Copper Catalyzed Enantioselective Reactions of 1,2-dicarbonyl Compounds and Electrochemical Synthesis of α-enaminones

Author:Li Ya Nan

Supervisor:wang zhi yong


Degree Year:2018





The research work of this thesis is divided into two parts:1.copper complexes catalyzed the asymmetric reactions of 1,2-dicarbonyl compounds;2.the synthesis of a-enaminones under electrochemical condition according to the research direction of the laboratory.The following are described separately.Part I.Asymmetric Reactions of Copper Catalyzed 1,2-Dicarbonyl Compounds1.Asymmetric hetero Diels-Alder reaction The Diels-Alder reaction is an important method to construct six-membered ring compounds,which has aroused widespread interest of organic chemists.With the tridentate ligand copper complex in laboratory,we developed the asymmetric hetero Diels-Alder reaction of Danishefsky’s Diene with glyoxals.The substrate had wide applicability and many dihydropyrones were provided with excellent enantioselectivities(up to 96%ee)and high yields(up to 96%).In addition,we have extended this catalytic system to the use of isatin as a substrate.Moreover,we also propose a reasonable and reliable reaction mechanism by separating intermediates.2.Asymmetric Henry reaction in waterThe Henry reaction is an important method of building C-C bond,and it has developed very well in organic solvents.However,the Henry reaction of pure water as a solvent is not yet perfect.In order to solve this problem,we succeeded in achieving a highly enantioselective Henry reaction of β,γ-unsaturated a-ketoesters with nitromethane in water by virtue of chiral copper complexes under the addition of surfactants and additives.A series of unsaturated β-nitro-a-hydroxy esters bearing tetrasubstituted carbon stereocenters were obtained exclusively with high yields and excellent enantioselectivities.In addition,we are able to achieve gram-scale asymmetric Henry reactions in water.3.Asymmetric Friedel-Crafts reactionThe Friedel-Crafts reaction is an important method of building C-C bond,and it is widely concerned by organic chemists.With the tridentate ligand copper complex in laboratory,we successfully achieved the chemoselective and enantioselective Friedel-Crafts reaction of pyrrole with isatin-derived β,γ-unsaturated a-ketoesters.It is worth mentioning that the reaction system is not afraid of water,and the target product could still be obtained in 90%yield and 92%enantioselectivity when 150 microliters of water is added.Part II.Synthesis of a-Enaminones under Electrochemical Condition The a-enaminones are widely found in natural products and are the key skeleton of many drug molecules with important biological activity.In this text,we developed a new method to realize the preparation of a-enaminones in good to excellent yields under mild conditions.This method requires no additional metal catalysts and oxidants.This reaction features high atom economy,easily available starting materials,metal-free process.The absolute configuration of the product was confirmed by X-ray crystal diffraction.