Enantioselective, Catalytic Vicinal Difluorination of Alkenes.

Enantioselective, Catalytic Vicinal Difluorination of Alkenes.
Angew Chem Int Ed Engl. 2018 Sep 26;:
Authors: Scheidt F, Schäfer M, Sarie J, Daniliuc C, Molloy J, Gilmour R
Abstract
The enantioselective, catalytic vicinal difluorination of alkenes is reported via I(I)/I(III) catalysis using a novel, C2-symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArI(III)F2 species is enabled by Selectfluor® oxidation and addition of an inexpensive HF•amine complex. The HF•amine ratio employed in this Umpolung 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 94:6 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95% yield).
PMID: 30255972 [PubMed - as supplied by publisher]

Source: Angewandte Chemie - September 26, 2018 Category: Chemistry Authors: Scheidt F, Schäfer M, Sarie J, Daniliuc C, Molloy J, Gilmour R Tags: Angew Chem Int Ed Engl Source Type: research