TY - JOUR
T1 - 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
T2 - a DFT study
AU - Donkor, Gideon
AU - Aniagyei, Albert
AU - Obuah, Collins
AU - Kumi, Joshua Atta
AU - Adei, Evans
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
PY - 2024/11
Y1 - 2024/11
N2 - 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.
AB - 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.
KW - 1, 2-Cyclooctadiene carboxylate
KW - 1-pyrrolidine-1-oxide
KW - C, N-diphenyl nitrone
KW - Cycloaddition reaction
UR - http://www.scopus.com/inward/record.url?scp=85205987622&partnerID=8YFLogxK
U2 - 10.1007/s00214-024-03148-3
DO - 10.1007/s00214-024-03148-3
M3 - Article
AN - SCOPUS:85205987622
SN - 1432-881X
VL - 143
JO - Theoretical Chemistry Accounts
JF - Theoretical Chemistry Accounts
IS - 11
M1 - 70
ER -