LAUSR

Abstract This work investigated computationally with density functional theory calculations at the M06/6-311G∗ level, the ring opening reaction of various methyl-, phenyl- and carbonyl- substituted aziridines to obtain azomethine ylides and the subsequent 1,3-dipolar cycloaddition reaction with acetaldehyde leading to 3-methyl and 4-methyl regioisomers and endo- and exo- stereoisomers. The activation barrier for the electrocyclic ring opening of the parent aziridine is very high (51.3 kcal/mol) but is lowered by at least 15.5 kcal/mol upon methyl and ester group substitutions. In the reaction of 1,3-diphenyl-2,2-methoxycarbonylaziridine A2 with acetaldehyde, the ring opening step is rate-determining with an activation barrier of 28.9 kcal/mol. The activation barrier for the formation of the 4-methyl isomer from this reaction is at least 7.4 kcal/mol lower than that for the formation of the 3-methyl isomer, which is in accord with the experimentally-observed regioselectivity. Also, the formation of the exo isomer is more favoured than the endo isomer as the barrier of the former is 2.7 kcal/mol compared to 6.1 kcal/mol for the latter. There is an inverse correlation between the activation barriers for the electrocyclic cleavage of the aziridines and the electrophilicities of the resulting azomethine ylides. The results are rationalized in terms of perturbation molecular orbital theory.