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Synlett 2003(6): 0797-0800
DOI: 10.1055/s-2003-38733
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A New Entry to Polyfunctionalized 4,5-trans Disubstituted Oxazolidin-2-ones from l-Aspartic Acid

Gianluigi Luppi, Claudia Tomasini*
Dipartimento di Chimica ‘G. Ciamician’, Alma Mater Studiorum, Università di Bologna, Via Selmi 2 - 40126 Bologna, Italy
e-Mail: tomasini@ciam.unibo.it;
Further Information

Publication History

Received 4 December 2002
Publication Date:
17 April 2003 (online)

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Abstract

A straightforward synthesis of enantiomerically pure (4R,5S)-5-oxazolidinecarboxylic acid, 2-oxo-4-[(t-butyldimethyl­silyloxy)methyl]-, benzyl ester and of (4S,5S)-4-oxazolidinecarboxylic acid, 2-oxo-5-[(t-butyldimethylsilyloxy)methyl]-, benzyl ester was envisaged starting from readily available l-aspartic acid. The key step is the diastereoselective addition of iodine with the introduction of a new stereogenic centre.

Key words

l-aspartic acid - carboxyaziridines - oxazolidin-2-ones - rearrangement - pseudopeptides

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Experimental Procedure: LiHMDS (2.2 mmol, 1 M soln. in THF, 2.2 mL) was added to a stirred solution of (S)-4a (1 mmol, 0.42 g) in anhyd toluene (10 mL) under nitrogen atmosphere at -20 °C. The mixture was stirred 45 min at
-20 °C, then iodine was added (1.5 mmol, 0.76 g) in anhyd toluene (10 mL). The mixture was stirred 1 h, then an aq sat. solution of Na2SO3 was added, and the organic layer was separated, washed with H2O, dried over Na2SO4 and the solvent was removed under reduced pressure. The iododerivative 7 was obtained in 93% yield (0.51 g) without any purification and dissolved in anhyd DMF (2 mL). The mixture was stirred under a microwave irradiation (210 W power, 2 min), then EtOAc was added (20 mL), and the organic layer was washed twice with 1 N aq solution of HCl, dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (cyclohexane-EtOAc 9:1 as eluant) and obtained as a white solid in 83% yield (0.28 g): Mp = 55-58 °C. IR(nujol): 3490, 3291, 1772, 1746, 1666 cm-1. 1H NMR (200 MHz, CDCl3): δ = 0.09 (s, 6 H, Me2Si), 0.88 (s, 9 H, t-Bu), 2.68 (ABX, J = 4.4, 4.8, 12.2 Hz, 2 H, CH2OSi), 3.92 (q, J = 4.4 Hz, CHN), 4.82 (d, J = 4.4 Hz, CHO), 5.27 (AB, J = 12.6 Hz, OCH 2Ph), 6.18 (br s, 1 H, NH), 7.25-7.42 (m, 5 H, Ph). 13C NMR (CDCl3): δ = -5.5, 25.7, 57.1, 64.1, 67.7, 74.6, 128.3, 128.6, 134.6, 158.0, 168.6. [α] d = +4.1 (c = 1.7 in CH2Cl2).

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Experimental Procedure: To a stirred solution of a 98:2 mixture of N-Boc aziridines (2S,3S)-5c and (2R,3S)-6c (0.3 mmol, 0.13 g) in anhyd dicloromethane (10 mL) was added Sn(OTf)2 (0.06 mmol, 25 mg). The mixture was stirred 20 h under nitrogen at r.t., then an aq sat. solution of Na2CO3 was added, the organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (cyclohexane-EtOAc 9:1 as eluant) and the product 2 was obtained in 80% yield (88 mg) as a low melting solid. IR (CH2Cl2): 3443, 1772, 1746 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.09 (s, 6 H, Me2Si), 0.88 (s, 9 H, t-Bu), 3.79 (dd, 1 H, J = 3.0, 11.7 Hz, 1 H, CHHOSi), 3.91 (dd, J = 3.6, 11.4 Hz, 1 H, CHHOSi), 4.43 (d, J = 5.1 Hz, CHN), 4.66-4.72 (m, 1 H, CHO), 5.23 (AB, J = 11.8 Hz, OCH 2 Ph), 5.33 (br s, 1 H, NH), 7.29-7.42 (m, 5 H, Ph). 13C NMR (CDCl3): δ = -5.3, 25.9, 54.9, 63.1, 68.1, 78.8, 128.8, 129.0, 129.1, 134.8, 157.9, 170.2. [α] d = +20.9 (c = 0.1 in CH2Cl2).