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Synlett 2003(1): 0083-0086
DOI: 10.1055/s-2003-36214
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Efficient 4-O-Alkylations of Tetronic Acids Involving Oxyphosphonium Intermediates

Franz F. Paintner*, Lars Allmendinger, Gerd Bauschke
Department Pharmazie - Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, Haus C, 81377 München, Germany
Fax: +49(89)21807247; e-Mail: franz.paintner@cup.uni-muenchen.de;
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Publication History

Received 20 August 2002
Publication Date:
18 December 2002 (online)

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Abstract

4-Alkoxy-5H-furan-2-ones were prepared in fair to high yields by regioselective 4-O-alkylation of tetronic acids with stoi­chiometric amounts of primary and secondary alcohols. This approach involves the intermediacy of (5-oxo-2,5-dihydrofuran-3-yloxy) phosphonium trifluoromethanesulfonates, which were generated in situ on reaction of tetronic acids with triphenylphosphonium anhydride trifluoromethanesulfonate (Hendrickson’s reagent).

Key words

tetronic acids - alkylations - regioselectivity - phosphonium ions - Mitsunobu reaction

    References

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9

Typical Procedure for the 4-O-Alkylation of Tetronic Acids:
To a stirred solution of triphenylphosphine oxide (584 mg, 2.1 mmol) in CH2Cl2 (2 mL) at 0 °C was added dropwise trifluoromethanesulfonic anhydride (168 µL, 1.0 mmol). After 15 min, when the reagent had precipitated, a solution of tetronic acid (100 mg, 1.0 mmol) and i-Pr2NEt (174 µL, 1.0 mmol) in CH2Cl2 (3 mL) was added. After the colorless precipitate had dissolved, the respective alcohol (1.0-1.2 mmol) was added dropwise, followed by i-Pr2NEt (209 µL, 1.25 mmol). Then the reaction mixture was allowed to warm to r.t. and stirred for 20 h, before it was concentrated under reduced pressure. The crude product was purified by flash chromatography.

10

4-Methoxy-5 H -furan-2-one ( 5a): Colourless crystals. Mp 48 °C (Lit.: [16] 63 °C). 1H NMR (500 MHz, CDCl3): δ = 3.92 (s, 3 H, CH3), 4.64 (d, 2 H, J = 1.1 Hz, 5-H), 5.12 (t, 1 H, J = 1.1 Hz, 3-H). 4-Benzyloxy-5 H -furan-2-one ( 5b): Colourless crystals. Mp 90 °C (Lit.: [16] 103-104 °C). 1H NMR (400 MHz, CDCl3): δ = 4.65 (d, 2 H, J = 1.3 Hz, 5-H), 5.06 (s, 2 H, CH2O), 5.18 (t, 1 H, J = 1.3 Hz, 3-H), 7.35-7.44 (m, 5 H, Harom).
4-Allyloxy-5 H -furan-2-one ( 5c): Colourless oil. IR(film): ν = 3123, 1778, 1745, 1627 cm-1. 1H NMR (500 MHz, CDCl3): δ = 4.58 (dt, 2 H, J = 1.3, 5.8 Hz, CH2O), 4.66 (d, 2 H, J = 1.1 Hz, 5-H), 5.11 (t, 1 H, J = 1.1 Hz, 3-H), 5.40 (ddd, 1 H, J = 1.2, 2.4, 10.5 Hz, CH=CH 2), 5.43 (ddd, 1 H, J = 1.2, 3.1, 17.3 Hz, CH=CH 2), 5.98 (ddt, 1 H, J = 5.8, 10.5, 17.2 Hz, CH=CH2). 13C NMR (125 MHz, CDCl3): δ = 67.9 (C-5), 73.2 (CH2O), 89.5 (C-3), 120.3 (CH=CH2), 130.2 (CH=CH2), 173.3 (C-2), 178.3 (C-4). MS (CI, CH5 +): m/z (%) = 141(100) [M + H+]. Anal. Calcd for C7H8O3 (140.1): C, 60.00; H, 5.75. Found: C, 59.98; H, 5.88.
4-Octyloxy-5 H -furan-2-one ( 5d): Colourless oil. IR (KBr): ν = 3124, 1778, 1747 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.82 (t, 3 H, J = 7.1 Hz, CH3), 1.16-1.39 (m, 10 H, CH2), 1.68-1.77 (q, 2 H, J = 6.7 Hz, CH 2CH2O), 3.99 (t, 2 H, J = 6.7 Hz, CH2O), 4.85 (d, 2 H, J = 1.1 Hz, 5-H), 5.38 (t, 1 H, J = 1.1 Hz, 3-H). 13C NMR (100 MHz, CDCl3): δ = 14.3 (C-8′), 22.6 (C-7′), 25.6 (C-3′), 28.4 (C-4′/C-5′), 29.1 (C-2′), 31.7 (C-6′), 67.9 (C-5), 73.1 (C-1′), 88.7 (C-3), 173.6 (C-2), 179.6 (C-4). MS (70 eV): m/z = 212 [M+]. Anal. Calcd for C12H20O3: C, 67.89; H, 9.50. Found: C, 67.89; H, 9.58.
4-Isopropoxy-5 H -furan-2-one ( 5e): [17] Colourless oil. 1H NMR (500 MHz, CDCl3): δ = 1.39 (d, 6 H, J = 6.2 Hz, CH3), 4.44 (sept, 1 H, J = 6.2 Hz, CH), 4.60 (d, 2 H, J = 1.1 Hz, 5-H), 5.03 (t, 1 H, J = 1.1 Hz, 3-H). 13C NMR (100 MHz, CDCl3): δ = 21.3 [(CH3)2], 68.2 (C-5), 76.6 (CH), 88.5 (C-3), 173.9 (C-2), 178.3 (C-4).
( R )-4-(1-Methylheptyloxy)-5 H -furan-2-one ( 5f): Colourless oil. [α]D 20 = +1.6 (c 1.08, CH2Cl2). IR(film): ν = 3118, 2932, 2858, 1775, 1749, 1625 cm-1. 1H NMR (500 MHz, CDCl3): δ = 0.89 (t, 3 H, J = 7.0 Hz, CH 3 CH2), 1.19-1.44 [m, 10 H, CH3(CH 2 )5], 1.35 (d, 1 H, J = 6.1 Hz, CH 3 CH), 1.61 (m, 1 H, CH 2 CH), 1.74 (m, 1 H, CH 2 CH), 4.27 (qt, 1 H, J = 6.1, 7.0 Hz, CH), 4.58 (dt, 1 H, J = 1.1, 16.4 Hz, 5-H), 4.63 (dt, 1 H, J = 1.1, 16.4 Hz, 5-H), 5.02 (t, 1 H, J = 1.1 Hz, 3-H). 13C NMR (100 MHz, CDCl3): δ = 14.0 (C-8′), 19.0 (C-1′), 22.8 (C-7′), 25.1 (C-4′), 29.0 (C-5′), 31.6 (C-6′), 35.6 (C-3′), 68.1 (C-5), 80.5 (C-2′), 88.3 (C-3), 174.0 (C-2), 178.7 (C-4). MS (CI, CH4): m/z = 213 [M + H+]. Anal. Calcd for C12H20O3 (212.3): C, 67.89; H, 9.50; Found: C, 67.79; H, 9.76.
4- tert -Butoxy-5 H -furan-2-one ( 5g): Colourless crystals. Mp 88-90 °C. IR (KBr): ν = 3120, 1740, 1612 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.50 (s, 9 H, CH3), 4.55 (d, 2 H, J = 1.2 Hz, 5-H), 5.09 (t, 1 H, J = 1.2 Hz, 3-H). MS (CI, CH4): m/z = 157 [M + H+]. HRMS: m/z calcd for C8H13O3 [M + H+]: 157.0865. Found: 157.0832.
( RS )-4-Methoxy-5-methyl-5 H -furan-2-one ( 5h): Colourless crystals. Mp 36 °C (Lit.: [18] 30-32 °C). 1H NMR (500 MHz, CDCl3): δ = 1.46 (d, 3 H, J = 6.7 Hz, CH3), 3.89 (s, 3 H, OCH3), 4.83 (dq, 1 H, J = 0.9, 6.7 Hz, 5-H), 5.05 (d, 1 H, J = 0.9 Hz, 3-H). 13C NMR (100 MHz, CDCl3): δ = 17.8 (CH3), 59.5 (CH3O), 75.3 (C-5), 88.0 (C-3), 172.5 (C-2), 183.5 (C-4).
( RS )-4-Benzyloxy-5-methyl-5 H -furan-2-one ( 5i): Colourless crystals. Mp 74 °C (Lit.: [16] 72 °C). IR (KBr): ν = 3121, 2980, 1750, 1621 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.49 (d, 3 H, J = 6.8 Hz, CH3), 4.88 (dq, 1 H, J = 0.9, 6.8 Hz, 5-H), 5.05 (d, 1 H, J = 11.6 Hz, CH2O), 5.08 (d, 1 H, J = 11.6 Hz, CH2O), 5.11 (d, 1 H, J = 0.9 Hz, 3-H), 7.35-7.45 (m, 5 H, Harom). MS (CI, CH4): m/z = 205 [M + H+]. Anal. Calcd for C12H12O3 (204.2): C, 70.58; H, 5.92. Found: C, 70.48; H, 5.82.
( RS )-4-Allyloxy-5-methyl-5 H -furan-2-one ( 5j): Colourless oil. IR(film): ν = 3119, 1755, 1633 cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.48 (d, 3 H, J = 6.8 Hz, CH3), 4.55 (dt, 2 H, J = 1.4, 5.7 Hz, CH2O), 4.85 (q, 1 H, J = 6.8 Hz, 5-H), 5.04 (s br 1 H, 3-H), 5.39 (ddd, 1 H, J = 1.0, 2.2, 10.4 Hz, CH=CH 2), 5.42 (ddd, 1 H, J = 1.1, 2.6, 17.3 Hz, CH=CH 2), 5.97 (ddt, 1 H, J = 5.7, 10.4, 17.3 Hz, CH=CH2). 13C NMR (100 MHz, CDCl3): δ = 17.8 (CH3), 73.1 (CH2O), 75.4 (C-5), 88.8 (C-3), 120.1 (CH=CH2), 130.3 (CH=CH2), 172.5 (C-2), 182.0 (C-4). MS (CI, CH4): m/z = 155 [M + H+]. HRMS: m/z calcd for C8H10O3 (EI): 154.0630. Found: 154.0669.