Citation: Yujian Mao, Xiaoting Song, Dandan Yuan, Yaoyu Lin, Junkai You, Yinan Zhang. Transannular C–H functionalizations of polycyclic aromatic compounds by covalently attached directing groups strategy[J]. Chinese Chemical Letters, ;2026, 37(11): 112341. doi: 10.1016/j.cclet.2025.112341 shu

Transannular C–H functionalizations of polycyclic aromatic compounds by covalently attached directing groups strategy

Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine Nanjing, Nanjing 210023, China

yinanzhang@njucm.edu.cn

Received Date: 16 October 2025
Revised Date: 19 December 2025
Accepted Date: 29 December 2025
Available Online: 30 December 2025

Figures(8)

Precisely controlling the regioselectivity on remote C–H bonds of polycyclic aromatic hydrocarbons could rapidly access to unique molecules among natural products, materials and pharmaceuticals. Compared to conventional homoannular C–H functionalizations, heteroannular remote C–H bonds are difficult to reach due to the lack of spatial or electronic biases. Herein, simple, commercially available nitrile-based directing templates have been well-designed to achieve the high-efficient transannular C7-H alkenylation, allylation, and acetoxylation in diverse polycyclic aromatic substrates. Excellent C7-regioselectivity was observed in the presence of the less-sterically but electronically similar C3-H bond. Detailed mechanistic studies revealed that Ag salt acts as co-catalyst in the C–H activation step by facilitating the formation of an active Pd−Ag bimetallic complex. Our findings not only necessitate a practical synthetic approach to useful polycyclic aromatic hydrocarbons and related natural products but also provide mechanistic insights for building hybridized catalysis in the remote C–H activation on (hetero)aromatic systems.
- C–H activation,
- Alkenylation,
- Covalently attached directing groups,
- Pd catalysis,
- Naphthalen
1. [1]
  Y.J. Mao, X.T. Song, W.W. Xu, et al., Nat. Prod. Rep. 42 (2025) 1946–1989. doi: 10.1039/d5np00032g
2. [2]
  C.C. Liu, Y. Ni, X.F. Lu, et al., Acc. Chem. Res. 52 (2019) 2309–2321. doi: 10.1021/acs.accounts.9b00257
3. [3]
  W.E. Acree, S.A. Tucker, J.C. Fetzer, Poly. Arom. Comp. 2 (1991) 75–105. doi: 10.1080/10406639108048933
4. [4]
  X. Ma, J. Wang, H. Tian, Acc. Chem. Res. 52 (2019) 738–748. doi: 10.1021/acs.accounts.8b00620
5. [5]
  L.A.M. Murray, S.M.K. McKinnie, B.S. Moore, J.H. George, Nat. Prod. Rep. 37 (2020) 1334–1366. doi: 10.1039/d0np00018c
6. [6]
  Y.D. Yang, Y.M. Wu, Z.Y. Bin, et al., J. Am. Chem. Soc. 146 (2024) 1224–1243. doi: 10.1021/jacs.3c12234
7. [7]
  X.T. Li, X. Gong, M. Zhao, et al., Org. Lett. 13 (2011) 5808–5811. doi: 10.1021/ol2023856
8. [8]
  L.H. Huang, Q. Li, C. Wang, C.Z. Qi, J. Org. Chem. 78 (2013) 3030–3038. doi: 10.1021/jo400017v
9. [9]
  L. Grigorjeva, O. Daugulis, Angew. Chem. Int. Ed. 53 (2014) 10209–10212. doi: 10.1002/anie.201404579
10. [10]
  Z.X. Li, S.Y. Sun, H.J. Qiao, et al., Org. Lett. 18 (2016) 4594–4597. doi: 10.1021/acs.orglett.6b02243
11. [11]
  S. Rej, N. Chatani, ACS Catal. 8 (2018) 6699–6706. doi: 10.1021/acscatal.8b01675
12. [12]
  B. Su, J.F. Hartwig, Angew. Chem. Int. Ed. 57 (2018) 10163–10167. doi: 10.1002/anie.201805086
13. [13]
  X.M. Yu, F. Yang, Y.S. Wu, Y.J. Wu, Org. Lett. 21 (2019) 1726–1729. doi: 10.1021/acs.orglett.9b00283
14. [14]
  M.L. Wang, M. Zhang, Y.Y. Luo, et al., Org. Lett. 22 (2020) 135–139. doi: 10.1021/acs.orglett.9b04046
15. [15]
  J. Jiang, D.D. Yuan, C.Z. Ma, et al., Org. Lett. 23 (2021) 279–284. doi: 10.1021/acs.orglett.0c03701
16. [16]
  Y.Q. Yao, S.T. Su, N. Wu, et al., Org. Chem. Front. 9 (2022) 5125–5132. doi: 10.1039/d2qo01131j
17. [17]
  Y.J. Mao, D.D. Yuan, J. Jiang, et al., Chem. Sci. 13 (2022) 2900–2908. doi: 10.1039/d1sc05899a
18. [18]
  Z. Liu, W.G. Han, J.B. Lan, et al., Angew. Chem. Int. Ed. 62 (2023) e202211412. doi: 10.1002/anie.202211412
19. [19]
  J.L. Yin, J. Li, H.H. Chen, et al., Nat. Synth. 2 (2023) 838–847. doi: 10.1038/s44160-023-00306-6
20. [20]
  S. Maji, S. Pradhan, K. Pidiyara, et al., Adv. Synth. Catal. 366 (2024) 838–843. doi: 10.1002/adsc.202300483
21. [21]
  S. Maji, P. Rawal, A. Ghosh, et al., JACS Au 4 (2024) 3679–3689. doi: 10.1021/jacsau.4c00660
22. [22]
  Y.J. Mao, X.T. Song, D.D. Yuan, et al., ACS Catal. 15 (2025) 3247–3255. doi: 10.1021/acscatal.4c07105
23. [23]
  W.B. Song, X.M. Shi, W. Li, et al., Chin. J. Chem. 43 (2025) 1121–1128. doi: 10.1002/cjoc.202401211
24. [24]
  Y.J. Mao, Z. Xia, L. Hu, Y. Zhang, Asian J. Org. Chem. 11 (2022) e202200198. doi: 10.1002/ajoc.202200198
25. [25]
  J. Jiang, Y.J. Mao, Y. Lin, J. Shen, Y. Zhang, Org. Chem. Front. 10 (2023) 2471–2475. doi: 10.1039/d3qo00005b
26. [26]
  J.A. Leitch, C.G. Frost, Chem. Soc. Rev. 46 (2017) 7145–7153. doi: 10.1039/C7CS00496F
27. [27]
  J.C. Wang, G.B. Dong, Chem. Rev. 119 (2019) 7478–7528. doi: 10.1021/acs.chemrev.9b00079
28. [28]
  J.E. Gillespie, A. Fanourakis, R.J. Phipps, J. Am. Chem. Soc. 144 (2022) 18195–18211. doi: 10.1021/jacs.2c08752
29. [29]
  S. Liang, M. Bolte, G. Manolikakes, Chem. Eur. J. 23 (2017) 96–100. doi: 10.1002/chem.201605101
30. [30]
  J.M. Li, Y.H. Wang, Y. Yu, et al., ACS Catal. 7 (2017) 2661–2667. doi: 10.1021/acscatal.6b03671
31. [31]
  H.M. Zhu, S.Y. Sun, H.J. Qiao, et al., Org. Lett. 20 (2018) 620–623. doi: 10.1021/acs.orglett.7b03749
32. [32]
  C.F. Jing, X.L. Chen, K. Sun, et al., Org. Lett. 21 (2019) 486–489. doi: 10.1021/acs.orglett.8b03768
33. [33]
  S. Pradhan, U. Dutta, J.P. Biswas, et al., Org. Lett. 26 (2024) 10946–10950. doi: 10.1021/acs.orglett.4c04104
34. [34]
  C. Sivaraj, S. Pradhan, T. Gandhi, D. Maiti, Org. Lett. 27 (2025) 1650–1655. doi: 10.1021/acs.orglett.4c04858
35. [35]
  M. Zhang, A.P. Luo, Y. Shi, et al., ACS Catal. 9 (2019) 11802–11807. doi: 10.1021/acscatal.9b04352
36. [36]
  Y.L.T. Fu, C.H. Chen, M.G. Huang, et al., ACS Catal. 12 (2022) 5036–5047. doi: 10.1021/acscatal.2c00839
37. [37]
  X.L. Luo, P.C. Hou, J.Y. Shen, et al., Nat. Commun. 15 (2024) 5552–5561. doi: 10.1038/s41467-024-49362-2
38. [38]
  D. Leow, G. Li, T.S. Mei, J.Q. Yu, Nature 486 (2012) 518–522. doi: 10.1038/nature11158
39. [39]
  G.R. Meng, N.Y.S. Lam, E.L. Lucas, et al., J. Am. Chem. Soc. 142 (2020) 10571–10591. doi: 10.1021/jacs.0c04074
40. [40]
  S.K. Sinha, S. Guin, S. Maiti, et al., Chem. Rev. 122 (2022) 5682–5841. doi: 10.1021/acs.chemrev.1c00220
41. [41]
  S. Bag, T. Patra, A. Modak, et al., J. Am. Chem. Soc. 137 (2015) 11888–11891. doi: 10.1021/jacs.5b06793
42. [42]
  T. Para, R. Watile, S. Agasti, et al., Chem. Commun. 52 (2016) 2027–2030. doi: 10.1039/C5CC09446A
43. [43]
  A. Maji, B. Bhaskararao, S. Singha, et al., Chem. Sci. 7 (2016) 3147–3153. doi: 10.1039/C5SC04060D
44. [44]
  E. Casali, P. Kalra, M. Brochetta, et al., Chem. Commun. 56 (2020) 7281–7284. doi: 10.1039/d0cc03172k
45. [45]
  P.F. Zhang, Q.X. Ma, Z.W. Jiang, et al., Chin. Chem. Lett. 35 (2024) 109361. doi: 10.1016/j.cclet.2023.109361
46. [46]
  Z.P. Zhang, K. Tanaka, J.Q. Yu, Nature 543 (2017) 538–542. doi: 10.1038/nature21418
47. [47]
  K. Ramakrishna, J.P. Biswas, S. Jana, et al., Angew. Chem. Int. Ed. 58 (2019) 13808–13812. doi: 10.1002/anie.201907544
48. [48]
  H. Shi, Y. Lu, J. Weng, et al., Nat. Chem. 12 (2020) 399–404. doi: 10.1038/s41557-020-0424-5
49. [49]
  Z.L. Fan, X.Y. Chen, K. Tanaka, et al., Nature 610 (2022) 87–93. doi: 10.1038/s41586-022-05175-1
50. [50]
  Z. Fan, M.E. Hoque, K. Wu, et al., J. Am. Chem. Soc. 147 (2025) 33850–33858. doi: 10.1021/jacs.5c10482
51. [51]
  X.Q. Ning, S.J. Lou, Y.J. Mao, Z.Y. Xu, D.Q. Xu, Org. Lett. 20 (2018) 2445–2448. doi: 10.1021/acs.orglett.8b00793
52. [52]
  Q. Shao, K. Wu, Z. Zhuang, et al., Acc. Chem. Res. 53 (2020) 833–851. doi: 10.1021/acs.accounts.9b00621
53. [53]
  U. Dutta, A. Modak, B. Bhaskararao, et al., ACS Catal. 7 (2017) 3162–3168. doi: 10.1021/acscatal.7b00247
54. [54]
  B.J. Naysmith, P.A. Hume, J. Sperry, M.A. Brimble, Nat. Prod. Rep. 34 (2017) 25–61. doi: 10.1039/C6NP00080K
55. [55]
  B. Yang, G.Y. Chen, X.P. Song, et al., Bioorg. Med. Chem. Lett. 23 (2013) 5748–5751. doi: 10.1016/j.bmcl.2013.01.112
56. [56]
  Y.F. Yang, G.J. Cheng, P. Liu, et al., J. Am. Chem. Soc. 136 (2014) 344–355. doi: 10.1021/ja410485g
57. [57]
  L.Z. Fang, T.G. Saint-Denis, B.L.H. Taylor, et al., J. Am. Chem. Soc. 139 (2017) 10702–10714. doi: 10.1021/jacs.7b03296
58. [58]
  Z.L. Fan, K.L. Bay, X.Y. Chen, et al., Angew. Chem. Int. Ed. 59 (2020) 4770–4777 doi: 10.1002/anie.201915624
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