title: Base-promoted isomerization of cis-4-formyl-2-azetidinones: chemoselective C4-epimerization vs rearrangement to cyclic enaminones.
abstract: Two simple, efficient, and complementary methods for the regiospecific C4-epimerization of cis-4-formyl-2-azetidinones 1-3 are described. The first method uses 40% aqueous dimethylamine as reagent in heterogeneous medium with benzene at room temperature, in the presence of benzyltributylammonium bromide (3-4 mol%) as the phase-transfer catalyst. This transformation tolerates alkyl, alkenyl, alkynyl, aryl, and alkoxy substituents at the C3 of the 2-azetidinone ring. However, limitations of this isomerization are as follows: (i) only N-(p-methoxyphenyl)-beta-lactams can be used, and (ii) transformation is less compatible with heteroatomic substituents bonded to the C3 position of the 2-azetidinone ring. A highly general solution to these problems relies on the use of sodium carbonate as the isomerization reagent in different solvents. We also describe a novel base-promoted rearrangement of the beta-lactam ring to cyclic enaminones 6 and 21, involving an E1cB-elimination reaction in cis-4-formyl-2-azetidinones.
authors.affiliation: Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, 28040-Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Alcaide
authors.forename: M F
authors.initials: MF
authors.lastname: Aly
authors.forename: C
authors.initials: C
authors.lastname: Rodríguez
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Vicente
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001384:Azetidines / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D007202:Indicators and Reagents; D007700:Kinetics; D007769:Lactams; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D001384:Azetidines; D007202:Indicators and Reagents; D007769:Lactams