Synthesis and asymmetric catalytic performance of one-handed helical poly(phenylacetylene)s bearing proline dipeptide pendants

Article abstract of DOI:10.1016/j.reactfunctpolym.2019.104392

One-handed helical substituted polyacetylene has received extensive attention due to its potential in chiral stationary phases and molecular recognition. Here, three one-handed helical poly(phenylacetylene)s bearing proline or proline dipeptide as the pen

Full text of DOI:10.1016/j.reactfunctpolym.2019.104392

ReactiveandFunctionalPolymers146(2020)104392
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Reactive and Functional Polymers
journal homepage: www.elsevier.com/locate/react
Synthesis and asymmetric catalytic performance of one-handed helical poly
(phenylacetylene)s bearing proline dipeptide pendants
Lijia Liua, Yaodong Wanga, Fuqingyun Wanga, Chunhong Zhanga,⁎, Yanli Zhoua, Zhengjin Zhoua,
Xudong Liua, Ruiqi Zhua, Hongxing Donga, Toshifumi Satohb
a Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering
University, Harbin 150001, PR China
b Faculty of Engineering, Hokkaido University, Sapporo 060-8628, Japan
A R T I C L E I N F O
A B S T R A C T
Keywords:
Asymmetric aldol reaction
Dipeptide
Helical polymer
Poly(phenylacetylene)s
Proline
One-handed helical substituted polyacetylene has received extensive attention due to its potential in chiral
stationary phases and molecular recognition. Here, three one-handed helical poly(phenylacetylene)s bearing
proline or proline dipeptide as the pendants (PPA-Pro, PPA-Pro-Pro and PPA-Pro-Hyp) were synthesized. As
the catalyst, the three helical polymers separately catalyzed the asymmetric aldol reaction of acetone with p-
nitrobenzaldehyde in a various media. The results indicate that PPA-Pro-Pro and PPA-Pro-Hyp bearing di-
peptide pendants showed the higher catalytic activity and enantioselectivity than the PPA-Pro bearing proline
pendants and the corresponding monomer catalysts. This indicates the synergistic effect of the dipeptide pen-
dants with the one-handed helical mainchain of the polymer catalyst. The polymer catalysts can be recycled and
maintain the catalytic performance after four circles. When imidazole was added to the reaction system, the
reaction yield could be efficiently improved without affecting the enantioselectivity.
1. Introduction
aldol reaction and show considerable enantioselectivity [20–23]. Ya-
shima reported one-handed helical poly(substituted acetylene)s bearing
Chirality is an asymmetric property of matter and one of the basic
properties in nature. Both macroscopic substances and microscopic
biological molecules are generally chiral, and the study on the natural
properties of biological chiral molecules is conducive to the artificial
synthesis of chiral drugs [1]. Although the pairs of enantiomeric com-
pounds have very similar physical and chemical properties to each
other, they behave differently in biology, because the function of bio-
molecules such as nucleic acids and proteins is determined by their
helical structure, which is an important factor to show biological ac-
tivity [2,3]. Inspired by the exquisite helical structures of the bioma-
cromolecules, wide studies have been conducted on the synthesis of
non-biological helical polymers [4–9], such as polymethyl methacrylate
and polymethylacrylamide [10,11], polyisocyanate [12,13], polysilane
[14], polyolefin [15], polyacetylene and its derivatives [16]. Among
these helical polymers, as a typical dynamic helical polymer, poly
(substituted acetylene)s attract broad attention due to its potential in
the fields such as chiral recognition [17], chiral separation [18], and
catalytic asymmetric reactions [19]. Deng synthesized a series of opti-
cally active poly(substituted acetylene)s bearing different chiral pen-
dants, which are utilized to catalyze asymmetric Michael reaction and
cinchona alkaloid pendants, the asymmetric aldol reactions are cata-
lyzed by the helical poly(substituted acetylene)s and shows the higher
ee values than the corresponding monomer catalysts [19]. The one-
handed helical main chain in these helical polymers is thought to form
synergistic effect with the chiral pendants, which plays important roles
in the improvement on enantioselectivity of these asymmetric reac-
tions. Therefore, developing polymer catalyst having one-handed he-
lical structure is one of important fields for asymmetric synthesis.
The formation of the carbon‑carbon bonds occupies an important
position in the field of asymmetric catalytic. Aldol reaction is one of
simple methods in producing carbon - carbon bonds. Generally, reac-
tion conditions for the asymmetric catalytic reaction are very sensitive,
some minor structural differences can lead to unexpected changes.
Therefore, the research of the relationship between the structure and
the catalytic performance of the catalysts is of great importance for
constructing chiral compounds. Proline, as a kind of natural small
molecule, is widely used in asymmetric catalysis. However, proline-
derivative catalyst has the common short comings as many small mo-
lecular catalysts, it is difficult to recover and reuse. In order to solve
these problems, immobilized or polymer-supported catalyst is a general
⁎ Correspondence author.
E-mail address: zhangchunhong97@163.com (C. Zhang).
https://doi.org/10.1016/j.reactfunctpolym.2019.104392
Received 16 June 2019; Received in revised form 16 October 2019; Accepted 18 October 2019
Availableonline31October2019
1381-5148/©2019ElsevierB.V.Allrightsreserved.

L. Liu, et al.
ReactiveandFunctionalPolymers146(2020)104392
method. However, in these polymer-supported catalysts, the polymer
merely as a carrier, and cannot improve the catalytic performance.
Further research was reported that the polymer catalyst was designed
as a helical conformation to simulate the structure of the enzyme [24],
and then synergistic effect of the helical conformation with the small
chiral ligand improved the catalytic efficiency and enantioselectivity.
Dipeptides are the simplest peptides that consist of two identical or
different amino acids. Compared with a single amino acid, dipeptides
can form a large number of hydrogen bonds when forming a helical
polymer, which is conducive to the stability of the polymer. At the same
time, dipeptides have two chiral centers, which can increase the se-
lectivity of asymmetric reactions [25]. Therefore, in this study, proline
or its dipeptide derivatives were introduced into the side chains of the
helical poly(phenylacetylene)s to produce the helical polymeric cata-
lysts, catalytic properties of the helical polymeric catalysts on the aldol
reaction of acetone with 4-nitrobenzaldehyde were systematically in-
vestigated.
4H, CO-CH, CH2, NH), 5.58 (s, 1H, H-C ≡ C), 7.12–7.78 (m, 4H,
AreH), 9.98 (s, 1H, NH-CO). IR (KBr): ν = 3346 (w), 3103 (w),
3099 (w), 3039 (w), 1705 cm−1 (s).
(2) PPA-Pro-Pro is
a yellow solid. (0.29 g, 89.30%) [1]HNMR
(500 MHz, DMSO‑d6, δ): 1.67–2.37 (m, 9H, CH2, NH), 2.86–3.12
(m, 2H, CH2), 4.07–4.51 (m, 4H, CH-CO, CH2), 5.80 (s, 1H, H-
C ≡ C), 6.62–7.35 (m, 4H, AreH), 10.20 (s, 1H, NH-CO). IR (KBr):
ν = 3335 (w), 3104 (w), 3048 (w), 3036 (w), 1705 cm−1 (s).
(3) PPA-Pro-Hyp is
a
yellow solid. (0.27 g, 87.40%) 1H NMR
(500 MHz, DMSO‑d6, δ): 1.84–2.14 (m, 6H, CH2), 3.60–4.50 (m,
9H, CH-CO, CH2, OH, NH), 5.73 (s, 1H, H-C ≡ C), 6.56–7.65 (m,
4H, AreH), 9.99 (s, 1H, NH-CO). IR (KBr): ν = 3303 (w), 3295 (w),
3183 (w), 3104 (w), 3064 (w), 1697 cm−1 (s).
2.4. Aldol reaction of acetone with p-nitrobenzaldehyde
Acetone and a solvent were added to a flusk containing p-ni-
trobenzaldehyde and the catalyst, and then the mixture was stirred at a
set temperature. The reaction was quenched with brine, and the pro-
duct was extracted with dichloromethane and saturated ammonium
chloride solution. The organic extract was dried over anhydrous
Na2SO4 and then concentrated by evaporation. The residue was purified
by column chromatography (SiO2, petroleum ether/ethyl acetate = 2/
3 v/v) to give product as a yellow solid. The ee was determined by chiral
HPLC analysis (Chiralpak AS-1 column, hexane/isopropanol 95/5, v/v,
1.0 mL min−1, λ = 254 nm), tR = 50.19 min, tS = 76.26 min.
2. Experimental
2.1. Materials
Fmoc-L-proline (purity 99%), Fmoc-L-hydroxyproline (purity 99%),
Fmoc-L-Proline dipeptide (purity 99%), cyclohexanone (purity99%)
and p-nitrobenzaldehyde (purity 98%) were purchased from Aladdin
Chemical Co., Ltd. (Shanghai, China). Morpholine (purity 99%) and 4-
(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium
chloride
(DMT-MM) (purity 98%) was purchased from Sahn Chemical
Technology Co., Ltd. (Shanghai, China). Triphenylphosphine (purity
99%) was purchased from J&K Chemical Co., Ltd. (Beijing, China). Rh
(nbd)BPh4 was prepared based on a previous report [26]. All solvents
used in the reactions were of analytical grade, carefully dried, and
distilled before use. Silica gel with a mean particle size of 37–56 μm for
column chromatography was purchased from Qingdao Haiyang Che-
mical Co., Ltd. (Qingdao, China).
3. Results and discussion
3.1. Synthesis of one-handed helical poly(phenylacetylene) catalyst
Three phenylacetylene precursor monomers having a protected
proline or proline dipeptide group were synthesized and then poly-
merized by a Rh catalyst (Rh(nbd)BPh4) to produce the corresponding
polymer precursors. (Scheme 1, PPA-Pro-Fmoc, PPA-Pro-Pro-Fmoc
and PPA-Pro-Hyp-Fmoc) Then, the deprotection reaction of the pre-
cursors produced the corresponding polymer catalysts, PPA-Pro having
proline as pendants, PPA-Pro-Pro having proline dipeptide as the
pendants and PPA-Pro-Hyp having proline-hydroxyproline dipeptide
as the pendants (Scheme 1) [28–31].
Solubility of the polymers and their precursors was tested at room
temperature (Table 1). Although the precursors showed good solubi-
lities in most organic solvents, the resulting polymeric catalysts showed
poor solubility in organic solvent and were merely soluble in high polar
solvent, such as DMSO, DMAc and methanol. It was thought to be due
to that after removing the protective groups, the steric resistance of the
polymer side chains is reduced, and the exposed amino group form the
intramolecular hydrogen bonds which reduced the solubility of the
polymer.
2.2. Instruments
The 1H NMR spectra (500 MHz) were recorded using a Bruker
AVANCE III-500 instrument at room temperature. IR spectra were ob-
tained with a Perkin-Elmer FTIR-100 spectrophotometer. The circular
dichroism (CD) and ultraviolet visible (UV − vis) spectra were mea-
sured in a 1-mm path length cell using a JASCO J-815 spectro-
polarimeter. The absolute configuration of aldol products was de-
termined by JASCO PU-2089 high performance liquid chromatograph
(HPLC) system equipped with UV − vis (JASCO-UV-2070), circular
dichroism (JASCO-CD-2095) detectors and a column of DAICEL CHI-
RALCEL AS-1 using a solution of hexane/2-propanol as eluent at a flow
rate of 1.0 mL min−1 according to the literature [27]. A solution of
aldol product (3.00 mg mL−1) was injected into the chromatographic
system through an intelligent sampler (JASCO AS-2055).
3.2. Chiroptical properties of the synthesized poly(phenylacetylene)
derivatives
2.3. Synthesis of the polymer catalysts
The specific optical rotation ([α]D20) of the polymer catalysts (PPA-
Pro, PPA-Pro-Pro and PPA-Pro-Hyp) and their monomers (PA-Pro, PA-
Pro-Pro and PA-Pro-Hyp) were separately measured at room tempera-
The polymer catalysts were synthesized according to the route
shown in Scheme 1 and S1 in the supporting information. The precursor
polymers were deprotected to produce the corresponding polymer
catalysts. The typical deprotection procedure is described as below.
PPA-Pro, for example. Morpholine (6.00 mL) was added to a solution of
precursor polymer (1.33 mmol) in DCM (6.00 mL), and the resulting
mixture was stirred at room temperature for 10 h. Then, the mixture
was precipitated in methanol, after filtration and dried in vacuo at room
temperature overnight, the polymer catalyst was obtained.
20
ture. The[α]D values of the polymer catalysts are very different from
those of the corresponding monomers. The sign of PPA-Pro's optical
rotation is opposite to its monomer PA-Pro [α]D20 = −42
(c = 1 mg mL−1 in DMSO), PPA-Pro[α]D20 = +4 (c = 1 mg mL−1 in
DMSO); and PPA-Pro-Pro and PPA-Pro-Hyp show the larger absolute
20
[α]D
values than their monomers, for instance, PA-Pro-Pro
[α]D20 = −143(c = 1 mg mL−1 in MeOH) and PPA-Pro-Pro
[α]D20 = −176(c = 1 mg mL−1 in MeOH); PA-Pro-Hyp [α]D20 = −70
(c = 1 mg mL−1 in DMSO) and PPA-Pro-Hyp [α]D20 = −234
(1) PPA-Pro is a yellow powder. (0.18 g, 71.20%) 1H NMR (500 MHz,
DMSO‑d6, δ): 1.98–2.22and 2.89–3.31 (m, 4H, CH2), 4.17–5.25 (m,
(c = 1 mg mL−1 in DMSO). The difference in [α]D value of the
20
2

L. Liu, et al.
ReactiveandFunctionalPolymers146(2020)104392
Scheme 1. Synthesis of poly(phenylacetylene) bearing L-proline or proline dipeptide pendants
their precursors. (Fig. 1 and FIG. S19) Both the polymer catalysts and
the precursor polymers showed the clear the split-type Cotton effects in
the range from 300 to 500 nm, which indicates that all the polymers
take one-handed helical structure in the main chain. PPA-Pro showed
the similar CD signals in DMSO, DMF and DMAc, (Fig. 1A) the first
positive Cotton effect at 380 nm and the second negative Cotton effect
at 335 nm. The methanol solution of PPA-Pro-Pro showed the first
negative Coton effect at 430 nm and the second positive Coton effect at
360 nm. (Fig. 1B) PPA-Pro-Hyp showed the first negative Cotton effect
at 380 nm and the second positive Cotton effect at 335 nm in DMSO,
(Fig. 1C) it is interesting that the CD profile of PPA-Pro-Hyp in me-
thanol was nearly mirror image of that found in DMSO, which indicates
the opposite helix sense of PPA-Pro-Hyp in DMSO and methanol.
Compare to the CD signal of the corresponding precursor polymers,
(FIG. S19) after removing the protective Fmoc groups in the precursors,
the CD signals of the resulting polymer catalysts weakened, which
might be due to the removal of the protective groups caused the hy-
drogen bonding between the adjacent side chains.
Table 1
Solubility of the synthesized polymers in different solvents.
Polymer
Solvent
CHCl3 DCM THF DMF DMSO DMAc MeOH H2O
PPA-Pro-Fmoc
PPA-Pro
PPA-Pro-Pro-Fmoc
PPA-Pro-Pro
PPA-Pro-Hyp-Fmoc ++
PPA-Pro-Hyp
++
−
++
−
++ ++ ++
+
++
+
−
+
++
+
+
−
++
−
−
−
−
++
−
−
−
−
−
−
−
−
−
+
+
−
++ ++
−
−
++ ++ ++
−
−
−
−
+
++
Note: ++: soluble(completely soluble under 1 mg mL−1);+: slightly soluble
(partly soluble under 1 mg mL−1);-: insoluble.
polymer catalyst from the corresponding monomer might due to some
reasons, such as the structure change from a monomer to a polymer; the
formed helical main chain; and the chiral spatial position of the chiral
pendants aggregated along with the main chain.
CD spectra of the polymer catalysts were measured together with
3

L. Liu, et al.
ReactiveandFunctionalPolymers146(2020)104392
B
C
(A)
10
15
10
5
PPA-Pro-Pro
PPA-Pro
PPA-Pro-Hyp
10
5
5
0
0
0
-5
DMF
DMAc
DMSO
DMSO
MeOH
MeOH
-5
-10
-15
-20
-5
-10
10
8
6
4
2
-10
8
6
4
2
0
6
4
2
0
0
550
300
350
400
450
500
550
300
350
400
450
500
550
350
400
450
500
Wavelength (nm)
Wavelength (nm)
Wavelength (nm)
Fig. 1. CD (up) and UV–vis (down) spectra of the polymer catalysts at different solvents. (c = 1 mg mL−1).
3.3. Asymmetric catalytic performance of the helical poly(phenylacetylene)
catalyst
pendants are lower than those of the monomer catalyst and the polymer
having the dipeptide pendants (PPA-Pro-Pro and PPA-Pro-Hyp).
(Table 2) These indicate that the dipeptide pendants and the helical
mainchain induced by the dipeptide pendants in PPA-Pro-Pro and PPA-
Pro-Hyp could form the synergistic effect to improve the catalytic ef-
ficiency and enantioselectivity. However, compare to the corresponding
monomer catalyst, the enantioselectivity and yield of PPA-Pro are si-
milar or lower, which suggested that the proline pendants in PPA-Pro
could not form the synergistic effect with the its helical mainchain.
The influence of solvent on the enantioselectivity and yield were
summarized in Table 2 and Fig. 2. It was found that the polymer cat-
alysts had the better enantioselectivity and acceptable yield in high
polar aprotic solvents, such as DMF and DMSO. It might be due to that
the high polar aprotic solvent could relax the intramolecular hydrogen
bonds between the side chains in the polymer and improve the sy-
nergistic effect between the pendants and the helical mainchain. The
Asymmetric aldol reactions of acetone with p-nitrobenzaldehyde
were separately catalyzed by the helical polymer catalysts, the results
were compared to those catalyzed by the monomer catalyst (Table 2).
The influences of the solvent on the reaction were investigated by
conducting the reaction in different solvents (H2O, DMF, DMSO, me-
thanol and Toluene). The results show that all the catalysts successfully
catalyzed the reaction and showed the certain enantioselectivity in
H2O, DMF, DMSO, MeOH and Toluene, (Table 2) the maximum en-
antioselectivity (ee = 34%) was realized in DMF and DMSO (Table 2,
entry 7–8). It was found that the polymer having the dipeptide pen-
dants (PPA-Pro-Pro and PPA-Pro-Hyp) showed the higher enantios-
electivity and yield than the corresponding monomer catalysts, how-
ever, the enantioselectivity and yield of PPA-Pro having proline as the
Table 2
The aldol reaction of acetone with p-nitrobenzaldehyde catalyzed by the monomer catalyst and helical polymer catalysts in different solventsa.
Entry
Time (d)
Solvent
Monomer catalyst
Catalyst
Polymer catalyst
Catalyst
c
c
Yieldb (%)
ee (%)
Yieldb (%)
ee (%)
1
2
3
4
5
6
7
8
3
7
7
7
7
3
7
7
7
7
3
7
7
7
7
H2O
DMF
DMSO
MeOH
Toluene
H2O
PA-Pro
56
25
13
25
18
40
27
23
20
21
45
28
20
22
17
13
19
32
12
11
3
17
19
7
9
6
25
28
11
13
PPA-Pro
69
13
13
35
24
75
52
52
33
23
67
48
47
38
55
7
17
15
14
9
PA-Pro-Pro
PA-Pro-Hyp
PPA-Pro-Pro
PPA-Pro-Hyp
3
DMF
34
34
17
10
6
27
33
12
13
DMSO
MeOH
Toluene
H2O
9
10
11
12
13
14
15
DMF
DMSO
MeOH
Toluene
a
The reaction was performed with p-nitrobenzaldehyde (0.3 mmol), acetone (3.0 mmol), catalyst (0.09 mmol) and DMSO (1.0 mL) at 25 °C.
Isolated yields.
For R enantiomer, determined by chiral HPLC analysis (Chiralpak AS-1) with hexane/isopropanol (95/5, v/v) as the eluent.
b
c
4

L. Liu, et al.
ReactiveandFunctionalPolymers146(2020)104392
(A)
PPA-Pro
PPA-Pro-Pro
PPA-Pro-Hyp
80
70
60
50
40
30
20
10
0
(B)
35
30
25
20
15
10
5
PPA-Pro
PPA-Pro-Pro
PPA-Pro-Hyp
0
DMF
DMSO
Toluene
H2O
MeOH
H2O
DMF
DMSO
Solvent
Toluene
MeOH
Solvent
Fig. 2. The ee value (A) and yield (B) of the aldol reactions of acetone with p-nitrobenzaldehyde catalyzed by the helical polymer catalyst in different solven.
protic solvent can form strong intermolecular hydrogen bonds with the
polymer and it might disturb the synergistic effect between the pen-
dants and the helical mainchain. For instance, PPA-Pro-Hyp showed
the opposite helical sense in aprotic DMSO and protic methanol
(Fig. 1C), the enantioselectivity in methanol was much lower than that
in DMSO (Table 2). It was thought that methanol form strong inter-
molecular hydrogen bonds with PPA-Pro-Hyp and make PPA-Pro-Hyp
take an opposite helical sense to that in DMSO, and the opposite helical
sense of the mainchain could not form synergistic effect with the di-
peptide pendants. As a result, the synergistic effect between the chiral
pendants and the helical mainchain on the asymmetric aldol reaction
was found in the polymer catalyst having proline dipeptide pendants;
the aprotic high polar solvent could improve the enantioselectivity and
catalytic efficiency of the helical polymer catalyst. Therefore, DMSO
was selected as the solvent for the reaction.
The reaction in H2O showed the highest yield, however, the en-
antioselectivity in H2O is very poor. This was thought to be due to the
water-accelerating effect in the proline-catalyzed aldol reaction ac-
cording to the reports by Pihko [32,33] and Amstrong [34]. The gen-
erally accepted enamine mechanism of the reaction is shown in Fig. 3.
In which, the ketone forms iminium intermediate with proline residue,
then the iminium converts to enamine to proceed the catalytic cycle.
However, in the absence of water, the aldehyde can also reacted with
proline to produce an off-cycle iminium ions (FIG. S22) [34], which
decreases the total catalyst concentration. Addition of water suppresses
formation of off-cycle iminium ions, and increases the total catalyst
concentration within the cycle, therefore, water accelerate the reaction
and give the higher yields.
In addition, the CD spectra of PPA-Pro-Pro in methanol/water were
measured as shown in FIG. S23, the CD intensity shows a downward
trend along with the increase of the water content in the system, which
indicate addition of water caused the decrease in helical preference of
the polymer. This is consistence with the trend that the ee values of the
reactions decreased with the increase of water content in methanol/
water system (TABLE S1). The monomer-catalyzed reactions were
conducted in water as the control, the obtained ee values are very poor
and similar to those of the reactions catalyzed by polymer catalysts in
high water content system (TABLEs S1 and 2). These indicate that the
water molecules disturb the helical structure of the polymers and de-
crease the synergistic effect between the pendants and the helical
mainchain so as to cause the low ee values of the reactions in water.
Then the effects of the amount of the polymer catalyst on the aldol
reaction was investigated in DMSO. (Table 3) For PPA-Pro, increasing
the catalyst amount in the reaction clearly improved the reaction yield
and enantioselectivity, although the maximum values are not high
(Table 3). Increasing the catalyst amount also improved the yields of
reactions catalyzed by PPA-Pro-Pro or PPA-Pro-Hyp, and slightly in-
creased the enantioselectivity of the reactions. In the case of PPA-Pro-
Pro,
when
the
catalyst
amount
([catalyst]/[p-ni-
trobenzaldehyde] × 100%) was 25 mol%, both the enantioselectivity
and the yield the reaction reached the highest value (58% and 38%,
respectively, Table 3, Entry 4). In the case of PPA-Pro-Hyp, the suitable
catalyst amount is 20 mol%, the yield and enantioselectivity reached
58% and 39%, respectively.
Additives have a certain impact on asymmetric catalytic effect, and
some additives can form a co-catalytic effect with the catalyst. As a
cocatalyst, imidazole can be combined with a variety of catalysts to
achieve high yield and ee value. For instance, without imidazole, the
PPA-Pro-Hyp catalyzed reaction needs 7 days and afforded the yield of
47% and the ee of 33% (Table 4, Entry 7); adding 10 mol% of imidazole
in the system shortened the reaction time to 3 days and afforded the
higher yield of 69%. Meanwhile, the enantioselectivity of the reaction
was well maintained, ee values before and after adding imidazole in the
reaction were 33% and 34%. In the cases of the other two polymer
catalysts, adding imidazole showed the similar acceleration effects on
the reaction. These results indicate that imidazole is an efficient coca-
talyst for this asymmetric reaction.
The acceleration by imidazole might due to that imidazole affects
the outcome of the enamine-forming step. The imidazole was thought
to interact with the α-proton in the iminium intermediate and make the
equilibrium shift to forming enamine (Fig. 4). As reported by Houk, the
Fig. 3. Proposed catalytic cycle for aldol reaction catalyzed by poly(phenyla-
cetylene)s bearing proline residues.
5

L. Liu, et al.
ReactiveandFunctionalPolymers146(2020)104392
Table 3
Effect of the amount of the polymer catalysts on the aldol reaction of acetone with p-nitrobenzaldehydea.
Entry
Catalyst (mol%)d
PPA-Pro
PPA-Pro-Pro
Yield(%)b
PPA-Pro-Hyp
Yield (%)b
eec (%)
eec (%)
Yield(%)b
eec (%)
1
2
3
4
5
10
15
20
25
30
13
14
18
21
27
15
14
17
20
17
52
58
57
58
54
34
34
37
38
33
47
44
58
46
48
33
35
39
35
35
a
The reaction was performed with p-nitrobenzaldehyde (0.3 mmol), acetone (3.0 mmol), catalyst and DMSO (1.0 mL) at 25 °C. Reaction time was 7 days.
Isolated yields.
For R enantiomer, determined by chiral HPLC analysis (Chiralpak AS-1) with hexane/isopropanol (95/5, v/v) as the eluent.
[Catalyst]/[p-nitrobenzaldehyde] × 100.
b
c
d
transition state leading to the enamine is approximately equal in energy
[35]
to the aldol addition step.
Therefore, adding imidazole in the pro-
line-catalyzedaldol reaction was thought to be favorable for enamine
formation so as to accelerate the reaction.
As mentioned above, the solubility of the helical polymer catalysts is
poor in most organic solvents; therefore, these polymer catalysts may
be easily recovered from the reaction mixture by filtration or cen-
trifuge. Hence, the recyclability of the polymer catalysts was in-
vestigated and the results were summarized in Table 5. It was found
that for all the polymer catalysts, the yield and the enantioselectivity of
reaction did not show clear change even after four cycles, which in-
dicate the polymer catalysts well maintained their reactivity and se-
lectivity after recycle, i.e., the polymer catalysts have the good re-
cyclability.
Fig. 4. Possible effect of imidazole on the enamine forming step of the proline-
catalyzed aldol reaction.
Pro-Pro and PPA-Pro-Hyp bearing dipeptide pendants showed the
higher catalytic activity and enantioselectivity than the PPA-Pro
bearing proline pendants. The catalytic activity and enantioselectivity
of PPA-Pro-Pro and PPA-Pro-Hyp were also higher than the corre-
sponding monomer catalysts at the same condition indicating the sy-
nergistic catalyze effect of the dipeptide pendants with the one-handed
helical mainchain of the polymers for the reaction. Adding imidazole
could efficiently accelerate the aldol reaction and afford the higher
yields without the decrease in enantioselectivity. All the polymer cat-
alysts showed good recyclability, the catalytic activity and enantios-
electivity of the catalysts were well maintained even after 4 cycles.
4. Conclusions
Three one-handed helical poly (phenylacetylene)s separately
bearing proline (PPA-Pro), proline-proline dipeptide (PPA-Pro-Pro)
and proline-hydroxyproline dipeptide (PPA-Pro-Hyp) as the pendants
were successfully synthesized. The Cotton effect patterns of the polymer
significantly affected by the solvent. The resulting three polymers were
separately utilized as the catalyst to catalyze the asymmetric aldol re-
action of acetone with p-nitrobenzaldehyde in a various media. PPA-
Table 4
The aldol reaction of acetone with p-nitrobenzaldehyde catalyzed by the helical polymer catalyst with the assistance of imidazolea.
Entry
Catalyst
PPA-Pro
Imidazole (mol %)d
Time (d)
Yield (%)b
eec (%)
1
2
3
4
5
6
7
8
9
0
7
4
3
7
4
3
7
4
3
33
41
64
52
64
77
47
58
69
15
15
15
34
33
31
33
33
34
5%
10%
0
5%
10%
0
PPA-Pro-Pro
PPA-Pro-Hyp
5%
10%
a
The reaction was performed with p-nitrobenzaldehyde (0.3 mmol), acetone (3.0 mmol), catalyst (0.075 mmol) imidazole and DMSO (1.0 mL) at 25 °C.
Isolated yields.
For R enantiomer, determined by chiral HPLC analysis (Chiralpak AS-1) with hexane/isopropanol (95/5, v/v) as the eluent.
[IMIDAZOLE]/[p-nitrobenzaldehyde] × 100%.
b
c
d
6

L. Liu, et al.
ReactiveandFunctionalPolymers146(2020)104392
Table 5
Recyclability of the helical polymer catalysts for the aldol reaction of acetone with p-nitrobenzaldehydea.
Entry
Catalyst
Yield (%)b
eec (%)
1
2
3
4
5
6
7
8
PPA-Pro
13c
10
12
17
13
52
49
51
54
52
47
43
46
47
44
15
16
15
15
14
34
33
34
34
34
33
33
31
30
33
(cycle 1)
(cycle 2)
(cycle 3)
(cycle 4)
PPA-Pro-Pro
(cycle 1)
(cycle 2)
(cycle 3)
(cycle 4)
PPA-Pro-Hyp
(cycle 1)
(cycle 2)
(cycle 3)
(cycle 4)
9
10
11
12
13
14
15
a
The reaction was performed with p-nitrobenzaldehyde (0.3 mmol), acetone (3.0 mmol), catalyst (0.075 mmol) and DMSO (1.0 mL) at 25 °C. Reaction time
was 7 days.
b
c
Isolated yields.
For R enantiomer, determined by chiral HPLC analysis (Chiralpak AS-1) with hexane/isopropanol (95/5, v/v) as the eluent.
Data availability
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Declaration of Competing Interest
The authors have no competing interests to declare
Acknowledgements
This work is financially s upported by the National Natural Science
Foundations of China (21576060, 21076049, 51373044, 21404027)
and Natural Science Foundation of Heilongjiang Province (E2016019),
the Fundamental Research Funds for the Central Universities
(3072019CF1011 and HEUCFQ1417). The authors are grateful for the
support.
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