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Reactions of cyclic β-alkoxyvinyl α-keto esters with heteroaromatic NCC-binucleophiles

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Chemistry of Heterocyclic Compounds Aims and scope

Reactions of five- and six-membered cyclic β-alkoxyvinyl α-keto esters and NCC-binucleophiles are described. The following binucleophiles were studied: heteroaromatic amines (pyrazoles, isoxazole, uracils, and isoquinolinone) and 2-(benzimidazolyl)acetonitrile. It was found that condensation proceeded regioselectively in the case of five-membered cyclic enone. Fused α-pyridine carboxylates, likely formed in situ, underwent lactonization, which resulted in six-membered lactones in moderate to excellent yields (53–91%). Only in the case of 3-unsubstituted 5-aminopyrazole, formation of γ-pyridine carboxylate followed by cyclization to isomeric lactone was observed. On the contrary, six-membered cyclic enone was reactive only toward heterocyclic amines under optimized conditions and provided open-chain α-pyridine carboxylates in 40–80% yield.

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The authors acknowledge Enamine Ltd. for financial support. Oleksandr O. Grygorenko was also financially supported by the Ministry of Education and Science of Ukraine (grant No. 19БФ037-03).

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Authors and Affiliations

  1. Enamine Ltd., 78 Chervonotkatska St, Kyiv, 02094, Ukraine

    Oleksandr O. Stepaniuk, Bohdan V. Vashchenko, Vitalii O. Matvienko, Ivan S. Kondratov, Andrey A. Tolmachev & Oleksandr O. Grygorenko

  2. Taras Shevchenko National University of Kyiv, 60 Volodymyrska St, Kyiv, 01601, Ukraine

    Oleksandr O. Stepaniuk, Bohdan V. Vashchenko, Andrey A. Tolmachev & Oleksandr O. Grygorenko

  3. V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1 Murmanska St, Kyiv, 02660, Ukraine

    Ivan S. Kondratov

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  1. Oleksandr O. Stepaniuk
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  2. Bohdan V. Vashchenko
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Correspondence to Oleksandr O. Grygorenko.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(3), 377–385

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Stepaniuk, O.O., Vashchenko, B.V., Matvienko, V.O. et al. Reactions of cyclic β-alkoxyvinyl α-keto esters with heteroaromatic NCC-binucleophiles. Chem Heterocycl Comp 56, 377–385 (2020). https://doi.org/10.1007/s10593-020-02670-z

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