Studies On Cu-Catalyzed Asymmetric C-Heteroatom Bond Coupling Reaction And Its Chiral Analysis

Chirality is one of the essential attributes of the natural world. The enantiomers of chemical drugs that have chiral factors have significant differences in pharmacological activities, metabolism and toxicity in the body. In general, only one of the two isomers is effective, the other one is ineffective or even harmful. Therefore, chiral resolution and chiral synthesis have become urgent needs to solve the problems in pharmacological research and the pharmaceutical industry in order to meet the urgent needs of optically pure compounds.Asymmetric synthesis reaction that transition metal catalyzed is an important method to obtain chiral compounds. Currently, it is still of great challenge to build Carbon-Heteroatom bond through CopperCatalyzed asymmetric coupling reactions. In this thesis, we choose Cu(I)to be catalyst and successfully constructe a coupling reaction that can obtain chiral carbon-hetero compound containing C-N bond by kinetic resolution strategies. The main work is as follows:1. The construction of the kinetic resolution about asymmetric C-N coupling reactionWe used 4-chloro-iodobenzene and reacemic tert-butanesulfinamide as the substrates, and enantioselectively synthesized the chiral N-aryl sulfinamide compounds through copper catalyzed intermolecular arylC-N coupling reactions. After a large number of experiments, the product have achieved 60% ee and 86% yield.2. The expansion of the kinetic resolution about asymmetric C-N coupling reactionWe explored the adaptability of the substrates further under the optimal condition, and found that the reaction had a good substrate adaptability. Electron-withdrawing or electron donating substituent groups on the halogenated aromatic have little effects, however the steric effect has a significant impact on the yield and enantioselectivity of products, especially when the substituents are ortho.3. Characterization of chiral productsDetect the absolute configuration and enantioselectivity of the products by chiral HPLC analysis and optical rotation.In this thesis, we studied Cu-Catalyzed Asymmetric C-N Coupling Reaction in detail, and successfully constructed the kinetic resolution of asymmetric aryl C-N coupling reaction. Besides, the absolute configuration of the chiral products was analyzed.