The Asymmetric Henry Reaction Catalyzed By Chiral Tridentate Schiff-Base Ligands And Their Polymer-Supported Ligands

Henry reaction is an important C-C bond forming reaction, the product β-nitroalcohol with wide application in the drug synthesis industry, which can be transformed to many useful chemical intermediates. Chiral tridentate Schiff-base is one of the promising ligands in the field of asymmetric catalysis, which can be applied in many asymmetric reactions. However, only a few studies used chiral tridentate Schiff-base ligands to catalyze asymmetric Henry reaction. Polymer-supported organocatalysts had some advantages such as easy to load, easy to recycle, reusable, good catalytic effect and so on which had made up for the deficiency of the small molecular catalysts, and these had injected new vitality for asymmetric catalysis. Therefore, the research of asymmetric Henry reaction which was catalyzed by using polymer-supported ligands has very important practical significance.In this paper,21kinds of ligands have been synthesized which were fourteen kinds of chiral tridentate Schiff-base ligands(Ll-L14), one kind of copper-complex catalyst(L15) and six Merrifield resin-supported chiral tridentate Schiff-base ligands(L16a-f). They were applied in catalytic asymmetric Henry reaction. The main contents and research results of this paper are as follows:1. The research status about various kinds of catalysts that applied in catalytic asymmetric Henry reaction in recent years were reviewed.2. Synthesis of chiral tridentate Schiff-base ligands.Treat the L-tyrosine methyl ester hydrochloride with Grignard reagent gave a chiral β-amino alcohols. Seven kinds of substituted salicylaldehyde were prepared from β-naphthol or salicylaldehyde. They were condensed in ethanol to give fourteen kinds of chiral tridentate Schiff-base ligands. The structures of these ligands had been character-rized by IR,1H NMR,13C NMR and MS.3. Asymmetric Henry reaction catalyzed by copper complexes of chiral tridentate Schiff-base ligands.The chiral tridentate Schiff-base ligands were applied in catalytic asymmetric Henry reaction of aldehyde with nitromethane. Different reaction conditions were tested in this process. The results showed that the ligand L1was the best catalyst. Under the optimized reaction conditions, different substrates had obtained very good results. Among them, the product with the asymmetric Henry reaction of o-chloro-benzaldoxime and nitromethane could obtain98%yield and98%ee value.4. Synthesis of Merrifield resin-supported chiral tridentate Schiff-base ligands and their application in catalytic asymmetric Henry reactionAccording to the results in chapter3, a kind of copper-complex catalyst(L15) and six Merrifield resin-supported chiral tridentate Schiff-base ligands(L16a-f) had been prepared. The structures of them had been characterized by IR. They were applied in catalytic asymmetric Henry reaction of aldehyde with nitromethane. Different reaction conditions were tested in this process. The results showed that under the optimal conditions, different substrates have obtained high yields(up to95%) and excellent enantioselectivities(up to90%ee). Compared to corresponding small molecule of copper-complex catalyst, their cycle performance were almost the same, the yields and ee values had little difference between them, but obvious the Merrifield resin-supported ligands had much more great advantages in recycling.