Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Zaragoza, 50009 Aragón, Spain.
Dipartimento di Scienze del Farmaco, Università di Catania, 95124 Catania, Italy.
Molecules. 2017 Aug 19;22(8):1371. doi: 10.3390/molecules22081371.
The 2-Aza-Cope rearrangement of γ-alkenyl nitrones is a rare example of the neutral thermal 2-aza-Cope process that usually takes place with cationic species. During the rearrangement, a redistribution of bonds and electronic density occurs in one kinetic step. However, the introduction of substituents with different steric requirements and electronic features might alter the activation energies and the synchronicity of the reaction. The electron localization function (ELF) analysis and its application to Bonding Evolution Theory (BET) analysis within the context of Molecular Electron Density Theory (MEDT) is an excellent tool to monitor the electron density along the reaction coordinate and thus investigate in detail bond breaking and formation and the corresponding energy barriers. By analyzing topological ELF calculations of seventeen 2-aza-Cope nitrone rearrangements with selected substituents, the main factors influencing the synchronicity of the process were investigated. This MEDT study results revealed that the rearrangement is a non-polar process mostly influenced by steric factors rather than by electronic ones, and confirms the pseudoradical character of the process rather than any pericyclic electron-reorganization.
γ-烯基硝酮的 2-氮杂 Cope 重排是中性热 2-氮杂 Cope 过程的罕见实例，该过程通常发生在阳离子物种中。在重排过程中，键和电子密度在一个动力学步骤中重新分布。然而，引入具有不同空间位阻和电子特性的取代基可能会改变反应的活化能和同步性。电子定域函数（ELF）分析及其在分子电子密度理论（MEDT）背景下的键合演化理论（BET）分析中的应用是监测反应坐标上电子密度的极好工具，从而可以详细研究键的断裂和形成以及相应的能垒。通过对十七个具有选定取代基的 2-氮杂 Cope 硝酮重排的拓扑 ELF 计算进行分析，研究了影响反应同步性的主要因素。这项 MEDT 研究结果表明，该重排是一个非极性过程，主要受空间位阻因素影响，而不是电子因素，并且证实了该过程的拟自由基性质，而不是任何周环电子重组。
