Radical cyclisation in heterocycle synthesis. Part 1. Sulfanyl radical addition–cyclisation of dienylamides for lactam synthesis

A new method for the synthesis of five- to eight-membered lactams by sulfanyl radical mediated addition–cyclisation of dienylamides is described. The sulfanyl radical addition–cyclisation of the dienylamide 1 was systematically investigated under four different conditions and was found to give the cyclised lactams 2–6 in 54–79% yield. The stereo- and regio-selectivity of sulfanyl radical addition–cyclisation was established from the preferential formation of the trans-cyclised lactam 3 and also from the substituent effects in the Cyclisation of the dienylamides 11–18. The sulfanyl radical mediated addition–cyclisation was successfully applied to the construction of the six- and eight-membered lactams 28a, b.