Design, Synthesis Of Axially Chiral Phosphine-Schiff Base Type Ligands Based On Binaphthyl Skeleton And Their Applications In Asymmetric Catalytic Reactions

This thesis was focused on the design and synthesis of axially chiral phosphine-Schiff base type ligands, and their applications in asymmetric catalytic reactions. It mainly includes two parts:one is to discover that axially chiral phosphine-Schiff base type ligands are effective ligands for Cu(Ⅰ)-catalyzed asymmetric reactions, including asymmetric Henry reaction,α-hydroxylation ofβ-ketoesters as well as a-chlorination ofβ-ketoesters; the other part is to use these ligands for palladium(Ⅱ)-catalyzed asymmetric reactions, including asymmetric allylic alkylation (AAA) and umpolung allylation of aldehydes.1 A series of novel axially chiral phosphine-Schiff base type ligands L1-L10 were designed and synthesized from optical pure 1,1'-binaphthyl-2,2'-diol (BINOL), and successfully applied in the Cu(Ⅰ)-catalyzed asymmetric Henry reaction. The corresponding adducts were obtained in moderate to good yields (28-87% yield) and good enantiomeric excesses (65-80% ee) under mild conditions. In addition, the active species of the catalytic system were explored by 1H NMR and 31P NMR spectroscopy studies on the reaction system. These studies suggest that Cu(Ⅰ) metal center can be potentially coordinated with the N, O and P atoms in ligand L4.2 Axially chiral phosphine-Schiff base type ligands L11 and L12, which have two phenolic hydroxy groups, were synthesized from optical pure 1,1'-binaphthyl-2,2'-diol (BINOL). These ligands were examined in Cu(Ⅰ)-catalyzed asymmetricα-hydroxylation ofβ-ketoesters. It was found that axially chiral phosphine-Schiff base type ligands L11 was an effective ligand for Cu(Ⅰ)-catalyzed asymmetricα-hydroxylation ofβ-ketoesters to give the corresponding products in high yields (90-99% yield) and moderate enantioselectivities (51-71% ee). By screening the various ligands, we found that the number of the phenolic hydroxy group in the chiral phosphine-Schiff base type ligands plays a very important role in chiral induction in this enantioselectiveα-hydroxylation ofβ-ketoesters. Although the real active species has not yet been fully understood, we believe that Cu(Ⅰ) metal center can be potentially coordinated with the N, O and P atoms in ligand L11 as we proposed in our previous studies.3 Axially chiral phosphine-Schiff base type ligand L12 is an effective ligand in Cu(Ⅰ)-catalyzed asymmetricα-chlorination ofβ-ketoesters to give the corresponding products in moderate enantioselectivities (50-82% ee) and good yields (78-99% yield) under mild conditions. Our catalytic system is a nice addition and extension of the area of asymmetric a-chlorination ofβ-ketoesters4 Axially chiral phosphine-Schiff base type ligands were examined in palladium(Ⅱ)-catalyzed asymmetric allylic alkylation. Axially chiral phosphine-Schiff base type ligand L12 is an effective ligand in palladium(Ⅱ)-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl-acetate with dimethyl malonate nucleophile to give the corresponding product in moderate enantioselectivity (71% ee) and yield (63% yield) under mild conditions. In addition, the effect of temperature, solvent and salt on this reaction was examined as well. We found that, using LiCl (10 mol%) as an additive,.there is an increase in the enantioselectivity.5 Axially chiral phosphine-Schiff base type ligand L3 is an effective ligand in palladium(II)-catalyzed and diethylzinc-mediated asymmetric umpolung allylation of aldehydes to give the corresponding products in moderate enantioselectivities (up to 68% ee) and good yields (25-94% yield). It was found that chiral ligands L11 and L12, which have two phenolic hydroxy groups, could not give the expected good results. In addition, the structure of the catalyst IV-C1 was determined through X-ray crystallography. The study may suggest that Pd(Ⅱ) metal center could be potentially coordinated with the N and P atoms in ligand L3 without O atom.6 The first example of chiral phosphine-catalyzed asymmetric allylic alkylation of MBH carbonates with oxindoles was examined. Some oxindoles, which may have biological significance in the natural compounds, were prepared in excellent enantioselectivies and good diastereoselectivies under the optimal conditions.