Carbonyl oxidation with hypervalent iodine reagents involves the functionalization of the α position of carbonyl compounds through the intermediacy of a hypervalent iodine(III) enolate species. This electrophilic intermediate may be attacked by a variety of nucleophiles or undergo rearrangement or elimination. Introduction Hypervalent iodine(III) compounds are attractive oxidizing agents because of their stability and selectivity. In the presence of enolizable carbonyl compounds, they are able to accomplish oxidative functionalization of the α position. A key iodine(III) enolate intermediate forms, which then undergoes either nucleophilic substitution (α-functionalization), elimination (dehydrogenation), or rearrangement. Common hypervalent iodine reagents used to effect these transformations include iodosylbenzene (PhIO), iodobenzene diacetate (PhI(OAc)2), Koser's reagent (PhI(OTs)OH), and (dichloroiodo)benzene (PhICl2). Mechanism and stereochemistry Prevailing mechanism The mechanism of carbonyl oxidation by iodine(III) reagents varies as a function of substrate structure and reaction conditions, but some generalizations are possible. Under basic conditions, the active iodinating species are iodine(III) compounds in which any relatively acidic ligands on iodine (such as acetate) have been replaced by alkoxide. In all cases, the α carbon forms a bond to iodine. Reduction of iodine(III) to iodine(I) then occurs via attack of a nucleophile on the now electrophilic α carbon. Under basic conditions, nucleophilic attack at the carbonyl carbon is faster than attack at the α carbon. Iodine displacement is actually accomplished intramolecularly by the carbonyl oxygen, which becomes the α-hydroxyl oxygen in the product. Rearrangements of the iodine(III) enolate species have been observed. Under acidic conditions, oxidations of aryl enol ethers lead to α-aryl esters via 1,2-aryl migration. Ring-contractive Favorskii rearrangements may take place under basic conditions (see equation (12) below). Stereochemistry Using a chromium carbonyl complex, it was shown that displacement of iodine likely occurs with inversion of configuration. Iodine approaches on the side opposite the chromium tricarbonyl unit due to steric hindrance. Invertive displacement leads to a syn relationship between chromium and the α hydroxyl group. Studies on the oxidation of unsaturated carbonyl compounds also provide stereochemical insight. Only the isomer with a syn relationship between the α-hydroxy and β-methoxy groups was observed. After nucleophilic attack by methoxide, iodine approaches the face opposite the methoxide. Invertive displacement by hydroxide then leads to the syn isomer. Scope and limitations Under protic conditions, ketones undergo α-hydroxylation and dimethyl acetal formation. Both iodosylbenzene and iodobenzene diacetate (IBD) can effect this transformation. This method can be used to synthesize α-hydroxy ketones after acidic hydrolysis of the ketal