Polycyclic Lactams via Cu(II)-Mediated Intramolecular Alkene Carboamination

Significance

Reported is a copper-promoted synthesis of polycyclic lactams from readily prepared amides containing a terminal double bond. A series of indolizidines and pyrrolizidines are obtained by tuning the starting material and reaction conditions. In cases for which 6-endo- or 5-exo- reaction pathways exist, higher temperatures were shown to favor 5-exo products. A reaction mechanism is proposed involving syn aminocupration and C-Cu bond homolysis to give the lactam with a methylene radical tether (e.g. structure A above), which then undergoes cyclization to form the polycyclic structure. This mechanism is analogous to that previously reported for the formation of sultams (S. Chemler and co-workersJ. Org. Chem. 2007, 72, 3896).