Asymmetric Reactions For Unsaturated Compounds Catalyzed By New Lewis Base Catalytic Systems

Chiral Lewis bases with lone pair electrons have been widely used in many asymmetric catalytic reactions by donating their electrons to various electrophiles,such as aldehydes,electron-deficient olefins,allenes and so on.Great progress in Lewis base catalysis has been made in recent decades;however,the substrates scope and activation modes are relatively limited.For example,the electron-deficient olefins withβ-substitutents or evenβ,β-disubstitutents are challenging under the catalysis of Lewis bases,probably because the classic Lewis base catalysts,such as tertiary phosphines and tertiary amines,are too bulky to attack theβ-position of those activated olefins.In addition,simple non-activated olefins are totally inert under the Lewis base catalysis.Herein,we hope to develop new chiral Lewis base catalytic systems and new activation modes,thus expanding the scope of substrates or even achieving more challenging asymmetric reactions.In this thesis,novel Pd(0)π-Lewis base catalyst and thiol/chiral Br(?)nsted base catalytic system were developed for the asymmetric transformations of the above-mentioned challenging substrates.This thesis includes five parts:the first part is a brief review of the strategies for the construction of all-carbon-based tetrasubstituted olefins:carbometallation of non-terminal alkynes,carbonyl olefination,coupling of existing olefins and elimination reactions and so on.In the second part,we developed a three-component reaction of 1,3-enyne,boronic acid and electrophilic imine catalyzed by Pd(0)complex as aπ-Lewis base,and constructed a series of all-carbon tetrasubstituted olefins containing a chiral carbon chain with high stereoselectivity and regioselectivity.In this reaction,Pd(0)could sever as aπ-Lewis base to activate 1,3-enyne by formingη~2-Pd complex,which leading the HOMO-raised of triple bond of 1,3-enyne,and then easily attack the imines to form the aza-palladacycles intermidate,finally delivering enantioenriched all-carbon-based tetrasubstituted olefins by a facile Suzuki coupling process.The new Pd(0)π-Lewis base catalyzed asymmetric tandem reaction provides a new strategy for constructing of the complex architectures.In the third part,we disclosed the intermolecular cross Rauhut-Currier reaction of 2-cyclopentenone withα-cyano chalcones under the double catalytic system combining 2-mercaptobenzoic acid and a chiral Br(?)nsted base.The RC product could further undergo[4+2]cyclization reaction with nitroalkenes to construct a series of bicyclic derivatives containing six consecutive stereogenic centers.In addition,a different reaction pattern was observed when 2-cyclohexenone was employed instead of 2-cyclopentenone,furnishing[4+2]annulation product under the same conditions withα-cyano chalcones with high activity,through a domino cross-RC reaction and intramolecular O-Michael addition sequence.The thiol/chiral Br(?)nsted base catalytic system has the advantages of less steric hindrance and stronger nucleophilicity,which are helpful to facilitate the asymmetric RC reactions and other reactions forβ-substituted electron-deficient olefins.In the fourth part,we successful realized an asymmetric intermolecular Rauhut-Currier reaction ofα’-alkylidene 2-cyclohexenones and(7-aza)isatinylidene malononitriles under the double activation catalysis of chiral Br(?)nsted base and2-mercaptobenzoic acid,finally affording formal 3-arylated spiro(7-aza)oxindole derivatives in fair to excellent enantioselectivity after a tandem cyclization/aromatization process(up to 92%yield,>96%ee).In addition,more complicated skeletons could be constructed via further transformations of the products,which may be helpful for drug discovery.This work further developed the application of the double thiol/chiral Br(?)nsted base catalysis system in the construction of complex frameworks.In the five part,the summary of the three works.