Asymmetric synthesis of O-acetylcyanohydrins by reaction of aldehydes with NaCN/KCN catalyzed by recyclable chiral dimeric titanium(IV)/vanadium(V) salen complexes

Article abstract of DOI:10.1002/ejoc.200600208

The efficient catalytic asymmetric addition of an inexpensive and nonvolatile cyanide source such as NaCN or KCN and acetic anhydride to various aldehydes was catalyzed by recyclable dimeric Ti^IV and V^V chiral salen complexes at -20°

Full text of DOI:10.1002/ejoc.200600208

FULL PAPER
DOI: 10.1002/ejoc.200600208
Asymmetric Synthesis of O-Acetylcyanohydrins by Reaction of Aldehydes
with NaCN/KCN Catalyzed by Recyclable Chiral Dimeric
Titanium(IV)/Vanadium(V) Salen Complexes
Noor-ul H. Khan,*[a] Santosh Agrawal,[a] Rukhsana I. Kureshy,[a] Sayed H. R. Abdi,[a]
Vishal J. Mayani,[a] and Raksh V. Jasra[a]
Keywords: Cyanohydrins / Catalysis / Dimeric TiIV/VV salen complexes
The efficient catalytic asymmetric addition of an inexpensive
and nonvolatile cyanide source such as NaCN or KCN and
acetic anhydride to various aldehydes was catalyzed by recy-
clable dimeric TiIV and VV chiral salen complexes at –20 °C.
High chiral induction (96% ee) in the O-acetylcyanohydrin
was obtained in the case of 2-fluorobenzaldehyde, and the
results achieved with sodium cyanide are quite comparable
to those with potassium cyanide. The chiral VV salen com-
plex was found to be the most efficient recyclable catalyst
reported so far in the literature, and was better than the TiIV
salen system. Both the catalysts were recovered after the first
use and recycled effectively four times.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
develop recyclable metal complexes using organic or inor-
ganic supports[13] and ionic liquids[14] as reaction media
where expensive and volatile trimethylsilyl cyanide was used
as source of cyanide. We have reported the development of
recyclable polymeric and dimeric chiral salen complexes for
enantioselective epoxidation and hydrolytic kinetic resolu-
tion of terminal epoxides.[15] Herein we are extending the
application of dimeric salen ligands by synthesizing titani-
um(IV) and vanadium(V) complexes 1 and 2, respectively,
for the asymmetric addition of nonvolatile and inexpensive
sodium cyanide and potassium cyanide to various alde-
hydes in the presence of acetic anhydride at –20 °C. Quanti-
tative yield (99%) of O-acetylcyanohydrin with high chiral
induction (ee up to 96%) was achieved in the case of 2-
fluorobenzaldehyde. Remarkably, with our methodology,
comparable yields and chiral inductions in the products
were achieved with sodium cyanide and potassium cyanide.
We also observed that the VV salen complex was the most
efficient recyclable catalyst reported so far in the literature,
and was a better catalyst than the TiIV salen complex.
Introduction
Chiral cyanohydrins are versatile building blocks for
pharmaceuticals, agrochemicals and specialty materials
bearing optically active multifunctional groups such as
amino alcohols, hydroxy acids, and amino acids.[1,2]
A
number of synthetic methods have been reported for the
synthesis of chiral cyanohydrins employing enzymes,[3] syn-
thetic peptides,[4] organocatalysts[5] and metal com-
plexes,[6–11] the latter being the most widely used over the
last decades.[6–11] Most of these hydrocyanation reactions
utilized trimethylsilyl cyanide (TMSCN) as a source of cya-
nide to achieve O-(trimethylsilyl)cyanohydrins. However, O-
(trimethylsilyl)cyanohydrins are labile and readily undergo
hydrolysis to form cyanohydrins that are prone to racemiza-
tion. In addition, cyanohydrins are frequently prepared at
very low temperatures while using toxic, highly volatile and
expensive hydrogen cyanide or trimethylsilyl cyanide. It is
therefore advantageous from synthetic and economic points
of view to obtain chemically O-protected chiral cyanohyd-
rins using an inexpensive and nonvolatile source of cyanide
e.g., potassium cyanide or sodium cyanide, under milder
conditions. In this direction, very efficient catalysts based
on bimetallic Ti–O–Ti and VV=O complexes were reported
by Belokon et al. using potassium cyanide as a cyanide
source to give high ee up to 92% at –42 °C.[12] As chiral
ligands are expensive, the recycling of chiral catalysts is
highly desirable. Recently, many efforts have been made to
Results and Discussion
The synthesis of dimeric salen ligand 1Ј (Figure 1) and
its precursors was carried out as described in reference.[15a]
The complexation of the dimeric salen ligand (1Ј) with
V(O)SO4·5H2O for catalyst 2 (Figure 2) was carried out in
ethanol, while catalyst 1 was generated in situ by the inter-
action of equimolar quantities of the chiral salen ligand
with Ti(OiPr)4 (Figure 3). These catalysts, 1 and 2, were
characterized by 1H NMR, optical rotation, IR, UV/Vis
and CHN microanalysis (see data given in Exp. Sect.). The
[a] Silicates and Catalysis Discipline, Central Salt and Marine
Chemicals Research Institute (CSMCRI),
Bhavnagar 364002, Gujarat, India
Fax: +91-0278-2566970
E-Mail: khan2593@yahoo.co.in
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formation of Ti–O–Ti complex 1 generated in situ was con-
firmed by recording the solution IR of the parent complex
TiL(OiPr)2 and after interaction with 1 equiv. water, which
forms catalyst 1 or species A (Scheme 1). The emergence of
a new band at 702 cm–1 indicates the formation of the Ti–
O–Ti complex. This band was absent in the complex TiL-
(OiPr)2 prior to the addition of water.[17] Catalyst 1 in solu-
tion was found to be in the cis-β-configuration, confirmed
1
by H-NMR, which gives two sets of azomethine protons
at δ = 7.80 and 8.18 ppm. These results are in consonance
with earlier reports.[12e,18] Further, we have also observed a
slight positive nonlinear correlation (Figure 4) of the ee of
catalyst 1 and the ee of 4a that supports the existence of
the cis-β-configuration in catalyst 1.[18a]
Figure 2. Structure of catalyst 2.
Figure 1. Structure of the ligand 1Ј.
Catalysts 1 and 2 were used for the asymmetric addition
of cyanide by using sodium cyanide and potassium cyanide
as nonvolatile and inexpensive cyanide sources to various
aldehydes namely, benzaldehyde (3a), 4-methoxybenzalde-
hyde (3b), 3-methoxybenzaldehyde (3c), 2-methoxybenzal-
dehyde (3d), 4-chlorobenzaldehyde (3e), 4-bromobenzalde-
hyde (3f), 4-fluorobenzaldehyde (3g) and 2-fluorobenzalde-
hyde (3h) in the presence of acetic anhydride at –20 °C, as
shown in Table 1 and Table 2. Initially, we conducted the Figure 3. Structure of catalyst 1.
Scheme 1. Probable mechanism for catalytic cycle of the asymmetric cyanation reaction.
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Asymmetric Synthesis of O-Acetylcyanohydrins
FULL PAPER
Table 1. Enantioselective synthesis of O-acetylcyanohydrins from
various aldehydes, potassium cyanide and acetic anhydride cata-
lyzed by dimeric chiral TiIV and VV complexes.
Figure 4. Nonlinearity effect of the catalyst 1.
Entry
Substrate
Conversion [%][a]
ee [%][b,d]
1 (2)
3 (4)
5 (6)
7 (8)
9 (10)
11 (12)
13 (14)
15 (16)
3a
3b
3c
3d
3e
3f
99[e] (99)[f]
91[e] (90)[f]
92[e] (93)[f]
90[e] (92)[f]
99[e] (99)[f]
99[e] (99)[f]
99[e] (99)[f]
99[e] (99)[f]
92 (93)[c]
88 (90)
89 (89)
89 (90)
90 (93)
90 (92)
91 (94)
95 (96)
experiments with benzaldehyde as a model substrate using
1
NaCN/KCN as source of cyanide. H and 13C NMR con-
firmed that product 4a was obtained exclusively, with no
formation of enolizable product (see data given in the Exp.
Sect.). It can be seen that the present catalytic protocol is
quite general for the range of substrates used in the present
study. However, the substituents on the benzaldehyde deriv-
atives had some influence on the reactivity and enantio-
selectivity of the reactions. While excellent conversions to
3g
3h
[a] The conversion was determined based on G. C. integral area.
[b] The ee was determined by using Chiralpak HPLC OD and AD
columns. [c] Values in parentheses are for catalyst 2. [d] The abso-
O-acetylcyanohydrin (yields up to 98–99%) (Table 1, entries lute configuration was assigned by comparison with literature data,
and was found to be S.[12b] [e] Conversion for catalysts 1. [f] Con-
1, 2, 9–16 and Table 2, entries 17, 18, 25–32) were obtained
for most of the aldehydes with both the catalysts in 8–10 h,
version for catalysts 2.
methoxy-substituted aldehydes (Table 1, entries 3–8 and
Table 2, entries 19–24) gave relatively lower conversions to
O-acetylcyanohydrin (conversion 90–93%). The lower con-
versions for 4-methoxybenzaldehyde were also observed
with BINOLAM-TiIV complexes.[9j] The best enantioinduc-
tion (96% ee) and quantitative yield of O-acetylcyano-
hydrin was obtained for 2-fluorobenzaldehyde using KCN
as the cyanide source with catalyst 2 (Entry 16). The chiral
induction in the O-acetylcyanohydrins utilizing the catalysts
1 and 2 followed this sequence: F-benzaldehyde Ͼ benzal-
dehyde Ͼ Cl-benzaldehyde Ͼ Br-benzaldehyde Ͼ MeO-
benzaldehyde, as shown in Figure 5. The overall perform-
ance of the VV chiral salen complex 2 was found to be the
most efficient recyclable system reported in literature so far,
better than the TiIV salen complex in terms of reactivity and
enantioselectivity. Further, the results obtained with sodium
cyanide as the cyanide source are fairly comparable with
those of KCN in terms of reactivity and enantioselectivity,
which is an important finding, considering that the former
is far less toxic than the latter. On conducting the cyanation
Table 2. Enantioselective synthesis of O-acetylcyanohydrins from
various aldehydes, sodium cyanide and acetic anhydride catalyzed
by dimeric complexes 1 and 2.
Entry
Substrate
Conversion [%][a]
ee [%][b,d]
17 (18)
19 (20)
21 (22)
23 (24)
25 (26)
27 (28)
29 (30)
31 (32)
3a
3b
3c
3d
3e
3f
99[e] (99)[f]
90[e] (90)[f]
91[e] (93)[f]
90[e] (91)[f]
98[e] (99)[f]
99[e] (99)[f]
98[e] (99)[f]
98[e] (99)[f]
89 (90)[c]
87 (88)
86 (88)
85 (87)
89 (91)
88 (90)
90 (92)
91 (93)
3g
3h
[a] The conversion was determined based on G. C. integral area.
[b] The ee was determined by using Chiralpak HPLC OD and AD
columns. [c] Values in parentheses are for catalyst 2. [d] The abso-
lute configuration was assigned by comparison with literature data
found to be S.[12b] [e] Conversion for catalysts 1. [f] Conversion for
catalysts 2.
It has been reported that the reactivity and enantio-
reaction with an aliphatic aldehyde such as valeraldehyde selectivity of O-acetylcyanohydrin formation using chiral
using catalyst 2 in the presence of KCN and acetic anhy- TiIV salen complexes is solvent-dependent.[6d] Thus, the ef-
dride at –20 °C, 87% conversion with 91% ee of O-acetylcy- fect of solvent using the complexes 1 and 2 on the asymmet-
anohydrin was achieved in 8 h. Furthermore, these results ric addition of KCN and acetic anhydride to benzaldehyde
are quite superior to the reported linear polymeric salen VV was carried out, and the results are shown in Table 3. Good
and linear salen TiIV catalysts.[6d] This may be due to an conversion (80–82%) and high ee (85–87%) were achieved
increase in active catalytic sites which are working in a co- when 1,2-dichloroethane (entries 35, 36) was used as the
operative manner.[15,16]
solvent, while in cases of toluene and THF, the conversions
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FULL PAPER
Figure 5. 3D view showing % ee vs. aldehydes (1) 3a, (2) 3b, (3) 3c, (4) 3d, (5) 3e, (6) 3f, (7) 3g, (8) 3h using the catalysts 1 and 2 with
KCN and NaCN.
(40–53%) and enantioselectivities (68–71% ee) were not Table 4. Effects of loading and temperature on conversion and ee
of O-acetylcyanohydrin using benzaldehyde as a representative sub-
strate, with KCN and catalysts 1 and 2.
high (Entries 37–40). Of all the solvents used, dichloro-
methane was found to be the solvent of choice (Entries 33,
34), and it showed better results than the previously re-
ported chiral cross-linked polymeric salen complexes with
TiIV.[6d]
Entry
Catalyst
loading
[mol-%]
Temp. [°C]
Conversion [%][a] ee [%][b]
41 (42)
43 (44)
45 (46)
47 (48)
49 (50)
5
2
1
5
5
–20
–20
–20
99 (99)
90 (92)
78 (80)
88 (89)
89 (91)
92 (93)[c]
91 (92)
90 (92)
70 (71)
60 (61)
Table 3. Effect of solvents on conversion and ee of O-acetylcya-
nohydrin using benzaldehyde as a representative substrate, with
KCN and catalysts 1 and 2.
–8
room temp.
Entry
Solvent
Conversion [%][a]
ee [%][b]
[a] The conversion was determined based on G. C. integral area.
[b] The ee was determined by using Chiralpak HPLC OD column.
[c] Values in parentheses are for catalyst 2.
33 (34)
35 (36)
37 (38)
39 (40)
dichloromethane
1,2-dichloroethane
toluene
99 (99)
80 (82)
40 (43)
50 (53)
92 (93)[c]
85 (87)
70 (71)
67 (68)
tetrahydrofuran
A plausible mechanism for the formation of O-acetylcya-
nohydrin is shown in Scheme 1. Catalyst 1 is activated by
the addition of acetic anhydride to give bis-acetate B, which
on reaction with KCN/NaCN in the presence of an alde-
[a] The conversion was determined based on G. C. integral area.
[b] The ee was determined by using Chiralpak HPLC OD columns.
[c] Results in parentheses are for catalyst 2.
Complexes 1 and 2 were also used to examine the influ- hyde gives species C. The nucleophilic attack by the CN
ence of catalyst loading and temperature variation on the group on the partially coordinated aldehydic carbon to spe-
formation of O-acetylcyanohydrin using benzaldehyde as cies D takes place, which facilitates the acylation of the tita-
the substrate and KCN as the cyanide source. The results nium-bound cyanohydrin to give the O-acetylcyanohydrin
are given in Table 4, where the best conversion (99%) and product. This titanium complex E either reacts with cyanide
ee (92–93%) were achieved at –20 °C with 5 mol-% (with to give bis-cyanide species F, or reacts with aldehyde to
respect to the salen unit) of the complexes 1 and 2 (Entries form species C, which further continues the catalytic cycle.
41, 42). On reducing the catalyst loading from 5 mol-% to It has been reported[18] that the catalytic cycle in the case
2 mol-% there is decrease in conversion to 90–92% (Entries of the VV salen complex proceeds in an intramolecular
43, 44) with similar ee (91–92%). On further decreasing the manner via the formation of a cis-β VV salen species in the
catalyst loading (1 mol-%), there is further decrease in con- same manner as reported[12b,18] for the Ti (salen) di-µ-oxo
version and ee (Entries 45, 46). Furthermore, the increase complex.
in reaction temperature had an adverse effect on the yield
Catalyst recycling studies were carried out by precipitat-
and enantioselectivity of the product (entries 47–50). These ing the catalyst by the addition of hexane to the post-cata-
observations are in consonance with those reported ear- lytic reaction mixture. To the recovered catalyst, fresh sub-
lier.[6d]
strates and reactants were supplied in similar manner as in
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Asymmetric Synthesis of O-Acetylcyanohydrins
FULL PAPER
measured with a Digipol 781 Automatic Polarimeter (Rudolph In-
struments).
the case of fresh catalyst. The data for four-time use of the
same catalyst is given in Table 5. The activity of the recycled
catalysts gradually decreased upon successive use, possibly
due to some physical loss of the catalyst with retention of
enantioselectivity. The recyclability of this catalytic system
Synthesis of Vanadium(V) Complex (2): The ligand 1Ј (0.499 g,
0.504 mmol) was dissolved in ethanol/CH2Cl2 (3:2, 15 mL), to
which an aqueous solution of vanadyl sulfate hydrate (0.255 g,
has advantages over previously reported linear and cross- 1.008 mmol in 2 mL water) was added dropwise under an inert at-
linked polymeric VV and TiIV salen complexes.
mosphere at room temperature. The resulting solution was refluxed
for 4 h and then cooled to room temperature with stirring for 2 h
while opening the side arm of the reaction flask. The solvent was
completely evaporated, and the residue was dissolved in CH2Cl2
(10 mL), washed with water (3×5 mL) and then with brine. The
organic layer was dried with anhydrous Na2SO4, filtered and evap-
orated to give the VV complex. Yield, 0.385 g, 68.02%. Melting
point: d. 200 °C. 1H NMR (200 MHz, CDCl3): δ = 0.82 (t, J = 7.2,
6 H), 1.33 (s, 18 H), 1.42 (s, 36 H), 1.6–2.3 (m, 16 H), 3.41 (q, J =
7.2, 4 H), 3.81 (m, 2 H), 3.92 (s, 2 H), 4.25 (m, 2 H), 7.48 (s, 2 H),
7.53 (s, 2 H), 7.68 (s, 2 H), 7.73 (s, 2 H), 8.52 (s, 2 H), 8.73 (s, 2
Table 5. Enantioselective synthesis of the O-acetylcyanohydrin with
benzaldehyde, potassium cyanide and acetic anhydride catalyzed by
recovered dimeric chiral TiIV and VV complexes.
Run
1
2
3
4
Time (h)
8 (8)
10 (9)
98 (99)
92 (93)
12 (10)
90 (92)
92 (93)
14 (12)
88 (90)
92 (93)
Conversion [%][a] 99 (99)[c]
ee [%][b]
92 (93)
[a] The conversion was determined based on G. C. integral area.
[b] The ee was determined by using Chiralpak HPLC OD column.
[c] Values in parentheses are for catalyst 2.
H) ppm. IR (KBr): ν = 3435, 2958, 2868, 2359, 1650, 1613, 1538,
˜
1465, 1437, 1389, 1361, 1317, 1269, 1253, 1227, 1171, 1028, 982,
+2
929, 834, 770, 748, 711, 643, 563 cm–1. C69H102N4O16S2V2
(1409.6): calcd. C 58.79, H 7.29, N 3.97; found C 58.85, H 7.32, N
3.99. λmax (ε): 252 (33915), 352 (12681), 421 (4114), 633 (1592).
[α]2D7 = –860 (c = 0.01, CHCl3). TOF-MS (ESI+): m/z 1160.4
[M+H]+.
Conclusions
Chiral dimeric titanium(IV) and vanadium(V) salen
complexes were used for the asymmetric addition of non-
volatile and inexpensive sodium cyanide and potassium cya-
nide as cyanide sources to various aldehydes in the presence
of acetic anhydride at –20 °C. Excellent yields (99%) of O-
acetylcyanohydrin and high chiral induction (up to 96% ee)
were achieved in the case of 2-fluorobenzaldehyde, and the
Procedure for TiIV Dimeric Salen-Catalyzed Asymmetric O-Acetyl-
cyanation of Aldehyde:
A solution of ligand 1Ј (98.0 mg,
0.099 mmol) and titanium tetraisopropoxide (58.0 µL, 0.198 mmol)
in dry CH2Cl2 (2 mL) was stirred at room temperature under nitro-
gen for 2 h. H2O (3.6 µL, 0.20 mmol) was added, and the reaction
mixture was again stirred at room temperature for 3 h. The re-
sulting yellow solution was cooled to –20 °C, and CH2Cl2 (2 mL),
results achieved with sodium cyanide are quite comparable tBuOH (0.2 mL, 2.09 mmol), H2O (20 µL, 1.11 mmol), benzalde-
to those of potassium cyanide. The VV salen complex also
hyde (0.202 mL, 1.98 mmol) and Ac2O (0.748 mL, 7.92 mmol) were
added in that sequence. Solid KCN (0.515 g, 7.92 mmol) was then
turned to be the most efficient recyclable system reported
added in small fractions over a period of 2 h with vigorous stirring,
so far in the literature. Both the catalysts were recovered
followed by the addition of CH2Cl2 (3 mL). After the completion
after their first use and recycled four times effectively.
of the reaction (8–10 h, determined byTLC), the reaction mass was
washed with water (3×5 mL) and brine. The organic layer was sep-
arated and dried with anhydrous Na2SO4. The solution was fil-
Experimental Section
tered, evaporated and the O-acetylcyanohydrin product was puri-
fied by flash column chromatography on silica gel (eluted with hex-
Vanadyl sulfate hydrate (Loba Chemie, India), titanium tetraisop-
ropoxide (Aldrich), KCN (Merck), NaCN (Robert Johnson), benz-
ane/ethyl acetate = 95:5). The enantiomeric excess of O-acetylcya-
1
nohydrin was determined by HPLC analysis. Catalyst 1. H NMR
aldehyde (3a), 4-methoxybenzaldehyde (3b), 3-methoxybenzalde-
(200 MHz, CDCl3): δ = 1.05 (s, 36 H), 1.22 (s, 36 H), 1.31 (s, 36
hyde (3c), 2-methoxybenzaldehyde (3d), 4-chlorobenzaldehyde (3e),
H), 2.5–2.6 (m, 32 H), 3.92 (s, 2 H), 3.94 (s, 2 H), 4.0–4.1 (m, 8
4-bromobenzaldehyde (3f), 4-fluorobenzaldehyde (3g), and 2-fluo-
H), 6.97 (s, 4 H), 7.05 (s, 4 H), 7.24 (s, 4 H), 7.43 (s, 4 H), 7.80 (s,
robenzaldehyde (3h) were purchased from Aldrich Chemicals and
4 H), 8.18 (s, 4 H) ppm. 13C (50 MHz, CDCl3): δ = 24.3, 24.7, 28.0,
were used as received. Dimeric chiral salen ligand 1Ј was synthe-
29.3, 30.2, 30.3, 31.4, 34.0, 35.0, 35.2, 40.7, 41.0, 65.2, 69.4, 121.3,
sized by the reported method.[15a] All the solvents were dried by
125.0, 127.1, 128.4, 128.8, 137.1, 138.2, 139.0, 139.5, 157.0,
standard procedures,[19] distilled and stored under nitrogen. Thin-
161.4 ppm. IR (KBr): ν = 1624, 702 cm–1. [α]27 = –320 (c = 0.01,
˜
D
layer chromatography was performed using aluminum TLC sheets
precoated with silica gel having a florescent UV indicator. NMR
CHCl3). C130H176N8O12Ti4 (2234.3): calcd. C 69.88, H 7.94, N
5.02; found C 69.10, H 7.97, N 5.01. TOF-MS (ESI+): m/z = 2235.8
spectra were obtained with
a Bruker F113V spectrometer
[M+H]+.
1
(200 MHz and 50 MHz for H and 13C respectively) and are refer-
enced internally with TMS. FTIR spectra were recorded on a Per-
kin–Elmer Spectrum GX spectrophotometer in a KBr window.
High-resolution mass spectra were obtained with LC-MS (Q-TOF)
LC (Waters), or MS (Micromass) instruments. For product purifi-
cation, flash chromatography was performed using silica gel 60–
200 mesh purchased from s. d. Fine-Chemicals Limited, Mumbai
(India). Enantiomeric excess (ee) were determined by HPLC (Shim-
adzu SCL-10AVP) using Daicel Chiralpak OD and AD chiral col-
umns with 2-propanol/hexane as eluent. Optical rotations were
Procedure for Vanadium(V) Dimeric Salen-Catalyzed Asymmetric
O-Acetylcyanation of Aldehyde: VV-salen catalyst 2 was dissolved
in CH2Cl2 (3 mL) and the solution was cooled to –20 °C. CH2Cl2
(2 mL), tBuOH (0.2 mL, 2.09 mmol), H2O (20 µL, 1.11 mmol),
benzaldehyde (0.202 mL, 1.98 mmol) and Ac2O (0.748 mL,
7.92 mmol) were added to the solution in that order. The addition
of KCN (0.515 g, 7.92 mmol) was done slowly during 2 h, followed
by addition of CH2Cl2 (3 mL). After the reaction was completed
(as detected by TLC), the reaction mass was washed with water
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(3×5 mL) followed by brine, and the organic layer was separated
and dried with anhydrous Na2SO4. The solution was filtered, evap-
orated and the O-acetylcyanohydrin product was purified by flash
column chromatography on silica gel (eluted with hexane/ethylace-
tate = 95:5). The enantiomeric excess of O-acetylcyanohydrin was
1
determined by HPLC analysis. 4a: H NMR (200 MHz, CDCl3): δ
= 2.11 (s, 3 H), 6.38 (s, 1 H), 7.40–7.52 (m, 5 H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 20.8, 63.3, 116.7, 128.3, 129.7, 130.8, 132.3,
169.4 ppm. [α]2D7 = –30.5 (c = 1, CH2Cl2) ppm. TOF-MS (ESI+):
m/z = 160.2 [M+H]+.
Acknowledgments
N. H. K. is thankful to DST and CSIR Network project on Cataly-
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Received: March 8, 2006
Published Online: May 9, 2006
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