syn/anti Switching by specific heteroatom-titanium coordination in the Mannich-like synthesis of 2,3-diaryl-?-amino acid derivatives

A very efficient synthesis of 2,3-diaryl-?-amino acid derivs. is realized by a TiCl4/Et3N-catalyzed Mannich-like reaction of arylacetic or arylthioacetic esters with aryl imines. The presence of an ortho-heteroatom group on the arylacetic moiety, able to coordinate to the Ti center, is of dramatic importance for the outcome of the reaction and to tune the syn/anti diastereoselection. In particular, with ortho-fluoro-, -chloro-, and -bromoarylacetates, the syn adduct was isolated as the largely prevalent isomer. When (-)-8-phenylmenthyl (2-fluorophenyl)acetate was used, the condensation with imines resulted in high diastereo- and enantioselectivity. In agreement with the stereochem. results and NMR, a conceivable reaction mechanism was proposed.