Skip to content
2000
Volume 23, Issue 1
  • ISSN: 1570-1786
  • E-ISSN: 1875-6255

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.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/loc/10.2174/0115701786398032250728103318
2025-08-04
2026-03-10

  • 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. BissetteA.J. FletcherS.P. Angew. Chem. Int. Ed.20135249128001282610.1002/anie.201303822
     [Google Scholar]
  2. VasasV. FernandoC. SantosM. KauffmanS. SzathmáryE. Biol. Direct201271110.1186/1745‑6150‑7‑1 22221860
     [Google Scholar]
  3. AshkenasyG. HermansT.M. OttoS. TaylorA.F. Chem. Soc. Rev.20174692543255410.1039/C7CS00117G 28418049
     [Google Scholar]
  4. SemenovS.N. KraftL.J. AinlaA. ZhaoM. BaghbanzadehM. CampbellV.E. KangK. FoxJ.M. WhitesidesG.M. Nature2016537762265666010.1038/nature19776 27680939
     [Google Scholar]
  5. DryzhakovM. MoranJ. ACS Catal.2016663670367310.1021/acscatal.6b00866
     [Google Scholar]
  6. SoaiK. ShibataT. MoriokaH. ChojiK. Nature1995378655976776810.1038/378767a0
     [Google Scholar]
  7. MatsumotoA. AbeT. HaraA. TobitaT. SasagawaT. KawasakiT. SoaiK. Angew. Chem. Int. Ed.20155450152181522110.1002/anie.201508036
     [Google Scholar]
  8. MaukschM. TsogoevaS.B. MartynovaI.M. WeiS. Angew. Chem. Int. Ed.200746339339610.1002/anie.200603517
     [Google Scholar]
  9. WangX. ZhangY. TanH. WangY. HanP. WangD.Z. J. Org. Chem.20107572403240610.1021/jo902500b 20196532
     [Google Scholar]
  10. SoaiK. KawasakiT. MatsumotoA. Tetrahedron201874161973199010.1016/j.tet.2018.02.040
     [Google Scholar]
  11. SemenovS.N. BeldingL. CaffertyB.J. MousaviM.P.S. FinogenovaA.M. CruzR.S. SkorbE.V. WhitesidesG.M. J. Am. Chem. Soc.201814032102211023210.1021/jacs.8b05048 30035540
     [Google Scholar]
  12. BlackmondD.G. Chem. Rev.2020120114831484710.1021/acs.chemrev.9b00557 31797671
     [Google Scholar]
  13. WangC. ZhangH. WellsL.A. LiuT. MengT. LiuQ. WalshP.J. KozlowskiM.C. JiaT. Nat. Commun.202112193210.1038/s41467‑021‑21156‑w 33568641
     [Google Scholar]
  14. HuiP. BrancaM. LimogesB. MavréF. Chem. Commun.20215786113741137710.1039/D1CC05121K 34647564
     [Google Scholar]
  15. XiangS-H. TanB. Nat. Commun.202011368610.1038/s41467‑020‑17494‑w 32703955
     [Google Scholar]
  16. HanopolskyiA.I. SmaliakV.A. NovichkovA.I. SemenovS.N. ChemSystemsChem202022000026
     [Google Scholar]
  17. TerronH.M. ParikhS.J. Abdul-HayS.O. SaharaT. KangD. DicksonD.W. SaftigP. LaFerlaF.M. LaneS. LeissringM.A. PelupessyP. JullienL. SzathmaryE. NgheP. Alzheimers Res. Ther.20241617010.1186/s13195‑024‑01443‑6 38575959
     [Google Scholar]
  18. BeaudryC.M. MalerichJ.P. TraunerD. Chem. Rev.2005105124757477810.1021/cr0406110 16351061
     [Google Scholar]
  19. UrabeD. AsabaT. InoueM. Chem. Rev.2015115179207923110.1021/cr500716f 25780815
     [Google Scholar]
  20. AthavaleS.V. SimonA. HoukK.N. DenmarkS.E. J. Am. Chem. Soc.202014243183871840610.1021/jacs.0c05994 33108874
     [Google Scholar]
  21. IvanovR. IvanovaE. MerkulovV. ZharkovM. KuchurovI. ZlotinS. Eur. J. Org. Chem.2023262520230036610.1002/ejoc.202300366
     [Google Scholar]
  22. DöhlerD. MichaelP. BinderW.H. Macromolecules20124583335334510.1021/ma300405v
     [Google Scholar]
  23. Paul-GorslineB.J. Org. Process Res. Dev.20242872481248710.1021/acs.oprd.4c00099
     [Google Scholar]
  24. HoepkerA.C. GuptaL. MaY. FagginM.F. CollumD.B. J. Am. Chem. Soc.2011133187135715110.1021/ja200906z 21500823
     [Google Scholar]
  25. ColabroyK.L. BegleyT.P. J. Am. Chem. Soc.2005127384084110.1021/ja0446395 15656614
     [Google Scholar]
  26. MataN.L. WengJ. TravisG.H. Proc. Natl. Acad. Sci. USA200097137154715910.1073/pnas.130110497 10852960
     [Google Scholar]
  27. VargasD.F. LarghiE.L. KaufmanT.S. Nat. Prod. Rep.201936235440110.1039/C8NP00014J 30090891
     [Google Scholar]
  28. RocheS.P. Organics20212437638710.3390/org2040021
     [Google Scholar]
  29. JiangX. ZengZ. HuaY. XuB. ShenY. XiongJ. QiuH. WuY. HuT. ZhangY. J. Am. Chem. Soc.202014236155851559410.1021/jacs.0c07680 32786746
     [Google Scholar]
  30. CaoY. PerryJ.S.M. ZhangE. TrinhA. KackerA. CruzS. CeballosH. PanA. HuangW. KouK.G.M. JACS Au2025531429143810.1021/jacsau.5c00047 40151253
     [Google Scholar]
  31. BaM. HeF. RenL. WhittinghamW.G. YangP. LiA. Angew. Chem. Int. Ed.2024632920231480010.1002/anie.202314800
     [Google Scholar]
  32. TanakaK. KatsumuraS. FukaseK. Sci. China Chem.2012551193010.1007/s11426‑011‑4466‑9
     [Google Scholar]
  33. LiN. HuangY. Org. Lett.202022239392939710.1021/acs.orglett.0c03725 33231467
     [Google Scholar]
  34. WoodwardR.B. HoffmannR. J. Am. Chem. Soc.196587239539710.1021/ja01080a054
     [Google Scholar]
  35. WoodwardR.B. HoffmannR. Angew. Chem. Int. Ed. Engl.196981178185310.1002/anie.196907811
     [Google Scholar]
  36. HoffmannR. WoodwardR.B. Acc. Chem. Res.196811172210.1021/ar50001a003
     [Google Scholar]
  37. BachT. GroschB. StrassnerT. HerdtweckE. J. Org. Chem.20036831107111610.1021/jo026602d 12558441
     [Google Scholar]
  38. ChapmanO.L. EianG.L. J. Am. Chem. Soc.196890195329533010.1021/ja01021a081
     [Google Scholar]
  39. HittD.M. O’ConnorJ.M. Chem. Rev.2011111127904792210.1021/cr2001542 21978178
     [Google Scholar]
  40. MünsterN. ParkerN.A. van DijkL. PatonR.S. SmithM.D. Angew. Chem. Int. Ed.201756329468947210.1002/anie.201705333
     [Google Scholar]
  41. ZhangZ. ChenH. KellerN. XiongQ. LiuL. LanY. BeinT. Li.J. Org Chem. Front20218143788379510.1039/D1QO00356A
     [Google Scholar]
  42. MaL. FengW. ShangH. LinX. XiY. New J. Chem.20214540189241893210.1039/D1NJ03218F
     [Google Scholar]
  43. OddyM.J. KuszaD.A. PetersenW.F. Org. Lett.202123228963896710.1021/acs.orglett.1c03487 34756046
     [Google Scholar]
  44. LvY.F. RenF.C. KuangM.T. MiaoY. LiZ.L. HuJ.M. ZhouJ. Org. Lett.202022176822682610.1021/acs.orglett.0c02335 32830986
     [Google Scholar]
  45. NarayanamaJ.M.R. StephensonJ. Chem. Soc. Rev.201140102
     [Google Scholar]
  46. ChenJ.R. HuX.Q. LuL.Q. XiaoW.J. Acc. Chem. Res.20164991911192310.1021/acs.accounts.6b00254 27551740
     [Google Scholar]
  47. WangE.B. FanQ. LuX. SunB. ZhangF.L. Org. Biomol. Chem.202422244968497210.1039/D4OB00656A 38825973
     [Google Scholar]
  48. CushmanM. MohanP. SmithE.C.R. J. Med. Chem.198427454454710.1021/jm00370a021 6708057
     [Google Scholar]
  49. AbeY. KayakiriH. SatohS. InoueT. SawadaY. InamuraN. AsanoM. AramoriI. HatoriC. SawaiH. OkuT. TanakaH. J. Med. Chem.199841214062407910.1021/jm980300f 9767643
     [Google Scholar]
  50. LiA.H. MoroS. ForsythN. MelmanN. JiX. JacobsonK.A. J. Med. Chem.199942470672110.1021/jm980550w 10052977
     [Google Scholar]
  51. NakanishiT. MasudaA. SuwaM. AkiyamaY. Hoshino-AbeN. SuzukiM. Bioorg. Med. Chem. Lett.200010202321232310.1016/S0960‑894X(00)00467‑4 11055347
     [Google Scholar]
  52. QinX. DingG. LuoZ. WangZ. ZhangS. LiH. GaoF. Dyes Pigments201613461361710.1016/j.dyepig.2016.07.041
     [Google Scholar]
  53. NaritaA. WangX.Y. FengX. MüllenK. Chem. Soc. Rev.201544186616664310.1039/C5CS00183H 26186682
     [Google Scholar]
  54. LiuW. ZhengC.J. WangK. ChenZ. ChenD.Y. LiF. OuX.M. DongY.P. ZhangX.H. ACS Appl. Mater. Interfaces2015734189301893610.1021/acsami.5b05648 26289611
     [Google Scholar]
  55. SasabeH. KidoJ. Chem. Mater.201123362163010.1021/cm1024052
     [Google Scholar]
  56. GaoY. JingY. LiL. ZhangJ. ChenX. MaY.N. J. Org. Chem.20208519121871219810.1021/acs.joc.0c01390 32872780
     [Google Scholar]
  57. XiaoT. LiL. LinG. WangQ. ZhangP. MaoZ. ZhouL. Green Chem.20141652418242110.1039/C3GC42517G
     [Google Scholar]
  58. LiX. LiangD. HuangW. SunH. WangL. RenM. WangB. MaY. Tetrahedron201773507094709910.1016/j.tet.2017.10.074
     [Google Scholar]
  59. XiJ. DongQ.L. LiuG.S. WangS. ChenL. YaoZ-J. Synlett2010111674
     [Google Scholar]
  60. ZhangQ.L. YuQ. MaL. LuX. FanQ.T. DuanT.S. ZhouY. ZhangF.L. J. Org. Chem.20218623172441724810.1021/acs.joc.1c02312 34807586
     [Google Scholar]
  61. ZhangQ.L. SunB. JiG. ZhangG. ZhangF.L. Org. Lett.202426111011510.1021/acs.orglett.3c03720 38157221
     [Google Scholar]
  62. ZhangQ-L. FanQ-T. ZhouY. ZhangJ. Org Chem. Front202411288410.1039/D4QO00140K
     [Google Scholar]
  63. IwaiT. AbeS. TakizawaS. MasaiH. TeraoJ. Chem. Sci.202415238873887910.1039/D4SC01046A
     [Google Scholar]
  64. KimY. IwaiT. FujiiS. UenoK. SawamuraM. Chemistry20212772289229310.1002/chem.202004053 33159337
     [Google Scholar]
  65. KaesC. Chem. Rev.2000100355310.1021/cr990376z 11749322
     [Google Scholar]
  66. KorpiH. SippolaV. FilpponenI. SipiläJ. KrauseO. LeskeläM. RepoT. Appl. Catal. A Gen.2006302225025610.1016/j.apcata.2006.01.020
     [Google Scholar]
  67. WangC. TangR. WanC. QinZ. ChenS. XuK. J. Mol. Struct.2023129113606610.1016/j.molstruc.2023.136066
     [Google Scholar]
/content/journals/loc/10.2174/0115701786398032250728103318
Loading
Visible Light-induced Autocatalytic Aza-6π Electrocyclization to Access Polysubstituted Phenanthridines
Lett. Org. Chem. 23, 51 (2026); 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
Keyword(s): autocatalytic; electrocyclization; late-stage functionalization; metal-free; oxidant-free; phenanthridines; Visible light

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