Design And Synthesis Of Novel Chiral Nitrogen-Containing Ligands And Their Applications In Catalytic Asymmetric Reactions

Catalytic asymmetric synthesis has emerged as an essential part in modern organic synthesis, and as the sole method involving amplification process of chirality in asymmetric synthesis, it has been also one of the most promising methods to obtain the chiral compounds. Research and development of novel chiral ligands have always been the focus, but also the difficulties of research in the field of asymmetric catalysis.Novel chiral N-contianing ligands were designed combined with structure features of 2,3-dihydroimidazo[1,2-a]pyridine(DHIP) scaffold, and the dissertation mainly focused on the design and synthesis of a series of novel chiral N-contianing ligands, including planar-chiral element introduced ligands, and also their applications in catalytic asymmetric reactions. Specifically including the following aspects:1. Deign and synthesis of novel chiral N-contianing ligands. Four series of novel chiral N-containing ligands,32 totally, based on DHIP (DHIIQ or Fc-DHIP) scaffold were prepared, integrated with "e-switch" concept, which no wonder would provide us adequate library of chiral ligands for the further screening in asymmetric catalysis and better understanding of the unique characteristics of the ligands.2. The application of N-containing ligands in asymmetric Michael reaction. The N-containing ligands were tested in asymmetric addition of glycine Schiff base to alkylidene malonates, and it was finally found that N,O-ligand (S, Sp)-L3 afforded the addition products in best results with 79-98% yield,67/33-94/6 dr and 89-93% ee, while up to 99% ee was obtained after simply recrystallisation for most compounds.3. The application of N-containing ligands in asymmetric Vinylogous Mannich reaction. A novel asymmetric Vinylogous Mannich reaction of TMSOF and imines derived from isatine was developed, and the sulfonamide ligand (S)-L2-8a was found suitable for the reaction well to give the best result in good yield, up to 99% ee and 99/1 dr. This method has provided a new route to synthesis chiral oxindoles with potential biological activity.4. Preliminary research on other applications of N-containing ligands. The N-containing ligands were also tested in asymmetric aza-Michael reaction and Michael addition of stork enamine to alkylidene malonates.