Catalytic Asymmetric Isatin Ketimines 1,2-addition Reaction And Nitrodienyne 1,4-addition Reaction

The classical 1,2-addition reaction and 1,4-addition reaction(Michael Reaction)is an important type of reaction of carbon-carbon bond-forming in organic synthesis.Furthermore,the majority of the products can be effectively converted into physiological activity molecules or intermediates.With the continuous development of chiral synthesis chemistry,catalytic asymmetric 1,2-addition reaction and 1,4-addition reaction has become a hot subject in the field of asymmetric catalysis.This dissertation turned mainly on the isatin N-Boc ketimines and nitrodienynes as substrates in asymmetric organic catalysis,including the following four parts.In the first part:the recent progress and application of the organocatalysis of conjugated nitroolefin 1,4-addition reaction,enantioselectivity construction of the challenging of vicinal tetrasubstituted stereocenters and organocatalytic asymmetric Mannich reaction between imines and aldehydes have been summarized.In the second part:we expand the application of primary amine-thiourea catalyst recently developed by us,the catalytic enantioselective conjugate addition of problematic aromatic ketones and acetone to nitrodienynes,high efficiently to obtain two kinds of 1,3-enynes compounds.Utilizing the resulting chiral functionalized 1,3-enynes as a starting point,we have developed unprecedented p-TSA-catalyzed divergent tandem annulations,which allow the rapid and efficient construction of various synthetically useful functionalized cyclic 1,5-diketones(R=Ar)and cyclic dienones(R=Me).In the third part:We have developed the tertiary amine-thiourea catalyzed asymmetric construction of vicinal tetrasubstituted stereocenters by the Mannich reaction of linear ?-substituted monothiomalonates(MTMs)with isatin N-Boc ketimines.High efficient and high enantioselective method has been constructed 3-aminooxindoles bearing vicinal tetrasubstituted stereocenters.Furthermore,the reaction also constitutes the first example of stereoselective synthesis of ?-amino thioesters bearing vicinal tetrasubstituted stereocenters.In the fourth part:Organocatalytic asymmetric Mannich reaction between isatin ketimines and acetaldehyde aqueous,one-pot method has been constructed ?-amino alcohol oxindoles.Gratifying,this method can be used to obtain ?-amino ester oxindoles rapidly,which is successfully applied to the synthesis of(-)-AG-041R.Currently,the enantio selectivity of the products are moderate,and further research has been carried out.