| The osmium-catalyzed asymmetric dihydroxylation (AD) and asymmetric amino-hydroxylation (AA) of olefins provide the most effective methods for the preparation of chiral vicinal diols and B-amino diols respectively. As the chiral source of asymmetric induction, the chiral ligands control the procedure of stereochemistry in reaction. So the key of asymmetric reaction is design and synthesis of the chiral ligands. The chiral catalysts employed in the AD and AA reactions are complexes of osmium tetroxide with the chiral ligands. Although the reactions have found wide applications in organic and pharmaceutical synthesis, the high cost of osmium and the chiral ligands has prevented their application in industry. To solve this problem, several methods have been introduced for the recovery and reuse of the ligands and osmium tetroxide. The main method is to anchor the ligand on organic polymer or inorganic carrier, which can be recovered by separation from system after reaction. Among of these carried-ligands, soluble polymer-supported ligands, which combine the advantages of homogeneous catalysis with the easy separation, have achieved good catalytic activity and enantioselectivity. But soluble polymer-supported ligands still required complicated synthetic manipulations. Furthermore, a great deal of diethyl ether was required to recover the ligands, which made large-scale industrialization difficult. Recently Kuang reported a recoverable and reusable free ligand that could be recovered by precipitation upon addition a little of diethyl ether. No significant decrease in activity and enatioselectivity was observed within the first four recycles. This project aims at the development of economical, simple and highly effective recoverable and reusable free ligands for the AD and AA reaction of olefins, and has made following progress.1. Design and synthesis of two recoverable and reusable free bis-cinchona alkaloid derivativesLigand 1 was synthesized through four steps synthesic manipulation. 3,6-dichoropyridazine was reacted with quinidyl and dihydroquinidyl in presence of NaH in DMF. The side of quinidyl was reacted with 2-mercaptoethanol in the presence of 2,2-azo-bis-isobutyronitrile (AIBN) in CHCl3, then was oxidezed in the presence of OsO4 and NMO to give ligand 1. Ligand 2 was synthesized through two steps synthesic manipulation. 3,6-dichoropyridazine was reacted with quinidyl in presence of NaH in DMF, then was oxidezed in the presence of OSO4 and NMO to give ligand 2.2. Evaluation of two free bis-cinchona alkaloid derivativesLigand 1 and 2 were applied to the homogeneous AD reaction of many olefins respectively in BuOH-H2O (1:1) system. When the reaction was finished, the ligand was extracted with CH2Cl2 and precipitated upon addition of diethyl ether followed by filtration. Ligand 2 was also applied to the homogeneous AD reaction of eight olefins in Me2CO-H2O (9:1) system. When the reaction was finished, the ligand could be separated from diols by extraction with diethyl ether. Furthermore, ligand 1 and 2 were applied to the homogeneous AA reaction of four olefins. Enantiomer excess (ee) values of the products were determined by chiral HPLC. The results can be summarized as follows: a. Ligand 1 and 2 deliver very good enantioselectivity (85-99 %ee) and chemical yield (74-91%) for several olefins in 'BuOH-H2O (1:1) system, b. Ligand 2 deliver much better enantioselectivity for trans-disubstituted olefins (80-99 %ee) than for terminal olefins (51-62% ee) in Me2CO-H2O (9:1) system, c. With ethyl cinnamic as substrate of the AD reaction, the recovered ligand 1 and 2 was reused in 'BuOH-H2O (1:1) system. When a small amount of OsO4 (30% of the total amount of the first run) was added, no significant decrease in activity and enatioselectivity was observed within the first three recycles. Unfortunately, recovery rate were low (67-77%). d. With Trans-Stilbene as substrate of the AD reaction, ligand 2 was reused in Me2CO-H2O(1:1) system for nine times to show very excellent yields (88-92%) and enantioselecti... |
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