Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel-Crafts alkylations

Article abstract of DOI:10.3762/bjoc.11.83

The first immobilization of a MacMillan's first generation organocatalyst onto dendritic support is described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a-c was tested in the asymmetric Friedel-Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles.

Full text of DOI:10.3762/bjoc.11.83

Multivalent polyglycerol supported imidazolidin-4-one
organocatalysts for enantioselective
Friedel–Crafts alkylations
Tommaso Pecchioli, Manoj Kumar Muthyala, Rainer Haag* and Mathias Christmann*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 730–738.
Institut für Chemie und Biochemie, Freie Universität Berlin,
Takustraße 3, 14195 Berlin, Germany
doi:10.3762/bjoc.11.83
Received: 06 March 2015
Accepted: 29 April 2015
Published: 12 May 2015
Email:
Rainer Haag* - haag@chemie.fu-berlin.de; Mathias Christmann* -
mathias.christmann@fu-berlin.de
This article is part of the Thematic Series "Multivalency as a chemical
organization and action principle".
* Corresponding author
Keywords:
Associate Editor: D. Dixon
Friedel–Crafts; homogeneous catalysis; hyperbranched polyglycerol;
imidazolidin-4-one; multivalency
© 2015 Pecchioli et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The first immobilization of a MacMillan’s first generation organocatalyst onto dendritic support is described. A modified tyrosine-
based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne–azide
cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent
organocatalysts 4a–c was tested in the asymmetric Friedel–Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A
variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monova-
lent analogues. The catalyst 4b showed excellent turnover rates and no loss of activity due to immobilization, albeit moderate
enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three
cycles.
Introduction
In nature, multivalent architectures, e.g., enzymes, bacteria or valent architectures for catalytic applications [9]. In general,
viruses, are responsible for cooperative interactions between both linear and various families of branched polymers such as
different interfaces or molecules [1]. The realization of the dendrimers, dendritic-hybrid and hyperbranched polymers are
concept of multivalency has attracted attention from different used as macromolecular support for catalysis [10-12]. Linear
fields ranging from medicine and biochemistry [2] to supra- polymers such as poly(ethylene glycol) (PEG) [13] or non-
molecular chemistry [3,4] and materials sciences [5]. However, cross-linked polystyrene (NCPS) [14] are readily available but
applications in catalysis are still limited [6-8]. Recently, the use suffer from poor loading capacity, while in the case of
of polymeric support has stimulated the development of multi- dendrimers, the highest loading can be achieved due to their
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extraordinary branching [15]. These well-defined molecules are The use of chiral imidazolidinones in organocatalysis has been
soluble in many organic solvents and can combine the advan- extensively reported for a wide range of enantioselective reac-
tages of hetero- and homogeneous catalysis [16,17]. However, tions involving α,β-unsaturated aldehydes, such as the
their tedious and multistep syntheses using either divergent or Diels–Alder reactions [50], 1,3-dipolar cycloadditions [51] and
convergent approaches are arguably the reason for their limited Friedel–Crafts alkylations [52,53]. To date, heterogenizations
use as support in organic synthesis [18]. To overcome these have been applied mainly in Diels–Alder reactions [54-61].
obstacles, a hybrid dendron-polymer might constitute a valu- Nevertheless, Friedel–Crafts alkylations are recently emerging
able alternative for high-loading platforms [19], despite the use as a compelling field of study as reported by Pericàs [62] and
of solid support such as polystyrene may lead to the disadvan- others [58,60]. The simple approach providing an enantioselect-
tage of operating in heterogeneous media. In contrast to the ive entry to new C–C bonds allows for the use of readily avail-
stepwise syntheses of dendrimers and dendron hybrids, the hy- able starting materials and can typically be carried out in
perbranched polymers can be easily obtained in kilogram scale THF–water mixtures. Our aim was to employ this transforma-
through one-pot reactions [10], maintaining properties such as tion as a benchmark in order to explore the efficiency of novel
high loading capacity combined with the solubility characteris- multivalent architectures.
tics of the respective dendrimers [20,21]. As a macromolecule,
the supported catalyst can be recovered from the reaction media Herein, we describe the first immobilization of imidazolidin-4-
by selective precipitation, dialysis or filtration techniques, one onto hyperbranched polyglycerol (hPG) and its application
depending on its particular physical properties. Hyperbranched as multivalent organocatalyst.
polymers like polytriallylsilane or polyglycerol have been used
in a wide range of transformations including aldol condensa- Results and Discussion
tions [22], Suzuki cross-couplings [23] and Diels–Alder reac- To explore the synthetic utility of hPG in organocatalysis, we
tions [24], to name a few, with metal complexes as catalytically here report the synthesis and application of a series of three
active principle.
multivalent dendronized imidazolidin-4-ones PG-95 (4a),
PG-57 (4b) and PG-30 (4c) representing different degrees of
The advent of organocatalysis has allowed for selective C–C functionalization: 95% (4a), 57% (4b) and 30% (4c), respect-
bond formation by using small organic molecules [25-31]. In ively. An (S)-tyrosine-derived imidazolidin-4-one 5 was
contrast to metal complexes, chiral or achiral organocatalysts anchored to the polymeric support through a CuAAC reaction.
are easily attached on supports. They do not suffer from metal Following the same strategy, a monovalent analog 8 bearing a
leaching and they can be reused more readily [32-36]. More- G1 glycerol dendron tail was also prepared for comparison with
over, their stability allows to perform reactions under mild and the multivalent systems 4a–c and evaluation of the possible
aerobic conditions and in the presence of water, both as presence of cooperative effects (Scheme 1).
co-solvent or the only solvent [37]. In the last years, several
reports on water effects in organocatalytic reactions were Polyglycerol 1 (Mn = 9000 g/mol, loading OH = 13.5 mmol/g,
published [38-42]. The use of supported catalyst has proven PDI = 1.87) was obtained following a previously reported
beneficial with regard to rate acceleration and increased selec- procedure by a one-step ring opening anionic polymerization
tivity due to formation of an aqueous microenvironment favored (ROAP) [49]. The controlled mesylation on hPG 1 yielded 2a–c
by the swelling properties of polymeric materials [43]. Particu- (95%, 57% and 30% of functionalization, respectively (for
larly, in the case of dendritic proline derivatives [44-46] and details see Supporting Information File 1)), which were
N-alkylimidazole decorated dendron-hybrids [47], the presence converted to the corresponding azides 3a–c [63,64]. Azide 6
of water was crucial for aldol and Baylis–Hillman reactions, as was prepared according to well-established protocols [65].
recently reported by Miller and Portnoy [48].
Consequently, we adopted the Sharpless–Fokin modification for
the Huisgen azide–alkyne cycloaddition [66] to achieve the
To the best of our knowledge, the immobilization of chiral final immobilization of the modified imidazolidin-4-one onto
organocatalysts on hyperbranched polymeric support has the hyperbranched polymer and on the G1 dendron [65]. The
remained unexplored. Therefore, we decided to use hyper- progress of the reaction was monitored by IR spectroscopy and
branched polyglycerol (hPG) [49] as a polymeric support. The TLC. Purification of the products 4a–c was carried out by
high local concentration of hydrophilic functionality present on washing with aqueous saturated EDTA solution followed by
its periphery is especially attractive since it might promote dialysis in methanol/chloroform mixture for 24 h, and then in
water coordination. These properties prompted us to investigate methanol and chloroform, respectively, for additional 12 h each.
the effects of high-loading support in asymmetric organocatal- The catalyst structures were confirmed by 1H and 13C NMR
ysis.
spectroscopy and the functionalization degrees of 4a–c were
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Beilstein J. Org. Chem. 2015, 11, 730–738.
Scheme 1: Synthesis of hyperbranched polyglycerol-supported and G1 dendronized imidazolidin-4-ones 4a–c and 8 using a CuAAC reaction. Reac-
tion conditions: (a) 1 (1.0 equiv), MsCl (1.2 equiv, with respect to degrees of functionalization), pyridine, 25 °C, 16 h, 76% 2a, 82% 2b and 87% 2c.
(b) 2a–c (1.0 equiv), NaN3 (3.0 equiv), DMF, 65 °C, 72 h, 72% 3a, 81% 3b and 86% 3c. (c) 3a–c (1.0 equiv), 5 (2.0 equiv), CuSO4·5H2O (0.2 equiv),
sodium ascorbate (2.0 equiv), THF/H2O 3:1 (v/v), 25 °C, 48 h, 71% 4a, 40% 4b and 35% 4c. (d) 6 (1.1 equiv), 5 (1.0 equiv), CuSO4·5H2O (0.1 equiv),
sodium ascorbate (0.2 equiv), DIPEA (0.1 equiv), THF/H2O 3:1 (v/v), 25 °C, 12 h, 70%. (e) 7, Dowex 50, MeOH, reflux, 12 h, 95%.
determined by correlating the aromatic with the polyglycerol and subsequent anchoring of the linker was realized through
backbone protons (for details see Supporting Information O-alkylation on phenol 10, leading to linkable catalyst 5 in
File 1).
excellent yield (Scheme 2).
The synthesis of modified imidazolidin-4-one 5 started with (S)- The reactivity of the multivalent catalysts 4a–c was investi-
tyrosine methyl ester hydrochloride (9). Following a protocol gated in the Friedel–Crafts alkylation of N-methylpyrrole (11)
by Zhang and co-workers [58], 10 was obtained in good yield with α,β-unsaturated aldehydes reported by MacMillan [53]. To
Scheme 2: Synthesis of tyrosine-based imidazolidin-4-one 5. Reaction conditions: (a) 9 (1.0 equiv), MeNH2 (5.0 equiv), EtOH, 25 °C, 20 h. (b) PTSA
(0.01 equiv), acetone, MeOH, reflux, 18 h, 79% (2 steps). (c) 10 (1.0 equiv), NaH (1.1 equiv), 6-chloro-1-hexyne (1.3 equiv), TBAI (0.01 equiv), DMF,
25 °C, 16 h, 88%.
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Beilstein J. Org. Chem. 2015, 11, 730–738.
make the results comparable, we normalized the loading of the strongly dependent on the solvent/water ratio and the catalysts
multivalent catalysts 4a–c with respect to the number of single 4a–c exhibited different activity with changes on the degrees of
anchored imidazolidin-4-ones. Therefore, a constant number of functionalization. In general, catalysts 4a and 4b were found to
catalytic units for each degree of functionalization was main- be more efficient in comparison to the less functionalized 4c.
tained. Initially, we decided to perform the reaction using trans- Probably, the poor ability of 4c to catalyze the model transfor-
cinnamaldehyde (12) as a model substrate and trifluoroacetic mation might be explained by its low solubility in the reaction
acid (TFA) as an additive. In a preliminary survey on the water medium, most likely due to the large number of free hydroxy
influence, a catalyst loading of 3.5 mol % in THF was selected groups on the periphery of the multivalent catalyst. Instead,
to allow 4a and 4b to operate under homogeneous conditions, catalysts 4a–c demonstrated to be completely soluble in chloro-
while in the same solvent 4c proved to be less soluble (Table 1). form and methanol. Unfortunately, the use of these solvents led
to decreased yields and selectivities of 13. Therefore, we
decided to further investigate the superior catalysts PG-95 (4a)
Table 1: Initial screening on the Friedel–Crafts alkylation of
N-methylpyrrole (11) with trans-cinnamaldehyde (12).a
and PG-57 (4b) in THF/H2O mixture.
As reported in the literature, immobilization of chiral imidazo-
lidin-4-ones on polymeric support might affect the formation of
the desired products and lead to decreased enantioselectivities
[58]. Indeed, in all the experiments reported in Table 1 the
enantiomeric excess of 13 was lower compared to MacMillan’s
original experiments [53]. In an attempt to improve the enan-
tiomeric ratios, we studied the influence of temperature using
the optimized conditions obtained for 4a and 4b in Table 1 (for
results, see Table 2).
Entry
Catalyst
THF/H2O (v/v) Yield (%)b ee (%)c
1
2
PG-95 (4a)
PG-57 (4b)
PG-30 (4c)
PG-95 (4a)
PG-57 (4b)
PG-30 (4c)
PG-95 (4a)
PG-57 (4b)
PG-30 (4c)
PG-95 (4a)
PG-57 (4b)
PG-30 (4c)
100:0
100:0
100:0
95:5
38
56
26
62
68
32
42
38
45
–d
–d
–d
66
69
56
68
66
59
59
60
54
–
3
4
5
95:5
Table 2: Influence of temperature in the Friedel–Crafts alkylation.a
6
95:5
7
90:10
90:10
90:10
0:100
0:100
0:100
8
9
10
11
12
–
–
aReaction conditions: trans-cinnamaldehyde (12, 0.25 mmol,
Entry
Catalyst
T (°C) t (h) Yield (%)b ee (%)c
1.0 equiv), N-methylpyrrole (11, 1.25 mmol, 5.0 equiv), catalyst 4a–c
(3.5 mol %), aq TFA (5 M; 3.5 mol %), 0.63 M with respect to trans-
cinnamaldehyde (12), 25 °C, 20 h. bIsolated yield. cDetermined by
chiral GC. dComplex mixture of products.
1
2
PG-95 (4a)
PG-57 (4b)
25
25
20
20
62
68
68
66
3
4
5
6
PG-95 (4a)
PG-57 (4b)
PG-95 (4a)
PG-57 (4b)
4
35
35
48
48
60
64
46
25
68
68
76
78
4
–24
–24
Moderate conversion of 13 were achieved using only THF as a
solvent and in presence of substoichiometric amounts of water
(0.4 equiv) [41]. Addition of water as co-solvent proved benefi-
cial for the formation of product 13. Notably, PG-95 (4a) and
PG-57 (4b) exhibited comparable trends and the best yield and
ee were observed when 5 vol % of water was added to the reac-
tion mixture (Table 1, entries 4 and 5). Increasing the water
content to 10 vol % resulted in incomplete conversion to 13 and
aReaction conditions: trans-cinnamaldehyde (12, 0.25 mmol,
1.0 equiv), N-methylpyrrole (11, 1.25 mmol, 5.0 equiv), catalyst 4a,b
(3.5 mol %), aq TFA (5 M; 3.5 mol %), THF/H2O 95:5 (v/v), 0.63 M with
respect to trans-cinnamaldehyde (12). bIsolated yield. cDetermined by
chiral GC.
lower ee values of the product (Table 1, entries 7 and 8). In case To our dismay, running the transformation at lower tempera-
of the more hydrophilic PG-30 (4c) the activity increased with tures did not lead to any significant improvements, although
the amount of water in the reaction medium; yields and selectiv- slight changes were observed. Carrying out the reactions at 4 °C
ities remained moderate. Attempts to carry out the reaction in gave similar ee values (Table 2, entries 3 and 4), whereas at
water as the only solvent were unsuccessful (Table 1, entries −24 °C the alkylation led to marginally increased selectivities,
10–12). As expected, the outcomes of this reaction were at the cost of a drop in the yield (Table 2, entries 5 and 6).
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Beilstein J. Org. Chem. 2015, 11, 730–738.
Nevertheless, the observed enantiomeric excess of the product
13 is still low when compared with those (93% ee, at −30 °C)
originally reported in the case of the traditional (S)-phenylala-
nine-based imidazolidin-4-one [53].
Table 4: Dilution experiments.a
Using the optimized solvent system (Table 1), we then turned
our attention to study the catalyst loading and further prove the
efficiency of multivalent 4a and 4b (Table 3).
Entry
Catalyst
Conc.
(M)b
THF/H2O
(v/v)
Yield
(%)c
ee
(%)d
1e
2e
PG-95 (4a)
PG-57 (4b)
0.63
0.63
97:3
97/3
66
65
68
67
Table 3: Catalyst loading study.a
3
4
5
6
PG-95 (4a)
PG-57 (4b)
PG-95 (4a)
PG-57 (4b)
0.30
0.30
0.10
0.10
98.5:1.5
98.5:1.5
99.5:0.5
99.5:0.5
70
87
68
70
<1f
29f
n.d.g
n.d.g
aReaction conditions: trans-cinnamaldehyde (12, 0.25 mmol,
1.0 equiv), N-methylpyrrole (11, 1.25 mmol, 5.0 equiv), catalyst 4a,b
(2 mol %), aq TFA (5 M; 2 mol %), 25 °C, 48 h. bWith respect to trans-
cinnamaldehyde (12). cIsolated yield. dDetermined by chiral GC.
etrans-Cinnamaldehyde (12, 0.50 mmol, 1.0 equiv), N-methylpyrrole
(11, 2.50 mmol, 5.0 equiv). fDetermined by 1H NMR. gn.d. = not deter-
mined.
Entry
Catalyst
Load.
(mol %)
THF/H2O
(v/v)
Yield
(%)b
ee
(%)c
1
2
3
4
5
6
PG-95 (4a)
PG-57 (4b)
PG-95 (4a)
PG-57 (4b)
PG-95 (4a)
PG-57 (4b)
2
2
2
2
1
1
95:5
95:5
43
62
66
65
46
50
59
64
68
67
67
74
97:3
97:3
98.5:1.5
98.5:1.5
The best yield and enantioselectivity of 13 was obtained using
PG-57 (4b) and lowering the concentration from 0.63 to 0.30 M
(Table 4, entry 4). Contrarily, PG-95 (4a) did not lead to any
appreciable improvement (Table 4, entry 3). By reducing the
concentration to 0.10 M, 4b gave only poor to moderate yields
while the efficiency of 4a decreased even more sharply and
only traces of product 13 were observed (Table 4, entries 5 and
6). On the other hand, the enantioselectivities remained
aReaction conditions: trans-cinnamaldehyde (12, 0.50 mmol,
1.0 equiv), N-methylpyrrole (11, 2.50 mmol, 5.0 equiv), catalyst 4a,b (2
or 1 mol %), aq TFA (5 M; 2 mol %, entries 1–4 or 1 mol %, entries 5
and 6), 0.63 M with respect to trans-cinnamaldehyde (12), 25 °C, 48 h.
bIsolated yield. cDetermined by chiral GC.
Initial attempts with 2 mol % of the multivalent 4a and 4b, unchanged passing from concentration of 0.63 M to more
using 5 vol % of water in THF led to the isolation of 13 in diluted conditions (0.30 M). This outcome might be attributed
moderate yield and slightly lower enantioselectivies, a result to the constant local neighborhood in the polymer periphery
even more pronounced in the case of PG-95 (4a) (Table 3, where the catalytic centers are located, therefore the concentra-
entries 1 and 2). Next, we questioned if in addition to a catalyst tion may not affect the chiral induction [24].
loading reduction also a concomitant reduction of the water
amount was necessary to maintain yield and enantiomeric ratio. After the completion of our systematic optimization of the reac-
Consistently, we reduced the water amount from 5 to 3 vol % tion parameters using the model transformation, the most active
and observed higher conversion to 13 and improved ee values catalyst 4b was selected for a screening of different enals in the
(Table 3, entries 3 and 4). Therefore, in the following experi- alkylation reaction of N-methylpyrrole (11). A study on the sub-
ments the catalyst/water ratio was kept constant. The excellent strate scope was further carried out under the established condi-
efficiency of the catalyst was confirmed with moderate to good tions (see Table 4, entry 4). A variety of substituted α,β-unsatu-
yields of 13 even though using 1 mol % of 4a and 4b, respect- rated aldehydes 14a–e was employed using 2 mol % PG-57
ively (Table 3, entries 5 and 6). Considering, for the supported (4b) in THF/H2O 98.5:1.5 (v/v) (Table 5).
case, a typical catalyst loading for this transformation to be 10
mol % in order to achieve good conversion [62], the loadings Multivalent catalyst 4b showed good to excellent activities in a
reported in Table 3 could be decreased by one order of magni- range of substrates and moderate to good enantiomeric ratios
tude.
for the formation of products 15a–e, as shown in Table 5. Elec-
tron-deficient aromatic enals 14d,e afforded higher yields and
After solvent and temperature screening, our studies were selectivities, confirming the strong influence of the substituent
focused on dilution experiments (Table 4).
(Table 5, entries 4 and 5). Contrarily, aliphatic enals 14a,b were
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Beilstein J. Org. Chem. 2015, 11, 730–738.
Table 5: Substrate scope.a
Entry
1
Substrate
Product
t (h)
Yield (%)b
86
ee (%)c
14a
14b
15a
15b
24
69
2
3
24
48
83
80
68
56
14c
14d
14e
15c
15d
15e
4
5
48
48
86
99
71
78
aReaction conditions: aldehyde 14a–e (0.25 mmol, 1.0 equiv), N-methylpyrrole (11, 1.25 mmol, 5.0 equiv), catalyst 4b (2 mol %), aq TFA (5 M;
2 mol %), THF/H2O 98.5:1.5 (v/v), 0.30 M with respect to aldehyde 14a–e, 25 °C. bIsolated yield. cDetermined by chiral GC.
well-tolerated and the outcomes were not affected significantly additional cooperative effects between the active catalytic sites.
(Table 5, entries 1 and 2).
Increased activities were observed compared to MacMillan’s
catalyst 16, albeit with lower enantioselectivity (Table 6, entries
In our studies on the utilization of hPG as a soluble support in 2, 3 and 4). Catalyst 4a showed turnover rates comparable with
organocatalysis, hyperbranched PG-95 (4a) and PG-57 (4b) the traditional imidizolidin-4-one 16 (Table 6, entries 1 and 4).
were finally compared with the monovalent G1-dendron imida- In conclusion, high- (PG-95, 4a) or low- (PG-30, 4c) loaded
zolidin-4-one 8 previously prepared and the original support were less active when compared to an intermediate
MacMillan’s first generation catalyst 16 using the optimum degree of functionalization (PG-57, 4b). In the case of PG-57
conditions (Table 6).
(4b) a good compromise between hydrophilicity and solubility
was achieved. The results reported in Table 6 point out that
As shown in Table 6, multivalent 4b and monovalent 8 afforded catalyst 4b was not suffering from diminished reactivity as
similar results (Table 6, entries 2 and 3), probably due to their often observed with immobilizations. Additionally the poly-
comparable high hydrophilicity. This outcome did not indicate meric support was found to be responsible for enhanced reactiv-
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Beilstein J. Org. Chem. 2015, 11, 730–738.
Table 6: Comparison of hPG catalysts 4a,b with monovalent analogue 8 and MacMillan’s first generation 16.a
Entry
Catalyst
Yield (%)b
ee (%)c
1
2
3
4
PG-95 (4a)
70
87
83
64
68
70
67
77
PG-57 (4b)
8
16
aReaction conditions: trans-cinnamaldehyde (12, 0.25 mmol, 1.0 equiv), N-methylpyrrole (11, 1.25 mmol, 5.0 equiv), cat. (2 mol %), aq TFA (5 M;
2 mol %), THF/H2O 98.5:1.5 (v/v), 0.30 M with respect to trans-cinnamaldehyde (12), 25 °C, 48 h. bIsolated yield. cDetermined by chiral GC.
ity with respect to the original imidazolidin-4-one 16. The pres-
Table 7: Catalyst recycle.a
ence of anchimeric assistance by hydroxy groups, in the hydrol-
ysis step of the iminium intermediate, might account for the
observed improved turnover rates.
To complete our studies on the generality of hPG catalysts,
finally, recycling of the polymer was studied. Heterogeneous
Entry
Cycle
Yield (%)b
ee (%)c
catalysis allowed for simple separations of the immobilized
species from the reaction media. Indeed, working under homo-
geneous conditions did not enable separation by simple filtra-
tion. On the other hand, the multivalent catalysts 4a and 4b
showed poor solubility in solvents with low polarity, thus
allowing for an easy recovery in 60–70% yield after selective
precipitation using Et2O. The utility of our soluble support was
examined in the catalytic efficiency of recovered PG-57 (4b)
(Table 7).
1d
2
1
2
3
65
54
45
67
65
65
3d
aReaction conditions: trans-cinnamaldehyde (12, 1.0 equiv),
N-methylpyrrole (11, 5.0 equiv), catalyst 4b (2 mol %), THF/H2O 97:3
(v/v), 0.63 M with respect to trans-cinnamaldehyde (12), 25 °C, 48 h.
bIsolated yield. cDetermined by chiral GLC. dAq TFA (5 M; 2 mol %)
was added to the reaction mixture.
Catalyst 4b was used three times in the asymmetric alkylation lower yields exhibited after each cycle might be attributed to the
reaction. The experiment showed constant enantiomeric ratios decreased solubility of the recovered polymer. For the same
although decreased activity and yields were observed. The reason, early attempts using the optimized parameters (conc.
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Beilstein J. Org. Chem. 2015, 11, 730–738.
References
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In summary, we have successfully employed a CuAAC strategy
in the first immobilization of a chiral imidazolidin-4-one onto
hyperbranched polyglycerol support and examined its effi-
ciency in organocatalysis. Catalyst 4c proved to be less soluble
in the reaction media compared to 4a and 4b, and showed poor
activity and selectivity. The soluble polymers 4a and 4b
enabled homogeneous reactions without loss of efficiency due
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catalyst, while 4b was shown to be superior. Nevertheless,
erosion in enantioselectivity was observed, probably as a conse-
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the dendritic architecture, where the catalytic sites are located.
The novel multivalent system 4b achieved good conversion to
afford product 13, even with low polymer loading (1 mol %)
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supported imidazolidin-4-ones. Moreover, 4b was shown to be
well-tolerated in a range of α,β-unsaturated aldehydes. The im-
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anchimeric assistance in the hydrolysis step of the iminium ion.
Interestingly, the presence of such an effect might offer oppor-
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