Intramolecular Keto Lactam Condensation: A Convenient and Straightforward Approach to Bicyclic Vinylogous Lactams

Abstract

Although the aldol condensation is a well‐known reaction, the aza‐type aldol condensation, namely, the intramolecular condensation of common keto lactams leading to bicyclic vinylogous lactams, is a highly demanding transformation, with potential applications in both organic synthesis and medicinal chemistry. The known methods for this type of cyclization require several steps. In this paper, we disclose a straightforward approach that consists of the in‐situ formation of silyl enol ethers with tert‐butyldimethylsilyl trifluoromethanesulfonate (TBDMSOTf), lactam activation with triflic anhydride (Tf2O), and a tandem cyclocondensation reaction. The reaction can be run in a one‐pot manner or in a two‐step fashion, both under mild conditions. The yields for the one‐pot version were 52–80 %. In some cases, the two‐step version gave higher overall yields (44–85 %) than the one‐pot version.