Understanding the different reactivity of ()- and ()-β-nitrostyrenes in [3+2] cycloaddition reactions. An MEDT study.

The experimental reactivity of isomeric ()- and ()-β-nitrostyrenes participating in [3+2] cycloaddition (32CA) reactions has been analysed on the basis of molecular electron density theory (MEDT) at the HF/6-311G(d,p), B3LYP/6-311G(d,p) and B97X-D/6-311G(d,p) computational levels. It was found that the polar 32CA reactions with 5,5-dimethylpyrroline--oxide proceed a one-step mechanism, characterised by the attack of the nucleophilic oxygen centre of the nitrone on the electrophilically activated β-position of these nitrostyrenes. This behaviour is completely understood by means of the analysis of the conceptual DFT reactivity indices. These 32CA reactions present low activation enthalpies of 4.4 () and 5.0 () kcal mol, and are () and () stereoselective (B3LYP), as well as completely regioselective (B97X-D, B3LYP). The less stable ()-β-nitrostyrene is more reactive than the ()-one (HF). ELF and AIM topological analyses of the reagents and TSs show the great similitude between their electronic structures. Finally, NCI allows explaining the stereoselectivity found in the reaction of ()-β-nitrostyrene. The present MEDT study explains the different reactivity, selectivity and competitiveness in the title reactions.