Regio- and Stereoselectivity of the 1,3-Dipolar Cycloaddition of Pyridinium-3-olates and Pyrazinium-3-olates with Methyl Methacrylate: A Density Functional Theory Exploration

Theoretical computations were performed on the 1,3-dipolar cycloaddition reactions of pyridinium-3-olates and pyrazinium-3- olates with methyl methacrylate employing density functional theory at the B3LYP/6-31G(d) level in the gas phase and in THF. The two possible regioisomeric pathways, forming 6-esters and 7-esters, along with the two stereoisomeric channels, endo and exo, have been considered. Thermodynamic and kinetic parameters calculated at room temperature have been analyzed while the regioselectivity has been interpreted using reactivity indices. The presence of the methyl group on the dipolarophile compared to methyl acrylate, increases the activation energy but decreases the reaction enthalpy in THF. The rate constants of these reactions have been determined using conventional transition state theory. The thermodynamic and kinetic preferences for the reactions of these pyridinium-3-olates and pyrazinium- 3-olates with methyl methacrylate, in the gas phase and THF, decrease in the order 6-exo > 7-exo > 6-endo > 7-endo. On comparing the reactions of pyridinium-3-olates and pyrazinium-3-olates with methyl acrylate, a different order is observed although the 6-exo cycloadduct remains the major product.