Amine Catalyst Alpha, Beta Unsaturated Carbonyl Compounds To The Study Of The Theory Of The Asymmetric Epoxidation Reaction

Enantioselective organocatalysis has been an important tool for constructingcomplex molecular scaffold owing to its high efficiency and high selectivity. So it has beenapplied widely in the fields of chemisty, pharmacy, biology and meterials. It requires efficientcatalysts to synthesize optically pure products in high yields via asymmetric organocatalyticreaction. Recently, a series of bifunctional chiral amines have been developed. The rigid tertiaryamine structure of cinchona alkaloid is a excellent chiral skeleton. The chiral diamine catalystsformed by incorporating primary amine group into the chiral scaffold are good choices forasymmetric organocatalysis. Thiourea with the strong ability of forming hydrogen bond, isreadily modified. Lewis basis functionality can be incorporated into it. thus activating both ofthe nucleophilic reagent and electrophilic reagent. In this paper, two kinds of chiral amines arechosen for investigation. The catalytic asymmetric epoxidation reaction and Michael-typecascade reaction have been investigated respectively using density functional theory.Conducting the theoretical studies on asymmetric organocatalytic reactions help us understandthe catalytic reaction process, ravel the role of bifunctional functionality played in the catalyticreaction as well as explain the experimental phenomenons. Thereby, provide theoretical guidefor developing or modifying organocatalysts.Cinchona alkaloid-derived chiral primary salts-catalyzed asymmetric epoxidation ofcyclic enone has been investigated using density functional theory. The results shows thatthe reaction proceeds in equatorial and axial pathways, yielding [2R,3R]-configuration and[2S,3S]-configuration product respectively. The catalyst serves as a bifunctional catalyst,The primary amine activates enone via forming iminium, while the tertiary amine canactivate H₂O₂ via deprotonation of H₂O₂. The catalytic reaction proceeds in two steps: step1is nucleophilic addition of hydroperoxyl toβ-C of enone with a simultaneous hydrogentransfer from H₂O₂ to tertiary amine. Step 2 is ring closure process. that is, formation ofC-O bond and cleavage of O-O bond with a simultaneous proton transfer from catalyst tohydroxyl. The enantioselecticity of the reaction is determined by the first step, while therate-limiting step is the ring-closure process. Equatorial pathway is favored over axial pathway, and [2R,3R]-configuration product is the main product. The mechanism issupported by the fact that the predicted er value is in agreement with the experimental data.Bifunctional-Thiourea–catalyzed asymmetric Michael-type cascade reaction ofβ,γ-unsaturatedα-keto esters andα-nitroketone has been investigated using densityfunctional theory. The results shows that the reaction proceeds in two pathways（denoted as Aand B）, yielding R-configuration and S-configuration product respectively. The reactionproceeds through a stepwise mechanism: First, the catalyst activate both of the nucleophileand the electrophile. Then reaction substrates undergo C-C bond formation, cyclization, C-Cbond cleavage, proton migration, dissociation of the complex, yielding products with therecovery of the catalyst. The enantioselecticity of the reaction is determined by theformation of the C-C bond. the rate-limiting steps are differert in the two channels. Inpathway A, the rate-limiting step is the migration of proton. while in the pathway B the C-Cbond-formation step is the rate-determining step. Path A is favored over B, R-configurationproduct is the main product. The mechanism is supported by the fact that the predicted eevalue is close to the experimental data.