Novel radical based routes to pyrrolidine trans-lactams

This thesis is concerned with the development of novel routes to the pyrrolidine trans-lactams 246, which proved to be HNE inhibitors, based on a radical cyclisation mediated by either samarium diiodide or tributyltin hydride. Chapter 2 describes the synthesis of precursors 214 and the radical cyclisation of a-aza radicals derived from N-(benzotriazolylalkyl) alkenylamines 264 mediated by samarium diiodide to access the trans-2,3-disubstituted pyrrolidines 267. After these results, the development of the synthetic route of pyrrolidine trans-lactam was described. The cyclisation of the pyrrolidine derivative 245 successfully gave pyrrolidine trans-lactam 253.