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Synlett 2008(19): 3046-3052  
DOI: 10.1055/s-0028-1087344
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

FeCl3-Catalyzed Propargylation-Cycloisomerization Tandem Reaction: A Facile One-Pot Synthesis of Substituted Furans

Wen-hua Ji, Ying-ming Pan, Su-yan Zhao, Zhuang-ping Zhan*
Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, P. R. of China
Fax: +86(592)2180318; e-Mail: zpzhan@xmu.edu.cn;
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Publication History

Received 1 July 2008
Publication Date:
12 November 2008 (online)

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Abstract

An efficient FeCl3-catalyzed tandem propargylation-­cycloisomerization reaction of propargylic alcohols or acetates with 1,3-dicarbonyl compounds, leading to the synthesis of substituted furans, has been developed.

Key words

furans - iron(III) chloride - propargylic acetates - propargylic alcohols - tandem reaction

    References and Notes

  • 1 Rossi RA. Pierini AB. Peñéñory AB. Chem. Rev.  2003,  103:  71 ; and references cited therein
    Google Scholar
  • 2 Winnik MA. Chem. Rev.  1981,  81:  491 ; and references cited therein
    CrossrefGoogle Scholar
  • 3a Zhan Z.-P. Cai X.-B. Wang S.-P. Yu J.-L. Liu H.-J. Cui Y.-Y. J. Org. Chem.  2007,  72:  9838 
    Google Scholar
  • 3b Zhan Z.-P. Wang S.-P. Cai X.-B. Liu H.-J. Yu J.-L. Cui Y.-Y. Adv. Synth. Catal.  2007,  349:  2097 
    Google Scholar
  • 3c Zhan Z.-P. Yu J.-L. Liu H.-J. Cui Y.-Y. Yang R.-F. Yang W.-Z. Li J.-P. J. Org. Chem.  2006,  71:  8298 
    Google Scholar
  • 3d Zhan Z.-P. Yang W.-Z. Yang R.-F. Yu J.-L. Liu H.-J. Chem. Commun.  2006,  3352 
    Google Scholar
  • 4 Nishibayashi Y. Yoshikawa M. Inada Y. Milton MD. Hidai M. Uemura S. Angew. Chem. Int. Ed.  2003,  42:  2681 
    CrossrefGoogle Scholar
  • 5 Cadierno V. Gimeno J. Nebra N. Adv. Synth. Catal.  2007,  349:  382 
    CrossrefGoogle Scholar
  • 6 Sanz R. Miguel D. Martínez A. Álvarez-Gutiérrez JM. Rodríguez F. Org. Lett.  2007,  9:  727 
    CrossrefPubMedGoogle Scholar
  • 7 Feng X.-B. Tan Z. Chen D. Shen Y.-M. Guo C.-C. Xiang J.-N. Zhu C.-L. Tetrahedron Lett.  2008,  49:  4110 
    CrossrefGoogle Scholar
  • 9 Gabriele has also reported that 4-ethyl-2-methylfuran could be obtained directly by treatment of (Z)-2-ethyl-5-trimethyl-silylpent-2-en-4-yn-1-ol with TBAF without added solvent followed by transfer distillation; however, PdI2 as the catalyst is needed in the absence of trimethylsilyl group (Scheme 3). See: Gabriele B. Salerno G. Lauria E. J. Org. Chem.  1999,  64:  7687 
    Google Scholar
  • For synthetic applications of the γ-effect and β-effect of silicon, see:
  • 10a Sakurai H. Imai T. Hosomi A. Tetrahedron Lett.  1977,  18:  4045 
    Google Scholar
  • 10b Hatanaka Y. Kuwajima I. Tetrahedron Lett.  1986,  27:  719 
    Google Scholar
  • 10c Antras F. Ahmar M. Cazes B. Tetrahedron Lett.  2001,  42:  8157 
    Google Scholar
  • 11 The percentages of the enol content of 1,3-dicarbonyl compounds in CCl4 follow the order: dibenzoylmethane (3d; 96%) > acetylacetone (3c; 80%) > ethyl acetoacetate (3a; 7.5%) > diethyl malonate (3f; 0.007%). See: Burdett JL. Rogers MT. J. Am. Chem. Soc.  1964,  86:  2105 
    CrossrefGoogle Scholar
8

General Procedure for Synthesis of Tetrasubstituted Furans: To a 5-mL flask, propargylic alcohols 1 or propargylic acetates 2 (0.5 mmol), 1,3-dicarbonyl compounds 3 (2.0 mmol), toluene (2.0 mL), and FeCl3 (0.025 mmol, 4 mg) were successively added. The reaction mixture was stirred at reflux, and monitored periodically by TLC. Upon completion, toluene was removed under reduced pressure by an aspirator, and then the residue was purified by silica gel column chromatography (EtOAc-hexane) to afford the corresponding tetrasubstituted furans 5. Data of selected compounds: 5ab: yellow solid; mp 50-
51 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 1.08 (d, 6 H, J = 6.0 Hz), 2.18 (s, 3 H), 2.56 (s, 3 H), 5.01 (sept, 1 H, J = 6.4 Hz), 7.22-7.25 (m, 2 H), 7.27-7.30 (m, 1 H), 7.32-7.37 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 11.7, 14.0, 21.7, 67.2, 113.9, 122.5, 126.7, 127.6, 130.1, 133.4, 146.9, 157.2, 163.9. IR (film): 1704 cm-¹. MS (ESI): m/z (%) = 281 (100) [M + Na+]. Anal. Calcd for C16H18O3: C, 74.39; H, 7.02. Found: C, 74.24; H, 7.19. 5ad: white solid; mp 117-118 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 2.46 (s, 3 H), 7.12-7.28 (m, 10 H), 7.35-7.39 (m, 1 H), 7.55-7.58 (m, 2 H), 7.80-7.82 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 12.3, 121.7, 123.5, 126.2, 126.9, 128.1, 128.2, 128.3, 128.4, 129.0, 129.7, 129.8, 132.2, 133.2, 137.4, 148.1, 150.8, 193.8. IR (film): 1669 cm-¹. MS (ESI): m/z (%) = 361 (100) [M + Na+]. Anal. Calcd for C24H18O2: C, 85.18; H, 5.36. Found: C, 85.31; H, 5.14. 5ae: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 2.12-2.19 (m, 2 H), 2.30 (s, 3 H), 2.46-2.49 (m, 2 H), 2.87 (t, 2 H, J = 6.4 Hz), 7.26-7.31 (m, 1 H), 7.34-7.39 (m, 4 H). ¹³C NMR (100 MHz, CDCl3): δ = 12.2, 22.7, 23.9, 38.9, 119.4, 119.9, 127.3, 128.1, 130.0, 131.9, 148.9, 165.9, 194.3. IR (film): 1675 cm-¹. MS (ESI): m/z (%) = 227 (36) [M + H+], 249 (100) [M + Na+]. Anal. Calcd for C15H14O2: C, 79.62; H, 6.24. Found: C, 79.79; H, 6.09. 5bb: pale yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 0.39 (d, 3 H,
J = 6.4 Hz), 0.68 (d, 3 H, J = 6.4 Hz), 2.11 (s, 3 H), 2.65 (s, 3 H), 4.68 (sept, 1 H, J = 6.4 Hz), 7.28-7.48 (m, 4 H), 7.64 (d, 1 H, J = 8.4 Hz), 7.81 (d, 1 H, J = 8.4 Hz), 7.84 (d, 1 H, J = 8.0 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 11.7, 13.7, 20.7, 21.3, 66.6, 115.3, 119.1, 125.1, 125.5, 125.6, 126.2, 127.4, 127.9, 131.9, 133.3, 133.4, 147.6, 157.6, 163.7. IR (film): 1704 cm-¹. HRMS: m/z calcd for C20H20O3: 308.1412; found: 308.1413. 5bd: pale yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 2.27 (s, 3 H), 7.03 (dd, app. t, 2 H, J = 7.6, 7.6 Hz), 7.17-7.32 (m, 6 H), 7.39-7.41 (m, 2 H), 7.62-7.67 (m, 5 H), 7.73-7.75 (m, 1 H), 7.84-7.86 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 12.5, 121.5, 123.2, 125.1, 125.7, 125.76, 126.1, 126.5, 127.8, 127.9, 128.2, 128.3, 128.4, 128.5, 129.4, 129.7, 129.9, 132.2, 132.7, 133.5, 137.4, 149.2, 151.9, 193.3. IR (film): 1658 cm-¹. MS (ESI): m/z (%) = 389 (100) [M + H+]. Anal. Calcd for C28H20O2: C, 86.57; H, 5.19. Found: C, 86.39; H, 5.34. 5da: white solid; mp 96-97 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 1.15 (t, 3 H, J = 7.2 Hz), 2.19 (s, 3 H), 2.57 (s, 3 H), 4.15 (q, 2 H, J = 7.2 Hz), 7.14 (d, 2 H, J = 8.4 Hz), 7.49 (d, 2 H, J = 8.4 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 11.7, 14.0, 14.1, 59.9, 113.2, 120.4, 120.9, 130.8, 131.7, 132.3, 147.2, 157.7, 164.1. IR (film): 1701 cm-¹. MS (ESI): m/z (%) = 345 (100), 347 (90) [M + Na+]. Anal. Calcd for C15H15BrO3: C, 55.75; H, 4.68. Found: C, 55.51; H, 4.82. 5dc: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 2.00 (s, 3 H), 2.17 (s, 3 H), 2.55 (s, 3 H), 7.14 (d, 2 H, J = 8.8 Hz), 7.55 (d, 2 H, J = 8.4 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 11.6, 14.3, 30.8, 119.8, 121.5, 122.8, 131.5, 131.6, 132.7, 147.2, 156.4, 195.5. IR (film): 1623 cm-¹. MS (ESI): m/z (%) = 315 (100), 317 (86) [M + Na+]. Anal. Calcd for C14H13BrO2: C, 57.36; H, 4.47. Found: C, 57.47; H, 4.29. 5ea: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 1.09 (t, 3 H, J = 7.2 Hz), 2.20 (s, 3 H), 2.58 (s, 3 H), 3.93 (s, 3 H), 4.12 (q, 2 H, J = 7.2 Hz), 7.33 (d, 2 H, J = 8.4 Hz), 8.03 (d, 2 H, J = 8.4 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 11.8, 13.9, 14.1, 52.1, 59.9, 113.3, 120.6, 128.4, 128.9, 130.0, 138.4, 147.5, 157.9, 164.1, 167.1. IR (film): 1723 cm-¹. HRMS: m/z calcd for C17H19O5H+: 303.1236; found: 303.1227. 5ec: yellow solid; mp 100-101 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 1.97 (s, 3 H), 2.18 (s, 3 H), 2.54 (s, 3 H), 3.94 (s, 3 H), 7.33 (d, 2 H, J = 8.4 Hz), 8.08 (d, 2 H, J = 8.4 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 11.6, 14.2, 30.7, 52.2, 120.1, 122.8, 129.0, 129.6, 129.8, 138.7, 147.3, 156.4, 166.8, 195.4. IR (film): 1725, 1671 cm-¹. MS (ESI): m/z (%) = 273 (18) [M + H+], 295 (100) [M + Na+]. Anal. Calcd for C16H16O4: C, 70.57; H, 5.92. Found: C, 70.85; H, 5.81. 5ga: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 0.84 (t, 3 H,
J = 6.8 Hz), 1.07 (t, 3 H, J = 7.2 Hz), 1.20-1.27 (m, 4 H), 1.54-1.62 (m, 2 H), 2.49 (t, 2 H, J = 7.6 Hz), 2.58 (s, 3 H), 4.09 (q, 2 H, J = 7.2 Hz), 7.22-7.24 (m, 2 H), 7.27-7.30 (m, 1 H), 7.31-7.36 (m, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.8, 13.9, 14.1, 22.3, 25.8, 28.2, 31.2, 59.7, 113.5, 121.2, 126.7, 127.5, 130.0, 133.4, 151.3, 157.4, 164.4. IR (film): 1712 cm-¹. MS (ESI): m/z (%) = 323 (100) [M + Na+]. Anal. Calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 75.80; H, 8.23. 5hc: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 0.84 (t, 3 H, J = 6.8 Hz), 1.18-1.28 (m, 4 H), 1.53-1.61 (m, 2 H), 1.90 (s, 3 H), 2.43 (t, 2 H, J = 8.0 Hz), 2.54 (s, 3 H), 3.75 (s, 3 H), 6.93 (d, 1 H, J = 8.4 Hz), 6.90-7.02 (m, 1 H), 7.16 (dd, 1 H, J = 7.6, 1.6 Hz), 7.32-7.36 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 13.9, 14.3, 22.3, 25.9, 28.1, 29.3, 31.2, 55.2, 110.6, 116.6, 120.6, 122.7, 123.2, 129.2, 131.4, 151.1, 155.8, 157.3, 196.2. IR (film): 1673 cm-¹. HRMS: m/z [M + H+] calcd for C19H25O3: 301.1806; found: 301.1798. 5ic: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 0.77 (t, 3 H,
J = 7.2 Hz), 1.09-1.22 (m, 4 H), 1.44-1.52 (m, 2 H), 1.88 (s, 3 H), 2.36 (t, 2 H, J = 7.6 Hz), 2.46 (s, 3 H), 7.09 (d, 2 H,
J = 8.4 Hz), 7.29 (d, 2 H, J = 8.4 Hz). ¹³C NMR (100 MHz, CDCl3): δ = 13.9, 14.4, 22.2, 25.7, 28.1, 30.8, 31.1, 119.5, 122.7, 128.6, 131.2, 132.3, 133.3, 151.3, 156.5, 195.5. IR (film): 1675 cm-¹. MS (ESI): m/z (%) = 305 (24) [M + H+], 327 (100) [M + Na+]. Anal. Calcd for C18H21ClO2: C, 70.93; H, 6.94. Found: C, 70.81; H, 7.09.