Bench-stable 2-halopyridinium ketene hemiaminals as new reagents for the synthesis of 2-aminopyridine derivatives

2-Chloro-1-(1-ethoxyvinyl)pyridinium triflate and several other bench-stable N-(1-alkoxyvinyl) 2-halopyridinium triflates have been developed as reagents for the synthesis of valuable 2-aminopyridine scaffolds via unusually mild SNAr substitu-tions with amine nucleophiles. Advantages of this approach include an operationally simple mix-and-stir procedure at room temperature or mild heat, ambient atmosphere, and without the need of transition metal catalysts, coupling reagents, or high-boiling solvents. The stable N-(1-ethoxyvinyl) moiety serves as a dual SNAr-activating group and pyridine N-protecting group that can be cleaved under thermal, acidic, or oxidative conditions. Preliminary results of other nucleophilic substitu-tions using oxygen, sulfur, and carbon-based nucleophiles are also demonstrated.