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.