The Study Of The Chiral Induction Effect On The Cinchona Alkaloid Derivatives Catalyzed Asymmetric Epoxidation And Cyanation Reactions

Chiral cyanohydrins has been one of the hot research spot of asymmetric catalysis area due to its high value in the pharmaceutical and pesticide development. The original reagent for the reaction of cyanation reaction is currently still focusing on the the trimethylsilyl cyanide, so using of the less toxic cyanide source is quite valuable in the asymmetry synthetize of chiral cyanohydrins.Asymmetric epoxidation reaction is one of the most effective means to build the chiral three-membered ring, and this paper focuses on the challenging area of epoxidation research. Trying to construct a new catalytic system to consummate the asymmetric epoxidation of N-alkenyl sulfonamides and aldimines, in order to enrich the catalytic system, and further apply the chiral cyclopropane(including oxaziridine) to the total synthesis area.Cinchona alkaloids contain many chiral centers, rigid backbone structure and adjustability, making them to be one of the "priviledge skeletons" in the asymmetric catalysis. Cinchona alkaloids and their derivatives as chiral catalysts and chiral auxiliary agents have been widely used in the field of asymmetric catalysis. Based on the cinchona alkaloids, we constructed and synthesized some new Schiff bases and thiourea catalysts and applied them to in these three asymmetric reactions. The experiment results were pretty good. And the transition state of the catalytic process we also disscussed. This work about the synthesis of high enantioselective cyanohydrins and asymmetric epoxides of challenge substrates, is of great importance for the theoretical and practical value. The main contents are summarized as follows:1. A new bifunctional Titanium/Schiff base catalyst was developed for the enantioselective cyanoformylation of aldehydes with ethyl cyanoformate. The reaction proceeded smoothly with a mild reaction condition to afford the cyanohydrins ethyl carbonates in high yields(up to 96%) and good enantioselectivities(up to 85% ee).2. The asymmetric epoxidation of various N-alkenyl sulfonamides in the presence of cinchona alkaloids derived Schiff base and Ti(Oi-Pr)4 is reported. Under mild reaction conditions, the epoxidations of a series of allylic sulfonamides and homoallylic sulfonamides using the titanium complex of Schiff base were performed in o-xylene with CHP to afford chiral epoxy sulfonamides in moderate to high yields(up to 95%) and excellent enantioselectivities(up to 97% ee).3. Catalytic enantioselective oxaziridination is one of the challenging reactions in the oxidation of organic molecules. In this article, a series of novel chiral thiourea moleculars were synthesized from natural cinchona alkaloids and primary amines. By using these molecules as organocatalysts and m-chloroperoxybenzoicacid(m-CPBA) as the oxidant, a methodology on highly enantioselective epoxidation of aldimines has been developed. Several optically active oxaziridines have been constructed in good yields(up to 95%) and moderate to excellent enantioselectivities(up to 99% ee). A plausible transition state was also proposed.Experiments results show that, in this thesis, these two types of new catalysts based on the cinchona alkaloid can be effectively and highly selectively applied into the three asymmetric catalytic reactions. These new developed chiral catalytic system are cheap, and easy for synthesizing under mild reaction conditions, and their catalytic effect are quite good. The subject may have some good influences on the chiral cyanohydrin synthesis, nitrogen olefins epoxidation reaction and oxygen mixed nitrogen heterocyclic propane and this work has shown some important theoretical significance and broad application prospects.