Surfactant-Aided Lewis Acid Catalysis
J. Am. Chem. Soc., Vol. 122, No. 30, 2000 7207
1
2
a-catalyzed aldol reaction of benzaldehyde with silyl enol ether
completed in 4 h at 30 °C (Figure 8, curve A). On the other
concentrated, and purified by silica gel chromatography to give the
desired product (82%).
Experimental Procedure for Kinetic Studies of the Aldol Reac-
tion of Benzaldehyde with 2 (for Initial Rate Determination, Figure
hand, when stirring was stopped after the initial 10 min, the
reaction was gradually slowed (Figure 8, curve B). During the
reactions without stirring, the reaction mixture, which was a
white dispersion at the beginning, gradually underwent phase
separation. These results suggest that the Sc-catalyzed reactions
take place at the colloid interface, the total area of which is
kept larger with stirring.
3
). The aldol reaction in water was carried out at 30 °C with a stirring
of 1400 rpm as described in the typical procedure for aldol reactions
in the presence of acetophenone (10-20 mol %) as an internal standard.
At the times as given in Figure 3, a small portion of the reaction mixture
was taken in a mixture of hexane and a saturated aqueous NaHCO
3
solution. Yields of the products in the hexane layer were measured by
the comparison of the peak areas of the products and acetophenone by
HPLC analysis (R-SIL-5A-06, YMC; hexane/ethyl acetate ) 9/1; flow
rate, 1 mL/min; retention time, acetophenone: 8.5 min, aldol product
Conclusions
We have developed several useful carbon-carbon bond-
forming reactions in water. The key is the use of newly
developed Lewis acid-surfactant-combined catalysts. While most
organic substrates are not soluble in water, stable colloidal
dispersions are formed immediately by combining the catalyst
and organic materials in water, and Lewis acid-catalyzed organic
reactions proceed smoothly. In addition, the surfactant-type
catalysts can be, in principle, removed from the reaction mixture
without using organic solvents. Although several Lewis acid-
catalyzed reactions have been demonstrated in this paper, this
method will be applied to a great number of other Lewis acid-
catalyzed reactions. Furthermore, the idea of the surfactant-type
catalysts is not limited to Lewis acid catalysis, and may be
applied to various types of catalytic reactions in water. In light
of the increased demand for reduction of organic solvents in
industry, new methods of catalysis in water should be urgently
developed. The surfactant-type catalysts described in this article
will contribute to progress in chemical processes by reducing
the use of organic solvents.
(
syn): 18.0 min, aldol product (anti): 21.8 min). The yields were
calculated as an average value of three experiments. For the reaction
in CH Cl , the reaction was quenched with a saturated aqueous NaHCO
solution, and the products were extracted with CH Cl . After evapora-
2
2
3
2
2
tion of the solvent, a mixture of 1 N HCl and THF (1:20) was added,
and the whole was stirred at 0 °C for 1 h. After evaporation of the
solvents, the mixture was dissolved in CH
aqueous NaHCO solution and then brine, dried over Na
concentrated. Acetophenone and hexane were added, and HPLC
analysis was carried out as described above.
2
Cl
2
, washed with a saturated
SO , and
3
2
4
Light Scattering Measurement. A dispersion of a LASC and
benzaldehyde (1:20) in water were diluted with water until the
dispersion became transparent, and then light scattering measurement
was performed by using Coulter Sub‚micron Particle Analyzer, model
N4MD (Coulter Electronics, Inc.).
TEM Analysis. One drop of the colloidal solution containing 1d
and benzaldehyde in water was placed onto a carbon-coated copper
grid, and then the excess solution was immediately removed with the
help of filter paper. The grid was kept in a desiccator for 3 days and
was then observed by TEM (JEM-100CX, JEOL Co.).
AFM Analysis. One drop of the colloidal solution was placed onto
a mica surface, and then the excess solution was immediately removed
with help of filter paper. The surface of the mica was imaged with a
Digital Instruments Nano Scope IIIa Scanning Probe Microscope
Controller and software.
Experimental Section
Preparation of 1a. To a solution of SDS (3.4 g, 11.6 mmol) in
water (100 mL) was added a solution of ScCl
3 2
‚6H O (1.0 g, 3.85 mmol)
in water (20 mL) at room temperature. White precipitates appeared
immediately, and the mixture was stirred for 10 min. The white solid
was filtered, washed with water (50 mL × 5), and dried (0.1 mmHg,
Experimental Procedure for a Study on the Effect of Stirring
Rates (Figure 8). For the reaction at 1400 rpm, the procedure same as
that for the initial rate study was used. For the reaction at 0 rpm, the
reaction mixture was stirred at 1400 rpm for the initial 10 min after
addition of 2 to a mixture of 1a, benzaldehyde, and water at 30 °C.
Then, the stirring was stopped, and the mixture was placed in a bath
(30 °C) without stirring. At the time as given in Figure 8, the reaction
was quenched, and the product was isolated. The yields of the product
were isolated yields.
2
0 h) to afford 1a (2.3 g, 71%); mp 240 °C; IR (KBr) 1165, 1300
-
1 1
cm ; H NMR (CD
m), 1.63-1.71 (6H, m), 4.11 (6H, t, J ) 6.6 Hz); C NMR (CD
δ 14.4, 23.7, 26.8, 30.3, 30.4, 30.5, 30.7, 30.7, 30.8, 30.8, 33.1, 70.6;
3
OD) δ 0.89 (9H, t, J ) 6.7 Hz), 1.20-1.44 (54H,
1
3
3
OD)
45
Sc NMR (CD
3
OD) δ -109.3; Anal. Calcd for C36
75 12 3 2
H O S Sc‚3H O:
C, 48.30; H, 9.12; S, 10.74. Found: C, 48.15; H, 9.02; S, 10.53.
Typical Experimental Procedure for LASC-Catalyzed Aldol
Reactions. To a LASC (0.05 mmol) in water (3 mL) was added an
aldehyde (0.50 mmol) and, after 10 min, a silyl enolate (0.75 mmol).
The mixture was stirred (∼1400 rpm) for 4 h at room temperature.
Acknowledgment. We are grateful to Professors Eishun
Tsuchida and Shinji Takeoka, Dr. Teruyuki Komatsu, and Dr.
Tetsuya Yanagimoto (Waseda University) for helpful discus-
sions and TEM and AFM observations, to Professor Takeshi
Iwatsubo (The University of Tokyo) for light microscopy
observations, to Dr. Kazuhisa Takahashi (Science University
of Tokyo) for light scattering experiments, and to Professor
Minoru Ueno (Science University of Tokyo) for helpful
discussion on dispersion systems. We also thank Mr. Tsuyoshi
Busujima for his technical supports. This work was partially
supported by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science, Sports, and Culture, Japan.
Y.M., T.W., and S.N. thank the JSPS fellowship for Japanese
Junior Scientists.
3
Brine and a saturated aqueous NaHCO solution were added, and the
aqueous layer was extracted with ethyl acetate. The organic layer was
dried and concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel to afford the desired aldol
adduct.
Typical Experimental Procedure for the LASC-Catalyzed Man-
nich-Type Reactions. To a LASC (0.025 mmol) in water (3 mL) was
added an amine (0.50 mmol), a silyl enolate (0.75 mmol), and an
aldehyde (0.50 mmol). The mixture was stirred (∼1400 rpm) for 5 h
3
at room temperature. Brine and a saturated aqueous NaHCO solution
were added, and the aqueous layer was extracted with ethyl acetate.
The organic layer was dried and concentrated under reduced pressure.
The residue was purified by silica gel chromatography to afford the
desired product.
Experimental Procedure for the 1a-Catalyzed Allylation Reac-
tion. To a suspension of 1a (0.025 mmol) in water (1.5 mL) was added
benzaldehyde (0.25 mmol) and tetraallyltin (0.075 mmol). After stirring
Supporting Information Available: Experimental proce-
dures, data for characterization of LASCs (1a-f) and com-
1
13
pounds 17-21, and H and C NMR spectra of 17-21 (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
∼1400 rpm) at room temperature for 10 h, the reaction was quenched
with a saturated aqueous NaHCO solution (5 mL). The product was
extracted with ethyl acetate, washed with brine, dried over Na SO
3
2
4
,
JA001420R