Recyclable catalyst for the asymmetric Henry reaction based on functionalized imidazolidine-4-one-copper(II) complexes supported by a polystyrene copolymer

Article abstract of DOI:10.1016/j.tetlet.2015.09.112

Imidazolidine-4-one derivatives were anchored by the thiol-ene click reaction to a swellable pearl-like polystyrene copolymer and their complexes with Cu(II) acetate were utilized as recyclable heterogeneous catalysts for the Henry reaction of substituted

Full text of DOI:10.1016/j.tetlet.2015.09.112

Tetrahedron Letters 56 (2015) 6240–6243
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Recyclable catalyst for the asymmetric Henry reaction based on
functionalized imidazolidine-4-one-copper(II) complexes supported
by a polystyrene copolymer
a
a,
⇑
a
b
a
Lydie Harmand , Pavel Drabina , Vladimír Pejchal , Lenka Husáková , Miloš Sedlák
a
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 May 2015
Revised 28 August 2015
Accepted 24 September 2015
Available online 28 September 2015
Imidazolidine-4-one derivatives were anchored by the thiol-ene click reaction to a swellable pearl-like
polystyrene copolymer and their complexes with Cu(II) acetate were utilized as recyclable heterogeneous
catalysts for the Henry reaction of substituted aldehydes with nitromethane. The corresponding 2-ni-
troethanols were mostly obtained in high yields (65–99%) and with enantioselectivities of up to 92%
ee. After a fivefold recycling of the catalyst, the decrease in enantioselectivity was negligible (
D 3% ee).
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Imidazolidine-4-one derivatives
Recyclable enantioselective catalyst
Henry reaction
Polystyrene
The asymmetric variant of the Henry reaction, between the
low stability against oxidation which is considered as a general
disadvantage for the long-term use of recyclable catalysts.
Therefore, we elected to anchor more stable chiral ligands based
on previously reported 2-(pyridine-2-yl)imidazolidine-4-one
derivatives to the above-mentioned pearl-like styrene copolymer.
Thus, the research presented herein describes the preparation
and characterization of these heterogeneous catalysts and an
examination of their catalytic efficiency and recyclability.
a
-carbon atom of an aliphatic nitro compound and the carbonyl
1
,2
carbon atom, produces up to two stereogenic centers.
The
prepared functionalized 2-nitroethanols represent important syn-
thetic building blocks that have been used in the syntheses of
many poly-functionalized compounds, especially pharmaceutical
1
i,2c,d
substances.
Implementation of this reaction necessitates the
presence of a suitable catalyst, frequently represented by Cu(II)
complexes based on enantiomerically pure ligands.1 However, a
disadvantage of most homogeneous catalysts consists of their dif-
ficult separation after reaction completion, which prevents their
reuse. In order to facilitate their isolation, purification and allow
recycling, a number of efficient homogeneous catalysts have been
,2
Among the 5-alkyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-
one derivatives described thus far, ligands based on the 5-isopropyl
and 5-tert-butyl derivatives represent the most catalytically effi-
cient variants when compared to the corresponding 5-benzyl
2
a,b,d
derivatives.
For this reason, (2R,5S)-5-isopropyl-5-methyl-2-
3
anchored to an heterogeneous carriers, including those suitable
(pyridine-2-yl)-3-(4-vinylbenzyl)imidazolidine-4-one (3a) and
(2S,5S)-5-isopropyl-5-methyl-2-(pyridine-2-yl)-3-(4-vinylbenzyl)-
imidazolidine-4-one (3b) were prepared (Scheme 1).
for the asymmetric Henry reaction.3 The key factor for the effi-
ciency of these heterogeneous catalysts has been determined as
the high swellability of a pearl-like polymeric carrier,6 which
for example include the copolymer of styrene, 4-vinylbenzyl
chloride and tetra(ethylene glycol)-bis(4-vinylbenzyl)ether (cross-
–5
,7
The synthesis of isopropyl derivatives 3a and 3b began with
easily
Hydrolysis
accessible
to the
(S)-2-amino-2,3-dimethylbutanamide.2
a
hydrochloride
of
(S)-2-amino-2,3-
5
linker 2%). Previously our group reported an immobilized copper
dimethylbutanoic acid was followed by treatment with phosgene
to give the corresponding N-carboxanhydride, (S)-4-isopropyl-4-
methyloxazolidine-2,5-dione (1). The 4-vinylbenzyl group was
next introduced in order to enable anchoring of the
imidazolidine-4-one fragment to the polymer by means of a
(
II) complex of (1R,2R)-1-amino-2-(2,3-dihydro-1H-isoindole-2-
yl)-1,2-diphenylethane as an efficient catalyst for the Henry
5
reaction. Unfortunately, this diamine-type catalyst displayed
8
thiol-ene click reaction. Reaction of N-carboxanhydride with 4-
9
⇑
Corresponding author. Tel.: +420 466 037 010; fax: +420 466 037 068.
E-mail address: pavel.drabina@upce.cz (P. Drabina).
vinylbenzylamine gave (S)-2-amino-2,3-dimethyl-N-(4-vinylben-
zyl)butanamide (2), which underwent acid-catalyzed ring-closure
http://dx.doi.org/10.1016/j.tetlet.2015.09.112
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0

L. Harmand et al. / Tetrahedron Letters 56 (2015) 6240–6243
6241
Scheme 1. Preparation of enantiomerically pure ligands 3a and 3b.
with pyridine-2-carbaldehyde to give a diastereomeric mixture of
a and 3b (1:4) which could be separated by column chromatogra-
3
phy. The configuration of the newly formed stereogenic center at
1
the 2-position of 3a and 3b was determined by H NMR NOESY
1
0
spectroscopy. The pearl-like copolymer ligand carrier was pre-
5
pared according to literature procedures and functional group
interchange of the chlorine for thiol was achieved by the reaction
with thiourea and subsequent hydrolysis of the isothiouronium
1
1
salt. Finally, the ligands were anchored to the modified polymer
by means of a thiol-ene click reaction (Scheme 2).8
Initially, the thermal variant of the thiol-ene click reaction, ini-
tiated by thermal decomposition of azobisisobutyronitrile (AIBN)
at reflux in toluene, was examined (Method A).8a However, since
heating of ligands 3a and 3b may be accompanied by
racemization,
a
second variant was also selected for
implementation (Method B). This photochemical reaction which
proceeded at 25 °C was initiated by the photo-induced
decomposition of 2,2-dimethoxy-2-phenylacetophenone (DPAP)
using a UV–visible lamp (kmax 365 nm, 40 W).8b Subsequently,
the modified polymers 4a and 4b were transformed by the
reaction with cupric acetate to give the corresponding catalyst
complex 5a and 5b (Scheme 2). The starting mercaptomethyl
polystyrene as well as polymers 4a and 4b and catalysts 5a and
Figure 1. Raman spectra of the mercapto-polystyrene (a); polymer 4a (b) and
catalyst 5a (c).
The synthesized catalysts were then tested in the Henry reac-
tion of nitromethane with various aldehydes in ethanol at 10 °C
(Table 1).
5
b were purified by extraction, and after drying, characterized by
12
microanalysis and Raman spectroscopy (Fig. 1). The nitrogen
contents in 4a and 4b indicated ligand loading on the polymer car-
First, we examined the catalytic activity of soluble complexes of
cupric acetate with ligands 3a,b which were prepared in situ. The
complex using ligand (2R,5S)-3a gave the corresponding 2-ni-
troethanols with the (R) configuration, whereas (2S,5S)-3b gave
À1
rier. The Raman band at 2572 cm (SAH stretching vibrations)
À1
and bands at 675 and 1251 cm
(CAS stretching vibrations)
typical for the SH group were observed and corresponded to the
mercaptomethyl polystyrene (Fig. 1a).11
A
new band at
1
products with an (S) configuration. The results given in Table 1
À1
1
703 cm (stretching vibration C@O) corresponded to polystyre-
(entries 1–8) showed that introduction of the 4-vinylbenzyl group
onto the 3-position of the imidazolidine skeleton led to an approx-
imate fourfold decrease of the reaction rate in comparison to the
nes 4a and 5a with grafted ligand 3a (Fig. 1b and c). The band at
À1
2
572 cm disappeared in the spectrum of 4a and 5a showing that
2
a
ligand 3a was well anchored to the polystyrene by a covalent bond
previously reported non-functionalized ligand. On the other
hand, imidazolidine-4-one (2S,5S)-3b bearing the 4-vinylbenzyl
group proceeded with high enantioselectivity (80–85% ee), in
comparison to the previously studied non-substituted (2S,5S)-
À1
via a ASA bridge. The new bands at 1410 and 1510 cm (COO
stretching symmetric and asymmetric vibrations), after coordina-
tion of copper(II) acetate, corresponded to the acetate functional
group in 5a (Fig. 1c). The Raman spectra of both 4a and 4b were
identical as well as the spectra of catalysts 5a and 5b.
2
a
derivative (25–27% ee); therefore 3b can be also considered for
immobilization.
Scheme 2. Preparation of catalysts 5a and 5b.

6
242
L. Harmand et al. / Tetrahedron Letters 56 (2015) 6240–6243
Table 1
Henry reaction of nitromethane with various aldehydes catalyzed by Cu(II) complexes
of 3a,b and polymeric catalysts 5a,b prepared by method A or B
a
b
eec,e
(%)
Entry
R
Catalyst
Time
days)
Conv /Yield
(%)
(
1
2
3
4
5
6
7
8
9
Ph
Ph
3a/Cu(OAc)
2
6
6
6
6
5
6
3
6
6
6
6
5
5
6
6
6
92 (78)
65 (59)
96 (81)
98 (80)
>99 (82)
98 (78)
89
À85
88
3b/Cu(OAc)
3a/Cu(OAc)
3b/Cu(OAc)
3a/Cu(OAc)
3b/Cu(OAc)
3a/Cu(OAc)
3b/Cu(OAc)
5a (A)
5a (B)
5b (A)
5b (B)
5a (B)
5b (B)
5a (B)
2
2-CH
2-CH
4-NO
4-NO
t-Bu
3
OPh
OPh
2
3
2
À80
2
Ph
Ph
2
81
2
2
À81
96
d
2
86
64
d
t-Bu
2
À82
2-CH
2-CH
2-CH
2-CH
4-NO
4-NO
t-Bu
3
OPh
OPh
OPh
OPh
35 (28)
59 (49)
48 (33)
99 (91)
>99 (87)
99 (80)
80
Figure 2. Recoverability of catalyst 5a (up to 5 times) in the catalytic enantiose-
lective Henry reaction of MeNO with t-BuCHO.
10
11
12
13
14
15
16
3
3
3
76
À42
À47
51
2
2
Ph
Ph
lidine-4-one (3b) were successfully anchored via the thiol-ene
click reaction to mercaptomethyl polystyrene to give recyclable
heterogeneous enantioselective catalysts 5a,b. The application of
these catalysts 5a,b to the Henry reaction resulted in some cases
to a decrease of enantioselectivity, which is commonly observed
2
À29
d
95
92
d
t-Bu
5b (B)
66
À69
a
Values of conversions were estimated by 1H NMR spectroscopy.
The yields of isolated products after chromatographic purification are in
parentheses.
The enantiomeric excess was determined by HPLC using a Chiralcel OD-H
column.
Only the chemical yields (not conversions) were determined due to the
volatility of pivaloyl aldehyde.
b
3
after immobilization of enantioselective catalysts. The use of
c
reagents on a polymeric carrier matrix did not practically affect
the observed catalytic activity and the conversions obtained with
supported catalysts 5a,b were comparable to the conversions
afforded by the analogous homogeneous catalysts 3a,b. Fivefold
recycling of the heterogeneous catalyst caused a significant
2a
d
e
The absolute configurations of prepared 2-nitroethanols were determined by
comparison to literature HPLC data.
decrease in yield (D 25%), but only a minor decrease of enantiose-
lectivity was observed. The newly synthesized 4-vinylbenzyl
ligands have high potential for the preparation of mechanically
robust monolithic columns for a flow reactor. The synthesized
ligands and catalysts possess a potential for application in the
Henry reaction.
Furthermore, we studied the catalytic activities of the heteroge-
neous polymer supported catalysts 5a,b (entries 9–16). In compar-
ison to the corresponding homogeneous catalysts, it was found
that in all cases, the enantioselectivity was decreased. On the other
hand, in most cases a decrease in conversion due to the presence of
the polymeric matrix was not observed. The largest difference in
enantioselectivity was observed between the homogeneous com-
plex of ligand 3b and heterogeneous catalyst 5b (B) for the reaction
of 4-nitrobenzaldehyde (entries 6 and 14). This decrease could
most likely be ascribed to the interaction of the electron-deficient
benzene ring of 4-nitrobenzaldehyde with the electron-rich
polymeric matrix which helped overcome the energetically less
advantageous transition states leading to the opposite enantiomer.
Acknowledgment
The authors acknowledge the financial support from the project
ˇ
GACR 14-00925S.
Supplementary data
Supplementary data (the synthetic procedures, NMR spectra
and HPLC data) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2015.09.112.
The smallest difference (
D 4% ee) was found for the reaction of
pivaloyl aldehyde with nitromethane catalyzed by complex 3b
and catalyst 5b (B) (entries 7 and 15). Moreover, we compared
the enantioselectivity differences of the catalysts prepared by
anchoring ligands using the thermal method 5a,b (A) (Method A)
and the photochemical method 5a,b (B) (Method B). The observed
difference in product enantiomeric purity in the case of the reac-
tion of 2-methoxybenzaldehyde catalyzed with 5b (A) and 5b (B)
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