Synthesis Of Chiral Thiazoiine And Triazole Compounds Arid Study On Application Of Thiazoiine Compounds In Asymmetric Michael Reaction

Chiral has shown its importance in many areas, such as biological sciences,chemistry, materials. In order to obtain a single configuration of chiral medicines,chiral catalysts were often used to catalyze the asymmetric catalytic reactions. Forexample, L-proline compounds and cinchona alkaloid compounds are effectivecatalysts which are widely used in asymmetric reactions. However, chiral thiazolinecatalysts, which could be synthesized from the commercially available L-cysteine,have not been widely employed, so it is essential and meaningful to synthesize thesenew chiral catalysts. We synthesized a series of chiral thiazoline catalysts andemployed them to asymmetric Michael addition reaction to demonstrate their catalyticactivities.With L-cysteine as raw, we obtained a series of thiazoline thiocyanates afterseven-step reaction. With L-proline as a starting material, after five-step reaction weobtain aminopyrrolidine. These structural blocks were connected by thiourea and thendeprotected BOC group to obtain a series of thiazoline catalysts18. Among thesecatalysts,18d can catalyze the Michael additions efficiently. We employed them toMichael addition reation of cyclohexane to β-nitrostyrenes. Acetic acid was chosen asadditive, dichloromethane as the solvent and at room temperature as optimalconditions. These chiral thiazoline showed excellent asymmetric catalytic results infollowing Michael addition reacitions with95%ee and99:1dr. The application ofthese thiaozline ligands provides an alternative amino acid derived catalyst for thefurther reaction development. As the special heterocyclic structure of1,2,3-triazole, it have multiple sites tobind with metal. It is a essential and potential block. However, triazole has not beenwidely employed in asymmetric catalysis, so it is meaningful in the synthesis of thesenew chiral catalysts. We synthesized a series of triazole ligands and plan to employthem to asymmetric reaction in order to demonstrate their catalytic activities. Withmethyl phenylpropargylate as raw via Huisgen reaction, substitution, hydrolysis,amidation and cycloaddion, a class of triazole-thiazoline ligands were obtained. Thesereactions were simple and efficient and the overall yields were70%。...