Copper And Chiral Lewis Base Cooperatively Catalyzed Asymmetric Cyclization Reactions

The concept of merging metal catalysis and organocatalysis is a promising strategy,which allows for the simultaneous or sequential activation and reorganization of multiple chemical bonds,and leads to chemical transformations that not be accessible without this combination.Recently,a variety of innovative transformations with exquisite reactivity and selectivity have been established under the synergy of metal complexes and organocatalysts.Copper,as an earth-abundant and non-precious metal catalyst,has unique activity in carbon-carbon triple bond activation,single electron transfer and many other reaction processes.Chiral Lewis bases are capable of enhancing both the electrophilic and nucleophilic character of molecules to which they are bound,and effectively control the stereoselectivity of the reaction.Therefore,the cooperation between copper complexes and chiral Lewis bases can offer reactivity and stereocontrol that is beyond each catalyst in isolation,and enable considerable synthetic shortcuts and synthetic economies in the synthesis of complex molecules.The theme of this thesis is mainly about copper and chiral Lewis base cooperatively catalyzed asymmetric cyclization reactions.First,the asymmetric catalytic decarboxylative[4+2]annulation of ethynyl benzoxazinanones and carboxylic acids has been established by cooperative copper and chiral isothiourea catalysis,leading to a variety of 3,4-dihydroquinolin-2-one derivatives with excellent yields and stereoselectivities.The stereoselective control of this reaction was accessed via the synergistic effect of the chiral copper complex and the chiral isothiourea catalyst.Then,we developed an efficient isothiourea-catalyzed stereoselective[4+2]annulation of α-chloro cyclic hydrazones with carboxylic acids.Under mild conditions,a series of functionalized 4,4a,5,6-tetrahydrobenzo[h]cinnoline-3(2H)-one derivatives with two consecutive stereocenters were obtained in high yields with excellent diastereo-and enantioselectivities.This reaction can be carried out smoothly at a gram scale,providing an efficient method for the synthesis of this valuable heterocyclic compound.The spirocyclic oxindole unit is a privileged heterocyclic moiety that is prevalent in a great number of pharmaceutical molecules and biologically active natural products.Highly stereoselective[3+3]and[3+4]annulations of isatin-derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones were enabled by cooper/N-heterocyclic carbene(NHC)cooperative catalysis,leading to a big library of spirooxindole derivatives in high levels of structural diversity and stereoselectivity.Mechanism experiments show that the NHC not only serves as a Lewis base catalyst to activate enals,but also a ligand of the copper to tune the metal catalysis.Finally,we achieved copper/NHC cooperatively catalyzed efficient kinetic resolution(KR)of racemic N-tosylaziridines by[3+3]annulation with isatin-derived enals,leading to highly enantioenriched N-tosylaziridine derivatives and a large library of spirooxindole derivatives with high levels of structural diversity and stereoselectivity.By changing the ratio of the multiple catalysts,we can switch the chemoselection between KR and dynamic kinetic asymmetric transformation(DyKAT)of racemic electron-rich aryl substituted N-tosylaziridines.