Bench-Stable 2-Halopyridinium Ketene Hemiaminals as 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 S N Ar substitutions with amine nucleophiles. Advantages of this approach include an operationally simple mix-and-stir procedure at room temperature or mild heat and ambient atmosphere and without the need for transition metal catalysts, coupling reagents, or high-boiling solvents. The stable N -(1-ethoxyvinyl) moiety serves as a dual S N Ar-activating group and pyridine N -protecting group that can be cleaved under thermal, acidic, or oxidative conditions. Preliminary results of other nucleophilic substitutions using oxygen-, sulfur-, and carbon-based nucleophiles are also demonstrated.