Synthesis Of New Chiral Ligands And Their Application In The Asymmetric Catalysis

The chiral secondary alcohols are important intermediates in the synthesis of drug, pesticide and spicery etc., and their numerous methods remain the focus of much research activity. Catalytic asymmetry addition of aldehydes and asymmetry reduction of prochiral ketones are two effective methods for preparation of chiral secondary alcohols. The methods play an important role in academic research and industry.The core of catalytic asymmetry reactions is design and synthesis of chiral catalyst. In this work, a series of chiral amino alcohols were synthesized from natural camphor and L-amino acids. And then camphor sulfonamide alcohols, camphor amide alcohols, p-toluene sulfonamide alcohols and hydroxyl camphor sulfonamide alcohols were respectively prepared by modified the amino alcohols. These ligands were used in asymmetry reduction of prochiral aromatic ketones and asymmetry addition of diethylzinc to aromatic aldehydes. Specific details are outlined as follows:Amino acid methyl ester hydrochlorides were prepared from L-phenylalanine, L-methionine, L-leucine and thionyl chloride in low temperature, and then seven chiral amino alcohols obtained by the reactions of amino acid methyl ester hydrochlorides with Grignard reagents. Six camphor sulfonamide alcohols, six p-toluene sulfonamide alcohols and six camphor amide alcohols were prepared by modifying the amino of these amino alcohols, such as sulfonylating, acylating etc. Four ligands of them were reduced by sodium borohydride to give four new chiral hydroxyl camphor sulfonamide alcohols. On the other hand, three new chiral hydroxyl camphor sulfonamides which have C2 symmetry structure and one chiral double hydroxyl sulfonamide alcohols were synthesized from natural camphor. All products were solid, and they were characterized with melting point, IR, specific rotation and 1H NMR.The catalytic performance of the complexes which were prepared from borane and chiral amino alcohols, chiral sulfonamide alcohols and p-toluene sulfonamide alcohols respectively was researched in asymmetry reduction of acetophenone. The best ligand was used to catalyze reduction of phenylethylketone, 2-chloroacetophenone, 2-bromoacetophenone, p-chloroacetophenone, p-bromoacetophenone, and p-methyl- acetophenone. The results showed that 90%~99% yield and 12.3%~70.4%e.e. were got when chiral amino alcohols were used as catalysts for reduction of acetophenone, 65.7%~99% yield and 0~33.0%e.e. obtained when chiral sulfonamide alcohols were used as catalysts for reduction of various prochiral ketones. Catalytic performance of the complexes of camphor sulfonamide alcohols and Ti(OiPr)4, and camphor amide alcohols in asymmetry addition of diethylzinc to aromatic aldehydes was researched. The results showed that better catalytic results were got in dichloromethane than in toluene when camphor sulfonamide alcohols were used as ligands, but the best asymmetric induction is only 19.6%e.e.; camphor sulfonamide alcohols with C2 symmetry structure catalyzed the addition of diethylzinc to aromatic aldehydes with 58%~89% yield and 17%~51%e.e.; camphor amide alcohols catalyzed the addition of diethylzinc to benzaldehyde with 48.4%~81.5% yield and 0~24.7%e.e. in hexane or dichloromethane.