Imidazolium-modified poly(l-leucine) catalyst: an efficient and recoverable catalyst for Juliá-Colonna reactions

Article abstract of DOI:10.1016/j.tetlet.2009.06.127

A novel, easily recyclable imidazolium-modified poly(amino acid) catalyst was prepared. This catalyst exhibits high activity for the asymmetric epoxidation of α,β-unsaturated ketones without any pre-activation. The enantioselectivity was up to 99% ee for

Full text of DOI:10.1016/j.tetlet.2009.06.127

Tetrahedron Letters 50 (2009) 5225–5227
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Tetrahedron Letters
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Imidazolium-modified poly(L-leucine) catalyst: an efficient and recoverable
catalyst for Juliá–Colonna reactions
*
*
Wenwei Qiu, Linmei He, Qi Chen, Wanrong Luo, Zhichao Yu, Fan Yang , Jie Tang
Institute of Medicinal Chemistry, Department of Chemistry, East China Normal University, Shanghai 200062, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel, easily recyclable imidazolium-modified poly(amino acid) catalyst was prepared. This catalyst
exhibits high activity for the asymmetric epoxidation of ,b-unsaturated ketones without any pre-activa-
Received 31 March 2009
Revised 25 June 2009
Accepted 30 June 2009
Available online 3 July 2009
a
tion. The enantioselectivity was up to 99% ee for epoxidation of p-methoxychalcone. Compared to clas-
sical Juliá–Colonna catalysts, this insoluble, powdery catalyst can dramatically reduce the reaction
time and can be easily recycled by a simple filtration after the reaction. More importantly, the recycled
catalyst has been successfully reused for seven cycles without deterioration in catalytic efficiency.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric epoxidation
Poly-(L-leucine)
Imidazolium
Chalcone
Chiral poly(amino acids) (PAA) such as polyleucine and polyal-
anine can be used as catalysts for asymmetric epoxidation of a,b-
or Aliquat 336 as a co-catalyst to increase the peroxide concentra-
tion in the organic phase.6,7 They also described another PLL cata-
lyst which was polymerized at a higher temperature and led to a
higher activity.7 These two protocols have the advantages of dra-
matically increasing Juliá–Colonna epoxidation reactivity, signifi-
cantly decreasing the catalyst amount and reducing the pre-
activation time (from 6 h to a few minutes).8 However, the prob-
lem of gel-like PAA in the recovery process still exists. Here, we re-
port the preparation and application of a novel PLL catalyst for
which amino acid polymerization is initiated by an imidazolium
unsaturated ketones, as reported by Juliá and Colonna in the
1980s.1 Juliá–Colonna enantioselective epoxidation subsequently
attracted great interest since chiral, non-racemic epoxides can
serve as building blocks for the synthesis of a wide variety of opti-
cally active compounds.2 However, for practical applications there
are at least three factors limiting the application of Juliá–Colonna
catalysts: (1) relatively high catalyst loading (ca. 200 wt %); (2)
long catalyst pre-activation and reaction times; and (3) it is diffi-
cult to recover the catalyst because of the voluminous gel-like cat-
alyst formed after the reaction.
with a
1-(3-Aminopropyl)-3-methylimidazolium9
X = Clꢀ, Brꢀ, BF4þ) was used as a nucleophilic initiator for polymer-
ization of the N-carboxyanhydride of -leucine (
-Leu NCA10) with
an initiator/
x-amino group.
([3-apmim][X],
Many efforts have been devoted to solving these problems.3,2b
Roberts and co-workers prepared a simply recyclable PAASiCat
(polyleucine adsorbed onto silica)4 with improved activity. We
L
L
L
-Leu NCA ratio of 1:30 to afford the white powdery
previously reported that silica gel-grafted poly(
L
-leucine) (PLL)
catalyst [3-apmim][X]-PLL.11 The structure of the catalyst was
characterized by 1H NMR and IR. For comparison, the traditional
catalyst n-BuNH2-PLL was also prepared by using the same initia-
via covalent bonding was an efficient and easily recoverable cata-
lyst for Juliá–Colonna asymmetric epoxidation with high enanti-
oselectivity.5 Although the silica gel-grafted immobilized PPL
eliminates the trouble of handling voluminous gel-like catalyst
during the work-up process, the amount of catalyst required for
the reaction was still very large in terms of weight percentage
(approximately 800 wt %).
tor/L-Leu NCA ratio (Scheme 1).
Asymmetric epoxidation of chalcones was carried out in DME
using sodium percarbonate as an oxidant and base, and [3-ap-
mim][Cl]-PLL, [3-apmim][Br]-PLL or [3-apmim][BF4]-PLL as the
catalyst (Scheme 2).12 The results are summarized in Table 1.
When the traditional catalyst n-BuNH2-PLL was used, the
enantioselectivity and yield were only 61% ee and 66% yield,
respectively, after 54 h (Table 1, run 4). Under the same reaction
conditions, the imidazolium-modified PAA [3-apmim]Cl-PLL cata-
lyzed reaction can provide the product in 95% ee and 96% yield
with a significantly reduced reaction time of 2 h (Table 1, run 1).
Geller et al. reported a phase-transfer catalyst (PTC) mediated
Juliá–Colonna epoxidation by using tetrabutylammonium bromide
* Corresponding authors. Fax: +86 21 62232100 (J.T.).
E-mail addresses: fyang@chem.ecnu.edu.cn (F. Yang), jtang@chem.ecnu.edu.cn
(J. Tang).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.127

5226
W. Qiu et al. / Tetrahedron Letters 50 (2009) 5225–5227
O
HN
X-
X-
THF, rt
O
H
n
N
N
NH2
+
N
N
N
N
H
n
H
O
O
[3-apmim][X]
X = Cl-, Br-, BF4
[3-apmim][X]-PLL
L
-Leu NCA
-
O
HN
O
H
THF, rt
n
N
n-BuNH2
+
N
H
O
H
O
n
L
-Leu NCA
n-BuNH2-PLL
Scheme 1. Preparation of catalysts [3-apmim][X]-PLL and n-BuNH2-PLL.
Table 3
O
O
Influence of catalyst amount on chalcone epoxidationa
aq. percarbonate, DME
catalyst
O
Ph
Ph
Ph
Ph
Entry
Catalystb (mol %)
Time (h)
Yieldc (%)
ee (%)
1
2
3
4
20
10
5
0.25
12
12
99
99
99
94
95
91
86
75
Scheme 2. Juliá–Colonna epoxidation of chalcone.
1
12
Table 1
Chalcone epoxidation catalyzed by [3-apmim][X]-PLLa
a
Catalyst [3-apmim][Cl]-PLL recovered from run 7 described in Table 2.
Catalyst amount based on chalcone.
Isolated yield.
b
c
Run
Catalystb
Time (h)
Yieldc (%)
ee (%)
1
2
3
4
[3-Apmim][Cl]-PLL
[3-Apmim][Br]-PLL
[3-Apmim][BF4]-PLL
n-BuNH2-PLL
2
7
7
96
93
89
66
95
94
94
61
54
15 min in the second run for [3-apmim]Cl-PLL. It is possible that
the catalyst was activated in the first run and the recycled catalyst
was more efficient to catalyze the reaction in the second run. After
each run, the powdery catalyst was almost completely recovered
by a simple filtration. In all the seven cycles, both the yield and
enantioselectivity had virtually no negative change (Table 2, run 7).
Since satisfactory enantioselectivity was obtained after only
several minutes for 20 mol % of catalyst [3-apmim]Cl-PLL, we
investigated the effect of decreasing the catalyst loading to 10, 5
and 1 mol %. The results are listed out in Table 3.
a
Catalyst 20 mol % (based on chalcone).
n-BuNH2-PLL pre-activated 24 h before use, [3-apmim][X]-PLL not pre-acti-
b
vated before use.
c
Isolated yield.
The other two modified PLL catalysts, [3-apmim]Br-PLL and [3-ap-
mim]BF4-PLL, also provided satisfactory results (Table 1, runs 2 and
3).
We postulated that addition of a terminal imidazolium group to
PLL could improve the physical properties of the catalyst and allow
its easy separation and recovery from the reaction system. More
importantly, introduction of the quaternary ammonium moiety
could provide the catalyst with phase transfer ability so that it
can transfer more hydroperoxide (HOOꢀ) from the aqueous phase
to the reactive sites, thus improving the efficiency of the catalyst.
The reusability of [3-apmim]Cl-PLL was also investigated. The
results are summarized in Table 2.
The amount of traditional catalysts required for Juliá–Colonna
reaction is usually 20 mol % relative to the substrate. As shown in
Table 3, when the loading of [3-apmim]Cl-PLL was decreased to
10 mol %, the enantioselectivity and yield remained almost un-
changed (Table 3, entry 2 vs entry 1). On further decreasing the
catalyst loading to 5 mol % and 1 mol %, the corresponding enanti-
oselectivity decreased to 86% ee (Table 3, entry 3) and 75% ee (Ta-
ble 3, entry 4). This reaction proceeds slowly in the absence of a
catalyst, therefore the spontaneously produced racemic epoxide
can be accounted for the decrease in enantioselectivity in the reac-
tions with a low catalyst loading.
It took the initial reaction 2 h to go to completion. However,
similar yield and enantioselectivity were obtained after only
It is worth noting that the molecular weight of the imidazoli-
um-modified PLL catalyst is much less than those of other inor-
ganic or organic supported catalysts,5 therefore the weight
percent of the catalysts is much less, even for a molar ratio of 20%.
Table 2
Reusability of catalyst [3-apmim][Cl]-PLL in chalcone epoxidationa
Run
Time
Yieldb (%)
ee (%)
The epoxidation of various (E)-a,b-unsaturated ketones was
1
2
3
4
5
6
7
2 h
96
94
98
99
99
99
99
95
95
95
95
96
94
95
screened by using [3-apmim]Cl-PLL as the catalyst. Almost all the
substrates gave the corresponding epoxides in excellent yield with
high enantioselectivity, except for the o-methoxy-substituted chal-
cone (Table 4).
All the reactions proceeded rapidly within 15 min or less. For
substrates bearing p-electron-donating substituents, excellent
yields and enantioselectivity could be obtained (Table 4, entries 1
and 2). Their p-electron-withdrawing substituted counterparts
afforded comparable results (Table 4, entries 4 and 5). Owing to
15 min
15 min
15 min
15 min
15 min
15 min
a
The catalyst was used at 20 mol % based on chalcone and recovered by filtration
and then washed with ethyl acetate.
b
Isolated yield.

W. Qiu et al. / Tetrahedron Letters 50 (2009) 5225–5227
5227
Table 4
References and notes
Enone epoxidation catalyzed by [3-apmim][Cl]-PLLa
1. (a) Juliá, S.; Masana, J.; Vega, J. C. Angew. Chem., Int. Ed. Engl. 1980, 19, 929–931;
(b) Juliá, S.; Guixer, J.; Masana, J.; Rocas, J.; Colonna, S.; Annuziata, R.; Molinari,
H. J. Chem. Soc., Perkin Trans. 1 1982, 1317–1324; (c) Colonna, S.; Molinari, H.;
Banfi, S.; Juliá, S.; Masana, J.; Alvarez, A. Tetrahedron 1983, 39, 1635–1641.
2. (a) Ebrahim, S.; Wills, M. Tetrahedron: Asymmetry 1997, 8, 3163–3173; (b)
Carde, L.; Davies, H.; Geller, T. P.; Roberts, S. M. Tetrahedron. Lett. 1999, 40,
5421–5424.
3. (a) Itsuno, S.; Sakakura, M.; Ito, K. J. Org. Chem. 1990, 55, 6047–6049; (b) Cappi,
M. W.; Chen, W. P.; Flood, R. W.; Liao, Y. W.; Roberts, S. M.; Skidmore, J.; Smith,
J. A.; Williamson, N. M. Chem. Commun. 1998, 1159–1160; (c) Flood, R. W.;
Geller, T. P.; Petty, S. A.; Roberts, S. M.; Skidmore, J.; Volk, M. Org. Lett. 2001, 3,
683–686; (d) Bentley, P. A.; Bergeron, S.; Cappi, M. W.; Hibbs, D. E.; Hursthouse,
M. B.; Nugent, T. C.; Pulido, R.; Roberts, S. M.; Wu, L. E. Chem. Commun. 1997,
739–740; (e) Allen, J. V.; Drauz, K.-H.; Flood, R. W.; Roberts, S. M.; Skidmore, J.
Tetrahedron Lett. 1999, 40, 5417–5420.
O
O
aq. percarbonate, DME
O
R1
R2
R1
R2
catalyst
Entry
R1
R2
Time (min)
Yieldb (%)
ee (%)
1
2
3
4
5
Ph
p-MeOC6H4
Ph
Ph
Ph
15
15
15
10
7
90
98
24
96
98
97
99
77
94
93
p-MeOC6H4
o-MeOC6H4
p-ClC6H4
Ph
p-ClC6H4
a
[3-Apmim][Cl]-PLL: recovered from the reactions described in Table 3,
20 mol %.
b
Isolated yield.
4. (a) Geller, T.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 1397–1398; (b)
Dhanda, A.; Drauz, K.-H.; Geller, T.; Roberts, S. M. Chirality 2000, 12, 313–317;
(c) Baars, S.; Drauz, K.-H.; Krimmer, H.-P.; Roberts, S. M.; Sander, J.; Skidmore,
J.; Zanardi, G. Org. Process Res. Dev. 2003, 7, 509–513; (d) Carrea, G.; Colonna, S.;
Meek, A. D.; Ottolina, G.; Robert, S. M. Tetrahedron: Asymmetry 2004, 15, 2945–
2949.
5. (a) Yang, F.; He, L.-M.; Yi, H.; Zou, G.; Tang, J.; He, M.-Y. J. Mol. Catal. A: Chem.
2007, 273, 1; (b) Yi, H.; Zou, G.; Li, Q.; Chen, Q.; Tang, J.; He, M. Y. Tetrahedron
Lett. 2005, 46, 5665–5668.
6. Geller, T.; Krüger, C. M.; Militzer, H.-C. Tetrahedron Lett. 2004, 45, 5069–5071.
7. (a) Geller, T.; Gerlach, A.; Krüger, C. M.; Militzer, H.-C. Tetrahedron Lett. 2004,
45, 5065–5067; (b) Geller, T.; Gerlach, A.; Krüger, C. M.; Militzer, H.-C. J. Mol.
Catal. A: Chem. 2006, 251, 71–77.
8. Flisak, J. R.; Gassman, P. G.; Lantos, I.; Mendelson, W. L. EP 403252 A2, 1990.
9. Katakai, R.; Iizuka, Y. J. Org. Chem. 1985, 50, 715–716.
the steric effect, the o-substituted substrate gave a much lower
yield (24%) with moderate enantioselectivity (77% ee) (Table 4, en-
try 3).
In conclusion, we developed a new type of imidazolium-modi-
fied PAA catalyst for asymmetric epoxidation of
a,b-unsaturated
ketones. This novel catalyst can effectively catalyze a highly enan-
tioselective chalcone epoxidation without any pre-activation. The
loading (weight percentage) of this catalyst was greatly decreased,
compared to those of classical Juliá–Colonna catalysts. Further-
more, the better catalytic efficiency of this catalyst insured the sig-
nificant reduction in reaction time. This insoluble, powdery
catalyst also allows a simple recovery procedure. After seven cy-
cles, no catalytic efficiency deterioration was observed in terms
of either enantioselectivity or yield.
10. Song, G.; Cai, Y.; Peng, Y. J. Comb. Chem. 2005, 7, 561–566.
11. Synthesis of imidazolium-modified PLL catalyst:
L-Leucine NCA (16 mmol,
2.514 g) was dissolved in anhydrous tetrahydrofuran (60 mL) under
a
nitrogen atmosphere and [3-apmim][X] (0.5 mmol) was added as an initiator
and the reaction mixture was stirred at rt for 72 h. The precipitate was filtered
and successively washed thrice with tetrahydrofuran and diethyl ether and
dried under vacuum to afford the asymmetric epoxidation catalyst [3-
apmim][X]-PLL as
a ) 3312, 2958, 2871, 1658,
white solid. IR (KBr, cmꢀ1
1548, 1468, 1385; 1H NMR (500 MHz, CF3CO2D) for [3-apmim]X-PLL (n = 10)
ppm: 9.38 (1H, proton of imidazolium), 8.19 (1H, proton of imidazolium), 8.07
(1H, proton of imidazolium).
Acknowledgments
This research was financially supported by the National Natural
Science Foundation of China (Grant No. 20772032). We also thank
the Laboratory of Organic Functional Molecules, Sino-French Institute
of ECNU for support.
12. Typical enone epoxidation procedure: Enone (1 mmol) was dissolved in DME
(7.5 mL) and water (7.5 mL). The percarbonate (1.5 mmol) and catalyst
(20 mol %) were successively added and the reaction mixture was stirred at
room temperature until the reaction was complete (monitored by TLC). The
catalyst was recovered by rapid filtration and washed with ethyl acetate. The
combined organic fractions were dried over anhydrous Na2SO4, and were then
evaporated in vacuo and purified by silica gel column chromatography (AcOEt/
petroleum 1:10–1:30) to afford the corresponding epoxide. The enantiomeric
excess was determined by chiral-phase HPLC analysis on a Chiralpak AD
column (eluent 10% i-PrOH in hexane, UV detection at 254 nm).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.06.127.