2-CF2H(D)-Imidazolium Salts: A Reagent Platform for Bis(Deuterio)Difluoromethylation of Alkenes Under Copper/Photoredox Dual Catalysis.

The difluoromethyl group (-CF2H) has emerged as a privileged motif in modern drug design due to its ability to modulate lipophilicity and metabolic stability. Its deuterated analogue, the (deuterio)difluoromethyl group (-CF2D), offers further potential for enhancing metabolic stability and enabling distinct intermolecular interactions. Molecules bearing vicinal difluoromethyl or (deuterio)difluoromethyl groups can serve as potential bioisosteres of pharmacologically important vicinal diols and amino alcohols. Consequently, the direct and simultaneous installation of two difluoromethyl and (deuterio)difluoromethyl groups across alkenes represents an important synthetic target. To address current limitations, we herein introduced 2-CF2H(D)-imidazolium salts as a robust, user-friendly reagent platform for both bis(difluoromethylation) and bis(deuterio)difluoromethylation of a broad range of alkenes, including aryl-substituted and less reactive alkyl derivatives. The synthetic utility of this method is demonstrated through late-stage functionalization and gram-scale synthesis of complex molecules. Preliminary mechanistic studies revealed their distinct behavior in copper and photoredox catalysis. As such, this work establishes these reagents as a versatile platform for the simultaneous formation of C─CF2H and C─CF2D bonds, representing a significant advance in the synthesis of valuable fluorinated and deuterated compounds.