Notes
J . Org. Chem., Vol. 64, No. 13, 1999 4951
(KBr) 1241 (s), 1125 (s), 1116 (s), 1086 (s), 1019 (s) cm-1. Anal.
Calcd for C17H19BrO: C, 58.13; H, 5.45. Found: C, 57.88; H,
5.42.3.
for 1 h. The reaction was quenched by the addition of methanol
(5 mL) and stirred at -20 °C for 25 min. The mixture was rinsed
into a separatory funnel and extracted with ether (3 × 25 mL).
The combined organic extracts were washed with water (3 × 25
mL) and brine (1 × 25 mL) and dried over Na2SO4 and filtered.
Removal of solvent afforded a residue which was purified by
flash chromatography (20% ethyl acetate in hexanes in the
presence of 1% triethylamine) to give the product as a clear oil
(0.42 g, 72%). The analysis of the crude reaction mixture by a
Chiracel OJ column revealed the enantiomer ratio to be 7:1. The
column was eluted with 100% EtOH at a flow rate of 1 mL/min.
The retention time of (R)-isomer was 21.3 min and (S)-isomer
was 17.6 min.
(()-1-[2-(2,2-Dim eth oxyeth yl)-4-(ben zyloxy)p h en yl]-2-[3-
(ben zyloxy)p h en yl]eth a n -1-ol (8). To a 100 mL flame-dried,
round-bottomed flask equipped with a magnetic stir bar, a
nitrogen balloon, and a septum were added bromoacetal 6 (2.85
g, 12 mmol) and freshly distilled THF (62 mL). The flask was
cooled to -78 °C in an IPA/dry ice bath. n-BuLi (5.5 mL, 13
mmol, 2.4 M solution in hexane) was added via a syringe over 5
min, and the mixture was allowed to stir at -78 °C for 1 h. To
the resulting yellow solution was added the aldehyde 7 (3.14 g,
13 mmol) as a solution in dry THF (5 mL). The reaction was
stirred at -78 °C for 1 h. The mixture warmed to the room
temperature and stirred for 1 h. The reaction was quenched by
addition of water and rinsed into a separatory funnel. The
mixture was extracted with ethyl acetate (3 × 25 mL), and the
organic extracts were washed with water (3 × 25 mL) and brine
(1 × 25 mL), dried over Na2SO4, and filtered. Removal of solvent
afforded a residue which was purified by flash chromatography
(20% ethyl acetate in hexanes in the presence of 1% triethy-
lamine) to give the product as a clear oil (4.3 g, 65%). An
analytical sample was obtained by taking a middle fraction from
Kin etic Resolu tion of r a c-8. (S)-(+)-1-[2-(2,2-Dim eth oxy-
eth yl)-4-(ben zyloxy)p h en yl-2-[3-(ben yloxy)p h en yl]eth a n -
1-ol (8). To a 25 mL flame-dried, round-bottomed flask equipped
with a magnetic stir bar, a nitrogen balloon, and a septum were
added rac-8 (1.29 g, 2.58 mmol) and the catalyst 13 (13 mg, 0.76
mol %) and dissolved in freshly distilled tert-amyl alcohol (17
mL) to give ca. 0.15 M solution. The flask was gently heated
with a hot gun to dissolve the catalyst. The flask was then placed
in a precooled bath at 0 °C. Freshly distilled TEA (0.27 mL, 1.93
mmol) was added in one portion and stirred for 5 min. To this
well-stirred solution, the freshly distilled Ac2O (0.18 mL, 1.93
mmol) was added via a syringe dropwise over 10 min. This
solution was allowed to stir at 0 °C for 50 h. TLC showed the
partial completion of the reaction. The reaction mixture was
filtered through a small plug of silica gel to remove the catalyst.
The filtrate was concentrated on a rotary evaporator. The
residue was then purified by flash chromatography (20% ethyl
acetate in hexanes in the presence of 1% triethylamine to give
acetate (R)-14 (0.61 g, 43.6%) and alcohol (S)-8 (0.68 g, 52.7%).
The analysis of the alcohol with a Chiracel OJ column eluted
with 100% EtOH revealed that the enantiomer ratio to be 27.6:
1
the flash chromatography. H NMR (250 MHz, CDCl3) δ 7.45-
7.28 (m, 11H), 7.20 (t, 1H, J ) 7.7 Hz), 6.92-6.81 (m, 5H), 5.11
(ddd, 1H, J ) 2.2 Hz, J ) 5.3 Hz, J ) 7.7 Hz), 5.05 (s, 2H), 5.01
(2H), 4.40 (t, 1H, J ) 5.10 Hz), 3.31 (s, 3H), 3.27 (s, 3H), 3.07-
3.02 (m, 2H), 2.95 (d, 1H, J ) 6.0 Hz), 2.91 (d, 1H, J ) 5.0 Hz),
2.72 (d, 1H, J ) 2.3 Hz). 13C NMR (62.9 MHz, CDCl3) δ 158.8,
157.8, 140.5, 137.0, 136.9, 135.8, 135.0, 129.4, 128.5, 128.0, 127.6,
127.4, 122.0, 116.8, 115.9, 133.2, 112.76, 106.9, 70.8, 69.9, 69.8,
54.3, 53.5, 44.0, 36.2. IR (Neat) 1595 (s), 1510 (s), 1458 (s), 1386
(s), 1249 (s) cm-1. Anal. Calcd for C32H34O5: C, 77.08; H, 6.87.
Found: C, 77.29; H, 7.08.
1-[2-(2,2-Dim eth oxyeth yl)-4-(ben zyloxy)ph en yl]-2-[3-(ben -
zyloxy)p h en yl]eth a n on e (10). To a 25 mL flame-dried, round-
bottomed flask equipped with a magnetic stir bar, a nitrogen
balloon, an addition funnel, and a septum were added oxalyl
chloride (0.196 mL, 2.25 mmol) and freshly distilled CH2Cl2 (9
mL). The flask was cooled to -78 °C in an IPA/dry ice bath. To
the flask, DMSO (0.32 mL, 4.5 mmol) was added through the
addition funnel over 5 min as a solution in 5 mL of CH2Cl2, and
the reaction was allowed to stir at -78 °C for 10 min. The alcohol
8 (0.90 g, 1.80 mmol) was then added as a solution in dry CH2-
Cl2 (5 mL). The reaction was allowed to stir at -78 °C for 30
min. Freshly distilled TEA (1.25 mL, 9.0 mmol) was added
dropwise via syringe, and the mixture was allowed to stir at
-78 °C for 1 h. TLC showed the completion of the reaction. The
reaction was quenched by addition of water (10 mL) and rinsed
into a separatory funnel. The mixture was extracted with CH2-
Cl2 (3 × 25 mL), and the combined organic extracts were washed
with water (3 × 25 mL) and brine (1 × 25 mL), dried over Na2-
SO4, and filtered. Solvent removal afforded a residue which was
purified by flash chromatography (10% ethyl acetate in hexanes
in the presence of 1% triethylamine) to give the product as clear
oil (0.83 g, 94%). An analytical sample was obtained by taking
a middle fraction from the flash chromatagraphy. 1H NMR (250
MHz, CDCl3) δ 7.74 (d, 1H, J ) 8.7 Hz), 7.42-7.31 (m, 11H),
6.92-6.82 (m, 5H), 5.08 (s, 2H), 5.01 (s, 2H), 4.44 (t, 1H, J )
5.4 Hz), 4.14 (s, 2H), 3.26 (s, 6H), 3.14 (d, 2H, J ) 5.4 Hz). 13C
NMR (62.9 MHz, CDCl3) δ 199.5, 160.8, 159.0, 140.6, 136.9,
136.5, 136.5, 136.3, 131.5, 130.4, 129.6, 128.6, 128.5, 128.1, 127.9,
127.4, 122.1, 119.4, 116.0, 113.1, 112.3, 105.3, 69.9, 69.9, 54.0,
48.1, 38.4. IR (neat) 1605 (s), 1572 (s), 1503 (s), 1241 (s), 1161
(s) cm-1. Anal. Calcd for C32H32O5: C, 77.40; H, 6.50. Found:
C, 77.70; H, 6.70.
1, [R]24 ) 10.6 (1.0, CH Cl). The acetate was reduced to the
D
alcohol with LiAlH4 in 96% yield and analyzed under the same
conditions. The enantiomeric ratio was measured to be 9:1, [R]24
) -9.52 (1.05, CH2Cl2).
D
2,8-Bis(ben zyloxy)-5,6,11,12-tetr ah ydr o-5,11-epoxydiben -
zo[a ,e]cyclocten e (9). To a 100 mL flame-dried, round-bot-
tomed flask equipped with a magnetic stir bar, a nitrogen
balloon, and a septum were added alcohol 8 (1.72 g, 3.4 mmol)
and freshly distilled CH2Cl2 (69 mL). The flask was then cooled
to -78 °C in an IPA/dry ice bath. To this solution was added
p-toluenesulfonic acid (59 mg, 0.31 mmol, 0.09 equiv) as a solid
in one portion, and the bath was removed. The solution was
allowed to come to room temperature and stirred for 6-8 h. To
the mixture was added solid K2CO3 and stirring was continued
for 10 min. The K2CO3 was removed by filtration. After removal
of the solvent, the residue was purified by flash chromatography
(10% ethyl acetate in hexanes) to give the product as a white
solid (1.49 g, 99%). An analytical sample was obtained by
recrystallization from hexane and ethyl acetate. mp 130-131
°C. 1H NMR (250 MHz, CDCl3) δ 7.35-7.21 (m, 10H), 6.94 (d,
2H, J ) 8.5 Hz), 6.73 (dd, 2H, J ) 2.5 Hz, J ) 8.4 Hz), 6.56 (d,
2H, J ) 2.3 Hz), 5.20 (d, 2H, J ) 5.6 Hz), 4.87 (s, 4H), 3.46 (dd,
2H, J ) 5.9 Hz, J ) 16.2 Hz), 2.65 (d, 2H, J ) 16.2 Hz). 13C
NMR (62.9 MHz, CDCl3) δ 157.5, 137.0, 133.0, 130.2, 128.4,
127.8, 127.4, 126.1, 114.4, 113.1, 69.8, 68.9, 36.5. IR (CH2Cl2)
1615 (s), 1506 (s), 1245 (s), 1030 (s) cm-1. Anal. Calcd for
C
30H26O3: C, 82.92; H, 6.03. Found: C, 83.00; H, 6.29.
2,8-Dih yd r oxy-5,6,11,12-tetr a h yd r o-5,11-ep oxyd iben zo-
[a ,e]cyclocten e (2). In an oven-dried pressure tube equipped
with a magnetic stir bar was dissolved dibenzyl ether 9 (1.32 g,
3.0 mmol) in 15 mL of a 1:1 mixture of methanol and ethyl
acetate to give ca. 0.2 M solution. To the pressure tube, Pd/C
(0.31 mg, 0.3 mmol, 10 mol %) was added in one portion, and
the vessel was purged with H2 several times. The tube was
pressurized to about 45 psi. This mixture was carefully allowed
to stir behind a safety shield for 6 h. The excess H2 was released,
and the mixture was filtered through Celite to remove the
catalyst. The filtrate was concentrated on a rotary evaporator.
The residue was purified by flash chromatography (50% ethyl
acetate in hexanes) to give the product as a white solid (0.766
g, 99%). An analytical sample was obtained by recrystallization
from acetone and toluene to give white crystals. mp 285-286
Asym m etr ic Redu ction of 10. (R)-(-)-1-[2-(2,2-Dim eth oxy-
ethyl)-4-(benzyloxy)phenyl]-2-[3-(benzyloxy)phenyl]ethan-1-ol
(8). To a 10 mL flame-dried recovery flask equipped with a
magnetic stir bar, a nitrogen balloon, and a septum was added
the oxazaborolidine 11 (0.38 g, 1.3 mmol) under nitrogen in a
glovebag. Freshly distilled methylene chloride (2.6 mL) was
added to give ca. 0.5 M solution. The flask was cooled to -20 °C
in methanol/ice/salt bath. To the solution of the oxazaborolidine,
the ketone 10 (0.65 g, 1.3 mmol) was added as a solution in 1
mL of dry methylene chloride over 10-15 min. After the addition
of all of the ketone, the mixture was allowed to stir at -20 °C
°C. (S,S)-2: [R]25 ) -16.24 (1.01, acetone), (R,R)-2: [R]25
)
D
D