Copper-Catalyzed O-Difluoromethylation of Functionalized Aliphatic Alcohols: Access to Complex Organic Molecules with an OCF₂H Group

A two-step synthetic strategy toward difluoromethyl ethers via a CuI-catalyzed reaction of the alcohols, bearing additional protected functionalities, with FSO₂CF₂CO₂H has been developed. The high potential of the developed protocol has been shown by preparing novel OCF₂H-analogues of GABA and L-proline. The described transformation has good functional group compatibility and can serve as a powerful synthetic tool for late-stage preparation of complex OCF₂H-containing organic compounds as well as building blocks for drug discovery.