Silver-Catalyzed Regioselective Synthesis of Benzo[b][1,7]naphthyridin-1(2H)-ones through a Water-Assisted Cascade Cyclization

Introduction: The benzonaphthyridine framework represents a pinnacle of structural elegance among nitrogen-fused heterocycles. As a rigid, highly conjugated π-system, its unique electronic architecture empowers cutting-edge applications in optoelectronics, fluorescent sensing, and in biological evaluation. Yet, despite their vast potential, building these highly customized structures remains a major challenge. Existing methods usually require long and complicated pathways. Furthermore, current approaches often fail to achieve the exact orientation and positioning of substituents, resulting in poor control over stereo and regioselectivity.

Methods: Here, we report an efficient one-pot multicomponent approach for the regioselective synthesis of fused benzo[b][1,7]naphthyridin-1(2H)-one derivatives through a silver-catalyzed cascade cyclization. The protocol employs water as a readily available reaction partner with o-alkynylcarbaldehyde and proceeds under mild reaction conditions, providing rapid access to structurally diverse products in good to excellent yields.

Results: The protocol exhibits broad substrate scope and functional-group tolerance, enabling efficient access to structurally diverse benzo[b][1,7]naphthyridinones. Furthermore, gram-scale experiments proceeded smoothly without appreciable loss of yield, demonstrating the robustness and synthetic practicality of the method. Structural analysis has been supported by ¹H and ¹³C NMR spectroscopy.

Conclusion: In summary, we have developed a novel silver-catalyzed methodology that significantly streamlines the assembly of intricate benzo[b][1,7]naphthyridinone architectures. These nitrogen-fused heterocycles hold substantial promise for advanced photophysical applications and as novel therapeutic leads. Overall, this work represents a versatile and practical platform for generating these highly functionalized naphthyridinones, bridging synthetic organic chemistry with materials science and drug discovery.