Enantioselective, Catalytic Vicinal Difluorination of Alkenes

The enantioselective, catalytic vicinal difluorination of alkenes is reported by I-I/I-III catalysis using a novel, C-2-symmetric resorcinol derivative. Catalyst turnover via in situ generation of an (ArIF2)-F-III species is enabled by Selectfluor oxidation and addition of an inexpensive HF-amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of BrOnsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95% yield).