Preparation of beta- and gamma-lactams from carbamoyl radicals derived from oxime oxalate amides.
A general synthetic route to oxime oxalate amides was developed and applied to the preparation of molecules incorporating N-benzyl-N-alkenyl amides linked with acetone oxime or benzaldoxime units. In addition, 2-substituted-thiazolidine-4-carboxylic acid methyl ester amides of oxalyl benzaldoxime were also prepared. It was shown by EPR spectroscopy that the oxalyl benzaldoxime amides dissociated to produce benziminyl and carbamoyl (aminoacyl) radicals when photolysed with 4-methoxyacetophenone as a photosensitizer. Carbamoyl radicals derived from N-alk-3-enyl oxime oxalate amides underwent ring closure to afford pyrrolidin-2-ones. The analogous N-alk-2-enyl precursors afforded azetidin-2-ones. Reactions of the cyclohexenyl and cinnamyl oxime oxalate amides afforded a bicyclic beta-lactam and a 3-benzyl-substituted beta-lactam respectively. Interestingly, both products were isolated as hydroxylated compounds. A thiazolidine-derived oxime oxalate amide containing an isobutenyl side chain also dissociated with production of the corresponding thiazolidinyl-carbamoyl radical, as shown by EPR spectroscopy. GC-MS evidence indicated that this radical cyclised to afford some of the corresponding penicillin derivative
Scanlan
Eoin M
EM
University of St. Andrews, School of Chemistry, St. Andrews, Fife, UK KY16 9ST.
Slawin
Alexandra M Z
AM
Walton
John C
JC
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000138:chemical synthesis / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D000577:Amides; D005609:Free Radicals; D007769:Lactams