Copper-Promoted Reductive Cross-Coupling for Cyanodifluoromethylation of (Hetero)aryl Iodides with BrCF<sub>2</sub>CN

The cyanodifluoromethyl group (-CF<sub>2</sub>CN) has emerged as a valuable fluorinated motif, with growing recognition for its potential applications in medicinal chemistry and materials science. However, its efficient incorporation into organic compounds remains a synthetic challenge. Herein, we report a copper-promoted reductive cross-coupling protocol for the cyanodifluoromethylation of (hetero)aryl iodides using bromodifluoroacetonitrile (BrCF<sub>2</sub>CN) as a cost-effective and readily available reagent. This method demonstrates broad substrate compatibility, delivering target products in moderate to good yields under mild and operationally simple conditions. Successful gram-scale synthesis and late-stage functionalization of complex molecules further highlight the utility of the protocol.

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Journal
Organic Letters
Published
2025-06-16
DOI
https://doi.org/10.1021/acs.orglett.5c02046
Primary Topic
Fluorine in Organic Chemistry
Type
article
Field-Weighted Citation Impact
0.00

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article

Copper-Promoted Reductive Cross-Coupling for Cyanodifluoromethylation of (Hetero)aryl Iodides with BrCF2CN

Qijian Ni, Zheng Wang, Jin‐Hong Lin, Ji‐Chang Xiao et al.
2 links
Organic Letters
Fluorine in Organic Chemistry
article

Copper-Promoted Reductive Cross-Coupling for Cyanodifluoromethylation of (Hetero)aryl Iodides with BrCF2CN

Qijian Ni, Zheng Wang, Jin‐Hong Lin, Ji‐Chang Xiao, Xinjun Yang
article en

Abstract

The cyanodifluoromethyl group (-CF<sub>2</sub>CN) has emerged as a valuable fluorinated motif, with growing recognition for its potential applications in medicinal chemistry and materials science. However, its efficient incorporation into organic compounds remains a synthetic challenge. Herein, we report a copper-promoted reductive cross-coupling protocol for the cyanodifluoromethylation of (hetero)aryl iodides using bromodifluoroacetonitrile (BrCF<sub>2</sub>CN) as a cost-effective and readily available reagent. This method demonstrates broad substrate compatibility, delivering target products in moderate to good yields under mild and operationally simple conditions. Successful gram-scale synthesis and late-stage functionalization of complex molecules further highlight the utility of the protocol.

Organic LettersVol. 27(25)
Shanghai University (CN), Shanghai Institute of Organic Chemistry (CN), Innovative Research (United States) (US), University of Chinese Academy of Sciences (CN)
National Natural Science Foundation of China, Chinese Academy of Sciences, Science and Technology Commission of Shanghai Municipality, National Key Research and Development Program of China
Clean water and sanitation
Openalex Percentile: Top 90%
Fluorine in Organic Chemistry
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