Asymmetric Syntheses of

Pleocarpenene and Pleocarpenone

Michael J. Williams, Holly L. Deak, Marc L. Snapper*
Journal of the American Chemical Society 2007, 129, 486 – 487

Educ. seminar in Biological Organic Chemistry

University of Innsbruck
Fabian T. Strelow, B.A./B.Sc.
Cyclobutadiene Cycloaddition / Cyclopropanation / Thermal rearrangement

Asymmetric Syntheses of
Pleocarpenene and Pleocarpenone
Michael J. Williams, Holly L. Deak, Marc L. Snapper*
Journal of the American Chemical Society 2007, 129, 486 – 487

Educ. seminar in Biological Organic Chemistry

University of Innsbruck
Fabian T. Strelow, B.A./B.Sc.
Introduction Pleocarphus revolutus

Fig. 1 Fig. 2 Fig. 3 Fig. 4

Fig. 1: Historia fisica y politica de Chile (1854), Fanerogamia No. 43

Fig. 2: J. L. Panero, Tree of Life Web Project (2009), http://tolweb.org [id 35255]
Fig. 4: http://floradechile.cl/dicotyle/species/cplrevol.htm (2014)
Fig. 3: M. Bonifacino, (2003), plantsystematics.org [ref. DOL6022]

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Objective Bicyclo [5.3.0] Ring Systems

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Overview

Part 1: Retrosynthesis
Part 2: Cyclobutadiene Cycloaddition
Part 3: Cyclopropanation
Part 4: Thermal Rearrangement

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Part 1 Retrosynthesis
Scheme 1: Retrosynthesis of Pleocarpenone and Pleocarpenene

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Part 1 Retrosynthesis
Scheme 1: Retrosynthesis of Pleocarpenone and Pleocarpenene

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Part 1 Retrosynthesis
Scheme 1: Retrosynthesis of Pleocarpenone and Pleocarpenene

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Part 1 Retrosynthesis
Scheme 1: Retrosynthesis of Pleocarpenone and Pleocarpenene

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Part 1 Retrosynthesis
Scheme 1: Retrosynthesis of Pleocarpenone and Pleocarpenene

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Part 1 Retrosynthesis
Scheme 1: Retrosynthesis of Pleocarpenone and Pleocarpenene

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Overview

Part 1: Retrosynthesis
Part 2: Cyclobutadiene Cycloaddition
Part 3: Cyclopropanation
Part 4: Thermal Rearrangement

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Part 2 (a) Cyclobutadiene Cycloaddition
Scheme 2a: Preparation of the Cyclobutene (5)

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Part 2 (a) Cyclobutadiene Cycloaddition
Scheme 2a: Preparation of the Cyclobutene (5)

Infobox Photochemical reaction pathway

≙ ≙

J. Org. Chem. (1963), 59, 21, 6437 – 6441

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Part 2 (a) Cyclobutadiene Cycloaddition
Scheme 2a: Preparation of the Cyclobutene (5)

Infobox: Iron complexes

Fe 8 VE Fe 8 VE C4H4 4 VE
(CO)5 10 VE (CO)4.5 9 VE Fe 8 VE
18 VE 17 VE (CO)3 6 VE
18 VE

Fe(CO)5 Fe2(CO)9 C4H4 Fe2(CO)9

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Part 2 (a) Cyclobutadiene Cycloaddition
Scheme 2a: Preparation of the Cyclobutene (5)

Infobox: Diisobutylaluminium hydride (DIBAL)

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Part 2 (a) Cyclobutadiene Cycloaddition
Scheme 2a: Preparation of the Cyclobutene (5)

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Part 2 (a) Cyclobutadiene Cycloaddition
Scheme 2a: Preparation of the Cyclobutene (5)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

Infobox: Olefin Metathesis using Hoyveda-Grubbs catalysts

Hoyveda-Grubbs catalyst II

adapted from Bildstein, Metallorganische Chemie, Chapt. 6 (2017)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

Infobox: Ceric ammonium nitrate (CAN) Cyclobutadien Cycloaddition

adapted from Chem.Rev. (2019), 119, 11291 – 11351)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

???

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5) Infobox: Corey-Bakshi-Shibata (CBS) reduction

adapted from Angew.Chem.Int.Ed. (1998), 37,1986 – 2012

(here: Methyl)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

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Part 2 (b) Cyclobutadiene Cycloaddition
Scheme 2b: Preparation of the Cyclobutene (5)

b
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Overview

Part 1: Retrosynthesis
Part 2: Cyclobutadiene Cycloaddition
Part 3: Cyclopropanation
Part 4: Thermal Rearrangement / Ozonolysis

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Part 3 Cyclopropanation
Scheme 3: Cyclopropanation of Cyclobutene (-)-5ß

Infobox: Lithium aluminium hydride (LAH)

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Part 3 Cyclopropanation
Scheme 3: Cyclopropanation of Cyclobutene (-)-5ß

Infobox: Protecting groups (TIPSCl and AcO2)

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 Part 3 Cyclopropanation
Scheme 3: Cyclopropanation of Cyclobutene (-)-5ß

Infobox: Cyclopropanation

Organometallics 2008, 27, 18, 4600-4610 / Pellissier et al. Asymmetric Synthesis of Three-Membered Rings 2017
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Part 3 Cyclopropanation
Scheme 3: Cyclopropanation of Cyclobutene (-)-5ß

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Overview

Part 1: Retrosynthesis
Part 2: Cyclobutadiene Cycloaddition
Part 3: Cyclopropanation
Part 4: Thermal Rearrangement / Ozonolysis

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 Part 4 Completion: Thermal rearrangement / Ozonolysis
Scheme 4: Completion of the Total Synthesis

Infobox: Thermal rearrangement Proposed Mechanism:

J. Am. Chem. Soc., 123, 21, 2001, 5152-5153; Org. Lett.,7, 26, 2005, 5785-5788
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Part 4 Completion: Thermal rearrangement / Ozonolysis
Scheme 4: Completion of the Total Synthesis

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Part 4 Completion: Thermal rearrangement / Ozonolysis
Scheme 4: Completion of the Total Synthesis

Infobox:

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Part 4 Completion: Thermal rearrangement / Ozonolysis
Scheme 4: Completion of the Total Synthesis

Infobox:

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Part 4 Completion: Thermal rearrangement / Ozonolysis
Scheme 4: Completion of the Total Synthesis

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Part 4 Completion: Thermal rearrangement / Ozonolysis
Scheme 4: Completion of the Total Synthesis

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Conclusion Key Steps

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Conclusion Key Steps

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Conclusion Key Steps

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Conclusion Key Steps

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Special Thanks

Univ.-Prof. Dr. Thomas Magauer Prof. Marc L. Snapper, Ph.D. Holly Deak, Ph.D Michael Williams, Ph.D.

Professor of Synthesis and Synthetic Methods Professor of Chemistry

Centre of Chemistry and Biomedicine CCB Merkert Center
Institute of Organic Chemistry Chemistry Department Faculty
Leopold-Franzens-University Innsbruck Boston College

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Thank you very much for your attention!

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