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 HF:amine 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 (>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).
Keywords: Brønsted acid; difluorination; enantioselectivity; iodine; organocatalysis.
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