Leveraging Isomerization of Azo Dyes and Imines for the Facile Synthesis of Oxadiazepines and Related Heterocycles

ABSTRACT Herein is described the mild cyclization of azo dyes to oxadiazepines via intramolecular S N Ar. Based on previous attempts showing the cyclization of perfluoro azo dyes in an ethanolic aqueous buffer at room temperature, various fluorinated aryl amines were coupled to aryl alcohols via in situ formed diazonium salts, followed by S N Ar ring closure at room temperature or with mild heating enabled by base and isomerization. The cyclization tolerates varied aryl fluoride electrophiles well, with yields ranging from 81% to quantitative, but exhibits significant competition with intermolecular side‐reactions with certain variations in the nucleophilic portion of the substrate, resulting in oligomerization. The cyclization reaction was also successful with analogous imines, owing to similar isomerization capabilities. Finally, kinetic studies enabled by UV–visible absorbance spectroscopy revealed photoactivation dramatically accelerated the cyclization. When irradiated with green light ( λ max = 522 nm), a 38‐fold increase in reaction rate was observed compared to no light. Further analysis revealed that the cyclization reaction is pseudo first‐order with respect to the substrate. These findings open the door to an improved photoactivated approach to bias the cyclization reaction toward the desired intramolecular products, unlocking difficult substrates that oligomerize under thermal reaction conditions. As an example, this new strategy enabled access to a difficult triazepine product.