Radical 4-exo-cyclizations onto O-alkyloxime acceptors: towards the synthesis of penicilliin-containing antibiotics

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Abstract

The 4-exo cyclizations of two types of carbamoyl radicals onto O-alkyloxime acceptor groups were studied as potential routes to 3-amino-substituted azetidinones and hence to penicillins. A general synthetic route to 'benzaldehyde oxime oxalate amides' (=2-[(benzylideneamino)oxy]-2-oxoacetamides; see, e.g., 10c) of 2-{[(benzyloxy)imino]methyl)-substituted thiazolidine-4-carboxylic acid methyl esters 9 was developed (Scheme 3). It was shown by EPR spectroscopy that these compounds underwent sensitized photodissociation to the corresponding carbamoyl radicals but that these did not ring close. An analogous open-chain precursor, benzaldehyde O-(benzylaminoacetaldehyde-O-benzyloxalyl)oxime, 15, lacking the 5-membered thiazolidine ring, was shown by EPR spectroscopy to release the corresponding carbamoyl radical (Scheme 4). The latter underwent 4-exo cyclization onto its C=NOBn bond in non-H-atom donor solvents. The rate constant for this cyclization was determined by the steady-state EPR method. Spectroscopic evidence indicated that the reverse ring-opening process was slower than cyclization.

Original languageEnglish
Pages (from-to)2133-2143
Number of pages11
JournalHelvetica Chimica Acta
Volume89
DOIs
Publication statusPublished - 2006

Keywords

  • ELECTRON-SPIN-RESONANCE
  • RING-OPENING REACTIONS
  • OXIME OXALATE AMIDES
  • CARBAMOYL RADICALS
  • GAMMA-LACTAMS
  • BETA-LACTAMS
  • INTRAMOLECULAR ADDITION
  • AMINOACYL RADICALS
  • 1-CARBAMOYL-1-METHYLCYCLOHEXA-2,5-DIENES
  • CYCLOBUTYLMETHYL

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