Organic compounds containing a gem-difluoromethylene group are
useful for a variety of applications in biological, pharmaceutical and materials
chemistry. Over the years a variety of synthetic protocols for this class of
compounds have been developed. They can be prepared from their corresponding
carbonyl compounds or through various derivatives such as oximes and
dithiolanes, electrophilic fluorinations of unsaturated compounds and enolates,
free-radical additions of halodifluoroalkanes to olefins, and nucleophilic
difluoromethylations of aldehydes and ketones. Other approaches involve methods
that utilize fluorinated compounds as synthons. Enantioselective gemdifluorination
reactions have emerged employing chiral auxiliaries such as
sulfinimines, and chiral Lewis acid catalysts. This review focuses on the recent
developments in this area, emphasizing the synthetic methods that can be
conveniently carried out and are potentially broadly applicable.
