Citation: Shuai Chen, Anzai Shi, Guoqing Yang, Pengfei Xie, Feng Liu, Youai Qiu. Electrochemical demethoxyl-cyanation of methoxyarenes via S_NAr[J]. Chinese Chemical Letters, ;2025, 36(9): 110810. doi: 10.1016/j.cclet.2024.110810 shu

Electrochemical demethoxyl-cyanation of methoxyarenes via S_NAr

Shuai Chen ^a ,
Anzai Shi ^a ,
Guoqing Yang ^a ,
Pengfei Xie ^a ,
Feng Liu ^{b, *,} ,
Youai Qiu ^{a, *,}

a.
State Key Laboratory and Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, College of Chemistry, Nankai University, Tianjin 300071, China
b.
Department of Chemistry, Fudan University, Shanghai 200438, China

liufeng@fudan.edu.cn

qiuyouai@nankai.edu.cn

Received Date: 22 November 2024
Revised Date: 26 December 2024
Accepted Date: 28 December 2024
Available Online: 29 December 2024

Figures(4)

Herein, a metal-free electrochemical demethoxyl-cyanation of methoxyarenes via aromatic nucleophilic substitution (S_NAr) using TMSCN as a cheap cyanide source under mild conditions has been presented. This transformation utilizes commercially available reagents, cheap electrodes, and simple equipment. Diverse aryl nitriles were successfully obtained in a direct and efficient way with broad substrate scope, excellent functional group tolerance, and selective C−O bond cleavage. Furthermore, late-stage modification of biorelevant compounds and gram-scale synthesis highlighted the potential application of the strategy. Mechanistic investigations suggest that the arene cation radical was considered as the key intermediate for the transformation, and undergoing the followed S_NAr process.
- Electrochemistry,
- Aromatic nucleophilic substitution (S_NAr),
- Cyanation,
- Aryl nitriles,
- Organic electrosynthesis
1. [1]
  R.A. Rossi, A.B. Pierini, A.B. Peñéñory. Chem. Rev. 103 (2003) 71-167.
2. [2]
  G.G. Wubbels, Tetrahedron Lett. 55 (2014) 5066-5069.
3. [3]
  M.P. Drapeau, T. Ollevier, M. Taillefer, Chem. Eur. J. 20 (2014) 5231-5236.
4. [4]
  C.F. Bernasconi, Acc. Chem. Res. 11 (1978) 147-152. doi: 10.1021/ar50124a004
5. [5]
  F.A. Carey, R.M. Giuliano, N.T. Allison, et al., Electrophilic and nucleophilic aromatic substitution, in Organic Chemistry ISE, 12th ed., McGraw-Hill Education, New York, 2024, pp. 478-533.
6. [6]
  M. Mąkosza, Chem. Soc. Rev. 39 (2010) 2855-2868. doi: 10.1039/b822559c
7. [7]
  C.N. Neumann, J.M. Hooker, T. Ritter, Nature 534 (2016) 369-373. doi: 10.1038/nature17667
8. [8]
  S.M. Wales, R.K. Saunthwal, J. Clayden, Acc. Chem. Res. 55 (2022) 1731-1747. doi: 10.1021/acs.accounts.2c00184
9. [9]
  M.L. Tan, Q.H. Guo, X.Y. Wang, et al., Angew. Chem. Int. Ed. 59 (2020) 23649-23658. doi: 10.1002/anie.202013149
10. [10]
  Z. Qiu, C.J. Li, Chem. Rev. 120 (2020) 10454-10515. doi: 10.1021/acs.chemrev.0c00088
11. [11]
  X. Cong, F. Fan, P. Ma, et al., J. Am. Chem. Soc. 139 (2017) 15182-15190. doi: 10.1021/jacs.7b08579
12. [12]
  K. Ouyang, W. Hao, W.X. Zhang, et al., Chem. Rev. 115 (2015) 12045-12090. doi: 10.1021/acs.chemrev.5b00386
13. [13]
  C.N. Neumann, T. Ritter, Acc. Chem. Res. 50 (2017) 2822-2833. doi: 10.1021/acs.accounts.7b00413
14. [14]
  M. Tobisu, N. Chatani, Acc. Chem. Res. 48 (2015) 1717-1726. doi: 10.1021/acs.accounts.5b00051
15. [15]
  N.E.S. Tay, D.A. Nicewicz, J. Am. Chem. Soc. 139 (2017) 16100-16104. doi: 10.1021/jacs.7b10076
16. [16]
  J. Lu, I. Paci, D.C. Leitch, Chem. Sci. 13 (2022) 12681-12695. doi: 10.1039/d2sc04041g
17. [17]
  Z. You, K. Higashida, T. Iwai, et al., Angew. Chem. Int. Ed. 60 (2021) 5778-5782. doi: 10.1002/anie.202013544
18. [18]
  F.L. Qing, X.Y. Liu, J.A. Ma, et al., CCS Chem. 4 (2022) 2518-2549. doi: 10.31635/ccschem.022.202201935
19. [19]
  P.S. Fier, J.F. Hartwig, J. Am. Chem. Soc. 134 (2012) 10795-10798. doi: 10.1021/ja304410x
20. [20]
  A.C. Sather, S.L. Buchwald, Acc. Chem. Res. 49 (2016) 2146-2157. doi: 10.1021/acs.accounts.6b00247
21. [21]
  L.S. Sharninghausen, S. Preshlock, S.T. Joy, et al., J. Am. Chem. Soc. 144 (2022) 7422-7429. doi: 10.1021/jacs.2c01959
22. [22]
  X. Wu, W. Chen, N. Holmberg-Douglas, et al., Chem 9 (2023) 343-362.
23. [23]
  N. Holmberg-Douglas, D.A. Nicewicz. Org. Lett. 21 (2019) 7114-7118. doi: 10.1021/acs.orglett.9b02678
24. [24]
  Z. Zhang, T. Niwa, K. Watanabe, et al., Angew. Chem. Int. Ed. 62 (2023) e202302956.
25. [25]
  L. Shi, M. Wang, C.A. Fan, et al., Org. Lett. 5 (2003) 3515-3517.
26. [26]
  Q. Shen, J.F. Hartwig, J. Am. Chem. Soc. 128 (2006) 10028-10029. doi: 10.1021/ja064005t
27. [27]
  Q.K. Kang, Y. Lin, Y. Li, et al., Angew. Chem. Int. Ed. 60 (2021) 20391-20399. doi: 10.1002/anie.202106440
28. [28]
  Y. Wang, C. Zhou, R. Wang, Green Chem. 17 (2015) 3910-3915.
29. [29]
  D.W. Widlicka, R.A. Singer, I. Hotham, et al., Org. Process Res. Dev. 28 (2024) 2732-2742. doi: 10.1021/acs.oprd.4c00108
30. [30]
  M. Majek, A. J. von Wangelin, Acc. Chem. Res. 49 (2016) 2316-2327. doi: 10.1021/acs.accounts.6b00293
31. [31]
  S. Pimparkar, A. Koodan, S. Maiti, et al., Chem. Commun. 57 (2021) 2210-2232. doi: 10.1039/d0cc07783f
32. [32]
  Y. Wang, W. Yu, C. Wang, et al., eScience 4 (2024) 100228.
33. [33]
  H.Y. Zhou, H.T. Tang, W.M. He, Chin. J. Catal. 46 (2023) 4-10.
34. [34]
  M. Yan, Y. Kawamata, P.S. Baran, Chem. Rev. 117 (2017) 13230-13319. doi: 10.1021/acs.chemrev.7b00397
35. [35]
  W. Zeng, Y. Qiu, Sci. China Chem. 67 (2024) 3223-3246.
36. [36]
  J. Zhong, Y. Yu, D. Zhang, et al., Chin. Chem. Lett. 32 (2021) 963-972.
37. [37]
  P. Li, Y. Wang, H. Zhao, Y. Qiu, Acc. Chem. Res. (2024) https://doi.org/10.1021/acs.accounts.4c00652. doi: 10.1021/acs.accounts.4c00652
38. [38]
  C. Zhu, N.W.J. Ang, T.H. Meyer, et al., ACS Central Sci. 7 (2021) 415-431. doi: 10.1021/acscentsci.0c01532
39. [39]
  Z. Zhang, Y. Lei, W. Huang, et al., Chin. Chem. Lett. 33 (2022) 3623-3631.
40. [40]
  Y. Yu, Y. Jiang, S. Wu, et al., Chin. Chem. Lett. 33 (2022) 2009-2014.
41. [41]
  Y. Yuan, J. Yang, A. Lei, Chem. Soc. Rev. 50 (2021) 10058-10086. doi: 10.1039/d1cs00150g
42. [42]
  S. Andreades, EW. Zahnow, J. Am. Chem. Soc. 91 (1969) 4181-4190. doi: 10.1021/ja01043a028
43. [43]
  R. Möckel, J. Hille, E. Winterling, et al., Angew. Chem. Int. Ed. 57 (2018) 442-445. doi: 10.1002/anie.201711293
44. [44]
  J. Li, S. Zhang, K. Xu, Chin. Chem. Lett. 32 (2021) 2729-2735.
45. [45]
  Y. Zhong, H. Xiong, J. Low, et al., eScience 3 (2023) 100086.
46. [46]
  X. Cheng, A. Lei, T. Mei, et al., CCS Chem. 4 (2022) 1120-1152. doi: 10.31635/ccschem.021.202101451
47. [47]
  T. Wang, F. He, W. Jiang, et al., Angew. Chem. Int. Ed. 63 (2024) e202316140.
48. [48]
  Y.M. Cai, X.T. Liu, L.L. Xu, et al., Angew. Chem. Int. Ed. 63 (2024) e202315222.
49. [49]
  M. Li, X. Cheng, Nat. Commun. 15 (2024) 7540.
50. [50]
  X. Liu, R. Liu, J. Qiu, et al., Angew. Chem. Int. Ed. 59 (2020) 13962-13967. doi: 10.1002/anie.202005765
51. [51]
  A. Shi, Y. Liu, R. Zhang, et al., eScience 4 (2024) 100255.
52. [52]
  Z. Zhao, R. Zhang, Y. Liu, et al., Nat. Commun. 15 (2024) 3832.
53. [53]
  Y. Wang, Q. Wang, L. Wu, et al., Nat. Commun. 15 (2024) 2780.
54. [54]
  T. Feng, S. Wang, Y. Liu, et al., Angew. Chem. Int. Ed. 61 (2022) e202115178.
55. [55]
  P. Li, C. Guo, S. Wang, et al., Nat. Commun. 13 (2022) 3774.
56. [56]
  Y. Wang, S. Tang, G. Yang, et al., Angew. Chem. Int. Ed. 61 (2022) e202207746.
57. [57]
  Y. Wang, Z. Zhao, D. Pan, et al., Angew. Chem. Int. Ed. 61 (2022) e202210201.
58. [58]
  Z. Zhao, Y. Liu, S. Wang, et al., Angew. Chem. Int. Ed. 62 (2023) e202214710.
59. [59]
  Y. Liu, P. Li, Y. Wang, et al., Angew. Chem. Int. Ed. 62 (2023) e202306679.
60. [60]
  K. Yang, T. Feng, Y. Qiu, et al., Angew. Chem. Int. Ed. 62 (2023) e202312803.
61. [61]
  P. Li, G. Kou, T. Feng, et al., Angew. Chem. Int. Ed. 62 (2023) e202311941.
62. [62]
  M. Liu, T. Feng, Y. Wang, et al., Nat. Commun. 14 (2023) 6467.
63. [63]
  V. Bonatto, R.F. Lameiro, F.R. Rocho, et al., RSC Med. Chem. 14 (2023) 201-217. doi: 10.1039/d2md00204c
64. [64]
  M. Liu, S. Li, Nat. Prod. Rep. 41 (2024) 649-671. doi: 10.1039/d3np00028a
65. [65]
  T. Ohshima, T. Komyoji, S. Mitani, et al., J. Pest Sci. 29 (2004) 147-152. doi: 10.1584/jpestics.29.147
66. [66]
  C. Jiang, P. Chen, G. Liu, et al., CCS Chem. 3 (2021) 1884-1893. doi: 10.31635/ccschem.020.202000435
67. [67]
  L. Guillemard, N. Kaplaneris, L. Ackermann, et al., Nat. Rev. Chem. 5 (2021) 522-545;. doi: 10.1038/s41570-021-00300-6
68. [68]
  R. Cannalire, S. Pelliccia, L. Sancineto, et al., Chem. Soc. Rev. 50 (2021) 766-897. doi: 10.1039/d0cs00493f
69. [69]
  J. Wencel-Delord, F. Glorius, Nat. Chem. 5 (2013) 369-375. doi: 10.1038/nchem.1607
70. [70]
  M. Guerram, Z.Z. Jiang, L.Y. Zhang, Chin. J. Nat. Med. 10 (2012) 161-169. doi: 10.3724/SP.J.1009.2012.00161
71. [71]
  S. Desbène, S. Giorgi-Renault. Curr. Med. Chem. Anti-Cancer Agents 2 (2002) 71-90.
72. [72]
  H. Ekiert, J. Świątkowska, E. Knut, et al., Front. Pharmacol. 12 (2021) 653993.
73. [73]
  P. Rossi, L. Bao, A. Luciani, et al., J. Agric. Food Chem. 55 (2007) 7332-7336. doi: 10.1021/jf070674u
74. [74]
  S. Y. Shim, Chem. Eur. J. 29 (2023) e202302620.
75. [75]
  J. Patocka, K. Kuca, Mil. Med. Sci. Lett. 82 (2013) 162-171. doi: 10.31482/mmsl.2013.026
76. [76]
  S. Burstein, M. Gut, Steroids 14 (1969) 207-217.
77. [77]
  L.V. Langenhove, R. Paul, Insect repellent finishes for textiles, in: Functional Finishes for Textiles, Elsevier Ltd., 2015, pp. 333-360.
78. [78]
  A.S. Wikaputri, D.J. Irvine, R.A. Stockman, et al., J. Agr. Food Res. 16 (2024) 101186.
79. [79]
  V.A. Pistritto, M.E. Schutzbach-Horton, D.A. Nicewicz, J. Am. Chem. Soc. 142 (2020) 17187-17194. doi: 10.1021/jacs.0c09296
80. [80]
  K.A. Margrey, J.B. McManus, S. Bonazzi, et al., J. Am. Chem. Soc. 139 (2017) 11288-11299. doi: 10.1021/jacs.7b06715
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2. [2]
  Qi Li , Zi-Lu Wang , Yun-He Xu . Copper-catalyzed 1,4-silylcyanation of 1,3-enynes: A silyl radical-initiated approach for synthesis of difunctionalized allenes. Chinese Chemical Letters, 2025, 36(3): 109991-. doi: 10.1016/j.cclet.2024.109991
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4. [4]
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Electrochemical demethoxyl-cyanation of methoxyarenes via SNAr

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通讯作者: 陈斌, bchen63@163.com

Electrochemical demethoxyl-cyanation of methoxyarenes via S_NAr