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.
Authors
- Qijian Ni (ORCID: https://orcid.org/0000-0002-3135-1271)
- Zheng Wang (ORCID: https://orcid.org/0000-0003-0608-8093)
- Jin‐Hong Lin (ORCID: https://orcid.org/0000-0002-7000-9540)
- Ji‐Chang Xiao (ORCID: https://orcid.org/0000-0001-8881-1796)
- Xinjun Yang
Institutions
- Shanghai University (CN)
- Shanghai Institute of Organic Chemistry (CN)
- Innovative Research (United States) (US)
- University of Chinese Academy of Sciences (CN)
Publication Details
- 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
Funders
- 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