Watanabe et al.
JOCArticle
for C12H15O535Cl 274.0608 (Mþ), found 274.0600. Anal. Calcd
for C12H15O5Cl: C 52.47, H 5.50. Found: C 52.29, H 5.35.
1-Chloro-3-ethynyl-2,5-dimethoxy-4-((methoxymethoxy)methyl)-
benzene (15). To a stirred solution of 13 (1.69 g, 6.15 mmol) in dry
MeOH (87.9 mL) were successively added at rt K2CO3 (2.13 g, 15.4
mmol) and a solution of the Ohira’s reagent 14 (1.77 g, 9.23 mmol)
in dry MeOH (29.3 mL). After 20 h at rt, 5% aqueous NaHCO3
solution was added at 0 °C and the mixture was extracted with
EtOAc. The extracts were washed with saturated aqueous NaCl
solution, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified with silica gel column chroma-
tography (180 g, 3:1 hexane-EtOAc) to afford 15 (1.17 g, 70%) as
colorless crystals: Rf 0.34 (3:1 hexane-EtOAc); mp 87-90 °C (not
recrystallized); IR (KBr, cm-1) 1580, 1480, 1300, 1240, 1150, 1100,
1030, 920; 1H NMR (300 MHz, CDCl3) δ 6.92 (1H, s), 4.73 (2H, s),
column chromatography (10 g, 2:1 hexane-EtOAc) to afford 7c
(48.5 mg, 58%) as red-brown solids and 18c (6.9 mg, 10%) as
red-brown solids. 7c: Rf 0.70 (2:1 hexane-EtOAc); IR (KBr,
cm-1) 3450, 1660, 1630, 1580, 1460, 1310, 1250, 1150, 1040, 980;
1H NMR (300 MHz, CDCl3) δ 13.80 (1H, s), 8.48 (1H, br d, J =
7.8 Hz), 8.13 (1H, s), 7.96 (1H, br d, J = 7.8 Hz), 7.71 (2H, m),
4.77 (2H, s), 4.76 (2H, s), 3.42 (3H, s), 1.05 (9H, s), 0.27 (6H, s);
13C NMR (75 MHz, CDCl3) δ -4.9, 16.8, 26.1, 55.5, 62.6, 96.7,
97.0, 108.6, 114.8, 122.1, 125.0, 127.3, 127.5, 129.2, 130.5, 131.4,
133.8, 136.1, 148.7, 162.8, 182.5, 185.5; HRMS (EI) m/z calcd
for C25H28O5Si 436.1706 (Mþ), found 436.1717. 18c: Rf 0.43 (2:1
hexane-EtOAc); IR (neat, cm-1) 3400, 1590, 1460, 1320, 1250,
1150, 1000, 930; 1H NMR (300 MHz, CDCl3) δ 7.34 (1H, s), 6.93
(1H, s), 5.72 (1H, s), 4.93 (2H, s), 4.73 (2H, s), 3.42 (3H, s), 1.00
(9H, s), 0.22 (6H, s); 13C NMR (75 MHz, CDCl3) δ -4.6, 16.6,
26.1, 55.9, 66.1, 96.0, 96.9, 105.8, 110.0, 119.2, 120.0, 122.2,
147.0, 149.5; HRMS (EI) m/z calcd for C17H25O4Si35Cl
356.1211 (Mþ), found 356.1203.
4.72 (2H, s), 3.88 (3H, s), 3.82 (3H, s), 3.52 (1H, s), 3.41 (3H, s); 13
C
NMR (75 MHz, CDCl3) δ 55.2, 56.3, 61.1, 61.7, 76.8, 85.9, 96.3,
113.5, 120.0, 128.1, 128.3, 151.4, 154.5; HRMS (EI) m/z calcd for
C13H15O435Cl 270.0659 (Mþ), found 270.0651. Anal. Calcd for
C13H15O4Cl: C 57.68, H 5.59. Found: C 57.67, H 5.47.
3-Ethynyl-2,3-dihydro-2,3,5-trihydroxy-2-((methoxymethoxy)-
methyl)-1,4-anthraquinone (20) from 7c. To a stirred solution of 7c
(24.2 mg, 0.0554 mmol) in a mixture of MeCN (0.33 mL), EtOAc
(0.33 mL), and water (0.11 mL) were added at 0 °C a 0.1 M
aqueous solution of RuCl3 (0.0388 mL, 0.00388 mmol) and
NaIO4 (35.6 mg, 0.166 mmol). After 15 min at 0 °C, saturated
aqueous Na2S2O3 solution was added and the mixture was
extracted with EtOAc. The extracts were washed with saturated
aqueous NaCl solution, dried over Na2SO4, and concentrated
under reduced pressure. The residue was purified with silica gel
column chromatography (2.0 g, 2:1 hexane-EtOAc) to afford
19c (8.7 mg, 33%) as pale yellow solids and 7c (5.4 mg, 22%) [19c:
3-((tert-Butyldimethylsilyl)ethynyl)-1-chloro-2,5-dimethoxy-
4-((methoxymethoxy)methyl)benzene (16c). To a stirred solution
of 15 (1.55 g, 5.73 mmol) in dry THF (95.5 mL) was added
at -78 °C a 1.59 M hexane solution of n-BuLi (4.69 mL, 7.46
mmol). After 10 min at -78 °C, TBSOTf (1.58 mL, 6.88 mmol)
was added and the mixture was stirred at -78 °C for 1 h. The
reaction mixture was warmed to 0 °C and quenched with
saturated aqueous NH4Cl solution. The mixture was extracted
with EtOAc and the extracts were washed with saturated aqu-
eous NaCl solution, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified with silica gel column
chromatography (60 g, 5:1 hexane-EtOAc) to afford 16c
(2.18 g, 99%) as a colorless syrup: Rf 0.74 (3:1 hexane-EtOAc);
1
Rf 0.56 (2:1 hexane-EtOAc); H NMR (300 MHz, CDCl3) δ
12.65 (1H, br s), 8.51 (1H, br d, J = 7.8 Hz), 8.11 (1H, s), 7.97
(1H, br d, J = 7.8 Hz), 7.74 (2H, m), 4.63 (2H, br s), 4.41 (1H, s),
3.96-4.40 (3H, m), 3.30 (3H, br s), 0.82 (9H, s), 0.08 (3H, s), 0.04
(3H, s);13C NMR(75MHz, CDCl3) δ -5.1, 16.6, 25.8, 55.7, 60.4,
68.1, 81.0, 95.9, 97.3, 99.5, 108.1, 120.9, 124.7, 127.4, 128.3, 128.9,
130.0, 131.3, 136.3, 162.2, 193.4, 194.7]. To a stirred solution of
19c (8.7 mg, 0.0185 mmol) in dry THF (0.924 mL) was added at
0 °C a 1.0 M THF solution of TBAF (0.0370 mL, 0.0370 mmol).
After 15 min at rt, saturated aqueous NH4Cl solution was added
and the mixture was extracted with EtOAc. The extracts were
washed with saturated aqueous NaCl solution, dried over
Na2SO4, and concentrated under reduced pressure. The residue
was purified with silica gel column chromatography (1.0 g, 1:2
hexane-EtOAc) to afford 20 (6.5 mg, 98%) as pale yellow solids:
Rf 0.19 (2:1 hexane-EtOAc); mp 160-164 °C (not recrystallized-
); IR (KBr, cm-1) 3400, 1690, 1650, 1460, 1380, 1260, 1150, 1100,
1000, 950; 1H NMR (300 MHz, CDCl3) δ 12.74 (1H, br s), 8.50
(1H, br d, J = 7.8 Hz), 8.12 (1H, s), 7.97 (1H, br d, J = 7.8 Hz),
7.74 (2H, m), 4.56 (1H, br s), 4.52 (2H, br s), 4.18 (1H, br d, J =
10.0Hz), 4.05(1H, brs), 3.94 (1H, brd, J =10.0Hz), 3.21 (3H, s),
2.80 (1H, s); 13C NMR (75 MHz, CDCl3) δ 55.7, 68.8, 77.2, 77.8,
78.9, 81.2, 97.0, 108.4, 121.0, 124.8, 127.6, 127.7, 129.1, 130.1,
131.5, 136.2, 162.6, 193.7, 195.2; HRMS (EI) m/z calcd for
C19H16O7 356.0896 (Mþ), found 356.0908. Anal. Calcd for
C19H16O7: C 64.04, H 4.53. Found: C 63.76, H 4.51.
1
IR (neat, cm-1) 1570, 1470, 1400, 1250, 1120, 1040; H NMR
(300 MHz, CDCl3) δ 6.88 (1H, s), 4.73 (4H, s), 3.88 (3H, s), 3.82
(3H, s), 3.42 (3H, s), 1.00 (9H, s), 0.22 (6H, s); 13C NMR (75
MHz, CDCl3) δ -4.7, 16.7, 26.1, 55.2, 56.3, 60.9, 62.3, 96.5,
98.4, 102.5, 113.1, 121.1, 127.8, 128.2, 151.2, 154.6; HRMS (EI)
m/z calcd for C19H29O4Si35Cl 384.1524 (Mþ), found 384.1518.
3-((tert-Butyldimethylsilyl)ethynyl)-5-hydroxy-2-((methoxyme-
thoxy)methyl)-1,4-anthraquinone (7c) and 3-((tert-Butyldime-
thylsilyl)ethynyl)-1-chloro-2,5-dihydroxy-4-((methoxymethoxy)-
methyl)benzene (18c). To a stirred solution of 16c (91.5 mg, 0.238
mmol) in MeCN (3.40 mL) was added at 0 °C a solution of CAN
(547 mg, 0.998 mmol) in water (2.00 mL). The reaction mixture
was stirred at 0 °C for 15 min. CAN (547 mg, 0.998 mmol) in
water (2.00 mL) was added at intervals of 15 min (three times).
Saturated aqueous NaHCO3 solution was added and the mix-
ture was extracted with EtOAc. The extracts were washed with
saturated aqueous NaCl solution, dried over Na2SO4, and
concentrated under reduced pressure. The residue was purified
with silica gel column chromatography (3.5 g, 5:1 hexane-
EtOAc) to afford 8c (71.4 mg, 85%) as a yellow syrup [Rf 0.89
(2:1 hexane-EtOAc); IR (neat, cm-1) 1680, 1650, 1580, 1250,
1150, 1100, 1050; 1H NMR (300 MHz, CDCl3) δ 7.03 (1H, s),
4.68 (2H, s), 4.56 (2H, s), 3.36 (3H, s), 0.99 (9H, s), 0.20 (6H, s);
13C NMR (75 MHz, CDCl3) δ -5.1, 16.7, 26.0, 55.4, 61.8, 95.8,
96.9, 115.5, 130.4, 134.1, 143.3, 144.3, 176.1, 183.5]. To a stirred
solution of (i-Pr)2NH (0.0266 mL, 0.190 mmol) in dry THF
(0.950 mL) was added at 0 °C a 1.55 M hexane solution of n-
BuLi (0.123 mL, 0.190 mmol). After 0.5 h at 0 °C, homophthalic
anhydride (9) (30.8 mg, 0.190 mmol) was added and the mixture
was warmed to rt. To this was added at rt 8c (67.3 mg, 0.190
mmol) in dry THF (2.72 mL). After 5 min at rt, saturated
aqueous NH4Cl solution was added at 0 °C and the mixture was
extracted with EtOAc. The extracts were washed with saturated
aqueous NaCl solution, dried over Na2SO4, and concentrated
under reduced pressure. The residue was purified with silica gel
3-Ethynyl-2,3-dihydro-2,3,5-trihydroxy-2-(hydroxymethyl)-
1,4-anthraquinone (6). To a stirred solution of 20 (13.8 mg,
0.0387 mmol) in CH2Cl2 (0.775 mL) was added at 0 °C TFA
(0.194 mL, 1.84 mmol). After 3 h at rt, saturated aqueous NH4Cl
solution was added and the mixture was extracted with EtOAc.
The extracts were washed with saturated aqueous NaCl solu-
tion, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified with silica gel column chro-
matography (2.0 g, 1:1 hexane-EtOAc) to afford 6 (11.8 mg,
98%) as pale yellow solids: Rf 0.40 (1:1 hexane-EtOAc); IR
(KBr, cm-1) 3490, 1700, 1640, 1380, 1260, 1150, 1070, 970; 1H
NMR (300 MHz, CDCl3) δ 12.34 (1H, br s), 8.52 (1H, br d, J =
5578 J. Org. Chem. Vol. 75, No. 16, 2010