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Synlett 2010(12): 1797-1802  
DOI: 10.1055/s-0030-1258121
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Epoxides to α-Mercapto-γ-lactones via Ionic Liquid Promoted Mercaptoacetylative Ring-Opening-Ring-Closing Cascade

Rajesh Patel, Vishnu P. Srivastava, Lal Dhar S. Yadav*
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
Fax: +91(532)2460533; e-Mail: ldsyadav@hotmail.com;
Further Information

Publication History

Received 28 April 2010
Publication Date:
30 June 2010 (online)

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Abstract

Task-specific ionic liquid promoted {[Bmim]OH} one-pot synthesis of α-mercapto-γ-lactones is reported. The present protocol involves regioselective epoxide ring opening and intramolecular translactonisation cascade. A variety of epoxides undergo this ring-opening-ring-closing cascade with 2-methyl-2-phenyl-1,3-­oxathiolan-5-one to afford α-mercapto-γ-lactones diastereoselectively in good to excellent yields. After isolation of the product, the ionic liquid [Bmim]OH could be easily recovered and reused without any loss of efficiency.

Key words

γ-lactones - epoxides - ionic liquids - cascade reactions - translactonization - stereoselective synthesis

15

General Procedure for the Synthesis of α-Mercapto-γ-lactones 4
To a stirred solution of 2-methyl-2-phenyl-1,3-oxathiolan-5-one (2, 1 mmol) in [Bmim]OH-H2O (0.5-1 mL, 4:1), epoxide 1 (1 mmol) was added dropwise and stirred at r.t. for 30 min, then the reaction mixture was stirred at 50 ˚C for 6-15 h (Table  [¹] ). After completion of reaction (monitored by TLC), the reaction mixture was cooled to r.t., diluted with H2O (5 mL), and extracted with EtOAc (3 × 5 mL), dried over anhyd Na2SO4, filtered, and evaporated to dryness.
A mixture of the crude product 4 and acetophenone thus obtained was subjected to silica gel column chromatography using EtOAc-n-hexane as eluent to afford an analytically pure sample of 4 and acetophenone, which was recycled to 2.¹4 After isolation of the product, the remaining aqueous layer containing the ionic liquid was washed with Et2O (2 × 5 mL) to remove any organic impurity, dried under vacuum at 90 ˚C to afford [Bmim]OH, which was used in subsequent runs without further purification.
Physical Data of Representative CompoundsCompound 4a ( cis / trans = 60:40) cis: IR (film): νmax = 2995, 2876, 2554, 1765, 1607, 1583, 1455 cm-¹. ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 2.25 (1 H, m), 2.39 (1 H, ddd, J = 13.2, 6.8, 6.7 Hz), 3.85 (1 H, dd, J = 7.7, 6.7 Hz), 5.28 (1 H, dd, J = 6.9, 6.8 Hz), 7.21-7.32 (m, 5 Harom). ¹³C NMR (100 MHz, CDCl3-TMS): δ = 41.1, 46.2, 80.1, 127.1, 128.8, 129.1, 140.1, 178.4. MS (EI): m/z = 194 [M+]. Anal. Calcd for C10H10O2S: C, 61.83; H, 5.19. Found: C, 62.2; H, 5.02.
trans: IR (film): νmax = 2993, 2876, 2558, 1767, 1609, 1582, 1453 cm-¹. ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 2.20 (1 H, m), 2.46 (1 H, ddd, J = 13.2, 6.8, 6.9 Hz), 3.88 (1 H, dd, J = 7.4, 6.9 Hz), 5.05 (1 H, dd, J = 10.3, 6.8 Hz), 7.23-7.36 (m, 5Harom).
Compound 4c ( cis / trans = 67:33)
cis: IR (film): νmax = 2998, 2875, 2554, 1768, 1605, 1585, 1456 cm-¹. ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 2.25 (1 H, m), 2.39 (1 H, ddd, J = 13.2, 6.8, 6.7 Hz), 3.83 (1 H, dd, J = 7.7, 6.7 Hz), 5.29 (1 H, dd, J = 6.9, 6.8 Hz), 7.21-7.34 (m, 2 Harom,), 7.58-7.61 (m, 2 Harom). ¹³C NMR (100 MHz, CDCl3-TMS): δ = 41.6, 46.9, 81.1, 129.6, 130.2, 132.3, 143.5, 178.5. MS (EI): m/z = 228 [M+], 230 [M + 2+]. Anal. Calcd for C10H9ClO2S: C, 52.52; H, 3.97. Found: C, 52.15; H, 4.29.
trans: IR (film): νmax = 3001, 2876, 2552, 1770, 1609, 1580, 1457 cm-¹. ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 2.20 (1 H, m), 2.46 (1 H, ddd, J = 13.2, 6.8, 6.9 Hz), 3.86 (1 H, dd, J = 7.4, 6.9 Hz), 5.07 (1 H, dd, J = 10.3, 6.8 Hz), 7.23-7.36 (m, 2 Harom), 7.57-7.62 (m, 2 Harom).

16

Isolation of 3a and 3c and their Conversion into the Corresponding α-Mercapto-γ-lactones 4a and 4c
The procedure followed was the same as described above for the synthesis of 4 except that the stirring time in this case was only 25-30 min at r.t. Purified by silica gel chromatography using EtOAc-n-hexane as eluent to afford an analytically pure sample of 3a and 3c. Finally, the intermediate alcohols 3a and 3c (1 mmol) were quantitatively converted into the corresponding γ-lactones 4a and 4b by stirring at 50 ˚C in [Bmim]OH-H2O (4:1) for 6.5 h.
Physical Data of Intermediate Alcohols 3a and 3cCompound 3a (Diastereomeric Mixture = 60:40)
Major: IR (film): νmax = 3435, 2965, 2878, 1775, 1605, 1581, 1456 cm-¹. ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 1.18 (3 H, s), 2.13-2.17 (2 H, m), 3.99 (1 H, dd, J = 12.0, 7.8 Hz), 4.91 (1 H, dd, J = 7.6, 5.7 Hz), 7.21-7.36 (m, 10Harom). ¹³C NMR (100 MHz; CDCl3-TMS): δ = 20.8, 37.2, 44.7, 77.2, 98.7, 127.1, 127.8, 128.4, 128.8, 129.1, 129.5, 139.8, 141.1, 177.2. MS (EI): m/z = 314 [M+]. Anal. Calcd for C18H18O3S: C, 68.76; H, 5.77. Found: C, 68.98; H, 5.40.
Minor: ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 1.19 (3 H, s), 2.15-2.20 (2 H, m), 3.89 (1 H, t, J = 2.2 Hz), 4.98 (1 H, dd, J = 7.8, 5.7 Hz), 7.21-7.34 (m, 10 Harom).
Compound 3c (Diasteriomeric Mixture = 67:33)
Major: IR (film): νmax = 3440, 2985, 2876, 1772, 1607, 1584, 1457 cm-¹. ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 1.21 (3 H, s), 2.16-2.20 (2 H, m), 3.92 (1 H, dd, J = 12.1, 7.8 Hz), 4.95 (1 H, dd, J = 7.5, 5.7 Hz), 7.21-7.52 (m, 7 Harom), 7.70-7.90 (m, 2 Harom). ¹³C NMR (100 MHz, CDCl3-TMS): δ = 21.7, 37.4, 44.9, 77.3, 98.6, 127.7, 128.9, 129.2, 129.8, 130.1, 132.2, 139.7, 142.5, 177.3. MS (EI): m/z = 348 [M+], 350 [M + 2+]. Anal. Calcd for C18H17ClO3S: C, 61.97; H, 4.91. Found: C, 62.20; H, 5.28.
Minor: ¹H NMR (400 MHz, CDCl3-D2O-TMS): δ = 1.19 (3 H, s), 2.17-2.22 (2 H, m), 3.89 (1 H, t, J = 2.3 Hz), 4.98 (1 H, dd, J = 7.8, 5.6 Hz), 7.22-7.54 (m, 7 Harom), 7.72 (m, 2 Harom).