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.Et2O or SnCl4-mediated type II carbonyl-ene cyclization of alkenylaldehydes 2 furnishes 3-methylene 5-hydroxycarbacephams along with the corresponding 3-halo 5-hydroxycarbacepham. The stereochemical outcome of these carbonyl-ene cyclizations leading to carbacepham derivatives can be explained in terms of six-membered, cyclic chair-like transition-state models. The formation of halocarbacepham derivatives is proposed to proceed by a stepwise mechanism.
Alcaide
Benito
B
Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense de Madrid, E-28040 Madrid, Spain. alcaideb@quim.ucm.es
Almendros
Pedro
P
Pardo
Carmen
C
Rodríguez-Ranera
Carolina
C
Rodríguez-Vicente
Alberto
A
D001384:Azetidines / Q000737:chemistry*; D002384:Catalysis; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D013237:Stereoisomerism
C116379:2-azetidinone; D001384:Azetidines; D002511:Cephalosporins; C026739:carbacephems