Thiourea Organocatalysts Bearing Multiple Hydrogen-bonding Donors And Their Application In Asymmetric Catalytic Reactions

Over the course of the last decade, asymmetric organocatalysis hasemerged as a new, powerful and environmentally friendly methodology for thecatalytic synthesis of enantiomerically pure organic compounds and also as oneof the most rapidly growing and competitive research area in synthetic organicchemistry besides metal and enzyme catalyses.As a chiral hydrogen bonding ligand, thiourea has a strong ability to formintermolecular hydrogen bonds with substrates, thus activating the reactants toget the purpose that the bifuntional effect could be realized due to the multiplehydrogen bonds between the catalyst and the substrates. It is now widely appliedin Michael addition, Aldol addition, Morita-Baylis-Hilllllan reacton, et al.In this thesis, a series of new modular bifunctional chiral thioureaorganocatalysts were synthesized from nature cinchona alkaloids and aminoacids, and their performance in asymmetric organocatalysis were investigated.The main work I have done consists mainly of following three parts: 1. A series of new modular bifunctional chiral thiourea organocatalystswere synthesized from nature cinchona alkaloids and amino acids.2. It was found that the bifunctional chiral thiourea catalysts are effectivefor the asymmetric Michael reaction of acetone to nitroalkenes.Especially the compound59c, prepared from quinine and phenylglycine,exhibits good catalytic activity. Under the optimum conditions, thereaction ran smoothly to get the corresponding products in up to92%yield and up to99%ee. We also studied the mechanism of this reaction,a transition-state model has been proposed to account for the excellentstereocontrol based on the X-ray single crystal structures of catalyst59cand product73h. The bifunctional chiral thiourea catalysts are alsoeffective for the asymmetric Michael reaction of acetylacetone tonitroalkenes. As the result shown, under the optimised conditions, usingcatalyst59e, the final products were obtained in good yields (up to95%)and high enantioselectivities (up to97%ee).3. The performance of these new modular bifunctional chiral thioureaorganocatalysts were also studied in asymmetric Aldol reaction andMBH reaction. When catalyst59j was used to catalyze Aldol reactionof acetone to4-nitrobenzaldehyde, as the result shown, the finalproducts were obtained in79%yield and76%ee. When59i wasapplied to catalyze MBH reaction between methyl acrylate andN-(p-chlorobenzenesulfonyl)imine (N-nosylimine), the correspondingproducts were obtained in54%yield and30%ee.To sum up, it was found that these new modular bifunctional chiralthiourea organocatalysts can be effectively applied in the asymmetric Michaelreaction of acetone to nitroalkenes and Michael addition of acetylacetone to nitroalkenes. It could be performed in mild reaction conditions, low cost, highyield and excellent enantioselectivity, and its adducts of the two reactions have avery important practical value in pharmaceutical and chemical areas, and thecatalystic processes provide a new catalytic system for the development of thetwo transformations. Our preliminary studied in the new modular bifunctionalchiral thiourea organocatalysts performance in asymmetric Aldol reaction andMBH reaction show that the organocatalysts have a very broad prospects inother asymmetric catalytic reactions.