Nicolas Demoulin

24/01/08

Literature review
Angewandte Chemie Int. Ed.
2007, Issues 42-48 2008, Issues 1-5 Synlett 2007, Issues 17-20 2008, Issues 1-2

Angew. Chem. Int. Ed. 2007, 46, 8050-8053 Metal-Catalytic Hydrogenation

P. A. Chase, G. C. Welch, T. Jurca, and D. W. Stephan*

Hydrogenation is one of the most important catalytic

method in synthetic organic chemistry (lab & industry) H2 cleanest reducing agent Addition of hydrogen to unsaturated organic

compounds usually mediated by homogeneous or

heterogeneous transition-metal catalysts (Ni, Pd,

Ru, Rh.)
2

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Only few hydrogenations involve non-transition-metal catalysts

O KOtBu T > 200C P(H2) > 100 bar OH

Albrecht Berkessel, Thomas J. S. Schubert, and Thomas N. Mller J. Am. Chem. Soc. 2002, 124, 8693-8698.

R1 R2 O R3 R4 H2N Ar O

Organocatalyst R2

R1 O

Hydrogen source EtO2C CO2Et N H

Thiourea cat.

HN R3

Ar R4

P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 116, 5248-5286; Angew. Chem. Int. Ed. 2004, 43, 5138. D. Menche, J. Hassfeld, J. Li, G. Menche, A. Ritter, S. Rudolph, Org. Lett., 2006, 8, 741-744. D. Menche, F. Arikan, Synlett, 2006, 841-844.

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Frustrated Lewis pairs

Bulky Lewis acid and base no Lewis adduct
H2, rt B(C6F5)3 F R2P F F F H2, rt B(C6H5)2 T>100C R= tBu or 2,4,6-Me3C6H2 H R2P F F PR3 R3PH HB(C6F5)3 F F H B(C6H5)2

G. C. Welch, R. R. S. Juan, J. D. Masuda, D. W. Stephan Science 2006, 314, 1124 . Gregory C. Welch and Douglas W. Stephan J. Am. Chem. Soc. 2007, 129, 1880 -1881.

F H B(C6H5)2

H R2P F F

Air & moisture stable Metal-free hydrogenation catalysts of imines, nitriles and aziridines

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Reduction of Imines
F F H B(C6H5)2 F F

N Ph

R H

Cat 5-10%mol in toluene H2 1-5 atm

HN Ph

H R2P

R= tBu (1) R= 2,4,6-Me3C6H2 (2)

Entry 1 2 3 4

Substrate
Ph N tBu
Ph N SO2Ph
Ph N Ph Ph

Cat 1 2 1 2 1

T(C ) 80 80 120 120 140

P(H2) atm 1 1 5 5 5

t(h) 1 1 10.5 16 1

Yield( %) 79 98 97 87

Product
Ph NH tBu

Bulky imines reduction (1-5)

Ph NH SO2Ph
Ph NH Ph Ph
Ph

5
Ph

88

Electron poor imines less reactive Less bulky imines react with the catalyst forming a strong adduct and inhibit it
Problem solved in presence of B(C6F5)3 Basicity of N center at stake
5

6
Ph

N Ph
B(C6F5)3 N Ph

120

48

5
Ph

NH Ph

120

46

57

NHB(C6F5)3 Ph

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Reaction with nitriles and aziridines

Cat (1) 5-10 %mol in toluene 120C, H2 5 atm
F F H B(C6H5)2 F F

CN

R NH2

H R2P

R= tBu (1)

Entry 1 2 3 4

Substrate MeCN
MeCNB(C6F5)3

t(h) 48 24 24 48

Yield (%) 0 75 84 99

Product
NH2 NH2 B(C6F5)3
Ph NH2 B(C6F5)3

Nitrile fonction clearly interacts with catalyst Problem solved in presence of activating B(C6F5)3 Ring opening of unactivated aziridines

Ph CNB(C6F5)3
CNB(C6F5)3 CNB(C6F5)3
Ph N Ph Ph

NH2 B(C6F5)3 NH2B(C6F5)3

5 6

1.5 -

98 0

Ph

H N Ph

Ph

Activated isonitriles dont react

B(C6F5)3isonitrile

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Mechanism for Bulky Imines and Aziridines

Ph Ph F R 2P F F F R 2P F WEAK ADDUCT Ph H N Ph Ph or HN Ph R' F F B(C6H5)2 R 2P F 2) Hydride attack Ph F or F F H B(C6H5)2 F H B(C6H5)2 H2 H2 N Ph or H2N Ph R' F H R 2P F F 1) Proton transfer F H B(C6H5)2 N Ph R' or H Ph Ph N Ph

H Ph

R' H

Ph N H Ph

The bulkier the imine is, the quicker the reaction is

Ph

tBu Cy3P H

F H B(C6H5)2 no adduct

31P, 11B, 19F NMR

F 1 eq. 1 eq.

Angew. Chem. Int. Ed. 2007, 46, 8050-8053

Mechanism for activated Imines and Nitriles

F H R2P H2 F F 1) Hydride attack F R' (C6F5)3B N H or R'' CN B(C6F5)3 B(C6H5)2 Ph H

F R2P F

F H B(C6H5)2 F R2P

(C6F5)3B B(C6H5)2 Ph or R''

R'

F 2) Proton transfer

N B(C6F5)
3

R''

H N B(C6F5)3 or

(C6F5)3B Ph

H R' N

Nitriles or less bulky imines Protection with B(C6F5)3

8

Angew. Chem. Int. Ed. 2007, 46, 8869-8871 Asymmetric Sommelet-Hauser Rearrangement of N-Benzylic Ammonium Salts
Eiji Tayama*, and Hiroshi Kimura
CO2tBu N CO2tBu 42%, ee > 99% tBuOK THF -40C, 6h CO2tBu -benzylated proline tert-butyl ester CO2tBu N CO2tBu 2,3 Sommelet-Hauser 1,2 Stevens

CO2tBu N

CsOH 1,2-dichloroethane -10C, 24h

96%, ee > 99% -aryl proline tert-butyl ester

Eiji Tayama*, Shintaro Nanbara and Takeshi Nakai, Chem. Lett . 2006, 35, 478-479.

C-N into new C-C Competion usually observed between Stevens & Sommelet-Hauser (SH) rearrangements So far, limited asymmetric SH rearrangement
9

Angew. Chem. Int. Ed. 2007, 46, 8869-8871

Asymmetric SH rearrangement
Para
N Br COOR* tBuOK THF N COOR*
R1 COOtBu COOMe COPh T(C) -40 -60 -60 -60 -60 -40 -40 t(h) 4 8 8 8 15 15 15 yield 95 85 82 82 93 46 0 dr S/R >98:2 >98:2 >98:2 97:3 >98:2 >98:2 -

R1 R1 -aryl N,N-dimethylglycine ester

CN CF3 H OMe

Good yields , good d.r EW groups accelerate the reaction

N R1 Br COOR* tBuOK THF R1 R1 = CN, -60C, 8h R1 = CF3, -60C, 15h 86%, S/R = 98/2 89%, S/R > 98/2 N

Ortho

COOR*

COOR* R1

0%

COOR* = COO

Meta

N Br R1

COOR* tBuOK THF

COOR*

COOR* R1

Ph

R1 R1 = CN, -60C R1 = CF3, -40C 67%, S/R > 98/2 90%, S/R > 98/2 6%, S/R > 98/2 0%

10

Angew. Chem. Int. Ed. 2007, 46, 8869-8871

Mechanism
ON O Ph 2,3 S-H N
(S)

O O Ph N
(S)

O O Ph

Concerted stereoselective [2,3] S-H Rearrangement

ON O N
(S)

Ortho

R1

O Ph R1

O Ph

ON

O N
(S)

O O Ph N >>
(S)

Meta
R1

O Ph

O Ph R1

R1

11

Angew. Chem. Int. Ed. 2008, 47, 350-352 One-Pot Multicomponent Synthesis of Indoles from 2-Iodobenzoic Acid
Olivier Leogane and Hlne Lebel

Wide variety of bioactive natural products with indoles framework Numerous methods to synthetize indoles
O I COOH I Nuc N R2 C O R1 N O Nuc R1 R2 R2 R1

Curtius rearrangement / palladium-catalysed indolization

12

Angew. Chem. Int. Ed. 2008, 47, 350-352

Study of the reaction

Palladium-catalysed indolization(1)
I NHCbz Pr Pd(OAc)2 (5%mol) LiCl (1 eq) DMF, 120C Na2CO3 (1.1 eq.), 3h Na2CO3 (3 eq.), 16h Pr Pr N H traces 85% N Cbz 48% 0% Pr Pr

Pr

Without LiCl no reaction With excess of LiCl, low yield

One-Pot Curtius rearrangement(2) / Palladium-catalysed indolization

I COOH 1. CbzCl, NaN3/DMF,75C tBuONa (15 mol%) 2. Pd(OAc)2 (5 mol%), base, LiCl DMF, 120C, Pr Pr Pr Pr N H

Entry 1 2

LiCl yes no

Base (eq.) K2CO3 (5) Na2CO3 (1.5)

Alkyne (eq.) 5.0 1.5

Yield (%) 29 71

NaCl formed during the Curtius rearrangement Synergic effect

3
4 5 6

no
no no no

K2CO3 (1.5)
Cs2CO3 (1.5) Na2CO3 (3) K2CO3 (3)

1.5
1.5 3.0 3.0

73
40 84 73

(1) Chris H. Senanayake Org. Lett. 2006, 8, 3271-3274 (2) Hlne Lebel and Olivier Leogane, Org. Lett. 2006, 8, 5717-5720

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Angew. Chem. Int. Ed. 2008, 47, 350-352

Scope of the reaction

I COOH 1. CbzCl, NaN3/DMF,75C tBuONa (15 mol%), 5h 2. Pd(OAc)2, base, Coupling agent DMF, 120C, 16h R2 R1 N H

Entry 1 2 3 4 5 6

Coupling agent
Ph Ph Na2CO3 tBu Me Na2CO3

Product
Ph Ph N H tBu
Me N H Ph
TMS N H

Yields (%) 77 56 82 50

Unsymmetrical alkynes Good yields and regiocontrol

Ph TMS Na2CO3

Bn

Ph

CHO DABCO
N H

BnO DABCO

CHO
N H

OBn

53 56

Moderate yields with aldehydes and ketones

O DABCO
N H

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Angew. Chem. Int. Ed. 2008, 47, 350-352

Scope of the reaction Synthesis of indole N-carboxamide derivatives

I COOH 1. PhOCOCl, NaN3 tBuONa (15 mol%) NMP,75C, 5h 2. R2R3NH, 75C, NMP, 3h 3. Pd(OAc)2,120C, 16h R1 R1
Pr Ph N N O O N N O N Pr

R1 R1 N O R2 N R3

Ph Ph N O

Ph

I COOH Curtius Rearrangement

I N

H C

N R2

R3

64%
Ph Ph N O N

68%
Pr Pr N O NH Ph Me

54%
Pr Pr N O N H Ph

R1 R1 N O R2 N R3 R1 R1 I NH O R2 N R3

62%

59%

39%

15

Angew. Chem. Int. Ed. 2008, 47, 586-588 Iron-Catalysed C-O Cross-Coupling of Phenols with Aryl Iodide
Olivia Bistri, Arkaitz Correa and Carsten Bolm*

Diaryl ether widely present in bioactive compounds Synthesized using transition-metal-catalyzed cross-coupling reactions (Co, Pd) Fe Chemistry: challenging, less expensive, less poluting, attractive industrial prospects
ArX N NH FeCl3 (10 mol%) dmeda (20 mol%) K3PO4, toluene 135C, 24h FeCl3 (10 mol%) dmeda (20 mol%) K3PO4, toluene 135C, 24h N Ar

I R NuH

Nu R

Arkaitz Correa and Carsten Bolm*, Angew. Chem. Int. Ed. 2007, 46, 8862-8865.

16

Angew. Chem. Int. Ed. 2008, 47, 586-588

Study of the reaction

OH I FeCl3 (10 mol%) dmeda (20 mol%) K3PO4, toluene 135C, 24h O 0%

Interplay between ligand, base, solvent strongly depend on the substrate

OH I [Fe] (0.1 eq) ligand (0.2 eq) base, solvent 135C,20h O

[Fe]: FeCl3, FeCl3.6H2O, Fe(acac)3 Base: K3PO4, Cs2CO3, NaOtBu, NaHCO3, Na2CO3, KOAc Solvent: toluene, MeCN, dioxane, DMF Ligand:
MeHN L1 NHMe N L2 COOH.HCl tBu O O L3 tBu

Optimized conditions: FeCl3 (10 mol%) L3 (20 mol%) CsCO3 (2 eq) DMF, 135C

H2N

L4

NH2

N L5

N H L6

COOH

17

Angew. Chem. Int. Ed. 2008, 47, 586-588

Scope of the reaction

OH R I FeCl3 (10 mol%) L3 (20 mol%) Cs2CO3, DMF 135C, 20h O R

tBu O L3 O

tBu

O O tBu 95% O Me 95% O MeO Me 95% O Cl 92% 99% 87% F 84% O 74% O O2N 0% O O O

85% O Ph

Excellent yields with electron-rich or electron-poor phenols Reaction fails to work when the phenol incorporates strongly electron-withdrawing groups
18

Angew. Chem. Int. Ed. 2008, 47, 586-588

Scope of the reaction

OH X FeCl3 (10 mol%) L3 (20 mol%) Cs2CO3, DMF 135C, 20h O R 0% 69% 85%

X=Cl X=Br X=I

tBu O L3 O

tBu

OH R

FeCl3 (10 mol%) L3 (20 mol%) Cs2CO3, DMF 135C, 20h

O R

Cl O O

OMe O Me O Cl

50% O OMe 78% O Cl 90%

0% O Me 87% O COOEt 78%

90% O F 78% O NO2 80%

87%

19

Some good reading

Protection-Group-Free Formal Synthesis of Platensimycin. J. Mulzer, Angew. Chem. Int. Ed. 2007, 46, 8074-8075.

Catalytic Enantioselective Passerini Three-Component reaction. MX. Wang and J. Zhu, Angew. Chem. Int. Ed. 2008, 47, 388-391.
Cyclic triolborates: Air and Water stable Ate complexes of Organoboronic Acids. Y. Yamamoto and N. Miyaura, Angew. Chem. Int. Ed. 2008, 47, 928-931.

Synthesis of -Ketoamides by a Molecular-Sieves-Promoted Formal Oxidative Coupling of Aliphatic Aldehydes with Isocyanides. JM. Grassot, G. Masson and J. Zhu, Angew. Chem. Int. Ed. 2008, 47, 947-950.
A Stable, Convertible Isonitrile as a Formic Acid Carbanion Equivalent and Its Application in Multicomponent Reactions. L.A. Wessjohann, Synlett. 2007, 20, 3188-3192. Novel Ir-SYNPHOS and Ir-DIFLUORPHOS Catalysts for Asymmetric Hydrogenation of Quinolines. JP. Gent, K. Mashima, V. Ratovelomanana-Vidal, Synlett 2007, 17,2743-2747.

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