Nickel‐Catalyzed C−I‐Selective C(sp2)−C(sp3) Cross‐Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides

Despite several methodologies established for C(sp2)−I selective C(sp2)−C(sp3) bond formations, achieving arene‐flanked quaternary carbons by cross‐coupling of tertiary alkyl precursors with bromo(iodo)arenes in a C(sp2)−I selective manner is rare. Here we report a general Ni‐catalyzed C(sp2)−I selective cross‐electrophile coupling (XEC) reaction, in which, beyond 3° alkyl bromides (for constructing arene‐flanked quaternary carbons), 2° and 1° alkyl bromides are also demonstrated to be viable coupling partners. Moreover, this mild XEC displays excellent C(sp2)−I selectivity and functional group compatibility. The practicality of this XEC is demonstrated in simplifying the routes to several medicinally relevant and synthetically challenging compounds. Extensive experiments show that the terpyridine‐ligated NiI halide can exclusively activate alkyl bromides, forming a NiI−alkyl complex through a Zn reduction. Attendant density functional theory (DFT) calculations reveal two different pathways for the oxidative addition of the NiI−alkyl complex to the C(sp2)−I bond of bromo(iodo)arenes, explaining both the high C(sp2)−I selectivity and generality of our XEC. A method for the C(sp2)−I selective cross‐electrophile coupling (XEC) of bromo(iodo)arenes with 3°, 2°, and 1°alkyl bromides is reported. This mild XEC displays a broad scope with demonstrated functional group tolerance and finds use in the streamlined preparation of synthetically challenging bioactive compounds. Given the prevalence of its building blocks and the substrate generality, this discovery will likely inspire numerous applications.