Xi Yang, Xu Youzhi, Fan Linlin, Wang Chenchen, Xia Tingting, Huang Genping, Qu Jingping, Chen Yifeng
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China.
Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, China.
Sci Adv. 2025 May 30;11(22):eadw4471. doi: 10.1126/sciadv.adw4471.
Indoles represent one of the most robust and synthetically versatile classes of heteroaromatic compounds. However, the stereoselective conversion of planar indole rings into three-dimensional indoline skeletons bearing multiple stereogenic centers remains a persistent challenge in organic synthesis. Herein, we describe an intermolecular catalytic asymmetric dearomatization of simple indoles via a palladium-catalyzed three-component cross-coupling reaction. By using readily accessible diazonium salts and aromatic boronic acids as arylative reagents under a ligand-swap strategy, this method enables the efficient construction of 2,3-diarylated indolines. Mechanistic studies reveal that the chiral BiOx ligand governs the highly stereoselective migratory insertion of the aryl-palladium intermediate into the indole's C═C double bond with complete diastereo- and regioselectivity, whereas the achiral fumarate ligand facilitates the reductive elimination step, as corroborated by density functional theory calculations. Furthermore, this protocol is extended to the dearomative diarylation of benzofurans, affording chiral 2,3-dihydrobenzofuran derivatives with high stereocontrol.
吲哚是最稳定且合成用途最广泛的杂环芳烃化合物类别之一。然而,将平面吲哚环立体选择性地转化为带有多个立体中心的三维二氢吲哚骨架,仍然是有机合成中一个长期存在的挑战。在此,我们描述了一种通过钯催化的三组分交叉偶联反应实现简单吲哚分子间催化不对称去芳构化的方法。在配体交换策略下,使用易于获得的重氮盐和芳基硼酸作为芳基化试剂,该方法能够高效构建2,3 - 二芳基二氢吲哚。机理研究表明,手性BiOx配体以完全的非对映和区域选择性控制芳基钯中间体向吲哚C═C双键的高度立体选择性迁移插入,而非手性富马酸酯配体则促进还原消除步骤,密度泛函理论计算证实了这一点。此外,该方案扩展到苯并呋喃的去芳构化二芳基化反应,可提供具有高立体控制的手性2,3 - 二氢苯并呋喃衍生物。