Direct Nucleophilic Difluoromethylation of Carbonyl Compounds

Phosphonium salt ([Ph₃P⁺CF₂H] Br^–, DFPB) was found to be an efficient nucleophilic difluoromethylation reagent. Although DFPB is known as a phosphonium ylide precursor, its reaction with carbonyl compounds under traditional “Wittig reaction conditions” did not give the expected Wittig difluoroolefinated products, but afforded the nucleophilic difluoromethylation products, α-CF₂H alcohols. Mechanistic investigation reveals that the unexpected transformation proceeded via the direct transfer of the CF₂H group, which resulted from the high P–O affinity.