Synthesis of 2,3-bifunctional imidazo[1,2-a]pyridines through cycloadditions of pyridinium ylides with N-cyano-4-methyl-N-phenylbenzenesulfonamide

• Published in: Tetrahedron letters 2023-01, Vol.115, p.154295, Article 154295
• Main Authors: Zhan, Gu, Zhao, Hongli, Li, Dong-Ai, Wu, Yuling, Fang, Huaying, Peng, Cheng, Han, Bo
• Format: Article
• Language: English
• Subjects: Cycloaddition; Heterocycle synthesis; Imidazo[1,2-a]pyridine; N-cyano-4-methyl-N-phenylbenzenesulfonamide; Pyridinium ylide
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2022.154295

Highly chemoselective synthesis of 2,3-bifunctional imidazo[1,2-a]pyridines was achieved through a [3 + 2] cycloadditions/oxidation reaction of pyridinium ylides with N-cyano-4-methyl-N-phenylbenzenesulfonamide, which serves as an activated nitrile. The strategy features high chemoselectivity, easily accessible materials, and broad substrate scope. [Display omitted] Imidazo[1,2-a]pyridine is recognized as a “drug prejudice” due to its wide applications in medicinal chemistry. In this work, we developed a [3 + 2] cycloadditions/oxidation reaction of pyridinium ylides with N-cyano-4-methyl-N-phenylbenzenesulfonamide for the synthesis of 2,3-bifunctional imidazo[1,2-a]pyridines. The N-cyano-4-methyl-N-phenylbenzenesulfonamide serves as an activated nitrile, exhibiting higher activity than common alkyl or aryl nitrile in the reaction. The strategy features high chemoselectivity, easily accessible materials, and broad substrate scope. The scale-up reaction demonstrated the practicability of this method, and the imidazo[1,2-a]pyridines products could be easily transformed into their derivatives.