Catalytic Enantioselective Friedel−Crafts Reactions of Aromatic Compounds with Glyoxylate: A Simple Procedure for the Synthesis of Optically Active Aromatic Mandelic Acid Esters

Abstract

The first catalytic highly enantioselective Friedel−Crafts reaction of aromatic compounds with glyoxylate catalyzed by chiral Lewis acids is presented. The reaction has been developed for mainly aromatic amines reacting with ethyl glyoxylate in the presence of chiral bisoxazoline−copper(II) complexes as the catalyst. A series of chiral bisoxazoline−copper(II) complexes have been tested as catalysts for the reaction with N,N-dimethylaniline and it has been found that a highly regio- and enantioselective Friedel−Crafts reaction takes place in the presence of especially tert-butyl bisoxazoline−copper(II). This reaction proceeds with the formation of exclusively the para-substituted isomer in up to 95% yield and 94% ee. The reaction has been investigated for N,N-dimethylaniline under different reaction conditions and has been developed to be a catalytic highly enantioselective reaction for meta-substituted N,N-dimethylanilines, containing either electron-withdrawing or electron-donating substituents. The cata...