Studies On The Catalytic Asymmetric Addition Of Diethylzinc To Aromatic Aldehydes And Catalytic Asymmetric Aldol Condensation

In this thesis, catalytic asymmetric addition of diethylzinc to aldehydes by N- substituted-p-amino alcohols and asymmetric aldol condensation by various chiral ligands have been investigated. I. Synthesis of N-substituted-t3-amino alcohols and application in catalytic asymmetric addition of diethylzinc to aromatic aldehydes. 1. Eight novel chiral ligands 2a-h were synthesized by using sodium triacetoxyborohydride as reducing agent in very mild conditions. Ligands 2a-h were obtained in high chemical yield and then configuration retention and were characterized by elemental analysis, IR, 1 and C NMR spectra. 2. Chiral ligands 2a-h were applied to catalyze the enantioselective addtion of diethylzinc to benzaldehyde. Among them, Iigand 2d was found to have shown the best asymmetric induction. When 5mol% ligand 2d was used to catalyze the enantioselective addition of diethylzinc to benzaldehyde, (R)- I -phenylpropan- 1 -ol was obtained with 91.8%ee. The optimal conditions were proved to be using 5mol% chiral ligands to catalyze the reaction at room temperature. Under these conditions, chiral ligand 2d was used to catalyze the addition of diethylzinc to various aldehydes including ortho-, para- and meta- substituted benzaldehydes, thiophene-2-carboxaldehyde and ferrocenyl aldehyde. The optical active second alcohols were obtained with high chemical and optical yields. The best asymmetric induction, as high as 98.3%ee, was obtained by using ferrocenyl aldehyde as substrate. 3. By comparing the molecular structure of ligands with their asymmetric induction efficiency, it was found that the excellent asymmetric induction efficiency of 2d can be attributed to the presence of steric hindrance of diphenyl groups at the a-carbon and the a-pyridylmethyl group at the j3梐mino nitrogen as a side chain. Based on our experimental findings and other groups?work, a possible mechanism was proposed. II. The catalytic asymmetric aldol condensation catalyzed by the metal complex of chiral second amines and titanium complex of chiral Schiff base. 1. Six novel chiral second amines were syhthesized and characterized by elemental analysis, IR, and NMR spectra. 2. Chiral ligands I, II and IV reacted with Bu擫i or MgEt2 to give the chiral catalysts which were used to catalyze the enantioselective aldol condensation of benzaldehyde with acetophenone. The reactions were carried out in ethereal solvents at -700C. The products were obtained in up to 17.2%ee. 3. Chiral ligands Il-Li and Ill-Li, prepared from II or III with Bu~Li, were used to catalyze the enantioselective aldol condensation of benzaldehyde with benzyl cyanide. The reactions were carried out in ethereal solvents at -700C. The enantiomeric excesses of the products were up to 31.5% in the case of catalysis by 4. Chiral Schiff base-titanium complex Va and Vb were used to catalyze the enantioselective aldol condensation of 1-substituted-I -trimethylsilyloxyethene with benzaldehyde. Smol% Va and Yb were used to catalyze the enantioselective aldol condensation of 1-trimethylsilyl-l-phenylethene with benzaldehyde. The enantiomeric excesses of the products were up to 30%. Smol% Ya and Yb were used to catalyze the enantioselective aldol condensation of 1 -trimethylsilyl- 1 -ethoxyethene with benzaldehyde. The products were obtain...