Silica-supported catalysts for ring-closing metathesis: Effects of linker group and microenvironment on recyclability

Article abstract of DOI:10.1039/b803663b

The interesting effects of the linker and microenvironment on the recyclability of well-defined silica-supported catalysts were examined, which demonstrated the excellent activity and reusability for the ring-closing metathesis (RCM) of a number of substr

Full text of DOI:10.1039/b803663b

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Silica-supported catalysts for ring-closing metathesis: effects of linker
group and microenvironment on recyclabilityw
Jaehong Lim, Su Seong Lee* and Jackie Y. Ying*
Received (in Cambridge, UK) 4th March 2008, Accepted 2nd May 2008
First published as an Advance Article on the web 17th July 2008
DOI: 10.1039/b803663b
The interesting effects of the linker and microenvironment on the
recyclability of well-defined silica-supported catalysts were ex-
amined, which demonstrated the excellent activity and reusability
for the ring-closing metathesis (RCM) of a number of substrates.
ligand exchange in refluxing dichloromethane (DCM) with the
aid of Cu(I) chloride,6a followed by filtration, washing, and
drying. Elemental analysis revealed that the ruthenium loading
was ca. 0.22 mmol gÀ1 in all derivatives of 7. 13C CP-MAS
NMR spectra also confirmed the smooth exchange process by
showing a decrease in olefin peaks upon conversion of 6 to 7
(See ESIw). With a ligand loading of ca. 0.34 mmol gÀ1 in the
corresponding 6, this implied that B70% of the immobilized
ligands were loaded with ruthenium.
Despite their great potential in ring-closing metathesis
(RCM),1 the well-defined ruthenium catalysts2 suffer from
some drawbacks associated with their high cost and leaching
problems.3 To address these challenges, significant efforts have
been devoted towards developing heterogenized catalysts.4,5 In
particular, covalent immobilization of the catalytic species on
polymer6 and silica7 supports has been examined. Taking
advantage of siliceous mesocellular foam (MCF)8 as a support
material,9 we have developed highly recyclable RCM catalysts
by tuning the linker group and microenvironment in the
heterogenized system. MCF is a stable mesoporous silica with
ultralarge, cell-like pores (24–42 nm) interconnected by win-
dows of 9–22 nm.8 This novel support material is well-suited
for fixing bulky complexes and facilitates substrate diffusion.10
The linear alkylsilane motif is particularly attractive as a linker
group with its robust and orthogonal nature. The known
bromide 311 was readily transformed to three types of alkyl-
chlorosilanes 5 with a variable linker length (Scheme 1). The
electron-rich aromatic nucleophile, in situ generated by the
Grignard protocol, proceeded smoothly to form a carbon–
silicon bond in the presence of excess alkyldichlorosilanes 4.
Unreacted 4 was thoroughly removed under reduced pressure
prior to the immobilization of 5 onto trimethylsilyl (TMS)-
precapped spherical MCF microparticles12 in the presence of
triethylamine (TEA). The remaining silanol groups in MCF
were further capped by treatment with hexamethyldisilazane
(HMDS) under vapor-phase conditions12 to minimize the
undesired interactions between the catalysts and the MCF
surface. The overall yields of the immobilized ligands 6 were
excellent (490% in three steps). The Fourier-transform infra-
red (FTIR) spectrum and the cross-polarization magic angle
spinning nuclear magnetic resonance (CP-MAS NMR) 13C
and 29Si spectra indicated the formation of well-dispersed
Hoveyda-type ligands on the surface of MCF (see ESIw).
The green heterogenized catalysts 7 were isolated by smooth
Efficient, complete RCM of diene 8 to the cyclized product 9
was achieved in 2 h over 5 mol% of 7b or 7c in DCM at
ambient temperature (Fig. 1). Interestingly, only 30% conver-
sion was attained with 7a in 2 h, which did not further progress
with time. It was obvious that the reaction rates were strongly
influenced by the ligand flexibility, and 7a was probably
located too close to the MCF surface, rendering most ruthe-
nium species latent in the catalytic cycle. The accessibility of
the diene to the catalytic core would likely determine the
initiation rate and the overall conversion rate. The short and
rigid linker in 7a deprived the ruthenium species of mobility,
sandwiching it between the MCF surface and the bulky N-
heterocyclic carbene (NHC) ligand. As a result, the initial
complexation of substrate 8 to trigger the catalytic cycle was
considerably blocked in the case of 7a, giving rise to a low
conversion rate as compared to 7b and 7c, which consisted of
more flexible linker moieties. It appeared that a two-carbon
linker was long enough to provide access of the diene to the
ruthenium, as demonstrated by the efficient RCM over 7b.
The recyclabilities of 7b and 7c were investigated for the
RCM of 8 in DCM at 50 1C (Fig. 2). The reaction time was
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The
Nanos, Singapore 138669. E-mail: sslee@ibn.a-star.edu.sg,
E-mail: jyying@ibn.a-star.edu.sg; Fax: (+65) 6478-9020
w Electronic supplementary information (ESI) available: Detailed
experimental procedures, and NMR spectra of the novel compounds
in Scheme 1 and the RCM products in Table 1. See DOI: 10.1039/
b803663b
Scheme 1 Synthetic pathway to the immobilized catalysts 7.
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Fig. 3 The microenvironment of catalysts 7d and 7e.
magnitude of diminished peaks in the 13C CP-MAS NMR
spectra of 7b and 7c after multiple runs confirmed that the
leaching of ruthenium species was more significant in 7c
(see ESIw).
To test our hypothesis, we have fabricated a system that
surrounded the flexible hydrocarbon subunit with similarly
featured precapping groups, so that the intermolecular inter-
ference among the reactive moieties could be suppressed. The
beneficial role of the precapping group was well elucidated in
our previous reports.14 In this case, we simultaneously grafted
precursor 5c (the flexible catalyst precursor) and linear hydro-
carbon groups (i.e., n-octyl group for 7d and perfluoro-n-
octylethyl group for 7e) onto uncapped MCF. In the course
of the catalytic runs, the linear hydrophobic precapping
moiety might stack along with the flexible linker group in 7c
to fixate the precatalysts on the hydrophobic surface (Fig. 3).
As expected, the recyclability of catalyst 7c was dramatically
improved by tuning the microenvironment to minimize the
decomposition of the reactive catalytic species 7d and 7e,
which demonstrated excellent recyclabilities that were almost
comparable to 7b (Fig. 2). The molar ratio of the precapping
group to catalyst should be ca. 2.6, assuming that the two
alkylchlorosilanes were grafted in similar rates according to
the initial amounts added.
Fig. 1 RCM of 8 over catalysts (K) 7a, (E) 7b and (’) 7c.
Ruthenium leaching from 7b and 7d in the RCM of 8 over
10 runs was measured by inductively coupled plasma-mass
spectroscopy (ICP-MS). On average, only 5 ppm and 8 ppm of
ruthenium were found in the reaction solutions in each run due
to the leaching from 7b and 7d, respectively. This low level of
ruthenium leaching could be attributed to the unique structure
of and synthesis scheme for 7, which included the use of
spherical siliceous MCF microparticles with well-defined,
ultralarge mesopores, partial precapping of silanols on the
support surface, mild and uniform ligand grafting, vapor-
phase postcapping of silanols, and efficient ruthenium loading.
Given the excellent recyclability of 7b and 7d, these catalysts
were further examined in the RCM reactions of various
substrates (Table 1). The RCM of an oxygen-containing diene
10 produced the six-membered ring 11 in excellent yields for 10
consecutive runs. The typical concern of intramolecular co-
ordination of the oxygen atom to the ruthenium–carbene
intermediate5a did not appear to be an issue in the RCM over
7b. Formation of the seven-membered ring 13 was also
efficient, and good activities were exhibited over 7 runs. The
catalyst 7b also proved effective for cyclizing a nitrogen-
containing diene 14, although a more sterically challenging
substrate 16 required an extended reaction time and the
catalyst showed substantial loss of activity after the initial
run. The RCM involving an electron-deficient carbonyl moiety
Fig. 2 RCM of 8 over catalysts 7 in DCM at 50 1C.
kept constant at 2 h to monitor the decrease in catalytic
activity over multiple runs. Despite their similar conversion
in the first run, the recyclabilities were dramatically different
for the ethyl and hexyl derivatives. While the ethyl derivative
7b maintained consistently high conversions ( Z 90%) up to 10
runs, a significant reduction in conversion was observed in the
recycling of the hexyl derivative 7c. The gradual loss of activity
could be attributed to the deactivation of the ruthenium–
carbene complex,13 possibly from the increased intermolecular
interference among the neighboring ligands (and/or catalysts)
associated with the flexible hexyl linker in 7c. This might lead
to permanent deactivation of the precatalysts and/or leaching
of the ruthenium species. With a decreasing number of intact
ruthenium–carbene complexes in the recycled 7c, the conver-
sions in the subsequent runs would be reduced. In contrast, the
ethyl derivative 7b could avoid intermolecular interference
with its relatively short and rigid linker group. Thus, excellent
recyclability was achieved by tuning the linker moiety at
the two-carbon chain in our system. A comparison of the
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Table 1 RCM of several dienes over 7b and 7d
Notes and references
Catalyst Substratea
Product
Run Conv (%)b
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3 Ruthenium residue levels must be less than 5 ppm and 0.5 ppm for
oral and parental drug products according to the guidelines of
European Agency for the Evaluation of Medicinal Products. For
details, see: A. Thayer, Chem. Eng. News, 2005, 83, 55.
¨
7b
1
4
7
10
97
97
96
97
11
10
7b
1
3
5
7
93
97
93
89
13
15
4 Selected articles: Q. Yao, Angew. Chem., Int. Ed., 2000, 39, 3896;
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7b
1
3
5
7
91
91
73
77
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Koch, K. Langemann, M. Liebl, C. Six and W. Leitner, J. Am.
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14c
7b
1
67
99e
45
20
2
3
17
16d
7d
1
4
7
10
83
78
89
79
6 J. S. Kingsbury, J. P. A. Harrity, P. J. Bonitatebus, Jr and A. H.
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19
21
18c
7d
1
4
7
10
99
97
95
87
8 P. Schmidt-Winkel, W. W. Lukens, Jr, D. Zhao, P. Yang, B. F.
Chmelka and G. D. Stucky, J. Am. Chem. Soc., 1999, 121, 254; P.
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20
a
b
Conditions: 5 mol% of 7, 50 1C, 1 h, 0.05 M in DCM. Determined
by gas chromatography (GC) or liquid chromatography (LC).
d
Performed for 2 h. Performed for 4 h. Performed for 20 h.
9 Selected recent articles: K. Vehlow, S. Maechling, K. Kohler and S.
¨
Blechert, J. Organomet. Chem., 2006, 691, 5267; F. Michalek, D.
c
e
Madge, J. Ruhe and W. Bannwarth, J. Organomet. Chem., 2006,
¨
¨
691, 5172; X. Elias, R. Pleixats, M. W. C. Man and J. J. E.
Moreau, Adv. Synth. Catal., 2007, 349, 1701.
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(substrate 18) was especially effective with 7d as the catalyst.
The reaction efficiency appeared sustainable, although the
initial run was not performed to completion. The seven-
membered ring 21 was formed more efficiently than its five-
membered ring analog 15, exhibiting good conversions up to
10 consecutive runs.
12 S. S. Lee, S. Hadinoto and J. Y. Ying, Adv. Synth. Catal., 2006,
348, 1248; Y. Han, S. S. Lee and J. Y. Ying, Chem. Mater., 2006,
18, 643; Y. Han, S. S. Lee and J. Y. Ying, Chem. Mater., 2007, 19,
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13 Spectroscopic evidence of the return of ruthenium carbene com-
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127, 4510.
14 J. Lim, S. S. Lee, S. N. Riduan and J. Y. Ying, Adv. Synth. Catal.,
2007, 349, 1066.
15 An example of RCM application in pharmaceutical industry:
T. Nicola, M. Brenner, K. Donsbach and P. Kreye, Org. Process
Res. Dev., 2005, 9, 513.
In conclusion, we have successfully developed highly active
and recyclable MCF-supported ruthenium catalysts for RCM
by optimizing the linker group and microenvironment. These
cost-effective and environmentally benign heterogenized cata-
lysts are of interest for industrial processes.15 The remarkably
low leaching of ruthenium species would be particularly
attractive in pharmaceuticals manufacturing.
This work is supported by the Institute of Bioengineering
and Nanotechnology (Biomedical Research Council, Agency
for Science, Technology and Research, Singapore).
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4314 | Chem. Commun., 2008, 4312–4314