Oxidative dearomatization of phenols promoted by hypervalent iodine species coupled with the addition of nucleophiles to the ring allows to obtain highly functionalized products, including chiral ones, that can serve as building blocks for the construction of complex molecules. Despite the high synthetic importance of the dearomatization of phenols promoted by hypervalent iodine oxidants, there have been a lack of proper understanding of the mechanism of this transformation, which has been a subject to only few, exclusively computational, studies. Furthermore, the reported results do not explain the enantioselectivity exhibited by the reaction, when it is performed in the presence of a chiral iodoarene reagent.<br/>In this context, for the first time, we have carried out a series of experimental mechanistic investigations to shed light on the pathway followed by the dearomatization of phenols promoted by hypervalent iodine species. Our studies, which included: kinetic and voltammetric measurements, characterization of intermediates using EPR and UV/VIS spectroscopy and mass spectrometry, as well as radical clock experiments, point to the key role of radical species in the mechanism of the reaction. Based on the obtained results, we propose a radical-chain mechanism, which explains the formation of non-racemic products and all the other existing experimental observations. Our findings provide implications for the development of novel synthetic methods based on the dearomatization of phenols employing iodine(III) oxidants and have an important bearing for the design of new chiral iodoarene catalysts.

Mechanistic studies on oxidative dearomatization of phenols promoted by hypervalent iodine(III) species

ACS Spring 2022

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