Enantioselective S_N2 Alkylation of Homoenolates by N‐Heterocyclic Carbene Catalysis

Abstract The 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 C_sp3 electrophiles through an S_N2 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 S_N2 mechanism.