Synthesis of Axially and Centrally Chiral Alkylidenecyclobutanes Enabled by Catalytic Enantioselective Allylboration

Abstract

A chiral phosphoric acid catalyzes asymmetric allylboration of stereodefined alkenylcyclobutyl boronates with aldehydes, constructing alcohol-functionalized alkylidenecyclobutanes (ACBs) bearing both axial and central chirality. The reaction proceeds under mild conditions with broad scope, affording products in high yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, 99% ee). Combining substrate stereocontrol with a Mitsunobu inversion allows selective switching of all three stereogenic centers of the ACBs using a single catalyst system. Utility is showcased by stereoselective syntheses of spiro[2.3]hexane and oxa-spiro[2.3]hexane bearing multiple stereocenters.