Asymmetric Construction of 3-Azabicyclo[3.1.0]hexane Skeleton with Five Contiguous Stereogenic Centers by Cu-Catalyzed 1,3-Dipolar Cycloaddition of Trisubstituted Cyclopropenes

Abstract

A highly diastereo- and enantioselective desymmetrization of prochiral cyclopropenes via a Cu(CH₃CN)₄BF₄/Ph-Phosferrox complex catalyzed 1,3-dipolar cycloaddition of azomethine ylides was described. A variety of complex 3-azabicyclo[3.1.0]hexane derivatives bearing five contiguous stereogenic centers and two all-carbon quaternary stereogenic centers were directly synthesized as a single isomer in excellent yields (up to 99%) and enantioselectivities (97 → 99% ee). Notably, various functional groups (CO₂R, CN, CONMe₂, and Ph) of cyclopropenes were found to be well-tolerated in this transformation. The cycloadduct was conveniently converted to a biologically important GABA derivative via LiAlH₄ reduction and subsequent hydrolysis.