Studies On The Design Of Novel Chiral Thioether-Phosphoramidite Ligand And Their Applications In Asymmetric Catalysis

With the continuous development of chiral drugs in pharmaceutical chemistry,the function of chiral compound in organism have been investigated more and more.Therefore,to develop more efficient method for asymmetric synthesis becomes a hot topic.It's no doult that the development of chiral ligands and catalysts is one of the key factors to realize the high efficiency and high selectivity of certain reactions.Based on the strategy of rational combination of two privileged backbones into one chiral scaffold,in this dissertation,we designed and synthesized one novel chiral thioether-phosphoramidite ligand containing both axial and central chirality and applied them in the metal catalyzed asymmetric catalysis.The detailed work are listed below:First,based on the concept of "rational combination of two privileged backbones into one scaffold",we developed a new class of chiral thioether-phosphoramidite ligands by combination of previlliged BINOL motifs and aminosulfide.By the moduler design of two mitifs,we introduced a set of substituents into P,S-ligand.Then,we applied these ligands in the Pd-catalyzed allylic reaction of indoles,furnishing the corresponding products with good yields(up to 99%yield)and good enantioselectivities(up to 98%ee).To furhter extend the application of our sulfoxide-phosphine ligand,we have developed Pd/sulfoxide-phosphine-catalyzed highly enantioselective allylic etherification and amination with a wide range of O-and N-nucleophiles.Successful transformations of the products into the corresponding chiral dihydrofuran and dihydropyrrole derivatives also highlighted the synthetic potential of these sulfoxide-phosphine ligands.In addition,we have described the application of our modular designed thioether-phosphoramidite ligand for highly enantioselective Cu(I)-catalyzed diastereodivergent 1,3-dipolar cycloaddition of azomethine ylides and nitroalkenes.Both of the densely functionalized endo-and exo-pyrrolidines can be obtained at will in good yields with excellent diastereo-and enantioselectivity.Mechanistic investigation suggests that the key to successful modulating the enforced sense of diastereoselectivity was presumably due to the tuning of the conformation and chiral environment of the catalyst by minor ligand modification.At last,we have successfully developed a copper-catalyzed asymmetric regio-reversed[3+2]cycloaddition of iminoesters with nitroolefins and CF3-containing alkenes.A wide range of polysubstituted chiral pyrrolidines bearing at least one chiral quaternary center were generated in high yields and with excellent regio-,diastereo-and enantioselectivities.The success of this reaction in achieving the umpolung of imines can be attributed to the use of our chiral P,S-ligand and the unique effect of the ?-aryl group of the iminoesters.