DFT study of 1,3-dipolar cycloaddition of azomethine imines with electron deficient dipolarophiles acrylonitrile, methylpropenoate, and dimethylmaleate

The 1,3-dipolar cycloaddition reactions of azomethine imines with some electron deficient dipolarophiles viz. acrylonitrile, methylpropenoate, and dimethylmaleate leading predominantly to 4-substituted pyrazolidines have been computationally studied which could be useful for the stereoselective synthesis of C-nucleosides. The mechanism of regioselectivity, chemoselectivity and diastereofacial selectivity were studied through the evaluation of activation parameters and philicity indices on the assumption of a concerted mechanism. The reactions were followed by performing transition state optimization, calculation of Intrinsic Reaction Coordinate and activation energies. The regioselectivity and reactivity were amply predicted by employing local and global electrophilicity and nucleophilicity indices. The reactions were considered to be nonpolar or at the most weakly polar on the basis of charge transfer calculated in the transition states. In the present cases, no facial selectivity could be observed due to energetic identity of the different enantiomeric transition states. A rationalization of the trends in regio- and chemoselectivity were also attempted in terms of chemical potential, hardness, global electrophilicity differences, local electrophilicity, local nucleophilicity, Pauling’s bond order and Wiberg bond indices in the transition state. Theoretical evaluation of rate constants for elementary reaction steps employing the transition state theory is very much useful for getting quantitative idea about the kinetic rates associated with those steps. Calculation of rate constants were performed with the Eyring’s TST rate equation and using total partition functions of the concerned species at different temperatures. The activation energy was recomputed for consistency from the slope of the plot of 1000/T vs. −log (k). All the computed results were derived from density functional calculations at the B3LYP/6-31G(d) level of theory. Considering the fact that the reactions are practically carried out in solutions, some calculations were performed in solvents of different polarity to examine its influence on the activation barrier or the reaction rate.