Substituent effects in the 1,3-dipolar cycloaddition reactions of 2-methylenecephalosporins with diazoalkanes

The 2-methylenecephalosporins 1 undergo stereoselective 1,3-dipolar cycloaddition reactions with diazoalkanes to give exclusively the spirocyclopropylcephalosporins 3. Substituens at C-3, C-4 and C-7 of the cephalosporin nucleus do not display a significant effect on the reactivity of the 2-exo double bond. However, reduction of the sulfoxides to sulfides has an inactivating influence. Reactions with substituted diazoalkanes proceed more slowly in every case. The results are explained by theoretical (PM3, AM1 and MNDO) calculations.