Citation: Wenyan Zhao, Tiantian Liang, Dongcheng Zheng, Jiali Qiu, Juan Zheng, Yandong Wu, Wenhan Xu, Liang Liu, Fei Ye. Nickel-catalyzed quantitative deuterated reduction of quinolines and alkenes[J]. Chinese Chemical Letters, ;2026, 37(8): 112035. doi: 10.1016/j.cclet.2025.112035 shu

Nickel-catalyzed quantitative deuterated reduction of quinolines and alkenes

Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China

liang.liu@ccnu.edu.cn

yef@ccnu.edu.cn

Received Date: 21 August 2025
Revised Date: 15 October 2025
Accepted Date: 29 October 2025
Available Online: 29 October 2025

Figures(7)

Site-selective deuterated reduction of quinoline to deuterium-labelled 1,2,3,4-tetrahydroquinoline scaffold can offer a powerful strategy for drug development, mechanistic studies, and synthesis of isotopically labeled standards. Existing deuterated reduction methods predominantly produce fully deuterated piperidines, lacking control over regioselectivity and deuterium stoichiometry. Herein, we report a Ni-catalyzed sequential deuteration protocol that enables regio- and multiplicity-controlled synthesis of mono-, di-, and tri-deuterated tetrahydroquinolines with simple deuterating reagents. Nucleophilic and electrophilic deuterating sources were combined to achieve site-selective reductive deuteration at 2-, 3- and 4-positions of quinolines. The method features broad functional group compatibility and delivers D-labeled tetrahydroquinolines in high yields with excellent positional deuterium incorporation. The protocol was further extended to the double-deuteration of different classes of olefins, quinoxalines and acridines, thus providing a unified platform for efficient synthesis of selectively D-labeled N-containing heterocycles and alkenes derivatives.
- Nickel-catalyzed,
- Quantitative deuterated,
- Reduction,
- Quinolines,
- Alkenes
1. [1]
  M.P. Wiesenfeldt, Z. Nairoukh, T. Dalton, et al., Angew. Chem. Int. Ed. 58 (2019) 10460–10476. doi: 10.1002/anie.201814471
2. [2]
  D.S. Wang, Q.A. Chen, S.M. Lu, et al., Chem. Rev. 112 (2012) 2557–2590. doi: 10.1021/cr200328h
3. [3]
  M. Rueping, A.P. Antonchick, T.A. Theissmann, Angew. Chem. Int. Ed. 45 (2006) 3683–3686. doi: 10.1002/anie.200600191
4. [4]
  R. Adam, J.R. Cabrero-Antonino, A. Spannenberg, et al., Angew. Chem. Int. Ed. 56 (2017) 1–6.
5. [5]
  Y. Wang, B.B. Dong, Z.K. Wang, et al., Org. Lett. 21 (2019) 3631–3634. doi: 10.1021/acs.orglett.9b01055
6. [6]
  S. Adak, S.E. Braley, M.K. Brown, Org. Lett. 26 (2024) 401–405. doi: 10.1021/acs.orglett.3c04096
7. [7]
  F. Chen, A. Surkus, L. He, et al., J. Am. Chem. Soc. 137 (2015) 11718–11724. doi: 10.1021/jacs.5b06496
8. [8]
  A. Karakulina, A. Gopakumar, I. AkÅok, et al., Angew. Chem. Int. Ed. 55 (2016) 292–296. doi: 10.1002/anie.201507945
9. [9]
  Y. Lu, Y. Yamamoto, A.I. Almansour, et al., Chin. J. Catal. 39 (2018) 1746–1752. doi: 10.1016/S1872-2067(18)63151-1
10. [10]
  D. Ren, L. He, L. Yu, J. Am. Chem. Soc. 134 (2012) 17592–17598. doi: 10.1021/ja3066978
11. [11]
  L. Lückemeier, T. De Vos, L. Schlichter, et al., J. Am. Chem. Soc. 146 (2024) 5864–5871. doi: 10.1021/jacs.3c11163
12. [12]
  T.L. Wang, L.G. Zhuo, Z.W. Li, et al., J. Am. Chem. Soc. 133 (2011) 9878–9891. doi: 10.1021/ja2023042
13. [13]
  S.M. Treacy, A.L. Smith, R.G. Bergman, et al., J. Am. Chem. Soc. 146 (2024) 29792–29800. doi: 10.1021/jacs.4c11482
14. [14]
  Z.L. Wang, L. Chen, G.L. Mao, et al., Chin. Chem. Lett. 31 (2020) 1890–1894. doi: 10.1016/j.cclet.2020.02.025
15. [15]
  M.H. Zhang, N. Zhang, Q. Zhao, et al., Chin. Chem. Lett. 36 (2025) 110081. doi: 10.1016/j.cclet.2024.110081
16. [16]
  L.Y. Huang, H. Zhang, Y.J. Cheng, et al., Chin. Chem. Lett. 33 (2022) 2569–2572. doi: 10.1016/j.cclet.2021.10.004
17. [17]
  F. Lovering, J. Bikker, C. Humblet, et al., J. Med. Chem. 52 (2009) 6752–6756. doi: 10.1021/jm901241e
18. [18]
  M. Aldeghi, S. Malhotra, D.L. Selwood, et al., Chem. Biol. Drug. Des. 83 (2014) 450–461. doi: 10.1111/cbdd.12260
19. [19]
  A. Kaithal, T. Wagener, P. Bellotti, et al., Angew. Chem. Int. Ed. 61 (2022) e202206687. doi: 10.1002/anie.202206687
20. [20]
  V. Sridharan, P.A. Suryavanshi, J.C. Menendez, Chem. Rev. 111 (2011) 7157–7259. doi: 10.1021/cr100307m
21. [21]
  I. Muthukrishnan, V. Sridharan, J.C. Menendez, Chem. Rev 119 (2019) 5057–5191. doi: 10.1021/acs.chemrev.8b00567
22. [22]
  P. Yadav, A. Kumar, I. Althagafi, et al., Curr. Top. Med. Chem. 21 (2021) 1587–1622. doi: 10.2174/1568026621666210526164208
23. [23]
  C. Schmidt, Nat. Biotechnol. 35 (2017) 493–494. doi: 10.1038/nbt0617-493
24. [24]
  J. Atzrodt, V. Derdau, W.J. Kerr, et al., Angew. Chem. Int. Ed. 57 (2018) 1758–1784. doi: 10.1002/anie.201704146
25. [25]
  S. Kopf, F. Bourriquen, W. Li, et al., Chem. Rev. 122 (2022) 6634–6718. doi: 10.1021/acs.chemrev.1c00795
26. [26]
  T. Piyali, M. Serafini, S. Cargnin, et al., J. Med. Chem. 62 (2019) 5276–5297. doi: 10.1021/acs.jmedchem.8b01808
27. [27]
  T.G. Gant, J. Med. Chem. 57 (2014) 3595–3611. doi: 10.1021/jm4007998
28. [28]
  J. Peng, G.P. Luo, C. Wu, et al., Chin. Chem. Lett. 36 (2025) 111255. doi: 10.1016/j.cclet.2025.111255
29. [29]
  A. Kumar, E. Yasmin, S. Dhole, T. Wagh, V. Arora, Patent, WO2023194812, 2023.
30. [30]
  A. Palazzolo, T. Naret, M. Daniel-Bertrand, et al., Angew. Chem. Int. Ed. 59 (2020) 20879–20884. doi: 10.1002/anie.202009258
31. [31]
  F.X. Bu, Y.Q. Deng, J. Xu, et al., Nature 634 (2024) 592–599. doi: 10.1038/s41586-024-07989-7
32. [32]
  M. Escolano, D. Gaviña, G. Alzuet-Piña, et al., Chem. Rev. 124 (2024) 1122–1246. doi: 10.1021/acs.chemrev.3c00625
33. [33]
  Z.K. Liu, L. Qin, Y. Wei, et al., Chin. J. Chem. 43 (2025) 1673–1678. doi: 10.1002/cjoc.70039
34. [34]
  L.J. Xiao, L. Cheng, W.M. Feng, et al., Angew. Chem. Int. Ed. 57 (2018) 461–464. doi: 10.1002/anie.201710735
35. [35]
  Y.L. He, Y.L. Cai, S.L. Zhu, J. Am. Chem. Soc. 139 (2017) 1061–1064. doi: 10.1021/jacs.6b11962
36. [36]
  H. Song, W.J. Zhang, H. Zhou, et al., ACS Catal. 13 (2023) 3644–3654. doi: 10.1021/acscatal.3c00559
37. [37]
  L. Kania, H. Unvera, Polyhedron 187 (2020) 114649. doi: 10.1016/j.poly.2020.114649
38. [38]
  Z.K. Zhang, S. Bera, C. Fan, et al., J. Am. Chem. Soc. 144 (2022) 7015–7029. doi: 10.1021/jacs.1c13482
39. [39]
  L.P. Meng, J.J. Yang, M. Duan, et al., Angew. Chem. Int. Ed. 60 (2021) 23584–23589. doi: 10.1002/anie.202109881
40. [40]
  J. Nguyen, A. Chong, G. Lalic, Chem. Sci. 10 (2019) 3231–3236. doi: 10.1039/c8sc05445b
41. [41]
  Y.Q. Li, Y.X. Luo, L. Peng, et al., Nat. Commun. 11 (2020) 417. doi: 10.1007/s10815-019-01652-1
42. [42]
  K. Vasudevan, B.L. Scott, S.K. Hanson, Eur. J. Inorg. Chem. 30 (2012) 4898–4906. doi: 10.1002/ejic.201200758
43. [43]
  J.D. Liu, H.G. Gong, S.L. Zhu, Angew. Chem. Int. Ed. 60 (2021) 4060–4064. doi: 10.1002/anie.202012614
44. [44]
  N.A. Eberhardt, H. Guan, Chem. Rev. 116 (2016) 8373–8426. doi: 10.1021/acs.chemrev.6b00259
45. [45]
  A. Tenaglia, E. Terranova, B. Waegell, J. Mol. Catal. 40 (1987) 281–287. doi: 10.1016/0304-5102(87)80092-5
46. [46]
  M.J. Tenorio, M.C. Puerta, P. Valerga, J. Chem. Soc., Dalton Trans. (1996) 1305–1308.
47. [47]
  X. Wen, X.Z. Shi, X.L. Qiao, et al., Chem. Commun. 53 (2017) 5372. doi: 10.1039/C7CC02140B
48. [48]
  F. Chen, X.Y. Zhao, W.H. Miao, et al., Chin. Chem. Lett. 36 (2025) 110239. doi: 10.1016/j.cclet.2024.110239
49. [49]
  J. Luo, L.J. Lu, M. Montag, et al., Nat. Chem. 15 (2023) 1384–1390. doi: 10.1038/s41557-023-01313-y
50. [50]
  A. Kurimoto, R.S. Sherbo, Y. Cao, et al., Nat. Catal. 3 (2020) 719–726. doi: 10.1038/s41929-020-0488-z
51. [51]
  Z.P. Vang, A. Reyes, R.E. Sonstrom, et al., J. Am. Chem. Soc. 143 (2021) 7707–7718. doi: 10.1021/jacs.1c00884
52. [52]
  M. Espinal-Viguri, S.E. Neale, N.T. Coles, et al., J. Am. Chem. Soc. 141 (2019) 572–582. doi: 10.1021/jacs.8b11553
53. [53]
  X.S. Wu, X.Y. Luo, C.C. Li, et al., Acta Pharmacol. Sin. 45 (2024) 1964–1977. doi: 10.1038/s41401-024-01274-z
54. [54]
  D. Behera, S. Thiyagarajan, P.K. Anjalikrishna, et al., ACS Catal. 11 (2021) 5885–5893. doi: 10.1021/acscatal.1c01148
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