Computational study of the 1,3-dipolar cycloaddition between methyl 2-trifluorobutynoate and substituted azides in terms of reactivity indices and activation parameters.

The 1,3-dipolar cycloaddition of methyl 2-trifluorobutynoate with various azides has been studied in terms of several theoretical approaches at DFT/B3LYP/6-311++G(d,p) level of theory. The mechanism of regioselectivity of these reactions was investigated through the evaluation of the potential energy surface of the cycloaddition process calculations and density DFT-based reactivity indices. These approaches were successfully applied to prediction of preferable regio-isomers for various reactions of 1,3-dipolar cycloadditions. The reactions were followed by performing transition state optimization, calculation of Intrinsic Reaction Coordinate and activation energies. Analysis of the geometries of the corresponding transition structures shows that the cycloaddition takes place along a single elementary step (one-step mechanism) but asynchronous mechanism. The calculation of the activation energies and reaction energies show that the 1,5-regioisomer for substituted phenyl azides as dipoles and the 1,4-regioisomer for substituted benzyl azides as dipoles are thermodynamically in all the cycloadditions reactions. The solvent effect was also studied in the solvent tert-butyl alcohol using self-consistent reaction field model. The observed regioselectivity was explained by using developed DFT-based reactivity descriptors, such as Fukui and Parr functions. The results were compared with experimental data to find a good agreement.