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

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

References

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13

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).

16

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).