Asymmetric Synthesis Of Oxindole Derivatives By Using The Chiral Bis(oxazoline)-Ni And Cinchona Alkaloid-derived Bifunctional Catalysts

Optically active oxindole derivatives constitute a ubiquitous structural motif in a variety of natural products and biologically active drug candidates. It is noteworthy that oxindoles bearing a quaternary carbon stereocenter at the 3-position of the indole ring play an important role in agricultural, pharmaceutical as well as biological chemistry. For example, chiral 3-amino-2-oxindoles have significant pharmaceutical and physiological properties. Therefore, chemists are devoted to constructing the 3-amino-2-oxindoles by some asymmetric strategies in recent years. As a result, some chiral catalysts for the asymmetric catalytic reaction were synthesized, and have been achieved the direct amination between anilines and 3,3-disubstituted oxindoles through asymmetric carbon-nitrogen bond-forming processes. The chiral tertiary alcohol framework occurs prevalently in a variety of natural products and biologically active compounds. Recently, tremendous efforts have been devoted to synthesize the attractive structures, by the ways of asymmetric oxidation, enantioselective desymmetrization, asymmetric carbenes insert secondary alcohols as well as nucleophilic addition. Among them, the aldol reaction of carbonyl compounds(ketones and aldehydes) with ketoesters is a straightforward way to obtain chiral tertiary alcohols. Based on the synthesis of the organocatalysts, we have reported the aldol reaction of the unsaturated ketoesters derivated from the isatins with acetophenones.In the first part of this thesis, some chiral catalysts were prepared according to the reported procedures. Our group synthesized some N,N- or N,O- chiral ligands and organocatalysts, such as bisoxazoles, salens, chiral thioureas and squaramides.The second part of this thesis mainly reported the bis(oxazoline)-Ni catalyzed asymmetric amination of anilines to 3,3-disubstituted oxindoles. After a series of screening optimization condition, which furnished the 3-amino-2-oxindoles with quaternary stereocenters in good yields with moderate enantioselectivities. Furthermore, we also investigated the stereoselective amination between 3,3-disubstituted oxindoles and α-amino-acid methyl esters at room temperature, which gave the desired products in high yields and moderate diastereoselectivities(up to 3.0:1 dr). In the third part of this thesis, we explored the asymmetric aldol reaction ketoesters with acetophenones catalyzed by chiral squaramide. In this reaction, the target products were provided in good yields and with good enantioselectivities.