Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study

Dresler, Ewa; Wróblewska, Aneta; Jasiński, Radomir

doi:10.3390/molecules29133042

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Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study

by

Ewa Dresler

¹,

Aneta Wróblewska

²

and

Radomir Jasiński

^3,*

¹

Łukasiewicz Research Network—Institute of Heavy Organic Synthesis “Blachownia”, Energetyków 9, 47-225 Kędzierzyn-Koźle, Poland

²

Department of Organic Chemistry, University of Lodz, Tamka 12, 91-403 Łódź, Poland

³

Institute of Organic Chemistry and Technology, Cracow University of Technology, Warszawska 24, 31-155 Cracow, Poland

^*

Author to whom correspondence should be addressed.

Molecules 2024, 29(13), 3042; https://doi.org/10.3390/molecules29133042

Submission received: 4 June 2024 / Revised: 21 June 2024 / Accepted: 24 June 2024 / Published: 26 June 2024

(This article belongs to the Special Issue Advances in the Synthesis of Heterocyclic Compounds and Their Applications)

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Abstract

Regioselectivity and the molecular mechanism of the [3+2] cycloaddition reaction between nitro-substituted formonitrile N-oxide 1 and electron-rich alkenes were explored on the basis of the wb97xd/6-311+G(d) (PCM) quantum chemical calculations. It was established that the thermodynamic factors allow for the formation of stable cycloadducts along all considered models. The analysis of the kinetic parameters of the main processes show that all [3+2] cycloadditions should be realized with full regioselectivity. In all cases, the formation of 5-substituted 3-nitro-2-isoxazolidines is clearly preferred. It is interesting that regiodirection is not determined by the local electrophile/nucleophile interactions but by steric effects. From a mechanistic point of view, all considered reactions should be treated as polar, one-step reactions. All attempts to locate the hypothetical zwitterionic intermediates along the cycloaddition paths were, however, not successful.

Keywords: [3+2] cycloaddition; isoxazolines; Gibbs free energy of activation; Gibbs free energy of reaction

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MDPI and ACS Style

Dresler, E.; Wróblewska, A.; Jasiński, R. Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study. Molecules 2024, 29, 3042. https://doi.org/10.3390/molecules29133042

AMA Style

Dresler E, Wróblewska A, Jasiński R. Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study. Molecules. 2024; 29(13):3042. https://doi.org/10.3390/molecules29133042

Chicago/Turabian Style

Dresler, Ewa, Aneta Wróblewska, and Radomir Jasiński. 2024. "Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study" Molecules 29, no. 13: 3042. https://doi.org/10.3390/molecules29133042

APA Style

Dresler, E., Wróblewska, A., & Jasiński, R. (2024). Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study. Molecules, 29(13), 3042. https://doi.org/10.3390/molecules29133042

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Energetic Aspects and Molecular Mechanism of 3-Nitro-substituted 2-Isoxazolines Formation via Nitrile N-Oxide [3+2] Cycloaddition: An MEDT Computational Study

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