Lin Wenhua, Alix Aurélien, Guillot Régis, Gandon Vincent, Bour Christophe
Institut de Chimie Moléculaire et des Matériaux d'Orsay, CNRS UMR 8182, Université Paris-Saclay, 17 Avenue des Sciences, 91400 Orsay, France.
Org Lett. 2024 Apr 19;26(15):3267-3272. doi: 10.1021/acs.orglett.4c00889. Epub 2024 Apr 4.
This study addresses the challenges associated with vinyl cation generation, a process that traditionally requires quite specific counterions. Described herein is a novel intramolecular vinylation of arenes catalyzed by aluminum(III) chloride, utilizing practical conditions and readily available vinyl triflates derived from 2-aceto-3-arylpropionates. Comprehensive experimental data support diverse carbocycle synthesis, exemplified by indenes and higher analogues. Control experiments verify the applicability of the vinylation protocol, and synthetic applications showcase a potent tubulin polymerization inhibitor with anticancer properties. Density functional theory computations reveal a Lewis-acid-driven mechanism involving triflate moiety abstraction to generate a reactive vinyl cation.
本研究探讨了与乙烯基阳离子生成相关的挑战，这一过程传统上需要相当特殊的抗衡离子。本文描述了一种由氯化铝催化的芳烃新型分子内乙烯基化反应，该反应利用了实际可行的条件以及由2-乙酰基-3-芳基丙酸酯衍生而来的易于获得的乙烯基三氟甲磺酸酯。全面的实验数据支持了多种碳环的合成，茚及其高级类似物即为例证。对照实验验证了乙烯基化反应方案的适用性，合成应用展示了一种具有抗癌特性的高效微管蛋白聚合抑制剂。密度泛函理论计算揭示了一种由路易斯酸驱动的机制，该机制涉及三氟甲磺酸酯部分的脱离以生成活性乙烯基阳离子。
