A Concise Approach to the 5-Oxo-6,7-Dihydrofuranopyrone Skeleton

Abstract

An efficient, stereoselective route to the 3-acetoxy-5-oxo-6,7-dihydrofuranopyrone skeleton from furan is described. The key steps in this approach include enzymatic desymmetrization of the meso-diol 5a and ROM-CM-RCM sequence achieved on a conveniently substituted derivative 3.

furan - methathesis - oxanorbornane - lipases - Diels-­Alder

References and Notes

1 Davies-Coleman MT. Rivett DE. In Progress in the Chemistry of Organic Natural Products   Vol. 55:  Herz W. Grisebach H. Kirb GW. Tamm C. Springer-Verlag; New York: 1989.  p.1 

2 Review: Blázquez MA. Bermejo A. Zafra-Polo MC. Cortés D. Phytochem. Anal.  1999,  10:  161 

See, for instance:

3a Sam TW. Yeu CS. Matsjeh S. Gan EK. Razak D. Mohamed AL. Tetrahedron Lett.  1987,  28:  2541 

3b Wu YC. Duh CY. Chang FR. Wang SK. Chang JJ. McPhail AT. Lee KH. J. Nat. Prod.  1991,  54:  1077 

Review:

4a Mereyala HB. Joe M. Curr. Med. Chem.: Anti-Cancer Agents  2001,  1:  293 

4b See also: Inayat-Hussain SH. Osman AB. Din LB. Taniguchi N. Toxicol. Lett.  2002,  131:  153 

5 Review: Zhao G. Wu B. Wu XY. Zhang YZ. Mini-Rev. Org. Chem.  2005,  2:  333 

6a Kowarski CR. Sarel S. J. Org. Chem.  1973,  38:  117 

6b See also: Baran A. Kazaz C. Secen H. Sütbeyaz Y. Tetrahedron  2003,  59:  3643 

7a

A mixture of vinylene carbonate (9.89 g, 115 mmol) and furane (1.60 g, 23 mmol) was heated in a sealed tube protected from the light at 150 °C during 12 h. After this time, the reaction crude was distilled in vacuo to give 8.80 g (102 mmol) of vinylene carbonate and 610 mg (66%) of mixture of endo- and exo-cycloadducts in a ratio (endo:exo) of 3.5:1 (evaluated by ¹H NMR).

7b

To a solution of endo:exo cycloadduct mixture (610 mg, 3.96 mmol) in MeOH (39.6 mL), K₂CO₃ (819.7 mg, 5.94 mmol) was added. The mixture was stirred at r.t. for 24 h. After this time the reaction crude was filtered through a pad of Celite^® and the solvent was distilled in vacuo. After purification by column chromatography (silica gel, hexane-EtOAc, 1:1) 379 mg (2.96 mmol) of 5a and 107 mg (0.08 mmol) of 5b were isolated (combined yield 5a + 5b, 486.8 mg, 3.8 mmol, 96%).
Compound 5a: ¹H NMR (200 MHz, CDCl₃): δ = 6.50 (d, 2 H, J = 0.9 Hz), 4.93 (dt, 2 H, J = 0.9, 2.2 Hz), 4.20 (m, 2 H), 2.30 (s, 1 H), 2.74 (s, 1 H) ppm. ¹³C NMR (200 MHz, CDCl₃): δ = 134.9, 80.31, 67.15 ppm. R _f = 0.24. Anal. Calcd for C₆H₈O₃: C, 56.24; H, 6.29. Found: C, 56.08; H, 6.35.

8 For a comprehensive review on enantioselective enzymatic desymmetrizations in organic synthesis, see: Garcia-Urdiales E. Alfonso I. Gotor V. Chem. Rev.  2005,  105:  313 

9a

To a solution of 100 mg (0.78 mmol) of 5a in vinylacetate (10 mL), 837 mg of CCL (Fluka) were added. The reaction mixture was stirred 5 h at r.t. After this time the reaction crude was filtered through a pad of Celite^® and purified by column chromatography (silica gel, hexane-EtOAc, 7:3) giving 110 mg (0.65 mmol, 83%) of compound 4 as a colorless oil.
Compound 4: ¹H NMR (200 MHz, CDCl₃): δ = 6.56 (dd, 1 H, J = 1.4, 5.6 Hz), 6.49 (dd, 1 H, J = 1.4, 5.6 Hz), 5.05 (dd, 1 H, J = 1.4, 3.8 Hz), 4.95 (m, 2 H), 4.40 (dd, 1 H, J = 4.4, 7.2 Hz), 2.06 (s, 3 H) ppm. ¹³C NMR (200 MHz, CDCl₃): δ = 170.43, 135,21, 135.02, 80.29, 78.77, 69.91, 67.86, 29.67, 20,69 ppm. R _f = 0.22; [α]_D ²⁴ -1.07 (c 0.93, CHCl₃). Anal. Calcd for C₈H₁₀O₄: C, 56.47; H, 5.92. Found: C, 56.25; H, 6.12.
The ee was determined by ¹⁹F NMR spectroscopy of the Mosher’s ester derivative of 4. See ref. 9b.
Compound 4: ¹⁹F NMR (250 MHz, CDCl₃): δ = -72.02 (major), -72.31 (minor) ppm; ee 92%.

9b Dale JA. Mosher HS. J. Am. Chem. Soc.  1973,  95:  512 

10

Compound 3: ¹H NMR (300 MHz, CDCl₃): δ = 6.49 (s, 2 H), 6.36 (dd, 1 H, J = 17.1, 1.5 Hz), 6.05 (dd, 1 H, J = 17.1, 10.5 Hz), 5.85 (dd, 1 H, J = 10.5, 1.5 Hz), 5.21 (m, 2 H), 5.13 (m, 2 H), 1.90 (s, 3 H) ppm. ¹³C NMR (300 MHz, CDCl₃): δ = 169.91, 165.04, 134.80, 134.71, 131.41, 127.50, 78.75, 78.67, 68.72, 68.67, 20.38 ppm. Anal. Calcd for C₁₁H₁₂O₅: C, 58.93; H, 5.39. Found: C, 57.89; H, 5.17. [α]_D ²⁴ -2.0 (c 1.1, CHCl₃).

For a review on the metathesis tandem reactions in oxa- and azanorbornene derivatives, see:

11a Arjona O. Csákӱ AG. Plumet J. Eur. J. Org. Chem.  2002,  611 

11b For a recent application, see: Maechling S. Norman SE. McKendrick JE. Basra S. Köppner K. Blechert S. Tetrahedron Lett.  2006,  47:  189 

For a comprehensive review on synthetic applications of oxanorbornene derivatives, see:

12a Vogel P. Cossy J. Plumet J. Arjona O. Tetrahedron  1999,  55:  13521 

12b Vogel P. Curr. Org. Chem.  2000,  65:  455 

12c Robina I. Vogel P. Synthesis  2005,  675 

12d Vogel P. In The Organic Chemistry of Sugars   Levy DE. Fugedi P. Taylor and Francis Group CRC; Boca Raton: 2006.  Chap. 13. p.629-725  

13

Commercially available Hoveyda-Grubbs catalyst 2nd generation shows efficiencies similar to Grubb’s catalyst 2nd generation, but with different substrate selectivity. Specifically, it catalyzes ring-closing, ring-opening, and cross-metathesis reactions of electron-deficient substrates.

14

To a solution of 3 (23 mg, 0.1 mmol) in CH₂Cl₂ (2.2 mL) under Ar, was added Hoveyda-Grubbs catalyst (3.2 mg, 0.005 mmol, 5 mol%) in CH₂Cl₂ (0.3 mL). After bubbling of a stream of ethylene, the reaction mixture was stirred for 24 h at r.t. The solvent was removed in vacuo providing compound 2 (21 mg, 0.090 mmol, 90%).
Compound 2: ¹H NMR (300 MHz, CDCl₃): δ = 6.43 (dd, 1 H, J = 1.5, 17.4 Hz), 6.13 (dd, 1 H, J = 10.5, 17.4 Hz), 5.90 (m, 1 H), 5.50 (m, 2 H), 5.36 (dm, 1 H, J = 17.2 Hz), 5.26 (dm, 1 H, J = 10.26), 4.58 (m, 2 H), 2.05 (s, 3 H) ppm. ¹³C NMR (300 MHz, CDCl₃): δ = 170.33, 165.05, 132.95, 132.37, 127.97, 119.76, 80.21, 74.02, 20.38 ppm. Anal. Calcd for C₁₁H₁₂O₅: C, 58.93; H, 5.39; found: C, 58.84; H, 5.44. [α]_D ²⁴ -2.8 (c 0.7, CHCl₃).