基于α-氢迁移策略构建杂环骨架的研究进展

doi:10.6023/cjoc202212036

摘要/Abstract

杂环化合物的高效构建是有机合成领域的重要课题, [m＋n]环化反应可将两个相对简单易得的反应底物进行组合, 是构建环状骨架的重要手段. 基于负氢迁移策略的[m＋n]环化反应将两个相对易得的底物原位生成负氢受体, 避免反应底物的预制, 具有高的原子和步骤经济性. 选取基于负氢迁移策略的[m＋n]环化反应为研究对象, 从通过该类反应所构建的氮杂、氧杂环骨架着手, 按照生成氮杂、氧杂环的大小进行分类, 综述了2018年以来基于负氢迁移策略的[m＋n]环化反应的研究进展, 并对该领域的发展方向进行了展望.

关键词: 杂环化合物, 负氢迁移策略, [m＋n]环化反应

The efficient construction of heterocyclic compounds is an important topic in the field of organic synthesis. [m＋n] cyclization reaction can form privilege molecules from the combination of two readily available reaction substrates, which is an important means for construction of cyclic skeletons. The [m＋n] cyclization reaction based on hydride transfer strategy can in situ generate hydride acceptor from two relatively simple substrates, avoiding the prefabrication of reaction substrates, which features high atom and step economy. In this review, the [m＋n] cyclization reactions based on hydride transfer strategy are selected as the research object. Starting from the framework of aza- and oxa-heterocycles constructed by this kind of reaction, this review is classified according to the size of the generated aza- and oxa-heterocycles. The recent progress of [m＋n] cyclization based on hydride transfer strategy since 2018 is summarized, and the development of this field is also prospected.

Key words: heterocyclic compounds, hydride-transfer strategy, [m＋n] cyclization

引用此文

陈玉琢, 孙红梅, 王亮, 胡方芝, 李帅帅. 基于α-氢迁移策略构建杂环骨架的研究进展[J]. 有机化学, 2023, 43(7): 2323-2337.

Yuzhuo Chen, Hongmei Sun, Liang Wang, Fangzhi Hu, Shuaishuai Li. Research Progress on Construction of Heterocyclic Skeletons Based on α-Hydride Transfer Strategy[J]. Chinese Journal of Organic Chemistry, 2023, 43(7): 2323-2337.

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图/表 19

图式1. 负氢迁移/环化策略高效构建杂环骨架

Scheme 1. Highly efficient construction of heterocycles via hydride transfer/cyclization strategy

图式2. 基于负氢迁移策略的形式上[5＋1]环化反应

Scheme 2. Formal [5＋1] cyclization via hydride transfer strategy

图式3. 2-甲基假吲哚为一碳合成子的形式上[5＋1]环化反应

Scheme 3. Formal [5＋1] cyclization with 2-methylindolenines as one-atom carbon synthons

图式4. α-甲基环状磺酰亚胺为一碳合成子的形式上[5＋1]环化反应

Scheme 4. Formal [5＋1] cyclization with α-methyl-N-sulfonyl imines as one-atom carbon synthons

图式5. 2-(1-苯基亚乙基)丙二腈为一碳合成子的形式上[5＋1]环化反应

Scheme 5. Formal [5＋1] cyclization with 2-(1-phenylethylidene)malononitriles as one-atom carbon synthons

图式6. 4-羟基香豆素为一碳合成子的形式上[5＋1]环化反应

Scheme 6. Formal [5＋1] cyclization with 4-hydroxycoumarin as one-atom carbon synthon

图式7. 氨基酸的氮为一氮合成子的形式上[5＋1]环化反应

Scheme 7. Formal [5＋1] cyclization with the nitrogen of amino acids as one-atom nitrogen synthons

图式8. 氧化吲哚为一碳合成子的形式上[5＋1]环化反应

Scheme 8. Formal [5＋1] cyclization with oxindoles as one-atom carbon synthons

图式9. 含有活泼亚甲基的开链亲核试剂为一碳合成子的形式上[5＋1]环化反应

Scheme 9. Formal [5＋1] cyclization with acyclic nucleophiles with active methylene as one-atom carbon synthons

图式10. 4-胺基靛红为五元合成子的形式上[5＋1]环化反应

Scheme 10. Formal [5＋1] cyclization with C4-amine-substituted isatins as five-atom synthons

图式11. 富电子酚为一碳合成子的形式上[5＋1]去芳香化-环化

Scheme 11. Formal [5＋1] dearomatization-cyclization with electron-rich phenols as one-atom carbon synthons

图式12. 4-羟基吲哚为一碳合成子的形式上[5＋1]去芳香化-环化

Scheme 12. Formal [5＋1] dearomatization-cyclization with 4-hydroxyindoles as one-atom carbon synthons

图式13. O-烷基取代邻氧苯甲醛为五元合成子的形式上[5＋1]去芳香化-环化

Scheme 13. Formal [5＋1] dearomatization-cyclization with O-alkyl ortho-oxybenzaldehydes as five-atom synthons

图式14. 含七元氮杂环结构的代表性药物分子

Scheme 14. Representative pharmaceutical molecules containing seven-membered aza-heterocycles

图式15. 氨基丙二酸酯为二元合成子的形式上[5＋2]环化

Scheme 15. Formal [5＋2] cyclization with aminomalonate as two-atom synthons

图式16. 3-取代吲哚为二元合成子的形式上[5＋2]环化

Scheme 16. Formal [5＋2] cyclization with 3-substituted indoles as two-atom synthons

图式17. 吲哚为二元碳合成子的形式上[5＋2]环化

Scheme 17. Formal [5＋2] cyclization with indoles as two-atom carbon synthons

图式18. 靛红为一碳合成子的形式上[6＋1]环化

Scheme 18. Formal [6＋1] cyclization with isatins as one-atom carbon synthons

图式19. 负氢迁移策略在喹啉酮构建中的应用

Scheme 19. Application of hydride transfer strategy in construction of quinolinone

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