Chemistry of Heterocyclic Compounds

, Volume 54, Issue 3, pp 292–301 | Cite as

Metal-catalyzed privileged 2- and 3-functionalized indole synthesis*

  • Arun K. SinhaEmail author
  • Danish Equbal
  • Mane Rajendra Uttam

This review summarizes the metal-catalyzed approaches for the synthesis of privileged 2- and 3-functionalized indoles via the Fischer indole synthesis, cycloaddition reaction, C–H activation reaction, and coupling reactions. Polycyclic derivatives of indole are also listed including triptamine-based pharmaceutical 5-HT1D agonist L 775,606. Some important mechanism studies are described in details in this review. The review covers literature for the last 20 years.


bioactive indole scaffolds functionalized indole heterocycles indole C–H activation metal catalysis 


  1. 1.
    Sundberg, R. J. The Chemistry of Indoles; Bloquist, A. T., Eds.; Academic Press: New York, 1970, p 1.Google Scholar
  2. 2.
    (a) Patil, S. A; Patil, R.; Miller, D. D. Future Med. Chem. 2012, 4, 2085. (b) Zhang, M.-Z; Mulholland, N; Beattie, D; Irwin, D; Gu, Y.-C; Chen, Q; Yang, G.-F; Clough, J. Eur. J. Med. Chem. 2013, 63, 22. (c). Funk, C. D. Nat. Rev. Drug Discovery 2005, 4, 664. (d) Giansanti, V; Piscitelli, F; Camboni, T; Prosperi, E; Regina, G. L; Parks, M; Silvestri, R; Scovassi, A. I. Oncol. Lett. 2010, 1, 109. (e) Sharma, V.; Kumar, P.; Pathak, D. J. Heterocycl. Chem. 2010, 47, 491. (f) Kaushik, N. K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.; Verma, A. K.; Choi, E. H. Molecules 2013, 18, 6620. (g) Singh, T. P.; Singh, O. M. Mini-Rev. Med. Chem. 2018, 18, 9.Google Scholar
  3. 3.
    (a) Bronner, S. M.; Im, G.-Y. J.; Garg, N. K. Heterocycles in Natural Product Synthesis; Majumdar, K. C., Chattopadhyay, S. K., Eds.; Wiley-VCH Verlag GmbH & Co, 2011, p. 221. (b) Sravanthi, T. V.; Manju, S. L. Eur. J. Pharm. Sci. 2016, 91, 1.Google Scholar
  4. 4.
    (a) Owczarczyk, Z. R.; Braunecker, W. A.; Garcia, A.; Larsen, R.; Nardes, A. M.; Kopidakis, N.; Ginley, D. S.; Olson, D. C. Macromolecules 2013, 46, 1350. (b) Nie, G.; Bai, Z.; Yu, W.; Zhang, L. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2385. (c) Manickam, M.; Iqbal, P.; Belloni, M.; Kumar, S.; Preece, J. A. Isr. J. Chem. 2012, 52, 917.Google Scholar
  5. 5.
    Joule, J. A. Indole and its Derivatives in Science of Synthesis. Houben–Weyl Methods of Molecular Transformations; Thomas, E. J., Ed.; Thieme: Stuttgart, 2000, Vol. 10, p. 361.Google Scholar
  6. 6.
    Li, H.; Zhu, Z.; Zhang, F.; Xie, S.; Li, H.; Li, P.; Zhou, X. ACS Catal. 2011, 1, 1604.CrossRefGoogle Scholar
  7. 7.
    Wang, Y.; Ye, L.; Zhang, L. Chem. Commun. 2011, 47, 7815.CrossRefGoogle Scholar
  8. 8.
    Wang, Y.; Liu, L.; Zhang, L. Chem. Sci. 2013, 4, 739.CrossRefGoogle Scholar
  9. 9.
    Wei, Y.; Deb, I.; Yoshikai, N. J. Am. Chem. Soc. 2012, 134, 9098.CrossRefPubMedGoogle Scholar
  10. 10.
    Hiroya, K.; Itoh, S.; Sakamoto, T. J. Org. Chem. 2004, 69, 1126.CrossRefPubMedGoogle Scholar
  11. 11.
    Cho, C. S.; Kim, J. H.; Shim, S. C. Tetrahedron Lett. 2000, 41, 1811.CrossRefGoogle Scholar
  12. 12.
    Ackermann, L. Org. Lett. 2005, 7, 439.CrossRefPubMedGoogle Scholar
  13. 13.
    Ohno, H.; Ohta, Y.; Oishi, S.; Fujii, N. Angew. Chem., Int. Ed. 2007, 46, 2295.CrossRefGoogle Scholar
  14. 14.
    Jiang, X.; Tang, W.; Xue, D.; Xiao, J.; Wang, C. ACS Catal. 2017, 7, 1831.CrossRefGoogle Scholar
  15. 15.
    Gati, W.; Couty, F.; Boubaker, T.; Rammah, M. M.; Rammah, M. B.; Evano, G. Org. Lett. 2013, 15, 3122.CrossRefPubMedGoogle Scholar
  16. 16.
    Fukuyama, T.; Chen, X.; Peng, G. J. Am. Chem. Soc. 1994, 116, 3127.CrossRefGoogle Scholar
  17. 17.
    Aoki, K.; Peat, A. J.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 3068.CrossRefGoogle Scholar
  18. 18.
    Schmidt, A. M.; Eilbracht, P. J. Org. Chem. 2005, 70, 5528.CrossRefPubMedGoogle Scholar
  19. 19.
    Kolhling, P.; Schmidt, A. M.; Eilbracht, P. Org. Lett. 2003, 5, 3213.CrossRefGoogle Scholar
  20. 20.
    Porcheddu, A.; Mura, M. G.; Luca, L. D.; Pizzetti, M.; Taddei, M. Org. Lett. 2012, 14, 6112.CrossRefPubMedGoogle Scholar
  21. 21.
    Lavekar, A. G.; Equbal, D.; Saima; Sinha, A. K. Adv. Synth. Catal. 2018, 360, 180.Google Scholar
  22. 22.
    Stuart, D. R.; Laperle, Megan, B.; Burgess, K. M. N.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 16474.Google Scholar
  23. 23.
    Wagaw, S.; Yang, B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 10251.CrossRefGoogle Scholar
  24. 24.
    Zhou, L.; Doyle, M. P. J. Org. Chem. 2009, 74, 9222.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Huang, F.; Wu, P.; Wang, L.; Chen, J.; Sun, C.; Yu, Z. J. Org. Chem. 2014, 79, 10553.CrossRefPubMedGoogle Scholar
  26. 26.
    Novikov, M. S.; Khlebnikov, A. F.; Rostovskii, N. V.; Tcyrulnikov, S.; Suhanova, A. A.; Zavyalov, K. V.; Yufit, D. S. J. Org. Chem. 2015, 80, 18.CrossRefPubMedGoogle Scholar
  27. 27.
    Nakazaki, M.; Yamamoto, K. J. Org. Chem. 1976, 41, 1877.CrossRefGoogle Scholar
  28. 28.
    Kawade, R. K.; Huang, P.-H.; Karad, S. N.; Liu, R.-S. Org. Biomol. Chem. 2014, 12, 737.CrossRefPubMedGoogle Scholar
  29. 29.
    Zhang, Z.-Z.; Liu, B.; Xu, J.-W.; Yan, S.-Y.; Shi, B.-F. Org. Lett. 2016, 18, 1776.CrossRefPubMedGoogle Scholar
  30. 30.
    Nakamura, I.; Nemoto, T.; Shiraiwa, N.; Terada, M. Org. Lett. 2009, 11, 1055.CrossRefPubMedGoogle Scholar
  31. 31.
    McAusland, D.; Seo, S.; Pintori, D. G.; Finlayson, J.; Greaney, M. F. Org. Lett. 2011, 13, 3667.CrossRefPubMedGoogle Scholar
  32. 32.
    Shen, Z.; Lu, X. Tetrahedron 2006, 62, 10896.CrossRefGoogle Scholar
  33. 33.
    Liu, B.; Song, C.; Sun, C.; Zhou, S.; Zhu, J. J. Am. Chem. Soc. 2013, 135, 16625.CrossRefPubMedGoogle Scholar
  34. 34.
    Takeda, A.; Kamijo, S.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 5662.CrossRefGoogle Scholar
  35. 35.
    Larock, R. C.; Yum, E. K.; Refvik, M. D. J. Org. Chem. 1998, 63, 7652.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Arun K. Sinha
    • 1
    • 2
    Email author
  • Danish Equbal
    • 1
  • Mane Rajendra Uttam
    • 1
    • 3
  1. 1.Medicinal and Process Chemistry DivisionCSIR-Central Drug Research InstituteLucknowIndia
  2. 2.Academy of Scientific and Innovative ResearchNew DelhiIndia
  3. 3.Department of Medicinal ChemistryNational Institute of Pharmaceutical Education and ResearchRaebareliIndia

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