Research On The Design, Synthesis And Application Of Novel Chiral Oxazoline Ligands

The N on the oxazoline ring contains a lone pair of electrons,which facilitates the ligand to complex with the metal ion to form a more stable coordination bond,which allows the oxazoline ligand to exhibit excellent broad spectrum of metal coordination.At the same time,the chiral group on the chiral oxazoline is close to the coordination center,so that the chiral organometallic complex formed by coordination with the metal can play a strong role in the asymmetric catalytic reaction process Chiral induction.Therefore,compounds with oxazoline rings have received much attention,especially ligands containing chiral oxazoline rings.Although the abundance of fluorine-containing organic compounds in nature is very low,fluorine atoms have strong electronegativity and low nucleophilic properties,and fluorine substituents can adjust the pKa of the molecule,change the acidity and alkalinity of nearby groups,and increase the molecular It is lipophilic and has the ability to provide metabolic stability and bioavailability.Because of this,it has become more and more useful in medicine,agrochemicals,and materials science.The incorporation of fluorine atoms into molecules can make the molecules acquire many beneficial physical and biological properties,leading to widespread attention in the field of materials and pharmaceutical research,and leading to the development of many new drugs with fluorine atoms,especially on sp~3-C.Therefore,the synthesis of chiral organic fluorides is an important current.Although there are certain difficulties in the synthesis of CF bonds,there are indeed some related synthetic methods reported,most of which use ligands and metal reagents to form a catalytic system,or through its The chiral coordination complex formed as a catalyst to achieve asymmetric fluorination.The research content of this thesis mainly includes the following three parts:(1)Based on previous research,our research group designed and synthesized a new NON-type chiral bisoxazoline ligand.After screening the reaction conditions,the optimal synthesis route of the ligand was finally determined.The ligand has the advantages of cheap and readily available raw materials,simple and efficient synthetic methods,mild synthetic conditions,easy operation,good repeatability,and strong stability.In addition,all synthetic intermediates can be prepared in large quantities,which enables the ligand to be further promoted and applied.The ligand has good solubility,stability and chemical activity,can be stored at room temperature for a long time,and the best storage is low temperature storage.(2)We further optimized the reaction conditions by replacing or modifying the raw materials used,but due to the outbreak of the new coronavirus,our experiments could not continue,so we only synthesized two NON-type chiral bisoxazolines with different substituents Ligand.(3)The effect of asymmetric fluorination ofβ-ketoesters on the catalytic system formed by the new NON-type chiral bisoxazoline ligands and metal reagents was explored.By screening the reaction conditions such as metal reagents and reaction solvents,we finally obtained the optimal reaction conditions.The experiments show that the new NON-type chiral bisoxazoline ligand 1aa we designed and synthesized can catalyze different asymmetric fluorination reactions ofβ-ketoesters,and show high catalytic activity and stereoselectivity.