The construction of chiral 3-acyl bicyclolactams via a RuPHOX/Pd catalyzed asymmetric allylic substitution cascade of α-carbonylamides

Abstract

A RuPHOX/Pd catalyzed asymmetric allylic substitution cascade of α-carbonylamides with an allylic meso-dicarbonate has been developed, providing chiral 3-acyl bicyclolactams bearing three vicinal carbon stereocenters in high yields and with up to 99% ee and >20 : 1 dr. Mechanistic studies based on control experiments and DFT calculations revealed that a dynamic kinetic resolution process should occur during the second step of the cascade reaction, which is responsible for the excellent diastereoselectivities of the desired products. The protocol could proceed on a gram-scale and the resulting products allow for various transformations, especially for the preparation of several natural products.