Enantioselective SN2 Alkylation of Homoenolates by N‐Heterocyclic Carbene Catalysis

Abstract

AbstractThe functionalization of the β‐carbon of enals with electrophiles is a signature umpolung reactivity of N‐heterocyclic carbene (NHC) derived homoenolates. However, only a limited number of electrophiles are shown to be compatible, with most of them being π‐electrophiles. In this study, the successful enantioselective β‐alkylation of homoenolates is reported using Csp3 electrophiles through an SN2 strategy. The protocol shows a broad scope regarding alkyl electrophiles, delivering good yields, and excellent enantioselectivities (up to 99% ee). It enables the installation of drug‐like structural motifs in either enals or alkylating agents, demonstrating its potential as a valuable tool for late‐stage modification. Furthermore, a concise synthetic route is presented to chiral pyrroloindoline‐type skeletons. Preliminary mechanistic studies support a direct SN2 mechanism.