Portela Susana, Fernández Israel
Departamento de Química Orgánica I and Centro de Innovación en Química Avanzada (ORFEO-CINQA), Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
J Org Chem. 2022 Jul 15;87(14):9307-9315. doi: 10.1021/acs.joc.2c01035. Epub 2022 Jul 6.
The poorly understood factors controlling the catalysis and selectivity in Lewis acid-promoted Diels-Alder cycloaddition reactions involving vinylazaarenes as dienophiles have been quantitatively explored in detail by means of computational methods. With the help of the activation strain model and the energy decomposition analysis methods, it is found that the remarkable acceleration induced by the catalysis is mainly due to a significant reduction of the Pauli repulsion between the key occupied π-molecular orbitals of the reactants and not due to the proposed stabilization of the lowest unoccupied molecular orbital (LUMO) of the dienophile. This computational approach has also been helpful to understand the reasons behind the extraordinary regio- and diastereoselectivity observed experimentally. The insight gained in this work allows us to predict even more reactive vinylazaarene dienophiles, which may be useful in organic synthesis.
通过计算方法，对在以乙烯基氮杂芳烃作为亲双烯体的路易斯酸促进的狄尔斯-阿尔德环加成反应中，控制催化作用和选择性的鲜为人知的因素进行了详细的定量研究。借助活化应变模型和能量分解分析方法，发现催化作用引起的显著加速主要是由于反应物关键占据π分子轨道之间的泡利排斥力显著降低，而不是由于所提出的亲双烯体最低未占据分子轨道（LUMO）的稳定化。这种计算方法也有助于理解实验中观察到的异常区域和非对映选择性背后的原因。这项工作中获得的见解使我们能够预测更具反应性的乙烯基氮杂芳烃亲双烯体，这在有机合成中可能是有用的。
