Bicyclic Imides with Bridgehead Nitrogen. Synthesis of an Anti-Bredt Bicyclic Hydantoin

Article abstract of DOI:10.1021/jo00305a014

The first synthesis of an anti-Bredt bicyclic hydantoin containing an imide bridgehead nitrogen was accomplished.In this procedure 3-bromo-ε-caprolactam (14) was converted to 3-cyano-ε-caprolactam (15).A key reaction was the phenylation of 15 using Ph5Bi to provide 3-cyano-3-phenyl-ε-caprolactam (18), although limitations of this procedure were revealed by unsuccessful efforts with closely related structures.Nitrile 18 was hydrolyzed to the 3-carboxamide 20, which underwent a Hofmann rearrangement in the presence of Pb(OAc)4 and 2,6-lutidine.The rearrangement of 20 was accompanied by intramolecular attack of the lactam nitrogen on the intermediate isocyanate to give the final product, 1,7-diaza-8,9-dioxo-6-phenylbicyclo<4.2.1>nonane (5).Thus 5 was formed from 14 in five steps and an overall yield of 17percent.The structural assignment of 5 was supported by an 15N NMR study.