glycerol. On the other hand, using glycerol as the hydrogen source in a transfer-hydrogenation system resulted in very high product yields, and glycerol was dehydrogenated to dihydroxyacetone, a valuable intermediate in the production of many chemicals [59, 60]. This new catalytic system did not produce large amounts of waste as with the metal hydride, and unlike hydrogenation with molecular hydrogen, neither special equipment nor precautions were necessary. Moreover, as was previously shown, glycerol also enabled easy product separation and catalyst recycling.
CHO OH a) CH2OH OH
Ru(p-cumene)Cl2-dimer, KOH

HO

24 h, 700C

+
Yield=99%

HO

OH

CHO OH b)

CH2OH OH Pd/C 5 h, 700C O

HO

+
Yield=100%

HO

OH

CHO OH c)

CH2OH OH Raney Nickel, NaOH 24 h, 700C O

3 HO

+
Yield=43%

HO

OH + 2 H2O

Figure 10. Transfer-hydrogenations of unsaturated organic compounds in glycerol [50].

Glycerol as a Sustainable Solvent for Homogeneous Catalysis

201

CONCLUSIONS AND PERSPECTIVES

Glycerol was found to be attractive as a sustainable solvent for organic reactions. A byproduct of fatty acid ester production from renewable sources, glycerol can be used as a solvent without purification. It has promising physical, chemical, and biological properties that make it non-volatile, non-hazardous, recyclable, and biodegradable, i.e., it is a green solvent. In addition, glycerol can dissolve many organic and inorganic compounds and transition metal complexes while also allowing easy product separation by extraction with glycerol immiscible solvents such as ethers, esters, and supercritical carbon dioxide. Glycerol was successfully used as a solvent in many catalytic and non-catalytic organic reactions, using homogeneous and heterogeneous chemo- and biocatalysts. In many reactions, the presence of glycerol as a solvent improved product yields and selectivities and enabled catalyst recycling, emulsion-like systems, and microwave promoted reactions. Furthermore, its high boiling point and polarity make glycerol the perfect candidate for non-conventional heating and mixing reactions such as the microwave-assisted reaction. Finally, glycerol can also be used as both solvent and reactant, such as in the catalytic transfer-hydrogenation of various unsaturated organic compounds and in the transesterification of alcohols. Despite glycerol's promise as a sustainable solvent for liquid phase catalytic and noncatalytic organic syntheses, there are several drawbacks to its utilization, including the low solubility of highly hydrophobic compounds in glycerol, the low solubilities of gases such as hydrogen and oxygen in glycerol that limit its applications in catalytic hydrogenation and aerobic oxidation, and the use of hazardous, hydrophobic organic solvents for product extraction and catalyst recycling. These weaknesses should be further studied with the aim to provide novel solutions. In addition, the effects of glycerol itself and of contaminants from its production process on reaction performance should also be explored further.

REFERENCES
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[11] Jacobs, P.A.; Vankelecom, I.F.J.; De Vos, D. Chiral Catalyst Immobilisation and Recycling, Wiley-VCH, Weinheim, Germany, 2000. [12] Klibanov, A. M. Nature 2001, 409, 241-246. [13] Yang, L.; Dordick, J. S.; Garde, S. Biophysical Journal 2004, 87, 812-821. [14] Cornils, B.; Herrmann, W. A. Applied Homogeneous Catalysis with Organometallic Compounds, Wiley-VCH, Weinheim, Germany, 2002. [15] Horvth, I. T.; Rbai, J. Science 1994, 266, 72-75. [16] Fish, R. H. Chemistry- A European Journal 1999, 5, 1677-1680. [17] Olivier-Bourbigou, H.; Magna, L. J. J. Mol. Catal. 2002, 182 , 419-437. [18] Dupont, J.; de Souza, R. F.; Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667-3691. [19] Welton, T. Coord. Chem. Rev. 2004, 248, 2459-2477. [20] Wasserscheid, P.; Welton, T. Ionic liquids in synthesis, Weinheim, Wiley-VCH, 2003. [21] Stock, F.; Hoffmann, J.; Ranke, J.; Strmann, R.; Ondruschka, B. Jastorff, B. Green Chem. 2004, 6, 286-290. [22] Ranke, J.; Mlter, K.; Stock, F.; Bottin-Weber, U.; Poczobutt, J.; Hoffmann, J.; Ondruschka, B.; Filser, J.; Jastorff, B. Ecotoxicol. Environ. Saf. 2004, 28, 396-404. [23] Hutchenson, K. W.; Foster, N. R. Innovations in supercritical fluids: science and technology, Washington, DC, American Chemical Society, 1995. [24] Johnston, K. P.; Penninger, J. M. L. Supercritical fluid science and technology, Washington, DC, American Chemical Society, 1989. [25] Arai, Y.; Sako, T.; Takebayashi, Y. Supercritical fluids: molecular interactions, physical properties and new applications, Berlin, Springer, 2002. [26] Mikami, K. Green reaction media in organic synthesis, Blackwell, 2005. [27] Brunner, G. Supercritical fluids as solvents and reaction media, Elsevir, 2004. [28] McHardy, J.; Sawan, P. Supercritical Fluid Cleaning: Fundamentals, Technology and Applications, Noyes Publ., 1998. [29] Lindsey, A. S.; Jesky, H. Chem. Rev. 1957, 57, 583-620. [30] Raventos, M.; Duarte, S.; Alarcon, R. Food Science and Technology International 2002, 8, 269-284. [31] McHugh, M. A.; Krukonis, V. J. Supercritical fluid extraction, principles and practice, Butterworths-Hienemann, Stoneham, 1994. [32] Ma, F.; Hanna, M. A. Bioresource Technol. 1999, 70, 1-15. [33] Kaieda, M.; Samukawa, T.; Kondo, A.; Fukuda, H. J Biosci. Bioeng. 2001, 91, 12-15. [34] Zhou, C. H.; Beltramini, J. N.; Fan, Y. X.; Lu, G. Q. Chem. Soc. Rev. 2008, 37, 527549. [35] Haag, R.; Sunder, A. Stumbe, J F. JACS 2000, 122, 2954-2955. [36] Kusunoki, Y.; Miyazawa, T.; Kunimori, K.; Tomishige, K. Catal. Commun. 2005, 6, 645-649. [37] Perosa, A.; Tundo, P.Ind. Eng. Chem. Res. 2005, 44, 8535-8537. [38] Demirel-Gulen, S.; Lucas, M.; Claus, P. Catal. Today, 2005, 102-103, 166-172. [39] Yazdani, S. S.; Gonzalez, R. Current Opinion in Biotech. 2007, 18, 213-219. [40] Wolfson, A.; Dlugy, C.; Shotland, Y. Environ. Chem. Lett. 2007, 5, 67-71. [41] Gu, Y.; Barrault, J.; Jrme, F. Adv. Synth. Catal. 2008, 350, 2007-2012. [42] Silveira, C. C.; Mendes, S. R.; Lbero, F. M.; Lenardo, E. J.; Perin, G. Tetrahedron letters 2009, 50, 6060-6063. [43] Wolfson, A.; Dlugy, C. Org. Commun. 2009, 2, 34-41.

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[44] Wolfson, A.; Dlugy, C. Chem. Papers 2007, 61, 228-232. [45] Wolfson, A.; Litvak, G.; Dlugy, C.; Shotland Y.; Tavor, D. Industrial Crops and Products 2009, 30, 78-81. [46] Silveira, C. C.; Mendes, S. R.; Lbero, F. M.; Lenardo, E. J.; Perin, G. Tetrahedron letters 2009, 50, 6060-6063. [47] Karam, A.; Villandier, N.; Delample, M.; Koerkamp, C. K.; Douliez, J. -P.; Granet, R.; Krausz, P.; Barrault, J.; Jrme, F. Chemistry, A Europenean J. 2008, 14, 1019610200. [48] Delample, M.; Villandier, N.; Douliez, J.-P.; Camy, S.; Condoret, J.-S.; Pouilloux, Y. ; Barrault, J.; Jrme, F. Green Chem. 2010, 12, 804808. [49] Dlugy, C.; Wolfson, A. Bioprocess and Biosystems Eng. 2007, 30, 327-330. [50] Wolfson, A.; Dlugy, C.; Shotland, Y.; Tavor, D. Tetrahedron letters 2009, 50, 59515953. [51] Tavor, D.; Sheviev, O.; Dlugy, C.; Wolfson, A. Canadian J. Chem. 2010, 88, 305-308. [52] Lenardo, E. J.; Trecha, D. O.; da C. Ferreira, P.; Jacob, R. G.; Perin, G. J. Braz. Chem. Soc. 2009, 20, 93-99. [53] Wolfson, A.; Dlugy, D.; Tavor, D.; Blumenfeld, J.; Shotland, Y. Tetrahedron: Asymmetry 2006, 17, 2043-2045. [54] Wolfson A.; Haddad N.; Dlugy C.; Tavor D.; Shotland Y. Org. Commun. 2008, 1, 9-16. [55] Leandro, H. A.; Piovan, L.; Pasquini, M. D. Tetrahedron: Asymmetry 2009 ,20, 15211525. [56] Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250-6284. [57] Tierney, J.; Lidstrom, P. Microwave Assisted Organic Synthesis, Blackwell, Oxford, 2004. [58] Arvela, R. K.; Leadbeater, N. E. J. Org. Chem. 2005, 70, 17861790. [59] Davis, W. R.; Tomsho, J.; Nikam, S.; Cook, E. M.; Somand, D.; Peliska, J. A. Biochem. 2000, 39, 14279-14291. [60] Kimura, H.; Tsuto, K. J. Am Oil Chem. Soc. 1993, 70, 1027-1030.

In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 7

HOMOGENEOUS CATALYSIS IN CARBONYLATIVE COUPLING REACTIONS

Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai-400 019. India.

ABSTRACT
Carbon monoxide is a ubiquitous molecule in organometallic chemistry and an important feedstock in multiple catalytic processes both at the laboratory and industrial levels. Palladium-catalyzed carbonylation reactions of alkenes/alkynes, aromatic halides with different nucleophiles have undergone rapid development since the pioneering work of Reppe and Heck, such that nowadays plethora of palladium catalysts and various synthetic protocols are available for the synthesis of aliphatic and aromatic carboxylic acids as well as their derivatives. The carboxylic acid and its derivatives like amides, esters, thioamides etc. and ketones prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products. The term carbonylation covers a large number of closely related reactions that all have in common that carbon monoxide is incorporated into a substrate by the addition of CO to an aryl-, benzyl- or vinylpalladium complex in presence of suitable nucleophiles. Various carbonylation reactions like alkoxycarbonylation, phenoxycarbonylation, aminocarbonylation, thiocarbonylation, carbonylative Suzuki coupling reaction, carbonylative Sonogashira coupling reaction etc. have been explored using palladium as a catalyst of choice. Palladium along with variety of ligands has been widely employed as homogeneous catalysts to affect carbonylation reactions. The scope of carbonylation reactions is also extended for the synthesis of pharmaceuticals and their important intermediates using carbonylation as the key step using homogeneous catalysis, which reveals that complex synthetic processes can be accomplished under carbonylation conditions.
*

Corresponding author: Tel.: +91 22 33612601; fax: +91 bhalchandra_bhnaage@yahoo.com, bm.bhanage@ictmumbai.edu.in.

22

33611020,

Email

address:

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

Herein, we summarize the recent developments in homogeneous catalysts and selected organic applications in this area.

INTRODUCTION
The development of environmentally benign and efficient synthetic methods continues to be a central goal of current research in chemistry. In this regard, catalysis and organometallic chemistry are key techniques for achieving these objectives and for contributing to a greener chemistry in the future. Among the different catalytic reactions, the refinement of readily available feedstock to more-functionalized products is of particular importance. Prime examples for such transformations are carbonylation processes, which make use of carbon monoxide currently the most important C1 building block. Hence, carbonylation represents industrial core technologies for converting various bulk chemicals into a diverse set of useful products of our daily life. For example, the conversion of olefins, the basic raw materials for the chemical industry, by carbonylation gives access to more valuable products such as aldehydes, alcohols and carboxylic acid derivatives. The term carbonylation was coined by W. Reppe during the thirties and is generally used to refer to those reactions in which CO alone or CO combined with other compounds (especially nucleophiles with mobile H-atoms) are introduced into particular substrates (Saturated or unsaturated). Carbonylation reactions rank among the most useful transformations homogeneously catalyzed by transition metal complexes, forming the basis for industrial and laboratory processes currently in practice [1-4]. Some of the initial scientific discoveries in this field gradually evolved into large-scale commercial carbonylation processes. Noteworthy among the commercial carbonylation processes are the oxo process (olefin hydroformylation) [5-7], the Reppe process (hydroxycarbonylation of acetylene to acrylic acid) and Monsanto process (carbonylation of methanol to acetic acid) [8] etc. These processes are employed worldwide to prepare millions of tones of commodity chemicals each year. Transition metal-catalyzed carbonylation of aryl halides in the presence of nucleophiles is an important methodology for the preparation of aromatic carbonyl compounds which includes ketones, amides, esters, acids and their derivatives [1-4]. The term carbonylation covers a large number of closely related reactions that all have in common that carbon monoxide is incorporated into a substrate by the addition of CO to an aryl-, benzyl- or vinylpalladium complex in the presence of various nucleophiles (Scheme 1). In general, aromatic halides are treated with an appropriate nucleophile in a carbon monoxide atmosphere in the presence of a catalytic amount of a palladium complex, whereby, the leaving group X is formally replaced by the nucleophile with incorporation of carbon monoxide molecule. Typically, the reactions require a stoichiometric amount of base to regenerate the catalyst. In general, aromatic halides are treated with an appropriate nucleophile in a carbon monoxide atmosphere in the presence of a catalytic amount of a palladium complex, whereby, the leaving group X is formally replaced by the nucleophile with incorporation of carbon monoxide molecule (Figure 1). Which of these products is obtained depends on the nucleophile: water (hydroxycarbonylation), alcohols (alkoxycarbonylation), amines (aminocarbonylation), alkyne (carbonylative Sonogashira), boronic acid (carbonylative

Homogeneous Catalysis in Carbonylative Coupling Reactions

207

Suzuki) etc. can be used. A variety of carbonylation products can be prepared from the same aromatic substrate simply by changing the nucleophile, an advantage with respect to biologically active compound libraries. O X Palladium Nu R + CO + Nu H R Base
X = Cl, Br, I, OTf, N2Nu = OH, OR1, NR2R3 .......

Scheme 1. Pd-catalyzed carbonylation of aryl halides.

Nowadays, the use of carbon monoxide as a carbonyl source for aldehydes, ketones, carboxylic acids and their derivatives in various transition metal-catalyzed reactions has become probably the most widespread methodology for homogeneous catalytic reactions.
O O O

NRR' R
R-NHR'

OH

OR

R-X

R-

O H

R-

X RO H2

O R R R

R-X

CO
' HR

R-X

R-SH
R-

SR

N R-

B R-

R-X

)2 H (O

RSnBu3 NRR' O R

R'RN

Figure 1. Pd-catalyzed carbonylation reactions.

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

The suggested mechanism for carbonylation reactions of aryl halide is shown in Figure 2. The key steps in the mechanism of carbonylation reactions are, i) oxidative addition of aryl halide to palladium to form aryl palladium halide complex; ii) insertion of carbon monoxide into aryl palladium halide complex to form acyl palladium halide intermediate; iii) reductive elimination to yield the product. Initially there is oxidative addition of aryl halide to palladium which forms aryl palladium halide complex (intermediate II). Coordination and migratory insertion of CO then forms acyl palladium halide complex (intermediate III). The intermediate III is then attacked by nucleophile and undergo reductive elimination to give carbonylated product. In the catalytic cycle base plays a crucial role to generate a active palladium species which then continues the catalytic cycle.

L Oxidative addition R Pd L II I

CO CO insertion L

RI PdLn I Base HI H

C O

Pd L III

L Pd L I

NuH

Reductive elimination R C O Nu

Figure 2. General mechanism for Pd-catalyzed carbonylation of aryl halide.

Among the various carbonylation reactions, carbonylative coupling reactions has gained considerable attention in recent years and several catalytic systems has been developed to affect theses transformations. It has been observed that mostly homogeneous transition metal catalysts are reported for carbonylative coupling reactions as they provide product in higher yield at ambient conditions. Some of important contributions in this area are summarized below.

CARBONYLATIVE SUZUKI COUPLING REACTION

Diarylketones constitute an interesting and versatile structural motif which is frequently present in natural products (e.g. Cotoin, Papaveraldine), in non-steroidal anti-inflammatory

Homogeneous Catalysis in Carbonylative Coupling Reactions

209

drugs (e.g. Suprofen, Ketoprofen) and occurs in UV screens (e.g. Sulisobenzone, Oxybenzone) (Figure 3). Typically, diaryl-ketones are prepared by FriedelCrafts acylation of ortho/para-directing arenes with acyl halides [9]. Unfortunately, this reaction requires overstoichiometric amounts of Lewis acid and the regioselectivity is often limited to the paraposition. Other synthetic strategies use cross-coupling reactions of benzoic halides with organotin compounds [10-12], palladium-catalyzed coupling of boronic acids with carboxylic anhydride [13] or nickel-catalyzed coupling reactions of aryl iodides with aromatic aldehydes [14]. An especially versatile approach for the synthesis of diarylketones [15] is the transitionmetal-catalyzed three-component cross-coupling of Aryl-X (X = Br, I, OTf, N2+) derivatives, carbon monoxide and aryl metal reagents. However, the coupling reaction of organoaluminium [16] or organosilane [17] compounds with electron-poor aryl halides is severely limited due to the formation of biaryl side products. Here, electron-withdrawing groups on the aryl ring accelerate the rate of transmetallation to form the ArPdAr intermediate and hinder the insertion of carbon monoxide into the ArPdX species. Palladium catalyzed carbonylative Suzuki coupling reaction is one of the most promising method for direct synthesis of biaryl ketones from carbon monoxide, aryl halide and aryl boronic acid.
O N OMe OMe OMe OMe OMe SO3H OMe O OH O OH

Papaveraldine

Sulisobenzone

Oxybenzone

OH

O S COOH

O COOH

HO

OMe

Cotoin

Suprofen

Ketoprofen

Figure 3. Applications of Carbonylative Suzuki coupling reaction.

In 1993, Suzuki et al. introduced the coupling of aryl boronic acids with aryl iodides for the synthesis of diarylketones (Suzuki carbonylation) (Scheme 2) [18]. In principle, these reactions provide a versatile tool for diarylketones synthesis as boronic acids are generally nontoxic and thermally, air and moisture stable. They used PdCl2(PPh3)2 as catalysts for this transformation. Thoroughly they have investigated effect of base on selectivity of the reaction, K2CO3 was found to give good yield of carbonylated products.

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Ar-B(OH)2 + CO

I-Ar '

PdCl2(PPh3)2 Base

Ar-CO-Ar '

Scheme 2. Palladium catalyzed Suzuki carbonylation reaction.

Later on in 1998 they have developed PdCl2/dppf as a versatile catalyst for the same reaction (Scheme 3) [19]. The catalyst was applicable for large variety of aryl electrophiles such as aryl iodide, aryl bromide and aryl triflates. Furthermore they have proposed a possible reaction mechanism.
PdCl2/dppf Base Z Y Z O C

B(OH)2 + CO + X Y

Scheme 3. PdCl2/dppf catalyzed carbonylative Suzuki reaction.

Castanet et al. reported a simple and efficient method for the syntesis of -pyridyl ketone from chloropyridines using Pd(OAc)2/imidazolium salt as a catalyst (Scheme 4) [20]. Various pyridine-chlorides were carbonylated with phenyl boronic acid to yield the desired product in moderate to good yields (51-86 %).

X N

Pd (OAc)2 - Imidazolium salt CO, PhB(OH)2, Base N

COPh

Scheme 4. Pd(OAc)2/imidazolium salt catalyzed carbonylative Suzuki reaction of halopyridines.

Further application of carbonylative Suzuki coupling reaction for the synthesis of pyridylketones was explored by Castanet and group (Scheme 5) [21]. They developed a high yielding protocol for the synthesis of -pyridyl ketone using PdCl2 (PCy3)2 as a catalysts of choice. The catalyst was applicable for various halopyridines providing moderate to excellent yield of the desired products. Palladium(II) acetate and N,N-bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride (2 mol%) was used to catalyze the carbonylative coupling of aryl diazonium tetrafluoroborate salts and aryl boronic acids to form aryl ketones by Song et al. (Scheme 6) [22]. The reaction was optimized with respect to various parameters such as time, temperature, CO pressure and solvent. The catalyst system was applicable for variety of aryl diazonium tetrafluoroborate salts and aryl boronic acids.

Homogeneous Catalysis in Carbonylative Coupling Reactions

211

Scheme 5. PdCl2 (PCy3)2 catalyzed carbonylative Suzuki reaction of halopyridines.

i-Pr Cl N I-Pr i-Pr

i-Pr

Ph-N2+ BF4 + (OH)2B-Ph

Pd (OAc)2 .

O Ph Ph

CO

Scheme 6. Carbonylative coupling of aryl diazonium tetrafluoroborate salts and aryl boronic acids.

Carbonylative Suzuki coupling reaction 1-iodo-cyclohexene and phenylboronic acid (or 3-trifluoromethoxy-phenylboronic acid) was carried out using Pd(PPh3)4 complex by Kollar and group (Scheme 7) [23]. The active catalyst Pd(0) is generated in-situ by the reaction of Pd(OAc)2 and PPh3. The catalyst shows excellent activity for less reactive substrate i.e. 1iodo-cyclohexene providing good to excellent yield of the desired product, however, substantial amount of byproduct was also forming in the reaction.

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

I Pd (PPh 3 )4 CO B(OH) 2

Pd (PPh 3 ) 4 CO OCF 3 B(OH) 2

OCF 3

Scheme 7. Carbonylative Suzuki coupling of 1-iodo-cyclohexene.

A new and efficient approach to the synthesis of -ketosulfoxides by carbonylative Suzuki coupling reaction between -bromo sulfoxide, carbon monoxide and aromatic boronic acids catalyzed by Pd(PPh3)4 has been developed by Asensio et al. (Scheme 8) [24]. The carbonylative cross-coupling reaction is strongly favored over competing direct crosscoupling and homo-coupling processes, except with boronic acids carrying strong electronwithdrawing substituents. The reaction takes place under very mild conditions and with high selectivity for a wide range of boronic acids. This method does not require an overpressure of carbon monoxide or special ligands.

O Ph S Br + ArB(OH)2

CO (1 atm), CsF Pd (PPh3)4 Ph

O S

O Ar

Scheme 8. Palladium-catalyzed three-component Suzuki cross-coupling reaction

Beller et al. reported Pd(OAc)2 /di-1-adamantyl-n-butylphosphine (cata CXium A) as highly active catalyst in the three-component Suzuki carbonylation reaction (Scheme 9) [25]. The catalyst system was applicable for a broad range of aryl/heteroaryl bromides and aryl boronic acids at low catalyst loadings. This reaction offers efficient access to various biologically active compounds as shown by the two-step preparation of Suprofen.
O Br
+ CO +

B(OH)2 Pd (OAc)2 / L MeO

MeO

P L

Scheme 9. Pd/L catalyzed carbonylative Suzuki coupling reaction.

Homogeneous Catalysis in Carbonylative Coupling Reactions

213

Bhanage and group reported the carbonylative Suzuki coupling reaction of aryl and heteroaryl iodides with variety of arylboronic acids catalyzed by a well defined and stable phosphine free palladium complex viz. palladium bis (2,2,6,6-tetramethyl-3,5heptanedionate) [Pd(TMHD)2] or Pd(OAc)2 as the catalyst (Scheme 10) [26]. The ease of preparation of complex, high solubility in organic solvents, indefinite shelf life, stability towards air and compatibility with various hindered and functionalized aryl/heteroaryl iodides and arylboronic acids makes it an ideal complex for carbonylative Suzuki coupling reactions.
O Pd(TMHD)2 R R1
R = CH3, OCH3, Br. R1 = CH3, OCH3, No2, Br. X = N, S. n = 1 or 2

B(OH)2 R
+ Pd(TMHD)2/Pd(OAc)2

O R

I R1 CO

I X

Scheme 10. Carbonylative Suzuki coupling reaction of aryl and heteroaryl iodide with phenylboronic acid.

CARBONYLATIVE SONOGASHIRA COUPLING REACTION

The carbonylation reaction in which aryl halide reacts with carbon monoxide and alkyne (as a nucleophile) to give alkynyl ketone as a product is known as carbonylative Sonogashira coupling reaction. Depending upon the combination of aryl halide and alkyne, range of alkynyl ketones can be produced. Mori and co-worker reported palladium catalyzed carbonylative Sonogashira coupling of terminal alkynes with aryl iodides under atmospheric pressure of carbon monoxide was accomplished by using aqueous ammonia as a base in THF with or without use of CuI (Scheme 11) [27]. The reaction was carried out at room temperature and furnishes 72% yield of corresponding ,-alkynyl ketone, while noncarbonylative coupling product is not obtained.

X + R H + CO

O cat PdCl2(PPh3)2 aq NH3 (0.5 M) room temp

Scheme 11. Palladium catalyzed carbonylative Sonogashira reactions.

Ryu et al. reported carbonylative three-component coupling reaction of aryl iodides with terminal alkynes catalyzed by PdCl2(PPh3)2 using an ionic liquid, [BMim]PF6, as the reaction medium, which resulted in good yields of ,-acetylenic ketones (Scheme 12) [28]. They have checked various ionic liquids, low-viscosity ionic liquid such as [BMim]NTf2 was not

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

suitable for this reaction, since the background Sonogashira coupling reaction, a competing reaction, also proceeded.

X + R H + CO

O PdCl2(PPh3)2 [BMim] PF6

Ar

Scheme 12. PdCl2(PPh3)2/[BMim]PF6 catalyzed carbonylative Sonogashira reactions.

Ziolkowski and group shows PdCl2(P(OPh)3)2 mediated carbonylative coupling of phenylacetylenes with aryl iodides in organic solvents and in ionic liquids (Scheme 13) [29]. With the aid of imidazolium ionic liquids, [BMim]PF6 or [MoCT]PF6 (BMim = 1-butyl-3methyl imidazolium cation, MoCT =1-methyl-3-octyl imidazolium cation) catalyst was recycled and used for four consecutive catalytic cycles retaining its high activity. The protocol was applicable for variety of substrates and moderate to good yields of desired ketones were obtained.

X + R + CO H

O PdCl2 (P(OPh)3)2 [BMim] PF6 or [MoCT] PF6

Scheme 13. PdCl2(P(OPh)3)2 mediated carbonylative Sonogashira reactions.

Ryu et al. also showed application of multiphase microflow system for palladium catalyzed carbonylative Sonogashira coupling reaction of aryl iodides with phenylacetylene (Scheme 14) [30]. They have developed low pressure microflow system for palladium catalyzed multiphase carbonylation reactions in an ionic liquid. The microflow system resulted in superior selectivity and higher yields for carbonylative Sonogashira coupling reactions of aryl iodides compared to the conventional batch system.

Me

Bu

Ph3P Pd Cl Ar-I

+ CO + Ph

Cl H [BMim]PF6, Et3N, 120 C

o

O Ar

Ph

Scheme 14. Palladium catalyzed carbonylative Sonogashira reactions using multiphase microflow system.

Homogeneous Catalysis in Carbonylative Coupling Reactions

215

Chen and group have developed carbonylative coupling reaction of aryl iodides with ferrocenylethyne catalyzed by PdCl2 using sodium dodecyl sulphonate (SDS) as surfactant and water as solvent (Scheme 15) [31]. The reaction gave much better yields of aryl ferrocenylethynyl ketones, which proceeded for 6 h at room temperature under a balloon pressure of carbon monoxide using Et3N as base. The catalytic system was applicable for large variety of aryl iodides providing moderate to excellent yield of the desired carbonyl products.
C CH Fe O PdCl2/PPh3, Et3N Fe SDS, water, 25 C
o

C C C Ar

CO + Ar-I

Scheme 15. Palladium catalyzed carbonylative Sonogashira reactions of ferrocenylethyne.

Foldes et al. reported a two-step synthesis of ferrocenyl pyrazole and pyrimidine derivatives based on carbonylative Sonogashira coupling of iodoferrocene with alkynes (Scheme 16) [23]. New ferrocenyl 1, 3, 5-trisubstituted pyrazoles and 2,4,6-trisubstituted pyrimidines were obtained by the addition-cyclocondensation reaction of the , -alkynyl ketones with hydrazines and guanidinium salts, respectively. The products were obtained with moderate to excellent yields and were characterized with the aid of various spectroscopic tools.
Ar
I

Fe

CO + Ar

CH

Palladium Cat. Fe O

N Fe N R'

Ar Fe N N

Ar

NHR'

Scheme 16. Pd catalyzed carbonylative Sonogashira reactions of iodo ferrocene.

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

A selective one-pot synthesis of carbonyl-containing N-heterocyclic compounds has been developed using a carbonylative Sonogashira/cyclisation sequence by Djakovitch et al. (Scheme 17) [33]. In order to get either indoxyl or 4-quinolone products selectively, various catalytic protocols such as CO pressure, temperature, catalyst identity, base and substrate/catalyst ratio were studied. The origin of the selectivity toward the 5-or 6-membered ring compounds was explained through the respective role of the various catalytic species involved, whether they are organic or metallic. The non-cyclic common intermediate was selectively prepared using [PdCl2(dppp)] as catalyst. By using a two-step multi-catalysis, i.e. {[Pd]+HNEt2}, 4-quinolones were obtained, whereas, with a tandem catalysis, i.e. {[Pd]/PR3}, indoxyls were synthesized.
O I

+
NH2

CO

[Pd], base, solvent N H or N H

NH2

Scheme 17. Preparation of heterocyclic scaffolds via Carbonylative Sonogashira/cyclisation path.

Bhanage et al. reported a facile protocol for carbonylative Sonogashira coupling reaction of aliphatic and aromatic alkynes with iodoaryls using a preformed Cu(TMHD)2 complex (Scheme 18) [34]. This is the first report in which a copper complex is used as a catalyst for carbonylative Sonogashira coupling reaction instead of palladium catalyst. The protocol was general in nature applicable for carbonylative Sonogashira coupling reaction of wide variety of aryl iodides with aromatic/aliphatic alkynes such as phenylacetylene, 1-hexyne and 1octyne etc.
O I R H +

CO Cu [TMHD]2
R

Scheme 18. Cu[TMHD]2 catalyzed carbonylative Sonogashira coupling reaction.

AMINOCARBONYLATION REACTIONS
Among the carbonylative coupling reactions aminocarbonylation reactions are widely explored because of appearance of amide functionality in various important compounds.

Homogeneous Catalysis in Carbonylative Coupling Reactions

217

Transition-metal catalyzed three-component cross-coupling reaction between amine, carbon monoxide and organic halides is now considered as a useful tool for the amide/anilide synthesis (Aminocarbonylation). Heck et al. reported palladium catalyzed selective and useful method for direct synthesis of amides via coupling of aryl, heterocyclic and alkenyl halides with primary/secondary amines in presence of carbon monoxide [35-36]. Advantages of this method include the broad availability of substrates and the high tolerance of palladium catalysts against a variety of functional groups. Therefore, this route has become a useful tool for the preparation of substituted amides, since those amides which are hardly available in conventional synthetic methods can be synthesized from easily available starting materials.
Me N N N HN N O H N Me N NH O Cl N H2N O C N

Cl

N H

Imatinib (Gleevec)

Boscalid

Procainamide

O O N N H C

O Ph NH2 Cl HO N

O NHPr

Mosapride

CJ-15,161, Pfizer k-Opioid receptor antagonist

Figure 4. Examples of carbonyl product in pharmaceutical and material research.

Amides/anilides are attractive targets in chemical synthesis because of their wide utility and occurrence in a number of interesting molecules. They have been found in biologically important natural products, pharmaceuticals and agrochemicals. Amides are widely used as an antiepileptic drug, anticonvulsants [37-38]. They are also used extensively in the polymer chemistry [39-41]. Whittall and group explored Bedford-type palladacycle complex in combination with dppf for the alkoxycarbonylation reactions (Scheme 19) [42]. They also extend the application of this complex for the aminocarbonylation reaction. This palladium complex acted as highly active catalyst for both the reactions showing compatibility with wide variety of substrates. Beller et al. demonstrated the aminocarbonylation of unprotected indoles with different N and O-nucleophiles using Pd/dppf as a catalyst (Scheme 20) [43]. Various indole carboxylic acid derivatives are accessible in excellent yield. For example, aminocarbonylation of 4-,5-,6, or 7-bromoindole with arylethylpiperazines provides a direct one-step synthesis for CNS active amphetamine derivatives. This is the first example for the carbonylation of unprotected bromoindoles with various nucleophiles involving cyclic and acyclic amines, alcohols, and

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Gee et al. had shown the application of microfluidic device for the rapid synthesis of amides via aminocarbonylation reactions (Scheme 21) [44]. They showed the application of microstructured device for first time to perform a gasliquid carbonylation reaction. The yields were moderate to good in very short period of time.
H N MeO O OMe
Pd [1] / dppf, CO

MeO O
+

Br

MeOH

MeO O OMe

Scheme 19. Palladacycle catalyzed carbonylation reactions.

Kollar et al. reported aminocarbonylation of 2-iodoaniline and derivatives using Pd(OAc)2/PPh3 as a catalytic system. 2-Iodoaniline derivatives were used as bifunctional substrates in palladium-catalysed carbonylation (Scheme 22) [45]. Depending on the substituents, two types of compounds were synthesised: having methyl or hydrogen in 4position 2-aryl-benzo[1,3]oxazin-4-one derivatives have been formed, chloro, bromo, cyano or nitro groups in the same position resulted in the formation of dibenzo[1,5]-diazocine-6,12dione derivatives. In the presence of various primary and secondary amines (t-butylamine, amino acid methyl esters) as N-nucleophiles 2-ketocarboxamides were obtained as major products in aminocarbonylation reaction with double carbon monoxide insertion.
NH Ar R Ar Br N H Nu NuH (RNH2, R2NH, ROH, H2O) N H Pd(PhCN)2Cl2 dppf, NEt3, CO O R N N N N H O

Scheme 20. Pd/dppf catalyzed aminocarbonylation of bromoindoles.

Homogeneous Catalysis in Carbonylative Coupling Reactions

219

X + R NH2 CO Pd-phosphine catalyst

O N H R

Scheme 21. Pd/phosphine catalyzed aminocarbonylation reaction.

R NH2 N R O O NH2 CO Pd (OAc)2 / PPh3 R I CO Pd (OAc)2 / PPh3 HN O R R O NH

R = H, CH3, Cl, Br, CN, NO2 etc.

Scheme 22. Aminocarbonylation of 2-iodo aniline.

An efficient Pd(OAc)2/PPh3 catalyzed protocol for the aminocarbonylation of heteroaryl iodides was reported Kollar and group (Scheme 23) [46]. Various primary and secondary amines, including amino acid methyl esters, were used as nucleophiles in palladium-catalysed aminocarbonylation of 2-iodopyridine, 3-iodopyridine and iodopyrazine. The reaction works well with electron-rich and electron-poor substrates on nucleophile.
CO, HNRR'
N I O

Pd(OAc)2 / PPh3

N O

NRR'

N O

NRR'

O I N

O NRR'' NRR''

CO, HNRR'' Pd(OAc)2 / PPh3

N

+
N

Scheme 23. Pd(OAc)2/PPh3 catalyzed aminocarbonylation of heteroaryl iodides.

The application of aminocarbonylation for the synthesis of novel N-acyl phosphonates with unprecedented structure was carried out by Kollar and group under mild and homogeneous reaction conditions (Scheme 24) [47]. The palladium-catalyzed aminocarbonylation of iodoalkenes (1-iodo-cyclohexene, 1-iodo-4-tert-butyl-cyclohexene, 1iodo-2-methyl-cyclohexene and -iodostyrene) with diethyl -aminobenzyl-phosphonate as

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

N-nucleophile resulted in the exclusive formation of carboxamides. The same reaction with iodoaromatics (iodobenzene, 2-iodothiophene) provided the corresponding carboxamide in high yields and some 2-keto-carboxamides as side products due to single and double carbon monoxide insertion, respectively. The highly selective formation of carboxamides to ketocarboxamides can be explained by favored single carbon monoxide insertion relative to double CO insertion. The reaction tolerates structural variation of the iodo-substrate. The high chemoselectivity and the easy work-up of the reaction mixtures make these reactions of synthetic importance.
H 2N H P (O) (OEt)2 O

H H N P (O) (OEt)2

CO Pd (OAc)2 /PPh3

Scheme 24. Aminocarbonylation of -aminobenzyl-phosphonate.

Further, aminocarbonylation of 1,8-diiodo-naphthalene with various primary and secondary amines in the presence of palladium(0) complexes formed in situ from palladium(II) acetate and triphenylphosphine was reported by Kollar and co-workers (Scheme 25) [48]. In the case of primary amines, depending on the amine to substrate ratio, two types of products have been obtained in highly chemoselective mode: dicarboxamides and Nsubstituted imides have been formed at high and low amine to substrate ratio, respectively. The reaction tolerates the ester functionality, so that amino acid esters could serve as Nnucleophiles and in this way, naphthalimides possessing stereogenic centre in the Nsubstituent could be synthesised. The high chemoselectivity, the easy work-up of the reaction mixtures, as well as the high functional group tolerance at the N-alkyl substituent and at the aryl moieties, make these reactions of synthetic importance.
CO, H2NR Pd (OAc)2 / PPh3
I I O N R O

Scheme 25. Aminocarbonylation of 1,8-di-iodo-naphthalene.

A method for the aminocarbonylation of aryl bromide using xantphos as a ligand has been reported recently by Buchwald and group (Scheme 26) [49]. The method is effective for the direct synthesis of Weinreb amides, 1 and 2 benzamides and methyl esters from the corresponding aryl bromides at atmospheric pressure of CO. The catalytic system was applicable for variety of substrates providing good to excellent yield of desired carbonylated products. In addition, a putative catalytic intermediate, (Xantphos)Pd(Br)benzoyl, was synthesized, and an X-ray crystal structure was also showed. This crystal structure revealed

Homogeneous Catalysis in Carbonylative Coupling Reactions

221

that this species possesses, in contrast to the majority of Pd-aryl complexes ligated by Xantphos, a cis-coordinated palladium center.
O Br R NucH, 1atm CO 2-3 % Pd(OAc)2 2-6 % Xantphos R Nuc

NucH = HN(OMe)Me, HNR2, MeOH

Scheme 26. Pd(OAc)2 /Xantphos catalyzed aminocarbonylation reaction.

Bhanage and co-workers reported the facile protocol for aminocarbonylation of aryl iodides with aromatic/aliphatic amines catalyzed by phosphine-free palladium catalysts in environmentally benign water as a solvent (Scheme 27) [50]. Excellent yields of desired amides were obtained by using only 0.5 mol% of the catalyst under optimized reaction conditions. The protocol is applicable for carbonylative coupling reactions of various electron rich, electron deficient and sterically hindered aryl iodides with different amines affording excellent yield of desired products.

X R

R2

N H

R3

CO, Pd (OAc)2
Et3N, Water, 8 h R

O NR2R3

R = H, CH3, OCH3, NO2

R2/R3 = H, alkyl or aryl

Scheme 27. Pd(OAc)2 catalyzed aminocarbonylation reactions.

Br

NaBH4

NH

Br

Pd (OAc)2 / PPh3 CO, K2CO3

LiAlH4

Scheme 28. Synthesis of protoberberine alkaloid using carbonylation reaction.

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

Orito et al. described preparation of protoberberine alkaloids which involves carbonylation as one of the major step during synthesis (Scheme 28) [51]. Dihydroisoquinolines, the BischlerNapieralski cyclization products reduced to corresponding 1-(20-bromo-30, 40-dialkoxybenzyl)- tetrahydroisoquinolines using NaBH4 as a reagent of choice. Carbonylation of 1-(20-bromo-30, 40-dialkoxybenzyl)tetrahydroisoquinolines by treatment with CO (1 atm) in the presence of Pd(OAc)2, PPh3 and excess K2CO3 in boiling toluene gives 8-oxoberbines in good yields. Further, by treating with excess LiAlH4, these lactams were converted almost quantitatively into protoberberine alkaloids.

ALKOXYCARBONYLATION AND HYDROXYCARBONYLATION REACTIONS

The carbonylation reaction in which aryl halide reacts with carbon monoxide and phenol/alcohol (nucleophile) to give esters as a product is called as alkoxycarbonylation reaction. Depending upon the phenol/alcohol employed one can get variety of aromatic or aliphatic esters.
CO Cl P P COOR

R'

ROH Pd(OAc)2

R'

Scheme 29. Alkoxycarbonylation of aryl chlorides

1.2 equiv PhOH 2 mol % Pd (OAc)2 4 mol % dcpp 2HBF4 1.5 equiv K2CO3, CO (1 atm) 4Ao MS, DMF or DMSO, 100-120 oC, 6-24 h
O OPh

Cl R

Scheme 30. Pd(dcpp)2.HBF4 catalyzed alkoxycarbonylation reaction.

Bessard et al. reported a facile protocol for the alkoxycarbonylation of aryl chlorides using palladium acetate in combination with phosphine containing ligands. They have shown the coupling of different aryl chlorides with variety of aliphatic alcohols which provides product in moderate to good yields (Scheme 29) [52].

Homogeneous Catalysis in Carbonylative Coupling Reactions

223

Buchwald et al. reported carbonylation of aryl chlorides at ambient CO pressure using Pd(dcpp)2.HBF4 as a efficient catalyst (Scheme 30) [53]. The catalyst was successfully used for aryl and heteroaryl chlorides in combination with variety of a aliphatic and aromatic alcohols. The catalyst is further employed for the synthesis of various acid derivatives via carbonylation reactions. Lei et al. demonstrated palladium-catalyzed alkoxycarbonylation of aryl iodides with a thiourea-oxazoline type ligand under mild conditions (Scheme 31) [54]. Various functional groups were tolerated and the yields were from moderate to excellent.

PdCl2(CH3CN)2, A Base, EtOH, CO(Ballon), 70 oC R

COOEt N S N O

Scheme 31. Palladium/thiourea-oxazoline catalyzed alkoxycarbonylation reaction.

Bhanage et al. reported an efficient protocol for the alkoxycarbonylation reaction of aryl iodide with alchohol and phenol as a nucleophile (Scheme 32) [55]. They employed Pd(TMHD)2 as a phosphine-free homogeneous catalysts. The catalyst systems were optimized with respect to various parameters and enabled carbonylation of electron-rich, electron-deficient and sterically hindered aryl iodides, with different types of phenols and alcohols affording excellent yields of the desired products.
O I R

Pd (TMHD)2 CO, H-Nu.

Nu

Scheme 32. Pd(TMHD)2 catalyzed alkoxycarbonylation reaction.

The palladium-catalyzed carbonylation of aryl halide with carbon monoxide and water is referred to as hydroxycarbonylation reaction. It allows the straightforward and atom-efficient preparation of aromatic carboxylic acids. Depending upon the aryl halide used variety of aromatic acids can be obtained. Buchwald et al. demonstrated a mild, functional group tolerant method of the preparation of phenyl acids and esters from aryl chlorides via palladium-catalyzed carbonylation reactions using atmospheric pressure of carbon monoxide (Scheme 33) [53]. They employed Pd(OAc)2/

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

dcpp.2HBF4 as a catalyst for these conversions. The system is applicable for the synthesis of variety of aryl and hetero aryl acid derivatives at low CO pressure.
Cl R

2 equiv H2O 2 mol % Pd (OAc)2 4 mol % dcpp 2HBF4 1.5 equiv K2CO3, CO (1 atm) DMSO, 100-120 oC, 15 h

O OH

Scheme 33. Hydroxycarbonylation of aryl chlorides.

MISCELLANEOUS REACTIONS
Alper et al. reported carbonylation of acid chlorides with o-iodoanilines to producedsubstituted-4H-3,1-benzoxazin-4-ones in good to excellent yields (Scheme 34) [56-57]. The reaction works well in the absence of phosphine containing ligands. The reaction is believed to proceed via in situ amide formation from o-iodoaniline and acid chloride, followed by oxidative addition to Pd(0), CO insertion, and intramolecular cyclization. The protocol was applicable for variety of substrates providing good to excellent yield of desired heterocycles.
R I NH2 + Cl O O R Pd(OAc)2 CO R N O R

Scheme 34. Palladium catalyzed carbonylation of acid chlorides with o-iodoanilines.

R I R O O

+ R
OH

R + CO

Pd (OAc)2, Pyridine n-Bu4NCl, DMF

R I

+
NHCOOEt

R + CO

Pd (OAc)2, Pyridine n-Bu4NCl, DMF Hydrolysis

N H

R O

Scheme 35. Synthesis of coumarins and 2-quinolones using carbonylation reaction.

Starting from o-iodophenols or N-substituted o-iodoanilines and internal alkynes, Larock and coworkers described several annulation processes involving heteronucleophilic attack on the acylpalladium intermediate generated through intermolecular insertion of the internal

Homogeneous Catalysis in Carbonylative Coupling Reactions

225

alkyne into s-aryl palladium complex followed by CO insertion for the synthesis of heterocyclic compounds. These annulation processes represents the first examples of intermolecular insertion of an alkyne on a s-aryl palladium complex occurring in preference to CO insertion and allow the exclusive formation of coumarins and 2-quinolones (Scheme 35) [58-60]. Under optimized settings coumarins and 2-quinolones were obtained in moderate to good yields. The selected reaction conditions utilize Pd(OAc)2, 2 equiv. of pyridine and nBu4NCl, under CO (1 atm) in DMF at 100120 C. Synthesis of 3-Substituted-3,4-dihydro-2H-1,3-benzothiazin-2-ones via palladiumcatalyzed carbonylation of 2-substituted-2,3-dihydro-1,2-benzisothiazoles was reported by Alper et al. (Scheme 36) [61]. The reaction occurs at ambient pressure and temperature using Pd(PPh3)4 as a highly active and regioselective catalyst. The carbonylative insertion process occurs in good to excellent yields with total regioselectivity at the N-S bond of benzisothiazole precursor and the reaction tolerates a number of substituents, including primary and secondary alkyl groups and benzylic and naphthylmethyl functionalities.
S N R Pd (PPh3)4 CO (300 psi), 80 oC Pyridine S N O R

Scheme 36. Palladium catalyzed carbonylation of benzisothiazoles.

Orito et al. reported Pd(II)-catalyzed direct aromatic carbonylation, which proceeds with remarkable site selectivity to afford a variety of five- or six-membered benzolactams from secondary o-phenylalkylamines in a phosphine-free catalytic system using Pd(OAc)2 and Cu(OAc)2 in an atmosphere of CO gas containing air (Scheme 37) [62]. The protocol was used for synthesis of wide range of heterocycles by C-H activation of phenylalkylamines without use of any expensive aryl halides under phosphine free conditions.
Pd (OAc)2 Cu (OAc)2 CO (1atm), toluene, reflux

(CH2)n NR n = 1 or 2

(CH2)n NR O

Scheme 37. Synthesis of benzolactams via palladium catalyzed carbonylation.

Alper et al. demonstrates palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones in single step (Scheme 38) [63]. A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields by the palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides and carbon monoxide. The reaction is believed to proceed via in situ formation of an amidine, followed by oxidative addition, CO insertion and intramolecular cyclization to give the substituted

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Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage

quinazolin-4(3H)-ones. The developed protocol was applicable for the synthesis of wide range of substituted quinazolin-4(3H)-ones.
R I + CO + NH2 Cl R1 O N R2 Pd(OAc)2 / PPh3 R N N R1 R2

Scheme 38. Cyclocarbonylation of o-iodoanilines with imidoyl chlorides.

Blaquiere et al. reported a novel strategy for the palladium-catalyzed multicomponent synthesis of trisubstituted triazoles via carbonylation reactions (Scheme 39) [64]. This approach features a wide scope, mild reaction temperatures and low carbon monoxide pressure. Total yields range from 41% to 79%, or 8094% per bond for the four bonds created. As such, this method compares favourably with direct C-H arylation technology. The protocol was applicable for the synthesis of wide variety of heterocycles and also underscored for the synthesis of druglike and/or pharmaceutically relevant molecules from commercially available materials.
I OH

Pd (OAc)2 / Xantphos + CO Et3N, DMF 4 - Hydrazino benzoic acid HOAc

N HOOC

OH N N HO

+
NH .HCl NH2 OH

Deferasirox

Scheme 39. Synthesis of deferasirox via Pd catalyzed multicomponent carbonylation reaction.

Recently, Beller et al. reported Carbonylative Heck coupling reactions of aryl and alkenyl triflates with aromatic olefins (Scheme 40) [65]. This method represents a missing link between the already established carbonylative Suzuki and Carbonylative Sonogashira reactions. Starting from easily available aryl and alkenyl triflates the corresponding unsaturated ketones are obtained good yields. The products obtained represent useful building blocks for the synthesis of numerous biologically active compounds.

ROTf + CO + R'

[(Cinnamyl) PdCl2] dppp toluene, NEt3 100 oC, 20 h

O R R'

Scheme 40. Palladium catalyzed carbonylative Heck coupling reactions.

Homogeneous Catalysis in Carbonylative Coupling Reactions

227

CONCLUSION
This review summarized the recent developments in the area of palladium-catalyzed carbonylative coupling reactions of aryl halides and related starting materials in homogeneous media. Since the original work of Heck and co-workers, various catalytic carbonylation reactions have been developed over the past decades, and nowadays ranges of palladium catalysts are available for these transformations. Thus an impressively diverse range of efficient catalytic systems based on palladium have been developed during past years that prove practical importance of carbonylative coupling reactions. However, having a plethora of new synthetic catalytic methods for carbonylative coupling reactions, the development of asymmetric catalysts for carbonylation reactions needs to be explored. With regards to sustainability, a major challenge will be the development of catalytic carbonylation reactions which do not use aryl halides as substrates, but directly employ arenes. Again most of the carbonylation reactions are reported with palladium catalysts however, these catalysts can be replaced by cheaper and easily available metal catalysts such as Cu, Fe etc. Thus, carbonylation reactions using such catalysts are indeed an area yet to discover.

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[29] Sans, V., Trzeciak, A. M., Luis, S., Ziolkowski, J. J. (2006). PdCl2(P(OPh)3)2 catalyzed coupling and carbonylative coupling of phenylacetylenes with aryl iodides in. Catal. Lett., 109, 37-41. [30] Rahman, M. T., Fukuyama, T., Kamata, N., Sato, M., Ryu, I. (2006). Low pressure Pdcatalyzed carbonylation in an ionic liquid using a multiphase microflow system. Chem. Commun., 2236-2238. [31] Li, C., Li, X., Zhu, Q., Cheng, H., Lv, Q., Chen, B. (2009). Convenient synthesis of ferrocenylethynyl ketones via carbonylative coupling of ferrocenylethyne with aryl iodides by using water as solvent. Catal Lett., 127, 152-157. [32] Feher, C., Kuik, A., Mark, L., Kollar, L., Skoda-Foldes, R. (2009). A two-step synthesis of ferrocenyl pyrazole and pyrimidine derivatives based on carbonylative Sonogashira coupling of iodoferrocene. Journal of Organometallic Chemistry, 694, 25, 4036-4041. [33] Genelot, M., Bendjeriou, A., Dufaud, V., Djakovitch, L. (2009). Optimised procedures for the one-pot selective syntheses of indoxyls and 4-quinolones by a carbonylative Sonogashira/cyclisation sequence. Applied Catalysis A: General, 369, 125-132. [34] Tambade, P. J., Patil, Y. P., Nandurkar, N. S., Bhanage, B. M. (2008). Copper catalyzed Pd-free carbonylative Sonogashira coupling reaction of aliphatic/aromatic alkynes with iodoaryls. Synlett, 6, 886-888. [35] Schoenberg, A., Bartoletti, I., Heck, R. F. (1974). Palladium-catalyzed carboalkoxylation of aryl, benzyl, and vinylic halides. J. Org. Chem., 39, 3318-3326. [36] Schoenberg, A., Heck, R. F. (1974). Palladium-catalyzed amidation of aryl, heterocyclic, and vinylic halides. J. Org. Chem., 39, 3327-3331. [37] Malawskai, B., Kulig, K., Gajda, J., Szczeblewki, D., Musaial, A., Wickowski, K., Maciag, D., Stables, J. P. (2007). Design, synthesis and pharmacological evaluation of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid with potential GABA-ergic activity. Part 6. Search for new anticonvulsant compounds. Acta Poloniae Pharmaceutica-Drug Research, 64, 127-137. [38] Luszczki, J. J., Swiader, M. J., Swiader, K., Paruszewski, R., Turski, W. A., Czuczwar, S. J. (2008). Anticonvulsant and acute adverse effect profiles of picolinic acid 2-fluorobenzylamide in various experimental seizure models and chimney test in mice. Fundamental & Clinical Pharmacology, 22, 69-74. [39] Yoneyama, M., Kakimoto, M., Imai, Y. (1989). Novel synthesis of polyesters by palladium-catalyzed polycondensation of aromatic dibromides, bisphenols, or aliphatic diols with carbon monoxide. Macromolecules, 22, 2593-2596. [40] Perry, R. J., Tuner, S. R., Blevins, R. W. (1993). Synthesis of linear, high-molecularweight aromatic polyamides by the palladium-catalyzed carbonylation and condensation of aromatic diiodides, diamines, and carbon monoxide. Macromolecules, 26, 1509-1513. [41] Kulkarni, S. M., Didgikar, M. R., Chaudhari, R. V. (2004). Synthesis of polyesteramides by palladium-catalyzed carbonylationpolycondensation of aromatic diiodides and amino alcohols. J. Mole. Catal. A: Chemical, 207, 2, 97-106. [42] Fairlamb, I., Grant, S., McCormack, P., Whittall, J. (2007). Alkoxy- and amidocarbonylation of functionalised aryl and heteroaryl halides catalysed by a Bedford palladacycle and dppf: A comparison with the primary Pd(II) precursors (PhCN)2PdCl2 and Pd(OAc)2. Dalton Trans., 859-865.

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[43] Kumar, K., Zapf, A., Michalik, D., Tillack, A., Heinrich, T., Bolttcher, H., Arlt, M., Beller, M. (2004). Palladium-catalyzed carbonylation of haloindoles: No need for protecting groups. Org. lett., 1, 7-10. [44] Miller, P. M., Long, N. J., Mello, A. J., Vilar, R., Passchier, J., Gee, A. (2006). Rapid formation of amides via carbonylative coupling reactions using a microfluidic device. Chem. Commun., 546-548. [45] Acs, P., Muller, E., Rangits, G., Lorand, T., Kollar L. (2006). Palladium-catalysed carbonylation of 4-substituted 2-iodoaniline derivatives: carbonylative cyclisation and aminocarbonylation. Tetrahedron, 62,12051-12056. [46] Takacs, A., Jakab, B., Petz, A., Kollar L. (2007). Homogeneous catalytic aminocarbonylation of nitrogencontaining iodo-heteroaromatics. Synthesis of Nsubstituted nicotinamide related compounds. Tetrahedron, 63, 10372-10378. [47] Takacs, A., Petz, A., Kollar L. (2008). Palladium-catalysed aminocarbonylation of iodoarenes and iodoalkenes with aminophosphonate as N-nucleophile. Tetrahedron, 64, 8726-8730. [48] Takacs, A., Acs, P., Kollar L. (2008). Facile synthesis of 1, 8-naphthalimides in palladium-catalysed aminocarbonylation of 1,8-diiodo-naphthalene. Tetrahedron, 64, 983-987. [49] Martinelli, J. R., Watson, D. A., Freckmann, D. M. M., Barder, T. E., Buchwald, S. L. (2008). Palladium-catalyzed carbonylation reactions of aryl bromides at atmospheric pressure: A general system based on xantphos. J. Org. Chem., 73, 7102-7107. [50] Tambade, P. J., Patil, Y. P., Bhanushali, M. J., Bhanage, B. M. (2008). Pd(OAc)2 catalyzed aminocarbonylation of aryl iodides with aromatic/aliphatic amines in water. Synthesis, 15, 2347-2352. [51] Orito, K., Miyazawa, M., Kanbayashi, R., Tokuda, M., Suginome, H. (1999). Synthesis of phthalideisoquinoline and protoberberine alkaloids and indolo[2,1-a]isoquinolines in a divergent route involving palladium(0)-catalyzed carbonylation. J. Org. Chem., 64, 6583-6596. [52] Paul, R., Bessard, Y. (1999). Selective alkoxycarbonylation of 2,3-dichloropyridines. Tetrahedron, 55, 393-404. [53] Watson, D. A., Fan, X., Buchwald, S. L. (2008). Carbonylation of aryl chlorides with oxygen nucleophiles at atmospheric pressure. Preparation of phenyl esters as acyl transfer agents and the direct preparation of alkyl esters and carboxylic acids. J. Org. Chem., 73, 7096-7102. [54] Liua, J., Liang, B., Shu, D., Hu, Y., Yang, Z., Lei, A. (2008). Alkoxycarbonylation of aryl iodides catalyzed by Pd with a thiourea type ligand under balloon pressure of CO. Tetrahedron, 64, 9581-9584. [55] Tambade, P. J., Patil, Y. P., Bhanage, B. M. (2009). Palladium bis(2,2,6,6-tetramethyl3,5-heptanedionate) catalyzed alkoxycarbonylation and aminocarbonylation reactions. App. Orgmet. Chem., 23, 235-240. [56] Larksarp, C., Alper, H. (2004). Palladium-catalyzed cyclocarbonylation of oiodoanilines with heterocumulenes: regioselective preparation of 4(3H)-quinazolinone derivatives. J. Org. Chem., 65, 2773-2777. [57] Larksarp, C., Alper, H. (1999). A simple synthesis of 2-substituted-4H-3,1-benzoxazin4-ones by palladium-catalyzed cyclocarbonylation of o-iodoanilines with acid chlorides. Org. Lett., 1, 1619-1622.

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[58] Kadnikov, D. V., Larock, R. C. (2000). Synthesis of coumarins via palladium-catalyzed carbonylative annulation of internal alkynes by o-idophenols. Org. Lett., 2, 3643-3646. [59] Kadnikov, D. V., Larock, R. C. (2003). Palladium-catalyzed carbonylative annulation of internal alkynes: Synthesis of 3,4-disubstituted coumarins. J. Org. Chem., 68, 94239432. [60] Kadnikov, D. V., Larock, R. C. (2004). Synthesis of 2-quinolones via palladiumcatalyzed carbonylative annulation of internal alkynes by N-substituted o-iodoanilines. J. Org. Chem., 69, 6772-6780. [61] Rescourio, G., Alper, H. (2008). Synthesis of 3-substituted-3,4-dihydro-2H-1,3benzothiazin- 2-ones via a highly regioselective palladium-catalyzed carbonylation of 2-substituted-2,3-dihydro-1,2-benzisothiazoles. J. Org. Chem., 73, 1612-1615. [62] Orito, K., Horibata, A., Nakamura, T., Ushito, H., Nagasaki, H., Yuguchi, M., Yamashita, S., Tokuda, M. (2004). Preparation of benzolactams by Pd(OAc)2 catalyzed direct aromatic carbonylation. J. Am. Chem. Soc., 126, 14342-14343. [63] Zheng Z., Alper, H. (2008). Palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones. Org. Lett., 10, 5, 829-832. [64] Staben, S. T., Blaquiere, N. (2009). Four-component synthesis of fully substituted 1,2,4-triazoles. Angew. Chem. Int. Ed., 48, 1-5. [65] Wu, X. F., Neumann, H., Beller, M. (2010). Palladium-catalyzed coupling reactions: carbonylative Heck reactions to give chalcones. Angew. Chem. Int. Ed., 49, 5284-5288.

In: Homogeneous Catalysts Editor: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers, Inc.

Chapter 8

SYNTHESIS, CHARACTERIZATION AND CATALYTIC STUD OF OXOVANADIUM (IV) COMPLEXES WITH TETRADENTATE SCHIFF BASES
A.P.A. Marques1,*, E.R. Dockal2, Ieda Lucia Viana Rosa1 and F.C. Skrobot3
LIEC CMDMC, DQ, Universidade Federal de So Carlos, So Carlos, SP, Brasil 2 Laboratrio de Snteses Inorgnicas, Catlises e Cintica, DQ, Universidade Federal de So Carlos, So Carlos, Brazil. 3 SENAI - Federao das Industrias do Estado do Paran, Centro Cvico, Curitiba, Brazil.
1

ABSTRACT
The synthesis, characterization and catalytic study of Oxovanadium (IV) complexes and yours precursors Schiff bases [N,N-bis(salicylidene)-1,2phenylenediamine], [N,N-bis(salicylidene)-1,3-phenylenediamine] and [N,Nbis(salicylidene)-1,3-xylylenediamine] are reported. The Schiff base ligands were characterized by elemental analysis, melting points, Fourier Transformed Infra-red spectroscopy, electronic spectroscopy and 1H and 13C Nuclear Magnetic Resonance spectra. The oxovanadium (IV) complexes were characterized by elemental analysis, melting points, Fourier Transformed Infra-red spectroscopy and electronic spectroscopy. The oxidation catalytic of methyl phenyl sulfide with the complexes in solution and heterogeneisated by means of supporting on alumina was studied. The catalytic reactions were accompanied by gas chromatography; the catalytic products were characterized by 1 H Nuclear Magnetic Resonance and Fourier Transformed Infra-red spectroscopy. The product of catalytic reaction, methyl phenyl sulfoxide, can be used as an intermediate in the fabrication of pharmaceuticals. The oxovanadium (IV) complex from the Schiff base [N,N-bis(salicylidene)-1,3-xylylenediamine] presents the best catalytic activity in homogeneous system probably due to its flexibility that favors the access of the substrate to active center in the catalysis.
*

Corresponding author. Tel.: + 55 16 3351 8214; E-mail address: apamarques@liec.ufscar.br

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Keywords: Oxovanadium (IV) complexes; Schiff base ligands; Synthesis; Catalytic Reaction.

1. INTRODUCTION
Vanadium has aroused the interest of researchers since the discovery that various marine species have this metal as an essential element [1]. Enzymes containing vanadium as an essential element were isolated in the 1980s. These enzymes are able to exercise the activities of nitrogenase and bromoperoxydase [1]. Nowadays, a lot of papers deal with the vanadium biochemistry [2]. Several vanadium compounds have recently been investigated in animal model systems as treatment for diabetes [3, 4], and studies in clinical trials in human beings with organic transition metal complex are been developed [5]. Oxovanadium (IV) complexes containing tetradentate Schiff bases have been the subject of various studies [6-12]. Tetradentate Schiff base complexes of Oxovanadium (IV), VO2+, are the subject of various studies in our laboratory [6, 8-10, 12]. The use of chiral Oxovanadium (IV) complexes in the preparation of chyral sulfoxide for the medicine industry has been widely studied [7]. One area of great interest also is the role of the vanadium species in the oxygen-atom or electron transfer reactions [2, 8]. The development of new supported catalysts which combine the properties of homogeneous catalysts with the benefits of heterogeneisation is of prime interest to the chemical industry at present. The advantages are arising from ease of handling, recovery, separation and recycling, coupled with the potential for automation which has become recognized by more and more rank-and-file industrial and academic synthetic chemistry [13, 14] Heterogeneisation of homogeneous catalysis, through the complex supported in alumina, not only solve the basic problem of catalyst separation, but also offer considerable economic benefits if recycling and re-use would be possible [15, 16]. However, in some catalytic reactions, the heterogeneisation of system can damage the reaction; the process of support of the complex can become the active center more impeded and damage the reaction. In this work, we describe the preparation and characterization of the Oxovanadium (IV) complex of the tetradentate Schiff bases: N,N-bis(salicylidene)-1,2-phenylenediamine, N,Nbis(salicylidene)-1,3-phenylenediamine and [N,N-bis(salicylidene)-1,3-xylylenediamine], named (salophen), (salmphen) and (salmxylen), respectively. The catalytic activity of the [VO(salophen)] [VO(salmphen)] and [VO(salmxylen)] in the oxidation of the methyl phenyl sulfide in acetonitrile, using tert-Butyl-Hydroperoxide as oxygen donnor in a homogeneous system and supported on -alumina was studied.

2. EXPERIMENTAL
2.1 Materials
All solvents and reagents were of commercial grade unless otherwise stated and were purchased from Merck and Aldrich. Methanol (MeOH), Ethanol (EtOH), acetonitrile (ACN), dimethylsulfoxide (DMSO) and chlorophormio (CHCl3) were used as received.

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2.2 Synthesis of Schiff Base (L)

The Schiff bases were prepared by condensing of the diamine (1,2-phenylenediamine, 1,3-phenylenediamine and 1,3-xylylenediamine) with the salicylaldehyde in a 1:2 proportion, in alcoholic solution (ethanol) [6-9]. The diamine (10 mmol) was added to a hot ethanol solution, 50mL; the salicylaldehyde (20 mmols) was added in this mixture after 30 min. The reactional system was stirred and warm at 60C for 150min. After cooling slowly to room temperature, the resulting precipitate was collected by filtration, washed with 20mL of distilled water and 10mL of ethanol twice. The ligands were dried in vacuum at room temperature.

2.3 Synthesis of [VIVO(Schiff Base)]

The complex [VO(salophen)], [VO(salmphen)] and [VO(salmxylen)] were prepared and purified using an adaptation of the methods described previously [6-9]. A solution of Oxovanadium (IV) sulfate (4.0mmol) in 20mL of distilled water was added to a hot ethanol solution, 50mL, containing 4.0 mmol of the Schiff base ligand and sodium acetate trihydrate (8.0 mmol). Although a precipitate formed almost immediately, the mixture was refluxed with stirring for 3h, according to Scheme 1. After cooling slowly to room temperature, the resulting precipitate was collected by filtration, washed with 20mL of distilled water and 10mL of methanol twice. The complex was purified by Soxhlet extraction using ethanol. The purified complex was dried in vacuum at room temperature. Schiff base + 2 NaOAc (Schiff base)2- + 2 HOAc + 2 Na+ VO2+ + (Schiff base)2- [VIVO(Schiff base)]
Scheme 1.

2.4 Characterization of Schiff Base (L) and [VIVO(Schiff Base)] ([VO(L)])

Elemental analyses (C, N, H) were performed in an EA-1108 CHNS-O Fisons apparatus. Fourier Transformed Infra-red (FTIR) spectra of the free ligand and the complex were recorded in the 250-4000 cm-1 range as pressed discs (1% by weight in CsI) with a Bomem Michelson 102 FTIR spectrophotometer. Electronic spectra were recorded in the 270-800 nm range in CHCl3 using a MultiSpec-1501 Shimadzu instrument. The 1H and 13C Nuclear Magnetic Resonance (NMR) spectra of the free ligand in DMSO were obtained using a Bruker ARX 400 MHz 9.4T spectrometer.

2.5 Preparation of the Catalysts [VO(L)]-Alumina

[VO(L)] (0.1mmol) was added to a mixture of 0.250 g of support -alumina in dichloromethano (25mL). This mixture was stirred and heated for 3 h. The solid was filtered

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and washed thoroughly with distilled water till the washings were colorless. This exchange procedure was repeated twice. The supported solid [VO(L)]-alumina obtained was dried at 100 C overnight.

2.6. Catalysts Characterization

Scanning electron microscopies (SEM) were recorded on Stereoscan 440. Thermogravimetric analysis (TGA) were carried out using the a TGA-951 thermogravimetric unit coupled to a TGA-2100 thermal analyzer, both from TA Instruments, using sample mass of ca. 7mg and a platinum sample holder under a N2 flow of 90mL min1. In all experiments, a 15 C min1 heating rate was used.

2.7. Oxidation of Methyl Phenyl Sulfide

Methyl phenyl sulfide (0.62mL, 5.3mmol) and 0.14g of the catalyst solids [VO(L)]alumina or the free complex [VO(L)] (0.169g, 0.34mmol) were added in ACN (25mL). To this mixture was added the oxygen donor tert-Butyl-Hydroperoxide (t-BuOOH) (0.88 mL, 5.5 molar aq. solution, 5.3 mmol). Gas chromatographic analyses were carried out on a Shimadzu chromatograph. Nitrogen was used as the carrier gas with a hydrogen flame ionization detector. The DB-1 capillary column (length, 30 m; internal diameter, 0.25 mm) was packed with 0.25 m Megabore film. The oxidation products were characterized by 1H RMN (CHCl3) and IR (1% by weight in CsI, cm-1). The oxidation products yields were calculated by the chromatograms area.

3. RESULTS AND DISCUSSION

The synthesis and characterization of the Schiff bases salophen and salmphen and yours complexes were described previously elsewhere [10]. The Schiff bases salophen salmphen and salmxylen and yours respectively complexes were stable in air, both in solution and in the crystalline state. The yield of the purified complex and the ligand were listed in Table 1, the yield variation between ligand and your respectively complex is probably due to differences in the solubility of these compounds. The values obtained for elemental analysis were consistent with the calculated ones to the molecular weight corresponding (Table 1) and the graphic of the structures of the Oxovanadium (IV) complexes in Figure 1. The elemental analyses indicate that the complex is monomeric specie formed by coordination of 1 mol of the metal ion and 1 mol of the Schiff base ligand. The melt points of the ligands Schiff base were minors that 100C and of the complexes were higher 360C and with short temperature variation, the small interval of temperature is one indicative that the compounds are pure (Table 1).

Synthesis, Characterization and Catalytic Stud of Oxovanadium

Table 1. Data of yield, melting point and elemental analysis of Oxovanadium (IV) complexes and the salmxylen ligand.
Compound [VO(salophen)] salmxylen Formula(Mol. Weight) (g mol ) C20H14N2O3V(381.28) C22H20N2O2(344.41) [VO(salmphen)] C20H14N2O3V(381.28) [VO(salmxylen)] C22H18N2O3V(409.33)
-1

237

Anal. Found (Anal. Calc.) (%) C 63.3(63.3) 62.8(63.3) 74.2(76.7) 63.7(64.6) H 3.7(3.7) 3.8(3.7) 6.4(5.8) 4.4(4.4) N 7.3(7.3) 7.2(7.3) 8.0(8.1) 6.8(6.8)

Yield (%) 99 84 98 86

M. P. (C) >360 >360 62 >360

HC O N O V O N CH

(a)

HC O

O V

CH O

(b)

H2C HC O N O V

CH2 N CH O

(c)
Figure 1. Structural representations of the complexes: [VO(salophen)] (a), [VO(salmphen)] (b) and [VO(salmxylen)] (c).

Figure 2 presents the FTIR spectra in the 200-4000cm-1 range of (salmxylen) (A) and [VO(salmxylen)] (B). The FTIR spectra of the free ligands and the complexes show various

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bands in the 200-4000cm-1 region. Table 2 lists the most important and characteristic bands of the FTIR spectra of the samples. The C=N stretching frequencies in the (salmxylen) occur at 1634cm-1 as reported for similar ligands [8-10, 12, 17] The complex C=N stretching frequency is expected to appear in lower frequencies when compared to the ligand. As it noticed in Figure 2, the C=N stretching frequency is observed at 1617cm-1, indicating a decrease in the bond order due to the coordinate bond of the metal with the azomethine nitrogen lone pair [1, 18, 19]. The C-N stretching frequency has been reported in the 13401020 cm-1 region [17, 20, 21]. In this case the band occurs near 1151cm-1 for the ligand and around 1154cm-1 for the respective complex. The C-O stretching frequencies were observed as strong bands at 1316 and 1116cm-1 for the ligand. For the complex they were noticed at 1312 and 1125cm-1. In similar compounds the C-O bands occur at 1390-1330 and 12601000cm-1 [17, 20, 21].The characteristic V=O stretching frequency in the Oxovanadium (IV) complexes appears as a medium-to-strong band at 980cm-1, Figure 2, i.e. within the 9501000cm-1 reported for similar Oxovanadium (IV) complexes [6, 8-10, 17, 18, 22, 23]. The band in 611cm-1 is assigned to (V-N) and 450cm-1 is assigned to (V-O) as reported in references [6, 8-10, 17, 18, 22, 23]. These bands were observed as new absorption peaks of the complex and are not present in the spectrum of the free ligand.
Table 2. Relevant IR frequencies (cm-1) of the ligands and Oxovanadium (IV) complexes.
Compound salmxylen [VO(salmxylen)] salophen [VO(salophen)] salmphen [VO(salmphen)]
(C=N) (C-N) (C-O) (V=O) (V-N) (V-O)

1634 1617 1616 1607 1622 1617

1151 1154 1315 1310 1215 1217

1316; 1116 1312; 1125 1366; 1193 1380; 1197 1279; 1200 1280; 1124

----980 ----985 ----968

----611 ----542 ----638

----450 ----389 ----457

Table 3 lists the bands of the electronic spectra of the Schiff base ligands in solutions of acetonitrile (ACN), trichloromethane (TCM) or dimethyl sulfoxide (DMSO), recorded in the 270-800nm region, theses spectra exhibit between four and two bands. The weak band, as a shoulder, at 361nm is assigned to n* transition involving molecular orbital of the C=N chromophore and the benzene ring [8, 9, 24-27]. The more important difference observed in the electronic spectra of the Oxovanadium (IV) complexes, compared to the free ligands, is the absence of the band assigned to pd transition, around of 420nm. The isolated benzene ring exhibits three characteristic absorptions around of 196-204, 210-244 and 255-278nm assigned to * type transitions [21]. The * transition of the C=C and C=N chromophores normally occur between 270 and 300nm [21]. The band around of 315-343nm observed in the ligand is assigned to * transition, which involves molecular orbitals essentially localized on the C=N group and the benzene ring. In the complex it was observed

Synthesis, Characterization and Catalytic Stud of Oxovanadium

239

the same band at the same wavelength. The strong absorption band around of 278-316nm observed only in the electronic spectra of the complex is assigned to *of the benzene ring [8-10, 21, 25-27].
[(sal)2(xilen)]

C=N [VO(sal)2(xilen)]

V=O C=N
4000 3000 2000 1000

Figure 2. FTIR spectra (200-4000 cm-1) of [(salmxylen)] and [VO(salmxylen)].

Table 3. Absorption data (nm) of electronic spectra of the Schiff base salophen, salmphen and salmxylen in solutions.
Ligand Attributions ACN * 343 274 210 196 * 328 267 226 204 * 315 255 215 ** Absorption Data (nm) Solvent TCM * 331 261 244 ** 361 328 262 243 ** * 317 257 ** ** DMSO * 343 278 ** ** * 316 ** ** ** * 316 ** ** **

salmph

n (C=N) (C=N) (C=C) (C=C) (C=C) n (C=N) (C=N) (C=C) (C=C) (C=C) n (C=N) (C=N) (C=C) (C=C) (C=C)

saloph

salmxy

*band absent or hidden; **band out of area permitted for the solvent.

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4 5

2 1 7

OH N
8 10 11 12 9 10 11

HO N
8

2 1 7

4 5

Figure 3. Numbering system of the carbon atoms for the RMN assignments.

The 1H and 13C NMR data of the Schiff base obtained from its spectra are given in Table 4 and numbering system is presented in Figure 3. The 1H NMR spectrum of the Schiff base in DMSO shows the peak characteristic of the OH as a singlet sign at 13.38ppm. The singlets at 8.43ppm and 4.79ppm correspond to the CH=N and -CH2N, respectively. The free ligand showed broad peaks between 7.45 and 6.87ppm due to hydrogen bonded phenolic protons [8, 21]. The 13C NMR spectrum of the tetradentate Schiff base in DMSO shows the peak concerned to CH=N at 165.8ppm. The sign of the carbon belonged to -CH2N group appears at 63.1 ppm. The peaks between 117.0 and 161.0 ppm are assigned to the phenyl. These values are in agreement with other similar Schiff base ligands [8, 27].
Table 4. 1H and 13C NMR data of the salmxylen ligands (chemical shifts in ppm).
Atom C1 C2 C3H C4H C5H C6H C7H C8H C9H C10 C11H C12H OH
s

H NMR (ppm) ----7.30-6.9mc 7.30-6.9mc 7.30-6.9mc 7.30-6.9mc 8.43s 4.79s 7.45s --7.33d 6.87t 13.38s

salmxylen 13 C NMR (ppm) 118.8 161.0 117.0 132.4 118.6 127.1 165.8 63.1 131.5 138.6 129.0 126.0 ---

, singlet; d, doublet; dd, doublet of doublets; t, triplet; mc, multiplet complex

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241

(a)

(b)

Fi igure 4. SEM im mages of [VO(s salmxylen)]alu umina (A) and alumina a (B) - 10 0m.

Figure 4 presents SEM images of [V VO(salmxylen) )]alumina (A A) and alumin na (B). The SE EM image sh how the varia ation in the surface of the e alumina afte er the adsorpt tion of the [V VO(salmxylen n)] and the di istribution ho omogeneous of o the comple ex in the surf face of the al lumina. al thermal ana alysis has been used to cha aracterize the complex hey yerogenized Differentia [2 28, 29]. Throu ugh this analy ysis, it can be noticed that th he alumina is thermal stabl le material. H However, the expected lo oss of mass s due to the organic li igand of the e catalysts [V VO(samxylen) )]-alumina was w practical lly impercep ptible, probab bly due to the low co oncentration of o [VO(samxylen)] in this su upport. Figure 5 pr resents the pr rogression of the t oxidation reactions of methyl m phenyl sulfide in alumina and th he presence of o free [VO(L L)], [VO(L)]pure -Alum mina, using t-B BuOOH as ox xygen donor and a ACN as solvent. s Table e 5 presents th he results of th he catalytic oxidation of m methyl phenyl sulfide for the studied syst tems. Figure 5 and Table 5 shows that th he catalytic sy ystems consisting of [VO(s salophen)]-alu umina and -a alumina witho out the comple ex, did not pr resent any ac ctivity on the e catalytic ox xidation of methyl m phenyl sulfide. Hom mogeneous, [V VO(salophen)] ], [VO(salmp phen)] and [V VO(salmxylen n)], and heter rogenized Oxovanadium (I IV) complexes, [VO(salmphen)]-alumina a and [VO(salmxylen)]-alu umina, present ted activity on n the catalytic c reaction. How wever, the het terogenized sy ystem showed considerable conversion on nly after 24 hours h of react tion to [VO(s salmphen)]-alu umina and [V VO(salmxylen) )]-alumina, m more longer tha at the homoge eneous systems. After 5 hou urs of reaction n only 6 mol% % of the sulfid de was oxidize ed to sulfoxid de when the [V VO(salmphen) )]-alumina cat talyst was use ed; while 69 mol% and 22 2 mol% of the e sulfoxide w produced for [VO(salm were mphen)] and [V VO(salophen)] ] homogeneou us catalysts, re espectively. The [VO(salmx xylen)] homogeneous catal lysts not presented catalyti ic activity in 5 hours, it sy ystem presente ed an less incr rease in the su ulfide oxidatio on after 24 hou urs of reaction n (8 mol%) an nd at 48 hou urs produced 15 mol% of sulfoxide. Th he [VO(salmx xylen)]-alumin na system, co ompared with h [VO(salmxy ylen)] homoge eneous system m, showed be more adequa ate because af fter 24 and 48 8 hours of reac ction this syst tem produced 87 and 92 mo ol% of sulfoxi ide, around of f ten times mo ore that the ho omogeneous sy ystem. Howev ver, the heterogeneous syste ems present ac ctivity catalyti ic only at reac ctions times lo onger. After one o day it was s observed an increase in th he product yield, y which values were e 73, 75, and a 87 mol% % for [VO(salophen)],

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[VO(salmphen)] and [VO(salmxylen)]-alumina, respectively. These oxidation reactions were monitored for one day when the conversion was stabilized at 95 mol% for [VO(salophen)], 100% for [VO(salmphen)] and 92 mol% for [VO(salmxylen)]-alumina. The results for [VO(salmxylen)]-alumina system show a differentiate increase after this time (92 mol%), compared to the 5 hours reaction (0 mol%). It was observed in [VO(salophen)] and [VO(salmphen)] systems the formation of two products for the sulfide oxidation, corresponding to 75 mol % of sulfoxide and 20 mol % of sulfone to [VO(salophen)] system and 83 mol % of sulfoxide and 17 mol % of sulfone to [VO(salmphen)] system.

100

80

Conversion (%)

60

[VO(salophen)]-alum and alum [VO(salmphen)]-alum [VO(salmxylen)]-alum [VO(salophen)] [VO(salmphen)] [VO(salmxylen)]

40

20

0 0 50 100 150 200 250 300 1000 1500 2000 2500 3000

Time (min)

Figure 5- Accompaniment of the oxidation reactions of methyl phenyl sulfide in the presence of [VO(salmphen)] (--), [VO(salmxylen)] (--), [VO(salophen)] (--), [VO(salmphen)]-alumina (-), [VO(salmxylen)]-alumina (--), [VO(salophen)]-alumina and -alumina pure (--).

In first the 240 minutes (four hours) the [VO(salophen)] does not promote the oxidation of the sulfide, whereas the catalytic [VO(salmphen)] system produced 42% of sulfoxide; however at long time of reaction both had converted sulfide to sulfoxide and sulfone. This characteristic suggests that the bridge in position 1,3 of [VO(salmphen)] becomes the active center more unimpeded than the bridge in position 1,2 of [VO(salophen)], what it facilitates the approach of the substrate to active center, consequently, the oxidation of this occurs more easily. The occurrence of the formation of sulfoxide and sulfone in the systems [VO(salophen)] and [VO(salmphen)] in solution it suggests that the active center possess high degree of desprotection what it facilitates the approach of the substrate, and, in the system [VO(salmxylen)] in solution the structure possess a distortion able to hinder the approach it substrate to the active center, diminishing the formation of product. It was observed that in the homogeneous catalytic system with intermediate structural flexibility and in the heterogeneous systems that possess complexes with additional flexible structures present better catalytic activity. These observations suggest that the alumina

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support becomes the molecule most rigid and with the more impeded active center, being thus, the capable complex of bigger distortion are what it possess betters conversions, in this case [VO(salmxylen)]. In the homogeneous system the complex is free and its distortions can turn the active center impeded, thus intervening with the catalytic reaction.
Table 5. Methyl phenyl sulfide conversion (mol%) in the [VO(L)], [VO(L)]-alumina and pure -alumina, where L: salmxylen, salmphen or salophen.
Time (min) [VO(salmxylen)] Methyl phenyl sulfide conversion (mol%) [VO(salmphen)] [VO(salophen)] Pure alumina homog. 60 120 180 240 300 1440 7200 0 0 0 0 0 8 34 heterog. 0 0 0 0 0 87 92 3 18 21 42 69 75 100 homog. heterog. 0 0 0 0 6 12 43 0 0 0 0 22 73 88 homog. heterog. 0 0 0 0 0 0 0 0 0 0 0 0 0 0

The products of oxidation of methyl phenyl sulfide were characterized by FTIR and 1H NMR data. The sulfide is characterized by S-C stretching (S-C) around 740cm-1. The S=O (S=O) and SO2 (SO2) stretchings are characterized by the bands at 1089 and 1161cm-1, respectively. The 1H NMR showed peaks near 2.48, 2.81 and 3.06ppm assigned to sulfide, sulfoxide and sulfone, respectively. These data are in agreement with chromatographic data, where the homogeneous systems present sulfoxide and sulfone as catalytic products only at long times of reactions (more than 24 hours). Long reaction time favors the re-oxidation of substrate, forming sulfone with sub-product. Because of this fact, it is suggested that long time of reaction is not recommended to the oxidation of sulfide to sulfoxide, consequently, the homogeneous catalysis is more efficient that the heterogeneous catalysis because promotes the oxidation in less time reaction.

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CONCLUSION
The results showed indicate that the synthesis of ligand and complex were efficient. The catalytic study demonstrated that pure alumina and [VO(salophen)]-alumina were not good catalysts in the oxidation of methyl phenyl sulfide. The catalysis results indicate a good activity of the catalysts [VO(L)] and [VO(L)]-alumina for the oxidization of methyl phenyl sulfide to sulfoxide, however, the superior time of reaction favors the re-oxidation of substrate, forming sulfone with sub-product. The homogeneous system was the best system to oxidation reaction of sulfide to sulfoxide, with good rate conversion. The [VO(salmphen)] system, showed an increase in the substrate oxidation compared to the other ones in minors time of reaction, probable because in [VO(salmphen)] system the catalytic active center is less impeded, facilitating the oxidation of the methyl phenyl sulfide.

ACKNOWLEDGMENTS
Financial support from the Fundao de Amparo Pesquisa do Estado de So Paulo (FAPESP), Coordenao de Aperfeioamento de Pessoal de Nvel Superior (CAPES) and Petrobras to cede the zeolite.

REFERENCES
[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] D. Rehder, Coordination Chemistry Reviews 1999, 182. A. Butler, C. J. Carrano, Coordination Chemistry Reviews 1991, 109, 61. D. C. Crans, Journal Inorganic Biochemistry 2000, 80, 123. K. H. Thompson, J. H. McNeill, C. Orvig, Chemical Reviews 1999, 99, 2561. A. B. Goldfine, G. Willksy, C. R. Kahn, A. S. Tracey, D. C. Crans, American Chemical Society Symposium Series 1998, 711, 353. H. L. David, M. Lonashiro, A. V. Benedett, J. R. Zamian, E. R. Dockal, Thermochimica Acta 1992, 202, 45. C. Bolm, Coordination Chemistry Reviews 2003, 237, 242. A. P. A. Marques, E. R. Dockal, F. C. Skrobot, I. L. Viana Rosa, Inorganic Chemistry Communications 2007, 10, 255. J. R. Zamian, E. R. Dockal, G. Castellano, G. Oliva, Polyhedron 1995, 14, 2411. J. R. Zamian, E. R. Dockal, Transition Metal Chemistry 1996, 21, 370. N. Herron, Inorganic Chemistry 1986, 25, 4714. P. E. Aranha, J. M. Souza, S. Romera, L. A. Ramos, M. P. dos Santos, E. R. Dockal, E. T. G. Cavalheiro, Thermochimica Acta 2007, 453, 9. M. Salavati-Niasari, S. H. Banitaba, Journal of Molecular Catalysis A: Chemical 2003, 201, 43. D. C. Sherrington, Polymer-supported synthesis, in: J.H. Clark (Ed.), Chemistry of Waste Minimisation, 1995. P. Hodge, in Solid Phase Synthesis (Ed.: R. Epton), SPCC (UK) Ltd., Birmingham, 1990.

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[16] D. Pini, A. Petri, A. Mastantuono, P. Salvadori, in Vhairal Reactions in Heterogenous Catalysts, (Eds.: G. Jannes, V. Dubois), Plenum Press, New York, 1995. [17] J. C. Pessoa, I. Cavaco, I. Correia, D. Costa, R. T. Henriques, R. D. Gillard, Inorganic Chimica Acta 2000, 305, 7. [18] G. A. Kolawole, K. S. Patel, Journal Coordenation Chemistry 1986, 14, 235. [19] K. P. Callahan, P. J. Duran, Inorganic Chemistry 1980, 19, 3211. [20] N. B. Colthup, L. H. Daly, S. E. Wiberley, Introduction to Infrared and Raman Spectroscopy, Academic Press, Inc., San Diego, 1990. [21] R. M. Silverstein, G. C. Bassler, T. C. Morril, Spectrometric Identification of Organic Compounds, Wiley, New York, 1991. [22] J. C. Pessoa, I. Tomaz, R. T. Henriques, Inorganic Chimica Acta 2003, 356, 121. [23] A. El-Dissouky, A. K. Shehata, G. El-Mahdey, Polyhedron 1997, 16, 1247. [24] J. R. Zamian, E. R. Dockal, G. Castellano, G. Oliva, Polyhedron 1995, 14, 2411. [25] E. H. F. Brittain, Introdution to Molecular Spectroscopy: theory and Experiment., Academic Press, London,, 1970. [26] B. Bosnich, Journal American Chemistry Society 1968, 90 627. [27] R. C. Felcio, E. T. G. Cavalheiro, E. R. Dockal, Polyhedron 2001, 20, 261. [28] H. Diegruber, P. J. Plath, G. Schultz-Ekloff, 1984, 24, 115. [29] S. P. Varkey, C. Ratnasamy, P. Ratnasamy, Journal Molecular Catalysis A: Chemstry 1998, 135, 295.

In: Homogeneous Catalysts Editors: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers. Inc.

Chapter 9

UNIQUE DESIGN TOOLS FOR THE SYNTHESIS AND DESIGN OF DENDRIMERS AS SUPPORTS FOR RECOVERABLE CATALYSTS AND REAGENTS AND THEIR APPLICATIONS IN ASYMMETRIC SYNTHESIS
Ashraf A. El-Shehawy*
Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea Kafr El-Sheikh University, Kafr El-Sheikh, Egypt

ABSTRACT
The use of soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer limitations, and therefore they should lead to systems with activities similar to their monomeric analogues. Catalysis seems to be a research area in which promising applications for dendrimers may be developed. Indeed, dendritic catalysts are nanosized, and as such they are, as biomolecules, easily isolable from homogeneous reaction media by precipitation, filtration, ultrafiltration or ultracentrifugation. In particular, dendrimers have recently attracted a lot of attention, since these well-defined macromolecular structures enable the construction of precisely controlled catalyst structures. This combination of features makes dendrimers suited to close the gap between homo- and heterogeneous catalysis, or, in other words, dendrimers will combine the advantages of homo- and heterogeneous catalysis. Dendrimers have a number of potential applications, but the present chapter is specifically focus on summarizing the major concepts for their properties as well as the most pronounced advances for their applications as supports for recoverable catalysts and reagents in asymmetric synthesis.
* Department of Nanobio Materials and Electronics, School of Materials Science and Engineering, and Research Institute for Solar & Sustainable Energies (RISE), Gwangju Institute of Science and Technology (GIST), 1 Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea (Tel.: +82 62 715 3463 & Fax: +82 62 9702304; E-mail: elshehawy2@yahoo.com) Department of Chemistry, Faculty of Science, Kafr El-Sheikh University, Kafr El-Sheikh 33516, Egypt (Tel.: +20 47 3215173 & Fax: +20 47 3215175)

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This chapter highlights some of the notable examples of the catalytic reactions using supported dendritic catalytic systems in such reactions as hydrogenation, hydroformylation, alkyation, epoxidation, dialkylzinc addition to aldehydes and imines, Heck and other Pd-catalyzed C-C bond formation. The intriguing properties of dendrimers in catalysis including activity, selectivity, stability, and recyclability will be addressed. Further key issues in this chapter relate to the deviating properties of dendrimers as compared to their linear macromolecular counterparts is considered.

Keywords: Dendrimers, hyperbranched polymers; dendritic catalysis; chiral dendrimers; chiral polymers; asymmetric synthesis; asymmetric catalysis, recoverable catalysts and reagents

1. INTRODUCTION
The development of well-defined catalysts that enable rapid and selective chemical transformations and can be separated completely from the products is still a paramount challenge.[1] The recent success of homogeneous catalysis is reflected in the number of applications that is known today both in the laboratory and in the industrial practice, but so far there is not a single solution to the catalyst-product separation problem. In fact, all unit operations for separation, including distillation, liquid-liquid separation or extraction, stripping, catalyst destruction, and crystallization, are being applied in industry. While several methods are being applied commercially, the search for new approaches continues. A widely studied approach to facilitate catalyst product separation is the attachment of homogeneous catalysts to insoluble organic, inorganic, or hybrid supports.[1b,e,h,i,k,2] Catalysts supported on highly cross-linked polymer beads generally suffer from diminished activity compared to the homogeneous analogues, which is because of a reduced accessibility.[1h,2,3] The use of soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer limitations, and therefore they should lead to systems with activities similar to their monomeric analogues.[1a-c, d,f,g,j,k,m,4] Dendrimers are a new class of polymeric materials. They are highly branched, monodisperse macromolecules. Furthermore, the high degree of branching renders entanglement of the polymers impossible, which results in low melt and solution viscosity. The structure of these materials has a great impact on their physical and chemical properties.[1a,k,l,5] As a result of their unique behavior, dendrimers are suitable for a wide range of biomedical and industrial applications.[1a,c,d,f-h,k-n,4a,6] Indeed, dendrimers offer a unique opportunity to combine the advantages of homogeneous and heterogeneous catalysis yet keep the well-defined molecular features required for a fully detailed analysis of the catalytic events. It is possible to tune the structure, size, shape, and solubility of dendrimers. Many of the intriguing properties of dendrimers as well as their syntheses and possible applications are discussed in excellent books and reviews that have been published by various experts in the field.[1a-d,f-i, l-n, 4a,b, 5c,6a,c] To give an answer to the question what can dendrimers add to the field of catalysis? we have to take a closer look at the ideal catalyst. From a catalytic point of view the ideal catalyst is highly active and selective under mild conditions, very stable and can be separated from the product using a relatively simple process. Right from the start, the regular monodisperse

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structure and multiarm topology of dendrimers inspired chemists to propose dendrimers with peripheral catalytic sites as soluble supported catalysts. In 1994, Tomalia and Dvornic discussed the promising outlook of surface functionalized dendrimer catalysts.[7] Dendritic catalysts are often proposed to fill the gap between homogeneous and heterogeneous catalysts. However, keeping in mind that heterogeneous systems generally contain at least 1012 active sites per conglomerated particle, it is fair to state that the class of dendritic catalysts, containing at most 1000 active sites, is closer to the monomeric homogeneous systems. A better formulation is that functionalized dendrimers potentially can combine the advantages of both homogeneous and heterogeneous catalytic systems. Dendrimers have some unique properties because of their globular shape and the presence of internal cavities. Their globular shape makes these systems more suitable for recycling than soluble polymersupported catalysts. The most important one is the possibility to encapsulate guest molecules in the macromolecule interior.[1c,m, 4a, 6b,c,8] In this chapter, we do not want to present a comprehensive or complete overview on the reported dendrimers, but, instead, we highlighted the most interesting studies that contribute to a better understanding the properties of dendrimers. Some of the notable examples on their uses as supports for recoverable catalysts and reagents in asymmetric synthesis will be discussed. The intriguing properties of dendrimers in catalysis including activity, selectivity, stability, and recyclability will be addressed. Further key issues in this chapter relate to the deviating properties of dendrimers as compared to their linear macromolecular counterparts. We hope to show that dendrimers are a unique class of macromolecules with a bright future ahead.

2. DENDRITIC STRUCTURES
In the first instance, dendritic catalysts were proposed to be easily recyclable homogeneous catalysts. The question is, however, if they also can provide systems that are either more active or selective or more stable than their homogeneous monomeric analogues? This would yield systems with interesting novel catalytic properties providing an intrinsic solution for the homogenous catalyst separation problem. These novel properties induced by the dendritic framework depend on the location of the functional group within the structure. One should distinguish periphery-functionalized (dendrimer or a dendritic wedge), corefunctionalized, and focal-point functionalized (dendritic wedge) systems (see Figure 1). A combination of these conceptual approaches might lead to systems with different catalytic centers, which are ideally suited for cascade reactions. Periphery-functionalized dendrimers have their ligand systems, and thus the metal complexes, at the surface of the dendrimer. The transition metals will be directly available for the substrate, in contrast to core-functionalized systems, for example, in which the substrate has to penetrate the dendrimer prior to reaction. This accessibility allows reaction rates that are comparable with homogeneous systems. On the other hand, the periphery-functionalized systems contain multiple reaction sites and ligands, which results in extremely high local catalyst and ligand concentrations. Furthermore, if a reaction proceeds by a bimetallic mechanism, the dendritic catalysts might show better performance than the monomeric species.[9] On the other hand, several deactivation mechanisms operate by a bimetallic

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mechanism, for example, ruthenium-catalyzed metathesis,[10] palladium-catalyzed reductive coupling of benzene and chlorobenzene,[11] and reactions that involve radicals.[12]

Figure 1. Catalytically active transistion metal complexes can be attached to the periphery (a), at the core (b), at the focal point of a wedge (c), and at the periphery of a wedgel.

In core- (and focal-point-) functionalized dendrimers, the catalyst could benefit especially from the site isolation created by the dendritic environment. Site-isolation effects in dendrimers can be beneficial for other functionalities.[13] For reactions that are deactivated by excess ligand or in cases in which a bimetallic deactivation mechanism is operative, corefunctionalized systems can specifically prevent such deactivation pathway, whereas periphery-functionalized systems might suffer from relative low activity. Core-functionalized dendrimers may benefit from the local catalyst environment created by the dendrimer. Effects of desolvation of the substrate during the penetration of the dendrimer might be of importance, but very little is known about these effects. In nature, enzymes make use of these effects when substrates enter the active site of such systems. Another significant difference between core- and periphery-functionalized dendrimers is the molecular weight per catalytic site. Much higher costs will be involved in the application of core-functionalized systems and application can also be limited by the solubility of the system (to dissolve 1 mmol of catalyst 20 gL-1 is required (MW 20 000 Da, 1 active site) compared to 1 gL-1 (MW 20 000 Da, 20 active sites). On the other hand, for corefunctionalized systems the solubility of the dendritic catalyst can be tuned by changing the end groups.

3. PURITY OF DENDRIMERS
Higher generation dendrimers reach molecular masses that in earlier days had not been accessible through directed organic reactions, apart from through polymerization reactions, which lead to products with a broad distribution of molecular masses (polydisperse).[14] They are modelled on natural globular biomacromolecules that are able to perform certain functions as a consequence of their defined three-dimensional formation through hydrogen bonds. Hence, the three-dimensional structure of high-molecular compounds, such as dendrimers, is of great interest, since the dendrimers differ from biological macromolecules,

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such as proteins, in their three-dimensional covalently linked skeleton. According to an early theoretical work on idealized structures,[15] it was postulated that dendrimers of lower generations take a rather flat, ellipsoidal shape. Assuming that in divergently synthesized dendrimers each branch is directed radially towards the outside and that the end groups lie on the surface of an ellipsoid, the macromolecules transform into a more spherical shape from a certain generation upwards (depending on the core molecule, branching multiplicity, and the length of the branch segment). Simple calculations have shown that the area of an end group on this ellipse becomes continually smaller with an increasing number of generations until a critical branched state, the so-called Starburst dense packing, is reached and prevents any further reaction.[16] Hence, the molecules are meant to be spherical constructions with a dense exterior and a loose interior with channels and cavities. Experimental results, for example, the inclusion of guest molecules and the viscosity, confirm this assumption. Thus, dendrimer chemistry has become a part of supramolecular chemistry. Generally, two conceptually different synthetic approaches for the construction of high generation dendrimers exist: the divergent approach and the convergent approach. Both approaches consist of a repetition of reaction steps, each repetition accounting for the creation of an additional generation. The two methodologies have their own characteristics, and therefore, the perfection of the final dendritic product is related to this synthetic approach. In the divergent synthesis, the dendrimer is grown in a stepwise manner from a central core, implying that numerous reactions have to be performed on a single molecule. Consequently, every reaction has to be very selective to ensure the integrity of the final product. For example, an average selectivity of 99.5% per reaction will, in the case of the synthesis of the fifth generation poly(propylene imine) dendrimer (64 amine end groups; 248 reactions, see Scheme 1), only result in 0.995248 = 29% of defect-free dendrimer.[17,18] Since every new generation of divergently produced dendrimer can hardly be purified, the presence of a small number of statistical defects cannot be avoided. Bearing this in mind, the divergent synthesis can be seen as the macromolecular approach toward dendrimers: the purity of the dendrimers is governed by statistics. The reality of statistical defect structures is also recognized in the iterative synthesis of polypeptides or polynucleotides on a solid support (the Merrifield synthesis),[19] so the knowledge gathered in this field should be considered when the perfection of dendritic structures is discussed.

Scheme 1. The synthesis of poly(propyleneimine)dendrimers (reaction A and B) and alternative unwanted reaction paths C and D. Path C illustrates missed Michael additions (either by an incomplete

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cynaoethylation or by a retro-Michael reaction). Paths C and D describe sefect reactions on going from one amine generation to the next.

In the convergent approach, the difficulty of many reactions that have to be performed on one molecule has been overcome by starting the synthesis of these dendrimers from the periphery and ending it at the core. In this fashion, a constant and low number of reaction sites are warranted in every reaction step throughout the synthesis. As a consequence, only a small number of side products can be formed in each reaction, and therefore, every new generation can be purified (although the purification of higher generation materials becomes increasingly troublesome). Thus, convergently produced dendrimers, which can be seen as dendrimers prepared in an organic chemistry approach, can be defect-free.

4. STRUCTURAL ANALYSIS OF DENDRIMERS

Dendrimers pertain both to the molecular chemistry world for their step by step controlled syntheses, and to the polymer world because of their repetitive structure made of monomers; thus they benefit from analytical techniques from both worlds. The characterization of dendrimers is rather complex due to the size and symmetry in these macromolecules. Caminade and Majoral et als have been surveyed the main analytical techniques used for the characterization of the chemical composition, the morphology, the shape, and the homogeneity of dendrimers.[18] This review included the use of NMR, IR, Raman, UVVisible, fluorescence, circular dichroism, X-ray diffraction, mass spectrometry, SAXS, SANS, Laser Light Scattering, microscopy, SEC, EPR, electrochemistry, electrophoresis, intrinsic viscosity, DSC, and dielectric spectroscopy in the characterization of dendritic macromolecules. Various NMR techniques (1H, 13C, 15N, 31P), elemental analyses, and chromatography techniques (HPLC, SEC) are widely used, but these techniques cannot reveal small amounts of impurities in, especially, higher generation dendrimers.[18,20] A progress in ESI (electrospray ionization) and MALDI (matrix-assisted laser desorption ionization) mass spectrometry allows for an in-depth analysis of dendrimers. ESI-MS has been used to identify the imperfections in both poly(propylene imine)[17b,20] and poly amido amine (PAMAM) dendrimers.[21] Both of these dendrimer types are made via a divergent synthesis and are very suitable for electrospray ionization due to their polar and basic nature. All generations of poly(propylene imine) dendrimers with either amine or nitrile end groups have been analyzed with ESI-MS to quantitatively determine the importance of various side reactions.[17b] In the approach followed, all possible side reactions have been grouped in two different pathways that describe the formation of defect structures on going from one amine generation to the next (see Scheme 1). One pathway accounts for incomplete cyanoethylations and retro-Michael reactions, the other pathway accounts for intramolecular amine formations (cyclizations).[22] With the ESI-MS spectra of all five generation poly(propylene imine) dendrimers in hand, the significance of both pathways has been calculated using an iterative computing process. Thus, every MS spectrum has been simulated. The simulation indicates a polydispersity (Mw/Mn) of 1.002 and a dendritic purity of ca. 23% for the fifth generation poly(propylene imine) dendrimer. Since the perfect structure is the dominant species in the final product, it seems more appropriate to discuss the

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mixture in terms of dendritic purity than in terms of polydispersity (the dendritic purity is defined as the percentage of dendritic material that is defect-free). ESI-MS studies on PAMAM dendrimers indicate defect structures arising from retroMichael additions and intramolecular lactam formations.[21] For a fourth generation PAMAM dendrimer (48 end groups), a polydispersity of 1.0007 has been reported.[21a] Interpretation of the published data reveals, however, a dendritic purity of at most 8%. MALDI-MS studies on other divergently produced higher generation dendrimers (i.e., Newkome-type dendrimers[23] and carbosilanes[24]) have also shown the presence of small numbers of imperfect structures. Metallodendrimers that have been studied with L-SIMS,[25] MALDI-MS,[16] and ESI-MS[26] are of lower generations, and consequently, these materials hardly contain defect structures, even though these materials have been produced in a divergent approach. Reinhoudt et al. have synthesized a third generation Pd(II) dendrimer with no observable defects in the mass spectrum.[27] Dendrimers synthesized via the convergent approach can be produced nearly pure, as confirmed by MS data. MALDI mass spectra of Frchet-type dendrimers display very limited amounts of impurities.[28] Moores phenylacetylene dendrimers have also been investigated with MALDI mass spectrometry.[29] For a dendrimer with a mass of 39 969 D, almost no impurities have been found.[30] ESI-MS data on carboxylate-terminated phenylacetylene dendrimers subscribe the high degree of purity that can be attained for these dendrimers.[28,29] The detailed mass studies that have been devoted to the characterization of dendrimers indicate the most important difference between both synthetic methodologies at hand. The polymeric nature of the divergent approach results in an accumulating number of statistical defect structures for every next generation. The defects are the result of the many reactions that have to be performed on the same molecular fragment. Furthermore, almost no possibilities exist for the purification of intermediate generations. The exponential growth in the number of reactions to be performed on higher generations makes it virtually impossible to produce perfect dendrimers of generations beyond five or six. Virtually no perfect structures will be present in even higher generation materials. The organic nature of the convergent approach results in defect-free dendrimers due to the limited number of reactions performed on the same molecule on going from one generation to the next. Additionally, it is possible to purify intermediate generations. The small differences in structural features of the divergently produced structures on one hand and the convergently synthesized structures on the other are not expressed in differences in overall properties of these two classes of dendrimers (for example, all investigated dendrimers show a maximum in the intrinsic viscosity as a function of their molecular weight). Therefore, dendrimers, regardless the way in which they have been prepared, can indeed be considered as the synthetic macromolecules with the most defined or most perfect primary structure known today.

5. DENDRIMERS VERSUS LINEAR MACROMOLECULES

Dendrimers are monodisperse macromolecules, unlike linear polymers. The classical polymerization process which results in linear polymers is usually random in nature and

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produces molecules of different sizes, whereas size and molecular mass of dendrimers can be specifically controlled during synthesis. Because of their molecular architecture, dendrimers show some significantly improved physical and chemical properties when compared to traditional linear polymers. When dendrimers in solution are considered, the occupied volume of a single molecule increases cubically with generation, whereas its mass increases exponentially. This typical growth pattern of dendritic molecules determines their solution properties and makes these properties deviate from those of linear molecules, especially at higher molecular weights. The intrinsic viscosity is a physical parameter for which such a deviation has been measured. In contrast to linear polymers (that obey the Mark-Houwink-Sakurada equation), the intrinsic viscosity of dendrimers is not increasing with molecular mass but reaches a maximum at a certain dendrimer generation (for polyaryl ether,[3a] poly(propylene imine),[31] and PAMAM dendrimers,[32] these maxima have been reported).[33,34] Also in the solid state, the growth pattern of dendrimers determines their physical characteristics. In general, it is believed that a gradual transition in overall shape, from a more extended arrangement for lower generation dendrimers to a compact and approximate globular shape for higher generation dendrimers, causes the deviation in physical behavior of dendrimers from those of linear macromolecules. Frchet et al. have studied several physical properties of polyether and polyester dendrimers.[35] The increase in glass transition temperature (Tg) of the dendrimers levels off at higher molecular weights, a phenomenon that is also observed for the linear analogues. For linear polymers in general, a leveling off of the Tg increase has been known for a long time, and this effect is explained by the declining influence of the end groups and the role of the entanglement molecular weight. Dendrimers have more end groups at higher masses, but, as opposed to linear macromolecules, dendrimers are not significantly entangled. The absence of entanglements in the higher generation materials is subscribed in a study on the melt viscosities of polyether dendrimers.[36] In another study by the same authors, it appears that the melt viscosity is a physical parameter that is very dependent on the type of end group in the dendrimer.[37] Miller et al. have compared the solubilities of 1,3,5-phenylene-based dendrimers with those of oligo-p-phenylenes.[38] Although m-phenylenes would have been more appropriate linear analogues, the study shows that the dendrimers have an enhanced solubility. Similar results have been obtained by Frchet et al. who have compared dendritic polyesters with their linear counterparts.[39] In contrast to the linear polyesters, the dendrimers are soluble in a vast range of organic solvents. The authors also note a marked difference in reactivity: the debenzylation of the polyesters via catalytic hydrogenation on Pd/C is only possible for the dendritic structures. Differences in solubility and reactivity have also been found between poly(propylene imine) dendrimers with nitrile end groups and poly(acrylonitrile). The nitrile dendrimers are soluble in various organic solvents, whereas their linear analogues are crystalline and only soluble in very polar solvents such as dimethylformamide and concentrated sulfuric acid. Due to this limited solubility, the catalytic hydrogenation of poly(acrylonitrile) is not possible, while dendritic polynitriles are easily hydrogenated.[31,40] For all these cases, the observed differences in solubility and reactivity have been attributed to the globular architecture of the dendrimers and the accessibility of the end groups of the dendrimer.

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The uniqueness of dendritic architectures has been shown in an elegant study by Hawker et al. in which polyether dendrimers are compared with their linear isomers (Figure 2).[41] Especially the fifth and sixth generation dendrimers display differing features when compared to their structural isomers. The hydrodynamic volume of the fifth generation polyether dendrimer is approximately 30% smaller than that of its linear analogue. The difference is ascribed to a more compact backfolded globular structure of the dendrimer. In addition, the fifth generation dendrimer is completely amorphous (a Tg of 42 C is recorded) and is soluble in a variety of organic solvents, whereas the linear analogue is highly crystalline and poorly soluble in THF, acetone, and chloroform. The Hawker investigation solidly confirms that the physical behavior of dendrimers is different from that of linear polymers, and equally important, it shows that dendrimers need to have a certain size to display significantly different physical behavior.

Figure 2. The fourth generation polyaryl ether dendrimer and its linear isomer.

6. APPLICATION OF DENDRIMERS
6.1. Asymmetric Transfer Hydrogenation
6.1.1. Asymmetric Transfer Hydrogenation to Olefins The first attempts to carry out asymmetric catalysis using chiral metallodendrimers were reported by Brunners group. These reports belong to the pioneering works in catalysis using metallodendrimers that appeared in 1994. Brunner designed dendritic catalysts containing dendritic phosphines which he called dendrizyme because of their hoped for similarities with enzymes.[42] Brunner et al. reported on a complex synthesized from a diphosphine core and dendritic branches containing menthyl groups (Figure 3).[43] The ligand was coordinated to RhI in situ by reaction with [Rh(4-COD)Cl]2. Application of the rhodium complex (Rh:substrate ratio 1:50) to the hydrogenation of acetamidocinnamic a cid after 20 h at 20 bar H2 pressure led the desired product with a small enantioselectivity (enantiomeric ratio of 51:49).[44] A very interesting feature of this early study, however, is that the rate of hydrogenation was higher in the presence of the dendritic diphosphine ligand having the dendritic wedge located at the meta position of the arene rings than with the nondendritic dppe. This spatial arrangement had a crucial role since, on the other hand, hydrogenation with a dendritic diphosphine having dendritic wedges in 2,5-position exhibited a 300-fold rate decrease while the enantioselectivities remained very weak.

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Figure 3. Brunners dendrizyme ligands reported in 1994 for the hydrogenation of acetamido cinnamic acid ( Rh-dendritic dppe ligang).

Figure 4. Kakkars organophosphie dendrimers with phosphorous atoms at the focal points (up to P46 on the figure).

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Kakkars group reported on an interesting organophosphine dendrimers with phosphorus atoms at the focal points (Figure 4).[45] The divergent construction involved reaction of (CH3)3SiNEt2 with P{(CH2)3OH}3 followed by sequential reactions of the dendrimer with these two reagents successively up to the P46 dendrimer. The metallodendrimers containing [RhCl(4-1,5-C8H12)PR3] moieties were best synthesized by reactions of these phosphorus dendrimers with [Rh(-Cl) (4-1,5-C8H12)]2 and were shown to catalyze the hydrogenation of 1-decene in a 1:200 metal-to-substrate ratio (25 C, 20 bar H2, 30 min, THF). The catalytic activity (turnover number about 200 molprod (molcat)-1 and turnover frequency about 400 molprod (molcat)-1 h-1) was found to be similar to that of the monometallic complex. There was a slight decrease in turnover frequencies upon growth of the RhI46 dendrimer. After one such cycle of hydrogenation using the Rh46 dendritic catalyst, the organic product was extracted into pentane and the Rh46 dendrimer was recrystallized from THF/hexane mixtures and reused with only 5% decrease in conversion, which favorably compares with supported catalysts.[45] Mizugaki et al. examined the selective hydrogenation of conjugated dienes to monoenes using an atmospheric pressure of H2 at 25 C by the dendritic catalyst DAB-dendr[N(CH2PPh2)2PdCl2]16 prepared by reaction of Reetzs dendritic phosphine (vide infra) with [PdCl2(PhCN)2].[46] The excellent selectivity of the hydrogenation of cyclopentadiene to cyclopentene is remarkable. The catalytic activity was higher than that of the corresponding monomer [PdCl2{PhN(CH2-PPh2)2}] and the polystyrene-bound catalyst. The metallodendrimer was less active than Pd/C and Pd/Al2O3, but these heterogeneous catalysts are not selective contrary to the dendritic catalyst. Another remarkable feature of this system is that the hydrogenation of 1,3-cyclooctadiene by the same dendritic-PdCl2 complex occurred with much higher rates than by the monometallic catalyst. Interestingly, this reaction was very efficient in ethanol in which the dendritic catalyst was not soluble whereas it was slow in DMF in which it was soluble. Thus, heterogeneization renders the system efficient. Rationalization of all these features would be speculative, but it seems that the active metallic sites are well accessible on the surface of the heterogeneous catalyst. The dendritic catalyst was easily recovered from reaction mixtures by centrifugation and reused without much loss of activity.[46] Togni et al. decorated 8-, 12-, and 16-branch dendrimers with ferrocenyldiphosphine ligands and also synthesized the corresponding rhodium(I) complexes (Figure 5).[47] These ferrocenylphosphine-rhodium(I) dendrimers catalyze the hydrogenation of dimethylitaconate (1) affording the desired product 2 (Scheme 2) with an enantioselectivity (ee) of 98%, which compares with the ee of 99% obtained for the monomeric Josiphos catalyst. Moreover, the dendritic catalyst can be separated from the reaction mixture using a nanofiltration membrane.[47] The Fan and Chan groups reported a series of dendritic BINAP ligands with Frchet-type polyether wedges and their ruthenium complexes as catalysts in asymmetric hydrogenation of 2-[p-(2-methylpropyl)phenyl]acrylic acid in methanol-toluene (1:1, v/v) at 50 C. The dendritic BINAP-Ru catalysts showed slightly higher enantioselectivity (ee = 92.6% with 100% conversion in 20 h) than Ru-BINAP (ee = 89.8%). The catalyst could be precipitated at the end of the reaction and then reused three times without loss of activity or enantioselectivity.[48]

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Figure 5. Example for Tongi dendrimers with optically active ferrocenyldiphosphine ligands.

O O O

Chiral dendritic catalyst H2

O O O

1
Scheme 2. Hydrogenation of dimethylitaconate.

(ee = 98%)

In an interesting approach, the first effort for the preparation of Pd-Rh bimetallic nanoparticles in the presence of poly(amidoamine) dendrimers with surface hydroxyl groups (fourth generation, PAMAM-OH) has been reported by Rhee et al.[49] Schematic illustration for the preparation of dendrimer-encapsulated bimetallic nanoparticles is represented in Scheme 3.

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Scheme 3. Schematic diagram for the preparation of dendrimer encapsulated Pd-Rh bimetallic nanoparticles.

The dendrimer-encapsulated PdRh bimetallic nanoparticles were applied as catalyst to the partial hydrogenation of 1,3-cyclooctadiene in ethanol/water mixture (v/v = 4/1). As shown in Figure 6, the dendrimer-encapsulated PdRh bimetallic nanoparticles were found to be effective in the hydrogenation reaction.[49] Different from the conventional polymer stabilized nanoparticles, the dendrimer-encapsulated nanoparticles are confined primarily by steric effects and therefore a substantial fraction of their surface is unpassivated and available for reactant to access in catalytic reactions. It is worth noting, however, that there exist apparent differences between two systems. While bimetallic nanoparticles with Pd content of 80% showed the highest activity in the case of Pt-Pd, the highest activity was achieved with a Pd/Rh ratio of 1/2 in PdRh system as shown in Figure 6. The cyclooctene selectivity at the complete conversion of 1,3-cyclooctadiene was higher than 99%, which is as high as that of the palladium or rhodium nanoparticle catalyst. In order to confirm the feasibility of catalyst recycling, after a reaction was completed, the catalyst was reused. It was found that the reaction performance was as good as that of the fresh one. This indicates that the dendrimerencapsulated PdRh bimetallic catalyst can be recycled and reused without a significant loss of its catalytic activity.

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Figure 6. Dependance of the catalytic activity of dendrimers encapsulated Pd-Rh bimetallic nanoparticles on its composition in the partial hydrogenation of 1,3-cyclooctadiene.

Gade et al. have been reported on the synthesis of a series of chiral phosphine functionalized poly(propyleneimine) (PPI) dendrimers by the reaction of carboxyl-linked C2chiral pyrphos ligand (pyrphos=3,4-bis(diphenylphosphino)pyrrolidine) with zeroth fourth (EDC)/1generation PPI using ethyl-N,N-dimethylaminopropylcarbodiimide hydroxybenzotriazol as a coupling reagent.[50] Metallation of the multi-site phosphines with [Rh(COD)2][BF4]cleanly yielded the cationic rhododendrimers containing up to 32 metal centers (for the fourth generation species). The relationship between the size/generation of the dendrimer and its catalytic properties was established in the asymmetric hydrogenation of Zmethyl--acetamidocinammate and dimethylitaconate. A decrease in both activity and selectivity of the synthesized rhododendrimers dendrimers was clearly observed on going to the higher generations. Moreover, an efficient strategy for the backbone functionalization of a tripodal phosphine ligand which allows its attachment to carbosilane dendritic supports has been developed by Gad et al.[51] These dendrimers were metallated with four and eight molar equivalents of [Rh(COD)2][BF4] in CH2Cl2, selectively yielding the desired metallated dendrimers. Comparative catalytic hydrogenation of styrene and 1-hexene using the metallodendrimers showed that the fixation to the low generation dendrimers did not alter the catalytic hydrogenation properties of the catalysts. Maarseveena et al. have been reported on the functionalization of the axially chiral BICOL backbone with two third generation carbosilane dendritic wedges and further elaborated to a phosphoramidite ligand. The chiral ligands 5 and 7 were prepared as shown in Schemes 4 and 5.[52]

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H N OR OR N H

CH3 N
.

i) MeI, NaH ii) TBAF iii) HMPT (95%)

N CH3

CH3 O P N O CH3

3. R = J (R)-BINOL) 4. R = TBS

TBSL, Et3N (100%)

(R)-5

Scheme 4. Synthesis of physphoramidite ligand 5 from (R)-BINOL.

Scheme 5. Synthesis of dendritic chiral ligand 7.

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The rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate 8 was used as the model reaction to study the catalytic behaviour of the new ligands (R)-5 and (R)-7 (Scheme 6 and Table 1). High enantioselectivities (up to 95% ee) were obtained when these monodentate ligands were applied in the rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate. When a ligand to rhodium ratio of 2.2 was used, the enantioselectivity induced by the rhodium complex based on ligand 3 (entry 3) was 93% (at full conversion). This shows the ability of the bicarbazole skeleton to induce high enantioselectivity. The catalytic behaviour of the dendritic analogue 5 was similar; in 2.5 h, product 8 was obtained quantitatively with an enantiomeric excess of 95% (entry 4).

Rh(COD)2BF4 (1 mol%) (R)-Ligand COOMe 8 H2 (5 bar) CH2Cl2, room temp. AcHN 9 COOMe

AcHN
Scheme 6.

Table 1. Asymmetric hydrogenation of methyl-2-acemtamidocinnamate 8.

Entry 1 2 3 4 5 6
a) b)

Ligand
Mono Phosph Mono Phosph

Ratio L/Rh 2.2 3.0 2.2 2.2 3.2 4.2

t (h) 2.0 2.0 2.5 2.5 2.5 2.5

Conv. (%)a 100 0 100 100 100 ~30

ee (%)b 95 --93 95 95 90

5 7 7 7

Determined by 1H NMR. Determined by chiral HPCL (Diacel OD, heptanes-isporpanol=9:1)

It is worth to mention that the Leeuwen group has examined the activity of Rh complexes of the dppf-type dendritic ligands in the hydrogenation of dimethylitaconate in a continuousflow membrane reactor. This shows a reasonable constant of formation of the product compared to the non-dendritic catalyst.[52,53] Fan and co-workers have been reported on the synthesis of a class of dendritic monodentate phosphoramidite ligands through substitution of the dimethylamino moiety in MonoPhos by the Frchet-type dendritic wedge and their application in the asymmetric hydrogenation of -dehydroamino acid esters and dimethylitaconate. The dendritic chiral ligands 10a-c were prepared in moderate yields. For comparison, a model compound of a small molecule 11 was also synthesized (Figure 7).[54] The rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate was first used as the model reaction to study the catalytic behavior of the dendritic ligands 10 and 11. The rhodium catalysts were prepared in situ by reaction of 2 equiv of the appropriate dendrimer ligands with [Rh(COD)2][BF4]in dichloromethane at room temperature. Typically, the reactions were carried out at room temperature in dichloromethane as the solvent. All catalysts gave high enantioselectivities (up to 97.9% ee), which are better than that obtained

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from Mono-Phos 11 (95%).[54,55] These results indicated that the size of the dendritic substituents on the nitrogen atom would not result in any negative effect on the selectivity, which is in contrast to the results obtained with the corresponding small monodentate phosphoramidite ligands bearing different substituents on the nitrogen atom.[54,56]

O O O O O O Ph N P O O O P O N

11

10a. (n= 0); 10b. (n= 1); 10c. n= 2)

Figure 7.

The same authors applied the same dendritic catalysts to the hydrogenation of other dehydroamino acid ester substrates.[54] Excellent enantioselectivities (up to 97.9 ee) were also achieved in all cases, which are better or comparable to those obtained from Mono-Phos 11. Hydrogenation of substrates with electron donating and withdrawing meta- or parasubstituents on the phenyl group gave slightly higher ee values as compared to the orthosubstituted substrates. It was noted that the dendritic catalysts showed slightly higher enantioselectivities for all ortho-substituted substrates than those obtained from the monomer ligand 11. Hydrogenation of dimethylitaconate also gave excellent enantioselectivities, which are better than those of Mono-Phos).[54,55]

Figure 8.

Carbosilane dendrimers (12-14; Figure 8) containing P-stereogenic monophosphines as terminal groups, Dend-{CH2PPhR}n (R=2-biphenylyl or 9-phenanthryl) were prepared.[57] The rhododendrimers Dend-{CH2PPhR(RhCl(COD))}n were cleanly obtained by reacting

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[RhCl(COD)]2 with the corresponding dendrimer in CH2Cl2 at room temperature. Recrystallization in CH2Cl2/diethyl ether gave the targeted rhododendrimers as yellow solids in good yields. They are soluble in most common organic solvents and were characterized by elemental analyses, 1H, 13C and 31P NMR spectroscopy, and ES mass spectrometry. The catalytic properties of the rhodium dendrimers were tested in the hydrogenation of dimethylitaconate. The model chiral compounds, (CH3)3Si{CH2PPhR(RhCl(COD))} and (CH3)3Si{CH2PPhR(RuCl2(p-cymene))}, were prepared in order to detect potential dendritic effects. All compounds were found to be active in the catalytic conditions tested, but low or null ee were found.[57] Fan et al have been recently designed and synthesized a new kind of dendritic pyrphos ligands bearing alkyl chains at the periphery for the Rh-catalyzed asymmetric hydrogenation of dehydroamino acids.[58] The new series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of (R,R)-3,4bis(biphenylphosphino)pyrrolidine (pyrphos) with peripherally alkyl-functionalized benzoic acid dendrons (Scheme 7).
H3C H2C H3C H2C n O COOH O H3C H2C n nO O H3C PPh2 H3C H2 C H2C O n O n C N PPh2 PPh2

H3 C

H 2C O n

PPh2 HN

(i)

15C-G1, n = 9 16C-G1, n = 15
9

H3C H2C
9

H 3C H3C H2C O COOH

H2C
9

H 3C H 2C
9

O O
9

O O O O C N PPh2 PPh2

H3C

H 2C

PPh2 HN PPh2

(i)

H3C

H2C

H3C

H2C

H3C H2C

O H 3C H 2C H3C
9

O
9

H3C H2C

O
9

O
9

H2C

(i) DCC, DMAP, CH2Cl2, r.t.

H3C H2C

17C-G2

Scheme 7. Synthesis of chiral deneritic pyprophos lignads.

With these chiral dendritic catalysts, the asymmetric hydrogenation of acetamidocinnamic acid (18) as a standard reference system for comparing their catalytic performance (Scheme 8).[58]

Scheme 8.

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As it was expected, the number and length of the alkyl end groups of the dendritic wedges influenced the reaction performance and the results depended on the solubility of the dendrimer in solvent. Full conversion and high enantioselectivity (up to 95.6% ee) for the first generation dendrimer ligand 15C-G1 was observed, which are similar to those previously reported for the soluble polymer-supported catalyst (95.5% ee). Interestingly, full conversion and high enantioselectivity (up to 97.8% ee) were observed in case of using dendrimer ligand 17C-G2.[58,59] It was found that these dendrimer-based catalysts with alkyl tailed at the periphery preferred to dissolve in a non-polar solvent system. In the case of the second-generation dendritic ligand 17C-G2, more than 99% of its Rh complex could be extracted to the nonpolar cyclohexane phase in a methanol/cyclohexane (2.0% H2O) biphasic system. The cyclohexane layer, which contained the catalyst 17C-G2-Rh(I), was separated and reused in the next run of reaction. The recovered catalyst was reused five times with similar enantioselectivity, albeit decreased activity until the fourth cycle (Table 2, entry 4).[58,60]
Table 2. Recycling of the catalyst 17c-G2-RH (I) in the asymmetric hydrogenation of acetamidocinnamic acid 18.

Entry 1 2 3 4 5

Cycle First Second Third Fourth Fifth

Conv. (%) 100 99 97 83 56

ee (%) 97.0 97.1 97.0 96.8 95.5

6.1.2. Asymmetric Transfer Hydrogenation to Ketones and Imines The chiral diamine core was discovered by Noyori for the catalysis of asymmetric transfer hydrogenation of acetophenone which [RuCl2(6-cymene)]2 is the Ru source and is available on the kilogram scale.[61] The dendrimers rather favorably compare with the parent nondendritic catalyst in terms of activity, and the enantioselectivity was retained. It was remarkable that, upon recycling the dendritic catalyst, the enantioselectivity was retained while the activity only decreased slightly. Deng et al. have been reported on the synthesis of multiple dendritic ligands 20-22 based on (R,R)-1,2-diphenylethylenediamine in a convergent approach (see Figure 9).[62] Their ruthenium complexes prepared in situ had good solubility in the reaction medium (azeotrope of formic acid and triethylamine). Initial experiments were conducted to test the catalytic activity of ruthenium(II) complexes of the dendritic ligands in the asymmetric transfer hydrogenation reaction of acetophenone which was used as the model substrate and the azeotrope of formic acid and triethylamine as the hydrogen source. Ru(II) complexes of (R,R)-TsDPEN (23) and (R,R)-N-(4-acetylaminophenylsulfonyl)-1,2diphenylethylenediamine (24) were selected as monomeric catalysts for comparison.[62] It was found that the macromolecular catalysts showed no significant difference in activity and enantioselectivity in the asymmetric transfer hydrogenation of acetophenone as

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compared with the monomeric catalysts 23 and 24. Good retention of catalytic activity and high enantioselectivity were observed in these dendritic catalysis. However, the glycine spacer had mild negative effects on the catalytic activity (entries 3 vs 4; Table 3).

O C O R O O

Ph S NH

Ph NH2

20. R = NH 21. R = NHCOCH2CHNH2

22. R = H
Figure 9.

Table 3. Comparison of Dendritic and Monomeric Catalysts in Asymmetic Transfer Hydrogenation of Acetophone a.

Reactions were conducted at 28oC for 20h. S/C=100. Conversions were determined by GC. c The average TOFs were calculated over the 5h reaction time. d Determined by GC with a Chrompack CP Chirasil-dex column (25m x 0.25mm).
b

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For exploring the scope and limitations of this reaction catalyzed by the dendritic catalysts, a variety of ketones and imines (see Figure 10) were applied in the asymmetric transfer hydrogenation with HCOOH-NEt3.[62] In general, excellent conversions with quantitative yields and for some cases a slightly higher enantioselectivities (up to 98.7% ee) were obtained using the dendritic catalysts. Considering the high local catalyst concentrations at the periphery, diones were tested for the possible synergic reactivity between catalytic units at the surface, while no apparent differences were noted.[62]

O n

O S

O N

O S N O

O Ph P N Ph

a. R = o-F b. R = p-F c. R = o-Cl d. R = o-Br e. R = p-Br

a. n = 1 b. n = 4

R a. R = Bn b. R = But

Figure 10.

Scheme 9. Synthesis of dendronized poly(BINAP)s.

Fan et al. reported on the synthesis of a new kind of dendronized polymeric chiral BINAP ligands and applied to the Ru-catalyzed asymmetric hydrogenation of simple aryl ketones and 2-arylacrylic acids. The dendronized poly(BINAP) ligands were synthesized as shown in Scheme 9.[63] These dendronized poly(Ru-BINAP) catalysts exhibited high catalytic activity and enantioselectivity, very similar to those obtained with the corresponding parent Ru(BINAP) and the Ru(BINAP)-cored dendrimers. It was found that the pendant dendrons

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had a major impact on the solubility and the catalytic properties of the polymeric ligands. These polymeric catalysts could be easily recovered from the reaction solution by using solvent precipitation, and the reused catalyst showed no loss of activity or enantioselectivity.[63] The catalytic efficiency of the dendronized poly(Ru-BINAP) catalytic system was further demonstrated in the asymmetric hydrogenation of 2-arylacrylic acids.[63] The Ru catalyst was prepared by mixing [Ru(benzene) Cl2]2 and the appropriate polymeric ligand in situ in hot DMF. High enantioselectivities were obtained in the asymmetric hydrogenation of 2-[p(2-methylpropyl)phenyl]acrylic acid and 2-phenylacrylic acid (82-83% ee), which were comparable to those obtained with Ru(BINAP) under otherwise identical reaction conditions. It was found that the size of the pendant dendrons also slightly influenced the enantioselectivity of the polymeric catalysts.[63] It is importantly to note that the Ru catalyst with the third generation pendant dendrons was used for the recycling experiments. Upon completion of the reaction, methanol was added to the reaction mixture and the catalyst was quantitatively precipitated and recovered via filtration. The recovered catalyst was reused for at least three cycles in the asymmetric hydrogenation of 2-methylacetophenone with similar enantioselectivity (~92% ee).[63] Hydrophobic Frchet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III) complexes have been prepared and applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen source.[64] The core-functionalized dendritic ligands 29a-d based on chiral 1,2-diaminocyclohexane (DACH) were smoothly prepared as illustrated in Scheme 10. The dendritic structures could be established through MS techniques (ESI HRMS or MALDITOFMS).

Scheme 10. Synthesis of dendritic DACH ligands.

With the desired chiral dendritic ligands 29a-d, the catalytic activity and enantioselectivity of their ruthenium or rhodium complexes were studied via the transfer hydrogenation of acetophenone, and also compared with the monomeric TsDACH-metal complex.[63,64] The transfer hydrogenation reactions was conducted in three different conditions for detailed comparison of the dendritic catalysis at 1 mol% catalyst loading: (a) [RuCl2(cymene)]2 as the metal precursor in DCM solution, the azeotrope of HCOOHNEt3 as

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the hydrogen source at 28 C; (b) [RuCl2(cymene)]2 as the metal precursor in aqueous solution, HCOONa as the hydrogen source at 35 C; (c) [RhCp*Cl2]2 as the metal precursor in aqueous solution, HCOONa as the hydrogen source at 40 C. Although quite different results were obtained under the above-mentioned three reaction conditions, in general, good retention of high enantioselectivity was observed for all dendritic catalysts as compared to the monomeric metal TsDACH-metal complex. It is worth to mention that the reduction of acetophenone took place smoothly at 0.1 mol% of 29bRh(III), furnishing a >99% conversion with 94% ee in 4 h.[64] The recyclability of these dendritic catalysts was then tested via the solvent precipitation method. The second generation dendritic 29bRh(III) complex at 1 mol% loading was employed in the transfer hydrogenation of acetophenone, as the example. The recycling use of dendritic 29b-Rh(III) catalyst was quite successful and excellent conversion (97%) and enantioselectivity (95% ee) were obtained even in the sixth run with some extension of the reaction time.[64] Subsequently, the above-mentioned protocol was extended to a range of aromatic, heteroaromatic and functionalized ketones (Figure 11), aiming to determine the potential applicability of the dendritic catalytic system in the asymmetric transfer hydrogenation in water. Excellent conversions (up to >99%) and high enantioselectivities (up to 97% ee) could be obtained.[64]

Figure 11. Structures of various ketones.

Deng et al. have been reported on the synthesis of tunable dendritic N-monosulfonyl ligands via direct N-monosulfonylization of the chiral dendritic vicinal diamines. The chiral dendritic N-arylsulfonyldiamine ligands (R,R)- and (S,S)-30 that are shown in Figure 12 were prepared in good to high yields (65-85%). The application of these dendritic ligands in the asymmetric transfer hydrogenation of ketones was investigated. For comparison, a monomeric ligand, (R,R)-31 was also prepared.[65] The asymmetric transfer hydrogenation was first studied using acetophenone as the model substrate. Compared to the complexes of monomeric ligand (R,R)-31, as well as TsDPEN, a slightly enhanced reactivity was observed for the dendritic catalysts, Ru[(R,R)-30] with similar enantioselectivities which are more active than those dendritic catalysts derived from amino-functionalized vicinal diamine (the TOF values are less than 12). However, when the third generation catalyst of Ru[(R,R)-30] was used, the reactivity had a notable drop in only 75% conversion (TOF value is 4.3) along with a slight decrease of enantioselectivity with the same reaction time. In general, the hydrogenated product was obtained with high yields (conversion was >99%) and high enantioselectivities up to 97.5% ee. Interestingly, the second generation catalyst of Ru[(R,R)30] could be recovered by precipitation with an addition of methanol after removed of DCM under reduced pressure and reused four times with slightly higher enantioselectivities (97.5, 97.2, 97.5 and 97.0% ee vs 96.1% ee).[65]

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Several aliphatic and aromatic ketones as substrates were also examined in the asymmetric hydrogenation reaction using the dendritic catalysts (R,R)- and (S,S)-30. In general, the conversions of ketones and enantioselectivities of the reduced products did not obviously change when using dendritic (R,R)- and/or (S,S)-30 as a ligand compared to the monomeric ligand (R,R)-31 and TsDPEN. The above-mentioned study showed an increase of enantioselectivities in the asymmetric reduction could be achieved by fine tuning of the coordinating amino group NH2 of chiral 1,2-diamines.[65]

O R1HN * R2HN * O

n MeO OMe

O NHSO2C6H4-p-CH3

H2N n

(R,R)-31

(R,R)- and (S,S)-30

Figure 12.

Fan and Shuai have been reported on the synthesis of a series of new chiral dendritic BIPHEP ligands and their applications in the Ru-catalyzed asymmetric hydrogenation of ketoesters were investigated.[66] The authors chose enantiopure MeO-BIPHEP as the starting compound to make the dendritic BIPHEP ligands 35a-c. The synthetic procedure is outlined in Scheme 11.

O O

Br
O O n

n O O O O n O

HO HO

PPh2 PPh2

a 95 %

HO HO

PPh2 PPh2
O

33
b

PPh2 PPh2
O

(R)-35
n=1, 35a, 84% n=2, 35b, 99% n=3, 35c, 99%

32
O

32

d 50%

PhCH2O PhCH2O

PPh2 PPh2
O

e 70%

PhCH2O PhCH2O

PPh2 PPh2

n=1, 34a, 55% n=2, 34b, 50% n=3, 34c, 60%

36

37

Scheme 11. Synthesis of dendritic BIPHEP Regents and conditions. (a) H2O2 (35%), CH3OH 2h at r.t; (b) 33, K2CO3, acetone, reflux; (c) NEt3/NBu3, toluene, reflux; (d) benzl bromide, K2CO3, acetone, reflux.

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In order to evaluate the catalytic efficiency of these dendritic ligands and the influence of the dendritic wedges on the enantioselectivity of a given reaction, the well-studied asymmetric hydrogenation of -ketoesters was selected as the standard reactions (Scheme 12). The Ru-catalyst was prepared by mixing [Ru(benzene)Cl2]2 and the proper dendrimer ligand in situ in hot DMF. The reaction was carried out in a CH2Cl2-ethanol mixture as the solvent under 40 atm of H2 pressure at 60 C for 24 h. For comparison, the model ligand 37 was performed under the same reaction conditions.[66]

O R1

O OR2

Dendritic Ru(BIPHEP), H2 CH2Cl2/ C2H5OH (1:1)

OH O R1 * OR2

Scheme 12. Asymmetic hydrogenation of B-ketoester catalyzed by dendritic Ru (BIP HEP) catalysts.

While all dendritic catalysts showed similar reactivity, the enantioselectivity varied dramatically with increase in generation from 1 to 3. For example, methyl 3-oxo-3phenylpropanoate was reduced with ca. 93.1% ee using the model small molecule Ru(37) catalyst. The enantioselectivity decreased to 92.0% ee with the first generation Ru(35a) catalyst and reached a minimum of 86.6% ee with the second generation Ru(35b) catalyst. Unexpectedly, with further increase of generation to 3, enantioselectivity increased slightly to 91.3% ee. This result indicated that similar catalytically active Ru-complex of Ru(35c) was formed under the reaction conditions despite the bulky dendritic substituents. This general trend was found to be true for all substrates used in this study.[66] It has been recently reported that the asymmetric hydrogenation of quinolines catalyzed by chiral dendritic catalysts derived from BINAP gave the corresponding products with high enantioselectivities (up to 93%), excellent catalytic activities (TOF up to 3450 h-1), and productivities (TON up to 43 000).[67] Frchet-type polyaryl ether dendrons were chosen for this study owing to their chemical inertness and inability to coordinate iridium. The synthetic pathway and structures of the dendritic ligands are shown in Scheme 13.

Scheme 13. Synthesis and Structures of Dendritic GnDenBINAP Ligands.

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Ashraf A. El-Shehawy

The effects of the solvents, temperature, hydrogen pressure, and additive on the activity and enantioselectivity were investigated by using the second-generation dendrimer catalyst, which was generated in situ from G2DenBINAP and [Ir(COD)Cl]2 (Table 4). A series of organic solvents were tested, and THF was found to be the best choice in terms of both conversion and enantioselectivity (entries 1-5). The enantioselectivity of the reaction was slightly increased at low temperature, but the reaction could be completed at prolonged time (entry 8). Notably, low conversion and enantioselectivity were observed under both higher and lower hydrogen pressure (entries 9 and 10). The reaction could not proceed without iodine as an additive (entry 13).[67]
Table 4. Asymmetric Hydrogenation of Quinaldine (38a) Catalyzed by Dendritic Ir (G2DenBINAP) Catalysta.

Reaction conditions: 0.25 mmol of quinaldine 38a in 1.25mL of solvent, 0.5 mol% of [Ir(COD)C1]2, 1.1.mol % of (S)-G2DenBINAP, I2/catalyst = 10 (mol/mol), 45 atm H2, 15-20oC. b Determined 1H NMR analysis of the crude product. c . Determined by HPCL anaylysis with Chirapak OJ-H column. The predominated product was in the Sconfiguration. d Reaction temperature = 50oC e Reaction temperature = 0oC. f H2 = 100 atm. g H2 = 10 at, h I2/catalyst = 1 (mol/mol). i I2 = 0 mol %.

The applications of the dendritic catalyst in the asymmetric hydrogenation of other 2substituted quinoline derivatives using G2DenBINAP as the ligand were further investigated

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273

(Table 5). In general, all substituted quinolines studied were hydrogenated with good enantioselectivities and conversions.[67] The reaction was found to be relatively insensitive to the length of the 2-alkylated side chain of quinolines, and high enantioselectivities and good yields have been consistently obtained (entries 1-3). Notably, under low catalyst loading, the reactions performed well, affording similar enantioselectivities, albeit low catalytic activities (entries 1-7). The authors then investigated the recyclability. G3DenBINAP-Ir-catalyzed asymmetric hydrogenation of 38a was chosen as the standard reaction. Upon the completion of the reaction, the catalyst was quantitatively precipitated by the addition of hexane and reused at least six times with similar enantioselectivities but at the expense of relatively low catalytic activities.[67]
Tabel 5. Catalytic Asymmetric Hydrogenation of Quinoline Derrivativesa.

Reaction conditions: 0.25 mmol of substrate in 1.25 mL of THF 0.25 mol% of Ir(G2DenBINAP) catalyst. 5 mol% of I2, 20-25oC, 1.5h. b Determined by 1H NMR analysis of the crude product. c Determined by HPCL analysis with Chirapak OJ-H (38a-c, 28i and 38j). AS-H 938d and 38e) and OD-H (38f-h and 38k) columns. d The Absolute configuration is assigned by comparison of the HPCL retention time with those reported in the literature data. e Data in brackets were obtained by usint 0.01% catalyst under the following conditions: 2.5 mmol of substrate in 5 mL of THF, 1.125 mol% of I2, 20-25oC, h. f Reaction time =36h.

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6.2. Hydroformylation
The hydroformylation reaction extensively used in research and industry, converts terminal olefins, carbon monoxide, and hydrogen into linear or branched aldehydes (Scheme 14).[68] The homogeneous catalysis, mostly based on rhodium and cobalt complexes, is the predominant approach to this process. However, during the last decade, there has been growing interest in developing various catalytic systems for the reaction to successfully recycle the expensive catalytic complexes.

CO

H2

Catalyst R

CHO

CHO

Scheme 14. Hydroformylation reaction.

The Reek and van Leeuwen group synthesized diphenylphosphine-functionalized carbosilane dendrimers Si{(CH2)nSi(CH3)2(CH2PPh2)}4 (n=2, 3; generations 1-3) and Si{(CH2)nSi(CH3)(CH2PPh2)2}4 (n=2, 3; generation 1, 2). These chiral ligands were used for the rhodium-catalyzed hydroformylation of 1-octene.[69] The diphenylphosphine functionalized carbosilane dendrimers with both monodentate and bidentate end groups were synthesized by hydrosilylation of the various generations of carbosilane dendrimers with chlorodimethylsilane or dichloromethylsilane followed by a reaction with lithium methyldiphenylphosphine-TMEDA (Scheme 15).[69,70]
Gx
i
m

Gx

Si

Cl
m

iv
46. x = 0, n = 0, m = 4 47. x = 1, n = 0, m = 12 48. x = 2, n = 0, m =36 49. x = 0, n = 1, m = 4 50. x = 1, n = 1, m = 12 51. x = 2, n = 1, m = 36

40. x = 0, n = 0, m = 4 41. x = 1, n = 0, m = 12 42. x = 2, n = 0, m =36 43. x = 0, n = 1, m = 4 44. x = 1, n = 1, m = 12 45. x = 2, n = 1, m = 36 ii

Gx

Si

PPh2

Gx
iii

Si

Cl
m

Gx

Gx

Cl Si Cl

v
m

Gx

Si

PPh2 PPh2

52. x = 0, n = 0, m = 4 53. x = 1, n = 0, m = 12 54. x = 0, n = 1, m = 4 55. x = 1, n = 1, m = 4

Gx is the generation x of the carbosilane dendimer, e.g. G0 = tetraallylsilane or tetravinylsilane

Scheme 15. Synthesis of diphenylphospine functionalized carbosilane dendrimers, reagents (i) HSiMe2CH2CI2 [Pt]; (ii) HSiMeCI2, (iii) HSiMeCI2 [Pt], (iv) Ph2PK; (v) Ph2PCH2Li-TEMEDA.

These diphenylphosphine terminated carbosilane dendrimers were used as ligands in the rhodium catalyzed hydroformylation of 1-octene. The catalyst was prepared in situ by mixing (acetylacetonato)dicarbonylrhodium(I) and the dendrimeric ligand under H2/CO pressure of 20 bar. Model compounds (H3C)3SiCH2PPh2 (56) and (H3C)2Si.CH2PPh2 (57) were used for comparison. The selectivity for the linear and branched aldehydes of the dendrimeric systems is the same as that of the model systems 56 and 57 (Table 6).[69-71] Neither isomerization of 1-octene nor hydrogenation to alkanes and alcohols was observed during the catalytic reactions. The dendrimeric structure, i.e., the different generations of dendrimers with

Unique Design Tools for the Synthesis and Design of Dendrimers

275

monodentate and bidentate end groups, has no influence on the selectivity of the reaction. However, differences in reaction rates between the various dendrimeric ligands have been observed. The dendrimers with bidentate end groups (14-16) give slower catalysts than the dendrimers with monodentate end groups (7-12), a difference that is also observed for the model compounds (56 and 57).[69-71] Reetz et al. modified Meijers 16-branch polypropylene imine dendrimer with chelating diphenylphosphine ligands, which led to a 32-branch phosphine dendrimer. This polyphosphine dendrimer formed complexes with various transition-metal groups such as PdMe2 or Rh(cod)BF4 (cod=1,5-cyclooctadiene) which had catalytic properties.[72,73] Hydroformylation of 1-octene with the RhI dendritic catalyst showed a turnover number comparable to that of the monomer. It was pointed out that such catalysts could be separable by membrane separation techniques.[72]
Table 6. Results of rhodium catalysed hydroformylation of 1-octene using various dendrimeric ligandsa.

T = 80oC, pco=pH2 =10 bar, [Rh] = 1mM, [1-octene] =638mM in toluene, P/Rh = 2.5, conversion after 1h.

Gong et al. synthesized four water-soluble dendritic phosphonated ligands based on PAMAM dendrimers of generation 3 (32 end groups) with the hydrophilic amine or sulfonic acid group on the surface of the dendrimer. For this purpose, the PAMAM dendrimers were allowed to react with [Ph2P(CH2OH)2]Cl and 1,3-propane sultone. The RhI dendritic complexes were used as the catalysts in the two-phase hydroformylation of styrene and 1octene under mild reaction conditions (40 C, 20 atm). High catalytic activity for both styrene and 1-octene and high selectivity for the isoaromatic aldehyde were found.[74] Cole-Hamiltons group reported on the synthesis of dendrimers based on polyhedral oligomeric silsesquioxanes cores with 16 PPh2 arms (Figure 13) that give much higher linear selectivities (14:1) than their small molecule analogues (3-4:1) in the hydroformylation of cyclooct-1-ene catalyzed by the RhI complex.[75-77]

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Ashraf A. El-Shehawy

In this metallodendrimer, the phosphorus atoms are separated by five atoms including one silicium atom, i.e., 4-7 within one arm, while this distance in the 5-10 range between arms (from molecular modeling). Indeed, analogous metallodendrimers containing only one more CH2 unit between the Si and P atoms showed no special selectivity enhancement over the monometallic catalysts. This positive dendritic effect was explained by the steric crowding and small arm length inducing eight membered ring bidentate coordination that enhances the linear selectivity. Fluxionality within the complex was also suggested based on 31 P NMR studies.[75-77] The cooperating groups of Alper, Arya, and Manzer[78,79] prepared a number of Rhbased supported dendritic catalysts and tested them in the hydroformylation of styrene, vinyl acetate, vinyl benzoate, and a number of other olefins. On silica, PAMAM dendrimers were converted into diphosphine ligands and further into Rh complexes (Scheme 16).[78a]

Figure 13. Cole-Hamilitons polyhedral silsesquioxane cores.

O SiO2 O O H N O O N N H NH2

Si

i 2 2

O SiO2 O O Si N O

H N

O N N H N

PPh2 PPh2

ii 2 2

O SiO2 O O

Si

N O

H N

O N N H N

Ph2 P Rh(CO )Cl 2 PPh2

(i) HPPh2 and CH2O & (ii) [Rh(CO)2Cl]2

Scheme 16. Preparation of silica-suported dendritic catalysts for hydrofrmyltion.

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277

Initially, only the ligands and complexes of the zero to second generations could effectively be formed. Because of steric hindrance, the functionalization and complexation of the third and fourth generations only occurred with extremely low efficiency. The catalysts demonstrated high activity and strong selectivity toward the branched product. The third-and fourth-generation catalysts were only marginally active at room temperature, probably because of the very low metal loading on the silica. Nevertheless, at 75 C, even these catalysts were active. Moreover, from the reported turnover rate measurements, it seems that the activity of the catalyst increased as a function of the generation. Regretfully, this point cannot be unequivocally concluded because, in this study and in subsequent reports from these groups, the catalysts were compared with an equal amount of silica/polymer rather than metal. The apparent turnover frequency is often affected by the initial amount of the catalyst. The improvement for the third- and fourth-generation catalysts was achieved through the elongation of the diamine fragment of the branching module of the PAMAM dendron.[79b] The extension of the branch length, the 1,2-diaminoethane being substituted by 1,4diaminobutane, 1,6-diaminohexane, or 1,12-diaminododecane, relieved steric crowding and presumably led to more dendron-like structures and an increase in the metal catalyst loading. The length extension indeed resulted in additional improvement in the activity and recyclability of the catalysts. The best results were achieved for the fourth-generation catalyst based on diaminododecane, which could be recycled four times without a loss of activity. The preparation of superior catalysts through changes in the design and generation of the dendritic template is remarkable, although exact conclusions regarding the change in activity per metal equivalent, as well as the existence and magnitude of the dendritic effect, cannot be drawn because the report did not contain critical data about the metal loading on silica. The same cooperating groups also prepared polyamidodendrons on polystyrene.[78a] The dendrons incorporating 3,5-diaminobenzoic acid based peptide-like monomers were decorated with diphosphine chelate ligands and their Rh complexes. The hydroformylation reaction again demonstrated high activity associated with this type of design of the catalytic system. The second- and third-generation derived catalysts were more active than the firstgeneration-derived one and could be recycled a number of times without a loss of activity. An additional study explored the influence of the isolation of the catalyst environment on the polystyrene supported catalytic systems in the hydroformylation reaction was also investigated. In this study, first- and second-generation dendrons were constructed on polystyrene, and the biphosphine-rhodium complex was attached to the first-generation module.[78b] In the second-generation dendrons, the outer layer modules did not carry metal and were used to isolate the catalytic site from the environment. Although the metal loading of the second-generation catalyst was lower than that of the first (because the number of metal atoms per dendron was equivalent for both), the reactivity and recyclability of the second generation-derived catalyst were notably better with some substrates (e.g., vinyl benzoate). This interesting dendritic effect again emphasizes the influence of the dendritic template architecture on the catalytic outcome. The two aforementioned catalytic systems on polystyrene were further evolved into a dendritic catalyst with lysine-containing peptide-like modules.[79c] Each monomer thus formed four propagation sites. First- and second-generation catalysts bearing 4 and 16 rhodium complexes, respectively, on each dendron were formed. These catalytic systems showed even higher reactivity (enabling room-temperature hydroformylation), excellent regioselectivity (higher than that of the first two systems, probably because of the lower

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Ashraf A. El-Shehawy

reaction temperature), and outstanding recyclability. This catalytic system was successfully applied to the carbonylative ring expansion of aziridines. Fan et al. have been reported on the synthesis of a new class of dendrimers functionalized with triphenylphosphines at the periphery by using convergent method (Figure 14).[80] The Frechets polyether dendrimer instead of poly(propyleneimine) (PPI) or poly(amidoamine) (PAMAM) dendrimers was chosen as the backbone, which is inert to almost all reactions. All of the obtained results clearly demonstrated the formation of monodispersed dendrimer functionalized with phosphines at the periphery. In this study, the rhodium-catalyzed hydroformylation of olefins was chosen as the model reaction. The catalysts were prepared in situ by mixing Rh(acac)(CO)2 and the dendritic ligand under a CO/H2 pressure of 20 bar. Styrene and 1-octene were chosen as the standard substrates.[80]. The results are summarized in Table 7.
OCH 2

PPh2 PPh2

Ph2P H3CC OCH2 PPh2

CH2O

O O C CH3 H3CC OCH2 O

OCH 2
OCH OCH
2

Ph2P

CH2O

58

59

PPh2 PPh2

Figure 14.
Figure 14.

60

Table 7. Hyedroformylation of olefins catalyzed by dendritic Rh (CO)2(PPh3)2 catalystsa.

Reactions were carried ot with 0.5m of olefin under the following reaction conditions: substrate/Rh =500:1; temperature =80oC: 2ml solvent. 20bar(CO/H2 =1). b Selectivity of aldehyde was more than 99%.

As shown in Table 7, high reactivity and regioselectivity for the first generation dendrimer catalyst was observed with low catalyst loading, which was comparable to the parent catalyst (entries 1 and 2). However, the second and third generation catalysts gave low

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279

regioselectivity and significantly decreased conversion (entries 3 and 4). The profound generation effect was due to the insolubility of the higher generation catalyst in toluene. Therefore, dichloromethane was chosen to be the reaction medium in order to sustain homogeneous reaction conditions for all generation catalysts. In comparison with those in toluene, high conversion was obtained (entries 7 and 8). The regioselectivity slightly decreased with increasing generation of the catalysts, albeit higher than that of the parent catalyst (entries 5-8). In contrast, hydroformylation of 1-octene gave the linear aldehyde as the main product. With phosphine:rhodium ratio = 10:1, similar regioselectivity was obtained for the dendritic systems and the parent catalyst (entries 9-12).[80] Interestingly, after PAMAM dendrimers have been successfully grown in SBA-15 mesoporous materials, Wilkinsons catalyst (RhCl(PPh3)3) precursor has been tethered on these dendritic supports to produce heterogeneous catalysts for hydroformylation reaction of styrene.[81,82] SBA-15 has been functionalized by two methods. In the passivation method, the silanols outside the SBA-15 pores have been passivated to preclude the rhodium precursor to be tethered outside the channels. The rhodium catalysts supported in the pore channels of this passivated SBA-15 show positive dendritic effects in enhancing the catalytic activity, regio-selectivity and stability of the catalyst by minimizing the leaching of the rhodium complex catalyst from the catalyst support to the liquid-phase media.[81,82]

6.3. Dialkylzinc Addition to Unsaturated Substrates

6.3.1. Dialkylzinc Addition to Aldehydes Meijer and Peerlings reported the first catalytic studies with high-generation dendrimers.[83-85] They studied the increased influence of conformational rigidity as the generation number increases in poly(propyleneimine) dendrimers on the asymmetric addition of diethylzinc to benzaldehyde catalyzed by optically active amino alcohols (Scheme 17). This reaction is indeed an ideal test reaction for the induction of asymmetry by amino alcohol catalysts.

O H

ZnEt2

2% Catalyst toluene / hexane *

OH

Scheme 17. Diethylzinc addition to benzaldehyde.

Poly(propyleneimine) dendrimers have been modified with (R)-phenyloxirane and their corresponding N-methylated derivatives (Figure 15), and these dendritic catalysts have been tested for the addition of diethylzinc to benzaldehyde. The chemical yields and ee drop as the dendritic generation of the catalyst increases (ee drops from 36% for the monofunctional catalyst to the fifth-generation dendritic catalyst).[83,85] Optically active R-styrene oxide was also brought into reaction with the amine-functionalized poly(propyleneimine) dendrimer yielding mainly the secondary alcohol-secondary amine functionalities. Reaction of diethylzinc with benzaldehyde using these dendritic catalysts led to a dramatic drop in enantiomeric excess, going from 11% to 0% for catalysts with 1-64 end groups. Thus, the

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Ashraf A. El-Shehawy

dendritic effect is negative in both of these cases. This negative dendritic effect was attributed to an increase in steric hindrance of the end groups at the periphery of the dendrimer, resulting in an increased difficulty for all end groups to adopt their preferred conformation in order to catalyze the diethylzinc addition. The presence of H-bonds greatly enhances this effect. Rheiner and Seebach used dendritic Ti-TADDOLates with Frchet-type branches up to the fourth generation (64 branches) in the enantioselective addition of Et2Zn to benzaldehyde.[86] There was no detectable decrease of selectivity (98:2) up to the second generation, and the rates hardly decreased up to the third generation. Enantiomeric branches caused no change for stereoselectivity within experimental error. The authors pointed out that there might be applications for special properties such as high molecular weight, good solubility, and spacing of central sites from cross-linked polymer matrixes.

Figure 15. Peerlijgs and Meijers poly (propylene imine) dendrimers modifield with -phenyloxirane for the catalytic asymmetric addition of diethylzinc to benzaldehyce.

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Seebach et al. used Frchets dendrimers with styryl end groups to cross-link a catalyst to a polystyrene support. The catalyst ligand core, TALDOL, is coordinated to Ti(IV) (Figure 16). It has been used for the enantioselective catalysis of nucleophilic addition of diethylzinc to aldehydes. High enantioselectivities were obtained for the addition of diethylzinc to aldehydes. The Ti(IV)-TADDOL dendritic polystyrene catalyst also has a much higher turnover rate than linear polystyrene analogues.[87,88] The same authors further extended their studies to such dendritic catalysts with spacers of variable length and flexibility and found remarkable features: (i) while the enantioselectivity is above 9:1 with all polymers of low loading, only the dendritic polymer gives rise to a constant selectivity of 98:2 in 20 sequential applications; (ii) the catalytic performances drop with increasing the chain length of the spacers between the TADDOL core and polymer backbone; (iii) the low-loaded dendritic catalyst beads with the shortest spacer keep their swelling properties high even after 20 runs, while all others do not swell as well after multiple reuse; (iv) the rate of reaction is the same with and without stirring using the beads of dendritic catalyst that has the shortest spacer filling the whole reaction volume under standard conditions. This means that diffusion of reactants and products to and from the active center is obtained.[89,90] Moreover, the authors investigated the use of membrane reactors in these enantioselective catalytic reactions. Therefore, they synthesized TADDOL derived dendritic catalysts with a molecular weight high enough to be retained inside a membrane that is impermeable to the catalyst but permeable to reactants and products.[91]

Figure 16. Seebachs denddritic Ti-TADDOLates coordinated with Ti(IV) with Frechet-type branches (homogeneous and heterogeneous on polystyrene support) for the enantioselective addition of diethylzinc to benzaldehyde.

Seebach and co-workers have been also synthesized a hexa-arm dendrimer and attached their ligand of C2 symmetry, TADDOL (,,,-tetraaryl-1,3-dioxolane-4,5-dimethanol) (Figure 17), and the Ti(OCHMe2) group at the periphery. Using this chiral metallodendrimer, the authors found that the enantiomeric addition of diethylzinc to benzaldehyde proceeded

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Ashraf A. El-Shehawy

with the same enantioselectivity (ee, 97%) as the monomeric chiral catalyst. The metallodendrimer, with a molecular weight of only 3833 Da, had to be separated by column chromatography rather than by ultrafiltration methods.[92,93]

Figure 17. Seebachs hexa-arm dendro,er attached to chiral TADDOL who related metallodendrimer with Ti(OCHMe2) group at the periphery.

Very interesting rigid dendrimers have been constructed by Pus group around an optically pure diacetate of 4,4,6,6-tetrabromo-1,1-bi-2-naphthol (Figure 18).[94] The G-2 dendrimer catalyzed the asymmetric alkylation of benzaldehyde with diethylzinc with a much higher catalytic activity (98.6% conversion in 24 h at room temperature) than (S)-BINOL (37% conversion under these conditions) and also generates the opposite enantiomeric product.[94] Both enantioselectivities of the dendrimer and BINOL are very low. This dramatic difference is due to the fact that the zinc complex formed from the reaction with BINOL is likely to exist as aggregates in solution through intermolecular Zn-OZn bonds which should greatly reduce the Lewis-acid activity of the zinc center. Such aggregate is not formed in the case of the dendrimer due to the bulky and rigid dendritic arms, yet the molecular models show that there is enough space allowing the substrate to approach the reaction center. High enantioselectivity in the presence of [Ti(O-i-Pr)4] was found for the dendrimer (100% conversion, 90% ee) as well as for BINOL (100% conversion, 89% ee), indicating that the catalytic center must be identical, i.e., monomeric, in both cases. The advantage of the dendrimer over BINOL is that it can be easily removed from the reaction mixture by precipitation with methanol.[94]

Unique Design Tools for the Synthesis and Design of Dendrimers

t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu

283

t-Bu

t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu

Figure 18. Pus rigid denderimers constructed around an optically pure diacetate of 4, 4,6,6tetrabromo-1,1-bi-2=naphthol.

O n O O OH OH O OH OH H N O O H N

O n O O N OH OH N O O

O n O

64 (n=0-3)

65 (n=0-3)

66 (n=0-3)

Figure 19.

Fan et al. have been reported on the synthesis of two kinds of dendritic chiral BINOL ligands through the condensation reaction between 2,2'-dihydroxy-1,1'-binaphthyl-3,3'-

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Ashraf A. El-Shehawy

dicarboxylic acid and Frchet-type polyether dendrons with primary and secondary amine at the focal point, respectively (see Figure 19). The chiral dendritic BINOL ligands 64-66 were successfully prepared in moderate yields through several chemical transformation reactions.[95] Asymmetric induction of the above-mentioned dendritic BINOL ligands in the enantioselective addition of ZnEt to aldehydes in the presence or in the absence of
2

Ti[OCH(CH ) ] was investigated.[95] For comparison, the corresponding zero generation

3 2 4

compounds 65-G and 66-G were also synthesized. All these dendritic chiral BINOL ligands
0 0

were found to be highly effective and chemoselective in the titanium-catalyzed addition of diethylzinc to benzaldehyde, which was converted to 1-phenyl-1-propanol in more than 98% yield and with no byproduct. As shown in Table 8, when using benzaldehyde as substrate, the size of the dendritic wedges of 65 did not significantly influence the enantioselectivity of the catalyst (entries 2-5). In order to further demonstrate the size/generation effect of the dendritic BINOL ligand 65, another two aldehydes were used as substrates. When using orthochlorinated benzaldehyde as substrate, similar enantioselectivities were obtained as compared with those of benzaldehyde (entries 7-9). In the case of meta-chlorinated benzaldehyde, slight decrease of ee was observed upon going from the first generation to the third generation dendrimer (entries 10-12). Upon completion of the reaction, chiral BINOL ligands were quantitatively precipitated by the addition of methanol and recovered via filtration. The recovered ligands showed the same enantioselectivity and reactivity (entry 6).[95]
Table 8. Asymmetric addition of diethylzinc to benzaldehyde catalyzed by (R)-Binol ligands in the presence of Ti[OCH(CH3)2]4a.

Benzaldehayde: ligand: ZnEt2 =1.0: 0.2:3 (molar ratio), reaction temperature = oC; solvent = toluene; reaction time =7hr. b Determined by chiral GLC analyses. The absolute confiruration of product is R. c Recycle chiral dendritic BINOL ligand was used.

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Table 9. Asymmetric addition of diethylzinc to benzaldehyce catalyzed by (R)-BINOL and dendritic BINOL ligands in the absence of Ti[OCH(CH3)2]4a.

Benzaldehyde : ligand : ZnET2 =1.0: 02: 3 (molar ratio), reaction temperature = 0 oC; solvent, toluene; reaction time = 7hr. b Determined by chiral GLC analyses. The absolute configuration of product is R.

The same authors also examined the use of these dendritic BINOL ligands in catalyzing the enantioselective reaction of benzaldehyde with diethylzinc in the absence of Ti[OCH(CH ) ] (Table 9).[95] It was found that these chiral dendritic ligands performed
3 2 4

very differently from the BINOL and 64. (R)-65 gave high conversion, albeit much lower enantioselectivity as compared to 64 (entries 1 and 2). In contrast to (R)-64 and (R)-65, (R)-66 offered the highest enantioselectivity in the asymmetric addition of diethylzinc to benzaldehyde in the absence of Ti[OCH(CH ) ] (Table 9, entries 3 and 4). This was possibly
3 2 4

due to the formation of better catalyst through the coordination of nitrogen on the linker to zinc atom. On the other hand, the enantioselectivity decreased upon going from 66-G to 660

G (entries 3 and 4).[95]

1

Recently, new Frchet-type dendritic BINOL ligands bearing several BINOL units at the periphery [(R)-67 and (R)-68] have been successfully synthesized (Figure 20). The (dendritic BINOL) Ti(IV) complexes were proved to be efficient catalysts for the enantioselective addition of diethylzinc to various kinds of aromatic aldehydes (Table 10). Dichloromethane was chosen as the reaction solvent, and the molar ratio of BINOL in dendritic ligands to Ti(O-iPr)4 was 1:10 as the reaction conditions.[96]

Figure 20.

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Ashraf A. El-Shehawy
Table 10. Asymmetric addition of diethylzinc to different aldehydes catalyzed by dendritic BINOL ligands.

As shown in Table 10, using the catalysts derived from these dendritic BINOL ligands, high yields and good enantioselectivities were achieved for benzaldehyde (entries 1-2), 1naphthaldehyde (entries 3-4), m-methoxybenzaldehyde (entries 5-6), and p-halobenzaldehyde (entries 9-14). As far as o-bromobenzaldehyde was concerned, moderate enantioselectivities (entries 15-16) with such ligands were obtained. As for p-methoxybenzaldehyde, the enantioselectivity decreased with the increase of generation (entries 7-8). When (R)-67-G0 and (R)-68-G1 were used, the addition of diethylzinc to benzaldehyde gave high enantioselectivity to afford the corresponding alcohols with 87.3% ee and 87.1% ee, respectively.[96] The recyclability of the dendritic ligand (R)-68-G1 (Figure 20) in the reaction system was examined. The dendritic ligand (R)-68-G1 was quantitatively precipitated by the addition of methanol and recovered via filtration. The recovered ligand was reused to the asymmetric addition of diethylzinc to benzaldehyde. After five times recycles, the yield and enantioselectivity were hardly reduced.[96] In an interesting approach, disulfides bearing (R)-1,1-bi-2-naphthol ((R)-BINOL) moieties at each terminal position have been successfully introduced on the surface of Au cluster (Scheme 18). TiBINOLate complex generated from the obtained monolayer-protected Au cluster (MPC) promoted catalytic asymmetric alkylation of benzaldehyde with Et2Zn affording the addition product in up to 98% yield with 86% ee. The high catalyst activity of MPC supported BINOL catalysts would reflect the naked character of BINOL moieties on the surface of MPC. After completion of the reaction, the BINOL-functionalized MPC was easily recovered.[97]

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Scheme 18.

Soai et al. have been reported on the synthesis of chiral dendrimers with three or six chiral -amino alcohol moieties on hyperbranched hydrocarbon chain-ends (Scheme 19). The enantioselective addition of dialkylzinc to aldehydes was examined using dendrimers 69 (G1) and 70 (G2) as chiral catalysts (Scheme 18). The results are summarized in Table 11.[98] In the presence of chiral dendrimer 69-(G1) (3.3 mol%), benzaldehyde (71a) was isopropylated with i-Pr2Zn to give (R)-2-methyl-1-phenylpropan-1-ol (72a) in high enantioselectivity (86% ee) (Table 11, entry 1). Furthermore, enantioselective isopropylation of benzaldehyde and 2-naphthaldehyde catalyzed by higher-generation dendrimer 70-(G2) yielded 72a and 72b in 80 and 86% ee, respectively (Table 11, entries 7 and 8). The catalysts 69-(G1) and 70-(G2) themselves are soluble in toluene, and were recovered and reused without any loss of enantioselectivity (Table 11, entries 2 and 3). Thus, the rigid backbones of 69-(G1) and 70-(G2) are effective at impairing an unfavorable intramolecular interaction between the catalytic sites.[98]

OH

OH

OH N N OH N N OH

69-(G1)

HO

R1 CHO + R2 2Zn 71a-c R2=i-Pr, Et

Chiral catalyst 69 or 70 (3.3 mol%) toluene

R1 R R2 OH 72a-c (R2=i-Pr) 73a-b (R2=Et)

N HO

HO

70-(G2)

Scheme 19.

Soai et al have been further reported on the synthesis of other structures of chiral dendrimers bearing also chiral -amino alcohols on their hyperbranched chain-ends. The dendritic chiral ligands 76 and 77 bearing four and eight sites of chiral amino alcohols, respectively, were prepared by attaching ephedrine derivatives at the periphery of polyamidoamine (PAMAM) (Figure 21). Chiral diamine 74 and diimine 75 possessing ephedrine moieties were also prepared. These chiral ligands serve as highly enantioselective

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Ashraf A. El-Shehawy

catalysts and ligands in the enantioselective addition of dialkylzincs to aldehydes with up to 93% ee.[99]
Table 11. Enantioselective alkylation of various aldehydes using chiral catalyst 69 (G1) and 70 (G2).
Aldehyde (71) R1 phenyl (R)- Alcoholb R
2

Entry 1 2 3 4 5d 6 7 8
a

Chiral catalyst 69-(G1) 69-(G1) 69-(G1)c 69-(G1) 69-(G1) 69-(G1) 70-(G2) 70-(G2) 72a 73a 73a 72b 73b 72c 72a 72b

Yield (%) 63 61 64 59 50 67 70 32

ee (%) 86 78 77 84 86 77 80 86

71a

i-pr Et Et i-pr Et i-pr i-pr i-pr

2-naphthyl p-tolyl phenyl 2-naphthyl

71b 71c 71a 71b

Reaction was perfomed in tulene, 2.2 molar equiv. of dialkylzinc was added to a solution of aldehyde and 3.3 mol% of chiral catalyst and the mixture was stirrect at room temperature for 15-96h. b .ee was determined by HPCL analysis using chiral column. Configuration of 72a and 72c are tentatively assigned based on that of 72a. c Recovered catalyst was used. d 4.1 molar equiv of diethylzinc was used.
HO N H N

N H

74

OH

HO N N

OH

HO

OH N N N N OH HN NH O

NH HN

HN NH HN

HO N NH

75

N HN HN

O N N

N O NH NH N O

HO

OH

O HN N OH NH

N O

O HN NH N HO

NH

N H HN HN

O N O N

HN O NH NH HN

HN NH

NH HN

N HO N N OH HO

N OH

76

77

Figure 21.

The same authors also synthesized chiral dendrimers 79 and 80 bearing four and 12 chiral ephedrine sites, respectively (Figure 22).[99] Chiral dimer 78 was also prepared. The

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289

carbosilane backbone is more flexible than the poly(phenylethyne) backbone, and the backbone hardly coordinates to dialkylzinc reagents. These chiral catalysts were employed in the enantioselective addition of dialkylzincs to aldehydes.[99] The ee reached 93% in the addition of diisopropylzinc to 3-phenylpropanal. When chiral dendritic catalyst 80 (1.7 mol%) bearing 12 chiral sites was employed, enantiomerically enriched sec-alcohols with 8393% ees were obtained. The highest, 93% ee, using catalyst 80 was attained in the enantioselective addition of diisopropylzinc to 3-phenylpropanal. Chiral dendritic catalyst 80 could be recovered and used without any loss of reactivity and enantioselectivity. It should be noted that the enantioselectivities attained by using chiral dendritic catalysts 79 and 80 are comparable with those attained by using chiral dimer catalyst 78 (Figure 22).[99]

OH N

Si

Si

N HO OH N OH Si N N OH OH N
Si

OH N N

OH

78

N Si Si Si Si
Si

OH

N
Si

OH

OH N

Si Si
Si

Si

Si

N
Si Si

HO

Si

Si

Si

Si Si N HO N N HO

Si

Si

HO

HO

N HO

HO

79

80

Figure 22.

Hu et al have been synthesized optically active ephedrine-bearing dendronized polymers 81 and 82 by using the Suzuki coupling polymerization (Figure 23). These polymers were obtained in high yields. They are soluble in common organic solvents such as THF, toluene, chloroform and dichloromethane. Gel permeation chromatography (GPC) analysis (polystyrene standards) shows the molecular weight of 81 is Mw = 141 100, Mn = 50 400 (PDI = 2.80).[100] The application of ephedrine-bearing dendronized polymers 81 and 82 as macromolecular chiral catalysts for the asymmetric addition of diethylzinc to benzaldehyde was investigated and compared the catalytic properties with their corresponding linear polymeric and dendritic chiral catalysts.[100] The dendronized polymers 81 and 82 were found to be more efficient than their corresponding linear polymeric. In the presence of 5 mol% of 81 or 82 (based on the polymer repeat unit) in toluene, diethylzinc adds to benzaldehyde to afford the addition product (R)-1-phenyl-1-propanol in 75% ee and 73% ee, respectively. Dendronized polymers 81 and 82 could be easily recovered by filtration and

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Ashraf A. El-Shehawy

reused. The recovered 81 shows the same reactivity and enantioselectivity (99% conversion of benzaldehyde after 12 h, 76% ee).[100]

HO
N

Ph

Ph

OH N

HO N

Ph

Ph

OH N

n n

OR

OR

n n

OR

OR

OR n

n OR

OR n

OR

81. n = 0 82. n = 1 R = n-C6H13

Figure 23.

N HO Ph Ph

N OH

N HO Ph Ph

N OH

Rhee et al have been reported on the first use of silica supported dendritic chiral auxiliaries for the enantioselective addition of diethylzinc to benzaldehyde. The dendritic chiral catalysts that are shown in Figure 24 were prepared via the reactions of various dendrimers with (1R, 2S)-ephedrine.[101,102]
O N N H N O O N N H N O N OH * * 2 2 2 2

O O Si O Silica

H N

Figure 24. Silica supported dendritic chiral B-amino alcohols.

Regardless of the catalyst used, the reaction yielded 1-phenyl-1-propanol as the major product with chemical yields up to 92% and enantioselectivities up to 62% ee. Benzyl alcohol is formed via the reduction of benzaldehyde by diethylzinc in the absence of catalyst and this reaction proceeds slowly in a competitive way. The reaction performance is strongly dependent upon both the number of generations and the amino group content of initiator sites. In all the cases with dendritic series, the conversion, selectivity, and enantioselectivity decreased with an increase in the number of generations. In addition, the reaction performance could be improved to the level of the homogeneous counterpart by increasing

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the diethylzinc concentration. Furthermore, the dendritic chiral catalyst could also be recycled and reused without a significant loss of catalytic activity.[101,102] El-Shehawy et al have recently described an interesting approach for the synthesis of a new kind of dendronized polymers with chiral ephedrine incorporation at the polystyrene hyperbranched chain-ends PS(Ephed)2-PS(Ephed)16 that are shown in Figure 25 with hydrocarbon backbone chains (i.e., without any heteroatoms either in the polystyrene main chain or in the dendritic chain-ends). These chiral dendrimers were evaluated as chiral ligands for the enantioselective diethylzinc addition to a series of aldehydes. According to his design, the polymer backbone hardly to coordinate with the dialkylzinc reagent and each chiral site of the dendritic chiral catalyst is anticipated to work independent of other chiral sites.[103]

Ph Ph Ph Me N OH Me OH Me N Me
* *

Ph Ph OH N Me Me Ph
* *

OH Me N

Ph

OH N Me

OH N Me

Me

Me

Ph Me

Me Me OH HO Ph N Me N Me

OH Me N Me N

Ph OH Me Ph OH N Me Me N Me Ph OH

Ph Me OH N Me

OH N Me

* *

Me

Me

Ph Me

Me N

Ph OH

Me

n
Me Ph N Me OH

n
Me OH Ph Me
*

n
Me N N Me
* *

n
OH Ph Me

Me OH N Me N Me OH Ph

Me Ph

Me Me

(1R, 2S)-PS(Ephed)2

OH

Ph

N Me OH

Me Me Ph
* *

N Me
* *

Ph HO

Me N Me Me Ph N Me Me Me N Me Ph OH Me N Me OH Ph

(1R, 2S)-PS(Ephed)4

OH

Me

Ph

OH

Me N

Ph N Me OH

(1R, 2S)-PS(Ephed)8a (1S, 2R)-PS(Ephed)8b Ephed = Ephedrine

Me Ph

OH Ph

OH

(1R, 2S)-PS(Ephed)16

Figure 25. Structures of chain-3nd functionalized polystyrenes having 2, 4, 8 and 16 chiral ephedrine moieties PS(Ephed).

The enantioselective diethylzinc addition reaction to benzaldehyde using the macromolecular chiral catalysts PS(Ephed)2-PS(Ephed)16 was first investigated. The results are summarized in Table 12. The chemical yield as well as the enantioselectivity of the addition product was increased markedly on using PS(Ephed)8a that having eight ephedrine moieties (90% and 94% ee, respectively, Table 12, entry 7). The influence of the molar ratios of the dendritic chiral catalyst was also examined (Table 12). Interestingly, the diethylzinc addition reaction to benzaldehyde using the recovered dendronized polymer PS(Ephed)8a afforded the addition product with a comparable result to that of entry 7 (entry 12). It is more interesting to note that the high enantioselectivity observed in the asymmetric diethylzinc addition to benzaldehyde using chiral dendrimer PS(Ephed)8a (90% ee, entry 7) was found to be comparable to that reported for the same reaction using the corresponding monomeric chiral catalyst (1R,2S)-N-benzylephedrine (92% ee, entry 7) under otherwise identical reaction conditions.

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Ashraf A. El-Shehawy

Table 12. Catalytic enantioselective diethylzinc addition to benzaldehyde using chiral dendrimers PS(Esped)2-PS(Ephed)16a.

All Reactions were performed in toluene at 0oC using 2.2M equiv of diethylzinc. Yields after purification by column Chromatography (hexane/ethyl acetate =4.1). c Determined by HPCL analysis on a chiral stationary phase (Chiralcel OD-H). d The absolute configureations were assigned by comparing the sign of their specific rotations with those reported in the literature. e Data in parentheses are obtained from the same reaction using (1R, 2S)-N-benzylephedrine.
b

Table 13. Catalytic enantioselective addition of dialkylzinc reagents to aldehydes using dendritic chiral PS(Ephed)8a a.

All Reactions were performed in toluene at 0oC using 2.2M equiv of diethylzinc and 6 mol% of chiral dendrimer. b Isiolated yields after flash Chromatography. c The ee values were determined by HPCL analysis using a chiral stationarly phase. d Absolut configurations were determined by comparing the sign of their specific rotations with those reported in the literature.

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The catalytic efficiency of the dendronized chiral catalyst PS(Ephed)8, bearing eight chiral sites of ephedrine moieties, was further demonstrated in the dialkylzinc addition reaction to a series of substituted aldehydes and the results are summarized in Table 13. The obtained results revealed that the dendritic chiral catalyst PS(Ephed)8a promotes the highly enantioselective addition of dialkylzinc reagents to all aromatic substituted aldehydes.[103] Interestingly, the enantioselectivity remarkably increases with more reactive substrates (compare entries 11 vs 7 and 9 and 12 vs 8 and 10, respectively, Table 13). Most importantly, the diisopropylzinc addition to 3-phenylpropanal proceeded in a highly enantioselective manner to give the corresponding secondary alcohol, 2-methyl-5-phenyl-3-pentanol with a high enantioselectivity of 95% ee (entry 13).[103]

6.3.2. Dialkylzinc Addition to Imines Soais and his co-workers have been made high efforts on the modification of PAMAM dendrimers with ephedrine ligands giving dendritic catalysts for the rarely reported addition of dialkylzinc to imines.[104-109] Soai et al. have been reported on the first example for the use of dendrimeric chiral ligands in the enantioselective alkylation of imines. Chiral diamines 74, 76, and 77 as well as diimines 75, 83, and 84 were prepared by loading a chiral ephedrine moieties on starburst PAMAM dendrimers (see Figures 21 and 26).[105]

HO N N

OH

OH N HO N N OH

N HN N NH O N HN HN O N O N O NH

N NH HN N O NH O

HO N

N N H HN N

O N O N

N O NH NH N N N

O NH

N O

N O

O HN N N

HO

OH OH

HN N

NH N HO

83

N HO

N OH

84

Figure 26.

These above-mentioned chiral dendrimers were used as chiral ligands for the enantioselective addition of diethylzinc to N-diphenylphosphinylimines. In the presence of chiral diimine 75 and diamine 74, N-diphenylphosphinylamine 86a with >90% ee was obtained. Dendrimeric chiral ligands 76, 77, 83, and 84 afforded 86a with moderate enantioselectivities. The results are shown in Table 14. Because dialkylzinc hardly adds to Nalkylimine even in the presence of amino alcohols, the N-alkylimine type chiral ligand 75 was not alkylated during the ethylation reaction of N-diphenylphosphinylimine 85a. There was very little difference in the enantioselectivities between the imino type and the corresponding amino type chiral ligands (75 and 74 & 83 and 76).[105]

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Ashraf A. El-Shehawy

Table 14. Enantioselective addition of diethylzinc to N-diphenyl-phosphinylimine 85a using varios dentic chiral ligands.
Ph N Ph Ph P O 85a Entry 1 2 3 4 5 6 chiral ligand toluene, r.t. Ph H Ph N P Ph Et O (R)-86a
(R)-86a

Et2Zn

Chiral Ligand (mol%) 75 74 83 76 84 77 50 50 50 50 50 25

Time (d) 2 2 2 2 2 3

Yyield (%) ee ( %) 54 46 32 18 12 8 92 92 43 40 39 30

Molar ratio immine: ET2ZN = 1:6.

Table 15. Enantioselective addition of diethylzinc to N-Diphenylphosphinylimines 85a-d.

Ph N Ph + Et2Zn P O 85a-d Imine 85
R phenyl 1-naphthyl 2-naphthyl p-tolyl phenyl 1-naphthyl 2-naphthyl p-tolyl phenyl 1-naphthyl 2-naphthyl p-tolyl

Ph

chiral ligand 50 mol%) toluene, r.t.

H Ph Ph * N Ph P Et O 86a-d Product 86 Yield (%) 86a 86b 86c 86d 86a 86b 86c 86d 86a 86b 86c 86d 54 27 52 54 46 11 41 38 32 10 25 22 ee (%) 92 74 90 93 92 71 89 93 43 11 47 56

Entry 1 2 3 4 5 6 7 8 9 10 11 12

Chiral Ligand 85a 85b 85c 85d 85a 85b 85c 85d 85a 85b 85c 85d 75 75 75 75 74 74 74 74 83 83 83 83

Time (d) 2 2 2 2 2 2 3 2 2 3 3 4

Molar ratio immine: Et2Zn = 1:6.

The enantioselective ethylation of various N-diphenylphosphinylimines (85a-d) in the presence of 50 mol% of chiral ligands 75, 74 and 83 (Table 15) was also investigated. Imines

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85a,c,d were ethylated to afford the corresponding addition products 86a,c,d with very high enantioselectivities in the presence of either chiral dendrimers 75 or 74. The enantioselectivities of the addition products with the para-tolyl substituent using 75 and 76 reached to 93% ee (entries 4 and 8).[105] In order to attain high enantioselectivity by using a chiral dendritic catalyst and ligand, it was necessary to avoid unfavorable coordination between the dialkylzinc reagent and the framework of the dendrimer. Thus, the same authors devised chiral dendrimers 69 and 70 with hydrocarbon [poly(phenylethyne)], i.e., without heteroatoms, with a backbone bearing three and six chiral ephedrine derivatives at the periphery, respectively (see, Scheme 19).[107,109] Each chiral site of the dendritic catalysts and ligands 69 and 70 is expected to work independently of other chiral sites because of the relatively rigid phenylethyne and approximately planar structure of the backbone. The enantioselective addition of diethylzinc to N-diphenylphosphinylimines using dendritic chiral ligands 69 and 70 was examined and the results are shown in Table 16.[106,109] Chiral dendrimer 69 (0.34 mol equiv) promotes the highly enantioselective addition of diethylzinc to N-diphenylphosphinylimines 10 to produce enantiomerically enriched (R)-N-diphenylphosphinylamines 11 with 71-94% ee in 73-80% yields (entries 1-4). Chiral dendrimer 70 (0.17 mol. equiv.) of a higher order generation also accelerates the reaction to give enantiomerically enriched (R)-N-diphenylphosphinylamines 11 with 85-90% ee in yields of 74-79% (entries 5-7). Table 16. Enantioselective addition of diethylzinc to various Ndiphenylphosphinylimines using chiral dentritic legands 69 and 70.

a b

All Reactions run in toluene at room temperature using 3.0 molar equiv of diethylzinc. Determined by HPCL analysis using a chiral stationary phase.

Chiral dendrimers 78-80 bearing two, four and 12 chiral ephedrine sites, respectively, (see Figure 22) have been also synthesized and evaluated as chiral ligands in enantioselective diethylzinc addition to N-diphenylphosphinylimines.[108,109] The carbosilane backbone is more flexible than the poly(phenylethyne) backbone, and the backbone hardly coordinates to dialkylzinc reagents. The results are shown in Table 17.

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Ashraf A. El-Shehawy
Table 17. Highly enantioselective addition of dialkylzincs to Ndiphenylphosphinylimines using chiral dendritic ligands 79.80 or chiral dimer 78.

Reactions was run in toluene at 0oC for 48 h using 3 molar equiv of diethylzinc. Determined by HPCL analysys using a chiral stationary phase. c Recovered chiral dendrimer was used.
b

As shown in Table 17, the enantioselective addition of diethylzinc to Ndiphenylphosphinylimine derived from 2-naphthaldehyde, promoted by chiral carbosilane dendrimer 79 (0.25 mol equiv), afforded the corresponding (R)-N-diphenylphosphinylimine with 92% ee (entry 1). Similarly, the addition of diethylzinc to the same imine using the chiral dendritic ligand of a higher generation 80 (0.13 mol equiv) afforded the corresponding (R)-Ndiphenylphosphinylimine with 92% ee in 70% yield (entry 7). The use of a lesser amount (0.083 mol. equiv.) of dendritic chiral ligand 80 also produced the imine with 90% ee in 70% yield (entry 8). Chiral ligand 79 was recovered and reused without any loss of reactivity and enantioselectivity (entries 1 and 2). Diisopropylzinc could also be used (entries 4 and 11). The enantioselectivities of chiral dendritic ligands 79 and 80 are comparable with those of chiral dimer 78. El-Shehawy et al. have recently described the synthesis and application of a new kind of dendronized polymers with chiral ephedrine incorporation at the polystyrene hyperbranched chain-ends PS(Ephed)n as highly effective chiral ligands for the enantioselective diethylzinc addition to a series of N-diphenylphosphinoyl arylimines (see Figure 25).[110] The enantioselective diethylzinc addition reaction to N-diphenylphosphinoyl benzaldimine 85a as a standard substrate using chiral dendrimers PS(Ephed)2-PS(Ephed)16, in toluene at room temperature for 48 h, was first examined. The obtained results are summarized in Table 18.[110]

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Table 18. Enantioselective diethylzinc addition to N-diphenylphospinoyl imine 85a using chiral dendrimers PS(Ephed)na.

All reactions were performed in toluene at room temperature using 3.0 molar equiv of diethylzinc and equimolar amounts of chiral polymer (based on the total number of ephedrine moieties against the imine) and imine 85a except for entry 7, which was perfomed using 1.5 molar equiv of chiral polymer. b Refers to the isolated yields wafter flash chromatography (hexane/ethylacetae). c Deterermined by HPLC analysis on a chiral column (Chiralpak AD). d The absolute configuration was assigned to be R by comparing the retention time on HPCL with those reported in literatur3e. e Values in parenthesis are obtained from the same reaction using 1.0 molar equiv of (1R, 2S)-Nbenzylephedrine as chiral ligand. f Values in parenthesis are obtained by using N-vinylbenzylephedrine copolymerized with strene and divinylbenzene as Chiral ligand.

Under the same reaction conditions, the enantioselectivity of the addition product 86a obtained by using PS(Ephed)8a (Table 18, entry 5) was higher than that observed in case of using PS(Ephed)16 (Table 18, entry 6) as chiral ligand. This was probably due to the fact that the environments of active sites at the polystyrene chain ends of PS(Ephed)8a might have enough space to work as a chiral ligand, while the active chiral sites of PS(Ephed)16 interfere either with each others and/or with the polymer backbone chains. Interestingly, on performing the diethylzinc addition reaction to benzaldimine 85a using each of PS(Ephed)2 and PS(Ephed)4, but for longer reaction times (Table 18, entries 2 and 4, respectively), the addition product 86a was obtained in higher yields with slightly higher enantioselectivities. It is worth to mention that all the dendritic chiral polymers used in this study are soluble in toluene and worked well as homogeneous chiral ligands during the reaction. Interestingly, the enantioselectivity observed in the diethylzinc addition reaction to imine 85a using chiral dendrimer PS(Ephed)8a (90% ee, Table 18, entry 5) was high as those obtained not only by using (1R,2S)-N-benzylephedrine (92% ee, entry 5) but also by using polystyrene supported with the same chiral moiety (89% ee, entry 5) as chiral ligand. Chiral polymer PS(Ephed)8b

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Ashraf A. El-Shehawy

worked well as chiral polymer PS(Ephed)8a and led smoothly to the desired secondary chiral amine 85a with almost the same chemical yield and enantioselectivity, but with reversed stereoselectivity (Table 18, entry 8).
Table 19. Enantioseletive diethylzinc addition to N-diphenylphosphinoy1 arylimines 85 using chiral dendrimer (1R, 2S)=PS(Ephed)8aa

All reations were performed in the toluene at room temperature for 48h using 3.0 molar equiv of diethylzinc and equimolar amounts of chiral polymer (based on the total number of the ephedrine moieties against immine) and imine 85 except for entry 14, which was performed using 0.5 molar equiv of chiral polymer. b Refers to the isolated yields after flash chromatography (hexane/ethlacetate). c Determined by hpcl analysis on a chiral column (Chiralcel OD or Chiralpak AD). d The absolute configuration was assigned by comparing the retention time on the HPCL with those reported in literature. e Recovered dendritic chiral polymer was used.

The diethylzinc addition reaction to a series of N-diphenylphosphinoyl arylimines (85), in the presence of the dendritic chiral ligand PS(Ephed)8a that showed the best result, was examined and the results are summarized in Table 19.[110] As it was expected, chiral dendrimer PS(Ephed)8a promotes the highly enantioselective addition of diethylzinc to all aromatic substituted phosphinoyl imines 85 to afford the corresponding enantiomerically enriched (R)-N-diphenylphosphinoylamides 86 with yields of 83-93% and enantioselectivities up to 93% ee (Table 18). It is interesting to note that phosphinoyl imines bearing parasubstituents on their phenyl groups would provide the corresponding N-phosphinoylamides

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with relatively higher enantioselectivity than their analogues having ortho- or metasubstituted phenyl groups. The chiral polymer was easily and quantitatively recovered by silica gel column chromatography followed by reprecipitation from its THF solution to a mixture of methanol and HCl. As shown in Table 19, the diethylzinc addition reaction to imine 85 (Ar=4-MeC6H4) using the recovered polymer PS(Ephed)8a afforded the corresponding addition product (entry 13) without any significant loss in the enantioselectivity as in entry 4. Since the author have used in this study an equimolar amount of the dendritic chiral polymer PS(Ephed)8a, based on the total number of the chiral sites at the periphery, against imines, the obtained high yields and enantioselectivities of the addition products suggested that nearly all of the chiral sites at the periphery of dendritic ligand PS(Ephed)8a worked effectively.[110]

Figure 27.

6.4. Epoxidation of Alkenes

Suslick and his co-workers have been designed dendritic chloromanganese(III) porphyrins (Figure 27) for the catalysis of epoxidation of alkenes with iodosylbenzene.[111,112] The dendritic wedges are first- and second-generation aromatic polyesters. They provide a confined environment, and the catalyst provides much better intramolecular and intermolecular regioselectivities than those obtained with unsubstituted 5,10,15,20-tetraphenylporphyrinatomanganese(III) cation. The least hindered double bond of unconjugated dienes such as 1,4-heptadiene and limonene is epoxidized preferably. Similarly, in the epoxidation of a mixture of 1-alkene and cyclooctene, the G2 dendritic metalloporphyrins showed 2- to 3-fold higher selectivity toward 1-alkenes relative to the nondendritic catalyst. This regioselectivity provided by the dendritic catalyst is by far not as

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Ashraf A. El-Shehawy

high, however, as that of the classical picket-fence porphyrin, 5,10,15,20-tetrakis(2,4,6triphenylphenylporphyrin).[111,112] The dendrimers 87-96 with and without peripheral vinyl groups were prepared via several synthetic procedures (Figure 28).[113] In most cases, the dendrimers were obtained in yields between 75 and 95% after purification by flash column chromatography, and they were fully characterized by 1H NMR, 13C NMR, and IR spectroscopy, by MALDI-TOF or Hi-ResMALDI spectrometry, and by elemental analysis.

Figure 28.

The manganese complexes of the dendritically substituted Salens were investigated to check whether the dendritic modification gives rise to any change in the catalytic activity in solution. Thus, Salens 87, 88, 91, and 92 were loaded with Mn by heating a solution of Salen and Mn(OAc)2.4H2O for several hours in EtOH/toluene, while air was bubbled through the reaction mixture, followed by stirring at room temperature for a further 12 h in the presence of LiCl. The epoxidation reactions were generally run with 20 mol% of Mn-Salen, two equivalents of m-chloroperbenzoic acid (m-CPBA) as oxidant and five equivalents of 4methylmorpholine-N-oxide (NMO) as additive in CH2Cl2 at -20 oC (Scheme 20).[113,114] The authors have been examined the epoxidation reaction on several phenyl substituted and the results are collected in Table 20.

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301

R1 R4

R2 R3

0.2 equiv Mn(Cl)-salen 2 equiv m-CPBA 5 equiv NMO CH2Cl2, -20 oC

O

R1 O R2 R4 R3 97a-f

a
O

c
O

Scheme 20. Epoxidation of various olefins mediated by Mn-salens 87, 88, 91 and 92. Mn (C1) in homogenous solution to give epoxied 97a-f. The corresponding Mn-Salens were prepared according to literature procedures.

Table 20. Solective and converstions obtained in the expoxidation of various olifins, mediated by Mn complexed of Salens 87, 88, 91 and 92 in homogenous solutions.

Epoxide 97 a a a a b b b c c c d d d d e e e e f f f
a

Salen 87 88 91 92 87 88 91 87 88 91 87 88 91 92 87 88 91 92 87 88 91

Conversion [%]a) 87 80 79 82 94 83 92 90 58 80 90 75 83 76 94 97 93 98 12 7 8

er 73:27 83:17 72:28 84:16 76:24 84:16 76:24 53:47 55:45 53:47 96:4 92:8 95:5 89:11 89:11 90:10 91:9 89:11 57:43 52:48 59:41

After 30 min, determined by capillary gas chromatography (CGC).

The selectivities and conversions obtained in the epoxidation of styrene ( 97a) with Salens 87 and 91 were comparable to those obtained with the corresponding (and

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Ashraf A. El-Shehawy

commercially available) Jacobsen catalyst under identical conditions (er 75:25, conversion complete after 1 h). In contrast, enantiomerically highly enriched products and high degrees of conversions were observed with dendritically modified Salens 87, 88, 91, and 92 in the epoxidation of 1-phenyl cyclohexene ( 97d), again comparable with the results obtained with the simple unsubstituted Jacobsen catalyst.[113,115,116] Also, epoxidation of dihydronaphthalene ( 97e) gave rise to high enantioselectivities, again similar to the results obtained with unsubstituted Jacobsen catalyst under the same conditions (er 91:9, conversion complete after 15 minutes), whereas in the case of trans-stilbene ( 97f) the enantiomer ratios were poor. In general, the selectivities obtained in homogeneous solution using Salens 87, 88, 91, and 92 are similar to those reported for the classical Jacobsen catalyst under comparable conditions. Neumann et al have been synthesized new metallosilicate catalysts by reacting a silanol capped dendrimer, Si[CH2CH2Si(CH3)2OH]4 with MCp2Cl2 (M = TiIV, MoVI, WVI and VV) (Scheme 21). The resulting Si[CH2CH2Si(CH3)2OMCp2Cl]4 compounds were incorporated in a silica matrix by the sol-gel method.[117]

Scheme 21.

The catalytic activity of the metallosilicates after calcination revealed excellent activity and selectivity towards epoxidation of alkenes. A preliminary assay to determine catalytic activity for epoxidation of alkenes with hydrogen peroxide and tert-butylhydroperoxide (TBHP) was carried out using cyclooctene, a highly reactive alkene, as a probe substrate. From the results as described in Table 21, it is clear that TBHP is more effective than H2O2 and that MoSiO2 > TiSiO2 > VSiO2 > WSiO2. Since MoSiO2 and TiSiO2 were both active and quite stable to reaction conditions when using anhydrous TBHP as oxidant, these materials were further tested for activity in epoxidation of a series of alkenes by TBHP (Table 22).[117] As may be expected, reactivity was clearly a function of the nucleophilicity of the alkene. Thus, the least nucleophilic terminal alkenes such as 1-octene and 1-decene were least reactive and required higher reaction temperatures for reasonable yields. Additionally, yields calculated for TBHP were high. 2-Methyl-2-heptene was more reactive than 2-octene but there was some loss of selectivity when the former was used as substrate.

Unique Design Tools for the Synthesis and Design of Dendrimers

Table 21. Expoxidation of cyclooctene catalysed by metallosilicates.a
Metallosilicate None Ti-SiO2 V-SiO2 Mo-SiO2 W-SiO2
a

303

Conversion (selectivity) (mol%)

Oxidant 30% H2O2 0 39 (98) 12 (94) 46 (99) 51 (85)

Oxidant 6 M TBHP 2 95 (99) 81 (95) >99 (99) 20 (99)

Reaction conditions: 1 mmol cyclooctene, 12 mg metallosilicate catalyst (2 mol% M on SiOd), 2 mmol 30% H2O2 + 1 ml methanol of 1 ml 2 M TBHP on n-decane, 60oC, 8h.

Table 22. Expoxidation of alkenes catalyzed by Ti-SiO2 and Mo-SiO2 with terbutylhydroperoxide. a
Conversion (selectivity) (mol%)

Substrate Cyclooctene Cyclohexene 1-octene

b

Ti-SiO2 95 (99) 44 (92) 25 (81) 17 (76) 21 (97) 29 (90)

Mo-SiO2 >99(99) 71 (93) 56 (95) 61 (95) 62 (98) 90 (90)

1-deceneb 2-octene 2-methyl-2-heptene

a

Reaction conditions: 1 mmol substrate, 12 mg metallosilicate catalyst (2 mol% M on SiOd), 1 ml 2M TBHP in n-decane, 60oC, 8h b 100oC

Table 23. Epoxidation of alkenols catalyzed by Mo-SiO2 with ter-butylhydroperoxide.a

Substrate cis-2-hexen-1-ol trans-2-hexen-1-ol cis-3-hexen-1-ol trans-3-hexen-1-ol 5-hexen-1-ol

a

Conversion (selectivity) (mol%)

74 (96) 87 (97) 60 (>99) 85 (>99) 6 (>99)

Reaction conditions: 1 mmol substrate, 12mg metallosilicate catalyst (2 mol% Mo on SiOd), 1ml 2M TBHP in n-decane, 60oC, 8h.

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The molybdenum containing silicate MoSiO2 was also surveyed for activity in the epoxidation of alkenols with anhydrous TBHP (Table 23).[117] Rather unusually the allylic alcohols were only slightly more reactive than the homoallylic alcohols, whereas 5-hexen-1ol reacted like a terminal alkene. Selectivity was high; in the case of allylic alcohols 3-4% of the allylic aldehyde was formed as by-product. The Kawi group[118] prepared a similar PAMAM on silica template while amino terminal groups were converted into salicylimines. These salen-imitating ligands were complexed with Mn(II) and used as catalysts in olefin epoxidation (Scheme 22 and Table 24), a reaction of growing importance in synthetic organic chemistry.[119-121]

O N H N N H NH2 NH2 (i)

O OH N N H O H N N O Mn N O O

(ii) Mn(CH3COO)2

O R Ph

Catalyst R = H or Ph Ph O

PAMAM-dervatized silica or regular silica

Scheme 22. Preparation of PAMAM-based supported dendritic Mn catalyst for the epoxidation reaction.

Remarkably, the catalytic activity per Mn equivalent increased dramatically with the dendron generation. Thus, in the epoxidation of styrene, the yield increased from 20% for generation 0 to 75% for the fourth-generation catalyst. Even though the Mn loading per gram of silica was almost equal for the second-, third-, and fourth-generation catalysts, the yield of the epoxidation of styrene increased more than twofold in this series.[119-121]
Table 24. Epoxidation of styrene with supported dendritic.
Catalyst generation 0 1 2 3 4 Yield (%) 20 26 36 53 75

Zhao et al have been established an operationally simple and mild protocol for the catalytic enantioselective epoxidation of enones using a series of chiral pyrrolidinylmethanolbased dendritic catalysts and tert-butyl hydroperoxide (TBHP) as an oxidant. The chiral dendrimers were synthesized as shown in Scheme 23.[122]

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305

Scheme 23.

Table 25. Screening reaction conditios for the epoxidation of 111a a).
O Cat./ TBHP solvent, rt O O

110a

111a

Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
a

Catalyst 105 105 104 106 107 108 109 106 107 + 4 MS 109 + 4 MS 109 + 4 MS 108 + 4 MS 108 + 4 MS 108 + 4 MS 108 + 4 MS

Solvent Hexane CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4/hexane = 1:1 Benzene CH2Cl2 CCl4

Oxidant TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP H2O2

T (oC) rt rt rt rt rt rt rt rt rt rt 0 rt rt rt rt

T (h) 48 144 120 144 144 144 144 144 144 144 144 96 96 144 48

Yield (%)b Trace 60 59 64 73 67 70 85 86 84 80 65 66 20 0

ee(%)c nde 66 41 67 68 69 71 69 73 74 13 66 69 54 ---

(config)d -------------------------------

Unless otherwise specified, the reaction was carried out with 1.2 equiv of TBHP in the presence of 30mol% of catalyst. b .After column chromatography. c Enantiomeric excess was determined by the HPCL analysis using chiral Daicel Chiralce OD column. d .The absolute configuration was determined to be (2R, 3S) bu comparison of the HPCL Cretention time with know data. e .Not determined.

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A preliminary study was performed to test the catalytic property of these reagents in the asymmetric organocatalytic epoxidation of enones 13a with TBHP (Table 25). In general, good conversion of enone 110a was achieved, and the corresponding optically active epoxide 111a was obtained in good yields. The enantioselectivities were moderate to good (41-71%), with the (2R,3S)-configured product 111a was formed predominantly (Table 25, entries 2-7). Among all the dendritic chiral catalysts evaluated in this reaction, the second-generation ligand 109 was the best one in terms of yield and ee (Table 25, entry 7).[122] To demonstrate the scope and potential for the organocatalytic epoxidation, a series of different substituted enones 110 were reacted with TBHP at room temperature in the presence of dendritic chiral ligand 109 (30 mol %) as the catalyst. The results are summarized in Table 26. As shown, almost all reactions proceeded in reasonable reaction times when 30 mol % of 109 was used at room temperature and diastereoisomerically pure trans-(2R,3S)-epoxides 111 were obtained. Different types of electronic substitution on the phenyl ring of the carbonyl group furnished results comparable to those achieved in the epoxidation of 110 (Table 26, entries 2-5). It was found that enones with para electron-withdrawing substituents in the phenyl group were all converted to the corresponding optically active epoxides in good yields and enantioselectivities (Table 26, entries 6 and 7). However, under the same reaction conditions, an electron-donating substituent did not react with TBHP, due to its low reactivity (Table 26, entry 8).[122]
Tabke 26. Catalytic enantioselective epoxidation of enones promoted by dentritic lignad 109 and TBHPa.

Unless otherwise specified the reaction was carried out with 1.2 equiv of TBHP in the presence of 30 mol% catalyst 109. b After colomn chromatography. c Enantiomeric excess was determined by the HPLC analysis by using the chiral column. d The Absolute configureation was determined to be (2R.3S) by comparison of the HPCL retention times with known data. e Using xx-diphenyl-L-prrrolidinemethanol as the bifuncion organocatalyst. f 50 mol % catalyst was used in this reaction. g Not determined

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The recyclability of these catalysts was examined. After the completion of the reaction, dry methanol was added to the reaction mixture, and the dendritic catalyst 109 was almost quantitatively precipitated and recovered via filtration. The recovered dendritic catalyst 109 was reused at least five times with little or no loss of activity and enantioselectivity (Table 27).[122]
Table 27. Recylcing use of dendritc catalyst 109 in asymmetric exposidation of chalcone 110 a.

Entry 1 2 3 4 5
a

Catalyst 109 109 (second) 109 (third) 109 (fourth) 109 (fifth)

T (h) 144 144 144 144 144

Yield (%)b 84 84 80 81 83

ee (%)c 74 73 72 73 72

Unless otherwise specified the reaction was carried out with 1.2 equiv of TBHP in the presence of 30 mol% of catalyst. b After column chromatography. c Enantiomeric excess was determined by the HPLC analysis using a chiral Daicel Chiralcel OD column.

6.5. Palladium-Catalyzed Asymmetric Reactions

Palladium catalysts are one of the most frequently used catalysts in organic synthesis. There is a large body of literature on palladodendrimer-catalyzed reactions during the last decade whereby the molecular palladium complex is covalently or supramolecularly attached to the dendrimer (including silica- or polymer-supported dendrons).[1m,123,124] This whole area has been recently reviewed in excellent and comprehensive reports by the groups of Newkome[125] and de Jess[126] with catalyzed reactions including alkene hydrogenation, hydrovinylation, polymerization, and copolymerization, carbon-carbon coupling (Stille, Suzuki-Miyaura, Sonogashira), allylic substitution, aldol-type condensation with isocyanoacetates, and Michael addition. As with other catalysts, the most important problems are the cost related to the catalyst efficiency including turnover number of the catalyst (TON), turnover frequency (TOF), and removal of the catalyst from the reaction mixtures for both economic (catalyst recycling) and ecological reasons (prevent pollution of the reaction product by the catalyst).[127-129] Chemoselectivity, regioselectivity, stereoselectivity, enantioselectivity, and diastereoselectivity, optimized with homogeneous catalysts, are the other key issues.[130] van Leeuwen is one of the pioneers of the field of dendrimer catalysis. When he was at Shell, his group reported a star-shaped hexaphosphine-palladium catalyst with a benzene core for polyketone formation from alternating CO/alkene polymerization. While the monometallic catalyst gave 50% fouling (precipitation of the polymer on the wall of the reactor), this star-shaped catalyst gave only 3% fouling, possibly for solubility reasons. This

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is also a very early dendritic effect.[69,131,132] The van Leeuwen group synthesized a series of diphosphine ligands centered on 1,1-bis-diphenylphosphinoferrocene bearing dendritic carbosilane substituents at the para aryl positions in a divergent manner (Figure 29).[132b]

Figure 29. van Leeuwsens diphospine lignads centered on 1.1-bis-diphenylphosphinoferrocene bearing dendritic carbosilane subsituents at the para aryl positions whose palladium complexes catalyze allyic alkylations.

Reactions with [Pd(MeCN)2Cl2] afforded the ferrocene-centered chelate complexes, and these metallodendrimers were shown to be efficient in palladium-catalyzed allylic alkylation (Scheme 24). The linear trans-product was mainly obtained. The rate of the reaction decreased, however, as the dendritic generation increased. This negative dendritic effect was attributed to the more difficult mass transport with increasing the steric bulk of the dendritic wedges and was more pronounced when going from generation 2 to 3. Remarkably, the size of the metallodendrimer also determined the selectivity of the allylic alkylation reaction, because the dendritic bulk hindered the attack of the nucleophile on the Pd-allyl moiety. Steric interactions between the branches and increase of the P-Pd-P bite angle preferentially lead to the linear product.[132b]

Unique Design Tools for the Synthesis and Design of Dendrimers

cata. Cl ( Pd Ph

309

Ph

+
O

EtO O O

OEt

+ L
EtO O O OEt

Ph

EtO O O

OEt

L= dendritic diphosphine

Scheme 24.

Scheme 25. Synthesis of chiral dendrimers 114-G3.

van Leeuwens group has also synthesized functionalized carbosilane dendrimers. Their palladium complexes have been used as catalysts in the allylic alkylation performed in a continuous membrane reactor.[132c] The second-generation carbosilane dendrimer served as a starting point. It is a white solid whose X-ray crystal structure could be determined and whose molecular volume of 2414 3 was anticipated to be large enough for separation of the catalyst from the reaction mixture by nanofiltration. The phosphine-functionalized dendrimers of generation 0, 1, and 2 were synthesized by hydrosilylation of double bonds with chlorodimethylsilane or dichloromethylsilane followed by reaction with Ph2PCH2Li/TMEDA. The dendritic phosphine of higher generation such as that with 72 phosphines could not be prepared because of steric congestion. The phosphine dendrimers were allowed to react with [PdCl-(3-C3H7)]2 yielding either bidendate palladium phosphine dendrimers or mixtures when monodentate dendritic phosphines were used as ligands. All the metallodendrimers were used as catalysts in the allylic alkylation of allyl trifluoroacetate and sodium diethyl methylmalonate yielding diethyl allylmethylmalonate. The reaction was first carried out in a batch process, and all the metallodendrimers showed a very high catalytic

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Ashraf A. El-Shehawy

activity. Using 0.2% of catalyst, the yield was larger than 80% after 30 min and only small differences of reaction rates were observed for the different catalysts. In a continuous process using a membrane reactor, the metallodendrimer containing 12 chelated palladium atoms with a calculated volume of about 7600 3 was used as the catalyst. The retention of this catalyst in the membrane reactor was determined to be 98.1%, which corresponds to a calculated value of only 25% of decreased activity after flushing the reactor 15 times. Samples taken from the flow were not catalytically active, which confirms that the observed decrease of activity was due to decomposition of the palladium complex and not to loss of the dendritic catalyst.[132c] Majoral et al. have been reported on the synthesis of a third generation phosphoruscontaining dendrimer possessing 24 chiral iminophosphine end groups derived from (2S)-2amino-1-(diphenylphosphinyl)-3-methylbutane. The reaction proceeded gently overnight at room temperature to yield the chiral dendrimer 3-G3 isolated in 88% yield after work up as a white powder, very sensitive to oxidation (Scheme 25).[133] In situ complexation of this dendrimer by [Pd(3-C3H5)Cl]2 affords a catalyst, which is used in asymmetric allylic alkylations of rac-(E)-diphenyl-2-propenyl acetate and pivalate. The percentage of conversion, the yield of isolated 2-(1,3-diphenylallyl)-malonic acid dimethyl ester, and its enantiomeric excess have been measured in each case, and were found to be good to very good (ee from 90% to 95%). Furthermore, the dendritic catalyst could be recovered and reused at least two times, with almost the same efficiency.[133] Majoral et al reported on the synthesis of chiral ferrocenyl phosphine-thioether ligands covalently bound on the periphery of 4 phosphorus dendrimers (generations 1-4) having a cyclotriphosphazene core and on one model compound.[134] The chiral dendrimer were obtained in nearly quantitative yield after work up. These dendrimers proved to be efficient ligands for the palladium-catalyzed asymmetric allylic substitution reaction of dimethylmalonate under classical conditions. The reaction times for completion were almost the same for the dendrimers of different sizes and the corresponding monomeric ligand.[134] In every case, isolated yields of the allylated products were very high and enantioselectivities very close to the one observed for the corresponding monomeric analogue (ee up to 93%). The reuse of the dendritic catalysts has been carried out simply by precipitation with pentane at the end of the catalytic reaction. Indeed, these organometallic dendrimers were found to be efficient soluble polymer-supported catalysts. Heck olefin arylation, one of the most widely used reactions in synthetic organic chemistry, was successfully accomplished in solution with aryl iodides, bromides, and even chlorides, using a variety of catalytic systems.[1d,124,135-137] Heterogeneous catalysis, however, was performed almost entirely with iodides or electron-deficient bromides,[138,139] mainly using metal palladium adsorbed on an inorganic support.[140] The uses of the Heck reaction encompass a vast spectrum of applications, from the synthesis of fine chemicals, drugs, and natural products to the preparation of novel materials and supramolecular devices, and include intermolecular and intramolecular versions as well as asymmetric variants.[1m,124] The biphosphine-terminated PAMAM-on-silica system prepared from ethylenediamine (see Scheme 16) was complexed to a dimethylpalladium fragment with (TMEDA)PdMe2 as a precursor. Before this study, similar soluble systems were prepared and studied by Reetz and coworkers.[137] As for Rh complexation, the poor functionalization of the third- and fourthgeneration-derived supported catalysts prevented their conclusive investigation. The zero-

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311

generation to second-generation supported catalysts demonstrated activity comparable to that of the homogeneous analogue in the Heck reaction of bromobenzene (Scheme 26).

X R + Y

Me Pd Me

NaOAc, DMF, 48 h, 120 oC

R Y

PAMAM-derivatized silica or regular silica

Scheme 26. Heck reaction catalyzed by PAMAM-based support catalysts.

Figure 30. Bidente third-generation DAD phosphinated Pd dendrimer for Sonogashira and Suzuki copling reactions.

Jayaraman compared three generations of Pd-alkylphosphine dendrimers in the Heck reactions with various olefins and reported that the second and third generations were found to exhibit better catalytic activity than the monomer and first-generation metallodendrimers.[141] This trend was also noted by Mapolie with poly(propyleneime)iminopropylpalladium [142]. On the other hand, three generations of bidentate DAB phosphinated Pd dendrimers that were found to be active in Sonogashira coupling of iodo- and bromobenzene with phenylacetylene showed a negative dendritic effect attributed to increasing steric effect as the generation increases (example for iodobenzene at 25 C, time for quantitative conversion: model: 30 min; first-generation: 15 h; secondgeneration: 40 h; third-generation: 48 h) (Figure 30). These metallodendrimers can be recovered and recycled with little decrease of efficiency up to seven cycles with bis-

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Ashraf A. El-Shehawy

cyclohexylaminoalkylephosphine ligands (conversion is 39% after 7 cycles for the thirdgeneration catalyst). The nature of the alkyl substituents (cyclohexyl versus tert-butyl) on the P ligand of the Pd catalyst also plays a role in efficiency, solubility and thus recycling ability.[143-145] A number of other Pd-catalyzed processes were examined with supported dendritic systems. The Suzuki reaction was found to be less sensitive to the nature of the dendritic backbone. The groups of Alper, Arya, and Manzer used the phosphinated PAMAMsilica constructs to immobilize a variety of Pd complexes. The formed structures were extensively studied and tested as heterogeneous catalysts in the iodoarene carbonylation reaction (Scheme 27).[146] Quantitative complexation was observed with zero-generation-to-secondgeneration-derived ligands for the PdCl2 fragment. However, for higher generations and with bulkier Pd fragments, only partial functionalization was achieved. The catalytic reaction was optimized, and quantitative conversions were readily obtained. With respect to the influence of the dendritic template structure on the reaction outcome, two trends were observed. First, higher generation-derived catalysts were characterized by lower Pd loadings and lower conversions per silica weight unit. However, when the reactivities per Pd equivalent (or TON/TOF as presented in this article) were compared, they were found to increase with the generation (Table 28). Second, the leaching of Pd from the support decreased upon an increase in the dendrimer generation. It is possible that some of the displayed activity resulted from Pd(0) nanoclusters immobilized inside the silica/dendritic matrix because blackening of the silica was usually observed under these reaction conditions and no reactivity with bromobenzene was observed (Pd metal catalysts are usually only reactive toward iodides, whereas palladiumphosphine complexes are expected to catalyze reactions of both iodobenzene and bromobenzene). Regardless of the true nature of the catalyst in the methoxycarbonylation reaction, the demonstrated dendritic effects were quite remarkable.

I R

X Pd P X R

O C OMe

PAMAM-derivatized silica or regular silica

(R= H; 4-NO2; 4-Me; 2-MeO; 4-MeO, 4-CF3; 4-I; 4-Br; 4-OH; 4-CH3CO; 4-I-C6H4)

Scheme 27. Carbonylation reaction catalyzed by PAMAM-based support catalysts the reagents and conditions are as follows: NET3, MeOH and CO.

Table 28. Methoxycarbonylation of Iodobenzene with Support Dentritic Catalysts.

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313

The Alper group[147] reported also on a Pd catalyzed transformation, hydroesterification of olefins (Scheme 28), based on C6-spacer-containing PAMAM dendritic catalysts supported on silica. Because of the longer diamine used in the PAMAM dendron construction, the phosphinepalladium catalyst could be prepared on up to fourth-generation dendrons. All the catalysts demonstrated high activity, a preference for the linear product, and moderate recyclability.

R1

+ R2OH + CO

X Pd P X

R1

CO2R2

R1 CO2R2

PAMAM-derivatized silica or regular silica

(Reagents and conditions: nonpolar solvent, 150 psi, and 115 oC)

Scheme 28. Hydroesterification reaction catalyzed by PAMAM-based support catalysts.

Moreover, silica-supported polyamidoamine (PAMAM) dendrimers with different spacer lengths were prepared.[148] After the introduction of diphenylphosphino groups, complexation to dibenzylidenepalladium(0) gave the desired silica-supported dendrimerpalladium catalyst complexes G0 to G4-C2-Pd (Figure 31). These catalysts showed activity towards the oxidation of terminal alkenes to methyl ketones. A dependence of catalytic activity on the spacer length of the diamine in PAMAM was observed. The authors have examined the catalytic activity of these dendrimer-Pd complexes towards the oxidation of terminal alkenes to methyl ketones using tert-butyl hydroperoxide as oxidant.[148]

Figure 31. Dendritic catalysts.

Initially the authors have attempted to oxidize terminal alkenes to methyl ketones under Wacker-type conditions using the catalysts G0 to G4-C2-Pd. Attempts to optimize the Wacker-type conditions using Pd complexes of silica-supported PAMAM dendrimers, as catalysts were unfruitful. Consequently, the oxidant was changed to tert-butyl hydroperoxide. As a benchmark, the catalytic performance of G0 was investigated using different alkenes. The addition of organic solvents inhibited the oxidation reaction, and thus the reactions were carried out under neat conditions. Cyclohexene gave the lowest yield not surprising because

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internal alkenes are usually less reactive than terminal alkenes (Table 29, entry 1). 1-Octene gave higher product yields than 1-decene and 1-tetradecene (Table 29, entries 2-4).[148]
Table 29. Oxidation of various alkenes using TBHP as oxidant.

Catalyst Go-Pd (dba), the Pd content in the reaction mixture was 0.5 mol% substrate (1.50 mmol). TBHP (1.65 mmol). 55o , C. 24h. [a] Yield by GC.

The catalytic activity also proved to be a function of the dendrimer backbone. The higher generations were less active when screened using 1-octene. Only the first-generation dendrimer complex gave the methyl ketone in reasonable yield (Table 30, entry 2). The second and third-generation dendrimer complexes gave poor yields (Table 30, entries 3 and 4). This poor activity was attributed to steric congestion of the dendrimer. This leads to the threshold for dendrimer growth being reached. Extending the chain length of the diamine used during dendrimer synthesis can bring relief to steric crowding.[148]
Table 30. The effect of dendrimer generation.

Catalyst Gn-Pd(dba). The Pd content in the reaction mixture was 0.5 mol%. 1-octene (1.50 mmol). TBHP (1.65 mmol). [a] Yield by GC.

The various silica-supported PAMAM-Pd catalysts displayed comparable activity towards the oxidation of 1-hexene. Extending the olefin length by two methylene groups starting from 1-hexene to 1-tetradecene gave different results. The different catalysts started to show different activities. The monomeric catalyst and 1st generation C6 and C12 catalysts once again gave comparable results. G2-C6 gave the highest conversion of 1-octene while G2C12 gave the lowest. A similar trend was observed for 1-decene. In the oxidation of 1tetradecene, the G0 and G2-C6 catalysts gave good yields while G2-C12 gave lower yields.[148] These catalysts could be recycled. The G0 catalyst can be reused up to eight times giving good yields of 2-octanone. Meanwhile, G1 and G2 complexes can be reused four

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315

times. This catalytic system could be applied to other substituted alkenes. 4-Methyl-1-pentene could be oxidized in comparable yield to 1-hexene. Good yields were obtained for the oxidation of 4-phenyl-1-butene. Interestingly, the longer chain diene, 1,8-nonadiene, was only oxidized at one double bond while 1,5-hexadiene gave a dimerization product in addition to single double bond oxidation. For terminal olefins with internal bonds like 5-vinyl-2norbornene, only the terminal double bond was oxidized.

7. CONCLUDING REMARKS
The use of soluble polymers provides an alternative platform for organic synthesis by incorporating beneficial aspects of both solution-phase and solid-phase chemistry. By establishing homogeneous reaction conditions while still facilitating product separation, soluble polymer-supported methodologies have demonstrated utility in a variety of areas including peptide synthesis, small-molecule organic synthesis, polymer-supported reagents, and polymer-supported catalysts. Although great strides have been made in the use of soluble polymers as supports for recoverable reagents and catalysts, considerable research remains to be done. It has been recognized that the nature of the macromolecular support plays a significant role in solid-phase organic synthesis. Compatibility problems between reagent or substrate and the polymer support can greatly limit the applications of a given support. To overcome these limitations, soluble polymer-supported reagents and catalysts have been utilized. Furthermore, in the case of substrates that possess limited solubility, covalent attachment to a soluble support would allow their use in a previously inaccessible range of synthetic applications. The refinement of current liquid-phase methodologies coupled with the development of new soluble polymeric supports tailored for organic synthesis combine to make soluble polymers an increasingly valuable tool for synthetic chemists. Over the past three decades, dendrimers have evolved from a concept to become a new class of polymers with a unique architecture and versatile chemical structures. Progress in controlled polymerization and synthesis techniques have led to the development of wellcontrolled dendrimers structures with a large number of surface groups that can be utilized to display a wide range of applications. Today, research on dendrimers is not only focused on disclosing aberrant or special features of dendrimers but considerable effort is also invested in the development of applications for dendrimers. Some studies in these fields have definitely shown that dendrimers have beneficial or even superior characteristics, although it should be noted that frequently more simple monomeric or polymeric systems are equally effective with respect to the investigated application. There is much more than the aesthetic attraction in the use of dendrimers in the field of catalysis. The perfect definition of catalytic sites and the clear possibility to recover the dendritic catalysts have been fully demonstrated. Seminal studies by van Leeuwen and Brunners dendrizyme concept opened the field of dendrimer catalysis, and then Reetz introduced recycling. The precision of the dendrimer structures, the specificity of their topology, and the variety of dendrimer generations provides a unique means to improve catalyst supports. Catalytic efficiency is very often marred by steric congestion at the metallodendritic surface. Steric congestion may sometimes result in positive dendritic effects in terms of selectivity. With peripheral catalyst loading, the multiple sites provide an exceptional density of catalysts, but steric constraints limit the access to the

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catalytic centers as shown by several of our examples. The design of star-shaped catalysts or first generation dendrimers, however, provided catalysts that were as efficient as mononuclear catalysts and could be recovered and reused, contrary to mononuclear catalysts. Many efforts have recently concentrated on the recovery of the dendritic catalysts using membrane reactors. Industrial applications with membrane reactors remain to be carried out, however, and this aspect is now becoming a major challenge. In some particular cases, interesting positive dendritic effects in catalysis have been shown by several authors. In most cases, however, what is hoped for is an efficiency in terms of turnover rates, yields, and stereoselectivities which is very close to that of the parent, nondendritic analogous catalysts. Many dendritic effects in catalysis have been observed, including increased/decreased activity, selectivity, and stability. It is clear from the contributions of many groups that dendrimers are suitable supports to prepare recyclable transition metal catalysts. Several separation techniques are applicable to these functionalized dendrimers including precipitation, two-phase catalysis, and immobilization of the dendrimer to insoluble support (polystyrene, silica). In addition, the large size and the globular structure of the dendrimers enable efficient separation by nanofiltration techniques. Nanofiltration can be performed batch-wise and in a continuous-flow membrane reactor (CFMR). The common problems involved in catalyst recycling also pertain to dendritic catalysts. These include dendrimer or catalyst decomposition, dendrimer leaching, metal leaching, and catalyst deactivation. Although dendritic catalysts have been applied in several reactions, more experiments are required to gain deeper insight in dendritic effects in catalysis and catalyst recycling. Since there is no single solution to the catalyst separation problem it is not expected that dendrimers will provide the general solution. The optimal process clearly depends on catalyst properties as stability, solubility, etc., as well as product properties. In the development of new recyclable catalysts systems based on dendrimers, the function of the dendritic part should be questioned.

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[111] [Bhyrappa P.; Young J. K.; Moore J. S.; Suslick K. S. J. Am. Chem. Soc. 1996, 118, 5708. [112] Bhyrappa P.; Young J. K.; Moore J. S.; Suslick K. S. J. Mol. Catal. A 1996, 113, 109. [113] Sellner H.; Karjalainen J. K.; Seebach D.Chem. Eur. J. 2001, 7, 2873. [114] Palucki, M.; McCormick G. J.; Jacobsen E. N. Tetrahedron Lett. 1995, 36, 5457. [115] (a) Canali L.; Cowan E.; Deleuze E,; Gibson C. L.; Sherrington D. C. Chem. Commun. 1998, 2561; (b) Canali L. ; Cowan E.; Deleuze H.; Gibson C. L.; Sherrington D. C. J. Chem. Soc. Perkin Trans. 1, 2000, 2055. [116] Brandes B. D.; Jacobsen E. N.; J. Org. Chem. 1994, 59, 4378. [117] Juwiler D.; Neumann R. Cat. Lett. 2001, 72, 241. [118] Bu J.; Judeh Z. M. A.; Ching C. B.; Kawi S. Catal. Lett. 2003, 85, 183. [119] Bregeault J. M. Dalton Trans 2003, 17, 3289. [120] Lane B. S.; Burgess K. Chem. Rev. 2003, 103, 2457. [121] Grigoropoulou G.; Clark J. H.; Elings J. A. Green Chem. 2003, 5, 1. [122] Liu X.; Li Y.; Wang G.; Chai Z.; Wu Y.; Zhao G. Tetrahedron: Asymmetry 2006, 17, 750. [123] Tsuji J. Modern Palladium Catalysis. Palladium Reagents and Catalysts: New Perspectives for the 21st Century; Wiley: Chichester, 2004. [124] (a) Beletskaya I. P.; Cheprakov A. V. Chem. Rev. 2000, 100, 3009; (b) Whitcombe N. J.; Hii K. K.; Gibson S. E. Tetrahedron 2001, 57, 7449; (c) Astruc D. Tetrahedron: Asymmetry 2010, 21, 1041. [125] (a) Hwang S.-H.; Shreiner C. D.; Moorefield C. N.; Newkome C. N. New J. Chem. 2007, 31, 1192; (b) Newkome G. R.; Shreiner C. Chem. Rev. 2010, 110, in press. [126] (a) Andrs R.; de Jesus E.; Flores J. C. New J. Chem. 2007, 31, 1161; (b) de Jess E.; Flores J. C. Ind. Eng. Chem. Res. 2008, 47, 7968; (c) Martinez-Olid F.; Benito J. M.; Flores J. C.; de Jesus E. Isr. J. Chem. 2009, 49, 99. [127] Gladysz J. A. Chem. Rev. 2002, 102, 3215. [128] Catalyst Separation, Recovery and Recycling; Cole-Hamilton D.; Toose R. P., Eds.; Springer: Heidelberg, 2006. [129] Recoverable and Recyclable Catalysts; Benaglia, M. Ed.; Wiley: Chichester, 2009. [130] Nicolaou K. C.; Bulger P. G.; Sarlah D. Angew. Chem., Int. Ed. 2005, 44, 4482. [131] Kleij R. A.; van Leeuwen P. W. N. M.; van der Made A. W.; EP0456317, 1991; Chem. Abstr. 1992, 116, 129870. [132] (a) Kranenburg M.; Kamer P. C. J.; van Leeuwen P. W. N. M. Eur. J. Inorg. Chem. 1998, 25; (b) Oosterom G. E.; van Haaren R. J.; Reek J. N. H.; Kamer P. C. J.; van Leeuwen P. W. N. M. Chem. Commun. 1999, 1119; (c) de Groot D.; Eggeling E. B.; de Wilde J. C.; Kooijman H.; van Haaren R. J.; van der Made A. W.; Spek A. L.; Vogt D.; Reek J. N. H.; Kamer P. C. J.; van Leeuwen P. W. N. M. Chem. Commun. 1999, 1623; (d) De Groot D.; Emmerink P. G.; Coucke C.; Reek J. N. H.; Kamer P. C. J.; van Leeuwen P. W. N. M. Inorg. Chem. Commun. 2000, 3, 711; (e) Oosterom G. E.; Reek J. N. H.; Kamer P. C. J.; van Leeuwen P. W. N. M. Angew. Chem., Int. Ed. Engl. 2001, 40, 1828. [133] Laurent R.; Caminade A.-M.; Majoral J.-P. Tetrahedron Lett. 2005, 46, 6503. [134] Routaboul L.; Vincendeau S.; Turrin C.-O.; Caminade A.-M.; Majoral J.-P.; Daran J.C.; Manoury E.; J. Organomet. Chem. 2007, 692, 1064. [135] Dahan A.; Portnoy M. Org. Lett. 2003, 5, 1197.

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In: Homogeneous Catalysts Editors: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers. Inc.

Chapter 10

RECENT STRATEGIES IN PHASE TRANSFER CATALYSIS AND ITS APPLICATION IN ORGANIC REACTIONS
P.A.Vivekanand and Maw-Ling Wang*
Hungkuang University, Taiwan, Republic of China.

ABSTRACT
In view of the increasing environmental and economical concerns, it is now imperative for chemists to invent as many environmentally benign catalytic reactions as possible. Successful completion of reactions involving lipophilic and hydrophilic reactants can be achieved by employing an environmentally benign technology viz., phase transfer catalysis (PTC). Some of the prominent features of the PTC include, improved reaction rates, lower reaction temperatures and the absence of expensive anhydrous or aprotic solvents. Owing to its simplicity and the low cost of most of the phase transfer catalysts, the PTC technology has found universal adoption. As a result, PTC is considered to have great potential for industrial-scale application. Nowadays, due to these salient features, it has become an important choice in organic synthesis and is widely applied in the manufacturing processes of specialty chemicals, such as drugs, pharmaceuticals, dyes, perfumes, additives for lubricants, pesticides, monomers etc. Due to ever increasing necessity of increasing the efficiency of PTC in industries, researchers incessantly invented new and novel phase transfer catalysts with more active-sites and higher efficiency. Asymmetric phase-transfer catalysis has attracted considerable attention as a convenient technique for the synthesis of chiral molecules. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been employed to achieve the goal for inducing asymmetry into product molecules. Currently, ingenious new analytical and process experimental techniques viz., ultrasound and microwave irradiation assisted PTC transformations have become immensely popular in promoting various organic reactions. Phase transfer catalysis will be of curiosity to
* Corresponding author: Department of Environmental Engineering, Safety and Health, Hungkuang University, Shalu, Taichung County, 43302 Taiwan, Republic of China. Tel: +886-4-2631-8652 ext.4175. Fax: +886-42652-9226. E-mail: chmmlw@sunrise.hk.edu.tw.

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anyone working in academia and industry that needs an up-to-date critical analysis and summary of catalysis research and applications. In view of the success and vitality of this technique, we have proposed to present recent happenings in the field of PTC and to study its applications to various organic reactions. Typical applications of PTC in silent, ultrasonic and microwave conditions are described. Further, kinetics of various organic reactions catalyzed by PTC carried out under a wide range of experimental conditions will be presented.

INTRODUCTION
In recent years, the greening of global chemical processes has become a foremost topic in the universe. The development of new synthetic methods that are more environmentally benign have been propelled by the growing importance of green chemistry in organic synthesis [1]. In general, green chemistry is the only way forwards: it merges expertise from physical, synthetic and biological chemists, together with that of, life scientists, environmentalist toxicologists, to deliver sustainable chemical design. Green chemistry [2], by the design of environmentally compatible chemical reactions, offers the tools to approach pollution and sustainability concerns at the source. Generally, chemical transformations, which produce in addition to the desired product large amounts of byproducts and waste, are less desirable. However by proficient design of chemical transformations we can reduce the required energy input in terms of mechanical, thermal, and other energy inputs, and the associated environmental impacts of excessive energy usage. The necessity of selective transformations in agrochemical and pharmaceutical industries is even larger since delicate bioactive compounds are often not robust enough to stand the conditions used in bulk chemistry. Catalysts aided selective transformations eliminate the requirement of stoichiometric auxiliary reagents and can eventually help to decrease the amounts of waste. In addition, they are able to carry out the necessary synthetic transformation in a more environmentally benign way. Thus, in view of the increasing environmental and economical concerns, it is now imperative for chemists to invent as many environmentally benign catalytic reactions as possible. Transformations of starting materials into desired final products of practical applications such as pharmaceuticals, plant protection agents, dyes, photographic chemicals, monomers etc., usually require a number of chemical operations in which additional reagents, catalysts, solvents, etc. are used. For successful completion of a reaction it is necessary that the reactants collide with each other as much as possible. However it is often noticed that these reactions are immiscible in nature. To alleviate the predicament of immiscibility it is necessary to ferry water soluble anionic reactant into organic soluble reactant/organic phase. Classical methods [3] to overcome this immiscibility include use of protic/aprotic solvents, high stirring speed, high temperature etc. Nevertheless these methods have their own shortcomings viz., high energy consumption, production of byproducts and difficulty in purification together with environmental pollution. As a consequence, these techniques are industrially unattractive, constrained and polluting. However, successful completion of reactions involving lipophilic and hydrophilic reactants can be achieved by employing an environmentally benign technology viz., phase transfer catalysis (PTC).

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GENESIS OF PHASE TRANSFER CATALYSIS

This key green approach [4], leading to waste minimization, utilizes water as the solvent and is applicable to a great variety of reactions in which inorganic and organic anions and also carbenes react with organic substrates. It makes use of heterogeneous two-phase systems-one phase (water) being a reservoir of reacting anions or base for generation of organic anions, whereas organic reactants and catalysts are located in the second, organic phase. The reacting anions are continuously introduced into the organic phase in the form of lipophilic ion-pairs with lipophilic cations supplied by the catalyst. Starks et al.[5] reported that nucleophilic aliphatic substitution reaction of an aqueous sodium solution with 1chlorooctane does not ordinarily take place because of immiscibility. By the addition of 1% of the quaternary ammonium, hexadecyl tributyl phosphonium bromide, cyanide ions are ferried into the organic phase from the water phase and 1-cyanooctane formed quantitatively in a matter of minutes. Some of the prominent features of the PTC include, improved reaction rates, lower reaction temperatures and the absence of expensive anhydrous or aprotic solvents.

Emergence of the Methodology

Owing to its simplicity and the low cost of most of the phase transfer catalysts, the PTC technology has found universal adoption. As a result, PTC is considered to have great potential for industrial-scale application. Nowadays, PTC becomes an important choice in organic synthesis [6] and is widely applied in the manufacturing processes of specialty chemicals, such as pharmaceuticals, dyes, perfumes, additives for lubricants, pesticides, and monomers for polymer synthesis. Frequently employed PTC are presented in Table 1 and is a very effective tool in many types of reactions, e.g., alkylation, oxidation, reduction, addition, hydrolysis, etherification, esterification, carbene addition, chiral reactions etc. Due to ever increasing necessity of increasing the efficiency of PTC in industries, researchers incessantly invented new and novel phase transfer catalysts with more active-sites [7-13] and higher efficiency. Escalating demand for homochiral commercial products in preference to their racemic counterparts has resulted in the rapid growth of numerous asymmetric transformations. Popularity of catalytic asymmetric reactions is due to the usage of only less than a stoichiometric amount of the chiral control element, often the most expensive reagent in the process. With the development of PTC, researchers placed much effort on the development of phase transfer catalysts which could induce asymmetry into product molecules [14]. Asymmetric PTC has been used in several types of reactions including, Michael additions [15], Darzens reactions [16], epoxidations [17], Diels-Alder cycloadditions [18], alkylation [19], Aldol condensations [20], and -hydroxylation of ketones [21]. Also, asymmetric Baylis-Hillman [22] reaction has been developed using derivatives of quinidine to effect the reaction of activated alkenes with aldehydes. Asymmetric phase-transfer catalysis has attracted considerable attention as a convenient technique for the synthesis of chiral molecules. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been employed to achieve the goal for inducing asymmetry into product molecules. Chiral centers in catalysts derived from the

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cinchona alkaloids are located both on the quaternary nitrogen and on the carbon framework [23]. In addition, Merrifield resin-bound cinchonidine and cinchonine have been employed as recoverable PTC catalysts [24, 25]. Furthermore, non-Cinchona chiral catalysts, such as TADDOL [26], spiro ammonium [27] and phosphonium salts [28], binaphthyl derived amines [29,30], and salen-metal complexes [31] have also been used in asymmetric PTC alkylations.
Table 1. Frequently Employed PT Agents
PTC Cost Activity and Recovery of Catalyst Stability and Utility Agent Crown ethers Highly active catalysts even under Stable and frequently Very Costlier basic conditions and at higher employed. temperatures. Recovery is difficult and their toxicity poses environmental pollution. Cryptands Highly reactive, except in the Stable. Used sometimes Costlier presence of strong acids. despite high costs and toxicity, due to higher reactivity. Quternary Ammonium salts PEG Recovery is relatively complicated and moderately active. Lower in activity and can be recovered easily. Fairly stable under basic conditions and up to 100 oC. Extensively used. More stable than quaternary ammonium salts hence often used. Thermally more stable than quaternary ammonium salts, but less stable under basic conditions. And widely used. Inexpensive Inexpensive

Quternary Fairly active and recovery is Phosphonium relatively difficult. salts

Expensive than quaternary ammonium salts.

PhaseTransfer Catalysis

Insoluble PTC

SolublePTC

IPTC RPTC

LLPTC

SLPTC

LLPTC

SLPTC

GLPTC

Figure 1. Classification of PTC Reactions.

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Classification of PTC
PTC reactions can be broadly classified into two main classes: soluble PTC and insoluble PTC (Figure 1). Within each class, depending on the actual phases involved, reactions are further classified as liquid-liquid PTC (LLPTC), gas-liquid PTC (GLPTC), and solid-liquid PTC (SLPTC). In some cases, the PT catalyst forms a separate liquid phase, and this variant of PTC can be grouped along with traditional insoluble PTC, where the PT catalyst is immobilized on a solid support. Other non-typical variants of PTC include inverse PTC (IPTC) and reverse PTC (RPTC) via a reverse transfer mechanism.

Mechanism of Phase Transfer Catalysis

Mechanism of PTC is broadly classified into two types based on kinetic criteria. Accordingly, two main mechanisms have been recognized in phase-transfer reactions: (a) the interfacial mechanism, typical in reactions promoted by alkali, where interfacial deprotonation converts an anion (such as a carbanion, oxanion or azanion), which is slowly extracted into the organic phase to swiftly react with an electrophilic substrate (Scheme 1a) and (b) the extraction mechanism where anions are rapidly transferred as ion-pairs from aqueous or solid phase into the organic phase where they slowly react with a substrate (Scheme 1b).

a) RX M+XQ+YQ+YRY M+YQ+YQ+XOrganic Phase Interface Aqueous Phase

M+Xb) RX M+XQ+YQ+Y-

M+YQ+Y-

RY M+Y-

Organic Phase Aqueous Phase

Q+X-

Scheme 1. Two types of PTC mechanism a) Interfacial mechanism b) Extraction Mechanism.

The distinction between these two mechanisms is always made based on influence of stirring speed and value of energy of activation [7, 9-13, 32]. To differentiate between the two mechanisms, kinetic run at significantly higher agitation speed is required, since the chemically controlled extraction mechanism is independent of the stirring speed above a certain value whereas the interfacial mechanism is strongly dependent on stirring speed. Further, to distinguish between the diffusion-controlled mechanism and other PTC/OH-

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mechanisms, the kinetic order and the energy of activation of the reaction become valid. If the energy of activation is above 10 kcal mol-1, then the mechanism operative is interfacial mechanism and extraction mechanism is operative if it is below 10 kcal mol-1.

INGENIOUS TECHNIQUES IN CONJUNCTION WITH PHASE TRANSFER CATALYSIS

Phase transfer catalysis will be of curiosity to anyone working in academia and industry that needs an up-to-date critical analysis and summary of catalysis research and applications. Currently, ingenious new analytical and process experimental techniques viz., ultrasound and microwave irradiation assisted PTC transformations have become immensely popular in promoting various organic reactions. Inventing selective, efficient and eco-friendly methods for applications in complex organic synthetic manipulations constitutes a major chemical research effort. In this regard, several non-conventional methods are emerging that involve reactions in aqueous media [33] or those that are accelerated by exposure to microwave [34-36] or ultrasound [3739] irradiation. These methods are now recognized as viable environmentally benign alternatives [3439]. Although, sonication methods have been initially applied to homogeneous reactions in a variety of solvents, this approach has now evolved into a useful technique in heterogeneous reactions. A vast majority of sonochemical applications in the synthesis deal with reactions involving metals [38, 40] organic phase insoluble reagents, or their aqueous solutions [38, 41-42]. Compared with the traditional methods, a large number of organic reactions can be carried out in higher yields, shorter reaction time and milder reaction conditions under ultrasonic irradiation [43]. Ultrasound irradiation is a transmission of a sound wave through a medium and is regarded as a form of energy for the excitation of reactants consequently enhancing the rate of diffusion [44-46]. Richards and Loomis [47] reported, on the chemical effects of high-power ultrasound, two types of chemical reaction: (i) the acceleration of conventional reactions by ultrasound and (ii) redox processes in aqueous solutions. In a liquid medium, the effects of ultrasound are produced due to the phenomenon called cavitation. When a liquid is irradiated by ultrasound, microbubbles can appear, grow and oscillate extremely quickly and even collapse violently if the acoustic pressure is high enough. The occurrence of these collapses near a solid surface will generate microjets and shock waves [48]. Moreover, in the liquid phase surrounding the particles, high micromixing will increase the heat and mass transfer and even the diffusion of species inside the pores of the solid [49]. Application of ultrasonic waves in organic synthesis (homogeneous and heterogeneous reactions) has been boosted in recent years [50-55]. Sonication of multiphase systems accelerates the reaction by ensuring a better contact between the different phases [56-57]. Further, they also increase the reaction rate and avoid the use of high reaction temperatures [58]. These days this environmental benign technology is combined with PTC with primary objective of optimizing reaction conditions [59-61]. Sonoication has been found to enhance this reaction of liquidliquid phase-transfer catalysts (LLPTC) bi-phase system. In uncatalyzed sonicated reactions, the chemical effects of ultrasound, attributed to intense local conditions generated due to cavitation bubble

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dynamics, i.e., the nucleation, formation, disappearance, and coalescence of vapour or gas bubbles in the ultrasonic field [62, 63]. The rate enhancement in PTC assisted reactions is due to mechanical effects, mainly through an enhancement in mass transfer. However in ultrasound in conjunction with PTC reactions systems, cavitational collapse near the liquid liquid interface disrupts the interface and impels jets of one liquid into the other, forming fine emulsions, and leading to a dramatic increase in the interfacial contact area across which transfer of species can take place [64]. It has been reported that a combination of PTC and ultrasound is often better than either of the two techniques alone [65, 66]. In such cases, the phase-transfer catalyst initiates the reaction by the transfer of species across the interface and ultrasound merely facilitates this transfer, possibly by increasing the interfacial area across which this transfer occurs [67]. Microwaves are electromagnetic with wavelengths ranging from as long as one meter to as short as one millimeter, or equivalently, with frequencies between 300 MHz (0.3 GHz) and 300 GHz. Microwave methodology is a novel approach towards clean and green chemistry and it is relatively a very convenient, safe and rapid methodology. Due to these features, microwave irradiation has been increasingly used as a synthetic tool in a number of studies. Even after a slow uptake of the technology, which has been attributed to its initial lack of controllability and reproducibility coupled with a general lack of understanding of the basics of microwave dielectric heating, there has been significant number of papers have appeared [6874]. Researchers have shown much interest in microwave-assisted chemistry to facilitate faster reactions and efforts are now being made to scale up reactions using this technology [75-77]. It has become recognized that many chemical reactions, which require heating are likely to proceed more rapidly using this different form of heating. Apart from their impact in mainstream organic synthesis, their influence in the field of medicinal chemistry [78-82], nanoparticle synthesis [83] etc., has been dramatic. The area is still burgeoning and this is in no small part due to the positive interaction between suppliers of microwave equipment and the research community. Significant advantage of microwave-enhanced chemistry is the reduction in the reaction times. It is clear that microwave chemistry can provide access to synthetic transformations, which may be prohibitively long or low yielding using conventional heating. Now a days there has been considerable interest in microwave assisted PTC reactions [84-98]. Rates of PTC reactions, as well as selectivity of the desired product, can be synergistically enhanced by using microwave irradiation. The resultant advantages in comparison to classical heating are especially spectacular. The application of microwave radiation-PTC offers new alternatives in sample preparation in terms of shorter reaction times and reduced solvent consumption.

SCOPE AND OBJECTIVES

In principle, we wanted to present in this chapter the application of recent PTC methodologies to the synthetically important organic reactions. Alkylation reactions, epoxidation, esterfication, Heck reaction, cyanation, Michael reaction, darzens reaction, Suzuki coupling, aziridine reaction and polymerization reactions, among others, were the

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reactions originally to be covered. Because of the abundant literature found on these topics, however, we decided to dedicate this first part only to the alkylation reactions, Heck reaction, aziridine reaction, epoxidation, and esterfication whereas the rest of the reactions will be studied in the second part in due course. The chapter is organized according to the subheadings presented in the following section, taking into account the different components and variety of conditions involved in the each of these reactions. Further, many of the contributions to this review are also analyzed from a critical point of view, with the aim of discussing the advantages and disadvantages that the different techniques offer and trying to select the best choice, when possible.

ALKYLATION REACTIONS
PTC catalyzed alkylation is an important process step in the manufacture of large number of drugs [99]. These days chemist show much interests in imide derivatives because of their numerous applications in biology [100,101] as well as synthetic [102] and polymer chemistry [103]. However, there are only a few papers [104,105] discussing the synthesis of imide derivatives under solid-liquid PTC (SL-PTC). The main advantage of using solid-liquid process in the reaction is to avoid the slow reaction rate due to hydration in the presence of water. It is expected that the synthesis of imide under ultrasonicPTC condition will be more efficient than conventional techniques.
O KOH, PTC Solvent, 40 C 2 3
0

Br O N H 1 O

N O KBr H2O

Scheme 2. N-alkylation of Succinimide with 1-bromo-3-phenylpropane under S-L-PTC conditions.

Recently, ultrasonic-PTC assisted synthesis of 1-(3-phenylpropyl)pyrrolidine-2,5-dione (3) was successfully carried out by the reaction of succinimide (1) with 1-bromo-3phenylpropane (2) in a small amount of KOH and organic solvent under solid-liquid phasetransfer catalysis condition [106] almost water free conditions [Scheme 2]. We investigated systematic kinetics of the reaction and predicted the reaction mechanism. Results indicate that the mass transfer resistance at the solid-liquid interface could be ignored when the agitation speed exceeds 200 rpm. The overall reaction was described by pseudo-first-order kinetics and the apparent activation energy in cyclohexanone was found to be 15.01 kcal/mol. The influence of the amount of tetrabutylammonium bromide on the apparent rate constant (kapp) was studied in range 0.0-0.65 g under ultrasonic standard reaction condition. From the plot of ln(1-x) versus time (Figure 2) it is clear that the apparent rate constant increased linearly with the increase in the amount of TBAB catalyst. In the control experiments (absence of TBAB), a conversion of 3.99% was observed after 2 h of reaction. On the other hand, when a small quantity of TBAB (0.05 g) was added to the reaction

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solution the conversion increased dramatically to 30.97% after 2 h of reaction. The concentration of quaternary ammonium cation (Q+) in organic phase solution, which affected the concentration of the active catalyst SUC-Q(org), was increased with the increased amount of TBAB catalyst. Thus, on increasing the amount of catalysts the kapp values increases (Table 2).
5

Amount of TBAB 0g 0.05 g 0.15 g 0.25 g 0.45 g 0.65 g

-Ln (1-X )

20

40

60

80

100

120

Time (min)
Figure 2. Effect of amount of TBAB on the rate of the reaction. 6.0 10-2 mol of succinimide, 6.0 10-3 mol of 1-bromo-3-phenylpropane, 1 g of KOH, 60 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 45 C, 800 rpm, 40 kHz (300 W).

Table 2. Influence of the amount of TBAB catalyst on the apparent rate constants, (kapp) a
Amount of TBAB (g) 0 0.05 0.15 0.25 0.45 0.65 Apparent Rate Constant kapp (x 10-3 min-1) 0.4 3.1 7.1 12.4 23 32

a Reaction conditions: 6.0 10-2 mol of succinimide, 6.0 10-3 mol of 1-bromo-3-phenylpropane, 1 g of KOH, 60 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 45 C, 800 rpm, 40 kHz, (300 W).

In order to investigate the influence of ultrasonic frequency on the PTC catalyzed alkyalation of succinmide, the reaction rates at 40 kHz and 120 kHz were compared with same output power of 300 W. The results are shown in Figure 3 and Table 3. In silent condition, the conversion is only 62% (kapp = 8 10-3 min-1), but in the presence of ultrasound the conversion is 76% (kapp = 12.4 10-3 min-1) and 90% (kapp = 19.3 10-3 min-1) for 40 and

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120 kHz, respectively. Thus, the ultrasonic effect enhances the rate 1.55 times with respect to the conventional method (agitation speed at 800 rpm only). From these observed results it is clear that the ultrasonic assisted phase-transfer catalysis significantly increased the reaction rate.
2.5

2.0

Ultrasound frequency 0 kHz 40 kHz 120 kHz

1.5

- Ln (1- X )

1.0

0.5

0.0

20

40

60

80

100

120

Time (min)
Figure 3. Plot of -ln(1 - X) of 1-bromo-3-phenylpropane versus time with various ultrasound frequency; 6.0 10-2 mol of succinimide, 6.0 10-3 mol of bromo-3-phenylpropane, 1 g of KOH, 60 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 0.25 g of TBAB, 45 C, 800 rpm.

Table 3. Influence of different ultrasound frequencies on the apparent rate constants (kapp) a
Ultrsound Frequency (kHz) 0 40 120 Apparent Rate Constant kapp (x 10-3 min-1) 8 12.4 19.3

a Reaction conditions: 6.0 10-2 mol of succinimide, 6.0 10-3 mol of 1-bromo-3-phenylpropane, 1 g of KOH, 60 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 0.25 g of TBAB, 45 C, 800 rpm (300 W).

Further we found that, the reaction rate is increased by increasing the amount of KOH and amount of SUC-H. However, the reaction rate is decreased by increasing the volume of water and cyclohexanone. We compared the influence of six solvents on the reaction and the order of reactivities of the six solvents is: cyclohexanone > acetophenone > o-

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dichlorobenzene > chlorobenzene > chloroform > toluene. Among the various PTCs tested tetraoctylammonium bromide (TOAB) showed significantly higher catalytic activity. Chiral nanosize molecules, derived from cinchonidine and Frchet dendritic wedges up to generation three, have been synthesized by Guillena et. al., [107] and demonstrated that these dendritic cinchonidine ammonium salts (Scheme 3) can be applied as phase transfer catalysts in the alkylation of N(diphenyliminemethylene)glycine (Scheme 4). For first generation catalysts a reversal on the stereoselectivity can be achieved by changing the nature of the inorganic base from KOH to NaOH. The study reveals efficiency of the catalysts are by reaching a moderate level of asymmetric induction, while the chiroptical properties are independent of the enantioselection achieved. By employing dialysis membranes satisfactory results have been obtained in the recovery and reuse of higher generation salts.

BrN + OR2 N 4

OR1

OR1

a; R1 = Bn, R2 = H b; R1 = Bn, R2 = Allyl c; R1 = Bn, R2 = Bn d; R1 = Me, R2 = H

Scheme 3. Chiral dendritic molecules used as phase transfer catalysts in the alkylation of a glycine imine ester.

Ph N Ph 5 CO2iPr

Cat (10 mol%), PhCH2Br, Base Solvent, T( C)

o

Ph N Ph 6 * CO2iPr Ph

Scheme 4. Alkylation of N(diphenyliminemethylene)glycine (5) with benzylbromide catalyzed by a new dendritic cinchonidine-derived ammonium salt (4a).

The development of more efficient PTCs is an important goal in organic synthesis so as to increase the catalytic efficiency of these catalysts. In this regard, one of the options is to increase the number of catalytic active sites in them. This led to the invention of multi-site phase transfer catalysts. Recently, Vivekanand and Balakrishnan [10] have synthesized and characterized a novel multi-site phase transfer reagent, viz., 1,3,5-tris((N,N,Ntriethylammonioum) methylphenyl)benzene trichloride (TEAMPBTC) and studied its utility

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P.A.Vivekanand and Maw-Ling Wang

in the synthesis of 2-(2-bromoethyl)-5,5- dimethylcyclohexane-1,3-dione by selective monoalkylation of dimedone under pseudo-first order reaction conditions. Further, they investigated the catalytic activity of a new quaternary ammonium salt, with three active sites, in the cycloalkylation of indene with 1,4-dibromobutane under pseudo-first order condition [11]. They found the catalytic activity of the new onium salt is superior compared to other commercial phase transfer catalysts under mild reaction conditions. The substitution of alkyl bromides (RBr) to sodium sulfide (Na2S), including linear and branched alkyl groups catalyzed by phase-transfer catalysts in combination with ultrasound obviously provides a more efficient synthetic approach for the preparation of thioethers [60]. We investigated a comprehensive kinetic study of thioether synthesis under influence of ultrasound assisted phase-transfer catalysis conditions. Mechanism of PTC assisted thioether synthesis is presented in Scheme 5. These PTC reactions were carried out in a liquidliquid two-phase medium. High yields of products were obtained in shorter reaction time using 4 mol% of the tetrabutylammonium bromide and ultrasound 28 kHz (200 W) conditions. However, in the absence of a phase-transfer catalyst and ultrasound, less than 5% conversion was detected even after 4 h of reaction.

2RBr

R2S Organic Phase

2RBr + (Q+)2S
+ +

2Q+Br-+ R2S

(2) Interface

2Na Br + (Q )2S

2Q+Br- + Na2S (1)

Aqueous Phase 2Na+BrScheme 5. PTC mechanism for the thioether synthesis.

Na2S

Rate of the two-phase reaction is influenced by the mass transfer as well as the chemical reaction. The effect of the agitation speed on the reaction rate is shown in Table 4. For agitation speed over 400 rpm, the rate of the reaction is insensitive to the agitation speed. This

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can be attributed to the active intermediate of the catalyst (Q2S), which is hydrophobic and likes to stay in the organic phase, i.e., it is easy to transfer the active intermediate of the catalyst from the aqueous phase to the organic phase, in which the interfacial area is not so important. Thus, the mass transfer rate reaches a constant value when the stirring speed is larger than 400 rpm. In the absence of stirring speed and in the presence of the effect of ultrasonic condition at 28 kHz (200 W) the observed rate constant is 9.8103 min1 and in vice-versa the kapp value at 500 rpm is 11.4103 min1. In the presence of both condition, i.e., at 500 rpm combined with the ultrasonic wave frequency 28 kHz (200 W) the kapp value is 41.7103 min1. From this observation, we infer that the ultrasonic effect enhances the rate 3.7 times with respect to the conventional method (stirring speed at 500 rpm only). Further, presence of ultrasonicwave results in increase in the collision rate between the organic and aqueous phase reactants and decrease the surface area between the two layers [108].
Table 4. Influence of the agitation speed on the apparent rate constants, kapp: 7g Na2S; 10 mL water; 4 mmol of 1-butyl bromide; 40 mL n-hexane, 4 mol% of TBAB; 500 rpm; 35 0C; 60 min of reaction.
Agitation Speed (rpm) 0 200 400 500 600 800 1000 kapp (x 10-3 min-1) 9.8 33.9 39.6 41.7 40.7 40.8 40.6

Figure 4. Conversions of various reactants with time: 7 g Na2S; 10 mL water; 40 mL of n-hexane; 4 mol% of TBAB; 0.5 g of biphenyl; 500 rpm; 35 0C; 60 min of reaction.

Influence of different alkylating agents on the rate of thioether synthesis is presented in Fig. 4 and Table 5. The reaction follows pseudo-first order law in the presence of PTC and

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excess amount of sodium sulfide. The kinetic investigation reveals that the most reactive organic reactant is allyl bromide and the reaction is 100% completed within 10 min for allyl bromide. It can be attribute to the the smaller molecular size and the conjugation of pi-bond. From 1-propyl bromide (1-C3H7Br) to 1-octyl bromide (1-C8H17Br) the kapp value decreases due to increasing the carbon chain of the molecules and (Q2S) is not able to properly interact with active site of the long chain alkyl bromides. Among the alkyl bromides sec-propyl bromide (2-C3H7Br) is the least reactive one because of steric hindrance in its reaction.
Table 5. Influence of alkylating agents on kapp: 7 g Na2S; 10 mL water; 4 mmol of 1butyl bromide; 40 mL of n-hexane; 4 mol% of TBAB; 500 rpm; 35 0C; 60 min of reactiona (200 W).
Alkyl Bromide 1-Propyl bromide 1-Butyl Bromide 1-Pentyl bromide 1-Hexyl bromide 1-Heptyl bromide 1-Octyl bromide 2-Propyl bromide Allyl bromidea
a- Reaction completed within 10 min.

kapp (x 10-3 min-1) 49.6 41.7 25.5 17.1 11.7 9.5 5.6 -

Figure 5. Influence of ultrasonic frequenzy on the conversion of 1-butyl bromide: 7 g Na2S; 10 mL water; 4 mmol of 1-butyl bromide; 40 ml of n-hexane; 4 mol% of TBAB;0.5 g of biphenyl; 500 rpm; 35 0C; 60 min of reaction.

Further, we compared the reaction rate at 28 kHz and 40 kHz having same output power of 200W. At 1 h, without ultrasonic irradiation the conversion is only 53%, but in the

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presence of ultrasonic the conversion is 91% and 97% for 28 kHz and 40 kHz, respectively (Fig. 5). These observed results indicate that ultrasonicassisted phase-transfer catalysis significantly increased the yield of the products. The same trend is also observed by Entezari and coworkers [109,110]. So the application of ultrasounds in organic synthesis is one of the popular areas in sonochemistry. Selective mono alkylation of isosorbide and isomannide was carried using tetrabutylammonium bromide and by using potassium hydroxide as a base by Chatti et al. [111a]. Further, O-alkylation of mono-benzylated isosorbide and isomannide was performed with various ,-dihalides or ditosylates using tetrabutylammonium bromide as phase transfer agent under microwave condition [111b]. In addition to the expected ethers 8 (a and b), some amounts of alkene 9 (a and b) were obtained resulting from a dehydrobromination on the common intermediate involved in SN2E2 competitive processes. The ambient reaction conditions (70% yield) involve the use of only 2% of catalyst in p-xylene for 5 min at 140 0C or in toluene for 15 min at 110 0C. In order to minimize the competitive elimination, halide leaving group was changed to tosylate when competitive SN2E2 processes is involved (Scheme 6).
HO O Br-(CH2)8 O O

O + OCH2Ph 7a 7b Br-(CH2)8-Br

KOH, TBAB

O OCH2Ph

CH2=CH-(CH2)6 O O

O O + OCH2Ph 9a 9b PhCH2O O

O (CH2)8 O O 8a 8b

O OCH2Ph

Scheme 6. Alkylation of isosorbide and isomannide performed under microwave assisted phase transfer catalysis condition.

2-Benzyloxyacetophenone (12) is utilized as a pharmaceutical intermediate for the manufacture of drugs such as antiaggregant, antihypertensive, platelet, lipoxygenase, diuretics, prostaglandin and, analgesics and for treatment of metabolic disorders. Novelties of low power microwave irradiated solidliquid phase transfer catalysis have been brought out in the selective O-alkylation of sodium salt of o-hydroxyacetophenone (OHAP, 10) with benzyl chloride (11) (Scheme 7) by using tetra-n-butylammonium bromide as a catalyst by Yadav et al. [112]. Authors indicate that microwave-PTC condition enhances the rate of the reaction. The conversion increased only upto a certain concentration of TBAB (6.7 105 mol cm-3). Above this concentration there was no further increase in the conversion. Authors attribute this to the fact that the reaction rate was fast and thus, mass transfer of ion pair from the liquid film to the bulk liquid was controlling beyond certain concentration of catalyst.

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Here the rate of mass transfer was less than the rate of reaction. On comparing four PTCs viz., tetra-n-butylammonium bromide (TBAB), tetra-n-butylammonium hydrogensulfate (TBAHS), tetra-n-propylammonium bromide (TPAB) and tetra-n-butylammonium iodide (TBAI), TBAB was found to more efficient catalyst for the reaction under study. This is a solidliquid PTC process in which the entire catalyst is in the organic liquid phase. The type of cations and anions present in the system greatly influences the solubility of solid nucleophile. In fact, the PTC breaks the crystal lattice and transports the nucleophile as Q+Y whose concentration depends on the type of PTC used. This is the case of homogeneous solubilization. Therefore, the activity of TBAB is much greater. The system elegantly forms a synergistic combination of SL PTC and microwave irradiation. The Gibbs free energy for solid dissolution with anion exchange reaction could be also evaluated.
Cl + 10 11 PTC/Solvent MW O O 12 + NaCl

ONa

Scheme 7 O-alkylation of o-Hydroxyacetophenone under MW-PTC condition.

Lee et al. [113] showed that the treatment of phenols (14) with nitroaryl fluorides (15), KF-alumina and Aliquat 336 under microwave irradiation in a domestic microwave oven afforded corresponding diaryl ethers (15) in high yields. Control experiments (absence of PTCs) resulted in small yield of ethers. Comprehensive screening of several phase transfer catalysts (Aliquat 336, 18-crown-6, and TBAB) together with various inorganic bases (K2CO3, CsF-Celite, and KF-alumina) in microwave promoted arylation reactions, reagents combination of 40% w/w potassium fluoride on alumina with Aliquat 336 appeared to be the most optimum reaction system in terms of yield and convenience. They reported sluggish reaction for the same arylation reactions with KF-alumina/ 18-crown-6 in acetonitrile reaction system even when the reaction is allowed for 84 h.

OH ArF R 13 14 KF-alumina/Alumina MW, 10 min

O-Ar

15

Scheme 8. O-alkylation of substituted phenols under MW-PTC condition.

Ethers are commercially attractive because of their extensive applications in the fine chemicals industry, such as anti-inflammatory, analgesic, and antipyretic drugs

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341

[114], ecologically clean additives to motor oils, non-toxic and high-octane gasoline additives [115117], perfumery [118] and plasticizer [119]. p-nitrophenetole was synthesized by the reaction of p-chloronitrobenzene with potassium ethoxide in a homogeneous system using benzyltriethylammonium chloride (BTEAC, Q+Cl-) as a phase transfer catalyst at 50 0C under microwave irradiation conditions [120].The mechanistic details of the reaction is presented in Scheme 9.

EtOH

KOH

in situ

EtO-K+

H2O

EtO-K+ +

Q+X(PTC)

in situ

KX EtO-Q+ + Quaternary ammonium ethoxide O

Cl EtO-K+ + No2 16 Cl EtO-Q+ + No2 16 Aromatic nucleophilic substitution reaction Aromatic nucleophilic substitution reaction

+ No2 17 O + No2 17

KCl

Q+X-

Scheme 9. Mechanism for aromatic nucleophilic substitution reaction between p-chloronitrobenzene and ethoxide ion in the presence of PTC conditions.

In this nucleophilic substitution reaction, the comparative reactivitys of eight different phase-transfer catalysts, such as BTEAC, BTEAB, TBAHS, TBAC, TEAB, TBAI, TEAC and TBAB was explored. The order of the activities for these eight quaternary ammonium salts is TBAI< TBAB <BTEAB < TEAB < TBAC < BTEAC < TBAHS <TEAC. The corresponding kapp values in using these quaternary ammonium salts are depicted in Table 6. Further we have compared the reactivity of microwave-PTC assisted reaction with ultrasonicPTC assisted reaction and silent-PTC reaction (Table 6). Kinetic results indicate that the microwave irradiation enhances the reaction. In general, the order of the distribution of halide ions in the organic phase is I- > Br- > Cl-, which reflects the Starks extraction mechanism. In contrast, in the ethoxylation of p-chloronitrobenzene, the order of the reactivities of the

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P.A.Vivekanand and Maw-Ling Wang

tetrabutylammonium cation group was found to be TBAHS > TBAC > TBAB > TBAI. Thus, smaller size of the anionic ion in the halide groups of PTCs is favorable for a high reaction rate. This phenomenon is more consistent with the interfacial reaction mechanism rather than the extraction reaction mechanism. For an interfacial reaction mechanism, the reaction rate is highly dependent on the concentration of the catalyst at the interface. For the quaternary ammonium cations with the same halide ion (chloride and bromide), the order of the activities of these PTCs is TEA cation > BTEA cation > TBA cation. Hence, it is obvious that a higher reactivity is obtained for a quaternary ammonium salt of less total carbon number. The activity of the catalyst is dependent on the structural characteristics of a quaternary ammonium cation. The yield of the product is correlated with the accessibility of the quaternary ammonium salt (Q+X-), which is a function of carbon in each chain. It is thus concluded that the order of the activities is consistent with the results indicated by Starks et al. [121].
Table 6. Influence of phase-transfer catalysts on the apparent rate constants, kapp: 8 g, KOH; 1 mL, water; 0.5 g, p-chloronitrobenzene; 30 mL, ethanol; 50 0C; 0.25 g, nonane; 15 min of reaction; microwave condition ; ultrasonic conditiona; silent condition.
PTCs TEAB kapp (x 10-2 min- 15.86 1 ,M.W Cond.) kapp (x 10-2 min- 1 ,Ultrasonic Cond.) kapp (x 10-2 min- 1 ,Silent Cond.)

TEAC 19.67 -

TBAI 13.95 2.84 2.29

TBAB 14.61 2.61 1.96

TBAC TBAHS BTEAB BTEAC 16.71 18.73 14.79 17.06 2.42 1.96 1.91 1.23 1.39 0.90 0.88 0.56

a Ultrasonic condition: 28 kHz, 200 W, agitation speed 600 rpm.

20

18

kapp x 10 (min )

-1

16

14

12

10 0.00

0.05

0.10

0.15

0.20

Amount of BTEAC (g)

Recent Strategies in Phase Transfer Catalysis and its Application

Figure 6. Influence of the amount of BTEAC on the apparent rate constants, kapp: 8 g, KOH; 1 mL, water; 0.5 g, p-chloronitrobenzene; 30 mL, ethanol; 50 0C; 0.25 g, nonane; 15 min of reaction; microwave condition.

343

In the absence of BTEAC, the conversion of p-chloronitrobenzene is low. Nonetheless, the reaction is greatly enhanced by adding a small quantity of the BTEAC catalyst. An optimum value of the BTEAC catalyst corresponds to a 0.1 g of BTEAC. A further increase in the amount of BTEAC makes the conversion of p-chloronitrobenzene decrease (Fig. 6). The decrease is probably due to the fact that the conversion of potassium ethoxide to quaternary ammonium ethoxide reaches a new equilibrium state. At higher concentration of Q+Cl-, the equilibrium tends to shift to the formation of potassium ethoxide and thus the quaternary ammonium ethoxide is decreased by Le Chateliers principle. Hence, the conversion of p-chloronitrobenzene is decreased with an increase in the amount of Q+Cl- at a higher concentration.

HECK REACTION
The formation of carboncarbon bonds is a fundamental reaction in metal-catalyzed organic synthesis, the efficiency of which has interested organic chemists for a long time ago. Heck reaction is one of the most popular methodologies for carbon-carbon coupling in synthetic organic chemistry due to its high chemoselectivity and mild reaction conditions [122]. This type of reaction is driven by the ability of Pd(0) complexes to undergo oxidative addition to C-X (X= Cl, Br and I) bonds followed by addition to olefinic compounds [123,124] (Scheme 10). Their mechanism are classified into two types viz., i) cationic mechanism or and ii) a neutral mechanism [125,126]. Former type of mechanism is operative when the X is OTf, OAc, or when Ag+, TI+, quaternary ammonium and phosphonium salts are used to help displacement from halides. On the other hand, the neutral mechanism is operative when X is -donor such as Cl, Br, or I- [127]. Owing to its mild reaction conditions, Heck reaction is widely used in pharmaceuticals, preparation of hydrocarbons, UV screens, polymerization chemistry, and in advanced enantioselective synthesis of natural products [128]. Generally, the Heck reaction works best for preparation of di-substituted olefins from mono-substituted ones and electron poor olefins tend to give higher yields. Olefins with variety of functional groups viz., esters, ethers, carboxylic acids, nitriles, phenols, dienes, can be employed however allylic alcohols tend to rearrange [129]. Now a days, the extensive study of Heck-type reactions [130-132] and their application in organic synthesis has led to the introduction of various improvements [133-135]. Addition of catalytic amount of quaternary salt (Q+X-) accelerates the reaction rate to a great extent and selectivity of the reaction [133,135-147].

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H R2 18

R1 R3 R 4X 19

Pd(0), Ligand, Base Solvent, Heat

R1 R2

R4 3 R3 20

Scheme 10. General Heck Reaction.

In recent past, Heck reaction assisted by phase transfer catalyst (PTC) has been developed into an efficient methodology for coupling of aryl halides with alkenes leading to substituted alkenes. The Heck reaction is an important methodology for the introduction of functionalized aryl moieties onto heterocyclic compounds in organic synthesis. Penalva et al. [148] explored direct arylation of activated thiophenes (21) using a Heck type reaction with a mixture of Pd(OAc)2 and tetra-n-butylammonium bromide as catalytic system. Unexpectedly, the reaction resulted in competitive formation of biaryls (24) resulting from an Ullmann type coupling (Scheme 11).

I NC S 21 22 "Pd" Base, PTC NC S 23 24

Scheme 11. Heck reaction between 2-cyanothiophene and iodobenzene.

R1 EWG ArX 25 EWG ArX R2 28 26 Ar R2 29 26 1-4 mol % Pd(OAc)2 TBAC, Cy2NMe DMAC, 85-100 0C Ar 27 EWG R1 EWG

R1 = H, CH2COOCH3 R2= CH3, Ar X = Br, I

Scheme 12. Modified Heck reaction using bulky amine bases in presence of tetrabutylammonium chloride.

Recent Strategies in Phase Transfer Catalysis and its Application

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The investigation reveals the influence of various parameters such as the nature of the base and the nature and/or the amount of the phase transfer agent on the reaction selectivity. Bases such as N, N-diisopropylethylamine leads specifically to the biaryl formation. In presence of stoichiometric amount of tetrabutyl ammonium bromide or a stoichiometric amount of tetraoctylammonium bromide with potassium carbonate as base, the competitive formation of biphenyl is inhibited. On the other hand, the behavior of the tetraalkylammonium salt is more dependent on counter ion nature than upon the alkyl chain length and only phase transfer agent bearing a bromide as the counter ion provides an active catalyst system than with other halide counter ions. Grtler and Buchwald [149] successfully explored coupling of activated olefins (25 & 28) with both electron-rich and electron-poor aryl halide (26) substrates by employing the Pd(OAc)2/ Cy2NMe/tetraethylammonium chloride system(Scheme 12). Labeling studies indicate that the source of this selectivity is thermodynamic in nature. Even ortho-substituted aryl halides, whose transformations are problematic under typical reaction conditions, were efficiently converted into the desired trisubstituted olefins under PTC condition. Nevertheless, in these cases a greater quantity of catalyst was required. When stoichiometric quantity of tetraethylammonium chloride is employed, the reaction proceeded with the shortest reaction times. The method displays good stereoselectivity and a high degree of functional group compatibility. Palladium-catalyzed Heck coupling reaction in water in the absence of any organic solvents using PTC-microwave technology was investigated by Wang et al. [150]. The arylation reaction of alkenes (30) with aryl iodides (31) proceeded smoothly under microwave irradiation to give exclusively the desired trans-products in good yield (Scheme 13).

Y + 30 RI

R Pd(PPh3)2Cl2,TBAB,K2CO3 H2O, MWI Ar Ar 32a-g

31 a = Ph(R), Ph(Y); b = Ph(R), COOH(Y); c = p-HO2CC6H4(R), COOMe(Y); d = p-O2NC6H4(R), Ph(Y); e = o-O2NC6H4(R), Ph(Y); f = p-CH3C6H4(R), Ph(Y); g = o- CH3C6H4(R), COOH(Y).
Scheme 13. Palladium and PTC catalyzed Heck cross coupling reaction under microwave irradiation.

They compared catalytic efficiency of PTC and various bases in the synthesis of stillbene using various onium salts, including tetrabutylammounium chloride (TBAC), tetrabutylammounium bromide (TBAB), tetrabutylammounium iodide (TBAI) and polyethyleneglycol (PEG). The following order illustrates the relative activity of different catalysts and bases: TBAB>TBAI>TBAC>PEG-400 & K2CO3>Na2CO3>NaHCO3>NaOH (Table 7). For comparison, the yields of the microwave irradiation assisted reaction and conventional heating reaction results are summarized in Table 8. The results showed that the synthesis of compounds 32ag under microwave irradiation were 1842 times faster than

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P.A.Vivekanand and Maw-Ling Wang

conventional heating. This ratio between the reaction time using conventional reflux and microwave irradiation (tc/tmw) under same conditions quantifies the microwave heating effect. PTC approach proceeds most efficiently when carried out in the presence of aqueous solution of sodium carbonate or hydroxide and catalytic amount of PT catalyst. Jeffery and Ferberone [151] reported one pot synthesis of unsymmetrical (or symmetrical) trans-stilbene derivatives based on two sequential PTC-Heck-type reactions effected in the presence of tetrabutylammonium salt-based catalyst systems, using haloarenes (31) and vinyltrimethylsilane (33) as double bond equivalent (Scheme 14). The procedure followed results in highly chemo-, regio-, and stereoselective products.
Table 7. Influence of Catalyst (PTC) and Base on the Formation of 32aa
Base K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 Na2CO3 NaHCO3 NaOH PTC No PTC PEG-400 TBAC TBAI TBAB TBAB TBAB TBAB Yield of 32ab 30 80 84 90 91 88 61 52

a-The reaction was carried out in H2O at a power level of 375W for 10 min under argon; b- Isolated yield.

Table 8. Role of Microwave and Conventional Heating in the Heck product formation
Product 32a 32b 32c 32d 32e 32f 32g Microwave heating (375 W) tmw(min) Yield (%) 10 91 10 88 10 92 10 89 10 86 10 89 10 93 Conventional Heating tc(min) Yield (%) 420 85 180 88 420 90 180 80 180 80 420 84 300 54

tc/tmw 42 18 42 18 18 42 30

SiMe3 33

ArI 31

1)cat.Pd(dba)2, KF, TBAC, Toluene, Room Temp. 2) removal of excess CH2-CHSiMe3 Ar 3)cat.PR3 or without PR3 Ar'X, DMF, K2CO3 65-105 0C

Ar'

34

Scheme 14. PTC assisted palladium-catalyzed synthesis of unsymmetrical stilbene derivatives.

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347

Unsymmetrical trans-stilbenes (34) obtained in high yields by treating aryl iodide with an excess of vinyltrimethylsilane, in the presence of potassium fluoride, tetra-n-butylammonium chloride and catalytic amounts of bis(dibenzylideneacetone)palladium (Scheme 14). In order to effect second Heck reaction the excess of vinyltrimethylsilane (33) was then removed under reduced pressure. The second Heck reaction was realized in wet N,Ndimethylformamide, in the presence of already present palladium catalyst and tetra-nbutylammonium chloride system and added potassium carbonate. This second step can be carried out either in presence or absence of phosphine ligand at room temperature (Table 9, entries 13). Further, heteroaromatic trans-stilbenes can be synthesized using this methodology (Table 9, entries 46). GCMS analyses of the reaction mixtures indicated a nearly exclusive formation of stilbene derivatives, with a very high isomeric selectivity for the (E) configuration ranging between 96 and 99%.
Table 9. Comparative yields of unsymmetrical stilbene derivatives synthesized by Heck reaction.
Entry Ar-X (31)
I

Ar-X (31)
I

PR3/Pdb

Temp (o C) Product (34)

Ar'

Yield [%][b] 90 60 (96) 72 (94) 66 (80) 60 (84) 72 (94)

1
MeO I Cl
I

0 0 2
I

65 85 65 65

Ar Ar= 4-OMeC6H4 Ar'= 4-ClC6H4 Ar' Ar Ar= 4-ClC6H4 Ar'= 2-naphthyl Ar'

2
Cl I

3
Cl MeO
I

Ar Ar= 4-ClC6H4 Ar'= 4-OMeC6H4

Ar'

2
Br

85

Ar Ar= 2-thienyl Ar'= 2-naphthyl

Ar'

2.5
I

105

Ar Ar= 2-thienyl Ar'= 4-N(Me)2-C6H4

Ar'

0
MeO

65

Ar Ar= 2-thienyl Ar'= 4-OMe-C6H4

Similarly symmetrical stilbene derivatives were synthesized by treating of 2 equiv. of an aryl iodide (31) with 1 equiv. of vinyltrimethylsilane (33) and were followed by arylation in wet DMF in the presence of palladium catalyst and tetra-n-butylammonium chloride (already present in the reaction mixture) and potassium carbonate (added), with or without triarylphosphine. Stilbene derivatives with a very high isomeric selectivity ranging between 95 and 99% were formed. The authors further confirmed the potential and efficiency of the described methodology by a concise, convenient, highly chemo-, regio-, and stereoselective synthesis of resveratrol (trans-3,5,4-trihydroxystilbene).

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AZIRIDINES
Aziridines are organic compounds containing one amine group and two methylene groups and are constituents of several molecules presenting biological activity, for example, azinomycins and mytomycins [152]. These nitrogen-containing heterocyclic compounds are frequently show up as substructures in natural products and also show potent biological activities[153]. For that reason, chemists would like to develop practical and convenient methods for constructing aziridine compounds. Researchers are particularly interested in terminal aziridines due to their facile ring-opening with various nucleophiles [154]. Synthesis of aziridines by conventional methods suffers from several disadvantages such as long reaction time, use of toxic and organic solvent, difficulty of recovery of high boiling solvent relative to the stability of aziridines, high reaction temperature and use of additives [155]. In this regard PTC methodology is can be applied in the synthesis of aziridines. Rolf Carlson et al. [156] have developed a practical, highly efficient and simple aziridinaton protocol for -bromo-2-cyclopenetenone derivatives 35 (Scheme 15). Also they have assessed different reaction conditions to apply tandem conjugate addition initiated ring closure (CAIRC) reactions and reported the synthesis of N-substituted bicyclic-a-ketoaziridines (37) from a series of primary amines (36) applying eight different PTCs particularly using tetrabutylammonium bromide, TBAB in H2O (Table 10). Most of the reactions gave similar results using various PTCs.

O Br RNH2 TBAB, H2O rt

O H R H 37(a-h) N

35

36(a-h)

R = phenylethyl(a), benzyl(b), furayl(c), cyclohexyl(d), allyl(e), propyl(f), butyl(g) and tert-butyl amine(h)
Scheme 15. Aziridinaton -bromo-2-cyclopenetenone using PTC protocol

Table 10. Effect of different some phase transfer catalysts on aziridination of -bromo-2cyclopenetenone in the presence of H2O at room temperature.
Entry No. 1 2 3 4 5 6 7 8 PTC Benzyldimethyl 2-hydroxymethylammonium chloride Tetrabutylammonium fluoride Tetrabutylammonium iodide Tetrabutylammonium terafluroborate Tetrabutylammonium hydrogen sulphate Tetrahexylammonium bromide Benzyltriethylammonium chloride Tetrabutylammonium bromide Yield of 37b (%) 89 54 88 79 82 87 74 91

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349

Especially, the aziridination reactions mediated by benzyldimethyl-2-hydroxyethyl ammonium chloride, Bu4NI, Hex4NBr and Bu4NBr (entries 1, 3, 6 and 8, respectively) proceeded in a similar manner with good to excellent yields.
Table 11. Influence of various aliphatic primary amines on aziridination of -bromo-2cyclopenetenone in presence of TBAB.
Entry No. 1 Amine 35b Time (h) 5 Product
O

Yield(%) 93

37b

35a

98
N

35c

37a O

91
o N

35d

37c O

90
N

37d

35e

96

37e

35 h

97
N

35f

37h O

95
N

37f

35g

94
N

37g

Further they examined the role of various aliphatic primary amines 35ah (phenylethyl, benzyl, furayl, cyclohexyl, allyl, propyl, butyl and tert-butyl amines, respectively) in the aziridination of -bromo-2-cyclopenetenone under PTC condition and observed excellent reactivity with all the tested amines (Table 11). Particularly, the reaction of t-BuNH2 (35h) was very fast and the reaction was completed within 1 h. Cyclization of 3-Arylamino-2-chloropropane nitriles, obtained by the interaction of arylamines with -chloroacrylontrile, is an efficient method under PTC condition to prepare N-aryl-2-cyanoaziridines [157].

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In general, phase transfer catalysis in presence of nitrogen- and phosphorus-based catalysts is carried out under strongly basic and nucleophilic conditions. Hence their utility under these strenuous conditions is well understood. Researchers have seldom employed carbocations as phase transfer agent under such conditions. Previous reports indicate the possibility of synthesis of stable carbocations [158]. Stable carbocations and triazatriangulenium ions were synthesized starting from tris(2,6-dimethoxyphenyl)carbenium ion and primary alkylamines [159-164]. Recently, there is an upsurge in interest in catalytic community about utility of these triazatriangulenium ions as phase transfer agent. Nicolas and Lacour [165] explored its utility in several classical PTC reactions and compared their efficiency to that of tetrabutylammonium bromide and 18-crown-6. In order to understand the partition ability, hydrophilicity and lipophilicity, they synthesized several triazatriangulenium cations bearing alkyl side chains of various lengths and polar/apolar character (Scheme 16) and followed various organic reactions viz., aziridination, dichlorocarbene addition, ester alkylation and alkene epoxidation.

MeO OMe + O O MeMe 38 [BF4]

OMe OMe

R-NH2 (excess) 170-180 oC

N +

39 [BF4]

N R 41% 40% 44% 44%

39a; R = (CH2)OH 39b; R = (CH2)CH3 39c; R = (CH2)5CH3 39d; R = (CH2)7CH3

Scheme 16. Synthesis of Triazatriangulenium Salts, [39a] [BF4]-[39d] [BF4].

Catalytic efficiency (Scheme 17 & Table 12) of these triazatriangulenium Cations were compared with TBAB in aziridine reaction of styrene (40) with a mixture of Chloramine-T (41) and diiodine by following Minakata and Komatsu protocol [166]. The order of the activities for these catalysts after five hours of reaction : [39a][BF4] < [39b][ BF4] < [39d][ BF4] < [39c][ BF4] < TBAB. Higher conversions and yields (80 and 85%) were reported by the authors by extending the reaction time to 15 and 24 h with salts TBAB and [39c][BF4], respectively.

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C6H5

+ 41

40

Ts O Cl cat.(10 mol%), I2 N S N Na O CH2Cl2 :H2O C6H5 20 0 C 42

Scheme 17. Aziridinaton of styrene (40) with chloramine-T (41) using PTC protocol.

Table 12. Aziridination of Styrene by Chloramine-T/I2 under PTC condition.

Entry 1 2 3 4 5 6 7 8 Catalyst TBAB [39a][BF4] [39b][BF4] [39c][BF4] [39d][BF4] TBAB [39c][BF4] no Time(h) 5 5 5 5 5 15 24 5 Yield (%) 30 5 7 23 16 80 85 3 Conversion (%) 37 7 9 28 20 95 100 5

+ O 43a (2 equiv)

Cl

N Na

Cbz

PhCH2N+Et3 Cl- (10 mol%) MeCN, RT, 2 h

Cbz

44

44: 80%

NaCl

PhCH2N+Et3 Cl-

Cl O

N _

Cbz _O

Cl N Cbz PhCH2N+Et3

PhCH2N+Et3

Scheme 18. Mechanism of aziridination of methyl vinyl ketone (43a) and chloramine- Cbz (44 ).

Minakata et al. [167] developed a simple synthetic method for the catalytic aziridination of electron deficient olefins with N-chloro-N-sodio benzyl carbamate based on solidliquid phase-transfer catalysis using BTEAC as phase transfer agent. Aziridination reaction between methyl vinyl ketone (43a) and chloramine- Cbz (44), was followed by using 10 mol % of BTEAC under solidliquid phase-transfer catalysis condition, afforded the aziridine product

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in 80% yield in 2 hours and for this reaction they proposed a rational mechanism. Initially, the sodium ion of chloramine- Cbz (44) is exchanged for an ammonium ion, subsequent Michael addition of the soluble nitrogen species to the enone gives the enolate and finally intramolecular cyclization affords the desired aziridine (Scheme 18). The successfully extended this protocol to Methyl acrylate (43b) and phenyl vinyl sulfone (43c). Unexpectedly, even in presence of only 1 equiv. of 43d, with an oxazolidinone auxiliary, was found to be a good substrate for the aziridination reaction. Resulting in high yields (Scheme 19 & Table 13). Olefins 43e and 43d afforded products in 60 and 58% yields respectively. Further, they explored asymmetric reactions by using chiral ammonium salt catalysts derived from cinchona alkaloids, yielding optically-active aziridines with an enantiomeric purity of up to 87% ee.

EWG 43

R1

Cl

Cbz N Na 44

BTEAC MeCN, RT

EWG 45

Cbz R1

Scheme 19. BTEAC catalyzed aziridination of electron-deficient olefins (43) with chloramine- Cbz (44).

Table 13. Influence of various electron-deficient olefins in the aziridination reactions.

Entry 1 2 3 4 5
a

EWG
MeO O
Ph S O O
O O O O O O N O N O N O

R1 H H H Me CO2Et

Equiv.a 2(43b) 2(43c) 1(43d) 2(43e) 1(43f)

Cat (mol%) 20 20 10 10 10

Time/h 24 4 4 24 24

yield (%) 85 89 93 60 58

Equiv. of 43

EPOXIDATION
Epoxidation of olefins is one of the most important reactions in organic synthesis as the epoxides are useful intermediates in the manufacturing of a variety of chemicals. Developing new catalysts that will utilize environmental friendly oxidants for alkene epoxidation as an

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alternative to the stoichiometric oxidation processes still continues to be a subject of interest [168-170]. Epoxidation of olefins is a classical PTC operation and has been the theme of numerous synthetic and mechanistic studies in the recent past [171-180]. Kinetic study of ultrasound assisted phase-transfer catalyzed epoxidation of 1,7-octadiene is greatly enhanced by using a cocatalyst of phosphotungstic acid in the presence of hydrogen peroxide in an organic solvent/aqueous solution two-phase medium [61]. The organic-phase reactions, including two series reactions, are the rate-controlling steps to produce two products, viz., 1,2-epoxy-7octene and 1,2,7,8-diepoxyoctane. An active intermediate of the catalyst (Q3PW12(O)nO40, where Q = R4N+) produced from the reaction of phosphotungstic acid, hydrogen peroxide, and Aliquat 336.

Aliquat 336 Phosphotungstate Acid Hydrogen Peroxide 45 (C8H14, A) 46 (C8H14O, B)

O O 47 (C8H14O, C)

Scheme 20. Epoxidation of 1,7-octadiene under PTC conditions.

For that, a rational mechanism is proposed as follows:

nH2O2 + H3PW12O40 ka,1 Aqueous Phase H3PW12(O)nO40 + nH2O

Q3PW12(O)nO40 + 3HCl

ka,2

H3PW12(O)nO40 + 3QCl Interface

Q3PW12(O)nO40 + H2O kQPWO Q3PW12(O)nO40 + C8H14

ka,3

Q3PW12(O)n-1O40 + H2O2 kQPWO

k1

Q3PW12(O)n-1O40 + C8H14O

Q3PW12(O)nO40 + C8H14O

k2

Q3PW12(O)n-1O40 + C8H14O2 Organic Phase

Scheme 21. Mechanism of epoxidation of 1,7-octadiene under PTC conditions.

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where ka,1 = first intrinsic rate constant in the aqueous solution, ka,2 = second intrinsic rate constant in the aqueous solution, ka,3 = third intrinsic rate constant in the aqueous solution, k1 = first intrinsic rate constant in the organic solution, k2 = second intrinsic rate constant in the organic solution, kQPW = mass-transfer coefficient of Q3PW12(O)n-1O40, kQPWO = mass-transfer coefficient of Q3PW12(O)nO40, and n is the number of peroxo oxygen atom with tungsten metal (W = O) firmed between the reaction of hydrogen peroxide (H2O2) and phosphotungstic acid (H3PW12O40). Mechanistically, the epoxidation of 1,7-octadiene involves several steps. First, an active intermediate H3PW12(O)nO40, which is a real oxidant, was formed from the reaction of phosphotungstic acid and hydrogen peroxide in the aqueous phase. An ionexchange reaction that took place between this real oxidant and phase-transfer catalyst to form the active intermediate of the catalyst Q3PW12(O)nO40 at the interphase between two phases. Then, this active intermediate of the catalyst Q3PW12(O)nO40, which is organic soluble, transfers to the organic phase and reacts with the organic-phase reactant (C8H14, A) to form the epoxides (C8H14O, B and C8H14O2, C).There are many active oxygens for this active intermediate of the catalyst. However, only one oxygen, providing for the epoxidation, supplies 1,7-octadiene. Therefore, the active intermediate of the catalyst is reduced to Q3PW12(O)n-1O40, which can be transferred to the interface for regeneration to produce the active intermediate of the catalyst. Thus, the overall reaction involves the ion exchange, the complex reaction in the aqueous phase, the organic-phase reaction, and the mass transfer of catalyst between two phases. A pseudo steady- state rate law is sufficient to describe the kinetics of epoxidation of 1,7-octadiene. We compared the catalytic efficiency of various commercial PTCs in the epoxidation of 1,7-octadiene. The quaternary ammonium salts used in this study include tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride (TBAC),trioctylmethylammonium chloride (Aliquat 336), tetraethylammonium chloride (TEAC), and tetrahexylammonium chloride (THAC), (Table 14) .Catalytic activity of these onium salts indicate that their efficiency in the epoxidation reaction depends primarily on two factors viz., i) total number of carbons in the salt and reactivity of halides. The kinetic investigations reveal that those quaternary ammonium salts with larger total carbon numbers possess higher catalytic reactivity. The main reason is that the organic-phase reaction is the rate-controlling step. Those larger total carbon number quaternary ammonium salts, which participate in the formation of the active intermediate of catalyst, prefer to stay in the organic phase, i.e., the concentration of the active intermediate of catalyst in the organic phase is increased with an increase in the total carbon numbers of the quaternary ammonium cations. Hence, almost no reaction occurs in using TEAC as the phase-transfer catalyst in the epoxidation of 1,7-octadiene in using phosphotungstic acid as the cocatalyst. Aliquat 336 and THAC have almost the same total number of carbon atoms in the quaternary ammonium cation. In comparison with the reactivity of these two quaternary ammonium salts, we found that the reactivity of Aliquat 336 is obviously larger than that of THAC because of the lack of unsymmetry in the alkyl groups of the quaternary ammonium cation. The steric hindrance for an unsymmetric quaternary cation is small when it is used to attack the double-bond compounds. Hence, these quaternary ammonium salts unsymmetric cation possess high reactivity. In addition, the order of reactivity of TBAI, TBAB, and TBAC is TBAI > TBAB > TBAC. Actually, the ion-exchange reaction of Q+(X-) with H3PW12O40 takes place in the aqueous phase to form a complex that is ready to transfer to the organic phase through the

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interface. The order of the selectivity constants K(X-) is K(I-) > K(Br-) > K(Cl-) [121]. Therefore, TBAI exhibits higher reactivity among these three quaternary ammonium salts. These three quaternary ammonium salts have the same total number of carbon atoms in the quaternary ammonium cation. However, the iodide ion (I-), which possesses higher activity, prefers to exchange with the phosphotungstic ion, leading to the formation of the active intermediate of the catalyst. The two corresponding apparent rate constants, kapp,1 and kapp,2, are shown in Table X. Obviously, Aliquat 336 possesses higher values of kapp,1 and kapp,2, and a smaller value of tB,max because of its higher reactivity.
Table 14. Influence of the quaternary ammonium salts on the conversion of 1,7octadiene: 35 ml of H2O2 (8%, 9.23 x 10-2 mol), 32 ml of chloroform, 9.09 x 10-3 mol of 1,7-octadiene, 5.77 x 10-4mol mol of quaternary ammonium salt, 1.92 x 10-4 mol of H3PW12O40, 3.24 x 10-3mol of biphenyl, 50 0C, 1000 rpm, ultrasound conditions (28 kHz, 200 W).
PTC TEAC 0 0

kapp1 (x 10-3min-1) kapp2 (x 10-3 min-1) tB,max (min)

TBAC 0.6 0.24 2545.25

TBAB 0.80 0.39 1752.35

TBAI 1.31 0.72 1014.46

THAC 3.2 1.02 524.47

Aliquat 336 20.26 8.54 73.71

Further, we examined the role of Aliquat 336 and the H3PW12O40 (cocatalyst) in the epoxidation of 1,7- octadiene. As shown in Fig. 7, it is found that the conversion of 1,7octadiene is low in using sodium tungstate and phosphoric acid as the cocatalyst. In epoxidation, the conversion of 1,7-octadiene is also low in the absence of Aliquat 336 and phosphotungstic acid or by individually using each compound. Without the addition of a cocatalyst, the epoxidation is still low only by hydrogen peroxide oxidation. The active intermediate of the catalyst H3PW12(O)nO40, which only stays in the aqueous phase, is not effectively transferred to the organic phase in the absence of Aliquat 336. In contrast, the reaction is enhanced only in the presence of both Aliquat 336 and the active cocatalyst H3PW12O40 To examine the influence of ultrasonic irradiation on the conversion of 1,7-octadiene, we compared the conversion of 1,7-octadiene in silent and ultrasonic conditions. At 120 min, without ultrasonic irradiation the conversion of 1,7-octadiene is only 76%, but in the presence of ultrasonic the conversion is 97% and almost 100% for 28 kHz and 40 kHz, respectively. Selective epoxidation of alkenes (norbornene, cyclohexene, limnone cyclooctene cyclohexene, styrene and cis-stilbene) with aqueous H2O2 as the oxidant in presence of Na9[SbW9O33] -methyl tricapryl ammonium chloride system was investigated by Ingle and Raj under solventless condition [181]. PTC assisted epoxidation of cyclooctene gave only the epoxide with near quantitative yields, even at ambient temperature conditions and shows no tendency to undergo allylic oxidation or cleaving of the epoxide like cyclohexene (Table 15). Epoxidation of cis-stilbene, another activated alkene, gave a mixture of both cis-stilbene oxide (88% selectivity) and trans-stilbene oxide (balance) as products at the maximum conversion of the substrate (conversion: 57%). Epoxidation of norbornene and cyclohexene, at lower substrate: oxidant ratio, resulted in excellent selectivity for the epoxide. However, on increasing the substrate: oxidant ratio, cyclohexene chiefly underwent allylic oxidation while

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norbornene gave norbornanone. Terminal alkenes are normally very less reactive but with this catalytic system, 1-octene gave a moderate conversion of 38% and showed >99% selectivity for the epoxide. In the case of limonene, stereoisomers of limonene-1,2-oxide was the only product obtained.

Figure 7. Effect of the phase-transfer catalyst and cocatalyst on the conversion of 1,7-octadiene: 35 ml of H2O2 (8%, 9.23 x 10-2 mol), 32 ml of chloroform, 9.09 x 10-3 mol of 1,7-octadiene, 5.77 x 10-4 mol of Aliquat 336, 1.92 x 10-4 mol of H3PW12O40, 1.44 x 10-3 mol of Na2WO4, 2.88 1013 mol of H3PO4, 3.24 x 10-3 mol of biphenyl, 50 0C, 1000 rpm, ultrasound conditions (28 kHz, 200 W).

Hydroxyl-terminated polybutadiene (HTPB) is widely used as fuel binder in composite solid propellants and adhesives and sealants [182-187]. Wang et al. [188] investigated PTC assisted epoxidation of hydroxyl-terminated polybutadiene (HTPB) via using H2O2 as the oxidant and ammonium tungstate hydrate and phosphoric acid as the cocatalysts in an acidic solution/organic solvent two-phase medium. To explore the influence of Aliquat 336 on the kinetics of epoxidation of HTPB, the amount of the catalyst was varied at constant amount of phosphoric acid and ammonium tungstate hydrate. The results indicate that the degree of epoxidation of HTPB increases from 5.3% to 47.7% with the increase in the amount of Aliquat 336 up to 0.76 mmol. A further increase in the amount of Aliquat 336 does not improve the reactivity. This is because of the active catalyst Q3{PO4[W(O)(O2)2]4} (Q+ was the quaternary cation), which possesses high reactivity to catalyze the epoxidation of olefins. By using a fixed amount of phosphoric acid and ammonium tungstate hydrate, the amount of the synthesized active catalyst was also maintained at a fixed value. However a higher amount of Aliquat 336 does not increase the amount of the active catalyst to enhance the

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reactivity. Optimum condition for the reaction was found to be 3:2, the molar ratio of Aliquat 336 to (NH4)5H5[H2-(WO4)6]H2O).
Table 15. Oxidation of various alkenes over Na9[SbW9O33] + PTC with aqueous H2O2 as oxidant at different temperatures and different substrate: oxidant ratios.
Entry No. Substrate 1 2 3 Norbornenea Norbornenea Cyclohexene Sub.:aqu. H2O2 Time (h) Temp. ratio (0C) 1:1 5 60 1:2 1:1 5 6 60 35 Conv. (%) Selectivity (%) 5 5 6 Norbornene epoxide (80) norbornanone (20) Norbornene epoxide (11) norbornanone (89) Cyclohexene epoxide (25) Cyclohexene-2-ol (41) Cyclohexene-2one (34) Cyclohexene epoxide (92) Cyclohexene diol (8) Cyclooctene epoxide (>99) Cyclooctene epoxide (>99) cis-stilbene epoxide (88) trans-stilbene epoxide (12) 1-Octene epoxide (>99)

4 5 6 7 8

Cyclohexene Cyclooctene Cyclooctene cis-stilbene 1-Octene

1:0.5 1:1 1:2 1:2 1:2

6 6 9 6 9

35 60 35 60 60

6 6 9 6 9

Reaction conditionsNa9[SbW9O33]: 0.01 mmol, PTC: 0.09 mmol, substrate: catalyst ratio (500:1). a 1ml toluene was used as solvent
OCH3 O
S S

O O

OCH3 O
R S

O N R O O

O N R O O

OCH3 O
S R

O N R

48

49

50

Scheme 22. Methyl -D-glucopyranoside- (48), methyl -D-mannopyranoside- (49) and methyl -Daltropyranoside-based (50) chiral crown ethers, R = CH2CH2CH2OH.

Mako et al. [189] synthesized various novel, optically active crown ether derivatives from -D-altropyranoside (Scheme 22). They investigated the catalytical potential of these crown ethers by following epoxidation of trans-chalcone with tert-butyl hydroperoxide

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P.A.Vivekanand and Maw-Ling Wang

(Scheme 23). The investigation revealed a significantly different asymmetric induction by D-glucopyranoside-, -D-mannopyranoside-, and -D-altropyranoside-based chiral crown catalysts. This Indicates the influence of absolute configuration of the crown-ring fused carbon atoms of the monosaccharides on the enantioselectivity. Molecular modeling (MCMM) and subsequent DFT calculations indicate that the use of mannopyranoside based crown ether (49) and that of glucopyranoside-based catalyst (48) results in the preferred formation of the opposite antipodes of the corresponding epoxyketone. In contrast, when altropyranoside-based crown (50) is employed as catalyst, practically no asymmetric induction was noticed.

O catalyst, t-BuOOH toluene, aq.20%NaOH 51

O H

O H

52

Scheme 23. Epoxidation of trans-chalcone with tert-butyl hydroperoxide using novel, optically active crown ether (50) as catalyst.

Recently, epoxidation of substituted chalcones and chalcone analogues (53) with tertbutylhydroperoxide catalyzed by the chiral monoaza-15-crown-5 lariat ethers annellated to methyl-4,6-O-benzylidene--D-glucopyranoside- or mannopyranoside have been investigated [190] and the results indicates significant asymmetric induction (Scheme 24). Also the study explains the importance of the position of the substituents in the aromatic ring of the chalcone on the chemical yields and enantiomeric excesses. The lowest enantioselectivities were obtained in the case of ortho-substituted model compounds and the highest ee values were found in the case of para-substituted models ortho-substituted model compounds (Table 16).

O Ar' 53 catalyst, t-BuOOH toluene, aq.20%NaOH Ar'

O R 54 S

Scheme 24. Epoxidation of substituted chalcones with tert-butyl hydroperoxide using crown catalyst.

Chalcones with electron- donating methyl-substituent afforded products 54bd in better yields (7290%) and the ee values increased according to the position of methyl group (71%, 87%, and 92%, respectively) (Table 16, entries 24). Authors reported a similar trend in the case of methoxy-substituents 54e-g. In the presence of catalyst 1, the yields were 5877%, while the ee values were in the range of 8495% (Table 16, entries 5-7). In the chlorophenyl epoxyketones cases, the products 54h-k were obtained in 6571% yields and the ee values increased according to the position of the chloro-substituent: the 2-chlorophenyl-, 3chlorophenyl-, and 4-chlorophenyl products were obtained in an ee of 69%, 79%, and 97%,

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respectively (Table 16, entries 810).Epoxidation of chalcones with electron-withdrawing nitrosubstitutent afforded epoxyketones 54l-n in 5566% yield with high (8099%) ee values(Table 16, entries 1113).The substituents close to the reaction center prevent the asymmetric induction, hence the further the substituents are placed from the reaction center, the higher the extent of enantioselectivity.
Table 16. Effect of substituents in chalcone on the asymmetric epoxidation in the presence of chiral crown ether 1 at 02 0C.
Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 Product 54a 54b 54c 54d 54e 54f 54g 54h 54i 54k 54l 54m 54n Ar Ph 2-CH3-Ph 3-CH3-Ph 4-CH3-Ph 2-CH3O-Ph 3-CH3O-Ph 4-CH3O-Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph 2-NO2-Ph 3-NO2-Ph 4-NO2-Ph Time(h) 1 4 2 2 8 2 3 3 2 2 1 1 2 Yield (%) 82 72 90 81 69 77 58 65 68 71 66 55 63 ee (%) 94 71 87 92 84 88 95 69 79 97 80 >99 96

The ultrasound irradiation assisted epoxidation [191] of chalcones with aqueous sodium hypochlorite catalyzed by benzyldimethyltetradecyl ammonium chloride afforded 2,3-epoxyl1,3-diaryl-1-propanones in good yield. On increasing the temperature to 3034 0C or 4044 0 C, the yield of epoxidation of benzalacetophenone increases to 79% and 83%, respectively (Entries 2 & 3; Table 17). In the absence of PTC, only 6% yield was observed (Entry 4; Table 17). On increasing the amount of benzyldimethyltetradecyl ammonium chloride from 0.025 mol equivalent catalyst to 0.05 mol equivalent, the yield of epoxide increases from 84% (Entry 5; Table 16); to 93% (Entry 6; Table 17).
Table 17. Influence of temperature and catalyst concentration on the epoxidation of benzalacetophenone with sodium hypochlorite catalyzed by PTC under ultrasound irradiationa. Temperature Yield(%) Entry Amount of Substrate/NaClO(mol) PTC(mmol) 1 0.05 1:1.5 22-26 48 2 0.05 1:1.5 30-34 79 3 0.05 1:1.5 40-44 83 4 0 1:1.8 40-44 6 5 0.025 1:1.8 40-44 84 6 0.05 1:1.8 40-44 93
a- Reaction time: 2 h.

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ESTERFICATION
In last decade, a great number of esters have been synthesized using the phase transfer catalysis methodology [192-202]. Yang and Peng [203] reported the esterification of sodium salicylate to synthesize butyl salicylate catalyzed by TBPB under ultrasound irradiation in a continuous two-phase-flow reactor. They investigated the effects of power and frequency of ultrasound on the third-liquid catalyzed esterification (Table 18). The product yields were 65.1% (silent, kapp = 0.0112 min-1), 78.2% (300 W, 28 kHz, kapp = 0.0215 min-1), 71.5% (300 W, 40 kHz, kapp = 0.0150 min-1), 71.2% (300 W, 50 kHz, kapp = 0.0148 min-1) and 69.3% (300 W, 80 kHz, kapp = 0.0135 min-1), decreasing with the increase of ultrasonic frequency. The higher frequency resulted in a larger sonic resistance and loss of energy during the sonic waves propagating through the medium. The effect of power of ultrasound on the reaction was performed at a frequency of 28 kHz. At 200 W, the kapp was found to be 0.0139 min-1; at 100 W the kapp was found to be 0.0108 min-1A high power of ultrasound offers much energy into the medium to enhance the reaction. PTC methodologies are used to activate carboxylate nucleophiles for the purpose of preparing ester derivatives of brominated poly (isobutylene-co-isoprene) (BIIR). TBAB plays a dual catalytic role in PTC esterifications of BIIR by rendering carboxylate anions nucleophilic and by isomerising exoallylic bromide into more reactive BrMe electrophiles [204]. The sensitivity of reaction rates to TBAB concentration is examined by the authors. The initial reaction rate generated by 0.1 equiv. catalyst was improved by a factor of 2.4 on increasing the catalyst loading to 0.75 equiv and by a factor of only 2.8 when 1.5 equiv of TBAB was employed. The results reveal that catalytic amounts of the catalysts do support an efficient process and that higher levels have a relatively small effect on reaction velocities. Knowledge of reaction fundamentals are used to prepare copolymers from BIIR and carboxylate-terminated polybutadiene (cBR) that phase-partition in the manner required for blend compatibilization applications.
Table 18. Effect of ultrasonic frequency and power on the esterfication of sodium salicylate.
Entry No. 1 2 3 4 5 6 7 Power (W) 0 300 300 300 300 100 200 Frequency(kHz) 0 28 40 50 80 28 28 Product Yielda organic exit (%) 65.1 78.2 71.5 71.2 69.3 64.3 69.8 in kapp(10-2 min-1) 1.12 2.15 1.50 1.48 1.35 1.08 1.39

An environment friendly method was developed for the alkylating esterification of 1hydroxy-3-phospholene oxides under solventless, phase transfer catalytic, and MW conditions [205]. The MW-promoted alkylations were carried out in solidliquid phase in the presence of 1 equiv. of potassium carbonate, in the absence of any solvent at 100 0C using

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different alkylating agents viz., benzyl bromide, ethyl iodide, n-propyl bromide, isopropyl bromide and n-butyl bromide (Scheme 23).

+ P HO O 55

K2CO3/TEBAC RX MW, 100 0C RO P O 56

X= Br, I R=Bn(a) Et(b), nPr(c), iPr(d), nBu(e).

Scheme 25. Esterification of 1-hydroxy-3-phospholene oxides under solventless, phase transfer catalytic and MW conditions.

Table 19. Esterification of 1-Hydroxy-3-methyl-3-phospholene 1-Oxide (55) by alkylation at 100 C in the presence of K2CO3.
Entry No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 RX PrBr EtI EtI n PrBr i PrBr i PrBr n BuBr n BuBr BnBr BnBr n BuBr n BuBr BnBr BnBr
n

TEBAC 5% 5% 5% 5% 5% 5% 5%

Mode of Heating MW MW MW MW MW MW MW MW MW MW a a a a

Irradiating Time/Heating Time(Hours) 1b 1b 1b 1b,c 1.5d 1b 1b 1b,c 1b,c 1b,c 1b 1b,c 1b,c 1b,c

Yield (%) 73 90 80 94 42 65 69 96 92 94 64 89 85 87

aThermal heating.

In the absence of triethylbenzylammonium chloride (TEBAC), the ethyl (56a), n-propyl (56b), n-butyl (56d), and benzyl (56e) esters were obtained in 80, 73, 69, and 92% yield, respectively, (Table 19, entries 1, 3, 7, and 9). However in the presence of 5% of TEBAC, all reactions went to completion and the yields were, in the above order, 90, 94, 96, and 94%, respectively (Table 19, entries 2, 4, 8, and 10). The authors reported that except in the case of benzyl bromide, the yields were significantly higher in the presence of 5% of TEBAC. Thus, the esterfication with reagents of normal reactivity may be promoted by the use of TEBAC.

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Further, for comparison purpose, some of the above reactions were also carried out under thermal conditions. Uncatalyzed thermal reaction of hydroxyphospholene oxide with n-butyl bromide and benzyl bromide, esters 56d-e were obtained after 1 h in 64 and 85%, respectively (Table 19, entries 11 and 13). On the other hand, in the presence of 5% of TEBAC, both alkylations were essentially completed as the isolated yields were 89 and 87%, respectively (Table 19, entries 12 and 14). The MW-promoted esterifications were more efficient than the thermal variations, resulting in improved yields (57%) (Table 19, entries 7 vs. 11, 8 vs. 12, 9 vs. 13, and 10 vs. 14).

CONCLUSION
Nowadays, PTC catalyzed reactions belong in the toolbox of each synthetic organic chemist and have been used in many fields of organic synthesis leading to products of various interests. Still there is an urge in their minds to find more and more methods that augment their catalytic activity. This can be achieved by optimizing reaction conditions by the use of ingenious new analytical techniques viz., ultrasound and microwave irradiation, or by the use onium salts with multi active sites. We have presented in this chapter some recent trends in the PTC catalyzed reactions viz., the alkylation reactions, Heck reaction, aziridine reaction, epoxidation and esterfication that highlight the efforts and interest in developing more efficient processes according to the new requirements of the chemistry of the 21st century. Ingenious new analytical and experimental techniques in conjunction with PTC have been compared with conventional PTC techniques. The comparison is very encouraging for future applications of these techniques in conjunction with PTC. The salient advantages of this green technology are easily recognized in the examples given. The chapter supports the growing importance shown by researchers for highly active onium salts with multiple number of active-sites. A vast array of experimental parameters, viz., substrates, catalytic system, bases, temperature, solvent, ultrasonic frequency and microwave power, influence on optimum reaction conditions have been outlined. Special features and mechanistic aspects are presented which helps us in understanding the practical value of this catalytic methodology. The development of PTC process in conjunction with various types of technologies delivers not only higher reactivity and stereoselectivity but also new synthetic opportunities, expanding the applicability of phase-transfer catalysis in modern organic synthesis. At present, the kinetic details of many PTC in conjunction with microwave/ultrasonic assisted reactions remain obscure. Improvements in reaction kinetics are expected with the advent of more systematic kinetic studies under these PTC conditions. Due to continuous improvements brought about by the advancements in the PTC technology, it can be predicted that how practical applications of PTCs can be further expanded in the future. However, continuous growth of PTC can be accelerated further only by the practicing chemists who will use the same brilliance and creativity that is the long tradition of catalysis and use it with the new perspective for transformative innovations for sustainability.

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[190] Mak, A.; Rapi, Z.; Keglevich, G.; Szllsy, .; Drahos, L.; Hegeds, L.; Bak, P. Tetrahedron: Asymm. 2010,21, 919. [191] Li, J.T.; Liu, X.F. Ultrason.Sonochem. 2008, 15, 330. [192] Joshi, S. R.; Sawant, S. B. Org.Proc.Res. & Dev. 2000, 4, 23. [193] Goetheer, E. L. V.; Baars, M. W. P. L.; Broeke, L. J. P. van den; Meijer, E. W.; Keurentjes, J. T. F.; Ind. Eng. Chem. Res. 2000, 39, 4634. [194] Yang, H.M.; Wu, P.I.; Li, C.M. Appl. Catal. A: Gen. 2000, 193,129. [195] Yang, H.M.; Wu, P.I. Appl. Catal. A: Gen. 2001,209, 17. [196] Pirkle W. H.; Snyder, S. E. Org. lett., 2001, 3, 1821. [197] Yang, H.M.; Lin, C.L. J. Mol. Catal. A: Chem. 2003, 206, 67. [198] Yang, H.M.;, Li, C. C. J. Mol. Catal. A: Chem. 2006,246, 255. [199] Castellanos, S.A. G.; Parent, J. S.; Whitney, R. A. Macromol. 2006, 39, 2514. [200] Yang, H.M.; Chen,C.H. J. Mol. Catal. A: Chem. 2009, 312, 107. [201] Chidambaram, M.; Sonavane, S. U.; Zerda, J. D. L.; Sasson, Y. Tetrahedron 2007,63,7696. [202] Gao, B.; Zhuang, R.; Guo, J. AIChE J. 2010, 56, 729. [203] Yang, H.M.; Peng, G.Y. Ultrason. Sonochem. 2010, 17, 239. [204] McLean, J. K.; Guillen-Castellanos, S. A.; Parent, J. S.; Whitney, R.A.; Kulbaba, K.; Osman, A. Ind. Eng. Chem. Res. 2009, 48, 10759. [205] Blint, E.; Jablonkai, E.; Blint, M.; Keglevich, G. Heteroatom Chem. 2010, 21, 211.

In: Homogeneous Catalysts Editors: Andrew C. Poehler

ISBN: 978-1-61122-894-6 2011 Nova Science Publishers. Inc.

Chapter 11

HEXENOIC ACIDS AND THEIR DERIVATIVES PREPARATION USING SELECTIVE HOMOGENEOUS CATALYSTS
Libor erven and Elika Leitmannov
Institute of Chemical Technology, Departement of Organic Technology, Czech Republic

INTRODUCTION
Some C6 unsaturated alcohols, aldehydes and acids are widely used in perfume chemistry. The easiest method for the preparation of hexenoic acids from the point of view of selectivity and simplicity is the selective hydrogenation of easily available sorbic acid (trans,trans-hex-2,4-dienoic acid). Depending on the catalyst used different regio and stereoisomers, can be obtained in various mixtures. From hexenoic alcohols the most commonly used compounds of this type are the socalled leaf alcohols, specifically cis-hex-3-en-1-ol and trans-hex-2-en-1-ol. These compounds can be prepared by selective hydrogenation of the sorbic alcohol obtained for example from the chemical reduction of sorbic acid. Details of the preparation of these compounds by hydrogenation using heterogeneous catalysts are given elsewhere [1-4]. The major disadvantages of the use of heterogeneous catalysts in this case are the low selectivity of the process (in the case of hex-3-enoic acid derivatives there is essentially no selectivity) and the use of sorbic acid itself is impossible. Instead salts or preferably methyl or ethyl esters are used, introducing another step to the process. The use of homogeneous catalysts opened new possibilities to carry out the hydrogenations and significantly higher selectivities of formation of the desired products. As stated above hexenoic acids and alcohols have very interesting fragrant properties. The titling of the two hexenols as leaf alcohols is partly reflective of their smell their fragrance resembles that of freshly cut grass. Perfumers [5] define their fragrance a little more precisely: cis-hex-3-en-1-ol is specified by its intense smell of fresh grass, it is a component of geraniol, lavender and brandy mint oil, it is added to flower aromas (lilac for example) and

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it can be used in imitations of mint and different fruit mixtures. trans-Hex-2-en-1-ol has in low notes a strong fruit smell (chrysanthemum or wine), it is sweeter and more fruity than cishex-3-en-1-ol and it is often used as a component of artificial strawberry. It is also used for a refreshing orange aroma and it is a component of artificial geraniol and lavender oil. transHex-2-en-1-oic acid has a warm fruit aroma after dilution, partly herbaceous and slightly acidic. It is used as an imitation of raspberry or in many other fruit aromas that require a caramel-acid note. The fragrant properties of hexenoic aldehydes are also very interesting for the perfume industry but the simplest method of preparation (aldol condensation) was not superseded by hydrogenation due to the low stability of aldehydes.

HOMOGENEOUS HYDROGENATION OF SORBIC ACID AND ITS DERIVATIVES

The homogeneous hydrogenation of sorbic acid and its derivatives can be defined by the position at which the hydrogen addition occurs. The addition of hydrogen at positions 2, 3 or 4 to the one of the double bonds of sorbic acid is defined as regioselective hydrogenation. In this type of reaction the trans configuration of the other double bond is preserved. When the hydrogen is added to positions 2 and 5 (generally called 1, 4 addition) both the cis and trans isomers can be formed. If in this reaction one of the isomers is formed preferentially the reaction is described as stereoselective hydrogenation. The following chapters detail the progress in the development of homogeneous organometallic catalysts for the selective hydrogenation of sorbic acid and its derivatives (esters, alcohols, salts).

ORGANOMETALLIC COMPLEXES BASED ON COBALT

The first homogeneous catalyst used for the hydrogenation of sorbic acid [6],[7] was K3[Co(CN)5]. The reaction was carried out at room temperature with a hydrogen pressure of 0.1 MPa at a 3.3:1 substrate: catalyst ratio in aqueous solution. Sorbic acid was added as its K+ salt and was selectively hydrogenated to the corresponding salt of trans-hex-2-enoic acid. In subsequent work [8] the selectivity was more precisely specified. The ratio of hexenoic acids was determined using gas chromatography. With water as a solvent the ratio of transhex-2- : trans-hex-3- : trans-hex-4-enoic acid was 82 : 17 : 1. In methanol the selectivity to trans-hex-2-enoic acid was higher, up to 95 %. The active species of the catalyst was the hydride [CoIII(CN)3H]3-. The authors of this work proposed that the hydrogen is not transferred in pairs and the -coordination of the olefin is not realized before hydrogen transfer. Synchronic formation of both 2- and hex-3-enoic acid was accounted for by rearrangement of the intermediate [9]. The mechanism of the reaction is shown in Figure 1.

Hexenoic Acids and Their Derivatives

[Co(CN)5H]3-

373

H X Co(CN)5
3-

X Co(CN)5
3-

Co(CN)5

3-

H X H

H X H

Figure 1. Hydrogenation[9] of dienes using [CoIII(CN)5H]3.

Selectivity to trans-hex-2-enoate was slowly decreased using natrium sorbate in the hydrogenation. Another step was to determine the effect of phase transfer compounds on the course of the reaction [10]. In the absence of a phase transfer compound the selectivity to trans-methyl-hex-2-enoate (hydrogenation of methylsorbate) was 90 %. In the presence of polyethyleneglycol (phase transfer compound) the selectivity decreased to 81 %. In a twophase water-dichloromethane system methyl-trans-2-enoate and trans-hex-3-enoate were formed in a 65:35 ratio. When benzyltriethylammoniumchloride was added to this system the proportion of trans-hex-3-enoate formed was increased to 75 %. The differences in the behavior of the reactions are probably a result of the different media in which the reactions occur [11]. Without phase transfer compounds the reaction takes place in the aqueous phase, in contrast when tetraalkylamonium compounds are present complexes such as [R4N]3 [Co(CN)5H] are formed and these are soluble in organic solvents. Due to this fact hydrogenation reactions in the presence of benzyltriethylammonium chloride take place in the organic phase. Sorbic acid was not hydrogenated under the chosen reaction conditions (room temperature, 0.1 MPa). A similar result was obtained by Alper [12] for the hydrogenation of potassium sorbate using similar conditions with a different phase transfer compound (beta-cyclodextrine). This author obtained yields for trans-hex-2- and trans-hex-3-enoate of 75% and 13 % respectively.

ORGANOMETALLIC COMPLEXES BASED ON RHODIUM

The investigations into the use of complexes based on cobalt were followed by the examination of different Rh complexes. For the hydrogenation of sorbic acid a series of different Rh complexes was tested [13] at room temperature with a hydrogen pressure of 0.3 Pa in basic solution. Using Wilkinsons catalyst [RhCl(PPh3)3] even at low conversion only saturated hexanoic acid was formed. On the other hand using [RhCl (PPh3)2 (Ph2PO2CCH=CMe2)] a mixture containing 52 % of hex-4-enoic acid and 48 % of hexanoic acid was obtained after total conversion of sorbic acid. In addition this complex was more active than Wilkisons catalyst.

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Another Rh catalyst used [14] was [H2RhIII(Ph2N3)2(PPh3)2]. At a hydrogen pressure of 0.1 MPa and a temperature of 30 40 C with DMSO as the solvent trans-hex-2-enoic acid with a small amount of trans-hex-3-enoic acid was obtained. Using temperatures higher than 50 C trans-hex-2-enoic acid was subsequently hydrogenated to hexanoic acid after the total conversion of sorbic acid. When other solvents were used the catalyst was significantly less active and selective.

ORGANOMETALLIC COMPLEXES BASED ON CHROMIUM

The hydrogenation of methyl sorbate to methyl-cis-hex-3-enoate was enabled [15] using complexes of the types [Cr(CO)3], [Cr(CO)6], [W(CO)3] and [(arene)Cr(CO)3]. Reactions were carried out at temperatures of 150 - 165 C, a hydrogen pressure of 4.8 MPa and a catalyst : substrate ratio of 1 : 9. The activity of the different complexes differs significantly depending on the ligand whereas selectivity was almost unaffected by the type of ligand. The authors detailed the results obtained through the comparison of different arene ligands. In cyclohexane solution the benzene complex showed the lowest activity (TOF = 2.4 h-1 at 165 C). The highest activity (at 150 C) was obtained using the complex with 3carbomethoxyanisol as an arene ligand. The obtained values of selectivity were from 91.8 to 98.9 % of methyl-cis-hex-3-enoate. In this work [15] it was found that the arene group is not necessary for this reaction as the complex [(cycloheptatriene)Cr(CO)3] showed a higher activity than the complexes [(aren)Cr(CO)3]. This demonstrates that the hydrogen was transferred directly to carbon atoms 2 and 5 of methylsorbate. The reaction path including 1,2-addition of hydrogen and the consecutive isomerisation was therefore eliminated. Based on these results the reaction mechanism generally accepted to date was formulated (Figure 2). The initial step of the catalysis is the dissociation of the arene ligand from the Cr complex followed by the formation of the coordinately unsaturated species [Cr(CO)3].

H2 Cr(CO3)Y

R H CO

Cr CO

X H

R H H
1

CO

Figure 2. Diene hydrogenation[15] using [(arene)Cr(CO)3] complexes S = solvent (THF, acetone), X = CO2Me, Y = arene.

During the study of the influence of the arene substituents on the structure and activity of the catalyst it was found that electron accepting substituents accelerate the catalytic reaction while electron donating groups significantly decrease the activity of the catalyst [16]. As a model reaction for the study of this phenomenon the hydrogenation of methyl sorbate to methyl-cis-hex-3-enoate was used. As stated above almost no influence on selectivity was observed and for almost all the catalysts with different substituents 100 % selectivity to desired methyl-cis-hex-3-enoate was obtained. The hydrogenations were performed in THF for 5 hours (6 MPa H2, 120C).

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It was demonstrated that the simple dissociation of the arene ligands from chromium resulted in higher activity of the catalyst. A comparison [17], of the arene complexes showed that a longer bond length between chromium and the carbon atoms of the arene ligand correlated with increased dissociation. In [(1,2,3-trimethoxybenzene)Cr(CO)3] the plane [18] formed from C-atoms of the ring was significantly deformed and this complex was active even at a temperature of 80C. This phenomenon was more evident in Cr-carbonyl complexes of the polyaromatic compounds like naphtalene, anthracene or phenanthrene. To date the most active compound was [(naphtalen)Cr(CO)3] that stereoselectively catalyzed hydrogenation [19] of methylsorbate at a temperature of 30 C and a hydrogen pressure of 0.1 MPa. The cause [20] of such high activity is probably the solvatation of the naphtalene complex in THF, forming [(THF)3Cr(CO)3]. In recent work a Cr complex with similarly high activity was prepared by Kndig [21]. The author prepared the 2-methylacrylate complex [(C6H6)Cr{CH2CH(CO2CH3)}] that catalyzed the hydrogenation of methylsorbate at room temperature and 0.1 MPa. The stereoselective hydrogenation of conjugated dienes using chromium catalysts is not limited to the hydrogenation of methylsorbate but was also used [17] for the synthesis of many other natural compounds. During these syntheses it was found that the reaction can be applied to molecules containing many different functional groups (non-conjugated double bonds, esters, ketones and carboxylic acids). Using some of these the Cr catalyst was successfully heterogenized [22] by mixing chromium hexacarbonyl with polystyrene. Heterogenization was accomplished by linking the Cr(CO)3 groups to the phenyl ring of polystyrene. The heterogeneous Cr catalyst had lower activity in comparison with [(aren)Cr(CO)3] complexes but had similar selectivity. The catalyst could be reused with no loss of selectivity. Unfortunately the attempt to reproduce the described heterogenization method followed by hydrogenation was not successful [23]. Using all the described heterogenized Cr catalysts very high leaching was observed and catalysts lost their activity after reuse. Furuhata [24] used 1,4-hydrogenation for the direct synthesis of cis-hex-3-en-1-ol from hexa-2,4-diene-1-ol. A temperature of 190 C and a hydrogen pressure of 5 MPa were necessary for reactions using all the [(arene)Cr(CO)3] complexes. The catalyst : substrate ratio was 1 : 20 and the desired cis-hex-3-en-1-ol was obtained with 96 % selectivity and TOF = 5 h-1. The direct 1,4-hydrogenation of sorbic acid using Cr complexes as catalysts failed. Sorbic acid and its potassium salt were hydrogenated [25] at 160 - 180 C and 5 MPa using chromium hexacarbonyl as the catalyst; a mixture of cis-, trans-hex-3-enoic and trans-hex-2enoic acids with trans-hex-2-enoic acid as the major component was obtained. In spite of their high selectivity, hydrogenations using chromium hexacarbonyl and [(aren)Cr(CO)3] complexes as catalysts have many disadvantages. From these disadvantages the main is toxicity of chromium carbonyl compounds, than high catalyst : substrate ratios . The problem is also that the industrial use of homogeneous Cr catalysts is not described and the reactions with heterogenized catalysts were not reproducible. And finally the stereoselective hydrogenation of sorbic acid itself is not possible.

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ORGANOMETALLIC COMPLEXES BASED ON RUTHENIUM

Heinen [26] synthesized a water soluble complex of ruthenium [RuCl2{P(CH2)3OH}]2 that catalyzed the hydrogenation of sorbic acid to trans-hex-4-enoic acid with 82 % selectivity in a two-phase water-ethylacetate system. When the reaction was carried out in a one-phase system (water) the selectivity was only 62 % and the rest of the mixture was composed of hexanoic acid. The increase in the selectivity for the desired product in the twophase system was probably due to the extraction of the primary (unsaturated) products of the reaction into the organic phase and the resulting shift of the equilibrium. The alternative to Cr catalysts mentioned above (preparation of cis-hex-3-enoic acid) was also developed by Heinen [27]. The water soluble [Cp*RuCl(CO){P((CH2)3OH)3}] complex catalyzed the hydrogenation of sorbic acid at 80 C and 5 MPa in a two-phase water-heptane system with 66 % selectivity to cis-hex-3-enoic acid. At 62 % conversion the reaction rate determined by TOF was 15.5 h-1. The main undesired product was saturated hexanoic acid, which was formed with 22 % selectivity. The stereoselective hydrogenation of sorbic alcohol was not possible using this complex. A particularly suitable catalyst for this reaction appeared [27] to be the cationic [Cp*Ru(MeCN)3]+ complex (the counter ion was triflate (Tf)). After the dissociation of the acetonitrile ligands and the addition of the diene a similar complex to the Cr systems was formed. When the reaction took place in a two-phase system with water as one of the phases strong leaching of the catalyst to the nonpolar phase was observed. A highly active catalytic system (80 C, 5 MPa) producing cis-hex-3-enoic acid with 67 % selectivity was obtained. The selectivity was strongly dependent on the conversion due to the isomeric activity of the system. When the catalyst was used for different sorbic acid derivatives the selectivity was strongly dependent on the dienic system. Sorbic alcohol was hydrogenated with 82 % selectivity (total conversion) to cis-hex-3-en-1-ol, the hydrogenation of sorbic aldehyde produced a mixture of hexenals. A further development was the use of a two-phase system with nitromethane as a polar phase; in this case the catalyst remained in the nitromethane phase in contrast with water as polar phase. Sorbic acid and its ethyl ester were hydrogenated in a two-phase nitromethane heptane system to cis-hex-3-enoic acid with 75 % selectivity or to ethyl-cis-hex-3-enoate with with 84 % selectivity. Using a hydrogen pressure of 5 MPa the TOF of sorbic acid was 15 h-1 and that of ethyl sorbate was 18 h-1 at 60 C. This catalytic system had [27] some disadvantages, namely low activity, selectivity of only up to 90 % and the impossibility of the use of nitrormethane as an industrial solvent as it is explosive at higher temperatures. Due to the absence of other ligands in the [Cp*Ru(MeCN)3]Tf complex it was deduced that the high selectivity probably results solely from the cationic RuCp* fragment. As a result the following reaction mechanism was proposed [28] (figure 3). The acetonitrile ligands dissociate stepwise from the catalyst and the molecule of sorbic acid is simultaneously added through its C=C double bonds. The addition of the dienic system where the diene is in the cis-conformation was proved by Mashima [29] based on the complexation reaction of (E,E,E,E)-1,8-diphenyl-1,3,5,7-octatetraene with [Cp*RuCl]4. The Cp*Ru(diene) complexes described by Fagan [30] contain the diene in the cis-conformation. After the complex formation with sorbic acid the oxidative addition of one molecule of hydrogen takes place. In this newly formed complex the positions 2 and 5 in the molecule of

Hexenoic Acids and Their Derivatives

377

sorbic acid are angled directly towards the hydride ligands and the transfer of hydrogen to these positions is very probable. In the final step of the catalytic cycle the cis-hex-3-enoic acid dissociates from the Ru center and the solvated Cp*Ru complex is free for the addition of a new molecule of sorbic acid. One face of the active center is blocked by the Cp* ligand and the other is available for reaction with the substrate molecules.
+ Ru NCMe CF3SO3-

MeCN

MeCN

+ S Ru S S

Tf +sorbic acid - 2S + kyselina sorbov -2S

- kys. cis-3-hexenov - cis-hex-3-enoic acid +S +S + S Ru S COOH

Tf Ru S

Tf -

COOH

+2S H Ru H

+ Tf COOH

+ H2 -S

Figure 3. Postulated mechanism[28] of sorbic acid hydrogenation to cis-hex-3-enoic acid (S = solvent).

This was the reason for the synthesis [28],[31],[32] of the model Cp*Ru complexes i.e. [Cp*Ru(4-MeCH=CHCH=CHCO2H)]+X- (X- = CF3SO3- or [B{C6H3(CF3)2-3,5}4]- (BARF)), that are were efficient complexes for the hydrogenation of sorbic acid to cis-hex-3-enoic acid and of sorbic alcohol to cis-hex-3-en-1-ol (leaf alcohol) under mild conditions using a twophase liquid system. Complexes were obtained as orange powder or crystals with yields of 72 % and 41 % respectively. The first of the complexes is soluble in polar solvents such as alcohols, nitromethane or sulfolane and is insoluble in nonpolar solvents such as ethers or alkanes. It can be used as a catalyst in liquid two-phase systems including nitromethane-dibuthylether, ethyleneglycol-MTBE or sulfolane-MTBE where the complex remains in the polar phase. After the reaction the catalyst can be simply separated by decantation. At 60 C the solvents in the nitromethane-dibutylether and sulfolane-MTBE systems become soluble but at room temperature they are insoluble. The results obtained showed that the naked [Cp*Ru]+

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particle is more active than the Ru catalysts used previously. To prove the reaction mechanism shown in Figure 3, a spectroscopic study of the hydrogenation was carried [33] out. It was found that the hydrogen was placed solely in positions 2 and 5 in sorbic acid molecule. On the both of the methylene groups of cis-hex-3-enoic acid exactly one proton was present (assigned by 1H-NMR). In subsequent work [34] the most selective catalyst was used in a two-phase system with MTBE and dibutylether as the non-polar product phase and the ionic liquid Bmim PF6 (1-nbutyl-3-methylimidazolium hexafluorophosphate) as the polar catalyst phase. In this system the activity of the catalyst was significantly higher in comparison with the system used previously (TOF up to 1100 h-1) but the selectivity to cis-hex-3-enoic acid was lower. Catalysts of the type [Cp*Ru (diene)]+X- can be used [35] for the hydrogenation of different dienes to their cis-unsaturated forms. The author used sorbic acid and sorbic alcohol and also cyclooctadiene. For the hydrogenation of sorbic aldehyde this type of catalyst is not applicable due to its deactivation by the aldehyde itself. Modifications of the counterion Xwere also tested as was the modification of the other ligand of the pentamethylcyclopentadiene complex by exchange with indenyl or fluorenyl. The catalysts obtained by these modifications can catalyze the hydrogenation of the chosen dienes with high selectivity and activity. The mechanism of the hydrogenation of different hexadiene compounds (acid or alcohol) was studied. It was confirmed [36] that the mechanism forming the desired product proceeded in accordance with the scheme shown above (Figure 3) but the reaction of the desired product with the Ru center to form of undesired side products was different for the both of the compounds. In the case of sorbic acid the undesired side products are the other hexenoic acids; in the case of sorbic alcohol the undesired side products are hemiacetals or acetals respectively. In the sorbic acid hydrogenation it was found that the monounsaturated acid formed could also interact with the Ru active particle (-electrons of C=C double bond and C=O carbonyl group) and hydrogenation does not stop at the desired cis-hex-3-enoic acid and the final product could be hexanoic acid. The undesired side products (other isomers of hexenoic acids) are formed by isomerisation on the active center. In the sorbic alcohol hydrogenation this reaction did not occur [37]. The undesired hemiacetals are formed due to the migration of the double bond on the chain forming the unstable monounsaturated aldehydes and by the reaction of these compounds with the alcohols present in the reaction. No saturated hexanol was detected in the mixture. Methyl and butyl esters of sorbic acid were also hydrogenated [38] using the optimal catalyst and a higher selectivity to the desired cis-unsaturated product was observed due to the decrease in electron density. The catalysts of the type [Cp*Ru (diene)]+X- can not only be used in two-phase or homogeneous systems as the immobilization of these catalysts was also successfully performed. Two types of heterogenization were tested at first the immobilisation using hydrogen binding [39] through the oxygen of the triflate ion. This interaction is nonbonding and no effect on selectivity was expected (this was confirmed in the sorbic acid hydrogenation; in the sorbic alcohol hydrogenation the selectivity was marginally lower due to the synergic effect). The second type of immobilization tested was using ionic exchange [40] of Na cations of different anionic clays with the cation of the active complex. This type of immobilization did not affect the selectivity and the catalyst could be reused with no loss of selectivity and minimal loss of activity.

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379

PREPARATION AND PROPERTIES OF [CP*RU (DIENE)]+CF3SO3

The optimal preparation of the catalyst is described in the patent [35]. 0.023 g of [Cp*RuCl2]n (0.08 mmol) was dissolved in diethylether (5 ml) with an excess of sorbic acid (1.3 mmol)(or another hydrogenated diene), zinc powder (2.3 mmol) and silver triflate (0.1 mmol). The mixture was stirred for 2.5 hour at ambient conditions. An orange solution was formed and after solvent evaporation and purification [Cp*Ru(sorbic acid)]CF3SO3 (0.08 mmol)was obtained as a powder. The prepared catalyst is soluble in polar solvents and slightly soluble in ethers. In the polar solvents fast degradation of the complex was observed (the solution quickly became brown). When alcohols were used as solvents it was found that longer carbon chains in the alcohols resulted in lower solubility of the complex and slower catalyst degradation. Water is a catalytic poison and causes catalyst deactivation. Air humidity causes slow catalyst deactivation and it is possible to store the catalyst in air for 24 hours with no loss of catalytic properties. The use of polar solvents results in the formation of strong (binding) interactions with the complex. Interactions with the Ru center could be formed by the free electron pairs [38] and saturation of the complex may occur in the first step (16 e- to 18 e-). The second step could be total solvatation (Figure 4) of the complex resulting in the formation of the clusters (Figure 5).
+ Tf Ru S COOH Ru S + Tf -

S S
Figure 4. Possible solvatation of the catalyst[38] (S =solvent).

+ Tf + Ru S S Ru S S Tf
-

Tf -

S Ru S S

Ru Tf -

+
Figure 5. One of the possible cluster.

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Table 1. Summary of the catalysts used for the hydrogenation of C6-dienic compounds
Catalyst K3[Co(CN)5] K3[Co(CN)5] K3[Co(CN)5] K3[Co(CN)5] Substrate Potassium sorbate Methylsorbate Methylsorbate Methylsorbate Product Sel. (%) Potassium trans-hex-2- 82 - 95 enoate Methyl-trans-hex-290 enoate Methyl-trans-hex-265 enoate Methyl-trans-hex-375 enoate
trans-Hex-4-enoic acid

Arrangement Homogeneous Homogeneous Two-phase Two-phase (+ phase transfer compound) Homogeneous Homogeneous Homogeneous Homogeneous Homogeneous Two-phase Homogeneous Two-phase Two-phase Two-phase Two-phase Two-phase Two-phase

Lit. [6]- [8] [10] [11] [12] [13] [14] [15] [19] [24] [25] [26] [26] [26] [27] [27] [27] [28], [31], [32] [28], [31], [32] [38] and [38]

[RhCl(PPh3)2(Ph2PO2CCH= Sorbic acid CMe2)] [H2RhIII(Ph2N3)2(PPh3)2] Sorbic acid [(aren)Cr(CO)3] Methylsorbate [(aren)Cr(CO)3] [(aren)Cr(CO)3] [RuCl2{P(CH2)3OH}]2 [RuCl2{P(CH2)3OH}]2 [Cp*RuCl(CO){P((CH2)3O H)3}] [Cp*Ru(MeCN)3]Tf [Cp*Ru(MeCN)3]Tf [Cp*Ru(MeCN)3]Tf [Cp*Ru(sorbic acid)]Tf Sorbic alcohol Sorbic acid Sorbic acid Sorbic acid Sorbic acid Sorbic acid Sorbic alcohol Ethylsorbate Sorbic acid

52

trans-Hex-2-enoic acid 90 Methyl-cis-hex-3-enoate 92-99 cis-Hex-3-en-1-ol trans-Hex-2-enoic acid trans-Hex-4-enoic acid cis-Hex-3-enoic acid cis-Hex-3-enoic acid cis-Hex-3-enoic acid cis-Hex-3-en-1-ol Ethyl-cis-hex-3-enoate cis-Hex-3-enoic acid cis-Hex-3-en-1-ol

96 40 82 62 66 67 82 84 96 94

[Cp*Ru(sorbic alcohol)]Tf Sorbic alcohol

[Cp*Ru(sorbic aldehyde)]Tf Sorbic aldehyde No selectivity [Cp*Ru(methylsorbate)]Tf Methylsorbate Methyl-cis-hex-3-enoate 96 [Cp*Ru(butylsorbate)]Tf [Cp*Ru(sorbic acid)]Tf [Cp*Ru(sorbic acid)]Tf Butylsorbate Sorbic acid Sorbic acid Butyl-cis-hex-3-enoate
cis-Hex-3-enoic acid cis-Hex-3-enoic acid cis-Hex-3-en-1-ol

99 97 97 85

[Cp*Ru(sorbic alcohol)]Tf Sorbic alcohol

Two-phase heteroegeneous Two-phase and [38] heterogeneous Heterogeneous [39] hydrogen binding Heterogeneous [40] ionic exchange Heterogeneous [39]

[RUCP*] FRAGMENT
The pentamethylcyclopentadienyl ligand (Cp*-ligand) is of particular importance in organoruthenium chemistry due to its ability to stabilise unsaturated ruthenium complexes. This property distinguishes it from the unsubstituted cyclopentadienyl ligand and is a result of the higher electron density of the Cp*-ligand. The coordinately unsaturated particles are the components of the catalytic cycle in the reactions catalyzed by transition metals. The first work dealing with catalytic hydrogenation of sorbic acid using RuCp* complexes were performed by Heinen [26],[27]. This author studied the

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381

[Cp*Ru(CO)(PR3)Cl] and [Cp*Ru(CO)(PR3)]Tf (R = alkyl) complexes but they had low catalytic activity. The [Cp*Ru(MeCN)3]Tf complex had significantly higher activity and contained relatively simply substitutable acetonitrile ligands. The catalytically active particle was probably the solvent stabilized lewis acid [RuCp*]+ fragment. The usual entry to RuCp* chemistry begins from the dark brown dimeric (polymeric) Ru(III) complex [Cp*RuCl2]2 that was examined independently in the groups of Bercaw [41] and Suzuki[42] (equation 1).
2 RuCl3.3H2O + Cp*H [Cp*RuCl2]2 + 2 HCl + 3 H2O equation 1

This complex can be reduced [43] byLi[Et3BH] to [Cp*RuCl]4 and in accordance with Koelle[44] using methanol in the presence of base to [Cp*Ru(-OMe)]2 (figure 6).
Cp* 2 [Cp*RuCl2]2 + 4 Li[Et3BH] Cp* Ru Ru Cl Cp* Cl Cl Cl Ru Cp* Ru + 4 LiCl + BEt3

Me O [Cp*RuCl2]2 +3 MeOH + 2 K2CO3 Ru O Me Ru

Figure 6. Reduction[43] of [Cp*RuCl2]2.

Typical reactions [45] of the tetrameric [Cp*RuCl]4 complex are shown in Figure 7. Its reaction with silver triflate in the presence of the well coordinating solvent acetonitrile gave the [Cp*Ru(NCMe)3]Tf complex that was the necessary precursor for the [Cp*Ru(arene)]+ compounds. Ligands including CO, phosphines or dienes decomposed the tetramers, forming 18e- complexes such as [Cp*RuL2Cl]. Oxidative addition of allylchloride gave the 18e- Ru(IV)-complex [Cp*Ru(3-all)Cl2]. This complex offers the possibility of many different reactions that are shown in the following scheme (figure 8). Detailed information is given in two reviews from Chaudret [46] and Koelle [47]. Donor ligands such as dppm or bipy can be added [44] to the complex. The methanolate bridges can be substituted by thiols [48] with retention of the structure. Treating [Cp*Ru(-OMe)]2 with strong acid after methanol elimination gave the noncharacterized solvent stabilized particle [Cp*Ru]+. This particle could be coordinated to by many different ligands. [Cp*Ru]+ has a high affinity for 6-electron systems as demonstrated by the formation of [Cp*Ru(aren)]+ cations after the reaction with cyclic olefins and the elimination of water. Through this the [Cp*Ru(C6H6)]Tf complex with two equivalents of hydrogen was

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obtained [49] after the reaction of [Cp*Ru(-OMe)]2 with triflouromethanesulphonic acid and cyclohexene at 80 C in methylenechoride. Besides the activation of C-H bonds described, the activation of C-C, C-O and C-Cl bonds could be also realized whereas C6-compounds such as cyclohexene are aromatized.
+ Ru NCMe + AgTf, MeCN +2L L = CO, PMe3 L Ru Cl L + dien 1/4 [Cp*RuCl]4 + C6Me6 +NH4PF6 - AgCl Cl Cl Ru Cl CF3SO3-

MeCN

MeCN

Ru Cl

Ru

Figure 7. Typical reactions[44] of [Cp*RuCl]4.

CONCLUSION
This text gave brief overview of the selective hydrogenation of sorbic acid and its derivatives, especially sorbic alcohol, using organometallic complexes with different central atoms to monounsaturated compounds. Trans-2 isomers can even be obtained using heterogenous catalysts so the main goal was the preparation of the cis-3 isomers. The use of different complexes based on Rh, Cr and Ru initially showed that the most selective complexes were those based on Cr. But these are surpassed by complexes with the simple structure [Cp*Ru(diene)]+ where the diene is the hydrogenated compound (sorbic acid or sorbic alcohol or other derivative). The selectivities in these cases are up to 98 %. The properties of these complexes are described in detail in the chapters.

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Cp*

OMe Ru OMe PPh2 C H2 PPh2 Ru

Cp* N

Ru N

OMe

+dppm [Cp*Ru(-OMe)]2 +RSH Cp* SMe Ru SMe + Ru Cp*

+ 2,2- bipyridin

+ CF3SO3H + Ru (S) CF3SO3-

80 C + Tf Ru F F
Figure 8. Typical reactions[47] of [Cp*Ru(OMe)]2.
-

+C6F6

+ Tf F Ru F F F

REFERENCES
[1] [2] [3] [4] [5] [6] [7] [8] erven L., Chloubov I.: Sejfen-Oele-Fette-Wachse 116, 549 (1990). Kluso P., Kukula P., Kyslingerov E., erven L.:React.Kinet.Catal.Lett. 59, 9-13 (1996). Kukula P., erven L.: Appl.Catal.A 177, 79-84 (1999). erven L., Fialov E., Rika V.: Coll. Czech. Chem.Commun. 54, 101 (1986). Arctander S.: Perfume and Flavour Chemicals, Montclair, N.Y. (1969), Published by author. De Vries B., Koninkl.Ned.Akad.Wetenschap.Proc.,Ser. B 63, 443 (1960). Kwiatek J., Mador I. L., Sezler J. K., J.Am.Chem.Soc. 84, 304 (1962). Mabrouk A.F., Dutton H.J., Cowan J.C.: J.Am.Oil Chem.Soc. 41, 153 (1964).

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Libor erven and Elika Leitmannov James B.R.: Comprehensive Organometallic Chemistry, Vol.8, Pergamon Press, Oxford, 305-312 (1982). Reger D.L., Habib M.M.: J.Mol.Catal. 7, 365-372 (1980). Reger D.L., Habib M.M., Fauth D.J.: J.Org.Chem. 45, 3880 (1980). Lee J.T., Alter H., J.Org.Chem. 55, 1854-1856 (1990). Iraqi A., Fairfax N.R., Preston S.A., Cupertino D.C., Irvine D.J., Cole-Hamilton D.J.: J.Chem.Soc. Dalton Trans. 1929 (1991). Kameda N., Igarashi R.: J.Chem.Soc.Japan 6, 577-579 (1994). Cais M., Frankel E.N., Rejoan A.: Tetrahedron Lett. 1919-1923 (1968). Frankel E.N., Selke E., Glass C.A.: J.Am.Chem.Soc. 90, 2446-2448 (1967). Shibasaki M., Sodeoka M.: Synthesis 643-658 (1993). Le Maux P., Saillard J.Y., Grandjean D., Jaouen G.: J.Org.Chem. 45, 4526 (1980). Cais M., Frankel D., Weidenbaum K.: Coord.Chem.Rev. 16, 27 (1975). Cais M., Yagupsky G.: Inorg.Chim.Acta 12, L27 (1975). Kundig E.P., Kondratenko M., Romanens P.: Angel.Chem. 110, 3329 (1998). Pittman C.U., Kim B.T., Douglas W.M.: J.Org.Chem. 40, 590-592 (1975). Awl R.A., Frankel E.N., Friedrich J.P., Pryde E.H.: J.Am. Oil Chem.Soc. 55, 577 (1978). Furuhata A., Onishi K., Fujita A., Kogami K.: Agric.Biol.Chem. 46, 1757 (1982). Vasilel A.A:, Serebryakov E.P.: Mendeleev Commun. 4-5 (1994). Heinen J., Sandoval-Tupayachi M., Driessen-Hoelscher B.: Catal.Today 48, 273-278 (1999). Heinen J., Driessen-Hoelscher B.: J.Organomet.Chem. 570, 141 (1998). Steines S., Englert U., Driessen-Hoelscher B.: Chem.Commun. 3, 217 (2000). Mashima K., Fukumoto H., Tani K.: Organometallics 17, 410 (1998). Fagan P.J., Mahoney W.S., Calabrese J.C., Williams I.D.: Organometallics 9, 1843 (1990). Driessen-Hoelscher B.: Synthetic Methods of Organometallic and Inorganic Chemistry 10, 94 (2002). Steines S.: Disertation thesis, Aachen (1999). Niessen H.G., Schleyer D., Wiemann S., Bargon J., Steines S., Driessen-Hoelscher B.: Magn.Res.Chem. 38, 747 (2000). Steines S., Wasserscheid P., Driessen-Hoelscher B.: J.Pract.Chem. 4, 342 (2000). Kirchhoff J., Fries G., Driessen-Hoelscher B., Kalz W., Nobis M.: EP 1394170 (2004) CAN 140:217811. Leitmannov E., Mal R., erven L.: Res.Chem.Intermed. 63-69 (2009). Leitmannov E., erven L.: J. Mol. Catal. A: 275, 153157(2007). Leitmannov E.: Disertation thesis, ICT Prague (2006). Leitmannov E., erven L.: J. Mol. Catal. A: 261, 242-245 (2007). Leitmannov E., erven L.: React. Kinet. Mech. Catal., 99, 79 (2010) Tiley T.D., Grubbs R.H., Bercaw J.E.: Organometallics 3, 274 (1984). Oshima N., Suzuki H., Moro-Oka Y.: Chem.Lett. 1161-1164 (1984). Fagan P.J., Ward M.D., Calabrese J.C.: J.Am.Chem.Soc. 111, 1698 (1989). Koelle U., Kossakowski J.: Chem.Commun. 549-551 (1988). Fagan P.J., Mahoney W.S., Calabrese J.C., Williams I.D.: Organometallics 9, 1843 (1990).

Hexenoic Acids and Their Derivatives [46] [47] [48] [49] Chaudret B., Bull.Soc.Chim.Fr. 132, 268 (1995). Koelle U.: Chem.Rev. 98, 1313 (1998). Koelle U.: J.Organomet.Chem. 423, C20 (1992). Rondon D., Chaudret B., He X.D., Labroue D.: J.Am.Chem.Soc. 113, 5671 (1991).

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Chapter 12

HOMOGENEOUS CATALYZED SUCCINOYLATION OF CELLULOSE IN IONIC LIQUIDS

C.F. Liu*1, A.P. Zhang1,2, W.Y. Li1, W. Lan1 and R.C. Sun1,3
State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou, China 2 Institute of of New Energy and New Material, South China Agricultural University, Guangzhou, China 3 Institute of Biomass Chemistry and Technology, Beijing Forestry University, Beijing, China
1

ABSTRACT
Homogeneous modification of sugarcane bagasse cellulose with succinic anhydride (SA) was catalyzed with three different catalysts including iodine, N-bromosuccinimide (NBS), and 4-dimethylaminopyridine (DMAP) in a solvent system containing 1-butyl-3methylimidazolium chloride ionic liquid ([C4mim]Cl) and dimethylsulfoxide (DMSO). The effects of the mass ratio of catalyst/SA, reaction time, and reaction temperature on the degree of substitute (DS) of cellulose were investigated. The results showed that the DS of cellulosic derivatives increased to 0.56-1.54 under the experimental conditions catalyzed with iodine, 0.92-2.31 with NBS, and 0.94-2.34 with DMAP, from 0.24 without any catalysts, indicating that these three catalysts were effective catalysts for cellulose succinoylation in ionic liquids. The possible mechanism of homogeneous succinoylation catalyzed with these catalysts and the actual role of these catalysts were also investigated. Fourier transform infrared and solid-state cross-polarization/magic angle spinning 13C NMR spectroscopies also provided evidence of catalyzed homogeneous succinoylation reaction. The results indicated that the reaction of hydroxyl groups at C-6, C-2, and C-3 positions in cellulose occurred.

Keywords: cellulose, succinoylation, catalyst, iodine, 4-dimethylaminopyridine, Nbromosuccinimide, ionic liquids

* Corresponding author, chfliu@scut.edu.cn

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1. INTRODUCTION
Recently, there is a growing urgency to develop novel bio-based products and other innovative technologies that can unhook widespread dependence on fossil fuel around all over the world [1]. Utilization of biomass, especially inedible lignocellulosic biomass, to create biofuels, bioenergy, biochemicals, biocomposites and a host of other bioproducts has attracted considerable attention around all over the world [2-4], even as one of the most important policy-oriented research activities in developed countries. US Department of Energy has targeted to achieve 10% of basic chemical building blocks arising from lignocellulose-derived renewables by 2020, and a further increase to 50% by 2050 [1]. The European Union has also developed a vision in which one-fourth of the EUs transportation fuels will be derived from biofuels by 2030 [5]. These political timetables result in critical challenges in biomass utilization. It has been estimated that about 50% of biomass in the world is lignocellulose, of which polysaccharides including cellulose and hemicelluloses account for over two-thirds [6]. Chemically, cellulose is a homopolymer composed of D-glucopyranose units linked by (14) glycosidic bonds [7], much of which is in a crystalline structure. It is about 35-43% of the dry lignocellulosic materials. Hemicelluloses, an amorphous complex polymer usually composed of xylose, arabinose, galactose, glucose, and mannose, are the second most abundant renewable materials after cellulose in plant cell walls [8], which account for about 25-35% of the dry lignocellulosic materials. The remainder is mostly lignin plus lesser amounts minerals, waxes, and other compounds [9]. The utilization of these biomacromolecules not only adds value to the biomass raw materials, but also contributes to reduce environmental concerns regarding the disposal of the residues [10]. The integrated utilization of lignocellulosic biomass is becoming the significant issue and development tendency. In the promising utilization pattern, the lignocellulosic biomass is firstly fractionated to three main components, that is, lignin, hemicelluloses, and cellulose, and then the isolated components are independently utilized to produce different products according to their own properties. The promising applications of cellulose include biofibers, biopolymers, biofuels, and biocomposites in native, degraded, or modified status [11,12]. Modification of cellulose represents one of the most versatile transformations as it provides access to a variety of biobased materials with valuable properties. Due to three hydroxyl groups available within one anhydroglucose units (AGU) in cellulose, a great variety of chemical modifications of cellulose are possible [13]. Chemical modifications of cellulose can introduce functional groups into the macromolecules in heterogeneous phase or homogeneous phase to improve the overall utilization of cellulosic polymers. Because more uniform and stable products can be obtained in homogeneous phase than heterogeneous phase, homogeneous cellulose functionalization has been one focus of cellulose research for a long time [14,15]. Acylation of cellulose with linear chain acylation reagents such as anhydride or chloride is the most common method to produce cellulosic bioproducts. Functionalization of cellulose using ionic liquids (ILs), one of the most promising green solvents, as reaction media has attracted much attention after cellulose was reported to be soluble in a variety of ILs with strong hydrogen bond acceptors as anions, such as chloride [16-19], formate [20], acetate [21-23], and alkylphosphate [20,24-26]. Cellulose acetylation with acetic anhydride or acetyl chloride has

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been extensively studied because of the wide application of cellulose acetate, and the results showed that cellulose acetates with high degree of substitution (DS) were easily prepared [18,27-30]. Carbanilation with phenyl isocyanate [29,31], acylation with lauroyl chloride [29], and perpropionylation with propionic anhydride [31] were also investigated in ILs. On the other hand, modification of cellulose with cyclic anhydride such as succinic anhydride are widely used to produce water absorbents for soil in agriculture, natural absorbents for the removal of heavy metal ions in wastewater treatment, medicine for drug delivery systems, and thermoplastic materials [32,33]. Moreover, the reaction results in a pendant carboxylic moiety attached to the cellulose molecules via a covalent ester bond, providing a site upon which further reactive chemistry is possible. However, our previous studies showed that succinoylation was much more difficult than acetylation, and only the cellulose derivatives with relatively low DS were obtained [34,35]. To increase cellulose succinoylation efficiency, three different catalysts including iodine (I2), 4-dimethylaminopyridine (DMAP) and N-bromosuccinimide (NBS) were explored in a reaction medium containing ionic liquid 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) based on their good catalytic effects on the esterification of alcohols. The cellulosic derivatives were then characterized by Fourier transform infrared (FT-IR), and solid-state CP/MAS 13C nuclear magnetic resonance (NMR) spectroscopies. The possible mechanisms of catalyzed succinoylation were discussed.

2. EXPERIMENTAL
2.1. Materials
Sugarcane bagasse (SCB) was obtained from Guangzhou, China. It was dried in sunlight and then cut into small pieces. The cut SCB was ground and screened to prepare 20-40 mesh size particles (450-900 m). Cellulose was isolated after delignification of ground SCB with sodium chlorite at pH 3.8-4.0 followed by alkaline extraction with 10% potassium hydroxide. Ionic liquid [C4mim]Cl was obtained from the Chemer Chemical Co., Ltd., Hangzhou, China, and used as received. All of other chemicals used were of analytical grade and purchased from Sigma-Aldrich, Guangzhou, China.

2.2. Homogeneous Succinoylation of Cellulose Catalyzed with I2, NBS, and DMAP
Dried SCB cellulose was added to [C4mim]Cl in three-necked flask. The mixture of cellulose/[C4mim]Cl was stirred up to 10 h at 80 oC under N2 atmosphere to guarantee the complete dissolution of cellulose. To the resulting cellulose solution, 5 mL of DMSO was added to reduce viscosity and achieve a suitable mixing. Then catalyzed succinoylation reaction was carried out according to the following procedures.

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2.2.1 Succinoylation Catalyzed with I2 I2 and SA was dissolved in 5 mL DMSO, and then added to the cellulose solution in [C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 1. The mixture was stirred under N2 atmosphere for the desired time. After the required time, 2 mL of saturated solution of sodium thiosulfate was added to the modified cellulose solution with agitation. The mixture was vigorously shaken for 2 min to guarantee complete transformation of iodine to iodide. Then the resulted mixture was slowly poured into 150 mL of isopropanol with agitation. The residues were filtrated out, washed thoroughly with isopropanol to eliminate ILs, unreacted anhydride, and byproducts, and then dried in a vacuum at 50 oC for 16 h. 2.2.2. Succinoylation Catalyzed with NBS NBS and SA was dissolved in 5 mL DMSO, and then added to the cellulose solution in [C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 2. The mixture was stirred under N2 atmosphere for the desired time. After the required time, the resulted mixture was slowly poured into 150 mL of isopropanol with agitation. The residues were filtrated out, washed thoroughly with isopropanol to eliminate ILs, unreacted anhydride, and byproducts, and then dried in a vacuum at 50 oC for 16 h. 2.2.3. Succinoylation Catalyzed with DMAP DMAP and SA was dissolved in 5 mL DMSO, and then added to the cellulose solution in [C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 3. The mixture was stirred under N2 atmosphere for the desired time. After the required time, the resulted mixture was slowly poured into 150 mL of isopropanol with agitation. The residues were filtrated out, washed thoroughly with isopropanol to eliminate ILs, unreacted anhydride, and byproducts, and then dried in a vacuum at 50 oC for 16 h.

2.3. Determination of Degree of Substitution

The DS of cellulosic derivatives was determined by direct titration method [36,37]. A known weight of the sample was dissolved in 10 mL of DMSO by stirring at 75 oC for 30 min. After cooling, 5-6 drops of phenolphthalein indicator were added. This solution was titrated against 0.01 M standard NaOH solution until a permanent pale pink color was seen. The DS was calculated by using the following equation:

where 162 g/mol is the molar mass of an AGU, 100 g/mol is the net increase in the mass of an AGU for each succinoyl substituted, m is the weight of sample analyzed, VNaOH is the volume of standard NaOH solution consumed in the titration, and cNaOH is the molarity of standard NaOH solution.

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2.4. Characterization of the Native and Succinylated Cellulose

Viscosity of the cellulose was measured by British Standard Methods for determination of limiting viscosity number of cellulose in dilute solutions, Part 1, cupriethylenediamine (CED) method (BS 6306, Part 1, 1982). The viscosity average DP (degree of polymerization) of cellulose was estimated from their intrinsic viscosity [] in CED hydroxide solution, P0.90=1.65[], where P is an indeterminate average DP [38]. Molecular weight (Mw) of cellulose was then calculated from P by multiplied by 162, the Mw of an AGU. The FT-IR spectra of the cellulose and succinylated cellulosic derivatives were recorded on an FT-IR spectrophotometer (Nicolet 510) from finely ground samples (1%) in KBr pellets in the range 4000-400 cm-1. Thirty-two scans were taken for each sample with a resolution of 2 cm-1 in the transmission mode. The solid-state CP/MAS 13C NMR spectra were obtained on a Bruker DRX-400 spectrometer with 5 mm MAS BBO probe employing both Cross Polarization and Magic Angle Spinning and each experiment was recorded at ambient temperature. The spectrometer operated at 100 MHz. Acquisition time was 0.034 s, the delay time 2 s, and the proton 90o pulse time 4.85 s. Each spectrum was obtained with an accumulation of 5000 scans.

3. RESULTS AND DISCUSSION

3.1. Succinoylation Catalyzed with Iodine
Delignification of SCB with sodium chlorite followed by alkaline extraction yielded 49.6% cellulose (based on the dry weight of SCB). The intrinsic viscosity, degree of polymerization, and molecular weight of the isolated cellulose were determined to be 378 mLg1, 1277, and 206800 gmol1, respectively.

Figure 1. Scheme for succinoylation of SCB cellulose with succinic anhydride.

Usually, SA reacts with cellulose O-H groups to form the monoester as shown in Figure 1. In the present study, succinoylation of the obtained cellulose with different catalysts in [C4mim]Cl/DMSO system was investigated to improve cellulose derivatizing efficiency. After cellulose was dissolved in [C4mim]Cl, the viscous cellulose solution obtained was diluted by DMSO to achieve suitable and clear mixture. Solid acylation reagent SA and catalysts previously dissolved in DMSO were added to the diluted solution to achieve homogeneous succinoylation reaction. Iodine has been reported recently as an effective catalyst for acetylation of alcohols and polysaccharides without solvents [39,40]. In the

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present study, we investigated the possibility of cellulose succinoylation catalyzed with iodine in [C4mim]Cl/DMSO to increase cellulose modification efficiency. Table 1 shows the effects of the parameters, including the mass ratio of I2/SA from 2% to 15%, reaction temperature from 85 to 110 oC, and reaction duration from 30 to 120 min, on DS of the succinylated cellulose. As shown in Table 1, compared with that obtained under the same conditions without any catalysts (DS=0.24, data not shown), DS of cellulose derivative obtained with the addition of 2% iodine (based on SA) increased to 0.56. This increment indicated that the efficiency of succinoylation in the presence of iodine increased, suggesting that iodine could be an effective catalyst for cellulose succinoylation in ionic liquids. The improvement of iodine dosage from 2% to 5%, 8%, 10% and 15% (based on SA) resulted in an improvement of the DS of cellulose derivatives from 0.56 to 0.84, 1.28, 1.41 and 1.39, respectively. Prolonging reaction duration from 30 min to 45, 60, and 90 min led to an increment in DS from 0.72 to 0.97, 1.41 and 1.52 respectively. However, DS decreased from 1.52 to 1.34 with a further increment of reaction duration from 90 min to 120 min. This decrement was probably due to the further reaction of succinic acid attached to cellulose with hydroxyl group in the near surroundings to form diesters in the presence of iodine. Raising reaction temperature from 85 o C to 90, 95, 100, 105 and 110 oC resulted in an increase in DS from 0.64 to 0.78, 0.92, 1.41,1.46 and 1.54, respectively. However, the maximum DS observed was only about half of the theoretical maximum vale 3. The similar decreased acylation of cellulose modified with lauroyl chloride was also reported in ILs [29].
Table 1. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using iodine as a catalyst.
Succinoylation conditions Cellulose (%) Molar ratioa 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 I2/SA (%) Temperature (oC) Duration (min) 2 100 60 5 100 60 8 100 60 10 100 60 15 100 60 10 100 30 10 100 45 10 100 90 10 100 120 10 85 60 10 90 60 10 95 60 10 105 60 10 110 60 Succinylated cellulose Sample No. DS 1 0.56 2 0.84 3 1.28 4 1.41 5 1.39 6 0.72 7 0.97 8 1.52 9 1.34 10 0.64 11 0.78 12 0.92 13 1.46 14 1.54

Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1.

In present study, the DS of cellulose derivatives increased from 0.24 without any catalysts to the range of 0.56-1.54 in the presence of iodine catalyst under the conditions given. The possible mechanism of iodine-catalyzed succinoylation and the actual role of iodine are not clear. However, a plausible explanation is that iodine might first be ionized into

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I+ and I in ILs. I+ in turn activates the carbonyl groups of SA to form as the acylation reagent for further reaction, as shown in Figure 2.

Figure 2. Possible mechanism of the iodine-catalyzed succinoylation of cellulose.

3.2. Succinoylation Catalyzed with NBS

NBS is an inexpensive and commercially available reagent that is traditionally used as an oxidizing agent or brominating agent in radical reactions and various electrophilic additions [41]. It is also a mild and efficient catalyst for acetylation of alcohols and phenols under mild reaction conditions [42]. In present study, cellulose succinoylation was discussed in [C4mim]Cl/DMSO system using 4:1 molar ratio of SA/AGU in cellulose, a mass ratio of NBS/SA between 0 and 20%, reaction temperature 90-120oC and reaction duration 30-240 min. Table 2 shows the DS of cellulose derivatives obtained with NBS catalyst. The addition of 1% NBS (based on SA) resulted in the DS enhancement from 0.24 to 1.27, indicating the significant improvement of succinoylation in the presence of NBS. An increase of NBS/SA mass ratio from 1% to 2% and 5% resulted in noticeable improvement of DS from 1.27 to 1.84 and 2.31, respectively. Clearly, the efficiency of cellulose succinoylation in [C4mim]Cl/DMSO system was significantly enhanced with catalysis of NBS compared with that without any catalysts. However, further improvement of NBS/SA mass ratio from 5% to 10% and 20% led to a reduction of DS from 2.31 to 1.55 and 1.23, respectively. The reason of this decrease in DS was probably due to the formation of diester in the presence of catalyst NBS by crosslinking of the produced succinic acid attached to cellulose, i.e., monoester, with other free hydroxyl groups in the surroundings. This decrement was also found in iodinecatalyzed succinylation. These results indicated that NBS could significantly improve the reaction efficiency of SA and cellulose in [C4mim]Cl/DMSO system. DS of cellulose derivatives reached 0.92 within 30 min, 1.31 with 45 min, 1.84 within 60 min, 1.92 in 75 min, 1.99 in 90 min, and 2.03 in 120 min when keeping the molar ratio of SA/AGU at 4:1, reaction temperature at 100 oC and NBS/SA mass ratio at 2%. Higher reaction temperature was also

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favorable to NBS-catalyzed succinoylation. Improving reaction temperature from 90 to 95, 100, 110 and 120 oC resulted in an enhancement in DS of cellulose derivatives from 1.67 to 1.74, 1.84, 1.98 and 2.25, respectively.
Table 2. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using NBS as a catalyst.
Succinoylation conditions Cellulose (%) Molar ratioa 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 2.0 4:1 NBS/SA (%) Temperature (oC) 1 100 2 100 5 100 10 100 20 100 2 100 2 100 2 100 2 100 2 100 2 100 2 90 2 95 2 110 2 120 Succinylated cellulose Duration (min) Sample No. DS 60 15 1.27 60 16 1.84 60 17 2.31 60 18 1.55 60 19 1.23 30 20 0.92 45 21 1.31 75 22 1.92 90 23 1.99 120 24 2.03 240 25 1.73 60 26 1.67 60 27 1.74 60 28 1.98 60 29 2.25

Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1.

Figure 3. Possible mechanism of the NBS-catalyzed succinoylation of cellulose.

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The DS of cellulose derivatives increased from 0.24 without any catalysts to the range of 0.92-2.31 in the presence of NBS catalyst under the conditions given. The possible mechanism of NBS-catalyzed succinoylation is shown in Figure 3. NBS might act as a source for Br+, which in turn activates the carbonyl groups of SA to produce the highly reactive acylating agent. This acylating agent reacts with hydroxyl groups of cellulose, which produce succinoylated cellulose upon elimination of NBS.

3.3. Succinoylation Catalyzed with DMAP

Pyridine has been found to be effective in the modification of wood with various long chain anhydrides, because it serves not only to swell the wood structure, thereby permiting effective ingress of reagent, but also catalyzes the reaction via nucleophilic mediated catalysis [43]. DMAP is a derivative of pyridine with the chemical formula (CH3)2NC5H4N. It is a very useful nucleophilic catalyst for a variety of reactions such as esterifications of alcohols with anhydrides. In comparison to pyridine, DMAP was found to be approximately 104 times more active when used as acylation catalyst [44]. It has been used in the synthesis of agrochemicals, pharmaceuticals and polymers as an acylation catalyst. In present study, we investigated the possibility of succinoylation catalyzed with DMAP in ILs. Table 3 shows the effects of the mass ratio of DMAP/SA from 1% to 15%, reaction temperature from 60 to 110 o C, and reaction duration from 30 to 120 min on DS of cellulose derivatives succinylated in [C4mim]Cl/DMSO system.
Table 3. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using DMAP as a catalyst.
Succinoylation conditions Cellulose (%) Molar ratioa DMAP/SA (%) Temperature (oC) 2.0 4:1 1 80 2.0 4:1 2 80 2.0 4:1 3 100 2.0 4:1 5 80 2.0 4:1 8 80 2.0 4:1 15 80 2.0 4:1 5 60 2.0 4:1 5 70 2.0 4:1 5 90 2.0 4:1 5 100 2.0 4:1 5 110 2.0 4:1 5 80 2.0 4:1 5 80 2.0 4:1 5 80 2.0 4:1 5 80 Succinylated cellulose Duration (min) Sample No. DS 60 60 60 60 60 60 60 60 60 60 60 30 45 90 120 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 0.94 1.19 1.52 1.78 1.88 1.69 1.55 1.75 2.19 2.34 1.93 1.28 1.52 1.49 1.38

Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1.

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As shown in Table 3, DS of cellulose derivative increased to 0.94 with addition of 1% DMAP (based on SA), indicating the enhanced succinoylation efficiency in [C4mim]Cl/DMSO in the presence of DMAP. The DS was improved from 0.94 to 1.19, 1.52, 1.78, and 1.88 with the enhancement of DMAP/SA mass ratio from 1% to 2%, 3%, 5%, and 8%, respectively. Further improvement of DMAP dosage from 8% to 15% led to slight decrease in DS from 1.88 to 1.69. The increase of reaction temperature from 60 to 70, 80, 90 and 100 oC resulted in an improvement of DS from 1.55 to 1.75, 1.78, 2.19, and 2.34, respectively. DS was slightly reduced from 2.34 to 1.93 with further improvement of reaction temperature from 100 to 110 oC. Holding DMAP/SA mass ratio at 5%, reaction temperature at 80 oC and molar ratio of SA/AGU at 4:1, DS of cellulose derivatives reached 1.28 within 30 min, 1.52 in 45 min, and 1.78 in 60 min. However, DS decreased from 1.78 to 1.49 and 1.38 with further elongation of reaction duration from 60 min to 90 and 120 min, respectively. The DS of cellulose derivatives increased to the range of 0.94-2.34 in the presence of DMAP catalyst under the conditions given. The possible mechanism of DMAP-catalyzed succinoylation of cellulose is similar to DMAP-catalyzed acetylation. Figure 4 illustrated the possible role of DMAP in catalyzed succinoylation. The nucleophilic attack of DMAP on a carbonyl group of succinic anhydride leads to intermediate, which could react with cellulose hydroxyl groups and produce cellulose ester.

Figure 4. Possible mechanism of the DMAP-catalyzed succinoylation of cellulose.

3.4. FT-IR Spectra

Figure 5 illustrates the FT-IR spectra of native cellulose and succinylated cellulose with or without catalysts. In spectrum 1, the absorbances at 3434, 2929, 1633, 1372, 1164, and 1049 cm-1 are associated with native cellulose. The strong adsorption at 3434 cm-1 is attributed to the stretching of hydroxyl groups and that one at 2929 cm-1 corresponds to the CH stretching. The band at 1633 cm-1 relates to the bending mode of the absorbed water. The peak at 1372 cm-1 is due to the O-H bending. The absorption band at 1164 cm-1 corresponds to C-O antisymmetric bridge stretching [45]. A strong peak at 1049 cm-1 arises from C-O-C pyranose ring skeletal vibration [46].

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Compared with spectrum 1, spectrum 2 of succinylated cellulose without any catalyst provides evidence of succinoylation by the occurrence of the absorbance at 1728 and 1574 cm-1. The former band at 1728 cm-1 is an overlapping of the absorptions by carbonyl groups in carboxyl acids and esters [47]. The latter band at 1574 cm-1 is originated from antisymmetric stretching of carboxylic anions [33], indicating the formation of monoester. More importantly, spectrum 3 of succinylated cellulose with iodine catalyst provides the more evidences of catalyzed succinoylation. The intensities of the two peaks at 1728 cm-1 for carbonyl groups and at 1574 cm-1 for carboxylic anions significantly increased. In addition, the intensity of the absorption band at 1164 cm-1 for C-O antisymmetric stretching clearly increased after succinoylation, suggesting that the catalyzed esterification reaction does occur.
100 95 90 85 80 75 %T 70 65 60 55 50 45 40 3500
3434 1728 1164 2929 1574 1412 3 1372 1633 2 1

1049

3000

2500 2000 Wavenumbers (cm-1)

1500

1000

Figure 5. FT-IR spectra of unmodified cellulose (spectrum 1), succinylated cellulose without any catalyst (spectrum 2) and with iodine as a catalyst (spectrum 3, sample 7).

Similar results were also found in the FT-IR spectra of succinylated cellulose samples catalyzed with NBS and DMAP (spectra not shown). It indicated that iodine, NBS and DMAP are efficient catalysts of cellulose succinoylation in [C4mim]Cl/DMSO. As expected, the absence of peaks at 1850 and 1780 cm-1 in spectra 2 and 3 for succinylated cellulose confirmed that the products are free of the unreacted SA.

3.5. Solid-State CP/MAS 13C-NMR

In the present study, the catalyzed succinoylation reaction of cellulose was also studied by solid-state CP/MAS 13C-NMR spectroscopy, and the spectra of unmodified cellulose (spectrum a), succinylated cellulose without any catalysts (spectrum b) and with NBS as a catalyst (spectrum c, sample 13) are shown in Figure 6.

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PPM
Figure 6. Solid state CP/MAS 13C-NMR spectra of unmodified cellulose (spectrum a), succinylated cellulose without any catalysts (spectrum b) and with NBS as a catalyst (spectrum c, sample 15).

As shown in Figure 6, all noticeable signals in spectrum a of unmodified cellulose are distributed in the region between 50 and 110 ppm for the carbon atoms of the carbohydrate moiety. Clearly, the signals at 85.2 ppm for C-4 of crystalline cellulose and 61.1 ppm for C-6 of crystalline cellulose disappeared in spectra b and c of succinylated cellulose, suggesting the complete disruption of cellulose crystalline structure during the dissolution and functionalization, which indicated that succinoylation reaction occurs in homogeneous phase. Evidently, the presence of the signals at 171.0 ppm for carboxylic group and 26.4 ppm for methylene group also provided evidence of succinoylation, which indicated the reaction shown in Figure 1 does occur. In spectrum c of cellulose derivative succinylated with NBS catalyst, the intensities of the signals at 171 ppm for carboxylic group and 26.4 ppm for methylene group significantly increased compared with that in spectrum b without any catalysts, indicating that NBS could significantly improve the modification efficiency of cellulose with SA in [C4mim]Cl/DMSO system. The three free hydroxyl groups at C-6, C-2, and C-3 position in AGU are the main reactive sites in cellulose. As shown in Figure 6, the intensity of the signal for C-6 decreased after succinoylation, and that at 67.8 ppm for C-2 and C-3 also decreased, which indicated the succinoylation reaction at C-6, C-2, and C-3 positions does occur. The similar observations were also found in the spectra of cellulose derivatives catalyzed with iodine and DMAP (spectra not shown). These results suggested that iodine, NBS, and DMAP are effective succinoylation catalysts of cellulose in [C4mim]Cl/DMSO.

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CONCLUSION
The homogeneous modification of sugarcane bagasse cellulose with succinic anhydride in solvent system containing ionic liquid 1-butyl-3-methylimizolium chloride and dimethylsulfoxide was catalyzed with three different catalysts including iodine, NBS, and DMAP. The results showed that these three catalysts could effectively improve the cellulose succinoylation. Under the given conditions the DS of cellulose derivatives increased from 0.24 to 0.56-1.54 with iodine catalyst, 0.92-2.31 with NBS catalyst, and 0.94-2.34 with DMAP catalyst. The possible mechanisms of homogeneous catalyzed succinoylation were also proposed. FT-IR and solid-state CP/MAS 13C-NMR spectroscopies also provided evidence for catalyzed succinoylation. The results indicated that the reaction of hydroxyl groups at C-6, C-2, and C-3 positions in cellulose all occurred.

ACKNOWLEDGMENTS
The authors are grateful for the financial support of this research from the National Natural Science Foundation of China (Nos. 30871994, 30972325, and 30710103906), the Guangdong Natural Science Foundation (No. 8451064101000409), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20070561040), Chinese Universities Scientific Fund (No. 2009ZZ0024), and National Basic Research Program of China (No. 2010CB732201)

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[43] Sun, RC; Sun, XF; Zhang, FY. Succinoylation of wheat straw hemicelluloses in n,ndimethylformamide/lithium chloride systems. Polymer International, 2001, 50, 803811. [44] Hill, CAS; Cetin, NS; Ozmen, N. Potential catalysts for the acetylation of wood. Holzforschung, 2000, 54, 269-272. [45] Sun, JX; Xu, F; Geng, ZC; Sun, XF; Sun, RC. Comparative study of cellulose isolated by totally chlorine-free method from wood and cereal straw. Journal of Applied Polymer Science, 2005, 97, 322-335. [46] Sun, RC; Tomkinson, J. Separation and characterization of cellulose from wheat straw. Separation Science and Technology, 2004, 39, 391-411. [47] Jayakumar, R; Balaji, R; Nanjundan, S. Studies on copolymers of 2-(nphthalimido)ethyl methacrylate with methyl methacrylate. European Polymer Journal, 2000, 36, 1659-1666.

In: Homogeneous Catalysts: Types, Reactions and Applications ISBN: 978-1-61122-894-6 Editor: Andrew C. Poehler 2011 Nova Science Publishers, Inc.

Chapter 13

PALLADIUM COMPLEXES OF N-HETEROCYCLIC CARBENES IN HOMOGENEOUS CATALYSIS AND BIOMEDICAL APPLICATIONS

*

Chandrakanta Dash and Prasenjit Ghosh*

Department of Chemistry Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India

ABSTRACT
The knowledge of the efficient formation of CX (X = C and N) bonds asymmetrically or otherwise is vital to contemporary organic synthesis. In this context notable is the contribution of Pd towards the development of the area. The specialty of Pd as a metal lies in its ability to efficiently construct numerous types of CX (X = C, N, O and S) bonds under ambient conditions. A key strength of Pd mediated synthesis thus lies in its chemo- and regio selectivities that facilitate the synthesis of intricate target molecules otherwise not conveniently accessible by traditional methods. Furthermore, Pd, being a late transition metal, inherently possesses important attributes like, the air and moisture stability and the functional group tolerance, which often are the key ingredients of a successful catalyst. Of late, the N-heterocyclic carbenes (NHC) have added a new chapter in the design, discovery and development of Pd catalysts, thereby generating an enormous interest in its palladium complexes in recent years. The strong -donating nature of the N-heterocyclic carbene ligand in the catalyst allows oxidative insertions of challenging substrates while the ligand topological steric demands promote the fast reductive elimination reactions, which together constitute two important steps in numerous catalysis cycles. Additionally, the strong palladiumN-heterocyclic carbene (PdNHC) interaction help stabilizes many catalytically important active species at low
*

A version of this chapter was also published in Palladium: Compounds, Production and Applications , edited by Kenneth M. Brady, Nova Science Publishers. It was submitted for appropriate modifications in an effort to encourage wider dissemination of research. Email: pghosh@chem.iitb.ac.in, Fax: +91-22-2572-3480.

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ligand to Pd ratios and also at high temperatures thereby broadening its scope of catalytic applicability. Apart from the CX (X = C and N) bond forming reactions, the Pd complexes of N-heterocyclic carbenes perform various other reactions like the oxidation reactions, Tsuji-Trost reaction and the polymerization reactions etc. Even extending further beyond chemical catalysis, the palladium N-heterocyclic carbene complexes exhibit promising potential in various biomedical applications like in the anticancer studies.

INTRODUCTION
Smart and efficient formation of strategic bonds represents a perennial challenge in the world of organic synthesis and has largely propelled the development of various types of CX (X = C, N, O and S) bond forming reactions into powerful synthetic tools in the ever expanding arsenal of organic methodologies.[1] In this context the transition metals occupy a special place particularly for their role in both the stochiometric and catalytic bond formations[2].Notable is the versatility of palladium that makes it interesting among metals for the expedient construction of numerous CX bonds (X = C, N, O and S) in varied challenging environments and thereby thriving as a metal of choice under catalytically demanding situations.[3,4] The metals popularity stems from providing convenient access to key steps of various preparative protocols for the compounds of industrial and academic interests.[5] The other important attributes of palladium lie in its robustness and high air and moisture stabilities that facilitate indefinite storage and easy handling of its compounds. Additionally, the palladium catalysts are often functional group tolerant thus allowing it to function in synthetically delicate conditions. Though numerous catalysis with palladium have long been reported under the Ligand Assisted Catalysis (LAC) conditions,[6] the use of well-defined catalysts is advantageous in many respects like in maintaining a strict control of the optimal 1:1 palladium/ligand ratio, that avoid not only the large use of expensive ligands but also eliminate the excess ligand removal step at the end of the catalysis. The N-heterocyclic carbenes (NHCs) are fast emerging as an important ancillary ligand of choice that provide an appropriate platform for designing effective transition metal catalysts for a variety of important transformations in recent years. They are often seen as convenient alternatives to the phosphines, N- and O-donor ligands ubiquitous in numerous homogeneous catalysts.[7,8] The N-heterocyclic carbenes are good -donors[9] that favor strong binding to metals in general, and thereby prevent catalyst leaching, an important attribute of a successful catalyst, owing to reduced ligand dissociation. Furthermore, because of their tighter binding, the N-heterocyclic carbenes stabilize many catalytically relevant intermediates via a combination of electronic and steric effects. Thus, the rising status of the N-heterocyclic carbene catalysts can be attributed to their superior performance, ease of preparation, air and moisture stability, non-toxicity and the high efficiency at low catalyst loading. A prominent hallmark of the palladium complexes in general and its N-heterocyclic carbene ones in particular is their ability to efficiently execute the catalytic formation of a variety of CX (X = C and N) bonds under amenable conditions, which is in sharp contrast to the other frequently encountered alkali and transition metal based reagents like that of Li, Mg and Zn etc. that mostly participate in stoichiometric bond formations and also, being extremely air and moisture sensitive, require stringent handling measures.

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Remarkable is the ever growing portfolio of catalytic transformations partaken by palladium N-heterocyclic carbene complexes that span from the CC bond forming reactions namely, the SuzukiMiyaura, HeckMizoroki, Sonogashira, Hiyama, Kumada-Tamao-Corriu, Negishi, Stille, -ketone arylation, hydroarylation and carbonylation reactions to the CN bond formations like the aryl amination and hydroamination reactions. The monograph presents recent developments in the emerging utility of palladium N-heterocyclic carbene complexes in the homogeneous catalysis and in their newly evolving biomedical applications. The flexibility in conveniently shuttling between different oxidation states allows palladium to participate in numerous catalytic cycles involving oxidation and reduction sequences in the form of oxidative addition and reductive elimination steps. Though Pd(0)/Pd(II) shuttle is more commonly encountered, the Pd(II)/Pd(IV) shuttle too have been reported in some cases. b In this context the well-characterized examples of the Pd(0), Pd(II) and Pd(IV) complexes of N-heterocyclic carbenes assume relevance. Additionally, the electronic effects of palladium, being a second row transition element, provide optimal reactivity for catalysis as the first row ones are noted for their high reactivity while the third row ones are comparatively inert and hence the both of these are not so effective as catalysts compared to the second row metals on many occasions.

Palladium(0) N-Heterocyclic Carbene Complexes

Recognizing the importance of Pd(0)/Pd(II) shuttle in many catalytic cycles, there have been conscious efforts in the past toward directly accessing these catalytic cycles through well-characterized intermediates. In this regard several Pd(0) complexes (121) of Nheterocyclic carbenes[10] have been synthesized (Figure 1), some even structurally characterized, and subsequently employed in various catalysis like the, SuzukiMiyaura, b,c,e,f,h HeckMizoroki, e,i Sonogashira, g telomerization of 1,3-dienesd and aryl aminationb,g reactions etc. Though much rare compared to the Pd(II) counterparts, the Pd(0) Nheterocyclic carbene complexes have been synthesized primarily by employing two successful strategies. First one, the simplest of the two approaches, involved the direct reaction of a Pd(0) species with a N-heterocyclic carbene ligandd,e,h,i,j (Scheme 1), while the second method involved either the reduction of a Pd(II) species in presence of a Nheterocyclic carbene ligand or the direct reduction of a palladium(II) N-heterocyclic carbene complex itself (Scheme 2) to yield the desired palladium(0) N-heterocyclic carbene complex.
a,b,c,f,g

Palladium(II) N-Heterocyclic Carbene Complexes

Among the three oxidation states, the Pd(II) is by far the most commonly observed one with the contemporary literature inundated with numerous palladium(II) N-heterocyclic carbene complexes mainly because of their new-found success in homogeneous catalysis. The palladium(II) N-heterocyclic carbene complexes are primarily synthesized by any of the following three routes, (i) by transmetallation of the silver N-heterocyclic carbene complexes, obtained from the reaction of an azolium salt and Ag2O, with Pd(II) precursors,[11] (ii) by the

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direct reaction of the azolium salts with Pd(II) precursors in presence of a base[12] and (iii) lastly, by the oxidative addition of an activated CH bond in an azolium salt on the metal center of a Pd(0) precursor (Scheme 3).[13]

Figure 1.

(NHC)2Pd

(NHC)2Pd

Pd(0)

(PR3)2Pd

NHC

Pd(0) (alkene)

(COD)Pd(alkene)

(NHC)Pd(alkene)
Scheme 1.

(NHC)2Pd(alkene)

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reduction [Pd(allyl)Cl]2 NHC (NHC)2Pd

reduction (NHC)Pd(allyl)Cl L (L = PR3 or NHC)

Scheme 2.

(NHC)Pd(L)

Scheme 3.

Palladium(IV) N-Heterocyclic Carbene Complexes

The Pd(IV) species are extremely rare compared to the Pd(0) and Pd(II) species and consequently, the Pd(II)/Pd(IV) shuttle is less invoked than the Pd(0)/Pd(II) shuttle in various palladium mediated catalytic cycles. The structurally characterized example of a Pd(IV) Nheterocyclic carbene complex (22) (Figure 2) remained elusive until recently with the appearance of a report of a Pd(IV) N-heterocyclic carbene complex synthesized judiciously by the oxidative addition of two chloride ligands to a Pd(II) complex, Pd[OCMe2CH2(1C{NCHCHNiPr}][benzo(h)quinoline], using PhICl2 (Scheme 4).[14]

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Figure 2.

Scheme 4.

The monograph next discusses the various catalysis performed by palladium Nheterocyclic carbene complexes.

CC Bond Forming Reactions

Palladium mediated catalytic CC bond formations under amenable conditions have revolutionized the world of organic synthesis in the last few decades and have emerged as versatile synthetic tools for the smart and expedient preparations of numerous target molecules today. Though the phosphines have traditionally enjoyed a wide spread utility in palladium mediated catalysis, of late, the N-heterocyclic carbenes are seeing unprecedented popularity in this area, even surpassing the phosphines on many occasions.

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409

SuzukiMiyaura Cross-Coupling Reaction

The SuzukiMiyaura reaction, involving the palladium catalyzed CC cross-coupling of organoboron derivatives with aryl-, vinyl- or alkyl halides, is among the highly used methods available today for the construction of the biaryl frameworks ubiquitous in numerous bioactive molecules, pharmaceuticals and natural products (Scheme 5). The popularity of the reaction primarily arises from its tolerance towards a broad range of functional groups and from the several other advantages normally associated with the use of organoboron reagents like its ease of accessibility, convenience in product isolation and minimal toxicity issues. The N-heterocyclic carbenes have largely propelled the development of the Suzuki Miyaura CC cross-coupling reaction in the last two decades to an extent that the reaction is now finding routine use in both industry and academia alike. It is worth mentioning that the N-heterocyclic carbenes were originally introduced by Hermann as late as in 1998[15] in the SuzukiMiyaura reaction long after the initial discovery of the cross-coupling reaction by Suzuki and Miyaura in 1979.[16] Initial phases of the developments of the catalyst design and discovery for the coupling reaction mainly rode on the back of phosphine based systems till the advent of N-heterocyclic carbenes in this area. Particularly interesting is the SuzukiMiyaura cross-coupling of aryl chloride substrates, which are more challenging by virtue of being less reactive in contrast to the aryl iodide and bromide ones that readily undergo the cross-coupling reaction. The aryl chlorides, being more abundant, diverse and inexpensive, are in great demand for use as substrates for the crosscoupling reaction. Thus, though obvious, a formidable challenge, from both the academic and industrial perspectives, lies in utilizing the cheap and readily available aryl chlorides for the cross-coupling reaction. The difficulty of achieving the SuzukiMiyaura coupling of aryl chlorides largely stems from the stronger CCl bond than the other CX (X = Br, I) bonds [bond dissociation energy (kcal/mol) for PhX: Cl (95), Br (80) and I (65)],[17] thereby making the coupling of aryl chlorides a topic of contemporary interest. In this regard it is worth mentioning that significant efforts have been made toward developing catalysts for the coupling of aryl chlorides with the first breakthrough appearing only in 1998 using custombuilt sterically demanding phosphine systems,[18] nearly two decades after the initial discovery of the SuzukiMiyaura reaction with the aryl bromide substrates,[16] and thereby underscoring the underlying challenges associated with the coupling of aryl chlorides. In keeping with the phenomenal successes of N-heterocyclic carbenes in catalysis, numerous attempts have been made in recent years in exploring their potential in the SuzukiMiyaura cross-coupling reaction.[19] Specific emphasis lay on designing suitable catalysts exhibiting high turnover numbers (TONs) or the ones with the ability to perform more challenging and also synthetically coveted aryl chloride coupling. The catalysis studies were performed either under Ligand Assisted Catalysis (LAC) conditions, involving the in situ generation of an active catalyst from the ligand and a metal precursor, or using well-defined precatalysts. Among the Ligand Assisted Catalysis (LAC) reported with the N-heterocyclic carbenes, notable is an unsymmetrically substituted imidazolium bromide salt 31 (Figure 3) which in presence of a palladium(0) precursor, Pd2(dba)3 (dba = dibenzylideneacetone), exhibited extremely high turnover number (TON) of 3.3 x 107 for the coupling of phenyl iodide with phenyl boronic acid.[20]

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Chandrakanta Dash and Prasenjit Ghosh

X + R'

Pd-NHC complex

R' +

R'

M = organoboranes (Suzuki) organostannanes (Stille) organomagnesium (Kumada) organozinc (Negishi) organosilicon (Hiyama) amines (Buchwald-Hartwig)

Sceme 5.
R N N Cl R R = 4-Me-C6H4 (23); 4-Et-C6H4 (24); 4-i-Pr-C6H4 (25); 4-Ph-C6H4 (26); 4-OEt-C6H4 (27) R R Ad N N Cl Ad i-Pr i-Pr O O N Br N Br

R = OMe (28); H (29); F (30)

31

c-hex Cl N c-hex Fe PPh2 N NI t-Bu

c-hex c-hex 32 33

Figure 3.

It is worth mentioning that catalysts with ultra-high turnover numbers (TONs) are primarily important from the point of utilizing only little amount of the expensive palladium metal as well as the N-heterocyclic carbene ligands for the catalysis. The catalysts exhibiting ultra-high turnover numbers enjoy an additional advantage of avoiding any tedious catalyst separation step often required at the end of the catalytic cycle and thereby adding to the overall cost effectivity of the process. Another ferrocenyl phosphine functionalized imidazolium iodide salt 33 (Figure 3) exhibited a remarkably high turnover number (TON) of up to 20,000 and a turnover frequency (TOF) of up to 10,000 h-1 for the cross-coupling of aryl bromides.[21] Significant breakthroughs have been achieved in the coupling of the more difficult aryl chloride substrates using N-heterocyclic carbenes. Specifically, a 1,3-dialkylperhydrobenzimidazolinium chloride salts 2327[22] and its related unsaturated counterparts, benzimidazolium chloride salts 2830[23], (Figure 3) carried out the cross-coupling of aryl chlorides at a relatively low temperature 80 C in good to excellent yields. Another sterically demanding phenanthryl derived N-heterocyclic carbene precursor 32[24] (Figure 3)

Palladium Complexes of N-Heterocyclic Carbenes

411

performed the cross-coupling of aryl chlorides under ambient conditions i.e., both at room temperature and at 50 C. In this regard it is worth mentioning that Buchwald introduced the use of sterically demanding phosphine ligands for the cross-coupling of aryl chlorides.[25] Parallel to the Ligand Assisted Catalysis (LAC) studies, efforts were directed toward designing Pd(0) and Pd(II) initiators of N-heterocyclic carbene ligands for the cross-coupling reaction. The use of well-defined transition metal based initiators is advantageous particularly with regard to avoiding a large excess of expensive N-heterocyclic carbene ligands often seen under Ligand Assisted Catalysis (LAC) conditions. However, the approach calls for greater efforts with synthesis and characterization of well-defined discrete catalyst complexes. Notable are several palladium(0) complexes of N-heterocyclic carbenes having both saturated and unsaturated imidazole frameworks of type 916 (Figure 1) that have been successfully employed in the SuzukiMiyaura cross-coupling reaction of aryl chlorides in good to excellent yields at 3 mol % of the catalyst loading. b,f,h Another bis-oxazoline derived Nheterocyclic carbene palladium(0) complex 17 carried out the coupling of sterically demanding 2,6-disubstituted aryl chlorides at a much lower catalyst loading of 0.03 mol % under ambient conditions in good to excellent yields. c A slight variant of the SuzukiMiyaura reaction employing aryldiazonium tetrafluoroborate salts as substrates instead of the ubiquitous aryl halides was reported using a palladium(0) N-heterocyclic carbene complex 21 at 50 C. e In sharp contrast to only a handful of examples known of Pd(0) precatalysts for the crosscoupling reaction, the Pd(II) counterparts have been extensively studied. The numerous palladium(II) N-heterocyclic carbene precatalysts that exist can be primarily classified into four types, (i) the mono-N-heterocyclic carbene complexes (A), (ii) bis-N-heterocyclic carbene complexes (B), (iii) the PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed complexes (C) and lastly, (iv) the mixed N-heterocyclic carbene and phosphine complexes (D) (Figure 4). Among the mono-N-heterocyclic carbene Pd(II) precatalysts, the (NHC)Pd(allyl)Cl types 3439[26] have been thoroughly studied by carrying out the variation of substituents on the allyl moiety like in 4042[27] as well as on the N-heterocyclic carbene ligand like in 4752[28] (Figure 5). Specifically, the air and moisture stable precatalysts 3438b showed high activity towards the cross-coupling of activated and unactivated aryl chloride and bromide substrates at 60-80 C in presence of NaOtBu as a base. On the contrary, the precatalyst 39a was found to be only moderately active in the SuzukiMiyaura coupling of aryl halides. The precatalysts, 4042, possessing different alkyl and aryl substituents on the allyl moiety, exhibited high cross-coupling activity under ambient conditions at room temperature. In particular, the precatalyst 42 performed the coupling of a wide range of aryl bromide, triflate and the chloride substrates with boronic acids at room temperature at an extremely low catalyst loading of 0.05 mol %. A similar type of naphthyl based (NHC)Pd(allyl)Cl precatalysts 4749c performed better than the precatalysts 37 and 38 at 80 C. Significant reactivity difference could be seen among the precatalysts 4749 in the coupling reaction performed at room temperature. Another precatalyst 50b carried out the coupling of aryl chlorides with 1-naphthalene-boronic acid at a low catalyst loading of 0.2 mol% in a short reaction time of 2 hours at 60 C.

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Figure 4.
i-Pr R N N R R N N R N i-Pr Pd Cl Pd Cl R R' R = t-Bu (34); 2,6-i-Pr2C6H3 (35); R = 2,6-i-Pr2C6H3 (37); mesityl (38); R = Me, R' = H (40); R = 2,6-i-Pr2C6H3 (43); mesityl (44) R = 2,6-i-Pr2C6H3 (45); mesityl (46) R = Me, R' = Me (41); 2-(Ph)C6H4 (39) mesityl (36) R = Ph, R' = H (42) N i-Pr Cl i-Pr R N N R R N N R

Pd

Pd Cl

Pd Cl

X R' R N Pd Cl N R R' O N OX Pd Cl R R = R' = i-Pr (47); R = R' = Me (48); R = H, R' = Me (49); X = (CH2)8 (50) R = H (51); Ph (52) 53 N O Cy2N O i-Pr N i-Pr N i-Pr Cl NCy2 N Mes N Pd N Mes i-Pr BF4

Pd

Figure 5.

Attempts toward designing mixed cyclopentadienyl and N-heterocyclic carbene systems of palladium, 4346[29] proved to be of limited success though these precatalysts performed the SuzukiMiyaura cross-coupling of a wide range of substrates including the chlorides in room temperature. In this regard it is noteworthy that cyclopentadienyl ligands have played a significant role in olefin polymerization, CH activation, hydrogen transfer reaction, hydroamination, hydration of terminal alkynes to aldehydes, asymmetric allylic alkylations, asymmetric Diels-Alder reaction etc.[30] Several ionic complexes of the types [(NHC)Pd(allyl)]+BF4-, 53,[31] and [(NHC)PdCl]+X- (X = BF4, PF6 and Cl), 5458,[32] have been found to be good for the coupling of aryl chloride, bromide and iodide substrates (Figure 6). The ionic complex 53 showed high activity in carrying out the cross-coupling at low catalyst loadings of 0.050.5 mol %. Another variation includes a series of N-chelated Nheterocyclic carbene palladium complexes 6062,[33] 6466[34] and 69[35] (Figures 6 and 7).

Palladium Complexes of N-Heterocyclic Carbenes

X N Br Pd Br N N Cl O N N R' O N N Pd Cl N N N N N Pd Cl Cl Ph N Ph N N O Fe N Pd Cl Ph

413

N N

N Pd Cl

R = Me, R' = n-Bu, X = BF4 (54); R = Me, R' = n-C7H15, X = BF4 (55); R = Me, R' = n-C7H15, X = PF6 (56); R = H, R' = n-Bu, X = BF4 (57); R = Me, R' = mesityl, X = Cl (58);

59

60

61

62

Me i-Pr N N Pd (OAc)2 N i-Pr i-Pr N Cl Me Me Pd S N N O O Pd N N N O Me O Me Pd Cl Cl N N

N i-Pr

63

64

65

66

Figure 6.

Of these, notable are the 60, 62 and 69 precatalysts that carried out the SuzukiMiyaura cross-coupling at low catalyst loadings. Of special mention is the 60 complex that exhibited high turnover number (TON) of up to 11,750 for the SuzukiMiyaura cross-coupling of an activated p-bromoacetophenone substituent with phenylboronic acid. a The other reported variations of precatalysts include mononuclear trans-[PdBr2(NHC)(imidazole)] (59)[36] and dinuclear [(NHC)Pd(-X)X]2 (X = halide) type 67,[37] 68[38] and 70[39] complexes, of which 70 efficiently catalyzed the SuzukiMiyaura cross-coupling at low catalyst loading under mild reaction conditions (Figure 7). The precatalyst 63[40] of the type (NHC)Pd(OAc)2 exhibited the cross-coupling of aryl chlorides and activated alkyl chlorides with aryl boronic acids. The bis-N-heterocyclic carbene palladium precatalysts primarily fall into two categories namely, the non-chelated (NHC)2PdX2 (X = halide) and the chelated-(NHC)2PdX2 (X = halide) type complexes (Figures 89). Notable is a non-chelated trans-(NHC)2PdX2 type complex 71[41] that exhibited ultra high turnover number (TON) of 1,09,600 for the cross coupling of o-bromobenzaldehyde with phenylboronic acid at 85 C in 12 hours of the reaction time. Similar type of non-chelated trans-(NHC)2PdX2 type complexes 7273[42], 81,[43] 9091[44] have been designed for the SuzukiMiyaura cross-coupling of aryl halides with aryl boronic acids. Specifically, the precatalysts 9091 performed the coupling reaction of 4-bromotoluene and phenylboronic acid at low catalyst loadings of 0.002 mol% exhibiting turnover numbers (TONs) of up to 13,700 at 85 C in 24 hours. The benzthiazoline derived precatalysts 7475[45] having a rare cis-geometry for unbridged non-chelated (NHC)2PdX2 type complexes showed turnover numbers (TONs) of up to 3,300 for the coupling of pbromobenzaldehyde with phenylboronic acid.

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Chandrakanta Dash and Prasenjit Ghosh

OMe N N Pd N N OMe N N n-Bu n-Bu Pd N N N N 2 2Cl i-Pr N i-Pr N i-Pr i-Pr Pd Cl Cl Cl i-Pr N i-Pr 70 Cl Pd i-Pr N i-Pr

N N R

R Br Pd Pd Br R N Br R N N

n-Bu n-Bu

Br

R = i-Pr (67); CH(Ph)2 (68)

69

Figure 7.

Quite interestingly, a 1,2,3-triazole derived abnormal N-heterocyclic carbene trans(NHC)2PdX2 type precatalyst 92[46] exhibited the cross-coupling of aryl bromides with aryl boronic acids. However, the observed activities were not too high. Adding to the structural diversity, an acyclic chelated diaminocarbene complex of type bis-(NHC)2PdCl2 93[47] has been reported for the cross-coupling of aryl bromide and chloride substrates with aryl boronic acids at 1 mol% of catalyst loading. The chelated cis-(NHC)2PdX2 type of complexes 8386[48] and 89[49] displayed the cross-coupling of aryl bromides with phenylboronic acid. Particularly, the o-xylyl-linked alkoxy benzimidazole precatalysts 8386 exhibited moderate to high activities, displaying turnover numbers (TON) of up to 26,000 for the coupling of aryl bromides with phenylboronic acid. Though chelated bis-(NHC)2PdX2 complexes often exhibit cisgeometries, unusual trans-dispositions were observed in the case of the 76 and 77 complexes, in which the two N-heterocyclic carbenes were linked by extended crown-ether linkages.[50] Quite importantly, the precatalysts, 7677, showed ultra high turnover numbers (TONs) of up to 99,000 for the coupling of aryl bromides with aryl boronic acids in neat water under aerobic conditions. Other chelated bis-N-heterocyclic carbene precatalysts 7880,[51] 82[52] and 8788[53] were found to be active for the cross-coupling of aryl and benzyl halides. The precatalysts 8788 performed the cross-coupling of aryl boronic acids with aryl and arylmethyl bromides in water. The third category involves PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalysts, which were originally designed with the intention of having a loosely bound throwaway ligand namely, a pyridine moiety, trans to the metal bound strongly -donating N-heterocyclic carbene ligand (Figure 10). The strong trans effect of the N-heterocyclic carbene ligand was anticipated to weaken the binding of the diagonally opposite throwaway pyridine ligand, which would thus dissociate and give away to the incoming substrate. Several variations of PEPPSI themed precatalysts bearing nonfunctionalized 9497, e,[54] the N/O-functionalized N-heterocyclic carbene sidearm substituents 98112[55] alongwith differently substituted pyridine variants 94114e, have been synthesized. Variation on the imidazole ring too has been attempted in the form of benzimidazole N-heterocyclic carbene PEPPSI precatalysts 113114. The precatalysts 9497 showed high activity in the SuzukiMiyaura cross-coupling of aryl bromide and chloride substrates with the various boron derivatives like aryl boronic acids and alkyl-9-BBN (9-BBN

Palladium Complexes of N-Heterocyclic Carbenes

415

= 9-borabicyclo[3.3.1]nonane). Significantly enough, the precatalyst 97a exhibited excellent catalytic activity in the coupling of sterically hindered aryl bromides and chlorides with aryl boronic acids to yield bulky tetra-ortho-substituted biaryl products in good yields under mild reaction conditions. The precatalyst 94b performed the cross-coupling of unactivated alkyl bromide and the aryl bromide and chloride substrates with alkyl-9- borabicyclo[3.3.1]nonane at room temperature. The N/O-functionalized N-heterocyclic carbene based PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) complexes 98100b were found to be excellent precatalysts not only for the commonly observed Csp2Csp2 coupling but also for the more challenging Csp3Csp2 cross-coupling at a low catalyst loading of 0.35 mol %. The PEPPSI precatalysts 101112 have been reported for the cross-coupling of aryl chlorides with phenylboronic acids in water at 1 mol % of catalyst loading. Notable are the N/O-functionalized N-heterocyclic carbene precatalysts 113114 that exhibited higher turnover numbers (TON) of up to 4,930 for the coupling of 4-bromotoluene with phenylboronic acid. The last category represents the mixed N-heterocyclic carbene and phosphine complexes, which are primarily of two types namely, the neutral (NHC)PdX2(PR3) and the ionic [(NHC)PdX(PR3)2]+X- complexes (Figures 1112). Both normal as well as abnormal Nheterocyclic carbene precatalysts have been reported for the above two classes. Quite remarkably, the (NHC)PdX2(PR3) type precatalyst 115[56] showed superior activity exhibiting ultra-high turnover numbers (TONs) of up to 106 for the aryl bromides and of up to 6,000 for the aryl chloride substrates with phenylboronic acids. The deactivated bromoarenes could also be efficiently coupled at a low catalyst loading of 0.005 mol %. The other variation of the (NHC)PdX2(PR3) type precatalysts, 124131, ,[57] 138141[58] and 143151,[59] have been reported for the cross-coupling of aryl bromide and chloride substrates with aryl boronic acids. The precatalysts, 124125, showed high turnover numbers (TONs) of up to 18,300 for the coupling of 4-bromotoluene with phenylboronic acid. The precatalysts 143146a have been used for the coupling of bulky aryl boronic acids with the aryl bromide and chloride substrates. A neutral (NHC)PdX2(PR3) type precatalyst of mixed abnormal pyrazole based N-heterocyclic carbene and phosphine ligands, 132133 have also been employed in the cross-coupling reaction.a The mixed abnormal N-heterocyclic carbene and phosphine complexes of the ionic type [(NHC)PdX(PR3)2]+X- precatalysts, 116123, b showed excellent activity for the crosscoupling of aryl bromide and chloride substrates with phenylboronic acids with the precatalyst 120 exhibiting ultra-high turnover number (TON) of up to 2,600,000 for the coupling of p-bromo acetophenone with phenylboronic acid. The pyrazole derived abnormal N-heterocyclic carbene precatalysts 134135a were reported for the cross-coupling for aryl bromides and chlorides with phenylboronic acids in aqueous medium at both room temperature and at 80 C. It is interesting to note that the ionic type [(NHC)PdX(PR3)2]+Xcomplexes 134135 are more active than the corresponding neutral (NHC)PdX2(PR3) ones 132133. A few examples of chelated bis phosphine/phosphite complexes 136137[60] and 142[61] have been reported for the cross-coupling of aryl and alkyl bromides. A few more examples of polymer supported precatalysts for the SuzukiMiyaura crosscoupling reactions are known,[62] however, these are beyond the purview of the present

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chapter that focuses on the utility of N-heterocyclic carbene based palladium complexes in homogeneous catalysis and biomedical applications.
LnPd(0) R R' R X

reductive elimination

oxidative addition

R LnPd R' LnPd

R X

R' transmetallation

R'

M = organoboranes (Suzuki) organostannanes (Stille) organomagnesium (Kumada) organozinc (Negishi) organosilicon (Hiyama) amines (Buchwald-Hartwig)

Scheme 6.

Important is the knowledge of the mechanism of a reaction for the design and discovery of new catalysts. Of the several views that persist of the SuzukiMiyaura cross-coupling reaction, the most commonly accepted one involve a Pd(0)/Pd(II) shuttle in its catalytic cycle (Scheme 6). The mechanism is proposed to proceed via an active Pd(0) species, often formed in situ from the reduction of Pd(II) precursors by a base or a phosphine ligand or an organic nucleophile etc. The electron rich Pd(0) species subsequently undergoes oxidative addition followed by transmetallation of organic nucleophile from an organoboron reagent. The final step involves a reductive elimination step yielding the desired cross-coupled product. More interestingly, the above mechanism has been found to be generic for many similar palladium catalyzed CC and CN cross-coupling reactions (Scheme 6).

HeckMizoroki Reaction
The palladium-mediated coupling of aryl and alkenyl iodides, bromides, triflates etc. with alkenes in the presence of a base is popularly known as the HeckMizoroki reaction (Scheme 7). As the name suggests it was first independently discovered by Mizoroki[63] and Heck[64] in the 1970s. Over the years because of its wide spread utility in complex natural product synthesis and in industrial processes, the HeckMizoroki reaction has grown into an important CC cross-coupling reaction. As was the case with SuzukiMiyaura coupling, here too, Herrmann first introduced N-heterocyclic carbenes in HeckMizoroki reaction in

Palladium Complexes of N-Heterocyclic Carbenes

417

1995,[65] even three years earlier than that he did the same for in SuzukiMiyaura coupling in 1998.

Scheme 7.

Subsequently, several reports of the application of N-heterocyclic carbenes in HeckMizoroki coupling have appeared over the years with many performed under Ligand Assisted Catalysis (LAC) conditions (Figure 13). Notable is a 1,3-bis(mesityl)-imidazolium chloride salt 152[66] that efficiently carried out the coupling of n-butyl acrylate with bromoarenes at different palladium to the ligand ratios of 1:1 and 1:2. Another saturated Nheterocyclic carbene precursor 153[67] performed intramolecular Heck reaction and decarbonylative Heck coupling. A bis(imidazolium) salt 154[68] was used as an ionic liquid in presence of PdCl2 for the Heck coupling of aryl halides with n-butyl acrylate. Quite significantly, a multidentate N-heterocyclic carbene ligand precursor 155[69] exhibited the coupling of aryl bromides with styrene and t-butyl acrylate. The 1,3dialkylperhydrobenzimidazolinium chloride salts 2327 (Figure 3) performed the coupling of aryl bromides with styrene in good to excellent yields. A new class of efficient triphenylarsinyl-functionalized N-heterocyclic carbene based precatalysts 157159a have been tested for the Heck, hydro-Heck, , domino-Heck reactions. Furthermore phosphine functionalized N-heterocyclic carbene ligand precursors, 156[70] and 160162[71] in presence of Pd(dba)2 exhibited the Heck coupling of a wide array of aryl bromides and iodides with n-butyl acrylates in excellent yields. Though Ligand Assisted Catalysis (LAC) was quite successful in the HeckMizoroki coupling, numerous attempts have also been made towards employing well-defined Pd(0) and Pd(II) complexes in the cross-coupling reaction. It is noteworthy that among well-defined palladium precatalysts, fewer reports exist of Pd(0) ones. A Pd(0) precatalyst 20i (Figure 1) performed the Heck coupling of 4-bromoacetophenone with n-butyl acrylate. Another palladium(0) precatalyst 21e (Figure 1) carried out the coupling of aryl diazonium salts with various olefinic substrates. However, there exists comparatively a lot more examples of welldefined Pd(II) precatalysts for the cross-coupling reaction than the palladium(0) ones. In this regard a variety of the mono-N-heterocyclic carbene Pd(II) precatalysts namely, 53, (Figure 5) 61, c (Figure 6) 69 (Figure 7) and 163181 (Figures 1415) have been designed. Interestingly enough, the precatalysts 163164, 170a and 179[73] stabilized by pyridine chelated N-heterocyclic carbene ligands exhibited high activities in the coupling reaction. Quite remarkably, the precatalyst 164b showed ultra-high turnover numbers (TONs) of up to 2,858,000 for the coupling of methyl acrylate and iodobenzene. Another precatalyst 181[74] supported over a pyrazole chelated N-heterocyclic carbene ligand as opposed to the aforementioned pyridine chelated N-heterocyclic carbene ones in the 163164, 170 and 179 complexes exhibited good activity in an ionic liquid medium of 1-butyl-3-methylimidazolium hexafluorophosphate, [(BMIm)(PF6)] salt. Along similar line, the pyrimidine chelated N-

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Chandrakanta Dash and Prasenjit Ghosh

heterocyclic carbene precatalysts[75] 66 (Figure 6) and 175178 (Figure 15) and a pyrazole chelated N-heterocyclic carbene precatalyst 180[76] (Figure 15) efficiently performed the HeckMizoroki couplings. A new class of mixed N-heterocyclic carbene-palladacycle precatalysts 165[77] and 171[78] was reported for the cross-coupling reaction (Figure 14). A precatalyst 165 exhibited very high turnover numbers (TONs) of up to 5,33,000 for the coupling of an activated 4bromoacetopheneone substrate with styrene. A highly air and moisture stable precatalyst 171 exhibited good to excellent yields for coupling of functionalized aryl and heteroaryl bromides and iodides with olefins. Several benzothiazoline based palladium precatalysts 168169 and 173 showed the high catalytic activity for the coupling of aryl bromides with t-butyl acrylate.[79] The mixed -diketonato N-heterocyclic carbene complexes 166167[80] and an acetate bridged dimer of the type 174[81] exhibited good cross-coupling activities. Apart from the mono-N-heterocyclic carbene precatalysts, the bis-N-heterocyclic carbene ones 182256 (type B, Figure 4) have been extensively studied for the cross-coupling reaction (Figures 1620). Quite interestingly, the precatalyst 187 exhibited the turnover numbers (TONs) of up to 13,000 after due optimization of the reaction conditions.[82] Variation of the substituent from a methyl group in 187 to a phenyl group in 188, led to significant increase in the turnover numbers (TONs) to up to 88,000. Similarly the precatalysts 203204 showed high turnover numbers (TONs) of up to 77,000. In this context worthy of mention are the six-membered cyclic diaminocarbene complexes 182183[83] that exhibited extremely high turnover numbers (TONs) of up to 9,97,000 for the coupling of 4bromoacetophenone with n-butyl acrylate. A homoleptic palladium precatalyst 205[84] showed ultra-high turnover numbers (TONs) of up to 8.08 x 108 for the cross-coupling of phenyl iodide and styrene. The precatalysts 184186[85] performed the Heck-Mizoroki coupling of t-butylacrylate and aryl halides. Specifically, a cationic amine tethered bis-Nheterocyclic carbene precatalyst 184 exhibited the high turnover numbers (TONs) of up to 34,700 in the coupling of t-butylacrylate and 4-bromoacetophenone. A series of palladium precatalysts 191201[86] of CNC-pincer ligand containing two N-heterocyclic carbene moieties connected to a pyridine core showed excellent performance in the HeckMizoroki reactions. A related variant 202c in the form of a CCC-pincer ligand was also found to be active in the cross-coupling reactions. Quite significantly, the precatalysts 197 and 202 were found to be thermally stable thereby facilitating the HeckMizoroki olefination of aryl chlorides at a high temperature. c Several other chelated cis-(NHC)2PdX2 type complexes namely, 8386, (Figure 8) 89, (Figure 9) 189190, (Figure 16) 220227, a,[87] (Figure 18) 234 (Figure 19) and 243254[88] (Figure 20) have been designed as precatalysts for the HeckMizoroki CC cross-coupling reactions. Of special mention are the o-xylyl linked alkoxy benzimidazole derived precatalysts 8386 that showed very high turnover numbers (TONs) of up to 1,800,000 for the coupling of n-butyl acrylate and iodobenzene. Similar type of o/m-xylyl linked imidazole derived precatalysts 220226a, a showed excellent activity for the coupling of aryl halides and n-butyl acrylate. The N-methylated benzimidazole derived precatalysts 209216[89] performed the HeckMizoroki arylations of t-butyl acrylate. It is worth noting that both the cis- 209 and trans- 210 isomers were equally active in the cross-coupling reaction. c The related cis-carboxylate palladium precatalysts 214216b showed high activities for the coupling of aryl halides and t-butylacrylate.

Palladium Complexes of N-Heterocyclic Carbenes

O R N N R' Cl Pd Cl N R R' N S S N O N X Pd X N N Cl Pd Cl N N O O N N R O O N Pd Cl N N R N N Cl Pd Cl N N

419

R R R = t-Bu, R' = CH22-(OMe)C6H4 (71); R = i-Pr, CH2CONHCH2Ph (72); X = Br (74); O2CCF3 (75) R = mesityl (76); 2,6-i-Pr2C6H3 (77) R = CH2Ph (78); n-Bu (79); R = CH2Ph; CH2CONHCH2Ph (73) CH2mesityl (80)

81

BuO N N N Pd Cl N BuO BuO N N N Pd N Br Br BuO BuO

BuO BuO N N N Pd N Br Br

OBu N OBu BuON N Pd N OBu

Br Br

BuO

82

5,6-BuO (83); 4,7-BuO (84)

85

86

Figure 8.
N O N Pd Br HO N N R N R Br N N Br Pd Br N N BuO N N I Pd BuO I N OBu N OBu

R = COOEt (87); COOH (88)

89

5,6-BuO (90); 4,7-BuO (91)

Me N N N Cl N Boc Ph Pd Ph Boc N Cl N N N Me 92 93 H Me N Pd Cl H N N

Me Me N Cl H

Figure 9.

The chelated cis-(NHC)2PdX2 type 241[90] and the non-chelated (NHC)2PdX2 type 255[91] precatalysts derived from chiral amines exhibited good catalytic activity in the Heck Mizoroki arylation reactions. An oxazoline derived trans-(NHC)2PdX2 type precatalyst 235[92] was found to be less active in the cross-coupling reaction. The non-chelated (NHC)2PdX2 type precatalysts 236237[93] showed good catalytic activities in double Heck Mizoroki coupling reactions with aryl dibromides yielding diacrylates.

420
R Cl N Pd N R Cl N Cl

Chandrakanta Dash and Prasenjit Ghosh

R R N N R' R' X Pd X N N N Br HOOC Pd N

Br HOOC

R = 2,6-i-Pr2C6H3 (94); 2,6-Et2C6H3 (95); mesityl (96); 2,6-i-pentC6H3 (97)

R = CH2Ph, R' = CH2CONH Bu, X = Cl (98); R = 2-(OH)C6H10, R' = CH2Ph, X = Cl (99); R = t-Bu, R' = CH22-(OMe)C6H4, X = Br (100)

R = CH2OMe, R' = mesityl (101); R = CH2OMe, R' = 2,3,5,6,-Me4C6H (102); R = CH2OMe, R' = 2,3,4,5,6,-Me5C6 (103)

R N N R' R = CH2OMe, R' = mesityl, X = COOH, X' = X'' = H (104); R = CH2OMe, R' = mesityl, X' = COOH, X = X'' = H (105); R = CH2OMe, R' = mesityl, X'' = COOH, X = X' = H (106); R = CH2OMe, R' = 2,3,5,6-Me4C6H, X = COOH, X' = X'' = H (107); R = CH2OMe, R' = 2,3,5,6-Me4C6H, X' = COOH, X = X'' = H (108); R = CH2OMe, R' = 2,3,5,6-Me4C6H, X'' = COOH, X = X' = H (109); R = CH2OMe, R' = 2,3,4,5,6-Me5C6, X = COOH, X' = X'' = H (110); R = CH2OMe, R' = 2,3,4,5,6-Me5C6, X' = COOH, X = X'' = H (111); R = CH2OMe, R' = 2,3,4,5,6-Me5C6, X'' = COOH, X = X' = H (112) Br Pd Br N X X' X'' BuO BuO N N I Pd I N Cl

5,6-BuO (113); 4,7-BuO (114)

Figure 10.

The precatalysts of the type (NHC)2Pd(Me)Cl, 206207a, and 217219, a, efficiently performed the cross-coupling reaction in good to excellent yields. Quite remarkably, the precatalyst 217a showed an extremely high turnover numbers (TONs) of up to 9,80,000 while a related precatalyst 218 showed up to 1,700,000. Another precatalyst 256 of the [(NHC)PdCl][PdCl3] type, exhibited turnover numbers (TONs) of up to 1,20,000 and a turnover frequency (TOF) greater than 4,500 h-1. A dicationic palladium precatalyst 242[94] showed turnover numbers (TONs) of up to 106 and a turnover frequency (TOF) of up to 5 x 104 h-1 for the coupling of n-butyl acrylate and aryl halide substrates. The PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed ones supported over functionalized benzimidazole N-heterocyclic carbenes namely 113114 exhibited high turnover numbers (TONs) of up to > 1,800,000 for the cross-coupling of iodobenzene and n-butyl acrylate. Lastly, several mixed N-heterocyclic carbene (NHC) and phosphine precatalysts namely, 115123b (Figure 11), 124125 (Figure 11), 136141, (Figure 12) and 257276,[95] (Figures 2122), have been employed in the HeckMizoroki cross-coupling reaction. Most of these palladium precatalysts mainly fall into two categories (i) the cationic [(NHC)PdX(PR3)2]+X- type complexes and (ii) the neutral (NHC)PdX2(PR3) ones. The palladium complexes 116123, b 136137and 257265a belong to the cationic [(NHC)PdX(PR3)2]+X- type. Quite significantly, the cationic precatalyst 137 of a Nheterocyclic carbene derived PCP-pincer ligand showed ultra-high turnover numbers (TONs) of up to 56,000,000 in the coupling of phenyl iodide with styrene. The other class of neutral (NHC)PdX2(PR3) type precatalysts include the 115b 124125, (Figure 11) 138141 (Figure 12) and 266268a complexes. Among these, notable is the precatalyst 124 that exhibited extremely high turnover numbers (TONs) of up to 1,713,000 for the coupling of iodobenzene and n-butyl acrylate.

Palladium Complexes of N-Heterocyclic Carbenes

BF4 X' i-Pr Ph3P N N i-Pr Ph3P X Pd PPh3 Cl X = NMe, X' = CH (116); X = CH, X' = NMe (117) BF4 X' X Ph3P N Me Ph3P Pd PPh3 Cl X = H (121); X = Me (122) Ph3P Pd PPh3 Cl Me N X BF4 Me N BF4

421

Pd Cl Cl

Pd PPh3 Cl

115

X = H, X' = H (118); X = Me, X' = H (119); X = H, X' = Me (120)

123

BuO

N N

PPh3 Pd I

S N R

L Pd Br Br R N N

PPh3 Pd I I R

PPh3 N N Pd I

OTf

BuO

PPh3

5,6-BuO (124); 4,7-BuO (125)

L = PPh3, R = CH2Ph (126); L = PPh3, R = n-Pr (127); L = PCy3, R = CH2Ph (128); L = PCy3, R = n-Pr (129); L = PPh2Py, R = CH2Ph (130); L = PPh2Py, R =n-Pr (131)

R = Ph (132); Me (133)

R = Ph (134); Me (135)

Figure 11.
Cl N Ph3P Pd Cl N PPh2 Ph3P N Pd N C Me R = Ph (138); 2-(CH3)C6H4 (139); Cy (140); t-Bu (141) R = 2,4-t-Bu2C6H3 (142) N N PPh2 N I Pd PR3 I t-Bu 2 2 BF4 t-Bu O P(OR)2 Pd PCy3 Cl

136

137

O Ph R3P N Pd Cl R = Ph (143); Cy (144) N Cl NHPh Ph R3P N Pd Cl N Cl

O NHPh N R N Pd P Ph Ph

Cl Cl

R = Ph (145); Cy (146)

R = mesityl (147); CH2C10H7 (148); CH2Ph (149);CH24-(F)C6H4 (150); CH23-(OMe)C6H4 (151)

Figure 12.

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Chandrakanta Dash and Prasenjit Ghosh

Scheme 8.

In addition to the large body of palladium precatalysts discussed above there exist a handful of examples of polymer supported ones for the HeckMizoroki cross-coupling reactionb,d,g,[96] that were employed under heterogeneous catalysis conditions and hence they fall outside the scope of the present discussion. The mechanism of HeckMizoroki cross-coupling reaction involves the Pd(0)/Pd(II) states in its catalytic cycle (Scheme 8). The mechanism initiates with an oxidative addition of an aryl or alkenyl halide on a catalytically active palladium(0) species to generate a palladium(II) intermediate, which reacts with an olefin to yield a palladium(II) alkyl complex. The palladium(II) alkyl complex then undergoes hydride elimination to form the desired cross-coupled product. The last step involves the base assisted elimination of HX from the palladium(II) complex, thus, regenerating the starting palladium(0) active species.

Stille Cross-Coupling Reaction

A convenient protocol for biaryl synthesis alongside the SuzukiMiyaura and Hiyama couplings is the Stille reaction that involves a CC cross-coupling of aryl halides with organostannens (Scheme 5).[97] However, the reactions wide spread utility is largely plagued by several major limitations like that of the toxicity issues with tin as a metal and the difficulties associated with removing the metal from the final reaction mixture. The Nheterocyclic carbenes were first introduced by Herrmann in the Stille coupling in 1999.[98]

Palladium Complexes of N-Heterocyclic Carbenes

423

Figure 13.

Figure 14.

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Chandrakanta Dash and Prasenjit Ghosh

Figure 15.

Figure 16.

Palladium Complexes of N-Heterocyclic Carbenes

2 N N Me I Pd I N N Me N N Me I Pd I N N Me N N 203 204 N N N Pd N X N Me N N X 2 BF4 Me N Me Pd Cl N Me Me N

425

X X

205

X = H (206); Me (207)

RR N N Cl Pd Cl N N N R X N Pd X N N R N N

N O Pd N O

O R R O

Me N N R Me Pd Cl

R N N Me

208

R = Me, X = I, cis (209); R = Me, X = I, trans (210); R = i-Pr, X= I, trans (211); R = i-Pr, X= Br, trans (212); R = i-Pr, X= O2CCF3, cis (213)

R = Me (214); CF3 (215); CF2CF3 (216)

R = CH2Ph (217); R = CH2Py (218); R = CH2CO2Me (219)

Figure 17.

Figure 18.

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Chandrakanta Dash and Prasenjit Ghosh

Figure 19.

Figure 20.

The mixed N-heterocyclic carbene and phosphine precatalysts 138141, (Figure 12) performed the cross-coupling of aryl halides with PhSnBu3 in good to excellent yields. Quite interestingly so, the addition of a fluoride salt e.g. tetrabutyl ammonium fluoride (TBAF), activated the organotin reagent towards the transmetallation step via the formation of an anionic hypervalent stannate intermediate. Several in situ generated palladium precatalysts obtained from the reaction of the N-heterocyclic carbene ligand precursors, 277279, (Figure 23) and a metal precursor, Pd(OAc)2, were reported for the coupling of phenyl- or vinyltrialkylstannanes with non-activated aryl chlorides and bromides.[99] A well defined PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalyst 97 (Figure 10) performed for the cross-coupling of a variety of challenging aryl or heteroaryl halides with thiophene-, furan-, pyrrole-, and thiazole-based organostannanes.[100]

Palladium Complexes of N-Heterocyclic Carbenes

427

Figure 21.

Figure 22.

The Stille coupling exhibits the same catalytic cycle frequently observed for the other palladium mediated CC cross-coupling reactions involving the oxidative addition, transmetallation and reductive elimination sequences (Scheme 6).[101]

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Chandrakanta Dash and Prasenjit Ghosh

KumadaTamaoCorriu (KTC) Cross-Coupling Reaction

The nickel- or palladium catalyzed cross-coupling of organomagnesium compounds, i.e. the Grignard reagents, with alkenyl and aryl halides or triflates is popularly known as the KumadaTamaoCorriu cross-coupling reaction (Scheme 5). The first cross-coupling of Grignard reagents with alkenyl or aryl halide substrates using nickel was reported independently by Kumada and Tamao[102] and Corriu[103] in 1972. Later in 1975, Murahashi reported the use of a palladium catalyst for the coupling reaction.[104] The utility of N-heterocyclic carbenes ligands in the KumadaTamaoCorriu crosscoupling was first reported by Nolan[105] in 1999, in which an in situ generated palladium precatalyst 277 was employed for the coupling of aryl Grignard reagents with aryl halide substrates. There only exists a handful of examples of well-defined Pd(0) and Pd(II) Nheterocyclic carbene complexes for the KumadaTamaoCorriu cross-coupling reaction. In particular, a well-defined palladium(0) naphthoquinone complex 21 (Figure 1) performed the cross-coupling of aryl magnesium bromide with alkyl chlorides under ambient conditions at room temperature.[106] The mono-N-heterocyclic carbene precatalyst 280 (Figure 24) of the type [(NHC)Pd(-Cl)Cl]2 exhibited high activity for the cross-coupling of aryl chloride substrates with Grignard reagents. Interestingly, the precatalyst 280 not only showed functional group tolerance towards nitrogen- and sulfur-based heterocycles but also carried out the coupling of sterically demanding partners.[107] The PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalysts 9496 (Figure 10) and 281 (Figure 24) of the type C (Figure 4) also performed the coupling of more challenging ortho-substituted and heterocyclic aryl halide substrates with Grignard reagents under ambient conditions.[108] Quite significantly, the precatalyst 94 performed the coupling even at a low temperature i.e. at -20 C. The KumadaTamaoCorriu coupling goes through the commonly observed catalytic cycle of a palladium mediated CC cross-coupling reaction (Scheme 6).

Negishi Cross-Coupling Reaction

A rather close variant of KumadaTamaoCorriu cross-coupling reaction is the Negishi reaction that involves the CC cross-coupling of organozinc reagents with organic halides or triflates catalyzed by nickel and palladium (Scheme 5).[109] So far only a few examples of palladium N-heterocyclic carbene mediated Negishi coupling have been reported. An in situ generated palladium precatalyst formed from the reaction of N-heterocyclic carbene ligand precursor, 1,3-bis(mesityl)-imidazolinium tetrafluoroborate 282 (Figure 25) and a palladium(0) precursor, Pd2(dba)3, exhibited low activity for the coupling of a alkyl bromide with a organozinc reagent in the presence of a stoichiometric amount of N-methylimidazole (NMI) as an organozinc activator.[110] Another the N-heterocyclic carbene ligand precursor 277 in presence of Pd2(dba)3 exhibited much higher conversions for the coupling of functionalized alkyl bromides and alkylzinc reagents at room temperature in the absence of any organozinc activator like that of N-methylimidazole (NMI).[111] A well-defined palladium precatalyst 94 efficiently carried out the coupling of alkyl or aryl halides and sulfonates with alkylzinc bromide or arylzinc chlorides at room temperature in the presence

Palladium Complexes of N-Heterocyclic Carbenes

429

of LiCl or LiBr as an additive.[112] The catalytic cycle of Negishi coupling resembles that of the KumadaTamaoCorriu coupling reaction (Scheme 6).[113]

Figure 23.

Figure 24.

Figure 25.

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Chandrakanta Dash and Prasenjit Ghosh

Hiyama Cross-Coupling Reaction

The Hiyama coupling[114] is a palladium mediated CC cross-coupling of organosilanes with aryl, alkenyl, or alkyl halides or pseudohalides (Scheme 5). In terms of utility, this reaction is similar to the SuzukiMiyaura and the Stille couplings, available for the construction of biaryl frameworks, but differs by using relatively inert organosilicon nucleophiles that require an activating agent like a fluoride ion or a base for the coupling to occur. The low cost, easy availability, environmentally benign nature, reagent stability and the functional group tolerance of the organosilicon reagents make Hiyama coupling an enticing option in organic synthesis. A major challenge however lies in enhancing the nucleophilicity of the inherently inert organosilicon reagents that arise out of very less electronegativity difference existing between Si and C atoms.[115] In this regard various anionic activators like F-, OH- and OR- have been effectively used to increase the nucleophilicity of the organosilicon reagent by facilitating coordination of the activating anion to the silicon center and thereby resulting in a more nucleophilic anionic pentacoordinated organosilicon reagent. Quite surprisingly, the utility of N-heterocyclic carbenes in Hiyama coupling has severely lagged behind than the other contemporary palladium catalyzed CC cross-coupling reactions. A N-heterocyclic carbene ligand precursor 277 in presence of Pd(OAc)2 under Ligand Assisted Catalysis (LAC) conditions performed the coupling of aryl bromides and chloride substrates with PhSi(OMe)3 in presence of a fluoride coinitiator.[116] A well-defined mono-N-heterocyclic carbene palladium precatalyst 66a showed high activity towards the cross-coupling of PhSi(OMe)3 with aryl chloride and bromide substrates in presence of tetrabutyl ammonium bromide (TBAF) as a fluoride coinitiator. The now-popular PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalysts of the type trans(NHC)PdX2(pyridine) 283288[117] (Figure 26) based on both the imidazoline 283286 and 1,2,4-triazole 287288 derived N-heterocyclic carbenes efficiently catalyzed the Hiyama coupling of a wide variety of aryl halides with organosilicon reagents like PhSi(OMe)3 and (CH2=CH)Si(OMe)3 under fluoride-free conditions but instead using inexpensive OH anion as an anionic activator. The Hiyama coupling too follows the commonly observed palladium mediated CC cross-coupling mechanistic pathway (Scheme 6). The fluoride anion or the base present in the reaction medium activates the organosilicon reagent thereby making it more amenable for transmetallation.

Sonogashira Cross-Coupling Reactions

The palladium mediated coupling of terminal alkynes with aryl or vinyl halides is popularly called the Sonogashira coupling (Scheme 9)[118] and as the name suggests it was first reported by Sonogashira and Hagihara in 1975. The Sonogashira cross-coupling provides a direct and convenient access to conjugated enyne and arylalkyne skeletons common in many natural products, agrochemicals, pharmaceuticals and engineered materials.[119] The most widely accepted Sonogashira protocol relies on using Cu salts as co-catalysts in a basic medium usually provided by amines.

Palladium Complexes of N-Heterocyclic Carbenes

431

Figure 26.

Scheme 9.

The Sonogashira coupling calls for stringent anaerobic conditions as the trace amounts of oxygen or even an oxidizing environment can yield unwanted homo-coupled products by Glaser coupling.[120] The air and moisture sensitivity of Sonogashira coupling primarily arises due to the formation of a Cuacetylide intermediate under the catalysis conditions. Thus, achieving Cu-free condition is a key challenge confronting Sonogashira coupling today. The use of N-heterocyclic carbenes in Sonogashira coupling was also first reported by Herrmann in 1998. Subsequently the various reports have appeared of the application of Nheterocyclic carbenes in Sonogashira coupling. A N-heterocyclic carbene ligand precursor 278 in presence of [(-allyl)PdCl]2 performed the coupling of alkyl bromide and iodide substrates with terminal alkynes.[121] Another interesting example is the coupling of trimethylsilylalkynes with deactivated bromoarenes and chlorobenzene by a in situ generated catalyst from reaction of the N-heterocyclic carbene precursor 152 (Figure 13) and Pd(OAc)2.[122] Several palladium well-defined precatalysts have been designed for the Sonogashira coupling. Quite significantly, a mono-N-heterocyclic carbene bound precatalyst 290[123] carried out the coupling of bromo- and iodoarenes with terminal acetylenes in the presence of CuI and PPh3 (Figure 27). Another palladium precatalyst 291[124] performed the Sonogashira coupling under analogous conditions. Interestingly enough, a palladium precatalyst 289 of a bioxazoline-derived N-heterocyclic carbene ligand catalyzed the coupling of primary and secondary alkyl halides with alkynes.[125] The precatalyst 289 showed excellent chemoselectivity and functional group tolerance in the cross-coupling reaction. The palladium precatalyst of the type (NHC)PdX2 292[126] and of the type (NHC)2PdX2 293296[127], efficiently carried out the coupling of a wide variety of aryl bromides and iodides with terminal acetylenes (Figure 27).

432

Chandrakanta Dash and Prasenjit Ghosh

Figure 27.

Particularly, the precatalysts 293294performed the Sonogashira coupling under amine free conditions whereas the precatalysts 292, 295296 did the same under both the Cu-and amine-free conditions. The PEPPSI themed precatalysts 283288 (Figure 26) and 297303[128] (Figure 27) were also active for the Sonogashira coupling of aryl bromides and iodides. Quite interestingly, the precatalysts of the type (NHC)2PdX2, 293294, showed higher activity compared to the (NHC)PdX2(pyridine) type ones, 98 (Figure 10) and 297, (Figure 27) under analogous conditions. The higher conversions observed for the (NHC)2PdX2 type precatalysts 293294 thus upholds the hypothesis that more electron rich metal centers act as better catalysts presumably by facilitating the aryl halide oxidative addition step. Along the same line of thought, the trans(abnormal-NHC)PdX2(pyridine) type palladium precatalyst, 300303[128] (Figure 27) supported over the more donating imidazo[1,2-a]pyridine based abnormal N-heterocyclic carbene ligands exhibited superior activity than those based on the normal N-heterocyclic carbene ligands. It is worth noting that the abnormal N-heterocyclic carbenes by virtue of the carbene center being adjacent to a single heteroatom as opposed to two heteroatoms in the case of normal N-heterocyclic carbenes are more electron rich and hence more -donating than the normal N-heterocyclic carbenes. The proposed mechanism for the Sonogashira coupling in presence of a copper cocatalyst involves two independent cycles i.e., (i) one for the production of the Cu-acetylide species and (ii) the other for its coupling with the desired aryl or alkyl species (Scheme 10). The transmetallation of copper acetylide to palladium is believed to be the rate-determining step. The above mechanism is, however, ruled out in the case of the Cu-free Sonogashira coupling, for which the coupling proceeds via a commonly observed Pd(0)/Pd(II) shuttle involving oxidative addition of aryl halide to a palladium(0) active species followed by coordination

Palladium Complexes of N-Heterocyclic Carbenes

433

and deprotonation of alkynes in the presence of a base, and which subsequently leads to the desired Sonogashira product by a final reductive elimination step (Scheme 11).

Scheme 10.

Arylation Reaction
The palladium N-heterocyclic carbene mediated arylation reaction observed in the literature can be classified into the following types.

(I). Arylation of Enolates The arylation of enolates is a powerful strategy for synthesizing a variety of high-value chemicals like, -arylated ketones, esters, nitriles and amides from simple aryl halides. A handful of examples of N-heterocyclic carbenes in arylation of enolates have been reported. The enantiomerically pure imidazolium triflates 304306[129] (Figure 28) in presence of palladium precursors like Pd(OAc)2 or Pd2(dba)3 have been employed in the synthesis of oxindoles by asymmetric -arylation of amides.

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Chandrakanta Dash and Prasenjit Ghosh

Scheme 11.

Scheme 12.

The reaction though proceeded in excellent yields but exhibited low enantioselectivity (Scheme 12). Other N-heterocyclic carbene precursors, 153 and 277, in presence of Pd(OAc)2 have been used in the inter- and intra molecular -arylation of amides.[130] Interestingly, a sterically demanding 1,3-di-(1-adamantylmethyl)-substituted saturated N-heterocyclic carbene precursor 307[131] in presence of Pd(OAc)2 carried out the -arylation reaction enantioselectively showing high enantiomeric excess (ee) but low yields. In this regard notable is a series of well-defined mono-N-heterocyclic carbene precatalysts 314316[132] (Figure 28) that exhibited high ee and high yields in the asymmetric -arylation of amides. A bis-(NHC)2PdX2 type precatalyst 320 (Figure 20) has been reported for -arylation of amides. Mono-N-heterocyclic carbene palladium precatalysts of the type (NHC)Pd(allyl)Cl 3437[133] (Figure 5) and 313 and the palladacycle 64[134] (Figure 6) performed the arylation of simple ketones with non-activated aryl chlorides, bromides, iodides, and triflates in the presence of NaOtBu (Scheme 13). The arylation occurred at the -position to the carbonyl group with preference for the less sterically hindered carbon atom in case of the

Palladium Complexes of N-Heterocyclic Carbenes

435

unsymmetrical ketones. Along the same line, another close variant of the type (NHC)Pd(acac)Cl, 317318,[135] was effective for the -arylation of ketones.

O R R'
Scheme 13.

Ar

Pd-NHC complex R

O Ar R'

Scheme 14.

Scheme 15.

(II). Direct Arylation Reactions Direct arylation reaction is an important method for constructing biaryl frameworks. The utility of N-heterocyclic carbenes in the direct arylation reaction has thus attracted attention lately. Notable is the precatalyst 312[136] (Figure 28) that showed high activity for the intramolecular direct arylation with aryl chlorides (Scheme 14). The use of N-heterocyclic carbene ligands as additives led to significant enhancement of reactivity, probably due to the preventive effect on catalyst decomposition at high reaction temperatures. These conditions allowed the formation of five- and six-membered rings bearing ether, amine, amide, or alkyl tethers. Another interesting method for the o-arylation of benzaldehyde derivatives was reported with the in situ generated palladium precatalyst from the reaction of N-heterocyclic carbene precursors 279, (Figure 23) and 308311[137] with Pd(OAc)2. More interestingly, the monoortho-substituted products were formed for the aryl chlorides while di-ortho-substituted products were observed for aryl bromides. The direct arylation of alkynes with aryl halides provides another convenient alternative to biaryl skeletons (Scheme 15). In this regard the well-defined precatalysts 319 and 321330

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Chandrakanta Dash and Prasenjit Ghosh

(Figure 29) efficiently performed the arylation of alkynes with aryl halide substrates. a,[138] The other well-characterized precatalysts that include the PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalysts, 321 and 322, and the mixed N-heterocyclic carbene and phosphine precatalysts, 323330, carried out the direct arylation alkynes with phenyl halides. The mixed N-heterocyclic carbene and phosphine precatalysts 323330 exhibited the superior activity compared to the PEPPSI themed ones 321322 of the type (NHC)PdCl2(pyridine) and also to the (NHC)2PdCl2 type 319 precatalyst for the direct arylation of alkynes with aryl halides. a
Ph N N Pd Ph Cl Cl Ph i-Pr N O 319 320 N O Ph Ph N N i-Pr I Pd I i-Pr

O N N

O i-Pr

Ph Cl Pd N Cl N

Ph Cl Pd N Ph Cl N

321

322

Ph N N R X Pd X R' PL3 Ph Cl N Pd Cl N PL3 R2P I Pd I N N Cy2P N Pd N N N

2 BF4

R = CH2Ph, R' = CH2CONHPh, X = Cl, L = Cy (323); R = R' = CH2Ph, X = Cl, L = Ph (324); R = R' = CH2Ph, X = Br, L = Ph (325)

L = Ph (326); Cy (327)

R = Ph (328); Cy (329)

330

Figure 29.

Hydroarylation Reactions
Hydroarylation of alkynes is a highly atom economic protocol that makes use of inexpensive starting materials like arenes. Fujiwara first reported the reaction of simple arenes with alkynes in trifluoroacetic acid (TFA) yielding stilbenes catalyzed by Pd(OAc)2.[139] Later, the N-heterocyclic carbene based palladium precatalysts 63 (Figure 6) and 331 (Figure 30) have been employed for the hydroarylation of ethyl propiolate that produced stilbene derivatives at room temperature (Scheme 16).[140] Another efficient precatalyst 332 exhibited high activity along with high chemo- and stereoselectivities for the hydroarylation of alkynes at a low catalyst loading of 0.1 mol %[141].

Palladium Complexes of N-Heterocyclic Carbenes

437

Figure 30.

O + OEt R

Pd-NHC complex R

COOEt + COOEt

COOEt

Scheme 16.

CN Bond Formation Reaction

The palladium mediated CN bond forming reactions are fundamentally important to organic synthesis like the CC cross-coupling ones and these reactions mainly are of two types (i) the BuchwaldHartwig amination reaction (Scheme 5) and (ii) the hydroamination reaction (Scheme 17). Due to its wide spread applicability, atom economy, and the product value, the CN bond forming reaction are of great importance to both industry and academia.

Scheme17.

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Chandrakanta Dash and Prasenjit Ghosh

BuchwaldHartwig Amination Reaction

First discovered independently by Buchwald[142] and Hartwig[143] in 1995, the BuchwaldHartwig reaction involves the coupling of aryl halides, triflates and tosylates with aryl or alkyl amines, amides, sulfonamides, imines, nitrogen-containing heterocycles and ammonia. The palladium precatalysts of bulky tertiary phosphines are often used in this transformation.[144] As the N-heterocyclic carbenes are often regarded as the phosphine substitutes their utility in the CN bond forming reaction is increasingly becoming popular. The N-heterocyclic carbene precursor 277[145] in presence of Pd2(dba)3 exhibited good to excellent conversions for the amination of aryl chlorides, bromides and iodides. Interestingly, an N-heterocyclic carbene precursor 277 in presence of Pd2(dba)3 carried out the amination of aryl chlorides with benzophenone imine.[146] The more electron rich N-heterocyclic carbene precursor [153] performed the N-arylation of indoles. Several other N-heterocyclic carbene precursors 333337 (Figure 31) have been reported for the amination reaction. b,[147] Quite significantly, the N-heterocyclic carbene precursor 333 in presence of Pd(dba)2, showed turnover numbers (TONs) of up to 5,000 for the amination of aryl chlorides. b The in situ generated bisimidazol based precatalysts, obtained from the reaction of 333334 with Pd2(dba)3, were successfully employed in coupling 7-azabicyclo[2.2.1]heptane with aryl and heteroaryl chlorides and bromides. a

Figure 31.

Several well-defined palladium(0) and palladium(II) precatalysts have been employed for the BuchwaldHartwig amination reaction. The palladium(0) precatalysts 1011 (Figure 1), 1516b (Figure 1) and 346[148] (Figure 32) have been reported for the amination reactions of aryl chloride substrates. Specifically, the precatalyst 15 and a mixed N-heterocyclic carbene and phosphine palladium(0) precatalyst, 346, showed excellent conversions for the amination

Palladium Complexes of N-Heterocyclic Carbenes

439

reactions of aryl chlorides with the primary, secondary and arylamines. Contrary to the fewer reports of well-defined palladium(0) complexes that exist, the palladium(II) counterparts have been rather extensively studied. In this context several mono-N-heterocyclic carbene palladium(II) precatalysts 35, b 37, b 52a (Figure 5), 64 (Figure 6), 70[149] (Figure 7), 338340[150] and 341345[151] (Figure 31) have been reported for the amination reaction. Quite significantly, the cinnamyl complexes 52a and 345 showed excellent activity in the BuchwaldHartwig amination. The precatalyst 345 efficiently carried out the amination reactions of a wide range of unactivated, neutral and activated chlorides and bromides with a variety of primary, secondary, alkyl, or arylamines at room temperature. The palladium alkyl derivatives 341342a were effective in the BuchwaldHartwig amination reaction of aryl chlorides. The air and moisture stable precatalysts 317318 (Figure 28) and 70 exhibited excellent activities for the amination of aryl chlorides and bromides with a variety of amines under mild conditions.

Figure 32.

The N-heterocyclic carbene-palladacycles 343344b showed BuchwaldHartwig amination for a range of unactivated aryl chloride substrates. Quite remarkably, the PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalyst 94 (type C, Figure 4) was effective for the amination reaction of electron-deficient, electron-rich aryl and heteroaryl chlorides and bromides with various sterically hindered and also functionalized drug-like aryl amines.[152] The mixed Nheterocyclic carbene and phosphine precatalysts 265 (Figure 21) and 347349 (Figure 32) were found to be active for the amination reaction of bromobenzene or 2-chloropyridine with morpholine. a The catalytic cycle proposed for the BuchwaldHartwig amination reaction is analogous to that of the other palladium mediated CC cross-coupling reactions like, SuzukiMiyaura, Hiyama, Stillle, Negishi and Kumada-Tamao-Corriu couplings involving a common Pd(0)/Pd(II) cycle.[153] The catalysis originates with the oxidative addition of aryl halide or pseudohalide to a palladium(0) active species followed by the coordination of the amine to the metal. Subsequently, the palladium bound coordinated amine undergoes deprotonation in the presence of a base. Finally, the reductive elimination step yields the amine product with the regeneration of palladium(0) active species (Scheme 6).

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Chandrakanta Dash and Prasenjit Ghosh

Hydroamination Reaction
Another important and also atom economic CN bond forming reaction is the hydroamination reaction that involves the formal addition of a NH bond across a CC multiple bond (Scheme 17). Hydroamination is sometime weakly exergonic or thermoneutral and therefore exhibits a very high negative entropy of the reaction making it thermodynamically less favorable.[154] In this context the transition metal catalyzed hydroamination reaction assumes relevance as it facilitates catalytic CN bond formation under amenable conditions with controlled chemo-, regio- and stereoselectivities and functional group tolerance.[155]
BF4 2 Ph N N Pd N N O t-Bu t-Bu H N t-Bu R' N 2BF4 N N R 2 2BF4

N Pd NCMe N N t-Bu

MeCN Pd NCMe N N R

i-Pr MeCN

350

351

R = t-Bu, R' = CH2Ph (352); R = mesityl, R' = H (353)

2 i-Pr N N N R R Br Pd Br N N N i-Pr Fe N P Pd R2 N P R2 Fe

2PF6

NCCH3

R = Et (354); CH2-CH=CH2 (355)

R = Ph (356); R = 3,5-(Me2)C6H3 (357)

Figure 33.

The utility of N-heterocyclic carbenes in the hydroamination reaction has received much less attention so far. In this regard significant a the mono-N-heterocyclic carbene precatalyst 350[156] (Figure 33) that carried out the hydroamination of methacrylonitrile with piperidine. Other well-defined palladium precatalysts 351353 of the type bis-(NHC)2PdX2 have been reported for the hydroamination of methacrylonitrile with secondary amines. A new class of palladium precatalysts 354355[157] of 1,2,4-triazole derived N-heterocyclic carbenes showed moderate to good conversions for the hydroamination of activated olefins under ambient conditions . Lastly, for the asymmetric hydroamination of methacrylonitrile with aliphatic amines, the mixed N-heterocyclic carbene and phosphine precatalysts, 356357,[158] exhibited high yields but low enantiomeric excess (ee).

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441

Oxidation Reaction
The oxidation reactions exhibited by palladium N-heterocyclic carbene complexes are mainly of the following two types,

(i). Oxidation of Alcohols Palladium(II) catalyzed oxidation of alcohols using molecular oxygen as an oxidant is a very useful transformation in organic synthesis (Scheme 18).[159] The use of palladium precatalyst of N-heterocyclic carbene in an oxidation reaction was first reported by Sigman in 2003.[160] The precatalyst 312 carried out the oxidation of a variety of benzylic and allylic alcohols to the corresponding aldehydes and ketones exhibiting turnover numbers (TONs) of up to 1,000. b Along the same line, the precatalysts 358359[161] (Figure 34) performed the aerobic oxidation of alcohols. Quite significantly, Stahl[162] isolated rare peroxo and hydroperoxo derivatives of palladium that are important intermediates in the oxidation catalysis. A detailed theoretical study on these complexes revealed that the solvent plays an important role on the reversibility of the oxygenation step. c The oxidation reactions using molecular oxygen as terminal oxidants have been successfully applied for the kinetic resolution of secondary alcohols and to the alkene hydroarylation reaction employing boronic esters (Scheme 19). Specifically, the chiral palladium precatalysts 360362[163] showed oxidative kinetic resolutions of secondary alcohols in good yields with moderate to good enantioselectivities. The precatalysts 280[164] carried out highly regioselective reductive coupling of arylboronic esters and styrene under aerobic conditions. In this reaction, the oxidative conditions are required for the oxidation of the alcoholic solvent to generate the active palladium(II) hydride intermediate, which reacts with alkene to yield a palladium alkyl species. Subsequent transmetallation and reductive elimination yield the desired product (Scheme 17).

OH Pd-NHC complex R
Scheme 18.

R'

R'

(II). Wacker Oxidation and Oxidative Cyclization Reactions Palladium catalyzed oxidation of terminal olefins to methyl ketones is popularly known as the Wacker oxidation and is used in the production of acetaldehyde on an industrial scale.[165] In this process stoichiometric CuCl2 is used as a cocatalyst under aerobic conditions.

442
i-Pr N i-Pr O R O O N i-Pr Pd O R i-Pr

Chandrakanta Dash and Prasenjit Ghosh

Ph Ph N R Cl Pd Cl N R Ph N

R Cl Pd Cl N R N Ph N N Pd N Me I I Me N N Pd N N Me I I Me

R = Me (358); t-Bu (359)

R = 2,3,5,6-Me4C6H (360)

361

362

Figure 34.

Scheme 19.

However, the reaction suffers from many drawbacks like the formation of chlorinated byproducts and from the issues associated with palladium decomposition. These have contributed to the growth of research in the area. Notable is a precatalyst 70 (Figure 7) that performed the oxidation of styrenes to acetophenones (Scheme 20).[166] An in situ generated precatalyst derived from the N-heterocyclic carbene ligand precursor 152 and palladium bistrifluoroacetate Pd(COOCF3)2 exhibited efficient intramolecular Wacker-type cyclization reaction under aerobic conditions (Scheme 21).[167]

Reduction Reaction
An in situ generated palladium precatalyst obtained from the reaction of N-heterocyclic carbene precursor 279[168] with Pd(dba)2, performed the dehalogenation of aryl bromides and chlorides at 100 C (Scheme 22). In this transformation the formation of a cationic palladium hydride intermediate is proposed and which is formed from the oxidative addition of a imidazolinium salt to a palladium(0) precursor species. Another well-defined complex 35 (Figure 5) of the type, [(NHC)Pd(allyl)Cl], have been reported for the dehalogenation of aryl chlorides. b A cationic bis-N-heterocyclic carbene precatalyst 363[169] carried out the hydrogenation reaction of cyclooctene to cyclooctane (Scheme 23). A mixed N-heterocyclic carbene and phosphine palladium(0) precatalyst 5 (Figure 1) of the type (NHC)Pd(PR3) performed the hydrogenation of olefins.[170]

Palladium Complexes of N-Heterocyclic Carbenes

443

Scheme 20.

R' Pd-NHC complex OH

Scheme 21.

R O R'

O2, toluene, 80 oC

Scheme 22.

Pd-NHC complex 1 atm H2 i-Pr N N N N i-Pr Pd NCMe NCMe 2 2 BF4

363

Scheme 23.

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Chandrakanta Dash and Prasenjit Ghosh

Tsuji-Trost Alkylation Reaction

Palladium catalyzed allylic substitution reaction has become a popular method of CC bond formation along the lines of various other CC cross-coupling reactions. Quite interestingly, though a palladium mediated allylic substitution reaction was reported by Tsuji in 1965,[171] the use of N-heterocyclic carbene in allylic alkylation reaction was only reported as late as in 2003.[172] An N-heterocyclic carbene precursor 277 (Figure 23) in presence of Pd2(dba)3 was found to be active for the allylic alkylation reaction (Scheme 24).[172,173]

Telomerization Reactions
(I). Telomerization of Dienes with Alcohols Telomerization is a 100 % atom economic process involving the formation of short oligomers from dienes. The palladium complexes are known to catalyze the reaction of dienes with a variety of nucleophiles.[174] Beller first employed a mono-N-heterocyclic carbene palladium(0) complex 18d (Figure 1) for the telomerization of butadiene with alcohols (Scheme 25). Quite remarkably, better chemoselectivity in terms of linear to branched product ratios were observed for the N-heterocyclic carbene precatalyst than the phosphine ones. (ii). Telomerization of Dienes with Amines Like the telomerization of dienes and alcohols, the telomerization of amines and dienes is also an interesting transformation for the formation of short oligomers. Nolan first employed a well-defined cationic palladium(II) percatalyst 364[175] for the telomerization of butadiene with amines under mild conditions (Scheme 26). The order of amine reactivity in the telomerization reaction was found to be as, secondary amines > primary amines > ammonia.

Polymerization Reactions
The use of palladium N-heterocyclic carbene complexes in polymerization reactions are relatively less explored compared to the other catalysis. The precatalysts 365377 (Figure 35) have been employed in a variety of polymerization reactions. In particular, the mono-Nheterocyclic carbene complex 365[176] performed the norbornene polymerization exhibiting very high activitiy of up to 108 g of polynorbornene (mol of Pd-1 h-1) in the presence of methylaluminoxane (MAO) as a coinitiator. Other mono-N-heterocyclic carbene precatalysts 35, 40, 42 (Figure 5) and 366367 carried out the polymerization of functionalized norbornene namely, 5-norbornene-2-methyl acetate.[177] Along the same line, the precatalysts 3536[178] and 368370 and the bis(aryloxide-N-heterocyclic carbene) precatalysts 373377[179] performed the polymerization of norbornene and its derivatives. The cationic bis-N-heterocyclic carbene precatalysts 371372[180] have been reported for the copolymerization of CO and C2H4.

Palladium Complexes of N-Heterocyclic Carbenes

445

Scheme 24.

OMe 2 + Pd-NHC complex MeOH + OMe

Scheme 25.
+ Pd-NHC complex RR'NH NRR'

i-Pr N i-Pr N

i-Pr

PF6

Pd

i-Pr NCMe

364

Scheme 26.

Cycloisomerization Reactions
The transition metal-catalyzed cycloisomerization of enyne systems is a powerful synthetic approach for the construction of intricate architectures in various target molecules[181]. A handful of examples of N-heterocyclic carbenes in the cycloisomerization reaction have been reported. Of particular mention is an N-heterocyclic carbene precursor 336,[182] which in the presence of Pd2(dba)3, carried out the bismetalative cyclization of enynes in the presence of Bu3SnSiMe3 (Scheme 27).

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Chandrakanta Dash and Prasenjit Ghosh

i-Pr N N Cl Pd Cl X PhPh N N Me i-Pr Pd i-Pr Cl N X R i-Pr R N N R Cl X MeCN Pd N NCMe R R R N N N 2 2X

Pd

365

X = H (366); Me (367)

R = Me, X = Br (368); R = i-Pr, X = Br (369); R = i-Pr, X = I (370)

R = mesityl, X = PF6 (371); R = Me, X = BF4 (372)

t-Bu

t-Bu

t-Bu

t-Bu O Pd O t-Bu

N N R R N

t-Bu R N O Pd

N N R t-Bu

t-Bu O Pd O t-Bu

N N t-Bu N t-Bu

O N

t-Bu R = Ph (373); mesityl (374)

t-Bu R = Me (375); i-Pr (376) Figure 35.

t-Bu 377

Figure 35.

A mono-N-heterocyclic carbene complex 367[183] (Figure 35), of the type (NHC)Pd(allyl)Cl, was employed for the cycloisomerization of 1,6-dienes forming various cyclic compounds. Quite significantly, the cycloisomerization reactions proceeded at room temperature with complete regioselectivity yielding the desired exo-methylene-containing products (Scheme 28). Another precatalyst 378[184] was reported for the cycloisomerization of alkylidenecyclopropanes that resulted in the corresponding 1-aryl dihydronaphthalenes in very high selectivity at room temperature (Scheme 29).

Scheme 27.

Figure 28.

Palladium Complexes of N-Heterocyclic Carbenes

447

R Pd-NHC complex

Mes N N Mes 378 Cl Pd Cl

Mes N N Mes

Scheme 29.

Addition Reactions
Designing highly efficient and enantioselective palladium N-heterocyclic carbene precatalysts remain an important goal in asymmetric synthesis. In this regard notable are the chiral precatalysts 379380[185] (Scheme 30) that performed the asymmetric conjugate addition of arylboronic acids to cyclic enones in good to high enantioselectivities. The same precatalysts 379380[186] were also employed for the allylation of aldehydes with allyltributyltin, CH2=CH-CH2SnBu3 (Scheme 31). A mixed N-heterocyclic carbene and phosphine precatalyst 381[187] was employed for the conjugate allylation reaction of ,-unsaturated N-acylpyrroles using allylboronic ester (Scheme 32). An in situ generated palladium precatalyst formed from the reaction of the Nheterocyclic carbene precursor 152 with Pd(OAc)2, was reported for the 1,4-addition of terminal alkynes to unsaturated carbonyl compounds (Scheme 33).[188] A thioether functionalized N-heterocyclic carbene precursor 382 [189](Scheme 34) in presence of [Pd(allyl)Cl]2 performed the 1,2-addition of boron reagents to aldehydes. A 1,1binaphthalenyl-2,2-diamine (BINAM) palladium precatalyst 383[190] (Scheme 35) was reported for the arylation of N-tosylimines with arylboronic acids in good to high enantioselectivities. Finally, a triazolyldiylidene derived palladium complex 384[191] (Scheme 36) was reported for the direct acylation of aryl iodides or bromides with aldehydes.

448

Chandrakanta Dash and Prasenjit Ghosh

O + ArB(OH)2 Pd-NHC complex

Ar

O Me O R Pd R O N N Me O

R = Me (379); CF3 (380)

Scheme 30.

RCHO
Scheme 31.

SnBu3

Pd-NHC complex R

OH

O N Ar +

Me Me Me Me

O O B O Cl N N Me 381 PPh2 Pd Pd-NHC complex N

Ar

Scheme 32.

Palladium Complexes of N-Heterocyclic Carbenes

449

O O R + R' Pd-NHC complex R R'

Scheme 33.

O R H + [B] R'

Pd-NHC complex R

OH R'

i-Pr N i-Pr N

Cl

PhS

382
Scheme 34.

Ts ArB(OH)2 +

N R

Pd-NHC complex

Ts Ar 2

NH R

2OTf

N Pd OH2 OH2

383
Scheme 35.

450

Chandrakanta Dash and Prasenjit Ghosh

O X + R' H

Pd-NHC complex

O R'

Me Cl MeCN Pd Cl N N N Me

Me Cl Pd Cl NCMe

384
Scheme 36.
R R Pd-NHC complex + R' H OH

R R OH X

RR O R'

R' Me Cl N Pd Cl N N N Me Cl Me Cl Pd N

385

Scheme 37.

Scheme 37.

Domino Reactions
There exist only a few reports of domino reactions involving sequential CC bond forming reactions catalyzed by palladium N-heterocyclic carbene complexes. Notable is a palladium N-heterocyclic carbene complex 385[192] (Scheme 37) that was successfully used for the domino Sonogashira and hydroalkoxylation reactions. Another precatalyst 94 catalyzed the synthesis of indoles by sequential aryl amination and Heck coupling reactions (Scheme 38).[193]

Palladium Complexes of N-Heterocyclic Carbenes

451

Scheme 38.

Palladium in Biomedical Application

Metallopharmaceuticals are emerging as prominent players in therapeutic and diagnostic medicine these days. Hence, the discovery and development of new metallodrugs is an increasingly popular area of research in medicinal inorganic chemistry in recent times.[194] Among the commonly used metallodrugs today are cisplatin, cis-(NH3)2PtCl2, and its second generation analog, carboplatin.[195] However, there exist several concerns with these metallodrugs like its effect on narrow spectrum range of cancer cells, low aqueous solubility, various toxicity issues in the form of nephrotoxicity, neurotoxicity and emetogenesis that constrict its broad based utility.[196] Hence, finding suitable alternate metallodrugs remains a key objectiveat the heart of research in this area. Palladium as a metal display similar structural preferences like platinum and also exhibit promising cytotoxicity and thus provides a viable alternative to the platinum based metallodrugs like cisplatin and carboplatin.[197] Moreover, the N-heterocyclic carbenes, though extremely successful in catalysis, remain largely unexplored in biomedical applications. Against this backdrop, the palladium complexes of N-heterocyclic carbenes 386388,[198] (Figure 36) were screened for their anticancer properties. Particularly interesting is the trans-(NHC)2PdX2 type 387 complex that was found to be more effective than not only a trans-(NHC)PdX2(pyridine) type 386 complex but also exhibited ca. 2-20 times greater inhibition on the proliferation of the three different commonly occurring human tumor cells namely, the cervical cancer (HeLa), breast cancer (MCF-7) and colon adenocarcinoma (HCT 116) cell lines than the much used metallodrug cisplatin under analogous in vitro conditions. The superior activity of the palladium Nheterocyclic carbene complex 387 compared to the commonly used metallodrug, cisplatin, further brightens the prospects of the N-heterocyclic carbene compounds in cancer therapy. Detailed mechanistic studies revealed that the 387 complex arrested the cell cycle at the G2/M transition phase of the cell division.

CONCLUSIONS
In summary, the palladium N-heterocyclic carbene complexes have made an indelible mark in chemical catalysis and are displaying promising traits in biomedical applications like in anticancer studies. In this context the success of N-heterocyclic carbene primarily arises due to their strong binding nature, that prevents catalyst leaching by suppressing ligand dissociation, and thus provides an ideal platform for designing palladium catalysts with

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Chandrakanta Dash and Prasenjit Ghosh

improved attributes as well as for synthesizing palladium compounds for biomedical application purposes.

t-Bu Cl N Pd N Cl N N N

t-Bu Cl N Pd Cl t-Bu N

Mes Cl N Pd N Mes Cl

Mes N N Mes

386
Figrue 36.

387

388

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[135] Winkelmann, O. H.; Riekstins, A.; Nolan, S. P.; Navarro, O. Organometallics 2009, 28, 58095813. [136] Campeau, L.-C.; Thansandote, P.; Fagnou, K. Org. Lett. 2005, 7, 18571860. [137] . Grbz, N.; zdemir, I.; etinkaya, B. Tetrahedron Lett. 2005, 46, 22732277. [138] Ho, C.-C.; Chatterjee, S.; Wu, T.-L.; Chan, K.-T.; Chang, Y.-W.; Hsiao, T.-H.; Lee, H. M. Organometallics 2009, 28, 28372847. [139] (a). Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633639. (b). Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am. Chem. Soc. 2000, 122, 72527263. [140] Viciu, M. S.; Stevens, E. D.; Petersen, J. L.; Nolan, S. P. Organometallics 2004, 23, 37523755. [141] Biffis, A.; Tubaro, C.; Buscemi, G.; Basato, M. Adv. Synth. Catal. 2008, 350, 189196. [142] . Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem. Int. Ed. Engl. 1995, 34, 13481350. [143] . Louie, J.; Hartwig, J. F. Tetrahedron Lett. 1995, 36, 36093612. [144] (a). Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 36943703. (b). Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 97229723. (c). Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 72157216. [145] Huang, J.; Grasa, G.; Nolan, S. P. Org. Lett. 1999, 1, 13071309. [146] Grasa, G. A.; Viciu, M. S.; Huang, J.; Nolan, S. P. J. Org. Chem. 2001, 66, 77297737. [147] (a). Cheng, J.; Trudell, M. L. Org. Lett. 2001, 3, 13711374. (b). Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F. Org. Lett. 2000, 2, 14231426. [148] . Titcomb, L. R.; Caddick, S.; Cloke, F. G. N.; Wilson, D. J.; McKerrecher, D. Chem. Commun. 2001, 13881389. [149] Viciu, M. S.; Kissling, R. M.; Stevens, E. D.; Nolan, S. P. Org. Lett. 2002, 4, 22292231. [150] Vieille-Petit, L.; Luan, X.; Mariz, R.; Blumentritt, S.; Linden, A.; Dorta, R. Eur. J. Inorg. Chem. 2009, 18611870. [151] (a). Esposito, O.; Gois, P. M. P.; Lewis, A. K. de K.; Caddick, S.; Cloke, F. G. N.; Hitchcock, P. B. Organometallics 2008, 27, 64116418. (b). Broggi, J.; Clavier, H.; Nolan, S. P. Organometallics 2008, 27, 55255531. [152] . Organ, M. G.; Abdel-Hadi, M.; Avola, S.; Dubovyk, I.; Hadei, N.; Kantchev, E. A. B.; OBrien, C. J.; Sayah, M.; Valente, C. Chem. Eur. J. 2008, 14, 24432452. [153] Lewis, A. K. de K.; Caddick, S.; Cloke, F. G. N.; Billingham, N. C.; Hitchcock, P. B.; Leonard, J. J. Am. Chem. Soc. 2003, 125, 1006610073. [154] (a). Hultzsch, K. C. Org. Biomol. Chem. 2005, 3, 18191824.(b). Fadini, L.; Togni, A. Chem. Commun. 2003, 3031. [155] (a). Lee, A. V.; Schafer, L. L. Eur. J. Inorg. Chem. 2007, 22432255. (b). Nobis, M.; Drieen-Hlscher, B. Angew. Chem. Int. Ed. 2001, 40, 39833985. [156] Dyson, G.; Frison, J.-C.; Simonovic, S.; Whitwood, A. C.; Douthwaite, R. E. Organometallics 2008, 27, 281288. [157] Dash. C.; Shaikh, M. M.; Butcher, R. J.; Ghosh, P. Dalton Trans. 2010, 39, 25152524. [158] Gischig, S.; Togni, A. Eur. J. Inorg. Chem. 2005, 47454754.

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[185] Zhang, T.; Shi, M. Chem. Eur. J. 2008, 14, 37593764. [186] Zhang, T.; Shi, M.; Zhao, M. Tetrahedron 2008, 64, 24122418. [187] . Shaghafi, M. B.; Kohn, B. L.; Jarvo, E. R. Org. Lett. 2008, 10, 47434746. [188] Zhou, L.; Chen, L.; Skouta, R.; Jiang, H.; Li. C.-J. Org. Biomol. Chem. 2008, 6, 29692977. [189] Kuriyama, M.; Shimazawa, R.; Shirai, R. J. Org. Chem. 2008, 73, 15971600. [190] Ma, G.-N.; Zhang, T.; Shi, M. Org. Lett. 2009, 11, 875878. [191] Zanardi, A.; Mata, J. A.; Peris, E. Organometallics 2009, 28, 14801483. [192] Zanardi, A.; Mata, J. A.; Peris, E. Organometallics 2009, 28, 43354339. [193] Shore, G.; Morin, S.; Mallik, D.; Organ, M. G. Chem. Eur. J. 2008, 14, 13511356. [194] .(a). Mascini, M.; Bagni, G.; Pietro, M. L. D.; Ravera, M.; Baracco, S.; Osella, D. BioMetals 2006, 19, 409418. (b). Kostova, I. Recent Patents on Anti-Cancer Drug Discovery 2006, 1, 122.(c). Farver, O. Textbook of Drug Design and Discovery (3rd Edition), Taylor & Francis Ltd., London, UK 2002, 364409. (d). Guo, Z.; Sadler, P. J. Advances in Inorganic Chemistry: Academic Press, 2000, 49, 183306. [195] (a). Fuertes, M. A.; Alonso, C.; Prez, J. M. Chem. Rev. 2003, 103, 645662. (b). Giese, B.; Deacon, G. B.; Kuduk-Jaworska, J.; McNaughton, D. Biopolymers (Biospectroscopy), 2002, 67, 294297. (c). Jamieson, E. R.; Lippard, S. J. Chem. Rev. 1999, 99, 24672498. [196] (a). Gianomenico, C.; Christen, M. United States Patent 6413953, 2000. (b). Lippert, B. Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug, Wiley-VCH, Weinheim, 1999.(c). Lippard, S.J. Progress in Inorganic Chemistry Bioinorganic Chemistry, Vol. 48, Wiley, Sydney, 1995. [197] (a). Navarro, M.; Pea, N. P.; Colmenares, I.; Gonzlez, T.; Arsenal, M.; Taylor, P. J. Inorg. Biochem. 2006, 100, 152157. (b). Friaza, G. G.; Fernndez-Botello, A.; Prez, J. M.; Prieto, M. J.; Moreno, V. J. Inorg. Biochem. 2006, 100, 13681377. (c). Friebolin, W.; Schilling, G.; Zller, M.; Amtmann, E. J. Med. Chem. 2005, 48, 7925 7931. (d). Guo, Z.; Sadler, P. J. Angew. Chem. Int. Ed. 1999, 38, 15121531. (e). Puthraya, K. H.; Srivastava, T. S.; Amonkar, A. J.; Adwankar, M. K.; Chitnis, M. P. J. Inorg. Biochem. 1985, 25, 207215. [198] (a). Teyssot, M.-L.; Jarrousse, A.-S.; Manin, M.; Chevry, A.; Roche, S.; Norre, F.; Beaudoin, C.; Morel, L.; Boyer, D.; Mahioue, R.; Gautier, A. Dalton Trans. 2009, 68946902. (b). Teyssot, M.-L.; Jarrousse, A.-S.; Chevry, A.; Haze, A. D.; Beaudoin, C.; Manin, M.; Nolan, S. P.; Dez-Gonzlez, S.; Morel, L.; Gautier, A. Chem. Eur. J. 2009, 15, 314318. (c). Ray, S.; Mohan, R.; Singh, J. K.; Samantaray, M. K.; Shaikh, M. M.; Panda, D.; Ghosh, P. J. Am. Chem. Soc. 2007, 129, 1504215053.

In: Homogeneous Catalysts: Types, Reactions and Applications ISBN: 978-1-61122-894-6 Editor: Andrew C. Poehler 2011 Nova Science Publishers, Inc.

Chapter 14

METHODS FOR ENHANCING THE ACTIVITY AND SELECTIVITY OF HOMOGENEOUS CATALYSTS IN THE OXIDATION PROCESSES
*

Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

Emanuel Inst. of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia

The application of metal-complex catalysis opens the possibility of regulating the relative rates of elementary stages CatO2, CatROOH, CatRO2 and in that way of controlling the rate and selectivity of processes of radical-chain oxidation [4]. By changing the ligand environment of the metal center or adding different activating compounds, it is possible to vary the yields of target products, and thus control the reaction selectivity. The catalyst performance is always accompanied by its deactivation. It should be mentioned that in its original form, a catalyst often represents only the precursor of real catalytic particles. By introducing various ligands-modifiers into reaction, it is possible to accelerate the formation of catalytically active species and prevent or hinder the processes that lead to catalyst deactivation. Understanding of the mechanisms of the additives action at the formation of catalyst active forms and mechanisms of regulation of the elementary stage of the radical-chain oxidation may apparently lead to the development of new, efficient catalytic systems and selective oxidation processes. In heterogeneous catalysis, the methods of modifying a catalyst by different additives that enhance its activity and prevent its deactivation were used rather extensively, whereas in homogenous catalysis, the use of various modifiers was not systematic. Studies aimed at investigation of the mechanism of action of additives were scarce. They were basically aimed at studying the effect of added ligands-modifiers on catalyst activity in chain initiation steps
*

A version of this chapter was also published in Selective Catalytic Hydrocarbons Oxidation: New Perspectives, by Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov, Nova Science Publishers. It was submitted for appropriate modifications in an effort to encourage wider dissemination of research.

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(the O2 activation, ROOH homolytic decomposition) [4, 7]. Moreover, in the majority of schemes of catalytic radical-chain oxidation of hydrocarbon, the O2 activation with transition metal complex was totally ignored. The additives, often being axial ligands for metal complexes, are considered in models, which mimic enzyme reaction center (mono- and dioxygenase). At present, the numerous examples of various catalytic reactions are known when addition of certain compounds in small amounts dramatically enhances the reaction rate and rarely the product yield. As a rule, the mechanisms of action of additives were not established, although the authors tentatively propose mechanistic explanations [9]. The works of Ellis and Lyons, and more recently that of Gray and Labinger, have identified the halogen-substituted metal porphyrinscatalyzed oxidation of alkanes into alcohols by dioxygen at the mild conditions (100oC) [10-13]. However, substituted alkanes, such as 2-methylbutane, 3-methylpentane, 2,3-dimethylbutane, and 1,2,3-trimethylbutane, are oxidized into a mixture of products due to oxidative carbon-carbon bond cleavage [11]. The including of halogen, electron-withdrawing substituents, into porphyrin ligand increases the stability of halogenated iron porphyrins in oxidative destruction and as result their activity [10, 11]. Though observed to increase, the stability of such complexes remained moderate, as indicated by the low conversion of alkanes. It is now generally agreed that oneelectron redox reactions and oxygen-centered free radical chemistry being about the oxidations in these systems are most probably the mechanisms similar to those proposed for biological oxidations by Cytochrome P-450 and methanemonooxygenase (through twoelectron oxygen-transfer processes at participation of an active high-valent metal-oxo oxidant) [12,13,14]. Perhalogenated iron porphyrins are known to be effective at decomposing alkyl hydroperoxides via free radicals formation [13,14].

III.1. IMMOBILIZATION OF HOMOGENEOUS CATALYST ON HETEROGENEOUS SUPPORT FOR INCREASE IN ACTIVITY AND SELECTIVITY OF CATALYST IN THE ALKYLARENS OXIDATIONS
Several studies were devoted to the processes of alkylarene oxidation in the presence of metal complexes immobilized on the surface of a polymer or mineral carrier (silica gel, zeolite) [15-21]. The potential advantages of using a solid catalyst include the case of its removal from the oxidation mixture and subsequent reuse and control of catalyst reactivity through its microenvironment exerted by the support. For example, metal complexes, heterogenised in the zeolite pores, are prevented from deactivation; the oxidation of the ligand by another complex cannot be realized. The increase in stability encapsulated salen complex arises from the protection of the inert zeolite framework, making complex degradation more difficult by sterically impeding the attack to the more reactive parts of the ligand, and the life of salen catalyst is prolonged [16]. At the same time, the zeolite influences the formation of products by steric and electronic influences on the transition state of the reaction; they also control the entry and departure of reagents and products. One of the limitations of zeolites are that their tunnel and pore sizes are no larger than about 10 [18]. The occluded catalytic complexes require a zeolite with caves or intersections, which are large enough to embed them. For these

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purposes, faujasites, containing super cages, are most frequently used [16]. The creation of mesopores in zeolite particles to increase accessibility to the internal surface has been the subject of many studies (mesopore-modified zeolites). It is known that postsynthesis hydrothermal dealumination and other chemical treatments form defect domains of 5 to 50 nm (which are attributed to mesopores) in faujasites, mainly zeolite Y [16]. The low activity of these zeolite catalysts is connected with their high hydrophility, as a result of low silicon to aluminum ration. The deactivation by sorption of polar products and solvent on pores of zeolite still remained a serious issue for oxidation of alkanes (with low polarity). Even with dealumination of the structure up to a silicon to aluminum ratio above 100, increased the activity only twice [16]. The creation of a hydrophobic environment around the active site was required to circumvent the activity and sorption problems. In the case of the reaction of cyclohexane oxidation to adipic acid with air in the presence of Fe aluminophosphate-31 (ALPO-31) (with narrow pore, 0.54-nm diameter), cyclohexane is easily adsorbed in the micro pores [18]. But desorption of initial products such as cyclohexylperoxide or cyclohexanone is slow. Consequently, subsequent radical reactions occur until the cyclohexyl ring is broken to form linear products that are sufficiently mobile to diffuse out of the molecular sieve. In contrast, with a large pore Fe ALPO-5, cyclohexanol and cyclohexanone account for ~ 60% of the oxidation products. Thus, localization of a free radical reaction inside micro pores seems to give rise to particular selectivity. Often, the catalytic activity is practically unchanged if supported metal complex is used. So the silicaand polymersupported iron(III) tetrakis(pentafluorophenyl)porphyrins, FeTF8PP, [17] catalyzed the ethylbenzene oxidation reactions by dioxygen into the same three products, -phenylethyl-hydroperoxide, methylphenylcarbinole, and acetophenone (1:1:1), as analogous homogeneous catalyst. This suggests the same reaction mechanism in both cases that these catalytic oxidations react by the same mechanism. However, in general, the heterogeneous catalytic ethylbenzene oxidation proceeds more slowly than homogeneous. The products yields are limited by the stability/activity ratio of iron porphyrin and these, in turn, are dependent mainly on catalyst loading and microenvironment provided by support. The neat and zeolite-Y-encapsulated copper complexes with tri- and tetraaza macrocyclic ligands such as 1,4,7-triazocyclononane, 1,4,7-trimethyl-1,4,7triazocyclononane, 1,4,7,10-tetraazocyclododecane, 1,4,7,10-tetramethyl-1,4,7,10tetraazocyclododecane, and 1,4,8,11-tetraazocyclotetradecane exhibit efficient catalytic activity in the regioselective oxidation of ethylbenzene using tert-butyl hydroperoxide [20]. Acetophenone was the major product; the small amounts of o- and p-hydroxyacetophenones were also formed, revealing that CH activation occurs at both the benzylic and aromatic ring carbon atoms. The latter is significant over the neat complexes in the homogeneous phase, while it is suppressed significantly in the case of the encapsulated complexes. Molecular isolation and the absence of intermolecular interactions (as revealed by EPR spectroscopy), synergism due to interaction with the zeolite framework and restricted access of the active site to ethylbenzene are the probable reasons for the differences in activity/selectivity of the encapsulated catalysts. The differences in selectivity are attributed to the formation of different types of active copperoxygen intermediates, such as side-on peroxide, -2:2peroxo (bis--oxo complexes), -1,2-peroxo- and Cu-hydroperoxo species, in different proportions over the neat and encapsulated complexes (AC species):

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It [21] is established that with an anisole-containing polypyridylamine, potential ligand L, a -1,2-peroxodicopper(II) complex [{LCuII}2(O22-)]2+ forms from the reaction of the mononuclear compound [CuI(L)(MeCN)]B(C6F5)4 (LCuI) with O2 in no coordinating solvents at -80C. Thermal decay of this peroxo complex in the presence of toluene or ethylbenzene leads to rarely seen C-H activation chemistry; benzaldehyde and acetophenone/ 1-phenylethanol mixture (~1:1), respectively, are formed. Very similar toluene oxygenation chemistry occurs with dicopper(III)-bis--oxo species [{BzLCuIII}2(-O2-)2]2+ [see Chapter VII]. Water soluble catalysts combining the properties of metal complexes and surfactants on the basis of terminally functionalized polyethylene glycols (PEG) and block-copolymers of ethylene oxide and propylene oxide with various combinations of ethylene and propylene oxide fragments were investigated [22]. Polymers, functionalized by dipyridyl and acetyl acetone, were used as ligands for preparation Co(II) complexes. Macro complexes PEG-acacCo turned out to be more active than their non-polymeric analogues in oxidation of ethylbenzene by dioxygen under the same temperature (120C). The only product was acetophenone. Cobalt remains fixed at the end of the polymer chain with acac-ligand and is surrounded by oxygen atoms of the PEG chain. Such surrounding is labile and does not preclude from activation of dioxygen. The activity of the liquid-phase polyhalogenated metalloporphyrins (Co, Mn, Fe) and supported catalysts (silica, polystyrene) and the cationic metalloporphyrins encapsulated in NaX zeolite are founded to be active for cyclooctane oxidation with molecular O2 into ketone and alcohol with primary ketone formation. In the last case, the ration c-one/c-ol is higher than in the use of supported on silica and polystyrene catalysts and, in fact, coincide with results, which are received with the cationic metalloporphyrins in solution. [23]. Mononuclear ruthenium complexes are catalysts for numerous reactions in solution, including oxidation, CC bond formation, and activation of CO2 and CH bonds. Dealuminated zeolite Y was used as a crystalline support for a mononuclear ruthenium complex synthesized from cis-Ru(acac)2(C2H4)2. It was established that in the presence of ethylene and H2 surface-bound catalytic active mononuclear cationic Ru(acac)(C2H4)22+ complex entered into a catalytic cycle for ethylene dimerization, aided by H2. The cationic Ru(acac)(C2H4)22+ complex, formed as result of the dissociation of half of the acac ligands from the ruthenium, was bonded to sites where acidic silanol groups had been presented [24].

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III.2. MODIFICATION OF METALLOCOMPLEX CATALYSTS BY ADDITION OF MONODENTATE AXIAL LIGANDS

The phenomenon of a substantial rise of not only initial rate (w0), but also the selectivity (S = [PEH] / [RH]100%) and conversion degree (C = [RH] / [RH]0100%) of alkylarens (ethylbenzene, cumene) oxidation to the corresponding hydroperoxides by molecular O2 upon addition of electron-donating monodentate ligands L2 (L2 = HMPA (hexamethylphosphorus triamide), dimethyl formamide (DMF), N-methyl pyrrolidone-2 (MP)), MSt (M = Li, Na, K) to transition metal complexes (L1)n (M = Ni(II), Co(II), Fe(III), L1=acac-) was discovered by authors of the articles [25-27]. The mechanism of control of M(L1)2 complexes catalytic activity by adding electrondonating monodentate ligands L2 (L2 = HMPA, DMF, MP, MSt) in the process of ethylbenzene oxidation (120C) was elucidated [28-31]. The coordination of exo ligand L2 to an M(L1)2 changes symmetry of complex and its oxidative-reductive activity. In that the catalytic activity of the in situ formed in situ primary complexes M(L1)2L2 (catalyst K1), containing ligands L2 in axial position is higher than that of original complexes Ni(L1)2, which is manifested in the acceleration of free radical formation in the steps of chain initiation (activation by O2) and homolytic decomposition of -phenyl ethyl hydroperoxide (PEH), and increase in initial oxidation rate (I macro stage) [60,61]. In this connection at the first macro stage, the selectivity of ethylbenzene oxidation into PEH is not high (SPEH,max = 80%). With process development, the increase in SPEH (SPEH,max 90%) in comparison with I macro stage, and decrease in reaction w, are observed (II macro stage). Ligands L2 control transformation of Ni(L1)2 complexes into more active selective particles (catalyst K2). In that, the rise in SPEH is reached at the expense of catalyst participation in activation reaction of O2, and inhibition of chain and heterolytic decomposition of PEH. Besides this, the direction of formation of side products, acetophenone (AP) and methylphenylcarbinol, (MPC), is changed from consequent (under hydroperoxide decomposition) to parallel at the expense of modified catalyst in the chain propagation (Cat + RO2). At the III macro stage, the sharp fall of the SPEH is associated with heterolysis of PEH to phenol and acetaldehyde, catalyzed by the completely transformed catalyst (catalyst K3) [29-31]. K1 K2 K3 We have established that in the case of use of nickel complexes Ni(L1)2 (L1=acac), selective catalyst K2 (II macro stage) is formed, as result of controlled by L2 ligand regioselective addition of O2 to nucleophilic carbon -atom of one of the ligands L1. Coordination of electron-donor exo ligand L2 with Ni(L1)2 stabilized the intermediate zwitter-ion L2(L1M(L1)+O2) and increased the probability of regio-selective insertion of O2 to acetylacetonate ligand activated by coordination with nickel(II) ion. The further incorporation of O2 into chelate cycle, accompanied by proton transfer and bonds redistribution in formed transition complex leads to break of cycle configuration with formation of (OAc-) ligand, acetaldehyde, and elimination of CO (Scheme 1-3) [29,31]. As a result of this process, reactive mono- and hetero-poly nuclear heteroligand complexes of general composition Nix(acac)y(L1ox)z(L2)n (L1ox= MeCOO-) (K2, "") are formed. Transformation of complexes

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K1, Ni(acac)2L2 (L2 = HMPA, DMF, MP, MSt)) leads to formation of homo bi- (L2 = HMPA, DMF, MP) or hetero-three nuclear (L2 = MSt, M=Na, Li, K) heteroligand complexes K2 (""): Ni2(OAc)3(acac)L2 (Scheme 1) [29,31]. The structure of the complex "A" with L2 =MP (HMPA) was confirmed kinetically and using various physicochemical methods of analysis (mass-spectrometry, electron and IR-spectroscopy, and element analysis).

Scheme III.2.1.

Scheme III.2.2.

Transformation of Ni(L1)2 (L1=enamac-, chelate group (O/NH)) is realized in the absence of activating ligands (L2) [30] (L1ox=NHCOMe- or MeCOO-) (Scheme 2) by analogy with reactions of oxygenation imitating the action of L-tryptophan-2,3-dioxygenase [32, 33].

Scheme III.2.3.
The principle scheme of oxygenation of ligand (acac) in complex with Ni(II), initiated with exo ligand L2. Similar change in complexes' ligand environment as a consequence of acetylacetonate ligand oxidative cleavage under the action of O2 was observed in --reactions catalyzed of the only known-to-date a Ni(II)-containing dioxygenase acireductone dioxygenase, ARD [34] and its models [35]. This applies to the functional enzyme models, namely, Cu(II)- and

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469

Fe(II)-containing quercetin 2,3-dioxygenases, which catalyze the decomposition of diketones in the enol form to carbonyl compounds with CO evolution. [36, 37].

The similarity of kinetic dependences in the parent processes of ethylbenzene oxidation in the presence of {Fe(III)(acac)3+L2} (L2=DMF) and {Ni(II) (acac)2+L2} (L2=DMF, HMPA) (120C) make it possible to assume that transformation of in situ formed Fe(II)(acac)2DMF complexes, into more reactive selective catalytic species could also be a result of ligand L2controlled regioselective addition of O2 to the -C atom of acetylacetonate ligand [38]. However, the favorable combination of the electronic and steric factors that operate during the inner- and outer-sphere (hydrogen bonding) coordination of DMF ligand to Fe(II)(acac)2 may promote the acetylacetonate ligand oxygenation by another route realized in the action of Fe(II) acetylacetone dioxygenase (Dke 1). In this case, oxygen adds to CC bond (rather than inserts into the C=C bond as in the catalysis with nickel(II) complexes with consequent breakdown of cycle configuration through Criegee mechanism) to afford intermediate B, i.e., an Fe complex with a chelate ligand containing 1,2-dioxetane fragment. The process is completed with the formation of the (OAc) chelate ligand and methylglyoxal as the second decomposition product of a modified acac-ring (Scheme 4) [39].

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Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

Scheme III.2.4.
The principle scheme of dioxygen-dependent conversion of 2,4-pentandione catalyzed by acetyl acetone dioxygenase Fe(II). As in the case of catalysis by Ni complexes in the ethylbenzene oxidation, catalyzed by Fe(II)(acac)2L2 complexes, the reactive selective transformation products are polynuclear hetero ligand complexes with the hypothetical structure: Fe(II)x(acac)y(OAc)z(L2)n (L2=DMF) [26,38]. The final product of the Fe(II)(acac)2 conversion is the complex Fe(OAc)2, which (as and Ni(OAc)2) catalyze heterolytic decomposition of PEH to phenol and acetaldehyde (Scheme 4). It is the formation of the completely oxidized form of Fe(OAc)2 catalyst that is responsible for the sharp drop of selectivity SPEH in the third macro stage [26, 29, 38].

We established that the mechanism of the ethylbenzene oxidation (1200C), catalyzed Fe(III)(acac)3 in the absence of the activating ligand L2 at rather high value of [Cat] (>510-3 mole/l) is changed. The MPC becomes the major product of oxidation, SMPC,0 50%. AP and

Methods for Enhancing the Activity and Selectivity

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MPC are produced not parallel, but AP is the product of MPC oxidation. Phenol, as acetophenone and methyl phenyl carbinol and PEH, is produced at the maximal rate from the very beginning of the reaction. The change of the catalysis mechanism may be due to variation in the reactivity of iron complexes. The transformation of Fe(III)(acac)3 into new catalytically active species, presumably, Fe(II)(acac)2Q, is proposed. The radical Q, which can result from the oxidation of the ligand (acac) with Fe(III) ion, is stable and inactive as an initiator of free-radical oxidation reactions [38]:

It was shown by us that this transformation is negligible in the concentration range of [Cat] 510-3 mole/l, which was used in our researches (see below). The transformation of the nascent Q(L1)2)Fe(II) complexes into more active selective catalyst of the hypothetical structure Fe(II)x(acac)y(OAc)z(Q)n during the Fe(III)(acac)3 catalyzed ethylbenzene oxidation most likely follows the described above mechanism (Scheme 4). The enzymatic cleavage of C-C bonds in -diketones has growing significance for various aspects of bioremediation, biocatalysis, and mammalian physiology, and the mechanisms by which this particular cleavage is achieved are surprisingly diverse [42], ranging from metal-assisted hydrolytic processes [42] to those catalyzed by dioxygenases [41]. Carbon monoxide, one of the products of (acac) - ligand oxygenate breakdown path, catalyzed with the only known-to-date an Ni(II)-containing dioxygenase-acireductone dioxygenase, ARD, and releasing at the oxygenation of Ni(L1)2L2 (Scheme 1-3), previously considered biologically relevant only as a toxic waste product, is now considered a candidate for a new class of neural messengers [41]. The established mechanism of catalysis of the system {Ni(L1)2+L2}, including the in situ formation of the prime complexes Ni(L1)2L2 and following the Ni(L1)2L2 oxygenation to more active selective catalysts, allow the solution to the problem of improving of catalyst of the selective oxidation.

Introduction of Activating Additives in the Course of Catalyzed Oxidation Process The formation of the active catalyst in the second macro stage of ethylbenzene oxidation catalyzed by the {Ni(II)(acac)2+L2} system was proved by us from the effect of the introduction of a fresh portion of Ni(II)(acac)2 complex in the stage of a well-developed process [33]. A method of affecting a chemical reaction not only in its initial stages but also in subsequent stages of the fully developed process is an effective way of optimizing complex multi-stage oxidation processes [8, 29]. It was established by us earlier that at the relatively low nickel catalyst concentration in the absence of L2, the selectivity of the ethylbenzene oxidation into PEH, catalyzed by Ni(L1)2 (1,510-4 mol/l), was sufficiently high: SPEH,max = 90%. But the growth in SPEH,max is not accompanied the growth in the conversion C. The value C into PEH in the ethylbenzene oxidation, catalyzed by Ni(L1)2 (1,510-4 mol/l), did not exceed C = 2-4% [29,30]. For an increase of conversion degree of oxidation at maintaining of SPEH,max not less than 90%, the method of catalytic system activation in developed oxidation process was used [8].

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Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

In the case of introduction of Ni(II)(acac)2 into ethylbenzene, oxidation reaction catalyzed by {Ni(II)(acac)2(1.510-4 mol/l)+HMPA(1.010-3 mol/l)} catalytic system the maximum possible conversion degree C, at which reaction selectivity is not less than SPEH = 90% is significantly increased (by a factor of 3) (Figure 1) [8, 29].

Figure III.2.1. Dependences of selectivity of ethylbenzene oxidation into PEH (SPEH) on conversion level of ethylbenzene (CPEH) in the presence of system {{Ni(II)(acac)2 +HMPA} without admixtures (1) and with 4.510-4 mol/l Ni(II)(acac)2 (2) added in the course of the oxidation. [Ni(II)(acac)2]0=1.510-4 mol/l, [HMPA]=1.010-3 mol/l, 120.

A prerequisite for the catalyst reactivation is introduction of additives at the instant the reaction reaches its steady-state mode with respect to SPEH (SPEH = SPEH,max). If additional amounts of catalyst were added in the moments corresponding to decrease in oxidation selectivity (SPEH < SPEH,max at C < 4% and C > 5-6%), no reactivation of catalytic system occurred. Mechanism of activation consists in increase of steady-state concentration of catalytically active complex "A" (see Scheme 1) responsible for selectivity of oxidation process. Activation proceeds in two stages: 1. The fast exchange interaction of the primary complex Ni(acac)2L2 with Ni(OAc)2 complex was formed during the ethylbenzene oxidation to afford a heteroligand complex Ni(acac)(OAc)L2: Ni(II)(acac)2L2 + Ni(II)(OAc)2 Ni(II)(acac)(OAc)L2 (1)

2. The second step is the regioselective oxygenation of the latter to form a binuclear Ni2(acac)(OAc)3L2 complex ("").

Methods for Enhancing the Activity and Selectivity Ni(II)(acac)(OAc)L2 + O2 Ni2(acac)(OAc)3L2 (2)

473

Activation of catalytic system {Ni(II)(acac)2+L2} by acacH additives testifies to favor of exchange interaction between Ni(II)(acac)2L2 and Ni(II)(OAc)2 (1). However, in this case, the degree of conversion CS=90% increased to the lesser extent as compared with the addition of Ni(acac)2 to this system, which was attributed to the oxidation of uncoordinated acetylacetone acacH [8]. The role of the second stage (2) in catalyst activation, namely, in the formation of a binuclear nickel complex, was proved by introducing electron-withdrawing additives. We have found [29] that the simultaneous addition of a fresh portion of Ni(II)(acac)2 and also a -acceptor E (tetracyanethylene (TCE) or chloranil (CA)) into {Ni(II)(acac)2+L2} catalytic system did not increase the degree of conversion CS=90%. The passivation of catalytic system upon the introduction of TCE or CA can be rationalized as follows: since electron affinity is increased in the raw 2(0.87) <C(1.3) < TCE(1.6, 2.2), -acceptors TCE and CA electrophylicaly attack acetylacetonate ligand by --atom stronger than O2 forming outspherical complexes and thus preventing the O2 addition by this bond and the formation of a reactive binuclear heteroligand complex. The appearance of new absorption in the electronic spectra of the mixtures {Ni(II)(acac)2+MP+E} as compared with the spectra of E and {Ni(II)(acac)2+MP} testify to the complexes with charge transfer CTC L2Ni(II)(acac)2E favor. The outer-sphere reaction of connection of E to -C atom of acetylacetonate ligand is followed by the formation of L2Ni(II)(acac)2E [8,29]. The increase in CS=90% does not take place in the case of the introduction of a fresh portion Co(II)(acac)2 in the ethylbenzene oxidation, catalyzed by {Co(II)(acac)2+ HMPA} system) unlike the results, received at the ethylbenzene oxidation, catalyzed by {Ni(II)(acac)2+L2}. At the introduction of a fresh portion of Co(II)(acac)2 to the ethylbenzene oxidation, catalyzed by Co(II)(acac)2 without additives, the increase in CS=90% occurs. In that, the conversion CS=90% increases from 5 to 9%. These results seems to be due to the another mechanism of transformation of the primary complexes Co(II)(acac)2L2 to more reactive selective catalyst. The possible mechanism includes the reaction of Co(II)(acac)2L2 with peroxide radicals with formation of catalytically active complexes of the probable structure [Co(III)(L1)2L2(RO2)] [8] (see below, Chap.III.3).

III.3. MODELING OF TRANSITION METAL COMPLEX CATALYSTS UPON ADDITION OF AMMONIUM QUATERNARY SALTS AND MACROCYCLE POLYETHERS AS LIGANDS-MODIFIERS. THE ROLE OF HYDROGEN-BONDING INTERACTIONS
Quaternary ammonium salts are well-known as cationic surfactants. In aqueous solution, amphiphilic molecules of these salts aggregate to micelles and at higher concentrations to lyotropic (typical member is CTAB, cetyltimethylammonium bromide) (or thermotropic) mesophases. Besides this, quaternary ammonium salts are used as phase-transfer catalysts and as ionic liquids (ILs) in the synthesis of nanosized catalysts [42-46].

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Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

As was shown earlier, in various catalytic reactions that occur in water- organic medium, quaternary ammonium salts R4NX can play two different roles. These salts can act as catalysts of phase transfer, but also R4NX salts are often directly involved in catalytic reaction itself. Thus, for example, in reactions of the oxobromination of aromatic compounds a lipophylic ammonium salt transfers H2O2 into the organic phase. At the same time, since it is a Lewis acid, it forms R4NBr(Br2)n or R4NBr(HBr)n adducts, thus activating Br2 or salts of HBr for electrophilic attack on the aromatic ring [44]. In the catalytic oxidation of styrene to benzaldehyde by H2O2 in water-organic solvent systems ammonium salts completely transfer H2O2 and catalyst (Ru, Pd) into the organic phase by forming hydrogen bonds. Moreover, the complex formation affects the properties of the catalyst by the changing of its activity (rate and selectivity of the reaction) [45]. In the oxidation of p-xylene in a water-organic system in the presence of CoBr2 and R4NBr, the catalytically active species are complexes CoBr2 with R4NBr [46]. It is known also that the catalytic activity of CTAB in the ROOH decomposition in the presence of metals compounds is dependent on structural changes in the formed inverse micelles [47, 48]. The ability of quaternary ammonium salts to complex formation with transition metals compounds was established. It was proved, for example, that (acac)2 (M=Ni, Cu) form with R4NX (X=(acac)-, R=Me) complexes of [R4N][(acac)3] structure. Spectral proofs of octahedral geometry for these complexes were obtained [49]. Complexes Me4NiBr3 were synthesized and their physical properties were studied [50]. The selective complexation ability of crown ethers is among their most attractive properties. Crown ethers are also of interest in biologically modeling of enzyme catalysis and as phase transfer catalysts [43, 51]. Intermolecular and intramolecular hydrogen bonds and other noncovalent interactions are specific in molecular recognition [51]. Interest in the study of structure and catalytic activity of nickel complexes (especially nickel complexes with macrocycle ligands) has increased recently in connection with the discovery of nickel-containing enzymes [52-53]. The latter is the already mentioned Ni(II)containing dioxygenase ARD [34]. It is established that active sites of urease are binuclear nickel complexes containing N/O-donor ligands. Cofactor of oxidation-reduction enzyme methyl-S-coenzyme-M-reductase in structure of methanogene bacteria is tetra-azamacrocycle nickel complex with hydrocorfine Ni(I)F430 axially coordinated inside of enzyme cavity. [NiFe]-hydrogenase, with an Ni(III) complex in active site. Superoxide dismutase contains a catalytic cycle Ni(II) Ni(III). To date, the incorporation of transition metals into the cavities of macrocycle polyether was confirmed by different physicochemical methods; moreover, the specific structure of resulting complexes is determined not only by the geometric compatibility between the metal atom and the crown-ether cavity, but also by the whole ensemble of electron and spatial factors induced by the metal atom, the polyether, the other ligand and also the solvent [54]. The ability of the quaternary ammonium salts as well as macrocycle polyethers to form complexes with transition metals compounds was used by us in designing new effective catalytic systems for ethylbenzene oxidation to -phenylethy hydroperoxide.

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Catalysis by Ni(L1)2 in the Presence of Ligand-modifiers L2

It was established by us earlier that the selectivity of the ethylbenzene oxidation into PEH, catalyzed by Ni(L1)2 at the relatively low nickel catalyst concentrations (1,510-4 mol/l), was sufficiently high: SPEH,max 90%. This fact may be expected from the analysis of the scheme of catalyzed oxidation, including participation of catalyst (Cat=M) in chain initiation under catalyst interaction with ROOH (1) and under interaction RH with O2 (1, 2), in chain propagation (Cat + RO2) (2) and assuming the chain decomposition of ROOH (4) and quadratic chain termination reaction (5) (Scheme III.3.1). The precipitation Cat in the chain propagation (2) makes it possible to explain the dependence of [ROOH]max and the maximal rate on catalyst concentration. In this case, the rate of reaction should be decreased, and [ROOH]max should be increased with decrease in [Cat]0 [3,8].

Scheme III.3.1.
Mn+ + O2 Mn+...O2 RH M(n+1)++ R + HO2 ROOH RO + OH RH + O2 R + HO2 R + O2 RO2RH ROOH + R RO2 + M products + (R) RH + (R) R + RH ROOH +Mn+ M(n+1)++ OH + RO RH
ROOH + R + M(n+1)+,

(1) (1) (1) (2) (2) (2) (3)

ROOH + RO2 products + (R) ROOH + M(n+1)+ Mn+ + RO2 + H+, 2 RO2 products RO2 + M products [ROOH]max =

(4) (4) (5) (5)

k2k2''[RH] k4 (k2'[M ] + k2''[RH])

k3[M ] 2k4k5 (k2[RH] + k2'[M ])

wmax = k22 [RH]2=

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Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

Really, we observed the decrease in the rate of reaction and the growth in [ROOH]max with the decrease in [Cat]0 (in the case of M(II)(L1)2] 1,510-4 mol/l (M=Ni(II), Co(II))). In that, the value SPEH,max also increased. We established that in this case, the direction of byproducts formation changed. Products AP and MPC are formed not from PEH but parallel with PEH, i.e. wP / wPEH 0 at t0, and furthermore wAP / wMPC 0 at t0, that indicates on parallelism of formation of AP and MPC (P = AP or MPC) [8]. As mentioned before, the growth in SPEH,max is not accompanied with the increase in the conversion C. The value C into PEH in the ethylbenzene oxidation, catalyzed by Ni(L1)2 (1,510-4 mol/l), was not exceeded C = 2-4% [61,62]. At these conditions, the addition of electron-donor monodentate ligands turned out to be low effective [8, 25, 29] and the change of SPEH,max and CS=90% under the introduction of additives L2 (L2 = HMPA, MP) into system, practically was not observed. As one can see early, the effective method for increase in parameter C at the conservation of SPEH,max not less than 90% in the ethylbenzene oxidation, catalyzed by {Ni(L1)2 (1,510-4 mol/l) + L2}, is the introduction of activated additives of Ni(II)(acac)2 into developed reaction. Coordination of 18C6 or R4NX with Ni(II)(acac)2 seemed to promote oxidative transformation of nickel (II) complexes (schemes 13) into catalytically active particles and result in increase in C at conservation of SPEH,max not less than 90%. Our assumption was based on the next literature data. For example, the ability of crown-ethers to catalyze electrophilic reactions of connection to -C-atom of acac--ligand is known [43, 55]. It is known that R4NX in hydrocarbon mediums forms with acetylacetone complexes with strong hydrogen bond R4N+(XHOCMe=CHCOMe) in which acetylacetone is totally enolyzed [55]. The controlled by R4NX regio-selective connection of O2 by -C-atom of (acac) ligand in complex (acac)nR4NX is probable enough. Various electrophilic reactions in complexes R4N+(XHOCMe=CHCOMe) proceed by -C-atom of acetylacetone [43, 55]. Obviously, the favorable combination of H-bonding and steric factors, appearing under coordination of 18C6 or R4NX, may not only accelerate the active multi-ligand complex formation (Schemes 1-4) but also hinder the transformation of active catalyst into inactive particles. Our assumption was confirmed. In that, the extraordinary results were received in the case of the introduction of 18C6 or Me4NBr additives into ethylbenzene oxidation catalyzed by complexes Ni(L1)2. A really significant increase in conversion degree of oxidation into PEH at maintenance of selectivity on level SPEH ~ 90% occurs. The degree of conversion into PEH is increased from 4-6 up to 12% for complexes of Ni(II)(acac)2 (Ni(O,O)2 chelate unit) with 18C6 (1:1 and 1:2) and from 12 up to 16% for complex of Ni(II)(enamac)2 (Ni(O,NH)2 chelate unit) with 18C6 (1:1); moreover, SPEH exceeded 90%. Furthermore, the addition of 18C6 substantially increases the initial rate w0 of reaction is (Figure 1). The maximum selectivity of ethylbenzene oxidation SPEH,max increases from 90% to 98-99% [8, 56, 57]. In the case of additives of Me4NBr into reaction of ethylbenzene oxidation catalyzed by Ni(II)(acac)2, the value of SPEH,max=95% is higher than under catalysis by Ni(II)(acac)2 without addition of L2. The SPEH,max is reached not at the beginning of reaction of ethylbenzene oxidation, as it occurs at the case of complexes with 18C6, but at C=2-3%.

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Selectivity remains in the limits 90% <S 95% to deeper transformation degrees of ethylbenzene C19% than in the presence of additives 18C6 (C12%) [8, 95, 96]. Additives of 18C6 or Me4NBr to ethylbenzene oxidation reaction catalyzed by Ni(L1)2 lead to significant hindering of heterolysis of PEH to afford phenol (PhOH). The latter reaction is responsible for the selectivity reduction in the fully developed process. In that, induction period of PhOH formation in the presence of Me4NBr additives considerably exceeded that of the case of 18C6 [56-59]. Influence of quaternary ammonium salt on catalytic activity of Ni(II)(acac)2 as selective catalyst of ethylbenzene oxidation into PEH extremely depends on the structure of radical R in ammonium cation. Thus, in the substitution of an n-C16H33 radical for one of methyl radicals in Me4NBr (if cetyltimethylammonium bromide (CTAB) is added) SPEH,max decrease from 95 to 80-82% [58,59]. However, the initial reaction rate w0 is significantly increased, in 4 times in comparison with catalysis of ethylbenzene oxidation by Ni(II)(acac)2 complex. The initial rate of PEH accumulation wPEH,0 is higher than in the case of ethylbenzene oxidation catalyzed by the system {Ni(II)(acac)2 + Me4NBr}. However, initial rates of accumulation of side products of reaction of AP with MPC are also significantly increased (Figure 3). The decrease in PEH selectivity connected with heterolysis of PEH. The phenol formation is observed in lower conversions of RH transformation. Analysis of consequence of ethylbenzene oxidation products formation catalyzed by systems {Ni(L1)2+18C6} and {Ni(II)(acac)2+R4NBr} showed that the mechanism of products formation is unchanged as compared with oxidations catalyzed by Ni(L1)2 or {Ni(L1)2+HMPA}. The products PEH, AP and MPC were established to be formed parallel (wP/wPEH 0 at t0) in the course of the process; AP and MPC were formed also parallel (wAP/wMPC0 at t0).

Ni(O,0)2 Ni(O,NH)2

14 12 10 8 6 4 2 0

12.64 8.61 6.25 5.38 2.36 0 0 0 0 9.65 8.15 4.44

Figure III.3.1. Dependences of initial rates w0 (mol l-1 s-1) on [186] concentration (mol/l) in ethylbenzene oxidation reactions catalyzed by {M(L1)2+186} (M=Ni(II), L1=acac-1, enamac-1). [M(L1)2]=1,510-4 mol/l, 120.

wo.10 5

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Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

Catalysis of ethylbenzene oxidation initiated by {Ni(II)(acac)2 + CTAB} system is not apparently associated with formation of micro phase such as inverse micelles, because the micellar effect of CTAB manifested at T < 100 [80] is, as a rule, insignificant at T 1200. Furthermore, as we saw the system {Ni(II)(acac)2 + CTAB} was not active in ROOH decomposition. For estimation of catalytic activity of nickel complexes as selective catalysts of ethylbenzene oxidation into -phenylethylhydroperoxide, we proposed to use parameter SC. The S is mean value of selectivity of oxidation into PEH, which evaluated a change of S in the course of oxidation from S0 at the beginning of reaction to some Slim (Slim is an arbitrary value chosen as a standard). C conversion at S = Slim. For comparable by value systems selectivity as Slim the value Slim = 80%, approximately equal to selectivity of non-catalyzed ethylbenzene oxidation into PEH at initial stages of reaction, was chosen. The value selectivity was carried out in the limits S0 S Slim (Smax > 80%) (Ni, Co), S0 S Slim (Smax = 80%) (Co) [8, 30]. As regards the parameter SC (SC ~ 24102 (%,%)) the system {Ni(II)(acac)2+Me4NBr} proved to be the most active in ethylbenzene oxidation into PEH as compared with systems {Ni(II)(L1)2+18C6(HMPA)} [57].

w0 , w.10 6 , mol l -1 s-1

I row-wPEH,0, II-wAP+MPC,0, III-wPEH, IV-wAP+MPC

70 60 50 40 30 20 10 0
000 0 27 21 11 2.6 1.1 2.2 2 1.8 1 2.6 1.3 19 29 23 16.7 17

61

27 15 2.7

Figure III.3.2. Dependences of initial rates w0 (mol l-1 s-1) and the rates w (mol l-1 s-1) in the ethylbenzene oxidations catalyzed by {M(L1)2+186} (M=Ni(II), L1=acac-1, enamac-1) on [R4NBr] (mol/l). [M(L1)2]=1,510-4 mol/l, 120.

Methods for Enhancin ng the Activity y and Selectivi ity

479

30 25 20 15 10 5 0 L =0(HMP PA) Me4 NBr N

2

24 .3 20.6

9 9.6

18C6

Fi igure III.3.3. Pa arameter SC10 0-2 (%,%) in the e ethylbenzene oxidation upon n catalysis by ca atalytic 2 -4 120C. sy ystems {Ni(II)(a acac)2+L } with h L2=Me4NBr, 18C6, 1 HMP. [Ni(II)(acac) [ ]= =1.5 10 mol/l, 2

Fi igure III.3.4. Electron absorpti ion spectra of aqueous a solution ns: 1--Ni(acac) )2, 2,3, {Ni(acac c)2+18C6}, 4, , {Ni(acac)2+MP}, 5, Hacac. [N Ni(acac)2]=110 0-4, [18C6]=210 0-4 (2), 110-3 (3), [MP]=110-1, 6 [H Hacac]=1,910-6 mol/l, 200C.

We establi ished that in the t presence of 18C6 or R4NBr alone, without nicke el complex au uto-catalytic developing d of f process with h initial rates by order, lo ower was obse erved. The SPEH , , equal to 85% (18C6 6) or 95% (M Me NBr) at the beginning of f ethylbenzene e oxidation, P max 4 w sharply re was educed with the increase of ethylbenz zene conversi ion degree. The T PhOH fo ormation is ob bserved from th he very beginn ning of reactio on.

48 80

Ludmila L I. Mat tienko, Larisa A. Mosolova and Gennady y E. Zaikov

-5 Fi igure III.3.5. Ab bsorption spectr ra of solutions (CHCl ( F 3) : 1 Fe(III)(acac) 3 (2,210 ), 2 6 -3 -3 {F Fe(III)(acac)3+R R4NBX}: 2 Me M 4NBr (2,310 ), 3 (2 2,310 ), 4 Bu B 4NBr (2,410-3), 5 -3 -3 0 Bu4NI (2,010 ), , 6 Et3C6H5NC Cl (2,610 mol/l), 20 C. (Spectra were record ded using R4NX X solutions as s a reference).

Synergetic effects of increase in para ameter w0 and d SC in the ethylbenzene oxidation, ca atalyzed by sy ystems {Ni(L1)2+18C6} and d {Ni(II)(acac)2+R4NBr}, points to the fo ormation of ac ctive complex xes Ni(L1)2 with w (L2) wi ith the follow wing composi ition 1:1 (L1= (acac), L2=18C6, R4NB Br), 1:2 (L1= (acac), (ena amac), L2=18 8C6) and also o of their tran nsformation pr roducts (Figu ure 1(a, b), 2) 2 [98]. The stability of polynuclear heteroligand complexes N x(L1)y(L1ox)z(L2)n (L1ox= MeCOO Ni M , L2=18C6, = R4NB Br) ("") for rmed in the course of ox xidation could d be due to the e formation of f both inter- an nd intra-molec cular hydrogen n bonds. In th his case, the fo ormation of su upramolecular structures is highly h probabl le [62-64]. It was esta ablished the influence i of the t chelate un nit on the act tivity of bicy yclic nickel 1 co omplexes Ni(L L )2 as selecti ive catalysts of o the ethylbe enzene oxidati ion into PEH [8, 30]. In th he absence of L2 selectivity y of the ethylb benzene oxida ation into PEH H not lower th han SPEH = 80 0%, increases s considerably y at catalysis by b Ni(II)(enam mac)2 (Ni(O,N NH)2 chelate unit) up to C=22% as com mpared to tha at for the oxi idation in the e presence of Ni(II)(acac)2 (Ni(O,O)2 ch helate unit) (C =11%). The T initial rat tes of the ox xidation is th he presence of o complex N Ni(II)(enamac) higher ~ in 2.6 times s (Figure 2). . Besides thi is, unlike ca atalysis by 2 N Ni(II)(acac) n the presence of the comple ex with the Ni i(O,NH)2 chel late unit, no fo ormation of 2 in ph henol (the pro oduct of hetero olysis of PEH H) was observed during firs st hours of oxi idation. By th he parameter SC = 15.910 02 (%,%), Ni( (II)(enamac)2 can be compa ared to the Ni(II)(acac) N 2 co omplexes with 18C6 or Me M 4NBr (Figu ure III.3.3, Ta able III.3.1). The more eff ficiency of N Ni(II)(enamac) a compared with w Ni(II)(aca ac)2 (w0, SC) is most likely y due to the 2 as catalyst as el lectron-donating NH grou ups in the coordination unit of the nickel com mplex. The tr ransformation of the catalys st into more ac ctive selective e intermediate complexes (th he increase

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in SC), occurs, in this case, in the absence of additives of activating axial ligand-modifiers L2 (Chap.III.2, Scheme III.2). The formation of complexes Ni(L1)2 with L2=18C6 or R4NBr was confirmed by UV spectra. At that, the coordination of ligand L2=18C6 or R4NBr with metal ion proceeds with preservation of ligand L1 in internal coordination sphere of complex Ni(L1)2 [8, 56-58]. For example, as can be seen from Figure III.3.4, when an aqueous solution of 18C6 is added to the Ni(acac)2 solution, a decrease in absorption intensity of acetylacetonate ion (acac) and a short-wave shift of the absorption maximum (spectra 1-3) take place (at that, ligands 18C6 and MP do not exhibit any absorption bands in region considered). A similar change in the intensity of the (acac) absorption band is observed in the absorption spectra of Ni(acac)2 when it is coordinated with monodentate ligand MP (spectrum 4). Evidently, the formation of a complex between Ni(acac)2 and 18C6 does not lead to displacement of the acetylacetonate ligand from the inner coordination sphere of Ni(II), because otherwise, the short-wave shift of the absorption band should be accompanied by a significant increase in the absorption of the solution at = 275 nm, which correspond to the absorption maximum of acetylacetone (spectrum 5) [56]. Under formation of complexes of Ni(acac)2 with R4NBr, in spite of axial coordination by the fifth coordination place of nickel (II) ion, the outer sphere coordination of R4NBr (H bonding) with acetylacetonate-ion is possible, too. The possibility of outer sphere coordination of quaternary ammonium salts R4NX with diketonates (Ni(II), Fe(III)) was demonstrated by us with UV spectrophotometry at the research of the absorption of Fe(III)(acac)3 solutions in the presence of solutions of various salts R4NX. In the UV edge of the spectrum, Fe complex Fe(III)(acac)3 exhibit an intense absorption band at = 37103 cm-1 (CHCl3) of the * transition of the conjugated cycle of the acetylacetonate ion [95, 96]. In the presence of salts R4NX (Me4NBr, CTAB, (C2H5)4NBr, (C2H5)3C6H5NCl and the other), a decrease in the intensity and a bathochromic shift of the absorption maximum to = 36103 cm-1 ( 10 nm) are observed (Figure 4). Such a change in the spectrum indicates the influence of R4NX coordinated in the outer sphere on conjugation in the ligand. The change in the conjugation in the chelate ring of acetylacetonate complex, when R4NX is coordinated in the outer coordination sphere of the metal, can be caused by participation of the oxygen atoms of the acetylacetonate ion in the formation of coordination bonds with the ammonium ion or hydrogen bonds with alkyl substituents of the ammonium ion [58,596]. For example, it was established that the absorption band of phenol associated with the * transition experiences a bathochromic shift of 500 cm-1 due to formation of hydrogen bonds with dioxane[65] The complexes of the Ni salts with 18C6 and 15C5 (Ni(NO3)218C66H2O (1), 2NiCl215C66H2O (2) are more effective catalysts of the ethylbenzene oxidation into PEH in comparison with systems {Ni(L1)218C6n} (SC = 16.010-2 (%,%) (1), S C = 19.610-2 (%,%) (2)) (Table III.3.1) [57]. In the presence of 1 and 2, the autocatalytic development of the ethylbenzene oxidation is observed. The transformation of 1 and 2 into the more active catalytic particles does not occur. Obviously, the presence of the (acac) ligand in the coordinate sphere of Ni complex is one of the necessary conditions for the high catalytic activity of complexes Ni(L1)218C6n, and also products of their transformation: polynuclear heteroligand complexes Nix(L1)y(L1ox)z(18C6)n.

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Table III.3.1. Parameter SC in the ethylbenzene oxidation reactions catalyzed by nickel and cobalt complexes. [Cat]=1.510-4 mol/l, 1200C
Cat Ni(enamac)2 {Ni(enamac)2+186} Ni(acac)2 {Ni(acac)2+186} Ni(NO3)21866H2O(1) 2NiCl21556H2O(2) {Co(acac)2+1862} 2Co(NO3)21866H2O(3) 2Co(NO3)21566H2O(4) SC10-2(%,%) 15.9 21.2 9.6 20.6 16.0 19.6 9.9 15.8 14.1

The higher values of parameter SC for complex 2 as compared with 1 seems to be due to the specific feature of binuclear complex NiCl2 with 15C5, and also due to the more stable bond of Ni crown-ether for NiCl2, and that may affect on the mechanism of catalysis.

Catalysis by Fe(III)(acac)3 in the Presence of Ligand-modifiers L2

As in the case of ethylbenzene oxidation catalyzed by nickel complexes (Ni(L1)2), at the catalysis by Fe(III)(acac)3 the SPEH,max increases as [Cat] is reduced. However, this increase is less significant, from SPEH = 42-46% to SPEH = 65%. We also observed a reduction in the rate of ethylbenzene oxidation with the decrease of [Fe(III)(acac)3]. However, the dependence of [PEH]max on [Fe(III)(acac)3] shows an extremum, suggesting that the mechanism of catalysis is more complicated in this case [38,59, 66]. Fe(III)(acac)3, and formed in the course of ethylbenzene oxidation Fe(II)(acac)2, are inactive in PEH decomposition [37,58, 65]. In our articles, it was established that in ethylbenzene oxidation catalyzed by Fe(III)(acac)3 in concentration interval [Cat]=(0.55)103 mol/l, (80, 120) the oxidation products MPC and AP as well as PEH are the major products. They are formed parallel both at the beginning of reaction and at deeper stages of oxidation: wP/wPEH and wAP/wMPC is constant and nonzero at t 0 (P=AP or MPC) [38,59, 66]. The effects of electron-donor exoligands-modifiers on parameters w, SPEH and C of the ethylbenzene oxidation catalyzed by Fe(III)(acac)3 were studied at [Cat] = 510-3 mol/l. In this case, [PEH] = [PEH]max. In the presence of electron-donor monodentate ligand HMPA SPEH,max is increased from 42 up to ~57% (80), conversion degree C from 5 up to 15% ([Cat] = 510-3 mol/l). These were the maximum effects of electron-donor monodentate ligands on the SPEH and C of ethylbenzene oxidation at catalysis by Fe(III)(acac)3 [38,59]. As shown above, in the course of oxidation, the Fe(II)HMPA complexes do not undergo transformation into more active catalysts of ethylbenzene oxidation to hydroperoxide. After the acceleration period caused by the formation of Fe(II) complexes via chain initiation by the Fe(III) complexes (see Chapter VI), which is longer than that in catalysis by Fe(III)(acac)3, the rate of the reaction under steady-state conditions is w = wmax = wlim (to ~ [PEH]max). The no additive (synergistic) effects of growth in rate w0 (DMF), wlim (HMPA) and the no

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monotonic character of the SC (see below) dependence on [L2] at [Fe(III)(acac)3] = const seems to be due to the activity of the resulting Fe(II)(acac)2L2 complexes, as well as the complexes produced as a result of the transformation of Fe(II)(acac)2L2 (L2 is DMF) during oxidation (Figure III.3.7.). In ethylbenzene oxidation in the presence of {Fe(III)(acac)3(510-3 mol/l)+ R4NBr(0.510-3 mol/l)} (R4NBr=CTAB) (80), the SPEH,max=65%, which is reached in the developed process (Figure 9a (1, 2)), is higher than in the case of use of additives of monodentate ligands HMPA, DMF [38,59]. The fast decrease in SPEH at the beginning steps of the process is connected with the transformation Fe(III) complexes in Fe(II) complexes in the course of ethylbenzene oxidation (the auto acceleration period of the reaction is observed), the increase in wPEH,0, decrease in wP,0, and [PEH]max at catalysis by complexes (Fe(II)(acac)2)x(R4NBr)y are observed. Then, the increase in SPEH occurs at the expense of significant decrease in AP and MPC formation rate in the process at parallel stages of chain propagation and chain quadratic termination (wP/wPEH 0 at t 0, wAP/wMPC 0 at t 0). The conversion degree is increased from C = 4 up to ~ 8% (at SPEH=40-65%) (Figure 9a). Additives of CTAB to ethylbenzene oxidation reaction catalyzed by Fe(III)(acac)3 lead to significant hindering of heterolysis of PEH with formation of phenol responsible for decrease in SPEH.

6 5 4 3 2 1 0

4.97 2.9

5.46

2.1

Figure III.3.6. Parameter S C10-2 (%,%) in the ethylbenzene oxidation upon catalysis by Fe(III)(acac)3 and catalytic systems {Fe(III)(acac)3+R4NBr} with R4NBr=Me4NBr, (C2H5)4NBr, CTAB. [Fe(III)(acac)3]=510-3 mol/l, [R4NBr]=0.510-3 mol/l, 80C.

The growth in SC is 2.6, 2.36, 1.4 times for R4NBr=CTAB, (2H5)4NBr), Me4NBr), respectively, in comparison with catalysis by Fe(III)(acac)3 (S C=2.1102 (%,%)) (Figure III.3.6). In a given case, for value Slim as standard, we accept Slim =40%, a value that approximately corresponds to the selectivity of ethylbenzene oxidation in the presence of ligand-free Fe(III)(acac)3 (510-3 mol/l) (80) under the steady-state reaction conditions, C is

{Fe(III)(acac)3+(C2H5 )4NBr}

{Fe(III)(acac)3+CTAB }

{Fe(III)(acac)3+Me4N Br}

Fe(III)(acac)3

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the conversion for which SPEH Slim. In the absence of a catalyst, the addition of L2 has practically no effect on selectivity of ethylbenzene oxidation reaction, and the reaction proceeds in the autocatalytic mode at w0 below that in the catalysis by Fe(III)(acac)3. The no-additive (synergetic) effects of growth in S C parameter and w0 observed in the reactions catalyzed by Fe(III)(acac)3 in the presence of R4NBr, and also obtained kinetic regularities of ethylbenzene oxidation indicate the formation catalytic active complexes [61] presumably of (Fe(II)(acac)2)x(R4NBr)y as well as the complexes, produced as a result of the transformation of (Fe(II)(acac)2)x(R4NBr)y during oxidation.

Figure III.3.7. Dependences of selectivity (SPEH) of ethylbenzene oxidation reactions on the conversion (C) catalyzed by Fe(III)(acac)3 in the absence of additives L2(,1) and in the presence of L2= DMF(, 2) or L2=HMPA (, 3) ([DMF]=510-2 mol/l, [HMPA]=510-2 mol/l). [Fe(III)(acac)3]=510-3 mol/l, 1200 C.

The most effect of increase in SC was obtained in the case of CTAB additives. As we saw at the catalysis by nickel complexes the presence of the CTAB additives, the value of SPEH,max is reduced down from 90 to 80-82% as compared with increase in SPEH,max (94%) in the presence of Me4NBr additives [38,59]. Due to the favorable combination of the electronic and steric factors appeared at inner and outer sphere coordination (hydrogen bonding) of CTAB with Fe(II)(acac)2, the oxidative degradation of the acetylacetonate ligand may follow dioxygenase-like mechanism, described by Scheme 4. There is a high probability of formation of stable complexes of structure Fe(II)x(acac)y(OAc)z(CTAB)n (B). Out-spherical coordination of CTAB evidently creates sterical hindrances for regio-selective oxidation of the (acac) ligand and the transformation of the intermediate complex (B) into the final product of dioxygenation. In the case of catalysis by the {Fe(III)(acac)3 + DMF} system, the complexes Fe(II)x(acac)y(OAc)z(DMF)n, forming in the process are not stable, though DMF like CTAB

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forms H-bonds with acetylacetonate ion [38]. The rapid decrease in SPEH was observed. SPEH,max at the catalysis by the {Fe(III)(acac)3 + DMF} system was not higher in fact than SPEH,max at the catalysis by the {Fe(III)(acac)3 in the absence of the additives (Figure III.3.7).

Figure III.3.8. Dependence of SPEH in the reactions of the oxidation of ethylbenzene catalyzed by Fe(III)(acac)3 () or catalytic systems {Fe(III)(acac)3+18C6} (, ). [Fe(III)(acac)3]=510-3 mol/l, 18C6] = 510-3 mol/l, - 510-4 mol/l. 800C.

With the use of HMPA as exo ligand, that did not form H bonds with chelate ring of Fe(II)(acac)2, the transformation of Fe(II)(acac)2)HMPA was not observed, although HMPA as electron-donor ligand was characterized with a higher DN value (after V. Gutmann) as compared with DMF (Figure III.3.7) [38]. Catalysis of ethylbenzene oxidation initiated by {Fe(III)(acac)3 + CTAB} system (80) in the case of application of the small concentrations R4NBr (0.510-3 mol/l) is not connected with formation of micro-phase by the type of inverse or sphere micelles. As we saw above, the system {Fe(III)(acac)3 + CTAB} was not active in decomposition of PEH. wP/wPEH 0 at t 0, wAP/wMPC 0 at t 0. Analogous mechanism of formation PEH, AP and MPC is observed at the use of Me4NBr and (2H5)4NBr additives, which do not form micelles. At the [CTAB] concentration [CTAB] = 510-3 mol/l the rate of the PEH accumulation and [PEH]max decreases significantly, since the probability of micelles formation obviously increases. Thus, we established the interesting factthe catalytic effect of small concentrations of quaternary ammonium salts, [R4NBr] = 0.510-3 mol/l, which in 10 times less than [Fe(III)(acac)3]. It is known that salts QX can form complexes with metal compounds of variable composition, which depends on the nature of solvent [59]. The formation of poly nuclear heteroligand complexes (Fe(II)(acac)2)x(R4NBr)y (and Fe(II)x(acac)y(OAc)z(R4NBr)n also seems to be probable. In reaction of the oxidation of ethylbenzene with dioxygen, catalyzed by Fe(III)(acac)3(510-3 mol/l) in the presence of 18C6 additives (80), the dependence of SPEH n has extremum, as in the case of use of additives of ligands DMF or R4NBr. SPEH,max = 70% ([18C6]0 = 0.510-3 mol/l) and SPEH,max = 75.7% ([186]0 = 510-3 mol/l) in the process

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are higher than SPEH,max = 65% in the case of use of CTAB as exo ligand-modifier [57,58,60] (Figure III.3.8). The addition of 18C6 in the ethylbenzene oxidation with dioxygen catalyzed by Fe(III)(acac)3 results in the redistribution of the major oxidation products. The significant increase in [PEH]max is observed ~ 1.6 or 1.7 times at [18C6] = 510-4 mol/l, 510-3 mol/l, at that decrease in [AP] and [MPC] ~ 4, 5 times, accordingly, occurs. Additives of 18C6 lead to significant hindering of heterolysis of PEH with of the formation of phenol, responsible for decrease in selectivity. In the presence of catalytic system {Fe(III)(acac)3+18C6}, synergetic effect of increase in SC parameter ~ 2,5 and 2,8 times at [18C6]0=0,510-3 mol/l and [18C6]0 = 510-3 mol/l, correspondingly, is observed in comparison with catalysis by Fe(III)(acac)3 (SC =2,1102 (%,%)) (Figure III.3.9) [57,58,60].
-2

SC10 (%,%)
7 6 5 4 3 2 1 0

5.89 5.3

2.1

[18C6]=0;

5.10-4 mol/l;

5.10-3 mol/l

Figure III.3.9. The values of parameter SC10-2 (%,%) in the reactions of the oxidation of ethylbenzene catalyzed by Fe(III)(acac)3 or catalytic systems {Fe(III)(acac)3+18C6}. [Fe(III)(acac)3]=510-3 mol/l, 800C.

Obtained kinetic regularities of the oxidation of ethylbenzene testify to formation, presumably, of (Fe(II)(acac)2)p(18C6)q complexes and products of their transformations in the course of oxidation. It is known that Fe(II) and Fe(III) halogens form complexes with crown-ethers of variable composition (1:1, 1:2, 2:1) and structure dependent on type of crown-ether and solvent [53]. Supposedly, due to the favorable combination of the electronic and steric factors appeared at inner and outer sphere coordination (hydrogen bonding) of 18C6 with Fe(II)(acac)2 (as also in the case of catalysis with complexes with CTAB [96]), there is a high probability of formation of sufficiently stable hetero ligand complexes of the common structure Fe(II)x(acac)y(OAc)z(18C6)n, the intermediate products of the oxygenation of (acac)ligands in the (Fe(II)(acac)2)p(18C6)q complexes by analogy to the catalysis by acetyl

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acetone dioxygenase (M = Fe(II)) (Dke 1) (Ch. III.2, Scheme 4) that results in the SPEH,max and C increase: {Fe(III)(acac)3+18C6}Fe(II)(acac)p(18C6)q+O2Fe(II)x(acac)y(OAc)z(18C6)n (I)

Catalysis by Co(II)(acac)2 in the Presence of Ligand-modifiers L2

As in the case of catalysis of the ethylbenzene oxidation by Ni(L1)2, in the absence of ligand-modifiers L2 the ethylbenzene oxidation, catalyzed by the relatively low Co(II)(acac)2 concentration (0.510-4 mol/l), the selectivity of the catalytic ethylbenzene oxidation into PEH was sufficiently high: SPEH,max ~ 86%. There was an interesting fact established. The appearance of PhOH in the oxidation products at the small [Co(II)(acac)2] 1.010-3 mol/l. The PEH heterolysis with the PhOH formation seems to be due the decrease in Co(II)/Co(III) ratio with the decrease in catalyst concentration [1,3]. The extreme dependence of SPEH on C at the small of [Co(II)(acac)2]=(0,5-5)10-4 mol/l seems to be due the catalyst transformation in the new catalyst not active in PEH decomposition. In the case of catalysis by Ni(II)(acac)2 at the low catalyst concentration (0.51.0)10-3 mol/l), SPEH,max was observed at the beginning of the ethylbenzene oxidation. The dependence of SPEH on C has extremum at the more values [Cat]0 1.010-2 mol/l [8, 57]. The more significant effect of mono dentate ligand-modifiers L2 not only on SPEH but on C also was discovered at the increase in [Cat]0. This effect of increase in both parameters SPEH and C depended from catalyst nature and was established for Ni(II)(acac)2 only. At the concentrations [Ni(II)(acac)2]0 > 1,510-4 mol/l the use of L2 (HMPA) additives results in the high SPEH,max =80-85% and C = 10-14% of the ethylbenzene oxidation. We established that L2 (HMPA) additives increase SPEH,max but do not change the conversion of the ethylbenzene oxidation into PEH, catalyzed by Co(II)(acac)2 [94]. In the case of catalysis by Fe complexes, we observed the increase in C in the presence mono dentate ligand-modifiers L2, at that, the small effect of increase in SPEH (L2=HMPA) was established or SPEH did not change practically (L2=DMF) [70]. The additives 18C6 cause significant increase in SPEH,max from 52% (Co(acac)2) up to 80% in the case of {Co(II)(acac)2(1.510-4 mol/l)+18C6(3.010-4 mol/l)}. But SPEH,max at ratio [Co(II)(acac)2]/ [18C6]=1:2 insignificant exceeds value SPEH,max =72.5% at the catalysis complexes Co(II)(acac)2HMPA and nearly coincides with SPEH,max in the ethylbenzene oxidation catalyzed by coordinated saturated complexes Co(II)(acac)22HMPA [33,94]. In spite of the considerable growth in SPEH,max the catalytic system {Co(II)(acac)2(1.510-4 mol/l) + 18C6(3.010-4 mol/l)} by parameter SC ( SC = 9.910-2 (%,%) SC in the presence of 1,510-4 mol/l Ni(II)(acac)2 without additives or in the presence HMPA) is less effective catalyst of ethylbenzene oxidation into PEH in comparison with {Ni(acac)2+18C6} (Figure III.3.3). The value w0 is increased in 1.6 times at [186]:[Co(acac)2]=2:1 ((w0)max) (Figure III.3.10) [8,57]. Synergetic effects of increase in parameter w0 (the maximum on the dependence w0 against [18C6]) is due to the formation of complexes with different ratio Co(acac)2:186 (2:1, 1:1, 1:2) [53,57,30]. As can be seen from Fig III.3.11., at the addition of an aqueous solution of 18C6 to the Co(II)(acac)2 solution, an increase in absorption intensity of acetylacetonate ion (acac) and a

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bathochromic shift of the absorption maximum from 280 nm (35.510-3 cm-1) to 290 nm (34.510-3 cm-1) take place. The similar changes in the intensity of the (acac) absorption band and shift of absorption band are characteristic for narrow, crown unseparated ion-pairs [56]. The formation of a complex between Co(II)(acac)2 and 18C6 occurs at preservation of ligand L1 in internal coordination sphere of Co(II) because at another case, the short-wave shift of the absorption band should be accompanied by a significant increase in the absorption of the solution at = 275 nm, which correspond to the absorption maximum of acetylacetone.

Figure III.3.10. Dependence of parameter w0 (10-4, mol/l) on [18C6] or [HMPA] in the beginning of the ethylbenzene oxidation (10 min) at the catalysis by {Co(II)(acac)2+18C6} or {Co(II(acac)2 + HMPA}. [Co(acac)2]=1.510-4 mol/l, 1200C. [L2]104 (mol/l).

Figure III.3.11. Absorption spectra of aqua solutions: of Co(II)(acac)2 (1), mixture {Co(acac)2 + 18C6} (),mixture {Co(acac)2 + P} ( ), and Hacac (). 200C.

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Figure III.3.12. Kinetics of PEH (1,2), PhOH (3,4), in the ethylbenzene oxidation, catalyzed by Co(II)(acac)2, in the absence (1,3) and in the presence (2,4) of 18C6. [Co(acac)2]=1.510-4 mol/l, [18C6]=3.010-4 mol/l. 1200C.

Unlike 18C6, the addition of monodentate ligand MP to the Co(II)(acac)2 solution leads to insignificant decrease in absorption intensity of (acac) ligand and hypsochromic shift of the absorption maximum (spectrum). The same changes in spectra are observed at the coordination of Ni(II)(acac)2 with MP (Figure III.3.4), and in the case of the coordination of axial monodentate ligands with the other metal acetylacetonates [57,70]. At the catalysis by {Co(II)(acac)2+18C6} system, the kinetic curves of the ethylbenzene oxidation products have characteristic inflections apparently caused by formation of complexes providing higher selectivity of ethylbenzene oxidation into PEH (Figure III.3.12, III.3.13) [8, 57]. In the presence of Co(II)(acac)2 and additives of 18C6 (or HMPA), the rate of accumulation of the products is maximum at the early stages of the reaction and passes through a minimum as the degree of oxidation increases. As mentioned above, the formation of active selective catalyst in the ethylbenzene oxidation, catalyzed by system {Co(II)(acac)2 + HMPA}, likely, did not follow the mechanism of the oxidation of (acac) ligand with the molecular oxygen. The analogy of ethylbenzene oxidation phenomena in these two cases of catalysis by {Co(II)(acac)2+18C6} and {Co(II(acac)2 + HMPA} seems to be due similar mechanism of catalyst transformation (see Chapter III.2). The Co(II) Co(III) transition under the action of peroxide radicals seems to be the most probable. The effects of increase in SPEH,max accompanied by decreases in rates of AP and MPC formation, are observed also at the catalysis by complex of Co(NO3)2 with 18C6 (2Co(NO3)218C66H2O) in the absence of (acac) ligand [94]. This fact probably testifies in favor the interaction of Co(II)(L1)21862 with RO2 radicals with the formation of active selective catalyst of structure [Co(III)(L1)21862(RO2)]. The similar complexes were assumed at the research of cumyl ROOH decomposition in the presence of adducts Co(II)(acac)2Py (L1=acac-, L2=Py (Py=pyridine)) [8,67,68]. The formation of Co(II)(acac)2

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complexes with peroxide radicals in the {Co(II)(acac)2+ROOH} system was not registered. As one can see before the Co(II)(acac)2 transformation, as a result of (acac) ligand, oxidation [7,57] evidently takes place in the course of the ethylbenzene oxidation, catalyzed with Co(II)(acac)2 in the absence of ligand - modifier L2.

Figure III.3.13. Kinetics of AP (1,2), MPC (3,4) in the ethylbenzene oxidation, catalyzed by Co(II)(acac)2, in the absence (1,3) and in the presence (2,4) of 18C6. [Co(acac)2]=1.510-4 mol/l, [18C6]=3.010-4 mol/l. 1200C.

At the coordination 18C6 (HMPA) with Co(II)(acac)2 (1.510-4 mol/l), the sequence of products formation of the ethylbenzene oxidation is unchanged. The products PEH, AP and MPC were established to be formed parallel (wP/wPEH 0 at t0), AP and MPC also parallel (wAP/wMPC0 at t0) throughout the reaction of ethylbenzene oxidation. Analogy tendency for the ratio of the rates of accumulation of products PEH, AP and MPC to change for reaction time t0 was observed at the catalysis by complex of Co(II) salt Co(NO3)2 with 18C6 (2Co(NO3)218C66H2O (3)) (Table III.3.1). The transformation of the Co(II) salts with crown-ethers depends on the nature of crown-ether and does not occur with complex 2Co(NO3)215C56H2O (4). By parameter SC the complexes of the Co(II) salts with 18C6 or 15C5 (3), (4) are more effective catalysts of the ethylbenzene oxidation into PEH in comparison with system {Co(acac)218C62} (SC = 15.810-2 (%,%) (3), SC = 14.310-2 (%,%) (4) [33,93]) unlike the tendency, established by us for complexes of the Ni salts with 18C6. The transformation of the Co(II) salts 3 (Co-186) occurs in the absence of ligand L1 (L1=(acac)-), and seems to be due to a result of interaction of 3 with RO2 radicals with the formation of active selective catalyst (Scheme III.3.2).

Scheme III.3.2.

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III.4. TRIPLE CATALYTIC SYSTEMS INCLUDING BIS (ACETYLACETONATE) NI(II) AND ADDITIVES OF ELECTRON-DONOR COMPOUND L2 AND PHENOL AS EXO LIGANDS
One of the most effective methods of control of selective ethylbenzene oxidation into phenylethylhydroperoxide with dioxygen may be the application of the third component of the catalytic system, phenol (PhOH), along with Ni(II)(acac)2 and the additives of electrondonor ligands L2 (L2= MSt (M=Na, Li), MP, HMPA) [69]. Previously, we established that in the reaction of the ethylbenzene oxidation, catalyzed by Ni(II)(acac)2 in the absence of ligand-modifiers L2 the sharp decrease of rate and selectivity at the initial stages of oxidation is connected with formation of complex Ni(II)(acac)2PhOH that was an effective inhibitor of the ethylbenzene oxidation: under the action of Ni(II)(acac)2PhOH, heterolytic decomposition of PEH into PhOH and acetaldehyde took place, and also Ni(II)(acac)2PhOH terminated the chains of oxidation reacting with RO2 radicals [3,5-6]. We discovered phenomenon of the considerable increase in the efficiency of selective ethylbenzene oxidation reaction into -phenylethylhydroperoxide with dioxygen in the presence of triple systems {Ni(II)(acac)2+L2+PhOH} (L2=MP, HMPA MSt (M=Na, Li)), parameters SC, the conversion degree C (at SPEH ~85 to 90%), and the hydroperoxide contents ([PEH]max), in comparison with catalysis by binary systems {Ni(II)(acac)2+L2}. In this case. the value of SPEH is high (about 85 to 90%) both at the beginning of the reaction and at the significant depth of the process, unlike the catalysis by {Ni(II)(acac)2 + L2}. In the latter case, as one can see higher, the dependence of SPEH on C has a well-defined extremum. For example, at the catalysis by {Ni(II)(acac)2 + MP} SPEHmax =85 to 87% at C ~ 8 to 10% (Figure III.4.1).

Figure III.4.1. Dependence of SPEH on C in reaction of ethylbenzene oxidation catalyzed by binary system {Ni(II)(acac)2+P} (, 1) and two triple systems {Ni(II)(acac)2+P+ PhOH} with [PhOH]= 310-3 mol/l (, 2) or 4.610-4 mol/l (, 3) and [Ni(II)(acac)2] = const = 310-3 mol/l, and [P] = const = 710-2 mol/l. 1200C.

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As is evident, phenomenal results were obtained in the case of application of system, including NaSt as L2 {Ni(II)(acac)2 (3.010-3 mol/l) + NaSt (3.010-3 mol/l) + PhOH (3.0103 mol/l)} (Table III.4.1). Parameter C > 35% at the SPEHmax =85-87%. Concentration [PEH]max = 1.6 -1.8 mol/l (27 mass %), that is higher than [PEH]max for all binary catalytic systems {Ni(II)(acac)2 + L2} studied by us earlier and also the most effective triple catalytic systems {Ni(II)(acac)2 + L2 + PhOH}. Parameter SC 30.1102 (%,%) is much higher than in the case of the other triple systems and the most active binary systems [33]. These data are protected by patent RU No.2237050. Registration date is 11.2.2004; the authors are L.I. Matienko and L.A. Mosolova; patent holder is Emanuel Institute of Biochemical Physics, Russian Academy of Sciences.
Table III.4.1.
[P], mol/l 0 0.310-2 3.010-2 7.010-2 21.010-2 20.010-2* SC10-2(%,%) 0 0.29 11.30 17.50 11.20 11.00

Table III.4.2.
[Ni(II)(acac)2], mol/l 1.010-3 3.010-3 5.010-3 SC10-2 (%,%) 15.41 17.47 12.65

Figure III.4.2. Dependence of parameter SC10-2(%,%) on [PhOH] in reaction of ethylbenzene oxidation catalyzed by {Ni(II)(acac)2+MP+PhOH}. [Ni(II)(acac)2] = const = 310-3 mol/l, [MP] = const = 710-2 mol/l. 120C.

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Mechanism of selective ethylbenzene oxidation into -phenylethylhydroperoxide in the presence of triple systems is demonstrated here on the example of {Ni(II)(acac)2 + MP + PhOH} system. While investigating dependence of parameter SC on [P] in oxidation reaction in the presence of {Ni(II)(acac)2 + MP + PhOH} at [Ni(II)(acac)2]=const=310-3 mol/l and [PhOH]=const=310-3 mol/l (120), it turned out that dependence is extreme (Table III.4.1.). Maximum value of SC is reached at [MP] = 710-2 mol/l (Smax=85-87%). Concentration [MP] = 710-2 mol/l corresponds to formation of complexes of Ni(II)(acac)2 with MP of structure 1:1 (in the absence of PhOH) [8, 69]. It is characteristic that the value (S C)max 2 =17.5102 (%,%) exceeds value S C for complexes Ni(II)(acac)2MP (11.910 (%,%)) and coordinated saturated complexes Ni(II)(acac)22MP. Observing the significant synergetic effect of parameter SC increase under catalysis by {Ni(II)(acac)2 + L2} in the presence of inhibitor phenol may be explained by unusual catalytic activity of formed triple complexes Ni(II)(acac)2(L2)(PhOH). This presumption is confirmed by dependences of SC on [Ni(II)(acac)2] at [PhOH]=const=310-3 mol/l and [P]=const=710-2 mol/l ((SC)max=17.47102 (%,%) at [Ni(II)(acac)2]=310-3 moll-1) (Table III.4.2.), and also of SC on [PhOH] at [Ni(II)(acac)2]=const=310-3 mol/l and [P]=const=710-2 mol/l. In the latter case, SC reaches the extremum (SC)max=17.5 and (SC)max =18.12102 (%,%) at two [PhOH] concentrations differing by an order of magnitude: [PhOH] = 310-3 and 4.610-4 mol/l accordingly (Figure III.4.1, III.4.2). The data, presented in Figure III.4.1, III.4.2, testify to the fact that in both of these cases, selective ethylbenzene oxidation into PEH is connected with formation of the catalytic active complexes with composition 1:1:1. The confirmation of these triple complexes formation in the process came from the comparison of kinetics of the products accumulation of the ethylbenzene oxidation catalyzed by two triple systems {Ni(II)(acac)2(310-3 mol/l) + P(710-2 mol/l) + PhOH} at [PhOH] = 310-3 or [PhOH] = 4.610-4 mol/l. Some differences observed at the initial stages of two reactions are caused by the different initial conditions of triple complexes Ni(II)(acac)2(L2)(PhOH) formation in the course of catalytic ethylbenzene oxidation in these cases. At catalysis by triple system {Ni(II)(acac)2+P+PhOH} with small [PhOH]=4.610-4 mol/l, the fast increase in the concentration of PhOH right up to [PhOH] = (3-5)10-3 mol/l (at t=0-5 h) is observed. [PhOH] = (3-5)10-3 mol/l corresponds to [PhOH] for the first combination {Ni(II)(acac)2 (3.010-3 mol/l) + P (7.010-2 mol/l) + PhOH (3.010-3 mol/l)} and to the formation of complexes of structure [(L1)2(L2)(PhOH)] (Figure III.4.3 (2)). The increase in the concentration of PhOH (a result of PEH heterolysis) at the beginning of the process may be due to the function of PhOH as an acid that became stronger in consequence of outer sphere coordination of PhOH with nickel complex Ni(II)(acac)2P [61]. This presumption is confirmed by the next facts. So the accumulation of PhOH, but not the consumption, with maximum initial rate wPhOH,0=wPhOH,max is observed upon addition of PhOH (3.010-3 mol/l) into the reaction of ethylbenzene oxidation catalyzed by coordinated saturated complexes Ni(II)(acac)22MP ([Ni(II)(acac)2] = 3.010-3 mol/l, [P] = 2.110-1 mol/l) (Figure III.4.4), and also in the case of the ethylbenzene oxidation catalyzed by binary system {Ni(II)(acac)2(3.010-3 mol/l) + PhOH(4.610-4 mol/l)} at [P] = 0 [69].

494

Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov

Figure III.4.3. Kinetics of accumulation of PhOH in reaction of ethylbenzene oxidation catalyzed by binary system {Ni(II)(acac)2+P} (1) and two triple systems {Ni(II)(acac)2 + P + PhOH} with variable values of [PhOH] = 4.610-4 mol/l (2) or 310-3 mol/l (3) and [Ni(II)(acac)2] = const = 310-3 mol/l, and [P] = const = 710-2 mol/l. 1200C.

Figure III.4.4. The dependences of SPEH () and [PhOH] () C in reaction of ethylbenzene oxidation in the presence of triple system {Ni(II)(acac)2 (3,010-3 mol/l)+(2,110-1 mol/l)+PhOH (3,010-3 mol/l)}, 1200C.

The consumption of PhOH at the beginning of the process in the presence of catalytic system {Ni(II)(acac)2 (3.010-3 mol/l) + MP (7.010-2 mol/l) + PhOH (3.010-3 mol/l)}with [PhOH] = 310-3 mol/l (Fig III.4.3 (3)) may be due to the formation of the triple complexes [(L1)2(L2)(PhOH)] and least of all due to consumption of PhOH as inhibitor in the reaction of chain termination, PhOH + RO2. The rate of PhOH consumption is actually unchanged in a wide interval of MP concentration (0.37.0)10-2 mol/l. Previously, it was established that the rate of RO2 formation in the ethylbenzene oxidation catalyzed by

Methods for Enhancing the Activity and Selectivity

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Ni(II)(acac)2 (3.010-3 mol/l) at the addition of MP increased significantly due to the increase in the activity of the formed complexes Ni(II)(acac)2MP in the reaction of chain initiation and homolytic decomposition of PEH [8, 26]. Similarity of phenomenology of the ethylbenzene oxidation in the presence of {Ni(II)(acac)2 (3.010-3 mol/l) + MP (7.010-2 mol/l) + PhOH (3.010-3 mol/l)} and {Ni(II)(acac)2 (3.010-3 mol/l) + NaSt (LiSt) (3.010-3 mol/l) + PhOH (3.010-3 mol/l)} allows assuming the analogous mechanism of selective catalysis realizing by triple complexes formed in the course of oxidations. Also, the parallel formation of PEH and side products AP and MPC is established in these two cases: wP/wPEH 0 at t0 (P=AP or MPC) and wAP/wMPC0 at t0 at the beginning of reaction and in developed reaction of ethylbenzene oxidation catalyzed by {Ni(II)(acac)2+L2+ PhOH} (L2 = NaSt (LiSt), MP). Increase in SPEH during the catalysis by complexes Ni(II)(acac)2L2PhOH (L2 = NaSt, MP) in comparison with non-catalyzed oxidation is connected with the change of direction of the formation of side products AP and MPC (AP and MPC are not formed from PEH, as it takes place in noncatalyzed oxidation) and also with hindering of heterolytic decomposition of PEH [69]. Interesting phenomenon was established. Depending on the ligand surrounding of nickel ion, the PhOH becomes both effective as a deactivating ligand and as an effective activating ligand. In the absence of the exo ligand L2, the coordination of PhOH to Ni(II)(acac)2 (complex 1:1) is favorable to heterolytic decomposition of PEH and inhibition of the ethylbenzene oxidation [3, 5-6]. In the presence of the exo ligand L2, the formed triple Ni(II)(acac)2L2PhOH complexes, that include PhOH, are the effective catalysts of the selective ethylbenzene oxidation to -phenylethylhydroperoxide with molecular O2. The advantage of these triple systems is a long-term activity of in situ formed complexes Ni(II)(acac)2L2PhOH, which are not transformed in the course of ethylbenzene oxidation. Apparently, the introduction of phenol, together with the {Ni(II)(acac)2 + L2} catalyst in the reaction system in the initial stage of ethylbenzene oxidation, is one of the most efficient methods of designing catalytic systems for the ethylbenzene oxidation to -phenylethylhydroperoxide. The high efficiency of three-component systems {Ni(II)(acac)2+MSt+ PhOH} (M= Na, Li) in the reaction of selective ethylbenzene oxidation to -phenylethylhydroperoxide was associated with the formation of extremely stable heteroligand complexes Ni(II)(acac)2MStPhOH, which resulted in considerable increase in the conversion of ethylbenzene to PEH and the yield of -phenylethylhydroperoxide.

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INDEX
A
absorption, 534, 542, 544, 552, 554 absorption spectra, 542, 544 academic aspects, x, 47 acceleration, 526, 546 acceptor, 534 acceptors, 534 accessibility, 26, 280, 282, 288, 385, 461, 523 accounting, 83, 283 acetaldehyde, 19, 498, 527, 530, 556 acetic acid, 12, 20, 234 acetone, 9, 16, 24, 25, 183, 193, 288, 421, 525, 530, 551 acetonitrile, 80, 159, 179, 267, 271, 383, 423, 428, 429 acetophenone, 9, 25, 300, 304, 305, 376, 469, 524, 525, 526, 531 acetylation, 437, 440, 442, 445, 451, 452 acidic, 526 acidity, 160 acrylate, 147, 217, 219, 220, 221, 222, 396, 470, 471, 472, 474 acrylic acid, 11, 21, 234, 291, 303 acrylonitrile, x, 48, 288 activated carbon, 11, 19, 30 activation, 522, 524, 525, 526, 532, 533, 534 activation energy, 51, 374 activation parameters, 51 active centers, xi, 26, 108, 110, 115, 117, 118, 122, 123, 124, 125, 128, 129, 134, 136, 138, 139 active oxygen, 399 active site, x, 7, 47, 48, 113, 118, 122, 138, 139, 150, 177, 281, 283, 336, 378, 380, 407, 523, 524, 536 acylation, 237, 437, 440, 441, 444, 450, 451, 505 adamantane, 152 adaptation, 267 additives, xv, 21, 76, 365, 368, 383, 392, 492, 521, 522, 533, 534, 538, 539, 544, 546, 548, 549, 550, 551, 552, 554, 556 adducts, 535, 555 adenocarcinoma, 509 adhesives, 401 adsorption, 26, 198, 274, 446 aerogels, 7, 198, 207 AFM, 191, 192 agencies, 213 aggregation, 25, 26, 174, 178, 189, 206 agriculture, 437 air, 523 alcohols, xiii, xv, xvi, 7, 8, 18, 20, 29, 49, 62, 65, 70, 74, 76, 80, 149, 187, 200, 209, 228, 234, 235, 247, 253, 254, 261, 310, 316, 324, 325, 327, 332, 344, 387, 417, 418, 424, 425, 426, 437, 440, 442, 444, 452, 497, 498, 501, 522 aldehydes, xiv, xv, xvi, 18, 26, 48, 49, 83, 179, 180, 184, 185, 206, 215, 218, 223, 234, 235, 237, 259, 280, 309, 310, 317, 321, 323, 324, 326, 327, 329, 330, 368, 417, 418, 425, 465, 498, 504, 505 algorithm, 165 aliphatic amines, 251, 262, 497 alkaloids, xv, 25, 252, 262, 366, 368, 396 alkanes, 522, 523 alkenes, xiii, 10, 18, 19, 31, 49, 69, 145, 220, 233, 339, 342, 353, 354, 355, 368, 387, 389, 400, 402, 470 alkoxycarbonylation, xiii, 233, 235, 247, 252, 253, 254, 262, 263 alkylarens, 526 alkylation, xii, 54, 144, 187, 188, 320, 324, 331, 348, 349, 368, 373, 374, 377, 381, 382, 383, 394, 406, 408, 501 alkylation reactions, 373, 408 AlR3, 115, 139 aluminium, x, 4, 107, 109, 112, 115, 118, 122, 124, 136, 138 aluminum, 523

500

Index
basic raw materials, 234 basicity, 159, 160, 163, 183, 206 behaviors, 217 Beijing, 435 bending, 446 benefits, 2, 266 benign, xv, 211, 212, 234, 251, 365, 366, 367, 371, 372, 485 benzene, 7, 8, 14, 20, 24, 25, 28, 148, 153, 166, 271, 282, 303, 306, 347, 378, 420 binding energies, 164 binuclear, 534, 536, 545 biocatalysis, 532 biocatalysts, 228 biochemistry, 266 biodegradability, 212 biodiesel, 212, 213, 222 bioenergy, 436 biofuel, 212 biological activity, 392 biological systems, x, 48 biologically active compounds, 61, 241, 258 biomass, 436, 449 biomaterials, 176, 205 biomedical applications, xvii, 456, 457, 469, 509 biopolymers, 436 bioremediation, 532 bis, x, xi, xiv, 8, 10, 17, 20, 63, 66, 107, 108, 109, 110, 112, 113, 114, 115, 116, 118, 120, 122, 124, 125, 128, 129, 130, 134, 137, 138, 139, 140, 146, 155, 156, 166, 167, 216, 223, 239, 242, 263, 265, 267, 294, 298, 348, 351, 390, 464, 466, 467, 469, 470, 471, 483, 490, 497, 499, 502, 524, 525 BMI, 10, 16, 20 bonding, 174, 198, 205, 529, 539, 544, 548, 551 bonds, xvii, 8, 14, 116, 174, 189, 257, 316, 320, 355, 386, 429, 436, 455, 456, 457, 462, 525, 527, 532, 535, 536, 543, 545, 549 branching, 29, 76, 137, 280, 283, 313 Brazil, 37, 265 breakdown, 529, 532 breast cancer, 509 Bruker DRX, 440 BTC, 199, 200 building blocks, 48, 257, 436 butadiene, 8, 20, 61, 501 Butcher, 101, 519 by-products, 210, 219, 538

amides, xiii, 18, 62, 74, 204, 233, 235, 246, 247, 251, 262, 489, 490, 494 amine, 13, 23, 49, 183, 185, 246, 250, 284, 285, 311, 316, 321, 337, 388, 392, 472, 487, 492, 496, 501 amino acid, 248, 249, 250, 258 aminocarbonylation, xiii, 233, 235, 246, 247, 248, 249, 250, 251, 262, 263 ammonia, 11, 24, 243, 260, 494, 501 ammonium salts, 15, 377, 384, 399, 535, 536, 544, 549 amorphous polymers, 177 analgesic, 383 anatase, 3 anchoring, 7 aniline, 12, 23, 30, 249 anticancer studies, xvii, 456, 509 anticonvulsant, 261 antidepressant, 146 antipyretic, 383 application, xvii, 521, 549, 556, 557 aqueous solution, 535, 542, 544, 552 aqueous suspension, 25 ARCO and Halcon processes, x, 48 arc-plasma method, 5 argon, 5, 390 aromatic compounds, 535 aromatic rings, 14, 150, 187 aromatics, 213 ascorbic acid, 23 Aspergillus terreus, 216 asymmetric chemistry, xi, 143 asymmetric hydrogenation, ix, xi, xii, 25, 144, 148, 165, 166, 291, 294, 296, 297, 298, 299, 302, 303, 305, 306, 307, 308 asymmetric synthesis, xiv, 145, 158, 166, 280, 281, 357, 504 asymmetry, xv, 316, 366, 368 atmosphere, 54, 200, 235, 256, 438, 439 atmospheric pressure, 26, 243, 251, 254, 262, 291 atoms, 29, 51, 52, 77, 78, 79, 81, 83, 113, 146, 149, 150, 153, 154, 157, 159, 161, 234, 290, 312, 314, 350, 421, 430, 485, 524, 525, 545 attachment, 197, 280, 294, 356 Au nanoparticles, 29 auto acceleration, 546 automation, 266 automatization, 163 awareness, 82

B
Baars, 415 bacteria, 536 barriers, 7, 26 cancer cells, 508 capillary, 269 carbohydrate, 151, 448

Index
carbohydrates, 28 carbon atoms, 83, 273, 399, 402, 420, 421, 448, 524 carbon dioxide, xiii, 7, 209, 212, 228 carbon materials, 9 carbon monoxide, xi, xiii, 11, 108, 110, 116, 233, 234, 235, 236, 238, 241, 242, 243, 244, 246, 248, 250, 252, 254, 257, 260, 261, 309 Carbon monoxide, xiii, 233, 532 carbon nanotubes, 3, 7, 11 carbonyl groups, 441, 444, 446 carbonylation, xiii, 233, 234, 235, 236, 237, 238, 239, 241, 242, 244, 247, 248, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 352, 457 carbonylative, ix, xiii, 234, 235, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 251, 256, 257, 258, 259, 260, 261, 262, 263, 314 carbonylative Sonogashira coupling reaction, xiii, 234, 242, 244, 246, 261 carboxyl, 446 carboxylic acid, xiii, 11, 15, 224, 233, 234, 235, 247, 254, 259, 262, 387, 422 carboxylic acids, xiii, 224, 233, 235, 254, 259, 262, 387, 422 carrier, 523 castor oil, 203 catalyst deactivation, xviii, 357, 426, 521 catalytic activity, xiv, 2, 3, 5, 8, 16, 24, 25, 26, 31, 56, 63, 73, 87, 88, 90, 92, 109, 118, 130, 183, 184, 189, 197, 198, 266, 267, 274, 276, 290, 291, 293, 300, 302, 304, 311, 316, 320, 328, 340, 342, 344, 350, 351, 353, 354, 377, 378, 407, 428, 468, 471, 473, 524, 526,535, 536, 539, 540, 545, 558 catalytic effect, 3, 437, 549 catalytic hydrogenation, 8, 14, 19, 27, 145, 223, 227, 228, 287, 294, 428 catalytic particles, xvii, 521, 545 catalytic properties, xi, xii, 10, 54, 61, 93, 108, 109, 110, 139, 173, 202, 282, 294, 298, 302, 311, 327, 426 catalytic step, ix, 47 cation, 243, 339, 374, 384, 399, 400, 402, 426, 539 cavities, 536 C-C, xiv, 19, 194, 220, 226, 280, 429, 510, 532 cell cycle, 509 cell line, 509 cellulose derivatives, 437, 441, 442, 444, 445, 448, 449 cellulose succinoylation, xvi, 435, 437, 440, 441, 442, 447, 449 cervical cancer, 509 cesium, 13 chain propagation, 117, 118, 527, 537, 547

501

chain termination, 537, 560 chain transfer, 118, 124, 125 chemical, ix, x, xi, xii, xvi, xvii, 4, 5, 13, 17, 20, 24, 25, 30, 47, 48, 49, 61, 143, 163, 174, 176, 178, 209, 210, 211, 212, 213, 214, 234, 247, 266, 273, 280, 285, 287, 307, 316, 321, 328, 329, 337, 356, 366, 367, 371, 372, 379, 403, 417, 436, 437, 444, 450, 451, 456, 509, 523, 532 chemical industry, 234, 266 chemical inertness, 307 chemical properties, xii, 209, 211, 214, 280, 287 chemical reactions, ix, x, 47, 48, 366, 372 chemical structures, 356 chemicals, 49, 227, 234, 235, 383, 438, 489 China, 173, 202, 365, 435, 438, 449 chiral catalyst, 62, 165, 319, 324, 327, 328, 329, 330, 346, 368 chiral center, 83 chiral molecules, xv, 366, 368 chiral product, xi, xii, 143, 144 chirality, 66, 83, 145, 147, 152 chitin, 23 chitosan, 23 chlorine, 9, 452 chlorobenzene, 17, 282, 377, 487 chloroform, 28, 88, 288, 327, 377, 400, 401 chromatograms, 269 chromatography, xiv, 265, 285, 319, 327, 338, 339, 419 chromium, 3, 108, 109, 130, 134, 137, 139, 140, 421, 422 Cinchona alkaloids, xv, 366, 368 cis, 525 City, 32 clarity, 52 classes, 160, 286, 369, 468 cleaner processes, ix, 47 cleavage, 13, 79, 202, 522, 528, 532 clinical trials, 266 closure, 392 clusters, 26, 29, 426 CNS, 247 CO2, 9, 15, 22, 24, 25, 26, 93, 212, 525 cobalt, 7, 108, 109, 120, 121, 122, 123, 124, 125, 128, 130, 139, 140, 310, 420, 545 cocatalyst, 397, 399, 400, 401, 488, 498 coenzyme, 536 collagen, 3 colon, 509 color, 183, 439 combustion, 8 commodity, 235 community, 69, 96, 372, 394

502

Index
coupling constants, 159 covalent bond, 153, 174, 178 creativity, 147, 408 critical analysis, xv, 366, 371 crown, 27, 383, 394, 402, 403, 404, 467, 536, 538, 545, 551, 552, 555 crystal structure, 92, 175, 251, 349 crystalline, 7, 9, 28, 155, 175, 176, 269, 288, 436, 448, 525 crystallites, 6 crystallization, 280 crystals, 177, 202, 424 CS, 534, 538 CTAB, 535, 539, 540, 544, 546, 547, 548, 549, 550, 551 cyanide, 367 cycles, xvii, 156, 161, 243, 303, 351, 456, 457, 460, 488 cyclodextrins, 10, 26 cyclohexane, 523 cyclohexanol, 8, 14, 523 cyclohexanone, 8, 14, 185, 374, 375, 376, 523 cyclohexyl, 523 cyclopentadiene, 291 cytotoxicity, 509 Czech Republic, 143, 166, 417

compatibility, 242, 247, 389, 536 competitive process, 381 compilation, ix, 1 complement, 157 complexity, xii, 144, 160, 161, 202 composites, 3, 7, 18, 20, 27, 31, 449, 450 composition, xi, 4, 53, 108, 109, 110, 116, 118, 120, 121, 122, 138, 210, 285, 527, 543, 550, 551, 559 compounds, ix, xiii, xv, xvi, xvii, 5, 9, 25, 31, 47, 50, 52, 53, 54, 56, 61, 65, 69, 74, 83, 92, 145, 163, 179, 203, 209, 211, 213, 214, 216, 218, 223, 227, 228, 234, 235, 238, 245, 246, 248, 256, 258, 259, 261, 262, 266, 269, 270, 298, 310, 321, 342, 366, 386, 387, 389, 392, 399, 403, 417, 419, 421, 422, 425, 427, 429, 430, 436, 456, 503, 505, 509, 521, 522, 528, 535, 536, 550 computational chemistry, xii, 144 computing, 158, 165, 285 concentration, 532, 533, 537, 541, 546, 549, 551, 559, 560 condensation, xvi, 5, 8, 27, 91, 215, 222, 223, 261, 320, 347, 418 conductivity, 212 configuration, 65, 157, 161, 164, 390, 402, 418, 527, 529 conjugated dienes, 291, 421 conjugation, 380, 544 conservation, 538 construction, xiv, 164, 178, 279, 283, 290, 456, 461, 485, 502 consumption, 373, 559, 560 contaminant, 31 contamination, 210 contradiction, 174 control, xvii, 521, 523, 526, 556 conversion, 522, 526, 530, 532, 533, 534, 538, 539, 540, 543, 546, 547, 548, 551, 556, 561 cooling, 179, 197, 267, 439 coordination, x, xi, xii, 5, 48, 51, 57, 65, 73, 74, 76, 77, 80, 92, 136, 144, 146, 154, 173, 174, 178, 192, 193, 195, 197, 198, 200, 202, 204, 206, 207, 222, 269, 312, 323, 332, 419, 485, 488, 496, 526, 527, 529, 539, 544, 548, 551, 552, 554, 555, 559, 561 copolymer, 6, 16, 22, 28, 224 copolymers, 406, 453, 525 copper, ix, 1, 3, 7, 49, 197, 207, 246, 488, 524 correlation, 18, 20, 155, 159, 160, 164, 203, 204 corrosion, 3 cosmetics, 212, 213 cost, xv, 29, 213, 347, 365, 367, 463, 485 cotton, 452 coumarins, 255, 256, 263

D
deacetylation, 65 decay, 525 decomposition, 5, 7, 10, 17, 22, 26, 51, 53, 54, 57, 79, 93, 210, 211, 221, 350, 357, 492, 499, 522, 526, 528, 530, 535, 537, 540, 546, 549, 551, 555, 556, 560, 561 decomposition reactions, 54 decomposition temperature, 53 defects, 284, 286 deformation, 174, 177 degradation, 23, 426, 523, 548 dendrimers, xiv, 2, 20, 26, 29, 213, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 290, 291, 292, 294, 298, 300, 302, 310, 311, 312, 314, 315, 316, 317, 319, 324, 325, 326, 328, 329, 331, 332, 334, 335, 339, 345, 349, 350, 351, 353, 354, 356, 357, 359 Denmark, 510, 517 density functional theory, 166 Department of Energy, 436 deposition, 3, 4, 23, 27, 31 derivatives, xiii, xvi, 9, 15, 26, 52, 53, 54, 57, 62, 66, 82, 83, 84, 88, 92, 93, 96, 148, 151, 182, 191, 204, 212, 213, 233, 234, 235, 238, 245, 247, 248, 253, 254, 258, 261, 262, 263, 308, 316, 326, 332,

Index
368, 373, 390, 391, 392, 402, 405, 417, 418, 423, 430, 435, 437, 439, 443, 461, 468, 492, 493, 495, 498, 502 desorption, 25, 285, 523 destruction, 280, 522 developed countries, 436 deviation, 287 DFT, 51, 80, 81, 95, 96, 157, 158, 160, 161, 162, 163, 166, 403 diabetes, 266 diacrylates, 473 dialysis, 377 diamines, 261, 305, 331 dielectric constant, 226 dienes, 339, 387, 419, 425, 429, 501, 503 diffraction, 176, 183, 185 diffusion, 183, 318, 370, 371 diffusivities, 177 diffusivity, 212 dihydroxyphenylalanine, 167 dimerization, 355, 525 dimethacrylate, 22, 198 dimethylformamide, 24, 288, 390, 452 dimethylsulfoxide, xvi, 267, 435, 449 discrimination, 74 discs, 268 dispersion, 9, 22, 25 displacement, 387, 544 disposition, 81 dissociation, 81, 421, 423, 456, 462, 509, 525 distillation, xiii, 209, 210, 211, 214, 225, 280 distilled water, 267, 268 distortions, 276 distributed computing, 163 diversity, 151, 467 DMAP, xvi, 435, 437, 438, 439, 444, 445, 446, 447, 449 DMF, 24, 189, 190, 200, 202, 214, 256, 291, 303, 306, 391, 526, 527, 529, 530, 546, 548, 549, 550, 552 DNA, 30 donor, 527, 536, 538, 546, 549, 556 dosage, 441, 445 double bonds, 69, 349, 418, 421, 423 dream, 31 drug delivery, 437 drug discovery, 164 drug release, 178 drugs, xv, 212, 213, 351, 365, 373, 382, 383 drying, 23, 176 DSC, 197, 285 dyes, xiii, xv, 23, 49, 233, 365, 367, 368

503

E
economical concerns, xv, 365, 366 editors, 413 Egypt, 279 electrochemistry, 285 electrodes, 31 electrolyte, 27 electromagnetic waves, 372 electron, 4, 27, 50, 56, 69, 83, 92, 114, 115, 150, 151, 159, 160, 176, 196, 238, 241, 249, 251, 254, 266, 268, 297, 346, 351, 387, 388, 396, 397, 404, 421, 425, 426, 428, 429, 470, 488, 494, 496, 522, 526, 527, 534, 536, 538, 544, 546, 549, 556 electron cyclotron resonance, 4 electron microscopy, 176 electron pairs, 426 electronic spectroscopy, xiv, 265 electrons, 425 electrophoresis, 285 electrospinning, 21 elongation, 313, 445 elucidation, 116 emission, 176 employment, 6 emulsions, 224, 372 enantiomers, 61, 74, 81 enantioselective synthesis, 387 enantioselectivity, xii, 65, 69, 76, 78, 79, 80, 144, 146, 147, 151, 161, 179, 289, 291, 296, 299, 300, 302, 303, 304, 305, 306, 307, 318, 319, 320, 321, 322, 324, 327, 328, 329, 330, 332, 335, 336, 338, 347, 402, 404, 490 encapsulated, 523, 524, 525 endothermic, 197 energy, 155, 157, 161, 162, 177, 210, 213, 219, 225, 366, 367, 370, 371, 405, 462 energy consumption, 210, 367 engineering, 175, 202, 203, 450 England, 32, 168 entanglements, 287 entropy, 496 environment, xvii, 521, 523, 528 environmental impact, 211, 212, 366 enzymatic, 532 enzymes, xi, 48, 49, 143, 148, 211, 214, 266, 283, 289, 450, 536 EPR, 115, 128, 134, 285, 524 equilibrium, 12, 51, 179, 204, 386, 422 equipment, 227, 372 ESI, 285, 286, 304, 359 ester, 23, 30, 179, 182, 206, 226, 228, 250, 297, 350, 377, 394, 405, 423, 437, 445, 505

504

Index
fluorescence, 193, 285 fluoxetine, 146 food products, 213 Ford, 142 formaldehyde, 6, 24, 29 formamide, 526 formula, 52, 64, 74, 159, 444 fouling, 348 foundations, 162 Fourier Transformed Infra-red spectroscopy, xiv, 265 fragments, 15, 352, 525 fragrant properties, xvi, 418 France, 33, 37, 38 free energy, 383 free radical, 522, 524, 526 freezing, 176 FTIR, 268, 270, 272, 276 functionalization, 294, 313, 351, 352, 437, 448, 451 furan, 17, 481

esters, xiii, xvi, 213, 222, 223, 228, 233, 235, 248, 249, 250, 251, 252, 254, 262, 296, 387, 405, 407, 417, 418, 421, 425, 446, 489, 498 ethanol, 4, 5, 11, 19, 21, 25, 28, 31, 65, 173, 198, 213, 267, 291, 293, 306, 385, 386, 450 etherification, 368 ethers, 214, 223, 228, 368, 381, 383, 387, 402, 403, 424, 426, 536, 538, 551, 555 ethyl acetate, xiii, 182, 209, 217, 223 ethylbenzene, 524, 525, 526, 529, 530, 531, 532, 533, 534, 536, 537, 538, 539, 540, 541, 542, 543, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561 ethylene, x, xi, 18, 20, 28, 107, 108, 109, 110, 111, 113, 114, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 130, 131, 132, 134, 135, 137, 138, 152, 198, 525 ethylene glycol, 22, 198 ethylene oxide, 28, 525 ethylene polymerization, x, xi, 107, 108, 109, 110, 111, 114, 116, 118, 120, 121, 123, 124, 125, 127, 128, 130, 131, 132, 134, 135, 138 European Union, 436 evaporation, 27, 216, 426 evolution, 528 excitation, 371 exercise, 266 experimental condition, xv, xvi, 366, 435 expertise, 161, 366 exposure, 193, 371 extraction, xiii, 25, 179, 209, 210, 211, 212, 216, 217, 221, 223, 224, 225, 228, 268, 280, 370, 384, 422, 438, 440

G
GCE, 28 gel, 3, 15, 22, 173, 174, 175, 176, 177, 178, 179, 180, 183, 184, 185, 188, 189, 190, 191, 192, 193, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 205, 207, 338, 523 gel formation, 183, 185 gelation, 15, 175, 176, 178, 179, 183, 187, 191, 197, 203, 204, 205, 206 geometry, 76, 158, 164, 467, 536 Germany, 98, 229, 511 glass transition, 287 glass transition temperature, 287 glasses, 4 glucose, 12, 29, 436 glutamate, 28 glycerin, 212 glycerol, ix, xii, 209, 212, 213, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224, 225, 226, 227, 228 glycine, 300, 377 glycol, 13, 22 glycoside, 203 gold nanoparticles, 28 GPC, 327 granules, 23 graphite, 12, 19 grass, xvi, 418 greening, 366 Grignard reagents, 52, 53, 483 groups, 526, 544 growth, 532, 538, 546, 547, 552 growth rate, 6

F
fabrication, xiv, 266 fatty acids, 222 FDA, 213 fiber, 3, 205 fibers, 6, 20, 205, 206, 451 fillers, 1, 6 films, 21, 26, 27, 30 filtration, xiv, 26, 30, 177, 187, 193, 218, 267, 279, 303, 321, 324, 327, 346 financial support, 166, 203, 449 fine tuning, 305 first generation, 20, 299, 307, 315, 321, 356, 377 fixation, 155, 294 flame, 5, 6, 15, 21, 269 flavor, 61 flexibility, xiv, 218, 266, 276, 317, 457 fluid, 189, 212, 229, 230 fluid extract, 230

Index
Guangdong, 449 Guangzhou, 173, 435, 438

505

H
hafnium, 5 halogen, 57, 58, 114, 121, 451, 522 halogenated, 522 halogens, 551 hardness, 6 Hawaii, 32, 38 hazards, 49 H-bonding, 182, 183, 187, 189, 191, 193, 197, 539 HDPE, 23 heating rate, 268 height, 192 hemicellulose, 450 heptane, 111, 112, 117, 119, 131, 132, 134, 135, 423, 494 heterogeneous, 521, 524 heterogeneous catalysis, xii, xiv, 2, 7, 173, 178, 219, 277, 279, 281, 476, 521 heterogeneous systems, 275, 276, 281 hexane, 15, 290, 309, 379, 380, 381 hexenoic acids, xv, xvi, 417, 418, 419, 425 high density polyethylene, 23 high oxidation state, x, 48 high-capacity virtual ligand libraries, xii, 144 high-molecular compounds, 283 high-throughput experimentation, xii, 144, 167 histidine, 182 homogeneity, 285 Homogeneous catalysts, iv, ix, 47 homogenous, 522 homolytic, 522, 526, 560 host, 27, 436 HTE, xii, 144, 165, 167 hybrid, 204, 280 hydrazine, 21 hydrides, 227 hydrocarbons, 11, 54, 214, 387 hydrogels, 174, 179, 203, 205, 452 hydrogen, 4, 6, 16, 25, 26, 30, 49, 51, 54, 65, 82, 91, 148, 161, 174, 176, 179, 180, 203, 205, 206, 213, 227, 228, 248, 269, 273, 283, 300, 304, 307, 309, 342, 393, 397, 398, 400, 418, 419, 420, 421, 422, 423, 425, 428, 429, 437, 465, 529, 535, 536, 538, 543, 545, 548, 551 hydrogen abstraction, 54 hydrogen atoms, 161 hydrogen bonds, 176, 283, 535, 536, 543, 545 hydrogen cyanide, 179, 180, 206 hydrogen peroxide, 49, 65, 82, 91, 342, 397, 398, 400

hydrogenation, xi, xii, xiii, xiv, xv, xvi, 3, 8, 14, 19, 25, 26, 144, 145, 147, 148, 152, 165, 166, 209, 215, 224, 227, 228, 280, 288, 289, 290, 291, 293, 294, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 310, 347, 359, 417, 418, 419, 420, 421, 422, 423, 424, 425, 427, 430, 499 hydrolysis, 5, 91, 92, 179, 182, 206, 368, 450 hydroperoxides, 49, 50, 66, 67, 80, 92, 522, 526 hydrophilicity, 394 hydrophility, 523 hydrophobic, 523 hydrosilylation, xii, 18, 144, 310, 349 hydrothermal, 523 hydrothermal process, 5 hydroxide, 5, 9, 381, 390, 438, 439 hydroxyapatite, 3, 13, 24 hydroxyl, xvii, 16, 26, 49, 179, 191, 226, 292, 401, 436, 437, 441, 442, 444, 445, 446, 448, 449 hydroxyl groups, xvii, 16, 191, 292, 436, 437, 442, 444, 445, 446, 448, 449 hyperbranched polymers, 29, 280 hypothesis, 488

I
ideal, 162, 210, 211, 242, 281, 316, 509 image, 192, 196, 198, 274 images, 181, 182, 186, 188, 190, 192, 195, 199, 200, 274 imagination, 96 imino, vii, ix, x, xi, 107, 108, 109, 110, 112, 113, 114, 115, 116, 118, 120, 122, 124, 125, 128, 129, 130, 134, 137, 138, 139, 140, 332 imitation, xvi, 418 immobilization, 205, 357, 425 impregnation, 9, 17, 21, 24, 28 impurities, 25, 177, 285, 286 in silico screening, xii, 144, 164 in situ, 526, 529, 532, 561 inactive, 531, 539, 546 India, 36, 233 indium, 31 induction, 52, 63, 75, 81, 147, 153, 179, 316, 321, 377, 402, 403, 404, 539 induction period, 539 Industrial, 230, 356, 413, 450 inert, 523 infancy, 202 inhibition, xi, 108, 110, 116, 509, 526, 561 inhibitor, 3, 556, 558, 560 initiation, 522, 526, 537, 546, 560 insertion, 13, 116, 236, 238, 248, 250, 255, 256, 257, 527 insulators, 8

506

Index

integration, 450 interaction, 524, 533, 534, 537, 555, 556 interface, 217, 372, 374, 385, 399 intermolecular interactions, 524 interphase, 399 interval, 546, 560 intrinsic viscosity, 121, 138, 285, 286, 287, 359, 439, 440 inversion, 193 iodine, xvi, 308, 435, 436, 437, 438, 440, 441, 442, 446, 447, 449, 452 ion implantation, 3 ion-exchange, 398, 399 ionic, 535 ionic liquids, xvi, 4, 6, 8, 15, 20, 25, 61, 211, 212, 243, 435, 436, 437, 441, 451, 535 ionization, 269, 285 ions, 3, 31, 197, 198, 211, 260, 367, 384, 388, 394 IR spectra, 439, 446, 447 IR spectroscopy, 159, 339 iridium, 25, 33, 307 iron, 4, 6, 49, 108, 109, 112, 113, 114, 115, 118, 120, 122, 123, 124, 125, 128, 130, 137, 140, 160, 522, 524, 531 irradiation, xv, 8, 28, 30, 88, 89, 226, 366, 371, 372, 373, 381, 383, 384, 389, 400, 404, 405, 407, 412 IR-spectroscopy, 527 isobutylene, 405 isolation, xiii, 177, 209, 282, 314, 461, 524 isomerization, 19, 31, 310 isomers, 288, 418, 425, 430, 472 isoprene, 405 Israel, 209 IV, vii, xiv, 265, 266, 267, 269, 271, 274, 317, 323, 429, 457, 460

L
lack of control, 372 lactic acid, 20 landscape, 163 lanthanum, 5 leaching, 316, 352, 357, 422, 423, 456, 509 lead, xiv, xvii, 56, 76, 82, 92, 96, 174, 191, 210, 279, 280, 282, 283, 348, 521, 539, 544, 547, 550 ligands, xvii, 521, 522, 524, 525, 526, 527, 528, 536, 538, 544, 546, 550, 551, 554, 556 light scattering, 191 lignin, 436 limitations, 523 linear, 523 linear macromolecule, 287 linear molecules, 287 linear polymers, 286, 287, 288 liposomes, 27 liquid phase, 174, 176, 210, 228, 370, 371, 372, 374, 382, 396, 406, 412 liquids, xvi, 4, 6, 8, 15, 20, 25, 61, 202, 203, 210, 211, 212, 216, 229, 243, 435, 436, 437, 441, 451, 535 lithium, 310, 452 loading, 524 localization, 524 low oxidation, x, 48 lubricants, xv, 365, 368 Luo, 27, 44, 169, 206, 411, 450, 452, 512, 513, 514 lying, x, 48, 63 lysine, 204, 314

M
macromolecules, 280, 281, 283, 285, 286, 437 magnesium, 6, 9, 483 magnet, 194 magnetic properties, 176 magnetism, 6, 194 magnitude, 122, 313 maintenance, 539 majority, 50, 92, 165, 210, 251, 371, 522 MALDI, 285, 286, 339 maltose, 30 manganese, 2, 3, 49, 340 manufacturing, xv, 365, 368, 397 MAO, x, xi, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 134, 135, 136, 137, 138, 139, 502 mapping, 163 MAS, 195, 437, 440, 447, 448, 449

J
Japan, 414, 432

K
ketones, xiii, 11, 26, 31, 49, 145, 149, 152, 233, 235, 237, 238, 239, 243, 244, 245, 257, 259, 260, 301, 302, 303, 304, 305, 353, 354, 368, 422, 489, 490, 498 kinetic curves, 111, 554 kinetic model, 51, 94 kinetic regularities, 547, 551 kinetic studies, 16, 23, 51, 408 kinetics, xv, 51, 83, 96, 366, 374, 399, 401, 408, 559 KOH, 11, 215, 222, 374, 375, 376, 377, 385, 386 Korea, 279

Index
mass spectrometry, 285, 286, 298 matrix, 1, 4, 6, 7, 12, 15, 23, 26, 29, 174, 176, 189, 285, 342, 352 mechanical properties, 8 mechanistic explanations, 522 media, xiv, 30, 148, 205, 210, 212, 229, 258, 279, 316, 371, 419, 437, 451 median, 74 melt, 269, 280, 287 melting, xiv, 15, 53, 265, 269 membranes, 8, 377 memory, 27 Mendeleev, 432 mesoporous materials, 315 messengers, 532 metabolic disorder, 382 metal complexes, 189, 368, 523, 525, 526 metal ion, 30, 176, 192, 202, 269, 437, 544 metal ions, 30, 176, 192, 437 metal nanoparticles, 1, 24, 26, 29 metal oxides, x, 2, 48 metallic nanoparticle-polymer, ix, 1 metallocenes, 109 metallogels, xii, 173, 193, 200, 202 metalloporphyrins, 525 metals, ix, 1, 2, 3, 5, 6, 70, 154, 371, 456, 457, 535, 536 meter, 372 methanol, 7, 20, 27, 30, 57, 195, 221, 222, 224, 234, 267, 291, 299, 303, 305, 320, 321, 324, 338, 346, 419, 428, 429 methodology, 235, 372, 387, 390, 391, 392, 405, 408 methyl group, 404, 471 methyl methacrylate, 22, 453 methyl phenyl sulfide, xiv, 265, 267, 274, 275, 276, 277 methylalumoxane, x, 107, 115 methylene blue, 23 methylene chloride, 65 Mexico, 32 mice, 261 micelles, 535, 540, 549 microcrystalline, 183 microemulsion, 15, 23 microenvironment, 523, 524 micrometer, 5, 174, 187 microorganism, 213 microscopy, 285 microspheres, 13 microwave heating, 225, 389 microwave radiation, 83, 373 migration, 425 Ministry of Education, 166

507

minors, 269, 277 mixing, 20, 122, 134, 147, 194, 200, 223, 228, 303, 306, 310, 314, 422, 438 MMA, 22, 29 MNDO, 158, 167 Mo catalysts, ix, x, 48 model system, 266, 310 modeling, 536 modelling, xi, xii, 144, 150, 158, 163, 165, 176 models, x, xii, 48, 52, 144, 154, 156, 160, 163, 165, 261, 320, 403, 522, 528 modules, 314 modulus, 177 moisture, x, xvii, 48, 92, 93, 238, 455, 456, 457, 464, 471, 486, 495 molar ratios, 329 mole, 29, 531, 532 molecular dynamics, 158 molecular mass, 203, 204, 283, 287 molecular oxygen, 31, 49, 74, 497, 498, 554 molecular structure, xi, 109, 137, 144, 175, 202 molecular weight distribution, x, 107, 108, 109, 113 molecules, xv, xvii, 2, 12, 16, 24, 152, 158, 161, 162, 163, 164, 174, 175, 177, 178, 179, 203, 216, 227, 247, 257, 281, 283, 287, 366, 368, 377, 380, 392, 421, 423, 437, 455, 461, 502, 535 molybdenum, x, 4, 48, 49, 54, 56, 65, 74, 88, 344 molybdoenzymes, x, 48 MOM, 206 momentum, 210 monolayer, 30, 324 monomers, xv, 137, 285, 313, 365, 367, 368 morphine, 145 morphology, 191, 193, 203, 285 Moscow, 521 motif, 74, 237 MoVI complexes, x, 48, 49, 50, 62, 63, 65, 73, 81 MP, 526, 527, 534, 538, 542, 544, 554, 556, 558, 560 MPA, 546 multiwalled carbon nanotubes, 14 MWD, 113, 114, 116, 117, 118, 120, 121, 122, 123, 125, 127, 128, 129, 134, 135, 136, 138, 139

N
N/O ligands, 78 NAD, 148 nanocomposites, 2, 3, 4, 5, 6, 7, 26, 29, 32 nanocrystals, 3, 5, 25 nanofibers, 5, 7, 9, 20, 206 nanomaterials, 1 nanometer, 5, 174, 202 nanometer scale, 174

508

Index

nanoparticles, 1, 2, 3, 4, 5, 6, 7, 8, 14, 19, 23, 25, 26, 28, 31, 33, 194, 195, 216, 292, 293 nanorods, 30 nanostructured materials, 32 nanostructures, 4, 6, 27, 30, 179 nanowires, 28 naphthalene, 15, 23, 250, 251, 262, 375, 376, 465 N-bromosuccinimide, xvi, 435, 436, 437, 452 NBS, xvi, 435, 437, 438, 442, 443, 444, 447, 448, 449, 452 negative effects, 300 neglect, 167 Netherlands, 358 neurotoxicity, 509 next generation, 286 NH2, 27, 305 NHC, xvii, 455, 464, 466, 467, 468, 469, 472, 473, 474, 483, 485, 487, 488, 490, 492, 497, 499, 503, 509 N-heterocyclic carbenes, xvii, 455, 456, 457, 461, 462, 463, 464, 467, 470, 474, 477, 483, 485, 487, 488, 489, 491, 494, 497, 503, 509 nickel, 3, 7, 108, 215, 237, 483, 527, 529, 532, 534, 536, 537, 538, 540, 542, 543, 544, 545, 546, 548, 559, 561 nicotinamide, 262 niobium, 4 nitrobenzene, 23, 26 nitrogen, 6, 23, 48, 109, 113, 176, 270, 297, 323, 368, 392, 394, 396, 483, 494 nitrogenase, 52, 266 nitroso compounds, 49 NMR, xvii, 15, 81, 93, 94, 115, 119, 122, 126, 128, 133, 137, 159, 163, 167, 176, 187, 193, 195, 197, 205, 268, 273, 276, 285, 298, 312, 339, 425, 436, 437, 440, 447, 448, 449 noble metals, ix, 1 nonane, 385, 386, 468 non-steroidal anti-inflammatory drugs, 237 norbornene, 355, 400, 501 Northern Ireland, 173 novel materials, 351 nuclear, 527, 550 nuclear magnetic resonance, 167, 437 Nuclear Magnetic Resonance, xiv, 265, 268 nucleation, 372 nuclei, 159 nucleophiles, xiii, 233, 234, 235, 247, 248, 249, 250, 262, 392, 405, 485, 501 nucleophilicity, 342, 485 null, 298

O
obstacles, 69 octane, 383 o-dichlorobenzene, 377 OH, 5, 11, 15, 25, 26, 65, 80, 273, 274, 292, 370, 485, 486, 537 oil, xvi, 83, 203, 214, 217, 221, 222, 226, 418 olefin epoxidation, x, 48, 50, 52, 55, 58, 61, 62, 63, 65, 66, 74, 78, 79, 80, 85, 87, 92, 95, 96, 344 olefins, x, 10, 20, 48, 55, 57, 66, 67, 70, 71, 74, 75, 76, 77, 80, 92, 96, 137, 234, 257, 309, 312, 314, 351, 353, 355, 387, 388, 396, 397, 402, 429, 471, 497, 498, 499 oleic acid, 5 oligomerization, 114, 125 oligomers, 109, 113, 501 operations, 367 opportunities, 408 optical properties, 3, 7 optimism, 175 optimization, xi, 143, 155, 471 organ, x, xiii, 18, 48, 52, 57, 82, 96, 164, 206, 233, 234, 259, 350, 418, 430 organic, 535 organic compounds, xiii, 48, 62, 148, 209, 211, 214, 216, 227, 228, 392 organic ligands, ix, 47, 74, 192 organic mediums, 11 organic polymers, 177 organic solvent, 535 organic solvents, 27, 29, 174, 189, 193, 195, 197, 204, 205, 212, 214, 216, 218, 223, 224, 225, 226, 228, 242, 243, 287, 288, 298, 308, 327, 354, 389, 419 organogels, xii, 173, 174, 179, 182, 197, 203 organomagnesium compounds, 483 organotin compounds, 237 osmium, 24 overlap, 167 Oxidation catalysis, x, 47 oxidation catalysts, x, 48 oxidation products, 49, 66, 92, 269, 523, 540, 546, 550, 551, 554 oxidation rate, 526 oxidative, 522, 526, 528, 538, 548 oxidative destruction, 522 oxide, 525 oxide nanoparticles, 7 Oxovanadium, vii, xiv, 265, 266, 267, 269, 271, 274 oxygen, 4, 5, 6, 12, 27, 48, 51, 75, 77, 78, 79, 81, 82, 87, 228, 262, 266, 267, 268, 274, 398, 425, 486, 522, 524, 525, 529, 545, 554

Index
oxygenation, 525, 528, 529, 532, 534, 551

509

P
Pacific, 38 Palladium-catalyzed carbonylation reactions, xiii, 233, 262 PAN, 6 parallel, 63, 66, 86, 89, 157, 527, 531, 538, 540, 546, 547, 555, 560 parallelism, xi, 144, 538 parameter, 538, 540, 543, 544, 545, 547, 550, 552, 553, 555, 558 particles, xvii, 521, 523, 526, 538, 539, 545 partition, 394, 406 passivation, 316, 534 patents, 50 pathways, 48, 88, 89, 91, 95, 146, 285 PCA, 164, 167 PCP, 474 PCR, 167 perfume chemistry, xv, 417 permeation, 327 peroxide, 49, 50, 51, 52, 93, 397, 398, 524, 534, 554, 555 petroleum, 176 pharmaceutical industry, ix, 47, 69, 164 pharmaceuticals, xiii, xiv, xv, 49, 61, 145, 212, 233, 234, 247, 266, 365, 367, 368, 387, 444, 461, 486 phase transfer catalysis, xv, 365, 367, 382, 394, 405 phenol, 7, 8, 14, 23, 24, 82, 252, 254, 527, 530, 539, 540, 544, 545, 547, 550, 556, 558, 561 phenol oxidation, 7 phenolphthalein, 439 phenomenology, 560 phenoxycarbonylation, xiii, 233 phenyl esters, 262 phenylalanine, 13 PhOH, 539, 543, 551, 554, 556, 557, 558, 559, 560, 561 phosphorus, 144, 145, 146, 147, 148, 150, 152, 155, 156, 157, 159, 160, 161, 163, 200, 290, 312, 350, 394 physical properties, 210, 212, 229, 287, 536 physicochemical, 527, 536 physicochemical methods, 527, 536 physics, 202 physiology, 532 plants, 210, 450 plasticity, 4 plasticizer, 213, 383 plastics, 49 platform, 355, 456, 509 platinum, ix, 1, 20, 26, 268, 509

play, 535 PMMA, 29, 198, 199 poison, 426 Poland, 37 polar groups, 109 polarity, 223, 228, 523 polarization, xvi, 436 pollution, 211, 347, 366, 367, 368 poly(methyl methacrylate), 29 polyamides, 261 polybutadiene, 401, 406 polycondensation, 261 polydispersity, 112, 121, 127, 285 polyesters, 213, 261, 287, 339 polyether, 287, 288, 291, 314, 320, 536 polyethylene, 525 polyimide, 30 polyisoprene, 22 polymer, ix, xii, 1, 5, 6, 13, 21, 27, 28, 48, 113, 114, 116, 120, 121, 124, 125, 129, 136, 137, 173, 178, 192, 193, 195, 197, 198, 202, 204, 205, 206, 207, 247, 280, 281, 285, 293, 299, 313, 317, 318, 327, 329, 336, 337, 338, 347, 348, 350, 355, 357, 368, 373, 436, 469, 476, 523, 524, 525 polymer chain, 124, 136, 525 polymer composites, ix, 1 polymer matrix, 1, 317 polymer molecule, 120, 121 polymer synthesis, 368 polymeric catalysts, 302, 303 polymeric materials, 280 polymeric products, 108 polymerization kinetics, 139 polymerization process, 109, 116, 287 polymerization temperature, 110, 119, 125, 127, 128, 130, 131, 134, 135, 136, 138, 139 polymerization time, 112, 113, 116, 117, 120, 123, 124, 127, 129, 130, 134, 139, 140 polymers, 2, 27, 28, 31, 108, 109, 113, 120, 124, 129, 136, 138, 174, 192, 197, 203, 204, 205, 280, 287, 318, 327, 329, 335, 336, 355, 356, 437, 444 polymorphism, 175, 203, 205 polypropylene, 311 polystyrene, 5, 12, 27, 29, 291, 313, 314, 317, 327, 329, 335, 336, 337, 357, 422, 525 pore, 523 porous materials, 176 porphyrins, 339, 522, 524 portfolio, 457 Portugal, 38, 47, 104 potassium, 216, 381, 383, 386, 388, 390, 391, 406, 420, 422, 438

510

Index
radius, 157 range, 532 rational design, xi, 144, 149, 158, 165, 178, 202 rationality, 175 raw materials, 436 reactant, xiii, 25, 209, 213, 221, 226, 228, 293, 367, 380, 399 reactants, xiii, xv, 209, 210, 212, 216, 223, 224, 226, 318, 365, 367, 371, 379, 380 reaction center, 2, 320, 404, 522 reaction mechanism, 51, 52, 65, 161, 165, 185, 239, 374, 385, 420, 423, 424, 524 reaction medium, 82, 137, 210, 213, 214, 216, 219, 221, 222, 243, 300, 315, 437, 451, 452, 486 reaction rate, xv, 21, 117, 129, 177, 211, 217, 282, 311, 350, 365, 367, 371, 373, 375, 376, 379, 381, 382, 385, 387, 405, 423, 522, 539 reaction temperature, xv, xvi, 65, 93, 125, 211, 225, 257, 314, 342, 365, 367, 372, 392, 435, 440, 441, 442, 443, 445, 492 reaction time, xvi, 56, 65, 89, 93, 123, 129, 224, 277, 304, 305, 336, 346, 350, 371, 372, 373, 378, 389, 392, 395, 435, 465, 466, 555 reactive sites, 179, 448 reactivity, xi, 4, 31, 51, 52, 54, 108, 110, 116, 117, 118, 124, 128, 134, 136, 139, 287, 301, 305, 307, 314, 315, 321, 327, 335, 342, 346, 352, 369, 384, 394, 399, 401, 407, 408, 457, 465, 492, 501, 523, 531 reading, 96 reagents, xiv, 49, 134, 185, 196, 210, 219, 238, 259, 267, 280, 281, 290, 327, 330, 334, 346, 355, 362, 366, 367, 371, 383, 407, 437, 457, 461, 483, 485, 486, 505, 523 reality, 162, 284 reasoning, 162 recognition, 174, 205, 536 recycling, xiii, 61, 177, 209, 211, 221, 226, 228, 266, 281, 293, 300, 303, 304, 347, 351, 356, 357 redistribution, 527, 550 redox, 522 reference system, 299 regenerate, 235 regeneration, 7, 399, 496 regioselectivity, 49, 82, 217, 237, 256, 314, 315, 339, 347, 503 regression, 164, 167 regulation, xviii, 521 rejection, xii, 144 relevance, x, 48, 61, 66, 457, 496 reliability, 165 relief, 355 Reppe and Heck, xiii, 233

precipitation, xiv, 31, 176, 279, 302, 304, 305, 320, 348, 350, 357, 537 preparation, xv, xvi, 21, 53, 69, 74, 78, 88, 91, 92, 108, 140, 176, 204, 235, 241, 242, 246, 252, 254, 262, 263, 266, 267, 292, 313, 351, 373, 378, 387, 417, 418, 422, 426, 430, 525 prevention, 210 principal component analysis, 167 principal component regression, 167 probability, 527, 548, 549, 551 probe, 75, 342, 440 project, 163 proliferation, 509 propagation, xi, 108, 110, 115, 117, 123, 124, 129, 136, 140, 175, 314, 527, 537, 547 propane, 17, 155, 156, 311 propionic anhydride, 437 propylene, 18, 28, 116, 213, 284, 285, 287, 288, 525 protection, 523 proteins, 283 protons, 273 prototypes, 162 PTC, xv, 365, 367, 368, 369, 370, 371, 372, 373, 374, 375, 377, 378, 379, 380, 382, 383, 384, 385, 387, 389, 390, 391, 392, 394, 395, 397, 398, 399, 400, 401, 402, 405, 407 pulp, 451 purification, 212, 217, 221, 228, 284, 286, 339, 367, 426 purines, 48 purity, 225, 284, 285, 286, 396 PVC, 29 PVP, 8, 16, 23, 28 pyridine ligands, x, 107, 109 pyrimidine, 245, 261, 471 pyrolysis, 5, 21, 24 pyromellitic dianhydride, 26

Q
quantum mechanics, 167 quaternary ammonium, 367, 369, 374, 378, 384, 386, 387, 399, 400, 535, 536, 539, 544, 549 quercetin, 528

R
race, 61, 62, 75, 368 radiation, 3 Radiation, 38 radical formation, 526 radical reactions, 442, 523 radicals, 282, 522, 535, 539, 554, 555, 556 radioactive carbon monoxide, xi, 108, 110

Index
reputation, 154 requirements, 69, 158, 161, 212, 408 researchers, xv, 266, 365, 368, 408 residues, 151, 436, 438, 439, 450 resistance, 57, 374, 405 resolution, 69, 73, 74, 76, 216, 226, 440, 498 resources, 158, 162, 213, 449 responsiveness, 176, 203 resveratrol, 391 Rh complexes, xi, 144, 296, 312, 314, 420 rhenium, 6, 49 rheology, 174, 205 rhodium, 14, 289, 291, 293, 296, 297, 298, 304, 310, 314, 315, 316 rings, 14, 109, 114, 120, 121, 129, 289, 492 ROOH, xvii, 50, 521, 522, 535, 537, 538, 540, 555 room temperature, 15, 24, 26, 27, 29, 65, 82, 93, 115, 204, 243, 244, 267, 297, 298, 313, 320, 335, 340, 346, 350, 390, 392, 418, 419, 420, 421, 424, 450, 464, 465, 468, 469, 483, 484, 493, 495, 503 Royal Society, 409 Ru catalysts, ix, xi, 144, 291, 424 Russia, 33, 521 Russian Academy of Sciences, 557 ruthenium, 8, 49, 282, 291, 300, 304, 422, 428, 525

511

S
salts, xvi, 17, 187, 203, 204, 205, 206, 211, 214, 216, 220, 239, 240, 245, 368, 369, 377, 384, 387, 389, 395, 399, 400, 407, 417, 418, 458, 463, 464, 470, 471, 486, 535, 536, 544, 545, 549, 555, 556 saturation, 426 scaling, 13 scandium, ix, 1, 2, 4 scarcity, 164 scattering, 3, 176, 205 Schiff bases, xiv, 265, 266, 267, 269 second generation, 26, 304, 305, 307, 313, 314, 317, 508 seizure, 261 self-assembly, 174, 182 sensing, 30, 178 sensitivity, 18, 163, 164, 212, 405, 486 sensors, 7 shape, x, 22, 29, 47, 154, 174, 281, 283, 285, 287 shear, 177 shock, 371 shock waves, 371 signals, 128, 134, 448 silanol groups, 526 silica, 3, 7, 8, 14, 21, 25, 26, 312, 313, 328, 338, 342, 344, 347, 351, 352, 353, 354, 355, 357, 523, 524, 525

silicon, 21, 485, 523 silver, 23, 426, 429, 458 similarity, 529 simulation, 205, 285 SiO2, 5, 7, 12, 17, 21, 25, 26, 30, 342, 344 sites, 525, 536 skeletal muscle, 3 skeleton, 283, 296 sodium, 12, 17, 21, 28, 30, 221, 244, 267, 350, 367, 378, 380, 382, 390, 396, 400, 404, 405, 406, 438, 440 sodium hydroxide, 21 sol-gel, 15, 26, 185, 189, 204, 342 solid phase, 370 solid state, 287 solubility, ix, 47, 53, 211, 216, 223, 224, 227, 228, 242, 269, 281, 283, 287, 299, 300, 302, 317, 348, 351, 356, 357, 382, 426, 451, 508 solvation, 216 solvent, 535, 536, 550, 551 solvent molecules, 191 solvents, xiii, xv, 49, 61, 62, 65, 89, 187, 189, 195, 198, 209, 210, 211, 212, 214, 216, 219, 225, 226, 228, 229, 267, 288, 307, 365, 367, 371, 376, 420, 424, 426, 437, 440, 525 sorption, 523 spatial, 536 speciation, 92, 94 species, xvii, 3, 7, 25, 31, 33, 51, 62, 65, 74, 79, 80, 83, 88, 92, 93, 94, 108, 115, 122, 127, 148, 160, 163, 164, 165, 173, 176, 195, 236, 238, 245, 251, 266, 282, 285, 294, 371, 372, 396, 419, 421, 456, 458, 460, 470, 476, 488, 496, 498, 499, 521, 524, 525, 529, 531, 535 specific surface, 177 specifications, 212 spectrophotometry, 544 spectroscopy, xiv, 51, 92, 93, 115, 159, 167, 197, 265, 285, 298, 447, 524, 527 spectrum, 544, 554 spin, 62, 115 sponge, 198, 199 Spring, 38 stability, 522, 523, 524, 543 stabilization efficiency, 10 stabilizers, 4, 10, 16, 26 stable complexes, 48, 548 stages, xvii, 521, 532, 533, 540, 546, 547, 554, 556, 559 starch, 452 states, 161, 457, 476 statistics, 284

512

Index
TEM, 176, 179, 181, 187, 188, 189, 190, 191, 192, 194, 195, 198, 199, 200, 202 temperature, 5, 6, 16, 26, 53, 57, 61, 80, 82, 127, 128, 130, 134, 135, 136, 139, 140, 161, 174, 176, 178, 179, 185, 204, 211, 212, 239, 245, 256, 267, 268, 269, 297, 307, 314, 335, 346, 367, 400, 404, 405, 408, 420, 421, 422, 440, 443, 445, 464, 472, 483, 484, 503, 525 TEOS, 21 testing, xi, 82, 96, 143, 160 tetrabutylammonium bromide, 374, 378, 381, 392, 394, 399 tetrahydrofuran, 8 TGA, 268 therapy, 509 thermal analysis, 274 thermal decomposition, 4, 5, 16 thermal stability, xi, 53, 88, 108, 110, 112, 118, 130, 138, 139 thin films, 4, 21 thioamides, xiii, 233 thiocarbonylation, xiii, 234 three-dimensional model, 164 tin, 31, 477 tin oxide, 31 titania, 18 titanium, 2, 3, 321 toluene, 5, 9, 14, 25, 26, 30, 64, 89, 111, 113, 117, 119, 120, 122, 124, 126, 128, 131, 132, 179, 182, 185, 195, 197, 226, 252, 291, 315, 325, 327, 335, 336, 340, 377, 382, 402, 525 tones, 235 topology, 281, 356 toxic waste, 214, 532 toxicity, 212, 368, 369, 422, 457, 461, 477, 509 toxicology, 212 traits, 509 transesterification, xiii, 209, 214, 217, 228 transfer, 522, 527, 534, 535, 536 transformation degrees, 539 transformation product, 530, 543 transformations, xv, 49, 69, 210, 213, 216, 219, 234, 237, 258, 280, 366, 368, 371, 372, 389, 437, 456, 457, 551 transition, 522, 523, 526, 527, 536, 544, 554 transition metal, ix, x, xi, xiii, xvii, 1, 49, 107, 108, 109, 110, 116, 138, 140, 155, 158, 209, 211, 221, 228, 234, 235, 237, 259, 266, 282, 356, 428, 455, 456, 464, 496, 502, 522, 526, 536 transition temperature, 3 transmission, 371, 440 transport, 177, 348 transportation, 436

stereoselectivity, xi, 18, 143, 146, 152, 161, 185, 317, 337, 347, 377, 389, 408 steric, 523, 529, 539, 548, 551 steroids, 69 storage, 25, 26, 177, 214, 456 stretching, 159, 270, 277, 446 strong interaction, 2 structural changes, 159, 176, 535 structural characteristics, 385 styrene, 3, 10, 14, 20, 24, 64, 65, 79, 93, 217, 218, 223, 224, 294, 311, 312, 316, 341, 344, 395, 400, 470, 471, 472, 474, 498, 535 substitutes, 494 substitution, 76, 150, 151, 161, 215, 216, 218, 226, 296, 346, 347, 350, 367, 378, 384, 437, 452, 501, 539 substrates, x, xi, xii, xvii, 13, 20, 26, 48, 49, 70, 74, 82, 92, 93, 96, 143, 151, 153, 209, 211, 221, 224, 234, 243, 246, 247, 248, 249, 251, 255, 258, 283, 297, 305, 307, 314, 321, 330, 356, 367, 389, 408, 455, 462, 463, 464, 465, 467, 468, 469, 471, 474, 483, 485, 487, 492, 494, 495 sugarcane, xvi, 435, 449, 450, 452 sulfate, 28, 267 sulfonamides, 494 sulfur, 48, 213, 483 sulfuric acid, 288 Sun, 10, 39, 42, 97, 101, 102, 142, 173, 362, 412, 450, 452 Superoxide, 536 suppliers, 372 supramolecular, 543 Supramolecular gels, xii, 173, 176, 177, 203, 205 surface area, 12, 27, 177, 198, 379 surfactant, 5, 22, 25, 27, 216, 223, 224, 244 surfactants, 525, 535 sustainability, 258, 366, 408 Suzuki coupling reaction, xiii, 234, 238, 239, 240, 241, 242, 260 swelling, 318 symmetry, 150, 285, 319, 526 synergistic, 546

T
Taiwan, 365 tantalum, 5 tar, 7 target, xvii, 160, 163, 455, 461, 502, 521 TCE, 534 technological advances, 158 technologies, 234, 408, 436 technology, xv, 365, 367, 372, 389, 408 telephone, 1

Index
trifluoroacetate, 9, 350 trifluoroacetic acid, 20, 493 triggers, 176 triglycerides, 213 triphenylphosphine, 250 tryptophan, 528 tumor cells, 509 tungsten, 3, 5, 49, 398 turnover, 16, 19, 93, 167, 193, 198, 290, 311, 313, 317, 347, 356, 462, 463, 466, 467, 468, 469, 471, 472, 474, 494, 498 twist, 31 volatility, 210

513

W
Washington, 98, 229, 411 waste, 49, 210, 227, 366, 367, 450, 451 wastewater, 437 water, 15, 28, 83, 91, 93, 151, 179, 195, 197, 203, 204, 211, 214, 216, 217, 218, 221, 222, 224, 226, 235, 244, 251, 254, 260, 267, 293, 303, 367, 374, 376, 389, 419, 422, 423, 437, 451, 467, 468, 535 wavelengths, 372 weak interaction, 189 wires, 203 wood, 444, 450, 452 workers, 9, 14, 20, 23, 52, 75, 76, 78, 80, 81, 108, 150, 152, 157, 160, 163, 250, 251, 258, 296, 319, 331, 339 worldwide, 235

U
ultrasonic frequency, 375, 406, 408 ultrasound, xv, 12, 366, 371, 372, 375, 376, 378, 397, 400, 401, 404, 405, 407 uniform, 6, 437 universe, 366 urea, 49, 69, 82, 175 urease, 536 UV irradiation, 27 UV radiation, 89

X
X-ray analysis, 155, 187 X-ray diffraction, 175, 176, 285 xylene, 535

V
vacuum, 24, 176, 267, 268, 438, 439 valence, 50, 155 validation, 165 values, 545, 550, 551, 560 vanadium, 3, 108, 109, 125, 127, 128, 129, 130, 137, 140, 266 vancomycin, 205 vapor, 4, 30, 211, 212, 214 variables, 14 variations, 407, 466, 468 velocity, 65 versatility, 215, 456 vibration, 446 viscosity, 179, 212, 243, 280, 283, 287, 438, 439, 451 vision, 436

Y
yeast, 216 yield, xi, xii, 5, 9, 14, 53, 56, 61, 62, 74, 79, 82, 83, 91, 112, 114, 121, 134, 136, 140, 143, 144, 178, 185, 198, 211, 216, 218, 219, 236, 237, 238, 239, 241, 243, 244, 251, 255, 269, 282, 321, 324, 329, 335, 337, 344, 346, 350, 354, 355, 381, 383, 385, 389, 396, 397, 404, 405, 458, 468, 476, 486, 498, 522, 561 yttrium, 4

Z
zeolites, 10, 177, 523 zinc, 158, 320, 323, 426, 451 zirconia, 4 zirconium, 4