Enantioselective S N 2 Alkylation of Homoenolates by N-Heterocyclic Carbene Catalysis.

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 N 2 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 N 2 mechanism.