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Synlett 2009(3): 395-398  
DOI: 10.1055/s-0028-1087531
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Carbonylation with CO2 and Phosphorus Electrophiles: A Convenient Method for the Synthesis of 2-Oxazolidinones from 1,2-Amino Alcohols

Jairo Paz, Carlos Pérez-Balado, Beatriz Iglesias, Luis Muñoz*
Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo, Spain
Fax: +34(986)812556; e-Mail: lmunoz@uvigo.es;
Further Information

Publication History

Received 2 July 2008
Publication Date:
21 January 2009 (online)

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Abstract

2-Oxazolidinones were prepared in good yields from 1,2-amino alcohols and CO2 in the presence of tetramethyl­phenylguanidine (PhTMG) as a base and a variety of phosphorus electrophiles under mild conditions. This procedure is advantageous over previous methodologies and relies on a novel carbonylation procedure that utilizes nontoxic CO2 and phosphorus electrophiles.

Key words

Oxazolidinones - 1,2-amino alcohols - carbonylation - guanidines.

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Purchased from Aldrich chemical company.

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Representative Procedure for the Synthesis of 2-Oxazolidinones 4a-j
A solution of (1S,2R)-norephedrine (3a, 210 mg, 1.39 mmol) and tetramethylphenylguanidine (290 mg, 1.52 mmol, 110 mol%) in anhyd MeCN (10 mL) was cooled to -40 ˚C with a dry ice-acetone bath. Carbon dioxide was slowly bubbled through the solution for 5 min, and then diphenylphosphoryl azide (DPPA) (0.30 mL, 1.39 mmol, 100 mol%) was added dropwise. Carbon dioxide bubbling was maintained for a further 15 min, and the reaction mixture was stirred overnight while it was slowly allowed to reach 20 ˚C. The resulting solution was concentrated almost to dryness. The residue was dissolved in CHCl3 (30 mL) and washed with a 10% Na2CO3 (previously saturated with NaCl) solution (1×). The aqueous layer was extracted with CHCl3. The combined organic layers were washed with 1 M HCl (previously saturated with NaCl) solution (1×). The aqueous layer was further extracted with CHCl3. The combined organic layers were dried over Na2SO4 and solvents removed under reduced pressure. The residue was purified by flash chromatography on SiO2 (hexanes-EtOAc, 4:1 to 2:1) to afford 185 mg of (4R,5S)-4-methyl-5-phenyloxazolidin-2-one (4a, 75% yield) as a white solid. ¹H NMR (400 MHz, CDCl3): δ = 7.45-7.27 (m, 5 H), 7.05 (s, 1 H), 5.72 (d, J = 8.1 Hz, 1 H), 4.25 (m, 1 H), 0.83 (d, J = 6.6 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 159.8, 134.8, 128.2, 128.1, 125.7, 80.8, 52.2, 17.2 ppm. IR (NaCl): ν = 3240, 2980, 1756 cm-¹. MS (EI+): m/z (%) = 239 (5) [M+], 107 (100), 104 (23). [α]D ²7 +162 (c 0.50, CHCl3).
(R)-Ethyl 2-Oxothiazolidine-4-carboxylate (4h): ¹H NMR (400 MHz, CDCl3): δ = 7.06 (br s, 1 H), 4.39 (ddd, J = 8.4, 4.8, 1.0 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H), 3.64 (dd, J = 11.4, 8.4 Hz, 1 H), 3.51 (dd, J = 11.4, 4.8 Hz, 1 H), 1.23 (t, J = 3 × 7.1 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 174.8, 170.0, 62.0, 55.9, 31.6, 13.8 ppm. IR (NaCl): ν = 3263, 2983, 1741 cm-¹. MS (EI+): m/z (%) = 175 (22), 102 (10), 74 (60). [α]D ²0 -53 (c 3.15, CHCl3).

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Unpublished results.