Synthesis of Medium Ring Nitrogen Heterocycles via a Tandem Copper-Catalyzed C−N Bond Formation−Ring-Expansion Process

A simple method for the preparation of medium ring heterocycles (7-, 8-, 9-, and 10-membered)
has been developed. The process employs a Cu-catalyzed coupling of a β-lactam with an aryl bromide or
iodide followed by intramolecular attack of a pendant amino group. In some instances, the intermediate
β-lactam is observable but can be converted to the aza-heterocycle by catalysis. Acetic acid was found to
be superior to transition metal complexes as a catalyst for this ring-expansion process.