Facile synthesis and mechanistic investigations of bicyclic oxo-gamma-lactams from simple caprolactams

The 6-azabicyclo[3.2.1]octane has been of great interest for medicinal chemists for some time now. Several natural products with a wide variety of different properties have been isolated and characterized such as Aphanorphine, Actinobolamine, Peduncularine or Lyconadin A. Here we describe the preparation of the Avibactam related 6-azabicyclo[3.2.1]octane bridged ring system, starting from a readily available caprolactam precursor. This straightforward approach consists of a Dieckmann-cyclization with an ester group in C-6 position. The cyclization results in an oxo-gamma-lactam system, which is believed to show enhanced reactivity towards nucleophilic ring opening.