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Enantioselective, Catalytic Vicinal Difluorination of Alkenes
Author(s) -
Scheidt Felix,
Schäfer Michael,
Sarie Jérôme C.,
Daniliuc Constantin G.,
Molloy John J.,
Gilmour Ryan
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201810328
Subject(s) - geminal , vicinal , enantioselective synthesis , selectfluor , amine gas treating , chemistry , catalysis , regioselectivity , selectivity , yield (engineering) , combinatorial chemistry , medicinal chemistry , organic chemistry , stereochemistry , materials science , metallurgy
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 ArI III F 2 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 CF 3 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).