氮杂吲哚啉及其衍生物的合成研究进展

doi:10.6023/cjoc202308025

摘要/Abstract

氮杂吲哚啉骨架广泛存在于多种生物活性分子和天然产物中, 有着显著的生物和药理活性, 受到了合成化学家的广泛关注. 然而, 由于氮原子所在吡啶环上的缺电子特性, 许多传统用于合成吲哚啉的方法不能有效构建氮杂吲哚啉骨架. 近年来, 化学工作者一直致力于探索氮杂吲哚啉骨架的合成并取得了一些进展. 根据反应类型的不同, 对近年来合成氮杂吲哚啉类化合物的反应及关键反应机理进行了综述和探讨, 并展望了该研究领域的未来发展前景.

关键词: 氮杂吲哚啉, 合成, 催化反应

The azaindoline skeleton exists in a wide range of bioactive molecules and natural products, and has significant biological and pharmaceutical activities. The synthesis of these compounds has attracted great attention from chemists. However, due to the electron-deficient nature of the pyridine ring where the nitrogen atom is located, many traditional methods for the synthesis of indoline cannot effectively construct the azaindoline skeleton. In recent years, chemists have been exploring the synthesis of azaindoline skeleton and have made some progress. According to the different reaction types, the synthesis of azaindolines in recent years and the key reaction mechanisms are reviewed and discussed, and the future development prospect of this research field is prospected.

Key words: azaindoline, synthesis, catalytic reaction

引用此文

叶浩, 张海滨, 吴亚男, 吴新星. 氮杂吲哚啉及其衍生物的合成研究进展[J]. 有机化学, 2024, 44(4): 1106-1123.

Hao Ye, Haibin Zhang, Ya'nan Wu, Xinxing Wu. Research Progress in the Synthesis of Azaindoline and Its Derivatives[J]. Chinese Journal of Organic Chemistry, 2024, 44(4): 1106-1123.

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图/表 34

图1. 含有氮杂吲哚啉骨架的生物活性分子

Figure 1. Azaindoline-containing bioactive molecules

图式1. 基于烯丙基钯中间体合成氮杂吲哚啉骨架

Scheme 1. Synthesis of azaindoline skeleton based on allylpalladium intermediate

图式2. 钯催化三组分反应合成氮杂吲哚啉骨架

Scheme 2. Synthesis of azaindoline skeleton by palladium-cata- lyzed three-component reaction

图式3. 钯催化C(sp3)—H活化反应合成氮杂吲哚啉骨架

Scheme 3. Synthesis of azaindoline skeleton by palladium-cata- lyzed C(sp3)—H activation reaction

图式4. 钯催化Heck环化/Suzuki偶联合成氮杂吲哚啉

Scheme 4. Palladium-catalyzed Heck cyclization/Suzuki coupling to synthesize azaindoline

图式5. 钯催化Heck环化/Sonogashira偶联合成氮杂吲哚啉

Scheme 5. Palladium-catalyzed Heck cyclization/Sonogashira coupling for the synthesis of azaindoline

图式6. 钯催化Heck环化/芳酚的去芳构螺环化合成氮杂吲哚啉

Scheme 6. Palladium-catalyzed Heck cyclization/dearomatization spirocyclization of phenol for the synthesis of azaindoline

图式7. 钯催化Heck环化/Hiyama偶联合成氮杂吲哚啉

Scheme 7. Palladium-catalyzed Heck cyclization/Hiyama coupling for the synthesis of azaindoline

图式8. 钯催化Heck环化/CO插入反应合成氮杂吲哚啉

Scheme 8. Palladium-catalyzed Heck cyclization/insertion of CO for the synthesis of azaindoline

图式9. 钯催化Heck环化/CO插入反应合成呋喃氮杂吲哚啉

Scheme 9. Palladium-catalyzed Heck cyclization/the insertion of CO for the synthesis of furoazaindoline

图式10. 钯催化分子内去芳构Heck环化合成氮杂吲哚酮

Scheme 10. Palladium-catalyzed intramolecular dearomative Heck cyclization for the synthesis of azaindolone

图式11. 钯催化3-硝基氮杂吲哚的去芳构甲氧基化/烯丙基化反应

Scheme 11. Palladium-catalyzed dearomative methoxyallylation of 3-nitroazaindole

图式12. 铁催化强C(sp3)—H键的胺化反应合成氮杂吲哚啉

Scheme 12. Iron-catalyzed amination of strong C(sp3)—H bonds to synthesize azaindoline

图式13. 钛催化环氧化合物开环环化合成氮杂吲哚啉

Scheme 13. Titanocene catalyzed epoxide-opening annulation to synthesize azaindoline

图式14. 钇催化官能化吡啶的C—H环化反应合成氮杂吲哚啉

Scheme 14. Yttrium-catalyzed synthesis of azaindolines via C—H cyclization of functionalized pyridines

图式15. 钇催化官能化吡啶的C—H环化反应机理

Scheme 15. Mechanism for yttrium-catalyzed C—H cyclization of functionalized pyridines

图式16. 无金属参与的多步反应合成氮杂吲哚啉

Scheme 16. Synthesis of azaindoline by multi-step reaction without metal catalyst

图式17. 自由基环化反应合成氮杂吲哚啉

Scheme 17. Synthesis of azaindoline by radical cyclization

图式18. 导向的邻位金属化/转金属化合成氮杂吲哚啉

Scheme 18. Synthesis of azaindoline by directed ortho-metal- lation/transmetallation approach

图式19. 自由基环化反应合成氮杂吲哚啉

Scheme 19. A free radical cyclizations for the synthesis of azaindoline

图式20. 三组分反应合成6-氮杂吲哚啉和它的三环衍生物

Scheme 20. Three-component synthesis of 6-azaindolines and its tricyclic derivatives

图式21. 基于“卤舞”过程合成碘代氮杂吲哚啉

Scheme 21. Synthesis of iodoazaindoline through the “halogen dance” process

图式22. 通过碳锂化反应制备氮杂吲哚啉

Scheme 22. Preparation of the isomeric azaindolines by intramolecular carbolithiation reaction

图式23. 通过自由基取代反应合成多氟5-氮杂吲哚啉

Scheme 23. Synthesis of polyfluorinated 5-azaindolines by free radical substitution reaction

图式24. 通过自由基取代反应合成多氟7-氮杂吲哚啉

Scheme 24. Synthesis of polyfluorinated 7-azaindolines by free radical substitution reaction

图式25. 酸性介质中分子内环化合成2,2-二取代氮杂吲哚啉

Scheme 25. Synthesis of 2,2-disubstituted azaindolines by intramolecular cyclization in acidic media

图式26. 氨基磺酸酯开环合成氮杂吲哚啉骨架

Scheme 26. Synthesis of azaindolines by the ring-opening of sulfamidates

图式27. 乙烯基吡啶胺分子间/内环缩合制备四种氮杂吲哚啉分子

Scheme 27. Synthesis of four azaindoline families by inter-/intramolecular annulative diamination of vinylpyridines

图式28. 氧化还原反应合成氮杂吲哚啉

Scheme 28. Synthesis of azaindoline by redox reaction

图式29. 阳离子导向环化不对称合成4-和6-氮杂吲哚啉

Scheme 29. Enantioselective synthesis of 4- and 6-azaindolines by a cation-directed cyclization

图式30. Fischer氮杂环化反应合成氮杂吲哚啉

Scheme 30. Synthesis of azaindoline by Fischer azaindolization reaction

图式31. 分子内Mannich反应相转移催化法合成4-氮杂吲哚啉

Scheme 31. Synthesis of 4-azaindolines using phase-transfer catalysis via an intramolecular Mannich reaction

图式32. 杂环-2,3-稠合氮杂吲哚啉衍生物的合成

Scheme 32. Syntheses of heterocycle-2,3-fused azaindoline derivatives

图式33. 2-氟-3-甲基吡啶与醛的串联反应合成7-氮杂吲哚啉

Scheme 33. Synthesis of 7-azaindoline through domino reactions of 2-fluoro-3-methylpyridine and aldehydes

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