REVIEW

Advances in the Construction Methods of Cyclopropane Skeleton and Their Applications

  • Guo Jun-feng ,
  • Li Chun-ying ,
  • Hu Rong-gui ,
  • Rong Hao-jie ,
  • Li Jiang-wei ,
  • Du Yong-mei ,
  • Qing Yue ,
  • Lu Jian ,
  • Sun Dao-an
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  • State Key Laboratory of Fluorine & Nitrogen Chemical, Xi’an Modern Chemistry Research Institute, Xi’an 710065, Shaanxi, China

Online published: 2025-11-11

Supported by

Project supported by the the open fund of state key laboratory of fluorine & nitrogen chemical (No. FDKFJJ202502) and national high-level talent special support program in the X field (No. X).

Abstract

The cyclopropane skeleton holds significant theoretical and practical value in diverse fields such as medicinal chemistry and fuel chemistry, owing to its highly strained ring structure and favorable lipophilicity. This review systematically summarizes the strategies developed over the past two decades for constructing the cyclopropane framework, including cycloaddition reactions of carbenes and carbenoids with alkenes, ylide-mediated cyclizations, metallocyclopropane-involved cyclopropanations, intramolecular cyclopropanations, as well as emerging photocatalytic, electrocatalytic, and enzymatic cyclopropanation methods. Emphasis is placed on the mechanistic pathways, substrate compatibility, and stereoselectivity of the products. Furthermore, this article highlights recent advances in the application of cyclopropane construction strategies across various domains, such as drug development (e.g., synthesis of antiviral and neuroregulatory agents), total synthesis of natural products, and the design of high-energy-density fuel molecules. Finally, future prospects for the development of cyclopropane synthesis are discussed, pointing to the importance of novel high-efficiency catalysts (e.g., nano-supported and porous framework catalysts), advanced photocatalytic technologies, and greener synthetic methodologies as key research directions.

Cite this article

Guo Jun-feng , Li Chun-ying , Hu Rong-gui , Rong Hao-jie , Li Jiang-wei , Du Yong-mei , Qing Yue , Lu Jian , Sun Dao-an . Advances in the Construction Methods of Cyclopropane Skeleton and Their Applications[J]. Chinese Journal of Organic Chemistry, 0 : 202507041 -202507041 . DOI: 10.6023/cjoc202507041

References

[1] Menchikov L. G.; Shulishov E. V.; Tomilov, Y. V. Russian Chemical Reviews.2021, 90, 199-230.
[2] Liu J.; Lin M.; Han P.; Yao G.; Jiang H. Microorganisms.2024, 12, 706.
[3] Cruz-Morales, P. Yin K.; Landera A.; Cort J. R.; Young R. P.; Kyle J. E. Joule.2022, 6, 1590-1605.
[4] Talele, T. T. Journal of Medicinal Chemistry.2016, 59, 8712-8756.
[5] Kelly C. B.; Thai‐Savard L.; Hu J.; Marder T. B.; Molander G. A.; Charette A. B. ChemCatChem.2024, 16, 14.
[6] Li T.; Jia D.; Zhou S.; Liu Z.; Chen J.; Ban T.; Li A.; Li H.; Gao H. Fuel.2024, 373,.
[7] Liu Q.; Jia T.; Pan L.; Shen Z.; Han Z.; Zhang X.; Zou J.-J. Fuel.2024, 358, 130342.
[8] Wessjohann L. A.; Brandt W.; Thiemann T. Chemical Reviews.2003, 103, 1625-1648.
[9] Jing W. B.; Yuan H.; Tang, G. L Chin. J. Org. Chem.2018, 38, 2324-2334 (in Chinese)
(金文兵, 袁华, 唐功利, 有机化学, 2018, 38, 2324-2334).
[10] Haym, I. & Brimble, M. A. Organic & Biomolecular Chemistry.2012, 10(38), 7649-7665.
[11] Tomilov Y. V.; Menchikov L. G.; Novikov R. A.; Ivanova O. A.; Trushkov, I. V. Russian Chemical Reviews.2018, 87, 201-250.
[12] Chen Z. L.; Xie, Y. & Xuan, J. European Journal of Organic Chemistry.2022, 44, 135-150.
[13] Herraiz A. G.; Suero M. G. Synthesis.2019, 51, 2821-2828.
[14] Milligan J. A.; Phelan J. P.; Polites V. C.; Kelly C. B.; Molander, G. A. Organic Letters.2018, 20, 6840-6844.
[15] Poudel D. P.; Pokhrel A.; Tak R. K.; Shankar M.; Giri R. Science.2023, 381, 545-553.
[16] Wang W.; Shen Z.; Zhang J.; Pan L.; Shi C.; Zhang X.; Zou J-J. Fuel.2024, 355, 129380.
[17] Wang W.; Pu B.; Ma C.; Shi C.; Pan L.; Zhang X.; Zou J-J. AIChE Journal.2023, 69, 7.
[18] Liu Y.; Shi C.; Pan L.; Zhang X.; Zou J.-J. Fuel.2022, 307.
[19] Yan, G B.; Kuang, C X.; Peng C.; Wang, J, B. Chin. J. Org. Chem.2009, 29, 813 (in Chinese)
(严国兵, 匡春香, 彭程, 王剑波, 有机化学, 2009, 29, 813).
[20] Zhu, L, M. Chin. J. Org. Chem.1991, 11, 437-442 (in Chinese)
(朱利民, 有机化学, 1991, 11, 437-442).
[21] Silberrad O.; Smart, B. J. Journal of the Chemical Society, Transactions.1906, 89, 172-179.
[22] Kim M. J.; Wang D. J.; Targos K.; Garcia U. A.; Harris A. F.; Guzei I. A.; Wickens, Z. K. Angewandte Chemie International Edition.2023, 62, 21.
[23] Nozaki H.; Moriuti S.; Yamabe M.; Noyori R. Tetrahedron Letters.1966, 7, 59-63.
[24] Raps F. C.; Hyster, T. K. ACS Central Science.2025, 11(7), 1029-1040.
[25] Ortiz de Montellano, P. R. in Annual Reports in Medicinal Chemistry.1984, 19, 201-211.
[26] Nefedov O. M.; Tomilov Y. V.; Kostitsyn A. B.; Dzhemilev U. M.; Dokitchev, V. A. Mendeleev Communications.1992, 2, 13-15.
[27] Dzhemilev U,; Dokichev V,; Dolgii, I. Russian Chemical Bulletin.1992, 41(10), 1846-1852.
[28] Yury V. T.; Dokitchev V. A.; Usein M. D.; Oleg, M. N. Russian Chemical Reviews.1993, 62, 799.
[29] Dzhemilev U. M.; Dokichev V. A.; Sultanov S. Z.; Khursan S. L.; Nefedov O. M.; Tomilov Y. V.; Kostitsyn, A. B. Bulletin of the Russian Academy of Sciences, Division of chemical science.1992, 41, 1846-1852.
[30] Ebner C.; Carreira, E. M. Chem Rev.2017, 117, 11651-11679.
[31] Thankachan A. P.; Sindhu K. S.; Krishnan K. K.; Anilkumar, G. Org Biomol Chem.2015, 13, 8780-8802.
[32] Wood A. B.; Cortes‐Clerget M.; Kincaid J. R. A.; Akkachairin B.; Singhania V.; Gallou F.; Lipshutz, B. H. Angewandte Chemie International Edition.2020, 59, 17587-17593.
[33] Kulinkovich, O. G. Chemical Reviews. 2003, 103, 2597-2632.
[34] Holman, R. W. Journal of Chemical Education.2005, 82, 1780.
[35] Charette A. B.; Beauchemin, A. M. Organic Reactions.2004, 34(19), 1-415.
[36] Repič O.; Vogt S. Tetrahedron Letters.1982, 23, 2729-2732.
[37] Liu Y.; Yang S.; Shi C.; Pan L.; Zhang X.; Zou, J.-J. Chemical Engineering Science.2024, 283, 119366.
[38] Gopinath P.; Chandrasekaran, S. The Journal of Organic Chemistry.2011, 76, 700-703.
[39] Buono F. G.; Eriksson M. C.; Yang B.-S.; Kapadia S. R.; Lee, H. Organic Process Research & Development.2014, 18, 1527-1534.
[40] Shestopalov A.; Shestopalov A.; Rodinovskaya L.; Zlotin S.; Nesterov V. Synlett.2003, 35(15), 2309-2312.
[41] Robiette R.; Marchand-Brynaert J. Synlett.2008, 4, 517-520.
[42] Aggarwal V. K.; Bi, J. Beilstein Journal of Organic Chemistry.2005, 1, 4.
[43] Tong, M H.; Zhang, X Y.; Wang, Y M.; Wang, Z, K. Chin. J. Org. Chem.2021, 41, 126-143 (in Chinese).
(仝明慧, 张欣宇, 王也铭, 王自坤, 有机化学, 2021, 41, 126-143).
[44] Goudreau S. R.; Marcoux D.; Charette, A. B. The Journal of Organic Chemistry.2009, 74, 470-473.
[45] Tao J.; Estrada C. D.; Murphy, G. K. Chemical Communications.2017, 53, 9004-9007.
[46] Zhang X.; Zeng R.; Feng X.Asian Journal of Organic Chemistry. 2018, 7, 2065-2068.
[47] Chidley T.; Jameel I.; Rizwan S.; Peixoto, P. A. Angewandte Chemie International Edition.2019, 58, 16959-16965.
[48] Frank, J. Journal of Physics A: Mathematical and General. 2006, 39, 5479-5493.
[49] Papageorgiou C. D.; Cubillo de Dios, M. A.; Ley S. V.; Gaunt, M. J. Angewandte Chemie International Edition.2004, 43, 4641-4644.
[50] Sun X.-L.; Tang, Y. Accounts of Chemical Research.2008, 41, 937-948.
[51] Li S.; Zhou, L. Chin. J. Org. Chem.2022, 42, 3944-3958 (in Chinese).
(李森, 周磊. 有机化学, 2022, 42, 3944-3958).
[52] Xie Y.; Xuan, J. Chin. J. Org. Chem.2022, 42, 4247-4256 (in Chinese).
(谢阳, 宣俊. 有机化学, 2022, 42, 4247-4256).
[53] Zhang Y.; An Y.; Sun J.; Ding A.; Wang Y.; Rios R.; Guo H. Tetrahedron Letters.2015, 56, 6499-6502.
[54] Sayes M.; Benoit G.; Charette, A. B. Angewandte Chemie International Edition.2018, 57, 13514-13518.
[55] Jie L.-H.; Guo B.; Song J.; Xu, H.-C. Journal of the American Chemical Society.2022, 144, 2343-2350.
[56] Liu, M. S.; Du, H. W.; Cui, J. F.; Shu, W. Angewandte Chemie (International ed. in English). 2022, 61, 41.
[57] Key H. M.; Dydio P.; Liu Z.; Rha J. Y. E.; Nazarenko, A. Seyedkazemi, V. ACS Central Science.2017, 3, 302-308.
[58] Zhang J.-m.; Hu Z.-p.; Zhao S.-q.; Yan M. Tetrahedron.2009, 65, 802-806.
[59] Anthes R.; Bello O.; Benoit S.; Chen C.-K.; Corbett E.; Corbett, R. M. Organic Process Research & Development.2008, 12, 168-177.
[60] Zhang X.; Yu S.; Liu Z.; Long Y.; Zhao J.; Xu, W. Organic Process Research & Development.2022, 26, 1054-1062.
[61] Li W.; Gao J. J.; Lorenz J. C.; Xu J.; Johnson J.; Ma, S. Organic Process Research & Development.2012, 16, 836-839.
[62] Bonku E. M.; Qin H.; Odilov A.; Yang F.; Xing X.; Wang X. Organic Process Research & Development. 2023, 27, 1984-1991.
[63] Zhang X.; Pan L.; Wang L.; Zou, J.-J. Chemical Engineering Science.2018, 180, 95-125.
[64] Wen L.; Shan S.; Lai W.; Shi J.; Li M.; Liu Y. Molecules.2023, 28, 7361.
[65] Wang X.; Jia T.; Pan L.; Liu Q.; Fang Y.; Zou J.-J.; Zhang, X. Transactions of Tianjin University.2020, 27, 87-109.
[66] Zarezin D. P.; Rudakova M. A.; Shorunov S. V.; Sultanova M. U.; Samoilov V. O.; Maximov A. L.; Bermeshev, M. V. Fuel Processing Technology.2022, 225, 107056.
[67] Jaffe R. L.; Karabeyoglu A. M.; Evans B. J.; Zilliac G.; Sherburn, M. S. in 49th AIAA/ASME/SAE/ASEE Joint Propulsion Conference.2013, 14(17), 3968.
[68] Liu Y.; Ma C.; Shi C.; Pan L.; Xie J.; Gong S.; Zou, J.-J. Fuel Processing Technology.2020, 201, 106339.
[69] Pan L.CN 111548830 A, 2021.
[70] Li, C Y.; Ma, Y B.; Xue, Y, N,; Yang, J, M,; Wang, B, Z. Chinese Journal of Energetic Materials.2012, 20, 151-154 (in Chinese).
(李春迎, 马洋博, 薛云娜, 杨建明, 王伯周, 含能材料, 2012, 20, 151-154).
[71] Yue X.; Li J. W.; Li C. Y.; Wang Z. X.; Du Y. M.; Sun D. A.; Ma H.; Lu J. RSC Advances.2024, 14, 39740-39746.
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