Immobilization of the Grubbs second-generation ruthenium-carbene complex on poly(ethylene glycol): A highly reactive and recyclable catalyst for ring-closing and cross-metathesis

Article abstract of DOI:10.1016/j.tetlet.2004.01.036

A poly(ethylene glycol)-bound Hoveyda-Grubbs Ru catalyst derived from the Grubbs second-generation Ru carbene complex was synthesized and shown to be highly reactive in the ring-closing metathesis of a wide variety of diene substrates, yielding di-, tri-, and tetra-substituted carbocyclic and heterocyclic olefins. The immobilized catalyst also proved to be highly reactive and recyclable in cross-metathesis and ring-opening/cross-metathesis. In all cases tested, the catalyst exhibited a high level of recyclability and reusability.

Full text of DOI:10.1016/j.tetlet.2004.01.036

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2447–2451
Immobilization of the Grubbs second-generation ruthenium-carbene
complex on poly(ethylene glycol): a highly reactive and recyclable
catalyst for ring-closing and cross-metathesis
Qingwei Yao* and Adalie Rodriguez Motta
Department of Chemistry and Biochemistry, The Michael Faraday Laboratories, Northern Illinois University, DeKalb, IL 60116, USA
Received 16 December 2003; revised 9January 2004; accepted 9January 2004
Abstract—A poly(ethylene glycol)-bound Hoveyda–Grubbs Ru catalyst derived from the Grubbs second-generation Ru carbene
complex was synthesized and shown to be highly reactive in the ring-closing metathesis of a wide variety of diene substrates, yielding
di-, tri-, and tetra-substituted carbocyclic and heterocyclic olefins. The immobilized catalyst also proved to be highly reactive and
recyclable in cross-metathesis and ring-opening/cross-metathesis. In all cases tested, the catalyst exhibited a high level of recyclability
and reusability.
Ó 2004 Elsevier Ltd. All rights reserved.
The advent of well-defined Ru carbene catalysts, most
notably, the Grubbs-type Ru benzylidenes 11a and 21b
(Fig. 1) has fueled the widespread application of olefin
metathesis.2 Another significant advance in this area is
the discovery by Hoveyda and co-workers of the robust
and recyclable Ru catalysts 3 and 4.3 The development
of immobilized Ru catalysts for olefin metathesis has
also attracted increasing interest since this would be
expected to further increase the practicality and effi-
ciency of the catalysts for this reaction. We4 and others5
have established that various polymeric and solid sup-
ports can be employed to immobilize these catalysts. In
particular, the air stable poly(ethylene glycol) mono-
methyl ether (MeO-PEG)-immobilized Ru catalyst 54a
derived from the Grubbs catalyst 1 was shown to exhibit
high activity in ring-closing diene metathesis (RCM)
under homogeneous conditions. This catalyst can be
conveniently recovered by precipitation with diethyl
ether and repeatedly reused without significant loss of its
activity, demonstrating the practical advantage of using
MeO-PEG as a soluble polymer6 to immobilize Ru
catalysts. We now wish to report the synthesis and
application of the more reactive poly(ethylene glycol)
(PEG)-immobilized Ru catalyst 6 derived from the
Grubbs second-generation catalyst 2 bearing a nucleo-
philic carbene ligand (SIMes).
L
Cl
L
Ru
O
Cl
Cl
Ru
1, 3: L = PCy3
2, 4: L =
Cl
Ph
PCy3
N
N
1, 2
3, 4
(SIMes)
5
MeO PEG O Succinyl
O
O
Cl
Ru
Cl
PCy3
Cl
Cl
O
Ru SIMes
Cl
SIMes Ru
Cl
O
6
O
O
O
O
O
O
PEG
O
O
Figure 1. Ru catalysts for olefin metathesis.
Catalyst 6 can be readily assembled as shown in Scheme
1. Based on our experience with the MeO-PEG-bound
catalyst 5 that has a Ru loading of approximately
0.1 mmol/g, we envisaged that the use of poly(ethylene
glycol) (PEG) that bears two OH groups on each
Keywords: Catalyst immobilization; Grubbs catalysts; Olefin meta-
thesis; Poly(ethylene glycol); Ruthenium.
* Corresponding author. Tel.: +1-815-753-6841; fax: +1-815-753-4802;
e-mail: qyao@niu.edu
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.036

2448
Q. Yao, A. R. Motta / Tetrahedron Letters 45 (2004) 2447–2451
Table 1. Recycling and reuse of PEG-bound Ru catalyst 6 in the RCM
of test diene 11a
O
O
glutaric anhydride
(1.5 eq)
Et3N (1.6 eq)
DMAP (0.2 eq)
THF, reflux, 16 h
69%
Ts
N
Ts
N
6 (2 mol % Ru)
O
O
CH2Cl2 (0.05 M)
12
11
1–4
∆, 1 h
OH
O
X
7
Cycle
(%) Conversionb
5
6
7
8
910
9
8, X = OH
>9
8
9
7
9
7
5
9
5
9
PivCl (1.5 eq), Et3N (1.5 eq)
Et2O, 0 oC - rt, 2 h, 92%
a All reactions were performed in refluxing CH2Cl2.
b Determined by 500 MHz 1H NMR spectroscopy.
9, X = OPiv
poly(ethylene glycol) (M.W. ~ 4600)
Et3N, DMAP, CH2Cl2, rt, 16h, 99%
Table 2. Recycling and reuse of PEG-bound Ru catalyst 6 in the RCM
of test diene 13a
O
O
Ts
Ts
N
N
O
O
O
O
O
Me
13
6 (5 mol % Ru)
CH2Cl2 (0.05 M)
∆, 2h
PEG
O
O
O
14
Me
10 (ligand loading: 0.39 mmol/g)
2, CuCl
Cycle
1
2–6
99
7–10 11–14 15
98 96 94
16
94
17
94
(%) Conversionb 100
6 (Ru loading ~ 0.32 mmol/g)
CH2Cl2, 40 oC
98%
a All reactions were performed in refluxing CH2Cl2.
b Determined by 500 MHz 1H NMR spectroscopy.
Scheme 1. Synthesis of the poly(ethylene glycol)-immobilized Ru
catalyst 6.
polymer chain would result in an increased overall
catalyst loading on the polymer. The known isopro-
poxystyrene derivative 75h was first treated with glutaric
anhydride in the presence of Et3N and DMAP to give
the monoacid 8. This material was then coupled to PEG,
through the mixed acid anhydride intermediate 9, to
afford the PEG-bound ligand 10 in essentially quanti-
To examine the scope of catalyst 6, we next focused on
its performance in the RCM of a variety of other
tri- and tetra-substituted dienes as well as in cross-
metathesis. As shown in Table 3, the activity of different
batches of catalyst 6 was uniformly high in the forma-
tion of tri-substituted carbocyclic (batch A) and het-
erocyclic olefins (batch B) with various ring sizes. These
dienes underwent clean and high yielding RCM using
either a freshly prepared or recycled catalyst. The cata-
lyst (batch C) also proved highly active even with the
tetra-substituted diene 27. As it could be expected, an
extended reaction time was necessary to achieve a high
conversion of the diene. Nevertheless, the catalyst was
clearly recyclable (cycles 1–3) even in the case of this
demanding diene and remained active after the third
cycle as tested with diene 13 (cycle 4).
1
tative yield based on 500 MHz H NMR spectroscopic
analysis as well as on the mass increase of the polymer.
Treatment of 10 with catalyst 2 in the presence of
CuCl3b resulted in a clean and quantitative exchange of
1
the styrene ligand as judged by H NMR spectroscopy
to give 6 as an air stable deep green powder in 98% yield
(loading 0.32 mmol/g).
The activity of 6 was then evaluated with the two test
dienes 11 (Table 1) and 13 (Table 2). As shown in Table
1, the disubstituted diene 11 underwent RCM in the
presence of 2 mol % Ru of 6 in CH2Cl2 at 40 °C to give
the cyclic olefin 12 in excellent conversion as indicated
Finally, the reactivity and recyclability of 6 were scru-
tinized by testing its performance in the cross-metathesis
(CM) reactions shown in Table 4. CM involving Ru
enoic carbene complexes9a;b has been reported only
recently with catalysts 29b;c and 4.10 Grubbs has
shown9a;b that these Ru carbenes are highly reactive but
are quite unstable and have much shorter lifetimes than
other alkylidene or benzylidene complexes. In the
absence of any information regarding the recyclability of
the parent catalyst 4 in these reactions,10;11 we wondered
whether or not the formation of an unstable Ru enoic
carbene from 6 would be detrimental to its regeneration.
To our delight, the CM dimerization of tert-butyl
acrylate proceeded uneventfully in the presence of only
2.5 mol % Ru of 6 (Table 4, cycle 1). The recycled cat-
alyst showed essentially equal efficacy in the CM
dimerization of n-butyl acrylate (cycle 2) as well as in the
1
by 500 MHz H NMR spectroscopy. As with the MeO-
PEG-bound catalyst 5, the recovery 6 from the reaction
mixture can be achieved by precipitation with diethyl
ether in air.7 Importantly, the recycled catalyst can be
reused for up to 10 cycles with only a very slight
decrease in activity after each recycling and reuse. The
high level of recyclability of catalyst 6 was further
established with the tri-substituted diene 13 (Table 2),
which cyclized cleanly in the presence of 5 mol % Ru of
6, with conversion still exceeding 90% even after 17
consecutive cycles. An average of less than 1% decrease
in the conversion of the diene after each cycle points to a
highly efficient, although not full, return of the catalyt-
ically active species (SIMes)Ru(Cl2)@CH2 to the PEG-
bound isopropoxystyrene ligand 10.8

Q. Yao, A. R. Motta / Tetrahedron Letters 45 (2004) 2447–2451
2449
Table 3. Activity and recyclability of PEG-bound Ru catalyst 6 in the RCM of various dienesa
Catalyst batch
Cycle
Diene
Product
Time
14
(%) Conversionb (yieldc)
E
E
Me
E
E
1A (3.2 mol % Ru)
1
1>98 (97)
16
18
20
17
Me
2
3
15
16
4
2
96 (93)
92 (89)
OBz
OBz Me
19
Me
4
1
18
19
2
3
90 (87)
Ts
N
Me
Ts
N
B (3.2 mol % Ru)
>98 (95)
21
Me
O
Me
Ph
Ph
O
23
Me
2
3
3
3
>98 (96)
97 (92)
22
24
O
O
Me
S
O
S
25
O
Me
O
O
Me
Ph
S
O
27
4
3
>98 (95)
39(37)
S
O
26
Ph
Me
Ts
N
Ts
N
C (5 mol % Ru)
1d
6.5
28
29
Me
Me
Me
Me
2d
3d
2
2
8
8
2 18
2 18
96 (93)
82 (79)
9
9
Ts
N
Ts
N
4e
3
86 (83)
14
13
Me
Me
a Unless otherwise noted, all reactions were performed in CH2Cl2 (0.05 M) at reflux.
b Determined by 500 MHz 1H NMR spectroscopy.
c Refers to isolated, pure products after silica gel chromatography.
d Performed in CH2Cl2 (0.4 M) at reflux.
e Performed with 3 mol % Ru relative to 13 in CH2Cl2 (0.05 M) at reflux.
ring-opening/cross-metathesis of the unstrained and
thermodynamically stable cyclohexene with either tert-
butyl acrylate (cycle 312) or methyl fumarate (cycle 4).
ble to the paradigmatic Grubbs second-generation
catalyst 2 and the Hoveyda–Grubbs second-generation
catalyst 4, in a broad range of olefin metathesis reac-
tions. Notable attributes of this new PEG-bound Ru
catalyst include its high level of recyclability and reus-
ability as well as its easy accessibility from commercially
available polymer and catalyst precursor.
In summary, we have shown that the poly(ethylene
glycol)-bound Ru carbene complex 6 can be conve-
niently prepared and exhibits high reactivity, compara-

2450
Q. Yao, A. R. Motta / Tetrahedron Letters 45 (2004) 2447–2451
Table 4. Activity and recyclability of Ru catalyst 6 in cross-metathesisa
Cycle
1c
Olefins (concn)
Product
O
Yieldb (%)
O
OtBu
88
30
31
tBuO
tBuO
O
(0.8M)
O
O
2c
91
18
OBu
BuO
BuO
O
(0.8M)
O
O
OtBu 30e
3d
tBuO
tBuO
(0.8M)
O
+
+
O
O
32e
81
68
( )4
tBuO
OtBu
(0.8M)
O
MeO
O
O
(0.8M)
4d
33
( )4
MeO
OMe
+
(0.8M)
a All reactions were performed in refluxing CH2Cl2 with 2.5 mol % Ru of catalyst 6.
b Refers to isolated, pure products after silica gel chromatography.
c Reaction time: 6 h.
d Reaction time: 4 h.
e See Ref. 12.
Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A.
H. J. Am. Chem. Soc. 2000, 122, 8168; Also see: (c)
Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett. 2000,
41, 9973; For related catalysts, see: (d) Zaja, M.; Connon,
S. J.; Dunne, A. M.; Rivard, M.; Buschmann, N.; Jiricek,
J.; Blechert, S. Tetrahedron 2003, 59, 6545; (e) Wakama-
tsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41, 794;
(f) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed.
2002, 41, 2403; (g) Crela, K.; Harutyunyan, S.; Mich-
rowska, A. Angew. Chem., Int. Ed. 2002, 41, 4038.
Acknowledgements
This work was supported by grants from the National
Institutes of Health (GM63522) and the Petroleum
Research Fund, administered by the American Chemi-
cal Society (36466-G1). We thank Ms. Gerri Hutson for
assistance in the synthesis of diene 16.
4. (a) Yao, Q. Angew. Chem., Int. Ed. 2000, 39, 3896; (b)
Yao, Q.; Zhang, Y. Angew. Chem., Int. Ed. 2003, 42, 3395;
(c) Yao, Q.; Zhang, Y. J. Am. Chem. Soc. 2004, 126, 74.
5. (a) Nguyen, S. T.; Grubbs, R. H. J. Organomet. Chem.
1995, 497, 195; (b) Ahmed, M.; Barrett, A. G. M.;
Braddock, D. C.; Cramp, S. M.; Procopiou, P. A.
Tetrahedron Lett. 1999, 40, 8657; (c) Ahmed, M.; Arnauld,
T.; Barrett, A. G. M.; Braddock, D. C.; Procopiou, P. A.
References and notes
1. (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1996, 118, 100; (b) Scholl, M.; Ding, S.; Lee, C. W.;
Grubbs, R. H. Org. Lett. 1999, 1, 953; For a related
catalyst, see: (c) Scholl, M.; Trnka, T. M.; Morgan, J. P.;
Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247; (d)
Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. F. J.
Am. Chem. Soc. 1999, 121, 2674.
2. Selected reviews: (a) Schuster, M.; Blechert, S. Angew.
Chem., Int. Ed. 1997, 36, 2036; (b) Armstrong, S. K. J.
Chem. Soc., Perkin. Trans. 1 1998, 371; (c) Grubbs, R. H.;
€
Synlett 2000, 1007; (d) Schurer, S. C.; Gessler, S.;
Buschmann, N.; Blechert, S. Angew. Chem., Int. Ed.
2000, 39, 3898; (e) Jafarpour, L.; Nolan, S. P. Org. Lett.
2000, 2, 4075; (f) Dowden, J.; Savovic, J. Chem. Commun.
2001, 37; (g) Mayr, M.; Mayr, B.; Buchmeiser, M. R.
Angew. Chem., Int. Ed. 2001, 40, 3839; (h) Kingsbury, J.
S.; Garber, S. B.; Giftos, J. M.; Gray, B. L.; Okamoto, M.
M.; Farrer, R. A.; Fourkas, J. T.; Hoveyda, A. H. Angew.
Chem., Int. Ed. 2001, 40, 4251; (i) Randl, S.; Buschmann,
N.; Connon, S. J.; Blechert, S. Synlett 2001, 10, 1547; (j)
Jafarpour, L.; Heck, M. P.; Baylon, C.; Lee, H. L.;
€
Chang, S. Tetrahedron 1998, 54, 4413; (d) Furstner, A.
Angew. Chem., Int. Ed. 2000, 39, 3012; (e) Trnka, T. M.;
Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18; (f) Blechert,
S. Angew. Chem., Int. Ed. 2003, 42, 1900.
3. (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.;
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Q. Yao, A. R. Motta / Tetrahedron Letters 45 (2004) 2447–2451
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Mioskowski, C.; Nolan, S. P. Organometallics 2002, 21,
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M.; Bieniek, M. Tetrahedron Lett. 2002, 43, 9055; (m)
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It is also informative to compare 6 with the PEG-bound
catalyst 15 that was previously reported by Lamaty and
co-workers5o and found to suffer significant decomposition
upon recycling:
O
O
PEG
O
O
155o
Cl
Ru
Cl
SIMes
Cl
Cl
Ru
SIMes
Ts
N
6. For leading reviews on the use of soluble polymer-
supported reagents and catalysts, see: (a) Gravert, D. J.;
Janda, K. D. Chem. Rev. 1997, 97, 489–510; (b) Harwig,
C. W.; Gravert, D. J.; Janda, K. D. Chemtracts-Org.
Chem. 1999, 12, 1–26; (c) Wentworth, P.; Janda, K. J.
Chem. Soc., Chem. Comm. 1999, 1917–1924; (d) Dicker-
son, T. J.; Reed, N. N.; Janda, K. D. Chem. Rev. 2002,
102, 3325; (e) Bergbreiter, D. E. Chem. Rev. 2002, 102,
3345.
7. All operations including concentration of the reaction
mixture, precipitation, filtration, and washing of the PEG-
bound catalyst with reagent grade diethyl ether were
carried out in vessels open to the air.
8. Although the exact nature of the decomposition of the
catalytically active species (SIMes)Ru(Cl2)@CH2 is not
clear at this time and a determination of metal leaching
has not been attempted, the high level of recyclability of 6
indicates that the return of (SIMes)Ru(Cl2)@CH2 to the
PEG-bound ligand 10 occurs much faster than its decom-
position:
Ts
N
15 (5 mol% Ru)
43% loss of Ru after
the first cycle
CH2Cl2, 40 oC, 1h
cycle 1: 100%;
cycle 5: 85%
The difference in the stability and recyclability between 6
and 15 reflects the subtle electronic and steric requirements
for the alkoxy ligand. Hoveyda has previously established
that substitution of the isoproxy group by a smaller and
less electron-donating methoxy group leads to less stable
Ru catalysts (see Ref. 3a).
9. (a) Ulman, M.; Belderrain, T. R.; Grubbs, R. H. Tetra-
hedron Lett. 2000, 41, 4689; (b) Choi, T.-L.; Lee, C. W.;
Chatterjee, A. K.; Grubbs, R. H. J. Am. Chem. Soc. 2001,
123, 10417; (c) Zee, C. W.; Choi, T.-L.; Grubbs, R. H. J.
Am. Chem. Soc. 2002, 124, 3224.
10. Randl, S.; Connon, S. J.; Blechert, S. Chem. Commun.
2001, 41, 1796.
11. Blechert and co-workers has previously reported the CM
of electron-deficient olefins and terminal olefins using a
recyclable Ru catalyst immobilized on Wang resin. How-
ever, it is mechanistically unlikely for a [Ru] ¼ COR
carbene to be involved in these reactions (see Ref. 5i).
12. Both products were isolated by silica gel chromatography
as a mixture and individual yields were calculated based
on 500 MHz 1H NMR integration of the olefinic
protons.
O
O
10
SIMes
Cl
Decomposition
6
Ru
Cl
regeneration