Mukaiyama aldol reaction catalyzed by mesoporous aluminosilicate

Article abstract of DOI:10.1246/cl.2009.700

In the presence of a mesoporous aluminosilicate Al-MCM-41, aldol reaction of various silyl enol ethers with both aromatic and aliphatic aldehydes proceeded under mild reaction conditions to afford the corresponding O-silylated aldol adducts in high yields. The solid acid catalyst was easily recovered and reusable three times. Copyright

Full text of DOI:10.1246/cl.2009.700

700
Chemistry Letters Vol.38, No.7 (2009)
Mukaiyama Aldol Reaction Catalyzed by Mesoporous Aluminosilicate
Suguru Ito, Hitoshi Yamaguchi, Yoshihiro Kubota, and Masatoshi AsamiÃ
Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University,
79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
(Received April 24, 2009; CL-090411; E-mail: m-asami@ynu.ac.jp)
Table 1. Aldol reaction of benzaldehyde with 2a
In the presence of a mesoporous aluminosilicate Al–MCM-
41, aldol reaction of various silyl enol ethers with both aromatic
and aliphatic aldehydes proceeded under mild reaction condi-
tions to afford the corresponding O-silylated aldol adducts in
high yields. The solid acid catalyst was easily recovered and re-
usable three times.
catalyst (30 mg)
O
OSiMe3
O
Me3SiO R
Ph
+
Ph
H
Ph solvent (0.5 M), 0 °C, 15 min
2a
Ph
3a (R = H)
4 (R = Me)
1a
(1.2 mmol)
(1.0 mmol)
Entry
Solvent
Catalyst
Yield of 3a/%a
1b,c
2
3
4
CH2Cl2
CH3CN
CH3CN
CH3CN
Al–MCM-41
Al–MCM-41
MCM-41
99
99
The Mukaiyama aldol reaction has been recognized as a fac-
ile and valuable method for the synthesis of ꢀ-hydroxy carbonyl
compounds, and a wide variety of catalysts are known to cata-
lyze the reaction.1 Along with increasing attention to the devel-
opment of environmentally benign heterogeneous catalytic sys-
tems, several heterogeneous catalysts have also been reported to
promote the reaction.2 For example, ordered mesoporous silica
MCM-41 was found to catalyze the reaction of silyl enol ethers
with acetals.2d Since MCM-41 possesses large uniform pores (2–
10 nm) and high surface area,3 it has been applied to many syn-
thetic transformations as a solid catalyst. Moreover, it is well
known that the catalytic activity of MCM-41 increases by incor-
porating metals, such as Ti, Sn, and Al, into its structure.4 Al-
though titanium- or tin-containing MCM-41 has been reported
to catalyze the Mukaiyama aldol reaction of aldehydes,2g,2i they
required relatively long reaction time and high reaction temper-
ature even using ketene silyl acetals as nucleophiles. The reac-
tions promoted by metal-incorporated MCM-41 were thus car-
ried out under rather severe reaction conditions usually,5 where-
as aluminium-incorporated MCM-41 (Al–MCM-41) has begun
to be used for some synthetic reactions under mild reaction con-
ditions, recently.6 Herein, we wish to report a remarkable accel-
eration of the aldol reaction of silyl enol ethers with aldehydes
by using Al–MCM-41 as a solid acid catalyst.
According to a literature procedure with slight modifica-
tion,7 Al–MCM-41 (Si/Al = 26) was synthesized8 and dried
at 120 ꢀC for 1 h under vacuum prior to use. Initially, the reaction
of benzaldehyde (1.0 mmol) with 1-phenyl-1-trimethylsiloxy-
ethene (2a) (1.5 mmol) was carried out in dichloromethane at
30 ꢀC in the presence of Al–MCM-41 (30 mg). The reaction
was complete within 15 min and afforded the corresponding ꢀ-
siloxy ketone, 1,3-diphenyl-3-trimethylsiloxypropan-1-one
(3a), in 99% yield (Table 1, Entry 1). In this case, the activity
of the catalyst was so high that the reaction of 2a with acetophe-
none, generated in the reaction mixture from silyl enol ether 2a,
also occurred, and undesired self-aldol adduct 4 (0.1 mmol) was
detected in the crude product. When the reaction was carried out
in acetonitrile at 0 ꢀC using 1.2 equiv of 2a, ꢀ-siloxy ketone 3a
was obtained in 99% yield without the formation of 4 (Entry 2).
Next, the reaction was examined in the presence of aluminium-
free MCM-41 or amorphous silica–alumina (SiO2–Al2O3, Si/
Al = 31) in acetonitrile at 0 ꢀC (Entries 3 and 4). In either case,
3a was not detected after 15 min. From these results, it is sug-
N.D.d
N.D.d
SiO2–Al2O3
aDetermined by 1H NMR analysis of the crude product using
nitromethane as an internal standard. bSilyl enol ether 2a
(1.5 mmol) was used and the reaction was carried out at
30 ꢀC. cSmall amount (0.1 mmol) of 1,3-diphenyl-3-tri-
d
methylsiloxybutan-1-one (4) was detected. Not detected.
Table 2. Aldol reaction of various aldehydes with 2a catalyzed
by Al–MCM-41
Al-MCM-41 (30 mg)
O
OSiMe3
Me3SiO
R
O
+
R
H
Ph CH3CN (0.5 M), 0 °C, 15 min
2a
Ph
3
1
(1.2 mmol)
(1.0 mmol)
Entry
R
Yield/%a
1
2
3
4
5
6
7
8
9
4-NO2C6H4
4-ClC6H4
90
92
87
95
94
86
92
80
74
81
67
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-MeOC6H4
2-Naphthyl
(E)-PhCH=CH
PhCH2CH2
c-C6H11
10
11b
t-Bu
aIsolated yield. Reaction was carried out for 2 h.
b
gested that high catalytic activity of Al–MCM-41 is attributed
to the presence of aluminium sites and ordered mesoporous
structure. Similar results were observed in the case of Al–
MCM-41-catalyzed cyanosilylation and allylation of carbonyl
compounds.6b,6d
The catalytic system was then applied to the reaction of var-
ious aldehydes with 2a. The results are summarized in Table 2.
Aromatic aldehydes, bearing electron-withdrawing or -donating
groups, gave the corresponding ꢀ-siloxy ketones 3 in high yields
(Entries 1–7). The reaction of 2a with (E)-cinnamaldehyde, 3-
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.7 (2009)
701
Table 3. Aldol reaction of benzaldehyde with various silyl enol
ethers catalyzed by Al–MCM-41
Table 4. Reuse of Al–MCM-41 in the reaction of benzaldehyde
with 2a9
OSi
R3
SiO
Ph
O
PhCHO
/mmol
Al–MCM-41
/mg
Time
/min
Al-MCM-41 (30 mg)
CH3CN (0.5 M)
O
R1
Run
Yield/%b
+
R3
Ph
H
R1 R2
R2
1
2
3
4
2.0
1.6
1.1
0.6
60
47
32
18
15
15
15
60
99
99
86
85
2
3
1a
(1.0 mmol)
(1.2 mmol)
Entry Silyl enol ether Temp/°C
Time/h Yield/%a
aThe reaction of benzaldehyde with 1.2 equiv of 2a was
carried out in acetonitrile (0.5 M) at 0 ꢀC. Isolated yield.
b
OSiMe3
1
30
0.5
88b
Ph 2b
OSiMe3
tones in moderate to high yields. The catalyst was easily recov-
ered and reusable three times.
2
0
0.25
86b
References and Notes
2c
OSiMe3
1
a) T. Mukaiyama, K. Narasaka, K. Banno, Chem. Lett. 1973, 1011.
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3
30
24
69
Ph
2d
2
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OTES
Ph
4
5
0
0
0.25
0.25
94
87
2e
OTBDMS
Ph
2f
b
aIsolated yield. Syn/anti = 3:2.
phenylpropanal, or cyclohexanecarboxaldehyde under the same
reaction conditions gave the corresponding adduct in good yields
(Entries 8–10). The reaction of pivalaldehyde with 2a was rela-
tively slow and the yield of the product was 67% even after the
reaction mixture was stirred for 2 h probably due to the steric
hindrance of pivalaldehyde (Entry 11).
3
4
5
C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuli, J. S. Beck,
Nature 1992, 359, 710.
´
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J. Mol. Catal. A: Chem. 2007, 266, 11. e) C. Xie, F. Liu, S. Yu,
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Graham, Tetrahedron Lett. 2007, 48, 4723. b) K. Iwanami, J.-C. Choi,
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The reaction of various silyl enol ethers with benzaldehyde
was also examined (Table 3). The reaction with 2b at 30 ꢀC for
30 min afforded the product in 88% yield as a diastereomeric
mixture (Entry 1). Cyclic silyl enol ether 2c also reacted with
benzaldehyde to give a diastereomeric mixture of the corre-
sponding adduct in 86% yield (Entry 2). When sterically hin-
dered silyl enol ether 2d was used, the reaction was sluggish
even at 30 ꢀC and the corresponding ꢀ-siloxy ketone was ob-
tained in 69% yield after 24 h (Entry 3). Triethylsilyl (TES) ether
and tert-butyldimethylsilyl (TBDMS) ether are often syntheti-
cally useful for the protection of hydroxy groups. Thus, the reac-
tions of TES ether 2e and TBDMS ether 2f with benzaldehyde
were also examined. In both cases, the reaction proceeded at
0 ꢀC for 15 min to afford the corresponding silyl ethers in 94
and 87% yields, respectively (Entries 4 and 5).
Finally, the recovery and reuse of Al–MCM-41 was exam-
ined in the reaction of benzaldehyde with 2a (Table 4). The cat-
alyst was recovered from the reaction mixture by filtration. The
catalyst was then washed with ether, dried at 70 ꢀC for 15 min,
treated at 120 ꢀC for 1 h under vacuum, and used in the next re-
action. Al–MCM-41 was reusable, although the catalytic activity
of the recovered catalyst slightly decreased after using three
times.
6
7
8
C.-Y. Chen, H.-X. Li, M. E. Davis, Microporous Mater. 1993, 2, 17.
The specific surface area (BET) and the average pore diameter (BJH)
were 1120 m2 gÀ1 and 2.7 nm, respectively.
9
Typical experimental procedure: Under an atmosphere of argon, to a
mixture of Al–MCM-41 (60 mg, dried prior to use at 120 ꢀC for 1 h un-
der vacuum) and benzaldehyde (0.213 g, 2.0 mmol) in acetonitrile
(3.0 mL), 1-phenyl-1-trimethylsiloxyethene (0.462 g, 2.4 mmol) in
acetonitrile (1.0 mL) was added through a syringe at 0 ꢀC. The reaction
mixture was stirred at 0 ꢀC for 15 min. The catalyst was removed by
filtration and washed with Et2O (40 mL). After the combined organic
solution was concentrated under reduced pressure, crude product was
purified by silica-gel column chromatography (hexane/Et2O = 20:1)
to afford 1,3-diphenyl-3-trimethylsiloxypropan-1-one10 as a colorless
oil (0.591 g, 99%). The product gave satisfactory IR and 1H, 13C NMR
spectra. The recovered catalyst was dried at 70 ꢀC for 15 min. Then, the
catalyst (47 mg) was dried at 120 ꢀC for 1 h under vacuum and used in a
second run.
In summary, the aldol reaction of various aldehydes with si-
lyl enol ethers were promoted under mild reaction conditions by
using Al–MCM-41 as a solid acid catalyst. This heterogeneous
catalytic system could afford silyl ethers of the ꢀ-hydroxy ke-
10 S. Torii, T. Inokuchi, S. Takagishi, H. Horike, H. Kuroda, K. Uneyama,
Bull. Chem. Soc. Jpn. 1987, 60, 2173.
Published on the web (Advance View) June 13, 2009; doi:10.1246/cl.2009.700