Asymmetric Michael Addition Of 5H-Oxazol-4-ones To α,β-Unsaturated Ketones Catalyzed By Novel Primary Amine Catalyst

In this thesis, we have realized the efficient and highly stereoselective asymmetric Michael addition of 5H-oxazol-4-ones toα,β-unsaturated ketones by utilizing novel primary amine catalysts.The first part of the research work is the design and synthesis of novel primary amine catalysts. According to the mechanism of primary amines in iminium and enamine catalysis we selected L-tertiary leucine as the starting material, and synthesized a series of bifunctional primary-secondary amine catalysts and primary-tertiary amine catalysts.Then we carried out detailed research of the methodology of primary amine-catalyzed Michael addition of 5H-oxazol-4-ones to a,p-unsaturated ketones. After a comprehensive study of different factors such as the chiral catalysts, solvent, additives, temperature and concentration, we have determined the optimum reaction conditions. Under the optimized reaction conditions, a wide range of substrates were found to be good reactants in the system, affording the adducts in excellent yields (up to 99%) with high enantioselectivities (up to 99% ee) and diastereoselectivities (> 99:1 dr).Through the simple switch of chiral catalyst systems, we have successfully realized the diastereodivergent asymmetric Michael addition. Under the optimal reaction conditions, the adducts could be afforded in satisfactory yield (up to 90%) and stereoselectivities (dr value as good as 2:98 and ee value as high as 88%). This method has opened up a new approach for the simple and high efficiency fulfillment of enantiomer-selective Michael addition reaction, also provided an alternative for constructing chiral 5,5-disubstituted oxazol-4-ones.