Chiral linear polymers bonded alternatively with salen and 1,4-dialkoxybenzene: Synthesis and application for Ti-catalyzed asymmetric TMSCN addition to aldehydes

Article abstract of DOI:10.1016/j.tetasy.2010.11.020

The synthesis of chiral linear polymers 1a-b having salen and 1,4-dioctyloxybenzene as alternate segments has been accomplished. The GPC analysis showed the molecular weights corresponding to ca. 15 (M_w = 10,999, M_n = 9165 and PDI = 1.20) repeating units for 1a and ca. 8 (M_w = 8547, M_n = 7883 and PDI = 1.08) repeating units for 1b. Polymers 1a-b have been studied with Ti(OⁱPr)₄ as a recyclable catalyst for the asymmetric addition of TMSCN to aldehydes while the selectivity of the polymer catalyst is identical to that of the monomer. The reactions are efficient affording the cyanohydrins with up to 88% ee. The selectivity of the polymer based catalyst 9a is found to be the same to that of the monomer 10a. The reaction provides the advantages of simplified product isolation and easy recovery and recyclability of polymer catalyst 9a without any loss of activity or selectivity.

Full text of DOI:10.1016/j.tetasy.2010.11.020

Tetrahedron: Asymmetry 21 (2010) 2834–2840
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chiral linear polymers bonded alternatively with salen and
1,4-dialkoxybenzene: synthesis and application for Ti-catalyzed asymmetric
TMSCN addition to aldehydes
⇑
Sekarpandi Sakthivel, Tharmalingam Punniyamurthy
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of chiral linear polymers 1a–b having salen and 1,4-dioctyloxybenzene as alternate seg-
ments has been accomplished. The GPC analysis showed the molecular weights corresponding to ca.
15 (Mw = 10,999, Mn = 9165 and PDI = 1.20) repeating units for 1a and ca. 8 (Mw = 8547, Mn = 7883 and
PDI = 1.08) repeating units for 1b. Polymers 1a–b have been studied with Ti(OiPr)4 as a recyclable catalyst
for the asymmetric addition of TMSCN to aldehydes while the selectivity of the polymer catalyst is iden-
tical to that of the monomer. The reactions are efficient affording the cyanohydrins with up to 88% ee. The
selectivity of the polymer based catalyst 9a is found to be the same to that of the monomer 10a. The reac-
tion provides the advantages of simplified product isolation and easy recovery and recyclability of poly-
mer catalyst 9a without any loss of activity or selectivity.
Received 20 October 2010
Accepted 25 November 2010
Available online 20 December 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
to give tetramethyl 2,5-dioctyloxyphenyldiboronate, which could
be hydrolyzed using 2 N HCl to provide conjugate segment 4 in
The application of chiral macromolecular catalysts in asymmet-
ric synthesis has attracted extensive attention,1 because they pro-
vide the advantages of simplified product isolation, easy recovery,
and recyclability of the generally quite expensive chiral catalysts
and potential use for continuous production. Chiral macromolecu-
lar catalysts can be divided into three classes: (i) polymer anchored
chiral catalysts;2 (ii) chiral dendritic catalysts;3 and (iii) chiral main
chain polymer catalysts.4 Among these, the last have the advanta-
ges of bearing more reactive sites along with the preservation of
the microenvironment of the reactive centers which is crucial for
the selectivity of the reaction. Herein we report the synthesis
and application of new chiral linear polymers 1a–b bonded alter-
natively with salen5 and 1,4-dioctyloxybenzene for the Ti-cata-
lyzed asymmetric TMSCN addition to aldehydes.
80% yield (Scheme 1).6
OC8H17
Br
OH
OC8H17
B(OH)2
i, ii
iii
Br
(HO)2B
OC8H17
OH
OC8H17
4
2
3
Scheme 1. Reagents and conditions: (i) C8H17Br (2.5 equiv), K2CO3 (2.5 equiv),
EtOH, 70 °C, 24 h, 80%; (ii) Br2, CHCl3, rt, 27 h, 90%; (iii) n-BuLi (2.3 equiv), B(OMe)3
(2.5 equiv), Et2O, ꢀ20 °C to rt, 12 h, 2 M HCl, rt, 0.5 h, 80%.
The synthesis of aldehyde 7 was next accomplished. Iodination
of 3-tert-butyl-2-hydroxybenzaldehyde 5 with iodinemonochlo-
ride in CH3COOH provided 3-tert-butyl-2-hydroxy-5-iodobenzal-
dehyde7 6 in 97% yield which could be C–C cross-coupled with 4
using Pd(PPh3)2Cl2 to give the target molecule 7 in 70% yield
(Scheme 2).
2. Results and discussion
The synthesis of 2,5-dioctyloxyphenyldiboronic acid 4 is shown
in Scheme 1. The reaction of hydroxyquinone 2 with 1-bromooc-
tane gave 1,4-dioctyloxybenzene in the presence of K2CO3 in 80%
yield which could be brominated using Br2 to afford 1,4-dibromo-
2,5-dioctyloxybenzene 3 in 90% yield. Compound 3 was reacted
with 2.3 equiv of n-BuLi followed by 2.5 equiv of trimethylborate
OHC H17C8O
HO
CHO
OH
OH
OH
CHO
CHO
i
ii
OC8H17
I
6
5
7
Scheme 2. Reagents and conditions: (i) ICl (1.5 equiv), AcOH, 120 °C, 5 h, 97%; (ii)
3-tert-butyl-2-hydroxy-5-iodobenzaldehyde (2.1 equiv), Pd(PPh3)2Cl2 (3 mol %),
PPh3 (9 mol %), Cs2CO3 (3 equiv), THF, 60 °C, 24 h, 70%.
⇑
Corresponding author.
E-mail address: tpunni@iitg.ernet.in (T. Punniyamurthy).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.11.020

S. Sakthivel, T. Punniyamurthy / Tetrahedron: Asymmetry 21 (2010) 2834–2840
2835
OC8H17
N
N
OC8H17
N
N
OC8H17
N
N
OC8H17
N
N
i
OH HO
t-Bu t-Bu H17C8O
OH HO
t-Bu t-Bu H17C8O
OH HO
t-Bu t-Bu H17C8O
OH HO
t-Bu t-Bu
H2N
NH2
H17C8O
8a
1a
Scheme 3. Synthesis of polymer 1a. Reagents and conditions: (i) 7, CHCl3, 45 °C, 5 h, 97%.
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
N
Ph
OC8H17
OC8H17
OC8H17
OC8H17
N
Ph
Ph
i
OH HO
t-Bu t-Bu H17C8O
OH HO
t-Bu t-Bu H17C8O
OH HO
t-Bu t-Bu H17C8O
OH HO
t-Bu t-Bu
H2N
NH2
H17C8O
8b
1b
Scheme 4. Synthesis of polymer 1b. Reagents and conditions: (i) 7, CHCl3, 45 °C, 5 h, 93%.
spectra recorded at 400 MHz were consistent with their structure.
The UV–vis spectra of the CHCl3 solutions of 1a–b exhibited maxi-
mum absorptions (kmax) at 323, 255, and 323, 266 nm, respectively
(Fig. 1).
0.5
0.4
0.3
0.2
0.1
Polymer 1a
Polymer 1b
O
R
N
R
N
R
N
R
N
Ti
O
O
O
HO
OH
t-Bu
10 R = -(CH2)4
t-Bu
t-Bu
t-Bu
-
10a R = -(CH2)4
-
To study their application for asymmetric catalysis, the poly-
mers 1a–b were reacted with Ti(OiPr)4 to afford a Ti–polymer com-
plex 9a–b as dark yellow solids (Scheme 5).8 Their catalytic
activities were compared in the TMSCN addition to aldehydes (Ta-
ble 1).8,9 The reaction conditions were optimized with p-methoxy-
benzaldehyde as a model substrate. As anticipated, the reaction
occurred efficiently with 1 mol % of 9a–b (with respect to the
repeating unit) to afford the desired cyanohydrin with up to 78%
ee. The selectivity was similar to that of the monomer catalyst
10a. Polymer catalyst 9a was found to be superior to 9b. The effect
of temperature was studied and 0 °C afforded the best results. It
was seen that CHCl3 was the solvent of choice, whereas CH2Cl2,
THF, and toluene gave inferior results. Control experiments con-
firmed that without Ti, no reaction occurred.
Using the optimized conditions, the scope of the procedure was
further explored (Table 2). The reactions of the aryl aldehydes with
2-Br, 2-Cl, 2-OCH3, 2-OC2H5, 2-OC3H5, 3-Br, and 4-CH3 substituents
were studied. The substrates readily proceeded to react with
TMSCN to give the corresponding cyanohydrins with up to 88%
ee. Likewise, 2-naphthaldehyde underwent reaction with TMSCN
to give the respective cyanohydrin in 90% yield and 74% ee, while
300
350
Wavelength (nm)
400
450
Figure 1. UV–vis spectra of polymers 1a–b in CHCl3.
The synthesis of polymers 1a–b was then carried out by conden-
sation of 7 with chiral (1R,2R)-diaminocyclohexane 8a and (1R,2R)-
diphenylethylenediamine 8b in CHCl3 (Schemes 3 and 4). The reac-
tions proceeded smoothly to afford polymers 1a–b in 93–97% yield.
Polymers 1a–b were soluble in common organic solvents, such as
THF, CHCl3, CH2Cl2, and toluene. The GPC analysis, with polystyrene
as the internal standard and THF as the eluent, exhibited their aver-
age molecular weights that corresponded to ca. 15 repeating units
for 1a (Mw = 10,999, Mn = 9165 and PDI = 1.20) and ca. 8 repeating
units for 1b (Mw = 8547, Mn = 7883 and PDI = 1.08). The 1H NMR
O
R
L
R
N
R
R
R
R
N
N
N
N
N
H2O
Ti
O
TiL4
Ti
L
O
O
OH
HO
O
O
16 h, rt
CH2Cl2
3 h, rt
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
L = OiPr
1a R = -(CH2)4
1b R = Ph
-
9a R = -(CH2)4
9b R = Ph
-
Scheme 5. Synthesis of chiral Ti–polymer complexes 9a–b.

2836
S. Sakthivel, T. Punniyamurthy / Tetrahedron: Asymmetry 21 (2010) 2834–2840
Table 1
polystyrene as an internal standard and THF as eluent. HPLC anal-
Optimization of the reaction conditions
ysis was carried out for acetylated cyanohydrin using Waters-2489
with Daicel Chiralcel OD-H column and for benzoylated cyanohy-
drin using Waters-2489 with Daicel Chiralcel OJ column. Elemental
OH
CN
1 mol% Catalyst
2 equiv TMSCN
CHO
analysis was carried out using
analyzer.
a Perkin–Elmer-2400 CHNS
Solvent, -5 °C-25 °C
48 h
H3CO
H3CO
Entry
Catalyst
Solvent
Temp. (°C)
Yield (%)a,b
ee (%)c
Config.d
4.2. 2,5-Dioctyloxyphenyldiboronic acid 46
1
2
3
4
5
6
7
8
9
9a
9b
9a
9a
9a
9a
9a
10a
1a
CHCl3
CHCl3
CH2Cl2
THF
Toluene
CHCl3
CHCl3
CHCl3
CHCl3
0
0
0
0
0
ꢀ5
25
0
95
90
90
Trace
70
90
95
97
n.r.
78
43
43
—
16
72
43
76
—
(S)
(S)
(S)
—
(S)
(S)
(S)
(S)
—
At first, n-BuLi (11.5 mL, 2.0 M in cyclohexane) was added to a
stirred solution of 1,4-dibromo-2,5-dioctyloxybenzene
3
(10 mmol, 4.92 g) in dry Et2O (40 mL) at ꢀ20 °C under nitrogen
atmosphere. After 1 h, trimethylborate (25 mmol, 2.8 mL) was
added and the mixture was allowed to warm up to room temper-
ature after which stirring was continued for an additional 12 h. The
reaction mixture was then treated with 2 M HCl (25 mL) and the
precipitate was collected by filtration and washed successively
with water (10 mL) and Et2O (20 mL) to give 4 as a colorless solid
in 80% (3.37 g) yield. Mp 140 °C, 1H NMR (400 MHz, DMSO-d6) d
7.79 (s, 4H), 7.16 (s, 2H), 3.97 (t, J = 6.4 Hz, 4H), 1.70 (t, J = 7.4 Hz,
4H), 1.38–1.24 (m, 20H), 0.84 (t, J = 6.6 Hz, 6H); 13C NMR
(100 MHz, CDCl3) d 156.9, 124.5, 118.0, 68.4, 31.1, 28.7, 28.65,
28.59, 25.4, 22.1, 13.9; FT-IR (KBr) 3498, 3362, 2941, 2921, 2870,
2852, 1495, 1470, 1417, 1389, 1299, 1272, 1205, 1127, 1083,
0
n.r. = no reaction.
a
p-Methoxybenzaldehyde (1 mmol), catalyst (1 mol % with respect to mono-
meric unit), TMSCN (2 mmol) and solvent (3 mL) were stirred for 48 h under an N2
atmosphere.
b
Isolated yield.
c
Determined by HPLC analysis of the acetyl derivative of the cyanohydrin with a
Chiralcel OD-H column using 99:1 n-hexane/2-propanol.
d
Determined by the sign of the specific rotation.
1049, 1002, 887, 804, 722, 652, 566 cmꢀ1
22H40B2O6: C, 62.59; H, 9.55. Found: C, 62.55; H, 9.59.
. Anal. Calcd for
the aliphatic aldehydes, propanal, isobutanal, and crotonal reacted
with TMSCN to afford the corresponding cyanohydrins in 90–95%
yield and 40–66% ee.
C
4.3. 3-tert-Butyl-2-hydroxy-5-iodobenzaldehyde 67
The advantage of this system is that catalyst 9a can be recov-
ered and recycled (Table 3). After completion, the reaction mixture
was concentrated (ca. 0.5 mL) and the resultant solution was trea-
ted with MeOH (ca. 0.5 mL). The precipitated out Ti–polymer cata-
lyst 9a precipitate was filtered, dried, and reused for a fresh
reaction of p-methoxybenzaldehyde with TMSCN. This process
was repeated for three runs and the reactions occured to afford
the target cyanohydrin with 93–95% yield and 78% ee. These re-
sults clearly suggest that the catalyst 9a can be recycled without
a loss of activity or selectivity.
To a stirred solution of 3-tert-butyl-2-hydroxybenzalde-hyde 5
(10 mmol, 1.78 g) in glacial CH3COOH (15 mL) at room tempera-
ture, iodinemonochloride (15 mmol, 2.43 g) in glacial CH3COOH
(7 mL) was added drop wise. Next, the mixture was refluxed for
5 h, cooled to room temperature, and treated with CH2Cl2
(25 mL) and water (15 mL). The organic layer was separated and
washed with brine (10 mL) and water (2 ꢁ 10 mL). Drying
(Na2SO4) and evaporation of the solvent gave a residue that was
purified on silica gel column chromatography using ethyl acetate
and hexane as eluent to give 6 as a pale yellow solid in 97%
(2.95 g) yield. Mp 55 °C, 1H NMR (400 MHz, CDCl3) d 11.72 (s,
1H), 9.78 (s, 1H), 7.70 (d, J = 2.4 Hz, 1H), 7.68 (t, J = 2 Hz, 2H),
1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) d 195.9, 160.9, 142.6,
141.4, 140.1, 122.6, 80.8, 35.1, 29.2; FT-IR (KBr) 3435, 3088,
2963, 2871, 2728, 1651, 1599, 1475, 1434, 1413, 1350,
3. Conclusions
In conclusion, the synthesis and application of chiral linear
polymers 1a–b with Ti(OiPr)4 have been described for cyanohydrin
synthesis. The system provides the advantages of simplified prod-
uct isolation, and easy recovery and recyclability of the polymer
catalyst 9a. Further exploration of this procedure for other poten-
tial reactions and the mechanism is currently pursued.
1303,1269, 1196, 1163, 1024, 930, 769, 756, 704, 559, 512 cmꢀ1
.
Anal. Calcd for C11H13IO2: C, 43.44; H, 4.31. Found: C, 43.47; H,
4.32.
4. Experimental section
4.1. General
4.4. Preparation of dialdehyde 7
To a stirred solution of aldehyde 6 (5.25 mmol, 1.6 g), 2,5-dioc-
tyloxyphenyldiboronic acid
4 (2.5 mmol, 1.05 g) and Cs2CO3
TMSCN (98%) and aldehydes were purchased from Aldrich.
Ti(OiPr) (98%) was procured from Acros Organics. Solvents were
purchased from Rankem and purified prior to use by standard pro-
cedure.10 Column chromatography was carried out with Rankem
60–120 mesh silica gel. Analytical TLC was performed with Rank-
em silica gel G and GF 254 plates. NMR spectra (400 MHz for 1H
and 100 MHz for 13C) were recorded using a DRX-400 Varian spec-
trometer using CDCl3 and DMSO-d6 as solvent and Me4Si as an
internal standard. Melting points were determined using Buchi
B-540 melting point apparatus and are uncorrected. FT-IR spectra
were obtained using Perkin–Elmer spectrum one spectrometer.
UV–vis spectra were recorded using Perkin–Elmer Lambda 25
UV/vis spectrometer. GPC analysis was performed on Waters-
2414 with stationary phase column StyragelÒ WAT044221 using
(7.5 mmol, 2.4 g) in THF (30 mL) under a nitrogen atmosphere
was added Pd(PPh3)2Cl2 (3 mol %) and PPh3 (9 mol %), and the mix-
ture was stirred at 60 °C for 24 h. The solvent was evaporated and
the residue was dissolved in CH2Cl2 (25 mL) and washed with brine
(5 mL) and water (2 ꢁ 10 mL). Drying (Na2SO4) and evaporation of
the solvent gave a solid that was purified on silica gel column chro-
matography using ethyl acetate and hexane as eluent to give 7 as a
pale yellow solid in 70% (1.21 g) yield. Mp 194 °C; 1H NMR
(400 MHz, CDCl3) d 11.80 (s, 2H), 9.91 (s, 2H), 7.81 (d, J = 2 Hz,
2H), 7.59 (d, J = 2 Hz, 2H), 6.94 (s, 2H), 3.94 (t, J = 6.4 Hz, 4H),
1.70–1.66 (m, 4H), 1.45 (s, 18H), 1.34–1.21 (m, 20H), 0.85 (t,
J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3) d 197.5, 160.6, 150.4,
137.8, 136.1, 132.6, 129.7, 129.5, 120.6, 115.7, 69.7, 35.2, 31.9,
29.7, 29.53, 29.48, 29.43, 26.4, 22.8, 14.3; FT-IR (KBr) 3433, 2930,

S. Sakthivel, T. Punniyamurthy / Tetrahedron: Asymmetry 21 (2010) 2834–2840
2837
Table 2
Chiral poly-Ti 9a catalyzed TMSCN addition to aldehydes
Entry
Aldehyde
CHO
Product
OH
Yielda,b (%)
95
eec (%)
50
Config.d
CN
1
n.d.
(S)
Br
Br
OH
CHO
Cl
CN
2
3
4
5
97
95
91
90
60
88
78
75
Cl
OH
CHO
OCH3
CHO
OC2H5
CHO
OC3H5
CHO
CN
(S)
OCH3
OH
CN
n.d.
n.d.
OC2H5
OH
CN
OC3H5
OH
CN
6
7
90
97
75
78
n.d.
Br
H3CO
H3C
Br
H3CO
H3C
CHO
OH
CN
(S)
CHO
OH
CN
8
9
97
90
68
74
(S)
(S)
CHO
OH
CN
H3C
H3C
CHO
CHO
OH
10
11
12
95e
90e
93
40f
66f
55f
n.d.
(S)
H3C
H3C
CN
OH
H3C
H3C
H3C
CN
OH
CHO
(S)
H3C
CN
a
b
c
d
e
f
Aldehyde (0.5 mmol), TMSCN (1 mmol), and 9a (1 mol % with respect to monomeric unit) were stirred at 0 °C for 48 h in CHCl3 (1.5 mL) under an N2 atmosphere.
Isolated yield.
Determined by HPLC analysis of the acetyl derivative of the cyanohydrin using a Chiralcel OD-H column with 99:1 n-hexane/2-propanol.
Determined by the sign of the specific rotation.
Reaction carried out on a 2.0 mmol scale of the aldehyde.
Determined by HPLC analysis of the benzoyl derivative of the cyanohydrin using a Chiralcel OJ column with 90:10 n-hexane/2-propanol.
2857, 1643, 1514, 1441, 1388, 1366, 1322, 1266, 1234, 1221, 1210,
1168, 1087, 1023, 960, 876, 783, 736, 709, 521 cmꢀ1. Anal. Calcd
for C44H62O6: C, 76.93; H, 9.10. Found: C, 76.97; H, 9.07.
130.2, 128.2, 118.6, 116.1, 72.8, 69.7, 35.1, 33.6, 32.0, 29.7, 29.6,
29.5, 26.5, 24.5, 22.8, 14.2; FT-IR (KBr): 3465, 2928, 2857, 1629,
1507, 1465, 1440, 1389, 1264, 1203, 1083, 1035, 973, 862, 802,
707 cmꢀ1; UV–vis (CHCl3): kmax 323, 255 nm; ½a 2D0
¼ þ231 (c
ꢂ
4.5. Synthesis of polymers 1a–b
0.026, CHCl3). Anal. Calcd for (C50H72N2O4)n C, 78.49; H, 9.49; N,
3.66. Found: C, 78.51; H, 9.45; N, 3.69.
4.5.1. Polymer 1a
To a solution of 7 (0.23 mmol, 158 mg) in CHCl3 (2 mL) was
added (1R,2R)-diaminocyclohexane 8a (0.23 mmol, 27 mg). The
mixture was stirred at 45 °C for 5 h and cooled to room tempera-
ture. Next, MeOH was added and the precipitate 1a was collected
by filtration as a yellow powder in 97% (171 mg) yield. GPC:
Mw = 10,999, Mn = 9165 (PDI 1.20); 1H NMR (400 MHz, CDCl3) d
8.39 (s, 2H), 7.56 (s, 2H), 7.24 (s, 2H), 6.85 (s, 2H), 3.87–3.81 (m,
4H), 1.94–1.21 (m, 52H), 0.86 (t, J = 7.2 Hz, 6H); 13C NMR
(100 MHz, CDCl3) d 165.5, 159.8, 150.4, 136.5, 131.4, 130.6,
4.5.2. Polymer 1b
To a solution of 7 (0.23 mmol, 158 mg) in CHCl3 (2 mL) was
added (1R,2R)-diphenylethylenediamine 8b (0.23 mmol, 49 mg)
and the mixture was stirred at 45 °C for 5 h. Isolation of 1b was
carried out as described for 1a as a yellow powder in 93%
(185 mg) yield. GPC: Mw = 8547, Mn = 7883 (PDI 1.08); 1H NMR
(400 MHz, CDCl3) d 8.41 (s, 2H), 7.59 (s, 2H), 7.25–7.21 (m, 12H),
6.84 (s, 2H), 4.81 (s, 2H), 3.82–3.79 (m, 4H), 1.63–1.19 (m, 42H),
0.83 (t, J = 6 Hz, 6H); 13C NMR (100 MHz, CDCl3) d (ppm): 167,

2838
S. Sakthivel, T. Punniyamurthy / Tetrahedron: Asymmetry 21 (2010) 2834–2840
Table 3
4.8. Preparation of 10a
Recyclability of the catalyst 9a
OH
Preparation of 10a was carried out as described for 9a from
monomer 10 (125 mol, 35 mg)
mol, 55 mg) and Ti(OiPr)4 (125
1 mol % 9a
2 equiv TMSCN
CHO
l
l
CN
in CH2Cl2 (4 mL) to provide 10a as a yellow solid (63 mg).
CHCl3, 0 oC, 48 h
H3CO
H3CO
ee (%)c
4.9. General procedure for the TMSCN addition to aldehydes
Run
Catalyst recoverability (%)
Product yield (%)
1a
2b
3b
99
99
99
95
93
93
78
78
78
To a stirred solution of aldehyde (0.5 mmol) and 9a (1 mol %
with respect to the monomeric unit) in dry CHCl3 (1.5 mL) was
added TMSCN (1 mmol) and the reaction mixture was stirred for
48 h under nitrogen atmosphere (Table 2). Progress of the reaction
was monitored by TLC using ethyl acetate and hexane as eluent.
The reaction mixture was then concentrated (ca. 0.5 mL) and
MeOH (0.5 mL) was added drop wise. The 9a precipitate was col-
lected and the filtrate was evaporated to give a residue which
was stirred with 2 M HCl (2 mL) in ethyl acetate (5 mL) for 1 h.
The resultant solution was extracted with ethyl acetate
(2 ꢁ 5 mL) and washed with brine (3 mL) and water (5 mL). Drying
(Na2SO4) and evaporation of the solvent gave a residue that was
purified by silica gel column chromatography using ethyl acetate
and hexane as eluent to afford analytically pure cyanohydrins.
a
p-Methoxybenzaldehyde (1 mmol), 9a (1 mol % with respect to monomeric
unit) and TMSCN (2 mmol) were stirred at 0 °C for 48 h in CHCl3 (3 mL) under an N2
atmosphere.
b
Recovered 9a used.
c
Determined by HPLC analysis of the acetyl derivative of the cyanohydrin with a
Chiralcel OD-H column using 99:1 n-hexane/2-propanol.
159.8, 150.4, 139.9, 136.6, 131.7, 130.8, 130.2, 128.5, 128.2, 127.7,
118.5, 116.1, 80.1, 69.7, 35.1, 31.9, 29.6, 29.5, 26.3, 22.8, 14.2; FT-IR
(KBr) 3445, 3062, 3031, 2954, 2926, 2856, 1626, 1507, 1453, 1439,
1390, 1376, 1264, 1202, 1087, 1028, 864, 801, 774, 698, 555 cmꢀ1
;
UV–vis (CHCl3): kmax 323, 266 nm; ½a D20
¼ þ95 (c 0.021, CHCl3).
ꢂ
4.10. General procedure for cyanohydrin acylation11
Anal. Calcd for (C58H74N2O4)n C, 80.70; H, 8.64; N, 3.25. Found: C,
80.68; H, 8.60; N, 3.27.
To a stirred solution of cyanohydrin (0.5 mmol) and pyridine
(0.6 mmol) in CHCl3 (1 mL) at 0 °C was added Ac2O (1.5 mmol) or
benzoyl chloride (1 mmol). The mixture was stirred at room tem-
perature for 1 h. The solvent was evaporated and the residue was
passed through a short pad of silica gel using ethyl acetate and
hexane to give the acetyl derivative whose ee was determined by
HPLC analysis.
4.6. Preparation of monomer 10
To a stirred solution of the (1R,2R)-diammoniumcyclohexane
mono-(+)-tartrate salt (1.97 mmol, 520 mg) and K2CO3
(3.94 mmol, 543 mg) in distilled water (3 mL) was added EtOH
(15 mL). The cloudy mixture was heated to 80 °C and an EtOH
(5 mL) solution of the aldehyde 5 (3.94 mmol, 702 mg) was added.
The resulting yellow colored slurry was stirred for 2 h at the same
temperature and water (3 mL) then added. The mixture was then
cooled to <5 °C over 2 h and maintained at that temperature for
an additional hour. The product was collected by vacuum filtration
and washed with EtOH (2 mL). The crude solid was redissolved in
CH2Cl2 (10 mL) and washed with water (2 ꢁ 5 mL) and brine
(3 mL). Drying (Na2SO4) and evaporation of the solvent gave 10
as a yellow powder in 97% yield (831 mg). Mp 75 °C; 1H NMR
(400 MHz, CDCl3) d 8.21 (s, 2H), 7.18 (dd, J = 1.2, 8 Hz, 2H), 6.92
(dd, J = 1.2, 7.2 Hz, 2H), 6.63 (t, J = 7.2 Hz, 2H), 3.26 (m, 2H),
1.91–1.41 (m, 8H), 1.33 (s, 18H); 13C NMR (100 MHz, CDCl3) d
165.7, 160.5, 137.2, 129.9, 129.4, 118.8, 117.9, 72.4, 34.9, 33.3,
29.5, 24.4; FT-IR (KBr) 3454, 2959, 2934, 2860, 1629, 1436, 1390,
359, 1306, 1264, 1199, 1144, 1083, 1037, 848, 800, 750,
4.10.1. (+)-2-Hydroxy-2-(2’-bromophenyl)acetonitrile (Table 2,
entry 1)12a
Colorless solid, yield 95%, mp 58 °C, ½a D20
¼ þ6:3 (c 1.09, CHCl3).
ꢂ
HPLC of the acetyl derivative: Chiralcel OD-H column, n-hexane/2-
propanol (99:1), wavelength: 254 nm, flow rate: 1 mL/min, reten-
tion time: 10.49 min, 13.42 min, 50% ee.
4.10.2. (S)-(+)-2-Hydroxy-2-(2’-chlorophenyl)acetonitrile
(Table 2, entry 2)12b
Colorless oil, yield 97%, ½a D20
ꢂ
¼ þ1:6 (c 0.43, CHCl3).12c HPLC of
the acetyl derivative: Chiralcel OD-H column, n-hexane/2-propanol
(99:1), wavelength 254 nm, flow rate: 1 mL/min, retention time:
9.26 min, 11.10 min, 60% ee.
691 cmꢀ1
28H38N2O2: C, 77.38; H, 8.81; N, 6.45. Found: C, 77.35; H, 8.76;
N, 6.51.
;
½
a 2D0
ꢂ
¼ ꢀ433 (c 0.25, CHCl3). Anal. Calcd for
4.10.3. (S)-(ꢀ)-2-Hydroxy-2-(2’-methoxyphenyl)acetonitrile
(Table 2, entry 3)12d
C
Colorless solid, yield 95%, mp 73 °C, ½a D20
¼ ꢀ23:9 (c 0.37,
ꢂ
CHCl3).12d HPLC of the acetyl derivative: Chiralcel OD-H column,
n-hexane/2-propanol (99:1), wavelength 254 nm, flow rate:
1 mL/min, retention time: 12.53 min, 14.22 min, 88% ee.
4.7. Preparation of the chiral poly-Ti catalysts8
4.7.1. Catalyst 9a
4.10.4. (ꢀ)-2-Hydroxy-2-(2’-ethoxyphenyl)acetonitrile (Table 2,
entry 4)
To a stirred solution of 1a (8.3
l
mol, 100 mg) in CH2Cl2 (3 mL)
was added a solution of Ti(OiPr)4 (125
lmol, 35 mg) in CH2Cl2
Colorless solid, yield 91%, mp 88 °C, 1H NMR (400 MHz, CDCl3) d
7.38–7.34 (m, 2H), 7.0–6.93 (m, 2H), 5.52 (d, J = 10.4 Hz, 1H), 4.2–
4.14 (m, 2H), 3.63 (d, J = 9.2 Hz, 1H), 1.49 (t, J = 7 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 156.2, 131.2, 128.1, 123.9, 121.1, 119.1, 112.1,
64.4, 60.6, 14.8; FT-IR (KBr): 3368, 2982, 2936, 2887, 2251, 1601,
1590, 1494, 1473, 1457, 1391, 1307, 1285, 1258, 1237, 1182,
1160, 1125, 1112, 1060, 1043, 927, 910, 796, 758, 721, 616,
(1 mL) at room temperature. After 3 h, water (0.1 mL) was added
and the stirring continued for an additional 16 h. The resultant
solution was concentrated in vacuo, and the residue was washed
with MeOH (5 mL) to afford 9a as yellow solid (106 mg).
4.7.2. Catalyst 9b
591 cmꢀ1, ½a 2D0
¼ ꢀ38 (c 0.61, CHCl3). Anal. Calcd for C10H11NO2:
ꢂ
The preparation of 9b was carried out as described for 9a from
polymer 1b (14.6
in CH2Cl2 (4 mL) and obtained as a yellow solid (108 mg).
l lmol, 33 mg)
mol, 100 mg) and Ti(OiPr)4 (117
C, 67.78; H, 6.26; N, 7.90. Found: C, 67.70; H, 6.32; N, 7.87.
HPLC of the acetyl derivative: Chiralcel OD-H column, n-hexane/

S. Sakthivel, T. Punniyamurthy / Tetrahedron: Asymmetry 21 (2010) 2834–2840
2839
2-propanol (99:1), wavelength 254 nm, flow rate: 1 mL/min, reten-
tion time: 8.78 min, 10.76 min, 78% ee.
nol (90:10), wavelength 254 nm, flow rate: 0.8 mL/min, retention
time: 9.83 min, 10.36 min, 55% ee.
4.11. Recyclability experiment
4.10.5. (+)-2-Hydroxy-2-(2’-allyloxyphenyl)acetonitrile (Table 2,
entry 5)
To a stirred solution of 4-methoxybenzaldehyde (0.5 mmol) and
9a (1 mol % with respect to the monomeric unit) in dry CHCl3
(1.5 mL) was added TMSCN (1 mmol) and the reaction mixture
was stirred for 48 h under a nitrogen atmosphere (Table 3). The
reaction mixture was then concentrated (ca. 0.5 mL) and MeOH
(0.5 mL) was added. The 9a precipitate was collected and reused
for a fresh reaction.
Oil, yield 90%, 1H NMR (400 MHz, CDCl3) d 7.39–7.34 (m, 2H),
7.69 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.10–6.02 (m, 1H),
5.57 (d, J = 6.8 Hz, 1H), 5.47–5.42 (td, J = 1.6, 9.2 Hz, 1H),
5.35–5.31 (m, 1H), 4.67–4.65 (m, 2H), 3.66 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 155.6, 132.4, 131, 128, 124, 121.3, 119,
118.3, 112.3, 69.3, 60.0. FT-IR (neat): 3463, 2923, 2855, 2253,
2071, 1650, 1491, 1458, 1287, 1252, 1185, 1162, 1120, 1030,
927, 812, 753, 699 cmꢀ1; ½a D20
¼ þ22:5 (c 0.75, CHCl3). Anal.
ꢂ
Acknowledgments
Calcd for
C11H11NO2: C, 69.83; H, 5.86; N, 7.40. Found: C,
69.79; H, 5.92; N, 7.36. HPLC of the acetyl derivative: Chiralcel
OD-H column, n-hexane/2-propanol (99:1), wavelength 254 nm,
flow rate: 1 mL/min, retention time: 10.55 min, 13.94 min, 75%
ee.
This work was supported by the Department of Science and
Technology, New Delhi, and Council of Scientific and Industrial Re-
search, New Delhi. One of us (S.S.) thanks CSIR for Junior Research
Fellowship.
4.10.6. (ꢀ)-2-Hydroxy-2-(3’-bromophenyl)acetonitrile (Table 2,
entry 6)12b
References
Colorless oil, yield 90%, ½a D20
¼ ꢀ19:5 (c 1.34, CHCl3). HPLC of
ꢂ
1. For some recent reviews, see: (a) Bergbreiter, D. E.; Tian, J.; Hongfa, C. Chem.
Rev. 2009, 109, 530; (b) Trindade, A. F.; Gois, P. M. P.; Afonso, C. A. M. Chem. Rev.
2009, 109, 418; (c) Madhavan, N.; Jones, C. W.; Weck, M. Acc. Chem. Res. 2008,
41, 1153; (d) Najera, C.; Sansano, J. M. Chem. Rev. 2007, 107, 4584; (e) Baleizao,
C.; Garcia, H. Chem. Rev. 2006, 106, 3987.
the acetyl derivative: Chiralcel OD-H column, n-hexane/2-propanol
(99:1), wavelength 254 nm, flow rate: 1 mL/min, retention time:
15.12 min, 16.36 min, 75% ee.12d
2. For some studies, see: (a) Reger, T. S.; Janda, K. D. J. Am. Chem. Soc. 2000, 122,
6929; (b) Haraguchi, N.; Tsuru, K.; Arakawa, Y.; Itsuno, S. Org. Biomol. Chem.
2009, 7, 69; (c) Chiwara, V. I.; Haraguchi, N.; Itsuno, S. J. Org. Chem. 2009, 74,
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Jones, C. W.; Weck, M. Chem. Eur. J. 2006, 12, 576; (g) Anyanwu, U. K.;
Venkataraman, D. Green Chem. 2005, 7, 424; (h) Annis, D. A.; Jacobsen, E. N. J.
Am. Chem. Soc. 1999, 121, 4147; (i) Song, C. E.; Roh, E. J.; Yu, B. M.; Chi, D. Y.;
Kim, S. C.; Lee, K. J. Chem. Commun. 2000, 615; (j) Smith, K.; Liu, C.; El-Hiti, G. A.
Org. Biomol. Chem. 2006, 4, 917; Zhang, H. D.; Zhang, Y. M.; Li, C. Tetrahedron:
Asymmetry 2005, 16, 2417; (l) Zheng, X.; Jones, C. W.; Weck, M. Adv. Synth.
Catal. 2008, 350, 255.
3. For some studies, see: (a) Sellner, H.; Karjalainen, J. K.; Seeback, D. Chem. Eur. J.
2001, 7, 2873; (b) Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000, 39,
3604; (c) Jiang, L.; Wu, T.-F.; Chen, Y.-C.; Zhu, J.; Deng, J.-G. Org. Biomol. Chem.
2006, 4, 3319; (d) Liu, W.; Cui, X.; Cun, L.; Wu, J.; Zhu, J.; Deng, J.; Fan, Q. Synlett
2005, 1591; (e) Nielsen, M.; Thomsen, A. H.; Jensen, T. R.; Jakobsen, H. J.;
Skibsted, J.; Gothelf, K. V. Eur. J. Org. Chem. 2005, 342.
4. For some studies, see: (a) Song, Y.; Yao, X.; Chen, H.; Pan, G.; Hu, X.; Zhen, Z. J.
Chem. Soc., Perkin Trans. 1 2008, 870; (b) Lere-Porte, J.-P.; Moreau, J. J. E.; Serein-
spirau, F.; Wakim, S. Tetrahedron Lett. 2001, 42, 3073; Jammi, S.; Rout, L.;
Punniyamurthy, T. Tetrahedron: Asymmetry 2007, 18, 2016; (d) Huang, W.;
Song, Y.; Bai, C.; Cao, G.; Zheng, Z. Tetrahedron Lett. 2004, 45, 4763; (e) Huang,
W.; Song, Y.; Wang, J.; Cao, G.; Zheng, Z. Tetrahedron 2004, 60, 10469; (f)
Minutolo, F.; Pini, D.; Salvadori, P. Tetrahedron Lett. 1996, 37, 3375; (g) Breysse,
E.; Pinel, C.; Lemaire, M. Tetrahedron: Asymmetry 1998, 9, 897; (h) Jammi, S.;
Rout, L.; Saha, P.; Akkilagunta, V. K.; Sanyasi, S.; Punniyamurthy, T. Inorg. Chem.
2008, 47, 5093.
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J. J. Am. Chem. Soc. 2010, 132, 11165; (b) Loy, R. N.; Jacobsen, E. N. J. Am. Chem.
Soc. 2009, 131, 2786; (c) Belser, T.; Jacobsen, E. N. Adv. Synth. Catal. 2008, 350,
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Doyle, A. G.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2007, 46, 3701; (f) Saito, B.;
Egami, H.; Katsuki, T. J. Am. Chem. Soc. 2007, 129, 1978; (g) Shimizu, H.;
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A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2005, 127, 62; (i) Taylor, M. S.; Zalatan, D.
N.; Lerchner, A. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2005, 127, 1313; (j)
Vanderwal, C. D.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 14724; (k) Sammis,
G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 9928.
4.10.7. (S)-(ꢀ)-2-Hydroxy-2-(4’-methoxyphenyl)acetonitrile
(Table 1, entry 7)
Colorless solid, yield 97%, mp 67 °C, ½a D20
¼ ꢀ32:4 (c 0.55,
ꢂ
CHCl3).12d HPLC of the acetyl derivative: Chiralcel OD-H column,
n-hexane/2-propanol (99:1), wavelength 254 nm, flow rate:
1 mL/min, retention time: 17.37 min, 19.08 min, 78% ee.
4.10.8. (S)-(ꢀ)-2-Hydroxy-2-(4’-methylphenyl)acetonitrile
(Table 2, entry 8)12d
Colorless oil, yield 97%, ½a D20
ꢂ
¼ ꢀ31:5 (c 0.51, CHCl3).12d HPLC of
the acetyl derivative: Chiralcel OD-H column, n-hexane/2-propanol
(99:1), wavelength 254 nm, flow rate: 1 mL/min, retention time:
10.10 min, 12.27 min, 68% ee.
4.10.9. (S)-(ꢀ)-2-Hydroxy-2-(2’-naphthyl)acetonitrile (Table 2,
entry 9)12e
Colorless solid, yield 90%, mp 119 °C, ½a D20
¼ ꢀ24:6 (c 1.16,
ꢂ
CHCl3).12e HPLC of the acetyl derivative: Chiralcel OD-H column,
n-hexane/2-propanol (99:1), wavelength 254 nm, flow rate:
1 mL/min, retention time: 26.67 min, 29.65 min, 74% ee.
4.10.10. (ꢀ)-2-Hydroxybutanenitrile (Table 2, entry 10)12b
Colorless liquid, yield 95%, ½a D20
¼ ꢀ10:3 (c 0.89, CHCl3). HPLC of
ꢂ
the benzoyl derivative: Chiralcel OJ column, n-hexane/2-propanol
(90:10), wavelength 254 nm, flow rate: 0.5 mL/min, retention
time: 16.57 min, 18.14 min, 40% ee.
4.10.11. (S)-(ꢀ)-2-Hydroxy-3-methylbutanenitrile (Table 2,
entry 11)12b
6. Maruyama, S.; Kawanishi, Y. J. Mater. Chem. 2002, 12, 2245.
Colorless liquid, yield 90%, ½a D20
ꢂ
¼ ꢀ10:5 (c 1.19, CHCl3).12e HPLC
7. Park, J.; Lang, K.; Abboud, K. A.; Hong, S. J. Am. Chem. Soc. 2008, 130, 16484.
8. Belokon, Y. N.; Caveda-Cepas, S.; Green, B.; Ikonnikov, N. S.; Khrustalev, V. N.;
Larichev, V. S.; Moscalenko, M. A.; North, M.; Orizu, C.; Tararov, V. I.; Tasinazzo,
M.; Timofeeva, G. I.; Yashkina, L. V. J. Am. Chem. Soc. 1999, 121, 3968.
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Gama, A.; Flores-Lopez, L. Z.; Aguirre, G.; Parra-Hake, M.; Somanathan, R.; Cole,
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C.; Pericas, M. A. Tetrahedron: Asymmetry 2006, 17, 151; (d) Moreno, R. M.;
Rosol, M.; Moyano, A. Tetrahedron: Asymmetry 2006, 17, 1089; (e) Belokon, Y.
N.; Chusov, D.; Borkin, D. A.; Yashkina, L. V.; Dmitriev, A. V.; Katayev, D.; North,
M. Tetrahedron: Asymmetry 2006, 17, 2328; (f) Uang, B.-J.; Fu, I.-P.; Hwang, C.-
of the benzoyl derivative: Chiralcel OJ column, n-hexane/2-propa-
nol (90:10), wavelength 254 nm, flow rate: 0.5 mL/min, retention
time: 12.04 min, 13.11 min, 66% ee.
4.10.12. (E)-(S)-(+)-2-Hydroxypent-3-enenitrile (Table 2, entry
12)12b
Colorless liquid, yield 93%, ½a D20
ꢂ
¼ þ10:5 (c 0.50, CHCl3).9d HPLC
of the benzoyl derivative: Chiralcel OJ column, n-hexane/2-propa-

2840
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