Silver-Catalyzed Cascade Annulation of ortho-Alkynyl Aldehydes with Sulfonamides: A Regioselective Access to Sulfonyl-Embedded Polycyclic Fused 1,7-Naphthyridines

Introduction: Polycyclic fused 1,7-naphthyridines constitute an important class of nitrogen-containing heterocycles found in biologically active molecules and functional materials. In particular, sulfonyl-embedded fused N-heterocycles have attracted considerable attention because of their diverse pharmacological properties and synthetic versatility. Consequently, the development of efficient and regioselective methods for accessing structurally diverse sulfonyl-containing 1,7-naphthyridines remains highly desirable. ortho-Alkynyl aldehydes have emerged as versatile building blocks for the construction of complex fused heterocycles under transition-metal catalysis. Herein, we report a silver-catalyzed cascade annulation of ortho-alkynyl aldehydes with sulfonamides for the regioselective synthesis of sulfonyl-embedded polycyclic fused 1,7-naphthyridines.

Methods: A series of ortho-alkynyl aldehydes and sulfonamides were synthesized and employed as substrates for the cascade annulation reaction. Optimization of reaction parameters identified AgNO₃ as the optimal catalyst under mild conditions. The substrate scope was explored using various substituted substrates, and the products were characterized by NMR spectroscopy and HRMS.

Results: AgNO₃ efficiently promoted the cascade annulation, affording sulfonyl-embedded polycyclic fused 1,7-naphthyridines in good to excellent yields. The methodology exhibited broad substrate scope, excellent functional group tolerance, and high regioselectivity, enabling rapid access to structurally diverse fused N-heterocyclic scaffolds under mild conditions.

Conclusion: An efficient AgNO₃-catalyzed cascade annulation strategy has been developed for the regioselective synthesis of sulfonyl-embedded polycyclic fused 1,7-naphthyridines, providing a practical approach to medicinally relevant fused N-heterocycles.