Catalytic Asymmetric Henry And Aza-Henry Reaction

Catalytic asymmetric synthesis is currently the most cost-effective route to prepare chiral drugs and its intermediates. Asymmetric Henry and Aza-Henry reaction are two important methods to form new carbon-carbon bonds in organic synthesis. Theβ-nitro alcohol and nitroamine adducts of those two reactions can be easily converted into important building blocks, such as chiral aldehydes,α-hydroxy ketones, carboxylic acids,β-amino alcohols,α-amino acids and 1,2-diamines according to the need.Generally, the catalysts used in asymmetric synthesis include metal complexes and organocatalysts. They are both useful and effective catalysts, and have been used in a number of asymmetric reactions. Herein, we use the most"privileged organic chirality inducers"—cinchona alkaloids to synthesize a series of chiral Schiff base ligands and a series of quaternary ammonium salts.The Schiff base ligands coupled with Cu(OAc)2 can catalyze the asymmetric Henry reaction. Quaternary ammonium salts were prepared for the asymmetric aza-Henry reaction as phase transfer catalysts. In this thesis, the preparation of the above catalysts and development of catalytic processes for two reactions were reported. The main works that we have done were shown in the following list:1. Prepared the Schiff base ligands from 9-amino(9-deoxy) cinchona alkaloids with benzaldehyde or its derivatives, then coupled with Cu(OAc)2 to get the Cu(II)/Schiff base complexs. The complexs were used as catalysts in the asymmetric Henry reaction of a viraety of aldehydes (included aromatic aldehydes, heterocyclic aldehyde and aliphatic aldehydes) with nitroalkane (included nitromethane and nitroethane). As the result shown, under the optimised conditions, Cu(II)/75a complex can catalyze the reaction with high performance. For the Henry adducts, up to 99% ee,75:25 dr,and 84% yield could be obtained. We also studied the mechanism of this reaction based on the X-ray single crystal structure of ligand 75a and experiment data.2. 10 kinds of quaternary ammonium salts were prepared by cinchona alkaloids and 2-chloromethylbenzimidazole or 1-(chloromethyl)-1H-benzotriazole. They were applied into asymmetric aza-Henry reaction of tert-butyl phenyl(phenylsulfonyl)methylcarbamate 90a or its derivatives 90b-u with nitroalkane. Under the selected conditions, we found that PTC 82a was the most outstanding one among them. In present of water, 82a can catalyze the aza-Henry reaction with up to 94% yield, 99% ee for an extremely broad substrate's scope. Even when the loading of catalyst decreased to 2 mol%, the enantioselectivity of the product hasn't decreased. When nitroethane instead of nitromethane was used, the products could be achieved with up to 99:1 dr, 99% ee and 78% yield.To sum up, we have succefully developed two new catalyst systems for the Henry and aza-Henry reaction with high enantioselectivity and diastereoselectivity, respectively. The loading of catalysts were low, and the corresponding products were useful. Also, the preparations of the catalysts were simple with low cost and high yields. So, those two catalystic processes are useful methods to synthesize the important buiding blocks of chiralβ-nitro alcohols and nitroamine compounds.