Enantioselective polar [2σ + 2π] cycloadditions of bicyclo[1.1.0]butanes and ortho-quinone methides enabled by chiral phosphoric acid catalysis

Abstract

Herein, we report a chiral phosphoric acid-catalyzed enantioselective synthesis of spiro-bicyclo[2.1.1]hexanes featuring vicinal tertiary–quaternary stereocenters. This method employs a formal [2σ + 2π] cycloaddition between bicyclo[1.1.0]butanes and ortho-quinone methides under mild conditions. The transformation exhibits broad functional group tolerance, providing access to diverse spiro-bicyclo[2.1.1]hexane derivatives in high yields (up to 96%) and enantioselectivities (up to 97 : 3 er). Experimental evidence supports a polar reaction mechanism distinct from previously reported radical pathways.