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A rapid access to fused polycyclic indolo[2,1-a]isoquinolins via Pd-catalyzed sequential Heck/C-H activation/amination reaction with diaziridinone

Junhua Li ,  Yu Fu ,  Yian Shi

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Citation:  Junhua Li, Yu Fu, Yian Shi. A rapid access to fused polycyclic indolo[2,1-a]isoquinolins via Pd-catalyzed sequential Heck/C-H activation/amination reaction with diaziridinone[J]. Chinese Chemical Letters, 2026, 37(3): 111376. doi: 10.1016/j.cclet.2025.111376 shu

A rapid access to fused polycyclic indolo[2,1-a]isoquinolins via Pd-catalyzed sequential Heck/C-H activation/amination reaction with diaziridinone

English

  • Indoles are one of the most ubiquitous nitrogen-containing heterocycles. Indolo[2,1-a]isoquinolines represent an important class of polycyclic fused indoles, and are present in a variety of bioactive molecules and pharmaceuticals, and materials (Fig. 1) [1–5]. In the past, considerable efforts have been made in constructing indolo[2,1-a]isoquinoline skeletons using various strategies, including radical [6–29] or metal-catalyzed [30–37] cascade cyclization processes. A Pd-catalyzed tandem Heck process also presents a powerful approach to this class of molecules [38–46] particularly for skeletons with additional fused ring(s) [47–50]. An introduction of a fused nitrogen heterocycle like pyrrole fused indolo[2,1-a]isoquinoline (6) would provide new structural diversities for the biological activities, and little has been reported for such type of molecules.

    Figure 1

    Figure 1.  Examples of bioactive indolo[2,1-a]isoquinolines.
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    Previously, we have found that a five-membered azacycle can be generated by reacting a pallada(Ⅱ)cycle (7) with di–tert-butyldiaziridinone (8) (Scheme 1) [51,52]. The reaction likely proceeded via four-membered pallada(Ⅳ)cycle 9 with simultaneous formation of two C—N bonds [51–64]. This bisamination process provides unique opportunities for the synthesis of structurally diverse N-heterocycles. Now we report that pyrrole fused indolo[2,1-a]isoquinolines (6) can be efficiently constructed from indole 12 by such reaction process via tandem Heck/C—H activation/amination through pallada(Ⅱ)cycle intermediate 13 (Scheme 2).

    Scheme 1

    Scheme 1.  Bisamination of pallada(Ⅱ)cycles with diaziridinone.
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    Scheme 2

    Scheme 2.  Pd-catalyzed sequential Heck/C—H activation/amination.
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    Indole 12a was used as the test substrate for initial studies. Various phosphine ligands were examined with 5 mol% Pd(OAc)2, and 2.0 equiv. of di–tert-butyldiaziridinone (8) in toluene at 110 ℃ (Table 1, entries 1–11) (for more details, see Table S1 in Supporting information). The ligand was found to be important to the reaction. The highest yield (58%) was obtained with PPhCy2 (Table 1, entry 7). Further investigation with additional Pd catalysts (Table 1, entries 12–14) and solvents (Table 1, entries 15–18) (for more details, see Table S1) did not lead to any improvement. It appeared that the reaction process was sensitive to the reaction temperature. The reaction went to completion at 130 ℃ while no product was observed at 90 ℃ (Table 1 entry 20 vs. entry 19). At 130 ℃, the reaction was completed within 4 h (Table 1, entry 21).

    Table 1

    Table 1.  Studies on the reaction conditions.a
    DownLoad: CSV
    Entry [Pd] Ligand Yield (%)b
    1 Pd(OAc)2 PPh3 43
    2 Pd(OAc)2 (o-MeOPh)3P 33
    3 Pd(OAc)2 (p-FPh)3P 26
    4 Pd(OAc)2 (2-thienyl)3P 30
    5 Pd(OAc)2 (2-furyl)3P 41
    6 Pd(OAc)2 PPh2Cy 36
    7 Pd(OAc)2 PPhCy2 58
    8 Pd(OAc)2 PCy3 33
    9 Pd(OAc)2 dppb 19
    10 Pd(OAc)2 dppf 25
    11 Pd(OAc)2 Xantphos 31
    12 PdCl2 PPhCy2 35
    13 PdI2 PPhCy2 23
    14 Pd(PPh3)4 PPhCy2 26
    15 Pd(OAc)2 (1,4-dioxane) PPhCy2 47
    16 Pd(OAc)2 (hexane) PPhCy2 27
    17 Pd(OAc)2 (DCE) PPhCy2 27
    18 Pd(OAc)2 (DME) PPhCy2 27
    19 Pd(OAc)2 (90 ℃) PPhCy2 NP
    20 Pd(OAc)2 (130 ℃) PPhCy2 99
    21 Pd(OAc)2 (130 ℃, 4 h) PPhCy2 99
    a All reactions were carried out with indole 12a (0.15 mmol), Pd (0.0075 mmol), ligand (0.015–0.030 mmol, Pd/P = 1/4), di– tert-butyldiaziridinone (8) (0.225 mmol), and Cs 2CO 3 (0.225 mmol) in PhCH 3 (1.5 mL) at 110 ℃ under N 2 for 48 h unless otherwise noted.
    b The yield was determined by 1H NMR analysis of the crude reaction mixture with 1,1,2,2-tetrachloroethane as internal standard.

    With the optimized reaction conditions, the substrate scope was subsequently investigated with a variety of indole substrates. As shown in Scheme 3, the reaction can be extended to various substituted 1-methacryloyl indoles, giving the corresponding pyrrole fused indolo[2,1-a]isoquinolines 6a-6j in 43%−99% isolated yields. High yield was also obtained with 1-(2-benzylacryloyl)indole (Scheme 3, 6k). A lower yield was obtained in the case of 1-(2-phenylacryloyl) indole (Scheme 3, 6l). 1-(2-Methylallyl) indoles were also effective for the reaction, giving the corresponding pyrrole fused indolo[2,1-a]isoquinolines 6m-6o in 81%−95% yields. Significantly lower yield was obtained when the methyl group on the olefin was replaced with the methyl ester group (Scheme 3, 6p). The reaction can also be applied to propargyl indoles to give the corresponding pyrrole fused indolo[2,1-a]isoquinolines 6q and 6r in 63%−70% yields with modified reaction conditions. The reaction process was not effective to indole 12s tethered with 3-methylbut-3-en-1-yl group (one carbon longer), giving a messy mixture under the reaction conditions. With modified conditions, indolo[3,2-b]indole 14s was isolated in 77% yield (Scheme 4) [65–80]. This reaction process also proceeded well with N-Me, Et, and Bn substituted indoles 12v-x, giving the corresponding indolo[3,2-b]indole 14v-x in 96%−98% yields (Scheme 4). Further studies showed that seven-membered ring product 6y can be isolated in 50% yield when the corresponding indole with a methyl at the indole's C-3 position (12y) used (Scheme 5).

    Scheme 3

    Scheme 3.  The reaction scope. All reactions were carried out with 12 (0.30 mmol), Pd(OAc)2 (0.015 mol), PPhCy2 (0.060 mmol), di–tert-butyldiaziridinone (8) (0.45 mmol), and Cs2CO3 (0.45 mmol) in PhCH3 (2.0 mL) at 130 ℃ under N2 for 4 h unless otherwise noted, the yield was isolated yield. a With 1.0 mL PhCH3. b For 12 h. c With Pd(OAc)2 (0.015 mol), (o-tolyl)3P (0.060 mmol), di–tert-butyldiaziridinone (8) (0.45 mmol), KOPiv (0.15 mmol), and Cs2CO3 (0.45 mmol) in DMF (1.0 mL) at 130 ℃ for 12 h.
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    Scheme 4

    Scheme 4.  The indole C-3 amination reaction.
    DownLoad: Full-Size Img PowerPoint

    Scheme 5

    Scheme 5.  The synthesis of seven-membered polycyclic indole 6y.
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    As exemplified with 6m, the reaction proceeded well at gram scale (Scheme 6). Several synthetic transformations were also carried out with 6m. The tert–butyl group can be removed with CF3SO3H/cyclohexane to give compound 15 in 76% yield. The benzylation of 6m with benzaldehyde, I2 and Et3SiH led to compound 16 in 82% yield [81]. The formylation of 6m with 1 equiv. of POCl3 afforded aldehyde 17 in 70% yield [82]. Bisaldehyde 18 can be obtained in 50% yield when excess of POCl3 used.

    Scheme 6

    Scheme 6.  Synthetic transformations of compound 6m.
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    A precise understanding of the reaction mechanism awaits further study. On the basis of earlier studies [51–57], a plausible catalytic cycle is outlined in Scheme 7 (with 12a as an example). The oxidative addition of Pd(0) to 12a led to Pd intermediate 19, which subsequently underwent an intramolecular carbopalladation to form alkyl Pd species 20. Pallada(Ⅱ)cycle 13 was then generated from 20 via aryl C—H activation [83–101]. The oxidative addition of 13 to di–tert-butyldiaziridinone (8) gave four-membered pallada(Ⅳ)cycle 21, which afforded pallada(Ⅳ)nitrene species 22 upon release of tBuNCO. At the end, pyrrole fused indolo[2,1-a]isoquinoline 6a was formed from 22 via two consecutive reductive eliminations with regeneration of the Pd catalyst.

    Scheme 7

    Scheme 7.  Proposed catalytic pathway.
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    In the case of 12s (Scheme 8), the formation of a seven-membered ring from Pd intermediate 23 was apparently unfavorable (path a). Instead, 23 could undergo a C—H activation at C-3 under proper reaction conditions to give pallada(Ⅱ)cycle 26 [102–106], which was aminated with di–tert-butyldiaziridinone (8) to form indolo[3,2-b]indole 14s (path b) [53]. The introduction of a methyl group at the indole's C-3 position suppressed path b and shifted the outcome towards the formation of the seven-membered ring product.

    Scheme 8

    Scheme 8.  Proposed catalytic pathway.
    DownLoad: Full-Size Img PowerPoint

    In summary, we have developed an efficient Pd-catalyzed sequential Heck/C—H activation/amination reaction process with alkene-tethered indole derivatives and di–tert-butyldiaziridinone, providing a variety of pyrrole fused indolo[2,1-a]isoquinoline polycycles bearing various functional groups. The reaction process provides ready access to structurally diverse indolo[2,1-a]isoquinoline compounds for biologically studies. In addition, indolo[3,2-b]indoles can be efficiently formed by varying N-substituents of indole substrates. The current work further illustrates the versatility of the diaziridinone for the construction of N-heterocycles. Further expansion of its synthetic utility is currently underway.

    Declaration of competing interest

    The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

    CRediT authorship contribution statement

    Junhua Li: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Yu Fu: Writing – original draft, Visualization, Validation, Software, Formal analysis, Data curation. Yian Shi: Writing – review & editing, Supervision, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.

    Acknowledgments

    We are grateful for generous financial support from the National Natural Science Foundation of China (Nos. 22271024, 21632005) and Changzhou University.

    Supplementary materials

    Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2025.111376.


    1. [1]

      R. Ambros, S. von Angerer, W. Wiegrebe, Arch. Pharm. 321 (1988) 743–747 (Weinheim). doi: 10.1002/ardp.19883211010

    2. [2]

      R. Ambros, M.R. Schneider, S. von Angerer, J. Med. Chem. 33 (1990) 153–160. doi: 10.1021/jm00163a026

    3. [3]

      M. Goldbrunner, G. Loidl, T. Polossek, A. Mannschreck, E. von Angerer, J. Med. Chem. 40 (1997) 3524–3533. doi: 10.1021/jm970177c

    4. [4]

      R. Faust, P.J. Garratt, R. Jones, et al., J. Med. Chem. 43 (2000) 1050–1061. doi: 10.1021/jm980684+

    5. [5]

      G.A. Kraus, V. Gupta, M. Kohut, N. Singh, Bioorg. Med. Chem. Lett. 19 (2009) 5539–5542. doi: 10.1016/j.bmcl.2009.08.057

    6. [6]

      N. Fuentes, W. Kong, L.F. Sanchez, E. Merino, C. Nevado, J. Am. Chem. Soc. 137 (2015) 964–973. doi: 10.1021/ja5115858

    7. [7]

      H. Huang, Y. Li, J. Org. Chem. 82 (2017) 4449–4457. doi: 10.1021/acs.joc.7b00350

    8. [8]

      Y.L. Wei, J.Q. Chen, B. Sun, P.F. Xu, Chem. Commun. 55 (2019) 5922–5925. doi: 10.1039/c9cc02388g

    9. [9]

      Y. Yuan, Y. Zheng, B. Xu, et al., ACS Catal. 10 (2020) 6676–6681. doi: 10.1021/acscatal.0c01324

    10. [10]

      S.S. Jiang, Y.T. Xiao, Y.C. Wu, et al., Org. Biomol. Chem. 18 (2020) 4843–4847. doi: 10.1039/d0ob00877j

    11. [11]

      K. Sun, G. Li, Y. Li, et al., Adv. Synth. Catal. 362 (2020) 1947–1954. doi: 10.1002/adsc.202000040

    12. [12]

      X.Y. Hu, H.F. Xu, Q. Chen, Y.L. Pan, J.Z. Chen, Org. Biomol. Chem. 19 (2021) 10376–10384. doi: 10.1039/d1ob01917a

    13. [13]

      X. Yuan, X. Duan, Y.S. Cui, et al., Org. Lett. 23 (2021) 1950–1954. doi: 10.1021/acs.orglett.1c00476

    14. [14]

      Y. Luo, T. Tian, Y. Nishihara, L. Lv, Z. Li, Chem. Commun. 57 (2021) 9276–9279. doi: 10.1039/d1cc03907e

    15. [15]

      F.L. Zeng, H.L. Zhu, X.L. Chen, L.B. Qu, B. Yu, Green Chem. 23 (2021) 3677–3682. doi: 10.1039/d1gc00938a

    16. [16]

      M.L. Liu, J.L. Wang, X.S. Li, W.H. Sun, X.Y. Liu, Org. Chem. Front. 9 (2022) 2438–2443. doi: 10.1039/d2qo00051b

    17. [17]

      G.C. Upreti, T. Singh, S. Ranjan, R.K. Gupta, A. Singh, ACS Omega 7 (2022) 29728–29733. doi: 10.1021/acsomega.2c02302

    18. [18]

      J.Q. Chen, X. Tu, B. Qin, et al., Org. Lett. 24 (2022) 642–647. doi: 10.1021/acs.orglett.1c04082

    19. [19]

      P. Zhao, Y. Wang, X. Wang, D. Zhuang, R. Yan, J. Org. Chem. 87 (2022) 9056–9068. doi: 10.1021/acs.joc.2c00735

    20. [20]

      S. Zhai, S. Qiu, S. Yang, et al., Chin. Chem. Lett. 33 (2022) 276–279. doi: 10.1016/j.cclet.2021.06.081

    21. [21]

      J.Z. Li, L. Mei, X.E. Cai, et al., Adv. Synth. Catal. 364 (2022) 2080–2085. doi: 10.1002/adsc.202200272

    22. [22]

      X. Yuan, J. Liu, L.Z. Qin, et al., Adv. Synth. Catal. 365 (2023) 555–567. doi: 10.1002/adsc.202201294

    23. [23]

      X.Q. Liu, Y. Guo, W.Q. Yu, et al., J. Org. Chem. 88 (2023) 9293–9305. doi: 10.1021/acs.joc.3c00863

    24. [24]

      L. Liu, Y. Zhang, W. Zhao, J. Li, Org. Lett. 25 (2023) 6251–6255. doi: 10.1021/acs.orglett.3c02009

    25. [25]

      Z. Tan, Y. Jiang, K. Xu, C. Zeng, J. Catal. 417 (2023) 473–480. doi: 10.1016/j.jcat.2022.12.033

    26. [26]

      D.L. Zhang, Z.Q. Zhu, Z.B. Xie, X.P. Zhang, Z.G. Le, New J. Chem. 47 (2023) 18354–18358. doi: 10.1039/d3nj03172a

    27. [27]

      Y. Tang, Y. Yang, Q. Zhou, et al., Org. Biomol. Chem. 21 (2023) 5254–5264. doi: 10.1039/d3ob00630a

    28. [28]

      D. Chen, X. Yang, D. Wang, et al., Org. Chem. Front. 10 (2023) 2482–2490. doi: 10.1039/d3qo00290j

    29. [29]

      S. Liu, C. Zhao, M. Pan, et al., J. Org. Chem. 88 (2023) 16352–16364. doi: 10.1021/acs.joc.3c01856

    30. [30]

      A.K. Verma, T. Kesharwani, J. Singh, V. Tandon, R.C. Larock, Angew. Chem. Int. Ed. 48 (2009) 1138–1143. doi: 10.1002/anie.200804427

    31. [31]

      K. Morimoto, K. Hirano, T. Satoh, M. Miura, Org. Lett. 12 (2010) 2068–2071. doi: 10.1021/ol100560k

    32. [32]

      L. Ackermann, L. Wang, A.V. Lygin, Chem. Sci. 3 (2012) 177–180. doi: 10.1039/C1SC00619C

    33. [33]

      A.K. Verma, R.R. Jha, R. Chaudhary, et al., J. Org. Chem. 77 (2012) 8191–8205. doi: 10.1021/jo301572p

    34. [34]

      S. Borthakur, B. Sarma, S. Gogoi, Org. Lett. 21 (2019) 7878–7882. doi: 10.1021/acs.orglett.9b02871

    35. [35]

      T.S. Zhang, Q. Zhao, W.J. Hao, S.J. Tu, B. Jiang, Chem. Asian J. 14 (2019) 1042–1049. doi: 10.1002/asia.201900050

    36. [36]

      C. Wu, J. Lin, X. Tian, Org. Lett. 25 (2023) 158–162. doi: 10.1021/acs.orglett.2c03973

    37. [37]

      H. Li, M. Mei, D. Wang, L. Zhou, Org. Chem. Front. 10 (2023) 1544–1550. doi: 10.1039/d2qo02008d

    38. [38]

      L.L. Sun, Z.Y. Liao, R.Y. Tang, C.L. Deng, X.G. Zhang, J. Org. Chem. 77 (2012) 2850–2856. doi: 10.1021/jo3000404

    39. [39]

      K. Alam, S.W. Hong, K.H. Oh, J.K. Park, Angew. Chem. Int. Ed. 56 (2017) 13387–13391. doi: 10.1002/anie.201705514

    40. [40]

      H. Lu, X. Yang, L. Zhou, et al., Org. Chem. Front. 7 (2020) 2016–2021. doi: 10.1039/d0qo00492h

    41. [41]

      J.S. Wang, J. Zhang, S. Wang, et al., J. Catal. 414 (2022) 313–318. doi: 10.1016/j.jcat.2022.09.023

    42. [42]

      S. Wang, J.S. Wang, J. Ying, X.F. Wu, Chin. Chem. Lett. 34 (2023) 107873. doi: 10.1016/j.cclet.2022.107873

    43. [43]

      S. Wang, S. Li, L. Liu, J. Ying, X.F. Wu, Org. Lett. 25 (2023) 821–825. doi: 10.1021/acs.orglett.2c04363

    44. [44]

      C.Y. Hou, H. Ma, R. Zhao, X. Qi, X.F. Wu, J. Catal. 439 (2024) 115765. doi: 10.1016/j.jcat.2024.115765

    45. [45]

      D. Chi, H. Qi, L. Wang, S. Chen, Chem. Commun. 60 (2024) 8613–8616. doi: 10.1039/d4cc02577f

    46. [46]

      Y. Xia, W. Li, M. Wei, et al., Org. Chem. Front. 11 (2024) 3491–3496. doi: 10.1039/d4qo00392f

    47. [47]

      X. Yang, H. Lu, X. Zhu, et al., Org. Lett. 21 (2019) 7284–7288. doi: 10.1021/acs.orglett.9b02541

    48. [48]

      L. Zhou, S. Qiao, F. Zhou, et al., Org. Lett. 23 (2021) 2878–2883. doi: 10.1021/acs.orglett.1c00493

    49. [49]

      M. Zhang, F. Zhou, X. Xuchen, et al., Org. Chem. Front. 8 (2021) 5687–5692. doi: 10.1039/d1qo00861g

    50. [50]

      H. Qi, D. Chi, S. Chen, Org. Lett. 24 (2022) 2910–2914. doi: 10.1021/acs.orglett.2c00882

    51. [51]

      T.A. Ramirez, Q. Wang, Y. Zhu, et al., Org. Lett. 15 (2013) 4210–4213. doi: 10.1021/ol401935c

    52. [52]

      H. Zheng, Y. Zhu, Y. Shi, Angew. Chem. Int. Ed. 53 (2014) 11280–11284. doi: 10.1002/anie.201405365

    53. [53]

      S. Debnath, L. Liang, M. Lu, Y. Shi, Org. Lett. 23 (2021) 3237–3242. doi: 10.1021/acs.orglett.1c00466

    54. [54]

      J. Li, J. Chen, L. Wang, Y. Shi, Org. Lett. 23 (2021) 3646–3651. doi: 10.1021/acs.orglett.1c01043

    55. [55]

      J. Wang, X. Sun, D. Hu, Y. Shi, Org. Lett. 23 (2021) 7561–7565. doi: 10.1021/acs.orglett.1c02757

    56. [56]

      J. Wang, D. Hu, X. Sun, H. Hong, Y. Shi, Org. Lett. 25 (2023) 2006–2011. doi: 10.1021/acs.orglett.3c00189

    57. [57]

      J. Li, Y. Liu, Y. Shi, Tetrahedron Lett. 147 (2024) 155158. doi: 10.1016/j.tetlet.2024.155158

    58. [58]

      C. Shao, B. Zhou, Z. Wu, X. Ji, Y. Zhang, Adv. Synth. Catal. 360 (2018) 887–892. doi: 10.1002/adsc.201701039

    59. [59]

      B. Zhou, Z. Wu, D. Ma, X. Ji, Y. Zhang, Org. Lett. 20 (2018) 6440–6443. doi: 10.1021/acs.orglett.8b02750

    60. [60]

      X. Sun, Z. Wu, W. Qi, et al., Org. Lett. 21 (2019) 6508–6512. doi: 10.1021/acs.orglett.9b02386

    61. [61]

      D. Ma, X. Ji, Z. Wu, et al., Adv. Synth. Catal. 361 (2019) 739–746. doi: 10.1002/adsc.201801367

    62. [62]

      C. Cheng, X. Zuo, D. Tu, B. Wan, Y. Zhang, Org. Lett. 22 (2020) 4985–4989. doi: 10.1021/acs.orglett.0c01513

    63. [63]

      L. Zhang, J. Chen, T. Zhong, et al., J. Org. Chem. 85 (2020) 10823–10834. doi: 10.1021/acs.joc.0c01365

    64. [64]

      J. Bajohr, A. Dupeux, D. Schenk, C. Jans, M. Lautens, Org. Lett. 25 (2023) 5361–5365. doi: 10.1021/acs.orglett.3c01941

    65. [65]

      P. Kaszynski, D.A. Dougherty, J. Org. Chem. 58 (1993) 5209–5220. doi: 10.1021/jo00071a034

    66. [66]

      M.M. Murray, P. Kaszynski, D.A. Kaisaki, W. Chang, D.A. Dougherty, J. Am. Chem. Soc. 116 (1994) 8152–8161. doi: 10.1021/ja00097a024

    67. [67]

      Y. Jin, K. Kim, S. Song, et al., Bull. Korean Chem. Soc. 27 (2006) 1043–1047. doi: 10.5012/bkcs.2006.27.7.1043

    68. [68]

      L. Qiu, C. Yu, N. Zhao, et al., Chem. Commun. 48 (2012) 12225–12227. doi: 10.1039/c2cc36689d

    69. [69]

      Y.Y. Lai, J.M. Yeh, C.E. Tsai, Y.J. Cheng, Eur. J. Org. Chem. (2013) 5076–5084. doi: 10.1002/ejoc.201300443

    70. [70]

      Z.R. Owczarczyk, W.A. Braunecker, A. Garcia, et al., Macromolecules 46 (2013) 1350–1360. doi: 10.1021/ma301987p

    71. [71]

      L. Qiu, X. Wang, N. Zhao, et al., J. Org. Chem. 79 (2014) 11339–11348. doi: 10.1021/jo501402n

    72. [72]

      L. Qiu, X. Zhuang, N. Zhao, et al., Chem. Commun. 50 (2014) 3324–3327. doi: 10.1039/C3CC49418G

    73. [73]

      M.J. Jiang, W.J. Xiao, J.C. Huang, W.S. Li, Y.Q. Mo, Tetrahedron 72 (2016) 979–984. doi: 10.1016/j.tet.2015.12.069

    74. [74]

      H.E. Ho, K. Oniwa, Y. Yamamoto, T. Jin, Org. Lett. 18 (2016) 2487–2490. doi: 10.1021/acs.orglett.6b01067

    75. [75]

      J. Yu, D. Zhang-Negrerie, Y. Du, Org. Lett. 18 (2016) 3322–3325. doi: 10.1021/acs.orglett.6b01343

    76. [76]

      J. Hwang, J. Park, Y.J. Kim, et al., Chem. Mater. 29 (2017) 2135–2140. doi: 10.1021/acs.chemmater.6b04745

    77. [77]

      T. Matsuda, H. Ito, Org. Biomol. Chem. 16 (2018) 6703–6707. doi: 10.1039/c8ob01837e

    78. [78]

      A. Shoberu, C.K. Li, Z.K. Tao, G.Y. Zhang, J.P. Zou, Adv. Synth. Catal. 361 (2019) 2255–2261. doi: 10.1002/adsc.201900070

    79. [79]

      Y. Wu, C. Pi, X. Cui, Y. Wu, Org. Lett. 22 (2020) 361–364. doi: 10.1021/acs.orglett.9b03768

    80. [80]

      X.H. Shan, B. Yang, J.P. Qu, Y.B. Kang, Chem. Commun. 56 (2020) 4063–4066. doi: 10.1039/d0cc01172j

    81. [81]

      X. Cheng, L. Wang, Y. Liu, et al., Eur. J. Org. Chem. (2022) e202200502.

    82. [82]

      M.Z. Zhang, N. Mulholland, A. Seville, et al., Tetrahedron 79 (2021) 131835. doi: 10.1016/j.tet.2020.131835

    83. [83]

      G. Dyker, Angew. Chem. Int. Ed. 38 (1999) 1698–1712. doi: 10.1002/(SICI)1521-3773(19990614)38:12<1698::AID-ANIE1698>3.0.CO;2-6

    84. [84]

      F. Kakiuchi, N. Chatani, Adv. Synth. Catal. 345 (2003) 1077–1101. doi: 10.1002/adsc.200303094

    85. [85]

      M. Catellani, Synlett (2003) 298–313.

    86. [86]

      D. Alberico, M.E. Scott, M. Lautens, Chem. Rev. 107 (2007) 174–238. doi: 10.1021/cr0509760

    87. [87]

      M. Catellani, E. Motti, N. Della Cá, Chem. Res. 41 (2008) 1512–1522. doi: 10.1021/ar800040u

    88. [88]

      K. Muñiz, Angew. Chem. Int. Ed. 48 (2009) 9412–9423. doi: 10.1002/anie.200903671

    89. [89]

      L. Ackermann, R. Vicente, A.R. Kapdi, Angew. Chem. Int. Ed. 48 (2009) 9792–9826. doi: 10.1002/anie.200902996

    90. [90]

      R. Jazzar, J. Hitce, A. Renaudat, J. Sofack-Kreutzer, O. Baudoin, Chem. Eur. J. 16 (2010) 2654–2672. doi: 10.1002/chem.200902374

    91. [91]

      L.M. Xu, B.J. Li, Z. Yang, Z.J. Shi, Chem. Soc. Rev. 39 (2010) 712–733. doi: 10.1039/B809912J

    92. [92]

      P. Sehnal, R.J.K. Taylor, I.J.S. Fairlamb, Chem. Rev. 110 (2010) 824–889. doi: 10.1021/cr9003242

    93. [93]

      F. Shi, R.C. Larock, Top. Curr. Chem. 292 (2010) 123–164.

    94. [94]

      L. McMurray, F. O'Hara, M.J. Gaunt, Chem. Soc. Rev. 40 (2011) 1885–1898. doi: 10.1039/c1cs15013h

    95. [95]

      J. Wencel-Delord, T. Droege, F. Liu, F. Glorius, Chem. Soc. Rev. 40 (2011) 4740–4761. doi: 10.1039/c1cs15083a

    96. [96]

      H.C. Malinakova, Top. Organomet. Chem. 35 (2011) 85–110.

    97. [97]

      N. Dastbaravardeh, M. Christakakou, M. Haider, M. Schnürch, Synthesis 46 (2014) 1421–1439. doi: 10.1055/s-0033-1338625

    98. [98]

      T. Jin, M. Terada, Tetrahedron Lett. 61 (2020) 151514. doi: 10.1016/j.tetlet.2019.151514

    99. [99]

      F. Zhang, L. Xin, Y. Yu, S. Liao, X. Huang, Synthesis 53 (2021) 238–254. doi: 10.1055/s-0040-1707268

    100. [100]

      J.R. Alexander, G. Dong, Green Synth. Catal. 2 (2021) 216–227.

    101. [101]

      X. Luo, W. Li, H. Lu, et al., Chin. Chem. Lett. 32 (2021) 713–716. doi: 10.1016/j.cclet.2020.07.005

    102. [102]

      L. Wu, G. Deng, Y. Liang, Org. Biomol. Chem. 15 (2017) 6808–6812. doi: 10.1039/C7OB01638G

    103. [103]

      Y. Yang, B. Zhou, X. Zhu, et al., Org. Lett. 20 (2018) 5402–5405. doi: 10.1021/acs.orglett.8b02310

    104. [104]

      M. Sun, X. Chen, Z. Feng, et al., Org. Chem. Front. 8 (2021) 6535–6540. doi: 10.1039/d1qo01103k

    105. [105]

      H.Q. Ni, P. Cooper, S. Yang, et al., Angew. Chem. Int. Ed. 61 (2022) e202114346. doi: 10.1002/anie.202114346

    106. [106]

      W. Li, Y. Yu, J. Yang, et al., Chem. Asian J. 19 (2024) e202301040. doi: 10.1002/asia.202301040

  • Figure 1  Examples of bioactive indolo[2,1-a]isoquinolines.

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    Scheme 1  Bisamination of pallada(Ⅱ)cycles with diaziridinone.

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    Scheme 2  Pd-catalyzed sequential Heck/C—H activation/amination.

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    Scheme 3  The reaction scope. All reactions were carried out with 12 (0.30 mmol), Pd(OAc)2 (0.015 mol), PPhCy2 (0.060 mmol), di–tert-butyldiaziridinone (8) (0.45 mmol), and Cs2CO3 (0.45 mmol) in PhCH3 (2.0 mL) at 130 ℃ under N2 for 4 h unless otherwise noted, the yield was isolated yield. a With 1.0 mL PhCH3. b For 12 h. c With Pd(OAc)2 (0.015 mol), (o-tolyl)3P (0.060 mmol), di–tert-butyldiaziridinone (8) (0.45 mmol), KOPiv (0.15 mmol), and Cs2CO3 (0.45 mmol) in DMF (1.0 mL) at 130 ℃ for 12 h.

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    Scheme 4  The indole C-3 amination reaction.

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    Scheme 5  The synthesis of seven-membered polycyclic indole 6y.

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    Scheme 6  Synthetic transformations of compound 6m.

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    Scheme 7  Proposed catalytic pathway.

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    Scheme 8  Proposed catalytic pathway.

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    Table 1.  Studies on the reaction conditions.a

    Entry [Pd] Ligand Yield (%)b
    1 Pd(OAc)2 PPh3 43
    2 Pd(OAc)2 (o-MeOPh)3P 33
    3 Pd(OAc)2 (p-FPh)3P 26
    4 Pd(OAc)2 (2-thienyl)3P 30
    5 Pd(OAc)2 (2-furyl)3P 41
    6 Pd(OAc)2 PPh2Cy 36
    7 Pd(OAc)2 PPhCy2 58
    8 Pd(OAc)2 PCy3 33
    9 Pd(OAc)2 dppb 19
    10 Pd(OAc)2 dppf 25
    11 Pd(OAc)2 Xantphos 31
    12 PdCl2 PPhCy2 35
    13 PdI2 PPhCy2 23
    14 Pd(PPh3)4 PPhCy2 26
    15 Pd(OAc)2 (1,4-dioxane) PPhCy2 47
    16 Pd(OAc)2 (hexane) PPhCy2 27
    17 Pd(OAc)2 (DCE) PPhCy2 27
    18 Pd(OAc)2 (DME) PPhCy2 27
    19 Pd(OAc)2 (90 ℃) PPhCy2 NP
    20 Pd(OAc)2 (130 ℃) PPhCy2 99
    21 Pd(OAc)2 (130 ℃, 4 h) PPhCy2 99
    a All reactions were carried out with indole 12a (0.15 mmol), Pd (0.0075 mmol), ligand (0.015–0.030 mmol, Pd/P = 1/4), di– tert-butyldiaziridinone (8) (0.225 mmol), and Cs 2CO 3 (0.225 mmol) in PhCH 3 (1.5 mL) at 110 ℃ under N 2 for 48 h unless otherwise noted.
    b The yield was determined by 1H NMR analysis of the crude reaction mixture with 1,1,2,2-tetrachloroethane as internal standard.
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  • 发布日期:  2026-03-15
  • 收稿日期:  2025-01-22
  • 接受日期:  2025-05-26
  • 修回日期:  2025-05-20
  • 网络出版日期:  2025-05-27
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