Asymmetric Reactions Catalyzed By Thiol Related Double Activation Catalytic Systems

Thiols/thiophenols are good nucleophiles,and the central sulfur atom has fewer substituents and lower steric hindrance compared with traditional Lewis bases(such as tertiary amines and tertiary phosphines).However,it has been seldom used in asymmetric Lewis base catalysis.The main reason is probably because the resource of chiral thiols is relaltively limited;and these catalysts are not easy to dissociate from the substrates after forming neutral sulfides,thus difficult to complete the catalytic cycle.Based on the above research backgrounds,we developed new double activation catalytic systems by combining achiral thiols with other chiral catalysts,and explored their application in asymmetric catalysis.This thesis includes the following five parts:The first part summarizes the research progress for the double activation catalysis in organic synthesis in recent years.In the second part,an efficient double catalytic system,combining chiral amine and 2-mercaptobenzoic acid,was applied for α’,β-regioselective [4+2] annulations of2-cyclopentenone with a diversity of activated alkenes,constructing multifunctional chiral bicycle[2.2.1]heptane scaffolds in good to excellent yields and enantioselectivity.The new double catalytic system activated the cyclic enone together,which further expanded the application of cooperative catalysis system and thiol catalysis in asymmetric synthesis.In the third part,we realized the α’,γ-regioselective asymmetric formal [5+3]annulation reaction between unmodified MBH alcohols and cyclic 1,3-dipoles by using a chiral primary amine/thiol double activation system.Achiral 2-mercaptobenzoic acid has proved to be crucial for the chemoselectivity and enantioselectivity of the reaction.Besides,a spectrum of tricyclic frameworks bearing substantial substitutions were produced in moderate to high yields with good to excellent stereoselectivity.In addition,the products could be further transformed to tricyclic frameworks bearing spirocyclic/fused skeletons via simple reactions.This reaction further expanded the application of the primary amine/thiol catalytic system.In the fourth part,we developed an asymmetric [3+2] cyclization reaction of γ-substituted allenoates with different electron-deficient olefins under the double activation catalysis system of chiral phosphine and achiral thiol,constructing cyclopentene skeletons with vicinal stereogenic centers.In addition,further transformation could be realized from the resulting products bearing an acidic C-H group,efficiently furnishing a variety of complex architectures.This project developed a new phosphine/thiol double Lewis base activation system for the first time,which provided a new strategy for the construction of polycyclic frameworks.The fifth part briefly summarizes the key contents of the above research work.