General Synthesis of 2-Substituted Benzoxazoles Based on TfO-Promoted Electrophilic Activation of Tertiary Amides.

We report a method for the synthesis of 2-substituted benzoxazoles from tertiary amides and 2-aminophenols in the presence of triflic anhydride (TfO) and 2-Fluoropyridine (2-F-Pyr). The cascade reaction involves the activation of the amide carbonyl group by TfO, nucleophilic addition, intramolecular cyclization, and elimination. Furthermore, we explore the scope of this method by varying both the amide and 2-aminophenol substrates, highlighting its versatility in the synthesis of a wide range of functionalized benzoxazole derivatives.