Palladium/Copper Co-catalyzed Tandem Cycloaddition/Oxygenation Reactions Of Conjugated Enediynes With Alkynes

Conjugated enediynes are important structural motifs in a myriad of biologically interesting natural products and pharmaceutical targets, they also serve as versatile building blocks in organic synthesis. Accordingly, the cyclization of conjugated enediynes is always the focus of research in organic synthesis in recent years. This dissertation demonstrates palladium/copper co-catalyzed tandem cycloaddition/oxygenation reactions of conjugated enediynes with alkynes and thus develops a new synthesis method for isoindolinone derivatives. The mechanism research indicates this is a unprecedented radical course of common participation of oxygen and water, which will be effectively beneficial to the future research of radical reaction and enediyne chemistry. The dissertation is consisted of two chapters.In the first chapter, we summarized the current research and trends of conjugated enediynes, which can be divided into seven main areas:classical Bergman reactions, reactions initiated by radicals, reactions initiated by electrophiles, reactions initiated by carbon nucleophiles, reactions initiated by nitrogen nucleophiles, reactions initiated by oxygen nucleophiles and reactions initiated by halopalladation.In the second chapter, we investigated the tandem cyclization of conjugated enediynes with alkynes in the presence of palladium and copper, obtained the complex of isoindolinone architectures. First we screened the reaction parameters, and this catalytic system has been found to be general for the cyclization of a broad range of enediynes with a variety of alkynes under the optimal reaction conditions. Through a careful study on the reaction mechanism, we find it is a unprecedented radical reaction requiring concerted efforts from water and oxygen.