S. Kobayashi et al. / Tetrahedron 67 (2011) 9087e9092
9091
washed with brine, dried over anhydrous MgSO4, and concentrated.
The residue was purified by flash chromatography on silica gel
(hexane/EtOAc¼4/1/1/1) to give 9 (9.0 mg, 0.025 mmol, 15%).
Conditions B: Aryl bromide 8 (358 mg, 1.18 mmol), geranyl
tributyltin (1.00 g, 2.36 mmol), (Ph3P)2PdCl2 (84.0 mg, 0.120 mmol),
and CsF (359 mg, 2.36 mmol) were dissolved in DMF (5.9 mL). The
solution was warmed to 80 ꢀC and stirred for 13 h. The insoluble
materials were removed by filtration through a pad of Celite and
successively washed with diethyl ether. The filtrate was treated
with saturated aqueous KF solution and stirred at room tempera-
ture for 1 h. The mixture was extracted with diethyl ether (3ꢂ), and
the combined organic layer was dried over anhydrous MgSO4 and
concentrated. The residue was purified by flash chromatography on
silica gel (hexane/EtOAc¼3/1) to give the coupling product 9
(370 mg, 1.03 mmol, 87%) as a colorless solid: 1H NMR (400 MHz,
43% for two steps), 13 (4.1 mg, 0.0068 mmol, 10% for two steps), 14
(22.5 mg, 0.0267 mmol, 37% in two steps), and the recovery of diol
11 (2.7 mg, 0.0074 mmol, 10%). Data for 11: colorless oil; 1H NMR
(400 MHz, CDCl3)
d 6.77 (s, 1H), 5.10e5.13 (m, 2H), 5.03e5.06 (m,
2H), 4.93 (s, 2H), 4.71 (d, 4H, J¼8.8 Hz), 3.84 (s, 3H), 3.62 (s, 3H),
3.33 (d, 2H, J¼6.4 Hz), 1.94e2.08 (m, 4H), 1.75 (s, 3H), 1.64 (s, 3H),
1.57 (s, 3H); 13C NMR (400 MHz, CDCl3)
d 158.3, 156.1, 140.1, 135.2,
131.4, 125.4, 124.3, 122.9, 122.6, 108.5, 100.4, 64.5, 57.5, 56.6, 55.7,
39.7, 26.7, 25.7, 23.6, 17.7, 16.3; FT-IR (KBr) 3311, 3235, 2926, 2855,
1604, 1577, 1458, 1400 cmꢁ1; MS (EI, 70 eV) m/z (%) 364 (Mþ, 2), 302
(49), 259 (30), 233 (100), 219 (65), 197 (96), 162 (26); HRMS (EI): m/
z calcd for C21H32O5: 364.2250, found: 364.2252. Data for 12: col-
orless oil; 1H NMR (400 MHz, CDCl3)
d 6.75 (s, 1H), 5.25 (s, 2H), 5.11
(m, 1H), 5.04 (m, 1H), 4.98 (s, 2H), 4.65 (d, 2H, J¼6.8 Hz), 3.83 (s,
3H), 3.63 (s, 3H), 3.33 (d, 2H, J¼6.4 Hz), 3.07 (t, 1H, J¼6.8 Hz, OH),
2.34 (t, 2H, J¼7.2 Hz), 2.08e1.95 (m, 4H), 1.75 (s, 3H), 1.64 (s, 3H),
1.60 (m, 2H), 1.57 (s, 3H), 1.25 (m, 24H), 0.88 (t, 3H, J¼6.4 Hz); 13C
CDCl3) d 6.65 (s, 1H, H4), 5.39 (s, 2H, MOM), 5.17 (s, 2H, H3), 5.15 (m,
1H, H20), 5.05 (m, 1H, H60), 3.90 (s, 3H, MOM), 3.58 (s, 3H, OMe),
3.45 (d, 2H, J¼6.8 Hz, H10), 2.04 (m, 2H, H50), 1.95 (m, 2H, H40), 1.77
(s, 3H, C30-Me), 1.64 (s, 3H, C70-Me), 1.57 (s, 3H, C70-Me); 13C NMR
NMR (100 MHz, CDCl3)
d 173.8, 158.3, 156.4, 135.4, 134.3, 131.5,
126.4, 124.3, 123.9, 122.6, 108.9, 100.4, 64.2, 57.6, 56.2, 55.8, 39.8,
34.5, 32.1, 29.8, 29.6, 29.5, 29.4, 29.3, 29.2, 26.7, 25.8, 25.1, 24.9, 23.8,
22.8, 17.8, 16.4, 14.3; FT-IR (KBr) 3460, 2954, 2917, 2849, 1740, 1604,
1578, 1467, 1395 cmꢁ1. Data for 13: colorless oil; 1H NMR (400 MHz,
(100 MHz, CDCl3)
d 169.3, 164.3, 155.0, 148.7, 135.7, 131.4, 124.6,
124.4, 121.9, 109.3, 101.1, 99.1, 68.8, 57.9, 56.2, 39.8, 26.7, 25.8, 23.0,
17.8, 16.3; FT-IR (KBr) 3124, 2925, 2844,1736,1698,1607,1467,1432,
1403, 1376 cmꢁ1; MS (EI, 70 eV) m/z (%) 360 (Mþ, 5), 315 (54), 261
(40), 259 (20), 247 (28); HRMS (EI): m/z calcd for C21H28O5:
360.1937, found: 360.1935.
CDCl3) d 6.85 (s, 1H), 5.27 (s, 2H), 5.13 (m, 1H), 5.04 (m, 1H), 4.94 (s,
2H), 4.71 (d, 2H, J¼6.4 Hz), 3.85 (s, 3H), 3.58 (s, 3H), 3.36 (d, 2H,
J¼6.4 Hz), 2.29 (t, 2H, J¼7.6 Hz), 2.08e1.94 (m, 4H), 1.75 (s, 3H), 1.64
(s, 3H), 1.60 (m, 2H), 1.57 (s, 3H), 1.26 (m, 24H), 0.88 (t, 3H,
4.1.8. (E)-6-(3,7-Dimethylocta-2,6-dienyl)-7-hydroxy-5-methoxyisob-
enzofuran-1(3H)-one (hericenone J, 10). To a solution of 9 (10.6 mg,
0.0294 mmol) in MeOH (1 mL) was added CSA (1.4 mg,
0.0059 mmol). The mixture was stirred at room temperature for 6
days before it was quenched by the addition of Et3N (1 mL). The re-
action mixture was concentrated and the residue was purified by
flash column chromatography on silica gel (hexane/EtOAc¼5/1) to
give hercenone J (10) (9.2 mg, 0.029 mmol, 99%) as a colorless solid;
J¼6.4 Hz); 13C NMR (75 MHz, CDCl3)
d 174.1, 159.2, 156.4, 140.2,
135.4, 131.5, 124.4, 123.5, 122.7, 119.3, 107.5, 100.9, 63.2, 59.1, 57.8,
55.8, 39.8, 34.5, 32.1, 29.83, 29.79, 29.7, 29.6, 29.5, 29.4, 29.3, 26.7,
25.8, 25.0, 23.7, 22.8, 17.8, 16.3, 14.3; FT-IR (KBr) 3444, 2917, 2848,
1739, 1708, 1604, 1578, 1463, 1427, 1403, 1384 cmꢁ1. Data for 14:
colorless oil; 1H NMR (400 MHz, CDCl3)
d 6.75 (s, 1H), 5.23 (s, 2H),
5.14 (s, 2H), 5.14 (m, 1H), 5.04 (m, 1H), 4.93 (s, 2H), 3.83 (s, 3H), 3.57
(s, 3H), 3.36 (d, 2H, J¼6.8 Hz), 2.37e2.26 (m, 4H), 2.05e1.95 (m, 4H),
1.74 (s, 3H), 1.64 (s, 3H), 1.60 (m, 4H), 1.57 (s, 3H), 1.26 (m, 48H), 0.88
1H NMR (400 MHz, CDCl3)
d 7.71 (s, 1H), 6.48 (s, 1H), 5.21 (s, 1H) 5.17
(t, 1H, J¼7.2 Hz), 5.04 (t, 1H, J¼6.8 Hz), 3.88 (s, 3H), 3.34 (d, 2H,
(t, 6H, J¼6.4 Hz); 13C NMR (100 MHz, CDCl3)
d 174.0, 173.7, 159.1,
J¼7.2 Hz), 2.03 (m, 2H), 1.95 (t, 2H, J¼7.6 Hz), 1.76 (s, 3H), 1.63 (s, 3H),
156.5, 135.4, 131.5, 124.5, 124.4, 122.7, 120.6, 108.6, 101.0, 64.1, 58.9,
57.8, 55.9, 39.9, 34.6, 34.6, 32.2, 29.9, 29.7, 29.6, 29.5, 29.4, 26.8,
25.9, 25.2, 23.8, 22.9, 17.9, 16.4, 14.4; FT-IR (KBr) 2955, 2917, 2849,
1.56 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 172.9 (C1), 164.9 (C5), 154.5
(C7), 146.1 (C3a), 135.9 (C30), 131.3 (C70), 124.4 (C60), 121.3 (C20), 116.9
(C6), 104.2 (C7a), 96.2 (C4), 70.5 (C3), 56.2 (OMe), 39.9 (C40), 26.7
(C50), 25.7 (C80), 21.6 (C10), 17.7 (C70-Me), 16.2 (C30-Me); FT-IR (KBr)
3427, 3002, 2979, 2920, 2859, 1736, 1698, 1619, 1492, 1467, 1449,
1349 cmꢁ1; MS (EI, 70 eV) m/z (%) 316 (Mþ, 8), 236 (28), 194 (57), 193
(100), 176 (24), 145 (24); HRMS (EI): m/z calcd for C19H24O4: 316.1675,
found: 316.1676.
1734, 1604, 1578, 1467, 1403 cmꢁ1
.
4.1.10. (E)-4-(3,7-Dimethylocta-2,6-dienyl)-2-formyl-3-hydroxy-5-
methoxybenzyl palmitate (hericene A, 15). To a solution of alcohol 12
(25.6 mg, 0.0425 mmol) in CH2Cl2 (3.2 mL) were added pyridine
(17.0
mL, 0.210 mmol) and DesseMartin periodinane (26.7 mg,
0.0630 mmol). The reaction mixture was stirred at room tempera-
ture for 3 h before it was quenched by the addition of saturated
aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution.
The mixture was stirred for 30 min and extracted with EtOAc (2ꢂ).
Thecombined organiclayerwas washed brine, driedoveranhydrous
MgSO4, and concentrated. The residue was purified by flash chro-
matography on silica gel (hexane/EtOAc¼10/1) to give aldehyde
(21.6 mg, 0.0360 mmol, 85%) as a colorless oil: 1H NMR (400 MHz,
4.1.9. (E)-4-(3,7-Dimethylocta-2,6-dienyl)-2-(hydroxymethyl)-5-
methoxy-3-(methoxymethoxy)benzyl palmitate (11). To a solution of
phthalide 9 (50.0 mg, 0.139 mmol) in THF (2.8 mL) was added
LiAlH4 (16.6 mg, 0.437 mmol) at 0 ꢀC. The mixture was stirred at
0 ꢀC for 30 min before it was quenched by the addition of H2O and
1 M aqueous NaOH solution. The resulting mixture was extracted
with EtOAc (3ꢂ), and the combined organic layer was washed with
1 M aqueous HCl solution, brine, dried over anhydrous MgSO4, and
concentrated to give diol 11 (53.8 mg). The diol 11 (26.0 mg,
0.0713 mmol) was dissolved in CH2Cl2 (1.5 mL) followed by the
CDCl3) d 10.35 (s, 1H), 6.83 (s, 1H), 5.52 (s, 2H), 5.11 (m, 1H), 5.03 (m,
1H), 5.02 (s, 2H), 3.90 (s, 3H), 3.56 (s, 3H), 3.36 (d, 2H, J¼6.4 Hz), 2.41
(t, 2H, J¼7.6 Hz), 2.07e1.97 (m, 4H), 1.76 (s, 3H), 1.68 (m, 2H), 1.64 (s,
3H), 1.57 (s, 3H), 1.25 (m, 24H), 0.88 (t, 3H, J¼7.6 Hz); 13C NMR
addition of pyridine (27
0.007 mmol), and palmitoyl chloride (11
The mixture was stirred at 0 ꢀC for 1 h and 11
m
L, 0.33 mmol), DMAP (0.8 mg,
L, 0.036 mmol) at 0 ꢀC.
L (0.036 mmol) each
m
(75 MHz, CDCl3) d 191.5, 173.4, 162.9, 161.3, 139.2, 136.0, 131.6, 124.3,
m
123.3,122.0,121.1,106.0,101.7, 64.4, 58.2, 55.9, 39.8, 34.6, 32.1, 29.83,
29.80, 29.76, 29.6, 29.5, 29.5, 29.4, 26.7, 25.8, 25.2, 23.1, 22.8, 17.8,
16.4,14.3; FT-IR (KBr) 2925, 2854,1742,1680,1598,1566,1465,1377,
1289, 1218, 1160, 1116, 1048 cmꢁ1; HRMS (FAB): m/z calcd for
C37H61O6 [MþH]þ 601.4468, found 601.4476.
of palmitoyl chloride was added twice at the intervals of 1 h with
stirring at 0 ꢀC. The reaction mixture was quenched with saturated
aqueous NaHCO3 solution and extracted with EtOAc (3ꢂ). The
combined organic layer was washed with brine, dried over anhy-
drous MgSO4, and concentrated. The residue was purified by flash
chromatography on silica gel (hexane/EtOAc¼15/1/6/1/3/1/1/
2 containing 5% MeOH) to give esters 12 (18.3 mg, 0.0304 mmol,
To a solution of the above aldehyde (7.0 mg, 0.012 mmol) in
CH2Cl2 (2 mL) was added Me2BBr (1.76 M in CH2Cl2, 11
mL,
0.019 mmol) at ꢁ78 ꢀC. The mixture was stirred at ꢁ78 ꢀC for 1.2 h