Silver-Mediated Synthesis of Furo[3,2-b]-β/γ-Lactams

Significance

The synthesis of furo[3,2-b]-γ-­lactams 2 via a silver(I)-mediated intramolecular formal 1,3-dipolar cycloaddition of oxo-N-propargylamides 1 is reported. The reaction shows broad substrate scope with respect to both the N-aryl (R^²) and ketone (R^¹) groups. Attempted cyclization of an internal alkyne led to recovery of the starting material, demonstrating the necessity of a terminal alkyne for the reaction to take place. The methodology was extended to the synthesis of a limited number of furo[3,2-b]-β-lactams in moderate yield. A stepwise 1,3-dipolar cycloaddition mechanism is proposed based on the isolation of key silver-containing intermediates in a control experiment.