Volume 136, Issue 38 e202407118
Forschungsartikel

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

Jian Luo

Jian Luo

Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah, 84322 United States

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Michael T. Davenport

Michael T. Davenport

Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, 84604 United States

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Dr. Prof. Daniel H. Ess

Corresponding Author

Dr. Prof. Daniel H. Ess

Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, 84604 United States

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Dr. Prof. T. Leo Liu

Corresponding Author

Dr. Prof. T. Leo Liu

Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, Utah, 84322 United States

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First published: 07 June 2024
Citations: 1

Abstract

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 an amine secondary ligand slows down the oxidative addition process of the Ni-polypyridine catalyst to the aryl bromide and a NiII 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 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, 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.

Conflict of Interests

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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