Journal Publications

J.G. Knight, S.W. Ainge, A.M. Harm, S.J. Harwood, H.I. Maughan, D.R. Armour, D.M. Hollinshead, and A.A. Jaxa-Chamiec, J. Am. Chem. Soc., 2000, 122, 2944.

Abstract: Palladium catalysed carbonylation [(Ph3P)2Pd(OAc)2 (5 mol%), CO (65 atm), EtOH, 70 oC, 5 days] of 5-ethenyl- and 5-(2-propenyl)-oxazolidin-2-ones gives rise to 3,6-dihydro-1H-pyridin-2-ones in 57-87% yields. The oxazolidinones are prepared from alpha-amino acids by addition of vinyl Grignard reagents to either the derived N-BOC-protected amino aldehydes or N-BOC-protected Weinreb amides followed by sodium hydride mediated cyclization of the resulting allylic alcohols. The enantiomeric purity of the valine-derived products 3,6-dihydro-6-(2-propyl)pyridin-2-one and 3,6-dihydro-6-(2-propyl)-5-methylpyridin-2-one were studied by chiral GC which showed that none of the enantiomeric pyridinones had formed during the synthesis. The N-BOC protected species, N-(tert-butyloxycarbonyl)-5-ethenyl-4-phenylmethyloxazolidin-2-one, did not produce the b-lactam under carbonylation in benzene and was found to give the ethoxycarbonylated product, ethyl (3E, 5S)-5-N-(tert-butyloxycarbonyl)amino-6- phenylhex-3-enoate, in 48% yield when ethanol was the solvent. The formation of the six-membered lactams rather than the expected b-lactams from N-unprotected vinyloxazolidinones may be due to initial formation of the b-lactam followed by isomerization under thermodynamic control, or may result from a thermodynamic preference for an anti-p-allyl palladium intermediate from which ring closure to the d-lactam would be geometrically favourable.