A. F. Barrero, M. M. Herrador, P. Arteaga, J. V. Catalán
less syrup. [α]D = +44.9 (c = 1.0, CH Cl ). IR (film): ν = 3431,
3078, 2928, 2866, 2843, 1645, 1441, 1409, 1378, 1264, 1101, 1058,
886 cm–1. HRMS (FAB): calcd. for C15H24O2Na [M + Na]+
259.1674; found 259.1673.
FULL PAPER
CH2Cl2 (1.5 mL) was then added, and the mixture was further
stirred at room temperature for 20 min. Aqueous 5% NaHSO3
(5 mL) was added, and the mixture was stirred for 10 min. It was
then diluted with CH2Cl2 (50 mL), and the organic layer was
washed with water and brine, dried with anhydrous Na2SO4, fil-
tered and concentrated in vacuo to yield a mixture of 7 and 9 (95%)
in a 1:8.5 ratio.
˜
2
2
1
Compound 11: H NMR (500 MHz, CDCl3, 25 °C): δ = 0.69 (s, 3
H, 14-H), 1.16 (q, J = 12.4 Hz, 1 H, 6β-H), 1.18–1.66 (m, 10 H, 2
1-H, 2 2-H, 6α-H, 7α-H, 2 8-H, 2 9-H), 1.70 (br. s, 1 H, OH), 1.76
(br. d, J = 12.2 Hz, 1 H, 5α-H), 1.98 (br. dt, J = 6.8, 12.4 Hz, 1 H,
3α-H), 2.30 (br. d, J = 12.4 Hz, 1 H, 3β-H), 2.71 (d, J = 4.7 Hz, 1
H, 13a-H), 2.89 (d, J = 4.7 Hz, 1 H, 13b-H), 3.71 (dd, J = 8.9,
12.2 Hz, 1 H, 12a-H), 3.85 (dd, J = 2.2, 12.2 Hz, 1 H, 12b-H), 4.40
(s, 1 H, 15a-H), 4.70 (s, 1 H, 15b-H) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 16.4 (CH3, C-14), 23.6 (CH2, C-2), 23.9 (CH2,
C-8), 25.6 (CH2, C-6), 36.3 (C, C-10), 37.0 (CH2, C-3), 40.7 (CH,
C-7), 40.8 (CH2, C-1)*, 42.0 (CH2, C-9)*, 49.0 (CH2, C-12), 49.7
(CH, C-5), 61.3 (CH2, C-13), 62.4 (C, C-11), 105.8 (CH2, C-15),
150.7 (C, C-4) ppm (signals denoted with an * are exchangeable).
Method D: This method is similar to method C, but the reaction
was carried out at 0 °C for 10 min to yield a mixture of 7 and 9
(90%) in a 1:2.3 ratio.
Method E: p-Toluenesulfonic acid (10 mg) was added to a stirred
solution of 6 (120 mg, 0.45 mmol) in benzene (8 mL) at 80 °C, and
the mixture was kept at reflux for 5 min. It was then diluted with
tert-butyl methyl ether (50 mL) and washed with aqueous NaHCO3
solution. The organic layer was washed with brine, dried with anhy-
drous Na2SO4, filtered and concentrated in vacuo to yield a mix-
ture of 7, 8 and 9 (93%) in a 1:2.3:2.8 ratio.
1
Method F: This method is similar to method E, but the reaction
was carried out at room temperature for 16 h to yield a mixture of
7, 8 and 9 (15%) in a 2.3:1:1.6 ratio and 6 (73%).
Compound 12: Distinct signals only: H NMR (500 MHz, CDCl3,
25 °C): δ = 2.72 (d, J = 4.7 Hz, 1 H, 13a-H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 22.9 (CH2, C-8), 26.6 (CH2, C-6), 48.9
(CH2, C-12), 61.4 (CH2, C-13), 105.7 (CH2, C-15) ppm.
Method G: Iodine (109 mg) was added to a stirred solution of 6
(114 mg, 0.43 mmol) in benzene (8 mL), and the mixture was kept
at room temperature for 5 h. Aqueous 5% NaHSO3 (5 mL) was
added, and the mixture was stirred for 10 min. It was then diluted
with tert-butyl methyl ether (50 mL), and the organic layer was
washed with water and brine, dried with anhydrous Na2SO4, fil-
tered and concentrated in vacuo to yield only 9 (81%).
Preparation of Kudtdiol (4) and 11-epi-Kudtdiol (15) by Reduction
of the 11+12 Mixture with LiEt3BH: LiEt3BH (1 in THF,
0.66 mL) was added to a cold (0 °C) solution of the mixture 11+12
(78 mg, 0.33 mmol) in dry THF (1 mL) under an argon atmo-
sphere. After 2.5 h, the mixture was hydrolyzed by the addition of
water (0.1 mL), 6 NaOH (0.1 mL) and water (0.3 mL), success-
ively. The mixture was then stirred at room temperature for 10 min
and filtered through a layer of silica gel/anhydrous Na2SO4 (2:1),
and the layer was then washed with tert-butyl methyl ether. The
organic layer was concentrated in vacuo to yield a crude product
that was purified by column chromatography over silica gel (hex-
ane/tert-butyl methyl ether, 95:5) to obtain a mixture of 4[16] and
13 in a 1:1 ratio (77 mg, 98%).
Method H: Thionyl chloride (0.90 mL) was added to a cold
(–40 °C) solution of 6 (106 mg, 0.40 mmol) in dry pyridine (8 mL),
and the mixture was kept at that temperature with stirring for
20 min. It was then poured into ice and extracted with tert-butyl
methyl ether (3ϫ100 mL). The organic layer was washed with 2
HCl (3ϫ100 mL), aqueous NaHCO3 solution (3ϫ100 mL) and
brine, dried with anhydrous Na2SO4, filtered and concentrated in
vacuo to yield a mixture of 7, 8 and 9 (95%) in a 2:1:1 ratio.
Kudtdiol (4) and 11-epi-Kudtdiol (13): Colourless syrup. [α]D
=
Preparation of β-Costol (9) by the Reduction of 7 with DIBAL: DI-
BAL (1 in hexane, 0.65 mL, 2.4 equiv.) was added to a cold
(–20 °C) solution of 7 (67 mg, 0.27 mmol) in dry toluene (5 mL)
under an argon atmosphere with stirring. After 15 min, water
(2 mL) was added to the mixture, and it was stirred at room tem-
perature for 20 min. The mixture was filtered through a layer of
silica gel/anhydrous Na2SO4 (2:1), and the layer was washed with
tert-butyl methyl ether. The organic layer was concentrated in
vacuo to yield a crude product that was purified by column
chromatography over silica gel (hexane/tert-butyl methyl ether,
80:20) to obtain 10[24] (57 mg, 96%).
+45.1 (c = 1.0, CH Cl ). IR (film): ν = 3425, 3079, 2964, 2934,
˜
2
2
2906, 2844, 1646, 1461, 1380, 1364, 1284, 1261, 1215, 1187, 1120,
1088, 1030, 1009, 886 cm–1. HRMS (FAB): calcd. for C15H26O2Na
[M + Na]+ 261.1830; found 261.1832.
11-epi-Kudtdiol (13): 1H NMR (500 MHz, CDCl3, 25 °C): δ = 0.70
(s, 3 H, 14-H), 0.77–0.99 (m, 3 H, 1β-H, 8a-H, 9a-H), 1.09 (q, J =
12.3 Hz, 1 H, 6β-H), 1.19–1.32 (m, 3 H, 1α-H, 2 2-H), 1.31 (s, 3
H, 13-H), 1.43–1.63 (m, 6 H, 6α-H, 7α-H, 8b-H, 9b-H, 2 OH), 1.76
(br. d, J = 12.3 Hz, 1 H, 5α-H), 1.99 (br. dt, J = 8.0, 11.8 Hz, 1 H,
3α-H), 2.31 (br. d, J = 12.6 Hz, 1 H, 3β-H), 3.77 (d, J = 9.0 Hz, 1
H, 12a-H), 4.04 (d, J = 9.0 Hz, 1 H, 12b-H), 4.40 (d, J = 1.1 Hz,
1 H, 15a-H), 4.70 (d, J = 1.1 Hz, 1 H, 15b-H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 16.5 (CH3, C-14), 22.0 (CH2, C-8),
23.7 (CH2, C-2), 24.7 (CH2, C-6), 24.8 (CH3, C-13), 36.2 (C, C-
10), 37.1 (CH2, C-3), 40.9 (CH, C-1)*, 42.0 (CH2, C-9)*, 47.6 (CH,
C-7), 49.7 (CH, C-5), 74.6 (CH2, C-12), 83.9 (C, C-11), 105.6 (CH2,
C-15), 151.0 (C, C-4) ppm (signals denoted with an * are exchange-
able).
Preparation of Epoxides 11 and 12 by the Epoxidation of 10 with
VO(acac)2/tBuOOH: VO(acac)2 (4.4 mg) was added to a solution
of 10 (121 mg, 0.55 mmol) in benzene (18 mL) under an argon at-
mosphere, and the mixture was heated at reflux for 10 min. tert-
Butyl hydroperoxide (5.0–6.0 in decane, 0.15 mL) was then
added, and the mixture was kept at reflux whilst stirring for 30 min.
After cooling to room temperature, the mixture was diluted with
EtOAc (40 mL) and washed with aqueous NaHCO3 solution and
brine, dried with anhydrous Na2SO4, filtered and concentrated in
vacuo to yield a crude product that was purified by column
chromatography over silica gel (hexane/tert-butyl methyl ether,
80:20) to obtain a mixture of epimers 11 and 12 it a 1:1 ratio
(120 mg, 92%).
Sharpless Asymmetric Epoxidation of 10: A mixture of powdered,
activated 4 Å molecular sieves (120 mg) and dry CH2Cl2 (2 mL)
was cooled to –20 °C. To this mixture was added titanium(IV) isop-
ropoxide (12 µL) and then -(–)-diethyl tartrate (8 µL) under an
argon atmosphere with vigorous stirring. The resulting mixture was
stirred for a further 15 min at –20 °C. At this point, a solution of
9 (80 mg) in dry CH2Cl2 (2 mL) was then added dropwise. After
(5S,7R,10R,11R)-11,13-Epoxyeudesm-4(15)-en-12-ol
(11)
and
(5S,7R,10R,11S)-11,13-Epoxyeudesm-4(15)-en-12-ol (12): Colour-
3592
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3589–3594