Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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A Stereoselective Synthesis of 2,4,5-Trisubstituted Tetrahydrofuran

2,4,5-Trisubstituted Tetrahydrofuran의 입체 선택적 합성

  • Yu, Byung-Chan (Division of Chemistry and Applied Chemistry, Mokwon University)
  • 유병찬 (목원대학교, 화학 및 응용화학부)
  • Published : 2004.02.20
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Abstract

Keywords

EXPERIMENTAL SECTION

General

1H NMR and 13C NMR spectra were recorded using 200 and 300 MHz NMR spectrometers. The chemical shifts are reported in ppm using CDCl3 as solvent and TMS as an internal standard. Infrared spectra were recorded Perkin Elmer Paragon 500 FTIR spectrometer. Flash chromatography was performed using E. Merck silica gel 60 (200-400 mesh).

(E)-3-Methyl-5-(benzyloxy)-3-penten-1-yne (2)

To a solution of 3.30 g (0.0343 mol) of the trans-alcohol 1 in 10 mL benzene was added 1.50 g (0.0377 mol) of NaH in 60% mineral oil at 0 ℃. After the hydrogen evolution stopped 6.20 g (0.036 mol) of benzyl bromide was added. The solution was stirred at 80 ℃ for 24 hrs. Water was added slowly at 0 ℃ and then 3% HCl was added. The aqueous layer was separated and extracted with ether three times. The extracts were washed with saturated sodium bicarbonate and subsequently with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel. Elution with 2% ether in hexanes afforded 4.26 g (67%) of the benzyl ether 2:

IR (film) ν 3300, 2100, 1470, 1600, 1450 cm-1; 1H NMR (200 MHz, CDCl3) d 7.34 (5H, s, phenyl Hs), 6.10 (1H, t, J=12.0 Hz, vinyl H ), 4.51 (2H, s, benzyl H), 4.10 (2H, d, J=13 Hz, -OCH2-), 2.84 (1H, s, acetylenic H ), 1.08 (3H, s, vinyl CH3) ppm; MS(EI), m/z(real intensity) 185(27), 149(22), 107(74), 91(100), 77(33), 65(20), 53(12).

(E)-4-Methyl-6-(benzyloxy)-4-hexen-2-yn-1-ol (3)

To a solution of 2.0 g (0.011 mol) of the benzyl ether 2 in 20 mL of THF was added 4.8 mL (0.012 mol) of 2.5 M n-BuLi in hexanes at -78 ℃. The solution was stirred for 1 hr and then an excess gaseous formaldehyde was passed into the solution. The solution was stirred for the additional hour. The reaction mixture was warmed to room temperature and quenched with water. The aqueous layer was separated and extracted with ether three times. The extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel. Elution with 40% ether in hexanes afforded 1.22 g (52%) of the alcohol 3: IR (film) ν 3400, 1030, 1600, 1450 cm-1; 1H NMR (200 MHz, CDCl3) d 7.33 (5H, m, phenyl Hs), 6.02 (1H, brt, J=12 Hz, vinyl H), 4.50 (2H, s, benzyl CH2) 4.38 (2H, s, -CH2OH), 4.09 (2H, d, J=13 Hz, -OCH2-), 1.78 (3H, s, vinyl CH3) ppm.

(E)-4-Methyl-4,5-epoxy-6-(benzyloxy)- 4-hexen-2-yn-1-ol (4)

To a solution of 2.30 g (0.0106 mol) of the enynol 3 in 25 mL of CHCl3 was added 3.67 g (0.0213 mol) of m-CPBA. The solution was stirred for 3.6 hrs at room temperature. The solution was quenched with saturated NaHCO3. The aqueous layer was separated and extracted with ether three times. The extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel. Elution with 50% ether in hexanes afforded 1.36 g (56%) of the epoxide 4: IR (film) 3450, 2250, 1600, 1450; 1H NMR (200 MHz, CDCl3) d 7.34 (5H, m, phenyl Hs), 4.56 (2H, ABX, JAX=11 Hz, JBX=10 Hz, JAB=22 Hz, benzylic CH2), 4.28 (2H, s, -CH2OH), 3.50 (2H, m, -OCH2-), 3.41 (1H, dd, JAX=11, JBX=10 Hz epoxide H), 1.49 (3H, s, vinyl CH3) ppm.

rel-(2S,5R)-4-Methyl-6-(benzyloxy)-2,3-hexadien-1,5-diol (5)

To a solution of 200 mg (0.696 mmol) of the trans-alkynyloxirane 4 in 3 mL of CH2Cl2 was added 0.23 mL of 1M DIBAH in hexanes at 0 ℃. The solution was stirred for 1.5 h and extracted with ether three times. The extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel. Elution with 75% ether in hexanes afforded 120 mg (60%) of the trans-allenediol 5a: IR (film) 3400, 1980, 1450; 1H NMR (200 MHz, CDCl3) 7.37 (5H, m, phenyl Hs), 5.54 (1H, brs, vinyl H), 4.60 (2H, s, benzylic Hs) 4.25 (1H, m, methane H), 4.10 (2H, d, J=2.0 Hz, CH2OH), 3.62 and 3.52 (2H, m, methylene), 3.20 (1H, brs, -OH), 2.91 (1H, brs, -OH), 1.77 (3H, s, vinyl CH3) ppm; 13C NMR (125 MHz. CDCl3) 199.70, 137.63, 128.45, 127.84, 102.98, 94.26, 73.45, 72.55, 71.22, 59.96, 15.64.

rel-(2R,5R)-(5-Benzyloxymethyl-4-methyl-2,5-dihydro-furan-2-ylmethoxy)-tert-butyl-dimethyl-silane (7)

To a solution of 110 mg (0.460 mmol) of the diol 5 in 3 mL of CH2Cl2 was added 77 mg (0.51 mmol) of ter-butyldimethylsilyl chloride, 0.38 mL (0.23 mmol) of DMAP and 0.38 mL (2.80 mmol) freshly distilled triethylamine. The reaction mixture was stirred for 2 hrs. Water was added. The aqueous solution was separated and extracted with ether three times. The extracts were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford the clean crude allenol 6. The allenol was treated with 70 mg (0.41 mmol) of silver nitrate and 41 mg (0.41 mmol) of calcium carbonate in 2 mL of a mixture of acetone and water (5:1). The solution was stirred overnight. The mixture was concentrated under reduced pressure. The residue was chromatographed on silica gel. Elution with 30% ether in hexanes afforded 130 mg (80%) of the dihydrofuran 7: IR (film) 3450, 1940, 1262; 1H NMR (200 MHz, CDCl3) d 7.34 (5H, m, phenyl Hs), 5.54 (H, brs , vinyl H), 4.88 (2H, m, methane Hs), 4.59 (2H, d, J=16 Hz, benzylic CH2), 3.69-3.52 (4H, m, -OCH2), 1.71 (3H, s, vinyl CH3), 0.89 (9H, s, SiC(CH3)3), 0.06 (6H, s, -Si(CH3)3) ppm; 13C NMR (75.5 MHz, CDCl3) 138.34, 137.34, 128.79, 128.27, 127.64, 127.47, 123.47, 87.29, 86.05, 73.39, 71.47, 66.29, 25.88, 18.31, 12.62, -5.33; MS(EI), m/z (rel intensity) 291(17), 203(18), 183(6), 145(6), 91(100), 73(33), 65(6).

rel-(2R,3R,5R)-[5-(tert-Butyl-dimethyl-silanyloxymethyl)-3-methyltetrahydrofuran-2-yl]-methanol (8)

To a solution of 130 mg (0.037 mmol) of the dihydrofuran in 2 mL of ethyl acetate was added 65 mg of palladium on charcol. The suspension was stirred for 2 days. The reaction mixture was filtered. The filtrate was concentrated undr reduced pressure. The residue was chromatographed on silica gel. Elution with 60% ether in hexanes afforded 81 mg (88%) of the tetrahydrofuran 8: IR (film) 3450, 1480, 1250; 1H NMR (300 MHz, CDCl3) d 3.98 (1H, m, H-5), 3.69 (1H, dt, J=8.7 Hz and 2.4 Hz , H-1), 3.57 (2H, d, J=4.5 Hz, -CH2OTBS), 3.50-3.42 (3H, m, -CH2OH), 2.09 (2H, m, methylene), 0.97 (3H, d, J=6.0 Hz, -CH3), 0.84 (9H, s, SiC(CH3)3), 0.08 (6H, s, -Si(CH3)3) ppm.

References

  1. Wierenga, M. In The Total Synthesis of Natural Products, Apsimon, J., Ed.; John Wiley & Sons; New York; 1981, 4, 263. https://doi.org/10.1002/9780470129678.ch3
  2. Paterson, A.; Mansuri, M. M. Tetrahedron 1985, 41, 3569. https://doi.org/10.1016/S0040-4020(01)91380-8
  3. Boeckman, R. H.; Goldstein, M. In The Total Synthesis of Natural Products, Apsimon, J., Ed.; John Wiley & Sons: New York; 1988, 7, 1.
  4. Polyether Antibiotics; Westly, J. W., Ed.; Marcel Dekker: New York, 1982; Vols. 1-2.
  5. Donnelly, D. M. X.; Meegan, M. J. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: New York, 1984, 3, 705.
  6. Danheiser, R. L.; Stoner, E. J.; Koyama, H.; Yamashita, D. S.; Klade, C. A. J. Am. Chem. Soc. 1989, 111, 4407. https://doi.org/10.1021/ja00194a040
  7. Evans, D. A.; Ratz, A. M.; Huff, B. E.; Sheppard, G. S. J. Am. Chem. Soc. 1995, 117, 3448. https://doi.org/10.1021/ja00117a014
  8. Dutton, C. J.; Banks, B. J.; Cooper, C. B. Nat. Prod. Rep. 1995, 12, 165. https://doi.org/10.1039/np9951200165
  9. Figadere, B. Acc. Chem. Res. 1995, 28, 359. https://doi.org/10.1021/ar00057a001
  10. Nicolaou, K. C. Tetrahedron 1977, 683.
  11. Back, T. G. Tetrahedron 1977, 3041.
  12. Marshall, J. A.; Yu, R. H.; Perkins, J. F. J. Org. Chem. 1995, 60, 5550. https://doi.org/10.1021/jo00122a040
  13. Molander, G. A.; Swallow, S. J. Org. Chem. 1994, 59, 7148. https://doi.org/10.1021/jo00102a051
  14. Marshall, J. A.; Pinney, K. G. J. Org. Chem. 1993, 58, 7180. https://doi.org/10.1021/jo00077a048
  15. Lipshutz, B. H. Chem. Rev. 1986, 86, 795. https://doi.org/10.1021/cr00075a005
  16. Angle, S. R.; El-Said, A. J. Am. Chem. Soc. 2002, 124, 3608. https://doi.org/10.1021/ja012193b
  17. Aggarwal, V.; Eames, J.; Villa, M.-J.; McIntyre, S.; Sansbury, F.; Warren, S. J. Chem. Soc., Perkin Trans, I 2000, 533.
  18. Rodriguez, J.; Rumbo, A.; Castedo, L.; Mascarenas, J. J. Org. Chem. 1999, 64, 4560. https://doi.org/10.1021/jo990233c
  19. Ghosh, A. K.; Liu, C J. Am. Chem. Soc. 2003, 125, 2374. https://doi.org/10.1021/ja021385j
  20. Pilli, R. A.; Riatto, V. B.; Vencato, I; Org. Lett. 2000, 2, 53. https://doi.org/10.1021/ol991194u
  21. Li, P.; Wang, T.; Emge, T.; Zhao, K. J. Am. Chem. Soc. 1998, 120, 7391. https://doi.org/10.1021/ja981414j
  22. Marshall, J. A.; Yu, B.-C.; J. Org. Chem. 1994, 59, 324. https://doi.org/10.1021/jo00081a009
  23. Siegel, S. Comprehensive Organic Synthesis Ed. Trost, B. A.; Pergamon Press; NewYork; vol 8; p 430.