Synthesis And Applications In Asymmetric Catalysis Of Adjustable Axially Chiral Ligands

Development of chiral ligands and chiral catalysts has always been a hot pot in the field of asymmetric catalytic synthesis.The representative axially chiral cores should be[1,1’-naphenyl]-2,2’-diol（BINOL）and 1,1’-spirobiindane-7,7’-diol（SPINOL）,and BINOL and SPINOL derivatives have been extensively evaluated as the useful chiral ligands and catalysts in asymmetric synthesis.However,variations of substituent groups usually occur at 2,2’,3,3’-positions for modification of BINOL skeleton or at 6,6’,7,7’-positions for modification of SPINOL skeleton,and modification of BINOL or SPINOL at other positions often are unsatisfactory due to their inherent structural limitations.Therefore,the development of adjustable axially chiral ligand skeletons is of great significance in the field of asymmetric catalysis.In this dissertation,the design and synthesis of adjustable axial chiral biphenyl ligands and their applications in asymmetric catalysis were investigated,and some important results were obtained as follows:11 new axially chiral[1,1’-biphenyl]-2,2’-diol ligands（BIPHNOL）with different substituent groups at 5,5’,6,6’-positions were designed and synthesized.The 11BIPHNOLs（S）-L1～L11 with adjustable dihedral angles were prepared via the sequential reduction,oxidation,Wittig reaction,fluoridation,halogenation and Suzuki coupling using（S）-6,6’-dimethoxybiphenyl-2,2’-dicarbaldehyde as the starting material.Single crystals of（S）-L1,（S）-L3,（S）-L5 and（S）-L8 were obtained.According to their X-ray diffraction data,dihedral angles of（S）-L1,（S）-L3,（S）-L5 and（S）-L8 are 83.2^o,88.3^o,80.4^o and 81.2^o,respectively.The results show that variation of 5,5’,6,6’-substituent groups can all change the dihedral angles.Highly efficient and enantioselective additions of diethylzinc or alkynes to aldehydes have been developed in the presence of our new axially chiral BIPHNOL.Some axially chiral phosphoramidite ligands and phosphoric acid catalysts derived from our BIPHNOL were effectively synthesized and evaluated,and palladium-catalyzed asymmetric cycloadditions in the presence of phosphoramidite ligands,and chiral phosphoric acid-catalyzed asymmetric synthesis of 1,1’-spirobiindane-7,7’-diol（SPINOL）derivative and[4+3]cyclization were realized in high yields with good enantioselectivity.A highly efficient and enantioselective palladium-catalyzed[4+2]cycloaddition of cyclic N-sulfimines and 2-（N-sulfonylaminomethyl）allyl tert-butyl carbonate was developed in the presence of our new phosphoramidite ligands.The protocol used 5 mol%Pd（dba）₂ as the catalyst,5 mol%phosphoramidite（S）-L20 as the ligand,toluene as the solvent,and the reactions were performed at room temperature for 10 h.22 chiral products were prepared in 70～97%yields with 80～>99%ee,and the method showed good tolerance of function groups.A new method for palladium-catalyzed[4+2]cycloaddition of electron deficient alkenes and 2-（N-sulfonylaminomethyl）allyl tert-butyl carbonate was developed in the presence of our new phosphoramidite ligands,in which 5 mol%Pd（dba）₂ was used as the catalyst,5 mol%phosphoramidite（S）-L20 as the ligand,acetonitrile as the solvent,and the reactions were performed at room temperature for 1 h.Eight chiral piperidines were prepared in up to 88%ee.Although the yields are high,the enantioselectivity is unsatisfactory.The present experiments showed the feasibility of the reaction,and we will optimize the enantioselectivity of the reaction by adjusting the ligand structures.