Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol

Abstract

Solvents such as 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) with a high capacity for donating hydrogen bonds generate solvates that enter into selective cross-coupling reactions of aryls upon oxidation. When electric current is employed for oxidation, reagent effects can be excluded and a decoupling of nucleophilicity from oxidation potential can be achieved. The addition of water or methanol to the electrolyte allows a shift of oxidation potentials in a specific range, creating suitable systems for selective anodic cross-coupling reactions. The shift in the redox potentials depends on the substitution pattern of the substrate employed. The concept has been expanded from arene-phenol to phenol-phenol as well as phenol-aniline cross-coupling. This driving force for selectivity in oxidative coupling might also explain previous findings using HFIP and hypervalent iodine reagents. A remarkable and tunable solvent effect is responsible for the highly selective cross-coupling of phenols with arenes, phenols or aniline derivatives (see scheme). The solvent mixture allows the decoupling of nucleophilicity and oxidation potential to some extent.