Carbene-catalyzed [2+2] cycloaddition of chloroaldehydes and isatin-derived ketimines for enantioselective synthesis of spirocyclic β-lactams

Abstract

An N-heterocyclic carbene-catalyzed asymmetric [2+2] cycloaddition reaction of α-chloroaldehydes with isatin-derived ketimines is developed. This protocol tolerates a wide range of substrates featuring various substitution patterns, and under mild, oxidant-free reaction conditions with low catalyst loading (5 mol%), a series of spirocyclic β-lactams can be efficiently prepared in moderate to good yields and excellent optical purities.