Regarding the mechanism of olefin metathesis with sol-gel-supported Ru-based complexes bearing a bidentate carbene ligand. Spectroscopic evidence for return of the propagating Ru carbene

Article abstract of DOI:10.1021/ja042668+

Two isotopically and structurally labeled Ru-based carbenes (2-d ₄ and 13) have been prepared and attached to the surface of monolithic sol-gel glass. The resulting glass-supported complexes (18-d _n and 19) exhibit significant catalytic activity in promoting olefin metathesis reactions and provide products of high purity. Through analysis of the derivatized glass pellets used in a sequence of catalytic ring-closing metathesis reactions mediated by various supported Ru carbenes, it is demonstrated that free Ru carbene intermediates in solution can be scavenged by support-bound styrene ether ligands prior to the onset of competing transition metal decomposition. The observations detailed herein provide rigorous evidence that the initially proposed release/return mechanism is, at least partially, operative. The present investigations shed light on a critical aspect of the mechanism of an important class of Ru-based metathesis complexes (those bearing a bidentate styrene ether ligand).

Full text of DOI:10.1021/ja042668+

Published on Web 03/08/2005
Regarding the Mechanism of Olefin Metathesis with
Sol-Gel-Supported Ru-Based Complexes Bearing a Bidentate
Carbene Ligand. Spectroscopic Evidence for Return of the
Propagating Ru Carbene
Jason S. Kingsbury and Amir H. Hoveyda*
Contribution from the Department of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02467
Received December 6, 2004; E-mail: amir.hoveyda@bc.edu
Abstract: Two isotopically and structurally labeled Ru-based carbenes (2-d4 and 13) have been prepared
and attached to the surface of monolithic sol-gel glass. The resulting glass-supported complexes (18-dn
and 19) exhibit significant catalytic activity in promoting olefin metathesis reactions and provide products
of high purity. Through analysis of the derivatized glass pellets used in a sequence of catalytic ring-closing
metathesis reactions mediated by various supported Ru carbenes, it is demonstrated that free Ru carbene
intermediates in solution can be scavenged by support-bound styrene ether ligands prior to the onset of
competing transition metal decomposition. The observations detailed herein provide rigorous evidence that
the initially proposed release/return mechanism is, at least partially, operative. The present investigations
shed light on a critical aspect of the mechanism of an important class of Ru-based metathesis complexes
(those bearing a bidentate styrene ether ligand).
Introduction
offer unique reactivity and selectivity levels that are at times
not available with other catalysts.2 Complexes 1-5, shown in
Research in these laboratories during the past several years
has involved the synthesis and development of a variety of Ru-
based catalysts (Chart 1) that promote various olefin metathesis
reactions1 efficiently and selectively.2 Since the preparation of
the first member of this family of complexes in 1996, various
achiral3 and chiral4 Ru carbenes have been designed and
developed that promote highly stereo- and enantioselective C-C
bond forming reactions. The Ru complexes depicted in Chart 1
Chart 1, are air-stable and can be readily purified by silica gel
chromatography; the majority of reactions promoted in the
presence of Ru catalysts 1-6 can be effected in air and with
undistilled commercial solvents.
The special attributes of the Ru-based complexes illustrated
in Chart 1 are largely due to the presence of a bidentate
carbene.2b As illustrated in Scheme 1, in contrast to precatalysts
represented by 7 5 and 8,6 which are likely activated by the loss
of PCy3 (fc),7 bidentate carbenes such as 1 and 2 are converted
to the catalytically active 14-electron Ru complex (b in Scheme
1) through dissociation of the Ru-O chelation followed by
olefin metathesis involving a substrate molecule (via a), leading
to the formation of isopropoxystyrene 9 (or a related derivative).
Recent studies8 indicate that the absence of released phosphine,
which can intercept and deactivate certain Ru carbenes (e.g., b
(1) For reviews on catalytic olefin metathesis, see: (a) Grubbs, R. H.; Miller,
S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446-452. (b) Schmalz, H.-G.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1833-1836. (c) Schuster, M.;
Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 2036-2056. (d) Ivin,
K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization;
Academic Press: San Diego, CA, 1997. (e) Furstner, A. Top. Catal. 1997,
4, 285-299. (f) Alkene Metathesis in Organic Synthesis; Furstner, A. Ed.;
Springer: Berlin, 1998. (g) Armstrong, S. K. J. Chem. Soc., Perkin Trans.
1 1998, 371-388. (h) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413-4450. (i) Randall, M. L.; Snapper, M. L. Strem Chem. 1998, 17,
1-9. (j) Phillips, A. J.; Abell, A. D. Aldrichimica Acta 1999, 32, 75-89.
(k) Wright, D. L. Curr. Org. Chem. 1999, 3, 211-240. (l) Furstner, A.
Angew. Chem., Int. Ed. 2000, 39, 3012-3043. (m) Trnka, T. M.; Grubbs,
R. H. Acc. Chem. Res. 2001, 34, 18-29. (n) Handbook of Olefin Metathesis;
Grubbs, R. H., Ed.; VCH-Wiley: Wienheim, Germany, 2003. (o) Schrock,
R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592-4633.
(2) For brief overviews regarding supported olefin metathesis catalysts, see:
(a) Kingsbury, J. S.; Hoveyda, A. H. In Polymeric Materials in Organic
Synthesis and Catalysis; Buchmeiser, M. R., Ed.; Wiley-VCH: Weinheim,
Germany, 2003; pp 467-502. (b) Hoveyda, A. H.; Gillingham, D. G.; Van
Veldhuizen, J. J.; Kataoka, O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J.
P. A. Org. Biol. Chem. 2004, 2, 8-23.
(4) (a) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A. H.
J. Am. Chem. Soc. 2002, 124, 4954-4955. (b) Van Veldhuizen, J. J.;
Gillingham, D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J. Am.
Chem. Soc. 2003, 125, 12502-12508. (c) Gillingham, D. G.; Kataoka, O.;
Garber, S. B.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 12288-12290.
See also: (d) Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, in press. (e) Seiders, T. J.;
Ward, D. W.; Grubbs, R. H. Org. Lett. 2001, 3, 3225-3228.
(5) (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2039-2041. (b) Schwab, P.; Grubbs, R. H.; Ziller,
J. W. J. Am. Chem. Soc. 1996, 118, 100-110.
(3) (a) Harrity, J. P. A.; Visser, M. S.; Gleason, J. D.; Hoveyda, A. H. J. Am.
Chem. Soc. 1997, 119, 1488-1489. (b) Harrity, J. P. A.; La, D. S.; Cefalo,
D. R.; Visser, M. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 2343-
2351. (c) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda,
A. H. J. Am. Chem. Soc. 1999, 121, 791-799. (d) Garber, S. B.; Kingsbury,
J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168-
8179. For a most recent supported variant of 2, see: (e) Clavier, H.; Audic,
N.; Mauduit, M.; Guillemin, J.-C. Chem. Commun. 2004, 2282-2283.
(6) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953-
956.
(7) Sanford, M. S.; Love, J. A. In Handbook of Olefin Metathesis; Grubbs, R.
H., Ed.; VCH-Wiley: Weinheim, Germany, 2003; Vol. 1, pp 112-131,
and references therein.
(8) (a) Love, J. A.; Morgan, J. P.; Trnka, T. M.; Grubbs, R. H. Angew. Chem.,
Int. Ed. 2002, 21, 4035-4037. (b) Love, J. A.; Sanford, M. S.; Day, M.
W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 10103-10109.
9
4510
J. AM. CHEM. SOC. 2005, 127, 4510-4517
10.1021/ja042668+ CCC: $30.25 © 2005 American Chemical Society

Sol−Gel-Supported Ru Carbenes in Olefin Metathesis
A R T I C L E S
Chart 1
Scheme 1. Mechanisms of Formation of a Metathesis-Active Ru-Based Complex
in Scheme 1), is one of the key reasons for the unique reactivity
profiles observed for complexes represented by 1 and 2.
Another noteworthy feature that originates from the bidentate
nature of the carbene ligands in 1-6 relates to the possibility
that the achiral Ru complexes in Chart 1 operate by a release/
return mechanism.3c,d As shown in Scheme 2, it is plausible
that the initial Ru complex (e.g., 1 or 2) can exist in equilibrium
with a metal carbene (release) such as e (to form 9). The original
metal complex, after initiating several catalytic olefin metathesis
cycles, may be regenerated through reaction of e with 9 (return).9
The release/return mechanism points to the possibility of
efficient homogeneous catalysis (released carbene) through the
use and recovery of a supported catalyst. Such considerations,
together with the unique reactivity of 1 and 2, have led to the
development of a number of related supported variants.2 One
example is the sol-gel complex 6,10 illustrated in Chart 1,
synthesized and examined in these laboratories. This supported
catalyst, which can be recycled up to 20 times,2b benefits from
at least one advantage that is imparted by the bidentate styrene
ligand: because Ru carbene release from the support backbone
into solution requires an initial metathesis reaction with a
substrate molecule, the amount of active catalyst released is
dependent on substrate concentration. The need for weighing
of each catalyst sample is therefore unnecessary, an attribute
that is noteworthy when the sol-gel-supported catalyst is
utilized in library synthesis.
A critical question regarding the catalytic activity of Ru-based
catalysts bearing bidentate styrene ligands is whether the release/
return mechanism is truly operative. One plausible alternative
(9) For related reports on supported Ru-based complexes bearing monodentate
carbenes used for olefin metathesis, where a similar release/return scenario
is suggested, see: (a) Barrett, A. G. M.; Cramp, S. M.; Roberts, R. S. Org.
Lett. 1999, 1, 1083-1086. (b) Ahmed, M.; Barrett, A. G. M.; Braddock,
D. C.; Cramp, S. M.; Procopiou, P. A. Tetrahedron Lett. 1999, 40, 8657-
8662. (c) Ahmed, M.; Arnauld, T.; Barrett, A. G. M.; Braddock, D. C.;
Procopiou, P. A. Synlett 2000, 1007-1009.
(10) 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, 4251-4256.
9
J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005 4511

A R T I C L E S
Kingsbury and Hoveyda
Scheme 2. Proposed Route for the Release, Catalytic Activity, and Return of Ru Complexes 1 and 2
Scheme 3
scenario is that Ru complexes such as 1 and 2, or the supported
complex 6, serve solely as sources of highly active Ru carbenes,
which, once released into solution in relatively small amounts,
promote reaction at a high rate before undergoing decomposition
(no return).11 That is, the recovered catalyst sample might
correspond to the portion of the initial catalyst loading that has
not been liberated from the styrene ligand. Regarding the latter
hypothesis, we recently illustrated that, with the more sterically
hindered chiral Ru complexes 3 and 4 (cf. Chart 1), it is indeed
likely that a return mechanism is not operative.4b
Herein, we detail the results of studies that unambiguously
illustrate that measurable amounts of achiral Ru carbene released
by a sol-gel-supported complex can return to the styrene ether
attached to the support surface. These studies provide clear
illustration of the validity of the release/return mechanism for
Ru-based complexes such as 1, 2, and 6. Mechanistic principles
implied by the studies described below are relevant to the mode
dendritic complex 5b, one that bears an N-heterocyclic carbene
(NHC). As depicted in Scheme 3, initial control experiments
indicated that, under identical conditions as mentioned above
(CH2Cl2, 40 °C, 3 h), a 1:4 mixture of the more reactive
dendrimer 5b (vs 5a) and 9 leads to a rapid distribution of the
Ru metal (52:48 ratio of dendritic:monomeric carbene proton
signals).
2. Initial Considerations Regarding Study of the Ru
Release/Return Mechanism. The complications regarding the
facile transfer of transition metal between styrene ether 9 and
dendrimer 5b caution that a similar strategy should not be used
for assessment of Ru return in the case of sol-gel-supported
complexes. Any metathesis reaction performed in the presence
of a homogeneous styrene, such as 9 or unmetalated 5b, cannot
confirm restoration of the precatalyst resting state, since 2 or
5b can be generated through cross-metathesis (CM) events on
the sol-gel surface. Nonetheless, we realized that we could
utilize advantageously the abovementioned CM reactions and
design experiments that allow us to investigate rigorously the
possibility of Ru-carbene return to sol-gel.
of action of Ru carbene derivatives prepared in other labora-
tories,12 based on complexes 1 and 2.
Results and Discussion
1. Preliminary Studies To Probe the Release/Return
Mechanism. The first opportunity to test the possibility of
release/return mechanism presented itself during our studies
regarding the catalytic activity of 5a, a dendritic structure based
on monophosphine complex 1. As summarized in Scheme 3,
the release/return hypothesis received support since we detected
efficient metal carbene transfer from dendritic to monomeric
styrene ether sites within minutes in the presence of an olefin
metathesis substrate.3d As depicted in Scheme 3, heating of a
homogeneous solution of 5a and 9 (1:4) in the absence of diene
substrate at 40 °C (3 h, CH2Cl2) does not give rise to Ru
1
crossover (1 is not detected by 400 MHz H NMR analysis).
This is in stark contrast to the related experiment involving
(11) Nguyen, S. T.; Trnka, T. M. In Handbook of Olefin Metathesis; Grubbs,
R. H., Ed.; VCH-Wiley: Wienheim, Germany, 2003; Vol. 1, p 77.
(12) For example, see: (a) Grela, K.; Harutyunyan, S.; Michrowska, A. Angew.
Chem., Int. Ed. 2002, 41, 4038-4040. (b) Grela, K.; Kim, M. Eur. J. Org.
Chem. 2003, 963-966. (c) Bujok, R.; Bleniek, M.; Masnyk, M.; Michrows-
ka, A.; Sarosiek, A.; Stepowska, H.; Arlt, D.; Grela, K. J. Org. Chem.
2004, 69, 6894-6896. (d) Michrowska, A.; Bujok, R.; Harutyunyan, S.;
Sashuk, V.; Dolgonos, G.; Grela, K. J. Am. Chem. Soc. 2004, 126, 9318-
9325. (e) Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41,
2403-2405. (f) Zaja, M.; Connon, S. J.; Dunne, A. M.; Rivard, M.;
Buschmann, N.; Jiricek, J.; Blechert, S. Tetrahedron 2003, 59, 6545-6558.
(g) Krause, J. O.; Zarka, M. T.; Anders, U.; Weberskirch, R.; Nuyken, O.;
Buchmeiser, M. R. Angew. Chem., Int. Ed. 2003, 42, 5965-5969. (h)
Krause, J. O.; Nuyken, O.; Wurst, K.; Buchmeiser, M. R. Chem. Eur. J.
2004, 10, 777-784.
Such studies would commence with the synthesis of isoto-
pically or structurally labeled versions of glass-supported Ru
carbene 6 (Chart 1). Subsequently, a representative olefin
metathesis reaction would be allowed to proceed in the same
reaction Vessel in the presence of glass samples that contain
Ru complexes bearing a labeled NHC ligand as well as samples
that contain unlabeled metal carbenes. After tracking of the
identity of individual glass pellets, labeled and unlabeled
9
4512 J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005

Sol−Gel-Supported Ru Carbenes in Olefin Metathesis
A R T I C L E S
Scheme 4. Synthesis of Ru-Carbene Complex 13
Scheme 5. Synthesis of Deuterated Ru Complexes 8-d4 and 2-d4
samples would be segregated. Facile exchange between styrene
ether 9 and NHC-based Ru carbenes would allow us to strip
the glass samples of their Ru content by treatment of the
recovered sol-gel pellets with solutions of isopropoxystyrene.
After recovery and chromatographic purification of the mono-
meric complex (2) we would be able to establish rigorously its
1
isotopic purity (by H NMR spectroscopy and/or mass spec-
trometry) and determine whether any crossover had occurred.
3. Synthesis of Labeled Ru Complexes. The first modified
Ru complex targeted for synthesis was Ru carbene 13 (Scheme
4), a structurally altered form of 2 (a complex lacking para
substitution at the two aryl groups on nitrogens). With estab-
lished procedures3d,6 in place for the synthesis of dihydroimi-
dazolylidene ligands, we judged that it would be most efficient
to use commercially available 2,6-dimethylaniline. We expected
the highly deshielded carbene proton of 13 to exhibit a unique
two-step, one-pot process (Scheme 4).14 However, the pro-
nounced and unpredictable instability of 12 led us to consider
using another labeled variant of Ru complex 2. Toward this
end, we judged that the diamine backbone would be the most
suitable site for incorporation of isotope labels, since the
imidazolinium ligand remains attached to the Ru complex3c,d,7
(vs the isopropoxystyrene ligand, which dissociates from the
metal and remains on the glass support during catalysis).
In designing an efficient synthesis of the isotopically labeled
heterocyclic ligand, we took note of a scalable synthesis of
glyoxal-d2-bis(sodium bisulfite)-O-d2 reported by Bertz.15 Thus,
with NaCNBD3 serving as an additional source of deuterium,
syntheses of Ru complexes 8-d4 and 2-d4 were achieved in the
manner illustrated in Scheme 5. Despite the initial low-yielding
step (11%), the sequence is straightforward and allows facile
access to gram quantities of labeled Ru complexes with >99
at. % D incorporation (400 MHz 1H NMR analysis). Each metal
carbene was easily purified by chromatography and fully
characterized.
As disclosed previously,10 we utilize ring-opening metathesis/
cross-metathesis (ROM/CM) as the means for preparing, in a
single operation, the tether that connects the metal complex to
the glass surface in addition to the catalytically active Ru carbene
bearing a bidentate styrene ether ligand (Scheme 6). This
approach avoids stepwise introduction of the linker, the bidentate
styrene ether, and the metal carbene. As shown in Scheme 6,
ROM/CM of triene 1616 with Grubbs’ Ru complex 8-d4 and
allylchlorodimethylsilane leads to the installment of an elec-
trophilic silyl chloride to be used later for attachment to sol-
gel glass, followed by metalation of the styrene ether moieties
(f17). Subsequent reaction of the silyl chloride with a free
1
chemical shift in its H NMR spectrum (vs complex 2). Thus,
Ru crossover from the sol-gel support to another glass support
and then to 9, based on the strategy described above, could be
recognized (and quantified) through the presence of two
downfield 1H NMR signals (RudCH) in a region of the
spectrum where trace impurities do not typically hinder analysis.
Ru complex 13 was synthesized in the manner illustrated in
Scheme 4. Diamine 10 was accessed by reductive amination of
the crystalline bis(imine) in the presence of NaCNBH3 (55%
overall yield after chromatography). Conversion to heterocycle
11 was effected upon exposure of 10 to triethyl orthoformate
and ammonium tetrafluoroborate at 120 °C. Although, on the
basis of previous reports, successive treatment of 11 with
potassium tert-butoxide and (PCy3)2Cl2RudCHPh (7) led to
efficient ligand exchange, the surprising instability of 12
rendered isolation difficult. Dark red-colored bands of 12 would
often elute cleanly from a silica gel column, only to decompose
in solution upon standing and/or during solvent removal.13 The
solution-phase degradation can be detected visually as it is
accompanied by a color change from red to dark purple.
Nevertheless, when carbene 12 was isolated in pure form despite
the above complications, it proved to be indefinitely stable when
stored as a crystalline solid under N2.
We could access sufficiently pure (>90%) samples of 12 to
be used for sol-gel functionalization (see below), and the
corresponding isopropoxy ether complex 13 was prepared as a
(13) Another (not necessarily mechanistically related) observation indicating that
alteration of the aryl substituents of an NHC ligand can have unexpected
effects on the stability and reactivity of the derived Ru carbenes can be
found in
a
recent synthesis of
a
related Ru carbene bearing 2,6-
(14) See the Supporting Information for details.
diisopropylphenyl substituents on the saturated NHC; a Ru hydride was
isolated as a major byproduct. See: Furstner, A.; Ackermann, L.; Gabor,
B.; Goddard, R.; Lehmann, C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R.
Chem. Eur. J. 2001, 7, 3236-3253.
(15) Bertz, S. H. J. Org. Chem. 1981, 46, 4088-4090.
(16) This compound is easily formed by ring-opening of commercially available
cis-5-norbornene-endo-2,3-dicarboxylic anhydride with 2 equiv of the
functionalized benzylic alcohol; for details, see ref 10.
9
J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005 4513

A R T I C L E S
Kingsbury and Hoveyda
Scheme 6. Immobilization of Isotopically Labeled Ru Complexes
Table 1. Preliminary Examination of Catalytic Activity of
Glass-Supported Ru Complexes
hydroxyl group on the glass surface anchors the catalyst to the
support. Ru complex 18-dn was thus prepared as dark green
glass pellets after washing with CH2Cl2 and drying under
vacuum (Ru loading ) 0.130 mmol/gram).17
Notwithstanding our concern regarding the stability and
activity of the unimolecular bis(desmethyl) complex 13 (cf.
Scheme 4), we prepared the derived polymeric variant (19) from
a sufficiently pure (>90%) sample of carbene 12. Supported
Ru complex 19 was recovered from the procedure shown in
Scheme 6 with a loading of 0.138 mmol/gram.
entry
catalyst
Ru loadinga (mmol/g)
convb (%)
1
2
3
6
0.122
0.130
0.138
83
92
63
18-dn
19
a Based on mass increase upon installation of Ru carbenes. b Determined
1
by 400 MHz H NMR analysis of the unpurified reaction mixture.
compared to that of the original glass-supported system 6. As
the data in entries 1 and 2 of Table 1 indicate, under identical
conditions (10 mol % Ru loading, 0.1 M CH2Cl2), complexes
6 and 18-dn delivered 83 and 92% conversion, respectively,
within 1 h at 22 °C.18 The difference in activity is minor;
moreover, the initial metal loading (millimoles per gram of
glass), which is likely unique for a given batch of catalyst, might
account for the small variation. Though measurably less
efficient, samples of supported complex 19 exhibited significant
olefin metathesis activity (63% conversion to 21 in 1 h; entry
3, Table 1). This finding proved critical as it allowed us to
incorporate 19 in the crossover experiments (together with 6
and 18-dn) as a second set of supporting data. We sought to
obtain additional findings due to the possibility that a minor
4. Initial Examination of Catalytic Activity of Glass-
Supported Ru Complexes. The catalytic activity of Ru-loaded
glass samples 18-dn and 19 was examined through a study where
RCM of tosyl acrylamide 20 served as the representative
transformation and the activity levels of the new complexes were
(17) The value was calculated from the mass increase following functionalization
of the glass surface.
(18) If stirring is allowed to proceed for a longer period, RCM proceeds to
>99% conversion for each catalyst. Reactions in Table 1 were stopped
abruptly at 1 h simply by drawing the reaction mixture away from the
catalyst pellet with a Pasteur pipet.
9
4514 J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005

Sol−Gel-Supported Ru Carbenes in Olefin Metathesis
A R T I C L E S
Scheme 7. Crossover Experiment with Labeled Glass-Supported Ru Complexes
impurity might give a false positive. Since we suspected that
only small amounts of Ru carbene released from the glass
support are likely sufficient to promote efficient conversion of
20 to 21 (see below for further discussion), we were concerned
that small impurities could lead to the appearance of signals in
1H NMR spectra (at ∼4.18 ppm, which corresponds to the
chemical shift of protons of the diamine backbone), leading to
the false conclusion that there is effective crossover (see below
for more detail). Inclusion of supported complex 19 would serve
as an internal check by providing a second means of measuring
Ru carbene transfer between different glass samples (appearance
of a new carbene proton signal at 16.45 ppm corresponding to
recovered 13).
5. Crossover Experiments with Labeled Glass-Supported
Ru Complexes. The key crossover experiments involving
various labeled glass-supported Ru-based complexes were
carried out as detailed below (Scheme 7). A total of four Ru-
containing sol-gels (two pellets, 0.0149 mmol of 18-dn; one
pellet, 0.0079 mmol of 19; one pellet, 0.0069 mmol of 6; 10
mol % Ru total) were used (in the same vessel), as illustrated
in Scheme 7, to catalyze five consecutive rounds of RCM on a
0.3 mmol scale (∼84 mg of 20). In each case, the reaction
proceeded to >99% conversion in 2 h (0.2 M CH2Cl2, 22 °C),
and the desired product was isolated without purification as an
off-white crystalline solid in >99% yield. It is important to note
that, after each run, each pellet was carefully rinsed with two
portions of CH2Cl2 (2.0 mL for 15 min) to ensure that there
were no unbound Ru complexes “trapped” within the sol-gel
glass cavities.
catalysts was not expended after five rounds, the second phase
of the experiment was initiated at this point to ensure efficient
retrieval of monomeric Ru carbenes (2, 2-d4, and 13) for
spectroscopic analysis.
After five rounds of RCM with pellets 18-dn, 19, and 6, the
two pellets of 18-dn were separated from pellets 6 and 19
(Scheme 7). The two pellets of 18-dn were then placed in a vial
which was charged with 0.5 mL of a 0.1 M solution of 9 in
CH2Cl2, capped (to discourage solvent loss) and heated to 40
°C. The initially colorless solution became bright green over
several hours as CM occurred. The solution was removed with
a Pasteur pipet; a fresh solution of 9 was added, and the
procedure was repeated until green discoloration could no longer
be observed in the supernatant (total of five times). The
combined styrene ether washes were concentrated to an oily
green residue consisting primarily of unreacted 9. Purification
of the monomeric Ru complex was carried out by silica gel
chromatography (CH2Cl2).
As may be expected, the major constituent of the material
isolated was the perdeuterio monomer 2-d4. However, we
established that, as depicted in Figure 2, both Ru complex 2
Two important points about the Ru-catalyzed RCM reactions
merit mention: (1) Each catalyst pellet contains a fingerprint
of markings in the form of small chips and scratches; as is
clearly shown in Figure 1, no two pellets are identical. As the
first RCM reaction was set up, each gel was carefully weighed
and scrutinized for its pattern of surface etchings. This allowed
us to identify each individual pellet to be properly tracked
throughout the course of the experiment. (2) As discussed
previously,10 continued recycling of the glass-supported Ru
catalysts results in slow but steady depletion of active sites.
Even though the metathesis activity of the combined three
Figure 1. Dark green glass pellets of supported Ru catalyst. Though each
supported Ru catalyst is recovered as dark green glass pellets, an individual
piece can be readily identified by its characteristic number and pattern of
surface markings.
9
J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005 4515

A R T I C L E S
Kingsbury and Hoveyda
by column chromatography. Careful analysis of the resulting
samples (400 MHz 1H NMR) did not reveal any signs of pellet-
to-pellet crossover. Thus, the results disclosed herein cannot
be ascribed to any ill-defined effects such as insufficient rinsing
of catalyst samples or the leaching of active carbenes from one
gel to another; any observed crossover discussed above must
therefore involve an olefin metathesis event.
Alternatively, it may be suggested that in pellets 6, 18-dn,
and 19 crossover may occur by dissociation of the NHC ligands
instead of the styrene ether. This would be entirely inconsistent
with what has been established regarding the mechanism of
olefin metathesis catalyzed by Ru-based complexes that bear
an NHC ligand.7,19
Conclusions
We have prepared two isotopically and structurally labeled
Ru-based carbenes (2-d4 and 13), which have been used to
derivatize the surface of monolithic samples of sol-gel glass.
Similar to previously reported 6, the resulting glass-supported
catalysts 18-dn and 19 exhibit significant catalytic activity in
promoting olefin metathesis reactions and provide products of
high purity without workup or purification. Analysis of glass
pellets used in a sequence of RCM reactions mediated by the
three supported Ru carbenes (effected in the same reaction
vessel) has allowed us to establish that free Ru-carbene
intermediates in solution can be scavenged by support-bound
styrene ether ligands prior to the onset of competing Ru
decomposition.
We must emphasize that the claim is not being made that
the class of achiral Ru carbenes in Chart 1 operate exclusively
by the release/return mechanism; we show here only that such
a scenario is feasible. The observed crossover is small (2%);
nonetheless, as suggested by previous observations,20 it is
possible that small amounts of released Ru carbene may be
responsible for olefin metathesis activity. The above studies shed
light on a critical aspect of the mechanism of achiral Ru-based
complexes bearing a bidentate styrene ether ligand (e.g., 1 and
2 in Chart 1), a class of robust and air-stable carbenes that are
becoming increasingly popular olefin metathesis catalysts.
Figure 2. 1H NMR (400 MHz) spectra for an authentic 2:3 mixture of 2
and 13 (top) and the monomeric Ru carbene recovered from complex 18-
dn (bottom).
(crossoVer from 6) and 13 (crossoVer from 19) could be cleanly
detected as components of the mixture. Also illustrated in Figure
2 (top) for comparison are the analogous regions taken from an
authentic spectrum of a 2:3 mixture of 2 and 13. The integral
values provided in Figure 2 allow us to quantify the amount of
Ru carbene that has been transferred from one pellet to another.
Recovered Ru complex 13 thus represents 1% of the mixture,
according to relative integration of the major carbene proton
signal at 16.56 ppm (2 and 2-d4) and the minor signal at 16.45
ppm (13). Moreover, an equal amount of 2 is present on the
basis of the fact that the 4H singlets at 4.18 (2) and 4.21 ppm
(13) are of equal intensity. These data confirm that a measurable
(2% total) amount of termination (return) occurs with glass-
supported Ru catalysts.
The findings outlined herein imply a number of intriguing
possibilities in designing catalytic olefin metathesis reactions
on support.21 One possibility would involve reaction of a
polymer-bound substrate catalyzed by a glass-supported Ru
carbene. In this scenario, a sterically unhindered (and preferably
volatile) alkene could be used as “chaperone” to shuttle the
active metal carbene through solution to the surface of the
(19) (a) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997,
119, 3887-3897. (b) Sanford, M. S.; Ulman, M.; Grubbs, R. H. J. Am.
Chem. Soc. 2001, 123, 749-750. (c) Sanford, M. S.; Love, J. A.; Grubbs,
R. H. J. Am. Chem. Soc. 2001, 123, 6543-6554. (d) Reference 8.
(20) Mechanistic studies involving chiral Ru complex 3 (Chart 1) and its
deuterated derivatives indicate that catalyst recovered in high yield (90%)
after olefin metathesis represents unreleased Ru carbene. Thus, even with
the less active chiral complex, bearing a bidentate and sterically bulky
ligand, high activity can be achieved with e10% released carbene. See ref
4b.
(21) For early examples of RCM with solid-supported substrates, see: (a) Miller,
S. J.; Blackwell, H. E.; Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 9606-
9614. (b) Schuster, M.; Pernerstorfer, J.; Blechert, S. Angew. Chem., Int.
Ed. Engl. 1996, 35, 1979-1980. (c) van Maarsveen, J. H.; den Hartog, J.
A. J.; Engelen, V.; Finner, E.; Visser, G.; Kruse, C. G. Tetrahedron Lett.
1996, 37, 8249-8252. (d) Peters, J.-U.; Blechert, S. Synlett 1997, 348-
350. (e) Nicolaou, K. C.; Winssinger, N.; Pastor, J.; Ninkovic, S.; Sarabia,
F.; He, Y.; Vourlomis, D.; Yang, Z.; Li, T.; Giannakakou, P.; Hamel, E.
Nature 1997, 387, 268-272.
6. Control Experiments and Alternative Scenario. The
appropriate control experiments have been carried out to validate
further the conclusions mentioned above. Experiments outlined
in Scheme 7 were repeated with fresh samples of catalyst in
the absence of the metathesis substrate. The four glass samples
were allowed to stir in CH2Cl2, and the solvent was routinely
replenished in precisely the same manner as the iterative
sequence of five metathesis reactions (above). The two labeled
sol-gel pellets 18-dn were “stripped” of Ru through subjection
with 9, and the resulting monomer 2-d4 was rigorously purified
9
4516 J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005

Sol−Gel-Supported Ru Carbenes in Olefin Metathesis
A R T I C L E S
polymer carrying the substrate. Such a process could be useful
as a ring closure/cleavage strategy, allowing the recovery of a
collection of small molecules from a solid support in parallel
without purification.
and a predoctoral fellowship to J.S.K.). We are grateful to
Professor Scott J. Miller for helpful discussions.
Supporting Information Available: Experimental procedures
and spectral data for catalysts and products (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. Financial support was provided by the
National Science Foundation (Grant CHE-0213009 to A.H.H.
JA042668+
9
J. AM. CHEM. SOC. VOL. 127, NO. 12, 2005 4517