Benmetir Sofiane, Benhamed Lakhdar, Tchouar Noureddine, Mohammad-Salim Haydar, de Julián-Ortiz Jesús Vicente, Ríos-Gutiérrez Mar, Domingo Luis R
Process and Environmental Engineering Laboratory (LIPE), Faculty of Chemistry, University of Science and Technology of Oran Mohamed BOUDIAF, P.O. Box 1503, El Mnaouer, 31000 Oran, Algeria.
Molecular Topology and Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, 46100 Valencia, Spain.
ACS Omega. 2025 Apr 3;10(14):13868-13879. doi: 10.1021/acsomega.4c07794. eCollection 2025 Apr 15.
The role of hydrogen bond and solvent effects on the regio- and diastereoselectivity of the [3 + 2] cycloaddition reaction (32CA) between 2,2-dimethylpropanenitrile oxide (NO) and -(cyclopent-2-en-1-yl)benzamide has been theoretically studied at the B3LYP/6-311++G(d,p) level using the molecular electron density theory (MEDT). Solvent effects of dichloromethane (DCM) and benzene were taken into account. The electron localization function (ELF) classifies NO as a three-atom component with a zwitterionic electronic structure, which participates in zwitterionic-type 32CA reactions. The reactions occur through a one-step mechanism and present high activation Gibbs free energies in DCM and in benzene, with a slight difference favoring the reaction in benzene. Along the intrinsic reaction coordinate reaction pathway, the topological analysis of the ELF shows the asynchronous formation of the C-C bond prior to the C-O bond by coupling the two-carbon pseudoradical centers. The low global electron density transfer indicates that these reactions have a nonpolar character, which accounts for their high Gibbs free activation energies. Analysis of the noncovalent interactions associated with the TSs reveals a hydrogen bond in the favored TS, which confirms its participation in the experimental selectivities.
在分子电子密度理论（MEDT）的B3LYP/6-311++G(d,p)水平下，从理论上研究了氢键和溶剂效应，对2,2-二甲基丙腈氧化物（NO）与β-(环戊-2-烯-1-基)苯甲酰胺之间的[3 + 2]环加成反应（32CA）的区域选择性和非对映选择性的影响。考虑了二氯甲烷（DCM）和苯的溶剂效应。电子定域函数（ELF）将NO归类为具有两性离子电子结构的三原子组分，其参与两性离子型32CA反应。反应通过一步机理发生，在DCM和苯中具有较高的活化吉布斯自由能，在苯中反应略占优势。沿着本征反应坐标反应途径，ELF的拓扑分析表明，通过耦合两个碳假自由基中心，C-C键在C-O键之前异步形成。低的整体电子密度转移表明这些反应具有非极性特征，这解释了它们较高的吉布斯自由活化能。对与过渡态相关的非共价相互作用的分析揭示了在有利的过渡态中存在氢键，这证实了其参与实验选择性。
