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

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.

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Publication Details

Journal
Nature Communications
Published
2025-11-28
DOI
https://doi.org/10.1038/s41467-025-65763-3
Citations
1
Primary Topic
Fluorine in Organic Chemistry
Type
article
Field-Weighted Citation Impact
0.79

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article

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

Niankai Fu, Minqiang Chai, Naifu Zhou
1 citations
Nature Communications
Fluorine in Organic Chemistry
0.79
article

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

Niankai Fu, Minqiang Chai, Naifu Zhou
article en
1 citations

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.

Nature CommunicationsVol. 16(1)
Chinese Academy of Sciences (CN), Beijing National Laboratory for Molecular Sciences (CN), Institute of Chemistry (CN), University of Chinese Academy of Sciences (CN)
National Natural Science Foundation of China, Chinese Academy of Sciences
Openalex Percentile: Top 21%
Fluorine in Organic Chemistry
0.79
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