of K2CO3 (solid) and the solution was filtered through Celite. The
filtrate was concentrated in vacuo and the resultant brown oil puri-
fied by column chromatography to afford (3-allyl-4-benzyloxy-
6,8-dimethoxy-2-naphthyl)methanol (2.21 g, 95%) as a white
semisolid. Found M+ 364.1676, C23H24O4 requires M+ 364.1675;
1H NMR (300 MHz; CDCl3; Me4Si) 7.98 (1H, s, 1-H), 7.54–7.32
(5H, m, OCH2PhH), 6.90 (1H, d, J 1.9, 5-H), 6.45 (1H, d, J 1.9,
7-H), 6.13–6.04 (1H, m, ArCH2CHCH2), 5.03 (1H, dq, J 10.1 and
1.7, ArCH2CHCH2 cis), 4.97 (2H, s, OCH2Ph), 4.92 (1H, dq, J
17.2 and 1.7, OCH2CHCH2 trans), 4.78 (2H, br s, ArCH2OH),
3.93 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.72 (2H, dt, J 5.5 and
1.7, ArCH2CHCH2) and 1.90 (1H, br s, OH); 13C NMR (75 MHz;
CDCl3) 158.6 (ArC–O), 156.9 (ArC–O), 152.2 (ArC–O), 137.6
(ArC), 137.6 (ArC), 135.2 (OCH2CHCH2), 129.4 (ArC), 128.6
(2 × ArCH), 128.3 (ArC), 128.0 (ArCH), 127.6 (2 × ArCH), 121.6
(ArC), 117.9 (ArCH2CHCH2), 115.3 (ArC), 97.6 (5-C), 92.6
(7-C), 75.9 (OCH2Ph), 63.8 (ArCH2OH), 55.5 (OCH3), 55.2 (OCH3)
and 30.3 (ArCH2CHCH2); max(film)/cm−1 3419br (O–H), 3002w
(CH), 2936w (C–H), 1630s and 1603s (CC) and 1203s (C–O);
m/z 364 (M+, 19%), 274 (20), 273 (100), 255 (36), 243 (18), 217
(21) and 91 (30).
J 6.4 and 3.1, ArCH(CH3)OH, D2O wash, q, J 6.4], 5.05 (1H, dq,
J 10.2 and 1.8, ArCH2CHCH2 cis), 4.98 (2H, s, OCH2Ph), 4.91
(1H, dq, J 17.2 and 1.8,ArCH2CHCH2 trans), 3.95 (3H, s, OCH3),
3.77 (3H, s, OCH3), 3.85–3.78 (1H, m, one of ArCH2CHCH2),
3.66–3.59 (1H, m, one of ArCH2CHCH2), 1.87 (1H, br d, J 3.1,
OH) and 1.57 [3H, d, J 6.4, ArCH(CH3)OH]; 13C NMR (75 MHz;
CDCl3) 158.5 (ArC–O), 157.0 (ArC–O), 152.0 (ArC–O), 140.2
(ArC), 137.8 (ArC), 137.7 (ArCH2CHCH2), 129.0 (ArC), 128.6
(2 × ArCH), 128.0 (ArCH), 127.6 (2 × ArCH), 127.4 (ArC), 121.9
(1-C), 115.4 (ArC), 114.6 (ArCH2CHCH2), 97.5 (5-C), 92.5 (7-C),
75.9 (OCH2Ph), 66.6 [ArCH(CH3)OH], 55.5 (OCH3), 55.2 (OCH3),
30.0 (ArCH2CHCH2) and 24.6 [ArCH(CH3)OH]; max(film)/cm−1
3502br (O–H), 3001w (CH), 2969w (C–H), 1629s and 1598s
(CC) and 1202s (C–O); m/z 378 (M+, 22%), 288 (24), 287 (100),
269 (62), 231 (39) and 91 (21).
5-Benzyloxy-7,9-dimethoxy-1,3-dimethyl-1H-
benzo[g]isochromene 32
To a solution of the alcohol 31 (1.52 g, 4.02 mmol) in DMF (20 cm3),
stirred at rt under oxygen, was added copper(II) chloride dihydrate
(0.68 g, 4.0 mmol) and palladium(II) chloride (0.07 g, 0.40 mmol)
in H2O (10 cm3). The resultant suspension, which turned black after
a few min, was left to stir for 3 h. The reaction mixture was poured
into H2O (100 cm3) and extracted with CH2Cl2 (3 × 100 cm3). The
combined extracts were dried (MgSO4), filtered through Celite and
the filtrate concentrated in vacuo. The resultant dark oil was puri-
fied by column chromatography (10% EtOAc–hexane) to afford the
product 32 (1.39 g, 92%) as a white, waxy solid. Recrystallisation
from 2-propanol gave white crystals, mp 97–98 °C (iPrOH). Found
M+ 376.1674, C24H24O4 requires M+ 376.1675; 1H NMR (300 MHz;
CDCl3; Me4Si) 7.50 (1H, s, 10-H), 7.44–7.22 (5H, m, OCH2PhH),
6.78 (1H, d, J 2.1, 6-H), 6.29 (1H, d, J 2.1, 8-H), 5.91 (1H, s, 4-H),
5.18 (1H, q, J 6.4, 1-H), 4.88 (2H, s, OCH2Ph), 3.82 (3H, s, OCH3),
3.68 (3H, s, OCH3), 1.88 (3H, s, 3-CH3) and 1.58 (3H, d, J 6.4,
1-CH3); 13C NMR (75 MHz; CDCl3) 158.4 (ArC–O), 156.8
(ArC–O), 154.5 (ArC–O), 145.5 (ArC), 137.8 (ArC), 129.6 (ArC),
129.4 (ArC), 128.5 (2 × ArCH), 128.0 (ArCH), 127.9 (2 × ArCH),
122.0 (ArC), 120.9 (ArC), 112.4 (10-C), 96.8 (4-C), 95.8 (6-C),
92.6 (8-C), 75.7 (OCH2Ph), 74.3 (1-C), 55.5 (OCH3), 55.2 (OCH3),
20.44 (1-CH3) and 19.9 (3-CH3); max(film)/cm−1 3030w (CH),
2936m (C–H), 1651m, 1627s, 1605s and 1580m (CC) and 1157s
(C–O); m/z 376 (M+, 19%), 286 (23), 285 (100), 267 (37), 167 (25),
149 (24), 71 (9) and 57 (18).
3-Allyl-4-benzyloxy-6,8-dimethoxy-2-naphthaldehyde 30
Pyridinium chlorochromate (0.65 g, 3.02 mmol) was dissolved in
dry acetonitrile (20 cm3) and poured into neutral alumina (10.00 g).
The suspension was dried in vacuo and to the solid was then added
a
solution of 3-allyl-4-benzyloxy-6,8-dimethoxy-2-hydroxy-
methylnaphthalene (1.00 g, 2.74 mmol) in CH2Cl2 (50 cm3). The
reaction mixture was left to stir under Ar at rt for 8 h. Filtration
through Celite, concentration on a rotary evaporator and purifica-
tion of the resultant yellow oil by column chromatography (30%
EtOAc–hexane) gave the desired aldehyde 30 (0.78 g, 78%) as
a white solid. Recrystallisation from EtOAc–hexane gave white
needles, mp 94.5–95.0 °C (EtOAc–hexane). Found M+ 362.1519,
C23H22O4 requires M+ 362.1518; 1H NMR (300 MHz; CDCl3;
Me4Si) 10.17 (1H, s, CHO), 8.49 (1H, s, 1-H), 7.54–7.37 (5H,
m, OCH2PhH), 6.92 (1H, d, J 2.0, 5-H), 6.49 (1H, d, J 2.0, 7-H),
6.18–6.09 (1H, m, ArCH2CHCH2), 5.03 (1H, dq, J 10.2 and
1.7, ArCH2CHCH2 cis), 4.99 (2H, s, OCH2Ph), 4.94 (1H, dq, J
17.2 and 1.7, ArCH2CHCH2 trans), 4.05 (2H, dt, J 5.6 and 1.7,
ArCH2CHCH2), 3.98 (3H, s, OCH3) and 3.79 (3H, s, OCH3);
13C NMR (75 MHz; CDCl3) 192.3 (CHO), 161.6 (ArC–O),
158.2 (ArC–O), 152.4 (ArC–O), 137.7 (ArC), 137.6 (ArC), 133.2
(ArCH2CHCH2), 130.2 (ArC), 129.3 (ArC), 128.6 (2 × ArCH),
128.2 (ArCH), 127.6 (2 × ArCH), 127.1 (ArC), 120.9 (C-1), 115.4
(ArCH2CHCH2), 98.2 (5-C), 93.2 (7-C), 76.1 (OCH2Ph), 55.7
(OCH3), 55.3 (OCH3) and 29.6 (ArCH2CHCH2); max(film)/cm−1
3005w (CH), 2938w (C–H), 2861w and 2723w (CHO), 1688s
(CO), 1622m (CC) and 1156s (C–O); m/z 362 (M+, 31%), 272
(19), 271 (100), 243 (40), 228 (24), 185 (11) and 91 (44).
(±)-cis-7,9-Dimethoxy-1,3-dimethyl-1H-benzo[g]isochroman-
5-ol 33
To a solution of the benzyloxyisochromene 32 (1.00 g, 2.66 mmol)
in CH2Cl2–dioxane (3:1, 25 cm3), stirred at rt under hydrogen
(1 atm), was added Pd/C (0.10 g, 10% w/w) and stirring continued
for 48 h. The reaction mixture was then filtered through Celite,
the filtrate concentrated in vacuo and the resultant oil purified by
column chromatography (10–30% EtOAc–hexane). This afforded
the desired product 33 as a mixture (3:1 cis:trans) of diastereomers
(0.39 g, 51%), as well as starting material (0.31 g). Recrystallisa-
tion of the product thus isolated from EtOAc–hexane gave solely
rac-cis-33 (0.27 g, 35%) as white leaflets which started subliming
at 138 °C and melted at 178–179 °C. Found M+ 288.1363, C17H20O4
requires M+ 288.1362; 1H NMR (300 MHz; CDCl3; Me4Si) 7.51
(1H, s, OH), 7.49 (1H, s, 10-H), 7.09 (1H, d, J 1.9, 6-H), 6.43 (1H,
d, J 1.9, 8-H), 4.95 (1H, q, J 6.2, 1-H), 3.94 (3H, s, OCH3), 3.90
(3H, s, OCH3), 3.90–3.81 (1H, m, 3-H), 2.95 (1H, dd, J 16.3 and 3.0,
4-H pseudo-equatorial), 2.61 (1H, dd, J 16.3 and 11.1, 4-H pseudo-
1-(3-Allyl-4-benzyloxy-6,8-dimethoxy-2-naphthyl)-1-ethanol
31
To a solution of methylmagnesium iodide [freshly prepared from
magnesium metal turnings (0.12 g, 4.9 mmol) and iodomethane
(0.31 cm3, 0.72 g, 5.1 mmol) in anhydrous Et2O (40 cm3)] stirred
at 0 °C under Ar, was added a solution of 3-allyl-4-benzyloxy-6,8-
dimethoxynaphthalene-2-carbaldehyde 30 (1.22 g, 3.37 mmol) in
dry THF (20 cm3). The resultant cloudy mixture was allowed to
warm up to rt over 8 h, re-cooled to 0 °C and quenched with H2O.
This was then poured into H2O (75 cm3) and extracted with EtOAc
(3 × 100 cm3). The combined organic layers were dried (MgSO4),
filtered through Celite and concentrated in vacuo. Purification of
the resultant oil by column chromatography (30% EtOAc–hexane)
gave the target alcohol (1.21 g, 95%) as a white solid. Recrystallisa-
tion from EtOAc–hexane gave white needles, mp 120.5–121.5 °C
(EtOAc–hexane). Found M+ 378.1831, C24H26O4 requires M+
378.1831; 1H NMR (300 MHz; CDCl3; Me4Si) 8.17 (1H, s, 1-H),
7.54–7.36 (5H, m, OCH2PhH), 6.90 (1H, d, J 2.0, 5-H), 6.46 (1H,
d, J 2.0, 7-H), 6.15–6.06 (1H, m, ArCH2CHCH2), 5.20 [1H, qd,
axial), 1.65 (3H, d, J 6.2, 1-CH3) and 1.35 (3H, d, J 6.2, 3-CH3); 13
C
NMR (75 MHz; CDCl3) 157.1 (ArC–O), 156.1 (ArC–O), 147.5
(ArC–O), 135.1 (ArC), 124.6 (ArC), 120.6 (ArC), 117.2 (ArC),
108.5 (10-C), 97.0 (6-C), 91.9 (8-C), 73.5 (1-C), 70.3 (3-C), 55.2
(OCH3), 55.1 (OCH3), 31.5 (4-C), 21.9 (1-CH3) and 21.8 (3-CH3);
max(film)/cm−1 3401br (O–H), 2967s (CH), 2932s (C–H), 1633m
and 1602s (CC) and 1152s (C–O); m/z 288 (M+, 72%), 273 (100),
244 (26), 229 (11), 128 (6), 115 (8) and 43 (9).
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 4 6 1 – 2 4 7 0
2 4 6 9