Design of main-chain polymers of chiral imidazolidinone for asymmetric organocatalysis application

Article abstract of DOI:10.1039/c2cc18115k

Main-chain polymers of chiral imidazolidinone were successfully synthesized by reaction of chiral imidazolidinone dimers with disulfonic acid. Chiral imidazolidinones were incorporated into the main-chain of the polymer by ionic bonding. These polymers co

Full text of DOI:10.1039/c2cc18115k

View Article Online / Journal Homepage / Table of Contents for this issue
This article is part of the
Chirality
web themed issue
Guest editors: David Amabilino and Eiji Yashima
All articles in this issue will be gathered together
online at
www.rsc.org/chiral

Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2012, 48, 4011–4013
www.rsc.org/chemcomm
COMMUNICATION
Design of main-chain polymers of chiral imidazolidinone for asymmetric
organocatalysis applicationwz
Naoki Haraguchi,* Hitomi Kiyono, Yu Takemura and Shinichi Itsuno
Received 28th December 2011, Accepted 2nd March 2012
DOI: 10.1039/c2cc18115k
Main-chain polymers of chiral imidazolidinone were successfully
synthesized by reaction of chiral imidazolidinone dimers with
disulfonic acid. Chiral imidazolidinones were incorporated into
the main-chain of the polymer by ionic bonding. These polymers
could be used as polymeric chiral organocatalysts for asymmetric
Diels–Alder reactions.
Fig. 1 Chiral imidazolidinones.
Polymer-immobilized chiral organocatalysts have attracted
increasing interest in recent decades,1 since the catalytic activity
of proline as a chiral organocatalyst was reported by List and
co-workers.2 Although many kinds of polymer-immobilized chiral
organocatalysts have been synthesized with the development of
design and practical use of a chiral organocatalyst, most effort was
paid to the development of side-chain- or end-functionalized
polymeric catalysts and the investigation of main-chain polymers
in which the chiral organocatalyst was incorporated into the main-
chain of the polymer has been limited. Poly(amino acid)3 and
poly(peptide)4 systems are examples of main-chain polymers
with a chiral organocatalyst and these are successfully used in
asymmetric reactions. The regularity of the repeating unit and the
rigidity of the main-chain backbone may provide a better defined
microenvironment at the catalytic sites and allow systematic
modification of their catalytic properties.
conventional immobilization by a covalent bond, the methodology
of immobilization by ionic interaction has certain advantages
because commercially available organocatalysts are directly used
for immobilization and the reaction via neutralization between a
sulfonated polymer and imidazolidinone proceeds under mild
conditions without side reactions. The immobilization technique
can be categorized as non-covalent immobilization of asymmetric
organocatalysts.16 Some facile immobilizations of imidazolidinones
using ionic interaction have also been reported by several groups.17
In this communication, we applied the ionic bond formation
between a chiral imidazolidinone and sulfonic acid to the synthesis
of a main-chain polymer of chiral imidazolidinone and employed
this as a novel self-supported chiral organocatalyst18 for asymmetric
Diels–Alder reaction.
The synthesis of main-chain polymers of chiral imidazolidinone
is illustrated in Scheme 1. To synthesize the chiral imidazolidinone
dimers, the phenyl group of 1a was modified for introducing
different linkages. The properties of the linkages, such as hydro-
phobicity, flexibility, and length, are of significance for the catalytic
activity of the chiral imidazolidinone derivative. A chiral
imidazolidinone derivative functionalized with a hydroxyl
group (2) was easily obtained from (S)-tyrosine in 497%
overall yield.6,19 The Williamson reaction of two equivalents
of 2 with dihalide (3) afforded chiral imidazolidinone dimers
(4a–4e), as shown in Scheme 1.
Among chiral organocatalysts, chiral imidazolidinone derivatives
(1a), originally designed and developed as chiral organocatalysts by
MacMillan and co-workers, are some of the most efficient organo-
catalysts5 (Fig. 1). Chiral imidazolidinone and its salt can be widely
applied to catalytic asymmetric reactions such as the Diels–Alder
reaction,6 1,3-dipolar cycloaddition,7 Friedel–Crafts alkylation,8
indole alkylation,9 a-chlorination of aldehydes,10 direct aldol
reaction,11 intramolecular Michael reaction,12 and epoxidation.13
Recently, we have found that the complex prepared from a
quaternary ammonium salt and a sulfonate is extremely stable
in both water and organic solvent.14 Using this knowledge, novel
ionic immobilization of chiral imidazolidinones onto polymers
has been developed by the reaction of polymers possessing
sulfonic acid and chiral imidazolidinone.15 Compared with the
The synthesis of chiral oxoimidazolidinium sulfonate is
generally very simple and quantitative. The reaction between
chiral imidazolidinone and sulfonic acid occurs readily to
afford the corresponding chiral oxoimidazolidinium sulfonate
in quantitative conversion. For example, reaction of 1a and
toluenesulfonic acid occurred immediately to afford chiral
oxoimidazolidinium sulfonate 1b. We then applied the oxoi-
midazolidinium sulfonate formation reaction to the main-
chain polymer synthesis. 2,6-Naphthalenedisulfonic acid (5)
was chosen as a disulfonic acid for this polymerization. 5 is easily
1-1 Hibarigaoka, Tenpaku-Cho, Toyohashi 441-8580, Japan.
E-mail: haraguchi@ens.tut.ac.jp; Fax: +81 532 43 5833;
Tel: +81 532 44 6812
w This article is part of the ChemComm ‘Chirality’ web themed issue.
z Electronic supplementary information (ESI) available: Synthetic
procedures of chiral imidazolidinone dimers and polymers and their
1H and 13C NMR data. See DOI: 10.1039/c2cc18115k
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 4011–4013 4011

Scheme 1 Synthesis of main-chain polymers of chiral imidazolidinone.
soluble in water, while 4a–4e are soluble in organic solvents, such as
CH2Cl2, methanol, N,N-dimethylformamide (DMF), and dimethyl
sulfoxide (DMSO). The polymerization of 4a–4e and 5 was carried
out by adding a CH2Cl2 solution of 4a–4e to an aqueous solution
of 5 at room temperature (Scheme 1).
A white precipitate was obtained as soon as the CH2Cl2 solution
of 4a–4e was added, which indicates that the polymerization is
relatively fast. Interestingly, only a slight reaction was observed
when the corresponding disulfonic acid disodium salt was used
instead of 5. After 24 h, the precipitated product was thoroughly
washed with dichloromethane and water to remove unreacted
4a–4e and 5, respectively. The yield was sufficiently high
(88–99%) and the solid obtained was insoluble both in water and
some organic solvents, such as CH2Cl2 and methanol, but was
soluble in DMF or DMSO.
The 1H and 13C NMR spectra of the product contained both the
oxoimidazolidinium and naphthalenedisulfonate moieties. The
number-average molecular weight (Mn) and molecular weight
distribution (Mw/Mn) of the product measured by gel permeation
chromatography (GPC) are summarized in Table 1. The Mn values
ranged from 19 to 93 kg molꢀ1 and the Mw/Mn values were greater
than 2. The degree of polymerization calculated from Mn and the
molecular weight of the repeating unit was greater than 20. These
results clearly indicated that these polymerizations proceeded via
polyaddition to afford main-chain polymers containing chiral
imidazolidinone moieties 6a–6e. We first used the original chiral
imidazolidinone (1a) as a chiral organocatalyst for the asymmetric
Diels–Alder reaction of 1,3-cyclopentadiene (8) and trans-
cinnamaldehyde (9) as a preliminary experiment (Scheme 2).
Scheme 2 Asymmetric Diels–Alder reaction.
Desired chiral adducts 10 and 11 were obtained quantitatively
and the ee values of 10 (exo isomer) and 11 (endo isomer) were
93% and 93%, respectively (entry 1 in Table 2).6 The chiral
imidazolidinone derivative with a toluene sulfonate anion (1b)
was also found to be effective for the reaction (entry 2). We next
used the chiral imidazolidinone dimers (7a–7e) (Fig. 2) which
were quantitatively obtained by the reaction of 4a–4e with HCl in
1,4-dioxane for the asymmetric Diels–Alder reaction. 7a–7e were
completely soluble in methanol and water mixed solvent. Chiral
imidazolidinones with an achiral linker (7a–7c) showed similar
diastereoselectivity and enantioselectivity to 1a (entries 3–5).
Interestingly, the enantioselectivity of chiral imidazolidinone with
a chiral linker (7d) decreased possibly because of the mismatch of
configuration between imidazolidinone and linker (entry 6). As
expected, higher enantioselectivity was observed when the linker
with the opposite configuration (7e) was employed (entry 7). Not
only these chiral imidazolidinone hydrochloric acid salts but the
chiral imidazolidinone with toluenesulfonate (7c0) were also
effective for the reaction (entry 8). The results indicate that the
catalytic activity of these chiral imidazolidinone dimers is
similar to that of the original chiral imidazolidinone catalyst.
Table 2 Asymmetric Diels–Alder reaction using monomeric and
dimeric chiral imidazolidinones
Time
Entry Catalyst (h)
Conv.
(%)
10/11a
(exo/endo) (%)
ee (10)b ee (11)b
Table 1 Characterization of the main-chain polymers of
chiral imidazolidinone
(%)
a
a
1
2
3
4
5
6
7
8
1a
1b
7a
7b
7c
7d
7e
7c0
7
7
4
4
499
499
499
98
55/45
55/45
55/45
56/44
56/44
57/43
59/41
57/43
93
92
92
92
91
80
91
89
93
88
94
92
92
73
93
94
Mn
Entry Polymer Yield (%) (kg molꢀ1
Mw
a
)
(kg molꢀ1 Mw/Mn DPb
)
1
2
3
4
5
6a
6b
6c
6d
6e
96
99
88
499
79
58.9
18.6
26.2
92.5
24.7
193
3.28
2.28
3.40
2.59
2.29
62
20
30
87
23
42.5
89.1
240
4
95
10
10
24
499
499
90
56.6
a
b
Measured by GPC. DP (degree of polymerization) = Mn(polymer)
a
b
/
Determined by 1H NMR. Determined by GC (Astec CHIRALDEX
B-PH column).
Mn(4+5)
.
c
This journal is The Royal Society of Chemistry 2012
4012 Chem. Commun., 2012, 48, 4011–4013

imidazolidinone and sulfonic acid. The main-chain polymers
of chiral imidazolidinone were successfully used as polymeric
chiral organocatalysts for the asymmetric Diels–Alder
reaction of trans-cinnamaldehyde and 1,3-cyclopentadiene.
The effect of disulfonic acid on the catalytic performance is
under investigation.
This work was partially supported by a Grant-in-Aid for
Scientific Research (No. 22750105) and by a Grant-in-Aid for
Scientific Research on Innovative Areas ‘‘Molecular Activation
Directed toward Straightforward Synthesis’’ (No. 2335003)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Fig. 2 Chiral imidazolidinone dimers.
Table 3 Asymmetric Diels–Alder reactions using main-chain polymers
of chiral imidazolidinone
10/11a ee (10)b ee (11)b
Entry Catalyst Time (h) Conv. (%) (exo/endo) (%)
(%)
1
2
3
4
6a
6b
6c
6d
6e
6c
6c
6c
6c
24
9
8
24
24
24
24
48
72
499
97
95
499
499
73
92
95
83
57/43
58/42
55/45
58/42
55/45
56/44
55/45
57/43
59/41
90
91
93
92
90
94
91
92
91
81
97
97
81
89
99
95
94
95
Notes and references
1 N. Haraguchi and S. Itsuno, in Polymeric Chiral Catalyst Design and
Chiral Polymer Synthesis, ed. S. Itsuno, Wiley, Hoboken, 2011, ch. 2,
pp. 17–61; B. Altava, M. I. Burguete and S. V. Luis, in The Power of
Functional Resins in Organic Synthesis, ed. J. T. Puche and
F. Albericio, Wiley-VCH, Weinheim, 2008, ch. 10, pp. 247–308;
F. Cozzi, Adv. Synth. Catal., 2006, 348, 1367–1390; M. Benaglia,
A. Puglisi and F. Cozzi, Chem. Rev., 2003, 103, 3401–3430.
2 B. List, R. A. Lerner and C. F. Barbas III, J. Am. Chem. Soc.,
2000, 122, 2395–2396.
3 S. Julia, J. Masana and J. C. Vega, Angew. Chem., Int. Ed. Engl.,
1980, 19, 929–931; S. Julia, J. Guixer, J. Masana, J. Rocas,
S. Colonna, R. Annunziata and H. Molinari, J. Chem. Soc., Perkin
Trans. 1, 1982, 1317–1324; S. Itsuno, M. Sakakura and K. Ito,
J. Org. Chem., 1990, 55, 6047–6049.
5
6c
7d
8e
9f
a
b
Determined by 1H NMR. Determined by GC (Astec CHIRAL-
c
d
DEX B-PH column). At 0 1C. 6c used in entry 3 was reused.
6c used in entry 7 was reused. 6c used in entry 8 was reused.
e
f
Encouraged by these results, these main-chain polymers of
4 D. R. Kelly and S. M. Roberts, Biopolymers, 2006, 84, 74–89;
E. A. C. Davie, S. M. Mennen, Y. Xu and S. J. Miller, Chem. Rev.,
2007, 107, 5759–5812.
5 G. Lelais and D. W. C. MacMillan, Aldrichimica Acta, 2006, 39, 79–87;
D. W. C. MacMillan, Nature, 2008, 455, 304–308; S. Mukherjee, J. W.
Yang, S. Hoffmann and B. List, Chem. Rev., 2007, 107, 5471–5569;
A. Erkkila, I. Majander and P. M. Pihko, Chem. Rev., 2007,
107, 5416–5470; G. Lelais and D. W. D. MacMillan, in New Frontiers
in Asymmetric Catalysis, ed. K. Mikami and M. Lautens, John Wiley &
Sons, 2007, pp. 319–331.
6 K. A. Ahrendt, C. J. Borths and D. W. C. MacMillan, J. Am.
Chem. Soc., 2000, 122, 4243–4244.
7 W. S. Jen, J. J. M. Wiener and D. W. C. MacMillan, J. Am. Chem.
Soc., 2000, 122, 9874–9875; S. Lee and D. W. C. MacMillan,
J. Am. Chem. Soc., 2007, 129, 15438–15439.
8 N. A. Pares and D. W. C. MacMillan, J. Am. Chem. Soc., 2001,
123, 4370–4371.
9 J. F. Austin and D. W. C. MacMillan, J. Am. Chem. Soc., 2002,
124, 1172–1173.
10 M. P. Brochu, S. P. Brown and D. W. C. MacMillan, J. Am. Chem.
Soc., 2004, 126, 4108–4109.
11 I. K. Mangion, A. B. Northrup and D. W. C. MacMillan, Angew.
Chem., Int. Ed., 2004, 43, 6722–6724.
chiral imidazolidinone (6a–6e) were used as organocatalysts in
the asymmetric Diels–Alder reaction under similar conditions in
order to investigate their catalytic activity (Table 3). 6a–6e were
not soluble but were suspended in methanol and water mixed
solvent, and the cycloaddition proceeded quantitatively within
24 h without side reactions. After the asymmetric Diels–Alder
reaction was complete, chiral adducts 10 and 11 were easily
obtained by washing the mixture with CH2Cl2. No destruction
of the complex of imidazolidinone and sulfonic acid was detected
by 1H NMR and GPC. In most cases, the ratio of 10/11
(exo/endo) was similar to that using 1. When 6a was used as a
chiral organocatalyst, the reaction occurred smoothly to afford 10
in 90% ee and 11 in 81% ee (entry 1). The enantioselectivity of 11
was increased to 97% when 6b and 6c were used (entries 2 and 3).
In the presence of 6c, the same reaction occurred with 95% yield,
and 93% ee for 10 and 97% ee for 11 (entry 3). The enantio-
selectivity of polymeric organocatalyst 6c was obviously higher
than that of the model catalyst 7c. When 6d was employed instead
of 7d, enhancement of the enantioselectivity was observed (entry 4).
In contrast, 6e showed a lower enantioselectivity than 7e (entry 5).
Lowering the reaction temperature enhanced the enantio-
selectivity of 6c (entry 6). Since these polymeric chiral catalysts
were not soluble in the mixed solvent used in the reaction, these
polymers could be easily separated from the reaction mixture. The
recovered polymer 6c could be reused for the same reaction with
similar enantiomeric excesses, while in slowly decreasing conver-
sions (entries 7–9). The Mn and Mw/Mn values of reused 6c by
GPC changed slightly after the reuse. The change might be caused
by partial hydrolytic degradation, which may give rise to the
decrease of conversion. This will probably be suppressed by using
more hydrophobic (or bulkier) substituents or linkers.
12 M. T. H. Fonseca and B. List, Angew. Chem., Int. Ed., 2004, 43,
3958–3960.
13 S. Lee and D. W. C. MacMillan, Tetrahedron, 2006, 62, 11413–11424.
14 Y. Arakawa, N. Haraguchi and S. Itsuno, Tetrahedron Lett., 2006, 47,
3239–3243; Y. Arakawa, N. Haraguchi and S. Itsuno, Angew. Chem.,
Int. Ed., 2008, 47, 8232–8235; N. Haraguchi, K. Tsuru, Y. Arakawa and
S. Itsuno, Org. Biomol. Chem., 2009, 7, 69–75; S. Itsuno, D. K. Paul,
M. A. Salam and N. Haraguchi, J. Am. Chem. Soc., 2010, 132,
2864–2865.
15 N. Haraguchi, Y. Takemura and S. Itsuno, Tetrahedron Lett.,
2010, 51, 1205–1208; S. Itsuno, M. M. Parvez and N. Haraguchi,
Polym. Chem., 2011, 2, 1942–1949.
16 L. Zhang, S. Luo and J.-P. Cheng, Catal. Sci. Technol., 2011, 1, 507–516.
17 T. Mitsudome, K. Nose, T. Mizugaki, K. Jitsukawa and K. Kaneda,
Tetrahedron Lett., 2008, 49, 5464–5466; Y. Chi, T. Scroggins and
M. J. Frechet, J. Am. Chem. Soc., 2008, 130, 6322–6323.
´
18 Z. Wang, G. Chen and K. Ding, Chem. Rev., 2009, 109, 322–359.
19 Y. Zhang, L. Zhao, S. S. Lee and J. Y. Ying, Adv. Synth. Catal.,
2006, 348, 2027–2032.
In conclusion, we have designed a novel type of main-chain
chiral polymer that comprises an ionic complex of a chiral
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 4011–4013 4013