The Design And Synthesis Of Novel N,O-Ligands And Their Applications In Catalyzed Asymmetric Reaction

This thesis mainly focused on the design and synthesis of novel N,O-bidentate Ligands and their applications in catalyzed asymmetric reaction. In the background of the applications of N,O-ligands are very limited, we designed and synthesized a series of new 1,2-dihydroimidazole based N,O-bidentate ligands. When the coordination of ligand to metal, we would like to come true that the coordinating atom could easily equilibrate fromπcoordination state to covalent a state during the catalytic cycle through aromatization. The applications of novel N,O-ligands in catalysed asymmetric Mannich addition, Michael addition and 1,3-dipolar cycloaddition are developed. The thesis includes four aspects of studies:1. Design and synthesis of novel 1,2-dihydroimidazole based N,O-ligandsL-Phenylglycinol was used as chiral source, we designed and synthesised new 1,2-dihydroimidazole quinoline based N,O-ligands L1 and 1,2-dihydroimidazole isoquinoline based N,O-ligands L2. Then, we synthesised chiral unnatural amino alcohol II-9,11-13,11-15 and 11-19. These amino alcohols were used as chiral source, we synthesized 1,2-dihydroimidazole quinoline based N,O-ligands L3-7.2. The application of N,O-ligands in catalysed asymmetric Mannich reactionWe developed efficient N,O-Ligand catalytic enantioselective Mannich reaction of glycinate derivatives with imines. The newly developed N,O-Cu(OAc)2 derived chiral complex was demonstrated as an efficient catalyst for inducing asymmetry in the synthesis of chiralα,β-diamino acid derivatives syn-as major products in excellent yields (53-90%), moderate dr (54:46-95:5) and enantioselectivities (56-85% ee).3. The application of N,O-ligands in catalysed asymmetric Michael additionWe developed the first highly efficient catalytic diastereo- and enantioselective 1,4-addition of glycine derivatives to alkylidene malonates in the presence of chiral N,O-Cu(OAc)2 complexes to afford 3-aryl glutamic acids derivatives in good yields (82-98%), moderate dr (80:20-89:11) and high stereoselectivities (up to 83% for anti and 90% for syn adducts respectively). Higher optical purity (up to 99% ee) of anti adducts were obtained after simple recrystallisation, and their conversion to free 3-aryl glutamic acids was demonstrated by a representative example, chlorpheg, via a one pot process in 72% yield.4. The application of N,O-ligands in catalysed asymmetric 1,3-dipolar cycloadditionWe developed a highly efficient catalytic enantioselective 1,3-dipolar cycloadditions of azomethine ylides with various alkylidene malonates. The newly developed N,O-Cu(OAc)2 derived chiral complex was demonstrated as an excellent catalyst for inducing asymmetry in the synthesis of highly functionalised pyrrolidines exo-as major products (as exo-adducts for most of substrates) in excellent yields (80-99%) and enantioselectivities (91-99% ee). In addition, we obtained a suitable crystal for determining the X-ray crystal structure of protonated N,O-ligand (V-9), instead of desired copper complex crystal, when the same equivalent of ligand L3 and Cu(OTf)2 were mixed in solvent. treatment of 9 with t-BuOK regenerated ligand L3. The reversible process between L3 and 9 provides ancillary support for our proposed catalytic cycle.