The chemistry of copper is extremely rich because it can easily access Cu0, CuI, CuII, and CuIII oxidation states allowing it to act through one-electron or two-electron processes. As a result, both radical pathways and powerful two-electron bond forming pathways via organmetallic intermediates, similar to those of palladium, can occur. In addition, the different oxidation states of copper associate well with a large number of different functional groups via Lewis acid interactions or π-coordination. In total, these feature confer a remarkably broad range of activities allowing copper to catalyze the oxidation and oxidative union of many substrates.

Oxygen is a highly atom economical, environmentally benign, and abundant oxidant, which makes it ideal in many ways.1 The high activation energies in the reactions of oxygen require that catalysts be employed.2 In combination with molecular oxygen, the chemistry of copper catalysis increases exponentially since oxygen can act as either a sink for electrons (oxidase activity) and/or as a source of oxygen atoms that are incorporated into the product (oxygenase activity). The oxidation of copper with oxygen is a facile process allowing catalytic turnover in net oxidative processes and ready access to the higher CuIII oxidation state, which enables a range of powerful transformations including two-electron reductive elimination to CuI. Molecular oxygen is also not hampered by toxic byproducts, being either reduced to water, occasionally via H2O2 (oxidase activity) or incorporated into the target structure with high atom economy (oxygenase activity). Such oxidations using oxygen or air (21% oxygen) have been employed safely in numerous commodity chemical continuous and batch processes.3

However, batch reactors employing volatile hydrocarbon solvents require that oxygen concentrations be kept low in the head space (typically <5–11%) to avoid flammable mixtures, which can limit the oxygen concentration in the reaction mixture.4,5,6 A number of alternate approaches have been developed allowing oxidation chemistry to be used safely across a broader array of conditions. For example, use of carbon dioxide instead of nitrogen as a diluent leads to reduced flammability.5 Alternately, water can be added to moderate the flammability allowing even pure oxygen to be employed.6 New reactor designs also allow pure oxygen to be used instead of diluted oxygen by maintaining gas bubbles in the solvent, which greatly improves reaction rates and prevents the build up of higher concentrations of oxygen in the head space.4a,7 Supercritical carbon dioxide has been found to be advantageous as a solvent due its chemical inertness towards oxidizing agents and its complete miscibility with oxygen or air over a wide range of temperatures.8 An number of flow technologies9 including flow reactors,10 capillary flow reactors,11 microchannel/microstructure structure reactors,12 and membrane reactors13 limit the amount of or afford separation of hydrocarbon/oxygen vapor phase thereby reducing the potential for explosions.

Enzymatic oxidizing systems based upon copper that exploit the many advantages and unique aspects of copper as a catalyst and oxygen as an oxidant as described in the preceding paragraphs are well known. They represent a powerful set of catalysts able to direct beautiful redox chemistry in a highly site-selective and stereoselective manner on simple as well as highly functionalized molecules. This ability has inspired organic chemists to discover small molecule catalysts that can emulate such processes. In addition, copper has been recognized as a powerful catalyst in several industrial processes (e.g. phenol polymerization, Glaser-Hay alkyne coupling) stimulating the study of the fundamental reaction steps and the organometallic copper intermediates. These studies have inspiried the development of nonenzymatic copper catalysts. For these reasons, the study of copper catalysis using molecular oxygen has undergone explosive growth, from 30 citations per year in the 1980s to over 300 citations per year in the 2000s.

A number of elegant reviews on the subject of catalytic copper oxidation chemistry have appeared. Most recently, reviews provide selected coverage of copper catalysts14 or a discussion of their use in the aerobic functionalization of C–H bonds.15 Other recent reviews cover copper and other metal catalysts with a range of oxidants, including oxygen, but several reaction types are not covered.16 Several other works provide a valuable overview of earlier efforts in the field.17 This review comprehensively covers copper catalyzed oxidation chemistry using oxygen as the oxidant up through 2011. Stoichiometric reactions with copper are discussed, as necessary, to put the development of the catalytic processes in context. Mixed metal systems utilizing copper, such as palladium catalyzed Wacker processes, are not included here. Decomposition reactions involving copper/oxygen and model systems of copper enzymes are not discussed exhaustively. To facilitate analysis of the reactions under discussion, the current mechanistic hypothesis is provided for each reaction. As our understanding of the basic chemical steps involving copper improve, it is expected that many of these mechanisms will evolve accordingly.

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Aerobic Copper-Catalyzed Organic Reactions

H2O2 is important in large-scale industrial processes and smaller on-site activities. The present industrial route to H2O2 involves hydrogenation of an anthraquinone and O2 oxidation of the resulting dihydroanthraquinone — a costly method and one that is impractical for routine on-site use. Electrosynthesis of H2O2 is cost-effective and applicable on both large and small scales. This Review describes methods to design and assess electrode materials for H2O2 electrosynthesis. H2O2 can be prepared by oxidizing H2O at efficient anodic catalysts such as those based on BiVO4. Alternatively, H2O2 forms by partially reducing O2 at cathodes featuring either noble metal alloys or doped carbon. In addition to the catalyst materials used, one must also consider the form and geometry of the electrodes and the type of reactor in order to strike a balance between properties such as mass transport and electroactive area, both of which substantially affect both the selectivity and rate of reaction. Research into catalyst materials and reactor designs is arguably quite mature, such that the future of H2O2 electrosynthesis will instead depend on the design of complete and efficient electrosynthesis systems, in which the complementary properties of the catalysts and the reactor lead to optimal selectivity and overall yield. Electrosynthesis is a practical and green route to hydrogen peroxide, and could reduce our dependence on less environmentally friendly oxidants. This Review describes catalyst and reactor designs for highly selective hydrogen peroxide electrosynthesis.

Electrochemical synthesis of hydrogen peroxide from water and oxygen

Electrosynthesis offers a powerful tool for the formation of anion and cation radical intermediates and for driving clean synthetic reactions without the need for additional chemical reagents. Recent advances in microfluidic reactor technologies triggered an opportunity for new microflow electrolysis reactions to be developed for novel and clean electrosynthetic processes. Naturally, two electrodes, anode and cathode, are required in all electrochemical processes and combining the two electrode processes into one “paired” reaction allows waste to be minimised. By decreasing the inter-electrode gap “paired” reactions may be further “coupled” by overlapping diffusion layers. The concept of “coupling” electrode processes is new and in some cases coupled processes in micro-flow cells are possible even in the absence of intentionally added electrolyte. The charged intermediates in the inter-electrode gap act as electrolyte and processes become “self-supported”. Hardly any examples of “coupled” paired electrochemical processes are known to date and both “paired” and “coupled” processes are reviewed here. Coupled electrode processes remain a challenge. In future “pairing” and “coupling” electrode processes into more complex reaction sequences will be the key to novel and clean flow-through microreactor processes and to novel chemistry.

Towards paired and coupled electrode reactions for clean organic microreactor electrosyntheses

Convergent paired electrosynthesis is an energy-efficient approach in organic synthesis; however, it is limited by the difficulty to match the innate redox properties of reaction partners. Here we use nickel catalysis to cross-couple the two intermediates generated at the two opposite electrodes of an electrochemical cell, achieving direct arylation of benzylic C–H bonds. This method yields a diverse set of diarylmethanes, which are important structural motifs in medicinal and materials chemistry. Preliminary mechanistic study suggests oxidation of a benzylic C–H bond, Ni-catalyzed C–C coupling, and reduction of a Ni intermediate as key elements of the catalytic cycle.

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Nickel catalysis enables convergent paired electrolysis for direct arylation of benzylic C–H bonds

Electrochemical behaviour of benzene on platinum electrodes

Direct Conversion of Benzene to Hydroquinone Mediated with Cu(I)/Cu(II) Redox System

A novel paired electrosynthesis of p-benzoquinone and hydroquinone from benzene

The combination of anodic oxidation of benzene on PbO 2 electrode with “cathodic oxidation of benzene” using Cu(I)/Cu(II) mediator in a single H-type electrolytic cell gives p-benzoquinone and hydroquinone in the total current efficiency of 94%.

Ryuichi Katayama

Papers

Direct Conversion of Benzene to Hydroquinone Mediated with Cu(I)/Cu(II) Redox System

A novel paired electrosynthesis of p-benzoquinone and hydroquinone from benzene

A Novel Paired Electrosynthesis of p‐Benzoquinone and Hydroquinone from Benzene.