Examining the Effects of Monomer and Catalyst Structure on the Mechanism of Ruthenium-Catalyzed Ring-Opening Metathesis Polymerization

Article abstract of DOI:10.1021/jacs.9b08835

The mechanism of Ru-catalyzed ring-opening metathesis polymerization (ROMP) is studied in detail using a pair of third generation ruthenium catalysts with varying sterics of the N-heterocyclic carbene (NHC) ligand. Experimental evidence for polymer chelation to the Ru center is presented in support of a monomer-dependent mechanism for polymerization of norbornene monomers using these fast-initiating catalysts. A series of kinetic experiments, including rate measurements for ROMP, rate measurements for initiation, monomer-dependent kinetic isotope effects, and activation parameters were useful for distinguishing chelating and nonchelating monomers and determining the effect of chelation on the polymerization mechanism. The formation of a chelated metallacycle is enforced by both the steric bulk of the NHC and by the geometry of the monomer, leading to a ground-state stabilization that slows the rate of polymerization and also alters the reactivity of the propagating Ru center toward different monomers in copolymerizations. The results presented here add to the body of mechanistic work for olefin metathesis and may inform the continued design of catalysts for ROMP to access new polymer architectures and materials.

Full text of DOI:10.1021/jacs.9b08835

Article
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
pubs.acs.org/JACS
Examining the Effects of Monomer and Catalyst Structure on the
Mechanism of Ruthenium-Catalyzed Ring-Opening Metathesis
Polymerization
William J. Wolf, Tzu-Pin Lin, 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, United States
*
S Supporting Information
ABSTRACT: The mechanism of Ru-catalyzed ring-opening metathesis polymerization (ROMP) is studied in detail using a
pair of third generation ruthenium catalysts with varying sterics of the N-heterocyclic carbene (NHC) ligand. Experimental
evidence for polymer chelation to the Ru center is presented in support of a monomer-dependent mechanism for
polymerization of norbornene monomers using these fast-initiating catalysts. A series of kinetic experiments, including rate
measurements for ROMP, rate measurements for initiation, monomer-dependent kinetic isotope effects, and activation
parameters were useful for distinguishing chelating and nonchelating monomers and determining the effect of chelation on the
polymerization mechanism. The formation of a chelated metallacycle is enforced by both the steric bulk of the NHC and by the
geometry of the monomer, leading to a ground-state stabilization that slows the rate of polymerization and also alters the
reactivity of the propagating Ru center toward different monomers in copolymerizations. The results presented here add to the
body of mechanistic work for olefin metathesis and may inform the continued design of catalysts for ROMP to access new
polymer architectures and materials.
INTRODUCTION
reactive 14-electron fragment that undergoes olefin binding,
cycloaddition, and cycloreversion to complete a single olefin
metathesis event. The third generation Ru catalyst has also
■
Olefin metathesis is an indispensable synthetic tool and is used
in a wide range of disciplines, from organic synthesis to
7
,8,11,12
1
been studied in detail, both experimentally
and
materials science. In particular, Ru-catalyzed metathesis is
1
3
computationally, and several distinct features of the
mechanism have been observed. For small, monosubstituted
olefins like 1-butene or ethyl vinyl ether, an associative
mechanism was proposed on the basis of computational work
by Grela and supported experimentally in a study of initiation
remarkably tolerant of a wide variety of functional groups and
conditions, and Ru metathesis catalysts have seen extensive use
in a myriad of applications. The ligands supporting the Ru
center can be tuned to imbue certain desirable properties to
the catalyst. From the parent first generation Ru catalyst 1,
substituting an N-heterocyclic carbene (NHC) ligand makes
the catalyst more active (2), a chelating benzylidene ligand
makes the catalyst precursor more robust
metalated catalysts can be used for Z-selective metathesis
1
4
of DMAP ligated catalysts with ethyl vinyl ether. For bulkier
olefins, such as 2-butene, a dissociative mechanism was
proposed that is identical to the well-established mechanism
by which second generation Ru catalysts operate. Slugovc and
co-workers demonstrated that the structure of the monomer
has a profound effect on the rate of polymerization and the
structure of the propagating Ru species, as the growing
2
3
,4
(3), cyclo-
5,6
(
4), and labile L-type ligands allow for rapid initiation or
7,8
substitution
(5) (Figure 1). The fast-initiating third
generation Ru catalysts like 5 are commonly used in polymer
synthesis and they catalyze the polymerization of cyclic olefins
in living fashion, allowing for a wide variety of uses in polymer
11
polymer chain can chelate to the metal center. More recently,
Matson and co-workers expanded upon this by using
macromonomers with varied ability to chelate to the Ru
9
and material science.
1
5
center. Faster polymerizations were realized by using
The mechanism of Ru-catalyzed olefin metathesis has been
1
0
studied in detail, and its general features are well-
1
established. For phosphine ligated first and second generation
Received: August 15, 2019
Ru catalysts, the dissociation of one L-type ligand generates a
©
XXXX American Chemical Society
A
DOI: 10.1021/jacs.9b08835
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Journal of the American Chemical Society
Article
Figure 1. Several Ru catalysts with tailored ligands that affect their reactivity or selectivity.
monomers that are less prone to chelation. Guirronet and co-
workers also showed that third generation Ru catalysts exist as
five-coordinate complexes in solution after the dissociation of
one of the pyridine ligands. This led to a unexpected zero-
(Scheme 1); the five-coordinate complex has been independ-
ently prepared and characterized to confirm its assignment. For
Scheme 1
12
order dependence on catalyst concentration for ROMP. We
found computational evidence in support of these phenomena
16
in our recent work on variably grafted bottlebrush polymers.
In continuing our study of Ru-catalyzed ROMP, we have
found experimental evidence for a number of important
mechanistic features. Using a pair of sterically differentiated
third generation Ru catalysts, we have found that norbornene
monomers can be classified based on their ability to chelate to
the Ru center and slow the rate of polymerization. Fast ligand
exchange results in a steady-state concentration of the
archetypal 14-electron Ru alkylidene. The mechanistic features
described here may help in designing new synthetic sequences
for making tailored polymers with catalyst control instead of
substrate control.
6
, we attempted to measure K using VT NMR: in CD Cl at
1 2 2
90 °C, two broad benzylidene resonances were observed at δ
−
1
9.4 and 18.6 ppm for the bis and monopyridine species,
respectively.
RESULTS AND DISCUSSION
■
The addition of pyridine (3 equiv) to a CD Cl solution of 6
2
2
Two different third generation Ru catalysts were prepared with
varying steric profiles, using the NHCs 1,3-Bis(2,4,6-trimethyl-
phenyl)-4,5-dihydroimidazol-2-ylidene (SIMes, 5) and 1,3-
Bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene
at −90 °C shifted the equilibrium to the bispyridine complex
and confirmed our assignment of each species. We were able to
construct a van’t Hoff plot over the range −130 °C to −100 °C
(Figure 3) using the low-freezing CDCl F as solvent and
2
1
7
(
SIPr, 6 ), as shown in Figure 2.
extrapolated these data to estimate K = 11 at 25 °C.
The larger K of 6 compared to 5 was attributed to the
1
1
increased steric bulk of SIPr (relative to SIMes) that
discourages ligand binding trans to the benyzlidene ligand.
At catalytically relevant concentrations (typically <0.1 mM)
this first equilibrium is large enough so that >99% of the Ru
species in solution is five-coordinate. The frequency of pyridine
exchange was measured using exchange spectroscopy
18
(
EXSY) and showed an effect from the NHC, with a higher
frequency of exchange observed for 5 than for 6. Activation
entropy for a second-order ligand exchange process is closer to
Figure 2. Two third generation Ru catalysts containing NHCs with
differing steric bulk.
‡
‡
zero for 5 (ΔS = 4 ± 6 J/mol·K) than for 2 (ΔS = +13 ± 6
J/mol·K, first-order ligand exchange) and was not consistent
with an exclusively dissociative mechanism. The activation
‡
The solution-state behavior of each catalyst was examined by
H NMR. Guironnet and co-workers reported that 5 loses a
entropy for pyridine exchange of 6 was more negative (ΔS =
1
−15 ± 6 J/mol·K) while both complexes exhibited similar
‡
pyridine ligand upon dissolution and the predominant species
in solution is the monopyridine complex 5a. They determined
ΔH (5 = 10.5 ± 0.4 and 6 = 10.0 ± 0.4 kcal/mol). The
synthesis of 5 from 2 by ligand exchange between PCy and
3
the dissociation constant (K ) for 5 to be 0.5 using variable
temperature NMR. Based on this precedent, we found that 6
also gave the monopyridine complex 6a in solution at 25 °C
pyridine was speculated to operate via an associative pathway,
1
12
and was attributed to the smaller size of pyridine relative to
7
PCy . The rate of exchange increases in the presence of higher
3
B
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1
Figure 3. (A) Low temperature H NMR array of 6 in CDCl F solution showing both the mono- (δ 18.8 ppm) and bispyridine (δ 19.3 ppm)
2
species. (B) The corresponding van’t Hoff plot for the equilibrium between 6 and 6a.
7
concentration of pyridine, further indicating that an associative
exchange pathway is viable.
borane has been measured to be 2.7(2) × 10 M−1 in
19
CH Cl . When 5a and 1 equiv of BPh were mixed in
2
2
3
We next investigated the dissociation of pyridine from the
five-coordinate complexes 5a and 6a (Figure 4) by
CD Cl solution, two new benzylidene resonances were
2 2
observed at δ 18.4 and 16.8 ppm at −10 °C (Figure 5A).
1
1
Upon warming to 25 °C, a H− H EXSY experiment showed
exchange between the two peaks (Figure 5B). We hypothe-
sized that these new benzylidene resonances could be assigned
to the μ-Cl bridged complexes 8a and 8b (Figure 5). Similar
dimeric Ru complexes have been observed as both
2
0,21
decomposition products of Ru metathesis catalysts
and
22
metathesis active complexes. A DOSY NMR experiment
showed that both benzylidene peaks corresponded to
complexes with smaller diffusion coefficients than that of the
parent monopyridine complex 5a by a factor of 1.2, and a mass
corresponding to a dimer could also be detected by ESI-MS
(
m/z = 1136 Da). When 6a was treated with BPh , only a
3
single new benzylidene resonance was observed at δ 18.3
which also corresponded to a species with a smaller diffusion
coefficient than 6a as measured by DOSY NMR. The addition
of pyridine to the reaction mixtures regenerated either 5a or
6
a, indicating that the complexes were configurationally stable
and that BPh did not react deleteriously with either complex.
3
Figure 4. Solid state structure of 6a. Ellipsoids are drawn at the 50%
probability level and hydrogen atoms have been omitted for clarity. C,
black; N, blue; Cl, green; Ru, teal.
These dimeric species could also be generated using (2,6-
23,24
ditert-butylpyridinium)tetrafluoroborate
as the pyridine
trap or by the reaction of styrene with Piers’ second generation
Ru phosphonium alkylidene. These complexes have not been
unambiguously characterized, but they indicate the highly
reactive and Lewis acidic nature of the 14-electron
intermediate and complicate the calculation of the dissociation
of pyridine from the five-coordinate complexes. Based on these
results, we have shown that 5a and 6a exhibit Lewis acidities
competitively trapping the pyridine with a Lewis acid. The
equilibrium for the dissociation of pyridine (K , Scheme 2) to
2
generate the 14-electron fragment 7 can be calculated from the
overall equilibrium and the equilibrium for the reaction of
pyridine with the trapping reagent. We chose BPh as the
3
trapping reagent because it was appreciably Lewis acidic. The
binding constant for pyridine to an analogous planar triaryl
similar to that of BPh or (2,6-di-tert-butylpyridinium)tetra-
3
fluoroborate (Table 1) and so K is estimated to be on the
2
−
6
−1
order of 10 M .
Scheme 2
The rate of pyridine trapping by either BPh or (2,6-di-tert-
3
butylpyridinium)tetrafluoroborate (rate of consumption of 5a
or 6a) was nearly instantaneous, even at −78 °C. The reaction
with BPh could only occur by dissociation of the pyridine
3
ligand from the Ru complex, evidence that the formation of the
1
4-electron species can proceed by a dissociative mechanism,
in analogy to second generation Ru metathesis catalysts.
The reactivity of each complex for ROMP was evaluated by
measuring the rates of polymerization for a series of
norbornene monomers. Each complex was a competent
C
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1
Figure 5. Dimerization of the 14-electron Ru bezylidene species in the presence of BPh as indicated by the formation of two new species in the H
3
NMR (A) which exchange with one another as detected by EXSY (B).
Table 1. Equilibrium Constants for Pyridine Dissociation,
shape was indicative of a rapid exchange of pyridine between
the free and bound states. This phenomenon is observed after
all of the monomer has been consumed, precluding its
attribution to monomer coordination to the Ru center.
Instead, we assign this behavior to a rapid and reversible
chelation by the polymer chain, as shown in the structure 5c-
xx-DME as shown in Figure 6B. Upon cooling, the resonance
resolved itself into two signals, again corresponding to a free
and a bound pyridine for 5b-xx-DME (Figure 6B). In the
absence of a Lewis basic moiety in the monomer, the resting
state of the active Ru species is a five-coordinate pyridine
adduct. If the monomer is substituted with a Lewis basic site
such as an ester, it competes with pyridine to bind to the metal
center. Slugovc and co-workers observed this same phenom-
enon when using the first and third generation Ru catalysts as
initiators for ROMP. Our recent work on variably grafted
brush polymers also identified chelation as an important factor
controlling the rates of polymerization of norbornene
K and K , for Each Catalyst at 25 °C
1
2
5
6
−
1
−1
K1
K2
0.5 M
11 M
a
∼10 M−1
−6
∼10 M−1
−6
a
Estimates of K2 based on the Brønsted acidity of (2,6-di-tert-
butylpyridinium)tetrafluoroborate and a dimerization constant of 100.
catalyst for the polymerization of these monomers, providing
both linear and bottlebrush polymers with excellent control of
molecular weight. The rate constants for the homopolymeriza-
tion of different types of monomers are shown in Table 2: all
monomers exhibited first-order behavior for more than 5 half-
lives. These data showed several interesting trends. For certain
monomer types, the rates of polymerization showed a strong
dependence on the structure of the catalyst, where the
polymerization catalyzed by 6 was slower than that of 5.
These monomers were all diester monomers of exo-exo (xx
prefix), endo-exo (dx prefix), or endo-endo (dd prefix) geometry.
Other monomers showed a much weaker dependence of the
rate of polymerization on the catalyst structure: these
monomers were all of the exo-imide type, xx-NMI xx-NPI,
or the macromonomers PS, PLA, or PDMS. endo-2,3-
Dimethyl-5-norbornene (dd-DMN) polymerizes very rapidly
at 25 °C (full conversion in less than 15 s), but at 0 °C the
rates of polymerization were similar for both complexes.
To probe the structure of the propagating Ru center, we
reacted each catalyst with 10 equiv of different monomers at
16
monomers.
Several different types of common norbornyl monomers
were analyzed in analogous fashion and classified as either
“
chelating” or “nonchelating,” as shown in Figure 6C (see
1
Supporting Information (SI) for H NMR spectra). The
chelating monomers are comprised of the diester monomers of
all three stereochemical types, with the endo, endo isomers
demonstrating the strongest chelation. The geometric
orientation of the endo substituents is likely responsible for
their propensity to chelate to the Ru center. For 5, the
exoimide group (e.g., xx-NMI) does not chelate to the Ru
center (even at [Ru] = 0.05 mM), as observed for both small
molecule monomers and the PDMS macromonomer. Similar
solution-state behavior was also observed for 6 with both
monomer types.
[
Ru] = 0.02 M in CD Cl . Both 5 and 6 exhibit two distinct
2 2
resonances for the ortho protons of pyridine: a free pyridine
and a bound pyridine as established by Guironnet and co-
workers. Similarly, when 5 is treated with 10 equiv of dd-
DMN, two distinct pyridine resonances are observed at 25 °C.
These resonances were assigned to the polymer-bound Ru
center 5b-dd-DMN, analogous in structure to 5 (Figure 6A).
In contrast, the reaction of 5 and the diester monomer xx-
DME gave only a single pyridine resonance at 25 °C. Its broad
We used the dimethyl ester monomer series (xx-DME, dx-
DME, and dd-DME) to probe the effect of stereochemical
configuration on the chelating behavior. The Ru catalysts were
reacted with 10 equiv of a particular monomer to form an
D
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Table 2. Measured Homopolymerization Rate Constants for a Series of Geometrically Differentiated Monomers Using 5 and 6
at 25 °C
(kobs, s− × 10 )
1
3
6 (kobs, s−1 × 103)
Relative rates (kobs(5)/kobs(6))
5
dx-DME
dd-DME
xx-DME
xx-NMI
dd-NMI
xx-NPI
x-ME
x-MOM
dx-DtBE
dd-DMN
8.02
0.65
18.6
28.3
0.3
13.5
106
14.4
1.3
1.56
0.39
5.15
22.1
0.07
9.64
29.6
4.1
0.1
13.0
2.2
8.4
9.8
5.1
1.7
3.6
1.3
4.3
1.4
3.6
3.5
13
0.9
1.0
1.0
1.16
a
a
12.0
2.1
8.6
PS (3 kDa)
PLA (3.2 kDa)
PDMS (1.3 kDa)
10.8
a
Rate constants measured at 0 °C.
oligomeric chain bound to the Ru center. All three monomers
showed temperature-dependent chelation, but the symmetry of
xx-DME presented a simpler system to analyze. The variable
temperature NMR array of 5-xx-DME is shown in Figure 7:
below −20 °C, two sharp peaks corresponding to the free (8.6
ppm) and Ru-bound (7.9 ppm) pyridine resonances were
visible. As the temperature increased, these peaks broadened
and eventually coalesced around 15 °C. The complex 6-xx-
DME showed a lower coalescence temperature (0 °C for 6)
and a larger equilibrium favoring the chelated state. This
phenomenon is attributed to the steric bulk of the SIPr ligand
that repels the alkylidene (as part of the growing polymer
chain) forcing it into a position to chelate to the Ru center.
so the ligand exchange was much more rapid than propagation
(see SI for simulated NMR spectra). In contrast, the oligomer
bound Ru species 5-xx-NMI or 6-xx-NMI both show two
distinct resonances for the pyridine ligands over a similar
temperature range (−20 to +25 °C) indicating that the exo-
substituted imide does not chelate to the metal center (see SI
for VT spectra).
From the pyridine bound state, an associative interchange
between the ligand and the chelating ester could proceed
through a single, ordered transition state in an associative
interchange mechanism. The associative interchange mecha-
nism requires the pyridine ligand to approach the Ru center
trans to the alkylidene ligand to open the chelating ring. The
25
NMR line shape analysis allowed us to estimate both the
frequency of exchange and the equilibrium between both
states. Under catalytically relevant concentrations (typically >1
mM), the majority of the Ru species was chelated, leading to a
ground state stabilization that results in slower rates of
polymerization for chelating monomers. The frequency of
exchange was estimated to be in excess of 100 s− at 25 °C, and
different values of K for 5 and 6 show that this position is
1
hindered by the aryl rings of the NHC (Figure 3), and so the
exchange between the chelated and pyridine-bound states
would be expected to be slower for 6-xx-DME than for 5-xx-
DME. However, the calculated frequencies of exchange were
faster for 6-xx-DME than for 5-xx-DME, inconsistent with an
associative exchange. In contrast, a dissociative exchange would
1
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1
Figure 6. (A) H NMR spectrum showing two pyridine resonances for the free (highlighted in red) and bound (highlighted in blue) pyridine
1
resonances for the oligo(dd-DMN) bound Ru catalyst. (B) H NMR spectra showing the coalescence of the free and bound pyridine resonances
for 5c-xx-DME at 25 °C (top), and the resolution of those resonances at −10 °C (bottom). (C) Different monomer types classified by chelating
ability.
1
Figure 7. Variable temperature H NMR array (400 MHz) showing the coalescence of free (8.6 ppm, highlighted with a red line) and bound (8.2−
7.9 ppm, highlighted with a blue line) pyridine signals for 5-xx-DME (A), 6-xx-DME (B).
proceed through the opening of the chelating metallacycle,
followed by coordination of the pyridine ligand (Figure 8).
This process is expected to be accelerated as the chelating
esters come into closer proximity to the Ru center due to steric
repulsion by the NHC (Figure 8).
These higher Ru concentrations were also amendable to
monitoring the initiation of the Ru catalysts. At 0 °C, the
measured values for initiation (k ) were not hindered by the
i
catalyst sterics for exo substituted monomers xx-NMI and xx-
DME for both 5 and 6 (Table 3, Scheme 3); the initiation of 6
with xx-NMI was observed to be faster than that for 5. In
F
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Figure 8. Two mechanistic proposals for the formation of the chelate ring, an associative exchange, and a dissociative exchange (favored).
Table 3. Initiation Rate Constants for Different Geometrical
Isomers of Norbornene
monomer, and the olefinic protons are pushed down as the
cycloaddition proceeds.
For endo substituted monomers, the five-membered ring
highlighted in blue) has four cis substituents (highlighted in
Monomer
5 (kobs × 103)
6 (kobs × 103)
(
−
1
−1
xx-DME
xx-NMI
dd-DME
dd-NMI
ki = 12(1) s
ki = 11(2) s
ki = 13(1) s
bold) which destabilizes the transition state and slows the rate
of metathesis. For exo monomers, this interaction is avoided
and the rates of initiation are faster. The opening of the chelate
ring is still an important step that influences the rate of
polymerization (compare the rates of ROMP for xx-DME
between 5 and 6), but the structure of the monomer influences
the rate of polymerization beyond providing an appropriate
geometry for chelation and suggests that the cycloaddition step
is the rate-determining step of ROMP.
−1
−1
ki = 16(1) s
−
1
1
−1
ki = 6.0(5) s
ki = 2.9(2) s
ki = 2.0(3) s
−
−1
ki = 1.1(2) s
contrast, both catalysts initiated more slowly in the presence of
the endo isomers dd-DME and dd-NMI, with 6 initiating less
rapidly than 5. The contrasting rates of initiation indicated that
the monomer geometry is also important in determining the
rates of polymerization, as the approach of the monomer and
the subsequent cycloaddition were affected by the geometry of
the norbornene substituents.
Steric clash between the approaching monomer and the Ru
catalyst is not expected to be the origin of this phenomenon,
since the approach of metal carbenes (and other electrophiles)
to the endo face of the monomer is known to be disfavored
relative to the approach to the exo face. Several titanium
metallacylobutanes have been isolated and characterized that
We next used a kinetic isotope effect (KIE) as a mechanistic
probe. We initially hypothesized that a rate-limiting cyclo-
addition step would exhibit an inverse secondary KIE, in
contrast to a rate-limiting olefin binding step, and so the two
steps could thus be differentiated. Several metathesis-active Ru
complexes have been characterized in the solid state with
olefins bound to the Ru center. The CC bond lengths of the
coordinated olefins did not differ significantly from the average
CC bond length (1.34 Å) for both side- and bottom-bound
26
1
exhibit this preference. Instead, the differences in initiation
rates can be rationalized by the induction of strain into the
norbornene ring system, as shown in Figure 9. The Ru
alkylidene approaches the exo face of the norbornene
complexes. In solution, the H NMR resonances of the bound
olefinic protons shifted upfield significantly, up to several ppm
for the sidebound olefins. While these ground state structures
do not necessarily reflect the transition state structures, it is
Scheme 3
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Figure 9. Proposed origin of rate differences for initiation for exo and endo substituted monomers.
Figure 10. Kinetic isotope effects for both a chelating (A) and a nonchelating (B) monomer. Each measured value represents a weighted average of
at least five independent rate measurements for each isotopologue at 25 °C.
Figure 11. Ring opening of the chelate prior to monomer coordination.
unlikely that a significant elongation of the CC bond occurs
at the transition state between free and bound olefin, and so an
inverse secondary KIE is not likely to be a result of olefin
result of olefin binding or cycloaddition. Instead, the observed
isotope effects for dx-DME may be classified as steric KIEs,
suggesting two possibilities: an associative type mechanism for
monomer coordinating to the Ru center or a dissociative
mechanism involving a crowded Ru center (Figure 10). For the
dissociative pathway, the alkylidene must rotate up into the
aryl ring of the NHC ligand, which is hindered by the
increasing size of the aryl rings on the NHC ligand, leading to
the increasing magnitude of the KIE. The steric profile of the
NHC has a smaller effect on the propagating Ru species for
nonchelating monomers, and the smaller KIEs for xx-NMI are
consistent with this mechanism. The steric bulk of 6 had a
small effect on the rate of polymerization of xx-NMI, as a small
KIE was observed (0.94(1)) which could be attributed to
monomer coordination to the Ru species. In contrast, an
associative interchange mechanism could also rationalize the
observed KIE for dx-DME, where steric clash between the
NHC and the incoming monomer would be alleviated by the
shorter C−D bonds. Ru benzylidene precatalysts like 3 have
been proposed to initiate via an associative interchange
2
7−29
binding.
For third generation catalysts ligated by DMAP,
the slow step of the catalytic pathway was proposed to be the
14
olefin association step. In contrast, the dynamics of ligand
exchange for the pyridine complexes are very rapid and suggest
that the rate-limiting step lies further along the reaction
pathway. For the first generation Ru metathesis catalyst, a
primary secondary KIE (1.7) has been observed in support of
30
the decomposition of the ruthenacyclobutane intermediate.
Using mass spectrometry, Chen and co-workers observed a
small secondary KIE of 1.04(4) for the ring opening of
31
norbornene with a deuterated benzylidene in the gas phase.
We prepared two different types of isotopically enriched
monomers: dx-DME-d for the chelating monomer and xx-
6
NMI-d6 as a nonchelating monomer. Independent rate
measurements were made for each isotopologue with each
catalyst at 25 °C (Figure 10).
For dx-DME, an inverse secondary KIE was observed for
both catalysts (Figure 10a) and the magnitude of the KIE
increased with the increasing bulk of the NHC. In contrast, the
polymerization of xx-NMI did not exhibit significant KIEs:
values around unity were measured for both catalysts (Figure
32
mechanism. In particular, Plenio and co-workers showed
that initiation of 3 and related derivatives is a combination of
both an associative interchange and dissociative exchange
mechanism, with smaller substrates favoring the associative
33
9
b), suggesting that the observed KIEs for dx-DME were not a
interchange pathway. Lloyd-Jones and co-workers have also
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Figure 12. Proposed mechanism for the ROMP of norbornene monomers.
shown that the reaction of third generation Ru catalysts with
vinyl ethers proceeds via a combination of both mechanisms,
with an associative interchange mechanism dominating at
simpler form in eq 2 when K [py] ≫ K K and K [M] . This
m
2
m
2
0
rate law is consistent with the experimental observations that
the polymerizations are first-order in monomer, are inverse
first-order in pyridine, and can rationalize the observed zero-
34
higher substrate concentration, supporting calculations by
Grela. For larger substrates such as norbornene and other
order dependence on [Ru]
dependence on [Ru] at lower concentrations of 5 (and
subsequently lower concentrations of pyridine) such that
K [py] ≈ K K and K [M] . The steric size of the NHC
. Additionally, we have observed a
0
3
3
disubstituted olefins, both experimental and computa-
0
1
3,16
tional
evidence support a dissociative mechanism. For
ROMP, the steric size of the NHC has a small effect on the
rate of polymerization for nonchelating monomers (Table 2)
which is consistent with a dissociative mechanism. For
chelating monomers, there is a pronounced steric effect on
the rates of polymerization and on the position of the chelating
equilibrium, and so the isotope effect may be assigned to the
interaction between the polymer chain and the NHC. For
bottom-bound metallacycles, the alkylidene must rotate up
into the aryl rings of the NHC, congestion which would be
alleviated by the shorter C−D bonds of the deuterated
polymer chain (Figure 11).
The polymerizations of both monomer types show a first-
order dependence on monomer concentration, and an inverse
first-order dependence on pyridine concentration. Interest-
ingly, the order in catalyst has been shown to be zero, as
established by Guirronnet and co-workers, and was assigned to
m
2
m
2
0
ligand has little effect on the observed rates of polymerization
for nonchelating monomers in support of a dissociative
mechanism for propagation. While exo-substituted imides are
geometrically unable to chelate to the metal center, the steric
size of the substituent interferes with the approach of the
monomer to the metal center, slowing the rate of polymer-
ization (xx-NMI vs xx-NPI, Table 2).
−
d[M]
dt
k [Ru] [M]
4
0
py]
K2
0
=
=
Km(
1 + [
+ [M]0
)
k K [Ru] [M]
4
2
0
0
k K + K [py] + K [M]
(1)
2
m
m
2
0
K = k−
+ k4
k3
3
the cancellation of [Ru] and [py] terms in the rate law. The
m
0
dissociative mechanism (cycle 1, Figure 12) fits with a
competitive inhibition model with the rate law shown in eq
−d[M]
dt
k K [Ru] [M]
4
2
0
0
≈
1
. For nonchelating monomers, fast and reversible pyridine
K [py]
m
(2)
dissociation produces a reactive 14-electron complex which
can then bind substrate and proceed with a productive
metathesis event, similar to the established mechanism for
The mechanism of polymerization of chelating monomers
has an additional equilibrium for the opening of the chelated
metallacycle (cycle 2, Figure 12). Rapid ligand exchange
between the pyridine-bound Ru species and the chelated
other Ru catalysts. Since we have estimated K to be on the
2
−
6
order of 10 , the rate law shown in eq 1 can be reduced to the
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Figure 13. Eyring plots for the polymerization of xx-NMI with 5 and 6 (A), xx-DME with 5 and 6 (B), and dd-DME with 5 and 6 (C).
Table 4. Activation Parameters for the Polymerization of Chelating and Non-Chelating Monomers Using 5 and 6
xx-NMI
xx-DME
dd-DME
‡
‡
‡
5
6
ΔS = −8 ± 2 J/mol·K
ΔS = −150 ± 6 J/mol·K
ΔS = −111 ± 8 J/mol·K
‡
‡
‡
ΔH = 19 ± 0.4 kcal/mol
ΔH = 9.3 ± 0.3 kcal/mol
ΔH = 13.8 ± 0.6 kcal/mol
‡
‡
‡
ΔS = −49 ± 3 J/mol·K
ΔS = −115 ± 6 J/mol·K
ΔS = −160 ± 3 J/mol·K
‡
‡
‡
ΔH = 16 ± 2 kcal/mol
ΔH = 12.3 ± 0.4 kcal/mol
ΔH = 10.6 ± 0.3 kcal/mol
species proceeds through the 14-electron intermediate, which
can proceed through a productive metathesis event, adding to
the growing polymer chain. For chelating monomers, the steric
size of the NHC ligand has a pronounced influence on the
between the two catalysts. A larger, negative value of ΔS‡
(−49(3) J/mol·K) was determined for the ROMP of xx-NMI
‡
with 6, with a ΔH of 16(2) kcal/mol. The ROMP of xx-DME
was evaluated over a similar temperature range, and a much
‡
rates of polymerization, since K favors the chelated resting
larger magnitude of ΔS was determined (−150 ± 5) J/mol·K)
5
‡
state due to steric repulsion between the alkylidene and the
NHC (eq 3). This effect is maximized when both the chelating
group and the NHC are large, as demonstrated by the large
with a ΔH of 9.3(3) kcal/mol.
Entropy is a much larger contributor to the activation energy
required for chelating monomers, and similarly large values
have been measured for the initiation of 3. The opening of the
chelate ring has a minor entropic cost compared to monomer
t
differences in the rate of polymerization of dx-D BE for 5 and
6
(Table 2).
‡
association, and so the composite value of ΔS most strongly
−
d[M]
dt
k K K [Ru] [M]
reflects the associative step. For the pyridine bound resting
state, the reversible dissociation of the pyridine ligand makes a
much larger contribution to the entropy, and so the composite
4
2
5
0
=
K K [py] + K K + K K K + K K [M]
m
5
2
m
2
5
m
2 5
(3)
‡
values of ΔS are less negative (near zero). Both exo and endo
Eyring analysis provided another means of distinguishing the
two monomer types. It is difficult to deconvolute the activation
substituted monomers (xx-DME and dd-DME, Table 4)
exhibited similarly large, negative activation entropies for
polymerization, supporting similar mechanisms that proceed
from a chelated Ru species.
35
parameters of a multistep mechanism, and so the measured
parameters reflect contributions from several reversible steps.
The ring opening of chelated Ru catalysts has been extensively
studied using Eyring analysis, and the measured activation
parameters differ from those observed for phosphine ligated
The mechanistic features described above are relevant to
38
both our own and others recent work on variably grafted
polymers. A variety of different polymer architectures can be
accessed rapidly and reliably by selecting an appropriate
macromonomer and small molecule diluent pair. The most
important step in these polymerizations is the crossover step,
which controls the rate at which both monomers are
incorporated into the growing polymer side chain. Mono-
mer/macromonomer pairs are chosen based on their
homopolymerization rates, and the reactivity ratios are then
evaluated to ensure that the desired polymer sequence (blocky,
gradient, or random) can be synthesized. This approach is
highly tunable, given the synthetic accessibility of a wide
variety of small molecule diluents and macromonomers. The
reactivity ratios are affected by the structure of the propagating
Ru center, which is in turn affected by the nature of the
monomer, according to the Mayo−Lewis model. A copoly-
merization of xx-NMI and dd-NMI not only demonstrated the
differences between the propagation of both monomers but
36
second generation Ru catalysts particularly with respect to
‡
activation entropies. Large, negative values of ΔS have been
observed for the initiation of 3 and its related derivatives using
3
3
‡
butyl vinyl ether in contrast to the positive values of ΔS for
phosphine catalysts that are indicative of phosphine dissoci-
ation. These entropies have been used to support an
associative exchange mechanism, but they are also consistent
with a dissociative mechanism proceeding through a rate-
37
limiting olefin association step.
The temperature profile for the polymerization of xx-NMI
using 5 is shown in Figure 13, with activation parameters
compiled in Table 4. A small, negative entropy of activation
‡
(
ΔS ) was determined (−8(2) J/mol·K) with an enthalpy of
‡
activation (ΔH ) of 19.0(4) kcal/mol. The temperature profile
for the polymerization of xx-NMI with 6 is similar over the
same temperature range, further highlighting the similarities
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Figure 14. Plots of ln([M ]/[M]) against time for the copolymerization of xx-NMI (blue, □) and dd-NMI (green, ◇) using 5 (left) or 6 (right),
0
compared to the homopolymerization rates of each monomer (xx-NMI (blue, ●) and dd-NMI (×)).
also showed how the structure of the propagating catalyst
affects the rate of polymerization. When the Ru site is chelated,
the addition of the next monomer into the polymer chain is
hindered: the incorporation of xx-NMI into the polymer chain
is slowed by the presence of dd-NMI relative to its
homopolymerization rate. Conversely, the presence of the
nonchelated Ru species accelerates the incorporation of the
subsequent monomer: the consumption of dd-NMI is
accelerated relative to its homopolymerization rate (Figure
monomer types, as chelation can be enforced by repulsion
between the growing polymer chain and the substituents of the
NHC ligand. In addition, the structure of the monomer was
also shown to be an important factor that influences the rate of
polymerization. Several key features distinguished the chelating
and nonchelating monomers from one another including
homopolymerization rates, initiation rates, activation parame-
ters, and KIEs, highlighting the influence that the monomer
structure imparts on the structure and reactivity of the
propagating Ru center. These results provide additional
mechanistic insights into the third generation mediated
ROMP and are particularly interesting in the context of our
continuing work on the design and synthesis of new polymers
and materials.
1
4). This effect is exaggerated when 6 is used as the initiator,
since the chelation is enforced more strongly.
The crossover rate constants (k12 and k ) and subsequent
21
reactivity ratios (r1 and r ) are strongly affected by the
2
structure of the catalyst, through enforcing the growing
polymer chain to chelate to the Ru center. Linear regression
allowed us to determine the reactivity ratios for the
copolymerization of xx-NMI and dd-NMI, highlighting the
difference between 5 and 6 and demonstrating how the
chelating ability of the polymer chain affects the reactivity of
the Ru center. The values of r and r are much more disparate
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.9b08835.
■
*
S
1
2
Experimental Procedures, NMR spectra, additional
kinetic plots (PDF)
Crystallographic information file for 6a (CIF)
for 5 than for 6, which can be attributed to the strongly
chelated Ru center present when 6 is used as the initiator.
CONCLUSIONS
■
AUTHOR INFORMATION
Corresponding Author
rhg@caltech.edu
ORCID
Tzu-Pin Lin: 0000-0001-7041-7213
Robert H. Grubbs: 0000-0002-0057-7817
Notes
■
*
The mechanism of Ru-catalyzed metathesis polymerization has
been examined as a function of catalyst structure, providing
experimental evidence for a number of mechanistic features.
Importantly, cyclic olefin monomers were classified as either
“
chelating” or “nonchelating” in reference to their ability to
form a stabilized metallacycle as the resting state of the active
Ru center. The influence of the steric environment of the
catalyst on chelation was demonstrated with different
The authors declare no competing financial interest.
K
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Journal of the American Chemical Society
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Metathesis Polymerization: The Significance of the Anchor Group.
ACKNOWLEDGMENTS
■
J. Am. Chem. Soc. 2016, 138 (22), 6998−7004.
W.J.W. gratefully acknowledges the Arnold O. Beckman
postdoctoral fellowship for financial support. We thank Dr.
David VanderVelde for assistance with NMR experiments, Dr.
Michael Takase for assistance with X-ray crystallography, and
Dr. Mona Shagholi for assistance with HRMS. We are also
indebted to Drs. Tonia Ahmed, Adam Johns, Allegra
Liberman-Martin, Chris Marotta, and Mr. Jiaming Li for
helpful discussions and assistance with preparing this manu-
script. We thank Materia Inc. for the generous donation of Ru
metathesis catalysts. We gratefully acknowledge Dr. Jase
Gehring for assistance with preparing figures.
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