Organocatalytic asymmetric umpolung reaction of cyanoketimines with 2-(bromomethyl)acrylate

Abstract

Chiral α-aminonitriles are not only versatile synthons in chemical synthesis, but also exist as motifs in a wide range of biologically active molecules. Consequently, the catalytic asymmetric synthesis of chiral α-aminonitriles has attracted considerable attention. Despite these significant progresses, the catalytic asymmetric synthesis of chiral α-aminonitriles bearing other synthetically useful functionalities remains desirable. We reported a catalytic asymmetric synthesis of chiral α-aminonitriles bearing a 2‑carbonyl allyl group via a catalytic umpolung reaction of cyanoketimines with 2-(bromomethyl)acrylate. This reaction demonstrates broad substrate scope, accommodating a wide range of aryl, heteroaryl and alkyl cyanoketimines. Given that both the aminonitrile and the 2‑carbonyl allyl moieties are versatile synthons in asymmetric synthesis, we anticipate that this reaction will serve as a valuable method for drug discovery and construction of complex chiral molecules.