G. Burtin et al., Tetrahydro-1,3-oxazin-6-ones as templates for the stereoselective synthesis of beta-substituted L-aspartic acids, J CHEM S P1, (20), 2000, pp. 3451-3459
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.