Selective functionalisation of aromatic alcohols with supramolecularly regulated gold(i) catalysts

Abstract

Phosphite-based Au(I) catalytic systems containing an array of structurally diverse polyether-based regulation sites were designed and synthesised. These catalysts have been successfully tested in the Au(I)-catalysed C–H functionalisation of phenols and related derivatives with gold–carbenes derived from diazo compounds. Regulation of the steric congestion around the catalytic Au(I) centre via ion–dipole interactions with an external regulation agent led to an enhancement of both the activity and selectivity of the reaction. This new approach in supramolecular gold(I) catalysis has been applied to the derivatisation of an array of substituted phenols and related substrates and to the preparation of an advanced synthetic intermediate of the anticancer agent tamoxifen. The effects of the regulation agent on the selectivity and yield of the reaction have been studied and rationalised using DFT-D calculations.