The Theoretical Study Of Michael Addition

The mechanism of Michael addition was investigated using density functional theory in order to explain the interesting but puzzling experimental phenomena. The computational results were consistent with the experimental results, and they could not only provide theoretical basis for the experiments but also offer guidelines for the improvement of the experiments.The first part of this thesis is the brief introduction to the development and application, the computational methods, the basis sets and the solvent models of quantum chemistry.The second part is the study to confirm what the roles of benzoic acid are in proline-catalyzed Michael addition. In asymmetric Michael addition between ketones and nitroolefins catalyzed by L-proline, we observed that the presence of benzoic acid or its derivatives could accelerate the reaction greatly, and different benzoic acid derivatives brought different yields. To explain the experimental phenomena, a density functional theory study was performed to elucidate the mechanism of proline-catalyzed asymmetric Michael addition with benzoic acid. The results of the theoretical calculation at the level of B3LYP/6-311+G(2df,p)//B3LYP/6-31G(d) demonstrated that benzoic acid played two major roles in the formation of nitroalkane:assisting proton transfer and activating the nitro group. In the stage of enamine formation from imine, the energy profiles of benzoic acid derivatives were also calculated to investigate the reasons why different benzoic acid derivatives caused different yields. The results demonstrated that the pKa value was the major factor for p-substituted benzoic acid derivatives to improve the yields, while for m/o-substituted benzoic acid derivatives both pKa value and electronic and steric effects could significantly increase the yields. The calculated results would be very helpful for understanding the reaction mechanism of Michael addition and provide some insights into the selection of efficient additives for similar experiments.The third part is the study of the mechanism of the reaction between 1H-1,2,3-triazole and alkynal. The reactants could produce the N-2 addition product with the E/Z ratio 95:5 in neutral or basic condition, however, the same reactants produced the N-1 addition product with the E/Z ratio 2:1 in acid condition. In order to explain the issues of the regioselectivity and the stereoselectivity, a density functional theory study was performed to explore the mechanism of aza-Michael addition. The results demonstrated that in neutral or basic condition, the energy profiles of the N-2 addition with E-conformation pathway were the lowest while the energy profiles of the N-2 addition with Z-conformation pathway were a little higher than that of the E-conformation pathway. In acidic condition, the key step was the addition of triazole to the carbocation, and in this stage the relative energy of the N-1 addition with E-conformation pathway was the lowest while the relative energy of the N-1 addition with Z-conformation pathway was higher than that of the E-conformation pathway. In addition, both the energy barriers of the N-1 addition with E-conformation and Z-conformation pathways were lower than 18 kcal/mol. This may be the reasons that the E/Z ratio was nearly up to 2:1. The computational results could reasonably explain the experimental phenomena.The last part (chapter 4) is the summary of the entire thesis.