一个由德国明斯特大学Frank Glorius带领的国际合作小组的一项最新研究，发展了双环氮杂芳烃与烯烃的光化学分子间去芳香性环加成反应。该研究于2021年3月26日发表于国际一流学术期刊《科学》杂志上。

研究人员揭示了一个能量转移介导的、高度区域和非对映选择性的、发生在双环氮杂芳烃和各种电子特性的烯烃间的分子间[4 + 2]去芳香性环加成反应。该方法绕开了常见的反应性和选择性问题，从而提供了以前难以获得或需要大量的合成努力方可获得的各种桥联多环化合物。

进一步密度泛函理论的计算研究阐明了机理，并解释了观测到的区域选择性和非对映选择性的起源。

据悉，去芳香性环加成反应是将平面芳烃转化为三维构型的一种理想手段，近年来在药物化学中越来越受到重视。喹啉类、异喹啉类和喹唑啉类虽然含有潜在的二烯和烯烃部分，但由于芳香体系固有的低反应活性和选择性，很少应用于环加成反应。

附：英文原文

Title: Photochemical intermolecular dearomative cycloaddition of bicyclic azaarenes with alkenes

Author: Jiajia Ma, Shuming Chen, Peter Bellotti, Renyu Guo, Felix Schfer, Arne Heusler, Xiaolong Zhang, Constantin Daniliuc, M. Kevin Brown, Kendall N. Houk, Frank Glorius

Issue&Volume: 2021/03/26

Abstract: Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges. Here, we disclose an energy transfer–mediated, highly regio- and diastereoselective intermolecular [4 + 2] dearomative cycloaddition reaction of these bicyclic azaarenes with a plethora of electronically diverse alkenes. This approach bypasses the general reactivity and selectivity issues, thereby providing various bridged polycycles that previously have been inaccessible or required elaborate synthetic efforts. Computational studies with density functional theory elucidate the mechanism and origins of the observed regio- and diastereoselectivities.

DOI: 10.1126/science.abg0720

Source: https://science.sciencemag.org/content/371/6536/1338