Design of Phosphinic Acid Catalysts with the Closest Stereogenicity at the α‑Position: Synthesis and Application of α‑Stereogenic Perfluoroalkyl Phosphinic Acid Catalysts

Chiral C₂-symmetric phosphinic acids were designed based on sterically demanding and helical chiral perfluoroalkyl groups at the closest α-position advancing asymmetric reaction environment and catalytic activity. The perfluoroalkyl catalysts, [(CF₃)₂F₂] and [(C₂F₅)₂F₂] phosphinic acids, were synthesized via a stereoselective addition/cyclization sequence of methyl phosphinate and deoxofluorination. These new classes of Brønsted acid catalysts were applied to an asymmetric Friedel–Crafts reaction to give up to 89% yield and 82% R-enantioselectivity, which is higher than those obtained with the parent phosphoric acid (42% and 55.5% S).