Nakamura Laboratory Experiment Manual 2010
Sample (Template) of Experimental Section1
General. All reactions dealing with air- or moisture-sensitive compounds were carried out in a dry
reaction vessel under nitrogen or argon. The water content of the solvent was confirmed with a
Karl-Fischer Moisture Titrator (MKC-210, Kyoto Electronics Company) to be less than 10 ppm.
Analytical thin-layer chromatography was performed on glass plates coated with 0.25 mm 230–400
mesh silica gel containing a fluorescent indicator (Merck). Gas-liquid chromatographic (GLC) analysis
was performed on a Shimadzu 14A or 14B machine equipped with glass capillary column HR-1
(0.25-mm i.d.  25 m). Analysis with high pressure liquid chromatography (HPLC) was performed on
JASCO HPLC system equipped with an ODS column (Senshu PEGASIL ODS 4.6 250 mm; column
temperature at 40 °C). Flash silica gel column chromatography was performed on silica gel 60N (Kanto,
spherical and neutral, 140–325 mesh) as described by Still.2 Gel permeation column chromatography
was performed on a Japan Analytical Industry LC-908 (eluent: chloroform) with JAIGEL 1H and 2H
polystyrene columns. The melting points of solid materials were determined on a Mel-Temp capillary
melting-point apparatus and were uncorrected. IR spectra were recorded on ASI Applied Systems
REACT IR1000 equipped with an attenuated total reflection (ATR) and are reported as wavenumber
() in cm-1. NMR spectra were measured on JEOL ECX-400, ECA-500 and Bruker AV-500
spectrometers and reported in parts per million from tetramethylsilane. 1H NMR spectra in CDCl3
were referenced internally to tetramethylsilane as a standard, and
resonance. Methyl, methylene, and methyne signals in
13C
13C
NMR spectra to the solvent
NMR spectra were assigned by DEPT
spectra. Routine mass spectra were acquired by atmospheric pressure ionization (APCI) using a
quadrupole mass analyzer on Shimadzu QP-8000 or Waters ZQ-S spectrometer, and high resolution
spectra by APCI or electrospray ionization (ESI) using a time-of-flight mass analyzer on JEOL
JMS-T100LC (AccuTOF) spectrometer with a calibration standard of polyethylene glycol (MW 1000).
X-ray diffraction study was carried out on a MacScience DIP2030 Imaging Plate diffractometer. Space
group determination, structural solution, and refinement were performed using a maXus program.
Materials. Unless otherwise noted, materials were purchased from Tokyo Kasei Co., Aldrich Inc., and
other commercial suppliers and used after appropriate purification before use. Anhydrous ethereal
1 General: General experimental procedures and methods for separation, purification and analysis.
The latter may be separated as Instrumentation section. Materials: Suppliers and/or methods
for preparation or purification of starting materials, reagents and solvents.
2.
Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923-2925.
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Nakamura Laboratory Experiment Manual 2010
solvents (stabilizer-free) were purchased from WAKO Pure Chemical and purified by a solvent
purification system (GlassContour) 3 equipped with columns of activated alumina and supported
copper catalyst (Q-5) prior to use. All other solvents were purified by distillation and stored over
molecular sieves 4Å. In(OTf)3 was purchased from Aldrich Inc. and used as received.
3E-[Ethoxy-[2-[2-oxo-3-[hydroxyphenylmethyl]-5-thiacyclohexyl]-carbene]pentacarbonylchromium
(10a)
and
3Z-[Ethoxy-[2-[2-oxo-3-[hydroxyphenylmethyl]-5-thiacyclohexyl]-carbene]pentacarbonylchromium
(10b). To a solution of diisopropylamine (0.35 mL, 2.50 mmol) in 1.0 mL of THF was added a 1.51 M
BuLi in hexane (1.56 ml, 2.30 mmol) at 0 °C. After 20 min, the solution was cooled to -70°C, and was
transferred to a solution of 8a (471 mg, 1.00 mmol; syn/anti = >97:3) in 1.5 mL of THF at -70｡C. After
30 min, a solution of benzaldehyde (0.158 mL, 0.56 mmol) in 1.0 mL of THF was added, and after
additional 15 min stirring, 4N HCl (2 mL) was added to the reddish reaction mixture. The red color
immediately disappeared upon addition of the aldehyde. After stirring for 15 min, the reaction
mixture was warmed to room temperature. The organic layer was exacted three times with 2 mL of
ether, and the combined organic extracts were washed successively with sat. NaHCO 3 and with sat.
NaCl. Drying over MgSO4 and concentration in vacuo afforded a red oily product (790 mg). TLC
analysis indicated the formation of the
cis (10a; Rf = 0.52, 7% EtOAc in hexane) and the trans isomer
(10b; Rf = 0.31). These isomers were separated by chromatography on silica gel (15 g, 5%~20% EtOAc
in hexane) to obtain 10a (321 mg, 51%, red crystals) and 10b (112 mg, 21%, a red oil). The E
stereochemistry of 10a reaction was assigned by the 1H NMR signal at  2.45 which showed 9.3 Hz
coupling between the two methynes protons , COCH-CHOH, and the Z-stereochemistry of 10b by the
signal at  2.65, which showed 2.5 Hz coupling.
10a: bp 129-135 °C (bath temp)/1.2 mmHg; IR (Nujol) 2250, 2010 (w, CC), 1640 (vs, C=O), 1300, 1240
(w) , 1150, 1110, 890, 750; 1H NMR (200 MHz, CDCl3)  0.87 (s, 3 H, CCH3), 1.27 (t, J = 8.0 Hz 3 H,
CH2CH3), 1.29 (s, 3 H, CCH3), 2.52 (q, J = 8.0 Hz , 2 H, CH2CH3), 3.32 (dd, J = 2.6, 12.2 Hz, 1 H,
OCHHC), 3.79 (dd, J = 2.6, 12.2 Hz, 1 H, OCHHC), 4.07 (d, J = 12.4 Hz, 1H, OCHHC), 4.17 (s, 1 H,
allylic, CH ), 4.26 (d, J = 12.0 Hz, 1 H, OCHHC) 6.95-7.37 (m, 10 H, aromatic CH); Anal. Calcd for
C26H26O2N2S: C, 72.53; H, 6.09; N, 6.51; S, 7.45. Found: C, 72.75; H, 6.39; N, 6.43; S, 7.20.
10b: mp 135-139 °C (dec); IR (CCl4) 3605, 2920, 2060 (CO), 1945 (w, CO), 1748 (vs, ester C=), 1718 (s,
ketone C=O), 1245, 658; 1H NMR (500 MHz, CDCl3),1.46 (t, J = 6.9 Hz, 3H), 2.35 (dd, J = 7.3, 13.8 Hz,
He),
3.
2.52 (dd, J = 7.8, 13.7 Hz, H f), 2.61 (dd, J = 3.7, 13.7 Hz, Hg), 2.68 (dd, J = 3.7, 13.8 Hz, H h), 2.86 (d,
Pangborn, A.B.; Giardello, M.A.; Grubbs, R.H.; Rosen R.K.; Timmers F.J. Organometallics 1996,
15, 1518-1520.
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Nakamura Laboratory Experiment Manual 2010
J = 3.7 Hz, Hk), 3.07-3.15 (m, Hd and Hi), 3.29 (dd, J = 3.7, 17.0 Hz, H b), 3.92 (ddd, J = 3.7, 11.0, 11.5 Hz,
Hc),
4.12 (dd, J = 11.5, 17.0 Hz, H a), 4.71-4.78 (m, J1/2 = 9 Hz, 1H),
7.15-7.43 (m, 10H;
13C
NMR
5.28 (dd, J = 3.7, 8.7 Hz, Hj),
(125 MHz, CDCl3) 14.8 (CH3), 33.9 (CH2), 34.9 (CH2), 41.6, (CH2) 56.4
(CH2), 58.8 (CH2), 66.7 (CH2), 73.8 (CH2), 78.1 (CH2), 126.7 (CH2), 127.2 (CH), 128.2 (CH), 128.6, 128.8,
128.8, 213.0 (C=O), 216.1 (C=O), 223.0 (C=O); Anal. Calcd for C28H26O8CrS: C, 58.53; H, 4.56. Found: C,
58.66; H, 4.75.
Coupling analysis indicated the diequatorial orientation of the two bulky groups on the
thiacyclohexanone ring and the threo stereochemistry of the aldol moiety.
The narrow
width of the
broad signal at  4.71-4.78 indicated the equatorial disposition of this methyne proton connected to the
carbenic oxygen atom, which in turn indicates cis-fusion of the two rings. This stereochemistry
indicates that the hydride reduction of the cyclohexanone carbonyl in 8 took place from the less
hindered side as expected.
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