Model Planar Diol Epoxides
J . Org. Chem., Vol. 64, No. 25, 1999 9055
evaporated. Column chromatography on Florisil using hexane/
ethyl acetate (first 97:3 and then 90:10) provided a solid
product. Dibenzoate 12 (420 mg, 82%) was obtained as a white
solid after recrystallization from hexane: mp 192 °C; 1H NMR
(CDCl3) δ 1.86 (AB quartet, 1, H5), 3.27 (m, 1, H5′), 4.81 (dd, 1,
chromatography on silica gel using hexane/ethyl acetate (9:1)
and then chloroform as an eluent provided pure 17 (23 mg,
75%): 1H NMR (acetone-d6) δ 7.40 (d, 1, H3, J 3,5 ) 1.4 Hz),
7.73 (dd, 1, H7, J 6,7 ) 7.0 Hz, J 7,8 ) 8.1 Hz), 7.89 (d, 1, H1 or
H2, J 1,2 ) 8.7 Hz), 7.90 (d, 1, H5, J 3,5 ) 1.4 Hz), 7.88-7.98 (m,
3, H9,10, H1 or H2), 8.00 (d, 1, H8, J 7,8 ) 8.1 Hz), 8.22 (d. 1, H6,
J 6,7 ) 7.0 Hz), 8.96 (s, 1, OH); 13C NMR (acetone-d6) δ 110.1,
117.1, 124.5, 126.1, 126.2, 126.26, 126.30, 127.0, 127.7, 128.5,
128.9, 129.4, 129.4, 134.0, 134.6, 138.1, 139.7, 160.3 (C-OH);
MS m/z (relative abundance) 242.1 (M+, 100); HRMS calcd for
H
5a, J 5,5a ) 12.6 Hz, J 5′,5a ) 4.70 Hz), 6.25-6.40 (m, 1, H4),
6.79 (d, 1, H3, J 3,4 ) 6.9 Hz), 7.30-8.30 (m, 17, aromatic); 13
C
NMR (CDCl3) δ 33.4, 44.6, 74.6, 77.1, 121.1, 123.6, 124.8, 125.2,
126.4, 127.1, 127.4, 128.1, 128.4, 128.5, 128.6, 129.8, 129.9,
130.0, 133.1, 136.2, 138.5, 145.2, 145.8, 166.2 (CdO), 166.9
(CdO). Anal. Calcd for C32H22O4: C, 81.69; H, 4.71. Found:
C, 81.67; H, 4.51.
C
18H10O 242.0732, found 242.0739.
Fremy’s salt (89 mg, 0.33 mol), dissolved in 2.5 mL of 0.17
3,4-Bis(ben zoyloxy)ben zo[gh i]flu or a n th en e (13). A so-
lution of tetrahydrodibenzoate 12 (1.50 g, 3.2 mmol) and DDQ
(2.91 g, 12.8 mmol) in 300 mL of dry benzene was heated at
reflux for 18 h. After cooling, the reaction mixture was filtered
through Celite and washed successively with 5% Na2S2O5,
water, 5% NaOH, and saturated NaCl solution. The organic
layer was dried over anhydrous MgSO4 and evaporated under
reduced pressure. The solid residue was subjected to column
chromatography on Florisil first with hexane/ethyl acetate (97:
3) and then with chloroform. Recrystallization from benzene
afforded pure 13 (1.13 g, 76%): mp 226-227 °C; 1H NMR
(CDCl3) δ 7.39 (s, 1, H5), 7.4-7.5 (4), 7.55-7.72 (m, 4), 7.90-
8.00 (m, 4), 8.07 (d, 1, J ) 8.2 Hz), 8.12-8.30 (m, 4); 13C NMR
(CDCl3) δ 120.6, 121.9, 122.1, 123.8, 125.0, 126.2, 126.8, 126.8,
127.1, 128.0, 128.4, 128.5, 128.6, 128.7, 128.8, 129.1, 130.3,
130.5, 132.1, 132.7, 133.7, 133.8, 135.5, 136.6, 139.2, 142.6,
164.5 (CdO), 164.9 (CdO); MS m/z (relative abundance) 466.1
(M+, 15), 105.0 (100); HRMS calcd for C32H18O4 466.1205, found
466.1206. Anal. Calcd for C32H18O4: C, 82.39; H, 3.89. Found:
C, 82.56; H, 3.95.
M potassium hydrogen phosphate (KH2PO4), was poured into
a solution of 17 (20 mg, 0.083 mmol) in 10 mL of dry benzene.
To the reaction mixture were added one drop of Adogen 464
and 2.5 mL of water, and then the mixture was stirred
vigorously for 30 min. The benzene layer was separated from
the water layer, and the water layer was back extracted with
benzene three times. The combined benzene layers were dried
over anhydrous MgSO4, and the benzene was evaporated
under reduced pressure. The 1H NMR spectrum of the residue
(13 mg) in CDCl3 showed two singlets at 6.9 and 7.3 ppm in a
ratio of 5.5 to 1, which correspond to the olefinic protons of
the desired 3,4-dione (15) and the 4,5-dione (18) isomer,
respectively.
tr a n s-3,4-Dih yd r oxy-3,4-d ih yd r ob en zo[gh i]flu or a n -
th en e (16). To a solution of 15 (184 mg, 0.72 mmol) in 125
mL of absolute ethanol was added NaBH4 (571 mg, 15.0 mmol),
and the mixture was bubbled with O2 at 0 °C in the dark. The
reaction progress was monitored by HPLC [C18 column (4.6
mm × 25 cm), with 60% methanol at the rate of 1.0 mL/min].
The retention time of the dihydrodiol product was 10.3 min.
The reduction was completed within 8-10 h. The excess
hydride was decomposed by adding water, and the solvent was
evaporated under reduced pressure using a dry ice/acetone
cooler. The solid residue was treated with ice water and
extracted with cold ether and ethyl acetate (1:1) several times.
The combined organic phase was dried over anhydrous MgSO4
and evaporated under diminished pressure to give about 115
mg of a solid residue. Chromatographically pure 16 (∼40 mg)
was obtained by HPLC separation on a semiprep C18 column
(10 mm × 250 mm) at 2.0 mL/min using a 30-min gradient of
20% to 45% acetronitrile/water: 1H NMR (acetone-d6) δ 5.08
Ben zo[gh i]flu or a n th en e-3,4-d ion e (15). Sodium meth-
oxide (3.96 mL, 0.5 M, 1.98 mmol) in methanol was added to
a solution of 16 (421 mg, 0.90 mmol) in 40 mL of dry THF,
and the reaction mixture was stirred under N2 at room
temperature. After 10 min, the reaction was quenched by
addition of water, and the solvent was removed under reduced
pressure. The resulting aqueous mixture was extracted with
methylene chloride, and the organic phase was dried over
anhydrous MgSO4. Evaporation of the solvent furnished the
catechol 14, which was used for the next step without further
purification: 1H NMR (CDCl3) δ 6.96 (s, 1, H5), 7.68 (dd, 1,
H7, J ) 8.0, 7.3 Hz), 7.77 (d, 1, J ) 8.8 Hz), 7.80 (d, 1, J ) 8.3
Hz), 7.87 (m, 2), 7.94 (m, 2); 13C NMR (CDCl3) δ 123.8, 124.0,
125.2, 125.5, 125.8, 126.7, 128.3, 128.6, 129.2, 129.5, 130.7,
133.1, 140.1, 141.5, 150.7, 175.8 (C-OH), 182.2 (C-OH). To a
solution of K2Cr2O7 (702 mg, 2.4 mmol) in 25 mL of 50%
sulfuric acid was added 14, and the mixture was stirred at
room temperature for 2 h. The reaction mixture was extracted
with benzene, and the organic layer was dried over anhydrous
MgSO4. Silica gel chromatography with dichloromethane/
hexane (6:4) as an eluent, followed by a recrystalization
(dichloromethane/hexane) gave the 3,4-dione 15 (184 mg, 80%)
(dd, 1, H4, J 3,4 ) 6.9 Hz, J 4,5 ) 3.3 Hz), 5.25 (d, 1, H3, J 3,4
)
6.9 Hz), 6.97 (d, 1, H5; J 4,5 ) 3.3 Hz), 7.58 (dd, 1, H7, J ) 7.1,
7.9 Hz), 7.74 (dd, 1, H2, J 1,2 ) 8.6 Hz, J 2,3 ) 1.2 Hz), 7.83 (d,
1, J ) 8.1 Hz), 7.88 (s, 2, H9,10), 7.91 (d, 1, J ) 8.1 Hz), 7.96
(d, 1, J ) 7.1 Hz).
tr a n s-3,4-Dih yd r oxy-syn -5,5a -ep oxy-3,4,5,5a -t et r a h y-
d r oben zo[gh i]flu or a n th en e (3). Compound 16 (115 mg, 0.44
mmol) and N-bromoacetamide (NBA, 62 mg, 0.45 mmol) were
dissolved in 45 mL of a 3:1 mixture of THF and H2O, and the
solution was stirred at 0 °C in the dark. The reaction progress
was monitored by HPLC [C18 column (4.6 mm × 25 cm), at
1.0 mL/min, 60% methanol/water]. The retention time of the
product was 4.45 min. After 4 h, it was necessary to add an
additional batch of NBA (30.8 mg, 0.23 mmol). After 6 h, the
solvent was removed under reduced pressure, and the residue
was partitioned between ice water and ethyl acetate (3 × 30
mL). The combined organic extracts were washed with satu-
rated NaHCO3 and saturated NaCl and dried with MgSO4.
Evaporation of the solvent under reduced pressure gave 19,
which was used for the next step without further purification
(∼140 mg). Chromatographically pure 19 was obtained by
HPLC on a C18 column (10 mm × 250 mm) at 2.0 mL/min using
50% methanol/water: 1H NMR (acetone-d6 with 3 drops of D2O)
δ 3.64 (dd, 1, H4, J 3,4 ) 2.4 Hz, J 4,5 ) 3.5 Hz), 4.15 (dd, 1, H5,
J 4,5 ) 3.5 Hz, J 3,5 ) 0.6 Hz), 5.10 (d, 1, H3, J 3,4 ) 2.4 Hz), 7.50
(d, 1, H2, J 1,2 ) 8.2 Hz), 7.56 (dd, 1, H7, J ) 7.8, 7.3 Hz), 7.75-
7.85 (m, 5, aromatic). To crude 19 (130 mg) in 100 mL of dry
THF was added potassium tert-butoxide (1.5 mL, 1 M in THF,
1.5 mmol). The reaction was kept at 0 °C under nitrogen in
the dark. The color of the solution turned immediately from
yellow to blue-green upon the addition of the base. The
reaction progress was monitored by HPLC on a C18 column
1
as red crystals: mp ∼285 °C; H NMR (CDCl3) δ 6.92 (s, 1,
H5), 7.68 (dd, 1, H7, J 6,7 ) 7.3 Hz, J 7,8 ) 8.2 Hz), 7.76 (d, 1,
H
10, J 9,10 ) 8.4 Hz), 7.77 (d, 1, H1, J 1,2 ) 9.1 Hz), 7.85 (d, 1,
H9, J 9,10 ) 8.4 Hz), 7.85 (d, 1, H8, J 7,8 ) 8.2 Hz), 7.93 (d, 1, H2,
J 1,2 ) 9.1 Hz), 7.94 (d, 1, H6, J 6,7 ) 7.3 Hz); 13C NMR (CDCl3)
δ 123.7, 124.0, 125.2, 125.5, 125.6, 126.6, 128.3, 128.6, 129.2,
129.4, 130.7, 133.0, 140.0, 140.5, 150.6, 176.5 (CdO), 182.1
(CdO); MS m/z (relative abundance) 256.0 (M+, 42), 200.1
(100); HRMS calcd for C18H8O2 256.0524, found 256.0536.
Anal. Calcd for C18H8O2: C, 87.79; H, 3.27. Found: C, 87.84;
H, 3.33.
4-Hyd r oxyben zo[gh i]flu or a n th en e (17). To a solution of
12 (60 mg, 0.13 mmol) in 6 mL of dry THF was added NaOCH3
(0.8 mL, 0.5 M, 20 mmol) in methanol, and the reaction
mixture was heated at 60 °C under nitrogen for 10 min. The
reaction was quenched by the addition of H2O and concen-
trated under reduced pressure. The residue was neutralized
by adding 6 M HCl, and the resulting aqueous solution was
extracted with ether (3 × 30 mL). The combined ether extracts
were washed with water and dried over anhydrous MgSO4,
and the solvent was removed under reduced pressure. Column