PAPER
Total Synthesis of Marchantinquinone
1407
The crude material was purified by CC [silica gel, Et2O/petroleum
ether (2:1)]; yield: 2.93 g (90%); yellowish crystals; mp: 65-66 ºC.
ArH), 7.60 (d, 1H, J = 2.0 Hz, ArH), 7.68 (d, 1H, J = 7.9 Hz, ArH),
7.84 (dd, 1H, J = 8.6, 2.0 Hz, ArH).
1H NMR: d = 2.71-2.75 (m, 2H, CH2), 2.82-2.86 (m, 2H, CH2),
3.71 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 3.92
(s, 6H, OCH3), 6.77 (d, 1H, J = 9.0 Hz, ArH), 6.83-6.86 (m, 3H,
ArH), 6.92 (dd, 1H, J = 9.1, 2.7 Hz, ArH), 7.01-7.05 (m, 4H, ArH),
7.60 (d, 1H, J = 2.0 Hz, ArH), 7.85 (dd, 1H, J = 8.5, 2.0 Hz, ArH),
8.00 (d, 1H, J = 9.1 Hz, ArH).
13C NMR: d = 26.76, 35.06, 52.34, 53.70, 56.37, 56.50, 56.61,
108.43, 110.87, 112.16, 115.78, 116.94, 117.94, 121.67, 123.46,
125.42, 126.94, 127.00, 129.96, 131.46, 137.02, 141.10, 141.27,
145.83, 146.16, 152.93, 155.51, 155.80, 162.61, 166.75.
13C NMR: d = 26.95, 35.16, 52.31, 52.49, 56.33, 56.48, 56.80,
107.73, 110.99, 112.14, 115.78, 116.22, 117.80, 119.99, 121.76,
123.20, 123.46, 125.91, 126.93, 129.76, 129.98, 131.96, 137.52,
142.25, 145.85, 147.07, 153.01, 155.54, 155.68, 159.02, 166.75,
167.18.
IR (film): n: 2950, 2820, 1721 (COOCH3), 1605, 1584, 1507, 1489,
1437, 1223, 1130 cm-1.
MS: m/z (%) = 572 (M+, 21), 301 (4), 271 (100).
Anal. Calcd. for C33H32O9: C, 69.22; H, 5.63. Found: C, 69.37; H,
5.79.
IR (KBr): n = 2950, 2830, 1736 (COOCH3), 1719 (COOCH3),
1609, 1578, 1509, 1489, 1437, 1343 (NO2), 1223, 1130 cm-1.
[3-(4-{2-[2-(3-Hydroxymethylphenoxy)-3,6-dimethoxyphe-
nyl]ethyl}phenoxy)-4-methoxyphenyl]methanol (14)
MS: m/z (%) = 617 (M+, 9), 271 (100).
Diol 14 was prepared in a similar way as described in the
literature17b by reduction of a solution of 13 [0.91 g, 1.6 mmol in
THF (15mL)] with LiAlH4 (0.18 g, 4.8 mmol). The crude was puri-
fied by CC (silica gel, Et2O); yield: 0.71 g (86%); colorless oil.
1H NMR: d = 2.70-2.72 (m, 2H, CH2), 2.82-2.84 (m, 2H, CH2),
3.72 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 4.54
(s, 2H, CH2OH), 4.62 (s, 2H, CH2OH), 6.73 (d, 1H, J = 8.9 Hz,
ArH), 6.74 (dd, 1H, J = 7.8, 2.0 Hz, ArH), 6.83 (m, 4H, ArH), 6.91
(d, 1H, J = 2.0 Hz, ArH), 6.96-7.02 (m, 4H, ArH), 7.07 (dd, 1H,
J = 9.0, 2.0 Hz ArH), 7.24 (t, 1H, J = 7.8 Hz, ArH).
13C NMR: d = 26.99, 35.06, 56.33, 56.56, 56.91, 65.13, 65.52,
107.49, 110.94, 113.12, 113.75, 114.39, 118.14, 119.25, 120.32,
123.10, 126.00, 129.93, 134.39, 137.49, 142.59, 143.04, 146.56,
147.30, 150.92, 153.05, 155.75, 159.22.
Anal. Calcd. for C33H31NO11: C, 64.18; H, 5.06; N, 2.27. Found: C,
64.03; H, 5.17; N, 2.01.
Methyl 3-(4-{2-[2-(4-Amino-3-methyoxycarbonylphenoxy)-3,6-
dimethoxyphenyl]ethyl}phenoxy)-4-methoxybenzoate (12)
The stilbene 11 (1.00 g, 1.6 mmol) was dissolved in EtOAc
(50 mL), palladium on activated charcoal (5% Pd/C, 50 mg/mmol)
was added and the hydrogenation performed at 3-5 bar for 2 h. The
catalyst was filtered off and the solvent removed in vacuo. The
crude material was purified by CC (aluminum oxide, EtOAc/petro-
leum ether): yield: 0.95 g (100%); colorless oil.
1H NMR: d = 2.69-2.73 (m, 2H, CH2), 2.85-2.89 (m, 2H, CH2),
3.73 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.86
(s, 3H, OCH3), 3.92 (s, 3H, OCH3), 5.44 (br s, 2H, ArNH2), 6.61 (d,
1H, J = 8.9 Hz, ArH), 6.70 (d, 1H, J = 8.9 Hz, ArH), 6.83 (d, 1H,
J = 8.9 Hz, ArH), 6.84 (d, 2H, J = 8.1 Hz, ArH), 6.89 (dd, 1H,
J = 8.9, 3.0 Hz, ArH), 7.02 (d, 1H, J = 8.6 Hz, ArH), 7.07 (d, 2H,
J = 8.1 Hz, ArH), 7.34 (d, 1H, J = 3.0 Hz, ArH), 7.60 (d, 1H,
J = 1.9 Hz, ArH), 7.85 (dd, 1H, J = 8.6, 1.9 Hz, ArH).
IR (film): n = 3412 (OH), 2950, 2820, 1609, 1584, 1507, 1489,
1442, 1260 cm-1.
MS: m/z (%) = 516 (M+, 18), 243 (100), 227 (26), 211 (9).
Anal. Calcd. for C31H32O7: C, 72.08; H, 6.24. Found: C, 72.38; H,
5.99.
13C NMR: d = 26.93, 35.16, 51.93, 52.32, 56.32, 56.50, 56.96,
107.29, 111.08, 111.52, 112.14, 116.22, 117.82, 118.22, 121.68,
122.77, 123.46, 126.10, 126.88, 130.02, 137.74, 143.19, 145.85,
145.91, 147.43, 149.96, 153.03, 155.52, 155.61, 166.77, 168.60.
2-{2-[4-(5-Chloromethyl-2-methoxyphenoxy)phenyl]ethyl}-3-
(3-chloromethylphenoxy)-1,4-dimethoxybenzene (15)
To a suspension of diol 14 (0.7 g, 1.4 mmol) in dry Et2O (15 mL)
was added dropwise thionyl chloride (0.71 g, 8.1 mmol) and the
mixture was refluxed for 2 h and then poured onto crushed ice. The
organic layer was washed with aqueous NaHCO3 (2 ¥ 25 mL) and
H2O, dried (MgSO4) and concentrated. The crude material was pu-
rified by CC (silica gel, Et2O); yield: 0.62 g (82%); colorless oil.
IR (film): n = 3480 (NH2), 3372 (NH2), 2950, 2820, 1717
(COOCH3), 1698 (COOCH3), 1604, 1590, 1507, 1489, 1437, 1291,
1278, 1257, 1244, 1130 cm-1.
MS: m/z (%) = 587 (M+, 100), 316 (3), 271 (64), 167 (50), 164 (18),
107 (5), 59 (6).
1H NMR: d = 2.68-2.72 (m, 2H, CH2), 2.82-2.86 (m, 2H, CH2),
3.73 (s, 3H, OCH3), 3.83 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 4.50
(s, 2H, CH2Cl), 4.54 (s, 2H, CH2Cl), 6.74 (d, 1H, J = 9.0 Hz, ArH),
6.78 (ddd, 1H, J = 7.9, 2.2, 0.8 Hz, ArH), 6.84-6.86 (m, 3H, ArH),
6.89 (t, 1H, J = 2.2 Hz, ArH), 6.94 (d, 1H, J = 2.2 Hz, ArH), 6.97
(d, 1H, J = 8.4 Hz, ArH), 7.02-7.04 (m, 3H, ArH), 7.12 (dd, 1H,
J = 8.4, 2.2 Hz, ArH), 7.25 (t, 1H, J = 7.9 Hz, ArH).
13C NMR: d = 27.03, 35.11, 46.34, 46.45, 56.34, 56.53, 56.85,
107.60, 110.85, 113.09, 115.30, 115.48, 118.02, 120.75, 122.09,
124.80, 126.00, 129.97, 130.11, 130.77, 137.56, 139.32, 142.38,
146.39, 147.25, 151.61, 153.00, 155.65, 159.19.
Anal. Calcd. for C33H33NO9: C, 67.45; H, 5.66; N, 2.38. Found: C,
67.60; H, 5.49; N, 2.19.
Methyl 3-(4-{-2-[3,6-Dimethoxy-2-(3-methyoxycarbonylphe-
noxy)phenyl]ethyl}phenoxy)-4-methoxybenzoate (13)
A solution of 12 (1.00 g, 1.7 mmol) in HOAc (10 mL) and concd
HCl (5 mL) was cooled to 0 ºC. Aqueous sodium nitrite [150 mg,
2 mmol in H2O (1 mL)] was added dropwise and the mixture was
stirred for 20 min. After addition of hypophosphorous acid (1.5 mL
of a 50% aqueous solution), the mixture was stirred for 12 h at 0 ºC.
It was extracted with Et2O (2 ¥ 10 mL) and the combined organic
layer washed with H2O and dried (MgSO4). The solvent was evap-
orated under reduced pressure and the residue was purified by CC
(silica gel, Et2O); yield: 0.70 g (70%); colorless oil.
1H NMR: d = 2.68-2.72 (m, 2H, CH2), 2.83-2.87 (m, 2H, CH2),
3.71 (s, 3H, OCH3), 3.82 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 3.89
(s, 3H, OCH3), 3.91 (s, 3H, OCH3), 6.73 (d, 1H, J = 8.9 Hz, ArH),
6.83 (d, 2H, J = 8.5 Hz, ArH), 6.85 (d, 1H, J = 8.9 Hz, ArH), 7.01
(d, 1H, J = 8.6 Hz, ArH), 7.03 (d, 2H, J = 8.5 Hz, ArH), 7.04 (m,
1H, ArH), 7.34 (t, 1H, J = 7.9 Hz, ArH), 7.51 (d, 1H, J = 1.5 Hz,
IR (film): n = 2950, 2820, 1607, 1584, 1507, 1489, 1441, 1260 cm-
1
.
MS: m/z (%) = 556 (M++4, 5), 554 (M++2, 20), 552 (M+, 29), 291
(17), 261 (100), 227 (17), 211 (18).
Anal. Calcd. for C31H30Cl2O5: C, 67.27; H, 5.46 Found: C, 66.97; H,
5.12.
Synthesis 2000, No. 10, 1403–1408 ISSN 0039-7881 © Thieme Stuttgart · New York