Regioselectivity of hetero Diels-Alder reactions between 1-aza-1,3-butadiene derivatives and dimethylvinylamine: A theoretical investigation

The regioselectivity of hetero Diels-Alder reactions between 1-aza-1,3-butadiene derivatives and dimethylvinylamine is elucidated by means of several theoretical approaches, namely, the Gazquez-Mendez rule based on the calculation of local softnesses, barrier activation calculations, maximum hardness principle, and the Houk rule based on the FMO theory. The calculations were performed at the B3LYP/6-31G(d) level of theory, and the obtained results are in agreement with available experimental results. Moreover, the present analysis shows that these inverse electron demand polar cycloadditions present a linear relationship between the activation barriers of the favored ortho regioisomers and the inverse of electrophilicity differences of the reagents.