Henry reaction catalyzed by recoverable enantioselective catalysts based on copper(II) complexes of α-methoxypoly(ethylene glycol)-b-poly(l-glutamic acid) and imidazolidine-4-one ligands

Article abstract of DOI:10.1016/j.tetasy.2014.01.001

Herein we describe the preparation and characterization of a recoverable catalyst for a Henry reaction based on a Cu(II) complex of block copolymer α-methoxypoly(ethylene glycol)-b-poly(l-glutamic acid) with (2R,5S)- or (2S,5R)-5-isopropyl-5-methyl-2-(pyr

Full text of DOI:10.1016/j.tetasy.2014.01.001

Tetrahedron: Asymmetry 25 (2014) 334–339
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Tetrahedron: Asymmetry
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Henry reaction catalyzed by recoverable enantioselective
catalysts based on copper(II) complexes of a-methoxypoly
(ethylene glycol)-b-poly(L-glutamic acid) and imidazolidine-4-one
ligands
b
a
a
Dattatry Shivajirao Bhosale a, Pavel Drabina a, , Jirí Palarcík , Jirí Hanusek , Miloš Sedlák
⇑
ˇ
ˇ
ˇ
a Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
b Institute of Environmental and Chemical Engineering, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 November 2013
Accepted 8 January 2014
Herein we describe the preparation and characterization of a recoverable catalyst for a Henry reaction
based on a Cu(II) complex of block copolymer
a-methoxypoly(ethylene glycol)-b-poly(L-glutamic acid)
with (2R,5S)- or (2S,5R)-5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one. The reactions of
substituted aldehydes with nitromethane catalyzed by these catalysts proceed with high chemical yield
(70–98%) and with high enantioselectivity (61–92% ee). The reaction mixture is in the form of a colloid
system and is formed by self-organized aggregates of the catalysts with average hydrodynamic particle
size of 189 3 nm (DLS). After sevenfold recycling, the catalyst exhibited no decrease in the enantioselec-
tivity and only a slight decrease (ca. 18%) in the yield for the Henry reaction of nitromethane with 2-
methoxybenzaldehyde.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
immobilized catalysts, consists of anchoring homogeneous
catalysts to a suitable carrier, such as a polymer or an inorganic
The asymmetric variant of the Henry reaction catalyzed by Cu(II)
complexes represents one of the basic reactions in which a new ste-
reogenic center is created by the formation of a carbon–carbon
bond.1 This reaction is often a key step in preparation of chiral,
enantiomerically pure substituted 2-nitroalcohols used in synthe-
ses of medical drugs.2 In our previous papers,1n,r,2e we have de-
scribed the preparation and characterization of eantiomerically
pure substituted imidazolidine-4-ones and their complexes with
Cu(II) ions, which were utilized as enantioselective catalysts of
the Henry reaction with different aldehydes with nitromethane.
In the case of the reaction of 2,2-dimethylpropanal with nitrometh-
ane catalyzed by a complex of (2R,5S)-5-isopropyl-5-methyl-2-
(pyridine-2-yl)imidazolidine-4-one with Cu(OAc)2, the product
showed1n up to 96% ee. However, the applications of homogeneous
catalysts are limited due to the impossibility of their recycling. The
last decade has seen an increase in the attractiveness and interest
concerning the possibility of recycling immobilized homogeneous
catalysts. Their use not only lowers the expense of the technological
processes, but also reduces the impacts of chemical production on
the environment. The heterogenization, that is, the preparation of
material. In the case of organic polymers, the applied polymers
can be insoluble, partly soluble, or completely soluble in the
reaction medium.3 The traditionally applied insoluble polymeric
carriers include spherical particles of styrene–divinylbenzene
copolymer (PS–DVB, Merrifield).4 The advantage of these systems
lies in the easy isolation of the catalyst from the reaction mixture
by means of filtration. However, a frequent problem appears in
the long reaction times and, hence, low degree of conversion, which
is caused by the slow diffusion of reactants through the polymeric
matrix to the active center of the catalyst.4 This problem can be
avoided by carrying out the reactions with catalysts anchored to
polymers that are soluble in the reaction medium, for example, to
functionalized poly(ethylene glycols).5 Another solution employs
micellar or vesicular systems known as self-organized nanoreac-
tors.6 The preparation of these systems makes use of classic
low-molecular surfactants,7 or amphiphilic block copolymers.8
Their micro- or nano-dimensions enable us to carry out the reaction
under pseudo-homogeneous conditions, which reduces the reac-
tion times. The crucial advantage of such hybrid systems lies in
the possibility of their isolation after the reaction (by precipitation
or dialysis) and repeated use.6
The literature1f,i,p describes several examples of immobilized
catalysts used for asymmetric Henry reactions. For instance,1i the
⇑
Corresponding author. Tel.: +420 466 037 010; fax: +420 466 037 068.
E-mail address: pavel.drabina@upce.cz (P. Drabina).
0957-4166/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2014.01.001

D. S. Bhosale et al. / Tetrahedron: Asymmetry 25 (2014) 334–339
335
reactions of benzaldehydes with nitromethane catalyzed by a series
of Cu(II) complexes derived from substituted (1R,2R)-cyclohexane-
1,2-diamines immobilized on the surface of silica achieved up to
61% ee. However, in this case the immobilization led to a decrease
in the enantioselectivity, as compared with the original homoge-
neous catalyst (72% ee).1i Another catalytic system based on the
Cu(II) complex of substituted (1R,2R)-cyclohexane-1,2-diaminobi-
thiophene immobilized on poly(ethylene glycol) achieved up to
93% ee, and the efficient recoverability was up to five cycles.1f The
asymmetric Henry reaction was also performed as a model reaction
using a unique self-organized catalytic system based on aggregates
prepared by coordination polymerization of Cu(II) with a ditopic
bisoxazoline ligand.1p The coordination polymer obtained was suc-
cessfully recycled for up to 11 catalytic cycles while retaining high
yields (>90%) and enantioselectivity (>90% ee).
I at 1652 cm–1 (C@O vibration), and amide II at 1548 cm–1 (N–H
and C–N vibration) for PEG-b-PGA. In the spectrum of PEG-b-PG-
Cu, the band of amide II was shifted to lower values (1541 cm–1
)
.
and in the case of PEG-b-PG-CuL-1(2) to the value of 1544 cm–1
The bands of the poly(ethylene glycol) chain in the range of
1466–842 cm–1 were virtually identical in the case of both the
block polymer itself and its copper(II) salt and complex. In contrast
to the spectra of PEG-b-PGA and PEG-b-PG-Cu, the FT-IR spectrum
of PEG-b-PG-Cu-L-1 contains an additional band at 1608 cm–1
which corresponds to the C@C stretching vibration of
a
2-substituted pyridine. Other differences in the FT-IR spectra of
PEG-b-PGA, PEG-b-PG-Cu a PEG-b-PG-CuL-1(2) can only be seen
in the fingerprint range (Fig. 1).
Herein our aim was to prepare and characterize recoverable
polymer–metal ion hybrid catalysts for the Henry reaction, based
on complexes of the Cu(II) salt of block copolymer
a-methoxy-
poly(ethylene glycol)-b-poly( -glutamic acid) (PEG-b-PGA) with
L
(2R,5S)- and (2S,5R)-5-isopropyl-5-methyl-2-(pyridine-2-yl)imi-
dazolidine-4-ones.1n It can be expected that the double hydrophilic
polymer functionalized in this way will create, in the reaction
medium, aggregated (micellar or vesicular) systems, that is, self-
organized micro- or nano-reactors. Another aim of our work was
to verify and evaluate the advantages of the newly suggested sys-
tem in comparison with the original catalyst.1n
2. Results and discussion
PEG-b-PGA was prepared by the well-known NCA method:9 the
ring-opening polymerization of
c-benzyl-L-glutamic acid N-carbox-
yanhydride, initiated by
a
-amino-x-methoxypoly(ethylene glycol)
Figure 1. FT-IR spectrum of PEG-b-PGA (a); PEG-b-PG-CuL-1 (b) and PEG-b-PG-Cu
(c).
(Mw = 5000). The results of the 1H NMR spectroscopy showed that
the poly(ethylene glycol) chain was statistically linked with 16
units of
c-benzyl-L-glutamic acid. The second reaction step was
Figure
2 presents the powder X-ray diffractograms of
deprotection of the
c
-carboxyl groups with hydrogen catalyzed
PEG-b-PG-Cu and PEG-b-PG-CuL-1(2), which are virtually identical
with the diffractogram of the starting polymer PEG-b-PGA. From
the diffractograms it can be seen that the copper(II) ions do not
form independent diffracting clusters but are dispersed in the
polymer PEG-b-PGA. The presence of a ligand in PEG-PG-CuL-1 or
in PEG-b-PG-CuL-2 does not cause any significant change in crystal
structure of the starting polymer PEG-b-PGA either.
by 10% Pd/C (20 bar, 25 °C, 10 h). The deprotection reaction course
was monitored by means of 1H NMR, using the disappearance of the
benzyl group signals at d 5.00 ppm (–O–CH2–C6H5, 2H) and at
7.33 ppm (–O–CH2–C6H5, 5H). The synthesized polymer PEG-b-
PGA (M = 6935 g mol–1) was purified by means of dialysis (MWCO
1000), and after lyophilization, it was characterized by means of
1H NMR, GPC, FT-IR, and microanalysis. The copper(II) salt of
The synthesized complexes PEG-b-PG-CuL-1 and PEG-b-PG-
CuL-2 form colloidal opalescent solutions in ethanol. The opales-
cence is caused by the formation of ethanol-soluble aggregates,
which were confirmed by means of dynamic light scattering
(DLS). Figure 3 presents the hydrodynamic size distribution of
the aggregates at the concentrations of PEG-b-PGACu-L-1:
25 mg mL–1 (189 3 nm) and 2.5 mg mL–1 (134 1 nm). It was
found that the size of the aggregates formed depends upon the
concentration of the polymeric complex in ethanol. This finding
corresponds to the presence of dynamic self-organized aggregates,
which can be arranged in both micellar and vesicular systems.6a
In the next part of our study, the prepared complexes
PEG-b-PG-CuL-1 and PEG-b-PG-CuL-2 were tested as recoverable
catalysts of the nitroaldol (Henry) reaction of benzaldehyde,
substituted benzaldehydes and 2,2-dimethylpropanal with nitro-
methane to give the corresponding 2-nitroalcohols (Table 1).
The Henry reaction took place in a colloid system containing the
corresponding aldehyde, nitromethane, ethanol, and catalyst. At a
concentration of 50 mg PEG-b-PG-CuL-1 in 2 mL of reaction mix-
ture, the average hydrodynamic size of the particles was
189 3 nm (DLS) (Fig. 3). The salt PEG-b-PG-Cu (6 mol %) alone
successfully catalyzed the Henry reaction of 2-methoxybenzalde-
hyde (92%); however, the enantioselectivity was negligible (ꢀ2%
ee), which is probably due to the relatively large distance between
a
-methoxypoly(ethylene glycol)-b-poly(L-glutamic)acid (PEG-b-
PG-Cu) was prepared by the reaction of an aqueous solution of
PEG-b-PGA with suspended copper(II) carbonate. The excess solid
copper(II) carbonate was removed by centrifuging, and the product
was isolated by lyophilization. The synthesized salt PEG-b-PG-Cu
was characterized by means of FT-IR (Fig. 1) and microanalysis,
with the copper content being determined by means of AAS. The
content of the copper(II) ions corresponds to one Cu(II) ion bound
to two carboxylic functional groups. According to earlier stud-
ies,9e,10 the peptide block of the salt PEG-b-PG-Cu in an aqueous
solution can assume either an
depending on the temperature and pH.
a-helix or random coil formation,
Subsequently, PEG-b-PG-Cu was dissolved in ethanol, and the
obtained solution was mixed with an ethanolic solution of (2S,5R)-
5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one (L-1)
or (2R,5S)-5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-
4-one (L-2). The amount of the added ligand L-1 or L-2 was
equivalent to the content of copper(II) (Scheme 1).
After the lyophilization, the synthesized catalysts PEG-b-PG-
CuL-1 and PEG-b-PG-CuL-2 were characterized by means of IR,
powder X-ray diffraction, microanalysis, and AAS. The FT-IR spec-
tra (Fig. 1) of PEG-b-PGA, PEG-b-PG-Cu, PEG-b-PG-CuL-1, and
PEG-b-PGA-CuL-2 are very similar and contain two bands: amide

336
D. S. Bhosale et al. / Tetrahedron: Asymmetry 25 (2014) 334–339
Scheme 1. Preparation of catalysts PEG-b-PG-CuL-1 and PEG-b-PG-CuL-2.
Figure 3. Hydrodynamic size distribution of aggregates at PEG-b-PG-CuL-1 con-
centrations: 25 mg mL–1 (solid line) and 2.5 mg mL–1 (dash line) in ethanol at 25 °C.
Figure 2. XRD patterns of PEG-b-PGA (a); PEG-b-PG-Cu (b) and PEG-b-PG-CuL-1(2)
(c).
methoxybenzaldehyde with nitromethane catalyzed by complex
PEG-b-PG-CuL-2 achieved a comparable yield (96%) and ee (91%);
however, it gave the product with an opposite configuration, that
is, (S)-1(2-methoxyphenyl)-2-nitroethanol.1n
the stereogenic center of poly(L-glutamic)acid and the Cu(II) ion.
Table 1 presents yields and enantiomeric excesses for the reactions
of the individual aldehydes in comparison with the literature,1n in
which the catalyst used was a combination of ligand L-1 and
copper(II) acetate. Table 1 shows that the application of catalyst
PEG-b-PG-CuL-1 (6 mol %) gave results comparable with the previ-
ous ones (entries 2 and 6). In some cases, the enantioselectivity
After the estimated reaction time, some ethanol was distilled
off, the distillation residue was mixed with diethyl ether, and the
precipitated solid catalyst was collected by centrifuging (Fig. 4).
The reaction products, that is, the respective functionalized 2-nit-
roalcohols, were obtained after distillation of combined diethyl
ether phases, centrifuging, and column chromatography. The
washed catalyst was dried in air at room temperature and then
reused.
was slightly decreased (entries 1 and 3;
D% ee: 6; 8). In the case
of the reactions of 4-bromobenzaldehyde and 4-phenylbenzalde-
hyde, the observed decrease in enantioselectivity was more signif-
Figure 5 shows a diagram of the change in yield and change in
enantiomeric excess attained in the individual cycles with
icant (Table entries 4 and 5;
D% ee: 14; 31). The reaction of 2-

D. S. Bhosale et al. / Tetrahedron: Asymmetry 25 (2014) 334–339
337
Table 1
repeated use of the catalyst PEG-b-PG-CuL-1 for the reaction of 2-
methoxybenzaldehyde with nitromethane. The data obtained
show that the catalyst does not exhibit any significant decrease
in enantioselectivity even after seven cycles (90–89% ee). Only a
very slight decrease was observed after more than eight cycles
(81–85% ee). On the other hand, the decrease in yield is more
significant, namely from 95% to 73% during the observed 10 cycles.
The yield decrease can be due to the mass loss of the catalyst
during recycling. In the first cycle, the amount of catalyst was
55 mg (6 mol %), and each subsequent cycle was connected
with a mild mass loss of the catalyst caused by handling (55 ?
53 ? 52 ? 50 ? 49 ? 47 ? 45 ? 43 ? 41 ? 39 mg; ca. 4 mol %).
Considering this fact, we studied the influence of the amount of
the catalyst (5; 2, and 0.5 mol%) on the Henry reaction of
2-methoxybenzaldehyde with nitromethane by determining the
conversion-time dependences (Fig. 6). The kinetic dependences
obtained show that the conversion decreases when decreasing
the amount of the catalyst.
Henry reaction of nitromethane with various aldehydes catalyzed by the L-1/
Cu(OAc)2 complex and recoverable catalyst PEG-b-PG-CuL-1
O
OH
catalyst (6 mol%)
EtOH, 10°C, 48 h
+
CH3NO2
NO2
*
A
H
A
a
Entry
Aldehyde
L-1/Cu(OAc)2
PEG-b-PG-CuL-1
Yieldb (%) eec (%)
98 84
A
Yieldb (%)
eec (%)
1
2
3
4
5
6
Ph
97
97
97
97
97
87
92
92
90
92
92
96
2-MeOC6H4
4-ClC6H4
4-BrC6H4
4-PhC6H4
t-Bu
96
91
89
98
70
90
84
61
78
92
a
b
c
The results were published1n in our previous work.
The values are yields of isolated substances after chromatographic purification.
The enantiomeric excesses determined by HPLC using Chiralcel OD-H or Chir-
alpak AD-H.
A further explanation for the conversion decrease after more
cycles can also be the lowering of chemical activity of the catalyst
during recycling. Therefore, we measured and compared the
kinetic dependences for the fresh catalyst and for the catalyst
which had been recycled ten times (Fig. 7). We found that the recy-
cled catalyst attained significantly lower conversion in whole time
range than the fresh catalyst. The results obtained can be summa-
rized that the observed decrease in conversion during the 10 cycles
(Fig. 5) was caused partly by the mass loss of catalyst and also by
the lowering of the chemical activity of the catalyst during the
recycling.
Figure 4. Principle of recycling of catalyst PEG-b-PG-CuL-1(2).
Figure 5. Proof of recoverability of PEG-b-PG-CuL-1 (up to 10 times) in the catalytic enantioselective Henry reaction of MeNO2 with 2-MeOC6H4CHO.
Figure 6. The time (h) dependence of conversion (%) of Henry reaction of MeNO2 with 2-MeOC6H4CHO catalyzed by different amounts of catalyst (PEG-b-PG-CuL-1):
5 mol % (ꢀ) 2 mol % (j) 0.5 mol % (N) at 10 °C.

338
D. S. Bhosale et al. / Tetrahedron: Asymmetry 25 (2014) 334–339
Figure 7. The time (h) dependence of conversion (%) of the Henry reaction of MeNO2 with 2-MeOC6H4CHO catalyzed by fresh catalyst (ꢀ) and catalyst after 10 cycles (j)
(PEG-b-PG-CuL-1, 3 mol %, 10 °C).
from 2° to 65° (2H) in 0.02° step with a counting time of 10 s
3. Conclusion
per step. The average particle size and size distribution of the
aggregates were determined by dynamic light scattering using a
Zetasizer Nano ZS (Malvern Instruments, UK). The measurements
were performed at the temperature of 25 °C with the scattering
angle of 173° using disposable sizing cuvettes in ethanol.
The results obtained confirmed that the synthesized complexes
PEG-b-PG-CuL-1 (L-2) catalyze the Henry reaction of functional-
ized aldehydes with nitromethane and give high chemical yields
(70–98%) and high enantioselectivity (61–92% ee). In contrast to
the original homogeneous complex of copper(II) acetate with (2R,
5S)-5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one,
the polymeric complex PEG-b-PG-CuL-1 (L-2) can be easily isolated
from the reaction mixture. Moreover, immobilization of the ligand
on the block copolymer enables the recovery of the catalyst from
the reaction mixture and its reuse. The achieved effectiveness
was very high even after several recycling steps (77% yield and
89% ee after 7 cycles). Only a minor decrease in the enantioselec-
4.2. Preparation of catalysts
4.2.1. Methoxypoly(ethylene glycol)-b-poly(
PEG-b-PGA
L
-glutamic acid)9
Mp 156–159 °C; 1H NMR: d 1.98 (m, CH2, 64H); 3.33 (s, CH3O,
3H); 3.43 (m, O–CH2CH2, 440H), 4.09 (m, CH, 16H); 8.21 (m, NH,
16H), 12.13 (bs, COOH, 16H) FT-IR:
m
/cmÀ1 3290, 2880, 1729,
1710, 1652, 1548, 1466, 1453, 1413, 1359, 1342, 1279, 1241,
1147, 1104, 1099, 1060, 962, 946, 842, 704, 607, 529, 509, 480,
412, 401; Mw/Mn = 1.28. Anal. Calcd for C301H557N17O158
(M = 6935 g mol–1) C, 52.02; H, 8.03; N, 3.43; Found: C, 51.83; H,
7.89; N, 3.64.
tivity (D9% ee) and the yield (D22%) was observed after ten cycles.
The kinetic dependences show that the conversion decrease is
caused by a lowered activity of the catalyst and also by the mass
loss of the catalyst during recycling.
4. Experimental
4.2.2. Methoxypoly(ethylene glycol)-b-poly(L-glutamic acid)
copper salt PEG-b-PG-Cu
4.1. Materials and methods
To a solution of PEG-b-PGA (693 mg; 0.1 mmol) in redistilled
water (30 mL) was added CuCO3 (248 mg; 2 mmol). After 24 h of
intensive mixing, the excess CuCO3 was removed by centrifuge
(3000 rpm; 30 min). The salt was isolated by lyophilization
The starting substances were purchased from Sigma–Aldrich.
Ethanol was dried over 4 Å molecular sieves before use. 1H NMR
spectra were recorded on
a Bruker Avance 400 instrument
(720 mg, 97%). FT-IR (KBr): m
/cmÀ1 3292, 2876, 1730, 1651, 1542,
(400.13 MHz for 1H). Chemical shifts d were referenced to a resid-
ual peak of the DMSO-d6 at 2.50 ppm. Gel permeation chromatog-
raphy’s HEMA-BIO columns (hydrophilic modification HEMAGel,
particle size 10 mm, porosity 40:100:300:1000) was used for the
estimation of Mw PEG-b-PGA at 25 °C using an RI detector. Redis-
tilled water (pH 7.1) was used as the eluent. The columns were cal-
ibrated with a series of standard PEGs (Merck) of various molecular
masses. The FT-IR spectra were measured in KBr pellets. The FT-IR
spectra of mulls were recorded in the region of 3500–700 cmÀ1 at
room temperature with a resolution of 4 cmÀ1 using an IFS-66/S
FT-IR spectrometer (Bruker, Germany). A demountable cell with
1466, 1409, 1359, 1341, 1279, 1241, 1144, 1099, 1060, 961, 946,
841, 818, 518, 509, 443, 426, 410; Anal. Calcdfor C301H541N17O158Cu8
(M = 7428 g mol–1) C, 52.02; H, 8.03; N, 3.43; Cu 6.85; Found: C,
51.83; H, 7.71; N, 3.70; Cu, 6.92.
4.2.3. PEG-b-PG-CuL-1 or PEG-b-PG-CuL-2
To a solution of PEG-b-PG-Cu (50 mg; 7
lmol) in anhydrous eth-
anol (5 mL) was added solution of L-1 or L-2 (12.2 mg;
a
0.023 mmol) in ethanol (5 mL). After 24 h, ethanol was removed
by distillation and the product was dried under vacuum (62 mg;
99%) FT-IR (KBr):
m
/cmÀ1 3293, 2873, 2358, 1716, 1652, 1608,
CaF2 windows and a 50 lm Teflon spacer was used. The microanal-
1544, 1466, 1402, 1359, 1341, 1279, 1241, 1144, 1099, 1060, 961,
947, 841, 765, 718, 571, 527, 519, 509, 461, 429, 409, 404. Anal.
Calcd for C397H677N41O166Cu8 (M = 9180 g molÀ1) C, 51.90; H,
7.37; N, 6.25; Cu, 5.55; Found: C, 52.23; H, 7.62; N, 6.36; Cu, 5.77.
yses were performed on an apparatus of FISONS Instruments, EA
1108 CHN. The determination of Cu was carried out with an Aavan-
ta P double beam atomic absorption spectrometer (GBC Scientific
Equipment Pty. Ltd, Australia) in the flame atomization mode.
Powder X-ray diffraction data (Cu K
on a D8 Advance diffractometer (Bruker AXS, Germany) with
Bragg–Brentano goniometer (radius 217.5 mm) equipped
with a secondary beam curved graphite monochromator and
Na(Tl)I scintillation detector. The generator was operated at
40 kV and 30 mA. The scan was performed at room temperature
a, k = 1.5418 Å) were collected
4.3. General procedure for the asymmetric Henry reaction
H–H
Complex PEG-b-PG-CuL-1 or PEG-b-PG-CuL-2 (55 mg, 6 lmol)
was stirred for 1 h in a mixture of ethanol (1.5 mL) and CH3NO2
(0.54 mL, 10 mmol). The solution was cooled to the appropriate

D. S. Bhosale et al. / Tetrahedron: Asymmetry 25 (2014) 334–339
339
(r) Drabina, P.; Karel, S.; Panov, I.; Sedlák, M. Tetrahedron: Asymmetry 2013, 24,
334–339.
temperature, and then the aldehyde (1 mmol) was added and the
mixture was stirred for 48 h. The solvents were removed under
reduced pressure, after which diethyl ether was added. The
catalyst was isolated by centrifugation (3000 rpm; 30 min) and
the crude catalyst was washed by diethyl ether (3 Â 2 mL). The
crude product was isolated after evaporation of the combined
diethyl ether phase and purified by column or flash chromatography
(AcOEt/hexane; 1:4 (v/v)). The enantiomeric excess was determined
by HPLC. The characterization data for all of the enantiomers of the
nitroalcohols were in accordance with the literature.1n
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Acknowledgement
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The authors acknowledge the financial support from the GACR
P106/11/058.
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