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

25 October 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


Cross-electrophile coupling
Electrochemical synthesis

Supplementary materials

Supplementary Materials
Experimental procedures, additional electrochemical, UV-Vis, and NMR analysis data, the details of DFT calculations, and compound characterization data.


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