PCET Photodecarboxylation for S N 2’‐Type Alkylation of gem ‐Dichlorocyclobutenones

Abstract Metal‐catalyzed nucleophilic S N 2’‐type alkylation of gem ‐dichlorocyclobutenones with organometallic reagents remained unsuccessful. Herein, we report an acridine‐catalyzed radical S N 2’ alkylation of both β‐alkyl and β‐aryl substituted gem ‐dichlorocyclobutenones with free carboxylic acids. In this process, Csp 3 ‐enriched 4‐alkylated 2‐chlorocyclobutenones are obtained with commendable functionality tolerance. A PCET photodecarboxylation enables for the first time S N 2’‐type alkylation of gem ‐dichlorocyclobutenones with β‐H‐containing carboxylic acids, addressing several challenges. This mild and scalable Csp 3 ─Csp 3 bond‐forging alkylation applies to the functionalization of natural product‐derived gem ‐dichlorocyclobutenones with carboxylic acid drugs, fatty acids, and steroids. The α‐chlorocyclobutenone product is further exploited in divergent organic synthesis via postsynthetic modification.