Unveiling Hydrogen Bonding and Solvent Effects on Directed Nitrile Oxide [3 + 2] Cycloaddition Reactions: Selectivity of 2,2-Dimethylpropane Nitrile Oxide with Cyclopentenylbenzamide: An MEDT Study

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 <i>N</i>-(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.