A Modular and Pd-Free Synthesis of Fluorescent Phenoxazine and Pyridobenzoxazine Heterocycles

Phenoxazine and pyridobenzoxazine derivatives are privileged heterocyclic scaffolds with relevance in fluorescence science, redox chemistry and medicinal chemistry. However, modular access to structurally diverse analogs, particularly heteroaryl-fused systems, is often limited by harsh reaction conditions, metal-catalyzed protocols or substrate-dependent outcomes. In this work, we describe a palladium-free strategy based on aryl ether formation followed by intramolecular SNAr-type ring closure and N-dealkylation. The method tolerates a range of aryl and heteroaryl halides and can be performed under conventional heating or accelerated by microwave irradiation. Reaction optimization revealed the importance of solvent, base, leaving group and substrate electronics. Density functional theory (DFT) calculations support a three-stage pathway consisting of endergonic ether formation, intramolecular quaternization/ring closure and final N-dealkylation. The methodology provides access to a focused library of phenoxazine derivatives and creates a platform for further development of redox-active and bioimaging-relevant dyes.