Palladium-Free Copper-Catalyzed Sonogashira Cross-Coupling At Room Temperature

Many antibiotics, liquid crystals, polymers, and optical or electronic materials were prepared via the Sonogashira reaction of terminal alkynes and aryl or vinyl halides, and the palladium and copper co-catalyzed coupling is a popular strategy for the construction of C(sp2)-C(sp) bonds. However, the drawbacks of the catalyst systems, such as air sensitivity, high cost, toxicity, limit their applications for industrial processes, so it is highly desirable to develop readily available and cheap catalyst systems instead of palladium catalysts to promote the coupling of terminal alkynes and aryl or vinyl halides. During the past more than ten years, several examples involving nickel and copper catalyzed Sonogashira reactions were reported, but the higher temperatures (80～130℃) and longer times were required. It is harmful for synthesising macromolecular compounds or thermodynamic sensitivity compounds. So it is meanful to develop a simple and general procedure for the Sonogashira Cross-Coupling reaction under mild condition. In this thesis, some results were obtained as follows:We have developed an efficient method for palladium-free copper-catalyzed Sonogashira cross-coupling of o-iodoacetanilide derivatives with terminal alkynes at room temperature, and the corresponding coupling products were obtained in good to excellent yields (62-90%) using CuI as catalyst, N-methylpyrrolidine-2-carboxamide as the ligand, CS2CO3as the base, DMF as the solvent, and the inexpensive catalyst system is of high tolerance towards various functional groups in the substrates. This represents the lowest reaction temperatures for copper-catalyzed Sonogashira cross-coupling thus far.