S. Fukuzawa, N. Nakano, T. Saitoh
FULL PAPER
Stoichiometric Reaction between Acetophenone (1a) and Samarium
Metal in iPrOH: The following information provides a typical ex-
perimental procedure for the reduction of ketones with samarium
metals. Under a nitrogen atmosphere, samarium powder (150 mg,
1.0 mmol) and a trace of iodine (10Ϫ15 mg, 0.04Ϫ0.06 mmol) were
placed in a 50 mL Schlenk tube fitted with a magnetic stirring bar.
Dry iPrOH (2.0 mL) was introduced by syringe through a septum
at room temperature. An exothermic reaction started within a few
minutes and the solution became dark purple to black; this obser-
vation may represent the formation of ‘‘samarium isopropyloxide’’.
After the solution had been stirred for 1 h at room temperature,
an iPrOH (1.0 mL) solution of acetophenone (120 mg, 1.0 mmol)
was added. The mixture was stirred at the same temperature for
20 h, during which the color of the solution became dark brown.
The solution was hydrolyzed with hydrochloric acid (0.1 mol/L,
25 mL), and the aqueous phase was extracted with three portions
of ethyl acetate (15 mL). The organic phase was washed with aque-
ous sodium thiosulfate (to remove the liberated iodine) and brine,
and was then dried with magnesium sulfate. GC/MS analysis of the
organic solution revealed the presence of 1-phenylethanol as the
major product and a small amount of the corresponding pinacol.
duction; the use of 7 afforded a 60% yield of 3a with 95%
ee (R). The catalytic reaction with 10 mol % of 7 to aceto-
phenone was not successful, giving only a 20% yield (based
on the ketone) with lower enantioselectivity (75% ee).
All products were known compounds and were characterized by
GC/MS on a capillary column (HP-5ms) by use of authentic
samples. The yields of products were determined by GC with bi-
phenyl as an internal standard. Some compounds were isolated by
preparative TLC (Merck Silica Gel 60 PF256) and their structures
Conclusion
1
were further confirmed by H NMR (300 MHz).
This in situ preparation of samarium isopropyloxide Enantioselective Reaction between Acetophenone (1a) and Sm/Chiral
Ligand in iPrOH: The ‘‘samarium isopropyloxide’’ (Sm, 0.5 mmol;
iPrOH, 3.0 mL) was prepared by the same procedure as described
above. After the solution had been stirred for 1 h at room tempera-
ture, a THF (1.0 mL) solution (1R,5R)-3-benzyl-1,5-diphenyl-3-az-
apentane-1,5-diol (7, 350 mg, 1.0 mmol) was added, and the mix-
ture was stirred for 1 h. Acetophenone (120 mg, 0.5 mmol) was
then added, and the resulting mixture was stirred at the same tem-
perature for 20 h, during which the color of the solution changed
to brown. The solution was hydrolyzed with hydrochloric acid (0.1
mol/L, 25 mL), and the aqueous phase was extracted with three
portions of ethyl acetate (15 mL). The organic phase was washed
with aqueous sodium thiosulfate (to remove the liberated iodine)
and brine, and was then dried with magnesium sulfate. Chiral GC
analysis (Chiraldex G-TA, 20 m, 80 °C) of the organic solution
revealed the presence of (R)-1-phenylethanol (Rt ϭ 15.5 min) as a
major product and the (S)-alcohol (Rt ϭ 14.2 min) as the minor
product.
should provide a convenient and efficient method of MPV
reduction without the need for a harmful mercury salt as
an activator for samarium. Furthermore, this method with
metallic samarium has an advantage over SmI2/iPrOH in
terms not only of atom economy but also of stereoselectiv-
ity of the chiral ketones.
Experimental Section
1
General: The H and 13C NMR spectra were recorded on a Varian
Mercury 300 NMR (300 MHz) spectrometer as solutions in
CDCl3. The chemical shifts are reported in δ units downfield from
the internal reference (Me4Si). The infrared spectra were obtained
with a JASCO Herschel FT/IR-230A spectrometer. The HPLC
analyses were carried out on a Hitachi L-7100 apparatus fitted with
a UV detector and chiral columns. The GC/MS analyses were car-
ried out on a HewlettϪPackard 5980/5972 instrument fitted with a
capillary column (HP-5ms, 0.25 mm, 30 m) with helium as carrier
gas. The optical rotations were determined on a JASCO DIP-370
apparatus. The elemental analyses were carried out with a Yanaco
CHN CORDER MT-5. Preparative TLC was conducted on a 20
ϫ 20 cm glass sheet coated with a 2-mm layer of Merck kieselgel
60 PF254. All the lanthanide metals (99.9%) were purchased from
Nippon Yttrium Co., Ltd. Lanthanum and cerium were obtained
as powders. Samarium and ytterbium were obtained as ingots and
scraped with a rasp and then used as powders (ca. 40 mesh). 2-
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2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2004, 2863Ϫ2867