Free radical cyclisation of enamides leading to biologically important gamma-lactams

This review describes the free radical cyclisation of enamides using tribut yltin hydride, manganese(III) acetate, copper(I) complexes or dichlorotris( triphenylphosphine)ruthenium(II). These cyclisations can proceed via either 4-exo or 5-endo pathways, to produce (beta- or gamma -lactam products. res pectively. In general. the reactions produce gamma -lactams derived from an unusual (disfavoured) 5-endo-trig radical cyclisation. These results can b e explained on the basis of a reversible cyclisation mechanism; the 4-exo c yclisation produces the kinetically favoured B-lactam while the 5-endo cycl isation produces the thermodynamically more stable gamma -lactam. (C) 2001 Academie des sciences / Editions scientifiques et medicales Elsevier SAS.