An analysis of the regioselectivity in hetero Diels-Alder reactions using DFT-based reactivity indexes

The regioselectivity of hetero Diels-Alder reactions (HDA) of 2-azabutadiene with aldehydes has been elucidated by means of Gazquez-Mendez rules, which are based on the calculation of local softnesses of the four terminal atoms involved in cyclization. The theoretical results obtained with the B3LYP/6-31G(d) method confirm the regioselectivities observed experimentally for all substituents (R=H, CH3, CN) present in the aldehyde reactant. The regioselectivities of these HDA reactions have been confirmed by the calculation of the activation barriers corresponding to the two cyclization modes, and also by the application of the Houk rule and the maximum hardness principle.