Carbonyl Allenylation/Free Radical Cyclization Sequence as a New Regio- and Stereocontrolled Access to Bi- and Tricyclic β-Lactams

Abstract

A novel approach to racemic and enantiopure nonconventional fused bi- and tricyclic beta-lactams has been developed by using regio- and stereocontrolled intramolecular free radical reactions in monocyclic 2-azetidinone-tethered allenynes and haloallenes. The access to allene cyclization precursors was achieved by metal-mediated carbonyl allenylation of appropriately substituted 4-oxoazetidine-2-carbaldehydes in an aqueous environment. The tin-promoted radical cyclizations of allene-beta-lactams are totally regioselective for the central allenic carbon, providing bi- and tricyclic beta-lactams containing a seven-membered ring.