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Synlett 2005(9): 1468-1470  
DOI: 10.1055/s-2005-869833
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of 4-Oxoalkenoic Acids from 2-Alkylfurans

Suresh Palani Annangudi, Mingjiang Sun, Robert G. Salomon*
Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA
Fax: +1(216)3683006; e-Mail: rgs@case.edu;
Further Information

Publication History

Received 8 March 2005
Publication Date:
10 May 2005 (online)

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Abstract

An efficient synthesis of 4-oxo-2-alkenoic acids is achieved by the reaction of 2-alkylfurans with sodium chlorite in acidic aqueous solution. The method is applicable to the total synthesis of biologically active phospholipids containing this functional array. The oxidation procedure also converts 2,5-dialkyl furans to α,β-unsaturated-γ-diketones in good yields.

Key words

furan oxidation - sodium chlorite - ring opening - oxidized phospholipids - α,β-unsaturated acids

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Typical Procedure for Furan Oxidation. To a magnetically stirred solution of alkyl furan 1 (0.1 mmol) in t-BuOH-H2O (5:1, v/v, 0.5 mL) was added NaH2PO4 (0.15 mmol), NaClO2 (0.3 mmol). The resulting mixture was stirred at r.t. for 2 h or until the yellow color disappears. Then, the solvent was removed on a rotary evaporator. The residue was extracted with CHCl3. The extract was washed with brine, dried on MgSO4 and passed through a short plug of Celite. The resulting butenolides are at least 90% pure by NMR.
Typical Procedure for cis / trans Isomerization.
To a solution of 2 in 2 mL THF-acetone-H2O (5:4:1) was added 10 µL of freshly distilled pyridine (1 mol%). The mixture was stirred for 2 h at r.t. Solvents were removed on a rotary evaporator and residual pyridine was removed in vacuo using a dry ice cooled trap. The residue was purified by flash chromatography on a silica gel column (30% EtOAc in hexanes) to afford the pure product 3.
Toluene-4-sulfonic Acid 4-(Furan-2-yl)butyl Ester ( 1e).
1H NMR (300 MHz, CD3Cl): δ = 7.77 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.4 Hz, 2 H), 7.25 (dd, J 1 = 1.8 Hz, J 2 = 0.9 Hz, 1 H), 6.24 (dd, J 1 = 3.0 Hz, J 2 = 1.8 Hz, 1 H), 5.92 (dd, J 1 = 3.0 Hz, J 2 = 0.9 Hz, 1 H), 4.01 (t, J = 6.3 Hz, 2 H), 2.56 (t, J = 6.6 Hz, 2 H), 2.43 (s, 3 H), 1.63-1.64 (4 H). 13C NMR (75 MHz, CD3Cl): δ = 155.1, 144.6, 140.8, 132.9, 129.7, 127.8, 110.0, 105.0, 70.1, 28.1, 27.0, 23.8, 21.5. HRMS (FAB): m/z calcd for C15H18O4S+ [M+]: 294.0926; found: 294.0924.
Toluene-4-sulfonic Acid 4-(2-Hydroxy-5-oxo-2,5-dihydrofuran-2-yl)butyl Ester ( 2e). 1H NMR (300 MHz, CDCl3): δ = 7.75 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 7.9 Hz, 2 H), 7.19 (d, J = 5.5 Hz, 1 H), 6.09 (d, J = 5.5 Hz, 1 H), 4.03 (m, 2 H), 2.43 (br s, 3 H), 1.40-1.80 (6 H).
4-Oxo-8-(toluene-4-sulphonyloxy)oct-2-enoic Acid ( 3e).
1H NMR (200 MHz, CDCl3): δ = 7.77 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 7.9 Hz, 2 H), 7.12 (d, J = 15.9 Hz, 1 H), 6.63 (d, J = 16.1 Hz, 1 H), 4.03 (m, 2 H), 2.62 (m, 2 H), 2.43 (br s, 3 H), 1.60-1.80 (4 H). 13C NMR (50 MHz, CDCl3): δ = 198.1, 168.1, 144.9, 144.8, 140.6, 132.9, 129.8, 127.8, 69.9, 40.5, 28.0, 21.6, 19.4. HRMS (FAB): m/z calcd for C15H19O6S+ [M + H+]: 327.0902; found: 327.0903.
5-Hydroxy-5-pentyl-5 H -furan-2-one ( 2d).
1H NMR (300 MHz, CDCl3): δ = 7.17 (d, J = 5.7 Hz, 1 H), 6.11 (d, J = 5.7 Hz, 1 H), 1.98 (m, 2 H), 1.28-1.41 (7 H), 0.87 (t, J = 6.3 Hz, 3 H). 8-( tert -Butyldimethylsilanyloxy)-4-oxooct-2 ( Z )-enoic Acid ( 3g).
TLC: 20% EtOAc in hexanes, R f = 0.37; yield 77%. 1H NMR (200 MHz, CDCl3): δ = 7.21 (d, J = 5.5 Hz, 1 H), 6.10 (d, J = 5.5 Hz, 1 H), 3.64 (t, J = 5.9 Hz, 2 H), 2.10-1.90 (2 H), 1.70-1.40 (4 H), 0.88 (s, 9 H), 0.05 (s, 6 H). 13C NMR (75 MHz, CDCl3): δ = 170.3, 154.2, 123.1, 108.0, 62.9, 36.9, 31.8, 25.9, 20.2, 18.3, -5.3. HRMS (FAB): m/z calcd for C14H27O4Si+ [M + H+]: 287.1673; found: 287.1679.
5-[3-( tert -Butyldimethylsilanyloxy)butyl]-5-hydroxy-5 H -furan-2-one ( 2h). TLC: 20% EtOAc in hexanes, R f = 0.3. 1H NMR (300 MHz, CDCl3, diastereomeric mixture): δ = 7.19 (d, J = 6.0 Hz, 0.7 H), 7.15 (d, J = 6.0 Hz, 0.3 H), 6.05 (1 H), 4.01 (m, 0.7 H), 3.95 (m, 0.3 H), 1.60-2.20 (6 H), 1.10-1.20 (6 H), 0.80-0.90 (9 H), -0.01-0.16 (6 H).
1-Palmitoyl-2-[1-carboxy-4-(2-hydroxy-5-oxo-2,5-dihydrofuran-2-yl)butanoyl]- sn -glycero-3-phospha-tidylcholine ( 2a).
1H NMR (300 MHz, CD3OD): δ = 7.41 (br s, 1 H), 6.15 (d, J = 6.0 Hz, 1 H), 5.25 (m, 2 H), 4.39 (m, 1 H), 4.28 (m, 2 H), 4.21 (m, 1 H), 4.01 (m, 2 H), 3.66 (m, 2 H), 3.23 (s, 9 H), 2.30-2.40 (4 H), 1.50-2.10 (6 H), 1.20-1.30 (24 H), 0.88 (t, J = 6.0 Hz, 3 H). HRMS (MALDI-TOF): m/z calcd for C32H59NO11P+ [MH+]: 664.3826; found: 664.3820.
1-Palmitoyl-2-[1-carboxy-8-(2-hydroxy-5-oxo-2,5-dihydrofuran-2-yl)octanoyl]- sn -glycero-3-phospha-tidylcholine ( 2b). 1H NMR (300 MHz, CD3OD): δ = 7.41 (br s, 1 H), 6.12 (d, J = 6.0 Hz, 1 H), 5.25 (m, 2 H), 4.40 (m, 1 H), 4.27 (m, 2 H), 4.16 (dd, J 1 = 12.6 Hz, J 2 = 6.3 Hz, 1 H), 4.01 (t, J = 5.1 Hz, 2 H), 3.66 (m, 2 H), 3.23 (s, 9 H), 2.30-2.40 (4 H), 1.50-2.10 (5 H), 1.20-1.30 (30 H), 0.88 (t, J = 6.0 Hz, 3 H). HRMS (MALDI-TOF): m/z calcd for C36H67NO11P+ [MH+]: 720.4457; found: 720.4424.

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9,12-Dioxooctadeca-10( Z ),13( E )-dienoic Acid ( 5j).
To a magnetically stirred solution of aldehyde 4j (39 mg, 0.14 mmol) in t-BuOH-H2O (5:1, v/v, 0.3 mL) and 2-methyl-2-butene (1.44 mmol, 720 µL, 2 M in THF) were added NaH2PO4 (30 mg, 0.22 mmol) and NaClO2 (40 mg, 0.4 mmol, 90%). The mixture was stirred at r.t. and monitored by TLC. The solvent was removed. The residue was purified by flash chromatography on a silica gel column (first eluted with 25% EtOAc in hexanes then EtOAc) affording yellowish crystals 5j. 1H NMR (200 MHz, CDCl3): δ = 6.83 (dt, J 1 = 16.0 Hz, J 2 = 6.8 Hz, 1 H), 6.48 (d, J = 12.0 Hz, 1 H), 6.38 (d, J = 12.0 Hz, 1 H), 6.18 (dt, J 1 = 16.0 Hz, J 2 = 1.5 Hz, 1 H), 2.52 (t, J = 7.2 Hz, 2 H), 2.10-2.40 (4 H), 1.10-1.80 (14 H), 0.91 (t, J = 7.4 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 202.9, 192.6, 179.6, 150.8, 136.9, 134.2, 130.2, 42.6, 34.0, 32.5, 30.1, 29.0, 28.9, 24.6, 23.4, 22.3, 13.9. HRMS (EI): m/z calcd for C18H28O4 + [M+]: 308.1988; found: 308.1978.