Electrostatic immobilization of an olefin metathesis pre-catalyst on iron oxide magnetic particles

Article abstract of DOI:10.1039/c1gc16084b

A quaternary ammonium Hoveyda-Grubbs olefin metathesis pre-catalyst has been reversibly immobilized on sulphonic acid-functionalised silica-coated iron oxide magnetic particles to affect ring closing metathesis with easy removal, reuse and regeneration.

Full text of DOI:10.1039/c1gc16084b

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COMMUNICATION
Electrostatic immobilization of an olefin metathesis pre-catalyst on iron
oxide magnetic particles
Matthew J. Byrnes, Andrew M. Hilton, Clint P. Woodward, William R. Jackson and Andrea J. Robinson*
Received 1st September 2011, Accepted 26th October 2011
DOI: 10.1039/c1gc16084b
A quaternary ammonium Hoveyda-Grubbs olefin metathe-
sis pre-catalyst has been reversibly immobilized on sul-
phonic acid-functionalised silica-coated iron oxide mag-
netic particles to affect ring closing metathesis with easy
removal, reuse and regeneration.
In this study the use of reversible electrostatic immobilization
of Hoveyda-Grubbs metathesis catalysts to sulphonated iron
oxide MPs has been investigated. The quartenary ammonium-
functionalised Ru-benzylidene pre-catalyst (1), was readily
attached to sulphonated MPs to generate a high functioning and
reloadable metathesis catalyst. Conveniently, the MP-catalyst
was easily magnetically retrieved and reused in subsequent
catalysis experiments and also readily recharged with fresh pre-
catalyst to maintain optimum performance (turn-over number
and frequency).
19
Introduction
Homogenous Grubbs-type pre-catalysts have played an im-
portant role in the application of olefin metathesis to organic
1,2
synthesis. Grafting of these homogeneous catalysts onto solid
supports can aid catalyst recycling and removal of metallic
3
residues from the product stream by filtration. This strategy,
Results and discussion
however, must take into consideration the effect of the solid
support on catalytic efficiencies. Immobilization of the catalysts
onto polymeric supports, for example, can often result in lower
Iron oxide magnetic particles with a shell of silica were prepared
via a co-precipitation reaction. The sulphonic acid groups were
installed by reacting 3-mercaptotrimethoxysilane with freshly
4
activity due to poorer substrate diffusion. Silica supports, on
prepared Si-coated Fe
mercapto groups with 30% H
acid present on the particles, as determined by titration with
3
O
4
MPs followed by oxidation of the
the other hand, are not subject to the same physiochemical
constraints (i.e. catalyst-polymer solvation) and the availability
of a large surface area for functionalisation aids the activity
2
O
2
. The amount of sulphonic
-
1
0
.1 M NaOH, ranged from 0.49 to 0.51 mmol g . Recrys-
tallised catalyst 1 was successfully immobilised onto the sodium
sulphonated iron oxide particles in dry, degassed CH Cl to form
5
of the final immobilized catalyst. However, final recovery
of silica-based catalysts from the reaction stream can still
be problematic. More recently, magnetic particles (MPs) have
been used as solid supports to conduct ‘pseudo-homogenous’
2
2
the MP-appended pre-catalyst 2 as shown in Scheme 1. ICP-
MS ruthenium analysis of the pre-catalyst 2 found that catalyst
6
transition-metal catalysed reactions. The application of an
external magnet readily separates the catalyst-loaded MPs from
the reaction products to eliminate the need for filtration and
7
facilitate catalyst recycling.
Towards this end, palladium, osmium and nickel catalysts
8–12
have been attached to MPs, and more recently, two examples
of covalent attachment of Hoveyda-Grubbs metathesis catalysts
13,14
to MPs have been reported.
Catalyst-tethering strategies
employed in the metathesis area to date largely involve immobi-
lization of the Ru-alkylidene catalysts via covalent attachment to
the neutral ligand (either phosphine or N-heterocyclic carbene),
15,16
the benzylidene or a chloride surrogate.
A few examples of
immobilisation via non-covalent modes have also been reported
and these include the use of p–p stacking and electrostatic
17,18
interactions.
School of Chemistry, Monash University, Clayton, 3800, Australia.
E-mail: andrea.robinson@monash.edu; Fax: +61 3 9905 4597; Tel: +61
3
9905 4553
Scheme 1
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Table 1 Activity and recycling of MP-loaded catalyst 2 in the conver-
sion of 3 to 4
a
b
Method (% conversion)
Ru (ppm)
Cycle
Time (h)
A
B
C
D
4
1
2
3
4
5
6
2
2
2
2
2
12
>95
>95
84
53
56
>95
>95
90
83
71
>95
>95
>95
86
81
n.d.
>95 200
>95 114
>95 100
>95 62
87
43
87
>95
n.d
Reactions run with 0.68 mol% catalyst loading and triplicate washing.
Methods A and B: RCM performed with 5 mL of 0.047 M 3 at room
temperature and reaction times of 2 h (Cycles 1–5) and 12 h (Cycle
6
). Method A uses DCM and Method B uses toluene. Methods C and
D: RCM performed with a nitrogen bleed using 5 mL of 0.047 M 3
at room temperature and reaction times of 2 h (Cycles 1–5) and 12 h
(
Cycle 6). Method C uses DCM and Method D uses toluene. n.d. = not
Fig. 1 NMR solutions of organics isolated from the RCM of 3.
Shown on the left is the solution after magnetic separation of the MP-
immobilised catalyst 2. The retrieved catalyst was recycled in subsequent
reactions. The solution on the right has not been treated to remove Ru-
containing residues and the catalyst 1 was not recovered.
a
1
determined. Conversions to 4 calculated by H NMR spectroscopy.
b
Residual ruthenium analysis in cyclised product 4 generated using
Method D.
loading was lower than that anticipated, with a value of 0.12
mmol g , possibly indicating a surface crowding effect and/or
inaccessible sulphonate groups. A SEM image of particles of
-
1
2
revealed that many of the particles had nanosized structure
Introduction of a bleed needle to purge ethylene byproduct
during reaction proved to be beneficial in both solvents over
5 consecutive runs (Table 1, Cycles 1–5, Methods C and D).
In toluene, high conversions (above 87%) were maintained over
5 consecutive cycles. In each cycle, solvent volume remained
constant over the 2 h reaction period, and high conversion to 4
(
<100 nm).
Ring closing metathesis (RCM) of diethyl diallylmalonate (3)
was chosen to evaluate the immobilized catalyst (Scheme 2). A
trial run using 0.68 mol% loading of 2 on substrate 3 showed
>
95% conversion to the cyclopentene 4 after 2 hours (Table
1
) and gave a clear solution after magnetic separation of the
was observed in both CH
2
2
Cl and toluene.
catalyst particles. Comparable conversion of 3 into 4 was also
obtained with catalyst 1, however removal of the ruthenium-
alkylidene catalyst and its decomposition products from the
ring-closed product 4 via organic-aqueous phase extraction and
chromatography was not as effective. A visual comparison of
the effectiveness of catalyst separation can be seen in Figure 1.
We considered that the observed decline of catalyst activity
over five runs could be explained in a number of ways: Physical
loss of the catalyst-MP construct, catalyst deactivation, or
ruthenium alkylidene leeching from the MPs. Gradual loss of
magnetic particles through failure to recover the MPs at the
end of each catalytic cycle would contribute to a decline in
reactivity. The use of a high strength recovery magnet (0.45T)
minimised this problem, however fine particulate material,
possibly resulting from mechanical degradation of the MPs
during stirring, could not be recovered. Catalyst loss via this
route, however, was considered to be minimal.
The stability of the catalyst system to oxygen and water was
then assessed. The use of degassed toluene which had not
been subjected to a drying procedure (i.e. used as supplied)
did not compromise catalyst reactivity (all conversions >95%),
whereas non-degassed, dry toluene significantly affected the
performance of the catalyst. Exposure of dried particles to
atmospheric conditions also compromised catalyst lifetime. It
is therefore important to protect the MP-catalyst system from
oxygen exposure by storing under an inert atmosphere at all
times after preparation. ICP-MS analysis of recovered 2 and
isolated samples of 4 from successive cycles revealed that the
Ru-loading on the MPs decreased with each successive cycle.
Furthermore, analysis of the organic samples showed significant
quantities of ruthenium ranging from 200 ppm for the first cycle
product to 43 ppm for the final product isolated from cycle 5
(Table 1). Analysis of the 5th cycle MP-catalyst 3 indicated a
Scheme 2
To test the recovery and reuse of the MP catalyst system,
a series of recycling experiments was conducted over 5 cycles
washing 3 ¥ 5 mL of solvent between each cycle) (Table 1)
keeping the reaction time constant.
The RCM of 3 was found to proceed smoothly with >95%
conversion over the first two cycles (Cycles 1 and 2) for
(
reactions performed in both CH
2
Cl (Method A) and toluene
2
(
Method B). However, a decrease in conversion was experienced
after the second cycle (Cycles 3–5, Methods A and B). The
reduction in conversion was less pronounced when performed
in toluene. High conversion (>80%), however, was reachieved
with a longer reaction time (12 h) in both cases (Cycle 6). In
addition to producing superior conversion, the use of toluene
also aided magnetic recovery by promoting particle aggregation
once magnetic stirring had ceased.
-
1
loading of 0.06 mmol g of ruthenium, a loss of ~50% of the
initial ruthenium content.
8
2 | Green Chem., 2012, 14, 81–84
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The loss of ruthenium and catalyst activity after only 4 cycles
under optimum reaction conditions (Method D) was perplexing
given that Jiang and coworkers, using a structurally related,
covalently ligated Hoveyda-Grubbs-MP catalyst construct, were
able to perform 13 sequential RCM reactions in near quan-
Experimental
General
All chemicals and solvents were used as purchased with the
following exceptions. Toluene was distilled over Na wire and
argon sparged prior to use. Dichloromethane was distilled
13
titative yield. While loss of MP-bound Ru could arise from
separation of the pre-catalyst 1 from the MP at the ionic
attachment site, the use of rigorously dried solvents protects
the catalyst construct from dissociation. Instead we believe
that ineffective recapture of in situ generated homogeneous Ru-
alkylidenes is the major cause of ruthenium leeching from the
over CaH and argon sparged prior to use. THF was distilled
2
from benzophenone and Na wire prior to use. TEOS refers
to tetraethoxysilane. Quaternary ammonium catalyst 1 was
prepared according to a literature method and recrystallised
19
from dichloromethane/hexane.
20
MPs. Significantly, Plenio and coworkers have recently shown
that the release-return mechanism does not play a significant
role in catalytic RCM cycles employing Hoveyda-Grubbs-type
1
H NMR spectra were acquired using a Bruker DPX 300
1
MHz spectrometer (300 MHz H) or a Bruker DRX 400 MHz
spectrometer (400 MHz H) as solutions in CDCl
shifts (d) were calibrated against the residual solvent peak.
ICP-MS analyses were conducted using the a previously
reported procedure by Dr Ian McDonald of Earth and Ocean
Sciences, Cardiff University.
1
3
. Chemical
21
catalysts. Hence, in general, immobilisation strategies via the
labile benzylidene ligand are likely to result in sub-optimum
performance. The initial value of 200 ppm in product 4 after cycle
23
1
(Table 1), however, is comparable to several other reported
trace residual Ru values obtained after a variety of metal-
22
removal treatments.
Once it was identified that the activity of the catalyst was
decreasing over time we chose to investigate whether the sub-
performing particles could be regenerated. The particles were
stripped of remaining catalyst by washing with 1 M HCl.
This process disrupted the electrostatic interaction between
the quaternised ligand and the particles. After washing with
additional portions of water and thorough drying, the particles
were retitrated with 0.1 M NaOH, giving a concordant value of
Preparation of sulphonic acid functionalised iron oxide
nanoparticles
A combined solution of FeCl
FeCl O (2.16 mL in 2 M HCl) was added to a rapidly
·4H
stirred solution of aqueous NH (281 mL, 0.7 M). A dark
brown precipitate of Fe formed instantly. The mixture was
3
.6H
2
O (8.63 mL, 1 M) and
2
2
3
3
O
4
stirred for 1 h before being magnetically separated. The bulk of
the solution was decanted from the particles, and the resultant
slurry of the magnetic particles (in 25 mL) was combined with
-
1
0
.44 mmol g , slightly lower than the initial preparation. ICP-
MS ruthenium analysis of the stripped MPs revealed a residual
-
1
ruthenium content of 0.018 mmol g . Attempted RCM of 3 with
these particles gave no conversion to 4 indicating that only non-
catalytically active ruthenium species and/or non-accessible 2
was bound to the MP.
water (25 mL), EtOH (175 mL) and NH (1.3 mL, 28%) before
3
dropwise addition of TEOS (1.3 g). The resulting mixture was
left to stir overnight. The ethanol was removed from the aqueous
solution by rotary evaporation and MeOH (500 mL) and NH
1.3 mL, 28%) added. 3-Mercaptopropyltrimethoxysilane (2.6
3
A fresh stoichiometric portion of catalyst 1 was then added to
the recovered MPs as previously described. ICP-MS analysis of
the regenerated Ru-magnetic particles gave a Ru analysis value
of 0.075 mmol g- which was lower than the original MP-pre-
(
g, 0.013 mol) was then added and the mixture was left to
stir for 3 days at room temperature. The particles were then
magnetically separated and the resulting slurry was washed
1
-
1
catalyst value of 0.12 mmol g . Additional catalysis runs were
performed with the reduced catalyst loading (adjusted to 0.43
mol% in contrast to the previously employed 0.68 mol% loading
shown in Table 1) and >95% yields for the RCM of 3 into
with water (500 mL) before the addition of H
2
2
O (30 mL,
3
0%). This solution was stirred overnight and then separated by
centrifugation. After the particles had been isolated they were
washed with 1 M HCl (25 mL) and water (2 ¥ 100 mL) before
the remaining solvent was removed by rotary evaporation. The
isolated particles were then dried under high vacuum (25–30%
yield).
4
were obtained over two successive reaction cycles using the
regenerated catalyst.
Conclusion
Titration of sulphonic acid functionalised iron oxide MPs
A quaternary ammonium Hoveyda-Grubbs olefin metathesis
pre-catalyst 1, which is readily accessed in one step from
commercially available second generation Grubbs catalyst, has
been successfully immobilized onto magnetically separable
nanosized iron oxide particles. The resultant ruthenium alkyli-
dene catalyst provided pseudo-homogeneous reactivity coupled
with an in-built facile recovery option. The use of electrostatic
attachment also enabled ready reloading of the catalyst and
reuse of the functionalised MPs. Magnetic retrieval of the
immobilised catalyst simplified product isolation and catalysis
recycling.
Sulphonic acid functionalised particles (239 mg) were sonicated
in brine (10 mL) until a homogeneous slurry was obtained. The
slurry was then titrated against NaOH (0.1 M) to neutral pH
(determined by a pH meter). The particles were then washed
with water (20 mL), reacidified by exposure to HCl (20 mL,
1 M) for 30 minutes, and then again washed with water (3 ¥
20 mL). This process was repeated until concordant titration
readings were obtained. The titrated particles were stored in a
glovebox and used for catalyst adhesion after drying under high
vacuum.
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Preparation of 2
Acknowledgements
Dry, deoxygenated CH
a nitrogen purged Schlenk flask containing 1 (25 mg, 0.029
mmol) and 50 mg of the ca. 0.5 mmol g sodium sulfonated
functionalised iron oxide magnetic particles (ca. 0.025 mmol).
The solution was stirred at room temperature for 3 h. The
particles were then magnetically separated, washed with dry,
2
Cl
2
(10 ml) was added via syringe to
This work was partially supported by an Early-Career Reseacher
Grant to MJB by the Faculty of Science, Monash University,
Australia. ICP-MS analyses were performed by Dr Ian McDon-
ald (Earth and Ocean Sciences, Cardiff University) with the
generous assistance of Prof. David Knight.
-
1
degassed CH
and stored in a glovebox prior to use.
2
Cl (5 ¥ 10 mL each), dried under high vacuum
2
References
1
2
3
A. H. Hoveyda and A. R. Zhugralin, Nature, 2007, 450, 243–251.
P. H. Deshmukh and S. Blechert, Dalton Trans., 2007, 2479–2491.
H. Clavier, K. Grela, A. Kirschning, M. Mauduit and S. P. Nolan,
Angew. Chem., Int. Ed., 2007, 46, 6786–6801.
RCM assessment of 2
Diethyl diallyl malonate 3 (5 mL of a 0.047 M stock solution
in dry degassed solvent) was added to an argon purged
Schlenk flask containing 2 (13.3 mg, ~0.68 mol%) and the
resulting solution was stirred at room temperature for 2 h.
The particles were magnetically separated over a five minute
period and then washed with the designated solvent (3 ¥
4
S. T. Nguyen and R. H. Grubbs, J. Organomet. Chem., 1995, 497,
1
95–200.
5 D. P. Allen, M. M. Van Wingerden and R. H. Grubbs, Org. Lett.,
009, 11, 1261–1264.
(a) A. H. Lu, L. Salabas and F. Schuth, Angew. Chem., Int. Ed., 2007,
6, 1222–1244; (b) V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M.
Bouhrara and J. M. Basset, Chem. Rev., 2011, 111, 3036–3075.
7 (a) P. D. Stevens, G. Li, J. Fan, M. Yen and Y. Gao, Chem. Commun.,
005, 4435–4437; (b) M. Shokouhimehr, Y. Piao, J. Kim, Y. Jang and
2
6
4
1
0 ml). This cycle was repeated 4 times with addition of
2
fresh substrate (5 mL of a 0.047 M stock solution in dry
degassed solvent). Both dichloromethane and toluene were used
as solvents. The use of a bleed needle was employed where
stated.
T. Hyeon, Angew. Chem., Int. Ed., 2007, 46, 7039–7043.
K-I. Fujita, S. Umeki, M. Yamazaki, T. Ainoya, T. Tsuchimoto and
H. Yasuda, Tetrahedron Lett., 2011, 52, 3137–3140.
8
9
J. Liu, X. Peng, W. Sun, Y. Zhao and C. Xia, Org. Lett., 2008, 10,
3
933–3936.
1
0 V. Polshettiwar and R. S. Varma, Chem.–Eur. J., 2009, 15, 1582–1586.
Regeneration of the catalyst particles
11 T. Hirakawa, S. Tanaka, N. Usuki, H. Kanzaki, M. Kishimoto and
M. Kitamura, Eur. J. Org. Chem., 2009, 789–792.
Spent catalyst particles 2 (70 mg) were washed with water (50
mL) before being dispersed in 1 M HCl (25 mL) and stirred for
12 R. Abu-Reziq, D. Wang, M. Post and H. Alper, Chem. Mater., 2008,
2
0, 2544–2550.
1
3 C. Che, W. Li, S. Lin, J. Chen, J. Zheng, C-C. Wu, Q. Zheng, G.
3
0 min at room temperature. The acid treated particles were
Zhang, Z. Yang and B. Jiang, Chem. Commun., 2009, 5990–5992.
14 Z. Yinghuai, L. Kuijin, N. Huimin, L. Chuanzhao, L. P. Stubbs, C.
then washed with water (2 ¥ 50 mL) and dried under high
vacuum. The cleaved particles were retitrated using the same
protocol as stated previously, giving a titration value of 0.44
F. Siong, T. Muihua and S. C. Peng, Adv. Synth. Catal., 2009, 351,
2
650–2656.
1
1
5 M. R. Buchmeiser, New J. Chem., 2004, 28, 549–557.
-
1
mmol g . After titration the particles were washed with water
3 ¥ 20 mL) and THF (1 ¥ 20 mL), then dried under high
vacuum.
Regeneration with catalyst 1 was performed by adding dry,
6 C. Coperet and J. M. Basset, Adv. Synth. Catal., 2007, 349, 78–92.
(
17 G. Liu, B. Wu, J. Zhang, X. Wang, M. Shao and J. Wang, Inorg.
Chem., 2009, 48, 2383–2390.
1
8 A. Michrowska, K. Mennecke, U. Kunz, A. Kirschning and K. Grela,
J. Am. Chem. Soc., 2006, 128, 13261–13267.
deoxygenated dichloromethane (5 ml) to a nitrogen-purged
19 A. Michrowska, L. Gulajski, Z. Kaczmarska, K. Mennecke, A.
Kirschning and K. Grela, Green Chem., 2006, 8, 685–688.
20 D. Rix, F. Caijo, I. Laurent, L. Gulajski, K. Grela and M. Mauduit,
Chem. Commun., 2007, 3771–3773.
Schlenk flask containing 1 (6.3 mg, 8.83 mmol) and 20 mg
of 0.44 mmol g-1 sodium sulfonated functionalised iron oxide
magnetic particles (ca. 0.025 mmol). The solution was stirred at
room temperature for 3 h. The particles were then magnetically
separated, washed with dry, degassed dichloromethane (5 ¥ 10
mL), dried under high vacuum and stored in a glovebox prior
to use.
2
2
2
1 T. Vorfalt, K. J. Wannowius, V. Thiel and H. Plenio, Chem.–Eur. J.,
2010, 16, 12312–12315.
2 G. C. Vougioukalakis and R. H. Grubbs, Chem. Rev., 2010, 110,
1
746–1787.
3 D. W. Knight, I. R. Morgan and A. J. Proctor, Tetrahedron Lett.,
2010, 51, 638–640.
8
4 | Green Chem., 2012, 14, 81–84
This journal is © The Royal Society of Chemistry 2012