Theoretical Study Of The Asymmetric Michael Addition Mechanism Catalyzed By Thiourea Bifunctional Catalyst

Enantioselective organocatalysis is widely used in the field of developing new chiral drugs and materials owing to its high efficiency and high selectivity. Chiral thiourea bifunctional catalyst posesses the feature of high catalytic activity and enantioselectivity, currently it has been widely used in a variety of asymmetric catalytic reactions. The asymmetric Michael addition reactions catalyzed by chiral tertiary amine thiourea bifunctional catalyst have been investigated using density functional theory in this paper. Conducting the theoretical studies help us understand the catalytic reaction mechanism and explain the experimental phenomenons. Thereby, provide a theoretical direction for the design and improvement of chiral thiourea bifunctional catalyst, and the synthesis of other chiral compounds.The main research contents and conclusions in this dissertation are as follows:The intramolecular oxy-Michael addition of ε-hydroxy-α,β-unsaturated ketones catalyzed by chiral tertiary amine thiourea bifunctional catalyst has been explored by performing density functional throry calculations. The results show that there are two configurations for the products of the reaction, in which(S)-configuration product is favored over the(R)-configuration product, consistent with the experimental results. The ratedetermining step is the formation of five-membered ring and the protonation of the catalyst. The enantioselectivity of the Michael addition reaction is controlled by the different spatial orientation of the substrate in initial interreaction between catalyst and substrate. The calculated ee value is matched with the experimental data.The [3+2] cycloaddition reaction of γ-hydroxy-α,β-unsaturated ketones with aldehydes or ketones catalyzed by chiral tertiary amine thiourea bifunctional catalyst has been studied with density functional method. Calculation results show that the reaction has two different pathways, the reaction path A generates(3S,5S)-configuration product, the reaction path B gives(3S,5R)-configuration product. The enantioselectivity is attributed to the proton transfer in tandem with the electrophilic addition, which is the rate-determining step as well. Path A is more favorable. The enantioselectivity of the reaction is studied in quantitative, the predicted ee value is close to the experimental data.Our DFT calculations reveal a new reaction mechanism of Michael addition catalyzed by bifunctional thiourea catalysts, which is the addition reaction and protonation of the catalyst take place in one step. The present DFT study provides the details of the reaction mechanisms and explains the experimental results well. These results may not only help us better understand the role of chiral tertiary amine thiourea catalyst in asymmetric catalysis, but also provide a theoretical basis for improvement and promotion of chiral tertiary amine thiourea catalyst.