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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;
Further Information

Publication History

Received 4 February 2003
Publication Date:
30 June 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

    References

  • 1a Rastrelli L. Berger I. Kubelka W. Caceres A. De Tommasi N. De Simone F. J. Nat. Prod.  1999,  62:  188 
    Search in Google Scholar
  • 1b Ahmad-Junan SA. Amos PC. Whiting DA. J. Chem. Soc., Perkin Trans. 1  1992,  539 
  • 1c Lami N. Kadota S. Tezuka Y. Kilkuchi T. Chem Pharm. Bull.  1990,  38:  1558 
    Search in Google Scholar
  • 1d Petkov E. Uzunov P. Kostova I. Somleva T. Ognyanov I. Planta Med.  1983,  47:  237 
    Search in Google Scholar
  • 1e Jennings RC. Ottridge AP. J. Chem. Soc., Perkin Trans 1  1984,  1733 
  • 2a Pratt GE. Jennings RC. Hamnett AF. Brooks GT. Nature (London)  1980,  284:  320 
    Search in Google Scholar
  • 2b Jennings RC. Tetrahedron Lett.  1982,  23:  2693 
    Search in Google Scholar
  • 2c Pranab M. Asok N. Venkateswaran RV. Tetrahedron  1996,  52:  10265 
    Search in Google Scholar
  • 2d David M. Sauleau J. Sauleau A. Bull. Soc. Chim. Fr.  1993,  130:  527 
    Search in Google Scholar
  • 3a Bohm BA. Introduction to Flavonoids   Harwood Academic publishers; Amsterdam: 1998. 
  • 3b The Flavonoids   Harborne JB. Mabry H. Chapman & Hall; New York: 1988. 
  • 4a Yang J. Fan S. Pei H. Zhu B. Xu W. Naganawa H. Hamada M. Takeuchi T. J. Antibiot.  1991,  44:  1277 
    Search in Google Scholar
  • 4b Suetsuna K. Osajima Y. Agric. Biol. Chem.  1989,  53:  241 
    Search in Google Scholar
  • 5 Hanessian S. Deoxy Sugars   American Chemical Society; Washington DC.: 1968. 
  • 6 Burnouf C. Lopez JC. Calvo-Flores FG. De los Angeles Laborde M. Olesker A. Lukacs G. J. Chem. Soc., Chem. Commun.  1990,  823 
  • 7a Dötz KH. Ehlenz R. Paetsch D. Angew. Chem. Int. Ed. Engl.  1997,  36:  2376 
    CrossrefSearch in Google Scholar
  • 7b Hallett MR. Painter JE. Ricketts D. Tetrahedron Lett.  1998,  39:  2851 
    CrossrefSearch in Google Scholar
  • 8a Das J. Schmidt RR. Eur. J. Org. Chem.  1998,  1609 
    Crossref
  • 8b Winterfeld GA. Ito Y. Ogawa T. Schmidt RR. Eur. J. Org. Chem.  1999,  1167 
    Crossref
  • 8c Winterfeld GA. Khodair AI. Schmidt RR. Eur. J. Org. Chem.  2003,  1009 
    Crossref
  • 8d

    Khodair, A. I.; Schmidt, R. R. Eur. J. Org. Chem., in print.
    Crossref
  • 8e Pachamuthu K. Gupta A. Das J. Schmidt RR. Vankar YD. Eur. J. Org. Chem.  2002,  1479 
    Crossref
  • 8f Winterfeld GA. Das J. Schmidt RR. Eur. J. Org. Chem.  2000,  3047 
    Crossref
  • 9a Lemieux RU. Nagabushan TL. O’Neill IK. Tetrahedron Lett.  1964,  5:  1909 
    Search in Google Scholar
  • 9b Lemieux RU. Nagabushan TL. O’Neill IK. Can. J. Chem.  1968,  46:  413 
    Search in Google Scholar
  • 10 Kraus GA. Thurston J. Thomas PJ. Tetrahedron Lett.  1988,  29:  1879 
    Search in Google Scholar
  • 11 Corey EJ. Estreicher H. Tetrahedron Lett.  1981,  22:  603 
    CrossrefSearch in Google Scholar
  • 13 Dufner G. Ph.D. Dissertation   Universität Konstanz; Germany: 1997. 
  • 14 Iida H. Tamazaki N. Kibayashi C. J. Org. Chem.  1987,  52:  1956 
    Search in Google Scholar
  • 15 Sunazuka T. Tabata N. Nagamitsu T. Tomoda H. Omura S. Tetrahedron Lett.  1993,  34:  6659 
    Search in Google Scholar
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.