Telmo N. Francisco, Nuno R. Candeias, Samuel Guieu, Joana L. C. Sousa, Rafael F. A. Gomes, Carlos A. M. Afonso, Artur M. S. Silva, Hélio M. T. Albuquerque
We report a green, multicomponent cascade synthesis of 3-aminopyridines via [1,3′-bipyridin]-1-ium intermediates undergoing Zincke aminolysis with ammonia supported by experimental evidence and DFT calculations. The method offers broad scope (>20 examples), good functional group tolerance, and scalability in batch and flow procedures. Synthetic utility is demonstrated through conversion into 3-halo, 3-hydroxy, and 3-thiopyridines, expanding the access to meta -substituted pyridines through peripheral editing of the unprotected amino group.