The copper-catalyzed N-arylation of amides, i.e., the Goldberg reaction, is an efficient method for the construction of products relevant to both industry and academic settings. Herein, we present mechanistic details concerning the catalytic and stoichiometric N-arylation of amides. In the context of the catalytic reaction, our findings reveal the importance of chelating diamine ligands in controlling the concentration of the active catalytic species. The consistency between the catalytic and stoichiometric results suggests that the activation of aryl halides occurs through a 1,2-diamine-ligated copper(l) amidate complex. Kinetic studies on the stoichiometric N-arylation of aryl iodides using 1,2-diamine ligated Cu(l) amidates also provide insights into the mechanism of aryl halide activation.
“Mechanistic Studies on the Copper-Catalyzed N-Arylation of Amides”, J. Am. Chem. Soc., 2009, 131(1), 78-88.