The ability of platinum and gold catalysts to effect powerful atom-economic transformations has led to a marked increase in their utilization. The quite remarkable correlation of their catalytic behavior with the available structural data, coordination chemistry, and organometallic reactivity patterns, including relativistic effects, allows the underlying principles of catalytic carbophilic activation by π acids to be formulated. The spectrum of reactivity extends beyond their utility as catalytic and benign alternatives to conventional stoichiometric π acids. The resulting reactivity profile allows this entire field of catalysis to be rationalized, and brings together the apparently disparate electrophilic metal carbene and nonclassical carbocation explanations. The advances in coupling, cycloisomerization, and structural reorganization—from the design of new transformations to the improvement to known reactions—are highlighted in this Review. The application of platinum- and gold-catalyzed transformations in natural product synthesis is also discussed.

Catalytic Carbophilic Activation: Catalysis by Platinum and Gold π Acids

Recent advances in olefin metathesis and its application in organic synthesis

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

Carbon-carbon bond forming reactions remain among the most important for the synthesis of organic structures. The transition metal alkylidene-catalyzed olefin metathesis reaction (eq 1) and the related transition metal alkylidene-mediated carbonyl olefination reaction (eq 2) are two such processes. Historically, olefin metathesis has been studied extensively both from the mechanistic standpoint and in the context of polymer synthesis. In contrast, its application to the synthesis of complex organic molecules and natural products has been limited. The related reaction, transition metal-mediated carbonyl olefination, is not as extensively studied mechanistically nor in synthetic applications. Among the reasons for this
gap in methodology has been the incompatibility of traditional catalysts with the polar functional groups
typically encountered in organic synthesis.

Ring-Closing Metathesis and Related Processes in Organic Synthesis

Carbon trifluoromethylation reactions of hydrocarbon derivatives and heteroarenes.

A two-step, catalytic synthesis of δ-hydroxy-γ-lactones from allylic acetates and bis(trimethylsilyl)ketene acetals

Reaction of diphenyltungstacarbene with cyclic enol ethers; structure of the insertion product

Formation and Selective Trapping of 2,5-Dihydropyridine and Its Isopropylidene Derivative by Tungsten(0) Alkylidene Complexes. X-ray Structure of the 5-Isopropylidene-2,5-dihydropyridine Adduct

Henri Rudler

Papers

A two-step, catalytic synthesis of δ-hydroxy-γ-lactones from allylic acetates and bis(trimethylsilyl)ketene acetals

Reaction of diphenyltungstacarbene with cyclic enol ethers; structure of the insertion product

Formation and Selective Trapping of 2,5-Dihydropyridine and Its Isopropylidene Derivative by Tungsten(0) Alkylidene Complexes. X-ray Structure of the 5-Isopropylidene-2,5-dihydropyridine Adduct

Synthesis of Functionalized Quinolizines and Homoquinolizines from N‐Alkynylaminocarbene Complexes of Chromium Intramolecular C–H Activation

Thiocarbene complexes of chromium: sulfur to carbon migration of an allyl group upon alkyne insertion