A molecular electron density theory study of [3 + 2] cycloaddition reactions of chiral azomethine ylides with β-nitrostyrene

Abstract

The molecular mechanism and selectivity of the [3 + 2] cycloaddition (32CA) reaction of a chiral azomethine ylide (AY) with β-nitrostyrene (NS) have been studied within the Molecular Electron Density Theory (MEDT) using DFT methods at the MPWB1K/6-31G(d) computational level. Analysis of the electronic structure of AY indicates that this species has a pseudodiradical structure that enables its participation in pdr-type 32CA reactions. Analysis of the conceptual DFT reactivity indices allows classifying the AY as a strong nucleophile and NS as a strong electrophile, suggesting a polar process, while Parr functions permit to predict a high regioselectivity. The 32CA reaction presents a relatively low activation enthalpy, 4.1 kcal·mol−1, and is completely regio- and stereoselective. ELF topological analysis allows characterising the molecular mechanism of these pdr-type 32CA reactions as a non-concerted two-stage one-step mechanism, the reaction being classified as a [2n + 2τ] process.