Mesoporous aluminosilicate-catalyzed Sakurai allylation and Mukaiyama aldol reaction of acetals

Article abstract of DOI:10.1016/j.tetlet.2010.06.034

In the presence of a catalytic amount of mesoporous aluminosilicate (Al-MCM-41), both allyltrimethylsilane and silyl enol ether reacted with various acetals under mild reaction conditions to afford the corresponding homoallyl ethers and β-alkoxy ketones,

Full text of DOI:10.1016/j.tetlet.2010.06.034

Tetrahedron Letters 51 (2010) 4243–4245
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Tetrahedron Letters
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Mesoporous aluminosilicate-catalyzed Sakurai allylation and Mukaiyama
aldol reaction of acetals
*
Suguru Ito, Akira Hayashi, Hirotomo Komai, Yoshihiro Kubota, Masatoshi Asami
Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University, Tokiwadai 79-5, Hodogaya-ku, Yokohama 240 8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
In the presence of a catalytic amount of mesoporous aluminosilicate (Al-MCM-41), both allyltrimethyl-
silane and silyl enol ether reacted with various acetals under mild reaction conditions to afford the cor-
responding homoallyl ethers and b-alkoxy ketones, respectively. The catalyst was easily recovered from
the reaction mixture and could be reused in the same reaction without a significant loss of catalytic activ-
ity. Moreover, Al-MCM-41 exhibited high chemoselectivity for acetal over aldehyde in the reactions.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 21 April 2010
Revised 2 June 2010
Accepted 7 June 2010
Available online 11 June 2010
Keywords:
Al-MCM-41
Solid acid catalyst
Sakurai allylation
Mukaiyama aldol reaction
Acetals are generally inert toward nucleophiles under basic
conditions, therefore they have been widely used as the protective
group of carbonyl compounds.1 On the other hand, acetals react
with allylsilanes (Sakurai allylation) or silyl enol ethers (Mukaiy-
ama aldol reaction) in the presence of Lewis acids to afford homo-
allyl ethers or b-alkoxy carbonyl compounds.2,3 These reactions are
recognized as valuable carbon–carbon bond-forming reactions in
organic synthesis because of the high synthetic utility of the prod-
ucts.4 Although a wide variety of catalysts are known to be effec-
tive for these reactions,5,6 the recovery and reuse of the catalysts
are generally difficult because most of them decompose during
work up of the reaction.
Along with the increasing attention to the development of envi-
ronmentally benign reaction systems, the replacement of conven-
tional Lewis acids to heterogeneous solid acids is important in
the current field of synthetic organic chemistry. Nevertheless,
there have been only few reports on allylation or aldol reaction
of acetals with allylsilanes or silyl enol ethers catalyzed by hetero-
geneous catalysts.7,8
In 2003, Iwamoto and co-workers reported that ordered meso-
porous silica MCM-41 catalyzed Mukaiyama aldol reaction of silyl
enol ethers with acetals under heterogeneous conditions.8c MCM-
41 possesses large uniform pores (2–10 nm) and a high surface
area,9 and it is well known that the catalytic activity of MCM-41 in-
creases by incorporating metals, such as Ti, Sn, and Al, into its
structure.10 Among them, aluminum incorporated MCM-41 (Al-
MCM-41) has been found to catalyze several synthetic reactions
under mild reaction conditions, recently.11 Herein, we report mild
and efficient catalytic systems for chemoselective reactions of ace-
tals and allylsilane or silyl enol ether by using Al-MCM-41.
At first, Sakurai allylation of benzaldehyde dimethyl acetal (1a)
with allyltrimethylsilane (2) was investigated (Table 1). In the
presence of Al-MCM-41 (30 mg, Si/Al = 26, dried prior to use at
120 °C for 1 h under vacuum),12,13 the reaction of 1a (1.0 mmol)
with 2 (1.5 mmol) in dichloromethane at 30 °C for 45 min afforded
4-methoxy-4-phenylbut-1-ene (3a) in 86% yield along with 7%
yield of 1-phenylbuta-1,3-diene (4) (entry 1). When the reaction
was carried out by using amorphous silica–alumina (SiO2–
Al2O3)14 or aluminum-free MCM-4115 in place of Al-MCM-41,
homoallyl ether 3a was not obtained (entries 2 and 3). Therefore,
it turned out that both the mesoporous structure and the presence
of aluminum moiety were necessary for the high catalytic activity
of Al-MCM-41 as was observed in the case of Al-MCM-41-cata-
lyzed allylation of aldehydes. By reducing the aluminum content
of the catalyst, the amount of 4 produced in the reaction decreased
and only 3a was obtained in 96% yield by using Al-MCM-41 (Si/
Al = 48) (entries 4 and 5).16
As high yield was achieved in the reaction of 1a, Al-MCM-41-
catalyzed allylation of various acetals was examined (Table 2).
Electron-withdrawing or electron-donating groups on the aromatic
ring did not affect the reaction, and the corresponding homoallyl
methyl ethers were obtained in 76–98% yields (entries 2–12). Ally-
lation of acetals derived from naphthaldehydes, (E)-cinnamalde-
hyde, and aliphatic aldehydes also proceeded to give the
corresponding product in good yields (entries 13–17). Benzalde-
hyde diethyl acetal was allylated as well, and the corresponding
homoallyl ethyl ether was obtained in 85% yield (entry 18). The
* Corresponding author. Tel./fax: +81 45 339 3968.
E-mail address: m-asami@ynu.ac.jp (M. Asami).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.034

4244
S. Ito et al. / Tetrahedron Letters 51 (2010) 4243–4245
Table 1
Al-MCM-41
MeO OMe
MeO
Allylation of benzaldehyde dimethyl acetal (1a) with allyltrimethylsilane (2)
(30 mg, Si/Al = 48)
SiMe3
+
OMe
CH2Cl2 (0.5 M)
30 ºC, 1.5 h
Ph
Catalyst (30 mg)
OMe
OMe
1a
5
2
3a
+
SiMe3
+
6 95%
(1.0 mmol)
(3.0 mmol)
CH2Cl2 (0.5 M)
30 ºC, 45 min
Ph
Ph
2
Scheme 1. Allylation of cyclohexanone dimethyl ketal (5) with allyltrimethylsilane
(2).
4
(1.0 mmol)
(1.5 mmol)
Entry
Catalyst
Si/Al
3aa (%)
4a (%)
1
2
3
4
5
Al-MCM-41
SiO2–Al2O3
MCM-41
Al-MCM-41
Al-MCM-41
26
31
1
86
0
0
91
96
7
0
0
4
Table 3
Reuse of Al-MCM-41a
34
48
Run
Al-MCM-41 (mg)
1a (mmol)
Time (min)
Yieldb (%)
Trace
1
2
3
4
60
50
34
20
2.0
1.7
1.1
0.7
45
45
45
90
93
94
94
94
Determined by 1H NMR analysis of the crude product using nitromethane as an
internal standard.
a
a
In the presence of Al-MCM-41 (30 mg/mmol, Si/Al = 48) the reaction of benz-
reaction of a ketal, cyclohexanone dimethyl ketal (5), with 3 equiv
of 2 afforded 1-allyl-1-methoxycyclohexane (6) in 95% yield
(Scheme 1).
aldehyde dimethyl acetal (1a) with 1.5 equiv of allyltrimethylsilane (2) was carried
out in dichloromethane (0.5 M) at 30 °C.
b
Isolated yield.
The recovery and reuse of the catalyst were examined in the
reaction of 1a with 2 (Table 3).17 After the reaction was completed,
the catalyst was recovered by filtration and dried at 70 °C for
15 min. The catalyst was then treated in the same manner as the
first run. The recovered catalyst could be reused three times for
the same reaction without significant loss of catalytic activity.
Next, a reaction of various acetals with 1-phenyl-1-trimethylsil-
oxyethene (7) (Mukaiyama aldol reaction) was investigated (Ta-
ble 4). The reaction of benzaldehyde dimethyl acetal (1a) with 7
under an optimized reaction condition of Al-MCM-41-catalyzed al-
dol reaction of aldehydes11e,18 afforded 3-methoxy-1,3-diphenyl-
propan-1-one in 95% yield, and the catalyst was reusable at least
three times (entry 1).19 The reaction did not proceed in the pres-
ence of SiO2–Al2O3 or MCM-41 under the same reaction conditions
(entries 2 and 3), though it was reported that MCM-41 could cata-
lyze the same reaction in toluene.8c The difference in catalytic
activity between the present MCM-41 and previously reported
Table 4
Aldol reaction of various acetals 1 with 1-phenyl-1-trimethylsiloxyethene (7)
Al-MCM-41
OMe O
OSiMe3 (30 mg/mmol, Si/Al = 23)
MeO OMe
R1
R2
+
R1
R2
Ph
CH3CN (0.5 M)
0 ºC, 1 h
Ph
1
7
8
(1.2 equiv)
Entry
R1
R2
H
Yielda (%)
1
Ph
95 (1st run)
92 (4th run)b
2c
3d
4
5
6
7
8
9
Ph
Ph
H
H
H
H
H
H
H
0
0
2-ClC6H4
3-ClC6H4
4-MeC6H4
4-MeOC6H4
c-C6H11
–(CH2)5–
90
78
89
90
89
85
a
b
c
Isolated yield.
Recovered catalyst was used.
SiO2–Al2O3 (30 mg/mmol, Si/Al = 31) was used in place of Al-MCM-41.
MCM-41 (30 mg/mmol, Si/Al = 1) was used in place of Al-MCM-41.
Table 2
Allylation of various acetals 1 with allyltrimethylsilane (2) catalyzed by Al-MCM-41
Al-MCM-41
d
(30 mg, Si/Al = 48)
OMe
OMe
1
OMe
SiMe3
+
CH2Cl2 (0.5 M)
30 ºC, 45 min
R
R
one8c is probably due to the difference of silica sources of MCM-
41.20 Other aromatic and aliphatic acetals and ketal were also re-
acted with 7 to afford the corresponding b-methoxy ketones 8 in
good yields (entries 4–9).
2
3
(1.0 mmol)
(1.5 mmol)
Entry
R
Yielda (%)
1
2
3
4
5
6
7
8
Ph
93
98
90
92
96
86
92
93
92
95
76
88
89
80
74
93
93
85
4-NO2C6H4
To estimate the chemoselectivity of the reactions, Al-MCM-41-
catalyzed allylation and aldol reaction of acetal 1a (1.0 mmol) were
carried out in the presence of benzaldehyde (9) (1.0 mmol) using 2
(1.0 mmol) and 7 (1.0 mmol), respectively. As shown in Scheme 2,
both reactions proceeded chemoselectively. Only 1a reacted with 2
or 7 to afford 3a or 8a, although the reactions of 9 with 2 or 7 pro-
ceeded smoothly under the same reaction conditions in the ab-
sence of 1a.11d,e With regard to the chemoselectivity of the
reaction, typical strong Lewis acids (e.g., TiCl4, BF3ꢀOEt2, and AlCl3)
are known to show poor chemoselectivity.6i Trimethylsilyl trifluo-
romethanesulfonate (TMSOTf) and MCM-41 were reported to cat-
alyze the aldol reaction of acetals in the presence of
aldehydes,6a,i,8c because they usually could not promote the reac-
tion of aldehydes and silyl enol ethers. Only MgI2 etherate was re-
ported to show chemoselectivity for acetals over aldehydes in the
reaction despite the fact that it could activate both acetals and
aldehydes.21 Among the catalysts that activate both acetals and
4-BrC6H4
2-BrC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-MeOC6H4
2-MeOC6H4
2-Naphthyl
1-Naphthyl
(E)-PhCH@CH
c-C6H11
9
10
11b
12
13
14
15
16
17
18c
PhCH2CH2
Ph
a
b
c
Isolated yield.
Allyltrimethylsilane (3.0 mmol) was used.
Benzaldehyde diethyl acetal was used.

S. Ito et al. / Tetrahedron Letters 51 (2010) 4243–4245
4245
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Mukaiyama, T.; Matsui, S.; Kashiwagi, K. Chem. Lett. 1989, 993; (e) Mukaiyama,
T.; Soga, T.; Takenoshita, H. Chem. Lett. 1989, 1273; (f) Kobayashi, S.; Hachiya,
I.; Takahori, T. Synthesis 1993, 371; (g) Geetha Saraswathy, V.; Sankararaman, S.
J. Chem. Soc., Perkin Trans. 2 1996, 29; (h) Kamata, M.; Yokoyama, Y.; Karasawa,
N.; Kato, M.; Hasegawa, E. Tetrahedron Lett. 1996, 37, 3483; (i) Ooi, T.; Tayama,
E.; Takahashi, M.; Maruoka, K. Tetrahedron Lett. 1997, 38, 7403; (j) Le Roux, C.;
Ciliberti, L.; Laurent-Robert, H.; Laporterie, A.; Dubac, J. Synlett 1998, 1249.
7. Kawai, M.; Onaka, M.; Izumi, Y. Chem. Lett. 1986, 381.
Al-MCM-41
OMe
OMe
(30 mg, Si/Al = 48)
SiMe3
+
+
PhCHO
CH2Cl2 (0.5 M)
30 ºC, 45 min
Ph
9
1a
2
(1.0 mmol) (1.0 mmol)
(1.0 mmol)
OMe
+
OSiMe3
Ph
Ph
8. (a) Mukaiyama, T.; Iwakiri, H. Chem. Lett. 1985, 1363; (b) Kawai, M.; Onaka, M.;
Izumi, Y. Chem. Lett. 1986, 1581; (c) Ishitani, H.; Iwamoto, M. Tetrahedron Lett.
2003, 44, 299.
3a
10
N.D.
(0.64 mmol)
9. Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.; Beck, J. S. Nature 1992,
359, 710.
10. (a) Corma, A.; García, H. Chem. Rev. 2002, 102, 3837; (b) Corma, A.; García, H.
Chem. Rev. 2003, 103, 4307.
11. (a) Robinson, M. W. C.; Buckle, R.; Mabbett, I.; Grant, G. M.; Graham, A. E.
Tetrahedron Lett. 2007, 48, 4723; (b) Iwanami, K.; Choi, J.-C.; Lu, B.; Sakakura,
T.; Yasuda, H. Chem. Commun. 2008, 1002; (c) Murata, H.; Ishitani, H.; Iwamoto,
M. Tetrahedron Lett. 2008, 49, 4788; (d) Ito, S.; Yamaguchi, H.; Kubota, Y.;
Asami, M. Tetrahedron Lett. 2009, 50, 2967; (e) Ito, S.; Yamaguchi, H.; Kubota,
Y.; Asami, M. Chem. Lett. 2009, 38, 700.
12. Chen, C.-Y.; Li, H.-X.; Davis, M. E. Micropor. Mater. 1993, 2, 17.
13. The specific surface area (BET) and the average pore diameter (BJH) were
1120 m2/g and 2.7 nm, respectively.
Al-MCM-41
OSiMe3
OMe
OMe
(30 mg, Si/Al = 23)
+
+
PhCHO
Ph
7
CH3CN (0.5 M)
0 ºC, 1 h
Ph
9
1a
(1.0 mmol) (1.0 mmol) (1.0 mmol)
OMe O
Me3SiO
O
+
Ph
Ph
Ph
Ph
8a
11
N.D.
(0.85 mmol)
14. Amorphous silica–alumina was synthesized according to the same procedure
as the one used in the synthesis of Al-MCM-41 without the addition of
surfactant, cethyltrimethylammonium bromide. The specific surface area (BET)
was 385 m2/g.
Scheme 2. Chemoselective allylation and aldol reaction of benzaldehyde dimethyl
acetal (1a).
15. Aluminum-free MCM-41 was synthesized according to the same procedure as
the one used in the synthesis of Al-MCM-41 without the addition of aluminum
source, Al(OiPr)3. The specific surface area (BET) and the average pore diameter
(BJH) were 1080 m2/g and 2.6 nm, respectively.
16. The specific surface areas of Al-MCM-41 (Si/Al = 34) and Al-MCM-41 (Si/
Al = 48) were 1101 and 1135 m2/g, respectively. The average pore diameter
(BJH) was 2.7 nm.
aldehydes in Sakurai allylation, no catalyst has been reported to
exhibit high acetal selectivity in the reaction, to the best of our
knowledge.
In summary, the reactions of allyltrimethylsilane and silyl enol
ether of acetophenone with various acetals were promoted under
mild reaction conditions by using Al-MCM-41 as a reusable solid
acid catalyst. Furthermore, it should be noted that Al-MCM-41 ef-
fected an interesting chemoselective activation of acetal over alde-
hyde in Sakurai allylation and Mukaiyama aldol reaction.
17. Typical experimental procedure for Al-MCM-41-catalyzed Sakurai allylation:
Under an atmosphere of argon, to a mixture of benzaldehyde dimethyl acetal
(0.304 g, 2.0 mmol) and Al-MCM-41 (60 mg, Si/Al = 48, dried prior to use at
120 °C for 1 h under vacuum) in dichloromethane (3.0 mL), allyltrimethylsilane
(0.343 g, 3.0 mmol) in dichloromethane (1.0 mL) was added through a syringe
at 30 °C. The reaction mixture was stirred at 30 °C for 45 min and the catalyst
was removed by filtration. After the filtrate was concentrated under reduced
pressure, almost pure homoallyl methyl ether was obtained. Further
purification by silica-gel column chromatography (hexane to hexane/
Acknowledgment
Et2O = 10:1) afforded 4-methoxy-4-phenylbut-1-ene5j as
a colorless oil
(0.301 g, 93%). The product gave satisfactory IR and 1H, 13C NMR spectra. The
recovered catalyst was dried at 70 °C for 15 min. Then, the catalyst (50 mg)
was dried at 120 °C for 1 h under vacuum and used in a second run.
18. Al-MCM-41 was newly synthesized according to the same manner as the one
used in allylation and previous aldol reaction of aldehydes. However, Si/Al ratio
was slightly different from each other. It was confirmed that there had been no
difference in catalytic activity between Al-MCM-41 (Si/Al = 26) and Al-MCM-
41 (Si/Al = 23).
Y.K. thanks New Energy and Industrial Technology Develop-
ment Organization (NEDO) for financial support.
References and notes
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19. Typical experimental procedure for Al-MCM-41-catalyzed Mukaiyama aldol
reaction: Under an atmosphere of argon, to
a mixture of benzaldehyde
3. Mukaiyama, T.; Hayashi, M. Chem. Lett. 1974, 15.
dimethyl acetal (0.304 g, 2.0 mmol) and Al-MCM-41 (60 mg, Si/Al = 23, dried
prior to use at 120 °C for 1 h under vacuum) 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 1 h and
the catalyst was removed by filtration. After the filtrate was concentrated
under reduced pressure, the crude product was purified by silica-gel column
4. Mukaiyama, T.; Murakami, M. Synthesis 1987, 1043.
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chromatography
(hexane/Et2O = 8:1)
to
afford
3-methoxy-1,3-
diphenylpropan-1-one22 as a colorless oil (0.456 g, 95%). The product gave
satisfactory IR and 1H, 13C NMR spectra. The recovered catalyst was dried at
70 °C for 15 min. Then, the catalyst (50 mg) was dried at 120 °C for 1 h under
vacuum and used in a second run.
20. Silica sources of present and previous MCM-41 were tetraethyl orthosilicate
and colloidal silica, respectively.
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