Research On Copper-Catalyzed Synthesis Of Thiochromanone Derivatives

After recent decades of development, transition metal catalyzed cross-coupling reaction has become an important method in the construction of C-C and C-X (N O S, et) bonds in modern organic synthesis. Although the common Pd and Ni catalyzed reaction usually went well, their shortcomings, such as higher prices, toxicity, and demanding unstable and higher virulent organophosphorus ligands created challenges for chemists. Recently, copper-catalyzed organic reactions have attracted considerable attention because of the low cost, low toxicity, and some efficient copper-catalyzed methods for the synthesis of heterocycles. In this article,4H-thiochromen-4-one derivatives were synthetized by reaction of -o-bromoacetophenones and β-oxodithioesters through Cu-catalyzed reactions. Details are as follows:In the first section, we summarized the utilization of the fascinating properties of β-oxodithioesters as building blocks in organosulfur moieties, different protocols of preparing thiopyranone derivatives as well as as their important bioactivities. Also copper catalyzed cross-coupling reaction was introduced.β-oxodithioesters are widely used in the synthesis of sulfur-containing heterocyclic compounds. With two electrophilic centers and three nucleophilic centers, which makes β-oxodithioesters show regioselective diversity.Thiopyranone is the thiohomologue of pyranone, a core constituent of many natural products. It is reported that thiochromenones, benzo-annelated thiopyranones which are related to the class of flavones, are potent drug candidates and serve as key intermediates for the synthesis of biologically active compounds. However, current reports on building up thiopyranone are relatively limited, and exploring new approaches to synthesizing these heterocyclic compounds was of great significance.In the second chapter, a high regioselective synthetic strategy of constructing novel 4H-thiochromen-4-ones through the Cu-catalyzed reactions of β-oxodithioesters with o-bromoacetophenones was developed. To screening the optimal conditions of the reaction, different kinds of catalysts, ligands, bases and solvents were investigated. After attempts, Cul as precatalyst (1.0 equiv.), L3 as ligand (1.0 equiv.), NaO-t-Bu as base (4 equiv.) in toluene at 80℃, and a ratio of la:2a= 2:1 were found to afford the best yield. jThe structures of all synthesized compounds were characterized by IR,1H NMR, 13C NMR, HRMS. Furthermore, HMBC was used to confirm the configuration of target products. The plausible mechanism was also presented.