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 , oxisidant-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.