Enantioselective three-component Ugi reaction catalyzed by chiral phosphoric acid

Abstract

A catalytic enantioselective three-component Ugi reaction was developed. SPINOL-derived phosphoric acid with bulky 2,4,6-tricyclohexylphenyl groups at the 6,6′ positions was found to be the best catalyst to afford α-amino amide derivatives in good to excellent yields (62% to 99%) and enantiocontrol (81% to >99% enantiomeric excess). This asymmetric reaction was applicable well to an array of aliphatic aldehydes. The gram-scale synthesis, modification of dapsone, and enantioselective synthesis of ( R )-Lacosamide underline the general utility of this methodology Influence of dihedral angles and substituents of the chiral phosphoric acids on the enantioselectivity was also discussed in this article.