Akihiro Orita et al.
COMMUNICATIONS
ene (5 mL) was added, and the mixture was stirred for
10 min. The organic layer was transferred to another flask
by a pipette, and to this layer were added MeOH (5 mL)
and one drop of 2N aqueous HCl. This mixture was stirred
at room temperature until the TMS ether had been com-
pletely hydrolyzed. After evaporation, the crude product
was subjected to GLC analysis to show the formation of the
desired aldol product (93%). By evaporation of the fluorous
layer, 1 (128.0 mg) was recovered.
solution to the organic phase after addition of toluene
for work-up, and the loss of this phase was not negli-
gible after repeated reactions. Apparently, the sur-
face-active character of 1, which plays a key role for
driving the reaction, caused the unfavorable solvent
loss. Bearing these results in mind, we changed the
solvents to FC-72/ether, in which the reaction rate is
much faster. Moreover, a small amount of FC-72 was
added concurrently with toluene dilution so as to
maintain the volume of this solvent at a constant level
and, hence, to minimize the catalyst loss. Gratifyingly,
the recycling efficacy was improved and the reaction
was repeated at least 5 times without any decrease in
the yield.
Representative Mukaiyama Aldol Reaction with
Recycled Catalyst 1 (Table 3, in FC-72/Et2O)
To
0.50 mmol),
(0.5 mL) and FC-72 (2.5 mL). Ketene silyl acetal
a
flask were added benzaldehyde (2a) (53.1 mg,
1
(132.0 mg, 0.025 mmol as dimer), ether
3
In conclusion, we have established fluorous surface-
active catalysis, by which Lewis acid-catalyzed reac-
tions are accelerated in fluorous/organic biphasic
media. The fluorous catalysts portions over both
(104.6 mg, 0.60 mmol) was added at room temperature, and
the mixture was stirred for 3 h at this temperature. After
consumption of 2a had been observed by TLC analysis, dry
toluene (5 mL) and FC-72 (0.2 mL) were added, and the
phases, and also helps organic substrate(s) and re- mixture was stirred for 10 min. The organic layer was trans-
ferred to another flask by a pipette, and to this layer were
added MeOH (5 mL) and one drop of 2N aqueous HCl.
This mixture was stirred at room temperature until the TMS
ether had been completely hydrolyzed. After evaporation,
the crude product was subjected to GLC analysis to show
the formation of the desired aldol product (92%). By use of
the fluorous layer, the second reaction was carried out.
agent(s) transfer into the fluorous phase to mediate
effective interactions of these reactants with the cata-
lyst. The use of biphasic conditions has enabled us to
establish a new catalyst-recycling system. The present
protocol offers a new version of the fluorous biphase
technology without the necessity for elevation of the
reaction temperature, and further development is in
progress.[13]
Representative Allylation Reaction (Table 2, entry 3)
To
a flask were added benzaldehyde (2a) (53.1 mg,
0.50 mmol), 4 (171.3 mg, 0.05 mmol as dimer), toluene
(0.5 mL) and FC-72 (2.5 mL). Tetraallytin (42.5 mg,
0.15 mmol) was added at room temperature, and the mix-
ture was stirred for 3 h at this temperature. Dry toluene
(5 mL) was added, and the mixture was stirred for 10 min.
The organic layer was transferred to another flask by a pip-
ette, and washed with brine. After evaporation, the crude
product was subjected to GLC analysis to show the forma-
tion of the allylation product (95%). By evaporation of the
fluorous layer, 1 (166.1 mg, 97%) was recovered.
Experimental Section
General Remarks
All reactions were carried out under an atmosphere of
argon with freshly distilled solvents, unless otherwise noted.
Tetrahydrofuran (THF) and ether were distilled from
sodium/benzophenone. Other solvents such as toluene,
hexane and CH2Cl2 were distilled from CaH2. FC-72 (3M)
was purchased and used without purification. Silica gel
(Daiso gel IR-60) was used for column chromatography.
NMR spectra were recorded at 258C on JEOL Lambda 300
and JEOL Lambda 500 instruments and calibrated with tet-
ramethylsilane (TMS) as an internal reference. All products
were characterized by comparison with the reported spectral
data of the authentic samples: methyl 2,2-dimethyl-3-hy-
droxy-3-phenylpropanoate,[14] methyl 2,2-dimethyl-3-hy-
droxy-5-phenylpentanoate,[15] methyl 2,2-dimethyl-3-hy-
droxy-5-phenyl-4-pentenoate,[16] methyl 2,2-dimethyl-3-(4-
chlorophenyl)-3-hydroxypropanoate,[17] methyl 3-hydroxy-3-
phenyl-2,2,3-trimethylpropanoate,[18] 4-hydroxy-4-phenylbut-
1-ene.[19]
Acknowledgements
This work was supported by the Grant-in-Aid for Scientific
Research and matching fund subsidy for private universities
from MEXT (Ministry of Education, Culture, Sports, Science
and Technology), Japan, and Okayama Prefecture Industrial
Promotion Foundation.
References
Representative Mukaiyama Aldol Reaction (Table 1,
entry 3)
[1] Handbook of Fluorous Chemistry, (Eds.: J. A. Gladysz,
D. P. Curran, I. T. Horvꢁth), Wiley-VCH: Weinheim,
Germany, 2004.
[2] a) I. T. Horvꢁth, J. Rꢁbai, Science 1994, 266, 72; b) I. T.
Horvꢁth, Acc. Chem. Res. 1998, 31, 641.
To
0.50 mmol), 1 (132.0 mg, 0.025 mmol as dimer), toluene
(0.5 mL) and FC-72 (2.5 mL). Ketene silyl acetal
a flask were added benzaldehyde (2a) (53.1 mg,
3
(104.6 mg, 0.60 mmol) was added at room temperature, and
the mixture was stirred for 9 h at this temperature. Dry tolu-
[3] C. Rocaboy, J. A. Gladysz, Tetrahedron 2002, 58, 4007.
1422
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1419 – 1423