Shedding light on the energetics, regioselectivity, stereoselectivity, and mechanistic aspects of [3 + 2] cycloaddition reaction between azomethine imines and 2‐sulfolene through molecular electron density theory

Abstract

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.

A DFT study on the mechanism of the formation of 1,4,2,3‐dithiadiazinanes by head‐to‐head [3 + 3] cyclodimerization of thiocarbonyl S‐imides

“…A broad variety of investigations regarding the related 32CA reactions by computational methods have been published during the last decade. [ 7,8,13 ]…”

“…Following Domingo's comprehensive theoretical studies, [ 5–8 ] we prefer to use this less prepossessed term TAC for these neutral compounds instead of the traditionally used name “1,3‐dipole,” which is not in accordance with their ground state electronic structure (GES). They readily undergo [3 + 2] cycloaddition (32CA) reactions with suitable unsaturated reactants to form five‐membered heterocycles.…”

“…In several cases, for instance, a stepwise diradical mechanism of 32CA reactions has been postulated. [ 7,8,13c,d ]…”