Electrochemical Deoxygenative Trifluoromethylallenylation of Propargylic Alcohols via Sodium-Mediated Pre-association

Abstract

We report an electrochemical protocol that enables the direct conversion of free propargylic alcohols into trifluoromethylated allenes through sodium-mediated radical C–O bond activation. The transformation proceeds via a pre-association mechanism between the propargylic alcohol and a trifluoromethyl sulfinate reagent, which organizes the reactive complex through Na⁺ coordination. This interaction lowers the energetic barrier of the intrinsically endothermic C–O bond cleavage, allowing a concerted radical addition pathway under mild electrochemical conditions. Combined experimental and computational studies, including NMR titration, kinetic analysis, and DFT calculations, reveal that sodium acts as an ion bridge, enabling selective CF₃ incorporation. The reaction exhibits broad substrate scope and high chemoselectivity, tolerating halogens, heteroarenes, and sensitive functional groups, and proving effective for the late-stage trifluoromethylation of natural products and pharmaceuticals.