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

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
• 2 Winnik MA. Chem. Rev.  1981,  81:  491 ; and references cited therein
• 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 
• 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 
• 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 
• 3d Zhan Z.-P. Yang W.-Z. Yang R.-F. Yu J.-L. Liu H.-J. Chem. Commun.  2006,  3352 
• 4 Nishibayashi Y. Yoshikawa M. Inada Y. Milton MD. Hidai M. Uemura S. Angew. Chem. Int. Ed.  2003,  42:  2681 
• 5 Cadierno V. Gimeno J. Nebra N. Adv. Synth. Catal.  2007,  349:  382 
• 6 Sanz R. Miguel D. Martínez A. Álvarez-Gutiérrez JM. Rodríguez F. Org. Lett.  2007,  9:  727 
• 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 
• 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 
• 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 
• 10b Hatanaka Y. Kuwajima I. Tetrahedron Lett.  1986,  27:  719 
• 10c Antras F. Ahmar M. Cazes B. Tetrahedron Lett.  2001,  42:  8157 
• 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 

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.