Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Ugi–Smiles and Ullmann reactions catalyzed by Schiff base derived from Tröger’s base and BINOL

  • 15 Accesses

Abstract

A Schiff base catalyst (1a) combining a Tröger’s base-NH2 and the (R)-BINOL-(CHO)2 was used to promote the Ugi-Smiles reaction. By using isocyanide, malononitrile, aldehydes and low-reactive unfunctionalized 1H-benzo[d]imidazole-2-thiols as substrates, thioimidazolidinone derivatives (6) were obtained with high yields under mild condition. Subsequently, the catalyst was used as the efficient ligand to promote the CuI-catalyzed Ullmann reaction of the products of Ugi-Smiles reaction to give imidazole-containing five-membered fused ring compounds (7). The results indicated that it is an efficient way to develop catalysts to combine TB and BINOL framework. Finally, the antitumor activities of products on human three positive breast cancer cells (MCF-7), human three negative breast cancer cells (MDA-MB-231), human alveolar epithelial cell (A549) and of cytotoxicity on human bronchial epithelial cell (HBE) of all products in vitro were evaluated. Some products showed great inhibition effect on cancer cells (IC50 on MCF-7 and MDA-MB-231 reached nanogram levels) and low toxicity to normal cells, which display their potential in the new drug development.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Scheme 2
Scheme 3
Fig. 4

References

  1. 1.

    E. Schnabel, H. Herzog, E. Hoffmann, I. Ugi, Angew. Chem. Int. Ed. 7, 380 (1968)

  2. 2.

    M.C. Pirrung, K.D. Sarma, J. Am. Chem. Soc. 126, 444 (2004)

  3. 3.

    Q. Lin, J.C. O’Neill, H.E. Blackwell, Org. Lett. 7, 4455 (2005)

  4. 4.

    J.P. Zhu, M. Choussy, F. Bonnaterre, Org. Lett. 8, 4351 (2006)

  5. 5.

    M. Sanudo, S. Marcaccini, S. Basurto, T. Torroba, J. Org. Chem. 71, 9544 (2006)

  6. 6.

    Z. Yang, Z. Xiang, T. Luo, K. Lu, Z. Xu, J. Chen, J. Comb. Chem. 8, 696 (2006)

  7. 7.

    J. Azuaje, A. El Maatougui, X. Garcia-Mera, E. Sotelo, ACS Comb. Sci. 16, 403 (2014)

  8. 8.

    L.C. Ajay, A.L. Chandgude, A. Dömling, Org. Lett. 19, 1228 (2017)

  9. 9.

    L. El Kaim, L. Grimaud, J. Oble, Angew. Chem. Int. Ed. 44, 7961 (2005)

  10. 10.

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

  11. 11.

    L.E. Kaim, M. Gizolme, L. Grimaud, J. Oble, J. Org. Chem. 72, 4169 (2007)

  12. 12.

    L.E. Kaïm, L. Grimaud, S.R. Purumandla, Tetrahedron Lett. 51, 4962 (2010)

  13. 13.

    A. Znabet, S. Blanken, E. Janssen, F.J. de Kanter, M. Helliwell, N.J. Turner, E. Ruijter, R.V. Orru, Org. Biomol. Chem. 10, 941 (2012)

  14. 14.

    A. Znabet, E. Ruijter, F.J.J. de Kanter, V. Kohler, M. Helliwell, N.J. Turner, R.V.A. Orru, Angew. Chem. Int. Ed. 49, 5289 (2010)

  15. 15.

    K. Katayama, K. Nakagawa, H. Takeda, A. Matsuda, S. Ichikawa, Org. Lett. 16, 428 (2014)

  16. 16.

    L. Moni, L. Banfi, A. Basso, A. Galatini, M. Spallarossa, R. Riva, J. Org. Chem. 79, 339 (2014)

  17. 17.

    P. Szczesniak, E. Maziarz, S. Stecko, B. Furman, J. Org. Chem. 80, 3621 (2015)

  18. 18.

    E. Kroon, K. Kurpiewska, J. Kalinowska-Tluscik, A. Dömling, Org. Lett. 18, 4762 (2016)

  19. 19.

    R.S. Borisov, A.I. Polyakov, L.A. Medvedeva, L.G. Voskressensky, Org. Lett. 12, 3894 (2010)

  20. 20.

    R.P. Timothy, S.J. Andrew, F.H. Rodger, W.D. Stevan, L.C. Jeffrey, W.N. David, Org. Lett. 9, 5119 (2007)

  21. 21.

    R. Riva, L. Banfi, A. Basso, V. Cerulli, G. Guanti, M. Pani, J. Org. Chem. 75, 5134 (2010)

  22. 22.

    Z. Xiang, T.P. Luo, K. Lu, J.Y. Cui, X.M. Shi, R. Fathi, Z. Yang, Org. Lett. 6, 3155 (2004)

  23. 23.

    T. Pirali, G.C. Tron, J. Zhu, Org. Lett. 8, 4145 (2006)

  24. 24.

    V.G. Nenajdenko, A.V. Gulevich, N.V. Sokolova, A.V. Mironov, E.S. Balenkova, Eur. J. Org. Chem. 8, 1445 (2010)

  25. 25.

    C.E.M. Salvador, B. Pieber, P.M. Neu, A. Torvisco, Z.A.C. Kleber, C.O. Kappe, J. Org. Chem. 80, 4590 (2015)

  26. 26.

    D.V. Vorobyeva, N.V. Sokolova, V.G. Nenajdenko, A.S. Peregudov, S.N. Osipov, Tetrahedron 68, 872 (2012)

  27. 27.

    N. Sharma, Z. Li, U.K. Sharma, E.V. Van der Eycken, Org. Lett. 16, 3884 (2014)

  28. 28.

    K. Lu, Y. Ma, M. Gao, Y. Liu, M. Li, C. Xu, X. Zhao, P. Yu, Org. Lett. 18, 5038 (2016)

  29. 29.

    X. Zhu, X.P. Xu, C. Sun, H.Y. Wang, K. Zhao, S.J. Ji, J. Comb. Chem. 12, 822 (2010)

  30. 30.

    J.Y. Wang, H.W. Ge, Y. Fang, X. Ren, S. Cao, G. Liu, Q.M. Li, B.J. Xu, Y. Wan, X.G. Han, H. Wu, Res. Chem. Intermed. 43, 631 (2017)

  31. 31.

    J. Tröger, F. Volkmer, J. Prakt. Chem. (Leipzig) 71, 236 (1905)

  32. 32.

    S. Satishkumar, M. Periasamy, Tetrahedron Asymmetry 20, 2257 (2009)

  33. 33.

    Z. Kejík, T. Bříza, M. Havlík, B. Dolenský, R. Kaplánek, J. Králová, I. Mikula, P. Martásek, Dyes Pigments 134, 212 (2016)

  34. 34.

    E.B. Veale, D.O. Frimannsson, M. Lawler, T. Gunnlaugsson, Org. Lett. 11, 4040 (2009)

  35. 35.

    A. Paul, B. Maji, S.K. Misra, A.K. Jain, K. Muniyappa, S. Bhattacharya, J. Med. Chem. 55, 7460 (2012)

  36. 36.

    Y.C. Xiao, L.L. Zhang, L. Xu, T.S. Chung, J. Membr. Sci. 521, 65 (2017)

  37. 37.

    F. Ishiwari, N. Takeuchi, T. Sato, H. Yamazaki, R. Osuga, J.N. Kondo, T. Fukushima, ACS Macro. Lett. 6, 775 (2017)

  38. 38.

    Ö.V. Rúnarsson, J. Artacho, K. Wärnmark, Eur. J. Org. Chem. 36, 7015 (2012)

  39. 39.

    R. Yuan, M.Q. Li, J.B. Xu, S.Y. Huang, S.L. Zhou, P. Zhang, J.J. Liu, H. Wu, Tetrahedron 72, 4081 (2016)

  40. 40.

    Y.S. Park, C.I. Grove, M. González-López, S. Urgaokar, J.C. Fettinger, J.T. Shaw, Angew. Chem. Int. Ed. 50, 3730 (2011)

  41. 41.

    W.Y. Han, Z.J. Wu, X.M. Zhang, W.C. Yuan, Org. Lett. 14, 976 (2012)

  42. 42.

    M.Q. Li, M.S. Dissertation, Jiangsu Normal University (2018)

  43. 43.

    R. Yuan, M.Q. Li, P. Zhang, Y. Wan, H. Wu, CN 108864109A (2018)

  44. 44.

    P.E. Fanta, Synthesis 1, 9 (1974)

  45. 45.

    T.D. Nelson, R.D. Crouch, Org. React. 63, 265 (2004)

Download references

Acknowledgements

We are grateful to the foundation of the “Priority Academic Program Development of Jiangsu Higher Education Institutions,” the “Natural Science Research Projects in Universities of Jiangsu Province” (19KJB430019), the “Science and Technology Foundation of Xuzhou” (KC19242), the “Aid Project for PhD Faculties in Jiangsu Normal University” (17XLR023) and the “Graduate Student Scientific Research Innovation Projects in Jiangsu Province” (KYCX18_2111 and KYCX18_2116) for financial support.

Author information

Correspondence to Yu Wan or Peng Zhang or Hui Wu.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 4198 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yuan, R., Li, M., Ren, X. et al. Ugi–Smiles and Ullmann reactions catalyzed by Schiff base derived from Tröger’s base and BINOL. Res Chem Intermed (2020). https://doi.org/10.1007/s11164-020-04091-1

Download citation

Keywords

  • Schiff base catalyst
  • Tröger’s base
  • Ugi-Smiles reaction
  • Ullmann reaction
  • Antitumor activity