Highly diastereo- and enantioselective synthesis of spiro β-lactams via copper-catalyzed Kinugasa/aldol cascade reaction

Abstract

Spiro β-lactams are important scaffolds in many bioactive compounds and natural products. The development of new synthetic methods for the formation of structurally diversified chiral spiro β-lactams is highly important for the discovery of novel bioactive structures. In this work, a copper(I)-catalyzed asymmetric Kinugasa/aldol-type cascade reaction of ketone-tethered propiolamides and nitrones is developed and a set of novel chiral spiro β-lactams with three contiguous stereogenic centers was achieved in satisfactory yields with high diastereo- and enantioselectivity. Control experiments suggested that a retro-aldol/aldol equilibrium process of the spirobilactam products is critical for the acquisition of high diastereoselectivity.