444
T. Saito et al. / Tetrahedron 67 (2011) 429e445
704 cmꢀ1
;
1H NMR (600 MHz, CDCl3)
d
7.68e7.62 (m, 4H),
J¼10.5 Hz,1H), 4.39 (d, J¼11.0 Hz,1H), 4.13 (br s,1H), 4.01 (dd, J¼13.0,
7.42e7.32 (m, 6H), 7.27e7.22 (m, 2H), 6.82e6.78 (m, 2H), 5.56 (dd,
J¼4.1, 2.0 Hz, 1H), 4.75 (d, J¼11.0 Hz, 1H), 4.48 (d, J¼11.0 Hz, 1H),
3.76 (s, 3H), 3.74 (m,1H), 3.70e3.61 (m, 2H), 3.58 (dd, J¼11.3, 3.8 Hz,
1H), 3.46 (dd, J¼11.3, 6.2 Hz, 1H), 3.41 (dd, J¼9.6, 2.0 Hz, 1H),
2.40e2.74 (m, 2H), 2.13 (m, 1H), 2.08 (s, 3H), 1.75 (dddd, J¼13.7, 7.2,
6.9, 2.5 Hz, 1H), 1.52 (m, 1H), 1.44 (m, 1H), 1.01 (s, 9H), 0.76 (d,
J¼6.9 Hz, 3H), 0.71 (d, J¼6.9 Hz, 3H); 13C NMR (150 MHz, CDCl3)
6.5 Hz, 1H), 3.81 (m, 1H), 3.74 (s, 3H), 3.66e3.55 (m, 2H), 3.56 (dd,
J¼10.5, 6.0 Hz, 1H), 3.47 (dd, J¼10.5, 4.5 Hz, 1H), 3.25 (dd, J¼9.0,
1.5 Hz, 1H), 2.49 (m, 1H), 2.38 (m, 1H), 2.30 (m, 1H), 2.12e2.01 (m,
2H), 2.01e1.88 (m, 3H), 1.52e1.36 (m, 4H), 1.00 (s, 9H), 0.87 (s, 9H),
0.86 (s, 9H), 0.69 (d, J¼7.0 Hz, 3H), 0.65 (d, J¼7.0 Hz, 3H), 0.04 (s, 3H),
0.01 (s, 3H), ꢀ0.01 (s, 6H); 13C NMR (125 MHz, CDCl3)
d 200.8, 158.8,
147.5, 138.4, 135.5 (ꢂ4), 134.14, 134.11, 131.9, 131.6, 129.42, 129.41,
129.2 (ꢂ2), 128.3 (ꢂ2), 127.6 (ꢂ2), 127.55 (ꢂ2), 127.54 (ꢂ3), 127.4,
125.6, 125.3, 123.7, 113.5 (ꢂ2), 86.2, 81.4, 77.5, 76.8, 75.6, 74.3, 73.4,
73.04, 73.01, 70.8, 62.9, 55.2, 38.5, 38.4, 34.5, 32.6, 28.1, 27.9, 27.2,
26.9 (ꢂ3), 25.9 (ꢂ3), 25.8 (ꢂ3),19.1,18.2,18.0,13.4,10.9, ꢀ4.1, ꢀ4.57,
ꢀ4.58, ꢀ5.0; HRMS (ESI) calcd for C68H100O9Si3Na [(MþNa)þ]
1167.6567, found 1167.6544.
d
170.0, 159.2, 135.5 (ꢂ4), 134.04, 134.01, 130.3, 129.6 (ꢂ2), 129.51,
129.48, 127.6 (ꢂ4), 113.7 (ꢂ2), 84.1, 81.8, 77.5, 73.8, 69.9, 67.9, 65.3,
62.6, 55.2, 39.1, 38.2, 28.2, 26.8 (ꢂ3), 24.1, 21.2,19.1,13.5,10.2; HRMS
(ESI) calcd for C39H52O7SiNa [(MþNa)þ] 683.3375, found 683.3360.
To a solution of the above diol (19.0 mg, 28.7
m
mol) and 2,6-
L) at 0 ꢁC was added
mmol). The resultant solution was stirred at
lutidine (16.7
TBSOTf (16.5
m
L, 143
mmol) in CH2Cl2 (500 m
m
L, 71.8
0
ꢁC for 45 min before it was quenched with saturated aqueous
4.1.36. C15eC36 segment 2. To a solution of enone 41 (17.3 mg,
NH4Cl solution. The mixture was extracted with EtOAc, and the
organic layer was washed with 1 M HCl solution, saturated aqueous
NaHCO3 solution, and brine, dried over Na2SO4, filtered, and con-
centrated under reduced pressure. The crude bis-TBS ether
(26.0 mg) was used for the next reaction without purification.
To a solution of the above bis-TBS ether (26.0 mg) in CH2Cl2
(1 mL) at ꢀ78 ꢁC was added DIBALH (1.04 M solution in hexanes,
15.1 mmol) in EtOH (755 mL) was added CeCl3$7H2O (8.4 mg, 23 mmol).
The resultant solution was stirred at room temperature for 20 min.
The solution was cooled to ꢀ40 ꢁC and treated with NaBH4 (0.68 mg,
18
m
mol). The resultant mixture was stirred at ꢀ40 ꢁC for 45 min
before it was quenched with saturated aqueous NH4Cl solution. The
mixture was extracted with EtOAc, and the organic layer was washed
with brine, dried over Na2SO4, filtered, and concentrated under re-
duced pressure. Purification of the residue by flash column chroma-
tography (silica gel, EtOAc/hexanes¼1/10 to 1/7) gave alcohol 2
69.0
mL, 71.8
m
mol). The resultant solution was stirred at ꢀ78 ꢁC for
40 min before it was quenched with MeOH. Saturated aqueous
potassium sodium tartrate solution was added, and the mixture
was diluted with EtOAc and vigorously stirred at room temperature
until the layers became clear. The organic layer was separated, and
the aqueous layer was extracted with EtOAc. The combined organic
layer was washed with brine, dried over Na2SO4, filtered, and
concentrated under reduced pressure. Purification of the residue by
column chromatography (silica gel, EtOAc/hexanes¼1/15 to 10/1)
gave alcohol 49 (22.7 mg, 93% for the two steps) as a colorless oil:
(15.8 mg, 91%) as a colorless oil: [
a]
D
28 þ10.4 (c 0.3, CHCl3); IR (film)
3478, 3066, 3039, 2954, 2928, 2985, 2856, 1249, 1090, 836, 776,
702 cmꢀ1; 1H NMR (600 MHz, CDCl3)
d 7.66e7.61 (m, 4H), 7.40e7.35
(m, 2H), 7.35e7.29 (m, 8H), 7.28e7.24 (m, 1H), 7.23e7.20 (m, 2H),
6.80e6.76 (m, 2H), 5.85 (dddd, J¼10.0, 5.5, 2.1, 2.0 Hz, 1H), 5.80 (m,
1H), 5.66 (dddd, J¼11.3, 9.2, 1.7, 1.7 Hz, 1H), 5.42 (ddd, J¼11.3, 8.6,
4.8 Hz,1H), 5.20 (s, 1H), 5.08 (d, J¼1.0 Hz, 1H), 4.87 (d, J¼11.0 Hz, 1H),
4.60 (dd, J¼8.9,1.1 Hz,1H), 4.59 (d, J¼12.1 Hz, 1H), 4.56 (d, J¼12.1 Hz,
1H), 4.43 (dd, J¼6.9, 6.9 Hz, 1H), 4.40 (d, J¼11.0 Hz, 1H), 4.07 (m, 1H),
3.93 (dd, J¼13.4, 6.5 Hz,1H), 3.89 (br s,1H), 3.82e3.77 (m, 2H), 3.74 (s,
3H), 3.67e3.59 (m, 2H), 3.55 (dd, J¼10.6, 6.2 Hz,1H), 3.46 (dd, J¼10.6,
4.4 Hz, 1H), 3.25 (dd, J¼9.2, 2.0 Hz, 1H), 2.75 (m, 1H), 2.52 (m, 1H),
2.16e1.98 (m, 5H), 1.98e1.86 (m, 2H), 1.71 (dddd, J¼11.7, 8.3, 7.9,
7.6 Hz, 1H), 1.52e1.38 (m, 3H), 1.00 (s, 9H), 0.87 (s, 9H), 0.86 (s, 9H),
0.73 (d, J¼6.8 Hz, 3H), 0.66 (d, J¼6.9 Hz, 3H), 0.06 (s, 3H), 0.03 (s, 3H),
1H NMR (600 MHz, CDCl3)
d 7.67e7.63 (m, 4H), 7.42e7.32 (m, 6H),
7.27e7.21 (m, 2H), 6.82e6.78 (m, 2H), 4.67 (d, J¼11.3 Hz, 1H), 4.55
(d, J¼11.3 Hz, 1H), 4.45 (m, 1H), 3.77 (m, 1H), 3.76 (s, 3H), 3.74e3.63
(m, 2H), 3.54 (dd, J¼10.0, 5.5 Hz, 1H), 3.52 (dd, J¼10.0, 5.5 Hz, 1H),
3.37 (dd, J¼9.3, 3.5 Hz, 1H), 2.45 (ddd, J¼16.8, 5.9, 2.1 Hz, 1H), 2.33
(ddd, J¼16.8, 5.5, 1.7 Hz,1H), 2.18 (d, J¼8.2 Hz,1H), 2.15 (m, 1H), 1.84
(m, 1H), 1.58 (m, 1H), 1.46 (m, 1H), 1.03 (s, 9H), 0.87 (s, 9H), 0.86 (s,
9H), 0.734 (d, J¼7.3 Hz, 3H), 0.728 (d, J¼6.9 Hz, 3H), 0.06 (s, 3H),
0.05 (s, 3H), 0.03 (s, 3H), 0.02 (s, 3H).
0.02 (s, 3H), 0.01 (s, 3H); 13C NMR (150 MHz, CDCl3)
d 158.8, 149.5,
138.4, 135.5 (ꢂ4), 134.17, 134.13, 132.6, 131.6, 129.4 (ꢂ2), 129.2 (ꢂ2),
128.3 (ꢂ2), 127.8, 127.57 (ꢂ2), 127.54 (ꢂ5), 125.8, 125.0, 113.6 (ꢂ2),
110.2, 86.6, 81.0, 79.6, 77.2, 74.1, 73.42, 73.37, 73.29, 73.07, 73.05, 70.9,
62.9, 55.2, 38.6, 38.3, 33.3, 31.5, 28.1, 27.9, 27.5, 26.9 (ꢂ3), 25.92 (ꢂ3),
25.87(ꢂ3),19.1,18.2,18.0,13.4,10.9,ꢀ4.3(ꢂ2), ꢀ4.4,ꢀ4.7;HRMS(ESI)
calcd for C68H102O9Si3Na [(MþNa)þ] 1169.6724, found 1169.6726.
4.1.35. Enone 41. To a suspension of thioester 42 (19.4 mg,
20.0
Pd2(dba)3 (1.80 mg, 1.97
THF (22 L, degassed) at room temperature was added a portion
(28 L, 8.16 mol) of a stock solution of triethylphosphite (48 L) in
THF (0.95 mL, degassed). After stirring for 25 min, a solution of
vinylstannane 27 (10.2 mg, 22.0 mol) in THF/hexanes (1/2, v/v,
600 L rinse, degassed) was added, and the resultant brown
Lþ250
mmol), copper(I) diphenylphosphinate(11.2mg, 39.9
mmol), and
m
mol) in hexanes (100 L, degassed) and
m
m
m
m
m
4.1.37. Acetonide 50. To a solution of alcohol 2 (6.3 mg, 5.5
m
mol) in
L) at room temperature was added TBAF (1.0 M solution
L, 27 mol). The resultant solution was allowed to warm
m
THF (600
in THF, 27
m
m
m
m
m
suspensionwas stirredat roomtemperaturefor 6 h. Themixturewas
diluted with hexane and filtered through a plug of Celite. The filtrate
was concentrated under reduced pressure, and the residue was
purified by flash column chromatography (silica gel, EtOAc/
hexanes¼1/40 to 1/20 to 1/10 to 1/5) to give enone 41 (17.0 mg, 74%)
as a pale yellow oil, along with unreacted thioester 42 (4.3 mg, 22%)
and homo-coupling product 38 (1.7 mg, ca. 14%, contaminated with
to 50 ꢁC. After being stirred at 50 ꢁC for 25 h, the solution was
concentrated under reduced pressure. The residue was purified by
flash column chromatography (silica gel, EtOAc/hexanes¼2/1 to 1/
0) to give a tetraol (4.7 mg) contaminated with some impurities,
which was used in the next reaction without further purification:
1H NMR (500 MHz, CDCl3)
d 7.34e7.31 (m, 4H), 7.29e7.24 (m, 3H),
7.86e7.82 (m, 2H), 5.92e5.85 (m, 2H), 5.79 (br d, J¼10.0 Hz, 1H),
5.63 (ddd, J¼10.5, 10.5, 6.0 Hz, 1H), 5.19 (s, 1H), 5.19 (s, 1H), 4.72 (d,
J¼11.0 Hz, 1H), 4.61e4.51 (m, 5H), 4.17 (br s, 1H), 4.06e3.99 (m, 2H),
3.85e3.77 (m, 2H), 3.77 (s, 3H), 3.66 (ddd, J¼11.0, 6.5, 6.5 Hz, 1H),
3.59 (ddd, J¼11.0, 6.5, 6.5 Hz, 1H), 3.54 (dd, J¼10.0, 6.0 Hz, 1H),
3.49e3.44 (m, 2H), 2.56 (ddd, J¼14.0, 10.0, 4.0 Hz, 1H), 2.23 (ddd,
J¼14.0, 12.5, 6.0 Hz, 1H), 2.16e2.08 (m, 2H), 2.06e1.99 (m, 2H),
1.99e1.83 (m, 3H), 1.59 (m, 1H), 1.57 (br s, 4H), 1.47e1.42 (m, 2H),
0.79 (d, J¼6.5 Hz, 3H), 0.73 (d, J¼7.5 Hz, 3H).
some impurities. Data for 41: [
a
]
27 þ8.7 (c 1.0, CHCl3); IR (film) 3032,
D
2954, 2929, 2893, 2856, 1683, 1514, 1471, 1250, 1091, 1038, 836, 777,
701 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 7.66e7.61 (m, 4H), 7.41e7.36
(m, 2H), 7.36e7.29 (m, 8H), 7.28e7.24 (m, 1H), 7.23e7.19 (m, 2H),
6.80e6.76 (m, 2H), 6.20 (s, 1H), 6.12 (s, 1H), 5.87 (m, 1H), 5.79 (br d,
J¼10.0 Hz, 1H), 5.67 (dd, J¼11.5, 9.5 Hz, 1H), 5.49 (ddd, J¼11.5, 7.5,
7.5 Hz,1H), 4.86 (d, J¼11.0 Hz,1H), 4.81 (dd, J¼6.7, 6.7 Hz,1H), 4.60 (d,
J¼12.5 Hz, 1H), 4.58 (m, 1H), 4.57 (d, J¼12.5 Hz, 1H), 4.53 (d,