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

Org Lett. 2025 Jun 27;27(25):6867-6871. doi: 10.1021/acs.orglett.5c02046. Epub 2025 Jun 16.

Abstract

The cyanodifluoromethyl group (-CF2CN) 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 (BrCF2CN) 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.