Furan Oxidation-Cyclization to Oxazepines: Favoring <i>7-exo-trig</i> over <i>6-endo-trig</i> and <i>5-exo-trig</i> Trajectories

The sequential oxidation-cyclization of hydroxyaminoalkylfurans to oxazepines is controlled by a regioselective <i>7-exo-trig</i> cyclization rather than the usually more favorable, <i>6-endo-trig</i> and <i>5-exo-trig</i> cyclizations. The key trajectory determinant is the generation of <i>Z</i>-dienones, which place the terminal substituents in close proximity. The versatile furan approach to oxazepines exploits an underdeveloped stereochemical feature allowing an efficient, regioselective, and robust route to variously substituted oxazepines ideal for bioactive discovery.