3 + 2] cycloaddition reaction of N,N′ cyclic azomethine imines toward highly electron‐deficient nitroalkenes: A molecular electron density theory study

Abstract

AbstractA 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‐β‐nitrostyrene 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.