Q. Zang, S. Gulab, B. L. Stocker, S. Baars, J. O. Hoberg
FULL PAPER
extracted with CH2Cl2 (3ϫ), and dried with MgSO4. Flash
chromatography (EtOAc/cyclohexane, 1:10) gave 17 (580 mg, 73%)
as a colorless oil. 1H NMR (CDCl3): δ = 7.24 (m, 5 H, Ph-H), 4.46
(s, 2 H, CH2Ph), 4.12 (s, 2 H, 4-H), 4.00 (q, J = 7.4 Hz, 2 H,
OCH2Me), 1.29 (s, 6 H, 2 Me), 1.09 (t, J = 7.4 Hz, 3 H, OCH2Me)
ppm. 13C NMR (CDCl3): δ = 205.5 (C-3), 172.9 (C-1), 136.9 (Ph),
128.3 (Ph), 127.9 (Ph), 127.5 (Ph), 73.1 (-OCH2Ph), 72.7 (C-4), 61.0
(10 mL). The mixture was stirred for 15 min before enol silane 4
(288 mg, 0.75 mmol) was added at the same temperature. The solu-
tion was warmed to –20 °C slowly and stirred overnight at that
temperature. The reaction was quenched by the addition of sat.
NH4Cl. The phases were separated, and the aqueous phase was
extracted with CH2Cl2 (3ϫ). The organic phases were combined,
washed with brine, and dried with anhydrous Na2SO4. After fil-
(OCH2Me), 53.2 (C-2), 21.6 (2 Me), 13.8 (OCH2Me) ppm. IR tration and concentration, the resulting oil was purified by flash
(neat): ν = 2930, 2339, 1786, 1722, 1505, 1275 cm–1.
chromatography (EtOAc/cyclohexane, 1:10) to yield 25 (418 mg,
76%) as a single isomer. 1H NMR (CDCl3): δ = (4-H and 6-H not
rigorously assigned): δ = 7.33–7.26 (m, 10 H, Ph), 4.54 (d, J =
11.3 Hz, 1 H, CH2Ph), 4.48 (s, 2 H, CH2Ph), 4.44 (d, J = 5.3 Hz,
1 H, 4-H), 4.46–4.36 (m, 1 H, 5-H), 4.41 (d, J = 11.3 Hz, 1 H,
CH2Ph), 4.31–4.25 (m, 1 H, 9-H), 3.79 (dd, J = 10.8, 4.3 Hz, 1 H,
11-H), 3.72 (dd, J = 10.8, 5.3 Hz, 1 H, 11-H), 3.65 (ddd, J = 8,3,
5.0, 4.3 Hz, 1 H, 10-H), 3.57 (d, J = 8.8 Hz, 1 H, 1-H), 3.51 (d, J
= 8.8 Hz, 1 H, 1-H), 3.35 (d, J = 5.3 Hz, 1 H, 5-H), 2.92–2.64 (m,
4 H, S-CH2-CH2-CH2-S), 2.42 (dd, J = 15.6, 8.3 Hz, 1 H, 6-H),
2.41 (dd, J = 15.4, 8.1 Hz, 1 H, 4-H), 2.28 (dd, J = 15.6, 8.6 Hz, 1
H, 6-H), 2.14 (dd, J = 15.4, 8.8 Hz, 1 H, 4-H), 1.96–1.86 (m, 2 H,
S-CH2-CH2-CH2-S), 1.38 (s, 3 H, CH3), 1.34 (s, 3 H, CH3), 1.29
(s, 3 H, CH3), 1.20 (s, 3 H, CH3), 0.90 [s, 9 H, SiC(CH3)3], 0.08 (s,
3 H, SiCH3), 0.07 (s, 3 H, SiCH3) ppm. 13C NMR (CDCl3): δ =
214.1, 137.8, 137.8, 128.2, 128.1, 127.6, 127.5, 127.5, 127.5, 109.0,
83.1, 81.0, 77.7, 75.4, 73.3, 71.7, 69.4, 63.2, 51.6, 48.5, 43.2, 41.2,
27.2, 26.9, 26.8, 26.3, 25.9, 25.8, 24.6, 22.1, 22.0, 18.3, –5.4,
˜
2-(2-{[(4R,5R)-5-{[(tert-Butyldimethylsilyl)oxy]methyl}-2,2-dimeth-
yl-1,3-dioxolan-4-yl]methyl}-1,3-dithian-2-yl)ethanol (9): To a solu-
tion of 2-bromoethanol (84 μL, 1.19 mmol) in THF/HMPA (10:1,
3.3 mL) at –15 °C was added tBuLi (700 μL, 1.19 mmol), and the
reaction mixture was stirred for 1 h at –15 °C. In a separate flask,
dithiane 8 (300 mg, 0.79 mmol) in THF/HMPA (10:1, 2.2 mL) was
cooled to –78 °C and tBuLi (465 μL, 0.79 mmol) was added to the
solution, and then stirred for 30 min at –78 °C. The initial mixture
was cannulated into the dithiane mixture at –78 °C, stirred for 2 h
at –78 °C, and then slowly warmed to room temperature. The reac-
tion was quenched by the addition of sat. NH4Cl. The phases were
separated, and the aqueous phase was extracted with CH2Cl2 (3ϫ).
The organic phases were combined, washed with sat. NaHCO3 and
brine, and dried with anhydrous Na2SO4. After filtration and con-
centration, the resulting oil was purified by flash chromatography
(EtOAc/cyclohexane, 1:3) to give 9 (280 mg, 83%) as a colorless
1
oil. H NMR (CDCl3): δ = 4.30 (ddd, J = 9.3, 8.3, 1.3 Hz, 1 H, 5-
–5.4 ppm. IR (neat): ν = 3440, 2930, 2850, 1710, 1460, 1370, 1250,
˜
H), 3.95–3.85 (m, 2 H, 1-H), 3.84 (dd, J = 10.6, 3.8 Hz, 1 H, 7-H),
3.75 (dd, J = 10.6, 5.5 Hz, 1 H, 7-H), 3.70 (ddd, J = 8.3, 5.5, 3.8 Hz,
1 H, 6-H), 2.83–2.68 (m, 4 H, S-CH2-CH2-CH2-S), 2.49 (d, J =
15.4 Hz, 1 H, 2-H), 2.41–2.23 (m, 3 H, 2-H, 6), 2.00–1.95 (m, 2 H,
S-CH2-CH2-CH2-S), 1.41 (s, 3 H, CH3), 1.38 (s, 3 H, CH3), 0.92 [s,
9 H, SiC(CH3)3], 0.10 [s, 6 H, Si(CH3)2] ppm. 13C NMR (CDCl3):
δ = 109.1, 80.8, 75.7, 63.2, 59.1, 51.3, 41.6, 40.8, 27.1, 26.9, 26.8,
1090, 840, 780, 740, 690 cm–1. MS: calcd. for C39H60O7S2Si [M +
H] 733.3629; found 733.3618.
(4R,5R,9R,10R)-1,4-Bis(benzyloxy)-11-(tert-butyldimethylsilyloxy)-
9,10-(2,2-dimethyl-1,3-dioxolane)-5-methoxy-2,2-dimethylundecan-
3,7-dione (26a): A solution of 25 (20 mg, 0.027 mmol) in CH2Cl2
was added to a mixture of Me3OBF4 (32 mg, 0.22 mmol) and 1,8-
bis(dimethylaminonaphthalene) (Proton Sponge, 47 mg,
0.22 mmol) in CH2Cl2 at room temperature. The mixture was
stirred for 2 h, and then the solvent was removed under reduced
pressure. Flash chromatography (EtOAc/cyclohexane, 1:10) gave
26.1, 25.9, 25.8, 25.0, 18.3, –5.4, –5.5 ppm. IR (neat): ν = 3450,
˜
2950, 2920, 2850, 1470, 1380, 1250, 1090, 840, 780 cm–1. MS: calcd.
for C19H38O4S2Si [M + H] 423.2060; found 423.2054.
1
2-(2-{[(4R,5R)-5-{[(tert-Butyldimethylsilyl)oxy]methyl}-2,2-dimeth-
yl-1,3-dioxolan-4-yl]methyl}-1,3-dithian-2-yl)acetaldehyde (3): To a
solution of oxalyl chloride (60 μL, 0.71 mmol) in CH2Cl2 (3 mL)
was added DMSO (102 μL, 1.42 mmol) at –78 °C. After 5 min, a
solution of alcohol 9 (150 mg, 0.35 mmol) in CH2Cl2 (3 mL) was
added, and the reaction mixture was stirred at –78 °C for 15 min.
Triethylamine was added, and the mixture was stirred for an ad-
ditional 15 min, then the reaction mixture was concentrated, dis-
solved in EtOAc/cyclohexane (1:10), filtered, and concentrated.
Flash chromatography (EtOAc/cyclohexane, 1:10) gave 3 (141 mg,
76%) as a pale yellow oil. 1H NMR (CDCl3): δ = 9.82 (dd, J =
2.3, 2.3 Hz, 1 H, 1-H), 4.30 (ddd, J = 9.8, 7.8, 1.3 Hz, 1 H, 5-H),
3.86 (ddd, J = 13.3, 3.5, 3.3 Hz, 1 H, 7-H), 3.76–3.67 (m, 2 H, 7-
H, 6-H), 3.01 (dd, J = 17.1, 2.8 Hz, 1 H, 2-H), 2.98 (dd, J = 17.1,
2.3 Hz, 1 H, 2-H), 2.93–2.75 (m, 4 H, S-CH2-CH2-CH2-S), 2.61 (d,
J = 15.1 Hz, 1 H, 4-H), 2.21 (d, J = 15.1, 9.8 Hz, 1 H, 4-H), 2.03–
1.93 (m, 2 H, S-CH2-CH2-CH2-S), 1.37 (s, 3 H, CH3), 1.35 (s, 3 H,
CH3), 0.92 [s, 9 H, SiC(CH3)3], 0.10 [s, 6 H, Si(CH3)2] ppm. 13C
NMR (CDCl3): δ = 207.7, 109.1, 80.8, 75.7, 63.2, 59.1, 51.3, 41.6,
26a (2 mg, 11%) as a colorless oil. H NMR (CDCl3): δ = 7.33–
7.22 (m, 10 H, Ph-H), 4.57 (d, J = 14.8 Hz, 1 H, CH2Ph), 4.53 (d,
J = 4.0 Hz, 1 H, C-4), 4.49 (d, J = 11.8 Hz, 2 H, CH2Ph), 4.28
(ddd, J = 7.8, 7.6, 4.0 Hz, 1 H, 9-H), 4.23 (d, J = 14.8 Hz, 1 H,
CH2Ph), 4.21 (ddd, J = 6.8, 5.5, 4.0 Hz, 1 H, 5-H), 3.80 (dd, J =
13.1, 7.1 Hz, 1 H, 11-H), 3.67 (dd, J = 13.1, 5.8 Hz, 1 H, 11-H),
3.66 (ddd, J = 7.6, 7.1, 5.8 Hz, 1 H, 10-H), 3.60 (d, J = 8.8 Hz, 1
H, 1-H), 3.48 (d, J = 8.8 Hz, 1 H, 1-H), 3.27 (s, 3 H, OCH3), 2.86
(dd, J = 17.6, 5.5 Hz, 1 H, 6-H), 2.69 (dd, J = 17.6, 6.8 Hz, 1 H,
6-H), 2.66 (dd, J = 16.4, 4.0 Hz, 1 H, 4-H), 2.61 (dd, J = 16.4,
7.8 Hz, 1 H, 4-H), 1.37 (s, 3 H, CH3), 1.37 (s, 3 H, CH3), 1.25 (s,
3 H, CH3), 1.18 (s, 3 H, CH3), 0.89 [s, 9 H, SiC(CH3)3], 0.07 (s, 3
H, SiCH3), 0.07 (s, 3 H, SiCH3) ppm.
(4R,5R,9R,10R)-1,4-Bis(benzyloxy)-11-(tert-butyldimethylsilyloxy)-
9,10-(2,2-dimethyl-1,3-dioxolane)-5-hydroxy-2,2-dimethylundecan-
3,7-dione (26b): A stirred mixture of 25 (37 mg, 0.05 mmol), MeI
(31 μL, 0.5 mmol), and CaCO3 (25 mg, 0.25 mmol) in MeCN
(1 mL)/H2O (0.1 mL) was stirred at room temperature overnight.
The reaction mixture was diluted with CH2Cl2, dried with Na2SO4,
filtered, and concentrated. Flash chromatography (EtOAc/cyclo-
hexane, 1:5) gave 26b (28 mg, 87%) as a yellow oil. 1H NMR
(CDCl3): δ = 7.36–7.62 (m, 10 H, Ph-H), 4.60 (d, J = 4.3 Hz, 1 H,
4-H), 4.53 (d, J = 11.3 Hz, 1 H, CH2Ph), 4.47 (s, 2 H, CH2Ph),
4.43 (br. s, 1 H, OH), 4.42 (d, J = 11.3 Hz, 1 H, CH2Ph), 4.27 (m,
1 H, 9-H), 3.81–3.76 (m, 1 H, 11-H), 3.71–3.65 (m, 2 H, 10-H, 11-
H), 3.51 (s, 2 H, 1-H), 3.40 (d, J = 5.0 Hz, 1 H, 5-H), 2.79–2.69
40.8, 27.1, 26.9, 26.1, 25.9, 25.0, 18.3, –5.4, –5.5 ppm. IR (neat): ν
˜
= 2920, 1720, 1250, 1090, 840 cm–1. MS: calcd. for C19H36O4S2Si
[M + H] 421.1901; found 421.1900.
(4R,5R,9R,10R)-1,4-Bis(benzyloxy)-11-(tert-butyldimethylsilyloxy)-
9,10-(2,2-dimethyl-1,3-dioxolane)-7-(1,3-dithiane)-5-hydroxy-2,2-di-
methylundecan-3-one (25): TiCl4 (164 μL, 1.50 mmol) was added to
a–78 °C solution of aldehyde 3 (630 mg, 1.50 mmol) in CH2Cl2
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Eur. J. Org. Chem. 2011, 4465–4471