Synthesis of N‐Substituted 4‐Pyridones From Skipped Diynones via Intramolecular Base or Ag(I)‐Catalyzed Hydroamination

Abstract Cs 2 CO 3 or CF 3 COOAg catalyze the intramolecular 6‐endo hydroamination of the Z‐enaminones derived from the Michael‐type addition of primary amines to skipped diynones, yielding N‐substituted 4‐pyridones in good to excellent yields. The transformation occurs in one‐pot operation, with the first step being noncatalyzed. While the Cs 2 CO 3 ‐catalyzed protocol is much faster, it fails to provide significant yields in the case of enaminones derived from aryl‐substituted diynones. On the other hand, the Ag(I)‐catalyzed one is a slower process but more widely applicable. Several N‐substituted 4‐pyridones inhibit SecA ATPase at micromolar concentrations.