Iodane-mediated and electrochemical oxidative transformations of 2-methoxy- and 2-methylphenols

Abstract

A series of 2-methoxy and 2-methylphenols have been submitted to oxygenative oxidation reactions using (1) the λ 3 -iodane DIB, (2) a non-explosive and non-moisture sensitive version of the λ 5 -iodane IBX, named SIBX for Stabilized IBX, and (3) anodic oxidation with the aim of identifying the best reaction conditions for preparing orthoquinonoid cyclohexadienone synthons. Both the use of DIB and anodic oxidation appeared equally valuable for making orthoquinone dimethyl ketals, but the λ 3 -and λ 5-iodane reagents are more appropriate to induce ortho-oxygenation of 2-methylphenols. In particular, SIBX emerged as a useful reagent for mediating ortho-hydroxylation into dimerizing orthoquinols, a tactic that can be applied to the synthesis of natural bis(monoterpenoids) such as aquaticol.

Oxidative Dearomatization of Phenols: Why, How and What For?

“…Interestingly, this reactivity could be unveiled by hydrolyzing the acetate ester to furnish dimer 103 in 40% yield (Scheme 29). 91 Similar two-step procedures have been previously followed by others to access related dimers of ortho-quinols, generated using lead tetraacetate. [120][121][122] We then surmised that this dimer could perhaps be directly obtained by performing the same reaction in the presence of water.…”

“…It can even constitute a competitive methodology when considering that the PIDAmediated oxidation of 72a in methanol at 0°C afforded dimer 74a in only 37% yield. 91…”

“…This was indeed accomplished by treating phenol 99 with PIDA in acetonitrilewater (9:1), but dimer 103 was isolated in only 27% yield, together with a much larger amount of the para-quinone 102 (Scheme 29). 91 This loss of the desired regioselectivity would be a consequence of the capacity of water, used as a cosolvent, to trap the PIDA-activated phenol 104 at its para-position, as well as at its methylated ortho-position. Thus, with such an excess of water, it appears that the weak electron-releasing methyl substituent at the 2-position does not play any role in directing the entry of the nucleophile at that locus.…”

Recent Advances in the Selective Oxidative Dearomatization of Phenols to o-Quinones and o-Quinols with Hypervalent Iodine Reagents

“…In this first report, oxidation with SIBX was compared to anodic and I(III)-mediated oxidation and found to be superior in both conversion and regioselectivity (Scheme 6). 19…”

“…Rather, it has been its precursor 2-iodoxybenzoic acid (16, IBX), its stabilized formulation S-IBX (17), and the sulfonate analogue IBS (18) that have seen broad application for the transformation of phenols to o-quinones and o-quinols. IBS has also seen catalytic applications starting from the I(I) pre-IBS (19) in combination with stoichiometric co-oxidants. Finally, a recent report from our laboratory described the first synthetic application of Bi(N)-HVIs (20), I(V) reagents possessing bidentate nitrogen ligands, for the dearomatization of particularly challenging electron-poor phenols.…”