32382-57-3Relevant academic research and scientific papers
Enantioselective, Catalytic Vicinal Difluorination of Alkenes
Scheidt, Felix,Sch?fer, Michael,Sarie, Jér?me C.,Daniliuc, Constantin G.,Molloy, John J.,Gilmour, Ryan
, p. 16431 - 16435 (2018/11/23)
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 ArIIIIF2 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 Br?nsted 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).
Catalytic Geminal Difluorination of Styrenes for the Construction of Fluorine-rich Bioisosteres
Scheidt, Felix,Neufeld, Jessica,Sch?fer, Michael,Thiehoff, Christian,Gilmour, Ryan
, p. 8073 - 8076 (2019/01/04)
A geminal difluorination of alkenes based on I(I)/I(III) catalysis is disclosed, which is compatible with a range of electronically and substitutionally diverse styrenes (27 examples, up to 89% yield). Employing inexpensive p-TolI as the organocatalyst, turnover is enabled by Selectfluor-mediated oxidation to generate the ArIF2 species in situ. Extension to include α-substituted styrenes bearing fluorine-containing groups is disclosed and provides an expansive platform for the generation of fluorine-rich architectures.
