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.