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Theoretical Study of the [2+3] Cycloaddition of Nitrones to Nitriles—Influence of Nitrile Substituent, Solvent and Lewis Acid Coordination
Author(s) -
Wagner Gabriele
Publication year - 2003
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200390172
Subject(s) - chemistry , nitrile , cycloaddition , lewis acids and bases , substituent , medicinal chemistry , nitrone , reaction mechanism , photochemistry , solvent effects , solvent , adduct , organic chemistry , catalysis
The [2+3] cycloaddition of nitrone PhCHN(Me)O to nitriles RCN (R=Me, Ph, CF 3 ) was studied using quantum chemical calculations at the HF/6‐31G* and B3LYP/6‐31G* level of theory. With MeCN and PhCN, the reaction occurs through a concerted mechanism and leads selectively to Δ 4 ‐1,2,4‐oxadiazolines rather than Δ 2 ‐1,2,5‐oxadiazolines. Electron withdrawing substituents such as CF 3 at the nitrile provoke a non‐synchronous bond formation, with the CO bond being established on an earlier stage than the CN bond. Additionally, the reaction becomes thermodynamically and kinetically more favourable. 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 CO 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 3 CN. Interaction of the Lewis acid with the nitrile in the course of 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.