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Evaluation of the mechanism, regio-, and diastereoselectivity of aza-Diels–Alder reactions of 2H-azirine under a Lewis acid catalyst

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Abstract

The molecular mechanism of the cycloaddition reactions of 2H-azirine with 1-methoxybutadiene and cyclohexadiene has been studied at the M06-2X/cc-pVDZ level of theory. Analysis of the energy results indicated that the meta/endo pathways are the most stable paths for all studied reactions. The presence of Lewis acid in these reactions decreases the activation energies markedly and increases the diastereoselectivities. Moreover, the nucleophilicity and electrophilicity of the reagents and selectivity of the reactions were analyzed by DFT reactivity indices. Analysis of electron localization function (ELF) indicated that the general processes of electronic changes for the meta/endo pathways of the cycloaddition reactions of 2H-azirine 1 and 1-Zn with 1-methoxy-1,3-butadiene 2 are similar, and both reactions take place via the one-step two-stage mechanism. However, in the presence of Lewis acid (LA) catalyst, the fragments are more separated, and the reaction proceeds through an earlier transition state (TS). The non-covalent interaction (NCI) topological analysis at the transition states reveals that only one strong, attractive interaction between the reaction sites is responsible for the highly asynchronous process in the presence of Lewis acids.

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Acknowledgements

The authors wish to acknowledge Dr Louise S. Price, University College London, UK, for reading the manuscript and providing valuable suggestions.

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Authors and Affiliations

  1. Department of Chemistry, Babol Branch, Islamic Azad University, Babol, Iran

    Mina Haghdadi & Kosar Norouzi

  2. Department of Chemistry, Jouybar Branch, Islamic Azad University, Jouybar, Iran

    Mahshid Hamzehloueian

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  1. Mina Haghdadi
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Contributions

All the authors contributed to the study conception and design. Calculations and optimization of structures were performed by Kosar Norouzi. Analysis, data collection, and writing the first draft of the manuscript were performed by Mina Haghdadi and Mahshid Hamzehloueian and all authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Haghdadi, M., Norouzi, K. & Hamzehloueian, M. Evaluation of the mechanism, regio-, and diastereoselectivity of aza-Diels–Alder reactions of 2H-azirine under a Lewis acid catalyst. Struct Chem 33, 445–456 (2022). https://doi.org/10.1007/s11224-021-01860-5

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