Research Progress on Asymmetric Smiles Rearrangement

doi:10.6023/cjoc202604048

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (9): 3523-3545.DOI: 10.6023/cjoc202604048 Previous Articles Next Articles

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不对称Smiles重排反应研究进展

郭振广^†, 高登元^†, 葛洛^*(), 邓卫平^*()

浙江师范大学化学与材料科学学院浙江省先进催化与吸附材料重点实验室浙江金华 321004

收稿日期:2026-04-28 修回日期:2026-05-16 发布日期:2026-05-27
通讯作者: 葛洛, 邓卫平
作者简介:
^† 共同第一作者
基金资助:
浙江省自然科学基金(LQN25B020007); 浙江省自然科学基金(LZ23B020003)

Research Progress on Asymmetric Smiles Rearrangement

Zhenguang Guo, Dengyuan Gao, Luo Ge^*(), Weiping Deng^*()

Zhejiang·Key·Laboratory of Advanced Catalysis·and·Adsorption·Materials, Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Science, Zhejiang Normal University, Jinhua, Zhejiang 321004

Received:2026-04-28 Revised:2026-05-16 Published:2026-05-27
Contact: Luo Ge, Weiping Deng
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
^† These authors contributed equally to this work
Supported by:
Zhejiang Provincial Natural Science Foundation(LQN25B020007); Zhejiang Provincial Natural Science Foundation(LZ23B020003)

The Smiles rearrangement is an important synthetic strategy for the efficient construction of carbon-carbon bonds via intramolecular aryl migration, which has been widely applied in the synthesis of pharmaceutical molecules, natural products, and functional materials. However, the development of its asymmetric transformation lags relatively behind, and no systematic review has been reported to date. This review classifies asymmetric Smiles rearrangements into two fundamental classes based on their reaction mechanisms: ionic and radical pathways. It systematically summarizes the design principles, reaction characteristics, and synthetic scope of each system under three well-established stereocontrol strategies: chiral substrate, chiral reagent, and chiral catalysis. Finally, the key challenges in this field are identified, and perspectives on future development directions and application prospects are presented, with the goal of providing a valuable reference for the development of new chiral synthetic methodologies.

Key words: Smiles rearrangement, asymmetric synthesis, chiral quaternary carbon stereocenter, aryl migration

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Zhenguang Guo, Dengyuan Gao, Luo Ge, Weiping Deng. Research Progress on Asymmetric Smiles Rearrangement[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3523-3545.

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Fig. & Tab. 34

Scheme 1. Smiles rearrangement

Scheme 2. Asymmetric aryl migration reaction of α‑methylbenzylurea

Scheme 3. Mechanism of stereoretentive aryl migration in α-methylbenzylureas

Scheme 4. Pyridyl migration in asymmetric Smiles rearrangement

Scheme 5. Stereoselective intramolecular α-arylation of self- stabilized non-racemic enolates

Scheme 6. Asymmetric aryl migration of carbamates

Scheme 7. Smiles rearrangement of proline sulfonamides

Scheme 8. Enantioselective synthesis of tertiary thiols by intramolecular arylation of thiocarbamates

Scheme 9. Asymmetric α-arylation of amino acid derivatives

Scheme 10. Enantioselective synthesis of tertiary thiols from allylic thiocarbamates

Scheme 11. Pseudoephedrine-directed asymmetric α-arylation of α-amino acid derivatives

Scheme 12. Intramolecular diastereoselective arylation of N‑carboxamido proline ester

Scheme 13. Asymmetric arylation of amino acids by self-regeneration of stereocenters

Scheme 14. Enantioselective aryl migration reaction directed by trans-2-aminocyclohexanol auxiliary

Scheme 15. Synthesis of chiral azepanes by organolithium-me- diated Smiles rearrangement

Scheme 16. Switchable Smiles rearrangement for the synthesis of axially chiral aniline derivatives

Scheme 17. Diastereoselective synthesis of bicyclic hydantoin derivatives bearing α-aryl quaternary stereocenters

Scheme 18. Asymmetric tandem lithiation-arylation reaction

Scheme 19. Amines bearing tertiary substituents by tandem enantioselective carbolithiation-Smiles rearrangement of vinylureas

Scheme 20. Enantioselective intramolecular α-arylation of benzylamine derivatives

Scheme 21. Asymmetric ring expansion and stereochemically retentive re-contraction of cyclic ureas

Scheme 22. Asymmetric, visible light-mediated radical sulfinyl-Smiles rearrangement

Scheme 23. Photoinduced radical sulfur dioxide insertion and Smiles rearrangement

Scheme 24. Stereoselective migratory heteroaryltrifluoromethylation of allylic amines via electrosynthesis

Scheme 25. Asymmetric, remote C(sp3)—H arylation via sulfinyl-Smiles rearrangement

Scheme 26. Photocatalytic asymmetric acyl radical Smiles rearrangement

Scheme 27. Photoredox radical Smiles rearrangement of N-sulfinyl acrylamides with bromodifluoroacetamides

Scheme 28. Asymmetric Smiles rearrangement with chiral sulfoxides

Scheme 29. Visible-light-mediated radical Smiles rearrangement via arylazo sulfones

Scheme 30. Photoinduced asymmetric Smiles rearrangement and radical sulfur dioxide insertion

Scheme 31. Chiral arylsulfinylamides as reagents for visible light-mediated asymmetric alkene aminoarylations

Scheme 32. Asymmetric radical aminoarylation of alkenes using chiral arylsulfinamides as bifunctional reagents

Scheme 33. Photoinduced asymmetric alkene aminohetarylation with chiral sulfoximine reagents

Scheme 34. Catalytic enantioselective Smiles rearrangement enabled by the directed evolution of P450 radical aryl migratases

References 38

[1]	(a) Warren, L. A.; Smiles, S. J. Chem. Soc. 1930, 1327.
	(b) Warren, L. A.; Smiles, S. J. Chem. Soc. 1930, 956.
	(c) Levi, A.; Warren, L. A.; Smiles, S. J. Chem. Soc. 1933, 1490.
[2]	(a) Chen, Z. M.; Zhang, X. M.; Tu, Y. Q. Chem. Soc. Rev. 2015, 44, 5220.
	(b) Coulibali, S.; Godou, T.; Canesi, S. Org. Lett. 2016, 18, 4348.
	(c) Lin, S.-B.; He, X.-R.; Meng, J.-P.; Gu, H.-N.; Zhang, P.-Z.; Wu, J. Chin. J. Org. Chem. 2017, 37, 1864 (in Chinese)
	(蔺松波, 何兴瑞, 孟金鹏, 顾海宁, 张培志, 吴军, 有机化学, 2017, 37, 1864.)
	(d) Holden, C. M.; Greaney, M. F. Chem.-Eur. J. 2017, 23, 8992.
	(e) Horst, B.; Verdoorn, D. S.; Hennig, S.; van der Heijden, G.; Ruijter, E. Angew. Chem., Int. Ed. 2022, 61, e202210592.
	(f) Signo, K.; Canesi, S. Org. Lett. 2022, 24, 4939.
[3]	(a) Truce, W. E.; Ray, W. J., Jr.; Norman, O. L.; Eickemeyer, D. B. J. Am. Chem. Soc. 1958, 80, 3625.
	(b) Snape, T. J. Chem. Soc. Rev. 2008, 37, 2452.
	(c) Xia, S.; Wang, L.-Y.; Zuo, H.; Li, Z.-B. Curr. Org. Synth. 2013, 10, 935.
	(d) Allart-Simon, I.; Gérard, S.; Sapi, J. Molecules 2016, 21, 878.
	(e) Whalley, D. M.; Greaney, M. F. Synthesis 2022, 54, 1908.
	(f) Simonian, N.; Guerinot, A.; Cossy, J. Synthesis 2023, 55, 1616.
[4]	(a) Chen, Y.; Chang, L.; Zuo, Z. Acta Chim. Sinica 2019, 77, 794 (in Chinese).
	(陈奕霖, 常亮, 左智伟, 化学学报, 2019, 77, 794.)
	(b) Allen, A. R.; Noten, E. A.; Stephenson, C. R. J. Chem. Rev. 2022, 122, 2695.
	(c) He, C.; Zhou, Y.; Duan, X.; Liu, L. Chin. J. Org. Chem. 2025, 45, 1478.
	(d) Wang, Y.; Zhang, X.; Kong, K.; Shu, C. Org. Chem. Front. 2025, 12, 4666.
	(e) Luo, N.; Jiang, J.; Suleman, M.; Liu, Z.; Huang, S.; Xiao, W.; Wu, J.; Huang, J. Chin. Chem. Lett. 2026, 37, 111556.
[5]	(a) Wales, S. M.; Saunthwal, R. K.; Clayden, J. Acc. Chem. Res. 2022, 55, 1731.
	(b) Chen, F.; Cao, Z.; Zhu, C. Angew. Chem., Int. Ed. 2025, 64, e202424667.
[6]	Clayden, J.; Dufour, J.; Grainger, D. M.; Helliwell, M. J. Am. Chem. Soc. 2007, 129, 7488.
[7]	Clayden, J.; Hennecke, U. Org. Lett. 2008, 10, 3567.
[8]	Lupi, V.; Penso, M.; Foschi, F.; Gassa, F.; Mihalia, V.; Tagliabue, A. Chem. Commun. 2009, 45, 5012.
[9]	Clayden, J.; Farnaby, W.; Grainger, D. M.; Hennecke, U.; Mancinelli, M.; Tetlow, D. J.; Hillier, I. H.; Vincent, M. A. J. Am. Chem. Soc. 2009, 131, 3410.
[10]	Fournier, A. M.; Brown, R. A.; Farnaby, W.; Miyatake-Ondozabal, H.; Clayden, J. Org. Lett. 2010, 12, 2222.
[11]	Foschi, F.; Landini, D.; Lupi, V.; Mihali, V.; Penso, M.; Pilati, T.; Tagliabue, A. Chem.-Eur. J. 2010, 16, 10667.
[12]	MacLellan, P.; Clayden, J. Chem. Commun. 2011, 47, 3395.
[13]	Tomohara, K.; Yoshimura, T.; Hyakutake, R.; Yang, P.; Kawabata, T. J. Am. Chem. Soc. 2013, 135, 13294.
[14]	Mingat, G.; MacLellan,, P.; Laars, M.; Clayden, J. Org. Lett., 2014, 16, 1252.
[15]	Atkinson, R. C.; Fernández-Nieto, F.; Mas Roselló, J.; Clayden, J. Angew. Chem., Int. Ed. 2015, 54, 8961.
[16]	Maury, J.; Clayden, J. J. Org. Chem. 2015, 80, 10757.
[17]	Leonard, D. J.; Ward, J. W.; Clayden, J. Nature 2018, 562, 105.
[18]	Mas-Roselló, J.; Okoha, M.; Clayden, J. Chem. Commun. 2018, 54, 10985.
[19]	Zawodny, W.; Montgomery, S. L.; Marshall, J. R.; Finnigan, J. D.; Turner, N. J.; Clayden, J. J. Am. Chem. Soc. 2018, 140, 17872.
[20]	Chang, X.; Zhang, Q.; Guo, C. Org. Lett. 2019, 21, 4915.
[21]	Taspinar, Ö.; Leonard, D. J.; Picois, N.; Göcke, C.; Žabka, M.; Sparkes, H. A.; Clayden, J. Angew. Chem., Int. Ed. 2025, 64, e202507713.
[22]	Tetlow, D. J.; Hennecke, U.; Raftery, J.; Waring, M. J.; Clarke, D. S.; Clayden, J. Org. Lett. 2010, 12, 5442.
[23]	Tait, M.; Donnard, M.; Minassi, A.; Lefranc, J.; Bechi, B.; Carbone, G.; O'Brien,, P.; Clayden, J. Org. Lett. 2013, 15, 34.
[24]	Saunthwal, R. K.; Schwarz, M.; Mallick, R. K.; Terry-Wright, W.; Clayden, J. Angew. Chem., Int. Ed. 2023, 62, e202216758.
[25]	Mallick, R. K.; Žabka, M.; Clayden, J. Angew. Chem., Int. Ed. 2024, 63, e202318417.
[26]	Hervieu, C.; Kirillova, M.S.; Suárez, T.; Müller, M.; Merino, E.; Nevado, C. Nat. Chem. 2021, 13, 327.
[27]	Huang, J.; Liu, F.; Zeng, L.-H.; Li, S.; Chen, Z.; Wu, J. Nat. Commun. 2022, 13, 7081.
[28]	Lan, J.; Lin, K.; Zhang, X.; Zhu, T. Green Chem. 2022, 24, 6138.
[29]	Hu, Y.; Hervieu, C.; Merino, E.; Nevado, C. Angew. Chem., nt. Ed. 2024, 63, e202319158.
[30]	Ma, W.-Y.; Leone, M.; Derat, E.; Retailleau,, P.; Reddy, C.R.; Neuville, L.; Masson, G. Angew. Chem., nt. Ed. 2024, 63, e202408154.
[31]	Tian, L.; Chen, P.; Ji, X.; Deng, G.-J.; Huang, H. Org. Lett. 2025, 27, 455.
[32]	Hu, Y.; Schreyer, T.; Nevado, C. Angew. Chem., nt. Ed. 2025, 64, e202509470.
[33]	Di Terlizzi, L.; Nicchio, L.; Montinho-Inacio, E.; Tiwari, N.; Derat, E.; Retailleau,, P.; Fagnoni, M.; Neuville, L.; Protti, S.; Masson, G. JACS Au 2025, 5, 4972.
[34]	Wang, C.; Xiao, W.; Wu, J. Org. Chem. Front. 2025, 12, 4469.
[35]	Hervieu, C.; Kirillova, M.S.; Hu, Y.; Cuesta-Galisteo, S.; Merino, E.; Nevado, C. Nat. Chem. 2024, 16, 607.
[36]	Noten, E.A.; Ng, C.H.; Wolesensky, R.M.; Stephenson, C. R. J. Nat. Chem. 2024, 16, 599.
[37]	Cao, Z.; Sun, Y.; Chen, Y.; Zhu, C. Angew. Chem., nt. Ed. 2024, 63, e202408177.
[38]	Fu, W.; Murcek, K.; Chen, J.; Liu, A.; Zhao, Y.; Liu, P.; Yang, Y. J. Am. Chem. Soc. 2025, 147, 12197.

不对称Smiles重排反应研究进展

Research Progress on Asymmetric Smiles Rearrangement

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Fig. & Tab. 34

References 38

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