[3 + 2] Cycloaddition reaction of disubstituted-3-benzylidene succinimide with C, N-disubstituted nitrile imines for synthesizing spiro-heterocycles: A computational study

• Published in: Computational and theoretical chemistry 2023-07, Vol.1225, p.114138, Article 114138
• Main Authors: Amankwah, Gabriel, Kwawu, Caroline R., Menkah, Elliot S., Adei, Evans
• Format: Article
• Language: English
• Subjects: Computations; Heterocycles; Selectivity; Spiropyrazolines
• ISSN: 2210-271X
• DOI: 10.1016/j.comptc.2023.114138

[Display omitted] •The TAC adds chemo-, regio-, stereoselectively across the olefinic functionality of the ethylene derivative.•ERGs and EWGs substituted simultaneously on the reacting species do not affect the energetic trend in the titled reaction.•The obtained GEDT values indicate a low polar character and a forward electron density flux for the reaction.•Dichloromethane solvation has no substantial effect on the observed energetic trends and selectivity in the gas phase computation. The relevance of spiro heterocycles in the biomedical sector is enormous. This computational work extensively investigates the stereo-, regio-, chemo-, and site- selectivities of the [3 + 2] cycloaddition reaction of disubstituted-3-benzylidene succinimide (3-BS) with C, N-disubstituted nitrile imines derivatives for the formation of spiro heterocycles. This study employs the B3LYP, B3LYP-D3, M06, M06-2X, and MPWB1K hybrid density functional calculations with the 6-311G(d, p) basis sets. Various computations show that the attachment of the nitrile imine across the olefinic functionality of the disubstituted-3-BS has relatively lower barriers compared to the carbonyl functionalities present. Generally, electron-releasing groups on disubstituted-3-BS increase the activation barriers, whereas electron-withdrawing groups significantly reduce the activation barrier. The GEDT values predicts a low polar character for the [3 + 2] Cycloaddition reaction. Results from local and global parr functions calculations are in accordance with the selectivities and energetic trends observed.