On the Mechanism of Phenolic Formylation Mediated by TiCl4 Complexes: Existence of Diradical Intermediates Induced by Valence Tautomerism

The conventional electrophilic intramolecular aromatic substitution pathway proposed by Cresp et al. [J. Chem. Soc., Perkin Trans. 1 1973, 340–345] is confirmed by the observed products of phenolic formylation mediated by TiCl4. However, when the nucleophilic path is quenched by appropriate ligand modification, the initial equilibria between the possible neutral complexes of TiCl4 with 3,5‐dimethoxyphenol and/or diethyl ether lead to different stable diradical intermediates induced by valence tautomerism that provide valuable activated reagents. Some of these species have been detected by EPR, characterized theoretically and captured by TEMPO, thus providing a consistent mechanism for the reaction with one or more equivalents of TEMPO per phenol. The mechanism of phenolic formylation mediated by TiCl4 has been investigated both theoretically and experimentally. Stable diradical intermediates induced by valence tautomerism have been detected and characterized. These diradical species are expected to be of fundamental significance in organic and bioorganic chemistry.