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Synlett 2006(11): 1739-1743  
DOI: 10.1055/s-2006-947330
LETTER
© Georg Thieme Verlag Stuttgart · New York

Formation of Isoxazoles Using Cerium Ammonium Nitrate (CAN): A One-Pot Synthesis of Glycomimetics

Sara Béha, Denis Giguère, Ramesh Patnam, René Roy*
Department of Chemistry, Université du Québec à Montréal, P. O. Box 8888, Succ. Centre-Ville Montréal, QC, H3C 3P8, Canada
Fax: +1(514)9874054; e-Mail: roy.rene@uqam.ca;
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Publication History

Received 29 March 2006
Publication Date:
04 July 2006 (online)

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Abstract

1,3-Dipolar cycloaddition reactions of carbohydrate dipolarophiles with cerium(IV) ammonium nitrate CAN(IV) in acetone, acetophenone, or pinacolone yielded the corresponding 3,5-disubstituted isoxazoles, stable pharmacophores for glycomimetic syntheses.

Key words

carbohydrates - cycloadditions - heterocycles - isoxazoles - CAN(IV)

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Typical Procedure for Isoxazole Synthesis Using CAN(IV).Method A, Neat Solvent. A mixture of acetylenic glycosides (0.5 mmol), ammonium cerium(IV) nitrate (0.5 mmol), and 4 Å MS in acetone (0.1 M) was stirred at reflux under nitrogen during 16-66 h (Table [2] ). The mixture was poured into a solution of aq NaHCO3 (2.0 mL) and filtered over a Celite® pad. The filtrate was washed with brine (2 × 2.0 mL) and extracted with CH2Cl2. The organic layer was then washed with brine (2 × 2.0 mL), dried over Na2SO4, and concentrated under reduced pressure. Pure isoxazoles were isolated as clear oil by column chromatography using a mixture of EtOAc and hexane.
Method B, Ketones in MeCN.
A mixture of acetylenic glycosides (0.0695 g, 0.2 mmol), ammonium cerium(IV) nitrate (0.348 g, 0.6 mmol), the appropriate ketone (2.0 mmol), and 4 Å MS in MeCN (3.5 mL) was stirred at reflux under nitrogen during 16-66 h. The mixture was poored into a solution of aq NaHCO3 (2.0 mL) and filtered over a Celite® pad. The filtrate was washed with brine (2 × 2.0 mL) and extracted with CH2Cl2. The organic layer was then washed with brine (2 × 2.0 mL), dried over Na2SO4, and concentrated under reduced pressure. Pure isoxazoles were isolated as clear oil by column chromatography using a mixture of EtOAc and hexane.
All new compounds gave satisfactory analytical and spectral data. Data for selected compounds are as follows.
Compound 1a: oil. 1H NMR (300 MHz, CDCl3): δ = 6.63 (s, 1 H), 5.34 (dd, 1 H, J = 3.3, 10.2 Hz), 5.30 (dd, 1 H, J = 1.1, 3.3 Hz), 5.16 (d, 1 H, J = 3.9 Hz), 5.13 (dd, 1 H, J = 10.2, 3.9 Hz), 4.75 (dq, 2 H, J = 13.7, 0.6 Hz), 4.17 (dq, 1 H, J = 1.1, 6.6 Hz), 2.65 (s, 3 H), 2.16, 2.08, 1.98 (3 s, 3 × 3 H), 1.13 (d, 3 H, J = 6.6 Hz). 13C NMR (300 MHz, CDCl3): δ = 191.7 (1 C), 170.5 (1 C), 170.0 (1 C), 169.7 (1 C), 161.9 (1 C), 118.4 (1 C), 101.9 (1 C), 96.2 (1 C), 70.8 (1 C), 67.7 (1 C), 67.6 (1 C), 65.0 (1 C), 60.3, (1 C), 27.2 (1 C), 20.7 (1 C), 20.6 (2 C), 15.7 (1 C). MS (ESI): m/z calcd for C18H23NO10Na: 436.13; found: 436.3 [M + Na+].
Compound 1b: oil. 1H NMR (300 MHz, CDCl3): δ = 8.29 (m, 2 H), 7.65 (m, 1 H), 7.52 (m, 2 H), 6.80 (s, 1 H, H-9), 5.38 (dd, 1 H, J = 3.3, 10.7 Hz), 5.32 (dd, 1 H, J = 1.1, 3.3 Hz), 5.21 (d, 1 H, J = 3.9 Hz), 5.15 (dd, 1 H, J = 10.7, 3.9 Hz), 4.81 (dq, 2 H, J = 13.7, 0.6 Hz), 4.21 (dq, 1 H, J = 1.1, 6.6 Hz), 2.17, 2.09, 1.99 (3 s, 3 × 3 H), 1.15 (d, 3 H, J = 6.6 Hz). 13C NMR (300 MHz, CDCl3): δ = 185.6 (1 C), 170.7 (1 C), 170.6 (1 C), 170.2 (1 C), 169.1 (1 C), 135.7 (1 C), 134.4 (1 C), 130.9 (1 C), 130.3 (1 C), 104.6 (1 C), 96.6 (1 C), 71.1 (1 C), 68.0 (1 C), 67.9 (1 C), 65.3 (1 C), 60.6, (1 C), 21.0 (1 C), 20.9 (2 C), 16.0 (1 C). MS (ESI): m/z calcd for C23H25NO10Na: 498.15; found: 498.3 [M + Na+].
Compound 1c: oil. 1H NMR (300 MHz, CDCl3): δ = 6.59 (s, 1 H), 5.34 (dd, 1 H, J = 3.3, 10.4 Hz), 5.29 (dd, 1 H, J = 1.1, 3.3 Hz), 5.16 (d, 1 H, J = 3.6 Hz), 5.12 (dd, 1 H, J = 10.4, 3.6 Hz), 4.74 (dq, 2 H, J = 13.7, 0.6 Hz), 4.17 (dq, 1 H, J = 1.1, 6.6 Hz), 2.15, 2.07, 1.97 (3 s, 3 × 3 H), 1.37, (s, 3 × 3 H), 1.11 (d, 3 H, J = 6.6 Hz). 13C NMR (300 MHz, CDCl3): δ = 199.4 (1 C), 170.4 (1 C), 170.3 (1 C), 169.8 (1 C), 168.2 (1 C), 160.4 (1 C), 104.0 (1 C), 96.3 (1 C), 70.8 (1 C), 67.7 (1 C), 67.6 (1 C), 65.0 (1 C), 60.3 (1 C), 44.6 (1 C), 26.5 (3 C), 20.6 (1 C), 20.5 (1 C), 20.4 (1 C), 15.7 (1 C). MS (ESI): m/z calcd for C21H29NO10Na: 478.18; found: 478.3 [M + Na+].
Compound 3a (Table [2] , entry 4): oil. 1H NMR (300 MHz, CDCl3): δ = 6.46 (s, 1 H), 5.25 (m, 3 H), 4.92 (d, 1 H, J = 1.8 Hz), 4.79 (d, 1 H, J = 12.4 Hz), 4.72 (d, 1 H, J = 12.4 Hz), 4.24 (dd, 1 H, J = 12.3, 5.4 Hz), 4.02 (m, 2 H), 2.62 (s, 3 H), 2.12, 2.08, 2.01, 1.98 (4 s, 4 × 3 H). 13C NMR (300 MHz, CDCl3): δ = 191.5 (1 C), 170.5 (1 C), 169.8 (1 C), 169.7 (1 C), 169.6 (1 C), 168.9 (1 C), 161.9 (1 C), 102.3 (1 C), 97.3 (1 C), 69.1 (1 C), 69.0 (1 C), 68.6 (1 C), 65.7 (1 C), 62.2 (1 C), 59.7 (1 C), 27.2 (1 C), 20.7 (1 C), 20.6 (2 C), 20.5 (1 C). MS (ESI): m/z calcd for C20H25NO12: 471.14; found: 472.1 [M + H+].
Compound 3b (Table [2] , entry 5): oil. 1H NMR (300 MHz, CDCl3): δ = 8.28 (d, 2 H, J = 8.2 Hz), 7.62 (1 H, t, J = 8.2 Hz), 7.53 (2 H, t, J = 8.2 Hz), 6.62 (s, 1 H), 5.30 (m, 3 H), 4.98 (d, 1 H, J = 1.8 Hz), 4.83 (d, 1 H, J = 12.4 Hz), 4.78 (d, 1 H, J = 12.4 Hz), 4.27 (m, 1 H), 4.05 (m, 2 H), 2.17, 2.10, 2.02, 1.99 (4 s, 4 × 3 H). 13C NMR (300 MHz, CDCl3): δ = 185.2 (1 C), 170.5 (1 C), 169.8 (1 C), 169.7 (1 C), 169.6 (1 C), 168.1 (1 C), 162.1 (1 C), 134.1 (1 C), 130.6 (1 C), 128.5 (1 C), 104.7 (1 C), 97.4 (1 C), 69.2 (1 C), 69.0 (1 C), 68.8 (1 C), 65.9 (1 C), 62.2 (1 C), 59.7 (1 C), 20.7 (1 C), 20.6 (2 C), 20.5 (1 C). MS (ESI): m/z calcd for C25H27NO12: 533.1; found: 534.1 [M + H+].