Elban and Hecht
dried (MgSO4) and concentrated under diminished pressure to afford
a crude residue. The residue was dissolved in 10 mL of CH2Cl2 at
0 °C and 1 mL of TFA was added dropwise. The reaction mixture
was stirred at room temperature for 1 h and concentrated under
diminished pressure, and the residue was coevaporated with 50 mL
of toluene. The resulting crude residue was purified by flash
chromatography on a silica gel column (15 cm × 2 cm). Step-
gradient elution with 1:1 ethyl acetate-hexanes f 100% ethyl
acetate gave 18 as a yellow-brown solid (eluted with ethyl
acetate): yield 0.63 g (50%); mp 192-194 °C; silica gel TLC Rf
0.08 (1:2 ethyl acetate-hexanes); IR (thin film, CH2Cl2) 1662, 1653,
at reflux for 18 h at which time it was filtered though a silica gel
plug and washed with ethyl acetate. The excess solvent was
removed under diminished pressure to afford a crude brown residue.
The residue was purified by flash chromatography on a silica gel
column (20 cm × 5 cm). Elution with 2% MeOH in CHCl3 as
eluant gave 24 as a yellow solid: yield 0.277 g (87%); mp 218-
220 °C; silica gel TLC Rf 0.42 (1:1 ethyl acetate-hexanes); IR
(thin film, CH2Cl2) 1683, 1558, 1317, 1081 cm-1; 1H NMR (CDCl3)
δ 2.43 (s, 3H), 2.48 (s, 3H), 3.96 (s, 3H), 3.99 (s, 3H), 4.01 (s,
3H), 6.79 (s, 1H), 7.33 (d, 2H, J ) 8.1 Hz), 7.58 (s, 1H), and 7.88
(d, 2H, J ) 8.4 Hz); 13C NMR (CDCl3) δ 21.7, 31.8, 56.6, 56.7,
57.0, 101.3, 107.1, 114.7, 118.1, 124.3, 128.9, 129.6, 131.7, 131.9,
132.0, 136.8, 142.0, 145.7, 159.3, 159.5, 160.0, 179.3, 182.1, and
197.9; mass spectrum (FAB), m/z 545.0676 (M + H)+ (C26H22ClO9S
requires 545.0673).
1
1330, 1042 cm-1; H NMR (CDCl3) δ 2.31 (s, 3H), 2.38 (s, 3H),
3.70 (s, 3H), 3.96 (s, 3H), 5.89 (s, 1H), 6.76 (s, 1H), 7.17 (d, 2H,
J ) 8.1 Hz), 7.60 (d, 2H, J ) 8.1 Hz), and 8.17 (s, 1H); 13C NMR
(CDCl3) δ 20.2, 21.6, 56.1, 61.2, 108.0, 109.7, 110.4, 118.2, 120.7,
125.2, 128.5, 128.8, 129.1, 132.4, 141.4, 144.9, 145.1, 150.4, 152.5,
164.9, and 176.2; mass spectrum (FAB), m/z 475.0620 (M + H)+
(C23H20ClO7S requires 475.0618).
3-Methoxymethoxybut-2-enoic Acid Methyl Ester (25a). To
a solution containing 5.0 mL (5.38 g, 46.3 mmol) of methyl
acetoacetate (12) in 150 mL of benzene at room temperature was
added 8.29 mL (8.44 g, 55.6 mmol) of DBU followed by 3.86 mL
(4.09 g, 50.9 mmol) of MOMCl. The reaction mixture was heated
to reflux for 1 h, quenched while hot with 100 mL of brine, and
extracted with three 100-mL portions of ethyl acetate. The combined
organic extract was dried (MgSO4) and concentrated under dimin-
ished pressure to afford a crude residue. The residue was purified
by flash chromatography on a silica gel column (20 cm × 5 cm).
Elution with 1:3 ethyl acetate-hexanes gave 25a as a colorless
oil: yield 3.37 g (45%); silica gel TLC Rf 0.83 (1:2 ethyl acetate-
Toluene-4-sulfonic Acid 7-Chloro-2-methyl-4,6,9-trioxo-6,9-
dihydro-4H-benzo[g]chromen-5-yl Ester (19). To a solution
containing 0.020 g (0.042 mmol) of 18 in 2 mL of AcOH at room
temperature was added 2 mL of HNO3. The reaction mixture was
stirred at room temperature for 1 h, then quenched carefully with
sat. aq NaHCO3, and extracted with three 50-mL portions of ethyl
acetate. The combined organic phase was dried (MgSO4) and
concentrated under diminished pressure to afford a crude yellow
solid. The crude residue was purified by flash chromatography on
a silica gel column (15 cm × 2 cm). Elution with 10% MeOH in
1:1 ethyl acetate-hexanes gave 19 as an orange solid: yield 0.018
g (96%); mp 202-204 °C; silica gel TLC Rf 0.41 (10% MeOH in
1:1 ethyl acetate-hexanes); IR (thin film, CH2Cl2) 1690, 1539,
1
hexanes); H NMR (CDCl3) δ 2.21 (s, 3H), 3.33 (s, 3H), 3.55 (s,
3H), 4.91 (s, 2H), and 5.13 (s, 1H); 13C NMR (CDCl3) δ 18.2,
50.5, 56.4, 93.4, 93.4, 167.8, and 169.8; mass spectrum (FAB),
m/z 161.0815 (M + H)+ (C7H13O4 requires 161.0814).
1
1348, 1065 cm-1; H NMR (CDCl3) δ 2.40 (s, 3H), 2.46 (s, 3H),
(1-Methoxy-3-methoxymethoxybuta-1,3-dienyloxy)trimethyl-
silane (25). To a solution containing 1.91 mL (1.38 g, 13.8 mmol)
of iPr2NH in 20 mL of THF at 0 °C was added 5.51 mL (13.8
mmol) of nBuLi (2.5 M in hexanes). The reaction mixture was
stirred at 0 °C for 30 min, at which time the reaction mixture was
chilled to -78 °C and stirred for an additional 30 min. A solution
containing 2.00 g (12.5 mmol) of 25a in 10 mL of THF at 25 °C
was added dropwise over a period of 15 min, and the reaction
mixture was stirred for 30 min at -78 °C. A solution containing
2.36 mL (2.01 g, 18.8 mmol) of TMSCl in 10 mL of THF at 25 °C
was added dropwise over a period of 15 min. The reaction mixture
was stirred at -78 °C for 30 min and then at room temperature for
an additional 1 h. The solvent was concentrated under diminished
pressure, and the residue was dissolved in hexanes and filtered
through a pad of Celite. The solvent was concentrated under
diminished pressure to afford pure 25 as a light yellow oil: yield
2.83 g (98%); silica gel TLC Rf was not recorded due to
decomposition on SiO2; 1H NMR (CDCl3) δ 0.21 (s, 9H), 3.39 (s,
3H), 3.53 (s, 3H), 3.99 (s, 1H), 4.18 (s, 1H), 4.40 (m, 1H), and
4.92 (s, 2H); 13C NMR (CDCl3) δ 0.2, 54.9, 55.9, 75.0, 83.0, 93.4,
155.8, and 158.9. Note: compound decomposes rapidly, and must
be used immediately.
2-Acetyl-6,8-dihydroxy-3-methoxy-1-tosyloxyanthraquino-
ne (26). To a solution containing 0.40 g (0.90 mmol) of 22 in 20
mL of benzene at room temperature was added 0.84 g (3.60 mmol)
of 25. The reaction mixture was stirred at room temperature for 18
h, quenched with 100 mL of 2 N HCl, and extracted with three
100-mL portions of ethyl acetate. The combined organic phase was
dried and concentrated under diminished pressure to afford a crude
brown solid. The residue was purified by flash chromatography on
a silica gel column (20 cm × 5 cm). Elution with 1:2 ethyl acetate-
hexanes gave a yellow oil which was dissolved in 20 mL of MeOH
at room temperature and treated with ∼1 mL of conc HCl. The
reaction mixture was heated to reflux and stirred for 18 h, and then
MeOH was removed under diminished pressure. The residue was
dissolved in 50 mL of H2O and extracted with three 100-mL
portions of CHCl3. The combined CHCl3 extract was dried (MgSO4)
and concentrated under diminished pressure to afford a crude brown
6.16 (s, 1H), 7.21 (s, 1H), 7.34 (d, 2H, J ) 8.7 Hz), 7.84 (d, 2H,
J ) 8.4 Hz), and 8.09 (s, 1H); 13C NMR (CDCl3) δ 20.1, 21.8,
113.1, 116.4, 121.6, 122.9, 128.9, 129.8, 132.3, 134.4, 135.1, 146.0,
146.7, 148.8, 159.6, 165.3, 173.2, 174.5, and 179.9; mass spectrum
(FAB), m/z 445.0147 (M + H)+ (C21H14ClO7S requires 445.0149).
2-Acetyl-3,6-dimethoxy-8-hydroxy-1-tosyloxyanthraquino-
ne (23). To a solution containing 0.44 g (1.01 mmol) of 22 in 20
mL of toluene at room temperature was added 0.41 g (2.01 mmol)
of 1,3-dimethoxy-1-trimethylsiloxy-1,3-butadiene.11 The reaction
mixture was heated to 90 °C for 2 h at which time the reaction
was quenched while hot with 100 mL of 6 N HCl-ice and extracted
with three 100-mL portions of ethyl acetate. The combined organic
phase was dried (MgSO4) and concentrated under diminished
pressure to afford a crude brown solid. The residue was purified
by flash chromatography on a silica gel column (20 cm × 5 cm).
Elution with 1:3 ethyl acetate-hexanes gave 23 as a yellow-orange
solid: yield 0.35 g (70%); mp 224-226 °C; silica gel TLC Rf 0.27
(1:2 ethyl acetate-hexanes); IR (thin film, CH2Cl2) 1684, 1338,
1
1213, 1178 cm-1; H NMR (CDCl3) δ 2.45 (s, 3H), 2.52 (s, 3H),
3.92 (s, 3H), 4.03 (s, 3H), 6.69 (d, 1H, J ) 2.4 Hz), 7.29 (d, 1H,
J ) 2.7 Hz), 7.33 (d, 2H, J ) 8.1 Hz), 7.80 (s, 1H), 7.83 (d, 2H,
J ) 8.4 Hz), and 12.65 (s, 1H); 13C NMR (CDCl3) δ 21.8, 31.9,
56.0, 56.9, 107.4, 108.5, 110.9, 120.8, 128.8, 129.7, 132.5, 132.7,
133.6, 136.7, 144.8, 146.0, 160.6, 165.2, 165.6, 181.1, 184.2, and
197.6; mass spectrum (FAB), m/z 497.0907 (M + H)+ (C25H21O9S
requires 497.0906).
2-Acetyl-5-chloro-1-tosyloxy-3,6,8-trimethoxyanthraquino-
ne (24). To a solution containing 0.29 g (0.58 mmol) of 23 in 30
mL of 5:1 CHCl3-MeCN at room temperature was added 0.24
mL (0.39 g, 2.92 mmol) of SO2Cl2. The reaction mixture was stirred
for 3 h, quenched with 200 mL sat. aq NaHCO3, and extracted
with three 100-mL portions of ethyl acetate. The combined organic
phase was dried over anhydrous MgSO4 and filtered, and excess
solvent was removed under diminished pressure to afford a crude
brown residue. The residue was dissolved in 200 mL of acetone,
and 0.81 g (5.84 mmol) of K2CO3 was added followed by 0.53
mL (5.84 mmol) of (MeO)2SO2. The reaction mixture was stirred
792 J. Org. Chem., Vol. 73, No. 3, 2008