Recyclable Enantioselective Catalysts Based on Copper(II) Complexes of 2-(Pyridine-2-yl)imidazolidine-4-thione: Their Application in Asymmetric Henry Reactions

Article abstract of DOI:10.1002/adsc.201600198

This paper describes the preparation of enantioselective catalysts based on derivatives of imidazolidine-4-thione and their subsequent anchoring by means of a sulfur atom on a polymeric carrier. First, we verified the catalytic activity and enantioselecti

Full text of DOI:10.1002/adsc.201600198

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DOI: 10.1002/adsc.201600198
Recyclable Enantioselective Catalysts Based on Copper(II)
Complexes of 2-(Pyridine-2-yl)imidazolidine-4-thione: Their
Application in Asymmetric Henry Reactions
a
a,
b
a
ˇ
ˇ
Gabriela Novꢀkovꢀ, Pavel Drabina, * Bozena Frumarovꢀ, and Milos Sedlꢀk
a
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentskꢀ 573,
532 10 Pardubice, Czech Republic
Fax : (+420)-466-037-068; Phone: (+420)-466-037-010; e-mail: pavel.drabina@upce.cz
Institute of Macromolecular Chemistry of Czech Academy of Sciences, v.v.i., Heyrovskꢁho nꢀm. 2, 16206 Prague, Czech
Republic
b
Received: February 23, 2016; Revised: April 18, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600198.
Abstract: This paper describes the preparation of over, the possibility of their separation and reuse
enantioselective catalysts based on derivatives of was studied. It was found that all the prepared im-
imidazolidine-4-thione and their subsequent anchor- mobilized catalysts are highly enantioselective (up to
ing by means of a sulfur atom on a polymeric carrier. 97% ee). Their recycling ability was tested in Henry
First, we verified the catalytic activity and enantiose- reaction of 2-methoxybenzaldehyde with nitrome-
lectivity in the Henry reaction of the homogeneous thane. It was found that they can be recycled more
variants of the catalysts, i.e., the copper(II) com- than ten times without any decrease of their enantio-
plexes of 2-(pyridine-2-yl)imidazolidine-4-thiones selectivity. Therefore, they present a better means of
and
4-benzylsufanyl-2-(pyridine-2-yl)imidazolines catalysis than the original copper(II) complexes of
themselves. It was found that these catalysts exhibit imidazolidine-4-ones from both economic as well as
high enantioselectivity (up to 98% ee). Subsequently, ecological points of view. Thus, such immobilized
the imidazolidine-4-thione catalysts were immobi- catalysts exhibit high application potential for the
lized by anchoring to polymeric carriers based on asymmetric Henry reaction.
a copolymer of styrene and 4-vinylbenzyl chloride.
These heterogeneous catalysts were analogously Keywords: asymmetric catalysis; enantioselectivity;
tested with regard to their catalytic activity and heterogeneous catalysis; immobilization; supported
enantioselectivity in the Henry reaction, and more- catalysts
Introduction
anchoring to an easily separable solid carrier. Suitable
carriers of homogeneous catalysts include, e.g., poly-
During the last two decades, a considerable number mers soluble in the reaction medium or spherical
of homogeneous enantioselective catalysts has been highly swelling polymers;[2g] furthermore, the group
developed, with the aim to enable the preparation of involves different types of inorganic carriers.[2h] How-
various chiral compounds having high optical purity.[1] ever, each of these types of carriers has both more or
However, the main disadvantage of these homogene- less serious advantages and disadvantages.[2]
ous catalysts is often a limited possibility of separa-
In the case of our original enantioselective cata-
tion and recycling which would be highly desirable lysts[3] for the asymmetric Henry reaction based on
with regard to their price and (in many cases) toxicity, copper(II) complexes of 2-(pyridine-2-yl)imidazoli-
i.e., with respect to the economic and ecological as- dine-4-one derivatives, we have recently studied their
pects of the catalytic process. This problem can gener- anchoring on three types of carriers: the block copo-
ally be solved by modification of homogeneous cata- lymer methoxypoly(ethylene glycol)-b-poly(l-gluta-
lysts into more easily separable forms (e.g., using a re- mic acid),[4] the pearl-type swelling copolymer poly-
lease-capture strategy,[2a,b] by employing their insolu-
ACHTUNGTREN[NUGN styrene-co-4-vinylbenzyl chloride-co-tetra(ethylene
bility in appropriate solvents[2c–f]) or application of im- glycol)-bis(4-vinylbenzyl) ether)][5] and the magnetic
mobilization of the homogeneous catalyst – its nanoparticles Fe3O4@SiO2.[6] However, in all the cases
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Scheme 2. Synthesis of ligands 2a-b and 3a-b.
one ligand 2a and/or 2b was (S)-2-amino-2,3-dime-
thylbutanethioamide (1). This thioamide was pre-
pared by thionation of the corresponding optically
pure amide using the procedure described for prepa-
ration of racemic compound 1.[8b] The subsequent
acid-catalyzed condensation of aminothioamide
1 with 2-acetylpyridine gave the required mixture of
epimeric imidazolidine-4-thiones 2a and 2b with the
Scheme 1.
we observed a certain decrease in enantioselectivity total yield of 66% (Scheme 2). The separation of indi-
as well as in catalytic activity of immobilized catalysts vidual epimers 2a and 2b was carried out by column
as compared with the original homogeneous forms. chromatography; the individual forms were present in
This fact challenged us to continue in the search lead- the ratio of ca 1.3/1.0 (2a/2b).
ing to an increase of these key parameters of the
enantioselective catalyst.
The absolute configuration at the stereogenic
centre in the 2-position of imidazolidine-4-thione de-
The new strategy of immobilization of 2-(pyridine- rivatives 2a and 2b was determined by means of
2-yl)imidazolidine-4-one derivatives consists in 1H NMR 1D NOESY spectroscopy, when the selec-
a simple modification of their structure – isolobal re- tive excitation of protons of the methyl group at the
placement of the oxygen atom in imidazolidine-4-one positions 2 and/or 5 of the imidazolidine-4-thione
cycle by sulfur – which allows anchoring of the ligand cycle either resulted in a positive increase of intensity
to a polymeric carrier (e.g., MerrifiedTM resin, Janda- of signal of the opposite methyl group (2S,5S – 2b), or
JelTM resin, etc.)[7] by means of an alkylation reaction the intensity did not increase (2R,5S – 2a). The abso-
À
involving formation of
a
covalent C S bond lute configuration determined on stereogenic centres
(Scheme 1). Thus, the aim of this present research of derivatives 2a and 2b in this way was in accordance
was the verification of the catalytic activity and enan- with the earlier findings:[3,9] during chromatographic
tioselectivity of both copper(II) complexes of newly separation, the derivatives with trans arrangement in
prepared 2-(pyridine-2-yl)imidazolidine-4-thione de- the imidazolidine-4-one cycle have a higher Rf factor.
rivatives and their immobilized forms in the asymmet- This phenomenon was observed in the cases of all of
ric Henry reaction and, furthermore, the effect of the earlier prepared 2-(pyridine-2-yl)imidazolidine-4-
multiple recycling of the anchored catalysts upon ones[3] as well as other chiral imidazolidine-4-one de-
these parameters.
rivatives, e.g., the MacMillan catalysts.[9]
The synthesized imidazolidine-4-thiones 2a and 2b
were stable to atmospheric oxygen and in aqueous
medium. However, it was found that in acid medium
the epimerization transformation of 2a into 2b and
Results and Discussion
The key intermediate in the preparation of the sulfur vice versa took place. This racemization process was
analogue of chiral 2-(pyridine-2-yl)imidazolidine-4- probably connected with acid-catalyzed opening of
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Table 1. Survey of experiments on the asymmetric Henry re-
action of nitromethane with aldehydes catalyzed by homo-
geneous catalysts Cu(OAc)2/2a and Cu(OAc)2/2b.
thiones 2a and 2b was studied in the asymmetric
Henry reaction. The main aim was verification of
their enantioselectivity and comparison with the earli-
er studied oxygen analogues – copper(II) complexes
of 2-(pyridine-2-yl)imidazolidine-4-ones.[3] The set of
aldehydes and reaction conditions were chosen with
the respect to the possibility of such comparison.
Table 1 and Table 2 summarize the attained conver-
sion values and optical yields for the individual alde-
hydes.
En-
try
R
2a
2b
Conv.[a] [%] ee[b] Conv.[a] [%] ee[b]
(Yield [%]) [%] (Yield [%]) [%]
Whereas the catalysis with complex of (2R,5S)-2a
gave the corresponding 2-nitroethanols with the R-
configuration in excess, the application of complex of
(2S,5S)-2b gave the products with the S-configuration
in excess. The ee values of products show that the
enantioselectivity of copper(II) complex of ligand 2a
is high (88–97% ee) and comparable with that of the
analogous complex of (2R,5S)-5-isopropyl-2,5-dimeth-
yl-2-(pyridine-2-yl)imidazolidine-4-one.[3a] Also the
conversion values under the given conditions were
high (67–99%). Surprisingly, the copper(II) complex
of the cis-form of the ligand [Cu(OAc)2/2b] also ex-
hibited a high enantioselectivity (70–94% ee), where-
as the oxygen analogue (derivative of imidazolidine-
4-one) did not reach such satisfactory results (for ben-
1
2
3
4
5
6
7
8
9
Ph
88 (80)
90
90
89
84
89
97
91
88
94
59 (48)
82 (76)
53 (50)
94 (86)
41 (33)
(58)
28 (15)
50 (42)
43 (31)
À85
À87
À75
À70
À84
À94
À84
À83
À84
2-CH3OC6H4 99 (95)
4-ClC6H4
4-NO2C6H4
4-PhC6H4
t-Bu
thien-2-yl
naphth-2-yl
PhCH2CH2
94 (86)
99 (91)
90 (77)
(98)
67 (53)
92 (85)
85 (74)
[a]
The conversion was determined by 1H NMR of crude
product.
The enantiomeric excess was determined by HPLC using
a Chiralcel OD-H or Chiralpak AD-H column.
[b]
imidazolidine-4-thione cycle giving the corresponding zaldehyde 23% ee).[3a] In the case of aromatic alde-
Schiff base and its subsequent recyclization. The de- hydes containing electron-donating groups (experi-
scribed process was not observed in the case of earlier ments 1, 2, 5 and 7) with the application of complex
prepared 2-(pyridine-2-yl)imidazolidine-4-one deriva- Cu(OAc)2/2b, the attained enantioselectivity was
tives,[3] but epimerization of the MacMillan catalysts higher (84–87% ee) than that obtained with aldehydes
at the 2-position by action of Yb(OTf)3 (1 mol%) in containing electron-withdrawing groups (experiments
chloroform under reflux (8 h) was observed.[9] For this 3 and 4; 75% and 70% ee, respectively). High ee
reason, it was necessary to carry out all handling with values were attained with aliphatic aldehydes (experi-
ligands 2a and 2b in neutral or basic medium, where ments 6 and 9). The conversions in the case of com-
this epimerization does not take place.
plex Cu(OAc)2/2b were considerably variable (28–
The catalytic activity of the in situ prepared cop- 94%) and they strongly depended on the reactivity/
per(II) complexes of 2-(pyridine-2-yl)imidazolidine-4- electrophilicity of the individual aldehyde used. These
Table 2. Survey of experiments on the asymmetric Henry reaction of nitroethane with aldehydes catalyzed by homogeneous
catalysts Cu(OAc)2/2a and Cu(OAc)2/2b.
R
2a
Conv.[a][%] (Yield [%])
dr[a] [%] (anti/syn)
ee[b] [%] (anti)
ee[b] [%] (syn)
Ph
86 (72)
89 (80)
46:54
65:35
76
84
92
76
2-CH3OC6H4
2b
Conv.[a] [%] (Yield [%])
dr[a] [%] (anti/syn)
ee[b] [%] (anti)
ee[b] [%] (syn)
Ph
97 (88)
99 (79)
48:52
67:33
À80
À83
À91
À91
2-CH3OC6H4
[a]
1
The conversion and dr were determined by H NMR of the crude product.
The enantiomeric excess was determined by HPLC using a Chiralpak AS-H column.
[b]
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Table 3. Survey of experiments on the asymmetric Henry re-
action of nitromethane with aldehydes catalyzed by homo-
geneous catalysts Cu(OAc)2/3a and Cu(OAc)2/3b.
experiments were repeated several times, which con-
firmed the results stated above.
These results (Table 1 and Table 2) show that the
copper(II) complexes of ligands 2a and 2b are effec-
tive homogeneous enantioselective catalysts for the
Henry reaction. Thanks to the finding that they do
not undergo racemization during the Henry reaction,
it was very promising to prepare their recyclable var-
iant using immobilization by means of anchoring to
a solid carrier.
En-
try
R
3a
3b
Conv.[a] [%] ee[b] Conv.[a] [%] ee[b]
(Yield [%]) [%] (Yield [%]) [%]
For the purpose of the intended immobilization of
1
2
3
4
Ph
98 (91)
85
86
82
98
98 (86)
99 (94)
99 (88)
(99)
À84
À83
À78
À95
À
ligands 2a and 2b by means a C S bond it was neces-
2-CH3OC6H4 99 (90)
4-NO2C6H4
t-Bu
sary to confirm the presumed regioselectivity of the
benzylation reaction at the thiolactam group. It was
found that the reaction of one equivalent of ligand 2a
or 2b and benzyl bromide produced selectively com-
pound 3a or, respectively, 3b (Scheme 2), which was
99 (89)
(99)
[a]
1
The conversion was determined by H NMR of the crude
product.
The enantiomeric excess was determined by HPLC using
a Chiralcel OD-H column.
[b]
1
confirmed by means of H and 13C NMR spectrosco-
py. The original chemical shift of the carbon atom in
thiolactam group C=S (d=209.1 ppm) of ligand 2a
was distinctly shifted to the value of 177.6 ppm, which 2a and 2b in order to enable mutual comparison.
corresponds with the formation of the bond arrange- Table 3 presents an overview of the results obtained.
À À
ment Bn S C=N in ligand 3a. The preparation of li-
From the ee values of the individual nitroaldols at-
gands 3a and 3b themselves had to be performed in tained by catalysis with copper(II) complexes of li-
the presence of base, because the hydrogen bromide gands 3a and 3b it follows that the enantioselectivity
being formed causes epimerization at the 2-position of both forms of catalyst is practically comparable.
of the imidazoline cycle. This phenomenon was veri- Comparison of the ee values obtained with the com-
fied by an experiment in which the addition of several plexes of ligands 2a-b vs. 3a-b shows that in the case
drops of trifluoroacetic acid to a methanolic solution of Cu(OAc)2/3a the enantioselectivity with aromatic
of compound 3a within 2 days resulted in the forma- aldehydes slightly decreased, namely by ca. 3–5% ee.
tion of a mixture of epimers 3a and 3b in the ratio of In the case of complex Cu(OAc)2/3b the enantioselec-
3/2; after 10 days this ratio 3a/3b was 8/9. Hence, tivity is comparable with that of complex Cu(OAc)2/
epimer 3b seems to be a thermodynamically more 2b, with exception of 4-nitrobenzaldehyde: here the
suitable form. The individual epimers 3a and 3b can ee value distinctly increased (50% vs. 78% ee). With
again be separated by means of column chromatogra- respect to the generally high ee values, it again can be
phy [SiO2/EtOAc:pentane:TEA (2:1:0.06); Rf(3a)= presumed that during the Henry reaction the epimeri-
0.66; Rf(3b)=0.50]. The preparation of benzyl deriva- zation at the 2-position of the imidazoline cycle of
tives of 3a and 3b was studied under both homogene- compounds 3a and 3b does not take place. The at-
ous (DBU/MeOH; Cs2CO3/MeOH) and heterogene- tained conversion values were practically quantitative
ous reaction conditions (K2CO3/acetone; K2CO3/ in the case of both derivatives Cu(OAc)2/3a and
MeOH). In all the cases, the reaction proceeded with Cu(OAc)2/3b, in contrast to the previous catalysts
full conversion and without epimerization at the 2-po- Cu(OAc)2/2a-b.
sition of the imidazoline cycle.
The preparation of immobilized catalysts 7–9 con-
The structure of copper(II) complexes of ligands 3a sisted in anchoring of ligands 2a or 2b on a polymeric
and 3b is closest to the structure of immobilized het- carrier, namely by the reaction of their thiolactam
erogeneous catalysts 7–9 (Scheme 1). Therefore, they group with the chloromethyl groups of the carrier
can be considered as a homogeneous variant of the leading to formation of modified polymers 4–6
catalysts whose catalytic activity and enantioselectivi- (Scheme 3). As polymer carriers we used three types
ty can serve as standard for evaluation of these pa- of swelling pearl-type copolymers of styrene and 4-vi-
rameters in immobilized heterogeneous catalysts 7–9. nylbenzyl chloride, which differed in the type of
The study was performed with four aldehydes (benz- cross-linking agent and molar amount of chlorometh-
ACHTUNGTRENNUNGaldehyde, 2-methoxybenzaldehyde, 4-nitrobenzalde- yl groups. In the first case (for 4a-b) it was a copoly-
hyde and 2,2-dimethylpropanal), the reaction condi- mer cross-linked with tetra(ethylene glycol)-bis(4-vi-
tions used (the amount of catalyst, solvent, reaction nylbenzyl) ether (2%) (ST-VBC-TEG). The size of
time and temperature) being the same as those in the particles of this pearl-type copolymer was determined
previous study on the catalytic activity of derivatives by means of DLS (200–800 mm),[7a] and the content of
À1
À
reactive groups CH2Cl was 1.56 mmolg . The other
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with a satisfactory yield (4% conversion, 508C, 5
days). Modified polymers 4–6 were characterized by
means of elemental analysis and Raman spectroscopy.
The content of residual chlorine in compounds 4–6
was under the limit of determination (<0.03% Cl).
Subsequently coordination of copper(II) acetate to
immobilized ligands was performed to obtain the het-
erogeneous catalysts 7–9 (Scheme 3). The copper con-
tent was determined by means of atomic absorption
spectroscopy.
Furthermore, the immobilized catalysts 7–9 were
studied as enantioselective catalysts for the asymmet-
ric Henry reaction (Table 4, Table 5, Table 6 and
Table 7). After the reaction, the catalyst was simply
separated by means of filtration and reused in the
next reaction cycle. From this point of view, Sheldonꢃs
filtration test was performed,[10] which involved sepa-
ration of the heterogeneous catalyst part way through
a reaction, followed by continuation of the reaction in
the absence of the immobilized catalyst. The result
was negative, with the reaction stopping completely
after the filtration. The comparison of conversion
Scheme 3. Synthesis of immobilized catalysts 7–9.
two copolymers adopted were commercially available, values (in many cases quantitative) and ee values ob-
viz. the MerrifieldTM resin[7b] (for 5a-b) (which con- tained with the individual heterogeneous catalysts 7–9
tained 1% divinylbenzene as cross-linking agent, and shows that their catalytic activity and enantioselectivi-
its chlorine content was 2.75 mmolgÀ1), and the Jan- ty are very high and not much different within the
daJelTM resin[7c] (for 6a-b) with cross-linking agent on three types of polymeric carrier. Moreover, it is obvi-
the basis of polytetrahydrofuran (2%) and with the ous that the immobilized catalysts 7–9 exhibit practi-
chlorine content of 0.48 mmolgÀ1. An important ben- cally identical catalytic activity and enantioselectivity
efit of all three copolymers is high swelling capacity as the homogeneous variants of catalysts Cu(OAc)2/
in polar solvents, which enables an easy penetration 3a and Cu(OAc)2/3b (Table 3). A certain interesting
of reactants to reactive groups of the copolymer. The fact is that in many cases the first catalytic cycle gave
anchoring procedure of ligands 2a and 2b on copoly- the products of Henry reaction with significantly
mer was performed at room temperature in dimethyl lower optical purity. In the first four catalytic cycles
sulfoxide in the presence of DBU. When methanol of application of catalysts 7–9, the ee value increased
was used as a solvent, the reaction did not proceed and then, in the following catalytic cycles, it remained
Table 4. Survey of experiments on the asymmetric Henry reaction of nitromethane with aldehydes catalyzed by immobilized
catalysts with the trans configuration 7a, 8a and 9a.
R (cat. cycle)
7a
8a
9a
Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield[%]) ee[b] [%] Conv.[a] [%] (Yield[%]) ee[b] [%]
Ph (1st)
Ph (2nd)
Ph (3rd)
98 (88)
95 (83)
96 (89)
75
79
79
62
75
75
92
93
92
99 (86)
98 (91)
97 (84)
100 (89)
99 (90)
97 (88)
(98)
82
84
83
72
77
80
95
96
95
98 (87)
99 (90)
99 (90)
100 (91)
100 (87)
99 (90)
(90)
76
83
83
60
72
72
94
95
96
4-NO2C6H4 (1st) 100 (95)
4-NO2C6H4 (2nd) 95 (79)
4-NO2C6H4 (3rd) 88 (81)
t-Bu (1st)
t-Bu (2nd)
t-Bu (3rd)
(93)
(97)
(98)
(91)
(99)
(86)
(94)
[a]
1
The conversion was determined by H NMR of the crude product.
[b]
The enantiomeric excess was determined by HPLC using a Chiralcel OD-H column.
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Table 5. Survey of experiments on the asymmetric Henry reaction of nitromethane with aldehydes catalyzed by immobilized
catalysts with the cis configuration 7b, 8b and 9b.
R (cat. cycle)
7b
8b
9b
Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield [%]) ee[b] [%]
Ph (1st)
Ph (2nd)
Ph (3rd)
98 (87)
96 (82)
97 (88)
À83
À86
À86
À73
À84
À85
À94
À94
À95
99 (85)
92 (80)
92 (78)
99 (90)
98 (87)
92 (77)
(99)
À85
À85
À88
À68
À81
À84
À95
À96
À94
99 (89)
97 (90)
95 (79)
99 (85)
99 (89)
95 (80)
(95)
À85
À88
À89
À69
À80
À84
À96
À96
À97
4-NO2C6H4 (1st) 100 (89)
4-NO2C6H4 (2nd) 98 (81)
4-NO2C6H4 (3rd) 95 (78)
t-Bu (1st)
t-Bu (2nd)
t-Bu (3rd)
(95)
(97)
(98)
(99)
(94)
(88)
(95)
[a]
1
The conversion was determined by H NMR of the crude product.
The enantiomeric excess was determined by HPLC using a Chiralcel OD-H column.
[b]
Table 6. Survey of experiments on the asymmetric Henry reaction of nitromethane with 2-methoxybenzaldehyde catalyzed
by immobilized catalysts with the trans configuration 7a, 8a and 9a.
Cat. cycle
7a
8a
9a
Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield [%]) ee[b] [%]
1st
98 (91)
99 (86)
99 (90)
99 (92)
87 (76)
97 (79)
86 (68)
91 (85)
95 (80)
78 (69)
83 (68)
69
79
78
79
81
80
81
80
80
81
81
98 (84)
98 (90)
97 (87)
98 (88)
97 (79)
81
82
84
84
84
99 (90)
98 (86)
99 (89)
99 (87)
99 (91)
74
78
78
80
80
2nd
3rd
4th
5th
6th
7th
8th
9th
10th
11th
[a]
1
The conversion was determined by H NMR of the crude product.
[b]
The enantiomeric excess was determined by HPLC using a Chiralcel OD-H column.
practically constant (Table 6 and Table 7). This phe- the Henry reaction of nitromethane with 2-methoxy-
nomenon was observed earlier with other immobi- benzaldehyde. The fresh catalysts 7a and 7b were acti-
lized enantioselective catalysts; however, it was not vated by suspending in a medium of i-PrOH (1 mL)
discussed in detail.[11] The problem mentioned can be and nitromethane (0.5 mL) for a period of 2 days at
solved by activation of the catalysts, which consists in the reaction temperature of 68C. After the catalyst
suspending the heterogeneous catalyst in reaction separation and subsequent use in the reaction, the
medium throughout a so-called induction period.[11] first catalytic cycle provided Henry reaction products
After separation, the catalyst can be used for the first with 78% ee (7a) and 82% ee (7b), which are signifi-
catalytic cycle, and the ee value attained is higher and cantly higher than the values obtained after applica-
close to that in subsequent cycles.[11a] This activation tion of non-activated catalysts 7a and 7b (Table 6 and
of catalyst was tested with derivatives 7a and 7b in Table 7). These findings can be explained by the hy-
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Table 7. Survey of experiments on the asymmetric Henry reaction of nitromethane with 2-methoxybenzaldehyde catalyzed
by immobilized catalysts with the cis configuration 7b, 8b and 9b.
Cat. cycle
7b
8b
9b
Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield [%]) ee[b] [%] Conv.[a] [%] (Yield [%]) ee[b] [%]
1
2
3
4
5
6
7
8
97 (84)
99 (90)
98 (88)
98 (81)
95 (82)
98 (90)
95 (79)
88 (75)
88 (78)
85 (72)
93 (85)
À74
À83
À83
À85
À87
À86
À86
À86
À86
À87
À87
96 (80)
98 (89)
97 (82)
97 (90)
97 (85)
À83
À86
À88
À90
À89
99 (91)
99 (88)
99 (89)
98 (85)
97 (89)
À85
À90
À90
À89
À90
9
10
11
[a]
1
The conversion was determined by H NMR of the crude product.
The enantiomeric excess was determined by HPLC using a Chiralcel OD-H column.
[b]
pothesis that the non-activated catalysts can contain comparable to the best of the previously described[2]
copper bounded not only to the chiral ligand, but also recyclable forms of catalysts (~90% ee) for the Henry
by non-specific coordination to the polymer carrier. reaction. However, the main advantage of catalysts 7–
The problem especially occurred in the case of immo- 9 compared with the above-mentioned catalytic forms
bilized catalysts 7a-b and 9a-b based on copolymer of consists in their easy separation (solid material) by
styrene/4-chloromethylstyrene cross-linked by tetra-
ACHTUNGTRENNUNG(ethylene glycol) (for 7a-b) or, respectively, polytetra-
hydrofuran (for 9a-b). These types of cross-linkers
could be possible ligands for coordination of copper
ion, therefore removing unreacted copper(II) acetate
from the polymer matrix of crude catalysts 7a-b and
9a-b by washing with methanol (using a Soxhlet ex-
tractor, 24 h) was not probably sufficient. On the
other hand, in the case of the catalysts 8a-b derived
from Merrifield resin (cross-linker is divinylbenzene),
there were less problems with the first catalytic cycle
(see Table 4, Table 5, Table 6 and Table 7), which can
be caused by the absence of the non-chiral copper
complexes in their polymer matrixes. From this point
of view, the catalysts 8a-b can be considered as better
candidates for the application in asymmetric synthe-
ses. The high recycling potential of catalysts 7–9 is ob-
vious from Figure 1, which displays no decrease of
enantioselectivity even after ten recycling procedures
(derivatives 7a-b). Starting from the seventh cycle, the
conversions were not completely quantitative; never-
theless they reached still high values (78–95%). This
mild decrease was probably caused by loss of catalyst
during recycling (filtration, decantation), which could
be prevented by modification of the reaction proce-
dure involving the “tea bag” method of catalysis.
Generally, the enantioselectivity and catalytic activity
Figure 1. Dependence of attained ee of 1-(2-methoxyphen-
yl)-2-nitroethanol on catalytic cycle with the use of catalysts
7a and 7b (the ee values are taken from Table 6 and
Table 7). The first cycles were also carried out with pre-acti-
of the immobilized catalysts 7–9 can be considered as vation of the catalysts (dashed lines).
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Table 8. Survey of experiments on the asymmetric Henry re-
action of nitromethane with 2-methoxybenzaldehyde with
application of catalysts Cu(OAc)2/2a-b, Cu(OAc)2/3a-b, 7a-
b and 9a-b at a temperature of À108C.
Catalyst
Conv.[a] [%] (Yield [%])
ee[b] [%]
Cu(OAc)2/2a
Cu(OAc)2/2b
Cu(OAc)2/3a
Cu(OAc)2/3b
7a
7b
8a
8b
9a
9b
49 (44)
34 (25)
83 (70)
89 (75)
99 (89)
99 (86)
72 (65)
89 (79)
99 (90)
99 (88)
93
À89
88
À91
83
À91
89
À91
86
À90
[a]
1
Figure 2. The time dependence (h) of conversion for reac-
The conversion was determined by H NMR of the crude
product.
The enantiomeric excess was determined by HPLC using
a Chiralcel OD-H column.
tion of MeNO2 with 2-methoxybenzaldehyde catalyzed by
[b]
~
5 mol% of homogeneous catalysts Cu(OAc)2/2a ( );
&
^
Cu(OAc)2/3a ( ) and heterogeneous catalyst 9a ( ) at 68C.
simple filtration, instead of precipitation of the solu- ous and heterogeneous forms of the catalysts, al-
ble form[2a–f] which can be connected with possible though the Henry reactions were completed early in
contamination of the Henry reaction products with the case of heterogeneous catalysts.
catalyst.
With regard to the confirmed higher catalytic activ-
Table 3, Table 4, Table 5, Table 6 and Table 7 show ity of heterogeneous catalysts 7–9, in the subsequent
that heterogeneous catalysts 7–9 exhibit a higher cata- study, we tested their enantioselectivity in the Henry
lytic activity than homogeneous catalysts Cu(OAc)2/ reaction at the temperature of À108C (Table 8). From
2a-b (Table 1). This fact was confirmed by means of the ee values found (~90%) it is obvious that the
a kinetic study describing the dependence of conver- enantioselectivity of catalysts Cu(OAc)2/3a-b and 7–9
sion on reaction time and performed in reaction of ni- increased (under these reaction conditions) up to the
tromethane with 2-methoxybenzaldehyde catalyzed level comparable with that of the homogeneous cata-
by Cu(OAc)2/2a; Cu(OAc)2/3a or 9a (Figure 2). The lyst Cu(OAc)2/2a-b (Table 1), and/or with the earlier
dependence shows that with application of immobi- prepared catalyst based on 2-(pyridine-2-yl)imidazoli-
lized heterogeneous catalyst 9, the conversion is dine-4-one.[3a] The conversion values at this lower
almost quantitative (99%) at the temperature of 68C temperature remained very high (72–99%). From the
within 10 h. On the other hand, both types of homo- above-given facts it follows that the homogeneous
geneous catalysts Cu(OAc)2/2a and Cu(OAc)2/3a catalyst Cu(OAc)2/2a provides high conversion values
identically gave after the same time a conversion of and ee in the products of the Henry reaction at the
only ca. 30% (after 30 h, the conversion was ca. temperature of 68C, whereas with application of het-
70%), which corresponds to reaction half-life t1/2 erogeneous forms of catalysts (7–9) is favourable to
~16 h. This phenomenon can be probably explained lower the temperature (to À108C), where these nitro-
by possible particular formation of dimeric/oligomeric aldols can be prepared in comparable optical purity
adducts[12] of homogeneous catalysts Cu(OAc)2/2a- and yield.
b and Cu(OAc)2/3a-b, which are catalytically inac-
tive.[13] In the case of heterogeneous catalysts 7–9 the
formation of these dimeric/oligomeric adducts is pro- Conclusions
hibited, which led to their enhanced catalytic activity.
The attempts included in Table 4, Table 5, Table 6 and In summary, it can be stated that the copper(II) com-
Table 7 were done with a reaction time of 6 days for plexes of synthesized 2-(pyridine-2-yl)imidazolidine-4-
overall comparison and evaluation of both homogene- thiones 2a-b and their benzyl derivatives 3a-b are effi-
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measured on the Thermo Fisher Scientific MALDI LTQ Or-
bitrap instrument. HPLC analyses were performed on
Watrex HPLC instrument with UV-Vis DAD (200–800 nm)
SYKAM 3240 and with chiral Daicel columns: Chiralcel
OD-H, Chiralpak AS-H and Chiralpak AD-H (250 mm ꢄ
4.6 mm).
cient homogeneous enantioselective catalysts of the
Henry reaction (up to 98% ee). Moreover, the immo-
bilized forms of these catalysts 7–9 exhibit a compara-
ble catalytic activity and enantioselectivity and can be
recycled more than ten times without any decrease in
the enantioselectivity. Their high enantioselectivity
classifies them as the best so far known enantioselec-
tive recyclable catalysts for the Henry reaction.[2d]
Two further reactions performed in the case of the
synthesis of immobilized catalysts 7–9, namely the
thionation of the starting (S)-2-amino-2,3-dimethylbu-
taneamide giving (S)-2-amino-2,3-dimethylbutane-
thioamide (1) (72%) and anchoring of ligands 2a-b on
polymeric carriers (82–99%), led to a lowering of the
total yield of this synthetic procedure as compared
with the yield of the synthesis of the original catalyst
Synthesis of Ligands 2 and 3
(S)-Amino-2,3-dimethylbutanethioamide (1): A mixture of
(S)-2-amino-2,3-dimethylbutanamide[8] (8.7 g, 67 mmol) and
P4S10 (17.4 g, 40 mmol) was refluxed in dry dioxane
(200 mL) for 10 h and then was stirred at room temperature
for 72 h. Dioxane was removed under reduced pressure, the
oily residue was diluted with cold aqueous NH3 (10%,
120 mL) and the mixture was extracted with CH2Cl2 (4ꢄ
50 mL). Organic extracts were combined and dried and the
based on 2-(pyridine-2-yl)imidazolidine-4-one deriva- solvent was distilled off. The crude product was purified by
tive.[3a] On the other hand, the immobilized catalysts
recrystallization from cyclohexane/EtOAc (5/1) to obtain
1 as a white crystalline solid 1; yield: 7.1 g (72%); mp 87–
7–9 can be recovered and reused more than ten times
and thus they are more advantageous not only eco-
nomically, but their application is also more environ-
ment-friendly. The synthesized polymeric catalysts 7–
9 possess a high application potential for the asym-
metric Henry reaction.
908C; [a]2D5: À74.7 (c 0.99, MeOH); 1H NMR (CDCl3,
400 MHz): d=9.47 (bs, 1H, CSNH2), 8.11 (bs, 1H, CSNH2),
3
2.69 (sp, J=6.8 Hz, 1H, CH), 1.41 (s, 3H, CH33), 1.32 (bs,
3
2H, NH2), 0.92 (d, J=6.8 Hz, 3H, i-Pr), 0.77 (d, J=6.8 Hz,
3H, i-Pr); 13C NMR (CDCl3, 100 MHz): d=215.7, 65.8, 35.8,
29.3, 17.3, 16.3; elemental analysis for C6H14N2S (146.25)
calcd.: C 49.28, H 9.65, N 19.15, S 21.92; found: C 49.45, H
9.39, N 19.17, S 22.04; HR-MS (ESI): m/z=147.09511 [M+
H]+, calcd. 147.09505 [M+H]+.
Experimental Section
5-Isopropyl-2,5-dimethyl-2-(pyridine-2-yl)imidazolidine-4-
thione (2a and 2b): A solution of thioamide 1 (370 mg,
2.5 mmol), 2-acetylpyridine (480 mg, 4 mmol) and p-
TSA·H2O (4.8 mg, 0.25 mmol) in 1,2-dichlorobenzene
(4 mL) was stirred at 1308C for 2 h. After evaporation of
the solvent under reduced pressure the obtained yellow oil
was treated with CH2Cl2 (6 mL) and a saturated aqueous so-
lution of Na2CO3 (6 mL). The organic layer was dried over
Na2SO4 and solvent was evaporated. The mixture of diaste-
reomers was separated by column chromatography [SiO2/
EtOAc/hexane (1/1), (v/v)].
General Information
If not otherwise stated, the starting chemicals and solvents
were obtained from Sigma–Aldrich or Acros Organic and
used without further purification. (S)-Amino-2,3-dimethyl-
butanamide was prepared according to a previously de-
scribed procedure.[8] 1H NMR spectra were recorded on
a Bruker Avance 400 instrument or Bruker Avance 500 in-
strument. Chemical shifts d were referenced to the residual
peak of the CDCl3 (7.26 ppm) or MeOD-d4 (3.31 ppm). The
13C NMR spectra were calibrated with respect to the middle
signal in the triplet of CDCl3 (77.23 ppm) or quintet of
MeOD-d4 (49.00 ppm). The Raman spectra were measured
at room temperature using an FT-IR spectrophotometer IFS
55 provided with a Raman FRA-106 accessory (Bruker) for
the back scattering method. The YAG:Nd3+ laser line
(1064 nm) was used for excitation. The resolution was
2 cmÀ1 and the laser power was 50 mW. The FT-Raman data
are presented in cmÀ1 (vw, very weak; w, weak; m, medium;
s, strong; sh, shoulder). The microanalyses were performed
on an apparatus from FISONS Instruments, EA 1108
CHNS. The determination of Cu was carried out with an
Avanta 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 MWS-3+ (Berghof, Ger-
many) microwave system with the maximum total output of
the microwave generator 1450 W. Quantification of Cu con-
centrations was performed by establishing a calibration
curve by linear regression. The optical rotation was mea-
sured on a Perkin–Elmer 341 instrument; the concentration
c was given in g/100 mL. High-resolution mass spectra were
(2R,5S)-5-Isopropyl-2,5-dimethyl-2-(pyridine-2-yl)imida-
zolidine-4-thione (2a): yield: 37%; colorless oil; Rf 0.46;
[a]2D5: À84.4 (c 0.8, MeOH); 1H NMR (CDCl3, 400 MHz):
d=9.61 (bs, 1H, CONH), 8.52 (m, 1H, Py), 7.72 (m, 1H,
Py), 7.66 (m, 1H, Py), 7.18 (m, 1H, Py), 2.61 (bs, 1H, NH),
2.32 (sp, 3J=6.8 Hz, 1H, CH), 1.71 (s, 3H, CH3), 1.13 (s,
3
3
3H, CH3), 1.02 (d, J=6.8 Hz, 3H, i-Pr), 1.00 (d, J=6.8 Hz,
3H, i-Pr); 13C NMR (CDCl3, 100 MHz): d=209.1, 163.4,
149.3, 137.3, 123.1, 119.5, 82.2, 77.7, 35.6, 30.3, 27.2, 18.2,
16.9; elemental analysis for C13H19N3S (249.38) calcd.: C
62.61, H 7.68, N 16.85, S 12.86; found: C 62.44, H 7.81, N
16.73, S 12.71; HR-MS (ESI): m/z=250.13729 [M+H]+,
calcd. 250.13722 [M+H]+.
(2S,5S)-5-Isopropyl-2,5-dimethyl-2-(pyridine-2-yl)imidazo-
lidine-4-thione (2b): yield: 29%; white crystalline solid; mp
1
128–1308C; Rf 0.30; [a]2D5: +19.3 (c 0.9, MeOH); H NMR
(CDCl3, 400 MHz): d=9.13 (bs, 1H, CONH), 8.51 (m, 1H,
Py), 7.73–7.66 (m, 2H, Py), 7.19 (m, 1H, Py), 2.43 (bs, 1H,
3
NH), 2.10 (sp, J=6.8 Hz, 1H, CH), 1.75 (s, 3H, CH3), 1.55
(s, 3H, CH3), 0.97 (d, 3J=6.8 Hz, 3H, i-Pr), 0.53 (d, 3J=
6.8 Hz, 3H, i-Pr); 13C NMR (CDCl3, 100 MHz): d=207.9,
162.7, 148.9, 137.1, 122.9, 119.3, 81.9, 77.1, 36.3, 32.6, 28.9,
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18.3, 16.8; elemental analysis for C13H19N3S (249.38) calcd.:
C 62.61, H 7.68, N 16.85, S 12.86; found: C 62.97, H 7.68, N
16.73, S 12.62; HR-MS (ESI): m/z=250.13691 [M+H]+,
calcd. 250.13722 [M+H]+.
4-Benzylsulfanyl-5-isopropyl-2,5-dimethyl-2-(pyridine-2-
yl)imidazoline (3a and 3b): To a suspension of ligand 2a or
2b (175 mg, 0.7 mmol) and K2CO3 (200 mg, 1.45 mmol) in
MeOH (3 mL) was added benzyl bromide (86 mL,
0.72 mmol) and mixture was stirred at room temperature for
2 days. Then, the reaction mixture was filtered and the sol-
vent was evaporated under reduced pressure.
(sh), 2904 (sh), 2914 (sh), 2924 (m), 2975 (w), 3001 (vw),
3036 (sh), 3054 (m).
Compound 4b: Prepared from swelling pearl-like copoly-
mer styrene-(4-vinylbenzyl chloride) cross-linked by means
of tetra(ethylene glycol)-bis(4-vinylbenzyl) ether (2%)[7a]
and ligand 2b. Yield: 82%; elemental analysis found: C
80.63, H 7.48, N 3.65, S 2.69; FT-Raman: n=220 (sh), 234
(w), 272 (vw), 407 (vw), 576 (vw), 621 (w), 642 (w), 674
(vw), 747 (sh), 758 (vw), 767 (sh), 790 (sh), 814 (sh), 833
(vw), 1002 (s), 1030 (w), 1046 (w), 1090 (vw), 1155 (w), 1183
(w), 1201 (w), 1240 (vw), 1299 (sh), 1327 (vw), 1369 (sh),
1448 (w), 1583 (m), 1602 (m), 1611 (sh), 2853 (sh), 2912
(sh), 2924 (m), 2975 (w), 3001 (vw), 3036 (sh), 3054 cmÀ1 (s).
Compound 5a: Prepared from MerrifieldTM resin (2.5–
4.0 mmolgÀ1 Cl, cross-linker 1%, 50–100 mesh) and ligand
2a. Yield: 86%; elemental analysis found: C 77.22, H 7.63, N
6.61, S 3.92; FT-Raman: n=218 (vw), 407 (vw), 576 (vw),
621 (w), 642 (w), 679 (vw), 709 (vw), 755 (vw), 790 (sh), 807
(sh), 836 (vw), 1002 (s), 1031 (w), 1046 (vw), 1088 (vw),
1112 vw), 1155 (vw), 1183 (w), 1203 (w), 1240 (w), 1296
(sh), 1311 (sh), 1326 (vw), 1363 (sh), 1448 (w), 1528 (vw),
1569 (sh), 1583 (w), 1602 (m), 1611 (m), 2857 (sh), 2910
(sh), 2925 (s), 2978 (m), 3000 (w), 3033 (sh), 3053 cmÀ1 (s).
Compound 5b: Prepared from MerrifieldTM resin (2.5–
4.0 mmolgÀ1 Cl, cross-linker 1%, 50–100 mesh) and ligand
2b. Yield: 89%; elemental analysis found: C 76.93, H 8.04,
N 6.28, S 3.61; FT-Raman: n=219 (vw), 409 (vw), 585 (vw),
621 (w), 642 (w), 671 (vw), 717 (vw), 747 (sh), 760 (vw), 790
(sh), 807 (sh), 830 (vw), 1002 (s), 1031 (w), 1046 (vw), 1088
(vw), 1155 (vw), 1183 (w), 1201 (w), 1240 (w), 1296 (sh),
1327 (vw), 1363 (sh), 1448 (w), 1528 (vw), 1583 (w), 1602
(s), 1611 (s), 2857 (sh), 2910 (sh), 2925 (s), 2978 (m), 3000
(w), 3033 (sh), 3053 cmÀ1 (s).
(2R,5S)-4-Benzylsulfanyl-5-isopropyl-2,5-dimethyl-2-(pyri-
dine-2-yl)imidazoline (3a): yield: 86%; yellow oil; [a]2D5:
1
À53.5 (c 1.0, MeOH); H NMR (MeOD-d4, 400 MHz): d=
8.47 (m, 1H, Py), 7.68 (m, 1H, Py), 7.46 (m, 1H, Py), 7.39
(m, 2H, Ph), 7.28–7.21 (m, 4H, Py+Ph), 4.40–4.31 (2ꢄ d,
3
2J=13.6 Hz, 2H, CH2), 1.77 (sp, J=6.8 Hz, 1H, CH), 1.64
3
(s, 3H, CH3), 1.01 (s, 3H, CH3), 0.96 (d, J=6.8 Hz, 3H, i-
Pr), 0.92 (d, 3J=6.8 Hz, 3H, i-Pr); 13C NMR (MeOD-d4,
100 MHz): d=177.6, 166.3, 149.2, 139.0, 138.2, 130.0, 129.4,
128.2, 123.5, 121.7, 93.4, 78.1, 35.7, 35.6, 31.5, 26.1, 18.7,
17.0; elemental analysis for C20H25N3S (339.5) calcd.: C
70.76, H 7.42, N 12.36, S 9.44; found: C 70.68, H 7.64, N
12.27, S 9.19; HR-MS (ESI): m/z=340.18398 [M+H]+,
calcd. 340.18419 [M+H]+.
(2S,5S)-4-Benzylsulfanyl-5-isopropyl-2,5-dimethyl-2-(pyri-
dine-2-yl)imidazoline (3b): yield: 89%; yellow oil; [a]2D5:
1
+31.7 (c 2.4, MeOH); H NMR (MeOD-d4, 400 MHz): d=
8.50 (m, 1H, Py), 7.75 (m, 1H, Py), 7.68 (m, 1H, Py), 7.38
(m, 2H, Ph), 7.29–7.22 (m, 4H, Py+Ph), 4.39–4.30 (2ꢄ d,
3
2J=13.2 Hz, 2H, CH2), 1.78 (sp, J=6.8 Hz, 1H, CH), 1.65
3
(s, 3H, CH3), 1.40 (s, 3H, CH3), 0.94 (d, J=6.8 Hz, 3H, i-
Pr), 0.46 (d, 3J=6.8 Hz, 3H, i-Pr); 13C NMR (MeOD-d4,
100 MHz): d=176.9, 164.7, 148.9, 139.0, 138.2, 130.1, 129.3,
128.2, 123.6, 122.4; 94.0, 78.2, 36.2, 35.8, 32.6, 27.6, 18.2,
17.3; elemental analysis for C20H25N3S (339.5) calcd.: C
70.76, H 7.42, N 12.36, S 9.44; found: C 70.58, H 7.31, N
12.39, S 9.21; HR-MS (ESI): m/z=340.18490 [M+H]+,
calcd. 340.18419 [M+H]+.
Compound 6a: Prepared from JandaJelTM resin (0.45–
0.70 mmolgÀ1 Cl, cross-linker 2%, 50–100 mesh) and ligand
2a. Yield: 99%; elemental analysis found: C 83.51, H 7.98, N
2.77, S 1.48; FT-Raman: n=217 (vw), 402 (vw), 621 (w), 642
(vw), 760 (vw), 796 (vw), 810 (sh), 840 (sh), 907 (vw), 966
(w), 1002 (s), 1030 (w), 1046 (sh), 1084 (vw), 1155 (w), 1183
(w), 1201 (vw), 1240 (m), 1297 (sh), 1325 (vw), 1367 (sh),
1450 (w), 1584 (w), 1602 (m), 1611 (sh), 2855(sh), 2910 (m),
2977 (w), 3000 (w), 3038 (sh), 3053 (s), 3162 cmÀ1 (vw).
Compound 6b: Prepared from JandaJelTM resin (0.45–
0.70 mmolgÀ1 Cl, cross-linker 2%, 50–100 mesh) and ligand
2b. Yield: 97%; elemental analysis found: C 84.07, H 7.83,
N 3.01, S 1.71; FT-Raman: 217 (vw), 406 (vw), 621 (w), 642
(vw), 760 (vw), 796 (vw), 810 (sh), 837 (sh), 907 (vw), 966
(w), 1002 (s), 1030 (w), 1046 (sh), 1084 (vw), 1155 (w), 1183
(w), 1201 (vw), 1240 (m), 1297 (sh), 1325 (vw), 1367 (sh),
1450 (w), 1584 (w), 1602 (m), 1611 (sh), 2855(sh), 2910 (m),
2977 (w), 3000 (w), 3038 (sh), 3053 (s), 3162 cmÀ1 (vw).
General Procedure for Immobilization of Ligands 2a
and 2b
To a solution of ligand 2a or 2b (250 mg, 1 mmol), DBU
(0.3 mL, 2 mmol) and NaI (4.5 mg, 0.03 mmol) in dry
DMSO (5 mL) was added a pearl-type chloromethylated
polystyrene support (0.66 mmol, calculated from Cl content)
and was stirred at room temperature for 5 days. After filtra-
tion and washing with methanol (5ꢄ 5 mL), the catalyst was
extracted in a Soxhlet extractor with methanol for 24 h and
then dried under vacuum.
Compound 4a: Prepared from swelling pearl-like copoly-
mer styrene-(4-vinylbenzyl chloride) cross-linked by means
of tetra(ethylene glycol)-bis(4-vinylbenzyl) ether (2%)[7a]
and ligand 2a. Yield: 83%; elemental analysis found: C
79.07, H 7.63, N 3.72, S 2.75; FT-Raman: n=217 (vw), 406
(vw), 576 (vw), 621 (w), 642 (w), 682 (vw), 747 (sh), 760
(vw), 790 (sh), 811 (sh), 837 (vw), 907 (vw), 928 (vw), 963
(vw), 1002 (s), 1030 (w), 1046 (w), 1090 (vw), 1155 (w), 1183
(w), 1201 (w), 1240 (vw), 1292 (sh), 1327 (vw), 1369 (sh),
1448 (w), 1584 (m), 1602 (m), 1611 (sh), 2852 (sh), 2872
General Procedure for Preparation of Heterogeneous
Catalysts 7–9
The suspension of polymer 4–6 (300 mg) in a solution of
copper(II) acetate (91 mg, 0.5 mmol) in methanol (12 mL)
was stirred for 24 h at room temperature. After filtration
and washing with methanol (5ꢄ 20 mL), the catalyst was ex-
tracted in a Soxhlet extractor with methanol for 24 h and
then dried under vacuum.
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Catalyst 7a: Yield: 97%; elemental analysis found: C
70.37, H 6.89, N 3.19, S 2.33, Cu 4.86; FT-Raman: n=508
(vw), 576 (vw), 621 (vw), 639 (vw), 673 (vw), 709 (vw), 790
(sh), 807 (sh), 829 (vw), 925 (vw), 1000 (s), 1027 (m), 1046
(sh), 1092 (vw), 1154 (vw), 1183 (w), 1201 (sh), 1240 (w),
1327 (vw), 1364 (sh), 1448 (w), 1583 (sh), 1602 (m),
2857(sh), 2907 (sh), 2926 (m), 2977 (w), 3003 (w), 3039 (sh),
3055 cmÀ1 (m).
Catalyst 7b: Yield: 93%; elemental analysis: found C
72.89, H 7.01, N 3.54, S 2.46, Cu 4.83; FT-Raman: n=221
(vw), 508 (vw), 576 (vw), 621 (vw), 639 (vw), 673 (vw), 709
(vw), 790 (sh), 807 (sh), 829 (vw), 925 (vw), 1000 (s), 1027
(w), 1046 (sh), 1095 (vw), 1154 (vw), 1183 (w), 1201 (sh),
1240 (w), 1327 (vw), 1364 (sh), 1448 (w), 1583 (sh), 1602
(m), 2857(sh), 2907 (sh), 2926 (m), 2980 (w), 3000 (w), 3039
(sh), 3055 cmÀ1 (m).
Catalyst 8a: Yield: 78%; elemental analysis found: C
68.41, H 7.04, N 4.93, S 2.97, Cu 6.12; FT-Raman: n=215
(vw), 239 (sh), 400 (vw), 621 (w), 642 (w), 680 (vw), 703
(vw), 759 (vw), 788 (sh), 806)vw), 837 (vw), 1001 (s), 1031
(w), 1043 (w), 1087 (vw), 1156 (vw), 1183 (w), 1199 (sh),
1245 (vw), 1317 (vw), 1447 (vw), 1583 (sh), 1605 (m),
2864(sh), 2926 (s), 2974 (m), 3002 (sh), 3054 cmÀ1 (s).
Catalyst 8b: Yield: 96%; elemental analysis found: C
70.12, H 7.54, N 4.76, S 2.89, Cu 5.39; FT-Raman: n=220
(sh), 236 (vw), 397 (vw), 549 (vw), 574 (vw), 622 (w), 641
(w), 677 (vw), 707 (vw), 756 (vw), 801 (sh), 832 (vw), 1001
(s), 1044 (sh), 1083 (vw), 1156 (vw), 1183 (w), 1199 (sh),
1243 (sh), 1312 (vw), 1447 (vw), 1583 (sh), 1605 (m),
2864(sh), 2926 (s), 2974 (m), 3002 (sh), 3054 cmÀ1 (s).
Catalyst 9a: Yield: 97%; elemental analysis found: C
79.80, H 7.77, N 2.25, S 1.25, Cu 2.47; FT-Raman: n=216
(vw), 576 (vw), 607 (vw), 620 (vw), 640 (vw), 754 (vw), 796
(vw), 832 (vw), 1001 (s), 1030 (w), 1080 (sh), 1154 (vw),
1183 (w), 1193 (sh), 1244 (vw), 1325 (vw), 1372 (sh), 1448
(w), 1562 (sh), 1583 (sh), 1602 (m), 2853 (sh), 2913 (sh),
2923 (m), 2974 (w), 3000 (w), 3035 (sh), 3053 cmÀ1 (s).
Catalyst 9b: Yield: 98%; elemental analysis found: C
80.23, H 7.56, N 2.40, S 1.36, Cu 2.56; FT-Raman: n=183
(sh), 214 (sh), 239 (m), 607 (vw), 623 (vw), 642 (vw), 754
(vw), 794 (vw), 831 (vw), 1001 (s), 1030 (w), 1086 (sh), 1154
(vw), 1182 (w), 1193 (sh), 1244 (vw), 1325 (vw), 1372 (sh),
1448 (w), 1562 (sh), 1583 (sh), 1602 (m), 2853 (sh), 2912
(m), 2923 (sh), 2974 (w), 3000 (w), 3035 (sh), 3053 cmÀ1 (m).
enantiomers of the nitro alcohols were in accordance with
data published previously.[3a]
Acknowledgements
The authors acknowledge the financial support from the proj-
ˇ
ect GACR 14-00925S.
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Recyclable Enantioselective Catalysts Based on Copper(II)
Complexes of 2-(Pyridine-2-yl)imidazolidine-4-thione: Their
Application in Asymmetric Henry Reactions
13
Adv. Synth. Catal. 2016, 358, 1 – 13
ˇ
Gabriela Novꢀkovꢀ, Pavel Drabina,* Bozena Frumarovꢀ,
ˇ
Milos Sedlꢀk
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