Polystyrene copolymer supported by substituted (1R,2R)-1,2-diphenylethane- 1,2-diamine-copper(II) complexes: A recyclable catalyst for asymmetric Henry reactions Dedicated to Professor Vladimír Machá?ek on the occasion of his 70th birthday

Article abstract of DOI:10.1016/j.tetasy.2014.04.004

Herein described the preparation of swelling pearl-like copolymer styrene - 4-vinylbenzyl chloride cross-linked by means of tetra(ethylene glycol)-bis(4-vinylbenzyl)ether (200-800 μm). The pearl-like polymer was used to anchor (1R,2R)-1-amino-2-(2,3-dihyd

Full text of DOI:10.1016/j.tetasy.2014.04.004

Tetrahedron: Asymmetry 25 (2014) 775–780
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Polystyrene copolymer supported by substituted (1R,2R)-1,
2-diphenylethane-1,2-diamine-copper(II) complexes: a recyclable
catalyst for asymmetric Henry reactions
a
a,
⇑
a
b
c
a
Ladislav Androvi cˇ , Pavel Drabina , Illia Panov , Bo zˇ ena Frumarová , Andréa Kalendová , Miloš Sedlák
a
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
Institute of Macromolecular Chemistry, ASCR, Heyrovsky sq. 2, 16206 Prague, Czech Republic
Institute of Chemistry and Technology of Macromolecular Materials, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 March 2014
Accepted 3 April 2014
Herein described the preparation of swelling pearl-like copolymer styrene—4-vinylbenzyl chloride cross-
linked by means of tetra(ethylene glycol)-bis(4-vinylbenzyl)ether (200–800 m). The pearl-like polymer
l
was used to anchor (1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenylethane by a cova-
lent bond; the product was subsequently transformed into the corresponding complex with Cu(II) ace-
tate. The synthesized catalyst was used for the catalysis of the Henry reaction of functionalized
aldehydes with nitromethane in ethanol. The reactions proceeded in a polymeric matrix of the swelling
catalyst at a rate comparable with the rates of reactions in a homogeneous medium. The corresponding
functionalized 2-nitroethanols were formed in quantitative yields (20 °C, 24 h) with enantiomeric excess
values of up to 96%. The catalyst was recycled five times without losing its effectiveness with regard to
the yield and enantioselectivity; only a partial mechanical degradation of the polymeric matrix occurred
due to stirring.
Dedicated to Professor Vladimír Machá cˇ ek
on the occasion of his 70th birthday
Ó 2014 Elsevier Ltd. All rights reserved.
1
. Introduction
All of the aforementioned homogeneous catalysts cannot be
easily separated from the reaction mixtures, and thus means they
The reaction of aliphatic nitro compounds with aldehydes or
ketones (the Henry reaction), in which a covalent bond is formed
between the carbonyl carbon atom and the -carbon atom of the
cannot be reused. Therefore, the immobilization of homogeneous
catalysts represents a method to prepare heterogeneous catalysts
that are easily recyclable. These catalysts are often based on
4
a
nitro compound is one of the essential reactions of organic
chemistry. The asymmetric variant of this synthesis requires the
spherical particles of suitably functionalized styrene–divinylben-
zene copolymer (PS-DVB, Merrifield). A big advantage of immobi-
1
5
application of a suitable chiral, enantiomerically pure ligand,
frequently in combination with metal ions; Cu(II) complexes are
lized catalysts is their easy separation from reaction media, both in
batch-wise and flow-reactor arrangements. However, the applica-
6
1
,2
the most successful. The products of this reaction are enantiome-
rically pure 2-nitroethanols, which represent significant building
blocks designed for the synthesis of many pharmaceutical
tion of these catalysts can be limited by long reaction times and
thus also low conversions, which is due to the slow diffusion pro-
cesses during the transport of the reactants in the polymeric ma-
3
1g,i,3c
5c
products. Several recently published papers
the preparation and characterization of enantiomerically pure
functionalized 2-(pyridine-2-yl)imidazolidine-4-ones, whose
have described
trix of the catalysts. The increase in efficiency of polymeric
carriers is based on the incorporation of a suitable cross-linker, dif-
ferent from that present in the original polymer used by Merrifield.
From the standpoint of the diffusion rate of polar reagents, it has
proved to be advantageous to cross-link polystyrene by means of
complexes with Cu(II) acetate represent very efficient catalysts
for the Henry reaction (up to 96% ee). Analogous very efficient
catalysts of the Henry reaction also include Cu(II) complexes based
7
polytetrahydrofuran (PTHF) units or poly(ethylene glycol)
1
c
8
on derivatives of (1R,2R)-1,2-diphenylethane-1,2-diamine or on
(PEG). When incorporating ethylene glycol units, the resulting
functionalized (1R,2R)-cyclohexane-1,2-diamine.1e
polymeric carrier combines the advantages of soluble polymer
(
PEG) and insoluble polymer (PS-DVB). Another option of modifica-
tion consists of the modification of the surface of PS-DVB by means
⇑
Corresponding author. Tel.: +420 466 037 010; fax: +420 466 037 068.
E-mail address: pavel.drabina@upce.cz (P. Drabina).
of functionalized PEG (PEG-grafting, TentaGel™, ArgoGel™).8b
http://dx.doi.org/10.1016/j.tetasy.2014.04.004
957-4166/Ó 2014 Elsevier Ltd. All rights reserved.
0

7
76
L. Androvi cˇ et al. / Tetrahedron: Asymmetry 25 (2014) 775–780
However, the results summarized in a review article5c show that
the PEG-cross-linked swelling pearl-like polymers are better with
regard to the rate of catalysis, than the pearl-like polymers modi-
fied only superficially (PEG-grafting). The chosen network poly-
meric carrier should, first of all, possess a sufficient swelling
capacity, and at the same time, it should posses a sufficient
Merrifield™ and JandaJel™. These polymers were subjected to
the reaction with (1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-
2-yl)-1,2-diphenylethane and subsequently with Cu(II) acetate
(Scheme 1).
The catalysts prepared were further tested in the Henry reac-
tion of 2-nitrobenzaldehyde with nitromethane. However, in both
cases with the commercial polymers, the reaction was slow, that is,
only ca. 5% conversion was achieved after one-week of reaction at
room temperature. Therefore, we prepared another polymeric car-
rier based on a swelling pearl-like copolymer of styrene (ST) and
4-vinylbenzyl chloride (VBC) transformed into a network by means
of tetra(ethylene glycol)-bis(4-vinylbenzyl) ether (TEGBVBE).8 The
difference between the polymer prepared in this way and the
commercial polymers consists in the type and amount of the
cross-linker used in the polymerization. The cross-linker used in
our case is more polar than polytetrahydrofuran, which was used
9
mechanical resistance. For this reason, the content of the network
agent in the polymer plays a key role: it usually varies between ca.
8
,9
1
% and 2% w/w. Herein our aim was to prepare and characterize
a recyclable catalyst based on a modified pearl-like polystyrene,
which would be applicable to asymmetric Henry reactions. The
main requirement to be met by the catalyst was to achieve high
conversion in real time while maintaining high enantioselectivity,
comparable with that of the original homogeneous catalysts. The
easy preparation of the catalysts from commercially available com-
pounds was also important.
a
7
in the case of polymer of JandaJel™ type. The preparation of the
copolymer was carried out by the well-known methodology of
2
. Results and discussion
7
–10
suspension polymerization
(Scheme 2).
The experimental implementation of the suspension polymeri-
zation is affected by many physical and chemical factors and rep-
The homogeneous catalyst designed for immobilization needs
to attain excellent results in homogeneous media.4 The reference
catalyst chosen in our case was the complex of a Cu(II) acetate with
9
,10
resents a relatively complex system.
One of the key factors for
the successful implementation of suspension polymerization is
the choice of the stabilization phase. In our case, 88% poly(vinyl
alcohol) was successfully used for the preparation of the stabiliza-
tion phase. The remaining poly(vinyl acetate) (ꢀ12%) is adsorbed
on the surface of the pearls that are formed and minimizes their
gluing together, that is, the formation of conglomerates.9 The
content of the cross-linker (TEGBVBE) in the amount of monomers
(
1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenyl-
ethane, which was modified with (S)-2,2-dibromomethyl-1,
1
seen that this catalyst catalyzes the Henry reaction of 2-nitrobenz-
aldehyde with nitromethane to give the corresponding 2-nitroeth-
anol with 98% ee, with the yield being quantitative after 24 h at
room temperature. The next key step of the preparation of the
-binaphthalene (catalyst A).1c,6 From the literature it can be
1c
,10
4
–9
(
2% w/w) was chosen on the basis of data following from the earlier
immobilized catalyst was the choice of suitable polymer.
we tested the commercially available chloromethylated polymers
First
studies performed with model copolymers based on polystyrene
Cl
polymer
Cu(OAc)2
N
NH2
DMSO, 48 h, 50 °C
N
HN
CH3OH, 24 h, rt
N
H N
Cu
polymer
polymer
AcO
OAc
Scheme 1. Immobilization of (1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenylethane onto a polymeric carrier with subsequent complexation with Cu(II)
acetate.
O
Cl
Cl
O
O
O
Bz2O2, 85 °C, 16 h
+
O
O
chlorobenzene/H O, PVA
2
3
3
Cl
Cl
Cl
Scheme 2. Suspension polymerization of styrene (ST), 4-vinylbenzyl chloride (VBC), and tetra(ethylene glycol)-bis(4-vinylbenzyl) ether (TEGBVBE).

L. Androvi cˇ et al. / Tetrahedron: Asymmetry 25 (2014) 775–780
777
with different contents of cross-linkers derived from the series of
8
bis(4-vinylbenzyl) ethers. The content of the cross-linker used in
our case proved to be advantageous in particular from the stand-
point of the high swelling ability of the polymer and the concom-
itant easy diffusion of reagents. The swelling ability of the polymer
was determined by a simple method,11 and in the case of 96% eth-
anol, it represents 11 mL/1 g polymer. However, with a cross-linker
content lower than 2% w/w the polymer lost its mechanical
strength and began to disintegrate as early as the subsequent
extraction of the residual monomers, which is always performed
after the polymerization is finished. The content of chlorine in
the copolymer ST–VBC–TEG was determined by microanalysis
(
Cl, 5.84%; 1.65 mmol/g). The size of the prepared spheres was
determined by means of optical microscopy and varied in the
range of 200–800 m (Fig. 1).
l
Figure 2. Raman spectra of the polymer ST–VBC–TEG (a); polymer ST–VBC–TEG
with anchored (1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenyl-
ethane (b) and catalyst B (c).
We next tested the polymeric catalyst B in the Henry reaction of
functionalized aldehydes with nitromethane: the corresponding 2-
1
c
nitroethanols are formed in non-racemic form. The results ob-
tained were compared with those published on the homogeneous
1
c
catalyst A (Table 1).
The configuration of the obtained functionalized 2-nitroetha-
1
c
nols was established as (S) when using catalyst A. The enantio-
meric excess was determined chromatographically using the
1
g
method described earlier. The results given in Table 1 indicate
that the yields obtained with polymeric heterogeneous catalyst B
are comparable with those obtained with the reference catalyst A
in homogeneous media. The prepared pearl-like copolymer
ST–VBC–TEG is advantageous for the Henry reactions studied with
regard to the overall reaction rate. In this case, the prepared poly-
meric matrix represents a system, which minimally affects the
overall reaction rate by diffusion processes. The reagents easily
reach the catalytic center, and the reaction product is easily trans-
ported from the polymeric matrix to the solution. The observed
slight lowering of the enantioselectivity of catalyst B compared
with that of catalyst A can be explained by the substituent at the
2-amino group. The functionalization with (S)-2,2-dibromometh-
yl-1,1-binaphthalene leads to different steric requirements of the
chelating ligand, as in the case of the differently N,N-dialkylated
Figure 1. Microscopic picture of the prepared pearl-like copolymer ST–VBC–TEG.
In the next step, the enantiomerically pure ligand ((1R,2R)-1-
amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenylethane) was
anchored to the prepared polymer by means of a covalent bond.
The reaction was carried out by heating the solution of the ligand
in dimethyl sulfoxide (50 °C) with the suspended polymer
ST–VBC–TEG (Scheme 1). The nitrogen content was determined by
microanalysis to be 2.26%, which corresponded to 0.83 mmol ligand
per 1 g polymer. The last step of the preparation of catalyst B
consisted of the coordination of Cu(II) acetate onto the modified
polymeric carrier. After extraction and drying of catalyst B, its Cu
content was determined by means of AAS. The determined copper
content (5.21%) indicated that one Cu(II) ion was attached to
two nitrogen atoms. The prepared starting copolymer, that is,
ST–VBC–TEG, the copolymer with the anchored ligand and the poly-
meric catalyst B were further characterized by means of Raman
spectrometry (Fig. 2), which proved to be successful in the character-
ization of the PS copolymers and is often used in combinatorial syn-
1
5
cyclohexane-1,2-diamines. Another factor is that the reference
catalyst A possesses a higher number of stereogenic centers than
the prepared catalyst B. The immobilization of a homogeneous cat-
alyst often leads to a decrease in its enantioselectivity due to unde-
sirable interactions of the substrate with the relatively rigid
4
polymeric matrix. The application of polymeric catalyst B was
connected to a decrease in enantioselectivity by ca. 5% ee in the
case of benzaldehyde, by ca. 8–9% ee in the case of 2-methoxy-
benzaldehyde (entries 1 and 2), and by ca. 15% ee in the case of
2- and 4-nitrobenzaldehyde (entries 6 and 7). However, in the
cases of aliphatic aldehydes, that is, n-pentanal, cyclohexanecarb-
aldehyde, and pivaloyl aldehyde (entries 8–10), the results were
virtually identical with those obtained in the case of the homoge-
neous catalyst A. The higher enantioselectivity observed in the
reactions of aliphatic aldehydes can probably be explained by their
lower interaction with the polymeric matrix itself. In the case of
8
b
thesis. This spectroscopic method has the advantages of being
rapid, consuming small amount of samples, and being non-destruc-
1
2
À1
12
tive. The Raman bands near 677 cm
(C–Cl vibrations) and
À1
1
266 cm (CH –Cl wagging vibrations) can be seen in the spec-
2
trum of the prepared copolymer ST–VBC–TEG. The anchoring of
the ligand to the copolymer caused the total disappearance of these
À1
bands and the appearance of new bands near 1562 cm (N–H defor-
mation vibrations in secondary amines), and an increase in the
À1
intensity of the bands near 1073 cm
8
and between 750 and
aromatic aldehydes, it is possible that a p–p interaction between
00 cm (C–N stretching vibrations in tertiary amines).13 The fol-
À1
the substrate and aromatic polymer takes place. It is highly
probable that these interactions cause a decrease in the activation
energy of the reaction path leading to the opposite enantiomer,
which means a decrease in the enantioselectivity. The worst
4
lowing formation of the complex with Cu(II) acetate was accompa-
À1
nied by the formation of a new band near 1704 cm (vibration of
1
4
acetate ion, which is bonded to Cu(II) ion as a unidentate ligand ).

7
78
L. Androvi cˇ et al. / Tetrahedron: Asymmetry 25 (2014) 775–780
Table 1
Henry reaction of nitromethane with various aldehydes catalyzed by recoverable polymeric catalysts
O
OH
catalyst A or B
+
CH3NO2
NO2
R
H
5 mol %
R
Entry
R
Catalyst Aa
Yieldd (%)
Catalyst Bc
Yieldd (%)
Time (h)
eee (%)
Time (h)
eee (%)
1
2
3
4
5
6
7
8
9
Ph
120
72
94b
>99
—
—
—
>99
>99
95
92
96
91
95
—
—
—
98
93
93
93
97
24
24
24
24
24
24
24
24
24
24
>99
96
>99
>99
98
>99
>99
>99
98
86
90
82
84
76
82
79
90
93
96
6 4
2-MeOC H
4-CNC
4-ClC
4-PhC
2-NO
4-NO
n-C H
4 9
t-C
c-C
6
H
4
6
H
4
6
H
4
2
C
C
6
H
H
4
24
24
48
48
48
2
6
4
4
H
H
9
1
0
6
11
97
a
b
c
Results published in previous work.1c Reaction conditions: solvent – n-PrOH (0.6 mL); rt; aldehyde (0.3 mmol); nitroethane (0.16 mL).
°C, 120 h.
Reaction conditions: solvent – EtOH (1.5 mL); rt; aldehyde (1 mmol); nitroethane (0.54 mL).
The values are isolated yields after chromatographic purification.
0
d
e
The enantiomeric excess determined by HPLC using Chiralcel OD-H or Chiralpak AD-H.
enantioselectivity (76% ee) was obtained with 4-phenylbenzalde-
hyde (entry 5), that is, a substrate which has two benzene rings
and which presumably will exhibit the strongest p–p interactions.
We also tested the possibility of recycling the catalyst B for the
reaction of pivaloyl aldehyde with nitromethane. From Figure 3 is
obvious that after 5 reaction cycles, neither a change in the yield
Furthermore, we verified the efficiency of catalysts containing
other available anchored optically active amines complexed with
Cu(II) acetate: (1R,2R)-1,2-diphenylethane-1,2-diamine (catalyst
C; Fig. 4), (1R,2R)-cyclohexane-1,2-diamine (catalyst D; Fig. 4).
Catalysts C and D were prepared and characterized similarly as
in the case of catalyst B. Catalysts C and D were tested under the
same conditions as those used with catalyst B in the reaction of
2-methoxybenzaldehyde (24 h, 18 °C). It was found out that under
these conditions, quantitative conversions are achieved in both
cases, but the corresponding functionalized (1S)-2-nitro-1-pheny-
lethan-1-ol is formed with a distinctly lower enantiomeric excess
values: 76% ee (catalyst C) and 53% ee (catalyst D).
(
ꢀ98%) nor a change in enantioselectivity (ꢀ93% ee) occurs. How-
ever, after the fourth reaction cycle, a visible mechanical degrada-
tion of polymeric matrix of catalyst was observed.
3
. Conclusion
The prepared swelling pearl-like copolymer ST–VBC–TEG con-
taining 2% w/w cross-linker was used to anchor (1R,2R)-1-amino-
-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenylethane, which was
2
subsequently transformed into a complex by reaction with Cu(II)
acetate. The reactions of functionalized aldehydes with nitrometh-
ane, catalyzed by this catalyst, proceed quantitatively and with
high enantioselectivity of up to 96% ee. The transport of reagents
in a polymeric matrix of catalyst carrier almost does not affect
the observed reaction rate. The reaction proceeds at a rate compa-
rable with that observed with the analogous homogeneous cata-
lyst. A slight decrease in enantioselectivity was observed in the
reactions of aromatic aldehydes, which can be explained by the
Figure 3. Proof of recoverability of catalyst B (up to 5 times) in the catalytic
enantioselective Henry reaction of MeNO with t-C H CHO.
2 4 9
The observed degradation of catalyst B was caused by the
mechanical effect of the stirrer during the reaction. However, the
mechanical effect of the stirrer could be eliminated by the use of
a flow-reactor. However, such an arrangement of the reaction will
always require the preparation of a strictly monodispersion poly-
p–p interactions between the substrate and the aromatic polymer.
Catalyst B can be recycled at least five times without any loss of
yield or enantioselectivity. After fivefold recycling, mechanical
degradation of the polymeric matrix of the catalyst was observed
6
meric carrier.
N
N
H N
H
N
N
HN
H N
HN
2
2
Cu
Cu
Cu
polymer
Cu
polymer
polymer
AcO
OAc
AcO
OAc
AcO
OAc
AcO
OAc
A
B
C
D
Figure 4. Structure of catalysts A–D.

L. Androvi cˇ et al. / Tetrahedron: Asymmetry 25 (2014) 775–780
779
due to mechanical stirring, which can probably be eliminated by
placing the catalyst in a flow-reactor. The prepared polymeric cat-
alyst possesses great potential for Henry reactions.
1156 (m), 1183 (m), 1200 (sh), 1266 (m), 1328 (w), 1370 (sh),
1450 (m), 1584 (m), 1603 (s), 1613 (s), 2853 (w), 2906 (m), 2960
(sh), 2976 (sh), 3005 (w), 3037 (sh), 3054 (s).
4
.2.2. (1R,2R)-1-Amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-
4
4
. Experimental
diphenylethane
The compound was prepared according to the procedure de-
.1. General
1
c 1
scribed in the literature.
H NMR (CDCl
3
): d 2.11 (br s, 2H);
3
4
.00–4.10 (m, 5H); 4.56 (d, J = 8.3 Hz, 1H); 7.08–7.25 (m, 14H);
Unless otherwise stated, the starting chemicals and solvents
1
3
3
C NMR (CDCl ): d 16.6, 55.2, 56.1, 56.1, 63.3, 73.1, 122.2, 126.6,
were purchased from Sigma–Aldrich or Fluka and used without
further purification. The H NMR spectra were recorded on a Bru-
ker Avance 400 instrument (400.13 MHz for 1H). Chemical shifts
1
1
26.8, 127.2, 127.7, 127.9, 128.0, 129.9, 136.2, 139.7, 142.9;
2
0
[a
]
D
= +20.8 (c 0.6, CHCl
3
).
d were referenced to residual peak of the CDCl
C NMR spectra were calibrated with respect to the middle signal
3
at 7.26 ppm. The
1
3
4
.2.3. General method for the immobilization of the chiral
amines
The suspension of the polymer (500 mg) in a solution of
1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenyl-
in the multiplet of solvent (d = 77.23 ppm). The Raman spectra
were measured at room temperature using FT-IR spectrophotome-
ter IFS 55 provided with Raman FRA-106 accessory (Bruker) for
back scattering method. The YAG: Nd3+ laser line (1064 nm) was
(
1
c
ethane
300 mg) or (1R,2R)-cyclohexane-1,2-diamine in dimethyl sulfox-
ide (10 mL) was heated at 50 °C under an argon atmosphere for
(300 mg) or (1R,2R)-1,2-diphenylethane-1,2-diamine
À1
(
used for excitation. The resolution was 2 cm and the laser power
À1
was 50 mW. The FT-Raman data are presented in cm (w, weak;
4
8 h. After cooling, the polymer was washed with water (50 mL),
m, medium; s, strong; sh, shoulder). The morphology and grain size
of the pearl-like polymer ST–VBC–TEG were determined by means
of an optical microscope Nikon Eclipse LV100D with a detachable
head having high resolution power Nikon DS-Fi1 with software
NIS Elements AR. The scanning head allows color scanning; the res-
olution of the CCD chip is 5.07 Mpix. The microanalyses were per-
formed on an apparatus of FISONS Instruments, EA 1108 CHN. The
determination of Cu was carried out with an Aavanta P double
beam atomic absorption spectrometer (GBC Scientific Equipment
Pty. Ltd, Australia) in the flame atomization mode. Microwave
digestion of samples was carried out in the Speedwave TM
MWS-3+ (Berghof, Germany) microwave system with the maxi-
mum total output of the microwave generator 1450 W. Quantifica-
tion of Cu concentrations was performed by establishing a
calibration curve by linear regression. Optical rotations were mea-
sured on a Perkin–Elmer 341 instrument; the concentration c is gi-
ven in g/100 mL.
5
% aqueous solution of NaHCO (50 mL), water (50 ml), methanol
3
(
50 mL), and tetrahydrofuran (50 ml). Next, the polymer was ex-
tracted with tetrahydrofuran in a Soxhlet extractor for 24 h. The
modified copolymer was dried under reduced pressure at 25 °C.
4
.2.3.1. Copolymer supported by (1R,2R)-1-amino-2-(2,3-dihy-
dro-1H-isoindole-2-yl)-1,2-diphenylethane. Yield: 590 mg; ele-
mental composition: C, 84.14; H, 7.18; N, 2.32; Cl, 0.03; FT-Raman:
2
1
20 (w), 620 (m), 642 (m), 760 (w), 792 (sh), 810 (w), 843 (w),
002 (s), 1031 (m), 1073 (w), 1156 (m), 1182 (m), 1202 (sh), 1308
(w), 1327 (w), 1370 (sh), 1427 (sh), 1450 (m), 1584 (m), 1605 (s),
2853 (w), 2906 (m), 2976 (w), 3002 (w), 3037 (sh), 3055 (s).
4.2.3.2. Copolymer supported by (1R,2R)-1,2-diphenylethane-
1,2-diamine. Yield: 580 mg; elemental composition: C, 86.71; H,
7.92; N, 2.18; Cl, 0.04; FT-Raman: 221 (w), 620 (m), 642 (w), 651
(
w), 759 (sh), 809 (w), 836 (w), 1001 (s), 1030 (m), 1038 (sh),
1
1
2
3
156 (m), 1170 (sh), 1182 (m), 1201 (sh), 1324 (w), 1364 (sh),
415 (w), 1449 (m), 1582 (sh), 1601 (s), 1611 (sh), 1646 (w),
852 (w), 2908 (m), 2975 (w), 3003 (w), 3037 (sh), 3053 (s),
059 (sh).
4
.2. Synthesis
4
.2.1. Suspension polymerization (preparation of ST–VBC–TEG
polymer)
The preparation of a pearl-like copolymer by suspension poly-
merization was performed according to the literature7 in a de-
,8a
4
.2.3.3. Copolymer supported by (1R,2R)-cyclohexane-1,2-dia-
mine. Yield: 560 mg; elemental composition: C, 84.63; H, 7.54;
N, 2.43; Cl, 0.03; FT-Raman: 220 (w), 620 (m), 642 (m), 760 (w),
fined apparatus of 500 mL volume, equipped with a floating stir
8
a
bar. The vessel was charged with a solution of sodium chloride
5 g) and poly(vinyl alcohol) (88% hydrolyzed polymer; M = 85–
24 kDa) (8 g) in water (200 mL), followed by a solution of benzoyl
peroxide (200 mg; 0.8 mmol), 4-vinylbenzyl chloride (1.96 g;
2.8 mmol), styrene (4 g; 27.6 mmol), and tetra(ethylene glycol)-
bis(4-vinylbenzyl) ether (120 mg; 0.32 mmol) in chlorobenzene
5 mL). The stirrer was adjusted at a rate of 600 rpm, and the tem-
perature of the reaction mixture was increased to 85 °C during
0 min. The obtained suspension of spherical particles of organic
phase was continuously stirred and kept at 85 °C for a period of
4 h. After cooling, the obtained pearl-like copolymer was col-
lected by filtration and washed with water (50 mL), methanol
1
1
1
3
002 (s), 1031 (m), 1073 (w), 1156 (m), 1182 (m), 1202 (sh),
308 (w), 1327 (w), 1370 (sh), 1427 (sh), 1450 (m), 1584 (m),
605 (s), 2853 (w), 2906 (m), 2976 (w), 3002 (w), 3037 (sh),
055 (s).
(
1
1
4
.2.4. General method of preparation of the catalysts
(
The copolymer was stirred with the corresponding anchored
diamine (500 mg) in a solution of Cu(II) acetate (50 mg) in metha-
nol (20 mL) at room temperature for 48 h. After filtration and
washing with methanol (3 Â 5 mL), the catalyst was extracted with
methanol in a Soxhlet extractor for 24 h and then dried under
reduced pressure at 25 °C.
3
2
(
(
3 Â 50 mL), acetonitrile (3 Â 50 mL), and tetrahydrofuran
3 Â 50 mL). Next, the polymer was extracted in Soxhlet extractor
4
.2.4.1. Catalyst B—copolymer supported by (1R,2R)-1-amino-2-
for 24 h with a mixture of acetonitrile and water (3:1) and 48 h
with tetrahydrofuran. The prepared pearl-like polymer (200–
(
2,3-dihydro-1H-isoindole-2-yl)-1,2-diphenylethane-Cu(OAc)
2
.
Yield: 580 mg; elemental composition: C, 83.29; H, 7.14; N, 2.22;
Cu, 5.21; FT-Raman: 217 (w), 620 (m), 642 (m), 760 (w), 792
8
00
lm) was dried under reduced pressure at 40 °C. The yield
was 5 g polymer of elemental composition: C, 83.62; H, 7.40; Cl,
.84; FT-Raman: 215 (w), 409 (w), 620 (m), 641 (m), 677 (m),
48 (w), 792 (sh), 811 (sh), 836 (w), 908 (w), 1002 (s), 1031 (m),
(
1
sh), 806 (w), 843 (w), 1002 (s), 1031 (m), 1073 (w), 1156 (m),
169 (sh), 1182 (m), 1203 (sh), 1306 (w), 1323 (w), 1370 (sh),
5
7

7
80
L. Androvi cˇ et al. / Tetrahedron: Asymmetry 25 (2014) 775–780
1
427 (sh), 1450 (m), 1584 (m), 1605 (s), 1704 (m), 2853 (w), 2906
determined by HPLC. The characterization data for the enantiomers
of the nitroalcohols were in accordance with the literature.1
(
m), 2976 (w), 3002 (w), 3037 (sh), 3055 (s).
4
.2.4.2. Catalyst C—copolymer supported by (1R,2R)-1,2-diphen-
ylethane-1,2-diamine-Cu(OAc) . Yield: 560 mg; elemental com-
position: C, 82.77; H, 7.56; N, 2.06; Cu, 5.32; FT-Raman: 223 (w),
Acknowledgment
2
The authors acknowledge the financial support from the project
ˇ
4
8
09 (w), 621 (m), 641 (w), 708 (w), 789 (sh), 792 (w), 811 (w),
41 (w), 909 (w), 1002 (s), 1031 (m), 1156 (m), 1182 (m), 1199
GACR 14-00925S.
(
(
3
sh), 1305 (sh), 1325 (w), 1369 (sh), 1450 (m), 1526 (w), 1583
m), 1602 (s), 2851 (w), 2905 (s), 2976 (w), 3001 (w), 3036 (sh),
053 (s), 3059 (sh).
References
1.
(a) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. T.; Downey, C. W. J.
Am. Chem. Soc. 2003, 125, 12692–12693; (b) Sedlák, M.; Drabina, P.; Keder, R.;
Hanusek, J.; Císa rˇ ová, I.; R u˚ zˇ i cˇ ka, A. J. Organomet. Chem. 2006, 691, 2623–2630;
(c) Arai, T.; Watanabe, M.; Yanagisawa, A. Org. Lett. 2007, 9, 3595–3597; (d)
Blay, G.; Domingo, L. R.; Hernández-Olmos, V.; Pedro, J. R. Chem. Eur. J. 2008, 14,
4
.2.4.3. Catalyst D—copolymer supported by (1R,2R)-cyclohex-
ane-1,2-diamine-Cu(OAc)
tion: C, 83.89; H, 7.36; N, 2.09; Cu, 4.86; FT-Raman: 218 (w), 410
2
. Yield: 550 mg; elemental composi-
4725–4730; (e) Constable, E. C.; Zhang, G.; Housecroft, C. E.; Neuburger, M.;
Schaffner, S.; Woggon, W.-D. New J. Chem. 2009, 33, 1064–1069; (f) Jones, M.
D.; Cooper, C. J.; Mahon, M. F.; Raithby, P. R.; Apperley, D.; Wolowska, J.;
Collison, D. J. Mol. Catal. A 2010, 325, 8–14; (g) Panov, I.; Drabina, P.; Pad eˇ lková,
Z.; Šim u˚ nek, P.; Sedlák, M. J. Org. Chem. 2011, 76, 4787–4793; (h) Tydlitát, J.;
Bureš, F.; Kulhánek, J.; Mlosto n´ , G.; R u˚ zˇ i cˇ ka, A. Tetrahedron: Asymmetry 2012,
23, 1010–1018; (i) Drabina, P.; Karel, S.; Panov, I.; Sedlák, M. Tetrahedron:
Asymmetry 2013, 24, 334–339; (j) Ananthi, N.; Velmati, S. Indian J. Chem., Sect B
(
(
(
(
(
w), 621 (m), 642 (w), 772 (sh), 800 (w), 842 (w), 1002 (s), 1032
m), 1076 (w), 1117 (w), 1155 (m), 1181 (m), 1198 (sh), 1327
w), 1372 (w), 1408 (w), 1445 (sh), 1450 (m), 1562 (sh), 1583
m), 1602 (s), 1642 (sh), 2856 (w), 2910 (m), 2930 (sh), 2976
w), 3000 (w), 3037 (sh), 3051 (s).
2013, 52, 87–108; (k) Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N. C.
Tetrahedron: Asymmetry 2006, 17, 3315–3326; (l) Palomo, C.; Oiarbide, M.;
Laso, A. Eur. J. Org. Chem. 2007, 2561–2574.
4
.2.4.4. Merrifield supported by (1R,2R)-1-amino-2-(2,3-dihy-
dro-1H-isoindole-2-yl)-1,2-diphenylethane-Cu(OAc) . Yield: 555
mg; elemental composition: C, 82.49; H, 7.59; N, 2.25; Cu, 2.38; FT-
Raman: 210 (w), 621 (m), 640 (m), 799 (w), 842 (w), 1001 (s), 1030
2
2. (a) Maggi, R.; Lanari, D.; Oro, C.; Sartori, G.; Vaccaro, L. Eur. J. Org. Chem. 2011,
551–5554; (b) Angulo, B.; García, J. I.; Herrerías, C. I.; Mayoral, J. A.; Minana, A.
5
C. J. Org. Chem. 2012, 77, 5525–5532; (c) Bandini, M.; Benaglia, M.; Sinisi, R.;
Tommasi, S.; Umani-Ronchi, A. Org. Lett. 2007, 11, 2151–2153; (d) Bhosale, D.
S.; Drabina, P.; Palar cˇ ík, J.; Hanusek, J.; Sedlák, M. Tetrahedron: Asymmetry 2014,
(
1
(
m), 1155 (m), 1182 (m), 1198 (m), 1209 (sh), 1328 (w), 1331 (w),
416 (w), 1445 (m), 1581 (m), 1603 (s), 1607 (sh), 2853 (w), 2913
m), 3004 (w), 3037 (sh), 3052 (s).
2
5, 334–339.
(a) Guo, Z.-L.; Deng, Y.-Q.; Zhong, S.; Lu, G. Tetrahedron: Asymmetry 2011, 22,
395–1399; (b) Arai, T.; Taneda, Y.; Endo, Y. Chem. Commun. 2010, 7936–7938;
c) Panov, I.; Drabina, P.; Hanusek, J.; Sedlák, M. Synlett 2013, 1280–1282.
Jimeno, C.; Sayalero, S.; Pericàs, M. A. In Heterogenized Homogenous Catalysts for
Fine Chemicals Production: Covalent Heterogenization of Asymmetric Catalysts on
Polymers and Nanoparticles; Barbaro, P., Liguori, F., Eds.; Springer Science and
Business Media: Dordrecht, 2010; pp 123–170.
3
4
.
.
1
(
4
.2.4.5. JandaJel supported by (1R,2R)-1-amino-2-(2,3-dihy-
dro-1H-isoindole-2-yl)-1,2-diphenylethane-Cu(OAc) Yield:
50 mg; elemental composition: C, 83.96; H, 7.62; N, 1.81; Cu,
2
.
5
1
7
1
1
2
5.
(a) Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149–2154; (b) McNamara, C. A.;
Dixon, M. J.; Bradley, M. Chem. Rev. 2002, 102, 3275–3300; (c) Kristensen, T. E.;
Hansen, T. Eur. J. Org. Chem. 2010, 3179–3204.
.86; FT-Raman: 220 (w), 409 (w), 620 (m), 642 (w), 799 (w),
01 (w), 759 (w), 795 (w), 809 (w), 841 (w), 905 (w), 1001 (s),
031 (m), 1070 (w), 1097 (sh), 1155 (m), 1182 (m), 1198 (sh),
327 (w), 1450 (w), 1583 (m), 1602 (s), 2852 (w), 2903 (m),
975 (m), 3001 (w), 3037 (sh), 3052 (s), 3163 (w), 3198 (w).
6. Arai, T.; Watanabe, M.; Fujiwara, A.; Yokoyama, N.; Yanagisawa, A. Angew.
Chem., Int. Ed. 2006, 45, 5978–5981.
7
8
.
.
Toy, P. H.; Janda, K. D. Tetrahedron Lett. 1999, 40, 6329–6332.
(a) Wilson, M. E.; Paech, K.; Zhou, W.-J.; Kurth, M. J. J. Org. Chem. 1998, 63,
5094–5099; (b) Grøtli, M.; Gotfredsen, C. H.; Rademann, J.; Buchardt, J.; Clark,
4
.3. General procedure for the asymmetric Henry reaction
A. J.; Duus, J. Ø.; Meldal, M. J. Comb. Chem. 2000, 2, 108–119.
Goodall, A. R.; Greenhill-Hooper, M. J. Macromol. Chem. Symp. 1990, 35–6, 499–
9.
5
07.
0. Dowding, P. J.; Vincent, B. Colloids Surf., A 2000, 161, 259–269.
11. Bouillon, I.; Soural, M.; Miller, M. J.; Krch nˇ ák, V. J. Comb. Chem. 2009, 11, 213–
15.
One of the catalysts (0.05 mmol Cu(II)) was stirred for 1 h in a
1
3 2
mixture of ethanol (1.5 mL) and CH NO (0.54 mL, 10 mmol). The
2
solution was cooled to the appropriate temperature, and then the
aldehyde (1 mmol) was added and the mixture was stirred for 24
h. The solvents were removed under reduced pressure, and diethyl
ether was added. The catalyst was isolated by filtration and washed
with ethanol (1 Â 2 mL) and diethyl ether (2 Â 2 mL). The crude
product was isolated after evaporation of the combined ethanol
and diethyl ether phase and purified by column or flash chromatog-
raphy (AcOEt/hexane; 1:4 (v/v)). The enantiomeric excess was
12. Altava, B.; Burguete, M. I.; García-Verdugo, E.; Luis, S. V.; Vicent, M. J.
Tetrahedron 2001, 57, 8675–8683.
13. Socrates, G. Infrared and Raman Characteristic Group Frequencies: Tables and
Charts, 3rd ed.; John Wiley & Sons: Chichester, 2001.
1
4. Nakamoto, K. Infrared and Raman Spectra of Inorganic and Coordination
Compounds. Part B: Applications in Coordination, Organometallic, and
Bioinorganic Chemistry, 5th ed.; John Wiley & Sons: New York, 1997.
15. Chunhong, Z.; Liu, F.; Gou, S. Tetrahedron: Asymmetry 2014, 25, 278–283.