Theoretical Study of the [2+3] Cycloaddition of Nitrones to Nitriles-Influence of Nitrile Substituent, Solvent and Lewis Acid Corrdination

摘要

The [2+3] cycloaddition of nitrone PhCH=N(Me)O to nitriles RC(ident to)N (R=Me, Ph, CF_3) was studied using quantum chemical calculations at the HF/6-31G and B3LYP/6-31G level o theory. With MeCN and PhCN, the reaction occurs through a concerted mechanism and leads selectively to DELTA~4-1,2,4-oxadiazolies rather than DELTA~2-1,2,5-oxadiazolines. Electron withdrawing substituents such as CF_3 at the nitrile provoke a non-synchronous bond formation, with the C-O bond being established on an earlier stage than the C-N bond. Additionally, the reaction becomes thermodynamically and kinetically more favorable. In the reaction of adducts of MeCN with BH_3 or BF_3 as model Lewis acids, the mechanism was found to change from fully concerted in the case of free MeCN towards a two-step reaction in the presence of BF_3, in which C-O bond formation occurs first. The BH_3-mediated reaction occupies an intermediate stage where ring formation occurs in one-step but non-simultaneously, similar to the reaction of CF_3CN. Interaction of the Lewis acid with the nitrile in the course f the reaction facilitates the cycloaddition by stabilizing transition states, intermediate and product rather than by activating the nitrile. The solvent influences the organic reaction mainly by lowering the energy of the reagents, thus leading to a higher activation barrier in a more polar solvent. In the Lewis acid mediated reaction, in contrast, the intermediate is strongly stabilised by a polar solvent and with that the synchronicity of the reaction changes in favour of a two-step mechanism.