Arylazide cycloaddition to methyl propiolate: DFT-based quantitative prediction of regioselectivity

Several 1-(4-substituted)-phenyl-4- or 5-methoxycarbonyl-1,2,3-triazoles have been synthesized by 1,3-dipolar cycloaddition of the corresponding arylazides to methyl propiolate in carbon tetrachloride. The regioselectivity of these reactions cannot be rationalized on the basis of the electronic demands of the reactants or frontier molecular-orbital theory. Therefore, we applied to this problem a quantitative formulation of the HSAB principle to this problem developed within density functional theory. Global and local reactivity indices were computed at B3LYP/6-311 + G(d,p) level both in vacuo and in carbon tetrachloride (by the COSMO approach). The direction of charge transfer upon reactive encounter has been determined and the computed regioselectivity has been shown to be in good agreement with the experimental results. The relationship between computed and experimental data and how it related to the transition state energy. On these grounds, a generalization of the local HSAB principle has been recently introduced, ([21]) which enables one to compute, from mu and s of the reactants only, the grand potential variation DeltaOmega([22]) due to the charge transfer occurring in the very first step of the bond-forming interaction between specific atoms of the reactants. For the above reasons, DeltaOmega is expected to be proportional to the transition state energy and to provide a quantitative prediction of regioselectivity without the need of locating the transition state. This method has been successfully applied by us to the 1,3-DC between nitrilimines and alkynyl- or alkenyl dipolarophiles.[23] Continuing our investigations, we present here the first quantitative prediction of the regioselectivity involved in the cycloaddition between 1-(4-substituted)phenylazides 2 and methyl propiolate 3, which is based upon the DFT theory and the HSAB principle.