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Strategy for the synthesis of 2,2-disubstituted 8-azachromanones via Horner–Wadsworth–Emmons olefination

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Chemistry of Heterocyclic Compounds Aims and scope

A series of 2,2-disubstituted 8-azachromanones, including spirocyclic compounds, have been synthesized via Horner–Wadsworth– Emmons reaction. Dimethyl methylphosphonate was acylated with methyl 2-methoxypyridine-3-carboxylate to afford the key intermediate – dimethyl [2-(2-methoxypyridin-3-yl)-2-oxoethyl]phosphonate. Further reaction of this phosphonate and ketones followed by treatment with TMSCl–NaI provided the target 8-azachromanones. Scope and limitations of the developed synthetic method have been investigated.

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Acknowledgement

The work was funded by Enamine Ltd. O. O. Grygorenko and A. V. Dobrydnev received additional funding from Ministry of Education and Science of Ukraine (grant 19BF037-03).

The authors thank Prof. A. A. Tolmachev for his encouragement and support, Mr. D. V. Bylina for HRMS measurements, and reviewer for his help with elucidation of the structure of compound 11.

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Authors and Affiliations

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

    Taras V. Omelian, Eugeniy N. Ostapchuk, Alexey V. Dobrydnev, Yehor S. Malets & Oleksandr O. Grygorenko

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

    Taras V. Omelian, Eugeniy N. Ostapchuk, Alexey V. Dobrydnev & Oleksandr O. Grygorenko

  3. V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, 1 Murmanska St, Kyiv, 02094, Ukraine

    Yehor S. Malets & Volodymyr S. Brovarets

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  1. Taras V. Omelian
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  2. Eugeniy N. Ostapchuk
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  3. Alexey V. Dobrydnev
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  4. Yehor S. Malets
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  5. Volodymyr S. Brovarets
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  6. Oleksandr O. Grygorenko
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Correspondence to Oleksandr O. Grygorenko.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(2), 213–218

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Omelian, T.V., Ostapchuk, E.N., Dobrydnev, A.V. et al. Strategy for the synthesis of 2,2-disubstituted 8-azachromanones via Horner–Wadsworth–Emmons olefination. Chem Heterocycl Comp 56, 213–218 (2020). https://doi.org/10.1007/s10593-020-02646-z

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  • DOI: https://doi.org/10.1007/s10593-020-02646-z

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