Skip to content
2000
image of Visible Light-induced Autocatalytic Aza-6π Electrocyclization to Access Polysubstituted Phenanthridines

Abstract

Autocatalytic reaction represents an appealing approach in organic chemistry and life sciences. The development of a novel autocatalytic mode for aza-6π electrocyclization reactions represents a promising protocol for the efficient construction of aromatic -heterocycles. Drawing inspiration from natural biosynthetic pathways for aromatic heterocycles, a wide variety of bioactive natural products can be synthesized efficiently using a biomimetic aza-6π electrocyclization strategy. However, conventional thermal catalysis inevitably suffers from a limited substrate scope and diversity. The photochemical protocol is considered a promising approach in elegant organic synthesis, but the application of photocatalysis in 6π electrocyclization has been rarely explored. In this context, we hypothesized that the aza-hexatriene system of phenanthridine precursor might cyclize with the intermediate imine, which could be formed from the reaction of 2-arylaniline and aldehyde source, respectively. Subsequently, the aza-hexatriene is excited by the corresponding phenanthridine energy transfer under visible light. The final intramolecular cyclization could generate the substituted phenanthridines. Herein, a novel visible light-induced autocatalytic aza-6π electrocyclization method was reported for the synthesis of diverse phenanthridines. A broad spectrum of 2-arylaniline and (hetero)aryl aldehydes could be well tolerated under metal- and oxidant-free conditions, affording the corresponding phenanthridines in moderate to good yields. This newly developed method represents a highly efficient and cost-effective synthetic protocol. The late-stage functionalization of celecoxib and bromopride derivatives also demonstrated the practical value of this method.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/loc/10.2174/0115701786398032250728103318
2025-08-04
2025-11-07

  • From This Site

    /content/journals/loc/10.2174/0115701786398032250728103318
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Bissette A.J. Fletcher S.P. Angew. Chem. Int. Ed. 2013 52 49 12800 12826 10.1002/anie.201303822
    [Google Scholar]
  2. Vasas V. Fernando C. Santos M. Kauffman S. Szathmáry E. Biol. Direct 2012 7 1 1 10.1186/1745‑6150‑7‑1 22221860
    [Google Scholar]
  3. Ashkenasy G. Hermans T.M. Otto S. Taylor A.F. Chem. Soc. Rev. 2017 46 9 2543 2554 10.1039/C7CS00117G 28418049
    [Google Scholar]
  4. Semenov S.N. Kraft L.J. Ainla A. Zhao M. Baghbanzadeh M. Campbell V.E. Kang K. Fox J.M. Whitesides G.M. Nature 2016 537 7622 656 660 10.1038/nature19776 27680939
    [Google Scholar]
  5. Dryzhakov M. Moran J. ACS Catal. 2016 6 6 3670 3673 10.1021/acscatal.6b00866
    [Google Scholar]
  6. Soai K. Shibata T. Morioka H. Choji K. Nature 1995 378 6559 767 768 10.1038/378767a0
    [Google Scholar]
  7. Matsumoto A. Abe T. Hara A. Tobita T. Sasagawa T. Kawasaki T. Soai K. Angew. Chem. Int. Ed. 2015 54 50 15218 15221 10.1002/anie.201508036
    [Google Scholar]
  8. Mauksch M. Tsogoeva S.B. Martynova I.M. Wei S. Angew. Chem. Int. Ed. 2007 46 3 393 396 10.1002/anie.200603517
    [Google Scholar]
  9. Wang X. Zhang Y. Tan H. Wang Y. Han P. Wang D.Z. J. Org. Chem. 2010 75 7 2403 2406 10.1021/jo902500b 20196532
    [Google Scholar]
  10. Soai K. Kawasaki T. Matsumoto A. Tetrahedron 2018 74 16 1973 1990 10.1016/j.tet.2018.02.040
    [Google Scholar]
  11. Semenov S.N. Belding L. Cafferty B.J. Mousavi M.P.S. Finogenova A.M. Cruz R.S. Skorb E.V. Whitesides G.M. J. Am. Chem. Soc. 2018 140 32 10221 10232 10.1021/jacs.8b05048 30035540
    [Google Scholar]
  12. Blackmond D.G. Chem. Rev. 2020 120 11 4831 4847 10.1021/acs.chemrev.9b00557 31797671
    [Google Scholar]
  13. Wang C. Zhang H. Wells L.A. Liu T. Meng T. Liu Q. Walsh P.J. Kozlowski M.C. Jia T. Nat. Commun. 2021 12 1 932 10.1038/s41467‑021‑21156‑w 33568641
    [Google Scholar]
  14. Hui P. Branca M. Limoges B. Mavré F. Chem. Commun. 2021 57 86 11374 11377 10.1039/D1CC05121K 34647564
    [Google Scholar]
  15. Xiang S-H. Tan B. Nat. Commun. 2020 11 3686 10.1038/s41467‑020‑17494‑w 32703955
    [Google Scholar]
  16. Hanopolskyi A.I. Smaliak V.A. Novichkov A.I. Semenov S.N. ChemSystemsChem 2020 2 2000026
    [Google Scholar]
  17. Terron H.M. Parikh S.J. Abdul-Hay S.O. Sahara T. Kang D. Dickson D.W. Saftig P. LaFerla F.M. Lane S. Leissring M.A. Pelupessy P. Jullien L. Szathmary E. Nghe P. Alzheimers Res. Ther. 2024 16 1 70 10.1186/s13195‑024‑01443‑6 38575959
    [Google Scholar]
  18. Beaudry C.M. Malerich J.P. Trauner D. Chem. Rev. 2005 105 12 4757 4778 10.1021/cr0406110 16351061
    [Google Scholar]
  19. Urabe D. Asaba T. Inoue M. Chem. Rev. 2015 115 17 9207 9231 10.1021/cr500716f 25780815
    [Google Scholar]
  20. Athavale S.V. Simon A. Houk K.N. Denmark S.E. J. Am. Chem. Soc. 2020 142 43 18387 18406 10.1021/jacs.0c05994 33108874
    [Google Scholar]
  21. Ivanov R. Ivanova E. Merkulov V. Zharkov M. Kuchurov I. Zlotin S. Eur. J. Org. Chem. 2023 26 25 202300366 10.1002/ejoc.202300366
    [Google Scholar]
  22. Döhler D. Michael P. Binder W.H. Macromolecules 2012 45 8 3335 3345 10.1021/ma300405v
    [Google Scholar]
  23. Paul-Gorsline B.J. Org. Process Res. Dev. 2024 28 7 2481 2487 10.1021/acs.oprd.4c00099
    [Google Scholar]
  24. Hoepker A.C. Gupta L. Ma Y. Faggin M.F. Collum D.B. J. Am. Chem. Soc. 2011 133 18 7135 7151 10.1021/ja200906z 21500823
    [Google Scholar]
  25. Colabroy K.L. Begley T.P. J. Am. Chem. Soc. 2005 127 3 840 841 10.1021/ja0446395 15656614
    [Google Scholar]
  26. Mata N.L. Weng J. Travis G.H. Proc. Natl. Acad. Sci. USA 2000 97 13 7154 7159 10.1073/pnas.130110497 10852960
    [Google Scholar]
  27. Vargas D.F. Larghi E.L. Kaufman T.S. Nat. Prod. Rep. 2019 36 2 354 401 10.1039/C8NP00014J 30090891
    [Google Scholar]
  28. Roche S.P. Organics 2021 2 4 376 387 10.3390/org2040021
    [Google Scholar]
  29. Jiang X. Zeng Z. Hua Y. Xu B. Shen Y. Xiong J. Qiu H. Wu Y. Hu T. Zhang Y. J. Am. Chem. Soc. 2020 142 36 15585 15594 10.1021/jacs.0c07680 32786746
    [Google Scholar]
  30. Cao Y. Perry J.S.M. Zhang E. Trinh A. Kacker A. Cruz S. Ceballos H. Pan A. Huang W. Kou K.G.M. JACS Au 2025 5 3 1429 1438 10.1021/jacsau.5c00047 40151253
    [Google Scholar]
  31. Ba M. He F. Ren L. Whittingham W.G. Yang P. Li A. Angew. Chem. Int. Ed. 2024 63 29 202314800 10.1002/anie.202314800
    [Google Scholar]
  32. Tanaka K. Katsumura S. Fukase K. Sci. China Chem. 2012 55 1 19 30 10.1007/s11426‑011‑4466‑9
    [Google Scholar]
  33. Li N. Huang Y. Org. Lett. 2020 22 23 9392 9397 10.1021/acs.orglett.0c03725 33231467
    [Google Scholar]
  34. Woodward R.B. Hoffmann R. J. Am. Chem. Soc. 1965 87 2 395 397 10.1021/ja01080a054
    [Google Scholar]
  35. Woodward R.B. Hoffmann R. Angew. Chem. Int. Ed. Engl. 1969 8 11 781 853 10.1002/anie.196907811
    [Google Scholar]
  36. Hoffmann R. Woodward R.B. Acc. Chem. Res. 1968 1 1 17 22 10.1021/ar50001a003
    [Google Scholar]
  37. Bach T. Grosch B. Strassner T. Herdtweck E. J. Org. Chem. 2003 68 3 1107 1116 10.1021/jo026602d 12558441
    [Google Scholar]
  38. Chapman O.L. Eian G.L. J. Am. Chem. Soc. 1968 90 19 5329 5330 10.1021/ja01021a081
    [Google Scholar]
  39. Hitt D.M. O’Connor J.M. Chem. Rev. 2011 111 12 7904 7922 10.1021/cr2001542 21978178
    [Google Scholar]
  40. Münster N. Parker N.A. van Dijk L. Paton R.S. Smith M.D. Angew. Chem. Int. Ed. 2017 56 32 9468 9472 10.1002/anie.201705333
    [Google Scholar]
  41. Zhang Z. Chen H. Keller N. Xiong Q. Liu L. Lan Y. Bein T. Li. J. Org Chem. Front 2021 8 14 3788 3795 10.1039/D1QO00356A
    [Google Scholar]
  42. Ma L. Feng W. Shang H. Lin X. Xi Y. New J. Chem. 2021 45 40 18924 18932 10.1039/D1NJ03218F
    [Google Scholar]
  43. Oddy M.J. Kusza D.A. Petersen W.F. Org. Lett. 2021 23 22 8963 8967 10.1021/acs.orglett.1c03487 34756046
    [Google Scholar]
  44. Lv Y.F. Ren F.C. Kuang M.T. Miao Y. Li Z.L. Hu J.M. Zhou J. Org. Lett. 2020 22 17 6822 6826 10.1021/acs.orglett.0c02335 32830986
    [Google Scholar]
  45. Narayanama J.M.R. Stephenson. J. Chem. Soc. Rev. 2011 40 102
    [Google Scholar]
  46. Chen J.R. Hu X.Q. Lu L.Q. Xiao W.J. Acc. Chem. Res. 2016 49 9 1911 1923 10.1021/acs.accounts.6b00254 27551740
    [Google Scholar]
  47. Wang E.B. Fan Q. Lu X. Sun B. Zhang F.L. Org. Biomol. Chem. 2024 22 24 4968 4972 10.1039/D4OB00656A 38825973
    [Google Scholar]
  48. Cushman M. Mohan P. Smith E.C.R. J. Med. Chem. 1984 27 4 544 547 10.1021/jm00370a021 6708057
    [Google Scholar]
  49. Abe Y. Kayakiri H. Satoh S. Inoue T. Sawada Y. Inamura N. Asano M. Aramori I. Hatori C. Sawai H. Oku T. Tanaka H. J. Med. Chem. 1998 41 21 4062 4079 10.1021/jm980300f 9767643
    [Google Scholar]
  50. Li A.H. Moro S. Forsyth N. Melman N. Ji X. Jacobson K.A. J. Med. Chem. 1999 42 4 706 721 10.1021/jm980550w 10052977
    [Google Scholar]
  51. Nakanishi T. Masuda A. Suwa M. Akiyama Y. Hoshino-Abe N. Suzuki M. Bioorg. Med. Chem. Lett. 2000 10 20 2321 2323 10.1016/S0960‑894X(00)00467‑4 11055347
    [Google Scholar]
  52. Qin X. Ding G. Luo Z. Wang Z. Zhang S. Li H. Gao F. Dyes Pigments 2016 134 613 617 10.1016/j.dyepig.2016.07.041
    [Google Scholar]
  53. Narita A. Wang X.Y. Feng X. Müllen K. Chem. Soc. Rev. 2015 44 18 6616 6643 10.1039/C5CS00183H 26186682
    [Google Scholar]
  54. Liu W. Zheng C.J. Wang K. Chen Z. Chen D.Y. Li F. Ou X.M. Dong Y.P. Zhang X.H. ACS Appl. Mater. Interfaces 2015 7 34 18930 18936 10.1021/acsami.5b05648 26289611
    [Google Scholar]
  55. Sasabe H. Kido. J. Chem. Mater. 2011 23 3 621 630 10.1021/cm1024052
    [Google Scholar]
  56. Gao Y. Jing Y. Li L. Zhang J. Chen X. Ma Y.N. J. Org. Chem. 2020 85 19 12187 12198 10.1021/acs.joc.0c01390 32872780
    [Google Scholar]
  57. Xiao T. Li L. Lin G. Wang Q. Zhang P. Mao Z. Zhou L. Green Chem. 2014 16 5 2418 2421 10.1039/C3GC42517G
    [Google Scholar]
  58. Li X. Liang D. Huang W. Sun H. Wang L. Ren M. Wang B. Ma Y. Tetrahedron 2017 73 50 7094 7099 10.1016/j.tet.2017.10.074
    [Google Scholar]
  59. Xi J. Dong Q.L. Liu G.S. Wang S. Chen L. Yao Z-J. Synlett 2010 11 1674
    [Google Scholar]
  60. Zhang Q.L. Yu Q. Ma L. Lu X. Fan Q.T. Duan T.S. Zhou Y. Zhang F.L. J. Org. Chem. 2021 86 23 17244 17248 10.1021/acs.joc.1c02312 34807586
    [Google Scholar]
  61. Zhang Q.L. Sun B. Ji G. Zhang G. Zhang F.L. Org. Lett. 2024 26 1 110 115 10.1021/acs.orglett.3c03720 38157221
    [Google Scholar]
  62. Zhang Q-L. Fan Q-T. Zhou Y. Zhang. J. Org Chem. Front 2024 11 2884 10.1039/D4QO00140K
    [Google Scholar]
  63. Iwai T. Abe S. Takizawa S. Masai H. Terao. J. Chem. Sci. 2024 15 23 8873 8879 10.1039/D4SC01046A
    [Google Scholar]
  64. Kim Y. Iwai T. Fujii S. Ueno K. Sawamura M. Chemistry 2021 27 7 2289 2293 10.1002/chem.202004053 33159337
    [Google Scholar]
  65. Kaes C. Chem. Rev. 2000 100 3553 10.1021/cr990376z 11749322
    [Google Scholar]
  66. Korpi H. Sippola V. Filpponen I. Sipilä J. Krause O. Leskelä M. Repo T. Appl. Catal. A Gen. 2006 302 2 250 256 10.1016/j.apcata.2006.01.020
    [Google Scholar]
  67. Wang C. Tang R. Wan C. Qin Z. Chen S. Xu K. J. Mol. Struct. 2023 1291 136066 10.1016/j.molstruc.2023.136066
    [Google Scholar]
/content/journals/loc/10.2174/0115701786398032250728103318
Loading
Visible Light-induced Autocatalytic Aza-6π Electrocyclization to Access Polysubstituted Phenanthridines
Bentham Science Publishers ; https://doi.org/10.2174/0115701786398032250728103318
/content/journals/loc/10.2174/0115701786398032250728103318
/content/journals/loc/10.2174/0115701786398032250728103318
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: late-stage functionalization ; electrocyclization ; metal-free ; oxidant-free ; Visible light ; phenanthridines ; autocatalytic

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test