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DOI: 10.1055/s-2003-45009
Oxone®-KI Induced Lactonization and Etherification of Unsaturated Acids and Alcohols: A Formal Synthesis of Mintlactone
Publication History
Publication Date:
19 December 2003 (online)
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Abstract
Unsaturated acids and alcohols interact with Oxone® and KI in acetonitrile-H2O and undergo iodolactonization and iodoetherification in short times with good yields. The reaction has been used for the formal synthesis of mintlactone starting from isopulegol.
Key words
Oxone® - cyclizations - iodolactonizations - iodoetherifications - mintlactone
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References
General Procedure for the Iolactonization and the Iodoetherification: To a stirred solution of 2 mmol of Oxone® in 5 mL of a 4:1 H2O-CH3CN mixture, 4 mmol of KI were added. After 10 min to the deep purple solution 1 mmol of the alkenoic acid (or the alkenol) in 2 mL of CH3CN was added. The reaction was followed by TLC. After the appropriate time (see Table [1] and Table [2] ) the reaction mixture was diluted with H2O (10 mL), washed with a sat. solution of Na2S2O3 and extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried and evaporated at reduced pressure. All the products resulted pure by 1H and 13C NMR.
1413C NMR (50.1 MHz, CDCl3): δ = 17.8, 41.0, 89.5, 126.0, 129.0, 129.4, 135.6, 173.7.
1513C NMR (50.1 MHz, CDCl3): δ = 9.7, 14.0, 25.7, 41.1, 90.3, 173.8.
1613C NMR (50.1 MHz, CDCl3): δ = 29.3, 32.1, 34.6, 36.0, 36.1, 92.4, 175.9.
17Yellow oil. IR(neat): 1727 cm-1. 1H NMR (200 MHz, CDCl3;): δ = 2.50-1.80 (m, 1 H), 1.80-2.10 (m, 2 H), 2.20 (m, 1 H), 2.30-2.70 (m, 2 H), 3.29 (dd, 1 H, J = 4.5, 10 Hz), 3.42 (dd, 1 H, J = 4.8, 10 Hz), 4.20-4.30 (m, 1 H). 13C NMR (50.1 MHz, CDCl3): δ = 7.5, 18.2, 28.0, 29.2, 78.8, 170.0.
21Oil. 1H NMR (200 MHz, CDCl3): δ = 1.00-1.70 (m, 4 H), 1.70-2.10 (m, 2 H), 3.00-3.70 (m, 4 H), 4.00-4.10 (m, 1 H). 13C NMR (50.1 MHz, CDCl3): δ = 10.1, 23.1, 25.6, 31.7, 68.8, 77.0.
22To a stirred solution of 6-methyl-5-hepten-2-one (Aldrich) (2 mmol) in 21 mL EtOH a solution of 40 mg (1 mmol) of NaBH4 in 2 mL of H2O was added. The reaction was monitored by TLC. At the end 10 mL of acetone were added and the mixture was evaporated at reduced pressure. The crude product was diluted with H2O (20 mL), acidified to pH 4 with a 4% solution of HCl and extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine, dried and evaporated. The residue was purified by column chromatography. Elution with CH2C12-MeOH 5% gave 210 mg (93%) of alcohol 17. Oil. 1H NMR (200 MHz, CDCl3): δ = 1.23 (d, 3 H, J = 6 Hz), 1.40-1.60 (m, 2 H), 1.66 (s, 3 H), 1.73 (s, 3 H), 2.11 (m, 2 H), 3.84 (m, 1 H), 5.17 (m, 1 H). 13C NMR (50.1 MHz, CDCl3): δ = 17.7, 23.4, 24.5, 25.7, 39.1, 67.9, 124.0, 132.4.
23Yellow oil. 1H NMR: δ = 1.10 (d, 3 H, J = 6.0 Hz), 1.30-1.50 (m, 2 H), 1.41 (s, 3 H), 1.50 (s, 3 H), 2.31 (m, 2 H), 3.82 (m, 1 H), 4.12 (dd, 1 H, J = 5.0, 12.0 Hz). 13C NMR: δ = 19.5, 22.2, 3 1.2, 34.5, 37.3, 38.5, 66.3.
273,6-Dimethyl-octahydro-1-benzofuran-3-ol(25). Oil. 1:1 Mixture of diastereoisomers. Yield 80%. 1H NMR: δ = 0.90-2.10 (m, 6 H), 0.97 (d, 3 H, J = 6.5 Hz), 1.25 (s, 3 H), 1.34 (s, 3 H), 3.20 (dd, 1 H, J = 4.0, 10.0 Hz), 3.26 (dd, 1 H, J = 4.0, 10.0 Hz), 3.67 (d, 1 H, J = 9.0 Hz), 3.79 (d, 1 H, J = 10.0 Hz), 3.86 (d, 1 H, J = 10.0 Hz), 3.87 (d, 1 H, J = 9.0 Hz). 13C NMR: δ = 21.4, 22.0, 22.0, 22.7, 22.8, 24.0, 31.0, 31.0, 34.2, 34.3, 40.2, 40.3, 54.8, 56.4, 77.4, 77.8, 81.2, 81.2, 82.3, 82.3.