Studies On The Synthesis Of Novel Chiral Diamine Ligands And Their Application In Asymmetric Organocatalysis

In organic reactions, asymmetric synthesis of chiral compounds plays a very important role. Asymmetric Henry reaction and Michael reaction are very effective reactions to the construction of C-C bonds, and the reaction products are also very valuable intermediates, which can be applied in the synthesis of many chiral drugs and bio-active natural compounds. So the design and synthesis of new and efficient catalysts are very important.In this thesis, a series of new kinds of chiral ligands with diamine substrate were designed and prepared. Through coordinating with different metal ions, the chiral ligands were applied in catalytic asymmetric Henry reaction and Michael reaction. The specific researches we have done were divided as the following two parts:1. The design and preparation of the ligands.Inexpensive isosteviol, which was prepared by hydrolysis rearrangement from stevioside, was used as raw materials. A total of nine novel chiral diamine ligands have been prepared by introduction of functional subunit on C-16 and C-4, respectively, of the isosteviol to form the tertiary-tertiary amine ligands, secondary-tertiary amine ligands, secondary-secondary amine ligands and amino alcohol ligands. The structures of the new compounds were characterized by IR, 1H NMR, 13 C NMR and HR-MS.2. The studies on the application of the ligands in the asymmetric Henry reaction and Michael reaction.1). The catalytic activities and stereoselectivities of the ligands derived from the C-16 modification of isosteviol, through coordinating with transition metal ions, were evaluated in the asymmetric Henry reaction. For the asymmetric Henry reaction of nitromethane and benzaldehyde, the ligand L2, coordinated with Cu(OAc)2?H2O, have exhibited the best catalytic performance. Goodish yield and enantioselectivities were achieved.2). The catalytic activities and stereoselectivities of the ligands derived from the C-4 modification of isosteviol were also evaluated in the asymmetric Henry reaction. In the asymmetric Henry reaction of nitromethane and benzaldehyde, the ligand L9 and L10, coordinated with Cu(OAc)2?H2O, respectively, have exhibited optimal catalytic performance. The optimized reaction conditions were: ethanol as the solvent; ligand loading, 10 mol%, Cu(OAc)2?H2O, 10 mol%; reaction temperature,-50 oC and 1 equivalent of triethylamine. Under the optimized conditions, the catalytic activities and stereoselectivities of the ligands were evaluated in the a symmetric Henry reaction of 21 aldehydes(aromatic aldehydes and aliphatic aldehydes) with nitromethane and 10 aldehydes(aromatic aldehydes and aliphatic aldehydes) with nitroethane. Excellent results were obtained(up to 95% yield, up to 96:4 anti : syn and up to 98% ee). At last, the transition states and reaction mechanism of the catalyzed asymmetric Henry reaction were proposed.3). The ligands were applied in the asymmetric Michael reaction. In the asymmetric Michael reaction of 4-hydroxycoumarin and β,γ-unsaturated α-keto methyl ester, the ligand L9, coordinated with Cu(OAc)2?H2O, have exhibited optimal catalytic performance. The yield was excellent(up to 94%), but the enantioselectivities was far from satisfactory(only 44% ee).