D.E. White et al. / Tetrahedron xxx (2014) 1e16
13
in round-bottomed flasks fitted with rubber septa. Air- and
moisture-sensitive chemicals were transferred via syringe or
stainless steel cannula. Flash chromatography was performed using
silica gel 60 (230e400 mesh) purchased from EM Science. Pre-
paratory TLC was performed on 20ꢂ20 cm silica gel 60 F254 plates
(0.25 mm thickness) precoated with a fluorescent indicator pur-
chased from EM Science.
Observed >99% ee as determined by chiral HPLC analysis of the 2-
naphthylsulfide derivative [obtained by ring opening with
0.8 equiv 2-naphthalenethiol and 0.8 equiv Et3N in MeOH (0.75 M)
at 4 ꢀC and subsequent purification of the terminal addition product
by preparatory TLC (40% EtOAc/hexanes); ChiracelÒ OD, 5% i-PrOH/
hexanes, 1 mL/min, 254 nm, tR (minor)¼18.4 min; tR (major)¼
22.3 min]. [
a
]
31 þ6.19ꢀ (neat); lit.52
[
a
]
D
22 þ14.8ꢀ (c 1.18, Et2O).
D
Materials: Unless otherwise stated, all reagents were purchased
ꢁ
from Acros, Sigma-Aldrich, Alfa Aesar, Lancaster, Pfaltz & Bauer,
4.3. Representative procedure for the PKR of terminal epox-
Strem, EM Science, or EMD Chemicals Inc. and used as received.
Racemic methyl glycidate was received as a generous gift from
Rhodia ChiRex. Solvent was distilled over CaH2 (CH2Cl2, CH3CN), Na
(benzene, toluene), or Na/benzophenone ketone (THF) where in-
dicated; otherwise, solvent was used directly from the bottle. An-
hydrous DMF, MeOH, and EtOH were obtained from Sigma-Aldrich
and packaged in a Sure/SealÔ bottle. Unless otherwise stated,
catalyst loadings were not corrected for the presence of residual
solvent. Measured values are rounded for convenience; calculations
were performed prior to rounding.
ides with catalyst (R,R)-4a: (2S)-1-phenoxyhexan-2-ol
A 5-mL round-bottomed flask equipped with a stir bar was
charged with phenol (235 mg, 2.5 mmol), (ꢃ)-1,2- epoxyhexane
(0.67 mL, 5.6 mmol), and distilled CH3CN (0.27 mL). A stock solution
of oligomeric cyclic (R,R)-(salen)Co(III) triflate 4a in distilled CH3CN
(0.0125 M, 15
mL, 0.00019 mmol) was added, and the flask was
sealed with a plastic cap. The reaction mixture was then stirred for
16 h at room temperature, at which time pyridinium p-toluene-
sulfonate (1 mg, 0.004 mmol) was added to quench the catalyst and
ensure complete oxidation to Co(III). The reaction was diluted with
Et2O (3 mL) and applied to a pad of silica gel. The pad was eluted
with Et2O (200 mL), and the filtrate washed with 1 N NaOH
(3ꢂ25 mL) and brine, respectively. After drying over MgSO4, solvent
was removed from the filtrate by rotary evaporation. The bulk of
remaining epoxide was removed from the crude product under
high vacuum. The product was purified by flash chromatography on
silica gel (15% EtOAc/hexanes) to give 445 mg (92%) of a clear oil in
99% ee as determined by chiral HPLC analysis [ChiracelÒ OD, 5%
EtOH/hexanes, 1 mL/min, 220 nm, tR (minor)¼6.9 min; tR (major)¼
Instrumentation: All solution state 1H NMR, 13C NMR, and 19F
NMR spectra were recorded using an Inova-600 (600 MHz), an
Inova-500 (500 MHz), or a Varian Mercury-400 (400 MHz) spec-
trometer. Chemical shifts for hydrogen are reported in parts per
million (ppm) downfield from tetramethylsilane and are referenced
to the resonances of residual protium in the NMR solvent: pyridine-
d5
3.30); DMSO-d6
a broad singlet between
(
d
8.71, 7.55, 7.19); CDCl3
2.49); acetone-d6
4.5 and 5.5 in pyridine-d5. Chemical
(
d
7.26); D2O (
d 4.79); CD3OD (d 4.78,
(d
(d
2.04). H2O appears as
d
d
shifts for carbon are reported in parts per million (ppm) downfield
from tetramethylsilane and are referenced to the resonances of the
10.1 min]. lH NMR (CD3OD)
d 7.22e7.27 (m, 2H), 6.88e6.94 (m, 3H),
NMR solvent, except D2O: pyridine-d5 (
d
149.9, 135.5, 123.5); CDCl3
3.82e3.92 (m, 3H), 1.58e1.67 (m, 1H), 1.45e1.58 (m, 2H), 1.31e1.45
(d
77.0); CD3OD ( 49.0); DMSO-d6
d
(d
39.5); acetone-d6 206.0,
(d
(m, 3H), 0.94 (dd, J¼7.2, 7.2 Hz, 3H). 13C NMR (CD3OD)
d
160.5,130.4,
29.8). Chemical shifts for carbon in D2O are reported in parts
per million (ppm) downfield from the hydrogen resonances of
the trimethylsilyl group of added of 3-(trimethylsilyl)-1-propane-
121.7, 115.6, 73.2, 71.0, 34.3, 28.9, 23.8, 14.4. IR (thin film) n 3407,
3063, 3042, 2957, 2932, 2872, 1599, 1497, 1458, 1379, 1335, 1300,
1244, 1173, 1136, 1078, 1040, 922, 883, 814, 754, 691, 613, 509 cmꢄ1
.
30
25
sulfonic acid, sodium salt (
d
0). IR spectra were recorded as KBr
[
a
]
þ19.4ꢀ (c 2.03, CH2Cl2); lit.6
[a
]
þ18.7ꢀ (c 1.25, CH2Cl2). MS
D
D
discs or as thin films on either NaCl or KBr plates on a PerkineElmer
FTIR 1600 or a Galaxy Series FTIR 3000 spectrophotometer. Optical
rotations were measured using a 2 mL cell with a 1 dm path length
on a Jasco DIP 370 digital polarimeter. Mass spectrometric data was
obtained at the Harvard University mass spectrometry facility or on
a Waters MicromassÒ ZQÔ mass spectrometer. Preparative HPLC
purification was performed on an Agilent 1100 Series instrument.
Chiral GC analyses were performed on a Hewlett Packard 5890
Series II gas chromatograph. Chiral HPLC analyses were performed
on a Hewlett-Packard 1050 or a Shimadzu VP-series instrument.
Chiral SFC analysis was performed on a Berger instrument.
(ApCI) m/z calcd for C12H17O 177.1, found 177.1 (100%) [MꢄOH]þ;
calcd for C12H19O2 195.1, found 195.1 (26%) [MþH]þ; calcd for
C
12H22NO2 212.2, found 212.1 (9%) [MþNH4]þ.
4.4. Representative procedure for the AKR of terminal epox-
ides with catalyst (R,R)-4a: (2S)-1-benzyloxy-2-hexanol
A 5-mL round-bottomed flask equipped with a stir bar was
charged with benzyl alcohol (0.26 mL, 2.5 mmol), (ꢃ)-1,2-
epoxyhexane (0.67 mL, 5.6 mmol), and distilled CH3CN
(0.066 mL). The flask was sealed with a plastic cap, and cooled to
4 ꢀC. A room temperature stock solution of oligomeric cyclic (R,R)-
4.2. Representative procedure for the HKR of terminal epox-
(salen)Co(III) triflate 4a in distilled CH3CN (0.0126 M, 200 mL,
ides with catalyst (R,R)-4a: (R)-butadiene monoxide
0.0025 mmol) was added, and the flask was resealed with the
plastic cap. The reaction mixture was then stirred for 24 h at 4 ꢀC, at
which time pyridinium p-toluenesulfonate (2 mg, 0.008 mmol) was
added to quench the catalyst and ensure complete oxidation to
Co(III). The reaction mixture was diluted with Et2O (3 mL) and
applied to a pad of silica gel after warming to room temperature.
The pad was eluted with Et2O (200 mL), and solvent was removed
from the filtrate by rotary evaporation. The bulk of remaining ep-
oxide was removed from the crude product under high vacuum.
Purified by flash chromatography on silica gel (20% EtOAc/hexanes)
to give 480 mg (92%) of a clear liquid in >99% ee as determined by
chiral HPLC analysis [(R,R)-Whelk-01 (Pirkle), 2% i-PrOH/hexanes,
1 mL/min, 215 nm, tR (minor)¼10.6 min; tR (major)¼11.5 min]. 1H
A 50-mL round-bottomed flask equipped with a stir bar was
charged with oligomeric cyclic (R,R)-(salen)Co(III) triflate 4a
(26.0 mg, 0.033 mmol) and placed in a room temperature water
bath. (ꢃ)-Butadiene monoxide (10.5 mL, 130 mmol) immediately
followed by H2O (1.64 mL, 91 mmol) in one portion were added. The
reaction flask was sealed with a septum secured by copper wire to
prevent substrate evaporation (CAUTION! An initial pressure
buildup is observed due to the volatility of the epoxide under the
exothermic reaction conditions. Care should be taken to use
equipment adequate for elevated pressures.). After stirring 24 h at
room temperature, resolved epoxide and excess H2O were vacuum
transferred (0.45 mm Hg, reaction pot: room temperature) to
a ꢄ78 ꢀC receiving flask. The epoxide was dried over MgSO4 and
filtered through a sand plug to give 3.28 g of a clear liquid containing
1% by mass 3-butene-1,2-diol. The corrected yield was 35%.
NMR (CD3OD)
d
7.29e7.37 (m, 4H), 7.26 (tt, J¼2.1, 6.8 Hz, 1H), 4.54
(d, J¼12.4 Hz,1H), 4.52 (d, J¼12.5 Hz,1H), 3.71 (dddd, J¼4.4, 6.5, 6.5,
7.4 Hz, 1H), 3.42 (dd, J¼4.2, 9.8 Hz, 1H), 3.37, (dd, J¼6.4, 9.8 Hz, 1H),
1.46e1.55 (m, 1H), 1.26e1.46 (m, 5H), 0.91 (dd, J¼7.1, 3H). 13C NMR