species have been invoked in many copper-catalyzed reactions, but until recently, experimental evidences were lacking. The advent of new spectroscopic techniques and the characterization of simple and stable catalyst models have been key to gain clear mechanistic insights into these important reactions. In this perspective, we will discuss these discoveries and the corresponding mechanistic proposals that derive from important reactions such as nucleophilic organocuprate chemistry for C-C bond formation, C-heteroatom cross-coupling reactions (Ullmann condensation reactions and halide-exchange processes) and direct C-H bond functionalizations catalyzed by copper.

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Recent studies have highlighted the ability of Cu(II) to catalyze the aerobic oxidative functionalization of C-H bonds; however, very little is known about the mechanisms of these reactions. Here, we describe the Cu(II)-catalyzed C-H methoxylation and amidation of a macrocylic arene substrate with O(2) as the stoichiometric oxidant. Kinetic and in situ spectroscopic studies demonstrate the involvement of three different oxidation states of Cu in the catalytic mechanism, including an aryl-Cu(III) intermediate. These observations establish a novel mechanistic pathway that has implications for numerous other Cu-catalyzed aerobic oxidation reactions.

Copper-catalyzed halide exchange reactions under very mild reaction conditions are described for the first time using a family of model aryl halide substrates. All combinations of halide exchange (I, Br, Cl, F) are observed using catalytic amounts of Cu(I). Strikingly, quantitative fluorination of aryl-X substrates is also achieved catalytically at room temperature, using common F(-) sources, via the intermediacy of aryl-Cu(III)-X species. Experimental and computational data support a redox Cu(I)/Cu(III) catalytic cycle involving aryl-X oxidative addition at the Cu(I) center, followed by halide exchange and reductive elimination steps. Additionally, defluorination of the aryl-F model system can be also achieved with Cu(I) at room temperature operating under a Cu(I)/Cu(III) redox pair.