Investigation of an Unusually Low-Temperature, Microwave-Assisted, Copper-Catalyzed Concurrent Tandem Catalytic Process for the Amidation of Aryl Bromides

An unusually low-temperature, concurrent tandem catalytic (CTC) process for the amidation of aryl bromides has been investigated. The aryl bromide is first converted to an aryl iodide via halogen exchange and the resulting aryl iodide is then transformed into the aryl amide. Optimized reaction conditions, with an isolated yield of aryl amide of 82%, were identified for the conversion of 4-bromotoluene to 4-(N-methylphenyl)-benzamide: 10 mol % CuI, 20 mol % N,N′-dimethylethylenediamine, 2 equiv of K3PO4, and 1.05 equiv of amide in 1,4-dioxane at 80 °C using microwave heating after 3 h. A copper iodide/diamine ligand system served as a multifunctional catalyst for both steps of the concurrent catalytic process with iodide present in substoichiometric amounts. A preliminary substrate scope study revealed moderate to excellent yields of products corresponding to the cross-coupling of a variety of aryl bromides and amides. Evidence for the amidation reaction proceeding through a CTC mechanism is discussed.