Research Progress on Construction of Medium-Sized Nitrogen/Oxygen Heterocycles Based on Radical Cascade Cyclization Strategy

doi:10.6023/A25120428

Acta Chimica Sinica ›› 2026, Vol. 84 ›› Issue (4): 572-600.DOI: 10.6023/A25120428 Previous Articles Next Articles

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基于自由基串联环化策略构建氮/氧杂中环化合物研究进展

张蒙爱, 靳皓冉, 孙凯^*(), 祝艳平^*(), 王薪^*()

烟台大学药学院山东烟台 264005

投稿日期:2025-12-30 发布日期:2026-01-28
通讯作者: 孙凯, 祝艳平, 王薪
作者简介:
张蒙爱, 女, 烟台大学药学院2024级研究生, 研究方向为有机氟化学、光化学合成、自由基策略构建中环.
靳皓冉, 女, 烟台大学药学院2024级本科生, 研究方向为有机氟化学、自由基策略中环构建.
孙凯, 男, 2020年入职烟台大学, 研究方向为有机硒化学、自由基策略构建中环.
祝艳平, 男, 烟台大学药学院副教授, 研究方向为光化学合成、金属催化碳氢键官能团化.
王薪, 女, 2023年入职烟台大学药学院, 研究方向为光化学合成、有机氟化学.
基金资助:
国家自然科学基金(52303015); 山东省自然科学基金(ZR2023MB135); 山东省自然科学基金(ZR2024QB086); 烟台大学研究生科研创新基金(KGIFYTU2510)

Research Progress on Construction of Medium-Sized Nitrogen/Oxygen Heterocycles Based on Radical Cascade Cyclization Strategy

Mengai Zhang, Haoran Jin, Kai Sun^*(), Yanping Zhu^*(), Xin Wang^*()

School of Pharmacy, Yantai University, Yantai, Shandong 264005, China

Received:2025-12-30 Published:2026-01-28
Contact: Kai Sun, Yanping Zhu, Xin Wang
Supported by:
National Natural Science Foundation of China(52303015); Shandong Provincial Natural Science Foundation(ZR2023MB135); Shandong Provincial Natural Science Foundation(ZR2024QB086); Yantai University Graduate Research Innovation Fund(KGIFYTU2510)

Medium-sized ring (7- to 12-membered) compounds possess unique molecular structures and biological activities. Widely distributed in natural products and pharmaceutically active molecules, they hold an important position in the research of organic chemistry and medicinal chemistry. In addition, in the field of materials science, medium-sized ring compounds offer numerous possibilities for the efficient synthesis of novel functional materials by virtue of their distinctive electronic distribution and spatial configuration. However, due to unfavorable entropic and enthalpic factors, as well as high transannular strain and strong conformational flexibility, the synthesis of medium-sized ring compounds is plagued by problems such as tedious procedures, low yields and poor functional group compatibility, which severely restricts the exploration, development and application of such compounds. Therefore, it is imperative to develop efficient, economical and structurally diverse synthetic strategies for medium-sized ring compounds. In recent years, the construction of medium-sized ring compounds via radical cascade cyclization has achieved considerable progress. This strategy generates highly reactive intermediates through radical pathways to trigger multiple consecutive transformations and forge multiple chemical bonds in one step, thus enabling the efficient synthesis of medium-sized ring compounds. It boasts numerous advantages including concise procedures, green and high efficiency, excellent functional group compatibility, high atom economy, and unique regio- and stereoselectivity, thereby providing a variety of strategies for the construction, development and application of medium-sized ring compounds. This paper summarizes the recent research advances in the synthesis of nitrogen/oxygen-containing medium-sized heterocyclic compounds via the radical cascade cyclization strategy, with a focus on the following two aspects: (1) Separately summarizing the synthetic strategies for 7-membered, 8-membered, and 9- to 12-membered ring compounds; (2) Focusing on the elaboration of the reaction mechanisms, substrate scopes and practical applications of representative reactions. This thesis aims to provide new synthetic insights for the construction of nitrogen/oxygen-containing medium-sized heterocyclic compounds through the radical cascade cyclization strategy and facilitate its applications in the fields of new drug research and development, chemical engineering, materials science and other related areas.

Key words: radical, cascade cyclization, medium-sized ring compounds, catalysis, mechanism study

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Mengai Zhang, Haoran Jin, Kai Sun, Yanping Zhu, Xin Wang. Research Progress on Construction of Medium-Sized Nitrogen/Oxygen Heterocycles Based on Radical Cascade Cyclization Strategy[J]. Acta Chimica Sinica, 2026, 84(4): 572-600.

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Fig. & Tab. 37

Figure 1. Nitrogen/oxygen-containing medium-sized heterocycles in pharmaceuticals and bioactive molecules

Scheme 1. Visible-light-mediated synthesis of polycyclic benzazepine derivatives

Scheme 2. Visible-light redox carbocyclization of alkylidenecyclopropanes

Scheme 3. Photocatalytic intramolecular radical cyclization of alkylidenecyclopropanes linked with α-bromoamides

Scheme 4. Photoinduced intramolecular carbosulfonylation of alkynes

Scheme 5. Photocatalytic synthesis of difluoroalkylated dioxodibenzothiazepines

Scheme 6. Photoinduced cyclization of 1-(allyloxy)-2-(1-arylvinyl)benzenes with sulfonyl chlorides

Scheme 7. Photoinduced three-component difluoroamidosulfonylation/dicyclization reaction

Scheme 8. Photocatalytic difluoromethylation of alkynes

Scheme 9. Photoinduced tandem cyanomethylation/cyclization of arylacetylenes or arylethylenes

Scheme 10. Photocatalytic Dowd-Beckwith radical-polar crossover reaction

Scheme 11. Visible-light-promoted selective sulfonylation and selenation of dienes

Scheme 12. Electrochemical selenylative carbocyclization of biaryl ynones

Scheme 13. Electrocatalytic synthesis of bridged or fused cyclic sulfonamides

Scheme 14. Electroinduced radical 7-endo cyclization of aryl diazonium salts

Scheme 15. Radical cycloaddition of diene compounds

Scheme 16. Potassium persulfate/iodine-promoted electrophilic selenylative cyclization reaction

Scheme 17. Radical tandem silylation/cyclization of 1,7-dienes

Scheme 18. Radical-promoted trifluoromethylthiolation of alkynes

Scheme 19. Radical cycloaddition/sulfonation of propargyl chalcones

Scheme 20. Copper-catalyzed remote-directed isocyanation of unactivated C(sp3)—H bonds

Scheme 21. Manganese-mediated radical addition/cyclization of isocyanides with arylboronic acids/diarylphosphine oxides

Scheme 22. Copper-catalyzed trifluoromethylation of 1,7-dienes

Scheme 23. Sulfonyl radical-induced regioselective cyclization of enamides-alkenes

Scheme 24. Photoinduced 8-/9-endo sulfonylcyclization reaction

Scheme 25. Visible-light-induced synthesis of carbazoloazocan-5-ones

Scheme 26. Chemoselective electrochemical selenocyclization of dienes

Scheme 27. Metal-free aminohalogenation of alkynes under visible-light irradiation

Scheme 28. Radical nitrogen-retaining cyclization of aryl diazonium salts

Scheme 29. Trivalent cobalt-carbene radical-catalyzed synthesis of eight-membered ring compounds

Scheme 30. Iron(III) chloride-catalyzed radical carbon-nitrogen coupling reaction

Scheme 31. Radical-mediated 1,2-formyl/carbonyl difunctionalization of alkenes

Scheme 32. Skeletal rearrangement reaction driven by remote C—C bond cleavage

Scheme 33. Photocatalytic synthesis of medium-ring lactams

Scheme 34. Oximyl trifluoromethylation of unactivated alkenes

Scheme 35. Electrochemical synthesis of fused medium-ring lactams

Scheme 36. Radical tandem trifluoromethylthiolation/cyclization of dienes

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基于自由基串联环化策略构建氮/氧杂中环化合物研究进展

Research Progress on Construction of Medium-Sized Nitrogen/Oxygen Heterocycles Based on Radical Cascade Cyclization Strategy

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