Organocatalytic cyclization-rearrangement cascade reaction: asymmetric construction of γ-lactams

Abstract

We report a chiral thiourea-catalyzed Michael/ring-reorganization cyclization of 3-methyleneoxindoles with N-(p-toluenesulfonyl)-α-amino ketones, facilitating the asymmetric synthesis of γ-lactams. This method efficiently generates a range of optically pure γ-lactams, in yields ranging from 60% to 86% and excellent stereoselectivity (up to 20 : 1 dr, >99% ee). The gram-scale experiments confirmed the scalability of the reaction without compromising the yield or stereoselectivity. Performed under mild conditions, this investigation showcases its potential applicability for synthesizing complex chiral γ-lactams with consecutive three chiral centers.