Formal C-H Alkylation of (Hetero)Arenes via one-pot Halogenation and Nickel-Catalyzed Cross-Electrophile Coupling Strategy

Abstract

Direct C(sp²)-C(sp³) bond formation via arene C-H alkylation remains a highly desired transformation in organic synthesis. Herein, we describe a versatile one-pot protocol that merges I₂/Selectfluor-mediated in situ C-H iodination with nickel-catalyzed reductive cross-electrophile coupling (XEC) to achieve formal C-H alkylation of a broad array of (hetero)arenes. This approach features broad substrate scope and excellent functional group tolerance, enabling effective late-stage alkylation of a number of pharmaceutically relevant scaffolds. Furthermore, ability to perform sequential alkylation at multiple sites of simple aromatics highlights the potential applications of this protocol in synthetic chemistry.