Weil-defined silica-supported olefin metathesis catalysts

Article abstract of DOI:10.1021/ol9000153

Two triethoxysilyl-functionalized N-heterocyclic carbene ligands have been synthesized and used to prepare the corresponding second-generation ruthenium olefin metathesis catalysts. These complexes were then grafted onto silica gel, and the resulting materials were efficient heterogeneous catalysts for a number of metathesis reactions. The solid-supported catalysts were shown to be recyclable over a number of reaction cycles, and no detectable levels of ruthenium were observed in reaction filtrates (ruthenium concentration of filtrate <5 ppb).

Full text of DOI:10.1021/ol9000153

ORGANIC
LETTERS
2009
Vol. 11, No. 6
1261-1264
Well-Defined Silica-Supported Olefin
Metathesis Catalysts
Daryl P. Allen,† Matthew M. Van Wingerden, and Robert H. Grubbs*
The Arnold and Mabel Beckman Laboratory of Chemical Synthesis, DiVision of
Chemistry and Chemical Engineering, California Institute of Technology,
Pasadena, California 91125
rhg@caltech.edu
Received January 5, 2009
ABSTRACT
Two triethoxysilyl-functionalized N-heterocyclic carbene ligands have been synthesized and used to prepare the corresponding second-
generation ruthenium olefin metathesis catalysts. These complexes were then grafted onto silica gel, and the resulting materials were efficient
heterogeneous catalysts for a number of metathesis reactions. The solid-supported catalysts were shown to be recyclable over a number of
reaction cycles, and no detectable levels of ruthenium were observed in reaction filtrates (ruthenium concentration of filtrate <5 ppb).
Olefin metathesis has emerged as a unique and powerful
transformation for the interconversion of olefinic hydrocar-
bons in both organic and polymer chemistry.1 The develop-
ment of well-defined ruthenium-based catalysts (1-3, Figure
1)2 has greatly expanded the scope and applications of this
process due to their increased tolerance of organic function-
3
ality, moisture, and oxygen. However, even with the
Figure 1.
Ruthenium-based olefin metathesis catalysts.2
advances in this area, catalyst lifetime and efficiency can
† Current address: Materia Inc., 60 N. San Gabriel Blvd, Pasadena, CA
91107.
represent a major limiting factor in the further advancement
of this technology. Thus, over the past decade, significant
emphasis has been placed on gaining a fundamental under-
standing of the various decomposition pathways leading to
catalyst deactivation.4 This has led to the advent of new
catalyst architectures that provide improved reactivity and/
or methods for eliminating or reducing particular decom-
postion pathways such as C-H activation of ortho N-aryl
substituents.5
(1) (a) Grubbs, R. H. Handbook of Metathesis; Wiley-VCH: Weinheim,
Germany, 2003. (b) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int.
Ed. 2003, 42, 4592–4633. (c) Ivin, K. J.; Mol, J. C. Olefin Metathesis and
Metathesis Polymerization; Academic Press: San Diego, CA, 1997.
(2) (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100–110. (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953–956. (c) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.;
Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168–8179.
(3) (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29.
(b) Grubbs, R. H. Tetrahedron 2004, 60, 7117–7140. (c) Schrodi, Y.;
Pederson, R. L. Aldrichim. Acta 2007, 40, 45–52. (d) Grubbs, R. H. AdV.
Synth. Catal. 2007, 349, 34–40.
10.1021/ol9000153 CCC: $40.75
Published on Web 02/24/2009
2009 American Chemical Society

Several decompostion pathways involve bimetallic species
due to the propensity for ruthenium to dimerize via thermo-
dynamically stable chloride (4 and 6) or carbide bridges (5)
(Figure 2).4b-e One approach to prevent these undesirable
cannot realize all the benefits of solid-phase catalysis, such as
desirable continuous flow processes.
Scheme 1. Synthesis of Ruthenium Complexes 15 and 16
Figure 2.
Various dimeric ruthenium decomposition products.4
bimolecular decomposition pathways is to immobilize the
catalyst onto a solid support that inhibits intermolecular
catalyst-catalyst interactions via site isolation.6 Furthermore,
supported catalysts have the added advantages of generating
products free of ruthenium contamination and possess the ability
to be recovered and subsequently recycled. A number of reports
have been published employing various strategies to obtain
solid-supported olefin metathesis catalysts.7 These consist of
anchoring the catalytic moiety, via a number of positions within
the catalyst framework, to a variety of solid supports, such as
organic polymers or inorganic oxides. Of the various strategies,
immobilization through a chelating benzylidene has been the
most widely employed. These catalysts operate via a release/
return phenomenon8 with all the catalytic activity arising from
a homogeneous species, which is susceptible to the same
bimetallic decomposition pathways. Likewise, such systems
(4) (a) Ulman, M.; Grubbs, R. H. J. Org. Chem. 1999, 64, 7202–7207.
(b) Amoroso, D.; Yap, G. P. A.; Fogg, D. E. Organometallics 2002, 21,
3335–3343. (c) Amoroso, D.; Snelgrove, J. L.; Conrad, J. C.; Drouin, S. D.;
Yap, G. P. A.; Fogg, D. E. AdV. Synth. Catal. 2002, 344, 757–763. (d)
Hong, S. H.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2004, 126,
7414–7415. (e) Hong, S. H.; Wenzel, A. G.; Salguero, T. T.; Day, M. W.;
Grubbs, R. H. J. Am. Chem. Soc. 2007, 129, 7961–7968. (f) Hong, S. H.;
Chlenow, A.; Day, M. W.; Grubbs, R. H. Angew. Chem., Int. Ed. 2007, 46,
5148–5151. (g) van Rensburg, W. J.; Steynberg, P. J.; Meyer, W. H.; Kirk,
M. M.; Forman, G. S. J. Am. Chem. Soc. 2004, 126, 14332–14333.
(5) (a) Berlin, J. M.; Campbell, K.; Ritter, T.; Funk, T. W.; Chlenov,
A.; Grubbs, R. H. Org. Lett. 2007, 9, 1339–1342. (b) Stewart, I. C.; Ung,
T.; Pletnev, A. A.; Berlin, J. M.; Grubbs, R. H.; Schrodi, Y. Org. Lett.
2007, 9, 1589–1592. (c) Anderson, D. R.; Lavallo, V.; O’Leary, D. J.;
Bertrand, G.; Grubbs, R. H. Angew. Chem., Int. Ed. 2007, 46, 7262–7265.
(d) Vougioukalakis, G. C.; Grubbs, R. H. J. Am. Chem. Soc. 2008, 130,
2234–2245. (e) Chung, C. K.; Grubbs, R. H. Org. Lett. 2008, 10, 2693–
2696.
Other strategies involve immobilization via alternative X-type
ligands that replace the ancillary chlorides, such as fluorinated
carboxylates,9 or via functionalized NHC ligands.10 The latter
is a very attractive approach as the NHC forms a strong bond
to the ruthenium center and is the most substitutionally inert
ligand within the catalyst coordination sphere.11 Herein, we
report the syntheses of two triethoxysilyl functionalized NHC
ligands (10 and 13) and their use in the generation of ruthenium
complexes 15 and 16.12 The subsequent grafting of these
complexes onto silica is described and the utility of the silica-
supported analogues as heterogeneous catalysts is evaluated.
The synthesis of 10 began with the allylation of bisimine 7
followed by reduction to furnish diamine 8. This was treated
with HCl and triethyl orthoformate to generate the imidazolium
(6) (a) Collman, J. P.; Belmont, J. A.; Brauman, J. J. J. Am. Chem. Soc.
1983, 105, 7288–7294. (b) Drago, R. S.; Pribich, D. C. Inorg. Chem. 1985,
24, 1983–1985. (c) Tollner, K.; Popovitv-Biro, R.; Lahav, M.; Milstein, D.
Science 1997, 278, 2100–2102. (d) Annis, D. A.; Jacobsen, E. N. J. Am.
Chem. Soc. 1999, 121, 4147–4154.
(7) For recent review articles, see: (a) Buchmeiser, M. R. New. J. Chem.
2004, 28, 549–557. (b) Coperet, C.; Basset, J.-M. AdV. Synth. Catal. 2007,
349, 78–92. (c) Clavier, H.; Grela, K.; Kirschning, A.; Mauduit, M.; Nolan,
S. P. Angew. Chem., Int. Ed. 2007, 46, 6786–6801.
(8) (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda,
A. H. J. Am. Chem. Soc. 1999, 121, 791–799. (b) Hoveyda, A. H.;
Gillingham, D. G.; van Veldhuizen, J. J.; Kataoka, O.; Garber, S. B.;
Kingsbury, J. S.; Harrity, J. P. A. Org. Biomol. Chem. 2004, 2, 8–23.
1262
Org. Lett., Vol. 11, No. 6, 2009

chloride 9. A Pt(0)-catalyzed hydrosilylation of 9 using HSiCl3
and subsequent treatment with ethanol/NEt3 produced the
triethoxysilyl backbone functionalized NHC salt 10. A similar
strategy was used to prepare NHC salt 13. Diamine 11 was
prepared in three steps from commercially available starting
materials (see the Supporting Information) and used to generate
p-allyl NHC salt 12. This was transformed to the triethoxysilyl-
functionalized NHC salt 13 via the Pt(0)-catalyzed hydrosily-
lation procedure described above. Ruthenium complexes 15 and
16 were subsequently prepared by deprotonation of the respec-
tive NHC salts, 10 and 13, with potassium bis(trimethylsilyl)-
amide and treatment of the resulting free carbene with ruthenium
complex 14.
an additional 50 min reaction time, the silica-supported
catalyst containing suspensions proceeded to >95% (15-SiO2)
and 86% (16-SiO2), whereas the filtered portions showed
no further reactivity (Figure 4). Thus, the catalytic activity
Next, solutions of 15 and 16 were stirred with silica at 25 °C
for 72 h to obtain the corresponding silica-supported catalysts
15-SiO2 and 16-SiO2 (Figure 3). At this time, the ruthenium-
Figure 4. Split tests to determine the degree of catalyst heterogene-
ity for 15-SiO2 and 16-SiO2. Reactions were performed in C6D6
(0.1 M) using 0.25-0.5 mol % of catalyst and percent conversion
1
determined by H NMR.
arises from the supported complex and not from catalyst that
leached from the solid support. Also worth noting is that
the filtered reaction mixture involving 15-SiO2 was analyzed
for ruthenium content and contained <5 ppb ruthenium
contamination (below detection limit of ICP-MS).
With the positive results obtained from the split tests, the
catalysts were next examined in a series of RCM reactions as
displayed in Table 1. The results show that both catalysts are
Figure 3. Silica-supported catalysts 15-SiO2 and 16-SiO2.
loaded material was transferred to a Soxhlet extraction thimble
and continuously extracted with CH2Cl2 for 48 h. This step was
necessary to remove any traces of 15 or 16 that were not
covalently immobilized to the silica support.
Table 1. RCM Reactions Employing 15-SiO2 and 16-SiO2
With silica-supported analogues 15-SiO2 and 16-SiO2 in
hand, we first wanted to gauge their catalytic activity, along
with determining their degree of heterogeneity. This was
necessary to ensure that the catalytic activity arises from the
supported catalyst and not from some actiVe species leaching
from the solid support. This was done by performing a split
or hot-filtration test.13 We examined the RCM of diethyl-
diallyl malonate at 60 °C for both supported catalysts, where,
after 10 min half of the reaction was filtered at a conversion
of 67% (15-SiO2) and 31% (16-SiO2), respectively. After
(9) For a representative example, see: Halbach, T. S.; Mix, S.; Fischer,
D.; Maechling, S.; Krause, J. O.; Sievers, C.; Blechert, S.; Nuyken, O.;
Buchmeiser, M. R. J. Org. Chem. 2005, 70, 4687–4694.
(10) For representative examples, see: (a) Schu¨rer, S. C.; Gessler, S.;
Buschmann, N.; Blechert, S. Angew. Chem., Int. Ed. 2000, 39, 3898–3901.
(b) Mayr, M.; Buchmeiser, M. R.; Wurst, K. AdV. Synth. Catal. 2002, 344,
712–719. (c) Pru¨hs, S.; Lehmann, C. W.; Fu¨rstner, A. Organometallics 2004,
23, 280–287.
(11) For evidence of exchange between the X-type ligands, see: Tanaka,
K.; Bo¨hm, V. P. W.; Chadwick, D.; Roeper, M.; Braddock, D. C.
Organometallics 2006, 25, 5696–5698.
(12) Merck & Co., Inc. have filed patents in this research area. For a
representative patent see: Koehler, K. Immobilizable N-heterocyclic Carbene
Metal Complexes with Alkoxysilyl Groups International Patent No. WO
2007/017047 A1.
a Reactions were not run to completion, rather only for the alloted time.
Percent conversions determined by 1H NMR. b ICP-MS analysis of the RCM
product isolated by filtration and concentration indicated <5 ppb ruthenium
contamination.
(13) Sheldon, R. A.; Wallau, M.; Arends, I. W. C. E.; Schuchardt, U.
Acc. Chem. Res. 1998, 31, 485–493.
Org. Lett., Vol. 11, No. 6, 2009
1263

competent, even at the low catalyst loadings employed (0.4 mol
%); however, in all cases the NHC backbone functionalized
15-SiO2 outperforms the p-N-aryl-derived 16-SiO2.14
Next, the supported catalysts were screened for the cross-
metathesis reaction between allylbenzene (21) and cis-1,4-
diacetoxy-2-butene (22) (eq 1).15 Again, 15-SiO2 outper-
formed 16-SiO2 supplying the cross product in 80% versus
30% yield after 2 h. However, 16-SiO2 did continue to
turnover, reaching a maximum of 53% conversion after
24 h.16
Figure 5. Recycling of 15-SiO2 for RCM of substrate 20. Reactions
were performed in C6H6 (0.1 M) using 0.75 mol % of 15-SiO2/
cycle and percent conversions determined by 1H NMR. Each cycle
was 2 h except for no. 5, which was run for 12 h.
The reason for the greater reactivity of 15-SiO2 compared
to 16-SiO2 is unknown; however, it is speculated to arise
from an interaction between the ruthenium active site and
the silica surface that is present in the case of 16-SiO2 but
is blocked by the steric bulk of the NHC ligand in the case
of 15-SiO2. RCM studies involving the homogeneous
complexes 15 and 16 were performed in hopes of gaining
insight into this matter and revealed that 16 had a slightly
longer induction period compared to 15, however this does
not appear to account for the sometimes dramatic differences
in activity observed for the supported analogues (see the
Supporting Information). The difference then is most likely
a function of the silica support.
that the catalyst was effectively recycled multiple times with
an eventual gradual decrease in activity.
In conclusion, we have successfully synthesized two
triethoxysilyl-functionalized NHC ligands and the corre-
sponding second-generation olefin metathesis catalysts which
were anchored onto silica to furnish silica-supported catalysts
15-SiO2 and 16-SiO2. These species were shown to be
competent catalysts for a variety of olefin metathesis reac-
tions, mimicking their homogeneous counterparts. Likewise,
the activity of the supported catalysts is truly heterogeneous
in nature as revealed by split tests and they can be recycled
multiple times. Most importantly, the catalysts do not leach
ruthenium under the standard reaction conditions as revealed
by ICP-MS analysis of filtered reaction solutions (ruthenium
concentration of filtrate <5 ppb in all cases).
We were next interested in gaining some information into
the recyclability of the supported catalysts. Due to the
increased reactivity of 15-SiO2, it was utilized for a recycling
experiment involving the RCM of diethylallylmethyallyl
malonate (20). The results are depicted in Figure 5 and show
Acknowledgment. We gratefully acknowledge financial
support from DOE Grant No. DE-FG02-08ER15933 to
R.H.G. and to NSERC of Canada for a postdoctoral
fellowship to D.P.A.
(14) A direct comparsion between the better heterogeneous catalyst 15-
SiO2 and the corresponding homogeneous catalyst 3 was not performed,
but it is estimated that 3 is approximately 2-3 times more active in terms
of reaction rate.
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds and
all procedures for catalytic studies. This material is available
free of charge via the Internet at http://pubs.acs.org.
(15) Ritter, T.; Hejl, A.; Wenzel, A. G.; Funk, T. W.; Grubbs, R. H.
Organometallics 2006, 25, 5740–5745.
(16) It was hoped that the bulky steric nature of the silica support may
influence the E/Z selectivity of 23; however, a plot of the E/Z ratio vs percent
conversion of 23 employing 15-SiO2 and 16-SiO2 reveals that the supported
catalysts behave similarly to homogeneous catalysts 1-3 (see the Supporting
Information).
OL9000153
1264
Org. Lett., Vol. 11, No. 6, 2009