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

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.<br>

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

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.<br>

Mechanism of Ni-Catalyzed Reductive 1,2-Dicarbofunctionalization of Alkenes

A mechanistic study on Ni-catalyzed reductive 1,2-dicarbofunctionalization of alkenes distinguishes the "radical chain" mechanism from the "sequential reduction" mechanism.

Mechanism of Ni-Catalyzed Reductive 1,2-Dicarbofunctionalization of Alkenes

A mechanistic study on Ni-catalyzed reductive 1,2-dicarbofunctionalization of alkenes distinguishes the "radical chain" mechanism from the "sequential reduction" mechanism.

Degenerative xanthate transfer to olefins under visible-light photocatalysis

The degenerative transfer of xanthates to olefins is enabled by the iridium-based photocatalyst [Ir{dF(CF3)ppy}2(dtbbpy)](PF6) under blue LED light irradiation. Detailed mechanistic investigations through kinetics and photophysical studies revealed that the process operates under a radical chain mechanism, which is initiated through triplet-sensitization of xanthates by the long-lived triplet state of the iridium-based photocatalyst.

α-Arylation of alkylamines with sulfonylarenes through a radical chain mechanism

A radical chain, conducted by a sulfonyl radical in a homolytic aromatic substitution mechanism, makes it possible to promote α-arylation of alkylamines with sulfonylarenes just by using a substoichiometric amount of a tert-butoxy radical precursor.

Stereoselective cobalt-catalyzed halofluoroalkylation of alkynes

Stereoselective additions of functionalized reagents to unsaturated hydrocarbons are attractive due to the high atom economy, modularity and rapid generation of complexity. We report a stereoselective cobalt-catalyzed (E)-halofluoroalkylation of alkynes/alkenes that under mild conditions (2 mol% cat., 20 °C, acetone/water, 3 h). This reaction operates via a radical chain mechanism involving terminal halogen atom transfer which obviates the need for a stoichiometric sacrificial reductant.