Oxidation of Phenolic Compounds with Organohypervalent Iodine Reagents

Moriarty, Robert M.; Prakash, Om


The oxidation of phenols is a key biochemical process in oxidative phosphorylation, and it is also important in numerous biosynthetic pathways. Controlled oxidative transformations of substituted phenols are found in many synthetic organic sequences. Accordingly, a large number of oxidizing agents for phenols have been developed. Useful reagents include Fremy’s salt (KSO3)2NO,and a wide variety of other redox metal-based oxidants such as Pb(IV), Mn(III), Tl(III), Cu(II), and Fe(III). Recently, organohypervalent iodine reagents have emerged as particularly useful agents for oxidizing phenols. In the area of natural product synthesis, organohypervalent iodine reagents have been used extensively to effect oxidative intramolecular bicyclization and spirocyclization. The focus of this chapter is on synthetic applications. The chapter also covers formation and applications of phenolic iodonium ylides.

The processes that occur during the oxidation of phenols with organohypervalent iodine reagents can be divided into two categories. The first category involves ligand exchange of the phenolic proton with the hypervalent iodine reagent to generate the O-I(III) intermediate, which is subsequently transformed to various products, depending upon the reaction conditions.

These transformations include oxidation of phenols to quinones and related compounds, formation of spirocyclic and oxygen heterocyclic compounds via oxidative intramolecular participation reactions, and intramolecular carbon-carbon bond formation via phenolic oxidative coupling. All of these reactions are driven by the reduction of iodine(III) [or iodine(V)] to iodine(I) (iodobenzene).

A second class of reactions that is discussed in this chapter includes formation of stable iodonium salts and ylides, which are important intermediates in organic synthesis. These reactions occur via carbon-I(III) bond formation without loss of iodobenzene.