α-Substituted β-Lactams via a Convenient Annelation of Imines

Abstract

In 1966 Bose and co-workers² introduced azidoacetyl chloride as a valuable reagent for β-lactam synthesis by the “acid chloride-imine method.”³ The azido group serves as a crypto amino function for further elaboration of the penicillin and cephalosporin side chain. The use of this reagent in β-lactam chemistry has proved very fruitful; the synthesis of trans penicillin V methyl ester,⁴ cephalosporins,⁵ penicillin,⁵ 4-mercapto-2-azetidinones,⁶ and other β-lactams have been achieved in various laboratories through the intermediacy of this reagent. Azidoacetyl chloride, like other azido compounds, however, tends to decompose with explosive violence if rigorous precautions are not observed. We have been engaged, therefore, in exploring alternative synthetic approaches to β-lactams which would make the use of azidoacetyl chloride unnecessary. In the present communication we wish to report a facile method for the preparation of α-azido-β-lactams and other 3-substituted-2- azetidinones without employing acid chlorides as reagents.