Cu-Catalyzed Enantioconvergent Oxygen-Centered Radical Cyclization

Abstract

Radical asymmetric cyclization has emerged as a powerful strategy for constructing ring structures. Although significant progress in carbon-centered radical cyclization, the catalytic asymmetric cyclization of oxygen-centered radicals, key species in many biological processes, remains challenging owing to their high oxidizing power and electrophilicity. Herein, we report an enantioconvergent oxygen-centered radical cyclization via Cu-catalyzed asymmetric C(sp3)−O oxidative coupling between the tertiary C(sp3)−H bond and the oxime O−H bond of racemic γ-ketoximes. This radical reaction proceeds efficiently under aerobic and mild conditions, affording a wide range of valuable isoxazolines bearing a fully substituted stereocenter in good yields with excellent enantioselectivity. Mechanistic studies were conducted to elucidate the origin of enantiocontrol, and and the synthetic utility of the method was demonstrated through the late-stage transformation of isoxazolines into polyhydroxy building blocks.