Rational and practical synthesis of α,α-difluoro-γ-lactams

Treatment of N-phenyl-iododifluoroacetamide (1) with terminal alkenes (2) in the presence of Na2S2O4 and NaHCO3 in CH3CN/H2O gave good yields of N-phenyl-2,2-difluoro-4-iodoalkanamide (3), which cyclized under strong basic conditions to afford N-phenyl-α,α-difluoro-γ-lactams (4). Or simply, these lactams 4 can be directly prepared in one-pot from 1 and 2 in the presence of Na2S2O4 and NaOH.

Graphical abstractTreatment of N-phenyl-iododifluoroacetamide (1) with terminal alkenes (2) in the presence of Na2S2O4 and NaHCO3 in CH3CN/H2O gave good yields of N-phenyl-2,2-difluoro-4-iodoalkanamide (3), which cyclized under strong basic conditions to afford N-phenyl-α,α-difluoro-γ-lactams (4). Or simply, these lactams 4 can be directly prepared in one-pot from 1 and 2 in the presence of Na2S2O4 and NaOH.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Iododifluoroacetamide reacted with alkenes to gave 2,2-difluoro-4-iodoalkanamide. ► 2,2-Difluoro-4-iodoalkanamide underwent cyclization to afford α,α-difluoro-γ-lactam. ► α,α-Difluoro-γ-lactam was prepared in one-pot from iododifluoroacetamide and alkene.