Lewis acid-assisted ene cyclization of 2-azetidinone-tethered enals: synthesis of enantiopure carbacepham derivatives.

Diastereocontrolled Lewis acid-catalyzed preparation of enantiopure carbacepham derivatives have been developed starting from 2-azetidinone-tethered enals. The BF3.Et2O-promoted reaction of alkenylaldehydes 1 and 16 is effective as carbocyclization protocol to afford 4-substituted 5-hydroxycarbacephams or 3-substituted 4,5-dihydroxycarbacephams, respectively, by a type I carbonyl-ene reaction, while the BF3.

Lewis acid-promoted intermolecular carbonyl-ene reaction of enantiopure 4-oxoazetidine-2-carbaldehydes. Rapid entry to novel fused polycyclic beta-lactams.

Lewis acid-promoted carbonyl-ene reaction of enantiomerically pure 4-oxoazetidine-2-carbaldehydes with various activated alkenes gives 4-[(1'-hydroxy)homoallyl]-beta-lactams with a very high level of syn diastereofacial selectivity. The above homoallylic alcohols are used for the diastereoselective preparation of fused bicyclic, tricyclic, and tetracyclic beta-lactams of nonconventional structure using tandem one-pot radical addition/cyclization or elimination-intramolecular Diels-Alder sequences. In addition, a novel domino process was discovered, the C4-N1 beta-lactam bond breakage/intramolecular Diels-Alder reaction.

Stereoselective Synthesis of Fused Bicyclic beta-Lactams through Radical Cyclization of Enyne-2-azetidinones(1).

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.