1198
N. Horasan Kishali et al. / Tetrahedron 67 (2011) 1193e1200
(1H, dm, B-part of AB-system, J¼9.9 Hz,]CH), 5.10e5.14 (1H, m,
AcOCH), 4.15 (1H, dt, A-part of AB-system, J¼11.1, 6.5 Hz,
AcOCHH),4.12 (1H, dt, B-part of AB-system, J¼11.1, 6.6 Hz, AcOCHH),
2.39e2.10 (3H, m, CHCH2CH2), 2.05 (3H, s, Me), 2.03 (3H, s, Me),
2.05e1.51 (4H, m, CH2CH]CHCH2). 13C NMR(100 MHz, CDCI3, ppm)
s, CH3), 2.04 (3H, s, CH3), 1.88 (1H, dt, J¼13.9 and 6.5 Hz,
CHCHaHbCH), 1.82e1.71 (2H, m, CH2), 1.59 (1H, ddt, J¼13.9, 7.1, and
6.5 Hz, CHCHaHbCH). 13C NMR (100 MHz, CDCI3)
d 171.2 (OC]O),
170.7 (OC]O), 133.1 (CH]CH), 127.5 (CH]CH), 67.9 (AcOCH), 63.3
(AcOCH2), 62.4 (HOCH), 32.6 (CH2), 29.8 (CH2), 29.5 (CH2), 20.9 (2C,
CH3). IR (KBr, cmꢃ1) 3391, 3037, 29.41, 2255, 1736, 1439, 1374, 1247,
1027, 977. Anal. Calcd for C12H18O5: C, 59.49; H, 7.49. Found: C,
59.23; H, 7.39.
d
170.5, 170.3, 125.3, 122.7, 69.9, 61.9, 32.6, 29.6, 29.5, 27.1, 20.7, 20.4.
IR (KBr, cmꢃ1) 3029, 2933, 2856, 1739, 1443, 1374, 1247, 1042, 992,
846, 674, 673. Anal. Calcd for. C12H18O4: C, 63.70; H, 8.02. Found: C,
63.70; H, 8.24.
4.8. rel-(1S,4S,5S)-4-(Acetyloxy)-5-[2-(acetyloxy)ethyl]cyclo-
4.6. Photo-oxygenation of diacetate 13b
hex-2-en-1-yl acetate (17)
A stirred solution of diacetate 13b (1.0 g, 4.4 mmol) in CH2Cl2
(150 mL) was added tetraphenylporphyrin (TPP, 50 mg). The
resulting mixture was irradiated with a projection lamp (500 W)
for 36 h at room temperature while oxygen was passed through the
solution. Removal of the solvent (30 ꢀC, 20 mmHg) and 1H NMR
spectroscopic analysis of the oily residue revealed that the con-
version was approximately 95% and two products 14 and 15 were
formed in a ratio of 5.1:1. Chromatography of the residue on silica
gel (100 g) eluting with hexane/ethylacetate (70:30) gave as the
first fraction rel-(1S,6R)-6-[2-(acetyloxy)ethyl]-4-oxocyclohex-2-en-
1-yl acetate (15): pale yellow liquid, (142 mg, 14.2%). 1H NMR
To a magnetically stirred solution of alcohol 16 (500 mg,
2.06 mmol) in CH2Cl2 (25 mL) was added acetyl chloride (400 mg,
5.1 mmol). The reaction mixture was stirred at room temperature for
6 h and then cooled to 0 ꢀC. After addition of water (100 mL), the
water phase was extracted with ether (3ꢂ30 mL). The combined
organic extracts was washed with NaHCO3 solution (2ꢂ10 mL) and
water (2ꢂ5 mL), and then dried over Na2SO4. Removal of the solvent
under reduced pressure gave triacetate 17 (550 mg, 94%) as a color-
less liquid. 1H NMR (400 MHz, CDCI3, ppm):
d 6.10 (1H, dd, A-part of
AB-system, J¼9.9, 4.9 Hz, HC]CH), 6.00 (1H, dd, B-part of AB-sys-
tem, J¼9.9, 4.6 Hz, HC]CH), 5.30e5.27 (1H, m, OCH), 5.22 (1H, t,
J¼4.3 Hz, OCH), 4.16 (1H, dt, A-part of AB-system, J¼11.1 and 6.8 Hz,
OCHaHb), 4.13 (1H, dt, B-part of AB-system, J¼11.1 and 6.5 Hz,
OCHaHb), 2.19e2.13 (1H, m, CH2CHCH2), 2.06 (3H, s, CH3), 2.05 (3H, s,
CH3), 2.04 (3H, s, CH3), 1.95e1.88 (1H, m, CHaHb), 1.84e1.75 (2H, m,
CHaHb and CHaHb), 1.62 (1H, dq J¼11.9 and 5.2 Hz, CHaHb). 13C NMR
(400 MHz, CDCI3, ppm)
d 6.91 (1H, dd, A-part of AB-system,
J¼10.0 Hz, 4.7 Hz, CH]CHCH), 6.02 (1H, d, B-part of AB-system,
J¼10.0 Hz, CH]CHCH), 5.42 (1H, t, J¼3.9 Hz, CHOAc), 4.13e4.03
(2H, m, CH2OAc), 2.57 (1H, dd, A-part of AB-system, J¼16.8, 10.9 Hz,
O]CCHaHb), 2.53e2.35 (3H, m, O]CCHaHb and CH) 2.12 (3H, s,
Me), 2.04 (3H, s, Me), 1.96 (1H, dq, J¼14.4, 6.6 Hz, OCH2CHaHb), 1.48
(1H, dq, J¼14.4 and 6.4 Hz, OCH2CHaHb). 13C NMR (100 MHz, CDCI3)
(100 MHz, CDCI3)
d 171.0 (OC]O), 170.5 (OC]O), 170.5 (OC]O),
129.8 (CH]CH), 129.2 (CH]CH), 67.3 (OCH), 66.1 (OCH), 62.3
(OCH2), 30.5, 29.5, 29.4, 21.1 (CH3), 20.9 (CH3), 20.9 (CH3). IR (KBr,
cmꢃ1): 3029, 2952,1739,1447,1374,1247,1027, 985, 919. Anal. Calcd
for C14H20O6: C, 59.14; H, 7.09. Found: C, 59.19; H, 7.34.
d
197.6 (C]O), 170.7 (OCO), 170.1 (OC]O), 144.1 (CH]CHCH), 131.6
(CH]CHCH), 67.4 (OCH), 61.6 (OCH2), 39.4 (CH2), 35.1 (CH2), 29.1
(CH2), 20.7 (CH3), 20.6 (CH3). ATR (cmꢃ1) 2958, 1733, 1684, 1369,
1213, 1023, 963, 892. Anal. Calcd for C12H16O5: C, 59.99; H, 6.71.
Found: C, 59.73; H, 6.95.
4.9. Epoxidation of 16 with m-CPBA
As the second fraction, the major product rel-(1S,6S)-6-[2-
(acetyloxy)ethyl]-4-hydroperoxycyclohex-2-en-1-yl acetate (14) was
isolated as viscous liquid (776 mg, 72%). 1H NMR (400 MHz, CDCI3)
To a stirred solution of 16 (200 mg, 0.83 mmol) in CH2Cl2 (8 mL)
was added m-CPBA 60% (310 mg, 1.66 mmol). The reaction mixture
was stirred overnight, the solid matter was removed by filtration,
and the filtrate was washed with saturated NaHCO3 (2ꢂ50 mL), and
water (50 mL), and dried over MgSO4. Removal of the solvent under
reduced pressure gave epoxide 22 (148 mg, 69%, yellow liquid). 1H
d
8.89 (1H, br s, eOOH), 6.13 (1H, dd, A-part of AB-system, J¼9.9,
5.2 Hz, CH]CH), 5.99 (1H, dd, B-part of AB-system, J¼9.9, 4.7 Hz,
CH]CH), 5.15 (1H, t, J¼4.3 Hz, AcOCH), 4.55e4.51 (2H, m,
eCH2OAc), 4.0 (1H, dt, J¼11.3, 5.2 Hz, HOOCH), 2.27 (1H, bd,
J¼14.3 Hz, CH), 2.08 (3H, s, CH3), 2.05 (3H, s, CH3), 2.0e2.08 (1H,
CHaHb), 1.79 (1H, ddt, A-part of AB-system, J¼14.5, 9.2 and 4.5 Hz,
CHaHb), 1.66 (1H, ddd, J¼14.4, 12.8 and 3.9 Hz, CHCHaHb), 1.57 (1H,
ddt, J¼14.4, 9.4, and 4.8 Hz, CHCHaHb). 13C NMR (100 MHz, CDCI3)
NMR (400 MHz, CDCI3)
d 5.34 (1H, br s, AcOCH), 4.2 (br s, 1H),
4.16e4.05 (4H, m, OH, HOCH, and OCH2), 3.45e3.38 (2H, m, epox-
ide), 2.17 (3H, s, CH3), 2.04 (3H, s, CH3), 2.08e2.02 (5H, m, CH, and
2CH2). 13C NMR (100 MHz, CDCI3) 171.0 (OC]O), 170.3 (OC]O),
68.9 (AcOCH), 63.1 (OCH2), 62.0 (HOCH), 54.7 (epoxide), 54.2 (OCH),
31.5, 30.9, 26.6, 20.9 (CH3), 20.8 (CH3). IR (KBr, cmꢃ1) 3469, 2938,
1734, 1438,1359, 1250,1047; HRMS (CI, Na): MNaþ, found 265.1059.
C12H18NaO5 requires 265.1052.
d
172.1 (OC]O), 170.6 (OC]O), 131.6 (CH]CH), 127.9 (CH]CH),
77.0 (HOOCH), 68.1 (OCH), 61.6 (OCH2), 30.4 (CH2) 29.2 (CH2), 26.0
(CH2), 21.0 (CH3), 20.09 (CH3). IR (KBr, cmꢃ1) 3403, 3029, 2960,
2933, 1736, 1439, 1381, 1254, 1035, 985, 765. Anal. Calcd for
C12H18O6: C, 55.81; H, 7.02. Found: C, 55.71; H, 7.08.
4.10. Epoxidation of 17 with dimethyldioxirane (DMD)
4.7. rel-(1S,4S,6S)-6-[2-(Acetyloxy)ethyl]-4-hydroxycyclohex-
2-en-1-yl acetate (16)
Dimethyldioxirane was prepared from acetone using potassium
monoperoxysulfate as described by Adam et al.29 To a magnetically
stirred solution of DMD (1.05 mmol, 0.07 M) in acetone (100 mL)
was added triacetate 17 (300 mg, 1.06 mmol) and stirred for 2 h at
ꢃ5 ꢀC then for 2 h at room temperature. Evaporation of the solvent
afforded a mixture of epoxides 19 and 20 in a ratio of 3:2. Purifi-
cation of the residue on neutral Al2O3 (50 g) eluting with ethyl
acetate/n-hexane (1:9) gave an epoxide mixture (231 mg, 73%) in
A solution of hydroperoxide 14 (500 mg, 1.94 mmol) in CH2Cl2
(25 mL) was added to magnetically stirred solution of Me2S
(309 mg, 5 mmol) in CH2Cl2 (25 mL) at room temperature. After the
addition was complete (ca. 10 min), the mixture was stirred for 6 h
and water (25 mL) was added. The organic phase was separated and
dried over Na2SO4. Evaporation of solvent in vacuo and gave pure
16 (460 mg, 98%) as pale yellow liquid. 1H NMR (400 MHz, CDCI3)
a
ratio of 2:1. 5-(Acetyloxy)-3-[2-(acetyloxy)ethyl]-7-oxabicyclo
d
6.02 (1H, dd, A-part of AB-system, J¼9.9, 4.2 Hz, CH]CH), 5.96
[4.1.0]hept-2-yl acetate (19/20).1H NMR (400 MHz, CDCI3)
d
5.33
(1H, dd, B-part of AB-system, J¼9.9, 4.6 Hz, CH]CH), 5.18 (1H, t,
J¼4.2 Hz, AcOCH), 4.25 (1H, q, J¼3.9 Hz, OCH), 4.17e4.11 (2H, m,
OCH2), 2.58 (1H, br s, eOH), 2.25e2.17 (1H, m, CH2CHCH2), 2.05 (3H,
(2H, br t, J¼3.2 Hz, AcOCH), 5.23e5.12 (1H, m, AcOCH), 5.10e5.05
(1H, m, AcOCH), 4.18e4.00 (2H, t, OCH2), 3.54 (1H, dd, J¼3.9 and
3.5 Hz, epoxide), 3.47 (1H, t, J¼3.8 Hz, epoxide), 3.3 (1H, dd, J¼3.5