化学学报 ›› 2024, Vol. 82 ›› Issue (6): 641-657.DOI: 10.6023/A24030094 上一篇    下一篇

综述

有机催化吲哚碳环官能团化研究进展

郑灏宁, 刘金宇*()   

  1. 成都理工大学材料与化学化工学院 成都 610059
  • 投稿日期:2024-03-20 发布日期:2024-05-06
  • 作者简介:

    刘金宇, 副教授. 主要从事串联反应、不对称有机催化、杂环化合物的合成、轴手性化合物的合成、氨基酸衍生物的合成工艺改进等方面的研究工作. 现工作于成都理工大学材料与化学化工学院(锂资源与锂电产业学院).

Research Progress on Organocatalytic Functionalization of Indole in the Carbocyclic Ring

Haoning Zheng, Jinyu Liu*()   

  1. College of Materials and Chemistry & Chemical Engineering, Chengdu University of Technology, Chengdu 610059
  • Received:2024-03-20 Published:2024-05-06
  • Contact: * E-mail: liujinyu19@cdut.edu.cn

吲哚骨架在药物分子、生物活性分子和天然产物中普遍存在, 因而引起合成化学家的广泛关注. 由于吲哚骨架的电子云密度特性, 使其反应位点多集中于五元杂环, 这也令吲哚骨架的合成与修饰也大多被焦聚在吡咯环. 吲哚碳环反应活性较低, 因而官能团化研究相对较少. 近几十年, 随着过渡金属领域的发展, 尤其是碳氢活化策略的提出, 吲哚碳环官能团化策略得到了一定的发展. 有机催化相比于过渡金属催化, 虽然在催化活性与底物使用范围上受限, 但也因为其在手性控制、成本和操作性上的优势, 被研究者们应用于吲哚碳环的官能团化, 并取得了迅速的发展. 重点综述了利用有机催化剂实现吲哚碳环官能团化的研究成果.

关键词: 吲哚碳环官能团化, 有机催化, 不对称合成, 串联反应, 轴手性

The indole skeletons have been extensively utilized due to their significant potential and broad applications as pharmaceutical agents, synthetic scaffolds, and chelating agents. Additionally, numerous natural products exhibiting biological activities or medicinal properties encompass the indole scaffold. Therefore, there is a growing focus on the synthesis and modification of indole derivatives, particularly on the asymmetric catalytic functionalization of indole scaffolds. The characteristics of electron cloud distribution in indole framework have led to a predominant focus on the functionalization of indole within the five-membered azole ring, particularly at C-3, C-2, and N-1 positions. In light of this observation, the focus of research on the synthesis and alteration of the indole backbone primarily centers on the azole ring. The functionalization of the indole in the carbocyclic ring is relatively uncommon, primarily attributed to its lower reactivity. Over the past decades, advancements in transition-metal catalysis, particularly the introduction of C—H activation strategy, have led to the development of various methods for achieving C—H functionalization of indoles within the carbocyclic ring. However, these approaches often necessitated the incorporation of directing or blocking groups in the azole ring, the application of harsh reaction conditions, or the utilization of transition metals as catalysts. In comparison to well-established metal catalysis, organocatalysis exhibits certain inherent limitations, including low catalytic activity, the requirement for high catalyst dosages, and moderate tolerance levels. However, these limitations have not hindered organocatalysis from emerging as a prominent method for functionalizing indole in the carbocyclic ring. This is attributed to its potential cost savings, time efficiency, energy conservation, simplified experimental procedures, excellent ability on control of chirality and reduced chemical waste generation. In this review, the functionalization strategy of indole in the carbocyclic ring through organocatalysis has been outlined. This strategy encompasses modifications at C-4, C-5, C-6, and C-7 positions, offering a novel avenue for the creation and advancement of techniques for organocatalytic functionalization of indole in the carbocyclic ring.

Key words: functionalization of indole in the carbocyclic ring, organocatalysis, asymmetric synthesis, cascade reaction, axial chirality