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

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.1 Introduction2 I(V): Hypervalent Iodine Reagents3 I(V)-Mediated Dearomatization to o-Quinones4 Bisnitrogen-Ligated I(V) Reagents: ortho Dearomatization of Electron-Poor Phenols5 I(V)-Mediated Dearomatization to o-Quinols6 Conclusion and Outlook

A Complementary Route for Alkene–Arene para-Cycloadditions by Visible-Light-Promoted Triplet Sensitization of Allenamides

“…Indeed, the formation of the 1,4-quinone is usually kinetically favored over that of the desired 1,2-quinone. Additionally, the relatively strong oxidative conditions that are usually required 6 7 8 limit the functional-group tolerance and reduce the atom economy of the approach.…”

Ambimodal Addition-Coupled Electron Transfer Mechanism in a Pb(IV)-Promoted Oxidative Dearomatization Reaction

“…The oxidative dearomatization reaction of phenols composes a widely used strategy in organic synthesis because of its ability to build complex molecular skeletons through mild reaction conditions and simple starting materials. − It has been achieved by treating phenols with oxidants such as hypervalent iodine species, , Pb­(IV) oxidants, as well as electrochemical methods . Among them, the Pb­(IV)-promoted oxidative dearomatization reaction, known as the Wessely reaction, has been a widely used methodology since its discovery in 1964 .…”

Interrupted SNAr-Alkylation Dearomatization

“…The centrality of aromatics has spurred numerous strategies to transform readily available precursors into high value products. Several methods effectively dearomatize fused aromatics, heteroaromatics, , and phenols, , whereas simple derivatives of benzene are more challenging because of the increased stability of the π-system . Despite the strongly reducing conditions, the classical dissolving metal reduction, and advantageous variants, remain the gold standard to access complex cyclohexadienes (Scheme A, 1 → 2 → 3 ).…”