Access to Enantioenriched -Hydroxy gem-Difluorinated Heterocyclic and Acyclic Derivatives through Rh(III)-Catalyzed Asymmetric Transfer Hydrogenation

We report a process to access a variety of enantioenriched alpha-gem-difluorinated alcohols. A Rh(III)-catalyzed asymmetric transfer hydrogenation method was developed in 85-98% yields and enantiomeric excesses ranging from 52% to >99%. The reduction proceeds under mild conditions with a range of difluorinated molecules including 3,3-difluorochromanone, 3,3-difluorothiochromanone, 3,3-difluoro-dihydroquinolinone and alpha-difluorinated beta-ketosulfone derivatives to provide the desired enantioenriched difluorinated alcohols which are valuable fluorinated building blocks.