Asymmetric addition of trimethylsilyl cyanide to aldehydes promoted by chiral polymeric vanadium(V) salen complex as an efficient and recyclable catalyst

Article abstract of DOI:10.1016/j.tetasy.2006.09.024

The asymmetric addition of trimethylsilyl cyanide to various aldehydes catalyzed by efficient new vanadyl polymeric salen complexes having 12 repeating salen units was investigated at room temperature. An excellent yield of the trimethylsilylether of cyanohydrins (up to 98%) with high chiral induction (96%) in case of 2-methylbenzaldehyde was achieved in 18 h. The catalyst recovered four times with retention of its performance.

Full text of DOI:10.1016/j.tetasy.2006.09.024

Tetrahedron: Asymmetry 17 (2006) 2659–2666
Asymmetric addition of trimethylsilyl cyanide to aldehydes
promoted by chiral polymeric vanadium(V) salen complex as
an efficient and recyclable catalyst
Noor-ul H. Khan,* Santosh Agrawal, Rukhsana I. Kureshy, Sayed H. R. Abdi,
Vishal J. Mayani and Raksh V. Jasra
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute (CSMCRI), G. B. Marg,
Bhavnagar 364 002, Gujarat, India
Received 23 August 2006; accepted 21 September 2006
Abstract—The asymmetric addition of trimethylsilyl cyanide to various aldehydes catalyzed by efficient new vanadyl polymeric salen
complexes having 12 repeating salen units was investigated at room temperature. An excellent yield of the trimethylsilylether of cyano-
hydrins (up to 98%) with high chiral induction (96%) in case of 2-methylbenzaldehyde was achieved in 18 h. The catalyst recovered four
times with retention of its performance.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, much effort has been made to develop recyclable
metal complexes involving multi-step surface modification
of the support and its binding with a catalytically active
complex using organic or inorganic supports11 and ionic
liquids12 as reaction media. Our groups have been involved
in developing recyclable polymeric and dimeric salen com-
plexes for various asymmetric organic transformations.13
Herein, we extend the application of a polymeric salen
ligand13c by synthesizing its vanadium(V) salen complexes
1 and 2 for the asymmetric addition of TMSCN to various
aldehydes at room temperature. An excellent yield (98%) of
trimethylsilylether of cyanohydrin derivatives with high chi-
ral induction (ee, up to 96%) was achieved in the case of 2-
methylbenzaldehyde with catalyst 1. In all catalytic runs,
the (R)-form of polymeric V(V) salen complexes converted
all aldehydes into (S)-cyanohydrins. To the best of our
knowledge, V(V) polymeric salen complex 1 is a more effi-
cient, recyclable catalyst for cyanosilylation reaction than
the complex 2 and chiral monomeric V(V) salen system.7b
Chiral cyanohydrins are highly versatile intermediates,
which can easily be converted into a wide range of valuable
classes of chiral compounds, such as a-amino acids, a-hy-
droxy acids, b-amino alcohols, vicinal diols, a-hydroxy
ketones.1,2 They also play an important role for the
preparation of a wide range of pharmaceuticals, agrochem-
icals and insecticides.3 Substantial progress has been made
towards the development of efficient methods for the prep-
aration of these compounds, with a growing emphasis on
the identification of enantioselective catalytic approaches
with practical potential.4,5 Several useful cyanation re-
agents have been reported in the literature.6 Among them
trimethylsilylcyanide (TMSCN) seems to be one of the
most effective and safe cyanation sources for nucleophilic
addition to carbonyl compounds in the presence of a chiral
catalyst.7–10
Although impressive enantio-induction have been obtained
in many cases, issues such as moderate temperature, reac-
tion conditions and recycling of the expensive chiral cata-
lyst need to be addressed for their practical application.
2. Results and discussion
Synthesis of polymeric V(V) salen complexes 1 and 2 was
carried out by the condensation of the mono tartrate salt
of (1R,2R)-(ꢀ)-diaminocyclohexane with 5,5-methylene-
di-3-tert-butyl salicylaldehyde/5,5-methylene-di-3-methyl
*
Corresponding author. Tel.: +91 0278 2567760; fax: +91 0278
2566970; e-mail: khan2593@yahoo.co.in
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.09.024

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N. H. Khan et al. / Tetrahedron: Asymmetry 17 (2006) 2659–2666
salicylaldehyde in (1:1) molar ratio in methanol followed
by insertion of vanadium (Scheme 1). The number of
repeating units and the average molecular weight of the
polymeric ligands, as measured by vapour pressure
osmometry, was ꢁ5400 and ꢁ4300 (n = 12), respectively.
1H NMR and IR spectra showed the absence of an alde-
hyde group in ligands 10 and 20 Scheme 1. The complexes
1 and 2 were characterized by H NMR, IR, UV–vis spec-
troscopy and microanalysis (data given in Experimental
section).
Electron withdrawing substituents such as F, Cl, Br, on the
aromatic ring gave moderate enantioselectivity (Table 1,
entries 3, 11 and 12) while electron donating groups, such
as MeO and Me, favours the enantioselectivity (Table 1,
entries 5, 7, 9, 10 and 13). Additionally, o-substituted benz-
aldehydes (Me, MeO) gave higher enantiomeric excesses
(Table 1, entries 5–7) than those of p-substituted benzalde-
hydes (Table 1, entries 9 and 13). This finding indicates that
not only electronic effects but also the position of substitu-
ents play a decisive role on the enantioselectivity of the
reaction. The best enantio-induction (ee, 96%) was ob-
tained with o-methylbenzaldehyde (Table 1, entry 5). The
overall performance of this catalyst is at par in terms of
reactivity and enantioselectivity with that of dimeric a
V(V) complex (5 mol %) using KCN/NaCN13b as a cyanide
source where the reaction was carried out at ꢀ20 ꢁC. When
carrying out the cyanation reaction with aliphatic
aldehydes, viz. n-butylaldehyde 3j, tert-butylaldehyde 3k,
iso-butylaldehyde 3l in presence of trimethylsilyl cyanide
(Table 1, entries 14–16) at room temperature, 94–99% con-
version with 81–85% ee of the cyanosilylether was achieved
in the case of n-butylaldehyde and tert-butylaldehyde
(Table 1, entries 14 and 15) respectively in 18 h. A moder-
ate conversion (76%) and ee (79%) was obtained with iso-
butylaldehyde (entry 16). In all catalytic runs the (R)-form
of the polymeric V(V) salen complexes converted aldehydes
into the (S)-cyanohydrins. These results are in consonance
with earlier reports in the literature.14
1
The catalytic asymmetric addition of trimethylsilyl cyanide
to benzaldehyde 3a, 4-fluorobenzaldehyde 3b, 2-methyl-
benzaldehyde 3c and 2-methoxybenzaldehyde 3d as repre-
sentative substrates was carried out at room temperature
1
using complexes 1 and 2 (data given in Table 1). H and
13C NMR data showed the exclusive formation of products
4a–d with no formation of the enolizable product (data gi-
ven in Experimental section). The data shown in Table 1 re-
vealed that the present catalytic protocol is quite general for
the range of substrates studied in the present study. Good to
excellent conversions were achieved with all substrates for
both the catalysts (entries 1–8) with high enantiomeric ex-
cess for the substrate 3c (entries 5 and 6) in 18 h as shown
by their turn over frequency (TOF) values. The overall per-
formance of complex 1 is better than complex 2. Complex 1
was explored further for the catalytic asymmetric addition
of trimethylsilyl cyanide to different aromatic aldehydes
viz. 4-methoxybenzaldehyde 3e, 3-methoxybenzaldehyde
3f, 4-chlorobenzaldehyde 3g, 4-bromobenzaldehyde 3h, 4-
methylbenzaldehyde 3i in order to examine the effect of
the substituents and their position on the ring on the enantio-
selectivity at room temperature whereby the trimethylsilyl-
ether derivatives of the corresponding cyanohydrins 4e–i
are formed as shown in Table 1.
The reactivity and enantioselectivity of the cyanation reac-
tion is strongly dependent upon the nature of the solvent
used.8d Therefore, catalytic enantioselective cyanation
reactions were conducted in different solvents, such as
dichloromethane, 1,2-dichloroethane, toluene and THF
using benzaldehyde as a representative substrate with cata-
O
O
H2
C
HO
OH
R
R
H3N
HO
NH3
OH
K2CO3 (2eq.)
H2O\EtOH
70-80°C
H2N
NH2
EtOH, Reflux
O2C
CO2
SO4Et
O
V
N
N
N
O
N
H2
C
H2
C
O
HO
OH
O
H
VOSO4. 5H2O
EtOH\H2O
reflux 4 h
H
R
R
R
R
n
n
1
Catalyst , R = tBu
Catalyst 2, R = CH3
Scheme 1. Synthesis of the complexes 1 and 2.

N. H. Khan et al. / Tetrahedron: Asymmetry 17 (2006) 2659–2666
2661
Table 1. Enantioselective addition of trimethylsilyl cyanide to various aldehydes catalyzed by polymeric V(V) complexes
CN
CN
(R)
O
1N HCl
MeOH
Polymeric V(V)
CH2Cl2, r.t.
(R)
R
TMSCN
OTMS
R
OH
R
H
5a-l
4a-l
3a-l
3a; R = phenyl
3b; R = 4-fluorophenyl
3c; R = 2-methylphenyl
3d; R = 2-methoxyphenyl
3e; R = 4-methoxyphenyl 3f; R = 3-methoxyphenyl
3g; R = 4-chlorophenyl
3j; R = n-butyl
3h; R = 4-bromophenyl
3k; R = t-butyl
3i; R = 4-methylphenyl
3l; R = iso-butyl
Entry
Substrate
Time (h)
Conversiona (%)
eeb (%)
TOF (hꢀ1 c
)
1 (2)d
3 (4)
5 (6)
7 (8)
9
10
11
12
13
3a
3b
3c
3d
3e
3f
18
18
18
18
18
18
18
18
18
18
18
18
97 (80)
85 (70)
98 (92)
93 (88)
85
89
86
88
94
94 (58)
80 (48)
96 (89)
89 (35)
86
82
77
79
92
5.38 (4.44)
4.72 (3.88)
5.44 (5.11)
5.16 (4.88)
4.72
4.94
4.77
4.88
5.22
3g
3h
3i
14
15
16
3j
99
94
76
85
81
79
5.50
5.22
4.22
3k
3l
All reactions carried out at room temperature.
a The conversion of the cyanosilylether was determined based on the GC integral area.
b The ee was determined by using a Chiralpak HPLC OD and AD column, after conversion to the corresponding acetate.
c TOF = [Product]/[Catalyst] · time (h).
d Results in parenthesis are for catalyst 2.
lyst 1 under identical reaction conditions. A good conver-
sion (88%) with good enantioselectivity was obtained with
1,2 dichloroethane (Table 2, entry 18) but on using THF
and toluene as a solvent the conversion was (78–65%) with
ee (65–70%) (Table 2, entries 19 and 20). The best results of
the model reaction were achieved with dichloromethane
(Table 2, entry 17).
a better outcome in terms of reaction time with little
improvement in conversion and retention of enantioselec-
tivity (Table 3, entries 22–24) compared to other additives
such as triphenylphosphine, triethylamine and pyridine
(Table 3, entries 21, 25 and 26). The additive quantity
was also varied using 4-phenylpyridine-N-oxide (1–10
Table 3. Data for the effect of additives on conversion and ee of enantio-
selective addition of trimethylsilyl cyanide to benzaldehydes, catalyzed by
polymeric chiral V(V) complex 1
Table 2. Data for the effect of solvents on conversion and ee of enantio-
selective addition of trimethylsilyl cyanide to benzaldehydes, catalyzed by
recovered polymeric chiral V(V) complex 1
Entry Additives
Mol % Time Conversiona eeb
Entry
Solvent
Conversiona (%)
eeb (%)
(h)
(%)
(%)
17
18
19
20
Dichloromethane
1,2-Dichloroethane
Toluene
97
88
65
78
94
79
70
65
21
22
Triphenylphosphine
Triphenylphosphine-
oxide
Pyridine-N-oxide
4-Phenyl pyridine-N-
oxide
Pyridine
Triethylamine
4-Phenyl pyridine-N- 10
5
5
12
12
90
99
69
94
THF
23
24
5
5
12
12
99
99
94
94
All reactions carried out at room temperature.
a The conversion of the cyanosilylether was determined based on the GC
integral area.
25
26
27
5
5
12
12
6
75
85
99
78
36
95
b The ee was determined by using a Chiralpak HPLC OD column, after
conversion to the corresponding acetate.
oxide
28
29
4-Phenyl pyridine-N-
oxide
4-Phenyl pyridine-N-
oxide
2.5
17
18
96
96
94
94
It has been reported in the literature that the use of an
additive greatly influences the reactivity and enantioselec-
tivity of the asymmetric cyanation reaction.15a–g We tested
triphenylphosphine, triphenylphosphine-oxide, triethyl-
amine, pyridine, pyridine-N-oxide and 4-phenylpyridine-
N-oxide (5 mol %) for this purpose using benzaldehyde as
a representative substrate with catalyst 1 with data are
given in Table 3. The use of O coordinating additives gave
1
All reaction carried out at room temperature.
a The conversion of the cyanosilylether was determined based on the GC
integral area.
b The ee was determined by using a Chiralpak HPLC OD column, after
conversion to the corresponding acetate.

2662
N. H. Khan et al. / Tetrahedron: Asymmetry 17 (2006) 2659–2666
mol %) as the representative additive with benzaldehyde as
the substrate under identical conditions and data are given
in Table 3. When using 4-phenylpyridine-N-oxide
(10 mol %) the catalytic reaction was completed in 6 h with
a slight improvement in ee (entry 27). On the contrary,
decreasing the amount of additive from 2.5 to 1 mol %
there is no improvement in conversion and ee of trimethyl-
silylether derivative of cyanohydrin (Table 3, entries 28 and
29). Thus, the use of 5 mol % additive is proved to be opti-
mal (Table 3, entry 24).
4
3
2
1
0
The reaction temperature and catalyst loading were also
found to be an essential factor for the enantioselective cya-
nation reaction. When carrying out the cyanation reaction
with 5 mol % catalyst at rt, using benzaldehyde as the rep-
resentative substrate, the same conversion (97%) with 94%
ee of trimethylsilylether (Table 4, entry 30) was obtained
with 1 mol % catalyst loading (Table 4, entry 33). Lowering
the temperature from rt to ꢀ20 ꢁC, greatly increases the
reaction time with a lower yield (71%) (Table 4, entry 31)
but there is an increase in ee (95%). An increase in reaction
temperature to 45 ꢁC resulted in a detrimental effect on the
reaction due to the instability of the adduct trimethylsilyl-
ether (Table 4, entry 32). Attempts to reduce the catalyst
loading from 1 to 0.1 mol % (entries 33 and 34) using benz-
aldehyde as a representative substrate gave 89% conversion
of trimethylsilylether with 88% ee (Table 4, entry 34).
0
20
40
60
80
100
Time (min)
Figure 1. Time dependent plot of the formation of trimethylsilylether at
room temperature, [catalyst 1] = 3.0 · 10ꢀ3 M, [benzaldehyde] = 399.3 ·
10ꢀ3 M, [TMSCN] = 1118.3 · 10ꢀ3 M.
catalyst 1 [1.5 · 10ꢀ3 M–12.2 · 10ꢀ3 M] at a constant con-
centration of benzaldehyde [399.3 · 10ꢀ3 M] and TMSCN
[1118.3 · 10ꢀ3 M]. From the kinetic data, a linear plot of
Kobs of the cyanosilylether formation versus log[catalyst]
with unit slopes (dlogKobs/dlog[catalyst] = 1) was ob-
tained, which passes through the origin, indicating that
the cyanation of benzaldehyde is first order with respect
to the concentration of the catalyst (Fig. 2).
Table 4. Data for the effect of catalyst loading and temperature on
conversion and ee of the trimethylsilylether derivative of cyanohydrin
using benzaldehyde as a representative substrate with catalyst 1
8
7
6
5
4
3
2
1
0
Entry
Catalyst loading
(mol %)
Temperature
(ꢁC)
Conversiona
(%)
eeb
(%)
30
31
32
33
34
5
5
1
1
rt
97
71
58
97
89
94
95
63
94
88
ꢀ20
45
rt
0.1
rt
All reactions carried out at room temperature.
a The conversion of the cyanosilylether was determined based on a GC
integral area.
b The ee was determined by using a Chiralpak HPLC OD column, after
conversion to the corresponding acetate.
0
5
10
[Catalyst 1] x 103 M
15
Figure 2. Plot of catalyst 1 versus Kobs at rt, [benzaldehyde] = 399.3 ·
10ꢀ3 M and [TMSCN] = 1118.3 · 10ꢀ3 M.
2.1. Kinetic studies
Kinetic experiments were performed with benzaldehyde as
a representative substrate as a function of the concentra-
tions of catalyst 1, benzaldehyde and TMSCN. A represen-
tative kinetic profile as a function of catalyst concentration
is given in Figure 1. It was generally observed from the
kinetic profiles, that the formation of products increased
linearly up to 5 min, after which a significant increase is
not observed. Therefore, the initial rate constants kobs were
determined from the data in this time range.
2.3. Dependence of the rate on benzaldehyde concentration
Kinetic experiments were carried out at different initial con-
centrations of benzaldehyde ranging from (198.1 · 10ꢀ3 M–
1597.4 · 10ꢀ3 M) by keeping the concentration of other
reactants and physical conditions constant from which the
rate was calculated and the plot of rate constant (Kobs) ver-
sus the concentration of benzaldehyde (dlogKobs
/
dlog[benzaldehyde] ꢁ 1) also showed the first dependence
of the reaction on the substrate concentration (Fig. 3).
2.2. Dependence of the rate on catalyst concentration
2.4. Dependence of the rate on TMSCN concentration
The cyanation reaction of benzaldehyde as representative
substrate was studied at room temperature by conducting
the kinetic experiments at different concentration of the
The effect of concentration of the TMSCN over the range
of (557.7 · 10ꢀ3 M–4475.3 · 10ꢀ3 M) on the rate of the

N. H. Khan et al. / Tetrahedron: Asymmetry 17 (2006) 2659–2666
2663
Table 5. Concentration dependent kinetics data for the cyanation of
benzaldehyde at rt
600
500
400
300
200
100
0
Reactants
Catalyst
[Concentration] · 103 M
kobs · 103 M minꢀ1
1.5
3.0
6.1
0.95
1.89
3.47
7.44
12.2
Benzaldehyde
TMSCN
198.1
399.3
798.7
81
127
239
495
1597.4
557.7
1118.3
2237.6
4475.3
201
212
208
222
0
500
1000
1500
2000
[Benzaldehyde] x 103 M
O
V
OSiMe3
O
Figure 3. Plot of Benzaldehyde versus Kobs at rt, [catalyst 1] = 3.0 ·
10ꢀ3 M and [TMSCN] = 1118.3 · 10ꢀ3 M.
H
Ph
H
Ph
CN
complex 1
+
O-X
cyanation of benzaldehyde were studied, keeping the cata-
lyst [3.0 · 10ꢀ3 M] and benzaldehyde [399.3 · 10ꢀ3 M] con-
centration as constant, which indicated a zero order
dependence in terms of the concentrations of TMSCN.
The tendency of following zero order kinetics during
cyanosilylation in term of concentration of TMSCN has
also been observed earlier16 (Fig. 4).
O
V
O
V
O
O-X
δ-
CN
δ+
Me3Si
O
Ph
H
Si face
A
Ph
H
300
225
150
75
B
Me3Si CN
+
O-X; additives where X=N/P
O-X
Scheme 2. Probable mechanism for the catalytic cynosilylation.
The interesting feature of this novel polymeric V(V) salen
complex is its inherent tendency to be precipitated out in
nonpolar solvent such as hexane due to its higher molecu-
lar weight and lower solubility in reaction medium. After
one catalytic cycle, the polymeric catalyst was recovered
and re-used for the subsequent runs of cyanosilylation of
2-methyl benzaldehyde as representative substrate by add-
ing fresh reactants. From the data in Table 6 it is evident
0
0
1000
2000
3000
4000
5000
[TMSCN] x 103 M
Figure 4. Plot of TMSCN versus Kobs at rt, [catalyst 1] = 3.0 · 10ꢀ3 M
and [benzaldehyde] = 399.3 · 10ꢀ3 M.
The kinetic data for TMSCN dependence for cyanation of
benzaldehyde are given in Table 5.
Table 6. Enantioselective addition of trimethylsilyl cyanide to 2-methyl-
benzaldehyde catalyzed by a polymeric chiral V(V) complex
On the basis of the kinetic data, it is evident that the reac-
tion is first order with respect to complex and the substrate,
benzaldehyde and zero order with respect to TMSCN. A
probable mechanism is shown in Scheme 2 where, in pres-
ence of an acidic complex the activation of the substrate,
benzaldehyde, takes place to form an intermediate A in
the rate determination step. This intermediate reacted in
a fast step with polarized TMSCN guided by the chiral
environment of the catalyst 1 to produce trimethylsilylether
of the respective cyanohydrin.
Run
1
2
3
4
Time (h)
18
98
96
20
98
96
20
96
96
20
94
96
Conversiona (%)
eeb (%)
All reactions carried out at room temperature.
a The conversion of the cyanosilylether was determined based on a GC
integral area.
b The ee was determined by using a Chiralpak HPLC OD column, after
conversion to the corresponding acetate.

2664
N. H. Khan et al. / Tetrahedron: Asymmetry 17 (2006) 2659–2666
that catalyst 1 worked well for up to four cycles with a
small decrease in reactivity due to some physical loss dur-
ing the post work up process with retained enantioselectiv-
ity of trimethylsilylether of cyanohydrin.
128.2, 132.0, 135.6, 160.6, 168.3. Anal. Calcd for
C31H43N2O8SVÅ+: C, 56.88, H, 6.57, N, 4.28. Found: C,
56. 92, H, 6.58, N, 4.30.
4.2. Synthesis of polymeric vanadium(V) complex 2
3. Conclusions
Ligand 20 (0.160 g, 0 .45 mmol) was dissolved in the mixed
solvent ethanol/CH2Cl2 (3:2, 10 ml) to which an aqueous
solution of vanadyl sulfate hydrate (0.115 g, 0.45 mmol in
2 ml water) was added dropwise under an inert atmosphere
at rt. The resulting solution was refluxed for 4 h and then
cooled to room temperature with an extended stirring for
12 h while opening the side arm of the reaction flask. The
solvent was completely evaporated and the residue dis-
solved in CH2Cl2 (10 ml), washed with water (3 · 5 ml)
and finally with brine. The organic layer was dried over
anhydrous Na2SO4, filtered and evaporated to give poly-
meric V(V) complex 2. Yield, 0.180 g, 69.5%; mp: 198–
Chiral recyclable polymeric vanadium(V) salen complexes
1 and 2 with 12 repeating salen units were synthesized
and used for the asymmetric addition of trimethylsilyl cya-
nide to various aldehydes at room temperature. The cata-
lyst 1 performed very well with 2-methyl benzaldehyde by
giving an excellent yield of trimethylsilylether of cyano-
hydrins up to (98%) with high chiral induction (96%) in
18 h with the added advantage of four times recyclability.
4. Experimental
ꢀ
205 ꢁC; IR: (KBr): m ¼ 3398, 2924, 2853, 1617, 1561,
1466, 1381, 1312, 1262, 1163, 1031, 973, 934, 839, 746,
27
709, 626, 568, 462 cmꢀ1; ½aꢂD ¼ ꢀ591 (c 0.05, CH2Cl2);
Vanadyl sulfate hydrate (Loba Chemie, India), benzalde-
hyde, 4-methoxybenzaldehyde, 3-methoxybenzaldehyde, 2-
methoxybenzaldehyde, 4-chlorobenzaldehyde, 4-bromo-
benzaldehyde, 4-fluorobenzaldehyde, n-butylaldehyde, iso-
butylaldehyde, 3-methylbutarldehyde, 4-phenyl pyridine-
N-oxide, triphenylphosphine-oxide (Aldrich), 2-methyl-
benzaldehyde, 4-methylbenzaldehyde, triphenylphosphine
(Merck Chemicals), trimethysilylcyanide (Acros), pyridine-
N-oxide (Fluka), triethylamine (S. D. Fine-Chem, India),
pyridine (Qualigens Fine Chem, India) were purchased
and used as received. Polymeric chiral salen ligand 10 and
20 was synthesized by a previously reported method.13c
1
kmax (e): 248 (31,512), 358 (10,375), 650 (1138); H NMR
(200 MHz, CDCl3): d = 0.87 (t, J = 7.3, 3H), 1.25 (s,
6H), 1.60–1.85 (m, 8H), 3.30 (q, J = 7.1, 2H), 3.42 (m,
2H), 3.77 (br s, 2H), 4.26 (m, 2H), 6.76–7.24 (m, 4H),
8.22 (br s, 2H) ppm. 13C NMR (50 MHz, CDCl3):
d = 13.7, 24.8, 34.1, 28.9, 30.0, 40.8, 73.6, 118.8, 129.1,
132.3, 133.8, 135.5, 158.2, 165.1. Anal. Calcd for
C25H31N2O8SVÅ+: C, 52.63, H, 5.48, N, 4.91. Found: C,
52.60, H, 5.51, N, 4.89.
4.3. Procedure for vanadium(V) polymeric salen-catalyzed
asymmetric addition of trimethylsilyl cyanide to aldehydes
All the solvents were dried using standard procedures,17
distilled and stored under nitrogen. The synthesis and char-
acterization of poly-[(R,R)-N,N0-bis-{3-(1,1-dimethyl-
ethyl)-5-methylene salicylidine} cyclohexane-1,2-diamine]
10 and its precursors was carried out as described.13c
V(V) salen catalyst 1 (0.006 g, 0.0125 mmol) was dissolved
in dry CH2Cl2 (3 ml) and the solution stirred at room tem-
perature under a nitrogen atmosphere. To this solution,
benzaldehyde (0.12 ml, 1.25 mmol) was added, followed
by the dropwise addition of TMSCN (0.33 ml, 2.50 mmol).
After the reaction was completed (as shown by TLC) the
mixture was concentrated and the compound purified by
flash column chromatography on silica gel (eluted with
hexane/ethylacetate = 95:5). The corresponding trimethyl-
silylether derivative of cyanohydrin was dissolved in
MeOH (3 ml) and then 1 N HCl (3 ml) was dropped to
the mixture. The mixture was stirred vigorously at room
temperature for 4 h. The aqueous solution was then ex-
tracted with CH2Cl2, and the combined organic layer dried
with anhydrous sodium sulfate. After evaporating the sol-
vent, the corresponding cyanohydrin was obtained. The ee
was determined by using Chiralpak HPLC OD and AD
column, after conversion to the corresponding acetate.
4.1. Synthesis of polymeric vanadium(V) complex 1
Ligand 10 (0.799 g, 1.79 mmol) was dissolved in the mixed
solvent ethanol/CH2Cl2 (3:2, 15 ml) to which an aqueous
solution of vanadyl sulfate hydrate (0.453 g, 1.79 mmol in
2 ml water) was added dropwise under an inert atmosphere
at rt. The resulting solution was refluxed for 4 h and then
cooled to room temperature with extended stirring for
12 h while opening the side arm of the reaction flask. The
solvent was completely evaporated and the residue dis-
solved in CH2Cl2 (10 ml), washed with water (3 · 5 ml)
and finally with brine. The organic layer was dried over
anhydrous Na2SO4, filtered and evaporated to give the
polymeric V(V) complex. Yield, 0.680 g, 73.9%; mp: 204–
ꢀ
210 ꢁC; IR: (KBr): m ¼ 3473, 2957, 2867, 1612, 1536,
1466, 1387, 1345, 1315, 216, 1177, 1030, 987, 887, 821,
4.3.1. (S)-2-O-Acetyl-2-phenyl acetonitrile (derived from
5a). 1H NMR (200 MHz, CDCl3): d = 2.11 (s, 3H), 6.38
(s, 1H), 7.40–7.52 (m, 5H); 13C NMR (50 MHz, CDCl3):
27
789, 748, 714, 662, 567 cmꢀ1; ½aꢂD ¼ ꢀ204:6 (c 0.05,
CH2Cl2); kmax (e): 236 (45,090), 404 (11,680), 630 (2620);
1H NMR (200 MHz, CDCl3): d = 0.85 (t, J = 7.2, 3H),
1.30 (s, 18H), 1.51–1.88 (m, 8H), 3.31 (q, J = 7.2, 2H),
3.39 (br s, 2H), 3.81 (m, 2H), 4.26 (m, 2H), 6.89–7.24 (m,
4H), 8.26 (br s, 2H) ppm. 13C NMR (50 MHz, CDCl3):
d = 13.4, 23.4, 26.2, 28.9, 30.0, 40.8, 63.6, 121.3, 126.4,
d = 20.8, 63.3, 116.7, 128.3, 129.7, 130.8, 132.3, 169.4;
27
½aꢂD ¼ ꢀ31:5 (c 1, CH2Cl2); TOF-MS (ESI+): m/z 160.2
(M+H)+; HPLC analysis: Chiralpak OD column,
hexane/isopropanol = 99:1, Flow rate 0.8 ml/min, tR1
19.61 min (minor), tR2 = 21.88 min (major).
=

N. H. Khan et al. / Tetrahedron: Asymmetry 17 (2006) 2659–2666
2665
4.3.2. (S)-2-O-Acetyl-2-(4-flourophenyl) acetonitrile (derived
from 5b). 1H NMR (200 MHz, CDCl3): d = 2.16 (s, 3H),
6.39 (s, 1H), 7.09–7.18 (m, 2H), 7.49–7.55 (m, 2H); 13C
MS (ESI+): m/z 153.10 (M+H)+; HPLC analysis: Chiralpak
OD column, hexane/isopropanol = 99:1, Flow rate 0.8 ml/
min, tR1 = 31.33 min (minor), tR2 = 37.01 min (major).
NMR (50 MHz, CDCl3): d = 21.0, 68.8, 116.7, 117.2,
27
129.4, 130.6, 160.9, 169.5; ½aꢂD ¼ ꢀ20:2 (c 1, CH2Cl2);
4.4. Recycling of the catalyst
TOF-MS (ESI+): m/z 195.19 (M+H); HPLC analysis:
Chiralpak AD column, hexane/isopropanol = 99:1, Flow
rate 0.8 ml/min, tR1 = 19.68 min (minor), tR2 = 21.44 min
(major).
At the end of the catalytic run (checked on TLC), the sol-
vent was completely removed under a reduced pressure.
The residue was extracted with hexane to remove the reac-
tants. The remaining solid was further washed with hexane
(10 ml), dried under a reduced pressure at 50 ꢁC for 1–2 h
and then used as the recovered catalyst for recycle experi-
ments of the cyanation of 2-methyl benzaldehyde.
4.3.3. (S)-2-O-Acetyl-2-(2-methylphenyl) acetonitrile (derived
from 5c). 1H NMR (200 MHz, CDCl3): d = 2.17 (s, 3H),
2.43 (s, 3H), 6.51 (s, 1H), 7.23–7.58 (m, 4H); 13C NMR
(50 MHz, CDCl3): d = 19.6, 21.0, 61.7, 113.2, 127.5, 129.2,
27
130.8, 131.2, 132.0, 138.2, 169.0; ½aꢂD ¼ ꢀ26:2 (c 1, CH2Cl2);
4.5. Cyanation reaction for kinetic measurement
TOF-MS (ESI+): m/z 191.03 (M+H)+; HPLC analysis:
Chiralpak AD column, hexane/isopropanol = 99:1, Flow
rate 0.8 ml/min, tR1 = 17.48 min (major), tR2 = 22.13 min
(minor).
Catalyst 1 (1.5 · 10ꢀ3 M–12.2 · 10ꢀ3 M) was dissolved in
3 ml of CH2Cl2 and then benzaldehyde (198.1 · 10ꢀ3 M–
1597.4 · 10ꢀ3 M) added. The stirred solution was then
reacted with TMSCN (198.1 · 10ꢀ3 M–1597.4 · 10ꢀ3 M)
at rt with constant stirring. To determine the rates of cya-
nation reaction, aliquots at an interval of 2 min were drawn
from the reaction mixture, quenched with anhydrous
Na2SO4 and analyzed on a GC.
4.3.4. (S)-2-O-Acetyl-2-(2-methoxyphenyl) acetonitrile (derived
from 5d). 1H NMR (200 MHz, CDCl3): d = 2.13 (s, 3H),
3.85 (s, 3H), 6.68 (s, 1H), 6.91–7.57 (m, 4H); 13C NMR
(50 MHz, CDCl3): d = 20.8, 56.2, 68.6, 111.7, 116.8, 121.2,
27
129.2, 132.3, 157.3, 169.3; ½aꢂD ¼ ꢀ25:6 (c 1, CH2Cl2); TOF-
MS (ESI+): m/z 207.14 (M+H)+; HPLC analysis: Chiralpak
OD column, hexane/isopropanol = 99:1, Flow rate 0.8 ml/
min, tR1 = 19.90 min (major), tR2 = 22.41 min (minor).
Acknowledgements
N. H. Khan is thankful to DST and CSIR Network project
on Catalysis for financial assistance and also thankful to
Dr. P. K. Ghosh, the Director, of the Institute for provid-
ing instrumentation facility.
4.3.5. (S)-2-O-Acetyl-2-(4-methoxyphenyl) acetonitrile (derived
from 5e). 1H NMR (200 MHz, CDCl3): d = 2.14 (s, 3H),
3.83 (s, 3H), 6.35 (s, 1H), 6.94 (d, J = 8.75, 2H), 7.44 (d,
J = 8.90, 2H); 13C NMR (50 MHz, CDCl3): d = 21.5, 56.1,
27
63.3, 115.1, 115.3, 130.3, 132.6, 161.9, 169.7; ½aꢂD ¼ ꢀ24:4 (c
1, CH2Cl2); TOF-MS (ESI+): m/z 207.18 (M+H)+; HPLC
analysis: Chiralpak OD column, hexane/isopropanol = 99:1,
Flow rate 0.8 ml/min: tR1 = 28.41 min (minor), tR2 = 32.71
min (major).
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