吲哚及其衍生物C2—C3键断裂的反应研究进展

doi:10.6023/cjoccjoc202203014

摘要/Abstract

吲哚结构单元广泛地存在于许多重要的天然产物和药物分子中, 被誉为药物活性结构中的明星分子. 鉴于吲哚系分子在临床治疗和药物研发领域的突出价值, 吲哚分子的高效构建、合成转化以及结构后期修饰一直是有机合成领域经久不衰的研究热点. 近年来, 吲哚及其衍生物C2—C3键断裂及重构串联反应在复杂分子构建以及药物分子合成方面发挥了重要作用, 吸引了化学工作者们广泛的研究兴趣. 系统总结了近年来吲哚及其衍生物参与的C2—C3键断裂/重构反应的研究进展, 并对相应的反应策略、底物适用范围和机理进行详细阐述.

关键词: 吲哚, 吲哚衍生物, C2—C3键断裂, 反应机理

Indole building blocks widely exist in many important natural products and drug molecules, and are known as star molecules in bioactive drugs. In view of the outstanding value of indole-based molecules in the field of clinical treatment and drug development, the efficient construction, synthetic transformation and late-stage modification of indole molecules has been an enduring research hotspot in the field of organic synthesis. In recent years, the C2—C3 bond cleavage and reconstruction of indoles have played an important role in the construction of complex molecules and the synthesis of drug molecules, attracting extensive research interests from chemists. This paper systematically summarizes the research progress of C2—C3 bond cleavage/reconstruction reactions of indole and its derivatives in recent years with particular emphasis on reaction strategies, substrate scope and mechanisms.

Key words: indole, indole derivatives, cleavage of C2—C3 bond, reaction mechanism

引用此文

黄泽鑫, 尹宇强, 贾丰成, 吴安心. 吲哚及其衍生物C2—C3键断裂的反应研究进展[J]. 有机化学, 2022, 42(7): 2028-2044.

Zexin Huang, Yuqiang Yin, Fengcheng Jia, Anxin Wu. Research Progress on C2—C3 Bond Cleavage of Indole and Its Derivatives[J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2028-2044.

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图/表 33

图式1. 钯催化吲哚和炔参与的扩环反应

Scheme 1. Palladium-catalyzed ring-expansion reaction of indoles with alkynes

图式2. 铜催化3-二烯基吲哚的氧化扩环反应

Scheme 2. Copper-catalyzed oxidative ring-expansion reaction of 3-dienylindoles

图式3. 吲哚和丁炔二酸酯参与的扩环反应

Scheme 3. Ring-expansion reaction of indoles with 2-butynedioates

图式4. 2-芳基吲哚氧化扩环反应合成2-芳基苯并噁嗪酮

Scheme 4. Oxidative ring-expanding reaction of 2-arylindoles for synthesis of 2-arylbenzoxazinones

图式5. 铜催化2-芳基吲哚和胺参与的需氧氧化扩环反应

Scheme 5. Copper-catalyzed aerobic oxidative ring-expanding reaction of 2?arylindoles with amines

图式6. 基于1H-吲哚C2—C3键切断的氧化环化合成2 -吲哚基苯并噁嗪酮类化合物

Scheme 6. Oxidative recyclization of 1H?indoles for synthesis of 2?indolylbenzoxazinones via cleavage of the C2-C3 bond

图式7. 铜催化2-芳基吲哚和脒盐参与的需氧氧化扩环反应构建八元氮杂环

Scheme 7. Copper-catalyzed construction of eight-membered rings via oxidative ring-expanding reaction of indoles with amidines

图式8. 可见光诱导的2-芳基吲哚和脒盐参与的氧化扩环反应

Scheme 8. Visible-light-induced oxidative ring expansion of indoles with amidines

图式9. 铜/氧促进的2-芳基吲哚和烯胺酮参与的氧化扩环反应

Scheme 9. Copper-catalyzed oxidative ring expansion of indoles and enaminone analogues

图式10. 可见光诱导吲哚衍生物参与的氧化扩环反应

Scheme 10. Visible light-induced aerobic oxidative ring expansion of indole derivatives

图式11. 铜催化的2-芳基吲哚与TMSN3的级联二叠氮化和扩环反应

Scheme 11. Copper-catalyzed diazidation and ring expansion cascade of 2-arylindoles with TMSN3

图式12. 利用亚硝酸丁酯诱导的亚硝化反应和三价铁促进的 C—C键断裂合成2-氨基苯甲腈类化合物

Scheme 12. Synthesis of 2?aminobenzonitriles through tert-butylnitrite (TBN)-mediated nitrosation reaction and sequential Iron(III)-catalyzed C—C bond cleavage of 2?arylindoles

图式13. 3-甲基吲哚与伯胺的选择性氧化裂解合成喹唑啉酮

Scheme 13. Selective oxidative cleavage of 3?methylindoles with primary amines a?ording quinazolinones

图式14. 极性溶剂下双氧水诱导的吲哚氧化断键

Scheme 14. Oxidative cleavage of indoles mediated by H2O2 in polar solvents

图式15. 2-吲哚酮C2—C3键插炔反应

Scheme 15. Aryne insertion into C2—C3 bond of indolin-2- ones

图式16. 碱促进的2-吲哚酮和炔参与的扩环反应

Scheme 16. Base-promoted ring expansion reaction of indolin- 2-ones with alkynyl ketones

图式17. 氧化吲哚衍生物氧化碎片化/骨架重排

Scheme 17. Oxidative fragmentations and skeletal rearrangements of oxindole derivatives

图式18. 3,3-二叠氮氧化吲哚参与的C—C键断键/重组

Scheme 18. 3,3-Diazidooxindole-involved C—C bond cleavage/reorganization

图式19. 过氧化吲哚-2-酮参与的氧化碎片化/骨架重排

Scheme 19. Oxidative fragmentation and skeletal rearrangement of peroxyoxindole

图式20. 氧气主导的2-吲哚酮C2—C3键断裂反应

Scheme 20. Oxygen-dominated C2—C3 bond cleavage of indolin-2-ones

图式21. 氧气主导的2-吲哚酮C2—C3键断裂反应

Scheme 21. Oxygen-dominated C2—C3 bond cleavage of indolin-2-ones

图式22. 涉及1,5-σ迁移螺环吲哚酮的扩环反应

Scheme 22. Ring expansion reaction of spirocyclic indolones involving 1,5-sigmatropic rearrangement

图式23. TBHP介导靛红和脒盐参与的氧化扩环反应

Scheme 23. TBHP-mediated oxidative ring expansion of isatins and amidine hydrochlorides

图式24. TBHP促进的串联氧化环化/中断Dimroth重排反应

Scheme 24. TBHP-promoted cascade oxidative cyclization and interrupted dimroth rearrangement

图式25. TBHP介导的靛红氧化扩环反应构建喹诺酮

Scheme 25. TBHP-mediated oxidative ring expansion of isatin to construct quinolones

图式26. 氧气促进的靛红和邻苯二胺参与的氧化扩环反应反应

Scheme 26. O2-promoted oxidative ring expansion of isatins and o-phenylene diamines

图式27. TBHP/TFA促进的靛红和四氢异喹啉参与的氧化环化反应

Scheme 27. TBHP/TFA promoted oxidative cyclization of isatins with 1,2,3,4-tetrahydroisoquinolines

图式28. 铜催化的N-吡啶基取代靛红参与的去羰基偶联反应

Scheme 28. Copper-catalyzed decarbonylation coupling of N-pyridyl-substituted isatins

图式29. 铜催化靛红和芳基酮酸参与的脱羧偶联反应

Scheme 29. Copper-catalyzed decarboxylative coupling reactions of isatins with arylglyoxylic acids

图式30. 铁催化的靛红和三氟乙酰亚氨基酰氯参与的串联反应

Scheme 30. Iron-catalyzed domino reaction of isatins and trifluoroacetimidoyl chlorides

图式31. 铜催化N-芳基取代靛红的脱羰基偶联反应

Scheme 31. Copper-catalyzed decarbonylation coupling of N-aryl substituted isatins

图式32. Et3N促进靛红相关的三组分串联环化反应

Scheme 32. Et3N-promoted three-component tandem cyclization related to isatins

图式33. p-TSA促进靛红相关的的三组分串联环化反应

Scheme 33. p-TSA-promoted three-component tandem cyclization related to isatins

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