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Highly regio- and diastereoselective synthesis of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles, based on a post-Ugi condensation: joint experimental and computational study

Journal of the Iranian Chemical Society volume 16, pages 1517–1526 (2019)Cite this article

Abstract

A novel series of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles were synthesized via a two-step pathway. In the first step, Ugi-four-component condensation of 2-formylindole, amines, (E)-4-alkoxy-4-oxobut-2-enoic acids, and isocyanides gave the corresponding Ugi-adducts. This adduct underwent intramolecular hydroamination in the presence of K2CO3 in CH3CN at room temperature to afford diastereoselective synthesis of a range of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles. A comparison of experimentally observed CD and UV–visible spectra with the theoretical DFT calculated ECD spectra was used to predict the major diastereomer.

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References

  1. B.M. Trost, Science 254, 1471 (1991)

    Article  CAS  PubMed  Google Scholar 

  2. L.F. Tietze, Chem. Rev. 96, 115 (1996)

    Article  CAS  PubMed  Google Scholar 

  3. P.A. Wender, S.T. Handy, D.L. Wright, Chem. Ind. 765, 767 (1997)

    Google Scholar 

  4. S.L. Schreiber, Science 287, 1964 (2000)

    Article  CAS  PubMed  Google Scholar 

  5. A. Dömling, I. Ugi, Angew. Chem. Int. Ed. 39, 3168 (2000)

    Article  Google Scholar 

  6. A. Domling, Chem. Rev. 106, 17 (2006)

    Article  CAS  PubMed  Google Scholar 

  7. J.D. Sunderhaus, S.F. Martin, Chem. Eur. J. 15, 1300 (2009)

    Article  CAS  PubMed  Google Scholar 

  8. B.B. Touré, D.G. Hall, Chem. Rev. 109, 4439 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. B. Ganem, Acc. Chem. Res. 42, 463 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. A. Váradi, T.C. Palmer, R.N. Dardashti, S. Majumdar, Molecules 21, 19 (2016)

    Article  CAS  Google Scholar 

  11. N.A. Afagh, A.K. Yudin, Angew. Chem. Int. Ed. 49, 262 (2010)

    Article  CAS  Google Scholar 

  12. U.K. Sharma, N. Sharma, D.D. Vachhania, E.V. Van der Eycken, Chem. Soc. Rev. 44, 1836 (2015)

    Article  CAS  PubMed  Google Scholar 

  13. I. Ugi, R. Meyr, U. Fetzer, C. Steinbrückner, Angew. Chem. 71, 386 (1959)

    Google Scholar 

  14. I. Ugi, C. Steinbrückner, Angew. Chem. 72, 2671960 (1959)

    Google Scholar 

  15. J. Isaacson, Y. Kobayashi, Angew. Chem. Int. Ed. 48, 1845 (2009)

    Article  CAS  Google Scholar 

  16. A. Dömling, B. Beck, U. Eichelberger, S. Sakamuri, S. Menon, Q.-Z. Chen, Y. Lu, L.A. Wessjohann, Angew. Chem. Int. Ed. 45, 7235 (2006)

    Article  Google Scholar 

  17. M.J. Thompson, B. Chen, J. Org. Chem. 74, 7084 (2009)

    Article  CAS  PubMed  Google Scholar 

  18. W. Erb, J.-P. Neuville, L. Zhu, J. Org. Chem. 74, 3109 (2009)

    Article  CAS  PubMed  Google Scholar 

  19. D.G. Riveraa, L.A. Wessjohann, J. Am. Chem. Soc. 131, 3721 (2009)

    Article  CAS  Google Scholar 

  20. D. Coffinier, L. El Kaim, L. Grimaud, Org. Lett. 11, 995 (2009)

    Article  CAS  PubMed  Google Scholar 

  21. L.A. Wessjohann, D.G. Rivera, O.E. Vercillo, Chem. Rev. 109, 796 (2009)

    Article  CAS  PubMed  Google Scholar 

  22. G. Cuny, M. Bois-Choussy, J. Zhu, J. Am. Chem. Soc. 126, 14475 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. U.K. Sharma, N. Sharma, D.D. Vachhani, E.V. Van der Eycken, Chem. Soc. Rev. 44, 1836 (2015)

    Article  CAS  PubMed  Google Scholar 

  24. A. Aygun, U. Pindur, Curr. Med. Chem. 10, 1113 (2003)

    Article  CAS  PubMed  Google Scholar 

  25. F.R. deSa´Alves, E.J. Barreiro, C.A. Fraga, Med. Chem. 9, 782 (2009)

    Google Scholar 

  26. M. Ishikura, K. Yamada, T. Abe, Nat. Prod. Rep. 27, 1630 (2010)

    Article  CAS  PubMed  Google Scholar 

  27. R.J. Sundberg, The Chemistry of Indoles (Academic Press, New York, 1970)

    Google Scholar 

  28. R.J. Sundberg, in Comprehensive Heterocyclic Chemistry, ed. by A.R. Katritzky, C.W. Rees (Pergamon Press, Oxford, 1984), Vol. 4

    Google Scholar 

  29. J.A. Joule, E.J. Thomas, ed., Science of Synthesis, Houben-Weyl Methods of Molecular Transformations, vol. 10 (George Thieme Verlag, Stuttgart, 2000), Chap. 10

    Google Scholar 

  30. G.W. Gribble, in Comprehensive Heterocyclic Chemistry II, vol. 2, ed. by A.R. Katritzky, C.W. Ress, E.F.V. Scriven, C.W. Bird (Pergamon Press, Oxford, 1996), p. 207

    Chapter  Google Scholar 

  31. R.J. Sundberg, Indoles, (Academic Press, London, 1996)

    Google Scholar 

  32. D. Zhou, P. Zhou, D.A. Evrard, K. Meagher, M. Webb, B.L. Harrison, D.M. Huryn, J. Golembieski, G.A. Hornby, L.E. Schechter, D.L. Smith, T.H. Andree, R.E. Mewshaw, Bioorg. Med. Chem. 16, 6707 (2008)

    Article  CAS  PubMed  Google Scholar 

  33. J.D. Williams, S.T. Nguyen, S. Gu, X. Ding, M.M. Butler, T.F. Tashjian, T.J. Opperman, T.L. Bowlin, R.G. Panchal, S. Bavari, N.P. Peet, D.T. Moir, Bioorg. Med. Chem. Lett. 21, 7790 (2013)

    Article  CAS  Google Scholar 

  34. M.Z. Zhang, Q. Chen, G.F. Yang, Eur. J. Med. Chem. 89, 421 (2015)

    Article  CAS  PubMed  Google Scholar 

  35. M. Shiri, Chem. Rev. 112, 3508 (2012)

    Article  CAS  PubMed  Google Scholar 

  36. M.M. Heravi, T. Alishiri, Adv. Heterocycl. Chem. 113, 1 (2014)

    Article  CAS  Google Scholar 

  37. M.M. Heravi, B. Talaei, Adv. Heterocycl. Chem. 113, 143 (2014)

    Article  CAS  Google Scholar 

  38. M.M. Heravi, S. Khaghaninejad, M. Mostofi, Adv. Heterocycl. Chem. 112, 1 (2014)

    Article  CAS  Google Scholar 

  39. M.M. Heravi, S. Khaghaninejad, N. Nazari, Adv. Heterocycl. Chem. 112, 183 (2014)

    Article  CAS  Google Scholar 

  40. M.M. Heravi, B. Talaei, Adv. Heterocycl. Chem. 114, 147 (2015)

    Article  CAS  Google Scholar 

  41. M.M. Heravi, V.F. Vavsari, Adv. Heterocycl. Chem. 114, 77 (2015)

    Article  CAS  Google Scholar 

  42. M.M. Heravi, V. Zadsirjan, Adv. Heterocycl. Chem. 117, 261 (2015)

    Article  CAS  Google Scholar 

  43. M.M. Heravi, B. Talaei, Adv. Heterocycl. Chem. 118, 195 (2016)

    Article  CAS  Google Scholar 

  44. M. Shiri, M. Ranjbar, Z. Yasaei, F. Zamanian, B. Notash, Org. Biomol. Chem. 15, 10073 (2017)

    Article  CAS  PubMed  Google Scholar 

  45. M. Shiri, Z. Faghihi, H.A. Oskouei, M.M. Heravi, B. Notash, Sh. Fazelzadeh, RSC Adv. 6, 92235 (2016)

    Article  CAS  Google Scholar 

  46. S. Sadjadi, M.M. Heravi, N. Nazari, RSC Adv. 6, 53203 (2016)

    Article  CAS  Google Scholar 

  47. F. Nemati, M.M. Heravi, A. Elhampour, RSC Adv. 5, 45775 (2015)

    Article  CAS  Google Scholar 

  48. M.M. Heravi, E. Hashemi, Y.S. Beheshtiha, K. Kamjou, M. Toolabi, N. Hosseintash, J. Mol. Catal. A Chem. 392, 173 (2014)

    Article  CAS  Google Scholar 

  49. M.M. Heravi, F. Mousavizadeh, N. Ghobadi, M. Tajbakhsh, Tetrahedron Lett. 55, 1226 (2014)

    Article  CAS  Google Scholar 

  50. M.M. Heravi, S. Moghimi, Tetrahedron Lett. 53, 392 (2012)

    Article  CAS  Google Scholar 

  51. M.M. Heravi, S. Sadjadi, N. Mokhtari Haj, H.A. Oskooie, F.F. Bamoharram, Catal. Commun. 10, 1643 (2009)

    Article  CAS  Google Scholar 

  52. M.M. Heravi, M. Daraie, Molecules 21, 441 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. A. Rezvanian, M.M. Heravi, Z. Shaabani, M. Tajbakhsh, Tetrahedron 73, 2017 (2009)

    Google Scholar 

  54. M. Shiri, Z. Bozorgpour-Savadjani, J. Iran. Chem. Soc. 12, 389 (2015)

    Article  CAS  Google Scholar 

  55. M. Shiri, S.Z. Mirpour-Marzoni, Z. Bozorgpour-Savadjani, B. Soleymanifard, H.G. Kruger, Monatsh. Chem. 145, 1947 (2014)

    Article  CAS  Google Scholar 

  56. S.M. hiri, B. Farajpour, Z. Bozorgpour-Savadjani, S.A. Shintre, N.A. Koorbanally, H.G. Kruger, B. Notash, Tetrahedron 71, 5531 (2015)

    Article  CAS  Google Scholar 

  57. B. Soleymanifard, M.M. Heravi, M. Shiri, M.A. Zolfigol, M. Rafiee, H.G. Kruger, T. Naicker, F. Rasekhmanesh, Tetrahedron Lett. 53, 3546 (2012)

    Article  CAS  Google Scholar 

  58. V. Zadsirjan, M. Shiri, M.M. Heravi, T. Hosseinnejad, S.A. Shintre, N.A. Koorbanally, Res. Chem. Intermed. 43, 2119 (2017)

    Article  CAS  Google Scholar 

  59. K. Maruoka, M. Akakura, S. Saito, T. Ooi, H. Yamamoto, J. Am. Chem. Soc. 116, 6153 (1994)

    Article  CAS  Google Scholar 

  60. H.J. Zhu, Organic Stereochemistry: Experimental and Computational Methods (2015), p. 163

  61. P.J. Stephens, N. Harada, Chirality 22, 229 (2010)

    CAS  PubMed  Google Scholar 

  62. S.S. Makhathini, S.K. Das, T. Singh, P.I. Arvidsson, H.G. Kruger, H. Gunosewoyo, T. Govender, T. Naicker, Arkivoc 3, 134 (2016)

    Google Scholar 

  63. G. Scalmani, M.J. Frisch, B. Mennucci, J. Tomasi, R. Cammi, V. Barone, J. Chem. Phys. 124, 94107 (2006)

    Article  CAS  PubMed  Google Scholar 

  64. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery, R.E. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B.G. Johnson, W. Chen, M.W. Wong, J.L. Andres, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian 98 (Revision A.1). (Gaussian, Inc., Pittsburgh PA, 1998)

    Google Scholar 

  65. R.G. Parr, W. Yang, Density-Functional Theory of Atoms and Molecules (Oxford University Press, Oxford, 1989)

    Google Scholar 

  66. R.M. Dickson, A.D. Becke, J. Phys. Chem. 100, 16105 (1196)

  67. K. Wolinski, J.F. Hilton, P.J. Pulay, J. Am. Chem. Soc. 112, 825 (1990)

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank the Alzahra University and Iran National Science Foundation (INSF) for financial support. We are also very grateful for Prof. Adolf Gogoll and Dr. Sandra Olsson from Uppsala University (Uppsala, Sweden) for doing experimental ECD and UV–visible spectroscopy.

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Authors and Affiliations

  1. Department of Chemistry, Alzahra University, Vanak, Tehran, 1993893973, Iran

    Morteza Shiri, Majid M. Heravi, Vahideh Zadsirjan & Mina Ghiasi

  2. School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa

    Suhas A. Shintre, Neil A. Koorbanally & Thishana Singh

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  1. Morteza Shiri
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Correspondence to Morteza Shiri or Majid M. Heravi.

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Shiri, M., Heravi, M.M., Zadsirjan, V. et al. Highly regio- and diastereoselective synthesis of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles, based on a post-Ugi condensation: joint experimental and computational study. J IRAN CHEM SOC 16, 1517–1526 (2019). https://doi.org/10.1007/s13738-019-01632-3

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Keywords

  • Ugi reaction
  • 2-Formylindole
  • Multicomponent reaction
  • α,β-Unsaturated acids
  • Cyclization
  • Intramolecular hydroamination
  • DFT
  • ECD spectra