Copper-Catalyzed Synthesis Of α-Trifluoromethylthio-Substituted Ketones

The incorporation of trifluoromethylthio (-SCF3) into organic molecules can significantly improve the physical, chemical and physiological properties of the compounds owing to their strong electron-withdrawing effect and high hydrophobicity parameter. Compounds containing trifluoromethylthio group are widely used in pharmaceutical, pesticide and material science, especially those trifluoromethylthio-substituted carbonyl compounds can be widely used as a raw material for organic synthesis.Three groups of methods for synthesizing trifluoromethylthio compounds have been reported:halogen-fluoro exchange reaction; trifluoromethyl reaction of sulfur compounds; reaction of aryl halides, boronic acids with trifluoromethylthio reagents. However, these reactions are generally limited by expensive and toxic reagents, the preparation of sulfur-containing precursors, a narrow substrate scope. It has been a hot field to synthesis the trifluoromethylthio group-containing compounds in a more economical, more environmental and more efficient method.In this thesis we use two different methods to synthesis the α-trifluoromethylthio ketones.1. The reaction of a copper reagent ((bpy)CuSCF3) with α-bromo aryl kentone was studied.The air-stable trifluoromethylthio copper reagent ((bpy)CuSCF3) was used as an organometallic trifluoromethylthio reagent, which was synthesized from CuF2 and bidentate nitrogen ligands 2,2’-Dipyridyl and this complex can react with a wide range of halides. After screening the reaction solvent,temperature and time,we ensured the optimal reaction conditions:CH2Cl2 as solvent,1.2 equiv CuSCF3 react with substrate(0.25 mmol) at 50℃ for 16 hour under nitrogen. Sixteen a-trifluoromethylthio-substituted ketones were synthesized. This reaction was accomplished in modest to excellent yields and can tolerate a variety of functionalities under mild conditions.2. We synthesis the a-trifluoromethylthio-substituted ketone by copper-catalyzed. By screening the inexpensive copper as a catalyst, the product was achieved by one pot reaction with trifluoromethyl reagent and sulfur powder. After screening different copper salts, ligands, solvents, and the amount of catalyst reaction,we ensured the optimal reaction conditions:0.2 equiv Cu(OTf)2as catalyst,0.2 equiv phen as ligand, CH2Cl2 as solvent,0.25 mmol α-bromo ketones react with 4 equiv of KF, Sg and CF3SiMe3 at 40℃ for 16 hour under nitrogen. This catalytic system was found more suitable for substrate containing an electron-donating groups and the isolated yield was more than 78%. Compared to the previous method this process has the advantages of more inexpensive, more environmentally friendly, easy to operate, and have great potential applications.