5984
Z. Ye et al. / Tetrahedron 67 (2011) 5979e5989
25
7.42e7.31 (m, 6H), 4.54 (s, 2H), 3.84e3.79 (m, 1H), 3.55e3.48 (m,
1H), 3.41e3.37 (m, 1H), 3.28 (s, 3H), 3.27e3.23 (m, 1H), 1.85e1.78
(m, 2H), 1.73e1.67 (m, 1H), 1.64e1.56 (m, 3H), 1.02 (s, 9H), 0.99 (d,
J¼6.8 Hz, 3H), 0.95 (d, J¼6.3 Hz, 3H), 0.90 (d, J¼6.7 Hz, 3H); 13C NMR
[
a
]
D
ꢀ2.64 (c 1.35, CHCl3); IR (film): 3489, 3074, 2956, 2931,
2857, 1472, 1379, 1253, 1105, 1038, 836, 775 cmꢀ1
(400 MHz, CDCl3) 7.69e7.66 (m, 4H), 7.43e7.33 (m, 6H),
;
1H NMR
d
5.60e5.53 (m, 1H), 5.45 (d, J¼15.8 Hz, 1H), 4.56 (s, 2H), 3.84e3.79
(m, 1H), 3.43e3.39 (m, 1H), 3.33 (s, 3H), 3.29e3.25 (m, 1H),
2.13e2.09 (m, 1H), 2.03e2.00 (m, 1H), 1.83e1.72 (m, 3H), 1.60e1.57
(m, 1H), 1.30e1.26 (m, 1H), 1.28 (s, 3H), 1.05 (s, 9H), 0.95 (d,
J¼6.3 Hz, 3H), 0.93e0.89 (m, 15H), 0.10 (s, 3H), 0.08 (s, 3H); 13C
(100 MHz, CDCl3)
d 154.4, 136.0, 135.9, 134.9, 134.3, 133.8, 130.0,
129.8, 129.6, 129.5, 127.6, 127.4, 123.9, 96.1, 80.9, 72.4, 55.7, 37.3,
35.5, 33.1, 31.8, 31.1, 27.1, 19.8, 19.4, 15.4, 15.0; MS (ESI): m/z 655.3,
[MþNa]þ; HRMS (ESI) calcd for C35H48O3N4SSiNaþ [MþNa]þ:
655.3109, found: 655.3109.
NMR (100 MHz, CDCl3)
d 136.0, 135.9, 135.5, 135.0, 134.3, 129.6,
To a solution of the above sulfide (520 mg, 0.822 mmol) in EtOH
(15 mL) was added mixed 30% aq H2O2 (0.93 mL, 8.22 mmol) and
ammonium molybdate (206 mg, 0.164 mmol) at room temperature.
The mixture was stirred for 24 h and diluted by the addition of
brine. The combined organic layers were extracted with EtOAc,
dried over Na2SO4, filtered, and concentrated. Purification on silica
gel (EtOAc/hexanes 1:10) provided sulfone 16 (500 mg, 92%) as
129.6, 129.5, 127.6, 127.4, 95.9, 81.0, 75.8, 72.6, 71.4, 65.9, 55.7, 37.3,
36.3, 34.8, 33.0, 27.1, 25.9, 23.8, 19.7, 19.4, 18.2, 15.5, 15.3, ꢀ2.2; MS
(ESI): m/z 679.5, [MþNa]þ; HRMS (ESI) calcd for C38H64O5Si2Naþ
[MþNa]þ: 679.4185, found: 679.4172.
To a solution of the above alcohol (250 mg, 0.380 mmol) in
CH2Cl2 (10 mL) was added DMP (323 mg, 0.761 mmol) and NaHCO3
(128 mg, 1.52 mmol). The reaction was stirred at room temperature
for 1 h before it was quenched with satd NaHCO3 and satd Na2S2O3.
The mixture was extracted with CH2Cl2, washed with brine, dried
over Na2SO4, concentrated and purified by flash chromatography
(Et2O/hexanes 1:20e1:10) to afford aldehyde (225 mg, 90%) as
a colorless oil.
27
[a
]
ꢀ25.3 (c 2.10, CHCl3); IR (film): 3071, 2960, 2931, 2858,
D
1594, 1498, 1463, 1428, 1342, 1107, 1037, 956, 822, 762 cmꢀ1
;
1H
NMR (400 MHz, CDCl3) 7.70e7.59 (m, 9H), 7.43e7.34 (m, 6H), 4.49
d
(dd, J¼16.1, 6.8 Hz, 2H), 3.90e3.80 (m, 2H), 3.68e3.60 (m, 1H),
3.39e3.35 (m, 1H), 3.31 (s, 3H), 2.05e1.98 (m, 1H), 1.86e1.79 (m,
2H), 1.71e1.65 (m, 1H), 1.57e1.53 (m, 1H), 1.38e1.32 (m, 1H), 1.03 (s,
9H), 0.99 (d, J¼7.3 Hz, 3H), 0.97 (d, J¼6.7 Hz, 3H), 0.91 (d, J¼6.7 Hz,
a colorless oil.
25
[
a
]
D
ꢀ16.2 (c 1.20, CHCl3); IR (film): 3074, 2958, 2931, 2857,
1676, 1472, 1379, 1254, 1105, 1037, 837, 739 cmꢀ1
;
1H NMR
(400 MHz, CDCl3) 9.33 (s, 1H), 7.68e7.65 (m, 4H), 7.44e7.34 (m,
d
3H); 13C NMR (100 MHz, CDCl3)
d
153.5, 136.0, 135.9, 134.9, 134.2,
6H), 5.77e5.70 (m, 1H), 5.24 (d, J¼15.3 Hz, 1H), 4.56 (s, 2H),
3.83e3.78 (m, 1H), 3.41e3.37 (m, 1H), 3.33 (s, 3H), 2.14e2.10 (m,
1H),1.83e1.70 (m, 3H),1.58e1.54 (m, 1H),1.38 (s, 3H),1.32e1.26 (m,
1H), 1.05 (s, 9H), 0.95 (d, J¼6.3 Hz, 3H), 0.93 (s, 9H), 0.90 (d,
J¼7.0 Hz, 3H), 0.86 (d, J¼6.8 Hz, 3H), 0.11 (s, 3H), 0.10 (s, 3H); 13C
133.2, 131.4, 129.7, 129.7, 129.5, 127.6, 127.4, 125.1, 96.2, 80.7, 72.4,
55.8, 54.5, 37.1, 35.2, 33.9, 27.1, 23.8, 20.0, 19.3, 15.6, 15.2; MS (ESI):
m/z 687.3, [MþNa]þ; HRMS (MALDI) calcd for C35H48N4O5SSiNaþ
[MþNa]þ: 687.3007, found: 687.3000.
NMR (100 MHz, CDCl3)
d 200.5, 136.0, 135.9, 135.0, 134.3, 132.7,
4.7. Olefin 18
131.1, 129.6, 129.5, 127.6, 127.4, 96.0, 80.9, 80.4, 72.5, 55.7, 37.3, 36.2,
34.8, 33.1, 27.1, 25.8, 22.9, 19.7, 19.4, 18.3, 15.4, 15.1, ꢀ2.2, ꢀ2.3; MS
(ESI): m/z 677.4, [MþNa]þ; HRMS (ESI) calcd for C38H62O5Si2Naþ
[MþNa]þ: 677.4028, found: 677.4042.
To a stirred solution of sulfone 16 (490 mg, 0.737 mmol) in 3 mL
of DMF/HMPA (3:1 v/v) was added LiHMDS (1.0 M in THF, 1.11 mL,
1.11 mmol) at ꢀ40 ꢁC. This was stirred for 10 min and followed by
the addition of aldehyde 17 (316 mg, 0.952 mmol) in 1.0 mL of DMF/
HMPA (3:1 v/v) via cannula. The reaction was allowed to warm
slowly to room temperature and stirred for 24 h before it was
quenched by the addition of satd NH4Cl solution. The layers were
separated and the aqueous layer was extracted with EtOAc. The
combined organic layers were washed with brine, dried over
Na2SO4, filtered, and concentrated. Purification on silica gel (hex-
anes) provided 18 (520 mg, 91%) as a colorless oil.
To
a stirred solution of the above aldehyde (196 mg,
0.299 mmol) in THF (5 mL) was added TBAF (1.0 M in THF, 0.36 mL,
0.36 mmol). The reaction was stirred at room temperature for
20 min before it was diluted with brine. The mixture was extracted
with EtOAc, dried over Na2SO4, concentrated and purified by flash
chromatography (EtOAc/hexanes 1:10e1:5) to afford 4 (136 mg,
84%) as a colorless oil.
26
[
a
]
D
ꢀ59.8 (c 1.85, CHCl3); IR (film): 3445, 3065, 2932, 1733,
1462, 1377, 1104, 1039, 821, 741 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
[a
]
29 ꢀ1.2 (c 2.15, CHCl3); IR (film): 3073, 2956, 2927, 2857, 1462,
d 9.37 (s, 1H), 7.69e7.66 (m, 4H), 7.44e7.35 (m, 6H), 5.78e5.70 (m,
D
1378, 1254, 1108, 1039, 835, 775 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
1H), 5.35 (d, J¼15.6 Hz, 1H), 4.56 (s, 2H), 3.87e3.80 (m, 1H),
3.42e3.38 (m, 1H), 3.33 (s, 3H), 3.31e3.27 (m, 1H), 2.18e2.15 (m,
1H), 1.86e1.71 (m, 3H), 1.58 (m, 1H), 1.38 (s, 3H), 1.41e1.33 (m, 1H),
1.06 (s, 9H), 0.96 (d, J¼6.3 Hz, 3H), 0.93 (s, 9H), 0.90 (d, J¼7.1 Hz,
3H), 0.86 (d, J¼6.8 Hz, 3H), 0.11 (s, 3H), 0.10 (s, 3H); 13C NMR
d
7.71e7.68 (m, 4H), 7.45e7.36 (m, 6H), 5.59e5.52 (m, 1H), 5.45 (d,
J¼15.5 Hz, 1H), 4.58 (s, 2H), 3.86e3.81 (m, 1H), 3.42e3.40 (m, 1H),
3.37 (m, 2H), 3.35 (s, 3H), 2.13e2.09 (m, 1H), 1.79e1.73 (m, 3H),
1.62e1.60 (m, 1H), 1.31e1.28 (m, 3H), 1.07 (s, 9H), 0.97 (d, J¼6.3 Hz,
3H), 0.93 (d, J¼6.8 Hz, 3H), 0.89 (m, 21H), 0.09 (s, 6H), 0.08 (s, 3H),
(100 MHz, CDCl3)
d 200.1, 136.0, 135.9, 134.9, 134.3, 133.3, 129.6,
0.05 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
136.8, 136.0, 135.9, 135.1,
129.6, 129.5, 127.6, 127.4, 96.0, 80.9, 78.1, 72.6, 55.7, 37.3, 36.0, 34.7,
32.9, 27.1, 22.6, 19.6, 19.4, 15.5, 15.2; MS (ESI): m/z 563.4, [MþNa]þ;
HRMS (ESI) calcd for C32H48O5SiNaþ [MþNa]þ: 563.3163, found:
563.3144.
134.3, 129.6, 129.4, 127.9, 127.6, 127.4, 95.9, 81.2, 75.7, 72.5, 71.6,
55.6, 37.4, 36.5, 35.0, 33.1, 27.1, 25.9, 24.5, 19.9, 19.4, 18.3, 18.2, 15.5,
14.9, ꢀ2.1, ꢀ5.4; MS (ESI): m/z 793.5, [MþNa]þ; HRMS (ESI) calcd
for C44H79O5Si3þ [MþH]þ: 771.5230, found: 771.5256.
4.8. Aldehyde 4
4.9. (R)-1-(2-((tert-Butyldimethylsilyl)oxy)-3-chloropropyl)
cyclopropyl 4-methyl benzenesulfonate (20)
To a stirred solution of compound 18 (520 mg, 0.674 mmol) in
THF (15 mL) was added pyridine (1.35 mL, 13.5 mmol) and HF$Py
(0.334 mL, 13.5 mmol). The mixture was stirred at room temper-
ature for 3 days before it was quenched with satd NaHCO3. The
reaction mixture was extracted with EtOAc, washed with brine,
dried over Na2SO4, concentrated and purified by flash chroma-
tography (EtOAc/hexanes 1:20) to afford alcohol (354 mg, 80%) as
a colorless oil.
To a solution of compound 13 (1.28 g, 7.68 mmol) in CH2Cl2
(20 mL) was added imidazole (784 mg, 11.52 mmol) and TBSCl
(1.51 g, 9.99 mmol) at 0 ꢁC. The reaction was stirred at room tem-
perature for 15 h before it was quenched with aq NaHCO3. The
mixture was extracted with CH2Cl2, washed with brine, dried over
Na2SO4, concentrated and purified by flash chromatography (Et2O/
hexanes 1:40) to afford TBS ether (2.0 g, 83%) as a colorless oil.