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For general accounts on MCPBA reactions, see:
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1a
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Trost BM.
Fleming I.
Pergamon Press;
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p.357-372
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1b
Paquette L.
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Prilezhaev N.
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For the well-known ‘butterfly’ mechanism of epoxidation see:
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3a
Bartlett PA.
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111
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For some recent reports on the radical hypothesis see:
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3b
Yamabe S.
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8
Typical Experimental Procedure.
To a stirred solution of 1 (1 mmol) in the solvent of choice at r.t. (see Table
[1]
), MCPBA was added in one portion. The reaction was stirred overnight and then diluted with H2O and CH2Cl2 (5 mL). The two phases were separated and the organic layer was dried over Na2SO4 and solvent was removed under reduced pressure. Compounds 2 and 3 were isolated by flash chromatography on silica gel (cyclo-hexane-ethyl acetate, 9:1 as eluent). The characterization of compound 3 is reported in ref. 7d. Commercially available MCPBA was used in the reactions. Purified peracid (according to J. Am. Chem. Soc. 1987, 109, 2770) was less reactive in the epoxidation, due to the lack of acid impurities.
Compound 2a: first diastereomer: R
f
= 0.44 (9:1, cyclo-hexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 1.02 (3 H, t, J = 7.6 Hz), 1.45-1.81 (2 H, m), 2.89 (1 H, dt, J = 1.8, 5.6 Hz), 3.45 (1 H, d, J = 1.8 Hz), 3.93 (1 H, d, J = 15.0 Hz), 4.59 (1 H, s), 4.97 (1 H, d, J = 15.0 Hz), 7.16-7.44 (10 H, m). 13C NMR (75 MHz, CDCl3): δ = 9.4 (CH3), 24.2 (CH2), 44.9 (CH2), 57.3 (CH), 58.9 (CH), 59.5 (CH), 68.8 (quat), 127.8 (CH), 127.9 (CH), 128.1 (CH), 128.4 (CH), 128.7 (CH), 128.9 (CH), 133.8 (quat), 134.0 (quat), 164.5 (CO). LC-ESI-MS (t
R 15.2 min): m/z = 386/388 [M + 1], 408/410 [M + Na]. IR (film): 2962, 2928, 1775, 1494, 1454, 1392, 1351, 1147, 1072 cm-1. Second diastereomer: R
f
= 0.30 (9:1, cyclohexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 1.05 (3 H, t, J = 7.2 Hz), 1.53-1.77 (2 H, m), 3.27 (1 H, d, J = 2.2 Hz), 3.57 (1 H, dt, J = 2.2, 5.6 Hz), 3.91 (1 H, d, J = 15.0 Hz), 4.78 (1 H, s), 4.99 (1 H, d, J = 15.0 Hz), 7.18-7.43 (10 H, m). 13C NMR (75 MHz, CDCl3): δ = 9.6 (CH3), 24.6 (CH2), 44.9 (CH2), 57.6 (CH), 58.7 (CH), 59.4 (CH), 68.4 (quat), 127.7 (CH), 127.9 (CH), 128.2 (CH), 128.4 (CH), 128.7 (CH), 129.0 (CH), 133.7 (quat), 133.9 (quat), 163.4 (CO). LC-ESI-MS (t
R 14.5 min): m/z = 386/388 [M + 1], 408/410 [M + Na]. IR (film): 3073, 2959, 2930, 1771, 1654, 1455, 1395, 1355, 1157, 1077 cm-1.
14 Microwave-assisted reactions have been performed on a Milestone Microsynth Labstation, dual magnetron system with pyramid diffuser, 1600 W power (800X2), maximum delivered power 1000 W, Easywave software. Conditions: 200 W fixed power, 5 min irradiation.
16 Compound 5: R
f
= 0.66 (8:2, cyclohexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 1.03 (3 H, t, J = 7.2 Hz), 1.53-1.74 (2 H, m), 2.87 (1 H, dt, J = 1.5, 5.4 Hz), 3.34 (1 H, dd, J = 1.5, 8.4 Hz), 3.85 (1 H, d, J = 8.4 Hz), 5.25 (2 H, s), 7.38 (5 H, m). 13C NMR (75 MHz, CDCl3): δ = 9.6 (CH3), 24.3 (CH2), 43.9 (CH2), 57.0 (CH), 60.5 (CH), 67.9 (CH), 128.2 (CH), 128.4 (CH), 128.6 (CH), 134.8 (quat), 167.5 (CO). IR (film): 3021, 2968, 1744, 1498, 1456, 1380, 1296, 1257, 1157, 1010 cm-1.
Compound 6: R
f
= 0.57 (8:2, cyclohexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 1.04 (3 H, t, J = 7.4 Hz), 1.91-2.06 (2 H, m), 4.24-4.54 (1 H, m), 5.21 (2 H, s), 6.00 (1 H, d, J = 15.4 Hz), 7.03 (1 H, dd, J = 15.4, 9.2 Hz), 7.25 (5 H, m). 13C NMR (75 MHz, CDCl3): δ = 12.1 (CH3), 31.2 (CH2), 52.9 (CH2), 66.6 (CH), 121.8 (CH), 128.6 (CH), 128.9 (CH), 129.9 (CH), 134.3 (quat), 135.7 (CH), 163.0 (CO). IR (film): 2955, 1867, 1755, 1442, 1252, 1218, 1994 cm-1.
19
Ring-Opening of Epoxide 5.
To a stirred solution of epoxide 5 (1 mmol) in 5 mL of dry CH2Cl2 at -78 °C, TiCl4 (1 mL, solution 1 M in CH2Cl2) was added. The reaction was stirred at this temperature for 3 h and then quenched with H2O. After diluting with CH2Cl2, the two phases were separated, the organic one was dried over Na2SO4 and solvent was removed under reduced pressure. Compound 7 was isolated, by flash chromatography on silica gel (cyclohexane-EtOAc, 8:2 as eluant).
Compound 7: R
f
= 0.52 (8:2, cyclohexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 1.08 (3 H, t, J = 7.5 Hz), 1.68-1.85 (1 H, ddq, J = 7.5, 9.3, 14.4 Hz), 1.95-2.09 (1 H, ddq, J = 7.5, 3.0, 14.4 Hz), 3.25 (1 H, d, J = 7.8 Hz), 4.04 (1 H, ddd, J = 3.0, 9.3, 3.0 Hz), 4.12 (1 H, ddd, J = 3.0, 7.8, 5.4 Hz), 4.65 (1 H, d, J = 5.4 Hz), 5.25 (2 H, s), 7.39 (5 H, m). 13C NMR (75 MHz, CDCl3): δ = 10.7 (CH3), 25.0 (CH2), 43.9 (CH2), 65.0 (CH), 68.0 (CH), 76.0 (CH), 128.2 (CH), 128.3 (CH), 128.7 (CH), 134.6 (quat), 169.0 (CO). IR (film): 3457, 2953, 2919, 1734, 1261, 1013 cm-1
Formation of Epoxide 8.
To a stirred solution of 7 (1 mmol) in 5 mL of dry THF at 0 °C, NaH (1.1 equiv, 26.5 mg) was added. The reaction was stirred at r.t. for 2 h and then quenched by addition of H2O. After removing THF under reduced pressure, the residue was diluted with EtOAc, and washed twice with H2O. The organic layer was separated, dried over Na2SO4 and solvent was removed under reduced pressure. Compound 8 was isolated, by flash chromatography on silica gel (cyclohexane-EtOAc, 9:1 as eluent).
Compound 8: R
f
= 0.54 (8:2, cyclohexane-EtOAc). 1H NMR (300 MHz, CDCl3): δ = 1.10 (3 H, t, J = 8.1 Hz), 1.63-1.96 (2 H, m), 3.39 (1 H, dd, J = 1.5, 4.5 Hz), 3.48 (1 H, d, J& nbsp;= 1.5 Hz), 3.50 (1 H, dt, J = 4.5, 8.1 Hz), 5.26 (2 H, s), 7.39 (5 H, m). 13C NMR (75 MHz, CDCl3): δ = 10.2 (CH3), 28.9 (CH2), 52.8 (CH2), 59.9 (CH), 61.6 (CH), 67.5 (CH), 128.2 (CH), 128.4 (CH), 128.7 (CH), 134.9 (quat), 167.9 (CO). IR (film): 3034, 2963, 1747, 1497, 1455, 1381, 1264, 1190, 1026 cm-1.