Enantioselective Carbonylative Cyclization of Alkenes with C–H Bonds for Synthesis of γ-Lactams Bearing an α-Quaternary Carbon

Abstract

The development of effective synthetic methods to construct γ-lactams bearing a chiral α-quaternary carbon from relatively inert C(O)–H bonds with alkenes has been an elusive challenge. Herein, we used a naphthylamine-derived phosphine oxide ligating Ni and Al bimetallic catalyst to realize a carbonylative cyclization of formyl C–H bonds with alkenes, highly regio- and enantioselectively constructing γ-lactams bearing a chiral α-quaternary carbon in up to 99% yield and 98% ee. These γ-lactams proved to be versatile synthetic precursors for many biologically active molecules.