Mechanistic studies of copper-catalyzed transformations: Organometallic oxidase and cross-coupling reactions

Both copper-catalyzed oxidative and non-oxidative reactions have received renewed interest in recent years. Prominent examples of oxidative copper-catalyzed reactions include the coupling of heteroatom nucleophiles with organoboronic derivatives (Chan-Evans-Lam reactions) and carbon-hydrogen bonds using dioxygen as a sacrificial oxidant, while the reaction of aryl halides with heteroatom nucleophiles (Ullmann-Goldberg reaction) is perhaps the most prominent example of a copper-catalyzed cross-coupling reaction. The mechanisms of copper-catalyzed oxidative and non-oxidative transformations are poorly understood, however, especially the oxidation states of copper involved during catalysis. Copper(I), copper(II), and copper(III) species are well-known; previous mechanistic proposals for both oxidative and non-oxidative coupling reactions have involved all three known oxidation states of copper. Discussed herein are studies examining the mechanisms of copper-catalyzed processes: the Chan-Evans-Lam reaction, the aerobic functionalization of arene carbon-hydrogen bonds, and an Ullmann-Goldberg-type reaction. Extensive attention is afforded to the oxidation states of copper during catalysis. Additionally, a detailed mechanistic study concerning the steps preceding the necessary transmetalation step in the Chan-Evans-Lam reaction conducted in methanol is presented, as is preliminary studies concerning the reaction mechanism in the presence of amide nucleophiles and when conducted in methylene chloride.