Transition-Metal-Catalyzed Allylic Substitution Reactions: Stereoselective Construction of α- and β-Substituted Carbonyl Compounds

Abstract

The stereoselective synthesis of α-and β-substituted carbonyl compounds remains a significant area of interest in organic chemistry. This is largely due to their ubiquity and versatility as synthetic intermediates and the importance of this functionality in a range of biologically important agents. In this context, the transition-metal-catalyzed allylic substitution provides an extremely powerful tool for the asymmetric construction of a variety of α-and β-tertiary and quaternary substituted carbonyl compounds. This review highlights pertinent historical developments of these reactions, from the seminal work with enolate equivalents to the more recent developments with unstabilized enolates and acyl anions. It also outlines the most important mechanistic aspects of these transformations in order to provide insight into the current scope and limitations and potential areas for further development.

Stereoselective Three-Component Allylic Alkylation Enabled by Dual Photoredox/Ni Catalysis

“…This is especially valuable in cases where a practical route toward polyfunctional and complex allylic molecules is needed . From a historical perspective, allylic alkylation has been greatly advanced by transition-metal-based catalysts such as those incorporating Pd, Cu, Ni, Ir, Mo, and Rh, among others . The in situ formation of electrophilic metal–allyl species and their merger with nucleophilic partners represents one of the most developed approaches for the construction of complex scaffolds featuring allyl skeletons (Scheme a).…”

Palladium-catalyzed enantioselective decarboxylative allylic alkylation of α-benzyl cyanoacetates: access to chiral acyclic quaternary carbon stereocenters

“…An alternative strategy is transition metal-catalyzed asymmetric allylic alkylation of prochiral enolates and enolate equivalents, which has become one of the most versatile methods for carbon-skeleton construction. 7 Although the catalytic asymmetric allylic alkylation using aldehydes, ketones and 1,3-dicarbonyl compounds as pro-nucleophiles ( e.g. , malonates and β-keto esters) was well developed, 7 the analogous process with nitrile substituted compounds as pro-nucleophiles remains underdeveloped.…”

“…7 Although the catalytic asymmetric allylic alkylation using aldehydes, ketones and 1,3-dicarbonyl compounds as pro-nucleophiles ( e.g. , malonates and β-keto esters) was well developed, 7 the analogous process with nitrile substituted compounds as pro-nucleophiles remains underdeveloped. 8,9,11 In 1996, Sawamura and Ito reported a Pd/Rh dual-catalytic system for the enantioselective allylic alkylation of α-substituted cyanoesters (Scheme 1a).…”

Nickel-Catalyzed Ligand-Controlled Regioselective Allylic Alkenylation of Allylic Alcohols with Easily Accessible Alkenyl Boronates: Synthesis of 1,4-Dienes

“…Transition-metal-catalyzed allylic substitution of allylic alcohol derivatives represents one of the most important methods for the construction of C–C or C–X bonds . Compared with the allylic esters or carbonates, the direct use of allylic alcohols as the electrophiles is highly challenging due to the poor leaving ability of the hydroxyl group; in addition, the acidic proton of the hydroxyl group is also problematic under metal-catalyzed conditions.…”