Synthesis Of New Oxazolinyl Phosphrous Ferrocene Ligands And Their Applications In Catalytic Asymmetric Reactions

As Ryoji Noyori said, who win the Nobel Prize in 2001, the synthetic chemistry should be economical, secure, environmentally friendly and resources and energy conserved. In the past semicentennial, great achievements have been got in the asymmetric catalytic field, especially in transition-metal catalytic enantionselective reactions. In recent years, new concepts and methods have been presented to solve the problems during the process in transition-metal catalyzed reactions, such as the high priced transition-metal complexes, complicated synthetic route of ligands and the environmental pollution by the heavy metal contamination.In this thesis, a new series planar chiral ferrocenyl oxazoline phosphine ligands were designed and synthesized, based on the classical chiral ferrocenyl oxazoline phosphine ligands and ionic tagged ligands/catalysts used in asymmetric reactions. On the basis of enantioselective [3+2] 1,3-dipolar cycloaddition, the new ferrocene ligands were employed to the Cu-catalyzed asymmetric 1,3-dipolar cycloadditions. Over 50 examples of polysubstituted pyrrolidines were obtained, with high isolated yields and excellent stereoselectivities. The proposed mechanisms of ferrocenyl oxazoline phosphine ligands used in 1,3-dipolar cycloaddition were studied detailedly by the experimental and theoretical mechanistic methods. In addition, the synthetic route of ferrocenyl oxazoline thiourea derivatives have been discussed. The planar chiral ferrocenyl oxazoline thiourea compounds were achieved by the combination of the classical thiourea derivatives and planar chiral ferrocenyl oxazoline derivatives.(1) Synthesis of new planar chiral ferrocenyl oxazoline phosphine ligands.From the ferrocenecarboxylic acid, the ionic-tagged planar chiral ferrocenyl oxazoline phosphine ligands 2.1 were synthesized in 7 steps. Although the synthetic route of the new ligand was longer than the route of classical ligand, the total yield of the ligands was satisfactory through the appropriate designing methods.Take advantage of the solubility in water, the anions in the ion-tagged ligand were transformed to PF6-, BF4-, I- and Cl O4- through ion-exchange. The ligands containing different anions could be dissolved in common polar organic solvents and ionic liquids with 1-butyl-3-methyl-imidazole ion.The siloxane-tagged ferrocenyl oxazoline phosphine ligand 2.2 had been also published. Although the further synthesis to the ionic-tagged ligands from(S, Rp)-4-(hydroxydimethyl)methyl-2-[(2-diphenylphosphino)ferrocenyl]oxazoline was denied, the siloxane-tagged ferrocenyl oxazoline phosphine ligand was revealed as an excellent ligand in enantioselective [3+2] 1,3-dipolar cycloaddition with high reactivity and stereochemistry control.(2) Application of ionic-tagged ferrocenyl oxazoline phosphine ligands in asymmetric cycloadditionThe effective catalytic system, used in asymmetric [3+2] 1,3-dipolar cycloaddition with nitroalkenes, was structured by the ionic-tagged ferrocenyl oxazoline phosphine ligands and Cu Cl O4, dichloromethane as the solvent and N,N-diisopropylethylamine as the additive base. The polysubstituted pyrrolidines were synthesized with high yields and excellent enantioselectivity. The diastereoselective ratio of cycloadducts was up to 98:2. The enantioselectivity of exo-product was up to 99.6% ee.The steric hindrance built by the ionic segments, which resulted better enantioselectivity than the classical ferrocenyl oxazoline phosphine ligands, was demonstrated by the experimental and theoretical studies. The cycloaddition could be reacted with weak base by the advantage of the electrostatic interaction between the imidazole ion and azomethine ylide, and the stabilization of conjugate acid by the anion in the ligand. Moreover, the Michael adduct as the by-product was restrained.Taking advantage of the solubility of ligands in ionic liquid, the asymmetric 1,3-dipolar cycloaddition was catalyzed in DCM/ionic liquids combined solvent. The Cu(I)-catalyst could be recycled and reused for at least 5 times. The cycloadduct 3.3i was afford greater than 91 % ee during four recycle times.(3) Application of siloxane-tagged ferrocenyl oxazoline phosphine ligands in asymmetric cycloaddition.The application between Cu(II) and ferrocenyl oxazoline phosphine ligand was reported firstly. The synthesized siloxane-substituted ligand was successfully applied in the enantioselective 1,3-dipolar cycloaddition of azomethine ylides with alkylidene malonates. The cycloaddition was proceeded in economical way, using only 4 mol% CuII-catalytic loading and 10 mol% additive base. The pyrrolidine 2,4,4-tricarboxylate derivatives were obtained in 77-99% yields, and up to 99.2% ee.(4) Design and synthesis of ferrocenyl oxazoline thiourea derivatives.The planar chrial ferrocenyl oxazoline thiourea derivatives were designed and synthesized, inspired by the bifunctional thioureas in asymmetric organocatalysts and new ferrocenyl oxazoline compounds. Three independent group, such as methyl, hydroxydiphenylmethyl and iodine, were synthesized as the planar substituent, connected with(S)-4-(tert-Butyldimethylsilyloxy)methyl-2-ferrocenyl oxazoline. Furthermore, the ferrocenyl oxazoline thiourea derivatives were obtained through the OTs-N3-NH2-thiourea synthetic route.