Asymmetric cyanosilylation of ketones catalyzed by recyclable polymer-supported copper(II) salen complexes

Article abstract of DOI:10.1016/j.tetasy.2010.07.029

Various ketones have undergone asymmetric trimethylsilylcyanation at room temperature with (CH₃)₃SiCN (TMSCN) in the presence of a chiral-supported Cu(salen) complex and Ph₃PO as the catalyst. Aromatic, aliphatic, and hete

Full text of DOI:10.1016/j.tetasy.2010.07.029

Tetrahedron: Asymmetry 21 (2010) 2265–2270
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric cyanosilylation of ketones catalyzed by recyclable
polymer-supported copper(II) salen complexes
⇑
Gurusamy Rajagopal , Shanmugam Selvaraj, Karuthamohamed Dhahagani
Department of Chemistry, Government Arts College, Melur 625 106, Madurai, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2010
Accepted 22 July 2010
Various ketones have undergone asymmetric trimethylsilylcyanation at room temperature with
(CH3)3SiCN (TMSCN) in the presence of a chiral-supported Cu(salen) complex and Ph3PO as the catalyst.
Aromatic, aliphatic, and heterocyclic ketones have been converted into the corresponding cyanohydrin
trimethylsilyl ethers in 83ꢀ96% yields with 52ꢀ84% ee. Several factors concerning the reactivity and
enantioselectivity have been discussed. A double activation where Cu(salen) plays the role of Lewis acid
and Ph3PO acts as a Lewis base is reported. Poly(ethylene glycol) monomethyl ether (MeO-PEG) has been
used as a soluble support while JandaJel (JJ) and Merrifield (MF) resins served as insoluble supports. Each
polymer is linked to the salen catalyst through a glutarate spacer. The soluble catalysts were recovered by
precipitation with a suitable solvent while the insoluble catalysts were simply filtered from the reaction
mixture. The JandaJel-attached Cu(salen) catalyst could be used for five cycles with the retention of effi-
ciency and the Merrifield-bound Cu(salen) catalyst was found to loose activity with each use.
Ó 2010 Published by Elsevier Ltd.
1. Introduction
their soluble counterparts.35 Some of these advantages are their
robustness, the increased air and moisture stability, ease of separa-
Chiral cyanohydrins are useful intermediates because their two
functional groups can be easily transformed into various homochi-
tion, and the potential recyclability, when used as heterogeneous
catalysts. The supports on which the metal complexes are immobi-
lized are inorganic or organic polymers. Typical inorganic supports
are oxides bearing surface hydroxyl groups, acting as36,37 (or being
precursors of) ligands for suitable metal-containing moieties.38–41
Using organic co-polymers as supports for transition metal com-
plexes allows us to conjugate the controllable flexibility of the ma-
trix with the possibility of fine tuning the physical properties
(polarity, swellability, morphology, etc.) of the material with a suit-
able combination of co-monomers and crosslinkers.
Chiral Cu complex catalysts for asymmetric reactions such
as aziridination,42 Diels–Alder reaction,43 cyclopropanation,44 and
carbenoid insertion of diazoacetates into the Si–H bond of si-
lanes45,46 have been studied and recently the complexes of Cu(II)
with chiral bidentate ligands of bisoxazolines for the asymmetric
Henry reaction have shown promising results.47 Although several
salen-based metal complexes have already been used for the
cyanosilylation of ketones, no work has been reported for copper
salen complexes.
ral ones, including
a
a
-hydroxy acids,1,2
a
-hydroxy aldehydes,3
-amino acid deriv-
-hydroxy ketones,3 b-hydroxy amines,2,3 and
a
atives.4 A number of catalysts for the asymmetric addition of
cyanide to carbonyl compounds5 are known, including synthetic
peptides and chiral transition metal complexes. Significant ad-
vances have been made in developing efficient catalysts for the
synthesis of chiral cyanohydrins6–9 using Snapper and Hoveyda’s
peptide-Al catalysts,10 Jacobsen’s thiourea catalysts,11 Feng’s dou-
ble-activation,12–20 an amino acid salt,21 and Deng’s chiral Lewis
base.22,23 In search for new methodologies, Belokon and North
have reported a bimetallic Ti(IV) salen complex24 while Shibasaki
et al. have used bifunctional catalysts with Ti(IV),25,26 Gd(OiPr)3,27
28
and Sm(OiPr)3 for the enantioselective cyanosilylation of ke-
tones. Kim et al. have reported Al and Mn monomeric salen com-
plexes for the cyanosilylation of ketones with triphenylphosphine
oxide as an additive at room temperature.29,30 Recently Khan
et al. reported31–33,1b,34 the use of polymeric metal vanadium and
manganese complexes as enantioselective catalysts for the cyano-
silylation of various carbonyl compounds.
2. Results and discussion
Supported metal complexes have continuouslyattracted increas-
ing interest because of the advantages that they offer with respect to
Acetophenone was chosen as a test substrate to determine the
best conditions for the cyanosilylation. The reactivityand enantiose-
lectivity of the cyanation reaction are strongly dependent upon the
nature of the solvent used.48 Therefore, catalytic enantioselective
⇑
Corresponding author. Tel.: +91 452 2416002; fax: +91 452 2415467.
E-mail address: rajagopal@yahoo.com (G. Rajagopal).
0957-4166/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2010.07.029

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G. Rajagopal et al. / Tetrahedron: Asymmetry 21 (2010) 2265–2270
cyanation reactions were conducted in different solvents, such as
1,2-dichloroethane, CH3CN, toluene, and THF with catalyst 6 under
identical reactionconditions. From Table 1, it canbe seen that CH2Cl2
was the most appropriate solvent (entries 1–6). Solvent CH3CN was
also a suitable solvent for this system with a slightly longer reaction
time (entry 7). The use of toluene and THF afforded a low yield of ni-
triles with longer reaction times (entries 8 and 9).
H3C
O Polymer
C
Si
N
Ar
O
Ph3PO
O
O
Cu
N
The catalyst loading and reaction temperature were also found
to be an essential factor for the enantioselective cyanation reac-
tion. To determine the effect of the catalytic loading in improving
the yield, we performed the reaction with 1–15 mol % of catalyst
6 in CH2Cl2. For 10–15 mol % catalytic loading, the reactions took
place with less reaction time and with high yields (entries 1 and
2). Further reduction in the amount of catalyst from 10 to
5 mol % gave 94% yield in 11 h (entry 3). We found that the reac-
tion proceeds even with 3 mol % of catalyst providing 94% yield
of nitriles within 10 h (entry 4). For 1–2 mol % of catalytic loading,
longer reaction time was required (entries 5 and 6). Lowering the
temperature from room temperature to ꢀ40 °C greatly increased
the reaction time with a slight increase in ee (entries 10–14). Nei-
ther the copper complex nor the Ph3PO induced any enantioselec-
tivity. The reaction appears to be catalyzed by a double activation
process that occurs through the catalysis of both chiral Lewis acid
and achiral Lewis base. The Cu(salen) complex functions as a weak
Lewis acid to activate the ketone oxygen and Ph3PO acts as a strong
Lewis base for the activation of TMSCN (Fig. 1). Based on above
observations, the reaction conditions of entry 4 were chosen for
the present asymmetric cyanosilylation of ketones at room tem-
perature because of the shorter reaction times and good ee.
To determine the efficiency of supported copper salen com-
plexes, we carried out the cyanosilylation of acetophenone in the
presence of Ph3PO as an additive under identical reaction condi-
tions and the results are summarized in Table 2. The soluble PEG
and insoluble Merrifield resin-based copper complexes have less
activity compared to an insoluble JandaJel-based copper complex
(Fig. 2). This may be due to the fact that the JandaJels contain flex-
ible tetrahydrofuran-derived crosslinkers and exhibit superior
swelling in common organic solvents. This increase in swelling
capacity implies a better contact between the reagents and sub-
strates linked to the resin. Furthermore, the increased swelling of
JandaJel would result in a better solvation of the reaction complex
N
Figure 1. Transition state involved in the enantioselective cyanosilylation of
ketones by double-activation catalysis.
Table 2
Cyanosilylation of acetophenone with various supported Cu(salen) complexes
Catalyst
Mol %
Time (h)
Yield (%)
ee (%)
PEG-Cu(salen)
JJ-Cu(salen)
Merrifield-Cu(salen)
3
3
3
22
10
20
85
94
86
67
84
60
N
O
N
Cu
O
O
O
O
O
= JandaJel(JJ) or Merrifiled(MF)
Figure 2. Structure of polymer supported copper complexes.
and would therefore minimize any loss of enantioselectivity result-
ing from heterogenization of the catalyst.
Table 1
Cyanosilylation of acetophenone under various reaction conditionsa
OTMS
O
Catalyst 6, solvent
(CH3)3SiCN, Ph3PO
CH3
CN
Entry
Catalyst loading (mol %)
Additive
Solvent
Temp (°C)
Time (h)
Yieldb (%)
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
10
5
3
2
1
3
3
3
3
3
3
3
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
Ph3PO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
Toluene
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
rt
rt
rt
rt
rt
rt
rt
rt
rt
8
9
96
94
94
94
95
90
90
70
80
95
94
93
93
94
78
80
83
84
77
70
65
51
40
85
86
86
86
84
11
10
15
20
15
40
40
25
36
45
60
72
0
ꢀ10
ꢀ20
ꢀ30
ꢀ40
3
a
Reagent and condition: 1.0 mmol of acetophenone; 1.0 mmol of TMSCN.
Isolated yield.
b

G. Rajagopal et al. / Tetrahedron: Asymmetry 21 (2010) 2265–2270
2267
Table 3
Addition of TMSCN to ketones catalyzed by supported JJ-Cu(salen) complex
Table 4
Studies on the recyclability of the polymer-bound catalysts at rt
Entry
Substrate
Time (h)
Yielda (%)
ee (%)
Catalyst
Run
Time (h)
Yielda (%)
ee (%)
PEG-Cu(salen)
1
2
3
4
1
2
3
4
5
1
2
3
4
5
22
23
25
30
15
15
16
18
18
20
24
30
35
40
90
88
85
70
90
88
85
80
75
80
70
68
65
50
65
62
60
50
80
78
75
70
65
60
51
42
41
40
O
1
10
94
84
CH3
O
JJ-Cu(salen)
CH3
2
3
4
5
12
16
9
90
91
90
89
67
60
70
71
MF-Cu(salen)
Cl
O
CH3
O
a
Cl
Isolated yields.
CH3
excellent isolated yield (83–94%) and ee (52–84%) for the products
were achieved in 9–18 h (entries 1–13).
F
O
Electronic and steric factors for different substituents on the
aromatic ring have little effect on the yield and ee. o-Chlorophen-
ylmethyl ketone appeared to be more susceptible to the steric ef-
fect compared to p-chloromethyl ketone resulting in a much
longer reaction time and high %ee (Table 3, entries 2 and3). p-Flu-
oro and bromo derivatives gave good enantioselectivity (Table 3,
entries 4 and 5). Electron-withdrawing substituents (Table 3, en-
tries 6–8) had a favorable influence on the cyanosilylation in terms
of reaction yield and gave moderate ee. Cyanosilylation of isobutyl-
phenone (entry 9) and naphthyl ketone gave good ee (Table 3, en-
tries 9 and 10). Moderate conversions (85–90%) and ee’s (52–63%)
were obtained when the cyanosilylation reaction was carried out
with 4-phenyl-3-buten-2-one (Table 3, entry 11) and aliphatic ke-
tones (Table 3, entries 12 and 13).
To access the recyclability of the polymer-bound Cu(salen) cat-
alyst, the catalytic runs were carried out for the cyanosilylation of
4-methoxy acetophenone which was taken as a representative
substrate by adding fresh reactants. After one catalytic cycle, by
adding hexane-cold ether mixture the PEG-bounded Cu(salen) cat-
alyst was precipitated out due to its high molecular weight and
lower solubility in the reaction medium. From the data in Table 4
it is evident that the PEG-based catalyst worked well for up to
three cycles with a small decrease in reactivity and enantioselec-
tivity. With limited success in recycling the soluble polymer-bound
catalysts, we hoped that the insoluble supports would provide a
more robust environment for the salen framework. Recovery of
both the JandaJel and the Merrifield resin-bound catalysts was eas-
ily accomplished by filtration of the reaction mixture. The JandaJel-
derived catalyst could be used five times without a significant drop
in selectivity. The Merrifield-bound catalyst lost activity with each
use and was essentially ineffective by the third recycle. It is not en-
tirely clear why the JandaJel-bound catalyst was slightly more ro-
bust than Merrifield-bound catalyst but this may be a consequence
of microenvironment effects caused by the resin.
CH3
9
Br
O
CH3
6
7
8
18
14
15
90
92
90
61
65
82
O2N
O
CH3
O
CH3
MeO
O
9
10
11
12
10
18
88
93
85
63
75
52
O
O
CH3
O
12
13
18
15
83
90
63
61
O
O
3. Conclusions
a
Isolated yield.
We have described the evaluation of soluble and insoluble poly-
mer-supported Cu(salen) complexes for use in asymmetric cyano-
silylation reactions. A highly efficient double activation catalysis by
supported Cu(salen)/Ph3PO has been developed for the enantiose-
lective cyanosilylation of various ketones. The cyanosilylation
takes place under comparatively mild conditions in terms of tem-
perature and reaction time. The JandaJel polymeric catalyst per-
formed well in terms of reactivity and enantioselectivity with the
Under the optimized reaction conditions as described earlier
(Table 1, entry 3), we extended this protocol of cyanosilylation
reaction to a variety of aromatic and aliphatic ketones using com-
plex 2 as catalyst. The data in Table 3 are indicative of the applica-
bility of this protocol over a range of substrates where good to

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G. Rajagopal et al. / Tetrahedron: Asymmetry 21 (2010) 2265–2270
added advantage of recyclability for five times. Further investiga-
tions to clarify the reaction mechanism and efforts to extend the
use of the present catalytic system to other organic transforma-
tions are currently in progress.
and the urea by-product was removed by filtering through a pad
of Celite. The filtrate was then concentrated to 5 mL and then
added dropwise into 200 mL of cold stirring diethyl ether. The yel-
low solid precipitate was filtered off, and dried under vacuum
(2.25 g, 77% yield): IR (KBr pellet) 3330, 2890 (b), 1756, 1737,
1630, 1461, 1349 cmꢀ1 1H NMR (300 MHz, CDCl3) d = 8.27 (s
;
4. Experimental
4.1. General
(br), 1H, –N@C–H), 8.20 (s (br), 1H), 7.31 (d, 1H), 6.95 (s (br),
1H), 6.88 (d, 1H), 6.73 (s (br), 1H,), 4.20 (m, 2H,), 3.34 (s, 3H),
2.54 (t, J = 7.3 Hz, 2H,), 2.42 (t, J = 7.3 Hz, 2H), 2.10–1.50 (m,
10H), 1.36 (s, 9H), 1.34 (s, 9H), 1.19 (s, 9H).
All ketones and polymers were purchased from Sigma–Aldrich.
1H and 13C NMR were taken utilizing a Varian Jemini 2000
(300 MHz) or a Varian Unity Inova 400 (400 MHz) or a Bruker
Avance 400 NMR spectrometer. The ee% was determined by chiral
HPLC column (DAICEL CHIRALCEL OJ-H, DAICEL CHIRALCEL OD-H
and DAICEL CHIRALCEL OB-H). Analytical high performance liquid
chromatography (HPLC) was performed on Gilson 305 series HPLC
using the indicated chiral column. All data was in accordance with
literature values. Absolute configurations were determined by the
specific rotation.49
4.1.4. General procedure for the preparation of insoluble (salen)
ligands: JJ-SALEN 4 and MF-SALEN 5
At first, DCC (2.1 equiv) was added to a solution of the insoluble
resin (JandaJel or Merrifield) (1 equiv), salen glutarate (mono-es-
ter) (1 equiv), and DMAP (0.5 equiv) in CH2Cl2 (15 mL/g of resin).
The reaction mixture was vigorously stirred at room temperature
for 24 h and filtered through a medium frit. The collected solid
was washed sequentially with water, methanol, CH2Cl2, ether,
and hexanes to give yellow beads. IR(KBr): JJ-SALEN: 3410, 1633,
1135, 1049, 988 cmꢀ1. MF-SALEN: 3390, 1607, 1389 cmꢀ1
4.1.1. Synthesis of unsymmetrical salen ligand 1
4.1.1.1. 2-tert-Butyl-6-({2-[(3,5,di-tert-butyl-2-hydroxy-benzyli-
dene)-amino]-cyclohexylimino}-methyl)-benzene-1,4-diol.
4.1.5. General Procedure for the synthesis of copper complexes:
JJ-SALEN-Cu 6 and MF-SALEN-Cu 7
To
a solution of 3,5-di-tert-butylsalicylaldehyde (1.72 g, 7.53
mmol) and 3-tert-butyl-2,5-dihydroxybenzaldehyde (0.48 g,
2.45 mmol) in CH2Cl2 (15 mL) was added (1R,2R)-diaminocyclo-
hexane (0.56 g, 4.89 mmol). The reaction mixture was allowed to
stir at 25 °C for 15 h, after which it was concentrated in vacuo to
give a yellow foam solid. This crude product (mixture of salen li-
gands) was purified by column chromatography on silica gel (gra-
dient elution: 1:20–1:1, diethyl ether/hexanes) to give 1 (0.68 g,
55% yield) as a yellow foam. IR (KBr pellet): 3350 (br), 2933,
A solution of polymer-supported 2-tert-butyl-6-({2-[(3,5-di-
tert-butyl-2-hydroxy-benzylidene)-amino]-cyclohexylimino}-
methyl)-benzene-1,4-diol (1 equiv) as prepared earlier was dis-
solved in mixed solvents of ethanol/CH2Cl2 (10:2, 15 ml) to which
a methanolic solution of copper acetate tetrahydrate (1.25 equiv)
was added dropwise under an inert atmosphere at room tempera-
ture. The resulting solution was refluxed for 24 h and then cooled
to room temperature and was stirred for a further 12 h. The solu-
tion was filtered through a medium frit and the collected solid
was washed with cold water, methanol, ether, and hexanes to give
a dark brown powder. IR(KBr): JJ-SALEN-Cu: 1559, 1530, 1350,
1287, 484 cmꢀ1; MF-SALEN-Cu : 3415, 1595, 1338, 473 cmꢀ1
2860, 1632, 1595 cmꢀ1 1H NMR (300 MHz, CDCl3) d = 8.20 (s,
;
1H), 8.10 (s, 1H), 6.85 (d, J = 2.4 Hz, 1H), 6.79 (d, J = 2.4 Hz, 1H),
6.44 (d, J = 3.2 Hz, 1H), 6.41 (d, J = 3.2 Hz, 1H), 3.25–3.19 (m, 2H),
2.0–1.95 (m, 8H), 1.31 (s, 18H), 1.19 (s, 9H). Anal. Calcd for
C32H46N2O3: C, 75.85; H, 9.15; N, 5.53. Found: C, 75.50; H, 9.45;
N, 5.30.
4.2. Procedure for supported Cu-salen-catalyzed asymmetric
addition of trimethylsilyl cyanide to ketones
4.1.2. Synthesis salen glutarate (mono-ester) 2
Into a 50 mL two-necked round-bottomed flask, fitted with a
nitrogen inlet, were placed a stirrer bar, glutaric anhydride (164
mg, 1.44 mmol), the unsymmetrical salen 1 (608 mg, 1.20 mmol),
DMAP (176 mg, 1.44 mmol), and anhydrous CH2Cl2 (6 mL). The mix-
ture was left to stir, under a nitrogen atmosphere, for 15 h at 25 °C
after which it was concentrated in vacuo. The crude yellow oil was
purified by flash column chromatography on silica gel (1:19, meth-
anol/CH2Cl2). The title compound was obtained as a foam yellow so-
lid (446 mg, 60% yield). IR (KBr pellet) 2940 (br), 1758, 1712, 1630,
1439 cmꢀ1; 1H NMR (300 MHz, CDCl3) d = 8.30 (s, 1H), 8.23 (s, 1H),
7.31 (d, J = 2.5 Hz, 1H), 7.10 (d, J = 2.5 Hz, 1H), 6.77–6.98 (m, 2H)
6.77–6.98 (m, 5H) 3.34 (m, 2H), 2.60 (t, J = 7.4 Hz, 2H), 2.50 (t,
J = 7.2 Hz, 2H), 2.05 (q, J = 7.4 Hz, 2H), 1.98–1.5 (m, 8H), 1.42 (s,
9H), 1.28 (s, 18H).; 13C NMR (100 MHz, CDCl3) d = 178.7, 171.8,
165.8, 158.2, 157.9, 141.3, 139.9, 138.8, 136.3, 126.9, 125.9, 122.7,
121.3, 118.2, 117.7, 72.4, 72.2, 53.4, 34.9, 33.9, 33.2, 32.9, 31.6,
31.4, 29.4, 29.1, 24.2, 22.7, 22.6, 19.7, 14.1. Anal. Calcd for
Supported Cu salen catalyst (3 mmol) was dissolved in dry
CH2Cl2 (3 ml) and the solution was stirred at room temperature
under a nitrogen atmosphere. To this solution, ketone (1 mmol)
was added, followed by the dropwise addition of TMSCN (1 equiv).
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/ethylace-
tate = 95:5). The silylethers thus obtained were identified by 1H
and 13C NMR data, which are consistent with the structure.
4.2.1. 2-Trimethylsilyloxy-2-phenylpropanenitrile (Table 3,
entry 1)
1H NMR (CDCl3) d 0.17 (s, 9H), 1.85 (s, 3H), 7.36–7.558 (m, 5H,
aromatic H); 13C NMR (CDCl3) d 0.89, 33.4, 71.4, 121.4, 124.4,
128.6, 141.8; ½a D24
¼ ꢀ15:1 (c 1.18, CHCl3) 84% ee; HRMS(MC) calcd
ꢁ
for C12H17NOSi: 219.1079; found: 219.1082 HPLC (DAICEL CHIRAL-
CEL OB-H, iPrOH/hexane = 1/99, flow = 0.25 mL/min) 13.7 and
14.6 min.
C37H52N2O6: C, 71.58; H, 8.44; N, 4.51. Found: C, 71.81; H, 8.55; N,
4.33.
4.2.2. 2-Trimethylsilyloxy-2-(40-chlorophenyl)propanenitrile
(Table 3, entry 2)
4.1.3. Synthesis of PEG-supported salen ligand 3
1H NMR (CDCl3) d 0.21 (s, 9H), 1.84 (s, 3H), 7.38 (m, 2H), 7.49
To a solution of PEG5000 (2.60 g, 0.52 mmol), the unsymmetrical
salen glutarate (mono-ester) (0.65 g, 1.04 mmol), and DMAP
(0.03 g, 0.26 mmol) in CH2Cl2 (20 mL) was added DCC (0.23 g,
1.10 mmol). The reaction mixture was stirred at 25 °C for 24 h
(m,2H); 13C NMR (CDCl3) d 1.0, 33.4, 71.0, 121.1, 126.0, 128.7,
134.5, 140.6; ½a D24
¼ ꢀ16:4 (c 1.78, CHCl3) 67% ee; HRMS (MC)
ꢁ
calcd for C12H16ClNOSi: 253.0690; found: 253.0687 HPLC (DAICEL

G. Rajagopal et al. / Tetrahedron: Asymmetry 21 (2010) 2265–2270
2269
CHIRALCEL OJ-H, iPrOH/hexane = 1/99, flow = 0.25 mL/min) 19.8
4.2.10. 2-(1-Naphthalen-1-yl)-2-
and 20.6 min.
(trimethylsilyloxy)propanenitrile (Table 3, entry 10)
1H NMR (CDCl3, 200 MHz): d = 0.23 (s, 9H), 2.2 (s, 3H), 7.41–
7.65 (m, 3H), 7.85–7.95 (m, 3H), 8.60 (d, 2.4 Hz ,1H); 13C NMR
(CDCl3, 100 MHz): d = 1.0, 31.6, 73.1, 121.7, 123.5, 124.5, 125.4,
125.7, 125.9, 129.07, 129.32, 130.10, 134.5, 135.8.
4.2.3. 2-Trimethylsilyloxy-2-(20-chlorophenyl)propanenitrile
(Table 3, entry 3)
1H NMR (CDCl3) d 0.28 (s, 9H), 1.99 (s, 3H), 7.25–7.40 (m, 3H
aromatic H), 7.68–7.71 (m, 1H aromatic H); 13C NMR (CDCl3) d
1.0, 33.4, 70.9, 121.0, 122.7, 124.8, 128.8, 129.9, 134.6, 144.0;
4.2.11. 2-Trimethylsilyloxy-2-methyl-4-phenyl-3-butenenitrile
(Table 3, entry 11)
½
a 2D4
ꢁ
¼ þ11:4 (c 1.20, CHCl3) 60% ee; HRMS(MC) calcd for
C12H16ClNOSi: 253.0691; found: 253.0687 HPLC (DAICEL CHIRAL-
1H NMR (CDCl3) d 0.24 (s, 9H), 1.74 (s, 3H), 6.16 (d, 1H), 6.84 (d,
CEL OD-H, iPrOH/hexane = 1/99, flow = 0.25 mL/min) 23.2 and
24.0 min.
1H) 7.25–7.40 (m, 5H); 13C NMR (CDCl3) d 1.4, 30.8, 69.9, 120.6,
126.9, 128.6, 128.7, 129.5, 130.9, 135.1 ½a D24
¼ ꢀ16:9 (c 2.1, CHCl3)
ꢁ
60% ee; HRMS(MC) calcd for
C14H19NOSi: 245.1236; found:
4.2.4. 2-Trimethylsilyloxy-2-(40-fluorophenyl)propanenitrile
(Table 3, entry 4)
245.1233 HPLC (DAICEL CHIRALCEL OJ-H, iPrOH/hexane = 1/99,
flow = 0.5 mL/min) 11.36 and 14.02 min.
1H NMR (CDCl3) d 0.18 (s, 9H), 1.84 (s, 3H), 7.08 (m, 2H), 7.52
(m, 2H); 13C NMR (CDCl3) d 1.0, 33.5, 71.0, 115.6, 121.4, 126.5,
4.2.12. 1-Trimethylsilyloxy-1,2,3,4-tetrahydronaphthalene-1-
carbonitrile (Table 3, entry 12)
138.0, 162.2; ½a D24
¼ þ16:4 (c 1.3, CHCl3) 70% ee; HRMS(MC) calcd
ꢁ
for C12H16FNOSi: 237.0985; found: 237.0981 HPLC (DAICEL CHI-
RALCEL OB-H, iPrOH/hexane = 1/99, flow = 0.25 mL/min) 16.4 and
18.5 min.
1H NMR (CDCl3, 200 MHz): d = 0.21 (s, 9H), 1.83–2.41 (m, 4H),
2.81 (t, 2H, J = 7.00 Hz), 7.09–7.29 (m, 3H), 7.61–7.66 (m, 1H). 13C
NMR (CDCl3, 100 MHz): d = 1.33, 18.69, 28.32, 37.73, 69.87,
122.11, 126.63, 128.02, 129.06, 129.26, 135.68, 136.11.
4.2.5. 2-Trimethylsilyloxy-2-(40-bromophenyl)propanenitrile
(Table 3, entry 5)
4.2.13. 2-Trimethylsilyloxy-2-furan-2-yl-propanenitrile
(Table 3, entry 13)
1H NMR (CDCl3) d 0.19 (s, 9H), 1.83 (s, 3H), 7.40–7.4 (m, 2H),
7.51–7.55 (m, 2H); 13C NMR (CDCl3) d 1.0, 33.4, 71.0, 121.1,
1H NMR (CDCl3, 200 MHz): d = 0.22 (s, 9H), 1.88 (s, 3H), 6.35–
6.40 (m, 1H), 6.47–6.50 (m, 1H), 7.41–7.43 (m, 1H); 13C NMR
(CDCl3, 100 MHz): d = 0.49, 28.37, 65.89, 108.14, 110.68, 120.23,
143.09, 151.63.
122.7, 126.3, 131.7, 141.2; ½a D22
¼ ꢀ14:8 (c 1.50, CHCl3) 71% ee;
ꢁ
HRMS(MC) calcd for C12H16BrNOSi: 297.0185; found: 297.0181
HPLC (DAICEL CHIRALCEL OB-H, iPrOH/hexane = 1/99, flow = 0.25
mL/min) 17.1 and 18.3 min.
Acknowledgment
4.2.6. 2-Trimethylsilyloxy-2-(40-nitrophenyl)propanenitrile
(Table 3, entry 6)
Financial support from the Department of Science and Technol-
ogy, New Delhi [Grant No: SR/FTP/CS-40/2007] is gratefully
acknowledged.
1H NMR (CDCl3) d 0.25 (s, 9H), 1.87 (s, 3H), 7.75 (d, 2H), 8.30 (d,
2H); 13C NMR (CDCl3) d 1.0, 33.5, 71.0, 115.6, 121.4, 126.5, 138.0,
162.2; ½a 2D2
¼ ꢀ14:4 (c 1.60, CHCl3) 61.2% ee) HRMS(MC) calcd
ꢁ
for C12H16N2O3Si: 264.0930; found: 264.0933 HPLC (DAICEL CHI-
RALCEL OJ-H, iPrOH/hexane = 1/99, flow = 0.25 mL/min) 20.3 and
21.2 min.
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