Green oxidation of alcohols using biomimetic Cu complexes and Cu enzymes as catalysts

The oxidation of alcohols to carbonyl compounds is one of the most fundamental and important processes in the fine chemical industry. The classical methodology is based on the stoichiometric use of heavy metals, notably Cr and Mn (1,2). Alternatively metal-free oxidation, such as the Swern and Pfitzner-Moffat protocols, is based on e.g., dimethylsulfoxide as oxidant in the presence of an activating reagent such as N,N′-dicyclohexylcarbodiimide, an acid anhydride or acid halide (3). Although the latter methods avoid the use of heavy metals, they usually involve moisture-sensitive oxidants and environmentally undesirable reaction media, such as chlorinated solvents. The desired oxidation of alcohols only requires the formal transfer of two hydrogen atoms, and therefore the atom economy of these methods is extremely disadvantageous. The current state of the art in alcohol oxidations relies on the use of chemocatalysts employing molecular oxygen or dihydrogen peroxide as the final oxidant. In this way water is the only byproduct formed. Among the best methods reported Pd (4), Pt (5,6), Ru (6) and W-based catalysts (7) have demonstrated large potential. In the search for new catalysts, Cu-based methods would constitute an attractive alternative (8,9). Copper is a cheap, non-toxic metal which is predominant in many enzymes which are involved in the oxidation of alcohols and phenolic structures (as e.g., in lignin). These copper-containing oxidases provide a wealth of inspiration to the design of efficient copper-catalysts. In this chapter we will deal with examples of biomimetic and biocatalytic copper-based redox-catalysts that could be used for the green and selective oxidation of alcohols. Copper-containing oxidases can be divided into enzymes with mononuclear copper-sites, dinuclear copper-sites, and enzymes with multinuclear copper sites (10). Many of these are employed by nature for the oxidative dehydrogenation of natural alcohols employing dioxygen as the ultimate oxidant. Besides alcohols, aliphatic and aromatic amines are also substrates for copper-oxidases. Major advances have been made toward understanding the structure/function relationship of the active sites in copper-containing oxidases. The publication of the crystal structures of galactose oxidase (11), catechol oxidase (12), and laccase (13) are important recent milestones. They also represent notable examples of mononuclear, dinuclear, and multinuclear active sites of copper oxidases respectively. The most appealing example for biocatalytic alcohol oxidation is no doubt formed by galactose oxidase (GOase). Galactose oxidase [E.C. 1.1.3] is secreted by certain fungi into the extracellular environment, where it functions as a broad-spectrum catalyst for oxidation of primary alcohols and a source of dihydrogen peroxide (14). The active site of GOase involves a mononuclear copper(II) species with a distorted square pyramidal geometry. It combines two distinct one-electron acceptors, a Cu(II) metal center and a stable protein free radical, into a metalloradical complex that functions as a two-electron redox unit during catalytic turnover. The enzyme itself shows - up till now - limited practical use, due to its low reactivity (see below), although some interesting examples have been reported. However, galactose oxidase has been the major source of inspiration for scientists over the last two decades in designing an efficient copper catalyst for the aerobic oxidation of alcohols, and excellent examples have been reported in the literature. A large part of this chapter will be devoted to biomimetic models of galactose oxidase and an overview will be given. A second copper-enzyme which has demonstrated large potential in the catalytic oxidation of alcohols is laccase (15). This blue-copper, one-electron transfer, enzyme requires mediators to extend its catalytic action. Significant progress in its use has been made in the last five years and an overview thereof will be given as well. Finally, the class of dinuclear-copper oxidases, catechol oxidases and tyrosinases, and mimics thereof, have shown to be of limited use in the oxidation of aliphatic and aromatic alcohols. Their potential lies in the oxidation of ortho-diphenols to the corresponding quinones. For an overview of these dinuclear copper oxidases, the reader is referred to the contributions of L. Casella and K.D. Karlin elsewhere in this Volume. © 2005 Elsevier Inc. All rights reserved.