Bergman cyclization reactions in fused enediynes: a DFT study

  • Avat Arman TaherpourEmail author
  • Parvin Ghasemi
Original Paper


(Z)-enediynes equipped with aliphatic n-membered ring undergo a thermal rearrangement known as the Bergman cyclization. The rearrangement of these molecules leads to formation of transition states and biradical intermediates. H-abstraction by the biradical intermediates occurred through external H-atom donor. The central point of this study was on the theoretical and computational studies of the pathways of the products and reactivity of reactants. The energy levels of the reactants, transition state forms, products, the free energies of reaction (rG and ∆G), the ∆EHOMO-LUMO, rate constant by using Eyring’ equation (k) and structural data were calculated by DFT-B3LYP/6-31G* method. The different aspects of the structural data and the relative energies (in kcal mol−1) of the transition states as well as the biradical intermediates (singlet (S) and triplet (T) in the cyclization reactions were investigated and discussed.

Graphical abstract


Bergman cyclization Enediynes para-Benzyne Reaction kinetic Ring size effect DFT 



The authors gratefully acknowledge the Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran, and the Research and Computational Lab of Theoretical Chemistry and Nano Structures of Razi University Kermanshah, Iran, for supporting this study.

Supplementary material

13738_2019_1666_MOESM1_ESM.doc (438 kb)
Supplementary material 1 (DOC 438 kb)


  1. 1.
    H. Maeda, D. Borders, T. Doyle, Enediyne Antibiotics as Antitumor Agents (In Marcel Dekker, New York, 1995)Google Scholar
  2. 2.
    A.L. Smith, K. Nicolaou, J. Med. Chem. 39, 2103–2117 (1996)CrossRefGoogle Scholar
  3. 3.
    R.G. Bergman, Acc. Chem. Res. 6, 25–31 (1973)CrossRefGoogle Scholar
  4. 4.
    R.R. Jones, R.G. Bergman, J. Am. Chem. Soc. 94, 660–661 (1972)CrossRefGoogle Scholar
  5. 5.
    L. Madden, L. Moskaleva, S. Kristyan, M. Lin, J. Phys. Chem. A 101, 6790–6797 (1997)CrossRefGoogle Scholar
  6. 6.
    L. Moskaleva, L. Madden, M. Lin, Phys. Chem. Chem. Phys. 1, 3967–3972 (1999)CrossRefGoogle Scholar
  7. 7.
    W. Bachmann, H. Clarke, J. Am. Chem. Soc. 49, 2089–2098 (1927)CrossRefGoogle Scholar
  8. 8.
    H.E. Bertorello, R.A. Rossi, R. Hoyos de Rossi, J. Org. Chem. 35, 3332–3338 (1970)CrossRefGoogle Scholar
  9. 9.
    W.H. Okamura, F. Sondheimer, J. Am. Chem. Soc. 89, 5991–5992 (1967)CrossRefGoogle Scholar
  10. 10.
    N. Darby, C. Kim, J. Salaün, K. Shelton, S. Takada, S.J. Masamune, Chem. Soc. D Chem. Commun. 23, 1516–1517 (1971)CrossRefGoogle Scholar
  11. 11.
    S. Masamune, N. Darby, Acc. Chem. Res. 5, 272–281 (1972)CrossRefGoogle Scholar
  12. 12.
    T.P. Lockhart, P.B. Comita, R.G. Bergman, J. Am. Chem. Soc. 103, 4082–4090 (1981)CrossRefGoogle Scholar
  13. 13.
    M. Prall, A. Wittkopp, P.R. Schreiner, Phys. Chem. A 105, 9265–9274 (2001)CrossRefGoogle Scholar
  14. 14.
    C.L. Perrin, B.L. Rodgers, J.M. O’Connor, J. Am. Chem. Soc. 129, 4795–4799 (2007)CrossRefGoogle Scholar
  15. 15.
    D.-C. Oh, P.G. Williams, C.A. Kauffman, P.R. Jensen, W. Fenical, Org. Lett. 8, 1021–1024 (2006)CrossRefGoogle Scholar
  16. 16.
    P.R. Schreiner, A. Navarro-Vázquez, M. Prall, Acc. Chem. Res. 38, 29–37 (2005)CrossRefGoogle Scholar
  17. 17.
    I. Yavari, A.A. Taherpour, M. Dadgar, J. Mol. Struct. THEOCHEM 422, 213–218 (1998)CrossRefGoogle Scholar
  18. 18.
    K. Nicolaou, Y. Ogawa, G. Zuccarello, E. Schweiger, T. Kumazawa, J. Am. Chem. Soc. 110, 4866–4868 (1988)CrossRefGoogle Scholar
  19. 19.
    D.M. Bowles, G.J. Palmer, C.A. Landis, J.L. Scott, J.E. Anthony, Tetrahedron 57, 3753–3762 (2001)CrossRefGoogle Scholar
  20. 20.
    P.R. Schreiner, J. Am. Chem. Soc. 120(17), 4184–4190 (1998)CrossRefGoogle Scholar
  21. 21.
    A.E. Clark, E.R. Davidson, J.M. Zaleski, J. Am. Chem. Soc. 123(11), 2650–2657 (2001)CrossRefGoogle Scholar
  22. 22.
    D. J. Estep, Investigating the cyclization of enediyne analogs using density functional theory, Texas Scholar Works, The University of Texas at Austin, University of Texas Libraries, 2012, USA. (
  23. 23.
    P.W. Atkins (ed.), Physical Chemistry (Oxford University Press, Oxford, 1998)Google Scholar
  24. 24.
    A.I. Krylov, Acc. Chem. Res. 39(2), 83–91 (2006)CrossRefGoogle Scholar
  25. 25.
    N. Orms, A.I. Krylov, Phys. Chem. Chem. Phys. 20, 13127–13144 (2018)CrossRefGoogle Scholar

Copyright information

© Iranian Chemical Society 2019

Authors and Affiliations

  1. 1.Department of Organic Chemistry, Faculty of ChemistryRazi UniversityKermanshahIran
  2. 2.Medical Biology Research CenterKermanshah University of Medical SciencesKermanshahIran

Personalised recommendations