The Applications Of Polymer Supported 2-Phenylimino-2-oxazolidine Chiral Auxiliary

In the process of the development of asymmetric synthesis, using the chiral auxiliaries is a widely used method in asymmetric synthesis. All kinds of chiral auxiliaries, such as oxazolidinone, thiazolidinethiones, prolinol, oxazoline, imidazoline, carbohydrate, sulfoxide and so on, have been widely used in asymmetric alkylations, Michael additions, Diels-Alder rections, Dipole cycloaddition reactions, and so on, and they all show good induction effect. 2-phenylimino-2-oxazolidine, as a new chiral auxiliary, displays noticeable effect in inducing asymmetric alkylations and there is no ring cleavage reaction happened in the removing of chiral auxiliary, so it has a very good application prospects in asymmetric synthesis.In order to recycle the chiral auxiliaries effectively, polymer supported chiral auxiliaries have been widely used. Non-cross-linked polystyrene (NCPS), as a soluble polymer, not only retains the characteristics of purification of solid phase synthesis, but also shows their advantages in homogeneous reactions, which improves the efficiency of the reaction and realizes the detection of reaction process by online analysis.Based on the excellent asymmetric inducing effect of 2-phenylimino-2-oxazolidine chiral auxiliary and the advantages of NCPS as a soluble supporter, in this paper we synthesized NCPS supported 2-phenylimino-2-oxazolidine chiral auxiliary using NCPS as a soluble supporter, and investigated its application in asymmetric alkylations.Using N-Boc-L-tyrosine ethyl ester as starting material, protected the phenolic group through benzyl group, reduced the ester group, removed the Boc group and reacted with phenyl isothiocyanate, and then treated by 4-methyl benzene sulfo-chloride and sodium hydroxide to obtain (S)-4-[4'-(benzoyloxy)phenyl]-2-phenylimino-2-oxa-zolidine. Removed of benzyl group from (S)-4-[4'-(benzoyloxy) phenyl]-2-phenylimino-2-oxa-zolidine and reacted with chlorine methylation linear polystyrene to give the NCPS supported 2-phenylimino-2-oxazolidine chiral auxiliary. After acylating with phenylacetyl chloride or propionyl chloride, and then asymmetric alkylating reaction was investigated by different alkylating agent such as benzyl bromide, allyl bromide and tetranitro-benzyl bromide. Using benzyl amine as removing reagent, we got the corresponding asymmetric alkylating products, which were determined by IR,1H NMR and13C NMR, and e.e values were determined by HPLC analyses.In order to investigate the inducing effect of NCPS supported 2-phenylimino-2-oxazolidine chiral auxiliary further, we designed the synthesis routes of Male Mouse pheromone components (S)-2-sec-butyl-4,5-dixydrothiazole on the basis of the reported synthetic methods of (S)-2-sec-butyl-4,5-dihydrothiazole. NCPS supported 2-phenylimino-2-oxazolidine was acylated by butyryl chloride, alkylated with methyl iodide and then treated with sodium ethoxide to give (S)-2-methylbutanoic acid ethyl ester as product, which was reacted with cysteamine hydrochloride to obtain the desired product (S)-2-sec-butyl-4,5-dihydrothiazole. Due to partly racemizatio, the e.e value of the product (S)-2-sec-Butyl-4,5-dihydrothiazole is 60%.