The unique catalytic role of water in aromatic C–H activation at neutral pH: a combined NMR and DFT study of polyphenolic compounds.

Direct activation of aromatic C–H bonds in polyphenolic compounds in a single step, without the use of late transition metals, is demonstrated with the use of D₂O and common phosphate buffer at neutral pD and near ambient temperatures. Detailed variable temperature and pD ¹H NMR studies were carried out to investigate, for the first time, the Gibbs activation energy (ΔG^‡), the activation enthalpy (ΔH^‡), and activation entropy (TΔS^‡) of H/D exchange reactions of the natural product catechin and the model compounds resorcinol and phloroglucinol. NMR and DFT calculations support a catalytic cycle comprising two water molecules in a keto–enol tautomeric process. The reduction of ΔG^‡ values due to the catalytic role of two molecules of water by a factor of 20–30 kcal mol⁻¹ and the resulting acceleration of the H/D exchange rate by a factor of 10²⁰–10³⁰ should be compared with a minor reduction in ΔG^‡ of 0.4 to 4.5 kcal mol⁻¹ due to the effect of an additional electron donating oxygen group and the deprotonation of OH groups. It can therefore be concluded that although the H/D exchange process can be accelerated by a small amount of an acid or a base to break a C–H bond, water as a catalyst plays the major role. This approach opens a new vistas for the combined use of NMR and DFT studies as tools to understand the molecular basis of the catalytic role of water. [ABSTRACT FROM AUTHOR]