Enantioselective, Catalytic Vicinal Difluorination of Alkenes.

ABSTRACT

The enantioselective, catalytic vicinal difluorination of alkenes is reported by II /IIII catalysis using a novel, C2 -symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIII F2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF-amine complex. The HFamine ratio employed in this process provides a handle for regioselective orthogonality as a function of Brønsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>201 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 9406 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95 % yield).