Polystyrene-supported TBD as an efficient and reusable organocatalyst for cyanosilylation of aldehydes, ketones, and imines

Article abstract of DOI:10.1016/j.tetlet.2011.12.070

Polystyrene-supported TBD (PS-TBD) catalyzes cyanosilylation of both aldehydes and ketones using TMSCN to give the corresponding products in high yields. Imines were also converted into the desired α-cyanoanimes under the same conditions. PS-TBD was easil

Full text of DOI:10.1016/j.tetlet.2011.12.070

Tetrahedron Letters 53 (2012) 1075–1077
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Polystyrene-supported TBD as an efficient and reusable organocatalyst
for cyanosilylation of aldehydes, ketones, and imines
⇑
Satoru Matsukawa , Syohei Fujikawa
Department of Science Education, Faculty of Education, Ibaraki University, Mito, Ibaraki 310-8512, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Polystyrene-supported TBD (PS-TBD) catalyzes cyanosilylation of both aldehydes and ketones using
TMSCN to give the corresponding products in high yields. Imines were also converted into the desired
Received 2 November 2011
Revised 9 December 2011
Accepted 19 December 2011
Available online 24 December 2011
a-cyanoanimes under the same conditions. PS-TBD was easily recovered and reused without significant
loss of catalytic activity.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Cyanosilylation
Organocatalyst
Basecatalyst
Polymercatalyst
Guanidine
Polymer-supported catalysts have attracted much attention in
recent decades due to their inherent advantages in synthetic chem-
istry, for example, simplification of reaction procedures including
easy recovery of the catalyst by filtration, application to automated
systems, and recycling of catalyst.1 1,5,7-Triazabicyclo[4,4,0]dec-5-
ene polystyrene (PS-TBD) is a polymer-supported organobase
catalyst, which consists of a bicyclic guanidine moiety (1,5,7-
triazabicyclo[4,4,0]dec-5-ene) anchored on polystyrene. It has
been used to mediate the alkylation of phenols, amines, active
methylene compounds, and thiols, esterification of carboxylic
acids, dehalogenation of organic halides, and high throughput syn-
thesis of aryl triflates and aryl nonaflates.2 PS-TBD also acts as a
good catalyst for the Henry reaction and the addition of dialkyl
phosphites to a variety of carbonyl compounds and imines.3 Re-
cently, Fringuelli and Pizzo reported PS-TBD catalyzed ring-
openings of epoxides, aldol-type condensations, and Michael addi-
tions.4,5 In the course of our investigations on organobase
catalyzed C–C bond formation using silylated nucleophiles,6 we
studied the use of PS-TBD as a base catalyst for the cyanosilylation
of carbonyl compounds.
have been developed to enhance the efficiency of this transforma-
tion.9 Organobase-catalyzed reactions10 have also been studied ac-
tively.11 Herein, we report that PS-TBD acts as an efficient and
reusable catalyst for the cyanosilylation of aldehydes and
ketones.12
Table 1
Optimization of the reaction conditions
N
N
N
(PS-TBD)
(1 mol%)
O
OSiMe
3
Me SiCN
+
3
solvent
time, rt
R
R
CN
R
1
1
2
R
2
Entry
Carbonyl compound
4-CH3OC6H4CHO
Solvent
Time
Yielda (%)
1
2
3
DMF
30 min
30 min
1 h
95
96
92
77
Cyanosilylation of carbonyl compounds is one of the most pop-
ular strategies to afford cyanohydrins, which can be conveniently
converted into various important polyfunctionalized building
blocks for the synthesis of many natural products and bioactive
CH3CN
CH2Cl2
THF
4
4 h
5
6
Et2O
4 h
4 h
42
50
SFCb
molecules, including
a-hydroxyl carbonyl compounds and b-
7
8
9
10
C6H5COCH3
CH3CN
DMF
CH2Cl2
SFC
1 h
95
amino alcohols.7,8 Consequently, many catalytic systems, such as
metal salts, organocatalysts, and inorganic solid acids and bases,
24 h
24 h
24 h
Trace
Trace
40
a
Isolated yield.
Solvent free condition.
⇑
Corresponding author. Tel./fax: +81 29 228 8234.
E-mail address: smatsuka@mx.ibaraki.ac.jp (S. Matsukawa).
b
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.070

1076
S. Matsukawa, S. Fujikawa / Tetrahedron Letters 53 (2012) 1075–1077
Table 2
Table 4
PS-TBD catalyzed cyanosilylation of various aldehydes
PS-TBD catalyzed cyanosilylation of various Imines
PS-TBD
PS-TBD
(2 mol%)
NR
NHR
3
O
OSiMe
3
(1 mol%)
3
Me SiCN
Me SiCN
+
3
+
3
CH CN
3
3 h, rt
CH CN
3
R
R
CN
R
R
CN
H
H
1
1
1
1
H
H
30 min, rt
Yielda (%)
Entry
R1
R3
Product
Yielda (%)
Entry
Carbonyl compound
Product
1
2
3
4
5
6
7
8b
C6H5
C6H5
C6H5CH2
4-CH3OC6H5
4-CH3OC6H5
C6H5
C6H5
C6H5
4-CH3OC6H5
5a
5b
5c
5d
5e
5f
95
95
80
92
88
75
85
72
1
2
3
4
5
6
7
8
9
4-CH3OC6H4CHO 1a
C6H5CHO 1b
2a
2b
2c
2d
2e
2f
2g
2h
2i
96
95
94
85
95
95
95
88
82
95
94
4-ClC6H4CHO 1c
4-NO2C6H4CHO 1d
4-(CH3)2NC6H4CHO 1e
1-Naphtaldehyde 1f
2-Naphtaldehyde 1g
C6H5CH2CH2CHO 1h
n-C8H17CHO 1i
4-ClC6H4
4-CH3OC6H4
4-CF3C6H4
2-Furanyl
5g
5h
C6H5CH2CH2
a
Isolated yield.
Imine was prepared in situ.
10
11
c- C6H11CHO 1j
2-Furfural 1k
2j
2k
b
a
Isolated yield.
O
H
OSiMe
PS-TBD
Table 3
PS-TBD catalyzed cyanosilylation of various ketones
3
(1 mol%)
CN
Me SiCN
+
3
H
CH CN
3
30 min, rt
MeO
MeO
PS-TBD
(2 mol%)
O
OSiMe
3
Me SiCN
+
3
Runs
1st
2nd
3rd
4th
5th
Yield (%)
CH CN
3
1 h, rt
R
R
CN
R
1
1
2
96
96
92
94
93
R
2
Entry
Carbonyl compound
Product
Yielda (%)
1
2
3
4
5
C6H5COCH3 3a
4a
4b
4c
4d
4e
4f
4g
4h
4i
95
98
91
94
90
95
96
92
91
95
84
4-CH3OC6H4COCH3 3b
4-ClC6H4COCH3 3c
4-NO2C6H4COCH3 3d
C6H5CH@CHCOCH3 3e
C6H5CH@CHCOC6H5 3f
C6H5CH2CH2COCH3 3g
Cyclohexanone 3h
C6H13COCH3 3i
OSiMe
3
PS-TBD
O
6
7
(2 mol%)
CN
CH
Me SiCN
3
3
+
CH
3
8b
9b
10
11b
CH CN
3
1 h, rt
C6H5COC6H5 3j
CF3COC6H5 3k
4j
4k
Runs
1st
2nd
3rd
4th
5th
Yield (%)
95
90
88
92
90
a
Isolated yield.
Reaction time: 2 h.
b
Initially, the cyanosilylation of p-anisaldehyde with trimethyl-
silyl cyanide was examined in the presence of 1 mol % PS-TBD.
The reaction was carried out by adding aldehyde and TMSCN to a
suspension of PS-TBD in various solvents. After the reaction was
completed, EtOAc was added to the mixture and PS-TBD was sep-
arated by filtration. The filtrate was concentrated under vacuum
and purified by column chromatography to afford the pure prod-
uct. The desired product was obtained in high yield at room tem-
perature in DMF, CH3CN, and CH2Cl2 (Table 1, entry 1–3). On the
other hand, the reaction in THF, Et2O, and SFC (solvent-free condi-
tion) was not effective. We next examined the cyanosilylation of
acetophenone. The reaction of acetophenone also proceeded
smoothly in CH3CN at room temperature (Table 1, entry 7). How-
ever, in this case, only a small amount of the product was obtained
in DMF and CH2Cl2. Thus, PS-TBD was found to act as an efficient
catalyst in the cyanosilylation of both aldehydes and ketones using
CH3CN as a solvent.
Scheme 1. Reuse of recovered PS-TBD.
presence of 2 mol % PS-TBD (Table 3). Aliphatic ketones worked
well, although slightly longer reaction times were required com-
pared to the reactions with aromatic ketones. Furthermore, we
have extended the present catalytic system to the reaction with
The corresponding a-aminonitriles were obtained in
good yield in the presence of 2 mol% PS-TBD (Table 4).
The recovery and reuse of PS-TBD are illustrated for the reaction
of p-anisaldehyde with TMSCN in Scheme 1. After the reaction was
completed, ethyl acetate was added to the reaction mixture and
the catalyst was recovered by filtration. The recovered catalyst
was washed, dried, and then reused. The catalyst was reused,
maintaining its catalytic activity after 5 times. The same result
was observed in the reaction of acetophenone.
In conclusion, we disclose that PS-TBD acts as an efficient and
reusable catalyst in the cyanosilylation of carbonyl compounds. A
wide range of aldehydes and ketones were shown to undergo
cyanosilylation in generally excellent yields. Furthermore, PS-TBD
was easily recovered and reused without loss of activity after 5
13,14
imines.
In order to clarify the scope of this reaction, several aldehydes
were examined in the presence of 1 mol % PS-TBD (Table 2). Aro-
matic aldehydes with either electron-donating or electron-with-
drawing groups afforded the corresponding products in high
yields. Aliphatic aldehydes also worked well. Additionally, the
reaction proceeded smoothly with various kinds of ketones in the

S. Matsukawa, S. Fujikawa / Tetrahedron Letters 53 (2012) 1075–1077
1077
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runs. Further investigation along these lines, including reactions
with other silylated nucleophiles, is currently underway.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.12.070.
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