Phosphoric-Acid-Catalyzed ortho -Selective Intramolecular Cyclodehydration Reaction of Phenols and Anilines

In this study, we report an organocatalyst-controlled ortho-selective intramolecular cyclodehydration of phenols and anilines. In the presence of 1 mol % of a phosphoric acid catalyst, resorcinol, 3-aminophenol, and 1,3-phenylenediamine derivatives underwent highly regioselective cyclodehydration to afford 4-hydroxybenzofuran, 4-hydroxyindole, 4-aminobenzofuran, and 4-aminoindole derivatives in up to 97% yield and >99:1 regioselectivity. The resulting products were further derivatized and applied in a formal synthesis of tambromycin. Kinetic studies and DFT calculations elucidated the regioselective reaction mechanism.