Copper And Organocatalysts Cooperatively Catalyzed Asymmetric Cascade Cyclizations

Copper,an earth-abundant and non-noble metal,has been increasingly coming into focus in organic synthesis in recent years.In the past decades,merging organocatalysis with copper catalysis has become a rapidly growing field in asymmetric catalysis.The synergistic combination of copper catalysis and either of chiral amine,chiral Br(?)nsted acid,chiral Br(?)nsted base or chiral Lewis base catalysis is able to expand the capability of individual catalysis and further allows many elusive or unattainable transformations to be accessed.Therefore,the development of new catalyst systems will be greatly valuable in organic synthesis.The research themes of this thesis will be focused on the development of catalytic enantioselective cascade cyclizations enabled by the cooperative catalysis of copper complexes and chiral bases for the manufacture of chiral heterocyclic compounds in high enantiomeric purity.The catalytic enantioselective decarboxylative propargylation/hydroamination reaction of ethynyl benzoxazinanones with malononitriles enabled by organo/copper cooperative catalysis has been established.A diverse range of densely functionalized 3-indolinmalononitrile derivatives could be obtained in good yields with high levels of enantioselectivity.It turns out that the matched chirality of chiral copper complex and the urea-cinchona organocatalyst allows this cascade decarboxylative propargylation/hydroamination reaction to give high enantioselectivity.Dihydrofurans have emerged as one of the most commonly observed classes of structural units in natural products and useful synthetic intermediates in organic synthesis.We have developed an organo/copper cooperatively catalyzed asymmetric decarboxylative[3+2]cycloaddition reaction of ethynylethylene carbonates with malononitrile to afford a series of optically active polysubstituted dihydrofurans in good yields with high levels of enantioselectivities.More importantly,the presence of the terminal alkynyl and cyano groups in the dihydrofuran products provides more opportunities for further structural modulation.A[3+3]cyclization reaction of a,(3-unsaturated aryl esters has been established by chiral isothiourea/copper and chiral isothiourea/Br(?)onsted acid cooperative catalysis,respectively.This protocol provides a highly efficient method for the rapid synthesis of valuable enantioenriched 3,4-DHP-2-ones.