Spontaneous formation of tricyclic lactones following the Castagnoli–Cushman reaction

Castagnoli–Cushman reaction of imines derived from 2-chloropyridine-3-carboxaldehyde with a cyclic anhydride (4-(methylsulfonyl)-morpholine-2,6-dione) conducted at 110°C in DMF over 1 h, as expected, led to a mixture of trans- and cis-configured carboxylic acids. However, the latter underwent a spontaneous intramolecular reaction of the carboxylic functionality onto the labile nearby 2-chloropyridine moiety to give the respective tricyclic lactones in 17–23% yield, along with 41–68% yield of the uncyclized trans-configured products (isolated as methyl esters).

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  1. 1.

    Dömling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168.

  2. 2.

    Sunderhaus, J. D.; Martin, S. F. Chem.–Eur. J. 2009, 15, 1300.

    CAS  Article  Google Scholar 

  3. 3.

    Krasavin, M.; Dar'in, D. Tetrahedron Lett. 2016, 57, 1635.

    CAS  Article  Google Scholar 

  4. 4.

    Beck, D. E.; Reddy, P. V.; Lv, W.; Abdelmalak, M.; Tender, G. S.; Lopez, S.; Agama, K.; Marchand, C.; Pommier, Y.; Cushman, M. J. Med. Chem. 2016, 59, 3840.

    CAS  Article  Google Scholar 

  5. 5.

    Ryabukhin, S. V.; Panov, D. M.; Granat, D. S.; Ostapchuk, E. N.; Kryvoruchko, D. V.; Grygorenko, O. O. ACS Comb. Sci. 2014, 16, 146.

    CAS  Article  Google Scholar 

  6. 6.

    Sarnpitak, P.; Krasavin, M. Tetrahedron Lett. 2014, 55, 2299.

    CAS  Article  Google Scholar 

  7. 7.

    Dar'in, D.; Bakulina, O.; Chizhova, M.; Krasavin, M. Org. Lett. 2015, 17, 3930.

    Article  Google Scholar 

  8. 8.

    González-López, M.; Shaw, J. T. Chem. Rev. 2009, 109, 164.

    Article  Google Scholar 

  9. 9.

    Dar'in, D.; Bakulina, O.; Nikolskaya, S.; Gluzdikov, I.; Krasavin, M. RSC Adv. 2016, 6, 49411.

    Article  Google Scholar 

  10. 10.

    Mancilla, T.; Canillo, L.; Zamudio-Rivera, L. S.; Beltrán, H. I.; Farán, N. Org. Prep. Proced. Int. 2002, 34, 87.

    CAS  Article  Google Scholar 

  11. 11.

    Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. J. Appl. Crystallogr. 2009, 42, 339.

    CAS  Article  Google Scholar 

  12. 12.

    Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, A64, 112.

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This research was supported by the Russian Science Foundation (project grant 14-50-00069).

NMR, mass spectrometry and X-ray diffraction studies were performed at the Research Center for Magnetic Resonance, the Center for Chemical Analysis and Materials Research and the Center for X-ray Diffraction Methods of Research park of Saint Petersburg State University.

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Correspondence to Mikhail Krasavin.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2017, 53(4), 474–479

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Usmanova, L., Bakulina, O., Dar’in, D. et al. Spontaneous formation of tricyclic lactones following the Castagnoli–Cushman reaction. Chem Heterocycl Comp 53, 474–479 (2017). https://doi.org/10.1007/s10593-017-2076-y

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  • tricyclic lactones-lactams
  • Castagnoli–Cushman reaction
  • intramolecular S NAr reaction
  • post-MCR modification