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Efficient Synthesis of Enantiomerically Pure β2-Amino Acids via Chiral Isoxazolidinones

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journal contribution
posted on 11.01.2003, 00:00 by Hee-Seung Lee, Jin-Seong Park, Byeong Moon Kim, Samuel H. Gellman
We report a practical and scalable synthetic route for the preparation of α-substituted β-amino acids (β2-amino acids). Michael addition of a chiral hydroxylamine, derived from α-methylbenzylamine, to an α-alkylacrylate followed by cyclization gives a diastereomeric mixture of α-substituted isoxazolidinones. These diastereomers are separable by column chromatography. Subsequent hydrogenation of the purified isoxazolidinones followed by Fmoc protection affords enantiomerically pure Fmoc-β2-amino acids, which are useful for β-peptide synthesis. This route provides access to both enantiomers of a protected β2-amino acid.