Tetrahydro-1,3-oxazin-6-ones as templates for the stereoselective synthesis of beta-substituted L-aspartic acids

Protected (4S)-4-carboxytetrahydro-1,3-oxazin-6-ones have been synthesised either by Baeyer-Villiger reaction on a 4-ketoproline derivative or, more d irectly, from an aspartate derivative. Two strategies have been used to dev elop these compounds as chiral templates in the synthesis of beta-substitut ed aspartic acids. In the first, formation of an enaminone using Bredereck' s reagent, followed by reaction with a Grignard reagent gave a series of al kylidene derivatives which could be reduced from the less hindered side by heterogeneous catalytic hydrogenation to give cis-oxazinones in a completel y stereoselective manner. Alternatively, an alkylation strategy, although t rans-selective, gave mixtures of isomers. The oxazinones were converted to beta-substituted aspartic acids and to regioselectively protected beta-subs tituted aspartic acids without loss of stereochemistry at either centre.