Enantioselective Functionalization of Vinylarenes
J . Org. Chem., Vol. 64, No. 26, 1999 9707
or argon) in flame-dried glassware. All reaction solvents were
dried according to literature procedures22 immediately prior
to use, and when necessary, they were purged of oxygen using
repeated freeze-pump-thaw cycles and stored under argon
in Schlenk flasks. With the exception of p-isobutylstyrene,
which was prepared in three steps using a literature proce-
dure,23 all vinylarenes and other reagents were purchased from
Aldrich Chemical Co. at the highest grade available and used
without further purification unless otherwise noted. Prior to
use, vinylarenes were distilled under partial vacuum and
percolated through a column of dry, neutral alumina. Neat
catecholborane was distilled under a partial vacuum of argon
(bp 65 °C at 57 mm Hg) to remove B2(catechol)3 and stored
under argon in a Schlenk flask at -25 °C. Pinacol (2,3-
dimethylbutane-2,3-diol) was dried via azeotropic distillation
with benzene and then recrystallized from anhydrous ether.
It was subsequently stored in a vacuum desiccator over P2O5.
Amylene (2-methyl-2-butene) was distilled under nitrogen
before use. The catalyst precursor [Rh(COD)2]BF4 was pre-
pared using a literature procedure24 and stored under argon.
The actual concentration of all organolithium bases used was
elucidated by titration25 against BHT and fluorene (Fluka).
NMR spectra were recorded as follows: 1H at 400 MHz, 13C
at 100 MHz, 11B at 128 MHz, all in CDCl3 containing 0.03%
TMS. Infrared spectra were obtained as thin films on NaCl
disks. Mass spectra were recorded on a double-focusing mass
spectrometer with 8 kV accelerating and 70 eV ionizing
voltages. Gas chromatography (He carrier, 12.5 psi of head
pressure, 1.15 mL/min flow) was performed with FID detection
using split/splitless injector (split ratio 50) and hexane solu-
tions. Retention times are given in minutes. All analyses were
performed using a 2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl-
â-cyclodextrin column (30 m, 0.25 mm diameter, 0.25 µm
thickness). Analytical thin-layer chromatography was per-
formed on silica gel plates with an F-254 indicator, and
visualization accomplished with UV light, KMnO4, or p-
anisaldehyde dip solutions. Column chromatography was
carried out with flash grade silica gel (200-430 mesh) using
Still’s method. Internal reaction temperatures were monitored
with a digital thermometer and a Teflon-coated probe.
Rep r esen ta tive Elu cid a tion of a n En a n tiom er ic Ex-
cess of H yd r ob or a t ion : Oxid a t ion of (R)-P in a col(1-
p h en yleth yl)bor on a te to (R)-1-P h en yleth a n ol. A small
portion of boronate ester (R)-2a (39.6 mg, 0.17 mmol) was
dissolved in 10 mL of diethyl ether. The flask was flushed with
nitrogen,26 and NaOH (1.5 mL of a 2 N aqueous solution, 3
mmol) was added at rt. Upon cooling to 0 °C, H2O2 (0.70 mL
of a 30% w/v aqueous solution, 0.61 mmol) was added dropwise
and the resulting solution stirred at 0 °C for 30 min and then
at rt for 2 h. The ethereal layer was separated. The aqueous
layer was extracted with ether (3 × 5 mL). The organic extracts
were combined, washed with brine (5 mL), and dried with
MgSO4. A 19.4 mg (99% yield) sample of spectroscopically pure
1-phenylethanol was obtained by flash chromatography (silica
gel, 4:1 hexane/Et2O). Its spectral properties were consistent
with the published data.27 The enantiomeric excess was
determined to be 93%28 by chiral GC (temperature protocol,
80 °C, 3 min, then increase 1 °C per min to 130 °C for 30 min;
retention time (R) ) 33.5 min., (S) ) 35.4 min).
(S)-P in a col(1-p h en ylet h yl)b or on a t e ((S)-2a ). [Rh-
(COD)2]+BF4- (24.7 mg, 0.060 mmol), (S)-(-)-BINAP (44.2 mg,
0.071 mmol), styrene (1a ) (0.35 mL, 3.1 mmol), catecholborane
(0.40 mL, 3.8 mmol), and pinacol (749.9 mg, 6.3 mmol) were
combined in a fashion identical to the preparation of (R)-2a
to afford 684.0 mg (95% yield) of spectroscopically pure (S)-
2a . Its spectroscopic properties were identical to those of its
epimer.
(S)-1-P h en yleth a n ol. A small portion of boronate ester (S)-
2a (39.2 mg, 0.17 mmol) was oxidized in a fashion analogous
to that of (R)-2a with basic hydrogen peroxide to afford, after
flash chromatography (silica gel, 4:1 hexane/Et2O), 19.3 mg
(93% yield) of spectroscopically pure 1-phenylethanol. Its
spectral properties were consistent with published data.27 The
enantiomeric excess was determined to be 90% by chiral GC
using the same temperature protocol as its epimer.
(R)-P in a col(1-(p -m et h ylp h en yl)et h yl)b or on a t e (2b ).
[Rh(COD)2]+BF4- (24.4 mg, 0.060 mmol), (R)-(+)-BINAP (43.6
mg, 0.070 mmol), p-methylstyrene (1b) (0.40 mL, 3.0 mmol),
catecholborane (0.39 mL, 3.7 mmol), and pinacol (741.3 mg,
6.3 mmol) were combined in a fashion analogous to that of
styrene (1a ), except that the reaction solution was kept
between -66 and -65 °C for 7 h, to afford 733.2 mg (99% yield)
of spectroscopically pure 2b. IR: 2982 (s), 1512 (s), 1358 (s),
Rep r esen ta tive Hyd r obor a tion Exp er im en t: P r ep a r a -
tion of (R)-P in a col(1-p h en yleth yl)bor on a te ((R)-2a ). In
a
10 mL round-bottomed flask (RBF), freshly prepared
1
[Rh(COD)2]+BF4 (24.1 mg, 0.061 mmol) and (R)-(+)-BINAP
(44.0 mg, 0.071 mmol) were suspended in 4 mL of dried,
deoxygenated DME. The suspension was stirred until a
homogeneous, orange-red solution was obtained (usually <10
min at rt). Freshly purified styrene (1a ) (0.35 mL, 3.1 mmol)
was then added to the reaction mixture and the resulting
solution stirred at rt for a further 10 min. Upon cooling to -66
°C (internal reaction temperature), catecholborane (0.40 mL,
3.8 mmol) was added as a solution in 2 mL of DME over 30
min. Care was taken to prevent the internal reaction temper-
ature from rising above -63 °C during addition. The reaction
solution was then kept between -66 and -63 °C for 4 h.
Pinacol (759.2 mg, 6.4 mmol) was added rapidly in one batch,
and the vessel was resealed and flushed with a vigorous flow
of nitrogen. The reaction solution was allowed to warm slowly
to rt overnight. The solvent was removed carefully at rt, and
the resulting black, oily residue was purified via flash chro-
matography (silica gel, 24:1 hexane/EtOAc) to afford 709.9 mg
(99% yield) of pinacol(1-phenylethyl)boronate ((R)-2a ). IR:
-
1146 (s). H NMR: δ 7.08 (m, 4 H), 2.38 (q, J ) 7.6 Hz, 1 H),
2.29 (s, 3 H), 1.30 (d, J ) 7.6 Hz, 3 H), 1.21 (s, 6H), 1.20 (s,
6H). 13C {1H} NMR: δ 141.9, 134.3, 129.0, 127.6, 83.2, 24.62,
24.59, 21.0, 17.3. 11B NMR: δ 30.1. MS (EI, 70 eV): m/e (rel
intens) 59.1 (77), 91.1 (44), 129.1 (100), 231.2 (6), 246.2 (10).
HRMS: calcd for C15H23BO2 246.1792, found 246.1809.
(R)-1-(p-Meth ylp h en yl)eth a n ol. A small portion of bor-
onate ester 2b (30.1 mg, 0.12 mmol) was oxidized in a fashion
analogous to that of (R)-2a with basic hydrogen peroxide to
afford, after flash chromatography (silica gel, 3:1 hexane/Et2O),
15.8 mg (97% yield) of spectroscopically pure 1-(p-methylphen-
yl)ethanol. Its spectral properties were consistent with pub-
lished data.29 The enantiomeric excess was determined to be
97% by chiral GC (temperature protocol, 100 °C, 3 min, then
increase 1 °C per min to 150 °C for 10 min; retention time
(R) ) 27.9 min, (S) ) 29.8 min).
(R)-P in a col(1-(p -ch lor op h en yl)et h yl)b or on a t e (2c).
[Rh(COD)2]+BF4- (16.3 mg, 0.040 mmol), (R)-(+)-BINAP (28.9
mg, 0.046 mmol), p-chlorostyrene (1c) (0.24 mL, 2.0 mmol),
catecholborane (0.25 mL, 2.3 mmol), and pinacol (531.8 mg,
4.5 mmol) were combined in a fashion analogous to that of
styrene (1a ), except that the reaction solution was kept
between -66 and -64 °C for 6 h, to afford 518.3 mg (97% yield)
1
2988 (s), 1490 (m), 1358 (s), 1146 (s). H NMR: δ 7.11-7.28
(m, 5H), 2.43 (q, J ) 7.6 Hz, 1 H), 1.33 (d, J ) 7.6 Hz, 3 H),
1.21 (s, 6H), 1.20 (s, 6H). 13C {1H} NMR: δ 145.0, 128.3, 127.8,
125.0, 83.3, 24.61, 24.57, 17.0. 11B NMR: δ 30.1. MS (EI, 70
eV): m/e (rel intens) 83.1 (59), 105.1 (81), 117.1 (29), 174.1
(16), 217.1 (40), 232.2 (100). HRMS: calcd for C14H21BO2
232.1635, obsd 232.1626.
(26) Oxygen is known to oxidize organoboranes in a stereorandom
fashion: see Brown, H. C. Organic Syntheses via Boranes; J ohn Wiley
& Sons: New York, 1975.
(27) Nagai, U.; Shishido, T.; Chiba, R.; Mitsuhashi, H. Tetrahedron
1965, 21, 1701.
(28) A similar yield at up to 96% ee can be obtained by carrying out
the reaction at -67 to -66 °C for 6 h.
(29) Ishizaki, T.; Miura, H.; Nohira, H. Nippon Kagaku Kaishi 1980,
1381.
(22) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon: New York, 1997.
(23) Parinello, G.; Stille, J . K. J . Am. Chem. Soc. 1987, 109, 7122.
(24) Schrock, R. R.; Osborn, J . A. J . Am. Chem. Soc. 1971, 93, 3089.
(25) Ogilvie, W. Personal communication.