The Study On The Application Of The Derivates Of Amino Acids To The Catalytic Asymmetric Henry Reaction

Known as one of the important C-C formation reactions, Henry reaction, also named as the nitroaldol reaction, is a classical named reaction which is the addition of the nucleophilic nitroalkanes to the electrophilic carbonyl compounds. The product of this reaction,β-nitro alcohol, can be converted to versatile useful synthons, such as, reduction to P-amino alcohol, oxidation to carbonyl compounds, which are important to the synthesis of many nature compounds and pharmaceuticals. Although a lot of good jobs have been done on the catalytic asymmetric Henry reaction since the pioneer work in 1992, many challenges still remained in this area. Considering the importance of Henry reaction, designing and developing new catalyst systems are strongly desired. The study included four parts:1. Asymmetric Henry Reaction Catalyzed by a Copper-Schiff-Base ComplexBased on our previous work, starting from the nature phenylalanine, we designed and prepared series of chiral Schiff-base ligands. The yield and enantioselectivity of Henry reaction were enhanced by the modification of the substituents on the phenol ring of Schiff-base. The preparation of this catalyst was easy and the materials were cheap. Different types of aldehydes could react smoothly with nitromethane, giving the resulting products with 67-91% yield and 81-96% ee.2. Theoretical Study on the Asymmetric Henry ReactionBased on our experimental work, we proposed a mechanism. The mechanism had been theoretical studied by computational calculations, aiming to gain the potential energy profiles of the structures of the intermediates and transition states of the copper-Schiff-base catalyzed asymmetric Henry reaction. The results were in good agreement with our former experimental observations. Moreover, we found that the rate-limiting step was the one which generated the active nitronate piece. And the structure of the transition state of C-C formation with the lowest energy was in accordance with the model advanced by D. A. Evans.3. High Enatioselective Henry Reaction in Water Catalyzed by a Copper tertiary Amine Complex and Applied in the synthesis of (S)-N-trans-Feruloyl Octopamine.Inspired by our theoretical study, we speculated that increasing another five member ring to the catalyst and increasing the electron-withdrawing ability of the substituents on the phenol ring would enhance the efficiency of the catalyst. Starting from nature proline, we synthesized the trident-ligand with the trifluoromethyl group. The new catalyst system was successfully applied to the asymmetric Henry reaction in water. Synthetic valuableβ-nitro alcohols were gained with good enantioselectivities (almost all above 95% ee). Futhermore, our catalyst system could tolerate the acataldehyede (commercial available as an aqueous solution) and the hydroxyl-bearing aldehydes. The synthesis of (S)-N-Trans-Feruloyl Octopamine was finished by this catalytic system without any protection or depretection steps.4.Anti-selective Catalystic Asymmetric Henry Reaction Catalyzed by a Copper tertiary Amine ComplexExicting by the excellent enantioselctive Henry reaction in water, this new catalytic system was applied to the anti-selective catalystic asymmetric Henry reaction. The nitroalkanes could be nitroethane or nitropropane.19 different aldehydes could reaction smoothly with nitroethane, giving theβ-nitro alcohols with good dr value (almost all above 15:1) and ee (almost all above 95%).