Design And Synthesis Of The Novel Catalyst And Synthetic Methodologies Of Two Kinds Of Privileged Scaffolds

This dissertation contains two chapters.The first chapter presents synthesis and application a novel catalyst. The 3-substituted-3-hydroxy-indolin-2-one, especially the chiral 3-substituted indol-3-hydroxy-2-indolin-2-one, is a very important privileged scaffold in a lot of therapeutic bioactive products. The structure of chiral 3-substituted indol-3-hydroxy-2-ketone can usually be obtained by asymmetric Aldol reaction, and we found that chiral 2-amino-pyrimidin-4(H)-one derivatives can be used for catalyzing asymmetric Aldol reaction. We designed a novel 2-aminopyrimidin-4-one derivative catalyst with bi-functional feature which was synthesized from commercially available quinidine, and applied it to enantioselective synthesis of 3-substituted -3-hydroxy-indolin-2-one for the first time. We firstly selected the asymmetric Aldol reaction of isatin and acetone as the model reaction to evaluate the catalyst’s activity and enantioselectivity. We screened solvent, catalyst loading, substrate equivalents, concentration of the reaction and other factors to determine the best reaction conditions. And finally we carried out the substrate scope of research, the ee value was up to 94% and the yield was up to 92%. So we found the catalyst has wide applicability. We have discovered a new type of small molecule bifunctional catalyst, and successfully applied it to Aldol reaction to synthesize the privileged skeleton of 3-substituted indole-3-hydroxy-2-one, which has potential biological activity. This work contributed to important application value.The second part is a study of the selective arylation reaction of indazole nitrogen in the aqueous phase. Indazole derivatives have got a lot of attention as its biological activity, in particular mono-substituted derivatives on 1-position of indazole, this kind of compounds has shown peculiar good biological activity and treatment effect in many aspects of disease application. Here we introduced the concept of green chemistry, and added the surfactant with aqueous solution instead of the traditional organic solution to solve the solubility problems, but also promoted the Ullmann coupling reaction. In this chapter, we choosed Ullmann coupling reaction of indazole and 4-iodotoluene as a model reaction, and screened a series of conditions, such as catalyst, ligand, surfactantst, temperature and other conditions to determine the best reaction conditions. It ensured that the entire reaction was green, under mild conditions, and could gave mono-substituted product of indazole ring efficiently. We found surfactant could be widely used in copper-catalyzed Ullmann coupling reaction to obtain the mono-substituted indazole derivatives efficiently through the substrate scope research. We have successfully developped a green and efficient method to synthesize mono-substituted derivatives on 1-position of indazole selectively which has potential biological activity. This method have better appliedvalue.