Highly efficient chemo- and regioselective silylation of -OH groups and cyanosilylation of aldehydes promoted by TiCl2(OTf)-SiO2 as a new recyclable catalyst

Article abstract of DOI:10.1016/j.jorganchem.2009.08.009

TiCl₂(OTf)-SiO₂ as an easy handling recyclable catalyst was applied for trimethylsilylation of diethyl α-hydroxyphosphonates, alcohols and phenols with high selectivity using HMDS as a silylating agent. Cyanotrimethylsilyl ethers were also obtained in excellent yields from treatment of aldehydes with TMSCN in the presence of this catalyst.

Full text of DOI:10.1016/j.jorganchem.2009.08.009

Journal of Organometallic Chemistry 694 (2009) 3923–3928
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Highly efficient chemo- and regioselective silylation of –OH groups
and cyanosilylation of aldehydes promoted by TiCl2(OTf)–SiO2 as a
new recyclable catalyst
*
**
Habib Firouzabadi , Nasser Iranpoor , Soghra Farahi
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 April 2009
Received in revised form 4 August 2009
Accepted 6 August 2009
Available online 11 August 2009
TiCl2(OTf)–SiO2 as an easy handling recyclable catalyst was applied for trimethylsilylation of diethyl
a-hydroxyphosphonates, alcohols and phenols with high selectivity using HMDS as a silylating agent.
Cyanotrimethylsilyl ethers were also obtained in excellent yields from treatment of aldehydes with
TMSCN in the presence of this catalyst.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
a-Hydroxyphosphonate
HMDS
Aldehyde
TMSCN
Cyanosilylation
Silica gel
1. Introduction
hazardous and not available chemicals such as DEAD, moisture
sensitive compounds and using organic solvents.
Functional group protection is an unavoidable process during
the multi-step synthesis. One of the most popular reactions for
masking hydroxyl functional groups is their transformation to silyl
ethers [1]. Preparation of silyl ethers is usually carried out by the
reaction of alcohols with silyl halides in the presence of stoichiom-
etric amount of an organic base. The most familiar bases used for
this purpose are: imidazole [2], 4-(N,N-dimethylamino)pyridine
[3], and N,N-diisopropylethylamine [4]. In these methods, separa-
tion of ammonium salts is a time consuming process.
Hexamethyldisilazane (HMDS) as an inexpensive and easy
available compound has been used for the preparation of trimeth-
ylsilyl ethers from hydroxyl compounds. The only by product of
this reaction is NH3 gas, which is a notable advantage for the meth-
od. The main drawback of HMDS is its poor silylating property [13].
However, this difficulty is overwhelmed by using various acid cat-
alysts such as ZnCl2 [14], K-10 montmorillonite [15,16], I2 [17],
H3PW12O40 [18], Cu(OTf)2 [19], LiClO4 [20], Mg(OTf)2 [21], Al(OTf)3
[22] and lithium perchlorate dispersed on silica gel [23].
Compounds carrying activated N–Br bonds; 1,3-dibromo-5,5-
diethylbarbituric acid and N,N,N0,N0-tetrabromobenzene-1,3-
disulfo- namide [24,25], LaCl3 [26], sulfonic acid-functionalized
ordered nanoporous silica [27], iron(III) trifluoroacetate [28] and
zirconyl triflate [29] have been used to activate HMDS for silylation
reaction.
Although silylation ability of HMDS has been improved by these
methods, yet some problems such as long reaction times, drastic
reaction conditions and sometimes, a tedious work-up should still
be overcome. However, introduction of new protocols using
stable, cost effective, recyclable and non-corrosive catalysts with
high efficiency are of great demand, especially for large-scale
operations.
Reaction of hydroxyl functional groups with R3Si–H catalyzed
by dirhodium(II) perfluorooctanoate {Rh2(PFO)4} [5], Ph2P–SiEt3/
diethyl azodicarboxylate (DEAD)/pyridinium p-toluenesulfonate
(PPTS) system [6] and with hexamethyldisilane using [PdCl(g3
-
C3H5)]2–PPh3 [7] have also provided silyl ethers. Preparation of si-
lyl ethers from allylsilane and silyl enol ethers in the presence of
catalytic amount of p-toluenesulfonic acid [8,9], I2 [10], trifluoro-
methanesulfonic acid [11] or Sc(OTf)3 [12] are also appeared in
the literature. Although these procedures provide improvements,
they suffer from expensive silylating agents and catalysts, using
* Corresponding author. Tel.: +98 711 2284822; fax: +98 711 2280926.
** Corresponding author.
E-mail addresses: firouzabadi@chem.susc.ac.ir (H. Firouzabadi), iranpoor@
chem.susc.ac.ir (N. Iranpoor).
a-Hydroxy nitriles or cyanohydrins are interesting compounds
in both chemistry and biology [30]. Cyanohydrins are precursors
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.08.009

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H. Firouzabadi et al. / Journal of Organometallic Chemistry 694 (2009) 3923–3928
of a number of valuable synthetic intermediates such as
a
-hydroxy
of librated HCl gas were in accord with the formation of TiCl2(OTf)–
SiO2.
acids, -amino acids and b-amino alcohols [31–35]. Cyanohydrins
a
have also been used as starting materials in the synthesis of
pharmaceuticals and natural products such as diltiazem, glycoside
amygdalin, and fenvalerate [36]. Because of their importance in or-
ganic synthesis, preparation of cyanohydrins has been extensively
studied. Traditionally, cyanohydrins are prepared by the addition
of highly toxic hydrogen cyanide to carbonyl compounds, which
is an equilibrium process [37–39]; while addition of base increases
the rate of the reaction [40]. Transhydrocyanation from acetone
cyanohydrin to the carbonyl compounds is another method of cya-
nohydrin preparation [41–45]. Reaction has been mediated under
basic conditions [41,42], or using lanthanide(III) alkoxides [43],
titanium-, zirconium-, and aluminum-based [44,45] reagents as
catalysts.
Acidic hydrolysis of cyanotrimethylsilyl ethers is further route
to obtain cyanohydrins [46,47]. These compounds are prepared
from the reaction of carbonyl compounds with TMSCN, and many
catalysts and reagents have been introduced to achieve this goal.
Various Lewis acids [48–66], base catalysts [67–70], solid catalysts
[71–74], organocatalysts [75–81], ionic liquids [82,83] and bifunc-
tional catalysts [84–87] have been employed to furnish cyanosily-
lation of carbonyl compounds with TMSCN. Although many
promising catalysts and reagents have been introduced to promote
this reaction, there is much room for the design and preparation of
new catalysts, which offer short reaction time, easier work-up and
can be recycled simply without considerable loss of their catalytic
abilities.
2.3. General procedure for the preparation of trimethylsilyl ethers
catalyzed by TiCl2(OTf)–SiO2
To the stirring mixture of HMDS (97 mg, 0.6 mmol) and an alco-
hol, phenol or
(30 mg, 0.01 mmol) was added at room temperature(alcohols and
phenols are soluble in HMDS; whereas, -hydroxyphosphonates
a-hydroxyphosphonate (1 mmol), TiCl2(OTf)–SiO2
a
appeared as a heterogeneous mixture). The reaction completed
after appropriate time (monitoring by TLC or GC). EtOAc or Et2O
(5 mL) was added to the reaction mixture and filtered. The catalyst
separated and washed with another portion of EtOAc or Et2O
(5 mL). To the combined resulting filtrates, H2O (5 mL) was added.
The organic layer decanted and dried over anhydrous Na2SO4 and
filtered. Evaporation of the solvent afforded the almost pure prod-
ucts. In a few cases, further purification performed by short pad of
Table 1
Trimethylsilylation of
a-hydroxyphosphonates catalyzed by solid TiCl2(OTf)–SiO2
with HMDS under neat conditions at room temperature.a
O
O
TiCl2(OTf)-SiO2 (1 mol%)
neat, r.t., 30 min
Ar
P(OEt)2
OH
1 mmol
Ar
P(OEt)2
HMDS
+
OSiMe3
0.6 mmol
Titanium tetrachloride (TiCl4) as a powerful Lewis acid has
found many applications in organic synthesis and industry. How-
ever, this compound is a liquid and highly aggressive material that
creates clouds of HCl when is exposed to air and moisture. There-
fore, its handling needs serious precautions. Recently, we have
introduced TiCl3(OTf) as a potential solid substitute for fuming li-
quid TiCl4 in a number of organic reactions [88–91].
Entry
Ar–
Isolated yield (%)
1
2
3
4
5
6
7
C6H5–
p-OCH3–C6H4–
o-Cl–C6H4–
p-NO2–C6H4–
m-NO2–C6H4–
p-Cl–C6H4–
90
90
94
95
98
92
90
2,6-Cl2C6H4–
Herein, we report TiCl2(OTf)–SiO2 as a silica bound Ti(IV) based
compound which is used for selective trimethylsilylation of diethyl
a
The equivalent ratios of substrate:HMDS:catalyst was 1:0.6:0.01.
a-hydroxyphosphonates, alcohols and phenols with (HMDS) at
room temperature. This catalyst has been also applied for efficient
preparation of cyanotrimethylsilyl ethers from the reaction of alde-
hydes with TMSCN.
Table 2
Trimethylsilylation of alcohols and phenols catalyzed by TiCl2(OTf)–SiO2 with HMDS
under neat conditions at room temperature.a
Entry
Substrate
Time (min)
Isolated yield (%)
2. Experimental
1
2
3
4
C6H5CH2OH
5
5
5
92
90
94
92
p-NO2–C6H4CH2OH
p-MeO–C6H4CH2OH
Ph2CHOH
2.1. General remarks
30
Chemicals were purchased from Merck and Fluka Chemical
Companies. IR spectra were run on a Shimadzu model 8300 FT-IR
spectrophotometer. NMR spectra were recorded on a Bruker
Avance DPX-250. The purity of the products and the progress of
the reactions were accomplished by TLC on silica gel polygram
SILG/UV254 plates or GC. ICP analysis was performed by a VARIAN
VISTA-PRO CCD Simultaneous ICP-OES.
5
25
95
OH
Ph
CH3
6
7
10
15
94
92
OH
OH
8
9
CH3(CH2)6CH2OH
PhCH2CH2OH
PhCH2CH2CH2OH
30
5
10
90
90
240
30
30
10
48 h
48 h
90
94
92
88
93
90
87
85
95b
nr
2.2. Preparation of the catalyst
10
11
12
13
14
15
16
17
18
TiCl3(OTf) was prepared according to the literature from the
reaction between TiCl4 and TfOH [92]. The catalyst [TiCl2(OTf)–
SiO2] was prepared by adding TiCl3(OTf) (0.61 g, 2 mmol) to dry sil-
ica gel (70–230 mesh, 6 g) in dry CH2Cl2 (15 mL) under nitrogen
atmosphere at room temperature. The reaction was performed
immediately by the evolution of HCl gas. After evaporation of the
solvent, the solid silica bound Ti(IV) catalyst was obtained in
6.53 g. The amount of the evolved HCl gas was measured by back
titration method. The weight increase of silica gel and the amounts
(CH2)5CH(OH)CH3
CH3
Menthol
Adamantanol
Phenol
2-Hydroxynaphthalene
Cholesterol
C6H5CH2NH2
C6H5CH2SH
nr
a
The equivalent ratios of substrate:HMDS:catalyst was 1:0.6:0.01.
The reaction was performed in CH2Cl2 as a solvent.
b

H. Firouzabadi et al. / Journal of Organometallic Chemistry 694 (2009) 3923–3928
3925
silica gel using the appropriate solvent and the desired products
Then, we applied this ratio to structurally diverse
a
-hydrox-
were obtained in 90–98% (Table 1) and 85–95% (Table 2) isolated
yields.
yphosphonates for their conversion to the corresponding a-trim-
ethylsilyloxyphosphonates effectively and the corresponding
desired products were isolated in excellent yields (88–98%) in
short reaction times (Table 1). Separation of the catalyst from the
reaction mixture performed very easily by a simple filtration,
which after drying was recycled for the subsequent reactions with-
out observable loss of its catalytic activity.
2.4. General procedure for cyanosilylation of aldehydes catalyzed by
TiCl2(OTf)–SiO2
TiCl2(OTf)–SiO2 (60 mg, 0.02 mmol) was added to a mixture of
an aldehyde (2 mmol) and TMSCN (0.30 mL, 2.4 mmol). The result-
ing mixture stirred at room temperature. After completion of the
reaction (as monitored by TLC or GC), EtOAc or any other appropri-
ate organic solvent (5 mL) was added to the reaction mixture and
the solid TiCl2(OTf)–SiO2 was filtered. The solid residue washed
with another portion of the solvent (5 mL) and filtered. The filtrates
combined and the solvent evaporated on a rotary evaporator to
isolate the crude product. Purification by a short column chroma-
tography on silica gel afforded the pure products in 85–94% iso-
lated yields (Table 5).
Then, we applied the optimized ratio from the preceding section
for silylation reactions of different alcohols and phenols under sim-
ilar reaction conditions. In the presence of this catalyst, benzylic
alcohols were readily transformed into their corresponding tri-
methylsilyl ethers in excellent yields (Table 2, entries 1–4). Allyl,
homoallyl and acid sensitive alcohols were also reacted under sim-
ilar reaction conditions without the formation of any rearrange-
ment or dehydration side products (Table 2, entries 5–7 and 12).
Reaction of primary alcohols in the presence of this catalyst pro-
ceeded smoothly in short reaction times in excellent yields (Table
2, entries 8–10). However, this catalyst was also effective for con-
version of -OH groups of secondary and tertiary alcohols to their
trimethylsilyl ethers in excellent yields without formation of any
dehydration or rearranged side products (Table 2, entries 11–13).
Silylation of phenolic substrates (Table 2, entries 14 and 15) with
HMDS under similar conditions was also performed smoothly
and cleanly in high yields. Conversion of cholesterol to its trimeth-
ylsilyl ether in the absence of solvent was not a clean and a
straightforward reaction. Then, this reaction was performed in
CH2Cl2 at room temperature with success and the silylated product
was isolated in a high yield within a short reaction time (Table 2,
entry 16). Trimethylsilylation of amines and thiols under similar
reaction conditions did not proceed at all (Table 2, entries 17 and
18).
3. Results and discussion
First, TiCl3(OTf) was immobilized on silica gel surface by the
addition of TiCl3(OTf) to a stirring suspension of dried silica gel
in dry CH2Cl2. Evaporation of the solvent provided TiCl2(OTf)–
SiO2 as an air and moisture stable compound. This compound
was applied as a catalyst for the preparation of trimethylsilyl and
trimethylcyanosilyl ethers.
3.1. Trimethylsilylation of
phenols
a-hydroxyphosphonates, alcohols and
a
-Trimethylsiloxyphosphonates are useful precursors for the
preparation of organic compounds which are attractive in biology
and in industry [93]. -Acidic hydrogen of -trimethylsiloxypho-
sphonates can be deprotonated with strong bases to generate
carbanionic species in the reaction mixture [94]. However, the
in situ generated -carbanionic species become important
synthons, which are equivalent to acyl anions and can take part
in carbon–carbon bond forming reactions. b, -Unsaturated
ketones, carboxylic acids, and unsymmetrical ketones can be pre-
pared by alkylation of the carbanionic species [95,96]. -Trim-
ethylsiloxyphosphonates are also easily converted to -hydroxy
Selectivity of the catalysts for chemical transformations is
important, especially, when the catalyst is used in multi-step syn-
thesis. We have found that in the presence of this catalyst, silyla-
tion of different –OH groups proceeded with high selectivity as
summarized in Table 3.
Recycling of the catalyst was explored upon silylation of benzyl
alcohol with HMDS in the presence of TiCl2(OTf)–SiO2 as a model
reaction. After completion of the reaction, CH2Cl2 was added to
the solvent less reaction mixture and the solid catalyst was simply
separated by filtration. The isolated catalyst dried in oven and re-
used for the similar reaction for six consecutive runs without ob-
servable loss in its catalytic activity. The level of Ti leaching into
the liquid phase was determined by inductively coupled plasma
atomic emission spectroscopy (ICP). The results showed that the
amount of leached Ti was 5.38 ppm after the reaction, correspond-
ing to a loss of 4.2% of the initially added catalyst.
a
a
a
-
a
c
a
a
ketones after alkaline hydrolysis of Si–O bond followed by elimina-
tion of dialkyl phosphate [97]. By consideration of the vast applica-
tions, the importance of silylation of
becomes relevant in organic synthesis.
a-hydroxyphosphonates
Silylation of
a-hydroxyphosphonates in the presence of cata-
lytic amounts of TiCl2(OTf)–SiO2 with HMDS was investigated.
In order to show the merit of the catalyst, we have compared
For this purpose and optimization of the reaction conditions, we
the results of silylation of diethyl a-hydroxy (phenylmethyl)phos-
have studied the reaction of diethyl
a-hydroxy (phenyl-
phonate using HMDS with some other catalysts such as different
metal triflates, silica gel and silica gel wetted with HCl solution
(Table 4). As it is evident from the results tabulated in the table,,
the reaction in the presence of Cu, Al and Mg triflates is faster than
that has been performed using LiOTf and TiCl2(OTf)–SiO2. However,
the reaction in the presence of TiCl2(OTf)–SiO2 required much less
molar equivalent of the catalyst. In addition, the heterogeneity of
TiCl2(OTf)–SiO2 facilitates its separation and recycling process.
The catalytic activity of TiCl2(OTf)–SiO2 has also been compared
with silica gel and silica gel moist with HCl, which their reactions
were completely failed.
methyl)phosphonate as a model compound with HMDS under sol-
vent-free conditions in the presence of TiCl2(OTf)–SiO2 as a catalyst
at room temperature. We have found that the optimized molar ra-
tio of substrate:HMDS:catalyst was 1:0.6:0.01 as presented in
Scheme 1.
O
O
TiCl2(OTf)-SiO2(1mol%)
neat, r.t., 30 min
Ph
P(OEt)2
Ph
P(OEt)2
HMDS
+
OSiMe3
90%
OH
The catalyst was stored in
a moisture ambient for two
0.6 mmol
1 mmol
weeks and after then, it was applied for the silylation reaction of
benzyl alcohol with HMDS. However, we observed that there was
no change in the catalytic activity of TiCl2(OTf)–SiO2 in this
reaction.
Scheme 1. Optimization conditions for silylation of
the reaction of diethyl -hydroxy (phenylmethyl)phosphonate with HMDS in the
presence of TiCl2(OTf)–SiO2 as a catalyst.
a-hydroxyphosphonates upon
a

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H. Firouzabadi et al. / Journal of Organometallic Chemistry 694 (2009) 3923–3928
Table 3
Competitive silylation reactions of alcohols using HMDS in the presence of solid TiCl2(OTf)–SiO2 at room temperature under solvent-free conditions.
R1OH (1mmol)
+
R2OH(1mmol)
R1OSiMe3
+
R2OSiMe3
TiCl2OTf-SiO2(1mol%)
neat, r.t.
HMDS
0.6 mmol
Entry
1
Substrate
Time (min)
Product
GC yield (%)
84
10
10
10
90
10
OH
OSiMe3
OH
OSiMe3
16
2
3
4
5
87
11
OSiMe3
OH
OSiMe3
OH
100
0
OH
OSiMe3
OSiMe3
OH
85
17
OH
OH
OSiMe3
OSiMe3
100
0
OH
OSiMe3
OH
OSiMe3
6
10
100
OH
OSiMe3
HS
HS
7
8
10
5
100
78
OH
OSiMe3
H2N
HO
H2N
OH
OH
Me3SiO
HO
OSiMe3
17
5
OSiMe3
Me3SiO

H. Firouzabadi et al. / Journal of Organometallic Chemistry 694 (2009) 3923–3928
3927
Table 6
O
OSiMe3
Reaction of benzaldehyde with trimethylsilyl cyanide in the presence of different
catalysts.
TiCl2(OTf)-SiO2 (1 mol%)
r.t., neat, 5 min
H
CN
TMSCN
H
+
O
OSiMe3
92%
1 mmol
1.2 mmol
catalyst
H
CN
H
TMSCN
+
Scheme 2. Optimization conditions for cyanosilylation of aldehydes upon the
reaction of benzaldehyde with TMSCN in the presence of TiCl2(OTf)–SiO2 as a
catalyst.
condition
Entry Catalyst
(mol%) Condition
Time
Yield Reference
(%)
1
2
AuCl3
1
1
CH2Cl2 (solvent),
r.t.
CH3CN (solvent),
r.t.,
30 min 100a [64]
Table 4
85b
[69]
Comparison between TiCl2(OTf)–SiO2 and some other promoters for silylation
reaction of diethyl
DMAP
1 h
a
-hydroxybenzylphosphonate with HMDS.
N2 atmosphere
CH2Cl2 (solvent),
r.t.
O
O
15 min 100a [79]
Lewis Acid
3
4
NIS
0.5
0.5
HMDS
P(OEt)2
P(OEt)2
+
10 min 91b
[78]
neat, r.t.
N-
THF, r.t.
OH
OSiMe3
1 mmol
Heterocyclic
carbenes
(NHC)
TiCl2(OTf)–
SiO2
Entry Lewis acid
Time
15 min
Immediately 96
Immediately 97
90 min
30 min
3 h
Yield (%)a
97b
Reference
5
1
Neat, r.t.
5 min 92b
–
1
2
3
4
5
6
7
Cu(OTf)2 (11 mol%)
Mg(OTf)2 (10 mol%)
Al(OTf)3 (10 mol%)
LiOTf (10 mol%)
TiCl2(OTf)–SiO2 (1 mol%)
Silica gel (30 mg)
[19]
[21]
[22]
[22]
–
Conversion yield assumed by 1H NMR analysis.
Isolated yield.
a
100c
90
Neglegible
Neglegible
b
–
–
Silica gel (30 mg) wetted
with HCl (0.03 mmol)
3 h
of TiCl2(OTf)–SiO2 in short reaction times. These results are shown
in Table 5.
a
b
c
Isolated yield.
In order to show the advantage of the catalyst, cyanosilylation
of benzaldehyde with TMSCN in the presence of TiCl2(OTf)–SiO2
was compared with some of the reported methods in Table 6. As
it is obvious from results of the table, the reaction in the presence
of the other catalysts has been performed in solvents, whereas, in
the presence of TiCl2(OTf)–SiO2 non-solvent condition was em-
ployed. In addition, TiCl2(OTf)–SiO2 is an easily recyclable hetero-
geneous catalyst, which resulted to a simple work-up of the
products.
The reaction has been carried out in CH3CN as solvent.
% Conversion based on 1H NMR.
Table 5
Trimethylcyanosilylation of aldehydes with TMSCN in the presence of TiCl2(OTf)–SiO2
(0.01 mmol) under neat conditions at room temperature.a
O
OSiMe3
TiCl2(OTf)-SiO2 (1 mol%)
r.t., neat
TMSCN
+
R
H
R
CN
H
1 mmol
1.2 mmol
4. Conclusion
Entry
Substrate
Time (min)
Isolated yield (%)
In this article, we have introduced an easy handling recyclable
solid titanium(IV) based catalyst; TiCl2(OTf)–SiO2, which has been
used to promote silylating ability of HMDS for the preparation of
1
2
3
4
5
6
7
8
C6H5CHO
5
5
5
92
94
92
87
96
85
86
92
85
85
91
90
p-CH3–C6H4CHO
p-OCH3–C6H4CHO
p-Cl–C6H4CHO
2,6-(Cl)2–C6H3CHO
m-NO2–C6H4CHO
p-NO2–C6H4CHO
Furfural
1-Naphthaldehyde
2-Naphthaldehyde
Cinemaldehyde
Heptanal
10
30
60
75
5
20
30
5
silyl ethers from
a-hydroxyphosphonates, alcohols and phenols.
The catalysts show high chemo- and regioselectivity between dif-
ferent substrates. TiCl2(OTf)–SiO2 has also been used as an effective
catalyst for cyanosilylation of different aldehydes. In the presence
of this catalyst, reactions proceeded under solvent-free conditions
and at short times in excellent yields. The strong feature of the
method is easy work-up of the products and simple recycling of
the heterogeneous catalyst.
9
10
11
12
5
a
The molar ratio of aldehyde:TMSCN:catalyst was 1:1.2:0.01.
Acknowledgement
3.2. Trimethylcyanosilylation of aldehydes
We gratefully acknowledge Iran TWAS Chapter based at ISMO
and Shiraz University Research Council for the support of this
study.
Among the reported methods for the preparation of cyanohy-
drins, cyanosilylation of carbonyl compounds with TMSCN has
been more considered. Therefore, we investigated the possibility
of using TiCl2(OTf)–SiO2 to catalyze cyanosilylation of carbonyl
compounds with TMSCN. First, reaction of benzaldehyde with
TMSCN in the presence of TiCl2(OTf)–SiO2 was studied and the
optimized ratio of substrate:TMSCN:catalyst for this reaction was
1 mmol:1.2 mmol:1 mol% as presented in Scheme 2.
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Then, the optimized condition subjected for cyanosilylation of
different aldehydes. Aromatic aldehydes with both electron-with-
drawing and electron-releasing groups, aliphatic,
a,b-unsaturated
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