Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

Abstract

SummaryDipolar addition of cyclic azomethine imines with cyclic vinyl sulfones gave rise to functionalized tricycles that exhibited fluxional behavior in solution at room temperature. The scope of the synthetic methodology was explored, and the origin of the fluxional behavior was probed by NMR methods together with DFT calculations. This behavior was ultimately attributed to stereochemical inversion at one of two nitrogen centers embedded in the tricyclic framework. Two tetracycles were also synthesized, and the degree of signal-broadening in the NMR spectra was found to depend on the presence of substitution next to the inverting nitrogen center.

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

“…Consequently, in terms of NCIs analysis, one can conclude that the entirely exo‐stereoselectivity predominance over the endo‐stereoselectivity in 32CA reaction of E ‐AI‐2 toward SF‐3 mainly arises from the more repulsive interactions between two interacting fragments in endo TS‐2n than those in exo TS‐2x . Indeed, repulsions between relatively bulky SO 2 functional group of SF moiety and some bonds of five‐membered ring in E‐AI moiety, in one hand, and additional repulsions between five‐ and six‐membered rings of E‐AI moiety in endo TS‐2n , on the other hand, are responsible for a destabilization of endo TS‐2n respect to exo TS‐2x rationalizing the quite predominance of latter TS over the former one, in excellent agreement with experimental findings …”

“…Therefore, the value of Gibbs free energy is accompanied with a large positive shift specifically in the presence of a polar solvent such as DMSO in which, because of the greater sum of dipole moments, reactants are more stabilized than the corresponding TS. These explanations evidence why the studied 32CA reaction should experimentally take place in the harsh reaction conditions (reflux for 24 hours in DMSO) to overcome the high barrier of TS‐2x , 27.8 kcal/mol (see Scheme ).…”

“…32CA reaction between E ‐AI‐2 and SF‐3 experimentally investigated by Wong and coworkers . See text for details…”

“…Herein, because of our ongoing interest in 32CA reactions, an MEDT study over the course of 32CA reaction of E ‐AI‐2 toward SF‐3 , experimentally investigated by Wong and coworkers (see Scheme ), is performed at the M06‐2X/6‐31G(d,p) computational level. Such an MEDT study is expected to enable us to determine the ground‐state electronic structure (GSES) of E ‐AI‐2 and, thus, predict the type of 32CA reaction which this species can participate in; evaluate the global reactivity indices derived from conceptual density functional theory (CDFT) and, therefore, predict the reactivity of species involved in the considered 32CA reaction as well as the magnitude of polarity of this reaction; analyze the potential energy surface (PES) of this 32CA reaction connecting reactants E ‐AI‐2 and SF‐3 to the corresponding cycloadducts.…”

A highly efficient [3+2] cycloaddition of nitrile oxides and azomethine imines to N-vinylpyrroles

“…A similar phenomenon is noted in the literature previously for compounds containing fragment of the pyrazolo[1,2-a]pyrazolone. 11 This broadening of signals is explained by inversion of nitrogen atoms in solution at room temperature. In the NMR spectra of cisisomers this broadening was not observed.…”