Electrochemical Dearomatizing Methoxylation of Phenols and Naphthols: Synthetic and Computational Studies.

The electrochemical oxidative dearomatizing methoxylation of phenols and naphthols was developed. It provides an alternative route for the preparation of methoxycyclohexadienones, important and versatile synthetic intermediates, that eliminates the need for stoichiometric high-energy chemical oxidants and generates hydrogen as a sole by-product. The reaction proceeds in a simple constant current mode, in an undivided cell, and it employs standardized instrumentation. A collection of methoxycyclohexadienones derived from various 2,4,6-tri-substituted phenols and 1-substituted-2-naphthols was obtained in moderate to excellent yields. These include a complex derivative of estrone, as well as methoxylated dearomatized 1,1'-bi-2-naphthols (BINOLs). The mechanism of the reaction was subject to profound investigations using density functional theory calculations. In particular, the reactivity of two key intermediates, phenoxyl radical and phenoxenium ion, was carefully examined. The obtained results shed light on the pathway leading to the desired product and rationalize experimentally observed selectivities regarding a side benzylic methoxylation and the preference for the functionalization at the para over the ortho position. They also uncover the structure-selectivity relationship, inversely correlating the steric bulk of the substrate with its propensity to undergo the side-reaction. Moreover, the loss of stereochemical information from enantiopure BINOL substrates during the reaction is rationalized by the computations.

Reductive Cross-Coupling of a Vinyl Thianthrenium Salt and Secondary Alkyl Iodides.

We report the first reductive vinylation of alkyl iodides. The reaction uses a vinyl thianthrenium salt, a palladium catalyst, and an alkyl zinc intermediate formed in situ to trap the Ln PdII (vinyl) complex formed after oxidative addition before it undergoes undesired homocoupling to form butadiene.

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

The oxidative 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. 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 the transformation proceeds by a radical-chain mechanism, with a phenoxyl 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 phenoxyl radical, the water molecule becomes activated by the interaction with the iodine(III) center, causing the Umpolung of this formally nucleophilic substrate. The radical-chain mechanism allows the rationalization of all existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.