Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters

Difluoromethylene-containing
compounds have attracted substantial
research interest over the past decades for their ability to mimic
biological functions of traditional functional groups while providing
a wide variety of pharmacological benefits bestowed by the C–F
bond. We report a novel strategy to access RCF2Br-containing
heterocycles by regio- and enantioselective bromocyclization of difluoroalkenes
enabled by chiral anion phase-transfer catalysis. The utility of this
methodology was highlighted through a synthesis of an analogue of
efavirenz, a drug used for treating HIV. Additionally, the synthetic
versatility of the CF2Br intermediates was showcased through
functionalization to a variety of enantioenriched α,α-difluoromethylene-containing
products.