Investigating the regio-, chemo- and stereoselectivities of the [3 + 2] cycloaddition reaction of 1-pyrroline-1-oxide and C, N-diphenyl nitrone with a 1, 2-cyclooctadiene carboxylate: a DFT study

Gideon Donkor, Albert Aniagyei, Collins Obuah, Joshua Atta Kumi, Evans Adei

Research output: Contribution to journalArticlepeer-review

Abstract

The [3 + 2] cycloaddition (32CA) reaction holds promise for synthesizing of biologically active heterocyclic compounds. However, to fully exploit its synthetic potential and utilize the reactivity of 1,2-cyclooctadiene as convenient building blocks in the one-step formation of complex cycloadducts, it is crucial to understand the regio- and stereochemical considerations associated with this reaction. Herein, density functional theory (DFT) study has been carried out to explore the chemo-, regio- and stereoselectivities of the 32CA reaction of 1-pyrrolidine-1-oxide (cyclic nitrone) and a C, N-diphenyl nitrones (acyclic nitrone) with a 1,2-cyclooctadiene carboxylate at the M062X/6-311G (d, p) level of theory. The preferred pathway involves the addition of the acyclic nitrone to the substituted olefinic bond of the allene to form 4-methylene isoxazolidine. The free activation energy of 1.8 kcal/mol and the associated rate constant of 7.50 × 1011 s−1 are calculated for the process. This is 113.5 times higher than the formation of 5-methylene isoxazolidine, its regioisomeric product. For the formation of 5-methylene isoxazolidine, the calculated free activation energy is 5.4 kcal/mol. Strong electron-releasing and electron-withdrawing groups lower the activation energies to speed up the reaction. Substituents on B2 (R = CH3 and CH2CH3) have slightly high activation energies compared to the parent reaction. The decrease in activation energies relative to the parent is CH3 < CH2CH3 < OCH3 < NH2. The acyclic and cyclic nitrone derivatives add across the atomic centers with the largest atomic spin densities as evidenced by the local electrophilic (PK+) and nucleophilic (PK) Parr functions of the various reaction centers. Results from the global electron density transfer (GEDT) reveal the low polar nature of the reactions.

Original languageEnglish
Article number70
JournalTheoretical Chemistry Accounts
Volume143
Issue number11
DOIs
Publication statusPublished - Nov 2024

Keywords

  • 1, 2-Cyclooctadiene carboxylate
  • 1-pyrrolidine-1-oxide
  • C, N-diphenyl nitrone
  • Cycloaddition reaction

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