Enantioselective aldol reaction of α-ketoester and Cyclopentaone catalyzed by L-proline

Article abstract of DOI:10.1002/cjoc.201090122

A concise and enantioselective synthesis of (S)-ethyl 2-cyclopentyl-2-hydroxy-2-arylacetate, a key intermediate for the muscarinic receptor, is reported. The tertiary stereogenic center was constructed with good stereoselectivity through the L-proline-catalyzed direct asymmetric aldol reaction of ethyl arylglyoxylate and cyclopentanone. The carbonyl of the condensation product was reduced using a modified Clemmensen reaction which provided an easier workup and was more environmentally acceptable. The enantioselectivity of the aldol reactions was between 58.3% -93.2%, which means that the stereoselective is efficient in controlling configuration of reaction product.

Full text of DOI:10.1002/cjoc.201090122

FULL PAPER
Enantioselective Aldol Reaction of α-Ketoester and
Cyclopentaone Catalyzed by L-Proline
Xiang, Jiminga,b(向纪明)
Li, Baolina,*(李宝林)
a School of Chemistry and Materials Science, Shaanxi Normal University, Xi'an, Shannxi 710062, China
b Department of Chemistry, Ankang University, Ankang, Shannxi 725000, China
A concise and enantioselective synthesis of (S)-ethyl 2-cyclopentyl-2-hydroxy-2-arylacetate, a key intermediate
for the muscarinic receptor, is reported. The tertiary stereogenic center was constructed with good stereoselectivity
through the L-proline-catalyzed direct asymmetric aldol reaction of ethyl arylglyoxylate and cyclopentanone. The
carbonyl of the condensation product was reduced using a modified Clemmensen reaction which provided an easier
workup and was more environmentally acceptable. The enantioselectivity of the aldol reactions was between 58.3%
—
93.2%, which means that the stereoselective is efficient in controlling configuration of reaction product.
Keywords α-hydroxy-α-cyclopentyl arylacetate, asymmetric synthesis, aldol reaction, L-proline, catalysis
Introduction
Racemic α-hydroxy-α-cyclopentyl arylacetate1,2 (1)
and α-hydroxy-α-cyclopentyl arylacetamide3-5 (2) (Fig-
ure 1) are widely prescribed muscarinic receptor an-
tagonists for the treatment of motion sickness, dizziness,
urinary frequency and urge incontinence. Racemic gly-
copyrronium bromide6 (3) (Figure 1) is also used in the
treatment of respiratory complaints, particularly asthma
or chronic obstructive pulmonary disease (COPD), but
has adverse effects including dry mouth, blurred vision,
headaches, and somnolence. Preliminary research indi-
cates that the (S)-enantiomer displays a better therapeu-
tic profile compared to the racemate.7 (S)-Ethyl 2-cyclo-
pentyl-2-hydroxy-2-phenylacetate (4) (Figure 1) is a key
intermediate for the preparation of these compounds and
thus has become an important target for asymmetric
synthesis.
Previously the racemate of 4 was prepared by the
addition of cycloalkyl magnesium bromides to ethyl
benzoyformate followed by basic hydrolysis.8 Asym-
metric synthesis of its congeners was obtained by chiral
dioxolane platform protocol followed by their hydroly-
sis and hydrogenation.9,10 In addition, its asymmetric
synthesis by addition of a cyclohexyl Grignard in the
presence of various additives to a chiral ketoamide of a
ketoester possessing a rigid benzocycloalkl-ene-derived
vicinal amino alcohol platform has also been reported.11
Herein, we report a practical synthesis of 4 with ex-
cellent enantioselectivity, high yield and easier workup
via L-proline-catalyzed asymmetric aldol reaction. The
aldol reaction is one of the most important car-
bon-carbon bond-forming reactions and has been stud-
Figure 1 The structure of α-hydroxy-α-cyclopentyl phenylace-
tate (amide).
ied extensively.12,13 Direct aldolization is atom econ-
omic, and thus it is an attractive method for the synthe-
sis of polyoxygenated compounds. Since it was reported
that L-proline could catalyze a direct asymmetric aldol
reaction, many L-proline-catalyzed direct asymmetric
syntheses have been published.14-16 In contrast to or-
ganocatalyzed direct aldolizations with aldehydes as
acceptors, those related with ketones as an acceptor are
rarely reported and thus are more challenging. However,
recently some L-proline-catalyzed direct aldol reactions
of α-keto ester with ketones have also been reported,7
and in the α-keto esters, the keto function is activated by
the ester group interacted with the electron-withdrawing
group, which can act as the aldol reaction acceptors. Shi
et al. has reported an aldol reaction of α-keto ester with
*
E-mail: baolinli@snnu.edu.cn; Tel.: 0086-0915-3261322; Fax: 0086-0915-3261778
Received October 18, 2009; revised February 2, 2010; accepted March 28, 2010.
Project supported by the National Natural Science Foundation of China (No. 20972090).
Chin. J. Chem. 2010, 28, 617— 621
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
617

Xiang & Li
FULL PAPER
cyclopent-2-enone,17 however, they employed expen-
sive tertiary-phosphines as catalyst. Although the L-pro-
line-catalyzed asymmetric aldol reaction between ethyl
phenylglyoxylate and cyclohexanone has been pub-
lished by Maruoka,18 the asymmetric direct aldol reac-
tion of arylglyoxylate with cyclopentanone to give
chiral tertiary carbon center compound has not been
reported yet. Inspired by Maruoka’s work, we report
here a convenient asymmetric synthetic route to
(S)-ethyl 2-cyclopentyl-2-hydroxy-2-phenylacetate via a
direct asymmetric aldol reaction from ethyl arylglyoxy-
late and cyclopentanone catalyzed by L-proline [Eq. (1)],
which forms a tertiary stereogenic center with good en-
antioselectivity. Compared with Maruoka’s aldol reac-
tion, the reduction of carbonyl group of the aldol reac-
tion products is more convenient and easily controlled
in this method.
a series of asymmetric aldol reactions of arylglyoxylate
analogues with cyclopentanone were investigated in the
presence of L-proline (Table 1).
Table 1 Result of proline-catalyzed asymmetric aldol reactions
Compd.
5a
R
H
Time/h Yielda/%
dr b/%
eec/%
93.2
81.3
83.8
81.0
68.0
60.3
58.3
—
72
96
96
96
36
36
36
120
86
78
＞
＞
＞
＞
＞
＞
＞
96
98
98
98
95
95
95
5b
Me
Et
5c
73
5d
i-Pr
F
70
5e
88
5f
Cl
90
5g
Br
84
5h
MeO
Trace
—
a Isolated yield after silica gel chromatography. b Determined by
1H NMR. c Determined by HPLC on a Daicel OD-H column.
When ethyl arylglyoxylate possessed a weak elec-
tron-withdrawing group (halogen) at the para position
in the aromatic ring, the proline-catalyzed direct asym-
metric aldol reaction was achieved in a higher yield,
shorter reaction time, but slightly weaker enantioselec-
tivity (Entries 5e, 5f, and 5g). When a weak alkyl elec-
tron-donating group was at the para position in the
aromatic ring, the reaction exhibited better stereoselec-
tivity albeit with a reduced chemical yield and a longer
reaction time (Entries 5b, 5c, and 5d). The active elec-
tron-donating group (CH3O) at the para position of the
benzene ring provided the product only in trace amounts.
The product of the intermolecular aldol reaction of
cyclopentanone was not found in the process.
Results and discussion
Although many reports on direct asymmetric aldol
reactions are based on the catalysis of L-proline, this is
the first time that a L-proline-catalyzed direct asymmet-
ric aldol reaction from ethyl arylglyoxylate with
cyclopentanone has been reported. We explored this
reaction, and the optimized result was obtained when
the reaction was performed in DMSO at room tempera-
ture. A survey of different reaction solvents including
DMSO, THF, methanol, ethanol and chloroform re-
vealed that while L-proline can be dissolved in the al-
cohols, the opposite is true for the α-ketoester. However,
because both are soluble in DMSO, this proved to be the
optimal solvent for the reaction. We found that a cata-
lytic amount of L-proline (30 mmol%) in DMSO at
room temperature gave the desired products in high
yield (＞70%) with good enantioselectivity. However,
by increasing the molar ratio of L-proline to 40 mol% or
50 mol% of L-proline, the yield and stereoselectivity of
5 were not obviously improved. The final reaction con-
ditions were 5 mmol of ethyl arylglyoxylate, 30 mmol%
L-proline, and 6 mmol of cyclopentanone in the pres-
ence of 3 mL of DMSO. The mixture was stirred at
room temperature until completion (monitored by TLC).
The solvent was then removed under reduced pressure
and the residue was purified by silica column chroma-
tography using petroleum ether and ethyl acetate (90/10,
V/V) as the eluents to give the corresponding products.
The ee of the major isomer was determined by HPLC
using a Daicel OD-H column with petroleum ether/ethyl
acetate (90/10, V/V). Using similar reaction conditions,
Then, we explored the asymmetric conversion of
cyclopentanone with arylglyoxylate, which showed ex-
cellent diastereoselectivity, the diastereomeric ratio of
1
anti/syn exceeded 95% according to H NMR analysis
of crude product. The enantiomeric excess (ee) of anti
isomer was determined by chiral phase HPLC analysis.
The aldol reactions involving enamine intermediates
have been studied theoretically.19 It was assumed that
the aldol reaction introduced ketone and the chiral
amine to generate an enamine intermediate,20 which
reacted with another carbonyl compound to generate
aldol adduct. In the enamine intermediate, it was more
stable with six-membered ring in the chair conformation
(І) through intramolecular hydrogen-bond than in the
boat conformation (II) (Figure 2).21 In the transition
state (I), the α-keto ester, cyclopentanone and L-proline
formed the E-enamine, which was lower in energy than
in the transition state (II) with Z-enamine.22 Thus, the
anti nucleophilic attack was the predominant product. In
the E-enamine intermediate, the ethoxycarbonyl may be
in axial bond or equatorial bond. When the ethoxycar-
bonyl was in equatorial bond, the five-membered ring
can be formed by intramolecular hydrogen bonds to
make the structure more stable. In this case, the anti
618
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 617— 621

Enantioselective Aldol Reaction of α-Ketoester and Cyclopentaone
attack led to the formation of S-isomer.23
perature for more than 36 h. The reaction progress was
monitored by TLC and considered complete when aryl
α-keto esters remains was used up. The solvent and
volatile material was removed under reduced pressure
and the residue was purified by silica column chroma-
tography using petroleum ether and ethyl acetate (9∶1,
V∶V) as eluent to give corresponding product.
(S)-Ethyl
2-hydroxy-2-(2-oxocyclopentyl)-2-
Figure 2 Potential transition states for aldol reaction.
phenylacetate (5a) Colorless oil, [α]2D0 －76.04 (c
1
0.55, acetone); yield 86%. H NMR (CDCl3) δ: 1.27 (t,
With this information in hand, we studied the con-
version of aldol product 5 to (S)-ethyl 2-cyclopentyl-
2-hydroxy-2-phenylacetate (4) [Eq. (2)]. First, the at-
tempted reduction of the ketone carbonyl group of 5 to
methylene under Wolff-Kishner conditions was unsuc-
cessful. In the presence of a strong base with high tem-
perature, it was easy to induce β-hydroxy elimination.
Reduction of the carbonyl group was achieved through a
modified Clemmensen reaction;24,25 the mixture of 5
and zinc dust was refluxed for 2 h in the presence of
concentrated HCl in alcohol to give 4, with good yield.
Compared with the traditional Clemmensen methods
using toxic Hg, this procedure was simple and friendly
for the environment. The configurations of 4 was also
determined by comparison of the optical rotation and
HPLC retention times with values published in the lit-
erature.
J＝7.1 Hz, 3H), 1.68—1.79 (m, 2H), 2.13—2.19 (m,
2H), 2.25—2.28 (m, 2H), 3.32 (t, J＝9.3 Hz, 1H), 4.21
(b, 1H, OH), 4.30 (q, J＝7.1 Hz, 2H), 7.23—7.41 (m,
3H), 7.62 (d, J＝7.2 Hz, 2H); 13C NMR (CDCl3) δ:
217.04, 174.44, 140.47, 128.19, 127.70, 125.68, 62.60,
56.48, 38.95, 24.65, 20.30, 13.89; IR (film) ν: 3478,
2975, 1743, 1720, 1601, 1494, 1467, 1448, 1368, 1250,
＋
＋
－1
740, 700 cm ; MS m/z (%): 262 (M , 5), 244 (M －
H2O, 100).
(S)-Ethyl 2-hydroxy-2-(2-oxocyclopentyl)-2-p-tol-
ylacetate (5b) Light yellow oil, yield 78%. [α]2D0
1
－41.16 (c 0.48, acetone); H NMR (CDCl3) δ: 1.29 (t,
J＝7.1 Hz, 3H), 1.70—1.79 (m, 2H), 2.14—2.18 (m,
2H), 2.27—2.29 (m, 2H), 2.33 (s, 3H), 3.30 (t, J＝9.4
Hz, 1H), 3.96 (b, 1H, OH), 4.23—4.33 (m, 2H), 7.14 (d,
J＝8.1 Hz, 2H), 7.48 (d, J＝8.1 Hz, 2H); 13C NMR
(CDCl3) δ: 217.45, 174.63, 137.49, 128.94, 125.62,
125.37, 62.60, 56.44, 39.03, 26.55, 24.69, 20.95, 20.33,
13.93; IR (film) ν: 3483, 2970, 1741, 1722, 1511, 1450,
＋
－1
1403, 1250, 846 cm ; MS m/z (%): 276 (M , 4), 258
(M＋－H2O, 100).
(S)-Ethyl 2-(4-ethylphenyl)-2-hydroxy-2-(2-oxo-
cyclopentyl)acetate (5c) Yellow oil, yield 73%. [α]2D0
1
－46.89 (c 0.58, acetone); H NMR (CDCl3) δ: 1.21 (t,
Experimental
J＝7.6 Hz, 3H), 1.28 (t, J＝7.1 Hz, 3H), 1.69—1.78 (m,
2H), 2.13—2.16 (m, 2H), 2.25—2.28 (m, 2H), 2.62 (q,
J＝7.6 Hz, 2H), 3.31 (t, J＝9.5 Hz, 1H), 4.00 (b, 1H,
OH), 4.17—4.35 (q, J＝7.1 Hz, 2H), 7.16 (d, J＝8.2 Hz,
2H), 7.52 (d, J＝8.2 Hz, 2H); 13C NMR (CDCl3) δ:
217.36, 174.61, 143.64, 137.73, 127.68, 125.67, 62.53,
56.47, 39.00, 28.35, 24.70, 20.32, 15.33, 13.92; IR (film)
ν: 3500, 2967, 1741, 1720,＋1511, 1454, 1404, 1249, 847
General
All chemicals used were of analytical grade and ob-
tained from commercial sources. Thin layer chroma-
tography (TLC) was carried out using glass sheets pre-
coated with silica gel GF254. IR spectra (liquid thin film)
were obtained using Nicolet FT-IR 200 spectrometer.
1H NMR and 13C NMR spectra were recorded on a
Bruker AVANCE 300 spectrometer. Chemical shifts
were referenced internally to tetramethylsilane (TMS).
Mass spectra were obtained on a VG-ZAB-HS mass
spectrometer. The ee of major isomer was determined
by Shimadzu LC-10ATVP high performance liquid
chromatography with ultraviolet detector, 150 mm×4.6
mm Daicel OD-H column, eluted with petroleum
ether/ethyl acetate (90/10, V∶V). Wzz-3 digital po-
larimeter.
＋
－1
cm ; MS m/z (%): 290 (M , 5), 272 (M －H2O, 100).
(S)-Ethyl 2-hydroxy-2-(4-isopropylphenyl)-2-(2-
oxocyclopentyl)acetate (5d) Yellow oil, yield 70%.
1
[α]2D0 －52.40 (c 0.32, acetone); H NMR (CDCl3) δ:
1.23 (d, J＝6.9 Hz, 6H), 1.29 (t, J＝7.1 Hz, 3H), 1.70—
1.80 (m, 2H), 2.14—2.17 (m, 2H), 2.26—2.29 (m, 2H),
2.89 (h, J＝6.9 Hz, 1H), 3.31 (t, J＝9.6 Hz, 1H), 3.97 (b,
1H, OH), 4.20—4.33 (m, 2H), 7.19 (d, J＝8.3 Hz, 2H),
7.51 (d, J＝8.3 Hz, 2H); 13C NMR (CDCl3) δ: 217.43,
174.62, 148.26, 137.75, 126.25, 125.68, 62.55, 56.54,
39.01, 33.63, 24.72, 23.88, 20.32, 13.93; IR (film) ν:
3497, 2962, 1742, 1723, 1604, 1510, 1464, 1404, 1248,
Preparation of (S)-ethyl 2-hydroxy-2-(2-cyclopenta-
nonyl) arylacetate
＋
＋
－1
848 cm ; MS m/z (%): 304 (M , 3), 286 (M －H2O,
General procedure A suitable equipped reaction
vessel was charged with 5 mmol of ethyl arylglyoxylate,
1.5 mmol of L-proline, 3 mL of DMSO and 6 mmol of
cyclopentanone. The mixture was stirred at room tem-
100).
(S)-Ethyl 2-(4-fluorophenyl)-2-hydroxy-2-(2-oxo-
cyclopentyl)acetate (5e) Colorless oil, yield 88%.
Chin. J. Chem. 2010, 28, 617— 621
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
619

Xiang & Li
FULL PAPER
1
[α]2D0 －37.64 (c 0.63, acetone); H NMR (CDCl3) δ:
1.31 (t, J＝7.2 Hz, 3H), 1.73—1.80 (m, 2H), 2.16—
2.23 (m, 2H), 2.29—2.31 (m, 2H), 3.30 (t, J＝9.2 Hz,
1H), 4.06 (b, 1H, OH), 4.24—4.38 (m, 2H), 7.03 (t, J＝
8.7 Hz, 2H), 7.58—7.62 (m, 2H); 13C NMR (CDCl3) δ:
217.02, 174.24, 163.98, 160.71, 136.18, 127.59, 114.95,
76.90, 62.72, 56.54, 38.88, 24.53, 20.24, 13.84; IR (film)
ν: 3496, 2976, 1741, 17－20, 1602, 1507, 1406, 1249,
175.65, 135.56, 128.07, 127.75, 125.11, 77.52, 62.37,
54.45, 32.40, 26.34, 14.09; IR (film) ν: 3511, 3058,
2954, 1－724, 1601, 1494, 1448, 1368, 1246, 1173, 734,
＋
＋
1
700 cm ; MS m/z (%): 248 (M , 12), 230 (M －H2O,
100).
Preparation of (S)-ethyl 2-cyclopentyl-2-hydroxy-
2-p-tolylacetate (4b) Light yellow oil, yield 76%.
[α]2D0 ＋7.40 (c 0.89, acetone); 1H NMR (CDCl3) δ: 1.28
(t, J＝6.8 Hz, 3H), 1.33—1.35 (m, 4H), 1.57—1.66 (m,
4H), 2.14—2.32 (m, 4H), 3.76 (b, 1H, OH), 4.14—4.26
(m, 2H), 7.17 (d, J＝6.1 Hz, 2H), 7.54 (d, J＝6.0 Hz,
2H); 13C NMR (CDCl3) δ: 175.80, 137.99, 136.91,
128.75, 125.86, 62.19, 57.57, 47.18, 32.41, 25.88, 20.99,
14.11; IR (film－) ν: 3513, 2955, 1724, 1512, 1445, 1244,
＋
1
1160, 1＋121, 848, 808 cm ; MS m/z (%): 280 (M , 5),
261 (M －H2O, 100).
(S)-Ethyl 2-(4-chlorophenyl)-2-hydroxy-2-(2-oxo-
cyclopentyl)acetate (5f) Light yellow oil, yield 90%.
1
[α]2D0 －37.81 (c 0.26, acetone); H NMR (CDCl3) δ:
1.30 (t, J＝7.1 Hz, 3H), 1.72—1.78 (m, 2H), 2.14—
2.17 (m, 2H), 2.28—2.30 (m, 2H), 3.28 (t, J＝9.9 Hz,
1H), 4.04 (b, 1H, OH), 4.23—4.37 (m, 2H), 7.31 (d, J＝
8.6 Hz, 2H), 7.56 (d, J＝8.6 Hz, 2H); 13C NMR (CDCl3)
δ: 216.92, 174.03, 139.05, 133.75, 128.35, 127.24,
76.94, 62.83, 56.46, 38.87, 24.52, 20.26, 13.88; IR (film)
ν: 3506, 2980, 1741, 1724, 1＋593, 1489, 1401, ＋1256, 851
＋
＋
1
1165, 1099 cm ; MS m/z (%): 262 (M , 10), 244 (M
－H2O, 100).
Conclusion
In summary, a practical method was described for
the synthesis of optically active tertiary α-hydroxyl aryl
esters with good enantioselectivities of up to 93.2%
based on the L-proline-catalyzed asymmetric aldol reac-
tion of cyclopentanone and arylglyoxylate derivatives.
Using a modified Clemmensen reduction, (S)-ethyl
2-cyclopentyl-2-hydroxy-2-phenylacetate (4) was easy
to synthesize. These asymmetric tertiary α-hydroxyl aryl
esters are valuable chiral synthons for the further prepa-
ration of complex chiral compounds. The fact that a
tertiary α-hydroxyl carbon center can be generated un-
der mild conditions may lead to new opportunities in
pharmaceutical syntheses.
－1
cm＋ ; MS m/z (%): 298 (M ＋2, 3), 296 (M , 9), 278
(M －H2O, 100).
(S)-Ethyl 2-(4-bromophenyl)-2-hydroxy-2-(2-oxo-
cyclopentyl)acetate (5g) Light yellow oil, yield 84%.
1
[α]2D0 －33.09 (c 0.14, acetone); H NMR (CDCl3) δ:
1.27 (t, J＝7.1 Hz, 3H), 1.72—1.78 (m, 2H), 2.15—
2.18 (m, 2H), 2.28—2.31 (m, 2H), 3.26 (t, J＝9.8 Hz,
1H), 4.03 (b, 1H, OH), 4.23—4.39 (m, 2H), 7.50 (s, 4H),
7.56 (d, J＝8.6 Hz, 2H); 13C NMR (CDCl3) δ: 216.99,
173.99, 139.55, 131.35, 127.58, 122.01, 77.10, 63.04,
56.45, 38.89, 24.53, 20.28, 13.91; IR (film) ν: 3508,
2976, 1－739, 1718, 1486, 1399, 1253, 1154, 849,＋804,
＋
1
767 cm＋ ; MS m/z (%): 342 (M ＋2, 4), 340 (M , 4),
322 (M －H2O, 100).
References
Preparation of (S)-ethyl 2-cyclopentyl-2-hydroxy-
2-phenylacetate (4a) A suitable equipped reaction
vessel was charged with 14 mmol of ethyl 2-hydroxy-2-
(2-cyclopentanonyl) mandelate, 0.7 mol of zinc powder
and 60 mL of anhydrous ethanol. The resulting slurry
was heated to reflux and stirred. 50 mL of concentrated
hydrochloric acid was charged slowly to the reaction
mixture with a well-controlled rate for 1 h, and stirring
was continued for about 2 h (monitored by TLC). Upon
completion, the reaction mixture was cooled to ambient
temperature, unreacted zinc powder was filtered out,
and the ethanol was distilled off under reduced pressure.
The solution was extracted three times with 30 mL of
ether each time, and the ether solutions were combined,
washed with 20 mL of water, dried over anhydrous
magnesium sulfate, and the solvent was removed by
distillation. The residue was purified by silica column
chromatography using petroleum ether and ethyl acetate
(9∶1, V∶V) as eluent to give corresponding product,
light yellow oil, yield 68%. [α]2D0 ＋7.56 (c 0.71,
1
2
3
4
5
Mitsuya, M.; Mase, T.; Tsuchiya, Y.; Kawakami, K. Bioorg.
Med. Chem. 1999, 7, 2555.
Mitsuya, M.; Ogino, Y.; Mase, T. J. Med. Chem. 2000, 43,
5017.
Kumar, N.; Kaur, K.; Aeron, S. Bioorg. Med. Chem. Lett.
2007, 17, 5256.
Mase, T.; Houpis, I. N.; Akao, A. J. Org. Chem. 2001, 66,
6775.
Mitsuya, M.; Ogino, Y.; Mase, T. Bioorg. Med. Chem. 2000,
8, 825.
Buchwald, P.; Bodor, N. J. Med. Chem. 2006, 49, 883.
Tang, Z.; Cun, L. P.; Jiang, Y. Z.; Gong, L. Z. Org. Lett.
2006, 8(7), 1263.
Shacklett, C. D.; Smith, H. A. J. Am. Chem. Soc. 1953, 75,
2654.
Han, X. Y.; Liu, H.; Chen, L. F.; Zhong, B. H.; Liu, K. L.
Bioorg. Med. Chem. Lett. 2005, 15, 1979.
6
7
8
9
10 Grover, P. T.; Bhongle, N. N.; Wald, S. A.; Senanayake, C.
H. J. Org. Chem. 2000, 65, 6283.
11 Senanayake, C. H.; Fang, K.; Grover, P. T.; Bakale, R. P.;
Vandenbossche, C. P.; Wald, S. A. Tetrahedron Lett. 1999,
40, 819.
1
acetone); H NMR (CDCl3) δ: 1.20 (t, J＝6.3 Hz, 3H),
1.24—1.34 (m, 4H), 1.57—1.68 (m, 4H), 2.11—2.16
(m, 1H), 3.79 (b, 1H, OH), 4.13—4.28 (m, 2H), 7.24—
7.36 (m, 3H), 7.59—7.67 (m, 2H); 13C NMR (CDCl3) δ:
12 Johnson, J. S.; Evans, D. Acc. Chem. Soc. Rev. 2004, 33,
432.
620
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 617— 621

Enantioselective Aldol Reaction of α-Ketoester and Cyclopentaone
13 Palomo, C.; Oiarbide, M.; Garcia, J. M. Chem. Soc. Rev.
2004, 33, 65.
20 Anders, B.; Nagaswamy, K.; Karl, A. J. Chem. Commun.
2002, 620.
14 Tang, Z.; Jiang, F.; Jiang, Y. Z. J. Am. Chem. Soc. 2003,
125, 5262.
15 Tang, Z.; Yang, Z. H.; Jiang, Y. Z. Org. Lett. 2004, 6, 2285.
16 Tang, Z.; Yang, Z. H.; Jiang, Y. Z. J. Am. Chem. Soc. 2005,
127, 9285.
17 Shi, M.; Zhang, W. Tetrahedron 2005, 61, 11887.
18 Tokuda, O.; Kano, T.; Gao, W. G.; Ikemoto, T.; Maruoka,
K. Org. Lett. 2005, 7, 5103.
21 Tang, Z.; Jiang, F.; Gong, L. Z.; Yu, L. T.; Jiang, Y. Z.; Wu,
Y. D. J. Am. Chem. Soc. 2003, 125, 5262.
22 Sakthivel, K.; Notz, W.; Bui, T.; Barbas, C. F. J. Am. Chem.
Soc. 2001, 123, 5260.
23 Tang, Z.; Yang, Z. H.; Chen, X. H.; Cun, L. F.; Jiang, Y. Z.;
Gong, L. Z. J. Am. Chem. Soc. 2005, 127, 9285.
24 Laura, A.; Pierangela, C.; Enzo, S.; Giancarlo, T. Steroids
2004, 69, 789.
19 Bahmanyar, S.; Houk, K. N. J. Am. Chem. Soc. 2001,
123(45), 11273.
25 John, R. W.; Depiing, C.; Dominic, W. Steroids 2002, 67,
1041.
(E0910183 Zhao, X.)
Chin. J. Chem. 2010, 28, 617— 621
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
621