Highly Enantioselective Friedel−Crafts Reaction of Aromatic Amines with Ethyl Glyoxylate Catalyzed by Chiral Titanium(IV) Complexes:  Practical Synthesis of Aminomandelic Acid Derivatives

Abstract

The asymmetric Friedel-Crafts reaction of a variety of N,N-dialkylanilines with ethyl glyoxylate has been achieved by the catalysis of titanium complexes of BINOL derivatives to give corresponding ethyl esters of p-N,N-dialkylaminomandelic acids in high yields (85-99%) and good to excellent enantioselectivities (80-96.6% ee) under the optimized reaction conditions, which has added a new catalyst for this class of reactions. The reaction could also be carried out at a reduced catalyst loading (1 mol %) in gram scale, which provided a practical synthesis of enantiopure aminomandelic acid derivatives.