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S. K. Ghosh et al. / Tetrahedron 62 (2006) 10485–10496
2H), 3.36 (s, 3H), 3.38 (m, 1H), 3.53 (m, 1H), 3.57 (t,
J¼6.0 Hz, 1H), 3.86 (dd J¼5.0, 6.0 Hz, 1H), 3.93 (dd,
J¼4.5, 6.5 Hz, 1H), 3.98 (dd, J¼3.5, 11.0 Hz, 1H), 4.56
(d, J¼11.5 Hz, 1H), 4.75 (d, J¼11.5 Hz, 1H), 7.29 (m,
1H), 7.34 (m, 4H); 13C NMR (500 MHz, CDCl3) d ꢀ5.4,
ꢀ5.4, 18.3, 25.0, 25.9, 28.6, 57.2, 62.8, 63.8, 70.9, 72.3,
79.0, 81.4, 127.7, 128.0, 128.4, 138.4; IR (film) cmꢀ1
3420br s, 3071w, 2930s, 2858s, 1671m, 1255m, 1085s;
mass spectrum (APCI): m/e 399.2 (M+H)+; ESIHRMS m/e
calcd for C21H38O5SiNa: 421.2381, found: 421.2384.
purified by flash column chromatography on silica gel [gra-
dient eluent: 2–10% EtOAc in hexanes] to provide cyclic
ketal 47 in 89% yield [5.00 mg]. Rf¼0.80 [25% EtOAc in
1
hexanes]; [a]2D3 28.9 [c 0.36, CHCl3]; H NMR (500 MHz,
CDCl3) d 1.06 (s, 9H), 1.45 (ddd, J¼4.0, 14.0, 14.0 Hz,
1H), 1.74 (ddd, J¼4.0, 14.0, 24.0 Hz, 1H), 1.88 (ddd,
J¼4.0, 4.0, 14.0 Hz, 1H), 1.95 (dddd, J¼4.0, 4.0, 8.0,
8.0 Hz, 1H), 3.23 (s, 3H), 3.25 (ddd, J¼5.0, 10.5, 10.5 Hz,
1H), 3.37 (ddd, J¼7.0, 7.0, 9.5 Hz, 1H), 3.40 (ddd, J¼7.0,
7.0, 9.5 Hz, 1H), 3.76 (d, J¼9.5 Hz, 1H), 3.92 (m, 3H),
4.73 (d, J¼11.5 Hz, 1H), 4.79 (d, J¼11.5 Hz, 1H), 5.00
(dd, J¼1.0, 10.5 Hz, 1H), 5.17 (dd, J¼1.5, 11.0 Hz, 1H),
5.31 (dd, J¼2.0, 17.5 Hz, 1H), 5.70 (dd, J¼11.0, 17.5 Hz,
1H), 5.78 (ddt, J¼10.5, 17.5, 7.0 Hz, 1H), 7.27–7.41 (m,
11H), 7.70 (m, 4H); 13C NMR (125 MHz, CDCl3) d 18.2,
24.1, 26.9, 34.0, 34.3, 56.0, 60.5, 64.5, 73.1, 73.6, 74.7,
80.9, 97.3, 116.2, 116.3, 127.2, 127.6, 127.6, 127.6, 127.9,
128.2, 129.5, 133.6, 133.8, 135.6, 135.7, 135.7, 138.8,
139.3; IR (film) cmꢀ1 3071w, 2929s, 2857s, 1456m,
1104s; mass spectrum (ESI): m/e 623.3 (M+Na)+.
4.5.2. Lactol 44. To a solution of the respective lactone
precursor [223.0 mg, 0.43 mmol] in Et2O [3 mL] was added
vinyl magnesium bromide [0.45 mL, 1 M] dropwise
at ꢀ78 ꢁC. The solution was stirred at ꢀ78 ꢁC for 1 h and
quenched with satd aq NH4Cl [5 mL] at ꢀ78 ꢁC. The
organic phase was separated and the aqueous fraction
was extracted with Et2O [3ꢂ5 mL]. The combined organic
phases were washed with satd aq NaCl, dried over
Na2SO4, and concentrated under reduced pressure. The crude
residue was purified by flash column chromatography on
silica gel [gradient eluent: 22–35% EtOAc in hexanes] to
lactol 44 in 73% yield [92.7 mg] as pale yellow oil based
on the starting material recovered [99.1 mg]. Lactone:
Rf¼0.32 [50% EtOAc in hexanes]; [a]2D3 5.00 [c 5.115,
4.5.4. Diene 46. Rf¼0.80 [25% EtOAc in hexanes]; [a]D23
ꢀ5.87 [c 0.92, CHCl3]; 1H NMR (300 MHz, CDCl3)
d 1.08 (s, 9H), 2.17 (t, J¼3.9 Hz, 2H), 3.40 (s, 3H), 3.74
(ddd, J¼3.0, 5.1, 10.2 Hz, 1H), 3.79 (ddd, J¼7.5, 7.5,
7.5 Hz, 1H), 3.93 (dd, J¼5.4, 11.4 Hz, 1H), 4.01 (dd,
J¼3.3, 11.4 Hz, 1H), 4.35 (dd, J¼14.5, 6.9 Hz, 1H), 4.56
(d, J¼11.8 Hz, 1H), 4.71 (dd, J¼3.9, 3.9 Hz, 1H), 4.84 (d,
J¼11.8 Hz, 1H), 4.97 (d, J¼10.8 Hz, 1H), 5.40 (d,
J¼17.1 Hz, 1H), 6.01 (dd, J¼10.8, 17.1 Hz, 1H), 7.43 (m,
11H), 7.75 (m, 4H); 13C NMR (75 MHz, CDCl3) d 19.1,
24.0, 26.7, 56.4, 63.4, 71.6, 72.5, 73.9, 78.0, 99.4, 112.5,
127.5, 127.6, 127.8, 128.2, 129.5, 131.6, 133.3, 135.6,
138.3, 148.9; IR (film) cmꢀ1 3070m, 2931s, 2858s, 1428m,
1112s; mass spectrum (APCI): m/e (% relative intensity)
529.2 (M+H)+; ESIHRMS m/e calcd for C33H41O4Si:
529.2769, found: 529.2780.
1
CHCl3]; H NMR (500 MHz, CDCl3) d 1.07 (s, 9H), 1.92
(m, 2H), 2.38 (ddd, J¼5.0, 5.0, 17.0 Hz, 1H), 2.61 (ddd,
J¼7.0, 10.5, 17.5 Hz, 1H), 3.29 (s, 3H), 3.74 (dd, J¼4.0,
8.0 Hz, 1H), 3.80 (m, 2H), 4.51 (d, J¼11.0 Hz, 1H), 4.61
(d, J¼11.0 Hz, 1H), 4.64 (dd, J¼3.5, 2.5 Hz, 1H), 7.25 (m,
2H), 7.31 (m, 3H), 7.39 (m, 4H), 7.41 (m, 2H), 7.68 (m,
4H); 13C NMR (75 MHz, CDCl3) d 19.0, 22.2, 25.9, 26.6,
55.8, 50.2, 62.4, 71.3, 73.4, 60.0, 81.2, 127.7, 127.8,
128.3, 129.8, 132.8, 132.9, 135.5, 137.7, 171.1; IR (film)
cmꢀ1 3070w, 2931s, 2858s, 1742s, 1428m, 1113s; mass
spectrum (APCI): m/e 519.2 (M+H)+; ESIHRMS m/e calcd
for C31H38NaO5Si: 541.2381, found: 541.2382. Compound
44: Rf¼0.32 [50% EtOAc in hexanes]; 1H NMR
(500 MHz, CDCl3) d 1.08 (s, 9H), 1.85 (m, 1H), 1.91
(m, 1H), 2.60 (ddd, J¼6.5, 9.0, 17.0 Hz, 1H), 2.71 (br, 1H),
2.73 (dddd, J¼6.0, 9.0, 17.0, 17.0 Hz, 1H), 3.28 (s, 3H),
3.38 (ddd, J¼4.5, 4.5, 8.5 Hz, 1H), 3.94 (ddd, J¼0.5, 5.0,
11.0 Hz, 1H), 3.61 (ddd, J¼3.5, 3.5, 7.5 Hz, 1H), 4.01
(ddd, J¼1.0, 3.5, 11.5 Hz, 1H), 4.53 (d, J¼11.5 Hz, 1H),
4.72 (d, J¼11.5 Hz, 1H), 5.80 (dd, J¼1.0, 10.5 Hz,
1H), 6.22 (d, J¼17.5 Hz, 1H), 6.35 (dd, J¼10.5, 17.5 Hz,
1H), 7.27–7.45 (m, 11H), 7.72 (m, 4H); 13C NMR
(125 MHz, CDCl3) d 19.2, 22.7, 26.9, 57.1, 64.2, 70.9,
72.3, 76.9, 79.0, 80.2, 96.5, 127.6, 127.7, 127.8, 127.9,
128.4, 129.8, 129.8, 133.0, 133.2, 135.6, 135.7, 135.7, 136.6,
138.4; IR (film) cmꢀ1 3459br s, 3069m, 2932s, 2859s,
1681m, 1428m, 1113s; mass spectrum (APCI): m/e 529.3
(MꢀH2O+H)+; ESIHRMS m/e calcd for C33H42O5SiNa:
569.2694, found: 569.2697.
4.5.5. Cyclic ketal 48. Rf¼0.80 [25% EtOAc in hexanes];
1
[a]2D3 46.1 [c 0.33, CHCl3]; H NMR (500 MHz, CDCl3)
d 1.06 (s, 9H), 1.48 (ddd, J¼4.0, 13.0, 13.0 Hz, 1H), 1.65
(dddd, J¼4.0, 13.0, 13.0, 13.0 Hz, 1H), 1.81 (m, 2H), 1.95
(m, 2H), 2.29 (ddd, J¼6.0, 6.0, 6.0 Hz, 1H), 3.15 (ddd,
J¼4.5, 10.5, 10.5 Hz, 1H), 3.21 (s, 3H), 3.39 (m, 5H), 3.49
(dd, J¼7.0, 14.0 Hz, 1H), 3.68 (d, J¼9.5 Hz, 1H), 3.92 (m,
3H), 4.74 (s, 2H), 5.00 (d, J¼10.5 Hz, 1H), 5.02 (dd,
J¼1.0, 11.0 Hz, 1H), 5.06 (d, J¼18.0 Hz, 1H), 5.07 (dd,
J¼1.5, 17.5 Hz, 1H), 5.79 (ddt, J¼10.0, 17.0, 7.0 Hz, 1H),
7.27–7.41 (m, 11H), 7.69 (m, 4H); 13C NMR (125 MHz,
CDCl3) d 19.2, 23.9, 26.9, 32.3, 34.2, 34.4, 36.1, 56.0,
59.2, 64.4, 66.7, 70.2, 73.1, 73.7, 74.8, 80.7, 98.0, 116.3,
116.4, 127.2, 127.6, 127.6, 127.6, 129.2, 129.5, 133.6,
133.8, 135.3, 135.5, 135.6, 135.6, 135.7, 139.2; IR (film)
cmꢀ1 3071m, 2931s, 2858s, 1428m, 1105s; mass spectrum
(ESI): m/e 695.6 (M+Na)+; ESIHRMS m/e calcd for
C41H56O6SiNa: 695.3738, found: 695.3760.
4.5.3. Cyclic ketal 47. To a solution of 44 [5.00 mg,
˚
0.0094 mmol] in CH2Cl2 [0.1 mL] were added MS 4 A
[10 mg] and 3-butene-1-ol [6.77 mg, 0.094 mmol] followed
by Tf2NH [2.64 mg, 0.0094 mmol] at ꢀ78 ꢁC. The solution
was stirred at ꢀ78 ꢁC for 5 min before quenching with Et3N
[0.10 mL] at ꢀ78 ꢁC. The mixture was warmed to rt and
filtered through Celite. After evaporation of the solvent
under reduced pressure, the resulting crude residue was
4.5.6. Cyclic ketal 50. To a solution of 44 [40.0 mg,
˚
0.075 mmol] in CH2Cl2 [0.8 mL] were added MS 4 A
[40 mg], alcohol 49 [187.0 mg, 0.75 mmol], and Tf2NH
[10.5 mg, 0.038 mmol] at ꢀ78 ꢁC. The solution was stirred
at ꢀ78 ꢁC for 15 min before quenching with Et3N [1 mL] at
ꢀ78 ꢁC. The mixture was warmed to rt and filtered through