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

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-beta-nitrostyrene 3 (NS-3) in dimethyl sulfoxide at 110 degrees 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.