Difluoromethylation of Alkyl Bromides and Iodides with TMSCF2H

We describe, for the first time, two protocols for direct difluoromethylation of unactivated alkyl bromides and iodides. Reactions of alkyl iodides with TMSCF2H were mediated by a copper catalyst using CsF as the activator, while reactions of less reactive alkyl bromides required a combination of palladium and a stoichiometric amount of CuI as the catalysts. Preliminary mechanistic studies of the synergistic Pd/Cu-catalyzed difluoromethylation of alkyl bromides suggest that it proceeds likely via a Pd(I)/Pd(III) catalytic cycle.

Automated summary

Two protocols for direct difluoromethylation of alkyl bromides and iodides are introduced, utilizing different catalysts and activators. Preliminary mechanistic studies suggest that the synergistic Pd/Cu-catalyzed difluoromethylation of alkyl bromides likely proceeds via a Pd(I)/Pd(III) catalytic cycle.