Synthesis Of Chiral N, O-Ligands And Their Applications In Asymmetric Oxidation Of Sulfides

Optically active sulfoxides have been widely used in asymmetric synthesis as important class of chiral auxiliaries, as well as bioactive ingredients in the pharmaceutical industry. Therefore, the preparation of chiral sulfoxides has significant academic and application value. In the last more than twenty years, various methods have been developed for the preparation of chiral sulfoxides. The asymmetric oxidation of sulfides catalyzed by chiral Schiff base/vanadium system has been considered as one of the most effective methods discovered thus far for hydrogen peroxide as oxidant, mild reaction conditions, high yields and so on.With this context, three typs of chiral ligands have been designed and synthesized, which were sixteen 3-aryl substituted salicylaldehyde chiral Schiff base ligands L^-L¹⁶, two chiral Schiff base ligands L¹⁷and L¹⁸, two chiral N,O-ligands L¹⁹ and L²⁰ based on tetrahydroquinoline backbone, Schiff base ligand L²¹ with two chiral centers, and Schiff base ligand L22 with three chiral centers.The catalytic system of chiral Schiff base ligands L¹-L¹⁸/VO(acac)₂ afforded high yields and moderate to good enantioselectivities for the asymmetric oxidation of phenyl methyl sulfide. The effects of the substituents on both the salicylaldehyde unit and the amino alcohol unit of Schiff base ligands on asymmetric sulfoxidation were explored. The results indicate that the larger steric hindrance in the amino alcohol unit of Schiff base ligands leads to higher enantioselectivity. Introduction of bromo atoms to the 3-position of the aryl group of substituted salicylaldehyde can enhance the enantioselectivity of sulfoxides. The position of bromo atoms has definite influence on the sulfoxidation of enantioselectivity. Under the optimized reaction conditions, the asymmetric oxidation of 4-bromophenyl methyl sulfide and 2-naphthyl methyl sulfide can give 80% ee and 90% ee catalyzed by L¹¹³/VO(acac)₂.Reaction conditions of asymmetric oxidation of phenyl methyl sulfide catalyzed by chiral N,O-ligand L¹⁹/VO(acac)₂ have been optimized. The optimized solvent is acetone, which is less toxic than methylenechloride used for Bolm catalytic system. High yields (80%-95%) and good enantioselectivities (66%-77% ee) were obtained for the asymmetric oxidation of sulfides catalyzed by L¹⁹/VO(acac)₂ system under optimized reaction conditions, while the ligand L²⁰ containing bromo atoms on the 3- and 5- positions of the phenol unit displayed low chiral inducement for the asymmetric oxidation of phenyl methyl sulfide. The catalytic properties and recycling capabilities of L²¹/VO(acac)₂ and L²²/VO(acac)₂ systems were explored. The two catalytic systems can be recycled twice and three times, respectively, with very low enantioselectivities for the oxidation of phenyl methyl sulfide with 30% H₂O₂ as oxidant in acetone.