A molecular electron density theory study on the [3+2] cycloaddition reaction of 5,5-dimethyl-1-pyrroline N-oxide...

In the present work, the [3 + 2] cycloaddition reaction of 5,5-dimethyl-1-pyrroline N-oxide (Nit-5) and 2-cyclopentenone (CPN-6), experimentally reported by Tamura et al., was theoretically studied using the newly introduced molecular electron density theory (MEDT). Based on the experimental findings, this reaction takes place in an O3-C4 regio- and an exo-stereospecific fashion to give corresponding [3 + 2] exo cycloadduct as the sole product. The results of the potential energy surface analysis indicated that the experimentally reported product is more favorable both thermodynamically and kinetically relative to other possible adducts. In complete agreement with the experimental outcomes, the conceptual density functional theory reactivity indices explained the reactivity and regioselectivity of the reaction. Calculation of global electron density transfer of the energetically most preferred transition state indicated that the electron density fluxes from Nit-5 as a nucleophilic species toward CPN-6 as an electrophilic species. Analysis of the molecular electrostatic potential map of the most favorable transition state showed that approach of Nit-5 and CPN-6 locates the oppositely charged regions over each other leading to attractive forces between two reagents rationalizing the exo stereoselectivity predominance. The molecular mechanism of the reactions was specified using electron localization function analysis over some relevant points along the intrinsic reaction coordinate profile of the most favorable transition state and the results indicated that this zwitterionic-type [3 + 2] cycloaddition reaction proceeds through a two-stage one-step mechanism. In fact, while the O3-C4 single bond is initialy formed between two fragments through donation of some electron density from the O3 oxygen lone electron-pairs of Nit-5 toward the C4 carbon atom of CPN-6, the delayed C1-C5 single bond begins to form via C1- to -C5 coupling of pseudodiracal centers created on theses atoms over the course of reaction.