| The osmium-catalyzed asymmetric dihydroxylation (AD) of olefins provides one of the most effective methods for the preparation of chiral vicinal diols. The chiral catalysts employed in the AD reactions are complexes of osmium tetroxide with chiral ligands. Although the reactions have found wide applications in organic and pharmaceutical synthesis, the high cost of osmium and the chiral ligands as well as the high toxicity of osmium compounds has prevented their use in industry. To solve this problem, several methods have been introduced for the recovery and reuse of the ligands and osmium tetroxide. One approach to recover the ligands is to anchor the ligand on an insoluble polymer. Despite the advantages of easy separation, the use of insoluble polymer-supported ligands suffered lowered catatytic activity and enantioselectivity due to the restriction of the polymer matrix, which resulted in limited mobility and accessibility to the active sites and thus obstructed the ligand-accelerated catalytic AD reaction. To combine the advantages of homogeneous catalysis with the easy separation of a ligand bound to the solid phase, cinchona alkaloid-type ligands were attached to a soluble polymer, polyethylene glycol monomethyl ether (PEG-OMe). Unfortunately, the PEG-bound mono-cinchona alkaloid ligand lacking anaromatic at its 9-O-position showed low enantioselectivity, and the PEG-bound bis-cinchona alkaloid ligands required complicated synthetic manipulations. This project aims at the development of simple and highly effective recoverable and reusable ligands for the AD reaction of olefins, and has made following progress.1. Design and synthesis of two novel soluble polymer-supported cinchona alkaloid-derived ligandsLigand 1 was synthesized through two different approaches, each involving two steps. In approach A, l-chloro-4-(9-(9-dihydroquinidinyl) phthalazine (I) was prepared according to the reported method. Then I was heated with PEG-OMe (MW-5000) in DMSO in the presence of NaH to give ligand 1. The overall yield of approach A was 64%. In approach B, a mixture of PEG-OMe (MW=5000), 1,4-dichlorophthalazine, K2CO3 and KOH in dry toluene was refluxed, with azeotropic removal of water, to give PEG-bound chlorophthalazine (II). Then II was treated with dihydroquinidine in dry toluene, with butyllithium as base, to give ligan 1. The overall yield of approach B was 86%. Both in approach A and B, 1,4-dichlorophthalazine was used as the coupling reagent to connect dihydroquinidine and PEG-OMe while providing an aromatic group at the 9-O-position of dihydroquinidine. Approach B is preferable for its high yield and convenience.Ligand 2 was synthesized through polycondensation of monomer 3, polyethylene glycol and terephthaloyl chloride in the presence of NEta. Monomer 3, which is a bis-cinchona alkaloid derivative, was synthesized through a three-step route. First, l,4-bis(9-Oquininyl)phthalazine (III) wasprepared according to the reported method. Then III was heated with 2-mercaptoethanol in the presence of 2,2-azobisisobutyronitrile (AIBN) in CHCls to givel,4-bis(9-O-ll-hydroxyethylthiodihydroquininyl)phthalazine (IV), which was oxidized to monomer 3.2. Evaluation of the soluble polymer-supported ligandsLigand 1 and 2 were applied to the homogeneous AD reaction of six olefins respectively. When the reaction was finished, the ligand was extracted with CFkCli and precipitated upon addition of diethyl ether followed by filtration. Enantiomer excess (ee) values of the products were determined by chiral HPLC. The results can be summarized as follows: a. Ligand 1 delivers much better enantioselectivity for fra玸-disubstituted olefins (93-98% ee) than for terminal olefins (79-90% ee). b. For the same olefins, ligand 1 produces considerably higher ees than the reported solube polymer-supported ligand DHQD-PEG-OMe, which lacks an aromatic group in the 9-0-position of dihydroquinidine. c. In general, ligand 2 showed better enantioselectivity than ligand 1, especially for terminal olefins (with the exception...
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