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The reactivity of tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxides

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Abstract

The present work is devoted to the study of the reactivity of tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxide framework. This scaffold possesses two reaction centers: the EWG-activated methylene group and the carbonyl functionality, which are the basic variation points. At the same time, the attached 3a-substituent had a significant impact on the course of the explored reactions and its role was also investigated. In this regard, the corresponding 3a-unsubstituted and 3a-methylated tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxides were chosen as model substances involved in chemical properties evaluation. With a view to pre-assess the activity of the model compounds, a deuteration study was conducted. Furthermore, the interaction with a variety of electrophilic and nucleophilic agents was explored. The most striking difference in the chemical behavior was observed in the reaction with the Wittig reagent triphenylcarbethoxymethylenephosphorane (Ph3P=CHCO2Me). In particular, unlike the 3a-unsubstituted substrate, the 3a-methylated one gave the unusual phosphonium betaine, namely 3a-methyl-2-[2-(triphenylphosphonio)acetyl]-3a,4,5,6-tetrahydropyrrolo[1,2-b]isothiazol-3-olate 1,1-dioxide. The proposed mechanistic insights of this reaction have been discovered.

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Acknowledgements

The work was funded by Enamine Ltd. A.V.D. was also funded by the Ministry of Education and Science of Ukraine (Grant No. 19БФ037-03). We thank Iryna Omelian for assistance with methodology, Svitlana Omelian for a fellowship and comments that greatly improved the manuscript, and Vitaliy Polovinko for providing the NMR experiments. The authors also show their gratitude to Prof. Andrey A. Tolmachev for his encouragement and support.

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Authors and Affiliations

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

    Taras V. Omelian, Alexey V. Dobrydnev, Oleksandr Yu. Utchenko & Eugeniy N. Ostapchuk

  2. Taras Shevchenko National University of Kyiv, Lva Tolstoho Street 12, Kyiv, 01033, Ukraine

    Taras V. Omelian, Alexey V. Dobrydnev, Eugeniy N. Ostapchuk & Yulian M. Volovenko

  3. SSI “Institute for Single Crystals” NAS of Ukraine, Nauky Avenue 60, Kharkiv, 61072, Ukraine

    Irina S. Konovalova

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  1. Taras V. Omelian
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  2. Alexey V. Dobrydnev
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  3. Oleksandr Yu. Utchenko
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  4. Eugeniy N. Ostapchuk
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  5. Irina S. Konovalova
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  6. Yulian M. Volovenko
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Correspondence to Alexey V. Dobrydnev.

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Omelian, T.V., Dobrydnev, A.V., Utchenko, O.Y. et al. The reactivity of tetrahydropyrrolo[1,2-b]isothiazol-3(2H)-one 1,1-dioxides. Monatsh Chem 151, 1759–1772 (2020). https://doi.org/10.1007/s00706-020-02694-3

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