PCET Photodecarboxylation for SN2'-Type Alkylation of gem-Dichlorocyclobutenones.

Abstract

Metal-catalyzed nucleophilic SN2'-type alkylation of gem-dichlorocyclobutenones with organometallic reagents remained unsuccessful. Herein, we report an acridine-catalyzed radical SN2' alkylation of both b-alkyl and b-aryl substituted gem-dichlorocyclobutenones with free carboxylic acids. In this process, Csp3-enriched 4-alkylated 2-chlorocyclobutenones are obtained with commendable functionality tolerance. A PCET photodecarboxylation enables for the first time SN2'-type alkylation of gem-dichlorocyclobutenones with b-H-containing carboxylic acids, addressing several challenges. This mild and scalable Csp3-Csp3 bond-forging alkylation applies to the functionalization of natural product-derived gem-dichlorocyclobutenones with carboxylic acid drugs, fatty acids and steroids. The a-chlorocyclobutenone product is further exploited in divergent organic synthesis via post-synthetic modification.