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

Abstract

This review describes the free radical cyclisation of enamides using tributyltin 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 β- or γ-lactam products, respectively. In general, the reactions produce γ-lactams derived from an unusual (disfavoured) 5-endo-trig radical cyclisation. These results can be explained on the basis of a reversible cyclisation mechanism; the 4-exo cyclisation produces the kinetically favoured β-lactam while the 5-endo cyclisation produces the thermodynamically more stable γ-lactam.