Study On Bisphosphine Ligand-controlled Asymmetric Hydrogenation To Synthesize Chiral ?-amidoboronic Esters

This thesis mainly focuses on the synthesis of ?-boryl enamides as the substrate for hydrogenation reaction,and then synthesis of chiral?-amidoboronic esters by asymmetric hydrogenation under the control of chiral bisphosphine ligand.In the synthesis of ?-boryl enamides,this thesis explored two synthetic routes.The first route,we started with simple amide compounds,then converted it to alkenyl iodide compounds through phosphorylation and iodination.Then,Pd-catalyzed Miyaura boration reaction achieved the synthesis of acyl-protected ?-boryl enamides in good yields.The second route,we adopted monovalent Cu-catalyzed alkyne amine borohydride reaction to achieve synthesis of sulfonyl protected ?-boryl enamides.For the first synthesis route,this paper synthesized four different reaction substrates protected by carbonyl.For the second synthesis route,this paper synthesized three different reaction substrates protected by sulfonyl.Subsequently,in this thesis,the asymmetric hydrogenation reaction of?-boryl enamide substrates has been studied.The pressure,temperature,and reaction time of the hydrogenation reaction were investigated,as well as the solvent,transition metal,and chiral phosphine ligand were screened.We successfully obtained the target compound of chiral ?-amidoboronic esters protected by p-toluenesulfonyl and benzyl with a yield of 99% and an ee value of 98%.In this reaction,the ferrocene-type chiral bisphosphine ligand has the best reaction effect.The steric resistance and electrical property of the ligands can be controlled by changing the substituents on the phosphines,thereby controlling the activity and enantioselectivity of the reaction.The ?-boryl enamides synthesized by us in this topic can not only be used as important substrates for the synthesis of ?-aminoboronic esters through asymmetric hydrogenation,but also can be used as important organic synthesis block for various substituted alkenes.In addition,the realization of the synthesis method of chiral ?-aminoboronic esters by asymmetric hydrogenation provides a possible industrial synthesis strategy for drugs containing chiral ?-aminoboronic acid fragments.Besides,chiral?-aminoboronic esters can also be used as important precursor compounds in the synthesis of various chiral amino acids.