Multicomponent Domino Approaches to the Persubstituted, Alkylene‐Bridged, and Hetero‐Fused CF 3 ‐γ‐Lactams

To synthesize persubstituted, alkylene‐bridged, and heterofused CF 3 ‐γ‐lactams, a domino strategy based on the multicomponent reaction of ethyl trifluoropyruvate and diethyl ketone with N,N ‐ and N,O ‐dinucleophilic reagents was developed. The structure of the final products depends on both the reaction conditions and the reagent ratio. It was found that bicyclic γ‐lactams and pyrrolidin‐2‐ones are predominantly formed under catalyst‐free conditions, whereas dual acid–base catalysis promotes the formation of N ‐hydroxyalkyl‐substituted dihydropyrrol‐2‐ones and bis(dihydropyrrol‐2‐one) derivatives linked by an alkylene bridge. The diastereomeric structures of the newly synthesized CF 3 ‐γ‐lactams were established by 1 H, 19 F, and 13 C NMR spectroscopy, including two‐dimensional NMR experiments, as well as by x‐ray crystallographic analysis. A plausible mechanism for the multicomponent reaction is proposed and supported by additional synthetic experiments. Among the synthesized compounds, several derivatives exhibited analgesic and antiviral activities.