Copper Catalyzed Enantioselective Reactions Of β,γ-unsaturated α-ketoester

With the rapid development of modern science and technology, people have better view and deeper investigation of pharmaceuticals. The help and harm of chiral pharmaceuticals for people have been found, which promote the development of chiral technology. Various asymmetric frameworks were constructed by organic chemists via designing and synthetizing a variety of chiral ligands or catalysts for enantioselective reactions. It provides a tremendrous chiral molecules library for the development of pharmaceutical chemistry.Many frequently-used molecules in synthetic chemistry were formed in the process of continuous development of organic chemistry. In other words, these compounds were easy to form various useful frameworks. And β,γ-unsaturated a-ketoester is one of these important compounds. The molecule involve double bond, ketone carbonyl group and ester group, which make it easy to construct important chiral molecular framework via some reactions.Based on the case, we employed developed copper complex as the catalyst. A variety of reactions of β,γ-unsaturated a-ketoester were developed to synthetize important chiral molecular frameworks. Herein, we will introduce the dissertation from three sections.In section one, we combined copper salt with ligand derived from proline to form the complex as the catalyst. We envisioned that the catalyst could coordinate with the double carbonyl groups of β,γ-unsaturated a-ketoester, so that the catalyst could control the reaction position of nucleophilic reagent Danishefsky’s diene. Then, chiral dihydropyranones bearing double bond were obtained with high yields and excellent enantioselectivities. And the like, chiral dihydropyranones bearing triple bond (alkynyl group) were also prepared in good yields and enantioselectivities. Next, whether the reaction pathway is concerted cycloaddition or stepwise Mukaiyama Aldol pathway? Then, some investigations on the reaction mechanism were took. The conclusion was that the reaction pathway is substrate-dependent.In section two, the Freidel-Crafts reaction of pyrrole with β,γ-unsaturated a-ketoester was developed. The strong solvent effect was found, and good result was acquired in iso-propanol. The alkyl adducts were efficiently obtained with high yields and enantioselectivities. Then the scope of the substrate was examined. On this basis, in consideration of the importance of chiral seven-membered ring compounds, we designed β,γ-unsaturated a-ketoester bearing the alkynyl group in ortho position of the phenyl group. Friedel-Crafts reaction occurred firstly via the standard condition, then chiral seven-membered ring compounds bearing pyrrole were obtained through the attack of pyrrole to the alkynyl group under the gold catalysis.In section three, after acquiring the 1,4-addition products, we wanted to obtain 1,2-addition adducts via different types of catalysts. Chiral tertiary alcohol frameworks bearing pyrrole were acquired with moderate yields and good enantioselectivities when the complex from copper salt and Schiff’s base ligand was used as the catalyst. The enantioselectivity was not only achieved, the chemoselectivity was realized.In conclusion, the dissertation developed different reactions of β,γ-unsaturated a-ketoester through chiral Lewis-acid catalyst. The catalyst was formed from copper slat as metal center and different aminoacid-derived compound as the ligand. A variety of chiral compounds bearing different framework were synthetized, which enriched the chiral molecular library and provide the basis of the better development of pharmaceutical chemistry.