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Highly diastereoselective four-component synthesis of polysubstituted 1,4,5,6-tetrahydropyridines

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Chemistry of Heterocyclic Compounds Aims and scope

A novel four-component diastereoselective synthesis of polysubstituted tetrahydropyridines is reported. The Michael addition – Mannich reaction – cyclization – dehydration cascade of benzylidenemalononitriles, esters of 3-oxocarboxylic acids, aromatic aldehydes, and ammonium acetate in methanol provides convenient access to 2-substituted alkyl (4SR,6RS)-4,6-diaryl-5,5-dicyano-1,4,5,6-tetrahydropyridine- 3-carboxylates with two stereocenters in 66–92% yields. The formation of products was highly stereoselective, with only one diastereomer formed. Ammonium acetate plays dual role acting as a base and as a nitrogen source. Structures of the synthesized compounds were confirmed by 1H, 13C NMR, IR, and mass spectral studies. The formation of single diastereomer was confirmed by singe crystal X-ray diffraction studies.

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Scientific Schools Development Program by N. D. Zelinsky Institute of Organic Chemistry is gratefully acknowledged. X-ray diffraction data were collected using the equipment of the Center for Molecular Composition Studies of the A. N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences.

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Authors and Affiliations

  1. N. D. Zelinsky Institute of Organic Chemistry, 47 Leninsky Ave, Moscow, 119991, Russia

    Anatoly N. Vereshchagin, Taygib M. Iliyasov, Kirill A. Karpenko, Vladimir A. Smirnov & Michail N. Elinson

  2. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya Sq, Moscow, 125047, Russia

    Vladimir A. Smirnov

  3. A. N. Nesmeyanov Institute of Organoelement Compounds, 28 Vavilova St, Moscow, 119991, Russia

    Ivan E. Ushakov

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  1. Anatoly N. Vereshchagin
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  2. Taygib M. Iliyasov
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  3. Kirill A. Karpenko
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  4. Vladimir A. Smirnov
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  5. Ivan E. Ushakov
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  6. Michail N. Elinson
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Correspondence to Anatoly N. Vereshchagin.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2021, 57(9), 929–933

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Vereshchagin, A.N., Iliyasov, T.M., Karpenko, K.A. et al. Highly diastereoselective four-component synthesis of polysubstituted 1,4,5,6-tetrahydropyridines. Chem Heterocycl Comp 57, 929–933 (2021). https://doi.org/10.1007/s10593-021-03002-5

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