A SEMIEMPIRICAL THEORETICAL-STUDY ON THE FORMATION OF BETA-LACTAMS FROM KETENES AND IMINES

Approximate self-consistent-field molecular orbital theory has been used to study the cyclization of ketenes and imines to beta-lactams. In order to account for the effect of substituents, several substituted ketenes and imines have been carefully chosen. Calculations demonstrate that the reaction proceeds via a nonconcerted two-step mechanism, in good agreement with related experimental evidence. The first step involves formation of the N1-C2 beta-lactam bond, and the second step leads to ring closure through formation of the C3-C4 bond. The transition state associated with this latter step has significant biradical character, especially when there is a carbonyl group at the C4 position. Further, it has been found that the experimental stereoselectivity of the reaction is correctly predicted by the calculations. A general model of the stereochemical trends of the Staudinger reaction is proposed on the basis of the possible different approaches of imines to ketenes as well as the perturbational effects induced by the substituents at the C3 and C4 positions of the beta-lactam ring.