CuSO₄·5H₂O/NaAsc Catalyzed C-O/C-S/C-C Coupling Reaction

Copper-catalyzed Ullmann coupling reaction is one of the most effective methods to build the C-O/C-S/C-C bonds has been widely used in medicine, pesticides, dyes etc.Classical Ullmann coupling reaction needs to use a amount of stoichiometric copper powder as catalyst, and also a higher temperature, bigger pressure and longer time for the reaction. In recent years, C-O/C-S/C-C coupling reactions under the catalysis of copper salt combined with ligand could reduce the amount of catalyst, shorten the time of reaction, milden the reaction conditions and strengthen the functional group tolerance, thus prompting Ullmann coupling reaction into "the Ullmann era". At present, most literatures used copper salts with poor stabilities that ligands mostly are low physiological compatibility of nitrogen and oxygen as catalysts, which makes the post-treatment difficult. Therefore, looking for a new catalyst and ligand becomes the focus in the copper catalytic reaction.In this paper, we use a homogeneous catalyst system CuSO4·5H2O/NaAsc composition to provide a cuprous salt in situ under the condition of without inert gas protection, which method is green, simple and easy to operate. In the catalytic system, we synthesized a series of C-O/C-S/C-C cross-coupling products. The main contents are as follows:1. Reviewing the classical Ullmann coupling reaction and the progress of research on C-O/C-S/C-C coupling reaction under the catalysis of copper salt and ligand.2. Achieving the halogenated aromatic hydroxy directly into phenol, phenol and halogenated etherification, halogenated aromatics and thiophenol sulfur etherification reaction under the CuSO4·5H2O/NaAsc catalytic system in a homogeneous environment. Whether on the benzene ring connect with electron-withdrawing or electron-donating, a ideal yield of target products could be obtained and the effect on the reaction space is also smaller.3. Attaining Csp³-Csp² cross-coupling reaction that is usually not easy to achieve. But under the catalysis of CuSO4·5H2O/NaAsc, We Explored the active methylene ?-arylation reactions of different carbonyl compounds?diethyl malonate, ethyl acetate, dibenzoyl methane, 2,4-pentanedione?. It was found that 2,4-pentanedione with different halogenated aromatic substituents to better yields get Csp³-Csp² cross-coupling products, other carbonyl compounds adaptability under the catalytic system is not very satisfactory.4. Sonogashira coupling reaction that often requires noble metal Pd and phosphorous ligand catalytic. We explored whether to adapt to the reaction of CuSO₄.5H₂O/NaAsc catalytic system. The results show that the benzene ring has aromatic halides and terminal alkyne electron withdrawing group or electron donating groups to obtain a higher yield desired products with a catalytic amount of CuSO₄.5H₂O/NaAsc under an inert gas.The above target product structures are characterized and confirmed by ¹H NMR, ¹³C NMR and HRMS.