Ni-Catalyzed Electrochemical Cross-Electrophile C(sp2)-C(sp3) Coupling via a NiII Aryl Amido Intermediate

Cross-electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp2)−C(sp3) bond construction, which is highly valuable in medicinal chemistry. Based on a key NiII aryl amido intermediate, we developed a highly selective and scalable Ni-catalyzed electrochemical XEC reaction between (hetero)aryl halides and primary and secondary alkyl halides. Experimental and computational mechanistic studies indicate that in the presence of a polypyridine primary ligand and an amine secondary ligand, there is in-situ formation of a NiII aryl amido intermediate. The NiII aryl amido intermediate stabilizes the NiII−aryl species to prevent the aryl−aryl homo-coupling side reactions and acts as a catalyst to activate the alkyl bromide substrates. This electrosynthesis system provides a facile and practical platform for the formation of (hetero)aryl−alkyl bonds using standard Ni catalysts under mild conditions, and the system is amenable to scalable flow synthesis.