Oxidation reactions promoted by copper centers in enzymes and by other catalysts are critical for transforming organic molecules for life processes and synthetic applications.1,2 A longstanding research objective has been to understand the mechanisms of such oxidation reactions, and in particular, to reveal how copper centers react with O2 or other oxidants and to determine the nature of the key resulting copper-oxygen intermediates responsible for attacking substrate C-H bonds.3 In general, it is postulated that Cu(I) centers in enzymes and other catalytic systems react with O2 to yield initial 1:1 Cu/O2 adducts; higher nuclearity species are important in multicopper systems,4 but we focus here only on mononuclear sites. A number of 1:1 Cu/O2 adducts have been identified in synthetic studies using suitably designed supporting ligands, and they have been described as end-on (1) or side-on (2) copper(II)-superoxide or copper(III)-peroxide species on the basis of computational and experimental evidence (Scheme 1).5 Armed with the precedent provided by these synthetic efforts, as well as more direct experimental and computational data on the catalytic systems themselves, a functional role for 1 and 2 in a variety of enzymes has been proposed.1,6 This role commonly involves a hydrogen atom transfer (HAT) from a substrate C-H bond in a key rate-determining step of the catalytic mechanism. Yet, while HAT reactions of discrete, well-characterized examples of complexes with moieties 1 and 2 have been observed, they typically only occur at reasonable rates with substrates having relatively low C-H bond dissociation free energies (weaker bonds than the catalytically relevant substrates).5,7 As a result, questions have been raised about the feasibility of intermediates 1 and 2 as oxidants in catalytic systems that transform substrates with strong C-H bonds such as, for example, particulate methane monooxygenase (pMMO), for which multicopper oxidants have been proposed, including dicopper species with monocopper-oxygen units.3c,8
An obvious alternative to 1 and 2 as intermediates that is inspired by the mechanistic paradigm for iron-containing catalysts9 is addition of protons and electrons prior to attack on substrate, resulting in scission of the O-O bond to yield a high valent metal-oxo species that would be a more potent oxidant (3, Scheme 1). While examples of well-characterized mononuclear iron(IV)-oxo complexes now abound, and advances in our understanding of their reactivity have been substantial,10 much less is known about copper congeners having a [CuO]+ core (3). Many proposals for the involvement of [CuO]+ species, as well as the protonated version [CuOH]2+ (4), in oxidation reactions have appeared, but supporting evidence is sparse and indirect, and such species have not been observed directly as discrete complexes in condensed phase.11 Compelling evidence for [CuO]+ has come from gas phase studies supplemented by theoretical calculations.12 These studies suggest extraordinarily high reactivity and strong thermodynamic driving forces for HAT reactions with C-H bonds by a species best described as a triplet copper(II)-oxyl radical. Computational work supports this bonding picture and similarly high reactivity for putative [CuO]+ intermediates in enzymes such as dopamine β-monooxygenase (DβM),13 peptidylglycine α-amidating monooxygenase (PHM),14 and lytic polysaccharide monooxygenase (LPMO).15 Inspired by these provocative findings and the overarching goal of defining the nature of copper-oxygen oxidants involved in metalloenzyme and other catalysts, we targeted complexes containing the [CuO]+ core for synthesis and characterization.
In this Account, we summarize our efforts to prepare complexes with the [CuO]+ and [CuOH]2+ cores. We first describe initial work aimed at accessing [CuO]+ complexes through oxidative decarboxylation of Cu(I)-α-ketoacid complexes and reactions of Cu(I) complexes with oxo-transfer reagents, before turning to more recent efforts to prepare and understand the properties of [CuOH]2+ compounds. The recently demonstrated ability of these [CuOH]2+ cores to attack strong C-H bonds has provided an experimental foundation for the hypothesis that such species are possible reactive intermediates in oxidation catalysis.