Recent Advances on the Synthesis of Spirofluorene-Based Compounds

doi:10.6023/cjoc202507025

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (3): 817-839.DOI: 10.6023/cjoc202507025 Previous Articles Next Articles

REVIEWS

螺芴基化合物的合成研究进展

韦翠, 刘金秋, 邓灿, 邹宁^*(), 周文俊^*()

内江师范学院化学与环境工程学院沱江流域特色农业资源四川省科技资源共享服务平台沱江流域特色农业资源四川省科技资源共享服务平台四川内江 641100

收稿日期:2025-07-19 修回日期:2025-10-26 发布日期:2025-11-19
通讯作者: 邹宁, 周文俊
基金资助:
四川省自然科学基金(2024NSFSC1127); 四川省自然科学基金(2024NSFSC0284); 精细化工助剂及表明活性剂四川省高校重点实验室开放基金(2024JXY06); 内江师范学院校级科研重点项目(2024ZDZ01); 及大学生创新创业训练计划(X2024014)

Recent Advances on the Synthesis of Spirofluorene-Based Compounds

Cui Wei, Jinqiu Liu, Can Deng, Ning Zou^*(), Wenjun Zhou^*()

Special Agricultural Resources in Tuojiang River Basin Sharing and Service Platform of Sichuan Province, School of Chemical and Environmental Engineering, Neijiang Normal University, Neijiang, Sichuan 641100

Received:2025-07-19 Revised:2025-10-26 Published:2025-11-19
Contact: Ning Zou, Wenjun Zhou
Supported by:
Natural Science Foundation of Sichuan Province(2024NSFSC1127); Natural Science Foundation of Sichuan Province(2024NSFSC0284); Open Fund of Key Laboratory of Fine Chemical Additives and Surfactants, Sichuan Provincial Universities(2024JXY06); Key Research Project of Neijiang Normal University(2024ZDZ01); Innovation and Entrepreneurship Training Program(X2024014)

Spirofluorene-based skeletons, widely found in biologically active molecules and various functional materials, represent a privileged scaffold in pharmaceutical and optoelectronic design due to their unique rigidity and stability, which lead to improve device luminescence efficiency, thermal stability and chemical stability. Nevertheless, the efficient synthesis of these compounds remains challenging owing to the steric hindrance and rigidity inherent to their spirocyclic architecture. New strategies and methods developed over the past decade for the synthesis of spirofluorene-based compounds, including cyclization, cycloaddition, and C—H activation reactions, are reviewed, aiming to provide insights for the efficient preparation of related structures.

Key words: spirofluorene-based compound, spirocyclic compound, cycloaddition, cyclization, C—H activation

Cite this article

Cui Wei, Jinqiu Liu, Can Deng, Ning Zou, Wenjun Zhou. Recent Advances on the Synthesis of Spirofluorene-Based Compounds[J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 817-839.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 44

Figure 1. Biologically active molecules and organic functional materials containing fluorene-based spirocyclic skeletons

Scheme 1. Nucleophilic addition/intramolecular spirocyclization cascade reaction to construct spirobifluorenes

Scheme 2. Iridium(III)-catalyzed diarylation/annulation cascade reaction to construct spirobifluorenes

Scheme 3. Rhodium-catalyzed enantioselective synthesis of helical dispirodihydro[2,1-c]indenofluorene derivatives

Scheme 4. FeCl3-mediated oxidative spirocyclization to form fluorene-based spirocyclic compounds

Scheme 5. Mechanism of FeCl3-mediated oxidative spirocyclization reaction

Scheme 6. Pd(0)-catalyzed cascade cyclization of methylenecyclopropanes for the construction of fluorene-based spirocyclic compounds

Scheme 7. Proposed mechanism for the palladium-catalyzed cascade cyclization of methylenecyclopropanes

Scheme 8. Copper-catalyzed oxidative dehydrogenative dearomatization to construct fluorene-based spirocyclic compounds

Scheme 9. Mechanism of synthesis of fluorene-based spirocyclic compounds by copper-catalyzed oxidative dehydrogenative dearomatization

Scheme 10. Electrochemical oxidation enabled radical dearomative spiroannulation for the synthesis of spirofluorene derivatives

Scheme 11. CF3SO3H-catalyzed intramolecular Friedel-Crafts reaction for the synthesis of fluorene-based spirocyclic

Scheme 12. Synthesis of spirofluorenylpiperidin-4-ones by [3＋2] cycloaddition/[1,3]-rearrangement strategy

Scheme 13. Synthesis of spirofluorenepyrrolidinones by [3＋2] cycloaddition/[1,3]-shift

Scheme 14. [3＋2] cycloaddition/ring contraction to construct spirofluorenyl-β-lactams

Scheme 15. [3＋2] cycloaddition to form spirofluorenyl-1,2,4-oxadiazinan-5-ones

Scheme 16. Gimeracil-catalyzed formal [4＋1] annulation for the synthesis of spirofluorenylpyrrolines

Scheme 17. Mechanism for gimeracil-catalyzed formal [4＋1] annulation for the synthesis of spirofluorenylpyrrolines

Scheme 18. Intermolecular SNAr reactions to form fluorene-based spirocyclic tetraarylmethanes

Scheme 19. Pd-catalyzed [3＋2] spiroannulation to synthesize spirofluorene architectures compounds

Scheme 20. Mechanism for Pd-catalyzed [3＋2] spiroannulation to access spirofluorene compounds

Scheme 21. BF3-promoted spiroannulation for the synthesis of fluorene-based spirolactones

Scheme 22. Proposed mechanism for the synthesis of spirofluorene-based lactones

Scheme 23. C—H bond activation to construct spirofluorenyl benzosultams

Scheme 24. Pd(0)-catalyzed [4＋1] spiroannulation for the one-step construction of [4,5]-spirofluorenes

Scheme 25. Pd-catalyzed [4＋1] spiroannulation for the construction of spirofluorenyl naphthalenones

Scheme 26. Pd-catalyzed selective decarboxylative annulation for the construction of spiro compounds

Scheme 27. Mechanism for Pd-catalyzed selective decarboxylative annulation

Scheme 28. C—H activation for the synthesis of spirobifluorenes

Scheme 29. C—H activation for the synthesis of spiro[4,5]fluorenes

Scheme 30. Chirality retention in Friedel-Crafts spiroannulation for iterative synthesis of spiro-bridged conjugated carbocycles

Scheme 31. Thermal rearrangements reaction of N-vinyl fluorenone nitrones to construct spirofluorenylisoxazolines

Scheme 32. Cross-coupling and intramolecular Heck reaction to construct spirocyclic structures

Scheme 33. One-pot cascade reaction to construct spiro‑diazafluorenes

Scheme 34. TiCl4-catalyzed consistent Friedel-Crafts reaction to construct spirofluorenyl oxindoles

Scheme 35. Mechanism of the TiCl₄-catalyzed tandem Friedel- Crafts reactions

Scheme 36. Palladium-catalyzed C-aryl functionalization to prepare spirofluorenyl compouds

Scheme 37. N-Heterocyclic carbene-catalyzed double michael addition to synthesize spirofluorenes

Scheme 38. Proposed mechanism for NHC-catalyzed double Michael addition of divinyl ketones (DVKs)

Scheme 39. Synthesis of spirofluorene derivatives via ring-closing metathesis and Suzuki-Miyaura coupling reactions

Scheme 40. [2＋2] cycloaddition/ringopening sequence reaction to obtain spiroacridines

Scheme 41. Probable mechanism for the synthesis of spiroacridines via a [2＋2] cycloaddition/ring-opening tandem reactions

Scheme 42. Triflic acid-promoted intermolecular condensation reactions to prepare spirofluorenyl compouds in one-pot

Scheme 43. Acid-catalyzed dehydration coupling reaction for the synthesis of spirobifluorenes

References 48

[1]	(a) Bach, U.; Lupo, D.; Comte, P.; Moser, J. E.; Weissörtel, F.; Salbeck, J.; Spreitzer, H.; Grätzel, M. Nature 1998, 395, 583.
	(b) Deng, Y.; Li, Y.; Li, X.; Yu, F.; Li, H.; Zhu, S.; Wang, B.; Chen, Z.; Feng, Q.; Xie, L.; Huang, W. Adv. Optical Mater. 2025, 13, 2402464.
	(c) Kim, J. Y.; Yasuda, T.; Yang, Y. S.; Matsumoto, N.; Adachi, C. Chem. Commun. 2014, 50, 1523.
[2]	(a) Poriel, C.; Rault-Berthelot, J. Chem. Soc. Rev. 2023, 52, 6754.
	(b) Urieta-Mora, J.; Garcia-Benito, I.; Molina-Ontoria, A.; Martín, N. Chem. Soc. Rev. 2018, 47, 8541.
	(c) Jiang, Y.; Liu, Y.-Y.; Liu, X.; Lin, H.; Gao, K.; Lai, W.-Y.; Huang, W. Chem. Soc. Rev. 2020, 49, 5885.
	(d) Samuel, I. D. W.; Turnbull, G. A. Chem. Rev. 2007, 107, 1272.
[3]	(a) Nguyen, W. H.; Bailie, C. D.; Unger, E. L.; McGehee, M. D. J. Am. Chem. Soc. 2014, 136, 10996.
	(b) Chan, C.-Y.; Wong, Y.-C.; Chan, M.-Y.; Cheung, S.-H.; So, S.-K.; Yam, V. W.-W. Chem. Mater. 2014, 26, 6585.
	(c) Das, A. S.; Nair, A. R.; Sreekumar, A.; Sivan, A. ChemistrySelect 2022, 7, e202201097.
[4]	(a) Saragi, T. P. I.; Spehr, T.; Siebert, A.; Fuhrmann-Lieker, T.; Salbeck, J. Chem. Rev. 2007, 107, 1011.
	(b) Cui, L.-S.; Xie, Y.-M.; Wang, Y.-K.; Zhong, C.; Deng, Y.-L.; Liu, X.-Y.; Jiang, Z. Q.; Liao, L.-S. Adv. Mater. 2015, 27, 4213.
[5]	Yu, M.-N.; Ou, C.-J.; Liu, B.; Lin, D.-Q.; Liu, Y.-Y.; Xue, W.; Lin, Z.-Q.; Lin, J.-Y.; Qian, Y.; Wang, S.-S.; Cao, H.-T.; Bian, L.-Y.; Xie, L.-H.; Huang, W. Chin. J. Polym. Sci. 2017, 35, 155.
[6]	(a) Clarkson, R. G.; Gomberg, M. J. Am. Chem. Soc. 1930, 52, 2881.
	(b) Sreekumar, A.; Nair, A. R.; Raksha, C.; Swayamprabha, S. S. Sivan, A. Top. Curr. Chem. 2025, 383, DOI: 10.1007/s41061-024- 00485-6.
[7]	Romain, M.; Thiery, S.; Shirinskaya, A.; Declairieux, C.; Tondelier, D.; Geffroy, B.; Jeannin, O.; Rault-Berthelot, J.; Métivier, R.; Poriel, C. Angew. Chem. Int. Ed. 2015, 54, 1176.
[8]	(a) Chan, C.-Y.; Wong, Y.-C.; Chan, M.-Y.; Cheung, S.-H.; So, S.-K.; Yam, V. W.-W. ACS Appl. Mater. Interfaces 2016, 8, 24782.
	(b) Wang, H.; Liu, Y.; Hu, W.; Xu, W.; Wang, P.; Wang, Y.; Luan, X. Org. Electron. 2018, 61, 376.
[9]	Hellwinkel, D.; Becker, T. Chem. Ber. 1989, 122, 1595.
[10]	Xiao, S.-J.; Lei, X.-X.; Xia, B.; Xu, D.-Q.; Xiao, H.-P.; Xu, H.-X.; Chen, F.; Ding, L.-S.; Zhou, Y. Tetrahedron Lett. 2014, 55, 5949.
[11]	Kador, P. F.; Lee, Y. S.; Rodriguez, L.; Sato, S.; Bartoszko-Malik, A.; Abdel-Ghany, Y. S.; Millel, D. D. Bioorg. Med. Chem. 1995, 3, 1313.
[12]	Moritomo, A.; Yamada, H.; Matsuzawa-Nomura, T.; Watanabe, T.; Itahana, H.; Oku, M.; Akuzawa, S.; Okada, M. Bioorg. Med. Chem. 2014, 22, 6026.
[13]	Gorin, D. J.; Watson, I. D. G.; Toste, F. D. J. Am. Chem. Soc. 2008, 130, 3736.
[14]	(a) Wang, X.-C.; Yan, R.-L.; Zhong, M.-J.; Liang, Y.-M. J. Org. Chem. 2012, 77, 2064.
	(b) Xu, X.; Li, T.; Li, X.; Shao, J. Synlett 2013, 24, 383.
[15]	Kaiser, R. P.; Hessler, F.; Mosinger, J.; Císařová I.; Kotora, M. Chem.-Eur. J. 2015, 21, 13577.
[16]	Luo, Y.; Liu, Z.; Yang, G.; Wang, T.; Bin, Z.; Lan, J.; Wu, D.; You, J. Angew. Chem., Int. Ed. 2021, 60, 18852.
[17]	Cadart, T.; Nečas, D.; Kaiser, R. P.; Favereau, L.; Císařová I.; Gyepes, R.; Hodačová J.; Kalíková K.; Bednárová L.; Crassous, J.; Kotora, M. Chem.-Eur. J. 2021, 27, 11279.
[18]	Zhao, J.; Asao, N.; Yamamoto, Y.; Jin, T. J. Am. Chem. Soc. 2014, 136, 9540.
[19]	Zhao, J.; Xu, Z.; Oniwa, K.; Aso, N.; Yamamoto, Y.; Jin, T. Angew. Chem., Int. Ed. 2016, 55, 259.
[20]	Fang, W.; Wei, Y.; Shi, M. Org. Lett. 2018, 20, 7141.
[21]	Chao, J.; Yue, Y.; Wang, K.; Guo, X.; Sun, C.; Xu, Y.; Liu, J. iScience 2022, 25, 105669.
[22]	Yue, Y.; Guo, X.; Zhang, J.; Zhang, Z.; Zhang, Y.; Tang, Q.; Bai, R.; Yi, H.; Liu, J. Chem.-Eur. J. 2024, 30, e202401303.
[23]	Hood, J. C.; Klumpp, D. A. J. Org. Chem. 2023, 88, 665.
[24]	Ma, X.-P.; Zhu, J.-F.; Wu, S.-Y.; Chen, C.-H.; Zou, N.; Liang, C.; Su, G.-F.; Mo, D.-L. J. Org. Chem. 2017, 82, 502.
[25]	Amrutha, U.; Babu, B. P.; Prathapan, S. J. Heterocycl. Chem. 2019, 56, 3236.
[26]	Wei, C.; Zhu, J.-F.; Zhang, J.-Q.; Deng, Q.; Mo, D.-L. Adv. Synth. Catal. 2019, 361, 3965.
[27]	Luo, Y.; Chen, C.-H.; Zhang, J.-Q.; Liang, C.; Mo, D.-L. Synthesis 2020, 52, 424.
[28]	Wei, C.; Zhang, J.-Q.; Zhang, J.-J.; Liang, C.; Mo, D.-L. Org. Chem. Front. 2020, 7, 1520.
[29]	Bhanuchandra, M.; Yorimitsu, H.; Osuka, A. Org. Lett. 2016, 18, 384.
[30]	Zuo, Z.; Wang, H.; Diao, Y.; Ge, Y.; Liu, J.; Luan, X. ACS Catal. 2018, 8, 11029.
[31]	Song, Q.; Zhang, Z.; Xie, X.; Ding, G.-Z.; Li, P.; Wang, L.; Miao, T. Org. Chem. Front. 2023, 10, 363.
[32]	Reddy, K. N.; Rao, M. V. K.; Sridhar, B.; Reddy, B. V. S. Eur. J. Org. Chem. 2017, 2017, 4085.
[33]	Tan, B.; Liu, L.; Zheng, H.; Cheng, T.; Zhu, D.; Yang, X.; Luan, X. Chem. Sci. 2020, 11, 10198.
[34]	Liang, W.; Yang, Y.; Yang, M.; Zhang, M.; Li, C.; Ran, Y.; Lan, J.; Bin, Z.; You, J. Angew. Chem., Int. Ed. 2021, 60, 3493.
[35]	Zhou, F.; Zhou, L.; Jing, P.; Sun, M.; Deng, G.; Liang, Y.; Yang, Y. Org. Lett. 2022, 24, 1400.
[36]	Wu, Y.; Wu, F.-W.; Zhou, K.; Li, Y.; Chen, L.; Wang, S.; Xu, Z.-Y.; Lou, S.-J.; Xu, D.-Q. Chem. Commun. 2022, 58, 6280.
[37]	Han, L.; Wei, X.; Yuan, Y.; Bai, L.; Wang, H.; Luan, X. Org. Lett. 2023, 25, 5619.
[38]	Pu, X.; Lu, Y.; Zhou, Z.; Yang, Y.; Zhang, C.; Yu, P.; Zhao, Y. S.; Lan, J.; You, J. Nat. Synth. 2025, 4, 1247.
[39]	Mo, D.-L.; Wink, D. A.; Anderson, L. L. Org. Lett. 2012, 14, 5180.
[40]	Barroso, R.; Valencia, R. A.; Cabal, M.-P.; Valdés, C. Org. Lett. 2014, 16, 2264.
[41]	Lin, D.; Wei, Y.; Ou, C.; Huang, H.; Xie, L.; Tang, L.; Huang, W. Org. Lett. 2016, 18, 6220.
[42]	Lim, J. W.; Moon, R. H.; Kim, S. Y.; Kim, J. N. Tetrahedron Lett. 2016, 57, 133.
[43]	Peng, X.; Luo, H.; Wu, F.; Zhu, D.; Ganesan, A.; Huang, P.; Wen, S. Adv. Synth. Catal. 2017, 359, 1152.
[44]	Xing, F.; Feng, Z.-N.; Wang, Y.; Du, G.-F.; Gu, C.-Z.; Dai, B.; He, L. Adv. Synth. Catal. 2018, 360, 1704.
[45]	Kotha, S.; Ali, R. J. Chem. Sci. 2019, 131, 66.
[46]	Wang, W.; Wan, H.; Du, G.; Dai, B.; He, L. Org. Lett. 2019, 21, 3496.
[47]	Ferreira, J. C.; Hood, J. C.; Klumpp, D. A. Tetrahedron 2022, 128, 133123.
[48]	Kato, Y.; Nishimura, K.; Nishii, Y.; Hirano, K. Chem. Sci. 2024, 15, 2112.

螺芴基化合物的合成研究进展

Recent Advances on the Synthesis of Spirofluorene-Based Compounds

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 44

References 48

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Yuan Gao, Yan Liu, Shiwu Li, Tiansheng Tang, Yukun Meng, Zhifei Zhao. N-Heterocyclic Carbene (NHC)-Catalyzed [3＋2] Cycloaddition to Highly Diastereoselective Synthesis of Spirooxindole-Fused Cyclopentanes [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 1008-1016.
[2]	Xinyu Liang, Chunchun Mi, Fujun Guo, Wenbin Xie, Qinqin Shi, Hui Huang. Desulfinative Cross-Coupling of Aryl Sodium Sulfinate with Aryl Sulfonium Salts [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 1000-1007.
[3]	Ke Zhou, Zeyong Wang, Yalin Li, Qian Zhang, Xinyue Li, Hanfang Zou, Mingzhong Zhang, Shengrong Guo, Tieqiao Chen. An Oxidative Strategy for Generating Trichloromethyl Radical from Carbon Tetrahalides: Transition-Metal-Free Synthesis of Trichloromethylated Oxindoles [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 974-985.
[4]	Yumeng He, Fengyuan Zhou, Nan Jiang, Yuqi Zhang, Jijiang Wang, Haojie Ma. Iodine-Catalyzed Intramolecular Cyclization for the Synthesis of 2-Hydroxy-indolin-3-ones [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 961-967.
[5]	Wenfu Cheng, Minghao Zhao, Yuchen Yang, Lijia Wang. The First Total Synthesis of N-Methyl Pratensilin B [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 670-677.
[6]	Wentao Guo, Shuyu Meng, Quanrui Wang. Intramolecular Cross-Coupling/[3,3]-Sulfonium Rearrangement of Alkynyl Sulfoxides for the Construction of Cycloalkano[c]furans [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 594-602.
[7]	Yiling Zeng, Fangpeng Liang, Hui Li, Rongrong Liu, Shiqing Li. Multi-component C—H Annulation of α-Oxocarboxylic Acids, Allynes and Primary Amines to Yield Isoquinolinium Skeletons [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 554-563.
[8]	Yan Luo, Zhangwei Liu, Zhaolei Hu, Hongyan Bi, Dongliang Mo. Recent Advances on the Synthesis of Ten-Membered Nitrogen Heterocyclic Compounds [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 420-442.
[9]	Wanting Liang, Siyi Chen, Enqi Xu, Xuebing Chen. Copper-Catalyzed Cyclization Reaction of 3-Nitrochromenes with Enaminones to Synthesize of 2H-Chromeno-pyrrole Derivatives [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 496-506.
[10]	Tao Liu, Yongbo Zhou, Tongqing Lang, Haibo Niu, Fei Chen, Zhihong Du, Chunbo Bo, Min Li, Ning Liu. Schiff Base Type Fe(III) Complexes Catalyzed Carbon Dioxide and Epoxides for Preparing Cyclic Carbonates [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 233-240.
[11]	Tianjiao Han, Qianqian Shi, Yundong Fu, Guangjian Mei. Regio-reversed [3＋2] Cycloaddition of Triketone Enones with Nitrones [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 146-155.
[12]	Yilin Chen, Jiayi Yue, Yiming Lin, Bingni Liu, Wen Dai, Hongping Zhu. Synthesis and Characterization of Silacyclopropenes [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 128-134.
[13]	Mengya Xu, Yifan Li, Yue Wang, Ruiping Han, Er-Qing Li. Silver/Ganphos-Catalyzed Enantioselective [3＋2] Cycloadditions of Azomethine Ylides: Access to the Spirocyclic Scaffolds [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3458-3468.
[14]	Xinghui Tao, Kaiyue Guo, Jitan Zhang, Meihua Xie, Jiaping Wu. Synthesis of Functionalized Azepinones and Phenanthridines via a Pd-Catalyzed ortho-C—H Amination/C—H Arylation Cyclization Cascade of Aryl Bromides [J]. Chinese Journal of Organic Chemistry, 2025, 45(8): 2825-2835.
[15]	Ting Mao, Linyuan Zeng, Jilin Wen, Jia Jia. Visible Light-Mediated Iridium-Catalyzed Debromocyclization of Aliphatic α-Bromotrifluoromethyl Groups [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2520-2528.