Asymmetric a Alkylation of Aldehydes: Efficiency with Elegance

摘要

Alkylations using the substitution reaction can be found in the first chapters of introductory level organic chemistry textbooks. Despite its apparent simplicity, the asymmetric a alkylation of aldehydes, even today, presents many unsolved practical problems. Unlike aldol, Mannich, and 1,4-addition reactions, direct a alkylations of aldehydes are often characterized by narrow substrate scope or low stereoselectivity, or often both. As the majority of diastereoselective a alkylations of carbonyl compounds developed use preformed metal or metalloid enolates, the replacement of these enolates by catalytically generated chiral enamines appears straightforward. Regardless of the daunting epimirization problem of the created asymmetric center, the challenge in developing an enantiocatalytic protocol for alkylation is to find reaction conditions for the synthesis of so-called unstabilized enolates in an environment where the nucleophilic catalyst may efficiently compete for the same substrate.