Tandem radical cyclisation of enamides mediated by tin hydride; pyrrolizidinone or indolizidinone ring formation

The tin hydride-mediated cyclisation of a variety of enamides under mild, n eutral reaction conditions has been investigated. Enamides derived from pyr uvate were reacted with R3SnH-AIBN to generate alpha-carbamoylmethyl radica ls which underwent 5-endo cyclisation to give Cyclic a-amino ester radicals . Subsequent 6-endo or 5-exo cyclisation was observed leading to the format ion of indolizidinone and pyrrolizidinone products respectively. The reacti on pathway was governed by the alkene substitution. If an electron rich dou ble bond was used the cyclisation was under thermodynamic control and a 6-m embered ring was observed. Five-membered rings were formed on reaction of t he alpha-amino ester radical with unsaturated esters or ketones. The ester or ketone functional group can stabilise the radical produced on 5-exo cycl isation and pyrrolizidinones could be prepared in up to 66% yield. Stannane by-products were also isolated from some reactions. These were thought to be derived from a competitive Michael-type addition of the tin radical to t he enamide double bond.