Citation: Baihui Zheng, Dandan Zhang, Baoping Ren, Yifei Li, Qun Liu, Ling Pan. Divergent site-selective synthesis of deuterated pyrroles from radical initiated cyclizations of N-propargyl enamines[J]. Chinese Chemical Letters, ;2026, 37(5): 111544. doi: 10.1016/j.cclet.2025.111544 shu

Divergent site-selective synthesis of deuterated pyrroles from radical initiated cyclizations of N-propargyl enamines

Jilin Province Key Laboratory of Organic Functional Molecular, Design & Synthesis, Department of Chemistry, Northeast Normal University, Changchun 130024, China

panl948@nenu.edu.cn

Received Date: 31 March 2025
Revised Date: 17 June 2025
Accepted Date: 3 July 2025
Available Online: 5 July 2025

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Although the incorporation of deuterium has been widely researched, controlled deuterium labelling at precise sites is still very challenging. Herein, efficient catalytic synthesis of deuterated pyrroles is focused, the radical cyclizations of N-propargyl enamines were achieved from photoredox-mediated deuterated water splitting, giving deuterated pyrroles with deuterations at the C(sp²) and C(sp³) precisely. One or two-sites-deuterium incorporation as well as the controllable deuteration label at multi-H/D-exchange-sites, such as a methyl group, have been realized in high selectivity and efficiency via the solvent-controlled divergent deuterations. A halogen effect between solvents and substrates was proposed to initiate different catalytic cycles for the deuterations. The broad tolerance to substrates, the gram scale synthesis under natural sunlight irradiation and its applications in the synthesis of drug analogues further verified their practicality.
- Deuterated water splitting,
- Divergent synthesis,
- Controllable label,
- Radical cyclization
1. [1]
  J. Atzrodt, V. Derdau, W.J. Kerr, et al., Angew. Chem. Int. Ed. 57 (2018) 1758–1784. doi: 10.1002/anie.201704146
2. [2]
  T. Pirali, M. Serafini, S. Cargnin, et al., J. Med. Chem. 62 (2019) 5276–5297. doi: 10.1021/acs.jmedchem.8b01808
3. [3]
  S. Kopf, F. Bourriquen, W. Li, et al., Chem. Rev. 122 (2022) 6634–6718. doi: 10.1021/acs.chemrev.1c00795
4. [4]
  C. Canlet, B.M. Fung, J. Phys. Chem. B 104 (2000) 6181–6185. doi: 10.1021/jp000509g
5. [5]
  L.H. Coudert, L. Margulès, C. Vastel, et al., A&A 624 (2019) A70. doi: 10.1051/0004-6361/201834827
6. [6]
  J. Atzrodt, V. Derdau, T. Fey, et al., Angew. Chem. Int. Ed. 46 (2007) 7744–7765. doi: 10.1002/anie.200700039
7. [7]
  J. Atzrodt, V. Derdau, W.J. Kerr, et al., Angew. Chem. Int. Ed. 57 (2018) 3022–3047. doi: 10.1002/anie.201708903
8. [8]
  A. Sattler, ACS Catal. 8 (2018) 2296–2312. doi: 10.1021/acscatal.7b04201
9. [9]
  F. Bu, Y. Deng, J. Xu, et al., Nature 634 (2024) 592–599. doi: 10.1038/s41586-024-07989-7
10. [10]
  G. Prakash, N. Paul, G.A. Oliver, et al., Chem. Soc. Rev. 51 (2022) 3123–3163. doi: 10.1039/d0cs01496f
11. [11]
  M. Zhang, X.A. Yuan, C. Zhu, et al., Angew. Chem. Int. Ed. 58 (2019) 312–316. doi: 10.1002/anie.201811522
12. [12]
  C. Liu, S. Han, M. Li, et al., Angew. Chem. Int. Ed. 59 (2020) 18527–18531. doi: 10.1002/anie.202009155
13. [13]
  N. Li, Y. Ning, X. Wu, et al., Chem. Sci. 12 (2021) 5505–5510. doi: 10.1039/d1sc00528f
14. [14]
  M. Valero, D. Bouzouita, A. Palazzolo, et al., Angew. Chem. Int. Ed. 59 (2020) 3517–3522. doi: 10.1002/anie.201914369
15. [15]
  Y. Kuang, H. Cao, H. Tang, et al., Chem. Sci. 11 (2020) 8912–8918. doi: 10.1039/d0sc02661a
16. [16]
  A. Kurimoto, R.S. Sherbo, Y. Cao, et al., Nat. Catal. 3 (2020) 719–726. doi: 10.1038/s41929-020-0488-z
17. [17]
  X. Liu, R. Liu, J. Qiu, et al., Angew. Chem. Int. Ed. 59 (2020) 13962–13967. doi: 10.1002/anie.202005765
18. [18]
  A. Suzuki, Y. Kamei, M. Yamashita, et al., Angew. Chem. Int. Ed. 135 (2023) e202214433. doi: 10.1002/ange.202214433
19. [19]
  D. Wood, S. Lin, Angew. Chem. Int. Ed. 62 (2023) e202218858. doi: 10.1002/anie.202218858
20. [20]
  Z.P. Vang, S.J. Hintzsche, J.R. Clarkv, Chem. Eur. J. 27 (2021) 9988–10000. doi: 10.1002/chem.202100635
21. [21]
  X. Zhou, T. Yu, G. Dong, J. Am. Chem. Soc. 144 (2022) 9570–9575. doi: 10.1021/jacs.2c04382
22. [22]
  Z. Zhang, C. Qiu, Y. Xu, et al., Nat. Commun. 11 (2020) 4722. doi: 10.1038/s41467-020-18458-w
23. [23]
  M. Abdellaoui, T. Deis, M.A. Wiethoff, et al., Adv. Synth. Catal. 365 (2023) 884–891. doi: 10.1002/adsc.202201410
24. [24]
  X. Dong, Z. Wang, H. Wang, et al., Chem. Sci. 11 (2020) 1026–1031. doi: 10.1039/c9sc05132e
25. [25]
  J. Xu, J. Fan, Y. Lou, et al., Nat. Commun. 12 (2021) 3983. doi: 10.1038/s41467-021-24259-6
26. [26]
  L. Wang, C. Liu, L. Li, et al., Chin. J. Chem. 40 (2022) 719–724. doi: 10.1002/cjoc.202100728
27. [27]
  J. Dong, M. Yu, F. Yue, et al., Org. Lett. 24 (2022) 2064–2068. doi: 10.1021/acs.orglett.2c00722
28. [28]
  Z. Sun, R. Ji, J. Wu, et al., Adv. Synth. Catal. 365 (2023) 476–481. doi: 10.1002/adsc.202201367
29. [29]
  Y. Fan, W. Ou, M. Chen, et al., Org. Lett. 25 (2023) 432–437. doi: 10.1021/acs.orglett.2c04154
30. [30]
  T. Constantin, M. Zanini, A. Regni, et al., Science 367 (2020) 1021–1026. doi: 10.1126/science.aba2419
31. [31]
  T. Patra, S. Mukherjee, J. Ma, et al., Angew. Chem. Int. Ed. 58 (2019) 10514–10520. doi: 10.1002/anie.201904671
32. [32]
  Z.Z. Zhou, J.H. Zhao, X.Y. Gou, et al., Org. Chem. Front. 6 (2019) 1649–1654. doi: 10.1039/c9qo00240e
33. [33]
  B. Zhang, C. Qiu, S. Wang, et al., Sci. Bull. 66 (2021) 562–569.
34. [34]
  X.L. Nan, Y. Wang, X.B. Li, et al., Chem. Commun. 57 (2021) 6768–6771. doi: 10.1039/d1cc02551a
35. [35]
  R. Zhou, L. Ma, X. Yang, et al., Org. Chem. Front. 8 (2021) 426–444. doi: 10.1039/d0qo01299h
36. [36]
  N. Li, Y. Li, X. Wu, et al., Chem. Soc. Rev. 51 (2022) 6291–6306. doi: 10.1039/d1cs00907a
37. [37]
  W. Ou, C. Qiu, C. Su, Chin. J. Catal. 43 (2022) 956–970.
38. [38]
  Y.Y. Loh, K. Nagao, A.J. Hoover, et al., Science 358 (2017) 1182–1187. doi: 10.1126/science.aap9674
39. [39]
  R. Zhou, J. Li, H.W. Cheo, et al., Chem. Sci. 10 (2019) 7340–7344. doi: 10.1039/c9sc02818h
40. [40]
  Y. Zhang, P. Ji, Y. Dong, et al., ACS Catal. 10 (2020) 2226–2230. doi: 10.1021/acscatal.9b05300
41. [41]
  Y. Li, Z. Ye, Y.M. Lin, et al., Nat. Commun. 12 (2021) 2894.
42. [42]
  K. Ban, K. Imai, S. Oyama, et al., Angew. Chem. Int. Ed. 62 (2023) e202311058. doi: 10.1002/anie.202311058
43. [43]
  J. Zhang, M. Jiao, Z. Lu, et al., Angew. Chem. Int. Ed. 63 (2024) e202409862. doi: 10.1002/anie.202409862
44. [44]
  M. Jiao J. Zhang, M. Wang, et al., Nat. Commun. 15 (2024) 5067. doi: 10.1038/s41467-024-48590-w
45. [45]
  W. Xiao, Y. Tian, L. Du, et al., Org. Lett. 27 (2025) 1112–1117. doi: 10.1021/acs.orglett.4c04516
46. [46]
  B. Zheng, X. Li, Y. Song, et al., Org. Lett. 23 (2021) 3453–3459. doi: 10.1021/acs.orglett.1c00915
47. [47]
  Q. Xu, X. Zhou, S. Zhang, et al., Org. Lett. 23 (2021) 4870–4875. doi: 10.1021/acs.orglett.1c01596
48. [48]
  B. Zheng, X. Li, S. Meng, et al., Org. Chem. Front. 10 (2023) 859–865. doi: 10.1039/d2qo01906j
49. [49]
  B. Zheng, J. Zhi, N. Wang, et al., Org. Chem. Front. 11 (2024) 500–507. doi: 10.1039/d3qo01849k
50. [50]
  Y. Song, B. Zheng, S. Yang, et al., Org. Lett. 25 (2023) 2372–2376. doi: 10.1021/acs.orglett.3c00890
51. [51]
  L. Pan, B. Zheng, X. Yang, et al., Adv. Synth. Catal. 363 (2021) 234–243. doi: 10.1002/adsc.202001001
52. [52]
  J. Steverlynck, R. Sitdikov, M. Rueping, Chem. Eur. J. 27 (2021) 11751–11772. doi: 10.1002/chem.202101179
53. [53]
  R. Caporaso, S. Manna, S. Zinken, et al., Chem. Commun. 52 (2016) 12486–12489.
54. [54]
  L. Hu, X. Liu, X. Liao, Angew. Chem. Int. Ed. 55 (2016) 9743–9747. doi: 10.1002/anie.201604406
55. [55]
  K. Komeyama, Y. Yamahata, I. Osaka, Org. Lett. 20 (2018) 4375–4378. doi: 10.1021/acs.orglett.8b01863
56. [56]
  H.F. Piedra, C. Valdés, M. Plaza, Chem. Sci. 14 (2023) 5545–5568. doi: 10.1039/d3sc01724a
57. [57]
  R. Miao, D. Wang, J. Xiao, et al., Phys. Chem. Chem. Phys. 22 (2020) 10212–10218. doi: 10.1039/d0cp00946f
58. [58]
  H.F. Piedra, M. Plaza, Chem. Sci. 14 (2023) 650–657. doi: 10.1039/d2sc05556b
59. [59]
  K. Kwon, R.T. Simons, M. Nandakumar, et al., Chem. Rev. 122 (2022) 2353–2428. doi: 10.1021/acs.chemrev.1c00444
60. [60]
  K. Zhang, D. Rombach, N.Y. Nçtel, et al., Angew. Chem. Int. Ed. 60 (2021) 22487–22495. doi: 10.1002/anie.202109235
61. [61]
  R. Giri, I. Mosiagin, I. Franzoni, et al., Angew. Chem. Int. Ed. 61 (2022) e202209143.
62. [62]
  S.K. Nanda, Adv. Synth. Catal. 365 (2023) 834–853.
63. [63]
  B. Sahoo, J.L. Li, F. Glorius, Angew. Chem. Int. Ed. 54 (2015) 11577–11580. doi: 10.1002/anie.201503210
64. [64]
  X.C. Xu, Y. Sang, M. Yang, et al., Org. Chem. Front. 11 (2024) 5502. doi: 10.1039/d4qo00652f
65. [65]
  P. Wang, Q. Zhao, W. Xiao, et al., Green Synth. Catal. 1 (2020) 42–51.
66. [66]
  J. Sun, G. Zheng, G. Zhang, et al., Org. Chem. Front. 12 (2025) 1671.
67. [67]
  Y. Li, J. Bao, Y. Zhang, et al., Chem 8 (2022) 1147–1163. doi: 10.3390/electronics11071147
68. [68]
  L. Wang, X. Huo, X. He, et al., Green Chem. 26 (2024) 8315–8322. doi: 10.1039/d3gc04109c
69. [69]
  L. Niu, S. Jin, M. Zhu, et al., Org. Lett. 27 (2025) 3183–3187. doi: 10.1021/acs.orglett.5c00471
70. [70]
  F. Parsaee, M.C. Senarathna, P.B. Kannangara, et al., Nat. Rev. Chem. 5 (2021) 486–499. doi: 10.1038/s41570-021-00284-3
71. [71]
  C.N. Kondoh, M.D.Y. Miura, M.D.T. Yamanaka, N. Engl. J. Med. 379 (2018) 1877–1878.
72. [72]
  G. Meng, C. Liu, S. Qin, et al., Res. Chem. Intermed. 41 (2015) 8941–8954. doi: 10.1007/s11164-015-1939-z
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