The 1,3-dipolar cycloaddition of 1H-pyridinium-3-olate and 1-methylpyridinium-3-olate with methyl acrylate: a density functional theory study

The 1,3-dipolar cycloaddition reaction of 1-substituted pyridinium 3-olates with methyl acrylate is studied using density functional theory (DFT) method at the B3LYP/6-31G(d) level. The molecular mechanisms of the possible stereo- and regio-chemical pathways are characterized and explored. Solvent effects are also evaluated by the polarizable continuum model (PCM). Analysis of the results shows that there are relevant differences in the reaction pathways between the gas phase and with solvent. Only results in solvent phase are in accord with literature experimental results where 6-substituted 8-azabicyclo[3.2.1]oct-3-en-2-ones are formed preferentially. These polar cycloaddition reactions take place through highly asynchronous transition states in which nucleophilic attack by C2/C6 of the pyridinium-3-olates on the more electrophilic centre of the methyl acrylate initiates the process. Analysis of global and local indexes of the reactants is evaluated in order to explain the observed regioselectivity. Rate constants are calculated at room temperature using conventional transition state theory.