183066-64-0Relevant articles and documents
C4,C4'-bis-β-lactam to fused bis-γ-lactam rearrangement
Alcaide,Martin-Cantalejo,Perez-Castells,Sierra,Monge
, p. 9156 - 9163 (2007/10/03)
Optically pure cis,cis-C4,C4'-bis-β-lactams 1a-d are obtained in good to excellent yields, in a single step, following two different approaches. Staudinger reaction of (S)-(4-phenyl-2-oxooxazolidinyl)acetyl chloride (2a) and p-anisyldiimine gave the corresponding bis-β-lactam 1a as a single enantiomer. The reaction of glyoxal diimine derived from (S)-α-phenylethylamine and different alkoxy-substituted acid chlorides gave diastereomeric mixtures of cis,cis-bis-β-lactams 1b-d, enantiomers at the bicyclic skeleton. The configuration of all compounds has been determined by X-ray diffraction analysis of enantiomerically pure aldehyde 4a and bis-β-lactam 1b-α. The remaining bicyclic lactams have been chemically correlated to compound 1b-α and their configurations assigned. Starting from enantiomerically pure 4-formyl-2-azetidinone 4b, sequential imine formation and ketene cycloaddition allowed the synthesis of differently substituted, optically pure cis,cis-C4,C4'-bis-β-lactams 1f-i in good overall yields. C4,C4'-Bis-β-lactams smoothly rearranged to fused trans,trans-bis-γ-lactams 7 upon basic treatment (NaOMe/MeOH) in a totally stereoselective process. The presence of alkyl groups attached to the lactam nitrogen inhibits the rearrangement. Differently substituted (aryl and alkyl substituents in either rings) bicyclic β-lactam systems gave the selective opening of the ring with the aromatic substituent attached to the lactam nitrogen. Monocyclic 2-azetidinones 8 with an amino ester side chain at C4 are then obtained. The synthesis of trans,cis-C4,C4'-bis-β-lactam 1j and trans,trans-C4,C4'-bis-β-lactam 1l has also been effected in the racemic form. Compound 1j with a trans,cis stereochemistry rearranged to cis,trans-bis-γ-lactam 7d in the presence of base while the trans,trans-bicycle 1l gave monocyclic 2-azetidinone 8c with an amino ester side chain. Finally, trans,trans-bis-γ-lactam 1l can be synthesized in a single step from glyoxal diimine 3a employing an excess of lithium isovalerate. A reaction pathway to account for all the observed data is proposed.
