Palladium/Porous Organophosphine Ligand Polymer Catalyzed Hydros Ilylation And Synthesis Of Quinazoline-dione Compounds

Organic synthetic drug chemistry is closely related to human life.It is the dream and pursuit of scientists to synthesize small drug molecules accurately and efficiently like "enzyme".In the past few decades,scientists have developed many metal / ligand catalysts,which are used to synthesize and large-scale production of many high valueadded drug chemicals（eg,pesticides or drug candidates or lead drugs）.The development of most catalysts is restricted by the disadvantages of high cost,low yield,heavy metal residue and environmental problems caused by post-treatment.Therefore,the development of a catalytic system with high catalytic efficiency,more cycles and less metal residue is an effective means to realize the green synthesis of organic drug molecules.In this paper,a variety of new porous organic phosphine ligand polymers were studied and prepared.These polymers are new organic porous materials prepared by modifying and polymerizing homogeneous organic ligands.Using the loading technology of "metal-ligand exchange method",we derived it into a polymer catalyst with monatomic particle size active center,and applied it to selective hydrosilylation and cyclization of quinazoline-dione compounds.The thesis is divided into three parts:Part 1: This chapter summarizes the types of commonly used catalytic systems containing organic phosphine ligands and their catalytic reaction types.We summarize the advantages and disadvantages of various phosphine ligands by analyzing the electronic effect of metal complexation process and the steric effect of ligand skeleton,and provides a basis for the preparation of porous organic phosphine ligand polymers.Part 2: Vinylsilane is an intermediate with low toxicity,good stability,and high activity,which has been widely used in chemical synthesis,drug synthesis,and polymer field.Hydrosilylation of alkynes is an important way to realize the synthesis of vinylsilane.There are few reports on the simultaneous high selective hydrosilylation of secondary silane and tertiary silane with inactive internal alkynes in the same catalytic system.On the basis of fully exploring the traditional homogeneous metal / ligand catalytic system,a porous organic ligand polymer with 1,2-bis（diphenylphosphine）ethane（dppe）ligand as the skeleton was synthesized.After "metal-ligand exchange” with bis（triphenylphosphine）palladium（II）chloride,a single active site palladium catalyst was obtained as Pd@POL-dppe.At the same time,various functional groups are introduced into the ligand polymer to adjust the electronic properties of the catalytic center metal,so as to realize the hydrosilylation of internal alkynes with high catalytic performance.Compared with the homogeneous catalytic system,the selectivity and catalytic efficiency of Pd@POL-dppe-1 catalyzed hydrosilylation have been greatly improved.Asymmetric internal alkynes with various structures can react smoothly,and the E/Z ratio of products is as high as 100:1.Part 3: Quinazoline-dione skeleton widely exists in natural products and drug molecules,and its synthesis method has always been a research hotspot in organic synthesis.The synthesis methods with high atomic economy often use o-bromoaniline and isonitrile as reaction substrates to realize the chemical synthesis of quinazolinedione compounds in carbon dioxide atmosphere,but this gas-liquid two-phase reaction often requivuires high pressure and high temperature.Therefore,how to synthesize quinazoline diketones under mild conditions is a very challenging topic.In this chapter,porous organic polymers with tribenzylphosphine ligands as the core framework were designed and synthesized,and further coordinated with palladium to obtain a single active site palladium metal catalyst as Pd@POL-TBZP.Firstly,the multi-stage pore structure that can easily adsorb carbon dioxide is the key to realize the transformation of reaction system pressure from high to low.Secondly,the electronic properties of metal active centers can be adjusted by tribenzylphosphine ligands,so that metals can be easily oxidized and inserted into C-Br bonds.In this chapter,quinazoline-diones were successfully synthesized from o-bromoaniline,isonitrile and carbon dioxide（atmospheric pressure）using Pd@POL-TBZP as catalyst.The reaction has the advantages of low cost,high catalytic efficiency and no reduction in catalytic activity after repeated use of the catalyst for 10 times,which has a certain industrial application prospect.