Unveiling thecb‐typeIntramolecular [3+2] Cycloaddition Reactions of Fluorinated Azomethine Ylides to Ester Carbonyls with a Molecular Electron Density Theory Perspective

Abstract

The carbenoid‐type (cb‐type) intramolecular [3+2] cycloaddition (IM32CA) reactions of four fluorinated azomethine ylides (AYs) bearing an ester carbonyl substituent have been studied from the molecular electron density theory (MEDT) perspective. The presence of two fluorine atoms in these species changes the pseudodiradical structure of the simplest AY to that of a carbenoid one, according to the cb‐type molecular reactivity of these IM32CA reactions. These IM32CA reactions present low activation energies, lesser than 3.0 kcal ⋅ mol−1, and a strongly exothermic character, more than −34.0 kcal ⋅ mol−1, showing a complete chemo‐ and regioselectivity. The presence of the electron‐withdrawing −CN group at the aryl ester framework increases the global electron density transfer (GEDT) at the transition state structure (TS), which fluxes from the nucleophilic AY moiety to the electrophilic carbonyl ester, diminishing the activation energy by 2 kcal ⋅ mol−1 relative to that of the phenyl substituent. Electron Localization Function and Atom‐in‐Molecules topological analyses of the most favorable TSs show the early character of these cb‐type IM32CA reactions. The present MEDT study makes it possible to establish that the carbenoid structure of these fluorinated AYs together with their supernucleophilic character are responsible for the high reactivity and selectivities shown by these three‐atom‐components participating in cb‐type 32CA reactions towards carbonyl compounds.