Chiral Spirocyclic Phosphoric Acid Catalyzed Asymmetric Tandem Reaction For Synthesis Of Tetrahydropyridine And Benzazepinoindole Derivatives

Chiral phosphoric acid is a highly efficient and enantioselective Br(?)nsted acid organocatalyst, which has been widely used in catalytic asymmetric synthesis, particularly in catalytic asymmetric tandem reactions. This dissertation mainly focuses on asymmetric tandem reactions catalyzed by chiral spirocyclic phosphoric acids (SPAs) invented by this group for the synthesis of some nitrogen-containing heterocyclic compounds. The results are:1. A highly enantioselective multicomponent tandem reaction (A2B2C type) catalyzed by chiral spirocyclic phosphoric acids has been developed. The first catalytic asymmetric pseudo five-component (A2B2C type) reaction between aromatic aldehydes, anilines and β-ketoesters afforded highly functionalized enantioenriched tetrahydropyridines with high levels of sterecontrol. Under the optimal reaction conditons of10mol%of (S)-6,6’-di-3,5-trifluoromethyl-phenyl-SPINOL-phosphoric acid, toluene,4A MS at-30℃, seventeen optically active tetrahydropyridine derivatives were obtained with up to>99%ee. Furthermore, the fully substituted tetrahydropyridine derivative was also obtained with excellent diastereo-and enantioselectivity. The absolute configuration of the product was confirmed by X-ray analysis. As a further demonstration of the utility of this protocol, the reduction of tetrahydropyridine produced the enantiomerically enriched piperidine.2. A general, mild and flexible method providing access to enantiomerically enriched benzazepinoindoles bearing trifluoromethylated quaternary stereocenters has been developed by utilizing the catalytic asymmetric Pictet-Spengler-type reaction. Under the optimal reaction conditons of5mol%of (S)-6,6’-di-3,5-trifluoromethyl-phenyl-SPINOL-phosphoric acid, dichloroethane,4A MS,and35℃to80℃, thirty-one optically active benzazepinoindoles were obtained in high yields with excellent enantioselectivities from C-2-linked o-aminobenzylindoles and phenyl trifluoromethyl ketones. The reaction employs the powerful and fully recyclable chiral spirocyclic phosphoric acid and involves a simple scalable experimental procedure without protecting group or activating group. The absolute configuration of the corresponding product was confirmed to be (S) by X-ray analysis. A theory of compution supported possible mechanism was proposed that the multifunctional nature of the chiral phosphoric acid concurrently activates both the nucleophilic group and electrophilic iminium intermediate.