Study On Chromatographic Enantioseparation Of Amino Acid Amides And Asymmetric Catalysis Of Sulfinamides

Most natural products have chirality.With the development of the research on the chiral substances,more and more chiral compounds have been widely used in medicine,fine chemicals and chiral materials.The enantiomers of chiral compounds have many similar physical and chemical properties.However,there are great differences in the performance for different isomers in vivo.Therefore,it is very important for people to obtain isomers which have a good effect on animal bodies.The usual methods for obtaining these single optical isomers are chiral resolution,chiral reagent transformations,asymmetric catalysis,and biosynthesis.This paper is divided into two parts: chromatographic enantioseperation of chiral amino acid amide derivatives by HPLC and synthesis of new chiral ligands and their application in asymmetric catalysis.Part one: Chromatographic enantioseperation of chiral amino acid amide derivatives.Among the many methods of chiral separation,chiral stationary phase method has been used more and more widely.Chiral amino acid amide derivatives as chiral drug intermediates are widely used.Although there are some studies on chromatographic enantioseparation of amino acid derivatives,study on chiral resolution of amino acid amide derivatives on chiral stationary phrases was rarely reported,chiral amino acid amide as important medicine intermediate,so study on separation by high performance liquid chromatography is also important.First of all,ten amino acid amide derivatives were synthesized according to our group reported synthetic methods.Then,chromatographic enantioseparation of the ten amino acid amide derivatives under various conditions was elvaluated in high performance liquid chromatography(HPLC),and thus the optimized chromatographiccondition was obtained.Secondly,under the optimized condition,the different conditions of the parameters are analyzed and compared.According to the difference of the structure of the compound,the effect of different groups on the separation effect was explained.A chromatographic enantioseparation mechanism is proposed.Part two: The asymmetric catalysis of N-aryl sulfinamide-olefin chiral ligands.Chiral ligands play an important role in asymmetric catalysis.At present,the chiral ligands such as phosphines,sulfoxides,and sulfinamides are commonly used as the "preveleged structures".First,several chiral sulfinamide-olefin ligands were synthesized based on the reported procedures.And then these chiral ligands were used in rhodim-catalyzed the conjugate addition of arylboric acid to cyclic ?,?-unsaturated ketones.The conditions for the ligands,bases and solvents were screened with cyclohexene and aryl boric acid as substrates.Secondly,under the optimized experimental conditions,the reaction of cyclohexenone,nitrostyrene,benzil,trifluoroacetophenone and a series of aryl boric acids were investigated.The results showed that nitrostyrene was not involved in the reaction.Benzil and trifluoroacetophenone reacted with aryl boric acids,but only low enantioselectivities were obtained.In summary,this thesis mainly studies HPLC chromatographic resolution of ten kinds of chiral amino acid amides.The effect of various factors,such as chiral solid phrases,column temperature,mobile phase on chromatographic separation of chiral amino acid amides are investigated.The chiral separation mechanism of chiral amino acid amides on chiral solid phases are explored from thermokinetic point.Chiral N-arylsulfinamide-olefin ligands used in rhodium-catalyzed enantioselective addition reactions are also studied in this thesis.