Mechanism of Iodine(III)-Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for Radical-Chain Pathway

10 April 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


In the recent years, the dearomatization of phenols with the addition of nucleophiles to the aromatic ring, induced by hypervalent iodine(III) reagents and catalysts, has emerged as a highly useful synthetic approach. However, experimental mechanistic studies of this important process have been extremely scarce. As a result, the mechanism of the reaction remained elusive and as of today there exist as many as three distinct mechanistic proposals. In this report, we describe systematic investigations of the dearomatizing hydroxylation of phenols using an array of experimental techniques. Kinetics, EPR spectroscopy, and reactions with radical probes demonstrate that all the previously suggested mechanisms are incorrect, and that the transformation in fact proceeds via a radical-chain mechanism, with the aryloxyl radical being the key chain-carrying intermediate. Moreover, UV and NMR spectroscopy, high-resolution mass spectrometry, and cyclic voltammetry show that before reacting with the aryloxyl radical, water molecule becomes activated by the interaction with the iodine(III) center, causing this formally nucleophilic substrate to act as an electrophile. The C–O bond formation is identified as the rate-determining step of the reaction. This step generates the dearomatized product and an iodanyl(II) species, which is the second chain-carrying radical. The radical-chain mechanism emerging from our investigations allows to rationalize all other existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.


phenol dearomatization
hypervalent iodine
mechanistic studies
radical-chain mechanism

Supplementary materials

SI dearomatization f


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.