Efficient asymmetric synthesis of 2,3-diamino-3-phenylpropanoic acid derivatives

An efficient, stereoselective synthesis of selectively-protected anti and syn, methyl 2-amino-3-Boc-amino)-3-phenylpropanoate is described. Preparation of syn beta -acetylamino-alpha -hydroxy ester was from isopropyl cinnamate via an acetamide-based Sharpless aminohydroxylation (AA), and its anti isomer was obtained via C-alpha epimerization of the syn isomer. For the installation of a second amino group, two different approaches, involving substitution of the beta -hydroxyl group with azide, were investigated. The first was a ring-opening reaction of trans-oxazoline-5-carboxylate with trimethylsilyl azide, which produced anti beta-(acetylamino)-alpha -azido esters, which then transformed into the anti isomer; whereas the cis-oxazoline-5-carboxylate was found to be unreactive under this reaction condition. The second approach used the Mitsunobu reaction of syn and anti beta-(Boc-amino)-alpha -hydroxy esters with hydrazoic acid, followed by catalytic hydrogenation, which gave both anti and syn isomers, respectively. (C) 2001 Elsevier Science Ltd. All rights reserved.