Studies On The Asymmetric Oxidation Of Sulfides Catalyzed By In-situ Generated Vanadium And Titanium Complexes With Chiral Schiff Base Ligands

Enantiopure sulfoxides are important chiral auxiliaries and synthons used in asymmetric synthesis, and also used as bioactive ingredients in the pharmaceutical industry for the special biological property of the chiral drugs containing a sulfinyl group with a defined configuration. Therefore, the preparation of chiral sulfoxides has a significant academic and application value. So far, asymmetric oxidation of sulfides catalyzed by transition metal complexes is the most effective method for the preparation of chiral sulfoxide. Among the catalysts used in asymmetric sulfoxidation, chiral Schiff base-metal (vanadium, iron, titanium, copper) systems have been considered as one of the most promising methods due to the following advantages: using an emvironmental benign oxidant, hydrogen peroxide, under mild conditions and giving sulfoxides in high yields.In this thesis, chiral Schiff bases L6a-g and L7a-g, prepared from the condensation reactions of chiral amino alcohols with the mono-, di-, tribromohydroxynaphthaldehyde or monoiodohydroxynaphthaldehyde L4a-d and L5a-d, which were prepared by controlled halogenation of 3-hydroxy-2-naphthaldehyde and 1-hydroxy-2-naphthaldehyde. Chiral Schiff bases L8c-e were prepared from 3,5-dicumenylsalicylaldehyde and inexpensive chiral amino alcohols. Chiral Schiff bases prepared were used in combination with VO(acac)2 or Ti(Oi-Pr)4 for the asymmetric oxidation of sulfides using H2O2 as terminal oxidant.Asymmetric oxidation of thioanisole catalyzed by VO(acac)2/L6a-g and L7a-g gave good-to-high yields (76-93%) and moderate-to-good enantioselectivities (67-82% ee) in dichloromethane at 0℃. Among these Schiff bases, dibromo-functionalized L6e and iodo-functionalized L7g gave high yields (91-93%) with good enantioselectivities (80-82% ee) for the oxidation of thioanisole. it was found that introduction of bromo or iodo substituents was capable of improving the yield and enantioselectiviy of analogous ligands L6h and L7h without halogen atom. Both the position and the number of the bromo or iodo substituent in the naphthyl ring of the Schiff base ligand can apparently influence the enantioselectivity. It delighted us to have found that the asymmetric oxidation of thioanisole in toluene at 0℃with these Schiff bases containing a halo-functionalized hydroxynaphthyl unit gave methyl phenyl sulfoxide in satisfactory isolated yields (48-62%) with high enantioselectivities (91-94% ee), which were further improved by a modified procedure with the ee value up to 98% ee in 62% yield using VO(acac)2/L7g as catalyst. The oxidations of other sulfides in toluene at 0℃with dibromo-and iodo-functionalized Schiff bases L7e and L7g as ligands using the modified procedure afforded the corresponding sulfoxides in 55-67% isolated yields with 95-99% ee. Kinetic resolution of racemic methyl phenyl sulfoxide was catalyzed by VO(acac)2/L6a-g and L7a-g in CH2Cl2 at room temperature. The selective factor obtained from the VO(acac)2/L7e system (S=15.6) is in the same level of the best result ever reported.The catalytic properties of the catalyst systems of Ti(Oi-Pr)4/(L8c-e) were studied. As a result, the enantiomeric excess of (S)-sulfoxide was up to 73% ee and the yield was 89% for the catalyst system of Ti(Oi-Pr)4/L8d in oxidation of thioanisole using H2O2 as oxidant in CH2Cl2 at 0℃. The reaction afforded good yield (84%) with a moderate enantioselectivity (62% ee) even with a low loading of Ti(Oi-Pr)4 (0.5 mol%). Enantioselectivity of the sulfoxides obtained was directly generated from asymmetric oxidation of sulfides, instead of the further kinetic resolution of sulfoxides. The experimental evidence shows that the chiral induction capability of the cumenyl-modified sterically hindered Schiff bases for sulfoxidation was better than the conventional Schiff bases bearing tert-butyl groups in the 3,5-positions of the salicylidenyl unit.