758
M. A. Brimble, C. V. Burgess
PAPER
1H NMR (400 MHz, CDCl3): d = 3.33 (s, 3 H, 8¢¢-H), 3.44–3.47 (m,
2 H, 6¢¢-H), 3.54–3.56 (m, 2 H, 5¢¢-H), 3.58 (s, 3 H, 2¢-OMe), 3.86
(s, 3 H, 4¢-OMe), 4.07 (t, J = 6.4 Hz, 1 H, CH2OH), 4.52 (s, 2 H, 1¢¢-
H), 4.60 (s, 2 H, 3¢¢-H), 4.76 (d, J = 6.4 Hz, 2 H, CH2OH), 6.43 (d,
J = 2.2 Hz, 1 H, 3¢-H), 6.65 (d, J = 2.2 Hz, 1 H, 5¢-H), 7.23–7.29 (m,
1 H, 5¢¢¢-H), 7.41–7.44 (m, 1 H, 6¢¢¢-H), 7.48–7.50 (m, 2 H, 3¢¢¢-H
and 4¢¢¢-H).
13C NMR (75 MHz, CDCl3): d = 55.5 (CH3, OMe), 55.98 (CH3,
OMe), 56.00 (CH2, CH2OH), 58.9 (CH3, C-8¢¢¢), 67.0 (CH2, C-5¢¢¢),
67.5 (CH2, C-1¢¢¢), 71.7 (CH2, C-6¢¢¢), 95.2 (CH2, C-3¢¢¢), 101.4 (CH,
C-4¢), 106.5 (CH, C-6¢), 122.6 (C, C-2¢), 127.1 (CH, C-5¢¢), 128.7
(CH, C-3¢¢), 131.1 (CH, C-6¢¢), 131.9 (CH, C-4¢¢), 137.1 (C, C-1¢¢),
139.1 (C, C-2¢¢), 141.3 (C, C-1¢), 159.2 (C, C-3¢), 159.4 (C, C-5¢),
200.3 (C, C-1).
13C NMR (100 MHz, CDCl3): d = 55.4 (CH3, OMe), 55.7 (CH3,
OMe), 58.9 (CH3, C-8¢¢), 64.7 (CH2, CH2OH), 66.91 (CH2, C-5¢¢),
66.94 (CH2, C-1¢¢), 71.6 (CH2, C-6¢¢), 94.9 (CH2, C-3¢¢), 98.1 (CH,
C-3¢), 105.2 (CH, C-5¢), 121.5 (C, C-1¢), 127.4 (CH, C-5¢¢¢), 130.4
(CH, C-3¢¢¢), 131.8 (CH, C-6¢¢¢), 132.5 (CH, C-4¢¢¢), 138.7 (C, C-
1¢¢¢), 139.1 (C, C-6¢), 141.7 (C, C-2¢¢¢), 158.8 (C, C-2¢), 161.9 (C, C-
4¢), 200.3 (C, C-1).
MS (EI, 70 eV): m/z (%) = 391 (8%) [M + H+], 373 (9), 285 (23),
255 (9), 152 (9), 124 (10).
HRMS–FAB: m/z [M + H+] calcd for C21H26O7: 391.1757; found:
391.1771.
MS (EI, 70 eV): m/z (%) = 372 (18) [M+ – H2O], 296 (26), 284 (55),
268 (31), 255 (40), 253 (34), 239 (46), 165 (23), 152 (19), 59 (19),
45 (100).
HRMS (EI): m/z [M – H2O]+ calcd for C21H26O7: 372.1573; found:
372.1568.
(2,4-Dimethoxy-6-{[(2-methoxyethoxy)methoxy]methyl}phe-
nyl)[2-(hydroxymethyl)-3,5-dimethoxyphenyl]methanone (14)
Compound 14 was prepared as described above for 9: 1.6 M n-BuLi
in hexane (0.15 mL, 0.24 mmol) and 8 (80 mg, 0.24 mmol) were
combined in anhyd THF (2 mL) at –78 °C under N2, and LiBr (10
mg, 0.20 mmol) and 5 (48 mg, 0.25 mmol) were added in anhyd
THF (1 mL).
[2-(Hydroxymethyl)-5-methoxyphenyl](2-{[(2-methoxy-
ethoxy)methoxy]methyl}phenyl)methanone (12)
Compound 12 was prepared as described above for 9: 1.6 M n-BuLi
in hexane (0.30 mL, 0.48 mmol) and 6 (129 mg, 0.47 mmol) were
combined in anhyd THF (2 mL) at –78 °C under N2, and LiBr (22
mg, 0.25 mmol) and 416,17 (82 mg, 0.50 mmol) were added in anhyd
THF (2 mL).
Yield: 34 mg (32%); colourless oil.
IR (film): 3432, 2924, 1647, 1152, 1039 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.33 (s, 3 H, 8¢¢-H), 3.46–3.49 (m,
2 H, 6¢¢-H), 3.57 (s, 3 H, 2¢-OMe), 3.59–3.62 (m, 2 H, 5¢¢-H), 3.67
(s, 3 H, 5¢¢¢-OMe), 3.85 (s, 3 H, 4¢-OMe), 3.87 (s, 3 H, 3¢¢¢-OMe),
4.55 (s, 2 H, 1¢¢-H), 4.64 (s, 2 H, 3¢¢-H), 4.71 (s, 2 H, CH2OH), 6.39
(d, J = 2.1 Hz, 1 H, 3¢-H), 6.47 (d, J = 2.4 Hz, 1 H, 6¢¢¢-H), 6.59 (d,
J = 2.4 Hz, 1 H, 4¢¢¢-H), 6.64 (d, J = 2.1 Hz, 1 H, 5¢-H).
Yield: 67 mg (40%); colourless oil.
IR (film): 3433, 2930, 1657, 1110, 1043 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.34 (s, 3 H, 8¢¢¢-H), 3.47–3.50
(m, 2 H, 6¢¢¢-H), 3.61–3.64 (m, 2 H, 5¢¢¢-H), 3.73 (s, 3 H, 5¢-OMe),
4.58 (d, J = 3.7 Hz, 2 H, CH2OH), 4.65 (s, 2 H, 3¢¢¢-H), 4.74 (s, 2 H,
1¢¢¢-H), 6.88 (d, J = 2.7 Hz, 1 H, 6¢-H), 7.03 (dd, J = 8.4, 2.7 Hz,
1 H, 4¢-H), 7.33 (ddd, J = 7.3, 7.3, 1.4 Hz, 1 H, 5¢¢-H), 7.37 (dd,
J = 7.3, 1.9 Hz, 1 H, 6¢¢-H), 7.43 (d, J = 8.4 Hz, 1 H, 3¢-H), 7.51
(ddd, J = 7.3, 7.3, 1.9 Hz, 1 H, 4¢¢-H), 7.57 (d, 1 H, J = 7.3 Hz, 3¢¢-
H).
13C NMR (100 MHz, CDCl3): d = 55.5 (CH3, C-8¢¢¢), 59.0 (CH3,
OMe), 63.8 (CH2, CH2OH), 67.0 (CH2, C-5¢¢¢), 67.4 (CH2, C-1¢¢¢),
71.7 (CH2, C-6¢¢¢), 95.2 (CH2, C-3¢¢¢), 117.0 (CH, C-4¢), 117.8 (CH,
C-6¢), 127.2 (CH, C-5¢¢), 128.9 (CH, C-3¢¢), 130.3 (CH, C-6¢¢), 131.5
(CH, C-4¢¢), 132.1 (CH, C-3¢), 134.4 (C, C-2¢), 137.8 (C, C-1¢¢),
138.5 (C, C-2¢¢), 139.2 (C, C-1¢), 158.5 (C, C-5¢), 200.7 (C, C-1).
13C NMR (75 MHz, CDCl3): d = 55.4 (CH3, OMe), 55.5 (CH3,
OMe), 55.6 (CH2, CH2OH), 55.9 (CH3, OMe), 56.1 (CH3, OMe),
58.9 (CH3, C-8¢¢), 67.0 (CH2, C-1¢¢ and C-5¢¢), 71.7 (CH2, C-6¢¢),
95.0 (CH2, C-3¢¢), 98.2 (CH, C-3¢), 101.5 (CH, C-4¢¢¢), 105.4 (CH,
C-5¢), 106.9 (CH, C-6¢¢¢), 121.5 (C, C-1¢), 122.4 (C, C-2¢¢¢), 139.6
(C, C-6¢), 142.7 (C, C-1¢¢¢), 159.1 (C, C-3¢¢¢), 159.3 (C, C-2¢), 159.4
(C, C-5¢¢¢), 162.1 (C, C-4¢), 199.9 (C, C-1).
MS (EI, 70 eV): m/z (%) = 432 (20) [M+ – H2O], 372 (15), 359 (38),
342 (100), 329 (15), 315 (42), 311 (52), 299 (35), 284 (18), 269
(13), 193 (47), 164 (36), 151 (34), 89 (16), 59 (47), 45 (35).
HRMS (EI): m/z [M – H2O]+ calcd for C23H30O9: 432.1784; found:
432.1776.
1,1¢-Spirobi(3H,3¢H)isobenzofuran (15)
MS (EI, 70 eV): m/z (%) = 342 (4) [M+ – H2O], 252 (73), 239 (38),
224 (62), 221 (53), 181 (30), 165 (30), 89 (39), 59 (100), 45 (39).
HRMS (EI): m/z [M – H2O]+ calcd for C20H24O6: 342.1459; found:
342.1459.
TMSBr (0.20 mL, 1.51 mmol) was added dropwise to a mixture of
9 (110 mg, 0.37 mmol) in anhyd CH2Cl2 (5 mL) containing 4-Å MS,
and the mixture was stirred at 0 °C under N2 for 30 min. The reac-
tion was quenched with sat. NaHCO3 (10 mL) and the mixture was
extracted with Et2O (2 × 10 mL). The organic layers were com-
bined, washed with H2O (10 mL), and dried (MgSO4). The solvents
were removed under reduced pressure and the crude product was
purified by flash chromatography (silica gel, hexane–EtOAc, 9:1,
then 4:1).
[2-(Hydroxymethyl)-3,5-dimethoxyphenyl](2-{[(2-methoxy-
ethoxy)methoxy]methyl}phenyl)methanone (13)
Compound 13 was prepared as described above for 9: 1.6 M n-BuLi
in hexane (0.25 mL, 0.40 mmol) and 6 (102 mg, 0.37 mmol) were
combined in anhyd THF (2 mL) at –78 °C under N2, and LiBr (17
mg, 0.20 mmol) and 518 (55 mg, 0.28 mmol) were added in anhyd
THF (1 mL).
Yield: 40 mg (53%); yellow solid; mp 96–98 °C.
IR (film): 2913, 2865, 1609, 1459, 1361, 1309, 1262, 1030, 1010,
926 cm–1.
Yield: 39 mg (35%); colourless oil.
IR (film): 3467, 2935, 1665, 1149, 1047 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.15 (d, J = 12.7 Hz, 2 H, 3-HA,
3¢-HA), 5.32 (d, J = 12.7 Hz, 2 H, 3-HB, 3¢-HB), 7.09 (d, J = 7.7 Hz,
2 H, 7-H, 7¢-H), 7.31 (dd, J = 7.7, 7.6 Hz, 2 H, 6-H, 6¢-H), 7.34 (d,
J = 7.5 Hz, 2 H, 4-H, 4¢-H), 7.41 (ddd, J = 7.6, 7.5, 0.9 Hz, 2 H, 5-
H, 5¢-H).
13C NMR (100 MHz, CDCl3): d = 71.6 (CH2, C-3, C-3¢), 119.6 (C,
C-1), 120.9 (CH, C-4, C-4¢), 123.3 (CH, C-7, C-7¢), 128.0 (CH, C-
6, C-6¢), 129.3 (CH, C-5, C-5¢), 139.3 (C, C-7a, C-7a¢), 140.1 (C, C-
3a, C-3a¢).
1H NMR (300 MHz, CDCl3): d = 3.28 (1 H, br s, CH2OH), 3.34 (s,
3 H, 8¢¢¢-H), 3.48–3.51 (m, 2 H, 6¢¢¢-H), 3.64–3.67 (m, 2 H, 5¢¢¢-H),
3.70 (s, 3 H, 5¢-OMe), 3.87 (s, 3 H, 3¢-OMe), 4.60 (s, 2 H, CH2OH),
4.71 (s, 2 H, 3¢¢¢-H), 4.82 (s, 2 H, 1¢¢¢-H), 6.39 (d, J = 2.4 Hz, 1 H,
6¢-H), 6.61 (d, J = 2.4 Hz, 1 H, 4¢-H), 7.30 (ddd, J = 7.6, 7.5, 0.9 Hz,
1 H, 5¢¢-H), 7.40 (dd, J = 7.6, 1.4 Hz, 1 H, 6¢¢-H), 7.50 (ddd, J = 7.5,
7.5, 1.4 Hz, 1 H, 4¢¢-H), 7.60 (d, J = 7.5 Hz, 1 H, 3¢¢-H).
Synthesis 2007, No. 5, 754–760 © Thieme Stuttgart · New York