Oxidative Coupling of Phenols and Phenol Ethers

Abstract

The ready oxidation of phenols to dimeric products has been well known for more than a century. The invaluable survey of the area by Musso1 lists over 20 papers published before 1900 on, for example: the formation of the dilactone (1) from gallic acid2 and its derivatives (1871);3 the production of both parapara and ortho-ortho coupled dimers from 1-naphthol (1873);4 the synthesis of the diphenoquinone (2),5 in 97% yield, from 2,5-dimethoxyphenol (1878); and the preparation of 2,2′-dihydroxybiphenyl from phenol itself (1878).6 Reagents used in such early work include iron(III) salts, potassium ferricyanide, oxygen and the halogens; electrochemical methods were also known, and enzyme-catalyzed reactions were reported in, for example, the oxidative dimerization of eugenol (1896).7 Extensive chemical investigations into this major reaction continued this century and further momentum was gained from the recognition of the role of oxidative coupling in biogenesis, signalled by the important and influential papers of Barton and Cohen,8 and of Erdtman and Wachtmeister.9 Subsequent biosynthetic investigations have confirmed the significance of the title reaction in the in vivo formation of many aromatic natural products including alkaloids (Battersby1 estimated that such coupling was involved in ca. 10% of known alkaloids), lignans, lignin, tannins, and plant and insect pigments. Many biomimetic studies of oxidative phenolic coupling were made, either for synthetic ends or to demonstrate possibilities in biological processes. Low chemical yields were often reported in such work, particularly in certain well-known alkaloid cases, and attention was turned to new reagents, e.g. manganese(III), vanadium(V) and thallium(III), which generally proved more effective. Further, oxidants such as vanadium(V) were found to effect coupling of phenol ethers, and interest was revived in the anodic oxidation of such aromatic substrates. The oxidation of phenol ethers has proved a valuable synthetic process, often more predictable and higher yielding than the corresponding phenol oxidations, and this reaction has been employed in recent years in a number of notable natural product syntheses.