Chiral SPA-catalyzed Asymmetric Synthesis Of Optical Active Nitrogen-containing Heterocyclic Compounds

Chiral phosphoric acid,as a novel chiral Br(?)nsted acid catalyst,is widely used in many organic asymmetric reactions,showing its advantages of high efficiency and high enantioselectivity and it has been considered as anprivilegedcatalyst.Chiral phosphoric acid catalysts contain both Lewis basic sites and Br(?)nsted acid sites in the molecule structure,which can activate both electrophilic and nucleophilic substrates,and thus it is a bifunctional organic catalyst.Because different types of reactions(even similar reactions of different substrates)have different requirements on the structure of the catalyst,it is a long-term task for synthetic chemists for innovating and designingthe novel structure(especially the framework)of the chiral phosphoric acid catalysts,developing new reactions,new methods and new strategies for asymmetric catalysis to synthesize more efficient and even more efficient reactions that catalyze important organic reactions.In this dissertation,a new type of chiral spirocyclic phosphoric acid(SPAs)based on a spinol framework developed by our research group is used to continue the development of new asymmetric catalytic applications with new reactions and new methods for nitrogen-containing heterocyclic compounds.This dissertation mainly contain following sections:Chapter one is the review paper on the synthesis and application of chiral SPAs in asymmetric catalysis,including Friedel-Crafts,Fischer Indolization,dearomatization,cycloaddition,insertion reaction,desymmetrization,Pictet-Spengler,multicomponent reaction,Conjugated addition reaction and so forth,and comparision of activity and enantioselectivity between chiral BINOL-phosphoric acid and SPA if possible.Chapter two is the asymmetric synthesis of benzazepinoindole derivatives with trifluoromethylated quaternary stereocenters by chiral phosphoric acid catalysis.An enantioselective aza-Friedel-Crafts reaction of trifluoromethyl dihydrobenzoazepinoindoles with pyrroles catalyzed by SPAs was developed.This methodology provides a facile route to CF3-and pyrrole-containing benzazepinoindoles bearing quaternary stereocenter in good yields and with moderate to excellent enantioselectivities(up to 93%ee).Indoles were also investigated as electron-rich aromatic substrates to afford the corresponding chiral heterocycles with good yields and considerable enantioselectivities.Introduction of CF3 shows a remarkable fluorine effect and increases the activation and stereoinduction.Chapter three describesthe SPA catalyed asymmetric 1,6-addition reaction for the construction of Unprotected 3,3-disubsitutited oxindole containg quaternary sterogenic centers.Un-protected Oxindole mehoid derivatives are reacted with indoles or pyrroles in the presence of SPA to make the C3 as quaternary seterogenic center,and afford to the unprotected 3,3-disubstituted oxindole derivatives containing quaternary centerwith moderate to excellent enantioselectivities.Chapter four describes the asymmetric synthesis of seven member cyclic amine catalyzed by SPAs.The reduction reaction ofseven member cyclic aldimines was carried out with hanzsctch ester and SPAsvia asymmetric transfer hydrogenation under mild condition to give the corressding seven member cyclic aminewith high yields and moderate to good enantioselectivities.