Semi-empirical study of cycloaddition reactions to form β-lactams from 2-amino-β-D-arabine[1′,2′:4,5]oxazoline (ureid) and ketenes

In this work we studied a ureid system, holding an imine skeleton with an endo (1) or exocyclic (2) double bond. Through a [2 + 2] cycloaddition reaction with ketene it forms β-lactam ring derivatives of spiro (3) or conjugate (4) types. The semi-empirical AM1 method was used to calculate the cycloaddition mechanism. Geometries of the reactants, transition states, intermediates and products were completely optimized and characterized in relation to their minimum or maximum nature on the potential energy surface. The cycloaddition reaction proceeds via non-concerted mechanism with the initial formation of an intermediate with some zwitterionic character. By rotation about the N 1 C 2 bond, this gives a second intermediate which leads to the final product after formation of the C 3 C 4 bond. The second step was found to be rate determining, with an activation energy of 29–33 kcal mol −1 . The reaction involving the endocyclic bond for formation of the conjugate product or the exocyclic bond for formation of the spiro product showed basically the same energy surface, with a slight (1–2 kcal mol −1 ) preference for the spiro product (3).