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. 2021;32(8):752-762.
doi: 10.1055/s-0037-1610760. Epub 2021 Jan 14.

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

Xiao Xiao  1   2 , Sarah E Wengryniuk  2
Affiliations

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

Xiao Xiao et al. Synlett. 2021.

Abstract

ortho-Quinones are valuable molecular frameworks with diverse applications across biology, materials, organic synthesis, catalysis, and coordination chemistry. Despite their broad utility, their synthesis remains challenging, in particular via the direct oxidation of readily accessible phenols, due to the need to affect regioselective ortho oxidation coupled with the sensitivity of the resulting o-quinone products. The perspective looks at the emergence of I(V) hypervalent iodine reagents as an effective class of oxidants for regioselective o-quinone synthesis. The application of these reagents in regioselective phenol oxidation to both o-quinones and o-quinols will be discussed, including a recent report from our laboratory on the first method for the oxidation of electron-deficient phenols using a novel nitrogen-ligated I(V) reagent. Also included are select examples of total syntheses utilizing this methodology as well as recent advancements in chiral I(V) reagent design for asymmetric phenol dearomatization.

Keywords: I(V) reagent; hypervalent iodine; ortho-quinol; ortho-quinone; phenol dearomatization.

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Figures

Figure 1
Figure 1
The diverse applications and reactivity of o-quinones
Figure 2
Figure 2
Regioselective oxidation of polycyclic arenols with IBX or IBS
Figure 3
Figure 3
Chiral I(V) scaffolds and their efficiency in asymmetric phenol dearomatization reactions
Scheme 1
Scheme 1
Synthesis of o-quinones: (A) synthetic challenges in the direct dearomatization of phenols; (B) common oxidant systems in phenol dearomatization
Scheme 2
Scheme 2
I(V) reagents: structure, general reactivity, and common reagents used in phenol dearomatization to o-quinones
Scheme 3
Scheme 3
Pettus’ first report of IBX-mediated phenol dearomatization
Scheme 4
Scheme 4
Total synthesis applications of IBX-mediated dearomatization en route to aiphanol and brazilin
Scheme 5
Scheme 5
Proposed mechanism and DFT study of I(V) ortho dearomatization
Scheme 6
Scheme 6
SIBX-mediated oxidation of phenols to o-quinones and o-quinols
Scheme 7
Scheme 7
Use of catalytic 5-Me-IBS in the regioselective oxidation of phenols to o-quinones
Scheme 8
Scheme 8
Development Bi(N)-HVI reagent class and application to dearomatization of electron-poor phenols to o-quinones
Scheme 9
Scheme 9
Scope of electron-deficient phenol dearomatization with Bi(N)-HVIs
Scheme 10
Scheme 10
Subsequent functionalizations of electron-poor o-quinones to densely functionalized catechols.
Scheme 11
Scheme 11
Site-selectivity in the oxidation of 2-alkyl phenols to o-quinols
Scheme 12
Scheme 12
Selective oxidation of 2-alkyl phenols and naphthols with SIBX
Scheme 13
Scheme 13
Use of catalytic IBS in the regioselective synthesis of o-quinol dimers. Introduction of an α-SiR3 group controls reactivity and enables cascade sequences.
Scheme 14
Scheme 14
Representative syntheses of o-quinol-based natural products using I(V)-mediated dearomatization
Scheme 15
Scheme 15
Enantioselective oxidative dearomatization of phenols to o-quinols
See this image and copyright information in PMC

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