Dual transition metal electrocatalysis for difluoromethylation of Aryl halides using potassium difluoroacetate

Naifu Zhou, Mingding Chai and Niankai Fu ()
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Naifu Zhou: Chinese Academy of Sciences, Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry
Mingding Chai: Chinese Academy of Sciences, Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry
Niankai Fu: Chinese Academy of Sciences, Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract The development of robust, practical, and chemoselective methods for introducing the difluoromethyl (CF₂H) group into organic molecules is highly sought after in the fields of pharmaceutical and agrochemical design. Herein, we report a Fe/Ni dual-transition-metal electrocatalytic strategy for difluoromethylation of (hetero)aryl halides, using difluoroacetate—the most abundant source of the CF₂H group—as an effective difluoromethylating reagent. A diverse array of aryl and heteroaryl halides, bearing synthetically useful functional groups, can be readily converted into the corresponding difluoromethylated products with good efficiency. This difluoromethylation protocol is readily scalable and is successfully applied to the preparation and late-stage functionalization of bioactive molecules.

Date: 2025
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DOI: 10.1038/s41467-025-65763-3

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