Substituent Effects in Modern Radical Chemistry

doi:10.6023/cjoc202605001

Chinese Journal of Organic Chemistry

REVIEW

现代自由基化学中的取代基效应

罗海天^a#, 桓臻^a#, 杨金东^a,*, 程津培^a,b,c

^a清华大学化学系基础分子科学中心北京 100084;
^b南开大学化学学院元素有机国家重点实验室天津 300071;
^c物质绿色创造与制造海河实验室天津 300192

收稿日期:2026-05-01 修回日期:2026-07-27
基金资助:
国家自然科学基金(Nos. 22222106, 21973052, 22193011, 21933008)以及海河实验室资助项目.

Substituent Effects in Modern Radical Chemistry

Hai-Tian Luo^a#, Zhen Huan^a#, Jin-Dong Yang^a,*, Jin-Pei Cheng^a,b,c

^a Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing 100084;
^b State Key Laboratory of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071;
^c Haihe Laboratory of Sustainable Chemical Transformations, Tianjin 300192

Received:2026-05-01 Revised:2026-07-27
Contact: * E-mail: jdyang@mail.tsinghua.edu.cn
About author:^#These two authors contributed equally.
Supported by:
National Natural Science Foundation of China (Nos. 22571181, 22193011, and 22393891) and the Haihe Laboratory of Sustainable Chemical Transformations

Substituent effects constitute an essential tool for establishing quantitative relationships between molecular structure and chemical behavior. Classical substituent parameters are primarily applicable to polar molecular systems and exhibit limited capability in describing electronic effects in open-shell systems involving spin delocalization. In recent years, a variety of quantitative approaches to substituent effects have been developed for organic radical systems, leading to an expansion of the available parameter scales and providing powerful tools for mechanistic elucidation and the design of new reactions. This review surveys representative advances over the past three decades in the study of substituent effects in radical chemistry, focusing on both the development of substituent parameters and their applications in mechanistic investigations. Particular emphasis is placed on the methodologies for parameter establishment, the underlying pattern that parameters reveal, and representative examples of their use in probing reaction mechanisms.

Key words: substituent effects, radical chemistry, linear free energy relationships, dual-parameter model, reaction mechanisms

Cite this article

Hai-Tian Luo, Zhen Huan, Jin-Dong Yang, Jin-Pei Cheng. Substituent Effects in Modern Radical Chemistry[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202605001.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

[1] Libit L.; Hoffmann R.J. Am. Chem. Soc. 1974, 96, 1370.
[2] Hammett L. P.J. Am. Chem. Soc. 1937, 59, 96.
[3] Hansch C.; Leo A.; Taft R. W.Chem. Rev. 1991, 91, 165.
[4] Yan M.; Lo J. C.; Edwards J. T.; Baran P. S.J. Am. Chem. Soc. 2016, 138, 12692.
[5] Cheng J.-P.; Luo S.; Jia Z.; Huang M.Chin. J. Org. Chem. 2021, 41, 3892. (in Chinese)
(黄谋新, 贾宗宾, 罗三中, 程津培, 有机化学, 2021, 41, 3892.)
[6] (a) Dust, J. M.; Arnold, D. R.J. Am. Chem. Soc. 1983, 105, 1221.
(b) Wayner, D. D. M.; Arnold, D. R.Can. J. Chem. 1985, 63, 2378.
[7] (a) Creary, X.; Mehrsheikh-Mohammadi, M. E.J. Org. Chem. 1986, 51, 1110.
(b) Creary, X.; Mehrsheikh-Mohammadi, M. E.; McDonald, S.J. Org. Chem. 1987, 52, 3254.
[8] Dinçtürk S.; Jackson R. A.; Townson M.; Aǧirbaş H.; Billingham N. C.; March G.J. Chem. Soc., Perkin Trans. 2 1981, 1121.
[9] Xu M.; Li Y.-B.; Wang H.; Glorius F.; Qi X.Angew. Chem. Int. Ed. 2025, 64, e202500522.
[10] Jiang X.; Ji G.J. Org. Chem. 1992, 57, 6051.
[11] Ji G.-Z.; Jiang X.-K.; Zhang Y.-H.; Yuan S.-G.; Yu C.-X.; Shi Y.-Q.; Zhang X.-L.; Shi W.-T.J. Phys. Org. Chem. 1990, 3, 643.
[12] Jiang X.-K.Acc. Chem. Res. 1997, 30, 283.
[13] Shin N. Y.; Tsui E.; Reinhold A.; Scholes G. D.; Bird M. J.; Knowles R. R.J. Am. Chem. Soc. 2022, 144, 21783.
[14] Cohen L. A.; Jones W. M.J. Am. Chem. Soc. 1963, 85, 3397.
[15] Xu E. Y.; Castanedo A.; Shin N. Y.; Kannadi Valloli, L.; Grills, D. C.; Bird, M. J.; Knowles, R. R.J. Am. Chem. Soc. 2025, 147, 21735.
[16] Binev I. G.; Kuzmanova R. B.; Kaneti J.; Juchnovski I. N.J. Chem. Soc., Perkin Trans. 2 1982, 1533.
[17] Stoyanov S. S.J. Phys. Chem. A 2010, 114, 5149.
[18] Baek Y.; Betley T. A.J. Am. Chem. Soc. 2019, 141, 7797.
[19] Lin Q.; Fu Y.; Liu P.; Diao T.J. Am. Chem. Soc. 2021, 143, 14196.
[20] (a) Spielvogel, E. H.; Yuan, J.; Hoffmann, N. M.; Diao, T.J. Am. Chem. Soc. 2025, 147, 19632.
(b) Shi, X.-N.; Wang, J.-L.; Chen, Z.; Wang, D.-K.; Wu, G.-Y.; Peng, J.-M.; Qi, X.; Zhuo, C.-X. J. Am. Chem. Soc. 2026, 148, 11274.
(c) Kong, C.; Jana, N.; Jones, C.; Driver, T. G. J. Am. Chem. Soc. 2016, 138, 13271.
[21] (a) Ho, C.; Leung, W.-H.; Che, C.-M.J. Chem. Soc., Dalton Trans. 1991, 2933.
(b) Che, C.-M.; Ho, C.; Lau, T.-C.J. Chem. Soc., Dalton Trans. 1991, 1901.
[22] Liu C.-J.; Yu W.-Y.; Che C.-M.; Yeung C.-H.J. Org. Chem. 1999, 64, 7365.
[23] (a) Schröder, K.; Enthaler, S.; Join, B.; Junge, K.; Beller, M.Adv. Synth. Catal. 2010, 352, 1771.
(b) Gelalcha, F. G.; Anilkumar, G.; Tse, M. K.; Brückner, A.; Beller, M.Chem. Eur. J. 2008, 14, 7687.
[24] Au S.-M.; Huang J.-S.; Yu W.-Y.; Fung W.-H.; Che C.-M.J. Am. Chem. Soc. 1999, 121, 9120.
[25] Leung S. K.-Y.; Tsui, W.-M.; Huang, J.-S.; Che, C.-M.; Liang, J.-L.; Zhu, N.J. Am. Chem. Soc. 2005, 127, 16629.
[26] Bagchi V.; Paraskevopoulou P.; Das P.; Chi L.; Wang Q.; Choudhury A.; Mathieson J. S.; Cronin L.; Pardue D. B.; Cundari T. R.; Mitrikas G.; Sanakis Y.; Stavropoulos P.J. Am. Chem. Soc. 2014, 136, 11362.
[27] Bagchi V.; Kalra A.; Das P.; Paraskevopoulou P.; Gorla S.; Ai L.; Wang Q.; Mohapatra S.; Choudhury A.; Sun Z.; Cundari T. R.; Stavropoulos P.ACS Catal. 2018, 8, 9183.
[28] Maestre L.; Sameera W. M.C.; Díaz-Requejo, M. M.; Maseras, F.; Pérez, P. J.J. Am. Chem. Soc. 2013, 135, 1338.
[29] van Leest, N. P.; Tepaske, M. A.; Venderbosch, B.; Oudsen, J.-P. H.; Tromp, M.; van der Vlugt, J. I.; de Bruin, B.ACS Catal. 2020, 10, 7449.
[30] Liu J.; Hu L.; Wang L.; Chen H.; Deng L.J. Am. Chem. Soc. 2017, 139, 3876.
[31] Epping R. F.J.; Hoeksma, M. M.; Bobylev, E. O.; Mathew, S.; de Bruin, B.Nat. Chem. 2022, 14, 550.
[32] (a) Kagawa, Y.; Oohora, K.; Himiyama, T.; Suzuki, A.; Hayashi, T.Angew. Chem. Int. Ed. 2024, 63, e202403485.
(b) Carminati, D. M.; Fasan, R. ACS Catal. 2019, 9, 9683.

现代自由基化学中的取代基效应

Substituent Effects in Modern Radical Chemistry

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Fan Zhang, Song Guo, Weicheng Yang, Jigang Zhao, Yong Luo. Analysis of the Nitration Process of Trifluoromethoxybenzene Based on Density Functional Theory (DFT) Calculations [J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2121-2128.
[2]	Yi-Fan Tan, Lei Jiao. Palladium-Catalyzed Radical Reactions via Pd(I) Pathway: A Brief Summary of Reaction Patterns and Recent Progress [J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1303-1319.
[3]	Xianting Huang, Xiaoqian Shen, Qingxu Wang, Zhongquan Liu. A Catalyst and Solvent-Free Photochemical Acylation of N-Heteroarenes with Keto Acids [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 951-960.
[4]	Tao Long, Shuzhong He, Chao Li. Research Progress on the Radical-Polar Crossover Reaction in Total Synthesis of Natural Products [J]. Chinese Journal of Organic Chemistry, 2025, 45(3): 748-763.
[5]	Deyue Xing, Yang Wang, Tingxuan Fang, Ruijun Xie, Xiao Li, Huijie Jia, Ning Zhu. Progress in the Synthesis of Benzothiazole-2-ones [J]. Chinese Journal of Organic Chemistry, 2025, 45(12): 4298-4314.
[6]	Weibao He, Rongnan Yi, Zi Yang, Zhilin Wu, He. Application Progress of Langlois Reagent in Electrochemical Trifluoromethylation Reactions [J]. Chinese Journal of Organic Chemistry, 2025, 45(10): 3534-3545.
[7]	Cen Zhou, Xin Zhao, Xiao Zhang. Research Progress in Benzene-Forming Cyclotrimerization Reactions [J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 42-55.
[8]	Yueling Liu, Xinxin Zhong, Ganbing Zhang. Density Functional Theory Study for Exploring the Mechanisms of the [3＋2] Cycloaddition Reactions between 1-R-3-Phenylpropylidenecyclopropane (R=Me/H) and Furfural Catalyzed by Pd(0) [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 660-667.
[9]	Tingting Liu, Yucai Hu, An Shen. Mechanism of Carbon-Carbon Coupling Reactions Catalyzed by Imine-Ligand-Assisted N-Heterocyclic Carbene Palladium Complexes [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 622-628.
[10]	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.
[11]	Yubing Shi, Wenji Bai, Weihua Mu, Jiangping Li, Jiawei Yu, Bing Lian. Research Progress on Density Functional Theory Study of Palladium-Catalyzed C—H Functionalization to Form C—X (X=O, N, F, I, …) Bonds [J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1346-1374.
[12]	Youcai Zhu, Xinxin Ding, Li Sun, Zhen Liu. Advances in the Production of Acrylic Acid and Its Derivatives by CO₂/C₂H₄ Coupling [J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 965-977.
[13]	Zheng Li, Yingchun Gu, Dazhen Xu, Xuening Fei, Lei Zhang. Density Functional Theory Study on the Mechanism of Organophosphine-Catalyzed [4+2] Cycloaddition Reaction [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 830-837.
[14]	Jintao Wu, Zhongquan Liu. Advances in Free-Radical Promoted C(sp³)—C(sp³) Bond Conversion [J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 16-32.
[15]	Man Xu, Yuanzhi Xia. Mechanistic Understanding of Rh(III)-Catalyzed Redox-Neutral C—H Activation/Annulation Reactions of N-Phenoxyacetamides and Methyleneoxetanones [J]. Chinese Journal of Organic Chemistry, 2021, 41(8): 3272-3278.