C-H Activation for Asymmetric Synthesis

Françoise Colobert, Joanna Wencel-Delord

• Publisher: Wiley-VCH
• Year: 2019
• Print ISBN: 9783527343409
• eBook ISBN: 9783527810864
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Physical & Theoretical Chemistry

Provides, in one handbook, comprehensive coverage of one of the hottest topics in stereoselective chemistry

Written by leading international authors in the field, this book introduces readers to C-H activation in asymmetric synthesis along with all of its facets. It presents stereoselective C-H functionalization with a broad coverage, from outer-sphere to inner-sphere C-H bond activation, and from the control of olefin geometry to the induction of point, planar and axial chirality. Moreover, methods wherein asymmetry is introduced either during the C-H activation or in a different elementary step are discussed.

Presented in two parts?asymmetric activation of C(sp3)-H bonds and stereoselective synthesis implying activation of C(sp2)-H bonds?CH-Activation for Asymmetric Synthesis showcases the diversity of stereogenic elements, which can now be constructed by C-H activation methods. Chapters in Part 1 cover: C(sp3)-H bond insertion by metal carbenoids and nitrenoids; stereoselective C-C bond and C-N bond forming reactions through C(sp3)?H bond insertion of metal nitrenoids; enantioselective intra- and intermolecular couplings; and more. Part 2 looks at: C-H activation involved in stereodiscriminant step; planar chirality; diastereoselective formation of alkenes through C(sp2)?H bond activation; amongst other methods.

-Covers one of the most rapidly developing fields in organic synthesis and catalysis
-Clearly structured in two parts (activation of sp3- and activation of sp2-H bonds)
-Edited by two leading experts in C-H activation in asymmetric synthesis

CH-Activation for Asymmetric Synthesis will be of high interest to chemists in academia, as well as those in the pharmaceutical and agrochemical industry.

Part I
Asymmetric Activation of C(sp³)

H Bonds

Part I.A
C(sp³)

H Bond Insertion by Metal Carbenoids and Nitrenoids

1
Stereoselective C

C Bond‐Forming Reactions Through C(sp³)

H Bond Insertion of Metal Carbenoids

Aoife M. Buckley¹, Thomas A. Brouder¹, Alan Ford¹, and Anita R. Maguire²

¹University College Cork, School of Chemistry, Analytical and Biological Chemistry Research Facility, College Road, T12K8AF Cork, Ireland

²University College Cork, School of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, College Road, T12K8AF Cork, Ireland

1.1 Introduction

The selective and efficient construction of complex molecules is one of the most challenging goals in organic synthesis. To access such intriguing molecules, innovative methodologies in bond formation are required compared to traditional functional group transformations. It is for this reason that selective functionalization of the ubiquitous but inert C

H bond is of great interest to the chemical community [1–4].

A challenging aspect in organic chemistry for decades has been the stereoselective carbon–carbon bond formation by activation of a C(sp³)

H bond in the synthesis of pharmaceuticals, natural products, and other industrially relevant targets. A powerful approach to achieve such useful C–H functionalization is via C(sp³)–H insertion by metal carbenoids [5–8]. Generation of the metal carbenoid can occur through a number of precursors such as diazo compounds, ylide derivatives, hydrazones, and, more recently, triazoles. In this chapter, we will exclusively discuss metal carbenoids derived from α‐diazocarbonyl compounds.

In order to take advantage of metal carbenoid‐induced C–H insertion, one must consider the reactivity of the electrophilic metal carbenoid. The synthetic utility of the free carbenes is limited by low selectivity in most reactions. In contrast, when nitrogen extrusion is facilitated by a transition metal, the resulting metal carbenoid retains the reaction scope of a free carbene while allowing highly selective transformations to occur (Figure 1.1).

Figure 1.1 Nitrogen extrusion from α‐diazocarbonyl compounds in the presence of a transition metal (TM) allows for more selective C

C bond formation through C(sp³)–H insertion.

Historically, copper was used as the transition metal source, but few examples of efficient and selective C–H insertion were reported. The key development in C–H insertion was the discovery by the Teyssié group that dirhodium(II) carboxylates catalyzed the intermolecular C–H insertion reaction of ethyl diazoacetate with alkanes [9]. Following this, Wenkert et al. [10] and Taber and Petty [11] highlighted the potential of intramolecular C–H insertion reactions of α‐diazocarbonyl compounds to lead to cyclopentanone derivatives. Importantly, it was demonstrated that C–H insertion takes place with retention of configuration at the react...

Table of contents

• Cover
• Table of Contents
• Foreword
• Part I: Asymmetric Activation of C(sp3)H Bonds
• Part I.A: C(sp3)H Bond Insertion by Metal Carbenoids and Nitrenoids
• Part I.B: C(sp3)‐H Activation as Stereodiscriminant Step
• Part II: Stereoselective Synthesis Implying Activation of C(sp2)H Bonds
• Index
• End User License Agreement