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Synlett 2004(2): 0368-0370  
DOI: 10.1055/s-2003-45009
LETTER
© Georg Thieme Verlag Stuttgart · New York

Oxone®-KI Induced Lactonization and Etherification of Unsaturated Acids and Alcohols: A Formal Synthesis of Mintlactone

Massimo Curini, Francesco Epifano, M. Carla Marcotullio*, Francesca Montanari
Dipartimento di Chimica e Tecnologia del Farmaco-Sez. Di Chimica Organica, Università degli Studi, via del Liceo 1, 06123 Perugia, Italy
Fax: +39(075)5855116; e-Mail: marcotu@unipg.it;
Further Information

Publication History

Received 11 November 2003
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

    References

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12

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.

14

13C NMR (50.1 MHz, CDCl3): δ = 17.8, 41.0, 89.5, 126.0, 129.0, 129.4, 135.6, 173.7.

15

13C NMR (50.1 MHz, CDCl3): δ = 9.7, 14.0, 25.7, 41.1, 90.3, 173.8.

16

13C NMR (50.1 MHz, CDCl3): δ = 29.3, 32.1, 34.6, 36.0, 36.1, 92.4, 175.9.

17

Yellow 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.

21

Oil. 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.

22

To 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.

23

Yellow 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.

27

3,6-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.