Construction Of Chiral Heterocycles By Copper Catalyzed Asymmetric Coupling Reaction

The chiral heterocyclic skeleton is a key structure in many drug molecules and natural products,and the chiral configuration is often closely related to its biological activity.Asymmetric coupling reactions catalyzed by transition metals are an important method for the construction of chiral heterocyclic compounds.Therefore,the development of cheap transition metal catalyzed carbon-carbon and carbon-nitrogen coupling reactions under mild conditions has important research value and has become a research hotspot in the field of synthetic chemistry.In this thesis,We used asymmetric copper-catalyzed synthesis strategy to realize the C-C coupling of 3-substituted amino-3-oxopropionate substrates and the C-N coupling reaction of malonamide substrates,and successfully constructed a series of chiral indole oxides and pyridone compounds.1.Copper-catalyzed asymmetric C-C coupling reaction of 3-substituted amino-3-oxopropionate substrates to construct chiral oxidized indolesThe catalytic system based on Cu I and a chiral diamine ligand realizes the intramolecular asymmetric aryl C-C coupling reaction of 3-substituted amino-3-oxopropionate substrates.This reaction can construct a series of chiral oxidized indole compounds with excellent yield,excellent enantioselectivity and wide substrates applicability under mild conditions.The problem that the substrate is easy to racemize and is not resistant to strong alkali is solved.2.Copper-catalyzed asymmetric C-N coupling reaction of malonamide substrates to construct dihydropyridone compoundsThe copper-catalyzed intramolecular alkenyl C-N coupling reaction of malonamide substrates was realized by asymmetric desymmetrical strategy.This reaction can obtain a series of chiral dihydropyridone compounds with good yield,moderate enantioselectivity and wide substrate applicability under mild conditions.