Olefin metathesis catalysts bearing a pH-responsive NHC ligand: A feasible approach to catalyst separation from RCM products

Article abstract of DOI:10.1039/b809793c

Two novel ruthenium-based olefin metathesis catalysts, H ₂ITap(PCy₃)Cl₂Ru=CH-Ph 12 and H ₂ITapCl₂Ru=CH-(C₆H₄-O-iPr) 13 (H₂ITap = 1,3-bis(2′,6′-dimethyl-4′- dimethylami

Full text of DOI:10.1039/b809793c

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Olefin metathesis catalysts bearing a pH-responsive NHC ligand: a feasible
approach to catalyst separation from RCM products†
Shawna L. Balof,a Steven J. P’Pool,a Nancy J. Berger,a Edward J. Valente,b Alan M. Shillerc and
Hans-Jo¨rg Schanz*a
Received 11th June 2008, Accepted 17th July 2008
First published as an Advance Article on the web 12th September 2008
DOI: 10.1039/b809793c
=
Two novel ruthenium-based olefin metathesis catalysts, H2ITap(PCy3)Cl2Ru CH–Ph 12 and
=
H2ITapCl2Ru CH–(C6H4–O–iPr) 13 (H2ITap = 1,3-bis(2¢,6¢-dimethyl-4¢-dimethylaminophenyl)-4,5-
dihydroimidazol-2-ylidene), were synthesized bearing a pH-responsive NHC ligand with two aromatic
NMe2 groups. The crystal structures of complexes 12 and 13 were determined via X-ray crystallography.
Both catalysts perform ring opening metathesis polymerization (ROMP) of cyclooctene (COE) at faster
=
rates than their commercially available counterparts H2IMes(PCy3)Cl2Ru CH–Ph 2 and
=
H2IMesCl2Ru CH–(C6H4–O–iPr) 3 (H2IMes = 1,3-bis(2¢,4¢,6¢-trimethylphenyl)-4,5-dihydroimidazol-
2-ylidene) and perform at similar rates during ring closing metathesis (RCM) of diethyldiallylmalonate
(DEDAM). Upon addition of 2 equiv. of HCl, catalyst 12 is converted into a mixture of several mono
and diprotonated Ru-carbene species 12¢ which are soluble in methanol but degrade within a few hours
at room temperature. Catalyst 13 can be protonated with 2 equiv. of HCl and the resulting complex 13¢
is moderately water-soluble. The complex is stable in aqueous solution in air for >4 h, but over
prolonged periods of time shows degradation in acidic media due to hydrolysis of the NHC–Ru bond.
Catalysts 12 and 13 perform RCM of diallylmalonic acid in acidic protic media with only moderate
activity at 50 ◦C and do not produce polymer in the ROMP of cationic 7-oxanorbornene derivative 14
under the same conditions. Catalyst 13 was used for Ru-seperation studies when RCM of DEDAM or
3,3-diallypentadione (DAP) was conducted in low-polar organic solution and the Ru-species was
subsequently precipitated by addition of strong acid. The Ru-species were removed by (1) filtration and
(2) filtration and subsequent extraction with water. The residual Ru-levels could be reduced to as far as
11 ppm (method 2) and 24 ppm (method 1) without the use of chromatography or other scavenging
methods.
after reaction is a major issue associated with homogeneous
Introduction
systems. Most commonly, column chromatography over silica
gel is employed. However on a large scale, this method is not
economically feasible and, additionally, often does not reduce
the ruthenium content in the product sufficiently below 10 ppm
Ru, the upper limit for pharmaceutical products.6,7 Ruthenium
scavenging based on chemical reagents8 and physical adsorption9
have been reported but often their utility is limited due to
economic reasons, high toxicity and/or long processing times.
More recent approaches have been based on using catalysts
with a modified solubility profile such as catalysts 410a and 5
Over the last decade, olefin metathesis has emerged as a powerful
technique in organic1 and polymer synthesis.2 Ru-based, single-
site catalysts such as Grubbs’ first and second generation catalysts
1 and 2, and Hoveyda–Grubbs’ catalyst 3 have become the center
of attention for many scientists due to their high tolerance towards
moisture and functional groups,3 and thus have significantly
expanded the scope of metathesis substrates. Furthermore, due
to their elevated inertness towards molecular oxygen in solution,
as particularly demonstrated for catalyst 3,4b several derivatives
have been successfully recycled and reused.4,5 Catalyst removal
aDepartment of Chemistry & Biochemistry, The University of Southern
Mississippi, 118 College Drive, Hattiesburg, MS 39406-5043, United States
of America. E-mail: hans.schanz@usm.edu
bDepartment of Chemistry & Biochemistry, Mississippi College, Clinton,
MS 39058, United States of America
cDepartment of Marine Science, The University of Southern Mississippi,
1020 Balch Blvd., Stennis Space Center, MS 39529, United States of
America
† Electronic supplementary information (ESI) available: 1H, 13C and
31P NMR spectra of the synthesized ligand precursor and its synthetic
intermediates 8–11, and Ru-complexes 12 and 13, as well as detailed kinetic
experimental data. CCDC reference numbers 690483 (for 12) and 690484
(for 13). For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b809793c
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which can be efficiently removed after reaction by flash column
chromatography or via extraction with water.10b,11 The application
of these separation methods dramatically reduced the amount
of ruthenium in the final product but did not accomplish the
reduction of the ruthenium contamination within the limits of the
pharmaceutical standard without additional purification.
Olefin metathesis in aqueous media was successfully carried out
with hydrophobic catalysts by sonication12 or in the presence of an
organic co-solvent13 or surfactant.14 Modifications of phosphine15
or pyridine ligands,16 reactive carbene moieties,17,18 and partic-
ularly N-heterocyclic carbene (NHC) ligands,10a,19,20 or combina-
tions thereof20 have furnished Ru-based catalysts with solubility in
protic and aqueous media. Neutrally-charged derivatives bearing
polyethyleneglycol (PEG) substituted NHC ligands, such as
catalyst 5, have been demonstrated to perform metathesis reactions
homogeneously in aqueous as well as non-protic organic media.10
Ionic NHC ligands which produce water-soluble metal complexes
have been previously reported,21–24 however not in conjunction
with Ru-based olefin metathesis catalysts. This is mainly due to a
solubility problem. The direct NHC/phosphine ligand exchange
reaction from first generation olefin metathesis catalysts, to date
the most common approach to obtain NHC-ligated derivatives,
requires low-polar solvent conditions such as hexanes or toluene to
go to completion.25,26 Under these conditions, ionic NHC ligands
are not sufficiently soluble. Therefore, to enable successful ligand
exchange, the N-heterocyclic carbene must be neutrally charged at
this stage. Grubbs et al. have produced metathesis catalyst 6, the
only derivative bearing a charged NHC ligand. The ammonium
group was initially introduced into the complex as a Boc-protected
moiety which is hydrolyzed and simultaneously protonated after
attachment to the metal center.20 To provide sufficient solubility
in aqueous media however, an additional positive charge was
introduced via the reactive carbene moiety.
Scheme 1 Synthesis of pH-responsive catalysts 12 and 13; (i) 1/KOtBu/
heptane, 24 h, 60 ◦C (70%); (ii) 2-i-propoxystyrene/CuCl, 2 h, 35 ◦C
(70%).
oxidative stability of Hoveyda–Grubbs-type catalysts.4b,5 The
yields (70% for 12 and 70% for 13) are comparable to those for
catalysts 1 and 2.
The dimethylamino groups in the H2ITap ligand were in-
troduced by starting out from phenylenediamine derivative 8
which was synthesized from commercially available N,N-3,5-
tetramethylaniline 7 in 45% overall yield.28 Following the literature
procedure for the synthesis of Grubbs’ second generation catalyst
2 with few modifications,25 aniline derivative 8 was converted
into the respective NHC ligand precursor salt 11 in three steps
(65% overall yield) via the intermediates 9 and 10 (Scheme 2).
In this process, we have developed an improved hydrogenation
procedure for diimine 9 with NaBH4 to afford the diamine 10.
The previously described reaction conditions for the synthesis of
analogous diamines25 required a slow addition of conc. HClaq at
0 ◦C to the solution of the double-Schiff base in thf in the presence
of excess NaBH4. This procedure afforded hydrolysis side products
in the synthesis of diamine 10 and therefore reduced the yields
significantly. Furthermore, the pure diamine must be isolated as
the hydrochloride salt first which then separately is extracted
with base to afford the pure diamine. In the new procedure,
we activated the NaBH4 with anhydrous boric acid (1.33 equiv.
relative to NaBH4). As the acid exhibited low solubility in the
solvent (thf), all reagents were added at once and the reaction was
stirred at slightly elevated temperature. The end of the reaction was
We wish to report the synthesis of the first pH-responsive, highly
active olefin metathesis catalysts with variable solubility profiles.
After performing ring closing metathesis (RCM), the catalysts
can be removed from the reaction mixture in a straightforward
protocol by acid addition and subsequent filtration to give
products with residual Ru levels as low as 24 ppm after simple
filtration and 11 ppm after additional extraction with water.
Results and discussion
Catalyst syntheses
Dimethylamino groups are ideal pH-responsive groups in Ru-
based olefin metathesis catalysts as they are compatible with
Ru-based olefin metathesis catalysts.27 We synthesized ligand
precursor 11 which contains two dimethylamino groups bound
to the aromatic NHC ligand substituents. The precursor salt
was directly used in situ with base and Grubbs’ catalyst 1 to
produce the second generation Grubbs-type catalyst 12 (Scheme 1)
bearing the H2ITap ligand (H2ITap = 1,3-bis(2¢,6¢-dimethyl-4¢-
dimethylaminophenyl)-4,5-dihydroimidazol-2-ylidene). The solid
complex has a light brownish color. Catalyst 12 was then converted
into the green-colored Hoveyda–Grubbs-type catalyst 13 with 2-
i-propoxystyrene in the presence of CuCl applying the literature
procedure for catalyst 2 (Scheme 1).4a The work-up is conducted
in air which is in agreement with the previously observed superb
Scheme 2 Preparation of H2ITap·HCl 11: (i) (1) NaNO2/conc. HClaq,
60 min, -5 ◦C, (2) Sn/HCl, 70 ◦C (45%); (ii) (CHO)2/MeOH [HCl],
24 h, RT (85%); (iii) NaBH4/H3BO3/thf, 60 min, 30 ◦C (88%);
(iv) HC(OEt)3/NH4Cl, 12 h, 130 ◦C (87%).
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determined by complete discoloration of the orange-red reaction
solution (usually between 30 and 60 min). The aqueous work-up
directly afforded the pure diamine 10 in high yields and purity.
moiety is in the apex. In complex 12, all bond distances and bond
angles involving the ruthenium center are in the same range as for
=
the (PCy3)Cl2Ru CHPh complex bearing a 1,3-dimesityl-1,4,5,6-
tetrahydropyrimidin-2-ylidene ligand29 (the only other crystal
=
structure published for a (PCy3)Cl2Ru CHPh complex with ◦a
Catalyst structures
˚
non-aromatic NHC ligand) within a margin of 0.01 A and 0.6 .
The structures of catalysts 12 and 13 in solid state could be
determined via X-ray crystallography (Fig. 1 and 2). Relevant bond
distances and angles for the complexes are summarized in Table 1.
Both complexes exhibit a distorted square pyramidal ligand
environment as usual for these Ru–carbene complexes. The base is
formed by the donor ligands and the chlorides, and the benzylidene
˚
The only exception is the Ru–CNHC distance of 2.075 A which is
˚
˚
actually shorter by more than 0.03 A (2.106 A). This bond distance
is more similar to the Ru–CNHC distance of the corresponding
˚
=
IMes(PCy3)Cl2Ru CHPh complex with 2.069 A (IMes = 1,3-
bis(2¢,4¢,6¢-trimethylphenyl)imidazol-2-ylidene).30 This is not sur-
prising as the mesityl substituents are less angled towards the
metal center in complex 12 than in the tetrahydropyrimidin-2-
ylidene complex due to the shortened NHC ligand backbone. As
a result, the steric interference with the benzylidene moiety is less
pronounced.29 This is also reflected in the longer distance between
the mesityl ipso-carbon atom to the benzylidene carbon atom in
complex 12 (3.01 A vs. 2.9 A). The short distance of the aromatic
ring to the carbene moiety was speculated to be responsible for
lowered metathesis activity of the tetrahydropyrimidin-2-ylidene
complex in comparison to catalyst 2.29
˚
˚
The structure of complex 13 consists of two discrete complexes
and one molecule of CH2Cl2 in solvation. The averaged bond
distances of both complexes are similar to those of H2IMes
complex 34a (deviations <0.01 A) with one exception. The distance
˚
between the Ru center and the benzylidene carbon atom is
˚
extremely short in complex 13 (1.735 A) and significantly shorter
˚
by almost 0.1 A than in complex 3. As the only structural difference
=
Fig. 1 ORTEP diagram of H2ITap(PCy3)Cl2Ru CHPh 12.
between the two complexes is the presence of the remote p-NMe2
groups in 13 instead of the p-methyl groups in 3, it is likely that
this shortening of the metal–carbene bond is less due to steric
reasons than electronic changes. In comparison to complex 3, the
trans bond angles at the metal center and the C–Ru–C cis angle
are slightly larger in complex 13 by approx. 2–3◦. However, the
C–Ru–O cis angle in 13 (78.1◦) is smaller by 1.3◦ than in 3. This
is unexpected due to the shorter Ru–carbene bond which should
cause a widening of this angle assuming comparable bond angles
in the relatively rigid benzylidene chelate. The small C–Ru–C cis
angle also causes a large distance between the mesityl ipso-carbon
˚
atom to the benzylidene carbon atom in complex 13 (3.08 A) in
comparison to PCy3 ligated complex 12.
=
Fig. 2 ORTEP diagram of H2ITapCl2Ru CH–(2-iPrO)C6H4 13.
Catalyst reactions with HCl
◦
˚
Table 1 Selected bond distances [A] and bond angles [ ] for complexes
12 and 13
Catalysts 12 and 13 are soluble in organic media such as
toluene, benzene, CH2Cl2 and ethyl acetate. Upon addition of DCl
(2 equiv.) both complexes precipitated from organic solution. The
precipitate of complex 12 did not exhibit good water solubility. The
31P NMR spectrum of the dried residue in D2O only indicates the
presence of the DPCy3+ salt at d = 30.8 ppm (t, 1J(31P1H) = 71 Hz),
whereas in d4-methanol the spectrum also indicated the presence
12
13
=
Ru C(H)
1.826(2)
1.735(9)
1.966(7)
2.260(5)
Ru–CNHC
Ru–O
2.0746(19)
—
Ru–P
Ru–Cl
2.4419(6)
2.4080(6)
2.3809(6)
—
+
of a (PCy3)Ru species at d = 28.2 ppm (s), alongside the DPCy3
2.330(2)
2.339(2)
+
salt. Both signals for the Ru species and the DPCy3 cation are
present in approx. 1 : 2 ratio. Very likely, the second equiv. DCl did
not afford the complete second protonation of the NHC ligand
but instead affords the partial protonation of the PCy3 ligand. The
presence of two ruthenium carbene species was observed in the 1H
NMR spectrum where two signals are present at d = 19.13 ppm
and 18.99 ppm (the typical benzylidene-H region) also in approx.
=
P–Ru C(H)
O–Ru C(H)
91.45(9)
—
99.49(9)
179.41(9)
—
—
=
78.1(3)
103.2(3)
—
178.5(3)
159.69(8)
=
C(H) Ru–CNHC
P–Ru–CNHC
O–Ru–CNHC
Cl–Ru–Cl
169.64(4)
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1 : 2 ratio which correlates to the degree of the protonation of the
PCy3 ligand. Therefore, the protonation should afford a dynamic
mixture of Ru complexes 12¢ of mono or diprotonated species
coordinated by a molecule of CD3OD or PCy3 (Scheme 3).
Similar ruthenium carbene complexes coordinated by weak O-
donor ligands have been formulated as they were also obtained
via the protonation of one phosphine ligand with DCl.31,32 After
several hours, the 31P NMR signal for the Ru species and the 1H
NMR signal for the benzylidene-H atoms disappeared indicating
the decomposition of the complexes 12¢ in this time period. The
low thermal stability of phosphine deficient Ru–carbene species
has been observed previously.31 Double protonation of complex
13, in contrast, affords complex 13¢ which is water soluble and
stable in 0.1 M DCl in D2O solution in air for more than 6 h
Scheme 4 Olefin metathesis reactions with catalysts 2, 3, 12, 13 in benzene
(20 ◦C). (a) ROMP of COE ([Ru] = 0.5 mM, 0.5% loading); (b) RCM of
DEDAM ([Ru] = 1.0 mM, 1.0% loading).
1
(Scheme 3). After 30 h, the H NMR spectrum of 13¢ in D2O
exhibited a new set of signals (4% relative intensity) due to the
formation of the double protonated NHC ligand precursor 11¢ as a
result of hydrolytic decomposition of the complex. The hydrolysis
of hydrophilic NHC ligands had been observed previously for
water-soluble Hoveyda–Grubbs-type catalysts 4 and 5.10a,20 Over
the course of 7 d at room temperature, 45% of complex 13¢ was
decomposed. It should be mentioned that the same experiment
under inert gas atmosphere exhibited a similar rate of hydrolytic
degradation.
Fig. 3 ROMP of COE with catalysts 2, 3, 12, 13 ([Ru] = 0.5 mM, 0.5%
catalyst loading).
Fig. 4 RCM of DEDAM with catalysts 2, 3, 12, 13 ([Ru] = 0.5 mM, 0.5%
catalyst loading).
Scheme 3 Reaction of catalysts 12 and 13 with DCl (2 equiv.).
similar, differences in catalytic activity should be mostly due to
electronic effects. Both H2ITap catalysts 12 and 13 were very active
in olefin metathesis and performed the ROMP of COE faster than
their H2IMes ligated counterparts 2 and 3. The evaluation of the
kinetic profiles suggests particularly for catalyst 13 that this is
mainly due to a faster rate of initiation as complex 3 exhibited
a significantly longer induction period before the dramatic rate
acceleration was observed. Such long induction times are typical
for slow-initiating but fast-propagating olefin metathesis catalysts
and thus strongly affect the overall reaction rates.3f ,g The PCy3-
ligated complexes 2 and 12 initiated significantly faster under
those conditions and afforded >80% conversion in less than 7 min
ROMP and RCM activities
The metathesis activity of complexes 12 and 13 was tested in
ring opening metathesis polymerization (ROMP) reactions of
cyclooctene (COE) and ring closing metathesis (RCM) reactions
of diethyldiallylmalonate (DEDAM) in benzene solution at room
temperature (Scheme 4, Fig. 3 and 4).32,33 The conversion was
monitored via 1H NMR spectroscopy and the results were
compared to catalyst 2 and 3 under identical conditions. As the
steric demands of the H2IMes and the H2ITap ligands are very
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(12) and 11 min (2) respectively in comparison to 38 min (3) and
28 min (13).
Catalyst separation studies
We utilized the pH-dependent solubility profile to separate cat-
alyst 13 from RCM reaction mixtures. Upon protonation, the
Ru complexes are converted into the dicationic species which
should exhibit low solubility in the organic reaction medium. We
conducted studies with DEDAM and 3,3-diallyl-2,4-pentanedione
(DAP). The reactions ([Ru] = 3.3 mM, 2% catalyst loading) were
In the RCM reactions, catalysts 2 and 12 performed at near-
identical rates. Similar to the ROMP reaction, both catalysts
exhibited a faster rate of initiation as the initial conversion
rates were higher than for catalysts 3 and 13 which exhibited
an induction period of 10–15 min. However, the conversion
with Hoveyda–Grubbs-type catalysts 3 and 11 accelerated and
performed at faster propagation rates. The overall conversions
after 60 min therefore were significantly higher (3: 67%; 13: 59%;
2, 12: 45%). Interestingly, catalyst 3 marginally outperformed
catalyst 13 in the RCM reaction, which is in contrast to the
performances observed for the ROMP reaction.
◦
carried out in toluene or ethyl acetate at 50 C for 30 min, then
quenched with ethyl vinyl ether for 10 min, and finally conc.
HClaq or H2SO4 (approx. 10 equiv. with respect to catalyst) was
added via microlitre syringe. The Ru species precipitated within
seconds. The slurry was filtered through a plug of Na2SO4, and the
solvent was removed under reduced pressure. The conversion was
determined via 1H NMR spectroscopy and aliquots of 20–22 mg
were taken and digested with conc. HNO3. The residual product
was extracted as t-butyl methyl ether solution with water, dried
and aliquots of 20–22 mg again were digested with conc. HNO3.
The ruthenium content of the digested samples was determined
via ICP (inductively coupled plasma) mass spectrometry.
Generally, all reactions under the described conditions afforded
>99% conversion. With one exception, the Ru contamination
could be reduced by up to 68% (entries 9 and 10, Table 2)
for the samples washed with water in comparison to those just
obtained after filtratrion. However, the overall product yield was
also reduced significantly by washing as a result of the small
amounts of RCM product. In one case (entries 5 and 6, Table 2),
the Ru content was higher after the wash, which may be due
to an experimental error. With respect to the substrate, products
obtained with DEDAM contained significantly lower amounts
ruthenium (prewash: 24–140 ppm; after wash: 11–48 ppm) than
the products obtained with DAP (prewash: 149–498 ppm; after
wash: 80–160 ppm). It is conceivable that the diketone product
functions as a reasonably good ligand for the metal and as a
consequence, the Ru removal becomes much less efficient. With
respect to acid and solvent, no clear trend is apparent. The lowest
The metathesis activity of complexes 12 and 13 was tested
in ring opening metathesis polymerization (ROMP) reactions
of cationic exo-7-oxanorbornene derivative 14 and ring closing
metathesis (RCM) reactions of diallylmalonic acid (DAM) in
acidic protic solution (Scheme 5). Catalyst 12 was used in 1 M
HClaq–2-propanol (1 : 9 v/v) solution and catalyst 13 was used
in 0.1 M HClaq solution. The catalyst loadings were 4% in all
experiments at [Ru] = 2.0 mM, and a reaction temperature of
◦
50 C. Generally, the catalytic performance was disappointingly
low for both catalysts. The ROMP of derivative 14 has been
demonstrated to be sufficiently fast with generally less active first-
generation (PCy3)2Ru CHPh catalysts in organic–alcoholic34 and
=
alcoholic–aqueous media17 at lower catalyst loadings, temperature
and reaction times. Under the described conditions, neither
catalyst 12 or 13 produced noticeable amounts of polymer in
60 min. Furthermore, the RCM of DAM reached only 56%
(12) and 44% (13) in 30 min and the reactions did not afford
further conversion after this time. These low conversion rates are
somewhat surprising, in particular as acidic conditions are known
to accelerate the initiation rates of the metathesis reaction.19,31c
Although the donating character of the H2ITap ligand is certainly
influenced by the conversion of the p-donating amino group into
the s-withdrawing ammonium group at the aryl substituents, the
variations between withdrawing and donating aryl substituents
have not been observed before to play an important role in the
catalyst activity.35 A more detailed investigation of the influence
of the pH on the rates of initiation and propagation for these
catalysts is currently ongoing.
Table 2 Efficiency of Ru removal for the RCM reactions of DEDAM
and DAP with catalyst 13 in toluene and ethyl acetate ([Ru] = 2 mM, 2%
loading) with addition of excess acid (conc. HClaq and H2SO4 [96%]) and
filtration (F) or filtration and subsequent extraction with H2O (W)
b
Entry Substrate Acid
Solvent Method Yield (%)a,
ppm Ruc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
DEDAM HCl
DEDAM HCl
DEDAM H2SO4 Toluene
DEDAM H2SO4 Toluene
DEDAM HCl
DEDAM HCl
DEDAM H2SO4 AcOEt
DEDAM H2SO4 AcOEt
Toluene
Toluene
F
W
F
W
F
W
F
W
F
W
F
W
F
W
F
86.5
58.8
72.0
60.3
76.9
52.9
85.7
45.7
43.2
68.9
79.1
44.5
78.2
63.3
68.1
44.3
82
48
24
11
34
45
140
48
498
160
213
80
335
144
149
90
AcOEt
AcOEt
DAP
DAP
DAP
DAP
DAP
DAP
DAP
DAP
HCl
HCl
H2SO4 Toluene
H2SO4 Toluene
HCl
HCl
H2SO4 AcOEt
H2SO4 AcOEt
Toluene
Toluene
AcOEt
AcOEt
W
Scheme 5 Olefin metathesis reactions with catalysts 12 and 13 in protic
acidic media. (a) ROMP of 14 ([Ru] = 2 mM [in 2-PrOH : 1 M HClaq,
9 : 1 v/v for 12; in 0.1 M HClaq for 13], 4% loading); (b) RCM of DAM
([Ru] = 2 mM [in 2-PrOH : 1 M HClaq, 9 : 1 v/v for 12; in 0.1 M HClaq for
13], 4% loading).
a All conversions of the substrates were determined to be >99%. b The
yields for method W are given with respect to the extraction only.
c Estimated determination limit <0.1 ppm.
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Ru contents in the RCM product were accomplished after filtration
and extraction with water when the reaction solution of DEDAM
in toluene was treated with H2SO4 (entries 3 and 4, Table 2). The
residual Ru levels of 24 ppm and 11 ppm are already very close to
the pharmaceutical standard of <10 ppm.
with complexes 12 and 13 (D2O, DCl–D2O, CD2Cl2, CDCl3) were
degassed prior to use. Other solvents were used as purchased.
Reagents were purchased from commercial sources, were degassed
and stored in the dry-box when directly used in combination
with organometallic complexes, and otherwise were used without
further purification. 2-i-Propoxystyrene,36 diethyldiallylmalonate
(DEDAM),37 diallylmalonic acid (DAM),38 3,3-diallylpentane-
2,4-dione (DAP),39 and monomer 1434a were synthesized according
to literature procedures. Grubbs’ catalyst 1 was purchased from
Aldrich, degassed and stored in the dry-box.
Conclusions
The first Grubbs-type (12) and Hoveyda–Grubbs-type (13) olefin
metathesis catalysts bearing a pH-responsive NHC ligand were
synthesized by introducing a p-NMe2 group to the benzene rings
of the ligand. Under neutral solvent conditions, the catalysts are
neutrally charged, soluble in organic solvents and have similar
activity in RCM and ROMP reactions as their non-functionalized,
commercially available counterparts. The NMe2 groups could be
protonated with HCl and the complexes become dicationic. In
complex 12, the addition of 2 equiv. HCl in methanol resulted in
the formation of an only moderately stable mixture of Ru species
only partially ligated by the PCy3 ligand. The residual ligand was
N,N-3,5-Tetramethyl-1,4-phenylenediamine (8)28
A solution of NaNO2 (9.922 g, 143.8 mmol) in water (20 mL)
was added slowly to a solution of N,N-3,5-tetramethylaniline 7
(20.032 g, 134.4 mmol) in conc. HClaq (50 mL) under vigorous
stirring via a capillary which was immersed in the reaction
◦
solution at -5 C over a period of 60 min. During the addition,
a yellow precipitate (4-nitroso-N,N-3,5-tetramethylaniline·HCl)
was formed.◦After the addition, the slurry was stirred for another
60 min at 0 C and then filtered cold through a Buchner funnel.
The yellow residue (4-nitroso-N,N-3,5-tetramethylaniline·HCl)
was washed with ethanol (3 ¥ 50 mL) and suction-dried for 60 min.
Then the powdered residue was added in small portions to a slurry
of powdered tin (7.360 g, 61.8 mmol) in conc. HClaq (50 mL)
at 70 ◦C. While adding the nitrosoaniline the solution turned
intensely yellow in color and reverted back to colorless within a few
seconds. Once all tin was consumed, the yellow color persisted. The
residual nitrosoaniline salt not used in the conversion was stored
for a later transformation. It should be noted that this procedure
avoids the addition of excess tin. Otherwise an insoluble precipitate
is formed during the basic work-up, and this causes a significant
reduction of the yield. The resulting slightly yellow solution was
slowly added to ice-cold 3 M aqueous NaOH (300 mL). The
aqueous phase was extracted with CH2Cl2 (3 ¥ 50 mL), and the
organic phases were combined and dried over NaSO4. The solvent
was removed to give compound 8 (9.770 g, 60.3 mmol, 45%) in
over 98% purity (1H NMR) as a golden-colored viscous liquid.
protonated and observed as DPCy3 Cl- salt via 31P NMR spec-
+
troscopy. The phosphine-ligated Ru species decomposes within
several hours at room temperature. Complex 13 was dissolved in
dilute HClaq (0.1 M) where it formed the diprotonated complex
13¢. The complex remained stable for several hours under non-inert
conditions. Slow hydrolysis afforded 45% decomposition after 7 d.
Both catalysts are active during the RCM of diallylmalonic acid in
protic media at 50 ◦C, however, the reactions proceeded at low rates
and did not afford complete conversions. The ROMP of cationic
oxanorbornene derivative 14 did not afford noticeable conversions
at 50 ◦C. It is likely that the NHC ligand in its protonated form is
significantly less s-donating and thus, the activity is dramatically
reduced. A protocol was developed to remove the ruthenium from
RCM reaction mixtures by acid addition and subsequent filtration.
The residual Ru contents in the isolated RCM products were as
low as 24 ppm after simple filtration, and as low as 11 ppm when
the isolated organic materials after filtration were additionally
extracted three times with water. These values are very close to
the pharmaceutical standard of <10 ppm Ru without applying
cost-intensive chromatography or chemical adsorption methods.
Further investigations are ongoing.
Glyoxalbis(4-dimethylamino-2,6-dimethylphenyl)imine (9)
Compound 8 (6.373 g, 39.4 mmol) was added to a solution of
40% aqueous glyoxal (3.852 g, 26.6 mmol) in methanol (100 mL)
and one drop of conc. HClaq (approx. 20 mL) and stirred for 24 h
at room temperature. During the reaction, a deep-yellow colored
precipitate was formed. The slurry was filtered, the residue was
washed with methanol (3 ¥ 20 mL), sucked dry and the dried in
Experimental
General procedures
All experiments with organometallic compounds were performed
under a dry nitrogen atmosphere using standard Schlenck tech-
niques or in an MBraun dry-box (O2 <2 ppm). NMR spectra
were recorded on a Varian Inova instrument (300.1 MHz for 1H,
◦
the vacuum oven at 60 C for 3 h to give compound 9 (5.874 g,
16.8 mmol, 85%) in >99% purity (1H NMR) as a golden-yellow
powder. H NMR (300.1 MHz, 20 ◦C, CDCl3) d 8.11 (s, 2 H,
1
75.9 MHz for 13C, and 121.4 MHz for 31P). H and 13C NMR
1
spectra were referenced to the residual solvent, 31P NMR spectra
were referenced using H3PO4 (d = 0 ppm) as external standard.
For sonication a Fischer Scientific Ultrasonic Cleaner FS 30 was
used. The bath temperature was set to 30 ◦C.
=
N CH), 6.50 (s, 4 H, C6H2), 2.94 (s, 12 H, N(CH3)2), 2.24 (C6H2–
◦
CH3); 13C NMR (75.9 MHz, 20 C, CDCl3) d 162.5 (N CH),
=
148.1, 140.6, 128.9, 112.8 (C6H2), 40.8 (N(CH3)2), 19.2 (C6H2–
CH3).
Materials and methods
N,N¢-Bis(4-dimethylamino-2,6-dimethylphenyl)ethylene-1,2-
diamine (10)
All solvents for manipulations under inert gas (heptane, thf,
CH2Cl2) were dried by passage through solvent purification
(MBraun-Auto-SPS). All NMR solvents used in combination
A solution of compound 9 (3.380 g, 9.66 mmol) in thf (100 mL)
containing NaBH4 (0.821 g, 21.6 mmol) and boric acid (1.781 g,
5796 | Dalton Trans., 2008, 5791–5799
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◦
28.8 mmol) was stirred at 30 C over a period of 60 min. In this
sonicated for 30 min in air and then filtered. The filter residue
was washed with water (10 mL) and methanol (3 ¥ 10 mL). The
resulting light brown powder was dried in the vacuum oven at
60 ◦C for 60 min to give catalyst 12 (794 mg, 0.86 mmol, 70%)
in >98% purity (1H and 31P NMR). Crystals suitable for X-ray
analysis were obtained from slow vapor diffusion of◦pentane into
a saturated solut◦ion of complex 12 in CH2Cl2 at -20 C. 1H NMR
time period the solution turned colorless. The solution was cooled
to room temperature and water (40 mL) was added carefully and
then conc. HClaq (10 mL) was added dropwise until the solution
stopped developing gas. The solution was warmed to 50 ◦C under
stirring for 10 min and then cooled to room temperature. The thf
was removed under reduced pressure and the aqueous solution
was neutralized with Na2CO3. The aqueous phase was extracted
with tBuOMe (60 mL), and the organic layer was washed with
brine (3 ¥ 40 mL). The organic phase then was dried over Na2SO4
and filtered. The solvent was removed under reduced pressure with
a rotary evaporator, and the residue was dried in the vacuum oven
=
(300.1 MHz, 20 C, CD2Cl2) d 19.02 (s, 1 H, Ru CH), 8.95 (br, 2
H), 7.07 (br, 3 H, C6H5), 6.49 (s, 4 H, C6H2), 3.91 (br, 4 H, N–CH2),
2.96 (s, 12 H, N(CH3)2), 2.72 (s, 12 H, C6H2–CH3), 2.42–2.60 (br m,
3 H), 2.12–2.37 (br m, 3 H), 1.92–2.05 (br m, 3 H), 1.29–1.55 (br m,
12 H), 0.92–1.12 (br m, 12 H, PCy3); 13C NMR (75.9 MHz, 20 ◦C,
◦
2
31 13
=
at 60 C for 2 h to give compound 10 (3.00 g, 8.47 mmol, 88%)
CD2Cl2) d 294.1 (br, Ru C), 221.4 (d, J[ P C] = 80.1 Hz, NHC-
as a colorless, viscous liquid in >98% purity (1H NMR) which
solidified at room temperature over 12 h. 1H NMR (300.1 MHz,
20 ◦C, CDCl3) d 6.51 (s, 4 H, C6H2), 3.11 (s, 4 H, NH–CH2),
2.89 (s, 12 H, N(CH3)2), 2.34 (s, 12 H, C6H2–CH3); 13C NMR
(75.9 MHz, 20 ◦C, CDCl3) d 146.7, 136.7, 131.5, 113.9 (C6H2),
49.7 (NH–CH2), 41.3 (N(CH3)2), 18.8 (C6H2–CH3).
C), 164.4, 129.7, 128.0, 127.5 (s, CH–C6H5), 152.1, 150.5, 150.1,
=
140.0 (br), 137.6 (br), 128.3, 112.3, 111.7 (s, NHC-Ph-CH), 53.1
(d, 4J[31P13C] = 3.3 Hz), 52.1 (s, N–CH2), 40.5, 40.4 (s, N(CH3)2),
20.9 (s), 19.3 (br, C6H2), 31.7 (d, 1J[31P13C] = 16.5 Hz), 29.6 (br),
3
1
28.3 (d, J[31P13C] = 10.2 Hz), 26.8 (s, PCy3-C); 31P{ H} NMR
(121.4 MHz, 20 ◦C, CD2Cl2) d 30.2 (s).
1,3-Bis(2,6-dimethyl-4-dimethylaminophenyl)-4,5-
dihydroimidazolium chloride, H2ITap·HCl (11)
=
H2ITapCl2Ru CH–(C6H4–O–iPr) (13)
Catalyst 12 (303 mg, 0.33 mmol) in CH2Cl2 (15 mL) was stirred at
room temperature under inert gas conditions with CuCl (36 mg,
0.40 mmol) and 2-i-propoxystyrene (54 mg, 0.33 mmol) for 2 h.
The solution turned from brown to green in this time period. Then
the solvent was removed under reduced pressure and the residue
was taken up in 10 mL of a mixture of CH2Cl2–heptane 1 : 1 v/v
in air. The solution was filtered, and then was loaded onto a flash
column with silica gel. The column was washed with a mixture
of CH2Cl2–ethanol 95 : 5 v/v until all green color was removed
from the stationary phase. The solvent was removed under reduced
pressure and the residue was taken up in CH2Cl2 (10 mL). Heptane
(30 mL) was added and the residual CH2Cl2 was removed under
reduced pressure. The product precipitated and the slurry was
filtered. The filter residue was washed with n-heptane (3 ¥ 10 mL),
A solution of diamine 10 (2.567 g, 7.25 mmol) and ammonium
chloride (380 mg, 7.22 mmol) in triethyl-ortho-formiate (30 mL)
was heated under stirring at 130 ◦C for 16 h. The excess triethyl-
ortho-formiate was distilled under reduced pressure (0.1 Torr) and
collected to be reused. Cyclohexane (30 mL) was added to the
◦
solid residue and sonicated for 30 min at 30 C. The slurry was
filtered, washed with cyclohexane (3 ¥ 20 mL), sucked dry on
the filter for 10 min and dried in the vacuum oven at 60 ◦C for
3 h to give compound 11 (2.499 g, 6.31 mmol, 87%) as a slightly
◦
1
off-white powder in >99% purity. H NMR (300.1 MHz, 20 C,
=
d6-DMSO) d 8.97 (s, 1 H, N–CH N), 6.55 (s, 4 H, C6H2), 4.37 (s, 4
H, N–CH2), 2.92 (s, 12◦H, N(CH3)2), 2.32 (s, 12 H, aryl-CH3); 13
C
=
NMR (75.9 MHz, 20 C, d6-DMSO) d 160.8 (N-CH N), 150.8,
135.9, 122.2, 111.7 (C6H2), 51.3 (N–CH2), 40.0 (N(CH3)2), 17.8
(C6H2–CH3).
◦
sucked dry for 5 min and dried in the vacuum oven at 60 C for
60 min to give catalyst 13 (162 mg, 0.23 mmol, 70%) as a green
powder in >98% purity (1H NMR). Crystals suitable for X-ray
analysis were obtained from slow layer diffusion of n-heptane into
a saturated solution of complex 13 in CH2Cl2 at room temperature.
NMR studies of H2ITap·(HCl)(DCl)2 (11¢)
Complex 11 (4.0 mg, mmol) was dissolved in 0.1 M DCl/D2O
◦
1
=
H NMR (300.1 MHz, 20 C, CDCl3) d 16.80 (s, 1 H, Ru CH),
(0.60 mL) and NMR spectra were recorded. 1H NMR (300.1 MHz,
◦
7.47 (m, 1 H), 7.01 (m, 1 H), 6.85 (m, 1 H), 6.78 (m, 1 H, C6H4), 6.58
(s, 4 H, NHC-C6H2), 4.15 (s, 4 H, N–CH2), 3.00 (s, 12 H, N(CH3)2),
2.44 (br, 12 H, NHC-Ph–CH3), 4.89 (sept., 3J[1H1H] = 6.0 Hz, 1
=
20 C, D2O) d 8.57 (s, 1 H, N–CH N), 7.25 (s, 4 H, C6H2), 4.31 (s,
4 H, N–CH2), 3.00 (s, 12 ◦H, N(CH3)2), 2.19 (s, 12 H, aryl-CH3);
13
=
C NMR (75.9 MHz, 20 C, CDCl3) d 160.0 (N–CH N), 142.7,
H, CH(CH3)2), 1.28 (d, 3J[1H1H] = 6.0 Hz, 6 H, CH(CH3)2); 13
C
139.1, 134.1, 121.0 (C6H2), 51.1 (N–CH2), 46.3 (N(CH3)2), 17.3
(C6H2–CH3).
◦
=
=
NMR (75.9 MHz, 20 C, CDCl3) d 299.0 (Ru C), 211.7 (N C–
=
N), 161.0, 150.8, 122.8, 122.2, 112.9, 112.2 (s, CH–C6H4), 152.2,
145.5, 129.3, 112.2 (s, C6H2), 74.8 (CH(CH3)2), 26.9 (CH(CH3)2),
40.8 (s, N(CH3)2), 21.1 (C6H2–CH3).
=
H2ITap(PCy3)Cl2Ru CH–Ph (12)
Ligand precursor 11 (637 mg, 1.61 mmol) and KOtBu (178 mg,
1.60 mmol) were heated under stirring to 60 ◦C in n-heptane
for 60 min under inert gas conditions. After cooling to room
temperature, Grubbs’ catalyst 1 (1.003 g, 1.22 mmol) was added
1H NMR investigation of the hydrolytic stability of
=
H2ITapCl2Ru CH–(C6H4–O–iPr)·(HCl)(DCl)2 (13¢)
◦
and the slurry was heated to 65 C for 24 h also under inert gas
Complex 13 (2.0 mg, 3 mmol) was dissolved in 0.1 M DCl/D2O
in air and kept at room temperature in an NMR tube. 1H NMR
spectra were recorded in certain time intervals and the intensities
were monitored for the corresponding NMR signals for complex
conditions. In this time period an orange-brownish precipitate
was formed. The solution then was cooled to room temperature,
the solvent was removed under reduced pressure and methanol
was added under non-inert conditions. The resulting slurry was
1
13¢ and the hydrolysis product H2ITap·(HCl)(DCl)2 (11¢). 13¢ H
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NMR (300.1 MHz, 20 ◦C, 0.1 M DCl/D2O) d 16.29 (s, 1 H,
Ru CH), 7.04 (s, 4 H, C6H2), 7.11 (m, 1 H), 6.49 (m, 1 H), 6.43
General procedure for RCM of DEDAM/DAP with catalyst 13
and subsequent Ru removal
=
(m, 2 H, C6H4), 4.46 (m, 1H, CH(CH3)2), 3.64 (s, 4 H, N–CH2),
2.81 (s, 12 H, N(CH3)2), 1.91 (s, 12 H, aryl-CH3), 0.58 (m, 6 H,
CH(CH3)2; 13C NMR (75.9 MHz, 20 ◦C, 0.1 M DCl/D2O) d
The substrate (DEDAM: 96 mg, 0.40 mmol; DAP: 108 mg,
0.60 mmol) was added to a solution of catalyst 13 (DEDAM:
5.4 mg, 8 mmol; DAP: 8.1 mg, 12 mmol) in toluene or ethyl acetate
(DEDAM: 2.0 mL; DAP: 3.0 mL) under inert gas conditions and
the solution was kept stirring for 60 min at 50 ◦C. Then the solution
was cooled to room temperature and acid (4 mL, conc. HClaq or
H2SO4 [96%]) was added under inert gas atmosphere and stirred
for another 2 min causing the formation of a precipitate. The
solution was filtered through Na2SO4, washed with the solvent
(3 ¥ 2 mL), and the solvent was removed under reduced pressure.
The product was dried in the vacuum (0.1 Torr) for 30 min. Isolated
yields were obtained in the range of 72–87% (DEDAM) and 43–
79% (DAP). 1H NMR was used to determine the conversion (all
>99%) by integration of distinct signals for the starting material
and RCM product [d 2.86 ppm (DEDAM-CH2) vs. d 3.16 ppm
(cyclopentene-CH2); d 2.65 ppm (DAP-CH2) vs. d 2.91 ppm
(cyclopentene-CH2)]. An aliquot of 20–22 mg was taken from
each reaction for Ru analysis via ICP MS. The residual product
was dissolved in t-butylmethyl ether (20 mL) and washed with
water (3 ¥ 20 mL), the organic phase was dried over Na2SO4 and
the solvent was removed and the product was dried in the vacuum
(0.1 Torr) for 30 min. Product recoveries after the washing steps
were between 44–69%. Again aliquots of 20–22 mg were taken for
Ru analysis via ICP MS.
=
=
(Ru C, n.o.), 207.2 (N C–N), 139.2, 132.1, 122.6, 122.0, 113.7 (1
=
signal n.o., CH–C6H4), 152.0, 145.0, 142.3, 120.4 (s, C6H2), 74.8
(CH(CH3)2), 26.9 (CH(CH3)2), 40.8 (s, N(CH3)2), 21.1 (C6H2–
CH3).
General procedure for ROMP of COE with catalysts 2, 3, 12, 13
COE (7.8 mL, 60 mmol) was added to the catalyst solution
(0.60 mL, 0.50 mM, 0.30 mmol [2, 12 in C6D6; 3, 13 in CDCl3])
under inert conditions via a microlitre syringe and the monomer
conversion was monitored via 1H NMR spectroscopy (300.1 MHz,
20 ◦C) by integration of the sufficiently separated multiplet signals
=
at d = 5.51 ppm (COE, CH–) and 5.46 ppm (polymer, CH) over
a period of 60 min.
General procedure for RCM of DEDAM with catalysts 2, 3, 12, 13
DEDAM (14.4 mL, 60 mmol) was added to the catalyst solution
(0.60 mL, 1.00 mM, 0.60 mmol [2, 12 in C6D6; 3, 13 in CDCl3])
under inert gas conditions via a microlitre syringe and the
1
monomer conversion was monitored via H NMR spectroscopy
(300.1 MHz, 20 ◦C) by integration of the sufficiently separated
multiplet signals at d = 2.87 ppm (DEDAM, allyl-CH2) and
3.16 ppm [cyclopentene-3,3-di(ethylcarboxylate), ring-CH2] over
a period of 2 h.
Crystal structure determination of complexes 12 and 13
˚
Deep brown crystals of 12 are triclinic, a = 9.6949(5) A, b =
◦
◦
˚
˚
13.969(2) A, c = 17.5080(7) A, a = 99.287(7) , b = 99.451(4) , g =
◦
3
˚
90.001(7) , volume = 2307.4(4) A , two molecules per cell in space
General procedure for ROMP of monomer 14 with catalysts 12
and 13 in acidic protic media
¯
group P1 (#2); very small green crystals of 13 are monoclinic, a =
◦
˚
˚
˚
19.6502(11) A, b = 10.9433(5) A, c = 33.440(2) A, b = 104.928(7) ,
The catalyst (8 mmol) and monomer 14 (67.8 mg, 0.50 mmol)
were dissolved in the protic solvent (12 in 2-PrOH–1 M HClaq
9 : 1 v/v; 13 0.1 M HClaq, 2.0 mL) under inert gas conditions
3
˚
volume = 6948.2(7) A , eight molecules per cell in space group
P21/a (#14). Data was collected with Mo-Ka radiation (l =
˚
0.71073 A) at 295(2) K, and an analytical absorption correction
◦
and the solution was heated to 50 C under stirring. An aliquot
was applied. Structures were solved with SHELXS-86;40 non-
H atoms were modeled with anisotropic vibrational parameters,
H atoms were located in difference electron density maps but
placed in idealized positions with isotropic vibrational parameters
20% larger than the equivalent isotropic vibrational factor of the
adjacent carbon atom. In each structure, aryl methyl hydrogens are
disordered over alternate trigonal positions; these were modeled
by refining occupancy factors. Structural models were refined
to convergence by full-matrix least-squares using SHELXL-97.41
Final R for 12 was 0.040 for 9628 reflections with I > 2s(I), 513
parameters, goodness-of-fit 1.04; for 13, final R was 0.086 for 5128
reflections with I > 2s(I), 774 parameters, goodness-of-fit 0.99.
(0.3 mL) was taken after 30 min, quenched with ethylvinyl
ether, dried under vacuum, and the monomer conversion was
◦
1
monitored via H NMR spectroscopy (300.1 MHz, 20 C, D2O)
by integration of the signals d 6.49 ppm (m, 2 H, 14), d
5.97 ppm (m, 2 trans-H, polymer) and d 5.81 ppm (m, 2 cis-H,
polymer).
General procedure for RCM of DAM with catalysts 12 and 13 in
acidic protic media
The catalyst (8 mmol) and DAM (36.8 mg, 0.20 mmol) were
dissolved in the protic solvent (12 in 2-PrOH–1 M HClaq 9 : 1 v/v;
13 0.1 M HClaq, 2.0 mL) under inert gas conditions and
the solution was heated to 50 ◦C under stirring. An aliquot
(0.3 mL) was taken after 30 min and 60 min, quenched with
ethylvinyl ether, dried under vacuum, and the monomer con-
ICP MS analyses
The aliquots of RCM product were digested in hot conc. HNO3
(1 mL). The solid residue was then dissolved in 0.16 M HNO3
containing 2 ppb In as an internal standard. The final analytical
solution contained about 0.67 mg of product per mL acid. Ru
was determined in this solution using a sector-field ICP-MS
(ThermoFinnigan Element 2). Equivalent results were obtained
from five different Ru isotopes (masses 99, 100, 101, 102, and 104);
1
version was monitored via H NMR spectroscopy (300.1 MHz,
20 ◦C, D2O) by integration of the signals d 2.58 (DAM-CH2)
and d 2.98 ppm (cyclopentene-CH2). The aliquots taken after
60 min indicated the same conversion level as those taken after
30 min.
5798 | Dalton Trans., 2008, 5791–5799
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View Article Online
likewise, no difference was noted between results obtained in low
resolution (m/Dm = 300) or medium resolution (m/Dm = 4000),
suggesting a lack of interferences. Blank samples of the digested
starting materials gave Ru contents of <0.1 ppm (DEDAM) and
0.6 ppm (DAP) Ru content.
9 (a) J. H. Cho and B. M. Kim, Org. Lett., 2003, 5, 531–533; (b) K.
McEleney, D. P. Allen, A. E. Holliday and C. M. Crudden, Org. Lett.,
2006, 8, 2663–2666.
10 (a) S. H. Hong and R. H. Grubbs, J. Am. Chem. Soc., 2006, 128, 3508–
3509; (b) S. H. Hong and R. H. Grubbs, Org. Lett., 2007, 9, 1955–1957.
11 D. Rix, F. Caijo, I. Laurant, L. Gulajski, K. Grela and M. Mauduit,
Chem. Commun., 2007, 3771–3773.
12 L. Gulajski, P. Sledz, A. Lupa and K. Grela, Green Chem., 2008, 10,
279–282.
Acknowledgements
13 D. M. Lynn, S. Kanaoka and R. H. Grubbs, J. Am. Chem. Soc., 1996,
118, 784–790.
This work was supported by the NSF Material Science Research
and Engineering Center (MRSEC) for Response Driven Films
(DMR-0213883, partial postdoctoral stipend for SJP and REU
stipend for NJB) and the University of Southern Mississippi
(Dean Research Initiative and Aubrey Keith Lucas and Ella Ginn
Lucas Endowment for Faculty Excellence Award for HJS). EJV
acknowledges MRI-0618148 and the W. M. Keck Foundation for
crystallographic resources.
14 (a) J. B. Binder, J. J. Blank and R. T. Raines, Org. Lett., 2007, 9, 4885–
4888; (b) B. H. Lipschutz, G. T. Aguinaldo, S. Ghorai and K. Voigtritter,
Org. Lett., 2008, 10, 1325–1328.
15 (a) D. M. Lynn, B. Mohr, R. H. Grubbs, L. M. Henling and M. W. Day,
J. Am. Chem. Soc., 2000, 122, 6601–6609; (b) D. M. Lynn, B. Mohr and
R. H. Grubbs, J. Am. Chem. Soc., 1998, 116, 1627–1628; (c) B. Mohr,
D. M. Lynn and R. H. Grubbs, Organometallics, 1996, 15, 4317–4325.
16 D. Samanta, K. Kratz, X. Zhang and T. Emrick, Macromolecules, 2008,
41, 530–532.
17 A. N. Roberts, A. C. Cochran, D. A. Rankin, A. L. Lowe and H.-J.
Schanz, Organometallics, 2007, 26, 6515–6518.
18 L. Gulajski, A. Michrowska, J. Naroznik, Z. Kaczmarska, L. Rupnicki
and K. Grela, ChemSusChem, 2008, 1, 1–8.
19 J. P. Gallivan, J. P. Jordan and R. H. Grubbs, Tetrahedron Lett., 2005,
46, 2577–2580.
20 J. P. Jordan and R. H. Grubbs, Angew. Chem., Int. Ed., 2007, 46, 5152–
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