Stereoselective formal [3+2] cycloaddition of N-alkylidene glycine ester anions to chiral Fischer alkenylcarbene complexes.: Asymmetric synthesis of 3,4,5-trisubstituted prolines

The reaction between N-alkylidene glycine ester enolates, generated from glycine esters aldimines with LDA in THF at low temperature, and chiral alkoxyalkenylcarbene complexes of chromium provided directly 2,4,5-trisubstituted-3-pyrrolidinylcarbene complexes with total exo selectivity and very high syn and facial diastereoselectivity when carbene complexes bearing the (-)-8-phenylmenthyloxy group were employed. Oxidation of the metal carbene moiety followed by basic hydrolysis of the esters afforded enantiomerically highly enriched syn,exo-3,4,5-trisubstituted prolines, whereas acidic hydrolysis of the same functional groups proceeded with epimerization at the alpha-amino acid center leading to anti,exo-3,4,5-trisubstituted prolines of very high enantiomeric purity as well.