Citation: Hong Xin, Shutao Wang, Li-Na Guo, Cheng Guan, Jinyi Liao, Zi-Hang Yuan, Zhengze Zhang, Xin-Hua Duan. An unusual carbon radical-mediated ring-opening/amination or esterification cascade of unstrained α-haloalkyl cycloketone derivatives[J]. Chinese Chemical Letters, ;2026, 37(7): 111939. doi: 10.1016/j.cclet.2025.111939 shu

An unusual carbon radical-mediated ring-opening/amination or esterification cascade of unstrained α-haloalkyl cycloketone derivatives

Hong Xin ^{a, 1} ,
Shutao Wang ^{a, 1} ,
Li-Na Guo ^a ,
Cheng Guan ^a ,
Jinyi Liao ^a ,
Zi-Hang Yuan ^a ,
Zhengze Zhang ^b ,
Xin-Hua Duan ^{a, b, *,}

a.
Department of Chemistry, School of Chemistry, Xi'an Key Laboratory of Sustainable Energy Material Chemistry and Engineering Research Center of Energy Storage, Materials and Devices, Ministry of Education Xi'an Jiaotong University, Xi'an 710049, China
b.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China

duanxh@xjtu.edu.cn

Received Date: 22 May 2025
Revised Date: 25 September 2025
Accepted Date: 9 October 2025
Available Online: 10 October 2025

Figures(8)

The carbon-centered radical induced C‒C bond cleavage in strained cyclopropane is a well-known process. However, achieving similar transformations in unstrained rings is still challenging. Herein, a novel inexpensive Cu-catalyzed strategy for the carbon-centered radical-mediated ring-opening/amination or esterification cascade of unstrained α-haloalkyl cycloketone derivatives is presented. Differ from the classical Dowd-Beckwith ring expansion reaction, a ring opening cascade occurred successfully under a simple copper/base catalytic system, yielding useful distal unsaturated amides and esters in good to excellent yields. Mechanistic studies and DFT calculations indicate that the halogen-bonding interaction between halide and base is crucial for the activation of the C‒Br bond. Furthermore, the formation of a bicyclic Cu-complex via bi-dentate coordination, including O–Cu–^•CH₂, seems to be a crucial factor that promotes ring opening rather than the conventional ring expansion. This work would not only bring new vitality for the radical-mediated C‒C bond cleavage, but also highlight the potential of protocol for synthesizing bioactive molecules.
- Carbon radical-mediated,
- C-C bond cleavage,
- Amination,
- Esterification,
- Halogen bond
1. [1]
  F. Song, T. Gou, B.Q. Wang, Z.J. Shi, Chem. Soc. Rev. 47 (2018) 7078–7115. doi: 10.1039/c8cs00253c
2. [2]
  X.X. Wu, C. Zhu, Chin. J. Chem. 37 (2019) 171–182. doi: 10.1002/cjoc.201800455
3. [3]
  S.P. Morcillo, Angew. Chem. Int. Ed. 58 (2019) 14044–14054. doi: 10.1002/anie.201905218
4. [4]
  P. Sivaguru, Z.K. Wang, G. Zanoni, X.H. Bi, Chem. Soc. Rev. 48 (2019) 2615–2656. doi: 10.1039/c8cs00386f
5. [5]
  Y.F. Liang, M. Bilal, L.Y. Tang, et al., Chem. Rev. 123 (2023) 12313–12370. doi: 10.1021/acs.chemrev.3c00219
6. [6]
  J.B. Roque, Y. Kuroda, L.T. Göttemann, R. Sarpong, Science 361 (2018) 171–174. doi: 10.1126/science.aat6365
7. [7]
  J.B. Roque, Y. Kuroda, L.T. Göttemann, R. Sarpong, Nature 564 (2018) 244–248. doi: 10.1038/s41586-018-0700-3
8. [8]
  A. Riahi, J. Muzart, M. Abe, N. Hoffmann, New J. Chem. 37 (2013) 2245–2249. doi: 10.1039/c3nj00457k
9. [9]
  A.S.K. Tsang, A. Kapat, F. Schoenebeck, J. Am. Chem. Soc. 138 (2016) 518–526. doi: 10.1021/jacs.5b08347
10. [10]
  H. Xin, X.H. Duan, L. Liu, L.N. Guo, Chem. Eur. J. 26 (2020) 11690–11694. doi: 10.1002/chem.202001032
11. [11]
  H. Xin, X.H. Duan, M. Yang, Y. Zhang, L.N. Guo, J. Org. Chem. 86 (2021) 8263–8273. doi: 10.1021/acs.joc.1c00708
12. [12]
  L. Deng, G. Dong, Trends Chem. 2 (2020) 183–198. doi: 10.1016/j.trechm.2019.12.002
13. [13]
  A. Matsumoto, K. Maruoka, Bull. Chem. Soc. Jpn. 94 (2021) 513–524. doi: 10.1246/bcsj.20200321
14. [14]
  H. Xin, Z.H. Yuan, M. Yang, et al., Green Chem. 23 (2021), 9549–9553. doi: 10.1039/d1gc03230e
15. [15]
  S. Liu, P. Ma, L. Zhang, et al., Chem. Sci. 14 (2023) 5220–5225. doi: 10.1039/d2sc06157k
16. [16]
  J.J. Guo, A. Hu, Z. Zuo, Tetrahedron Lett. 59 (2018) 2103–2111. doi: 10.1016/j.tetlet.2018.04.060
17. [17]
  L. Chang, Q. An, L. Duan, K. Feng, Z. Zuo, Chem. Rev. 122 (2022) 2429–2486. doi: 10.1021/acs.chemrev.1c00256
18. [18]
  P.R. Murray, J.H. Cox, N.D. Chiappini, et al., Chem. Rev. 122 (2022) 2017–2291. doi: 10.1021/acs.chemrev.1c00374
19. [19]
  X. Fan, H. Zhao, J. Yu, X. Bao, C. Zhu, Org. Chem. Front. 3 (2016) 227–232. doi: 10.1039/C5QO00368G
20. [20]
  D. Wang, J. Mao, C. Zhu, Chem. Sci. 9 (2018) 5805–5809. doi: 10.1039/c8sc01763h
21. [21]
  H. Yan, G.S. Smith, F.E. Chen, Green Synth. Catal. 3 (2022) 219–226.
22. [22]
  R.N. Yi, W.M. He, Chin. Chem. Lett. 36 (2025) 110787. doi: 10.1016/j.cclet.2024.110787
23. [23]
  X. Wu, C. Zhu, Chem. Rec. 18 (2018) 587–598. doi: 10.1002/tcr.201700090
24. [24]
  M. Wang, M. Li, S. Yang, et al., Nat. Commun. 11 (2020) 672–679. doi: 10.1038/s41467-020-14435-5
25. [25]
  P. Dowd, S.C. Choi, J. Am. Chem. Soc. 109 (1987) 3493–3494. doi: 10.1021/ja00245a069
26. [26]
  P. Dowd, S.C. Choi, J. Am. Chem. Soc. 109 (1987) 6548–6549. doi: 10.1021/ja00255a071
27. [27]
  A.L.J. Beckwith, D.M. O'Shea, S. Gerba, S.W. Westwood, J. Chem. Soc., Chem. Commun. 9 (1987) 666–667.
28. [28]
  A.L.J. Beckwith, D.M. O'Shea, S.W. Westwood, J. Am. Chem. Soc. 110 (1988) 2565–2575. doi: 10.1021/ja00216a033
29. [29]
  K. Nishikawa, T. Ando, K. Maeda, T. Morita, Y. Yoshimi, Org. Lett. 15 (2013) 636–638. doi: 10.1021/ol303460u
30. [30]
  E. Hasegawa, M. Tateyama, T. Hoshi, et al., Tetrahedron 70 (2014) 2776–2783. doi: 10.1016/j.tet.2014.02.078
31. [31]
  M. Deguchi, A. Fujiya, E. Yamaguchi, et al., RSC Adv. 8 (2018) 15825–15830. doi: 10.1039/c8ra02383b
32. [32]
  L. Chen, L.N. Guo, S. Liu, L. Liu, X.H. Duan, Chem. Sci. 12 (2021) 1791–1795. doi: 10.1039/d0sc04399k
33. [33]
  H. Xin, L.N. Guo, M. Yang, et al., Org. Chem. Front. 10 (2023) 1147–1152. doi: 10.1039/d2qo02001g
34. [34]
  T. Songha, G.A. Kadam, D.P. Hari, Chem. Sci. 14 (2023) 6930–6935. doi: 10.1039/D3SC01908J
35. [35]
  Q. Zhang, M.F. Chiou, C. Ye, et al., Chem. Sci. 13 (2022) 6836–6841. doi: 10.1039/d2sc00902a
36. [36]
  T. Hashimoto, Y. Kawamata, K. Maruoka, Nat. Chem. 6 (2014) 702–705. doi: 10.1038/nchem.1998
37. [37]
  Z.Q. Zhang, X.Y. Meng, J. Sheng, Q. Lan, X.S. Wang, Org. Lett. 21 (2019) 8256–8260. doi: 10.1021/acs.orglett.9b03012
38. [38]
  F.F. Feng, J.A. Ma, D. Cahard, J. Org. Chem. 86 (2021) 13808–13816. doi: 10.1021/acs.joc.1c01886
39. [39]
  Y. Liu, J.L. Sui, W.Q. Yu, et al., J. Org. Chem. 88 (2023) 8563–8575. doi: 10.1021/acs.joc.3c00486
40. [40]
  Y. Zhang, C. Zhao, C. Ma, et al., Angew. Chem. Int. Ed. 62 (2023) e202300166. doi: 10.1002/anie.202300166
41. [41]
  C. Zhao, W. Ma, K. Liu, et al., Org. Chem. Front. 11 (2024) 4663–4670. doi: 10.1039/d4qo00996g
42. [42]
  P.R. Khoury, J.D. Goddard, W. Tam, Tetrahedron 60 (2004) 8103–8112. doi: 10.1016/j.tet.2004.06.100
43. [43]
  J.W. Zhang, Y.R. Wang, J.H. Pan, et al., Angew. Chem. Int. Ed. 59 (2020) 3900–3904. doi: 10.1002/anie.201914623
44. [44]
  J. Hierold, T. Hsia, D.W. Lupton, Org. Biomol. Chem. 9 (2011) 783–792. doi: 10.1039/C0OB00632G
45. [45]
  A. Elhage, P. Costa, A. Nasim, A.E. Lanterna, J.C. Scaiano, J. Phys. Chem. A 123 (2019) 10224–10229. doi: 10.1021/acs.jpca.9b06716
46. [46]
  H.F. Piedra, M. Plaza, Chem. Sci. 14 (2023) 650–657. doi: 10.1039/d2sc05556b
47. [47]
  P. Dowd, W. Zhang, Chem. Rev. 93 (1993) 2091–2115. doi: 10.1021/cr00022a007
48. [48]
  A.J. Clark, Chem. Soc. Rev. 31 (2002) 1–11.
49. [49]
  K.W. Shimkin, D.A. Waton, Beilstein J. Org. Chem. 11 (2015) 2278–2288. doi: 10.3762/bjoc.11.248
50. [50]
  Q.M. Kainz, C.D. Matier, A. Bar-toszewicz, et al., Science 351 (2016) 681–684. doi: 10.1126/science.aad8313
51. [51]
  A. Hossain, A. Bhattacharyya, O. Reiser, Science 364 (2019) eaav9713. doi: 10.1126/science.aav9713
52. [52]
  Y. Luo, Y. Li, J. Wu, et al., Science 381 (2023) 1072–1079. doi: 10.1126/science.adg9232
1. [1]
  Wen-Jing Li , Jun-Bo Wang , Yu-Heng Liu , Mo Zhang , Zhan-Hui Zhang . Molybdenum-doped carbon nitride as an efficient heterogeneous catalyst for direct amination of nitroarenes with arylboronic acids. Chinese Chemical Letters, 2025, 36(3): 110001-. doi: 10.1016/j.cclet.2024.110001
2. [2]
  Guang Zeng , Yue Zeng , Huamin Hu , Yaqing Bai , Fangjie Nie , Junfei Duan , Zhaoyong Chen , Qi-Long Zhu . Regulating pore structure and pseudo-graphitic phase of hard carbon anode towards enhanced sodium storage performance. Chinese Chemical Letters, 2025, 36(7): 110122-. doi: 10.1016/j.cclet.2024.110122
3. [3]
  Zhikang Wu , Guoyong Dai , Qi Li , Zheyu Wei , Shi Ru , Jianda Li , Hongli Jia , Dejin Zang , Mirjana Čolović , Yongge Wei . POV-based molecular catalysts for highly efficient esterification of alcohols with aldehydes as acylating agents. Chinese Chemical Letters, 2024, 35(8): 109061-. doi: 10.1016/j.cclet.2023.109061
4. [4]
  Wen-Tao Ouyang , Jun Jiang , Yan-Fang Jiang , Ting Li , Yuan-Yuan Liu , Hong-Tao Ji , Li-Juan Ou , Wei-Min He . Sono-photocatalytic amination of quinoxalin-2(1H)-ones with aliphatic amines. Chinese Chemical Letters, 2024, 35(10): 110038-. doi: 10.1016/j.cclet.2024.110038
5. [5]
  Chong-Yang Shi , Jian-Xing Gong , Zhen Li , Chao Shu , Long-Wu Ye , Qing Sun , Bo Zhou , Xin-Qi Zhu . Gold-catalyzed intermolecular amination of allyl azides with ynamides: Efficient construction of 3-azabicyclo[3.1.0] scaffold. Chinese Chemical Letters, 2025, 36(2): 109895-. doi: 10.1016/j.cclet.2024.109895
6. [6]
  Jun-Ting Mo , Zheng Wang . Achieving tunable long persistent luminescence in metal organic halides based on pyridine solvent. Chinese Chemical Letters, 2024, 35(9): 109360-. doi: 10.1016/j.cclet.2023.109360
7. [7]
  Boqiang Wang , Yongzhuo Xu , Jiajia Wang , Muyang Yang , Guo-Jun Deng , Wen Shao . Transition-metal free trifluoromethylimination of alkenes enabled by direct activation of N-unprotected ketimines. Chinese Chemical Letters, 2024, 35(9): 109502-. doi: 10.1016/j.cclet.2024.109502
8. [8]
  Shan-Shan Li , Juan Luo , Shu-Nuo Liang , Dan-Na Chen , Li-Ning Chen , Cheng-Xue Pan , Peng-Ju Xia . Efficient and regioselective C=S bond difunctionalization through a three-component radical relay strategy. Chinese Chemical Letters, 2025, 36(6): 110424-. doi: 10.1016/j.cclet.2024.110424
9. [9]
  Jing Ren , Feng-Huan Du , Xiaowei Chen , Chi Zhang . Monofluoroiodane(Ⅲ) reagent mediated Wagner−Meerwein rearrangement fluorination: Construction of quaternary C(sp³)−F bond. Chinese Chemical Letters, 2026, 37(5): 111407-. doi: 10.1016/j.cclet.2025.111407
10. [10]
  Jia-Sheng Wang , Lin-Heng He , Yan-Ting Liu , Yu-Ting Wu , Hai-Tao Zhu , Sheng-Hua Wang , Yu-Yu Tan , Wei-Min He , Yong-Hong Zhang . Synergistic homogeneous photochemical and halogen-bond catalysis toward antitumor sulfonylated fused (hetero)arenes. Chinese Chemical Letters, 2026, 37(5): 112373-. doi: 10.1016/j.cclet.2026.112373
11. [11]
  Peng Wang , Jianjun Wang , Ni Song , Xin Zhou , Ming Li . Radical dehydroxymethylative fluorination of aliphatic primary alcohols and diverse functionalization of α-fluoroimides via BF₃·OEt₂-catalyzed C‒F bond activation. Chinese Chemical Letters, 2025, 36(1): 109748-. doi: 10.1016/j.cclet.2024.109748
12. [12]
  Shaofeng Gong , Zi-Wei Deng , Chao Wu , Wei-Min He . Stabilized carbon radical-mediated three-component functionalization of amino acid/peptide derivatives. Chinese Chemical Letters, 2025, 36(5): 110936-. doi: 10.1016/j.cclet.2025.110936
13. [13]
  Junmeng Luo , Qiongqiong Wan , Suming Chen . Chemistry-driven mass spectrometry for structural lipidomics at the C=C bond isomer level. Chinese Chemical Letters, 2025, 36(1): 109836-. doi: 10.1016/j.cclet.2024.109836
14. [14]
  Tian-Zhang Wang , Le-Yu Tang , Yu-Qiu Guan , Lingfei Hu , Gang Lu , Yu-Feng Liang . Nickel-catalyzed reductive alkynylation of ketoimines via unstrained C–C bond activation. Chinese Chemical Letters, 2025, 36(11): 111050-. doi: 10.1016/j.cclet.2025.111050
15. [15]
  Guodong Xu , Chengcai Sheng , Xiaomeng Zhao , Tuojiang Zhang , Zongtang Liu , Jun Dong . Reform of Comprehensive Organic Chemistry Experiments in the Context of Emerging Engineering Education: A Case Study on the Improved Preparation of Benzocaine. University Chemistry, 2024, 39(11): 286-295. doi: 10.12461/PKU.DXHX202403094
16. [16]
  Qiongqiong Wan , Yanan Xiao , Guifang Feng , Xin Dong , Wenjing Nie , Ming Gao , Qingtao Meng , Suming Chen . Visible-light-activated aziridination reaction enables simultaneous resolving of C=C bond location and the sn-position isomers in lipids. Chinese Chemical Letters, 2024, 35(4): 108775-. doi: 10.1016/j.cclet.2023.108775
17. [17]
  Guoju Guo , Xufeng Li , Jie Ma , Yongjia Shi , Jian Lv , Daoshan Yang . Photocatalyst/metal-free sequential C–N/C–S bond formation: Synthesis of S-arylisothioureas via photoinduced EDA complex activation. Chinese Chemical Letters, 2024, 35(11): 110024-. doi: 10.1016/j.cclet.2024.110024
18. [18]
  Yi Luo , Lin Dong . Multicomponent remote C(sp²)-H bond addition by Ru catalysis: An efficient access to the alkylarylation of 2H-imidazoles. Chinese Chemical Letters, 2024, 35(10): 109648-. doi: 10.1016/j.cclet.2024.109648
19. [19]
  Yang Li , Yanan Dong , Zhihong Wei , Changzeng Yan , Zhen Li , Lin He , Yuehui Li . Fluoride-promoted Ni-catalyzed cyanation of C–O bond using CO₂ and NH₃. Chinese Chemical Letters, 2025, 36(5): 110206-. doi: 10.1016/j.cclet.2024.110206
20. [20]
  Xiangyang Ji , Yishuang Chen , Peng Zhang , Shaojia Song , Jian Liu , Weiyu Song . Boosting the first C–H bond activation of propane on rod-like V/CeO₂ catalyst by photo-assisted thermal catalysis. Chinese Chemical Letters, 2025, 36(5): 110719-. doi: 10.1016/j.cclet.2024.110719

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(18)
HTML views(1)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142