Monatshefte für Chemie - Chemical Monthly

, Volume 149, Issue 6, pp 1069–1074 | Cite as

Electrochemical cascade assembling of heterocyclic ketones and two molecules of malononitrile: facile and efficient ‘one-pot’ approach to 6-heterospiro[2.5]octane-1,1,2,2-tetracarbonitrile scaffold

  • Michail N. Elinson
  • Anatoly N. Vereshchagin
  • Alexander D. Korshunov
  • Tatiana A. Zaimovskaya
  • Mikhail P. Egorov
Original Paper


The electrochemically induced reaction of heterocyclic ketones and two equivalents of malononitrile in an undivided cell in alcohols in the presence of sodium bromide as mediator leading to the selective formation of substituted 6-heterospirocyclopropane-1,1,2,2-tetracarbonitriles in 50–75% yields as a result of the complex cascade process has been investigated. This new electrocatalytic cascade process smoothly proceeds with different types of heterocyclic ketones and resulted in ‘one-pot’ formation of 6-heterospirocyclopropane-1,1,2,2-tetracarbonitriles with prominent pharmacological and physiological activity. The application of this electrochemical cascade method to the formation of medicinally relevant substituted 6-heterospiro[2.5]octane-1,1,2,2-tetracarbonitriles is also beneficial from the viewpoint of diversity-oriented large-scale processes.

Graphical abstract


Electrochemical process Cascade reaction Heterocyclic ketones Malononitrile 6-Heterospiro[2.5]octane-1,1,2,2-tetracarbonitrile 6-Heterospirocyclopropane-1,1,2,2-tetracarbonitrile 



The authors gratefully acknowledge the financial support of the Presidential Scholarship Program for State Support of Leading Science Schools of Russian Federation (Project no. 8012.2016.3).


  1. 1.
    Patchett AA, Nargund RP (2000) Ann Rep Med Chem 35:289CrossRefGoogle Scholar
  2. 2.
    DeSimone RW, Currie KS, Mitchell SA, Darrow JW, Pippin DA (2004) Comb Chem High Throughput Screen 7:473CrossRefGoogle Scholar
  3. 3.
    Poupaert J, Carato P, Colacino E (2005) Curr Med Chem 12:877CrossRefGoogle Scholar
  4. 4.
    Chen DY-K, Pouwer RH, Richard J-A (2012) Chem Soc Rev 41:4631CrossRefGoogle Scholar
  5. 5.
    Yamaguchi K, Kazuta Y, Hirano K, Yamada S, Matsuda A, Shuto S (2008) Bioorg Med Chem 16:8875CrossRefGoogle Scholar
  6. 6.
    Roman DL, Talbot JN, Roof RA, Sunahara KK, Traynor JR, Neubig RR (2007) Mol Pharmacol 71:169CrossRefGoogle Scholar
  7. 7.
    Henry P (2006) Methods and compositions for specific inhibition of protein splicing by small molecules. WO 2006079057 A2, 2006. Chem Abstr 145:202957Google Scholar
  8. 8.
    Xu P-F, Wang W (eds) (2014) Catalytic cascade reactions. Wiley, Hoboken, NJGoogle Scholar
  9. 9.
    Grondal C, Jeanty M, Enders D (2010) Nat Chem 2:167CrossRefGoogle Scholar
  10. 10.
    Higson S, Subrizi F, Sheppard TD, Hailes HC (2016) Green Chem 18:855CrossRefGoogle Scholar
  11. 11.
    Hammerich O, Speiser B (eds) (2015) Organic electrochemistry, 5th edn. CRS PressTaylor & Francis Group, New YorkGoogle Scholar
  12. 12.
    Fuchigami T, Atobe M, Inagi S (eds) (2015) Fundamentals and applications of organic electrochemistry: synthesis, materials, devices. John Wiley & Sons Ltd, ChichesterGoogle Scholar
  13. 13.
    Frontana-Uribe BA, Little RD, Ibanez JG, Palma A, Vasquez-Medrano R (2010) Green Chem 12:2099CrossRefGoogle Scholar
  14. 14.
    Elinson MN, Dorofeeva EO, Vereshchagin AN, Nikishin GI (2015) Russ Chem Rev 84:485CrossRefGoogle Scholar
  15. 15.
    Nikishin GI, Elinson MN, Feducovich SK (1986) Russ Chem Bull 35:1749CrossRefGoogle Scholar
  16. 16.
    Elinson MN, Lizunova TL, Dekaprilevich MO, Struchkov YT, Nikishin GI (1993) Mendeleev Commun 34:192CrossRefGoogle Scholar
  17. 17.
    Elinson MN, Feducovich SK, Bushuev SG, Zakharenkov AA, Pashchenko DV, Nikishin GI (1998) Mendeleev Commun 8:15CrossRefGoogle Scholar
  18. 18.
    Elinson MN, Feducovich SK, Starikova ZA, Vereshchagin AN, Nikishin GI (2004) Tetrahedron 60:11743CrossRefGoogle Scholar
  19. 19.
    Elinson MN, Feducovich SK, Starikova ZA, Vereshchagin AN, Gorbunov SV, Nikishin GI (2005) Tetrahedron Lett 46:6389CrossRefGoogle Scholar
  20. 20.
    Nikishin GI, Elinson MN, Lizunova TL, Ugrak BI (1991) Tetrahedron Lett 32:2655CrossRefGoogle Scholar
  21. 21.
    Elinson MN, Lizunova TL, Ugrak BI, Dekaprilevich MO, Nikishin GI, Struchkov YT (1993) Tetrahedron Lett 34:5795CrossRefGoogle Scholar
  22. 22.
    Vereshchagin AN, Elinson MN, Zaimovskaya TA, Nikishin GI (2008) Tetrahedron 64:9766CrossRefGoogle Scholar
  23. 23.
    Vereshchagin AN, Elinson MN, Egorov MP (2015) RCS Adv 5:98522Google Scholar
  24. 24.
    Laroche C, Behr J-B, Szymoniak J, Bertus P, Schutz C, Vogel P, Plantier-Royon R (2006) Bioorg Med Chem 14:4047CrossRefGoogle Scholar
  25. 25.
    Sandanayaka VP, Prashad AS, Yang Y, Williamson RT, Lin YI, Mansour TS (2003) J Med Chem 46:2569CrossRefGoogle Scholar
  26. 26.
    Jiang T, Kuhen KL, Wolff K, Yin H, Bieza K, Caldwell J, Bursulaya B, Wub TY-H, He Y (2006) Bioorg Med Chem Lett 16:2105CrossRefGoogle Scholar
  27. 27.
    Dorofeeva EO, Elinson MN, Vereshchagin AN, Stepanov NO, Bushmarinov IS, Belyakov PA, Sokolova OO, Nikishin GI (2012) RCS Adv 2:4444Google Scholar
  28. 28.
    Elinson MN, Dorofeeva EO, Vereshchagin AN, Nasybullin RF, Egorov MP (2015) Catal Sci Technol 5:2384CrossRefGoogle Scholar
  29. 29.
    Francke R, Little RD (2014) Chem Rev 43:2492CrossRefGoogle Scholar
  30. 30.
    Ogibin YN, Elinson MN, Nikishin GI (2009) Russ Chem Rev 78:89CrossRefGoogle Scholar
  31. 31.
    Nikishin GI, Elinson MN, Makhova IV (1988) Angew Chem Int Ed 27:1716CrossRefGoogle Scholar
  32. 32.
    Elinson MN, Dorofeev AS, Feducovich SK, Belyakov PA, Nikishin GI (2007) Eur J Org Chem 18:3023CrossRefGoogle Scholar
  33. 33.
    Zhang ZL, Su JH, Zha ZG, Wang ZY (2013) Chem Eur J 19:17711CrossRefGoogle Scholar
  34. 34.
    Wender PA (2014) Nat Prod Rep 31:433CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Michail N. Elinson
    • 1
  • Anatoly N. Vereshchagin
    • 1
  • Alexander D. Korshunov
    • 1
  • Tatiana A. Zaimovskaya
    • 2
  • Mikhail P. Egorov
    • 1
  1. 1.N. D. Zelinsky Institute of Organic ChemistryRussian Academy of SciencesMoscowRussian Federation
  2. 2.A. V. Topchiev Institute of Petrochemical SynthesisRussian Academy of SciencesMoscowRussian Federation

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