1,3-Dipolar cycloadditions of azomethine ylides with chiral acrylates derived from methyl ( S)- and ( R)-lactate: diastereo- and enantioselective synthesis of polysubstituted prolines

Abstract

The 1,3-dipolar cycloaddition of acrylates derived from methyl ( R)- and ( S)-lactate, as chiral dipolarophiles, with glycine and alanine derived azomethine ylides is described for the first time. By using the corresponding silver metallo-azomethine ylides polysubstituted endo-prolines were obtained with high diastereo- and enantioselectivity. The process occurs at room temperature in toluene with 10 mol % of AgOAc by using either KOH or Et 3N as bases, also in substoichiometric amounts. Under these mild reaction conditions, enantiomerically enriched polysubstituted prolines resulting from an endo approach were obtained in general in high yields and de (86–99%). The absolute configuration of the resulting prolinates can be determined on the basis of X-ray diffraction analysis.