Highly efficient desymmetrization of cyclopropenes to azabicyclo[3.1.0]hexanes with five continuous stereogenic centers by copper-catalyzed [3 + 2] cycloadditions

Abstract

An unprecedented copper-catalyzed desymmetrization/cycloaddition of 1,1-disubstituted cyclopropenes to azabicyclo[3.1.0]hexane-based heterocycles containing cyclopropane and pyrrolidine motif has been developed. The salient features of the one-time simultaneous construction of five continuous carbon-stereogenic centers for the straightforward and atom-economical synthesis of chiral azabicyclo[3.1.0]hexane derivatives include a general and broad substrate scope with high yields as well as excellent diastereoselectivities (>99 : 1 dr) and excellent enantioselectivities (up to >99% ee). In addition, it is probable that the weak coordination of an amide moiety on 1,1-disubstituted cyclopropenes with the copper complex is the main reason for the tuning of the stereoselectivity of the cycloaddition reaction.