Visible light-mediated 1,3-acylative chlorination of cyclopropanes employing benzoyl chloride as bifunctional reagents in NHC catalysis

Abstract

Chlorine-substituted ketones are crucial intermediates in organic synthesis, and acyl chlorination of chemical feedstocks employing commercially available benzoyl chloride provides an atom-and-step economic route for their synthesis. While atom-transfer radical addition (ATRA) has proven effective for 1,2-acyl chlorination, the efficient realization of 1,3-acyl chlorination has remained a considerable challenge. In this study, an NHC/photocatalyst dual-catalyzed system was developed to facilitate the 1,3-acyl chlorination of cyclopropanes using benzoyl chloride as a bifunctional reagent. This strategy also enables the synthesis of acyl-cyclopropanes with quaternary carbon centers through a nucleophilic annulation process. The practical utility of this approach was demonstrated through large-scale synthesis, product derivatization, and the preparation of analogs of anti-psychotics, including haloperidol, melperone and fluanisone.