Inorganic/organic salts as heterogeneous basic catalysts for cyanosilylation of carbonyl compounds

Article abstract of DOI:10.1055/s-2004-829569

The addition of TMSCN to carbonyl compounds catalyzed by K ₂CO₃ as heterogeneous catalyst gave the corresponding cyanohydrin trimethylsilyl ethers from 20 minutes to 24 hours with 62% to 99% yields without solvent at room temperature

Full text of DOI:10.1055/s-2004-829569

1776
LETTER
Inorganic/Organic Salts as Heterogeneous Basic Catalysts for Cyanosilylation
of Carbonyl Compounds
Heterogeneous
B
i
asic
C
a
n
talysts for
C
yanosi
H
lylation of Carboneyl Compou a
,
nds Yan Li,a Xiaoming Feng,*a,b Guolin Zhangc
a
Key Laboratory of Green Chemistry & Technology (Sichuan University), Ministry of Education, College of Chemistry,
Sichuan University, Chengdu 610064, P. R. China
Fax +86(28) 85418249; E-mail: xmfeng@scu.edu.cn
b
c
State Key Laboratory of Applied Organic Chemistry, Lanzhou 730000, P. R. China
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, P. R. China
Received 16 May 2004
tempt to catalyze the asymmetric version by chiral organic
salts. As result, we disclosed a convenient method for the
synthesis of cyanohydrin trimethylsilyl ethers using
K2CO3 as heterogeneous catalyst without solvent
Abstract: The addition of TMSCN to carbonyl compounds cata-
lyzed by K2CO3 as heterogeneous catalyst gave the corresponding
cyanohydrin trimethylsilyl ethers from 20 minutes to 24 hours with
62% to 99% yields without solvent at room temperature. Moreover,
it was found that chiral organic salts as heterogeneous catalysts also (Scheme 1) and then investigated the asymmetric cyanos-
can catalyze the asymmetric version and afford the corresponding
ilylation of benzaldehyde and acetophenone by using so-
products with up to 99% yield and 12.4% ee.
dium D-gluconate.
Key words: heterogeneous catalysis, potassium carbonate, cyano-
silylation, cyanohydrins, carbonyl compounds
O
OTMS
3 mol% or 30 mol% K2CO3
1.2 equiv TMSCN, r.t.
R1
R2
R1
CN
R2
The use of heterogeneous catalysts allows a simplification
of the purification step to a simple filtration, separating
the catalyst from the reaction media. Heterogeneous basic
catalysis including inorganic and organic salts is an area
of growing interest which has been recently reviewed.1
Compared with that of homogeneous catalysts, the utiliza-
tion of heterogeneous catalysts in liqiuid-phase organic
reactions have the following advantages: (1) Higher reac-
tivities and selectivities are often realized, owing to the
specific structures of solid surfaces where organic sub-
strates are adsorbed, oriented, and activated. (2) A work-
up procedure is only filtration of the solid catalysts, and
the products are easily isolable.2
Scheme 1 Cyanosilylation of carbonyl compounds in the presence
of K2CO3
Table 1 Cyanosilylation of Benzaldehyde Catalyzed by Saltsa
Entry
Salts
Time (h)
Yield (%)b
1
2
3
4
5
6
7
Li2CO3
Na2CO3
K2CO3
CaCO3
KCl
1
6
86
99
–
1
0.6
1
1
–
Cyanosilylation of carbonyl compounds is one of the most
powerful procedure for the synthesis of cyanohydrins,
which can easily be converted to various important build-
ing blocks.3–6 Many homogeneous catalysts have been
used to promote this reaction (Lewis acid or Lewis base,
etc.).7 Among these examples, our group has also devel-
oped a bifunctional catalyst with N-oxide dipolar
moieties8 and a double activation method (CDAM).9
Comparatively, only a few examples of heterogeneous ca-
talyses have been reported using Montmorillonite K-10,10
Clayfen11 as acidic catalysts or HAP, CaO, MgO,2
Zr(KPO4)212 and diamino-functionalized mesoporous13 as
basic catalysts.
NaHCO3
NaOAc
1
–
1
82
a All reactions were carried out in Et2O with 3 mol% indicated salt at
r.t.
b Isolated yield.
Our studies started with benzaldehyde as a test substrate.
The results of the screening of salts were listed in Table 1
and revealed that univalent metal carbonates were active
in this reaction (Table 1, entries 1–3) and then K2CO3 was
found to be the most promising catalyst (Table 1, entry 3).
The amount of catalyst was revealed to be an important
parameter for the attainment of high yield in short time.
The more catalyst was used, the more rapid the reaction
was carried out. To touch the minimized loading of cata-
lyst, we found that 3 mol% of K2CO3 was enough to get
the excellent yield of 99% in CH2Cl2 within one hour at
room temperature. Under the same conditions, a solvent
study showed that Et2O provided the best result of 99%
In this communication, our research focused on looking
for other heterogeneous catalysts for cyanosilylation of
carbonyl compounds and furthermore took an initial at-
SYNLETT 2004, No. 10, pp 1776–1778
0
9
.0
8
.2
0
0
4
Advanced online publication: 28.07.2004
DOI: 10.1055/s-2004-829569; Art ID: U14204ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Heterogeneous Basic Catalysts for Cyanosilylation of Carbonyl Compounds
1777
yield in only 40 minutes (Table 1, entry 3).14 Considering ucts in 99% yields in only several hours (Table 2, entries
the green process, under solvent-free condition, benzalde- 13–17). It was shown that these ketones were more active
hyde was treated with 1.2 equivalents TMSCN in the pres- than aromatic or heterocyclic ketones in current catalytic
ence of 3 mol% K2CO3 at room temperature. It was found system.
that the result under solvent-free condition was good as
The mechanism of the reaction probably involves the ac-
that obtained when Et2O as solvent (Table 2, entry 1).
tivation of TMSCN by its coordination with the basic sites
Subsequently, a study of acetophenone as a test substrate
of K2CO3 and subsequent release of nucleophilic cyanide
of ketones showed that 30 mol% of K2CO3 was necessary
ion.12,15
to get the corresponding product in 91% yield in 24 hours
In addition, it was found that NaOAc as well as Na2CO3
(Table 2, entry 9).
had the same activity to catalyze the cyanosilylation of
Encouraged by the results obtained for benzaldehyde and
benzaldehyde (Table 1, entries 2 and 7). We speculated
acetophenone, we investigated a number of other alde-
that the use of chiral organic salts would catalyze the
hydes and ketones to probe their behavior under the cur-
asymmetric cyanosilylation of benzaldehyde and ace-
rent catalytic conditions. The results are listed in Table 2.
tophenone. Therefore, we chose three accessible chiral or-
ganic salts (Figure 1) to test the reaction, with the results
listed in Table 3.
Table 2 Cyanosilylation of Carbonyl Compounds Catalyzed by
K2CO3 without Solvent16
Entry
1
Carbonyl compounds
Time (h)
Yield (%)a
99
OH
OH
OH
HO
O
OH
O
NH2
NaO
NaO
ONa
Benzaldehyde
0.6
0.3
0.3
1.5
6
ONa
NaO
HO
D-3
O
OH
O
O
2
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
4-Methylbenzaldehyde
4-Methoxybenzaldehyde
(E)-3-Phenyl-2-propenal
2-Furfural
99
D-1
L-2
3
99
Figure 1 Chiral organic salts
4
91
Table 3 Asymmetric Cyanosilylation of Carbonyl Compounds Cat-
5
93
alyzed by Chiral Organic Saltsa
6
3
82
Entry Salts
Carbonyl compounds Time
(h)
Yield ee
(%)b
(%)
7
2
96
1
2
3
D-1
L-2
D-3
Benzaldehyde
Acetophenone
Benzaldehyde
Acetophenone
Benzaldehyde
Acetophenone
90
90
20
20
90
90
99
3.0c
0.1d
8
n-Butyraldehyde
1
99
99
9
Acetophenone
24
24
24
24
9
91
99
1.1c
10
11
12
13
14
15
16
17
4-Chloroacetophenone
4-Methylacetophenone
1-(Thiophen-2-yl)ethanone
(E)-4-Phenyl-3-buten-2-one
Benzylacetone
94
75
0.6d
62
99
12.4c
11.0d
68
99
99
a All reactions were carried out in Et2O with 3 mol% (for benzalde-
hyde) or 30 mol% (for acetophenone) indicated salt at –20 °C.
b Isolated yield.
6.5
6
99
2-Heptanone
99
c Determined by HPLC on Chiralcel OD, after converted to its corre-
sponding acetate.
Cyclohexanone
6
99
d Determined by chiral GC analysis on Chirasil DEX CB.
3,3-Dimethyl-2-butanone
4.5
99
a Isolated yield.
The results indicated that carboxylic sodium was highly
active for cyanosilyation of both aldehydes and ketones,
especially the salt of L-2 (Table 3, entry 2). Furthermore,
it was implied that the utilization of chiral organic salts to
the asymmetric version was feasible (Table 3, entry 3).
Notably, D-3 was recovered by filtration in >98% yield
from the asymmetric cyanosilylation of acetophenone.
Subsequently, the reusability of D-3 was checked and
showed consistent both activity (98% yield) and enanti-
oselectivity (11.3% ee).
Aromatic, a,b-unsaturated, heterocyclic and aliphatic al-
dehydes reacted with TMSCN in the presence of K2CO3
to afford the corresponding products in very short time
(Table 2, entries 1–8). By contrast to aldehydes, ketones
were difficult substrates because of their low reactivity
and required larger amount of catalyst (30 mol%) and
longer reaction time (Table 2, entries 9–17). In 24 hours,
most aromatic and heterocyclic ketones gave the corre-
sponding trimethylsilyl ethers in 62–99% yields (Table 2,
entries 9–12). However, aliphatic, a,b-saturated as well as
a,b-unsaturated ketones afforded the corresponding prod-
In conclusion, K2CO3 was found to be an excellent hetero-
geneous basic catalyst for cyanosilylation of carbonyl
compounds under mild conditions. General application,
Synlett 2004, No. 10, 1776–1778 © Thieme Stuttgart · New York

1778
B. He et al.
LETTER
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(16) General Procedures for Cyanosilylation of Carbonyl
Compounds: To a mixture of carbonyl compound (2 mmol)
and K2CO3 (8 mg, 0.06 mmol for aldehydes or 83 mg, 0.60
mmol for ketones) was added trimethylsilyl cyanide (328
mL, 2.40 mmol) at r.t. The reaction was monitored by TLC.
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simply work-up, cheap catalyst, free of solvent and room
temperature are additional advantages of this procedure.
Moreover, it provided a feasible direction of asymmetric
cyanosilylation for carbonyl compounds by using the
chiral organic salts. Further research based on the modifi-
cation of glucose or other nature sugar salts to improve
enantioselectivity is underway.
Acknowledgment
We thank the National Natural Science Foundation of China (No.
20225206, 20390050 and 20372050) and the Ministry of Education,
P. R. China (No. 01144, 104209 and others), for financial support.
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