Radical-Mediated Reactions of alpha-Bromo Aluminium Thioacetals, alpha-Bromothioesters, and Xanthates for Thiolactone Synthesis

Thiolactones have attracted considerable attention in recent years as bioactive natural products, lead compounds for drug discovery, molecular probes, and reagents for polymerisation. We have investigated radical-mediated C-C bond forming reactions as a strategy for thiolactone synthesis. Cyclisation of an alpha-bromo aluminium thioacetal was investigated under radical conditions. It was found that at low temperature, a radical fragmentation and rearrangement process occurs. A putative reaction mechanism involving a previously unreported aluminium templated thiol-ene step for the rearrangement process is presented. Cyclisation reactions of alpha-bromo thioesters and alpha-xanthate thioesters under radical mediated conditions furnished the desired thiolactones in moderate yields