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Two approaches toward the regio- and stereoselective synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro-[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles]

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Chemistry of Heterocyclic Compounds Aims and scope

A regio- and stereoselective method for the synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]-pyrrolidine-1,3'-oxindoles] in 24–79% yields, based on the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with azomethine ylides generated in situ from benzylamines and isatins by refluxing in CH2Cl2 for 24 h has been developed. 3-Phenyl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles] were obtained in 36–71% yields via the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromene, isatins, and L-phenylglycine proceeding in EtOH at 60°C for 5 h. The resulting compounds exhibited cytotoxic activity against human cervical cancer HeLa cells in the micromolar concentration range.

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This work was carried out with the financial support of the Russian Foundation for Basic Research (project 20-03-00716) and within the framework of the State Assignment of the Ministry of Science and Higher Education of the Russian Federation (project FEUZ-2020-0052).

The authors are grateful to the staff of the Center for Collective Use “Spectroscopy and Analysis of Organic Compounds” of Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences and the Laboratory of Complex Investigations and Expert Evaluation of Organic Materials of Ural Federal University for assistance in conducting physicochemical studies.

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Authors and Affiliations

  1. Institute of Natural Sciences and Mathematics of the Ural Federal University named after the first President of Russia B. N. Yeltsin, 51 Lenin Ave, Yekaterinburg, 620000, Russia

    Vladislav Yu. Korotaev, Savelii V. Barkovskii, Igor B. Kutyashev, Maria V. Ulitko, Alexey Yu. Barkov, Nikolay S. Zimnitskiy, Ivan А. Kochnev & Vyacheslav Ya. Sosnovskikh

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  1. Vladislav Yu. Korotaev
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  2. Savelii V. Barkovskii
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  3. Igor B. Kutyashev
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  4. Maria V. Ulitko
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  5. Alexey Yu. Barkov
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  6. Nikolay S. Zimnitskiy
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  7. Ivan А. Kochnev
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  8. Vyacheslav Ya. Sosnovskikh
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Correspondence to Vladislav Yu. Korotaev.

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Dedicated to the memory of Professor, Doctor of Chemical Sciences A. Ya. Zapevalov

Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2021, 57(6), 679–690

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Korotaev, V.Y., Barkovskii, S.V., Kutyashev, I.B. et al. Two approaches toward the regio- and stereoselective synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro-[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles]. Chem Heterocycl Comp 57, 679–690 (2021). https://doi.org/10.1007/s10593-021-02967-7

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