Design of Heterogeneous Organocatalyst for the Asymmetric Michael Addition of Aldehydes to Maleimides

Article abstract of DOI:10.1002/cctc.201800919

Asymmetric Michael additions of isobutyraldehyde to maleimides catalyzed by optically pure diamines and their sulfonamides were investigated to develop heterogeneous chiral catalysts for these reactions. Encouraging results, i. e. complete transformations

Full text of DOI:10.1002/cctc.201800919

Accepted Article
Title: Design of heterogeneous organocatalyst for the asymmetric
Michael addition of aldehydes to maleimides
Authors: György Szöllösi and Viktória Kozma
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Design of heterogeneous organocatalyst for the asymmetric
Michael addition of aldehydes to maleimides
György Szőllősi,*[a] and Viktória Kozma[b]
Dedicated to Prof. Mihály Bartók on his 85th birthday.
Abstract: Asymmetric Michael additions of isobutyraldehyde to
maleimides catalysed by optically pure diamines and their
sulfonamides were investigated to develop heterogeneous chiral
catalysts for these reactions. Encouraging results, i.e. complete
transformations and optically pure products, were obtained using
para-toluenesulfonamide or methanesulfonamide derivatives. Chiral
solid materials were prepared by covalent bonding of the diamines on
sulfonyl chloride functionalized supports. Immobilization of the amines
was confirmed by FT-IR spectroscopy. The heterogeneous catalyst
prepared by bonding optically pure 1,2-diphenylethane-1,2-diamine to
polystyrene support was highly enantioselective, giving results
approaching those obtained using soluble sulfonamide derivatives.
The anchored catalyst was recyclable few times keeping its activity
followed by gradual small decrease in conversion, however, still
providing high, up to 97%, enantiomeric excesses. These materials
are among the first efficient recyclable catalysts used in the
enantioselective Michael addition of aldehydes to maleimides.
maleimides result in the formation of chiral succinimide
derivatives,[7] which may be transformed in valuable biologically
active products.[8] Aliphatic aldehydes are among the frequently
investigated carbon nucleophiles. Various chiral amine
derivatives were used as catalysts in these reactions,[9] such as
primary diamine derivatives having 1,2-diphenylethylene or 1,2-
cyclohexyl backbone bearing a hydrogen-bond donor group.[7,10]
These reactions occur through enamine type mechanisms, during
which the enamine formed by condensation of the aldehyde and
catalyst reacts with the maleimide interacting with the catalyst
through hydrogen-bonds. Among the most efficient hydrogen-
bond donors is the sulfonamide group. Tuning the catalyst
structure by modification of the steric and electronic properties of
the substituents on the sulfonamide group was used to improve
the performance of the catalysts. However, increasing the
complexity of these organocatalysts diminished their major
advantages, such as their low price and availability.
Since the reports of Noyori and co-workers on the use of chiral
1,2-diamine sulfonamides as ligands,[11] various diamine
derivatives
were
applied
as
chiral
ligands
and
Introduction
organocatalyst.[7,10,12] During the present work our aim was to
examine the effect of the structure of 1,2-diamine sulfonamides,
in order to use these results in the development of efficient
heterogeneous chiral organocatalyst for the asymmetric Michael
addition of aldehydes to maleimides. To our knowledge,
heterogeneous catalysts have not been applied in these
enantioselective additions so far.
Asymmetric catalytic procedures are the most versatile methods
to produce optically pure chiral chemicals.[1] During the last few
decades optically pure organocatalysts became frequently
applied in the synthesis of chiral organic building blocks.[2] Initially
natural compounds and their simple, easily prepared derivatives
were employed. Broadening the applicability of these catalysts
required finely tuned derivatives. Accordingly, similar with the
chiral metal complexes,[3,4] heterogenization of organocatalysts
became of paramount importance to obtain products using
economic, sustainable and environmentally benign processes.[3,5]
Chiral organocatalysts are applied in various C-C bond
forming enantioselective reactions. Among these, conjugate
additions and more specifically, Michael additions, have
outstanding practical importance, due to the possible application
of a large variety, structurally diverse Michael donors and
acceptors.[6] Asymmetric additions of carbon nucleophiles on
Results and Discussion
Effect of the catalyst structure
Additions to N-phenylmaleimide (1a) and N-benzylmaleimide (1b)
of isobutyraldehyde (2) were selected as test reactions (Scheme
1) for studying the influence of the chiral catalyst structure. We
focused our investigations on using commercially available 1,2-
cyclohexane and 1,2-diphenylethane derivatives (see Figure 1).
Simple para-toluenesulfonamide derivatives were not yet applied
as catalysts in these reactions. Selected results are summarized
in Table 1. During an initial screening with using 1a and (S,S)-7
catalyst in toluene, ClCH2CH2Cl or CHCl3 solvents the best results
were obtained in the latter, both at room temperature (rt, 24°C)
and 70°C (not included). Thus, further investigations were carried
out in CHCl3.
[a]
[b]
Dr. Gy. Szőllősi
MTA-SZTE Stereochemistry Research Group
6720 Szeged, Dóm tér 8, Hungary.
E-mail: szollosi@chem.u-szeged.hu
V. Kozma
Department of Organic Chemistry
University of Szeged
6720 Szeged, Dóm tér 8, Hungary
In accordance with previous reports both diamines, (R,R)-4
and (S,S)-6, were less efficient than the corresponding
sulfonamides ((R,R)-5 and (S,S)-7) and provided lower
conversions and ee values in reactions of both 1a and 1b,
Supporting information for this article is given via a link at the end of
the document.
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respectively. Close to complete conversions could be reached
Preparation and application of heterogeneous chiral
with
the
cyclohexane-1,2-diamine
derived
para-
catalysts
toluenesulfonamide derivative (R,R)-5 in 5 hours at rt using 2
equivalents (eq.) isobutyraldehyde (Table 1, entry 3). However,
the product resulted only in 95% ee. In contrast, using the 1,2-
diphenylethane-1,2-diamine derivative (S,S)-7 longer reaction
time (24 h), higher temperature (70°C) and higher reactant
concentrations (less solvent) were necessary for close to
complete transformation of the maleimide derivatives (entry 5).
Satisfyingly, this catalyst afforded the 3a product as single
enantiomer (ee over 99%), whereas 3b also resulted in high ee
(up to 99%). At rt the transformation of the maleimides was not
complete even in less solvent following 3 days (entries 6, 7). Slight
differences in the results obtained in reactions of 1a and 1b were
observed, especially when the amount of 2 and catalyst were
reduced to half (entries 8, 9). Products resulted in one day
reactions using doubled amounts of reactants could be isolated in
high yields (entry 5). Interestingly, the methanesulfonamide
(R,R)-8 was similarly or even more efficient as the para-
toluenesulfonamide derivatives (entry 10). Based on these results
we considered possible that bonding optically pure 1,2-
diphenylethane-1,2-diamine through either aromatic or aliphatic
sulfonamide groups to insoluble supports may provide efficient
enantioselective heterogeneous catalysts for the above reactions.
This type of chiral solid materials were prepared and used
previously as chiral ligands for preparing heterogenized metal
complexes.[3e,13]
Immobilization of chiral organocatalysts on insoluble supports is
a convenient method to prepare enantioselective heterogeneous
chiral catalysts.[3,5,14] Various solid catalysts were developed for
application in asymmetric Michael additions.[13] However, to our
knowledge heterogeneous chiral catalysts were not yet applied in
the enantioselective addition of aldehydes to maleimide
derivatives. According to results obtained in homogeneously
catalyzed reactions using optically pure 1,2-diamine-derived
sulfonamides, anchoring 1,2-diamines by sulfonamide linkers on
solid materials may results in efficient chiral catalysts, due to
formation of the sulfonamide hydrogen-bond donor group on the
surface during immobilization. Several sulfonyl chloride
functionalized inorganic and organic materials are available
commercially, which may be used as supports. Applying such
materials we have prepared chiral solids both from optically pure
cyclohexane-1,2-diamines and 1,2-diphenylethane-1,2-diamines,
respectively (Scheme 2). Supports used in these experiments had
different functional group loadings, different particle sizes,
moreover the resins were cross-linked to different extent, as
indicated by suppliers (see Experimental Section). Therefore, the
obtained materials contained various amounts of anchored chiral
amine, as calculated based on their N contents, as follows: 9-R,R-
6 0.75 mmol/g; 10-R,R-6 1.15 mmol/g, 10-S,S-6 1.15 mmol/g, 11-
S,S-6 1.25 mmol/g and 10-R,R-4 1.10 mmol/g, respectively.
Immobilization of the chiral diamines by covalent bonding on
supports was examined by infrared spectroscopy (FT-IR). The
FT-IR spectra of 10-S,S-6 and 10-R,R-6 are shown in Figure 2 (b,
c). These spectra were compared with that of the sulfonyl chloride
functionalized support 10 (Figure 2, a) and those of (S,S)-7 and
(S,S)-6 (Figure 2, d, e). The two chiral solids gave identical
spectra. In accordance with previously published observations,[15]
the symmetric O=S=O valence vibration band (at 1367 cm-1 in the
spectrum of 10) appeared at 1323 cm-1 in the spectra of the chiral
solids, whereas the asymmetric O=S=O band shifted from 1168
cm-1 (in the spectrum of 10) to 1142 cm-1. Additionally the band
corresponding to the stretching vibration of the C‒N bond may be
identified at 1094 cm-1. Several other absorption bands found in
the spectrum of (S,S)-7 also appeared in the spectra of the chiral
resins overlapped with the characteristic vibration bands of the
polymer support. The broad intense band at 1662 cm-1 may be
attributed to swelling of the polymer in N,N-dimethylformamide
(DMF), the solvent used during the preparation of these materials.
The above observations are indicative of polymer-bonded
sulfonamide group formation.[15] Accordingly, we concluded that
the chiral diamines were immobilized on the resin by sulfonamide
linker groups.
Scheme 1. Addition of isobutyraldehyde (2) to N-phenylmaleimide (1a) or N-
benzylmaleimide (1b).
The scanning electron micrographs of the support 10 and 10-
S,S-6 showed that the spherical shape of the particles were not
altered during the preparation of the chiral catalyst (Figure 3).
However, the particle diameter increased from 70-120 m to 130-
170 m due to swelling of the polymer in DMF; the presence of
this solvent was detected by FT-IR spectroscopy (see above).
This means a 2-6 fold increase in the volume of the particles.
Figure 1. Structures of the chiral 1,2-diamine derivatives used as catalysts.
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Table 1. Enantioselective addition of 2 to 1a or 1b catalysed by chiral 1,2-diamines and their sulfonamides.[a]
3a
3b
Entry
Catalyst
Vol(CHCl3); T
t [h]
Conv 1a[b] [%]
ee[c] [%]
Conv 1b[b] [%]
ee[c] [%]
[mL; °C]
1[d]
2[d]
3
(R,R)-4
(R,R)-5
(R,R)-5
(S,S)-6
(S,S)-7
(S,S)-7
(S,S)-7
(S,S)-7
(S,S)-7
(R,R)-8
2; 24
2; 24
2; 24
1; 70
1; 70
1; 24
0.5; 24
1; 70
1; 70
1; 70
3
22
92
5 (R)
95 (R)
95 (R)
75 (S)
>99 (S)
99 (S)
>99 (S)
>99 (S)
97 (S)
>99 (R)
18
73
8 (R)
89 (R)
90 (R)
72 (S)
98 (S)
98 (S)
99 (S)
97 (S)
97 (S)
99 (R)
3
5
>99
93
93
4
24
24
72
72
24
24
24
88
5
98; 88[f]
55
95; 86[f]
43
6
7
71
62
8[d]
9[d,e]
10
99
92
88
80
99
98
[a] Reaction conditions: 0.03 mmol catalyst, 0.3 mmol 1a or 1b and 1.2 mmol 2 in CHCl3 solvent. [b] Conversions of 1a or 1b determined by gas-
chromatography (GC). [c] Enantiomeric excess (ee) determined by GC, in brackets the absolute configuration (abs. conf.) of the product according to
previous reports[10]. [d] Using 0.6 mmol 2. [e] 0.015 mmol catalyst. [f] Isolated yields of purified (by flash-chromatography) products obtained in reactions
using 0.6 mmol 1a or 1b.
Scheme 2. Chiral solid catalysts prepared by immobilization of optically pure diamines through sulfonamide linkers (abbreviation of the
catalysts: support-abs. conf.-diamine).
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catalysts (entries 1, 2 and 8), as compared with materials
obtained from 10. We assume that the silica surface had
detrimental effect on the catalytic performance (9-R,R-6), due to
involvement of the oxide surface both in bonding the diamine and
in the asymmetric reaction. Moreover, upon recycling of the used
catalyst the conversion decreased significantly (entry 3). The poor
results obtained with catalyst 11-S,S-6 may be ascribed to less
accessible catalytic species under the reaction conditions
(different solvents are used during immobilization and Michael
additions, i.e. DMF and CHCl3, respectively) as compared with the
catalysts prepared from 10.
Slightly lower ees were attained with catalysts prepared using
10 as support as compared with the soluble sulfonamide (S,S)-7
(entries 5-7). However, these values were much higher as
compared with those resulted by the use of diamine (S,S)-6.
These results showed that immobilization of diamines by
sulfonamide linkers to solid materials may result in efficient chiral
catalyst when a proper support is used. Lower ee was obtained
using the immobilized cyclohexane-1,2-diamine 10-R,R-4 (entry
4), when compared with (R,R)-5, however, this solid catalyst also
performed better than the corresponding soluble diamine (R,R)-4.
Figure 2. FT-IR spectra of 10 (a), 10-S,S-6 (b), 10-R,R-6 (c), (S,S)-7 (d) and
(S,S)-6 (e).
Table 2. Enantioselective addition of 2 to 1a catalysed by 1,2-diamines
immobilized on the support through sulfonamide groups.[a]
Entry
1
Catalyst
T [°C]
70
t [h]
24
Conv[b] [%]
ee[c] [%]
86 (R)
90 (R)
82 (R)
62 (R)
96 (R)
96 (S)
95 (S)
87 (S)
64 (S)
92 (S)
9-R,R-6
54
86
2
9-R,R-6
24
168
168
24
3[d]
4
9-R,R-6
24
46
10-R,R-4
24
>99
95[e]
94
5
10-R,R-6
70
24
6
10-S,S-6
70
24
7
10-S,S-6
24
72
44
8
11-S,S-6[f]
(S,S)-6 + TsOH[g]
(S,S)-6 + TsOH[h]
70
24
35
9
70
24
80
10
70
24
25
[a] Reactions performed using 100 mg chiral catalyst, 0.3 mmol 1a and 1.2
mmol 2 in 1 mL CHCl3. [b] Conversions of 1a determined by GC. [c]
Enantiomeric excess (ee) determined by GC, in brackets the abs. conf. of
the excess enantiomer. [d] Result with reused catalyst. [e] The product was
isolated in 80% yield. [f] 60 mg catalyst. [g] Reaction using 0.03 mmol
(S,S)-6 and 0.015 mmol TsOH. [h] Reaction using 0.03 mmol (S,S)-6 and
0.03 mmol TsOH.
Figure 3. SEM micrographs of 10 (a) and 10-S,S-6 (b).
Results obtained using the chiral solid catalysts in the addition
of 2 to 1a are summarized in Table 2. All heterogeneous chiral
materials provided better ees than the corresponding soluble
diamines, i.e. (S,S)-6 or (R,R)-4 (compare Table 1, entries 1 and
4 with Table 2). Using the functionalized silica gel 9 or the
polystyrene (PSt) resin 11 (higher degree of cross-linking as
compared with 10, see Experimental Section) as supports for
bonding 6, resulted in less active and less enantioselective
We considered possible that the lower ee values obtained with
solid catalyst may be due to the presence of the corresponding
chiral diamine bonded by ionic interactions on sulfonic acid
surface groups. These groups could be generated during the
immobilization process by hydrolysis of the surface sulfonyl
chloride in the presence of trace amounts of water. Accordingly,
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control experiments were carried out to check the effect of a
sulfonic acids using (S,S)-6 catalyst and para-toluenesulfonic acid
(TsOH) additive (entries 9, 10). Half eq. acid (as compared with
the chiral diamine) resulted in decrease in the conversion and ee
(compare Table 1, entry 4 with Table 2, entry 9). In presence of 1
eq. TsOH the conversion decreased drastically and the ee
approached, but didn’t reached those obtained with the catalyst
10-S,S-6 or the soluble sulfonamide (S,S)-7. These results
confirmed that the presence of surface sulfonic acid groups might
decrease slightly both the conversion and the ee. However, the
high stereoselectivities obtained using the solid catalysts may be
attributed to the active surface sites resulted by bonding 1,2-
diamines through sulfonamide linkers.
The recyclability of the enantioselective catalysts obtained
using the polymeric support 10 was also examined. Selected
results obtained by reusing these catalysts are shown in Figure 4.
The activity of 10-S,S-6 decreased gradually starting from the
forth use while the ee value was unaltered even in the sixth run
(Figure 4, a). The conversion decrease may be attributed to either
deactivation of the surface chiral centers or the decrease of the
number of the active sites due to deterioration of the solid material
during reactions. However, the high ee values showed that the
remaining sites were unaffectedly stereoselective. The catalyst
having surface-bonded cyclohexane-1,2-diamine (10-R,R-4) also
started to lose its activity following three uses (Figure 4, b).
Interestingly, during the first three reactions the ee increased from
62% to 85%, followed by small decrease in succeeding runs. This
initial ee increase may be explained by the previously suggested
immobilization of the diamine by ionic bonding. These species will
catalyze the reaction with lower stereoselectivity. However, may
leach easily into solution during reactions. Accordingly, the
remaining covalently bonded chiral sites will provide higher
enantioselectivities in the second and third run as compared with
the first. Following this the deterioration and deactivation of the
chiral surface sites occurs.
Leaching of the material due to mechanical deterioration
during stirring was verified using catalyst 10-S,S-6 in experiments
carried out at room temperature by shaking the reaction mixture
instead of magnetic stirring. The conversion hardly decreased
even in the fifth run (from 44% to 41%), whereas the ee remained
95%. Thus, the decrease of the catalyst activity may be ascribed
in part to leaching of the material owing to attrition of the particles.
Deterioration of the catalyst particles during reactions was
checked by SEM measurements (Figure 5). Using magnetic
stirring the catalyst shredded in small pieces following five
reactions (b). By shaking the mixture besides some smaller
catalyst pieces most of the particles kept their spherical shape
and size (c). However, irreversible transformation of the surface
primary chiral amines by reaction with the excess aldehyde is also
a possible reason of catalyst deactivation, as suggested in other
Figure 4. Conversions (black bars) and ees (grey bars) obtained in recycling
experiments of 10-S,S-6 (a) and 10-R,R-4 (b) catalysts in the Michael addition
of 2 to 1a; for reaction conditions see Table 2 entry 6 (a) and entry 4 (b).
The performances of the above heterogeneous chiral
catalysts were also examined in the addition of 2 to 1b. The
amount of 2 was reduced to half (2 eq. instead of 4) in order to
diminish the effect of the undesired irreversible transformation of
the surface primary amine in reactions with the large excess of
aldehyde. We also kept the conversions at slightly lower values to
reveal clearly the catalysts performances upon reuse. Selected
results are presented in Table 3. Similar tendencies were
observed in this reaction, as in the previous (1a + 2). The initial
activity of 10-S,S-6, which afforded around 85% conversions in
three consecutive reactions, decreased in the fourth run, while the
ee didn’t alter by recycling the catalyst. In this reaction ee values
as high as 97% could be obtained. Increase in the ee by recycling
of 10-S,S-4 was observed in this reaction, too, similarly with the
reaction of 1a, accompanied by a more significant conversion
decrease as compared with the 10-S,S-6 catalyst.
asymmetric
reactions
catalyzed
by
heterogenized
organocatalysts.[16]
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Figure 5. SEM micrographs of the as prepared 10-S,S-6 (a), 10-S,S-6 following 5 runs using magnetic stirring (b) or using agitation in a shaker (c).
small decrease in conversions, however still providing high, up to
97%, enantiomeric excesses. These chiral solid materials are the
first heterogeneous catalysts, which were used in the
Table 3. Enantioselective addition of 2 to 1b catalysed by 1,2-diamines
immobilized through sulfonamide linkers.[a]
enantioselective addition of an aldehyde to maleimides.
Entry
Catalyst
Run nr.
T [°C]
Conv[b] [%]
ee[c] [%]
Experimental Section
1
10-R,R-6
10-R,R-6
10-R,R-6
10-R,R-6
10-R,R-6
10-S,S-6
10-R,R-4
10-R,R-4
10-R,R-4
10-R,R-4
1
2
3
4
1
1
1
2
3
4
70
70
70
70
24
70
24
24
24
24
83[d]
86[d]
84[d]
75
97 (R)
97 (R)
97 (R)
97 (R)
96 (R)
97 (S)
61 (R)
78 (R)
85 (R)
86 (R)
Supports used for preparing the heterogeneous chiral catalysts: 4-ethyl
benzenesulfonyl chloride functionalized silica gel, 200-400 mesh, 1
mmol/g loading (9, Aldrich); polymer-bound sulfonyl chloride, 100-200
mesh, 1.5-2.0 mmol/g loading, 1 % cross-linked (10, Aldrich) and polymer-
bound sulfonyl chloride, 70-90 mesh, 2.5-3.0 mmol/g loading, 8.5 % cross-
linked with divinylbenzene (11, Aldrich) were commercial products. The
optically pure diamines and sulfonamides, maleimides and
isobutyraldehyde were obtained from Aldrich and used without purification.
Solvents and reagents used in the preparation of the catalysts, in the
asymmetric Michael additions and during chromatographic purifications
were of analytical grade.
2
3
4
5[e]
6
25
81
7
>99
>99
92
8
Preparation and characterization of the heterogeneous catalysts
9
All heterogeneous catalysts were prepared according to the following
procedure, however, the support or reactants quantities were modified
depending on the support functional group loading. In a 50 mL cylindrical
glass flask having two inlets and containing a glass filter (Merrifield vessel)
1 g functionalized support (10) was suspended in 10 mL DMF. Following
5 min. swelling 4 mmol Et3N and 4 mmol (S,S)-6 was added and the
suspension was shaken 24 h. The liquid was removed by suction and the
remaining solid material was washed once with 10 mL DMF and twice with
10 mL CH2Cl2, dried at rt and stored in a glass vial until use. By this method
1.11 g 10-S,S-6 catalyst was obtained from 10 and (S,S)-6. The chiral
compound content was calculated based on results of elemental analysis
using a Perkin-Elmer 2400 CHNS elemental analyser. Infrared spectra
were collected with a Bio-Rad Digilab Divison FTS-65A/896 FT-IR
spectrometer operated in diffuse reflectance mode between 4000 and 400
cm-1 at 2 cm-1 resolution by averaging 256 scans. Scanning electron
microscopic (SEM) measurements were carried out on a Hitachi S-4700
Tyle II FE-SEM microscope. The samples were mounted on a conductive
carbon tape and sputter coated by a thin Au/Pd layer in Ar atmosphere
prior to measurements.
10
70
[a] 100 mg chiral catalyst, 0.3 mmol 1b and 0.6 mmol 2 in 1 cm3 CHCl3, 24
h. [b] Conversions of 1b determined by GC. [c] Enantiomeric excess (ee)
determined by GC, abs. conf. of the excess enantiomer. [d] Products
obtained in these runs were unified and isolated in 75% yield. [e] t 72 h.
Conclusions
In the present study, we designed heterogeneous chiral materials
to catalyse the asymmetric Michael addition of aldehydes to N-
substituted maleimides. For this purpose the performances of
simple optically pure 1,2-diamines and their commercially
available sulfonamides were investigated. According to the
results of these experiments we found promising the
immobilization of the diamines through sulfonamide linkers
starting from sulfonyl chloride functionalized supports. The chiral
solid catalysts obtained using a polystyrene support and optically
pure 1,2-diphenylethane-1,2-diamines were highly active and
enantioselective heterogeneous catalysts, giving results which
approached those attained with soluble catalysts. The catalysts
were recyclable keeping their activity few runs followed by gradual
Michael additions: general procedure and product analysis
Michael additions were carried in 4 mL closed glass vials. In a typical run
the given amount of catalyst was introduced into the reactor dissolved or
suspended in the given amount of CHCl3 followed by addition of 0.3 mmol
N-fenil- or N-benzylmaleimide and the required amount of
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isobutyraldehyde (0.6 or 1.2 mmol). The vial was closed and was either
stirred or shaken at room temperature or immersed in a preheated oil bath
and stirred magnetically. After the given time the mixture was diluted to 3
mL with CHCl3. The soluble catalysts were extracted with 1 mL saturated
NH4Cl aqueous solution, the aqueous phase was washed twice with 2 mL
CHCl3, the unified organic phases were dried over MgSO4 and analysed.
The suspensions obtained using heterogeneous catalysts were diluted to
3 mL with CHCl3 and the catalyst was centrifuged. The solid was washed
twice with 1 mL CHCl3 and the obtained unified organic solution was
treated as described for homogeneous reactions.
Products were identified by mass spectrometric analysis using Agilent
Techn. 6890N GC - 5973 MSD and a 30 m DB1-MS UI capillary column.
Conversions and enantiomeric excesses (ee) were determined by gas-
chromatographic analysis using Agilent 6890N GC-FID equipped with a 30
m Cyclosil-B chiral capillary column (Agilent, J&W) and n-decane as
internal standard. Products were isolated by flash chromatography on
silica gel 60, 40-63 μm, using hexane isomers/ethyl acetate 2/1 (3a) or 4/1
(3b) mixtures as eluent. The purity of the fractions were checked by thin-
layer chromatography on Kieselgel-G (Merck Si 254 F) layers. NMR
spectra of the purified products were recorded on a Bruker Ascend 500
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Acknowledgements
Financial support of the Hungarian National Science Foundation
through OTKA Grant K 109278 is appreciated. The work was
supported by the ÚNKP-17-2-II. New National Excellence
Program of the Ministry of Human Capacities, Hungary (V.
Kozma.). The authors thank to Tamás Gyulavári, Prof. Klára
Hernádi, Dr. Gábor Varga and Dr. Gergő Motyán for their help in
characterization of the chiral solid catalysts.
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Conflict of interest
The authors declare no conflict of interest.
Keywords: Michael addition; asymmetric; heterogeneous;
organocatalyst; maleimide
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Entry for the Table of Contents
FULL PAPER
Bonding of optically pure 1,2-
diamines on polystyrene supports by
sulfonamide groups resulted in
efficient H-bond donor linkers
necessary to obtain active
heterogenized organocatalyst for the
enantioselective Michael addition of
isobutyraldehyde to maleimides. The
performances of the recyclable
heterogeneous catalysts
György Szőllősi* and Viktória Kozma
Page No. – Page No.
Design of heterogeneous
organocatalyst for the asymmetric
Michael addition of aldehydes to
maleimides
approached that of the
corresponding soluble sulfonamides.
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