Construction of chiral γ-lactam scaffolds via asymmetric cascade [3 + 2] annulation of N-alkoxyacrylamides catalyzed by a chiral-at-metal rhodium complex

Abstract

An efficient asymmetric cascade [3 + 2] annulation of N-alkoxyacrylamides with α,β-unsaturated 2-acyl imidazoles catalyzed by a chiral-at-metal rhodium complex has been developed. Enantioenriched γ-lactam derivatives bearing three contiguous tertiary stereocenters were obtained in generally high yields (up to 95%) and good stereoselectivities (up to >20 : 1 dr, 97% ee). Remarkably, as little as 0.2 mol% of the chiral Rh(III) complex enables a gram-scale reaction with good yield and enantioselectivity. This reaction represents the first catalytic asymmetric [3 + 2] annulation of N-alkoxyacrylamides using a chiral Lewis acid as the catalyst, which will expand the scope of catalytic asymmetric reactions of N-alkoxyacrylamide derivatives.