Abstract

The copper-catalyzed aerobic oxygenation of phenols is an attractive green method for the preparation of reactive and synthetically useful ortho-quinones. Recently, the Lumb group has developed fully catalytic conditions to perform this reaction with unsurpassed simplicity and efficiency. This reaction employs catalytic amounts of copper(I) and N,N’-di-tert-butylethylenediamine (DBED) as the supporting ligand. Our group unveiled the mechanism of this reaction with 4-tert-butylphenol, and showed that the oxygenation proceeded via side-on peroxodicopper(II) core (SP) and copper(II)-semiquinone (SQ) intermediates. However, not all substrates behave equally under these or similar reaction conditions, with some substrates undergoing oxygenation with subsequent C–O coupling, some undergoing only oxygenation, and some undergoing radical-based C–C coupling. In order to better understand the selectivity of the reaction, we screened a library of ligands with different nitrogen donors and denticities on the substrate that only undergoes to ortho-oxygenation (3,5-di-tert-butylphenol). We present an extensive mechanistic study on the oxygenation reaction, including characterization of intermediates and kinetic studies. We employ UV-Vis spectroscopy between –120 and 25 C as the main technique due to the colour of the reaction intermediates and products. We show that ligands that are successful at providing a good yield of quinones at room temperature are those who stabilize a SP core at low temperature. This core is the same as that in oxy-tyrosinase, the enzyme acting in the first step of melanin biosynthesis. Overall, this correlation provides a link between stoichiometric bio-inorganic studies at low temperatures and catalytic activity at room temperature, opening avenues for further reaction improvement.