3
812 J. Am. Chem. Soc., Vol. 118, No. 16, 1996
Uno et al.
Experimental Section
residue was purified by flash chromatography on a 2 × 18 cm silica
gel column (25% [v/v] ethyl acetate in hexanes; R ) 0.36), affording
f
General Methods. Unless otherwise noted, materials were obtained
from commercial suppliers and used without further purification.
8
1
1
1
7
2 mg (76%) of a colorless oil: IR (film) 3064, 3015, 2936, 2864,
-1 1
735, 1460, 1427, 1220, 1127 cm ; H NMR (400 MHz, CDCl ) δ
3
Pyridine and CH
prior to use. THF was distilled under N
immediately prior to use. All aqueous solutions were prepared from
distilled H O which was further purified on a Milli-Q purification
2
Cl
2
were distilled under N
2
from CaH
from Na/benzophenone
2
immediately
.30 (m, 2H), 2.19 (t, 2H, J ) 7.6), 3.63 (s, 3H), 5.15 (s, 2H), 5.28 (t,
2
H, J ) 4.8), 7.35 (dt, 2H, J ) 7.4, 0.9), 7.42 (dt, 2H, J ) 7.6, 1.4),
13
.45 (dd, 2H, J ) 1.3, 7.5), 7.89 (d, 2H, J ) 7.5), 10.5 (br s, 1H);
C
2
NMR (100.6 MHz, CDCl
3
) δ 23.5, 24.7, 33.9, 34.2, 51.4, 74.5, 103.9,
system. All moisture sensitive reactions were carried out in oven-dried
glassware under a positive pressure of dry nitrogen. Analytical thin
layer chromatography was performed on 0.25 mm precoated silica gel
plates (Merck Fertigplatten, 60F-254, Art. 5765); compounds were
visualized by UV light or by staining with iodine, ninhydrin, or
phosphomolybdate. Flash silica gel chromatography was performed
on Merck Kieselgel 60, 230-400 mesh.
Melting points were determined on a Meltemp device and are
uncorrected. IR spectra were recorded on a Mattson Polaris Fourier
transform spectrophotometer as thin films on NaCl plates or KBr pellets.
Optical rotations were determined at 589 nm (sodium D line) with a
Perkin-Elmer Model 241 polarimeter and a 10 cm path length cell.
Rotations are reported as standard degree values ([R]
) °obs[path
length (dm)][concentration (g/mL)]). UV spectra were recorded in 10
mm quartz cells on a Kontron Uvikon 860 spectrophotometer equipped
with a constant temperature cell holder. H resonances are reported in
units of parts per million downfield from tetramethylsilane (TMS).
+
123.3, 128.2, 129.2, 130.3, 131.4, 132.0, 174.0; mass spectrum (FAB )
+
+
+
22 4
m/e 339.0 (MH ), 345.0 (MLi ); exact mass calcd for C21H O Li
3
45.1678, found 345.1671.
cis-O,O′-(5-Carboxypentylidene)-9,10-dihydrophenanthrene-9,-
0-diol (1). Ester 2 (34.7 mg, 103 µmol) was dissolved in 1 mL of
1
ethanol, and 210 µL of 1 M aqueous NaOH was added. The reaction
was stirred at 25 °C for 24 h, after which time TLC analysis (25%
[
v/v] ethyl acetate in hexanes) showed no starting material. Ethanol
was removed by concentration in Vacuo. The residue was taken up in
.5 mL of CHCl
and washed with 1.5 mL of 1 M HCl. The organic
1
3
layer was separated, dried over anhydrous sodium sulfate, filtered, and
concentrated in Vacuo, affording 29 mg (87%) of a white solid: mp
D
1
1
2
35-137 °C; IR (KBr) 3046 (br), 2923, 2885, 1700, 1453, 1423, 1300,
-1
1
246, 1200, 1138, 1000 cm ; H NMR (400 MHz, CDCl
H), 1.45 (m, 4H), 2.19 (t, 2H, J ) 5.0), 5.13 (s, 2H), 5.27 (t, 1H, J
4.7), 7.32 (dt, 2H, J ) 1.1, 7.4), 7.40 (dt, 2H, J ) 1.4, 7.6), 7.53
3
) δ 1.30 (m,
1
)
13
(
dd, 2H, J ) 1.4, 7.5), 7.87 (d, 2H, J ) 7.8); C NMR (100.6 MHz,
CDCl ) δ 23.4, 24.4, 33.8, 34.2, 74.6, 103.9, 123.3, 128.2, 129.2, 130.3,
31.5, 132.0, 179.4; mass spectrum (FAB ) m/e 324 (M ); exact mass
calcd for C20 324.1361, found 324.1352.
13
Coupling constants (J) are given in hertz. All C spectra were proton-
3
13
decoupled, and C resonances are reported in units of parts per million
downfield from TMS.
+
+
1
20 4
H O
Methyl 5-(Chlorocarbonyl)pentanoate (8). To adipic acid monom-
ethyl ester (25.0 g, 0.156 mol) in 50 mL of benzene was added oxalyl
chloride (25.0 g, 0.197 mol) over 3 min at 25 °C. The reaction was
stirred at the same temperature for 30 min and then heated at reflux
for another 30 min, after which time no starting acid was detected by
IR. Benzene was removed by evaporation on a rotary evaporator. The
resulting red residue was purified by distillation under reduced pressure,
affording 25.2 g (91%) of a colorless oil: bp 51.5-52.0 °C (0.25 Torr);
cis-O,O′-[5-[N-(2-Aminoethyl)carbamoyl]pentylidene]-9,10-dihy-
drophenanthrene-9,10-diol (3). Compound 1 (500 mg, 1.54 mmol)
was added to ethylenediamine (0.93 g, 1.54 mmol), N-hydroxysuccin-
imide (0.177 g, 1.54 mmol), and 1,3-dicyclohexylcarbodiimide (0.317
g, 1.54 mmol) in 50 mL of chloroform and stirred at 25 °C for 1 h.
The precipitate was filtered off, and the reaction was washed twice
with 50 mL of water and once with 50 mL of saturated aqueous sodium
bicarbonate, dried over anhydrous sodium sulfate, filtered, and con-
centrated in Vacuo to afford 338 mg (60%) of an off-white solid: mp
-
1
1
IR (film) 2955, 2872, 1801, 1740, 1438, 1205 cm ; H NMR (400
MHz, CDCl ) δ 1.56 (m, 4H), 2.19 (t, 2H, J ) 6.8), 2.79 (t, 2H, J )
3
9
1
1
5
9-103 °C; IR (KBr) 3323 (br), 3069, 2946, 2923, 2869, 1650, 1539,
1
3
6
4
6
.8), 3.51 (s, 3H); C NMR (100.6 MHz, CDCl
6.3, 51.2, 172.9, 173.0. Anal. Calcd for C
.21; Cl, 19.85. Found: C, 47.50; H, 6.38; Cl, 19.48.
Methyl 5-Formylpentanoate (9). This procedure was adapted from
3
) δ 23.3, 24.1, 32.9,
7 3
H11ClO : C, 47.07; H,
-1
1
450, 1125, 1070 cm ; H NMR (400 MHz, CDCl
) δ 1.27 (m, 2H),
3
.45 (m, 2H), 1.52 (m, 2H), 2.03 (t, 2H, J ) 7.6), 2.75 (t, 2H, J )
.8), 3.22 (q, 2H, J ) 5.8), 3.50 (br s, 2H), 5.13 (s, 2H), 5.26 (t, 1H,
J ) 4.8), 5.83 (br s, 1H), 7.36 (t, 2H, J ) 7.4), 7.34 (t, 2H, J ) 6.9),
1
1
that of Burgstaher et al. In a 1 L round bottom flask were placed
13
7
.53 (d, 2H, J ) 6.1), 7.87 (d, 2H, J ) 7.2); C NMR (100.6 MHz,
5
00 mL of THF, 10% palladium on activated carbon (0.893 g), and
,6-lutidine (5.82 mL, 50.0 mmol) under N , and the flask was charged
. To the reaction was added acid chloride 8 (8.93 g, 50.0 mmol)
dropwise over 3 min, and hydrogenation was performed using a H
CDCl
3
) δ 23.5, 25.4, 34.1, 36.4, 41.1, 41.4, 74.4, 103.9, 123.2, 128.2,
2
2
+
1
29.1, 130.3, 131.3, 131.9, 173.4; mass spectrum (FAB ) m/e 367
with H
2
+
(
MH ); exact mass calcd for C22
(S)-Methyl-(S or R)-dibenzo[f,h]-1,4-dioxacyclodeca-6,8-diene
4 and 6). Sodium hydride (1.60 g, 60% in oil, 40.0 mmol) was placed
27 2 3
H N O 367.2021, found 367.2017.
2
2
balloon at 25 °C for 14 h with vigorous agitation. The catalyst and
white precipitate formed during the reaction were filtered off using a
Celite pad on filter paper, and the filtrate was concentrated in Vacuo.
The residue was taken up in 100 mL of ether, washed with 50 mL of
(
in a 500 mL flask equipped with a condenser, washed three times with
2
1
0 mL of petroleum ether, and suspended in 300 mL of THF. (S)-
,2-Propanediol (732 µL, 10.0 mmol) was added, and the reaction was
1
M HCl, saturated aqueous sodium bicarbonate, and saturated aqueous
heated at reflux for 2 h. A solution of 2,2′-bis(bromomethyl)biphenyl
NaCl, dried over anhydrous magnesium sulfate, filtered, and concen-
trated in Vacuo. The resulting colorless residue was purified by
distillation under reduced pressure, affording 3.86 g (53%) of a colorless
oil: bp 54.0-54.5 °C (0.45 Torr); IR (film) 2945, 2745, 1732, 1191,
(3.40 g, 10.0 mmol) in 50 mL of THF was added in one portion, and
the reaction was heated at reflux for an additional 16 h. The remaining
sodium hydride was destroyed by addition of water, and the reaction
mixture was concentrated in Vacuo. The residue was taken up in 50
mL of water and extracted three times with 50 mL of ether. The
combined organic layers were washed with 100 mL of saturated aqueous
NaCl, dried over anhydrous magnesium sulfate, filtered, and concen-
trated in Vacuo. The residue was distilled using a Buchi GKR-51
apparatus to remove high boiling point byproducts. Two diastereomeric
products were isolated from the distillate by flash chromatography on
a 2.5 × 25 cm silica gel column (9% [v/v] ethyl acetate in hexanes;
-
1
1
1
2
164 cm ; H NMR (400 MHz, CDCl
H), 2.43 (m, 2H), 3.64 (s, 3H), 9.73 (d, 1H, J ) 1.3); C NMR (100.6
) δ 21.2, 24.1, 33.3, 43.1, 51.1, 173.2, 201.7. Anal. Calcd
: C, 58.32; H, 8.39. Found: C, 58.43; H, 8.56.
3
) δ 1.63 (m, 4H), 2.31 (m,
13
MHz, CDCl
12 3
for C H O
3
7
cis-O,O′-[5-(Methoxylcarbonyl)pentylidene]-9,10-dihydrophenan-
threne-9,10-diol (2). A mixture of cis-9,10-dihydrophenanthrene-9,-
1
2
1
0-diol (68 mg, 320 µmol), aldehyde 9 (55 mg, 380 µmol), and
p-toluenesulfonic acid monohydrate (6.1 mg, 32 µmol) in 3 mL of THF
was stirred at 25 °C for 20 h. Ten milliliters of chloroform was added,
and the reaction mixture was washed with 1 mL of saturated aqueous
sodium bicarbonate. The organic layer was separated, dried over
anhydrous sodium sulfate, filtered, and concentrated in Vacuo. The
R
f
(4) ) 0.23; R (6) ) 0.18), affording colorless solids, 282 mg (11%)
f
for 4 and 256 mg (10%) for 6. Each isomer was further purified by
recrystallization from petroleum ether to yield colorless needles. Data
for 4: mp 112-114 °C; IR (KBr) 3015, 2986, 2967, 2917, 2653, 1077
-1
1
cm ; H NMR (250 MHz, CDCl
1
)
3
) δ 1.10 (d, 3H, J ) 6.5), 3.23 (dd,
H, J ) 12.9, 7.0), 3.56 (ddq, 1H, J ) 2.2, 7.0, 6.5), 3.70 (dd, 1H, J
(
11) Burgstahler, A. W.; Weigel, L. O.; Shaefer, L. G. Synthesis 1976,
67-768.
12) Criegee, R.; Marchand, B.; Wannowius, H. Ann. Chem. 1942, 550,
2.2, 12.9), 4.44 (d, 1H, J ) 10.1), 4.52 (d, 1H, J ) 11.1), 4.54 (d,
7
9
1
H, J ) 10.1), 4.80 (d, 1H, J ) 11.1), 7.12 (d, 2H, J ) 7.3), 7.36 (m,
(
9.
13
3
4H), 7.36 (m, 2H); C NMR (100.6 MHz, CDCl ) δ 17.9, 69.6, 70.6,