Qing Bin, Yang Zhuang, Wu Zhenwei, Zhang Zichun, Zhou Yuqiao, Yan Xinlong, Liu Yangbin, Feng Xiaoming
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Laboratory of Natural and Targeted Small Molecule Drugs, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
J Am Chem Soc. 2025 Mar 5;147(9):7729-7740. doi: 10.1021/jacs.4c17425. Epub 2025 Jan 27.
The absolute and relative configurations of bioactive chiral molecules are typically relevant to their biological properties. It is thus highly important and desirable to construct all possible stereoisomers of a lead candidate or a given bioactive natural compound. Synergistic dual catalysis has been recognized as a reliable synthetic strategy for a variety of predictable stereodivergent transformations. Despite the impressive progress made in this field, stereodivergent carbon-carbon bond-formation reactions involving stabilized nucleophiles remain elusive. Herein, we report an iridium- and magnesium-catalyzed one-pot sequential allylic alkylation/nucleophilic alkylation cascade process for the stereodivergent synthesis of all four stereoisomers of 3,3'-disubstituted oxindoles through a three-component reaction. A diverse array of products is readily prepared with high functional group compatibility in good yields with excellent diastereo- and enantioselectivities. Subsequently, the stereodivergent total synthesis of four stereoisomers of the spirooxindole alkaloid trigolutes B and D has been accomplished through a concise and unified synthetic route using the same set of starting materials.
具有生物活性的手性分子的绝对构型和相对构型通常与其生物学性质相关。因此，构建先导候选物或特定生物活性天然化合物的所有可能立体异构体是非常重要且必要的。协同双催化已被公认为是用于各种可预测的立体发散转化的可靠合成策略。尽管该领域取得了令人瞩目的进展，但涉及稳定亲核试剂的立体发散碳-碳键形成反应仍然难以实现。在此，我们报道了一种铱和镁催化的一锅法顺序烯丙基烷基化/亲核烷基化串联过程，通过三组分反应立体发散地合成3,3'-二取代氧化吲哚的所有四种立体异构体。通过该方法可以轻松制备出各种产物，具有高官能团兼容性，产率良好，非对映选择性和对映选择性优异。随后，使用同一组起始原料，通过简洁统一的合成路线完成了螺环氧化吲哚生物碱trigolutes B和D的四种立体异构体的立体发散全合成。
