A molecular electron density theory (MEDT) study at the M06-2X/6-31G(d,p) computational level was performed over [3 + 2] cycloaddition (32CA) reaction of azomethine imine 2 (AI-2) toward highly electron-deficient trans-βnitrostyrene 3 (NS-3) in dimethyl sulfoxide at 110°C. While this reaction can take place through two N3-C4 and N3-C5 regioselective reaction channels, in excellent agreement with the experimental outcomes, the calculated rate constants reveal that the N3-C4 regioselective reaction channel leading to [3 + 2] cycloadduct CA-1n in a high endo stereoselective fashion is entirely preferred over the N3-C5 one. Analysis of the electrophilic and nucleophilic Parr functions computed at the reactive sites of separate reagents allows to explain N3-C4 regioselectivity, while the endo stereoselectivity can be rationalized through non-covalent interaction analysis in the competitive transition state structures. The electron localization function analysis performed along the stepwise formation of CA-1n permits to figure out the molecular mechanism of zwitterionic type (zw-type) 32CA reaction between AI-2 and NS-3. Indeed, within the N3 nucleophilic attack of AI-2 at the electrophilically activated C4 atom of NS-3, the first N3-C4 single bond at intermediate IN-1n is formed through donation of part of non-bonding electron density of the N3 nitrogen atom in AI moiety to the C4 carbon atom of NS moiety. In the subsequent step, the formation of the second C1-C5 single bond via C1-to-C5 coupling of these pseudoradical centers closes the five-membered ring in CA-1n.The stepwise formation of CA-1n should be related to the highly polar character of the studied reaction.

In the light of Molecular Electron Density Theory (MEDT), [3 + 2] cycloaddition (32CA) reaction between E‐azomethine imine (E‐AI‐2) and 2‐sulfolene (SF‐3) was explored at the M06‐2X/6‐31G(d,p) computational level. Calculated global reactivity indices classify E‐AI‐2 and SF‐3 as, respectively, a strong nucleophile and a moderate electrophile. The generation of cycloadduct CA‐2x, as the sole product, takes place along an irreversible pathway acting as the driving force to proceed such zwitterionic type (zw‐type) 32CA reaction. Analysis of the electrophilic and nucleophilic Parr functions, computed at the reactive sites of reactants, rationalizes the entirely N3‐C4 regioselectivity observed experimentally. Moreover, the exo‐stereoselectivity predominance is explained through non‐covalent interactions (NCIs) analysis over the two competitive exo TS‐2x and endo TS‐2n involved in the energetically more preferred regioselective pathway. An exploration of electron localization function (ELF) of the most relevant points located along the intrinsic reaction coordinate (IRC) profile of TS‐2x elucidates the molecular mechanism of the studied [3 + 2] cycloaddition reaction. Indeed, this reaction follows a nonconcerted two‐stage one‐step molecular mechanism providing two different patterns regarding carbon‐carbon (C–C) and carbon‐heteroatom (C–N) single bonds formation.