NHC-catalyzed generation of difluorocarbene and its application to difluoromethylation of oxygen nucleophiles

Controlled generation of difluorocarbene was effected by an NHC catalyst under mild conditions starting from trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate (TFDA). Cyclohexenones and tetralones were treated with TFDA in the presence of catalytic amounts of N,N′-dimesitylimidazolium chloride and sodium carbonate. The ketones were difluoromethylated with the generated difluorocarbene to afford enol difluoromethyl ethers without difluorocyclopropanation. The ethers thus obtained were dehydrogenated with DDQ to furnish aryl difluoromethyl ethers in high yield. Under similar conditions, secondary amides underwent difluoromethylation selectively on the oxygen atom to give difluoromethyl imidates, which allows the formation of 2-difluoromethoxypyridines.