Asymmetric Michael–Mannich cascade reaction of azomethine ylides with isatin-derived trifluoromethyl acrylates catalyzed by a Cu(i) catalyst

Abstract

An efficient, reliable and atom-economic strategy employing azomethine ylides with isatin-derived trifluoromethyl acrylates has been developed using a Michael–Mannich cascade reaction to afford spirooxindole-pyrrolidine products featuring vicinal quaternary carbon centers at the C3 and C4 positions. The corresponding products are generated with a broad substrate scope, good functional group tolerance and high stereoselectivity. In addition, subsequent amplification experiments and derivations further demonstrated the applicability of the synthetic methodology. Density functional theory calculation shed light on the reaction mechanism, demonstrating that it proceeded via a Michael–Mannich cascade reaction rather than a concerted [3 + 2] cycloaddition.