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Synlett 2003(9): 1355-1357
DOI: 10.1055/s-2003-40325
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Diels-Alder Reaction of 2-Nitro Glycals: A New Route to the Synthesis of Benzopyrans

Kandasamy Pachamuthu, Richard R. Schmidt*
Department of Chemistry, University of Konstanz, Fach M 725, 78457 Konstanz, Germany
e-Mail: Richard.Schmidt@uni-konstanz.de;
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Publikationsverlauf

Received 4 February 2003
Publikationsdatum:
30. Juni 2003 (online)

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Abstract

Synthesis of different benzopyrans was achieved by Diels-Alder reaction of 2-nitro glycals with Danishefky’s diene, hydrolysis of the enol ether moiety, and subsequent elimination of the nitro and methoxy group.

Key words

2-nitro glycals - Diels-Alder reaction - chromans - benzopyrans - benzannulated dihydropyrans - C-glycosides

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12

General experimental procedure for 6, 9, 10 and 12: A solution of 2-nitro glycal (1 mmol) and Danishefky’s diene (1.1 mmol) in dry toluene (2 mL) was refluxed under argon for 36 h. The reaction mixture was allowed to cool and the toluene was removed under reduced pressure. Then a mixture of THF-10% H2SO4 in H2O (2:1) was added and stirred at room temperature for 30 min. The product was isolated by extractive workup followed by filtration by column chromatography. The hydrolyzed product was dissolved in 1 M NaOCH3 in methanol (2 mL) and heated at 50 °C for 1.5 h. Methanol was evaporated followed by neutralization with saturated aq NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over anhydrous MgSO4. Evaporation of the solvent yielded the benzannulated pyrans.
For compound 5: A mixture of hydrolyzed products 3 and 4 and DBN (3 equiv) in toluene (2 mL) was refluxed for 24 h. The reaction mixture was neutralized with aq NH4Cl after removal of the toluene followed by extraction with ethyl acetate. The organic layer was washed with dilute HCl, water, brine and dried over anhydrous MgSO4. Evaporation of the solvent and purification by column chromatography yielded the product 5 in 68% yield.
Some selected data:
5: [α]D 20 = -39.1 (c 1, CHCl3); 1H NMR (250 MHz): δ 2.86 (br s, 1 H), 3.45-3.55 (m, 2 H), 3.59 (dd, J = 1.99, 7.82 Hz, 1 H), 3.93 (d, J = 10.8 Hz, 1 H), 4.09 (d, J = 10.8 Hz, 1 H), 4.19 (br s, 1 H), 4.25 (d, J = 11.46 Hz, 1 H), 4.44 (d, J = 11.46 Hz, 1 H), 4.43-4.54 (m, 3 H), 5.37 (br s, 1 H), 6.81-6.85 (m, 2 H), 6.93-6.97 (m, 2 H), 7.18-7.35 (m, 15 H). 13C NMR (62.9 MHz): δ 69.7, 70.4, 71.2, 73.3, 73.9, 80.3, 81.1, 115.4, 127.6, 127.7, 127.9, 128.2, 128.3, 129.1, 130.5, 137.5, 137.8, 156.1. MALDI: m/z 507 (M + Na+). Calcd: C, 76.80; H, 6.66. Found: C, 76.55; H, 6.39.
6: [α]D 20 = +6.3 (c 1, CHCl3); 1H NMR (250 MHz): δ 3.71-3.83 (m, 2 H), 4.14 (dd, J = 2.2 Hz, 3.2 Hz, 1 H), 4.34 (td, J = 1.4 Hz, 5.9 Hz, 1 H), 4.44 (d, J= 11.9 Hz, 1 H), 4.53 (d, J = 11.9 Hz, 1 H), 4.57-4.86 (m, 5 H), 5.14 (br s, 1 H), 6.29 (d, J = 2.4 Hz, 1 H), 6.39 (dd, J = 2.5 Hz, 8.3 Hz, 1 H), 7.20-7.40 (m, 16 H). 13C NMR (62.9 MHz): δ 69.1, 70.1, 71.8, 73.1, 73.5, 74.0, 75.8, 103.1, 108.6, 114.0, 127.7, 127.8, 128.1, 128.3, 128.4, 129.3, 137.7, 138.1, 153.9, 156.7. MALDI: m/z 505 (M + Na+). Calcd: C, 77.16; H, 6.27. Found: C, 76.82; H, 6.57.
9: [α]D 20 = +26.7 (c 1, CHCl3); 1H NMR (250 MHz): δ 3.7-3.89 (m, 2 H), 4.04 (t, J = 6.1 Hz, 1 H), 4.29-4.35 (m, 1 H), 4.58-4.80 (m, 7 H), 5.4 (br s, 1 H), 6.34 (d, J = 2.43 Hz, 1 H), 6.4 (dd, J = 2.44 Hz, 8.34 Hz, 1 H), 7.1 (d, J = 8.38 Hz, 1 H), 7.23-7.37 (m, 15 H). 13C NMR (62.9 MHz): δ 69.0, 71.2, 73.1, 73.5, 73.6, 76.1, 77.01, 103.3, 109, 113.9, 127.7, 127.9, 128.0, 128.5, 130.2, 137.8, 138.2, 154.6, 156.7. MALDI: m/z 505(M + Na+).
10: [α]D 20 = +30.1 (c 1, CHCl3); 1H NMR (250 MHz): δ 3.53-3.92 (m, 6 H), 4.35-4.92(m, 17 H), 5.18 (br s, 1 H), 5.34 (d, J = 3.6 Hz, 1 H), 6.37 (d, J = 2.18 Hz, 1 H), 6.42 (dd, J = 2.32 Hz, 8.24 Hz, 1 H), 7.12 (dd, J = 3.26 Hz, 7.06 Hz, 1 H), 7.24-7.30 (m, 30 H). 13C NMR (62.9 MHz): δ 68.4, 69.0, 69.4, 70.9, 72.9, 73.3, 73.4, 74.5, 75.0, 75.5, 76.9, 80.0, 81.7, 96.1, 103.7, 109.1, 112.7, 127.6, 127.7, 127.8, 127.9, 128.3, 128.4, 131.1, 137.9, 138.0, 138.1, 138.3, 138.8, 154.9, 156.9. MALDI: m/z 937 (M + Na+).
12: [α]D 20 = -27.1 (c 1, CHCl3); 1H NMR (250 MHz): δ 1.46 (d, J = 6.48 Hz, 3 H), 3.69 (dd, J = 6.83 Hz, 8.08 Hz, 1 H), 4.11-4.19 (m, 1 H), 4.65-4.88 (m, 6 H), 6.27 (d, J = 2.48 Hz, 1 H), 6.40 (dd, J = 2.51 Hz, 8.39 Hz, 1 H), 7.15 (dd, J = 0.64 Hz, 8.41 Hz, 1 H), 7.23-7.36 (m, 10 H). 13C NMR (62.9 MHz): δ 17.9, 71.5, 73.7, 74.4, 77.3, 79.1, 102.9, 109.0, 114.7, 127.7, 127.87, 127.89, 127.9, 128.5, 129.8, 137.8, 138.2, 155.0, 156.5. Cald: C, 76.57; H, 6.43. Found: C, 76.25; H, 6.32.
15: [α]D 20 = +53.6 (c 0.5, CHCl3); 1H NMR (600 MHz): δ 2.02, 2.12 (2 s, 6 H), 2.25-2.33 (m, 1 H), 2.4-2.5 (m, 1 H), 2.9 (t, J = 6.7 Hz, 1 H), 3.77 (s, 3 H), 4.2-4.35 (m, 3 H), 5.08-5.17 (m, 3 H), 5.8-5.9 (m, 1 H), 6.46 (d, J = 1 Hz, 1 H), 6.53 (dd, J = 2.5 Hz, 8.4 Hz, 1 H), 6.98 (d, J = 8.5 Hz, 1 H). 13C NMR (150.8 MHz): δ 20.8, 21.0, 38.4, 41.5, 55.3, 63.3, 68.0, 69.9, 101.2, 108.5, 118.0, 130.5, 134.8, 153.5, 159.4, 170.4, 170.7. Calcd: C, 64.66; H, 6.63. Found: C, 64.95; H, 7.0.
17: [α]D 20 = +29.6 (c 1, CHCl3); 1H NMR (250 MHz): δ 1.98, 2.0, 2.1 (3 s, 9H), 2.77 (d, J = 6.9 Hz, 2 H), 3.75 (s, 3 H), 4.07 (dd, J = 6.8 Hz, 11.8 Hz, 1 H), 4.23 (dd, J = 4.6 Hz, 11.8 Hz, 1 H), 5.13-5.26 (m, 2 H), 6.92-7.2 (m, 4 H). 13C NMR (62.9 MHz): δ 20.6, 20.7, 21.0, 36.2, 62.2, 70.6, 72.0, 121.6, 130.2, 133.6, 149.6, 169.3, 170.0, 170.4.