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

Chiral C-2-symmetric phosphinic acids were designed based on sterically demanding and helical chiral perfluoroalkyl groups at the closest alpha-position advancing asymmetric reaction environment and catalytic activity. The perfluoroalkyl catalysts, [(CF3)(2)F-2] and [(C2F5)(2)F-2] phosphinic acids, were synthesized via a stereoselective addition/cyclization sequence of methyl phosphinate and deoxofluorination. These new classes of Bronsted 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).