Stereoselective Synthesis of Fused Bicyclic β-Lactams through Radical Cyclization of Enyne-2-azetidinones1

A convenient, stereoselective entry to racemic and enantiomerically pure fused bicyclic beta-lactams has been developed that involves the radical-mediated cycloisomerization of easily available monocyclic enyne-beta-lactams as the key synthetic step. These compounds are obtained provided that an activated double bond is present as a radical acceptor. In the absence of this condition, new forms of reactivity were observed, including C3-C4 bond cleavage of the beta-lactam ring to yield tetrahydropyridine derivatives and 1,5-radical translocation to yield new bicyclic derivatives. Some simple transformations were tested on representative examples of the different types of bicyclic systems prepared to demonstrate their potential as intermediates in the preparation of other differently functionalized systems.