A Three-Step General Synthesis of 2-Azetidinones Bearing N-Dehydroamino Acid Side Chains

Abstract

An efficient, three-step synthesis of N-vinyl-2-azetidinones 7 selenylation, and finally m-CPBA treatment, afforded Nvinyl-2-azetidinones 7 in fair to excellent yields, with starting from α-or β-amino ester imines 4 has been developed. Staudinger reaction between imines 4 and a retention at the remaining stereocenters of the starting material. Two examples of the use of compounds 7 to prepare ketene precursor gave 2-azetidinones 5. Enolate formation on the amino ester moiety of the 2-azetidinone 5, bi-and tricyclic 2-azetidinones are presented. Introductionrived from α-or β-amino esters. Our approach is based on the sequential Staudinger reaction between a ketene precurThe increasing resistance of bacteria to commonly used sor and an amino ester imine, followed by α-selenylation of β-lactam antibiotics [1] and the ever-growing new appli-the amino ester moiety of the 2-azetidinone, and finally, cations of these products in fields ranging from enzyme in-oxidative deseleniation to produce the desired compounds. hibition [2] to the use of 2-azetidinones as raw materials for To the best of our knowledge, the sole precedent for the use developing new synthetic methodologies [3] have triggered a of a seleno derivative to prepare an N-vinyl-2-azetidinone renewed interest in developing new routes to polycyclic β-is the treatment of β-lactam 2, prepared by cycloaddition lactam systems. Our own interest in this field has resulted of azidoacetyl chloride to the imine 1, with m-CPBA/ in new approaches to the synthesis of bi-and polycyclic 2-iPr 2 NH to afford compound 3 (Scheme 1).