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

Abstract Cross‐electrophile coupling (XEC) between aryl halides and alkyl halides is a streamlined approach for C(sp 2 )−C(sp 3 ) bond construction, which is highly valuable in medicinal chemistry. Based on a key Ni II 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 an amine secondary ligand slows down the oxidative addition process of the Ni‐polypyridine catalyst to the aryl bromide and a Ni II aryl amido intermediate is formed in situ during the reaction process. The relatively slow oxidative addition is beneficial for enhancing the selectivity of the XEC reaction. The Ni II aryl amido intermediate stabilizes the Ni II –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, practical, and scalable platform for the formation of (hetero)aryl–alkyl bonds using standard Ni catalysts under mild conditions. The mechanistic insights from this work could serve as a great foundation for future studies on Ni‐catalyzed cross‐couplings.