Synthesis of Optically Pure 2-Azetidinones Having N-Dehydroamino Acid Side-Chains

An efficient, three step synthesis of optically pure N-vinyl-2-azetidinones 1 starting from α- or β-amino ester imines has been developed. Staudinger reaction between amino ester derived imines and ketene precursors gave 2-azetidinones 2. Enolate formation on the amino ester moiety of the optically pure 2-azetidinones 2, selenylation and, finally, MCPBA treatment afforded N-vinyl-2-azetidinones 1 in good to excellent yields, with total retention of the stereochemistry of the starting material. Compounds 2 bear the functionality needed to place a carboxy group contiguous to the lactam nitrogen, a structural feature common to all the active β-lactam antibiotics.

enantiopure N-vinyl-2-azetidinones - aminoester imines - Staudinger reaction