Organocatalytic Asymmetric Michael Addition Reaction And Its Application In The Synthesis Of 16-Azaequilenins

This thesis mainly focused on Michael addition catalyzed by organocatalysts. We firstly design and synthesis demethylquinine salts and these soluble salts have been shown as a kind of efficient novel catalyst for asymmetric Michael addition of malonate to nitroalkenes in water, up to 93% yield and 90%ee. It is useful for construction of special quaternary carbon centes. We also use our catalysis system to construct main skeleton of 16-azaequilenins. This thesis include the following parts:1. The progress on the study of organocatalysis Michael addition during ten years (review). The review introduced some general example of Michael additions and application in synthesis, meanwhile, we also introduced organocatalyzed Michael addition in details.2. An enantioselective Michael addition of malonate to nitroalkenes catalyzed by low loading demethylquinine salts in water. First, design and synthesis of demethylquinine salts were introduced in details. We research the catalytic system in water through Michael addition, and pay close attention to the properties of catalysts in water.3. A mild method for the asymmetric construction of quaternary carbon centers in water was introduced. Quaternary carbon centers have been developed through Michael addition of trisubstituted carbon nucleophile to nitroalkenes catalyzed by low loading sodium demethylquinine salt in water, up to 91% yield and 88%ee. We also obtained moderate to good diastereoselectivities for adjacent stereocenter. The enlarged reaction system has little impact to the property of the catalyst.4. Synthesis of 16-azaequilenins based on asymmetric Michael addition. 16-azaequilenins have good physiological activity, construction of its skeleton based on our catalytic system have been finished, the key step is asymmetric Michael addition catalyzed by demethylquinine salts in water. The importent intermediate was obtained.