A Ligand-Enabled Palladium-Catalyzed Highly para-Selective Difluoromethylation of Aromatic Ketones

A practical and highly para-selective C-H difluoromethylation of aromatic ketones has been developed by employing tetrakis(triphenylphosphine)palladium(0) as the catalyst and triphenylphosphine as the ligand. In addition to general aromatic ketones, this transformation was compatible with bioactive compounds and well-known drugs, such as oxybenzone, ketoprofen, zaltoprofen, and propafenone. Moreover, a mechanistic study revealed that a palladium intermediate coordinated by a carbonyl group promotes highly para-selective difluoromethylation.