Bottlenecks in the prediction of regioselectivity of [4 + 2] cycloaddition reactions: an assessment of reactivity descriptors

Abstract

B3LYP/6-31G(d) calculations were performed to obtain all the transition states and products for the 128 distinct reaction channels of Diels-Alder reactions by taking all possible combinations from a series of dienes (1N-a, 1N-b, 2N, 1P-a, 1P-b, 2P, 1O, 1S) and dienophiles (NE, PE, OE, SE, AE, OHE, MeE, CNE). The predictive ability of the values to gauge the regioselectivity of the putative [4 + 2] cycloaddition reactions is analysed. No correlation is obtained between the reaction energies and activation energies. The extent of asynchronicity is measured based on the bond order analysis. DFT-based descriptors such as the local softness (s_k⁺ and s_k⁻), Fukui function indices (f_k⁺ and f_k⁻), global electrophilicity index (ω) and local electrophilicity index (ω_k) were found to be better than the conventional FMO predictions.