New insights into the mechanism of phenolic oxidation with phenyliodonium(III) reagents

Oxidative Conversion of Arenols into ortho ‐Quinols and ortho ‐Quinone Monoketals – A Useful Tactic in Organic Synthesis

“…Curiously, they only obtained para-quinol acetates with PIDA, whereas LTA gave ortho-quinol acetates from the same starting phenols. In 1988, Pelter and co-workers reinvestigated the use of PIDA to oxidize phenols in MeOH and thus introduced the PIDA-mediated oxidative methoxylation of phenols, referred to herein as the Pelter oxidation [106][107][108]. In 1987, Tamura [109] had reported the use of another less nucleophilic hypervalent iodine reagent, phenyliodonium(III) bis(trifluoroacetate) (PIFA), to promote the oxidative alkoxylation of arenols.…”

“…Both routes are driven by the reduc- tive conversion of trivalent iodine into monovalent iodine and first imply the formation of the aryloxyiodonium(III) species 56a, which can then either undergo direct nucleophilic attack (route a) or dissociate to furnish a solvated phenoxenium cation 56b (route b) ( Figure 18). Pelter and collaborators recently concluded that the process is most likely to proceed via a phenoxenium ion of type 56b (route b) on the basis of the following arguments: (1) the phenyliodonium(III) group is an extremely powerful nucleofuge with a leaving ability about 10 6 times that of the triflate group; (2) Mulliken charge semiempirical calculations of a series of 2-and 4-substituted phenoxenium cations predict the observed regiochemistry of the nucleophilic attack with accuracy (vide infra), and (3) reactions performed on 2-alkoxyphenols in a chiral environment displayed a complete lack of stereochemical control [108,111]. As alluded to above, and demonstrated many times experimentally, the regiochemistry of the methanol attack (i.e., ortho-57 vs. para-58) depends more on the electronic nature of the ring substituents than on their steric demand.…”

“…Y ¼ H, Me), as well as at C-6. Alkylphenols such as 2,3-dimethylphenol, 3,5-dimethylphenol, 2-benzyl-and 4-benzylphenol, and 2,4,6-tri-tert-butylphenol show a net preference for attack at C-4 [108].…”

Antitumor benzothiazoles. 13. (Diacetoxy)iodobenzene (DAIB) oxidation of 2-(4-hydroxy-3-methoxyphenyl)benzothiazole and related compounds in the presence of dienophiles

“…3 It is known that simple 2-methoxyphenols, substituted with an EWG in the 4-position (5), when oxidised using DAIB in methanol generate pcarbocation reactive intermediates (6) (Scheme 1) which react with the methanol to produce ortho-quinone monoketals (7) (OQMs). 6 Although these compounds are often too unstable to isolate (in contrast to 2-acyloxy-2-alkoxy-3,5-cyclohexadieones) 3,7 their presence in the reaction mixture may be inferred by the isolation of their Diels-Alder dimers. 8,9 A number of recent publications have demonstrated that trapping OQMs, Our own interest in this chemistry stems from our efforts to understand both the role of oxidation of phenols in their biological activity and the routes by which they may be oxidised during bioactivating/deactivating processes.…”

Diastereoselective spiroannulation of phenolic derivatives: Effect of steric hindrance on the diastereoselectivity.

“…48 In the oxidations examined by the Kurti group, it was found that there was a total lack of diastereo and enantioselectivity, thus giving support to the formation of the phenoxenium ion 18.…”