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S. Abel et al.
FEATURE ARTICLE
13C NMR (75.5 MHz, CDCl3): δ = Ð4.80, 4.67, 14.21, 16.45, 19.43,
25.92, 29.55, 30.70, 30.72, 56.70, 58.38, 73.64, 75.37, 75.52, 91.60,
99.57, 100.7, 127.8, 129.1, 133.4, 140.1.
3.7 Hz), 3.82 (1H, dd, J =10.3, 2.1 Hz), 3.87 (1H, d, J = 1.9 Hz),
4.67 (1H, dd, J = 7.3, 5.9 Hz), 5.39 (1H, dd, J = 15.4, 8.5 Hz), 5.76
(1H, dd, J = 15.4, 7.7 Hz), 7.24Ð7.73 (15 × 1H, m).
13C NMR (75.5 MHz, CDCl3): δ = Ð2.70, Ð2.67, 10.08, 15.79,
18.34, 18.41, 19.96, 20.06, 19.33, 25.73, 25.89, 26.87, 30.76, 30.90,
33.85, 34.75, 38.04, 39.05, 39.31, 47.75, 56.23, 57.25, 58.64, 70.48,
70.56, 74.52, 78.48, 83.76, 84.78, 101.1, 125.9, 126.2, 127.45,
127.5, 128.4, 129.6, 133.9, 134.4, 135.8, 136.0, 139.9, 144.9, 169.6.
Anal. Calcd. for C26H42O5SSi (494.8): C, 63.11; H, 8.56. Found: C,
62.89; H, 8.33.
Julia coupling between 2a and 22. Synthesis of product 25
Sulfone 22 (120 mg, 0.24 mmol) was dissolved in anhyd THF
(3 mL) and anhyd toluene (3 mL), the solution was purged with Ar
and cooled to Ð78¡C. Then, a 1.6 M solution of t-BuLi (150 µL,
0.24 mmol) was added dropwise to the mixture which became yel-
low. After 20 min at Ð78¡C, a solution of aldehyde 2a3 (76.0 mg,
0.19 mmol) in THF (1 mL) and toluene (1 mL) was added and the
mixture was stirred for further 70 min at Ð78¡C. Then, it was hydro-
lyzed with sat. aq NH4Cl (10 mL), warmed to r.t. and partitioned be-
tween H2O and Et2O. The aqueous phase was extracted with Et2O
(3 × 25 mL), the combined organic phases were washed with brine,
dried (Na2SO4) and concentrated in vacuo. Unreacted 2a was sepa-
rated from the crude by flash chromatography on silica gel (pen-
tane/Et2O = 5/2 → 1/1). The mixed fractions of 25 and remaining
sulfone 22 were dissolved in pyridine (3 mL) and treated with ben-
zoyl chloride (50 µL). After stirring overnight at r.t., the mixture
was hydrolyzed with sat. aq NaHCO3 and partitioned between H2O
and Et2O. The aqueous phase was extracted with Et2O (3 × 10 mL)
the combined organic phases were washed with aq. NaHCO3 (2 ×
20 mL) and with brine and dried (Na2SO4). After concentration in
vacuo the crude product was coevaporated 3 times with toluene and
dried under high vacuum. Subsequently, the crude benzoylated
product was dissolved in anhyd EtOAc (4 mL) and anhyd MeOH
(2 mL) under Ar. The mixture was cooled to Ð30¡C and treated with
5% sodium amalgam (560 mg, 1.20 mmol), then stirred at Ð20¡C
for 5 h. After hydrolysis with sat. aq NH4Cl (10 mL) at Ð20¡C, the
temperature was raised to r.t., and the liquid phase decanted from
mercury. Water and Et2O were added, the aqueous phase was ex-
tracted with Et2O (3 × 10 mL), the combined organic phases were
washed with brine and dried (Na2SO4). After concentration in vac-
uo, the crude product was purified by flash chromatography on sil-
ica gel (pentane/EtOAc = 5/1). The trans-alkene 25 was obtained in
35% yield (34 mg). Rf = 0.36 (pentane /Et2O = 3/1).
Thexyldimethylsilyl 17-Bromo-5-O-(tert-butyldiphenylsilyl)-2-
desmethyl-17-deoxy-17-epi-3-O-methyl-1,17-secosoraphenic
ester (33)
The crude TDMS ester 31 was treated with NEt3 (600 µL,
4.30 mmol) and a 2.6 M solution of α-bromoenamine 32 (1.54 mL,
4.00 mmol) in dibromomethane. After 1 h at r.t. the mixture was hy-
drolyzed with H2O (60.0 µL, 3.33 mmol), dried (Na2SO4), and con-
centrated in vacuo. The crude product was purified by flash
chromatography on silica gel (CH2Cl2/Et2O = 0/1 → 20/1). Bro-
mide 33 (715 mg, 728 µmol, 91% from 30) was isolated as a light
yellow oil. Rf = 0.80 (CH2Cl2/MeOH = 20/1).
1H NMR (300 MHz, CDCl3): δ = 0.29, 0.31 (2 × 3H, 2 s), 0.76 (3H,
d, J = 7.4 Hz), 0.84 (3H, d, J = 7.1 Hz), 0.87 (2 × 3H, d, J = 9.5 Hz),
0.88 (2 × 3H, s), 1.08 (9H, s), 1.20Ð1.70 (10 × 1H, m), 2.33 (1H, m),
2.57 (1H, d, J = 15.4 Hz), 2.92 (1H, d, J = 15.3 Hz), 2.92, 3.25, 3.28,
3.40 (4 × 3H, 4 s), 3.15 (1H, m), 3.26 (1H, s), 3.52 (1H, dd, J = 8.5,
3.6 Hz), 3.82 (1H, dd, J =10.4, 2.0 Hz), 3.86 (1H, d, J = 2.1 Hz),
4.95 (1H, dd, J = 7.7, 7.4 Hz), 5.39 (1H, dd, J = 15.5, 8.3 Hz), 5.77
(1H, dd, J = 15.4, 7.7 Hz), 7.24Ð7.73 (15 × 1H, m).
13C NMR (75.5 MHz, CDCl3): δ = Ð2.71, 10.09, 15.76, 18.34,
18.42, 19.32, 19.95, 20.05, 24.62, 25.16, 26.87, 28.35, 30.72, 33.83,
34.73, 38.02, 39.27, 39.97, 47.74, 55.56, 56.23, 57.26, 58.74, 70.43,
70.55, 78.44, 83.62, 84.80, 101.1, 126.2, 127.2, 127.5, 128.3, 129.6,
135.8, 136.0, 133.8, 134.4, 140.1, 146, 169.5.
MS (FAB, NBA + KCl): m/z = 1019, 1021.
MS (FAB, NBA ): m/z = 663, 661, 325, 323, 255, 239, 213, 199,
197, 157, 135, 91, 73.
Anal. Calcd. for C53H81BrO8Si2 (982.31): C, 64.81; H, 8.31. Found
C, 64.41; H, 8.57.
1H NMR (300 MHz, CDCl3): δ = Ð0.16, 0.01 (2 × 3H, s), 0.12, 0.13
(2 × 3H, s), 0.87 (9H, s), 0.90 (3H, d, J = 6.7 Hz), 0.94 (12H, m),
1.36, 1.38 (2 x 3H, s), 1.30Ð1.50 (5H, m), 1.55Ð1.80 (3H, m), 1.88Ð
1.98 (1H, m), 2.28Ð2.40 (1H, m), 3.16 (1H, m), 3.24 (3H, s), 3.39
(3H, s), 3.46 (3H, s), 3.52 (2H, m), 3.90 (1H, dd, J = 8.6, 2.0 Hz),
4.01 (1H, d, J = 8.6 Hz), 4.60 (1H, dd, J = 5.3 Hz), 5.38 (1H, dd, J
= 15.7, 8.4), 5.63 (1H, dd, J = 15.7, 7.2), 7.18Ð7.30 (5H, m).
13C NMR (75.5 MHz, CDCl3): δ = Ð4.96, Ð4.83, Ð4.53, 5.05, 14.60,
18.21, 19.49, 25.73, 25.84, 25.87, 25.99, 29.79 (2C), 31.22, 37.32,
40.98, 55.94, 56.68, 58.54, 73.85, 75.01, 75.77, 77.01, 83.62, 84.74,
91.50, 99.39, 101.1, 125.8, 126.7, 127.9, 139.3, 145.8.
17-Bromo-5-O-(tert-butyldiphenylsilyl)-2-desmethyl-17-deoxy-
17-epi-3-O-methyl-1,17-secosoraphenic acid (34)
In a 25 mL flask, the TDMS ester 33 (220 mg, 224 µmol) was
stirred in a mixture of acetone (8.0 mL), H2O (2.0 mL), and Et3N
(0.5 mL) at r.t. After 15 min, the mixture was treated with a 1M aq.
solution of NaH2PO4 (50 mL, pH = 4) and the aqueous phase ex-
tracted with CH2Cl2 (3 × 20 mL). The combined organic phases
were dried (Na2SO4), and concentrated in vacuo at r.t. The crude
carboxylic acid 34 (236 mg) was isolated as a very unstable product
and was directly used in the next step without further purification.
Rf = 0.42 (CH2Cl2/MeOH = 20/1).
Anal. Calcd. for C42H74O6Si2 (731.2): C, 68.99; H, 10.20. Found: C,
69.13; H, 10.35.
5-O-(tert-Butyldiphenylsilyl)-2-desmethyl-3-O-methyl-
soraphen (35)
Thexyldimethylsilyl 5-O-(tert-Butyldiphenylsilyl)-2-desmethyl-
17-hydroxy-3-O-methyl-1,17-secosoraphenic ester (31)
In a 100 mL flask the acid 30 (622 mg, 800 µmol) was dissolved in
anhyd CH2Cl2 (40 mL) under Ar and treated at 0¡C with Et3N
(600 µL, 4.30 mmol) and thexyldimethylsilyl chloride (200 µL,
1.02 mmol). After 20 min at r.t. the crude product 31 was directly used
without workup in the next step. Rf = 0.62 (CH2Cl2/MeOH = 20/1).
1H NMR (300 MHz, CDCl3): δ = 0.27, 0.31 (2 × 3H, 2 s), 0.76 (3H,
d, J = 7.4 Hz), 0.83 (3H, d, J = 6.8 Hz), 0.87 (2 × 3H, d, J = 9.6 Hz),
0.88 (2 × 3H, s), 1.08 (9H, s), 1.10Ð1.85 (10 × 1H, m), 2.34 (1H, m),
2.57 (1H, d, J = 15.4 Hz), 2.92 (1H, d, J = 15.3 Hz), 2.92, 3.24, 3.28,
3.40 (4 × 3H, 4 s), 3.14 (1H, m), 3.42 (1H, s), 3.54 (1H, dd, J = 8.4,
In a 500 mL flask, the crude carboxylic acid 34 (236 mg) was dis-
solved in anhyd DMF (200 mL) under Ar and treated with finely
powdered anhyd Cs2CO3 (1.00 g, 3.07 mmol). After 1 day the mix-
ture was treated with a 1M aq solution of NaH2PO4 (500 mL) and
the aqueous phase extracted with Et2O(5 × 100 mL). The combined
organic phases were washed with water (3 × 100 mL), dried
(Na2SO4), and concentrated in vacuo. After evaporation of residual
DMF under high vacuum, the crude product 35 was purified by
flash chromatography on silica gel (CH2Cl2/Et2O = 25/1 → 10/1).
The protected norsoraphen 35 (85.0 mg, 112 µmol, 50% from 33)
was obtained as a white foam. Rf = 0.52 (CH2Cl2/Et2O = 9/1).
1H NMR (300 MHz, CDCl3): δ = 0.74 (3H, d, J = 7.4 Hz), 0.81 (3H,
d, J = 6.6 Hz), 1.11 (9H, s), 1.14Ð1.73 (9 × 1H, m), 2.39 (1H, m),
Synthesis 1999, No. 1, 188–197 ISSN 0039-7881 © Thieme Stuttgart · New York