Synthesis Of Pyridyl Oxazoline Ligands And Their Applications In Asymmetric Catalysis

Chiral pyridyl mono(oxazoline) ligands (â…¢,â…£) and C₂-symmetric bis(oxazoline)ligand (â…¤) have been synthesized from the intermidiate (â… ) of anti-AIDS drugAmprenavir and the starting material chiral amino alcohol (â…¡) through a series ofapproaches. In addition, we demonstrate the effectiveness of the ligands in sometypical asymmetric benchmark-reactions, addition of diethylzinc to benzaldehyde andHenry reaction. The main works of this dissertation are listed as follows:1. Pyridine amide (â…¦) was synthesized by diastereoselective reduction ofcompound (â… ) to form the alcohol chial center, deprotection to give the key aminoalcohol (â…¥), and coupling with picolinic acid. Pyridine mono(oxazoline) ligand (â…¢)was prepared by using TBS protection, mesylation and ring closure with n-BuLi.2. Chiral ligands (â…£) and (â…¤) were synthesized from amino alcohol (â…£) whichacts as both chiral source and starting material. The amino alcohol (â…¥) was convertedto the corresponding hydroxyl amides after reaction with picolinic acid andpyridine-2,6-dicarbonyl dichloride respectively. After deprotection of the Boc andbenzoylation, pyridine mono(oxazoline) ligand (â…£) and bis(oxazoline) ligand (â…¤)were synthesized by cyclization in the presence of MsCl.3. The chiral ligands (â…¢,â…£,â…¤) were used as catalyst to promote theasymmetric addition of diethylzinc to benzaldehyde. The calalytic capability of theligand (â…¢) and ligand (â…£) was quite different, which shows that the substituentgroups on C-5' have great effect on the enantioselectivity. It was shown that themono(oxazoline) ligand (â…£) and C₂-symmetric bis(oxazoline) ligand (â…¤) induced theproduct with two opposite absolute configuration. In addition, C₂-symmetricbis(oxazoline) ligand (â…¤) shows better catalytic capability than the mono(oxazoline)ligand (â…£).4. Chiral ligands (â…£) and (â…¤) and their complexes with acetate copper wereused as enantioselective catalysts in asymmetric Henry reaction of benzaldehyde withnitromethane. The investigation indicated that the mono(oxazoline) ligand (â…£) gave higher enantioselectivity (50.3% ee) than the C₂-symmetric bis(oxazoline) ligand (V)(24.5% ee). A plausible mechanism for the opposite absolute configuration of theproducts has been proposed.