Catalyst-Free Synthesis of Functionalized 4-Substituted-4H-Benzo[d][1,3]oxazines via Intramolecular Cyclization of ortho-Amide-N-tosylhydrazones

Functionalized 4-aryl-4H-benzo[d][1,3]oxazines are synthesized under transition-metal-freeconditionsusing ortho-amide-N-tosylhydrazones.This synthetic method uses readily available N-tosylhydrazonesas the diazo compound precursors and involves an intramolecular ringclosure reaction mediated by a protic polar additive (iPrOH). A wide range of functionalized oxazines are obtained by thisstraightforward method in good to excellent yields. Furthermore, theviability of our strategy is illustrated by the gram-scale elaborationof a bromo-substituted 4H-benzo[d][1,3]oxazine and its post-functionalization by palladium-catalyzedcross-couplings.

Automated summary

Functionalized 4-aryl-4H-benzo[d][1,3]oxazines were synthesized using ortho-amide-N-tosylhydrazones under transition-metal-free conditions. This method utilizes readily available N-tosylhydrazones as the diazo compound precursors and involves an intramolecular ring closure reaction mediated by a protic polar additive (iPrOH), resulting in a wide range of functionalized oxazines in good to excellent yields. Additionally, the feasibility of this strategy was demonstrated by the gram-scale elaboration of a bromo-substituted 4H-benzo[d][1,3]oxazine and its post-functionalization through palladium-catalyzed cross-couplings.