Synthesis of 8-Membered Benzosultam-Bridged 1,4-Benzoxazines via Cascade Oxetane Ring-Opening Cyclization/S N Ar Cycloetherification

A transition-metal-free, tandem one-pot double cyclization of N -(2-(3-oxetanyloxy)aryl)-2-fluoroarenesulfonamides has been developed, providing an unprecedented entry into 8-membered benzosultam-bridged 1,4-benzoxazines. The reaction proceeds via an initial intramolecular 6- exo -tet oxetane ring-opening cyclization, followed by a rapid, concomitant S N Ar cycloetherification to deliver the desired products in high yields (up to 92%). When applied to N -(2-(3-oxetanyloxy)aryl)-4-nitroarenesulfonamides, the reaction shifts to a second, unprecedented two-step cascade sequence combining the oxetane ring-opening cyclization step with a desulfonylative Smiles rearrangement to afford 2-substituted 1,4-benzoxazines. Notably, under more forcing conditions, this reaction can be extended into a three-step cascade process involving a classical Smiles rearrangement as the terminating step.