Noyori–Ikariya Asymmetric Transfer Hydrogenation of Prochiral α-CF₃ and α-SF₅ Ketones

As the demand for both fluoropharmaceuticals and single enantiomer drugs increases, there is a need for enantioselective synthetic methods toward chiral fluorinated molecules. Trifluoromethyl (CF₃) and the emerging pentafluorosulfanyl (SF₅) fluorinated groups bear characteristic high electronegativity and lipophilicity, while exhibiting distinct steric properties, which make them attractive substituents in drug discovery. Our group's previous exploration of the gold-catalyzed hydration of CF₃- and SF₅-alkynes to furnish the corresponding α-CF₃- and α-SF₅-ketones presents an accessible springboard for the enantioselective synthesis of β-CF₃ and β-SF₅ alcohols. To this end, Noyori-Ikariya asymmetric transfer hydrogenation (ATH) conditions afforded high enantioselectivity (up to 96% ee) and yields (up to 84%) across a scope of eight CF₃ and six SF₅ substrates.