ABSTRACT
Acrolein dimerization is a intriguing case since the reaction does not occur to form the electronically preferred regioisomeric adduct. Various explanations have been suggested to rationalize this experimental regioselectivity, however, none of these arguments had been convincing enough. In this work, the hetero Diels-Alder acrolein dimerization was theoretically investigated using DFT and MP2 methods. The influence of nucleophilic/electrophilic interactions and non-covalent interactions (NCI) in the regiospecificity of the reaction were analyzed. Our results show that the NCI at the transition state are the key factor controlling the regiospecificity in this reaction. Besides, we found that the choice of calculation method can have an effect on the prediction of the mechanism in the reaction, as all DFT methods forecast a one-step hetero Diels-Alder acrolein dimerization, while MP2 predicts a stepwise description for the lower energy reaction channel.
ABSTRACT
Mechanistic theoretical studies about the feasibility of the traditional proposed mechanism of formation for icetexane diterpene dimer grandione were assessed using density functional method at the M06-2X/6-31G(d,p) level of theory. Bulk water solvent effects were taken into account implicitly using the polarizable continuum model (SCI-PCM). The results were compared with the selectivity found in the biomimetic synthesis performed by experimental research groups. The relative free energy calculation shows that the one-step H-DA formation mechanism nominated in the literature is not a viable mechanism. We found that an alternative competing Tandem pathway is consistent with the experimental trends. Thus, our results suggested that the compound grandione is formed via a H-DA/retro-Claisen rearrangement and not by the traditional H-DA mechanism proposed early in the experimental studies. The H-DA initial step produce a biecyclic adduct followed by a domino retro-Claisen rearrangement that releases the energy strain of the bicyclic intermediary. Steric issues and hyperconjugation interactions are the mainly factors driving the reaction nature and the selectivity in the formation reaction. Finally, the enzymatic assistance for dimer formation was analyzed in terms of the calculated transition state energy barrier.
