Synthesis of imidazolium-tagged ruthenium carbene complex: Remarkable activity and reusability in regard to olefin metathesis in ionic liquids

Article abstract of DOI:10.1055/s-2008-1077888

We have demonstrated the synthesis of a new ionic liquid supported ruthenium carbene complex 1a,b and its applications to olefin metathesis. These catalysts can be used for ring-closing metathesis in the construction of five-to-eight-membered rings with h

Full text of DOI:10.1055/s-2008-1077888

LETTER
1805
Synthesis of Imidazolium-Tagged Ruthenium Carbene Complex: Remarkable
Activity and Reusability in Regard to Olefin Metathesis in Ionic Liquids
S
ynthesis of Imida
i
zolium
d
-TaggedRut
e
henium
C
ar
a
bene
C
om
p
k
lex i Wakamatsu,* Yuri Saito, Masami Masubuchi, Reiko Fujita
Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan
E-mail: hiwaka@tohoku-pharm.ac.jp
Received 11 March 2008
CHO
CHO
Abstract: We have demonstrated the synthesis of a new ionic liq-
uid supported ruthenium carbene complex 1a,b and its applications
to olefin metathesis. These catalysts can be used for ring-closing
metathesis in the construction of five-to-eight-membered rings with
high activity and good recyclability.
HO
O
a
b
AcO
AcO
2
3
Keywords: ruthenium, catalysis, metathesis, ionic liquids, carbene
complexes
O
O
c
Br
O
HO
5
Olefin metathesis1 has become a powerful method for the
synthesis of carbon–carbon double bonds, and a large
number of applications for natural product synthesis have
already been reported using ruthenium- or molybdenum-
catalyzed ring-closing metathesis (RCM). Since cross
metathesis (CM)2 and enyne metathesis3 are also useful
for the synthesis of acyclic unsaturated compounds and
1,3-diene derivatives, the metathesis reaction is one of the
most important methods in the field of synthetic organic
chemistry. On the other hand, ionic liquids have attracted
attention as a reaction field in organic chemistry, due to
alternative organic solvents and their interesting proper-
ties which provide a wide range of good solubility for or-
ganic and inorganic compounds.4 Since the first examples
of ionic liquids for metal-catalyzed propene dimerization
by Chauvin et al.5 and ethylene polymerization by Wilkes
et al.,6 extensive transition-metal-catalyzed reactions in
ionic liquids have been reported. Initial attempts at alkene
metathesis in ionic liquids have already succeeded.7 Also,
several interesting results in regard to the ionic ruthenium
initiator, which has excellent reusability combined with
high activity, have recently been described.8
4
O
d
e
N
N
O
6
X–
N+
O
N
O
7 X = I
8a X = BF4
8b X = PF6
f
g
Scheme 1 Synthesis of new ligands 8. Reagents and conditions:
a) i-PrBr, K2CO3, 4 Å MS, DMF, 50 °C, 12 h, 97%; b) KOt-Bu,
Ph3PCH3Br, Et2O, 0 °C, 50 min, then K2CO3, MeOH, r.t., 3 h, 95%;
c) NaH, DMF, r.t., 1 h, then Br(CH2)4Br, r.t., 30 min, 70%;
d) C3H3N2Na, r.t., 1.5 h, 91%; e) MeI, r.t., 2 h; f) AgBF4, CH2Cl2, r.t.,
18 h, 56%; g) AgPF6, CH2Cl2, r.t., 18 h, 73%.
Herein we report the synthesis of a highly active rutheni-
um carbene complex with very good recyclability for
RCM in ionic liquid media. We planned to prepare com-
plex 1 (Figure 1). We thought that ortho substitution of
the benzylidene ligand should have high reactivity due to
fast initiation by steric repulsion,9 and that the imidazoli-
um ion structure should provide good immobilization for
ionic liquids as a solvent and reusability for the ruthenium
carbene complex after isolation of the product.
MesN
Cl
NMes
Cl
Ru
O
X–
N+
N
O
1a X = BF4
1b X = PF6
3-Acetoxy-2-isopropoxy-benzaldehyde (3) was synthe-
sized from 210 by alkylation with isopropyl bromide in the
presence of K2CO3 in DMF (Scheme 1). The Wittig reac-
tion of methylene ylide with 3, followed by deacetylation,
yielded 4, which was transformed into 5 by alkylation
with 1,4-dibromobutane. The introduction of an imida-
zole ring was achieved by the coupling of imidazole sodi-
um salt with 5 to give 6 in 91% yield. Methylation of 6
Figure 1 Ionic liquid supported highly active ruthenium catalysts
SYNLETT 2008, No. 12, pp 1805–1808
Advanced online publication: 19.06.2008
DOI: 10.1055/s-2008-1077888; Art ID: U01908ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
8

1806
H. Wakamatsu et al.
LETTER
Table 3 RCM of Miscellaneous Substrates Using 1ba
MesN
Cl
NMes
Cl
Entry 1
MesN
Cl
NMes
Cl
Ru
O
a
Cycle Substrates
Products
Time (min) Yield (%)b
Ru
X–
Ph
PCy3
N+
N
O
1
<5
<5
99
99
9
N
N
Ts
Ts
13
1a X = BF4
1b X = PF6
12
Scheme 2 Preparation of ionic liquid supported ruthenium cata-
lysts. Reagents and conditions: a) 8a or 8b, CuCl, CH2Cl2, reflux, 9 h.
2
TsN
TsN
15
14
3
10
90
99
98
EtO2C
CO2Et
EtO2C
CO2Et
N
N
Ts
11
10
Ts
17
16
Scheme 3 Ring-closing metathesis of diethyl diallylmalonate 10
with methyl iodide, followed by anion exchange with sil-
ver tetrafluoroborate or silver hexafluorophosphate, pro-
vided 8a (56%) and 8b (73%), respectively.
4
TsN
TsN
19
18
When a 1.0 equivalent of ligand 8 was exposed to 911 in
the presence of CuCl in CH2Cl2 under reflux for 9 hours,
the anticipated ruthenium complex 1 was obtained
(Scheme 2).12 In the 1H NMR study of complex 1, it was
revealed that the isopropoxy group coordinated to the ru-
thenium metal, because of the chemical shift of the car-
bine proton at d = 16.6 ppm.13
5
12
12
13
13
180
93
8c
6
48 h
Entry 2
Cycle Substrates
Products
Time (min) Yield (%)b
1
10
10
99
92
N
N
Table 1 Ring-closing metathesis of 10 Using Ionic Liquid Support-
ed Ruthenium Catalyst 1aa
Ts
Ts
21
20
Entry Solventb
Cycle
1
2
2
3
TsN
TsN
Time/yield of 11 (%)c
22
23
1
2
CH2Cl2/[Bmim]BF4 0.5 h/94
CH2Cl2/[Bmim]PF6 10 min/85
2.5 h/44d
–
30 min/89
2.5 h/71e
O
3
5
89
O
Ph
a Reaction conditions: 1a (5 mol%), CH2Cl2–ionic liquid (9:1), r.t.
b [Bmim]: 1-butyl-3-methylimidazolium.
c Isolated yield.
Ph
Ph
Ph
25
24
d Starting material 10 was recovered in 51% yield.
e Starting material 10 was recovered in 25% yield.
4
5
6
7
8
12
12
12
12
12
13
13
13
13
13
15
97
97
98
95
44d
20
30
Table 2 Ring-closing metathesis of 10 Using Ionic Liquid Support-
ed Ruthenium Catalyst 1ba
120
48 h
Cycle
Time
1
2
3
4
5
6
a Reaction conditions: 1b (5 mol%), CH2Cl2–[Bmim]PF6 (9:1), r.t.
b Isolated yield.
10 min 15 min 20 min 30 min 2.5 h 48 h
93 95 91 77
32c
Yield of 11 (%)b 90
c Starting material 12 was recovered in 90% yield.
d Starting material 12 was recovered in 52% yield.
a Reaction conditions: 1b (5 mol%), CH2Cl2–[Bmim]PF6 (9:1), r.t.
b Isolated yield.
c Starting material 10 was recovered in 58% yield.
Synlett 2008, No. 12, 1805–1808 © Thieme Stuttgart · New York

LETTER
Synthesis of Imidazolium-Tagged Ruthenium Carbene Complex
1807
(2) For reviews on cross metathesis, see: (a) Gibson, S. E.;
Keen, S. P. Top. Organomet. Chem. 1998, 1, 155.
(b) Connon, S. J.; Blechert, S. Angew. Chem. Int. Ed. 2003,
42, 1900. (c) Vernall, A. J.; Abell, A. D. Aldrichimica Acta
2003, 36, 93.
(3) For reviews on enyne metathesis, see: (a) Mori, M. Top.
Organomet. Chem. 1998, 1, 133. (b) Poulsen, C. S.;
Madsen, R. Synthesis 2003, 1. (c) Diver, S. T.; Giessert, A.
J. Chem. Rev. 2004, 104, 1317. (d) Mori, M. J. Mol. Catal.
A: Chem. 2004, 213, 73. (e) Mori, M. Adv. Synth. Catal.
2007, 349, 121.
(4) (a) Ionic Liquids in Synthesis; Wasserschid, P.; Welton, T.,
Eds.; Wiley-VCH: Weinheim, 2003. (b) Welton, T. Chem.
Rev. 1999, 99, 2071. (c) Wasserschid, P.; Keim, W. Angew.
Chem. Int. Ed. 2000, 39, 3772. (d) Sheldon, R. Chem.
Commun. 2001, 2399. (e) Dupont, J.; de Souza, R. F.;
Suarez, P. A. Z. Chem. Rev. 2002, 102, 3667. (f) Zhao, H.;
Malhotra, S. V. Aldrichimica Acta 2002, 35, 75.
At first, RCM of diethyl diallylmalonate 10 (Scheme 3)
using new catalyst 1a was attempted (Table 1). When the
reaction was carried out under an argon atmosphere in the
presence of 5 mol% 1a in CH2Cl2/[Bmim]BF4 (9:1) at
room temperature, the starting material was consumed af-
ter 0.5 hours to provide 11 in 94% yield (entry 1, cycle 1).
After extraction of the product from an ionic liquid with
Et2O,14 a second loading of 10 was added to an ionic liquid
containing ruthenium carbene complex 1a. The reuse of
1a was achieved, and cyclization product 11 was obtained
in 44% yield (entry 1, cycle 2). The effect of a counter-
anion on ionic liquid as a solvent was examined by chang-
–
–
ing from BF4 to PF6 (entry 2).
When the first run of 10 with 1a in CH2Cl2/[Bmim]PF6
(9:1) was done, a quick conversion of 10 to 11 was ob-
served and 11 was isolated in 85% yield (cycle 1). A grat-
ifying result was obtained in the second run, and the third
cycle led to a 71% yield of 11 and a longer reaction time.
(g) Pârvulescu, V. I.; Hardacre, C. Chem. Rev. 2007, 107,
2615.
(5) Chauvin, Y.; Gilbert, B.; Guibard, I. J. Chem. Soc., Chem.
Commun. 1990, 1715.
Catalyst 1b was also examined in regard to RCM of 10
(Table 2). Ring-closing metathesis was carried out in the
presence of 5 mol% 1b at room temperature. Continuous
fast conversion was observed, and reliable reusability was
realized until the fifth cycle.
(6) Carlin, R. T.; Wilkes, J. S. J. Mol. Catal. 1990, 63, 125.
(7) (a) Buijsman, R. C.; van Vuuren, E.; Sterrenburg, J. G. Org.
Lett. 2001, 3, 3785. (b) Sémeril, D.; Olivier-Bourbigou, H.;
Bruneau, C.; Dixneuf, P. H. Chem. Commun. 2002, 146.
(c) Csihony, S.; Fischmeister, C.; Bruneau, C.; Horváth, I.
T.; Dixneuf, P. H. New J. Chem. 2002, 26, 1667. (d) Ding,
X.; Lv, X.; Hui, B.; Chen, Z.; Xiao, M.; Guo, B.; Tang, W.
Tetrahedron Lett. 2006, 47, 2921. (e) Williams, D. B. G.;
Ajam, M.; Ranwell, A. Organometallics 2006, 25, 3088.
(f) Han, S.-H.; Hirakawa, T.; Fukuba, T.; Hayase, S.;
Kawatsura, M.; Itoh, T. Tetrahedron: Asymmetry 2007, 18,
2484.
(8) (a) Audic, N.; Clavier, H.; Mauduit, M.; Guillemin, J.-C.
J. Am. Chem. Soc. 2003, 125, 9248. (b) Yao, Q.; Zhang, Y.
Angew. Chem. Int. Ed. 2003, 42, 3395. (c) Clavier, H.;
Audic, N.; Mauduit, M.; Guillemin, J.-C. Chem. Commun.
2004, 2282. (d) Thurier, C.; Fischmeister, C.; Bruneau, C.;
Olivier-Bourbigou, H.; Dixneuf, P. H. J. Mol. Catal. A:
Chem. 2007, 268, 127. (e) Rix, D.; Caïjo, F.; Laurent, I.;
Gulajski, L.; Grela, K.; Mauduit, M. Chem. Commun. 2007,
3771.
(9) (a) Wakamatsu, H.; Blechert, S. Angew. Chem. Int. Ed.
2002, 41, 794. (b) Wakamatsu, H.; Blechert, S. Angew.
Chem. Int. Ed. 2002, 41, 2403. (c) Buschmann, N.;
Wakamatsu, H.; Blechert, S. Synlett 2004, 667.
(10) (a) Kemp, D. S.; Wang, S.-W.; Mollan, R. C.; Hsia, S.-L.;
Confalone, P. N. Tetrahedron 1974, 30, 3677. (b) Nicolosi,
G.; Piattelli, M.; Sanfilippo, C. Tetrahedron 1993, 49, 3143.
(11) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953.
Next, tolerance for miscellaneous substrates with recycla-
bility was tested (Table 3). The construction of five-to-
eight-membered rings smoothly proceeded by the same
catalyst in an ionic liquid solution to provide products in
quantitative yield (entry 1, cycle 1–4), and additional ring
closure of a five-membered ring also succeeded (cycle 5).
Trisubstituted olefin was obtained in high yield (entry 2,
cycles 1 and 2), and ene-yne metathesis proceeded to pro-
vide diene derivative 25 (cycle 3) with good reusability of
the catalyst (cycles 4–7).
We have studied the synthesis of a new ionic liquid sup-
ported ruthenium carbene complex 1a,b and its applica-
tions to olefin metathesis. These catalysts can be used for
ring-closing metathesis of miscellaneous substrates with
excellent activity and very good recyclability. Further
studies of ionic liquid supported catalysts and the field of
metathesis in ionic liquids are in progress in our laborato-
ry.
Acknowledgment
This work was supported by Tohoku Pharmaceutical University.
(12) Procedure for the Synthesis of Catalyst 1b
To a solution of 9 (184.9 mg, 0.22 mmol) and CuCl (21.6
mg, 0.22 mmol) in CH2Cl2 (20 mL) was added 8b (120.3 mg,
0.26 mmol). The reaction mixture was stirred at reflux for 9
h under argon atmosphere. The volatiles were removed
under reduce pressure. The residue was purified by column
chromatography on SiO2 (CH2Cl2–acetone, 3:1) to afford 1b
(137.2 mg, 68%). 1H NMR (400 MHz, CD2Cl2): d = 1.14 (d,
J = 6.3 Hz, 6 H), 1.66–1.74 (m, 2 H), 1.89–1.94 (m, 2 H),
2.20–2.65 (br, 18 H), 3.72 (s, 3 H), 4.06 (t, J = 5.7 Hz, 2 H),
4.08 (t, J = 6.9 Hz, 2 H), 4.16 (s, 4 H), 5.64 (sept, J = 6.3 Hz,
1 H), 6.56 (dd, J = 1.3, 7.5 Hz, 1 H), 6.87 (dd, J = 7.5, 8.2
Hz, 1 H), 7.06 (br, 4 H), 7.11 (dd, J = 1.3, 8.2 Hz, 1 H), 7.13
(dd, J = 1.9, 1.9 Hz, 1 H), 7.25 (dd, J = 1.3, 1.9 Hz, 1 H),
8.48 (br, 1 H), 16.57 (s, 1 H). 13C NMR (100 MHz, CD2Cl2):
References and Notes
(1) (a) Handbook of Metathesis, Vol. 1-3; Grubbs, R. H., Ed.;
Wiley-VCH: Weinheim, 2003. (b) For selected general
review, see: Topics in Organometallic Chemistry, Vol. 1;
Fürstner, A., Ed.; Springer: Berlin, Heidelberg, 1998.
(c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl.
1997, 36, 2037. (d) Grubbs, R. H.; Chang, S. Tetrahedron
1998, 54, 4413. (e) Fürstner, A. Angew. Chem. Int. Ed.
2000, 39, 3012. (f) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D.
Angew. Chem. Int. Ed. 2005, 44, 4490. (g) Hoveyda, A. H.;
Zhugralin, A. R. Nature (London) 2007, 450, 243.
Synlett 2008, No. 12, 1805–1808 © Thieme Stuttgart · New York

1808
H. Wakamatsu et al.
LETTER
d = 19.6, 21.2, 21.7, 25.4, 26.9, 36.6, 49.9, 51.8, 68.8, 81.0,
115.9, 122.7, 123.9, 124.3, 129.6, 136.0, 136.1, 138.5,
139.3, 140.3, 148.3, 148.6, 210.0, 298.3. IR (KBr): n = 1574
(w), 1470 (m), 1269 (m) cm–1. HRMS–FAB: m/z calcd for
C39H5135Cl2N4O2102Ru: 779.2433; found: 779.2454. Anal.
Calcd for C39H51Cl2F6N4O2PRu: C, 50.65; H, 5.56; N, 6.06.
Found: C, 50.62; H, 5.58; N, 5.82.
(14) Typical Procedure for Metathesis Reaction Promoted by
Ionic Liquid Supported Ruthenium Catalyst
To a catalyst solution of 1b (38.1 mg, 0.04 mmol) in
[Bmim]PF6 (1 mL) was added 10 (0.20 mL, 0.82 mmol) in
CH2Cl2 (9 mL). The reaction mixture was stirred at r.t. until
starting material was consumed. After the volatiles were
removed under reduce pressure, ionic liquid phase was
extracted with Et2O (several times). The ethereal phase was
evaporated to provide 11, and the ionic liquid phase was
dried under reduce pressure to use a catalyst solution for the
next cycle.
(13) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A.
H. J. Am. Chem. Soc. 2000, 122, 8168. (b) Gessler, S.;
Randl, S.; Blechert, S. Tetrahedron Lett. 2000, 41, 9973.
Synlett 2008, No. 12, 1805–1808 © Thieme Stuttgart · New York

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