Asymmetric Synthesis Of Oxindoles And Chroman Derivatives With A Quaternary Center Via Organocatalytic Cascade Reactions

Synthesis of chiral compounds with a quaternary center via organocatalytic cascade reactions is studied in this thesis which is composed of three parts:Part1:The research process of the synthesis of chiral compounds with quaternary centers via organocatalytic cascade reactions in recent years is reviewedAs an important research area of organocatalysis, organocatalytic cascade reaction has been concerned widely and studied deeply. With the enrichment and perfection of new activation modes, new catalysts and catalytic systems, the efficient synthetic methods of organocatalytic cascade reaction have also developed rapidly. Through one-pot multistep reactions, complicated chiral products can be obtained from simple and readily available substrates via organocatalytic cascade reactions which have the advantages of mild reaction conditions, simple operation and good stereoselectivity control. Therefore, it is significant to synthesise nature products and bioactive molecules via novel asymmetric organocatalytic cascade reactions.Part2: Organocatalytic asymmetric multicomponent cascade reaction:an efficient strategy for the synthesis of spiro[pyrrolidin-3,2’-oxindoles]The spiro[pyrrolidin-3,2’-oxindoles] are privileged structural motifs that can be found in a large number of clinical Pharmaceuticals and natural spirooxindole alkaloids. With very simple and readily available starting materials, we have successfully established a catalytic enantioselective route to the biologically important spiro[pyrrolidin-3,2’-oxindole] scaffold using a bifunctional squaramide. Three new bonds and four contiguous stereogenic centers including one quaternary stereocenter were established in a single operation with reasonable yields and good stereoselectivity. More important, the application of biomimetic1,3-proton shift in asymmetric cascade reaction has never been reported (the first case was reported when we contributed). This transformation not only provided an efficient synthetic method for spiro[pyrrolidin-3,2’-oxindoles], but also extended the application of biomimetic1,3-proton shift. Part3:Organocatalytic asymmetric cascade reaction:an efficient strategy for the synthesis of chromeno[4,3-b]pyrrolidine derivativesChromeno[4,3-b]pyrrolidine are important structural motifs possessing a wide range of biologically activities, therefore, efficient methods for the expeditious generating of such compou-nds are highly desired for its rarely synthetic methods. We have developed an efficient strategy involving1,3-dipolar cycloaddition and intramolecular transesterification for the synthesis of chromeno[4,3-b]pyrrolidine derivatives between o-hydroxy aromatic aldimines and alkylidene azlactones using a bifunctional thiourea. With low catalyst loading and short reaction time, three new bonds and three contiguous stereogenic centers including one quaternary stereocenter were established in high yields and excellent stereoselectivity under mild conditions. A gram scale synthesis has also been tested to demonstrate the potential utility of this methodology.