Copper-Catalyzed Oxidative [3 + 2] Cycloaddition of N-Alkyl Pyridinium Salts to Imidazo[1,2-a]pyridines

A copper-catalyzed reaction of pyridinium salts and trimethylsilyl cyanide (TMSCN) in the presence of diethyl phosphite is developed. This reaction, which allows the single-step construction of biologically important 2-cyanoimidazo[1,2-a]pyridine from readily available starting materials, is realized for the first time and is feasible at the gram scale. The scope of the protocol is demonstrated with 27 examples. A consecutive double cyanation and cyclization can be achieved in this one-pot process. TMSCN plays a dual role not only as the "CN" source but also as the coupling partner for the cyclization of imidazo[1,2-a]pyridines.