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 beta-lactam with an aryl bromide or iodide followed by intramolecular attack of a pendant amino group. In some instances, the intermediate beta-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.
Klapars
Artis
A
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Parris
Sean
S
Anderson
Kevin W
KW
Buchwald
Stephen L
SL
D000588:Amines / Q000138:chemical synthesis*; D001555:Benzene Derivatives / Q000138:chemical synthesis; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis*; D007769:Lactams / Q000138:chemical synthesis*
D000588:Amines; D001555:Benzene Derivatives; D006574:Heterocyclic Compounds, 2-Ring; D007769:Lactams; D003300:Copper