Yu Lemao, Cai Ruonan, Lv Lujing, Dong Huaping, Xu Yingjie, Zhang Qiang, Shen Runpu
College of Chemical & Biological Engineering, Zhejiang University, Hangzhou 310018, China.
Zhejiang Engineering Research Center of Fat-Soluble Vitamin, Shaoxing 312000, China.
Org Biomol Chem. 2025 Jan 22;23(4):774-792. doi: 10.1039/d4ob01692k.
The oxidative C2-C3 π bond activation strategy is the most efficient tool to synthesize oxygen-containing indoline, which frequently appears in natural products with various biological activities as structural units. Recently, the oxidation-induced cascade strategy through oxygenation activation of the indolic C2-C3 π bond of indoles has received much attention for its use in efficiently establishing complex indoline with oxygen-containing molecular architectures, and holds tremendous potential in the total synthesis of indole alkaloids. It can be carried out using potential activated indole radical cations or imine cation intermediates produced oxidative C2-C3 π bond activation of indole with various nucleophiles or ring-forming reagents by employing simple and non-decorated indoles as starting substrates. Herein, we have reviewed recent advances in the oxidation-induced cascade strategies connecting intra-cyclization or inter-annulation reactions, nucleophilic or radical additions and rearrangement the oxidative C2-C3 π bond activation of indoles over the past two decades, providing diverse oxygen-containing indolines such as indoxyls, indoline oxygen-heterocycles and indolones. The features and mechanisms of different types of oxidation-induced cascade reactions have been summarized and represented, and examples have been given of their asymmetric reactions and applications in the total synthesis of indole alkaloids.
氧化C2-C3 π键活化策略是合成含氧化吲哚啉最有效的方法，含氧化吲哚啉作为结构单元频繁出现在具有各种生物活性的天然产物中。最近，通过吲哚的吲哚C2-C3 π键的氧合活化进行的氧化诱导级联策略因其在高效构建具有含氧分子结构的复杂吲哚啉方面的应用而备受关注，并且在吲哚生物碱的全合成中具有巨大潜力。它可以通过使用简单且未修饰的吲哚作为起始底物，利用各种亲核试剂或成环试剂对吲哚进行氧化C2-C3 π键活化产生的潜在活化吲哚自由基阳离子或亚胺阳离子中间体来实现。在此，我们综述了过去二十年来在连接环内环化或环间环化反应、亲核或自由基加成以及重排与吲哚的氧化C2-C3 π键活化的氧化诱导级联策略方面的最新进展，提供了多种含氧化吲哚啉，如吲哚酚、吲哚啉氧杂环和吲哚酮。总结并阐述了不同类型氧化诱导级联反应的特点和机理，并给出了它们的不对称反应以及在吲哚生物碱全合成中的应用实例。
