Ring-closing metathesis reactions: Interpretation of conversion-time data

Article abstract of DOI:10.1002/chem.201204150

Conversion-time data were recorded for various ring-closing metathesis (RCM) reactions that lead to five- or six-membered cyclic olefins by using different precatalysts of the Hoveyda type. Slowly activated precatalysts were found to produce more RCM product than rapidly activated complexes, but this comes at the price of slower product formation. A kinetic model for the analysis of the conversion-time data was derived, which is based on the conversion of the precatalyst (Pcat) into the active species (Acat), with the rate constant k_act, followed by two parallel reactions: 1) the catalytic reaction, which utilizes Acat to convert reactants into products, with the rate k _cat, and 2) the conversion of Acat into the inactive species (Dcat), with the rate k_dec. The calculations employ two experimental parameters: the concentration of the substrate (c(S)) at a given time and the rate of substrate conversion (-dc(S)/dt). This provides a direct measure of the concentration of Acat and enables the calculation of the pseudo-first-order rate constants k_act, k_cat, and k_dec and of k _S (for the RCM conversion of the respective substrate by Acat). Most of the RCM reactions studied with different precatalysts are characterized by fast k_cat rates and by the k_dec value being greater than the k_act value, which leads to quasistationarity for Acat. The active species formed during the activation step was shown to be the same, regardless of the nature of different Pcats. The decomposition of Acat occurs along two parallel pathways, a unimolecular (or pseudo-first-order) reaction and a bimolecular reaction involving two ruthenium complexes. Electron-deficient precatalysts display higher rates of catalyst deactivation than their electron-rich relatives. Slowly initiating Pcats act as a reservoir, by generating small stationary concentrations of Acat. Based on this, it can be understood why the use of different precatalysts results in different substrate conversions in olefin metathesis reactions. Copyright

Full text of DOI:10.1002/chem.201204150

FULL PAPER
DOI: 10.1002/chem.201204150
Ring-Closing Metathesis Reactions: Interpretation of Conversion–Time Data
Vasco Thiel,[a] Klaus-Jꢀrgen Wannowius,[a] Christiane Wolff,[b] Christina M. Thiele,[b] and
Herbert Plenio*[a]
Abstract: Conversion–time data were
recorded for various ring-closing meta-
thesis (RCM) reactions that lead to
five- or six-membered cyclic olefins by
using different precatalysts of the Hov-
eyda type. Slowly activated precatalysts
were found to produce more RCM
product than rapidly activated com-
plexes, but this comes at the price of
slower product formation. A kinetic
model for the analysis of the conver-
sion–time data was derived, which is
based on the conversion of the precata-
lyst (Pcat) into the active species
(Acat), with the rate constant kact, fol-
lowed by two parallel reactions: 1) the
catalytic reaction, which utilizes Acat
to convert reactants into products, with
the rate kcat, and 2) the conversion of
Acat into the inactive species (Dcat),
with the rate kdec. The calculations
employ two experimental parameters:
the concentration of the substrate
(c(S)) at a given time and the rate of
substrate conversion (ꢀdc(S)/dt). This
provides a direct measure of the con-
centration of Acat and enables the cal-
culation of the pseudo-first-order rate
constants kact, kcat, and kdec and of kS
(for the RCM conversion of the respec-
tive substrate by Acat). Most of the
RCM reactions studied with different
precatalysts are characterized by fast
kcat rates and by the kdec value being
greater than the kact value, which leads
to quasistationarity for Acat. The
active species formed during the activa-
tion step was shown to be the same, re-
gardless of the nature of different
Pcats. The decomposition of Acat
occurs along two parallel pathways,
a unimolecular (or pseudo-first-order)
reaction and a bimolecular reaction in-
volving two ruthenium complexes.
Electron-deficient precatalysts display
higher rates of catalyst deactivation
than their electron-rich relatives.
Slowly initiating Pcats act as a reservoir,
by generating small stationary concen-
trations of Acat. Based on this, it can
be understood why the use of different
precatalysts results in different sub-
strate conversions in olefin metathesis
reactions.
Keywords: homogeneous catalysis ·
kinetics · reaction mechanisms ·
ring-closing metathesis
Introduction
sence of significant side reactions, the respective conver-
sion–time data of the catalytic transformation, in principle,
contain all of the information needed to calculate the three
basic kinetic parameters underlying such transformations.
So far, this is a very general approach. We are specifically
interested in homogeneous transition-metal-catalyzed olefin
metathesis reactions,[3] which are powerful tools in organic,[4]
pharmaceutical,[5] and polymer chemistry.[6] Ruthenium com-
plexes of the Grubbs type are well defined and stable preca-
talysts,[7] which are well suited for kinetic and mechanistic
studies. It is an intrinsic feature of metathesis catalysts that
catalytically active species (Acat) are formed from a precata-
lyst (Pcat) in an activation step. This step can be followed
by UV/Vis spectroscopy, because the symmetry of the
ligand field around ruthenium and the donor strength of the
ligands modulate the d–d bands of ruthenium, as well as the
charge-transfer bands. The mechanism of precatalyst activa-
tion has been studied in detail for different classes of preca-
talysts, such as first-[8] and second-generation[9] Grubbs, Hov-
eyda,[10] or Piers type complexes,[11] by using a variety of ex-
perimental techniques[12] and computational tools.[13] For
Hoveyda type complexes, it was shown that the substitution
of the ether oxygen atom by the olefin is the rate-determin-
ing step. This reaction can occur along two parallel mecha-
nistic pathways: One is a dissociative mechanism, whereas
The course of a homogeneously catalyzed chemical reaction
is primarily controlled by three basic steps: the rate of pre-
catalyst activation (kact), the rate of the desired catalytic
transformation (kcat), and the rate of catalyst deactivation
(kdec).[1] Mass transport, which is of fundamental importance
in heterogeneous catalysis, is often less significant in homo-
geneous catalysis.[2] In order to better understand catalytic
transformations, it is desirable to know the rate laws and
rate constants for those three steps, which govern the time-
dependent formation of the reaction products. In the ab-
[a] Dr. V. Thiel, Dr. K.-J. Wannowius, Prof. Dr. H. Plenio
Organometallic Chemistry
Petersenstrasse 18, TU Darmstadt, 64287 Darmstadt (Germany)
E-mail: plenio@tu-darmstadt.de
[b] Dipl.-Ing. C. Wolff, Prof. Dr. C. M. Thiele
Clemens-Schçpf-Institut fꢀr Organische Chemie und Biochemie
Petersenstrasse 22, TU Darmstadt, 64287 Darmstadt (Germany)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201204150. It contains the ex-
perimental details, derivation of formal kinetics, additional conver-
sion–time and derivation plots.
Chem. Eur. J. 2013, 19, 16403 – 16414
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16403

the other step depends on the concentration of the olefinic
substrates and was suggested to correspond either to an as-
sociative[10a] or an interchange mechanism.[10b,c,14] This activa-
tion step is then followed by the catalytic reaction, which
leads to the conversion of substrates, and by a parallel reac-
tion of the active species, which generates the inactive com-
plex (Dcat).
Results and Discussion
Precatalysts and RCM reactions studied: All ruthenium
complexes (Scheme 2) employed in the present study were
synthesized according to literature procedures.[10b,14]
The decomposition of first- and second-generation
Grubbs complexes with phosphine ligands and of Piers type
complexes[15] was also studied. The low stability of the prop-
agating species in ring-closing metathesis (RCM) reactions
and the longevity of the propagating species in ring-opening
metathesis polymerization (ROMP) led to the proposal of
ruthenium methylidene complexes being the key species in
such (unimolecular)[16] decomposition reactions,[16a] possibly
through CH activation reactions with the N-heterocyclic car-
bene (NHC) ligand[15,17] or the formation of ruthenium hy-
drides.[18] Consequently, the design of phosphine or NHC li-
gands has a significant influence on the stability and reactiv-
ity of the active species.[19] It was later shown that the phos-
phine can take part in decomposition reactions through
attack on the ruthenium methylidene.[16b,20] Consequently,
for the phosphine-free Hoveyda type complexes, a different
picture may result. The decomposition/deactivation of such
complexes is less well understood and was found to generate
unidentified ruthenium hydride species and various other or-
ganic products upon reaction with ethene.[16b,21] However,
the rate of this reaction was found to be comparable to that
of the phosphine-containing catalysts. It is thus likely that
other modes, which are slightly slower than the phosphine-
induced decomposition, are available.[16b] In the real world,
various trace impurities in the reaction mixture also need to
be considered, for their contribution to the observed decom-
position/deactivation of the active species.[22]
Scheme 2. Schematic representation of the Hoveyda complexes studied
and explanation of nomenclature used: 1
(NO2), 2(F), 2(OiPr), and 2(NEt2).
ACHTUGNTRENNU(GN NO2), 1(H), 1ACHTUNGTREG(NNNU OiPr), 1ACHTUNGTRENNUNG(NEt2),
2
G
N
ACHTUNGTRENNUNG
We decided to study in detail RCM reactions leading to
five- and six-membered rings (Scheme 3), because such cyc-
lization reactions can be assumed to be highly selective and
irreversible,[23] which simplifies the kinetic treatment. Such
rings are known to form rapidly in RCM reactions, and typi-
cally, this is a clean transformation of a reactant into
a single product and ethene.[24]
In order to obtain more insight into ring-closing metathe-
sis reactions, we propose herein a simplified kinetic treat-
ment, in which the entire olefin metathesis reaction is divid-
ed into three relevant processes (Scheme 1): activation, cat-
alysis, and deactivation. Each of these three steps may con-
sist of a sequence of individual reactions. We wish to report
herein on two different kinetic models, which utilize the
conversion–time data of various ring-closing metathesis re-
actions to obtain the respective rate constants, kact, kcat, and
Scheme 3. Ring-closing metathesis reactions studied. Ts: toluene-4-sulfo-
nyl; Boc: tert-butoxycarbonyl.
kdec
.
The formation of RCM products as a function of time
(conversion–time data) was determined by NMR spectros-
copy. Although catalyst initiation can be followed by UV/
Vis spectroscopy,[14] this method appears to be less straight-
forward for the observation of catalysis and deactivation.
1H NMR measurements with [D8]toluene as the solvent
were employed to measure concentration changes (by NMR
integrals) of the reactants and RCM products. The spectra
were collected during 5 s, followed by a relaxation delay of
25 s. Consequently, the minimum time between the data
points is 30 s. Spin–lattice relaxation time (T1) measure-
Scheme 1. Formal kinetics of catalyzed olefin metathesis reactions. Pcat:
precatalyst; Acat: active catalyst; Dcat: deactivated complex.
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Chem. Eur. J. 2013, 19, 16403 – 16414

Kinetics of Ring-Closing Metathesis Reactions
ments (inversion recovery sequence) with
FULL PAPER
a
substrate
result in the same degree of nonproductive olefin metathesis
(DEDAM) and product sample in [D8]toluene gave T1 <5 s.
Due to constraints in the NMR setup, the first spectrum is
measured 60–90 s after mixing of the reactants. Typical con-
version–time plots are built from 50–200 NMR spectra for
each reaction. This procedure leads to the accurate conver-
sion–time data needed for the kinetic analysis.
reactions. Furthermore, [RuCl2ACHTUNGRTENNU(G SIMes)ACHTUNGRTEN(NUNG =CHR)]-based cata-
lysts in RCM reactions have been shown to suffer from
<10% of nonproductive catalysis (SIMes: (S)-1,3-bis-(2,4,6-
trimethylphenyl)imidazol-2-ylidene).[25a]
Obviously, the final conversion values of RCM reactions
depend on the amount of precatalyst used. However, over-
proportional precatalyst loading is needed to reach higher
substrate conversion. Consequently, the turn-over-number
(ton) is decreased with higher precatalyst loadings and at
higher precatalyst concentrations. In the series of precata-
Conversion–time plots for the RCM of DEDAM by employ-
ing 1
ings: The conversion–time data for the RCM reaction at c-
(DEDAM)=0.1 molLꢀ1 with three different precatalysts,
1(H), 1(NO2), and 1(NEt2), were recorded at 303 K. Exem-
ACHTUNGTRENNUNG(NEt2), 1(H), and 1AHCUTTGNREN(NGUN NO2) at different precatalyst load-
T
lysts 1ACTHUGNTREN(NUG NEt2), 1(H), and 1ACTHUNGTRENN(UNG NO2), the first complex appears
A
U
to be the most efficient precatalyst for the conversion of
DEDAM. All three ruthenium complexes can be expected
to afford the same catalytically active species following pre-
catalyst activation, so the different yields from RCM reac-
tions employing various precatalysts are surprising. Howev-
er, the different behavior of dissimilar precatalysts in cataly-
sis is well known in the olefin metathesis community,[26] al-
though it is not understood so far.
plary data are displayed in Figure 1 (see also Figures S4 and
S5 in the Supporting Information), and the final conversion
values (F1) for all of the reactions are given in Table 1.
Conversion–time plots for various substrate and precatalyst
combinations: The unexpected differences in the yields of
the RCM reactions with DEDAM prompted us to systemati-
cally study this phenomenon for a wider range of precata-
lysts and RCM substrates. The reactions of DEDAM (Fig-
ure S26 in the Supporting Information), of NTs5 (Figure S29
in the Supporting Information), and of NBoc6 (Figure 2)
Figure 1. Experimental conversion–time plots for the RCM of DEDAM
at cACHTUNGTRENNUNG
(DEDAM)=0.1 molLꢀ1 and precatalyst at c(1(H))=2.5ꢂ10ꢀ5– 30ꢂ
10ꢀ5 molLꢀ1 (corresponds to 250, 500, 1000, 2000, and 3000 ppm Pcat
loading, bottom to top) in [D8]toluene at 303 K.
Table 1. Final conversions (F1) and turnover numbers (ton) for the reac-
(NEt2) with DEDAM (c=0.1 molLꢀ1) at
tions of 1(H), 1ACHTUNGTRENNUNG(NO2), and 1ACHUTNGTRENNGUN
303 K.
1
G
1(H)
F1 (ton)
1ACTHNGURETNNU(G NO2)
F1 (ton)
c
(Pcat) [molLꢀ1
]
1.0ꢂ10ꢀ5
2.5ꢂ10ꢀ5
5ꢂ10ꢀ5
100
250
500
1000
1500
2000
3000
0.24
0.42
0.65
0.89
G
–
–
E
ACHTUNGTRENNUNG
E
ACHTUNGTRENNUNG
10ꢂ10ꢀ5
15ꢂ10ꢀ5
20ꢂ10ꢀ5
30ꢂ10ꢀ5
N
ACHTUNGTRENNUNG
Figure 2. Experimental conversion–time curves for the RCM of NBoc6
–
–
–
–
0.92
0.96
ACHTUNGTRENNUNG
with precatalysts 1
(NBoc6)=0.1 molLꢀ1 and c
200 ppm Pcat loading) at 303 K in [D8]toluene.
A
N
ACHUTGTNERNNGU(NO2), 2(F), and 1ACHTUNGTRENNUNG(OiPr) at
T
–
–
c
N
ACHTUNGTRENNUNG
G
The observed rate of product formation represents the
rate of productive RCM reactions. It is known that, for
olefin metathesis reactions with certain precatalysts, a signifi-
cant amount of nonproductive (or degenerate) olefin meta-
thesis reactions takes place,[25] which is not taken into ac-
count here. This appears justified, because we initially
assume (and later show) that the catalytic species formed
from the different precatalysts are identical. This should
with precatalysts 1
G
ACHTUGTNNERNUG(NO2), 2(F), 2HCATUNGTREN(NUNG OiPr), 1(H), 1-
A
U
yields of those reactions and of three more data sets, taken
at 323 K and with an additional substrate (DEBAM6), are
summarized in Table 2.
The conclusions that can be drawn from these data are
clear: Different precatalysts lead to different substrate con-
Chem. Eur. J. 2013, 19, 16403 – 16414
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www.chemeurj.org
16405

H. Plenio et al.
Table 2. Final conversions (F1) for the reactions of eight precatalysts with five RCM
substrates at 303 K or 323 K.
analysis and maximum-likelihood estimations to un-
derstand solvent effects in RCM reactions.[29] This
approach was criticized by Percy and co-workers,
who reported on numerical simulations of conver-
sion–time curves in various solvents, to finally con-
clude that a more robust model is needed for the
successful interpretation of kinetic data.[30]
On the basis of Scheme 1, Equation (1) has been
derived (see the Supporting Information for formal
kinetics), which can describe the conversion–time
curves.
Complex F1,[a,c]
F1,[a,d]
F1,[a,e]
F1,[a,c]
F1,[b,c]
F1,[b,c]
F1,[b,d]
DEDAM NTs5
NBoc6
NTs6
DEDAM DEBAM6 NTs5
1
U
0.32
0.37
0.20
0.27
0.23
0.33
0.25
0.21
0.22
–
0.32
0.52
–
0.89
0.42
0.39
0.45
–
0.24
0.48
–
0.56
–
–
–
–
0.42
0.61
0.55
–
0.42
0.42
0.55
0.67
0.39
0.45
–
0.57
–
–
–
–
0.61
0.76
–
0.86
–
–
–
–
1
1
2
2(F)
2
2
0.39
0.34
–
[a] 303 K. [b] 323 K. [c] 250 ppm [Ru]. [d] 100 ppm [Ru]. [e] 200 ppm [Ru].
À
ꢀ
Á
À
Á
ꢂ
ꢁꢃ
ð1Þ
actt
dect
1 ꢀ eꢀk
1 ꢀ eꢀk
kact
kdec ꢀ kact
F ¼ 1 ꢀ exp ꢀkcat
ꢁ
ꢁ
ꢀ
kact
kdec
versions for the RCM reactions of the respective substrates.
Upon analyzing the nature of the precatalysts and the re-
spective yields for the conversion of a certain substrate, we
find that slowly initiating complexes lead to better substrate
conversion than rapidly initiating precatalysts. This trend
was also observed in other studies.[27] However, this comes
at the price of a much longer reaction time. Once again, this
result is surprising, given the assumption that all of the pre-
catalysts employed lead to the same catalytically active spe-
cies.
with kcat ¼ kS ꢁ c0ðPcatÞ and kact¼kdec
In the three-parameter equation [Eq. (1)], F is the fraction
of conversion of substrate S to product P. kact, kcat, and kdec
stand for the pseudo-first-order rate constants of activation,
catalysis, and deactivation, respectively. c0
ACTHNUTRGNE(NUG Pcat) denotes the
initial concentration of the precatalyst. This approach is
based on several reasonable criteria: 1) Activation and deac-
tivation are consecutive steps;[31] 2) activation is a pseudo-
first-order process, during which only a small amount of sub-
strate S is consumed; 3) the deactivation reaction of Acat is
a first-order step and is independent of substrate; 4) the cat-
alysis is first order with regard to substrate, as well as active
catalyst; and 5) the catalysis does not consume Acat.
The parameters in Equation (1) are best obtained experi-
mentally. The calculation of various time–conversion curves
based on Equation (1) gave good fits (based on R2) with the
experimental data. However, the fit residuals (DF; Figure 3)
do not center on zero but instead reveal systematic devia-
tions of the experimental and fitted data. This is why we be-
lieve that not all of the assumptions made in the derivation
of Equation (1) apply in the present system. Nonetheless,
Equation (1) still appears to be helpful for obtaining
RCM reactions at different concentrations of Pcat and sub-
strate: A series of RCM reactions at a constant ratio of c-
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
or 0.5 molLꢀ1) and precatalyst was performed, to enable
data analysis of RCM reactions under different reaction
conditions. Such an experiment could also provide hints con-
cerning the mechanism of catalyst deactivation.When the
final yields of the different reactions were compared,
a modest increase in the final conversion value, F1, from
0.46 to 0.54 with the increase in the absolute concentration
of the reactants is observed. At this point, two interpreta-
tions of these results are considered: I) If the predominant
decomposition reaction of the catalytically active species is
bimolecular (meaning the reaction of two ruthenium com-
plexes), an increase in the concentration of Acat should
lead to an increase in the deactivation rate and to lower sub-
strate conversion, or II) there is evidence in the literature
that an increased concentration of the substrates in RCM
reactions leads to a stabilization of the active species[28] and,
consequently, to higher product yields. This will be discussed
later in more detail.
Model I: In principle, the conversion–time data for catalytic
reactions contain the information necessary to fully under-
stand the associated reaction kinetics. Based on a formal ki-
netic approach (Scheme 1), the extraction of the relevant
parameters, kact, kcat, and kdec, was attempted from an analy-
sis of the respective conversion–time data. This has been
tried before for RCM reactions employing second-genera-
tion Grubbs complexes, but the approach met with only lim-
ited success. Adjiman et al. applied reaction-progress kinetic
Figure 3. Experimental (triangles) and fitted (line) conversion–time
curves for the RCM of DEDAM (c=0.1 molLꢀ1
) with 1(H) (c=
0.2 mmolLꢀ1) at 303 K by using Equation (1) and including the fit residu-
als, DF (bottom line).
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Chem. Eur. J. 2013, 19, 16403 – 16414

Kinetics of Ring-Closing Metathesis Reactions
FULL PAPER
a rough estimate of the time-dependent conversion for the
experimental chemist. Equation (2) can be obtained from
Equation (1) by extrapolation to t!1. Based on Equa-
tion (2), the ratio kcat/kdec can be approximated, that is, the
influence of experimental modifications in a given system
on kdec and kcat is directly available.
tion (4), the ordinate is a direct measure of the concentra-
tion of the active catalytic species in the course of the RCM
reaction. The statistical analysis of the fit displayed in
Figure 4 yields very good R2 data, and in addition to that,
the fit residuals (DF) are statistically distributed around
zero. This fit (and others shown in the Supporting Informa-
tion) provides excellent support for the usefulness of the
analysis of the conversion–time curves by using Equa-
tion (4).
ꢂ
ꢃ
kcat
kdec
F1 ¼ 1 ꢀ exp ꢀ
ð2Þ
ꢂ
ꢃ
ꢂ
ꢃ
Model II: The absence of fully satisfactory results from
Equation (1) forced us to try a different approach. Based on
the simplified reaction diagram (Scheme 1), the new method
employs two experimental parameters, namely the concen-
tration of the substrate (c(S)) at a given time and the rate of
the reaction of the substrate (ꢀdc(S)/dt) at the same time.
From a series of NMR spectra measured over the course of
the reaction, the concentrations of substrate and product are
obtained directly, whereas the slopes of the conversion–time
curves are a measure of the concentration of the active cata-
lyst. An important assumption in this scenario is that the
catalysis step should be second order, in accordance with
Equation (3).
dcðSÞ
dt
cðSÞ
dF
dt
ð1 ꢀ FÞ
ꢀ
ð4Þ
¼
¼ kS ꢁ cðAcatÞ
In text books of physical chemistry, the time dependency of
the concentration of an intermediate is described by Equa-
tion (5) for unimolecular reactions.[34] This equation is valid
for kact <kdec as well as for kact >kdec and requires that both
precatalyst activation and catalyst deactivation are
(pseudo)-first-order processes.
Â
Ã
kact
ðkdec ꢀ kact
cðAcatÞ ¼ c0ðPcatÞ ꢁ
ꢁ eꢀk ꢀ eꢀk
ð5Þ
actꢁt
decꢁt
Þ
Combination of Equation (3) with Equations (4) and (5)
yields Equation (6), which describes the time dependence of
the concentration of the active catalyst, multiplied by the bi-
molecular rate constant, kS, for the catalysis step.
dcðSÞ
ð3Þ
ꢀ
¼ kS ꢁ cðAcatÞ ꢁ cðSÞ
dt
This implies that ring closure occurs much faster than the in-
itial metathesis step (coordination of the diene to rutheni-
um). This is a reasonable assumption for RCM reactions
with two different terminal olefins,[32] and it is known that
RCM reactions leading to trisubstituted olefins are nearly as
efficient as those leading to disubstituted olefins; only reac-
tions leading to tetrasubstituted olefins are drastically slow-
er.[22b,33]
ꢂ
ꢃ
dcðSÞ
dt
cðSÞ
ꢀ
Â
Ã
kact
ðkdec ꢀ kactÞ
ð6Þ
actꢁt
decꢁt
¼ kS ꢁ c0ðPcatÞ ꢁ
ꢁ eꢀk ꢀ eꢀk
At this point, instead of kact and kdec, we need to use kslow
and kfast, as indicated in Equation (7), in which Amp is the
amplitude. We will discuss the assignment of these rate con-
stants separately.
The NMR-based conversion–time data enable the experi-
mental determination of the rate of substrate conversion
(ꢀdc(S)/dt), as well as of the olefin concentration as a func-
tion of time. A typical plot of the terms in Equation (4)
versus time is shown in Figure 4, and according to Equa-
kslow
ðkfast ꢀ kslow
Amp ¼ kS ꢁ c0ðPcatÞ ꢁ
ð7Þ
Þ
Assignment of the rate constants kslow and kfast: The deriva-
tion of Equation (3) for the concentration of the intermedi-
ate active catalyst for Scheme 1 is the same if kact <kdec or
kact >kdec. The question now arises into how this assignment
can be done and which of the two rate constants, kact and
kdec, belongs to the fast step and which to the slow step in
Scheme 1. The ordinate in Figure 4 corresponds to the con-
centration of the active species kS·cACHTUNGTRENN(UG Acat). For kdec >kact,
only small concentrations of the active catalyst are observed.
To aid the assignment, we take into account the fact that
precatalysts bearing electron-donating substituents on the
benzylidene moiety reduce the rate of initiation. As a conse-
quence, the concentration of the intermediate Acat should
Figure 4. Experimental (black dots) and fitted (line) conversion–time
be drastically reduced upon going from 1
Based on these findings, the assignments kfast =kdec and
slow =kact can be done [Eq. (8a)].[35]
ACHTUGTNERNNUG(NO2) to 1ACHTUNGTRENNUNG(NEt2).
curves for the RCM of DEDAM (c=0.1 molLꢀ1
) with 1(H) (c=
0.2 mmolLꢀ1) at 303 K by using Equation (4) and including the fit residu-
als, DF (bottom line).
k
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H. Plenio et al.
kact
ðkdec ꢀ kact
vation rate depends on the nature of the precatalyst but is
independent of the concentration of Pcat (see Figure 5),
whereas the kact value was previously shown to depend on
the substrate concentration.[14]
Amp ¼ kS ꢁ c0ðPcatÞ ꢁ
ð8aÞ
Þ
A basic rule in reaction kinetics is that, in a sequence of two
consecutive steps, the faster process is seen (if at all) at
shorter times.[36] It follows that Acat forms with the rate of
its deactivation and decomposes with the rate of its activa-
tion. With the abbreviation kcat ¼ kS ꢁ c0ðPcatÞ, Equa-
tion (8b) is obtained, which means that the kcat value can be
calculated from Amp and the two rate constants kdec and
kact.
Deactivation of Acat (two-step data analysis): In order to
better understand the mechanism of the decomposition re-
action, the respective kdec rate constants were calculated by
employing Equation (8), based on the conversion–time data
for the RCM reactions of DEDAM catalyzed by the various
precatalysts (Table 3).
kact
ðkdec ꢀ kact
kact
ðkdec ꢀ kactÞ
A plot of kdec versus c0
ACTHNUTRGNEU(GN Pcat) (Figure 6) shows a linear de-
pendence and reveals a second-order process with a non-
zero intercept. The intercept represents the (pseudo)-first-
order rate constant kdec1 of unimolecular deactivation
Amp ¼ kS ꢁ c0ðPcatÞ ꢁ
¼ kcat
ꢁ
ð8bÞ
Þ
We thus conclude that the fit to Equation (8a) yields the
two rate constants kslow =kact and kfast =kdec, as well as the
amplitude (Amp), which is a direct measure of cACHTNUTRGNE(UNG Acat). The
concentration of Acat will be very small if kact is small.
Based on kdec >kact, the early concept (release–return mech-
anism) that the precatalyst will be reformed following the
catalytic reaction can be ruled out.[37] For kdec @kact, this also
leads to stationary-state conditions (Bodenstein kinetics) for
Acat. There is independent evidence for the short lifetime
of the catalytically active species in RCM reactions. Sijbes-
ma and co-workers noticed that, with a mechanically activat-
ed olefin metathesis catalyst, the catalytic activity disap-
peared shortly after the mechanical activation of the preca-
talyst by ultrasound was switched off.[28b,38] Lemcoff and co-
workers also reported a related phenomenon with light-
switchable precatalysts.[39] Model II now allows the calcula-
tion of the three rate constants kact, kcat, and kdec based upon
the conversion–time curves for the respective RCM conver-
sions of DEDAM, NTs5, and NBoc6 with the different pre-
catalysts in the experiments presented before.
Table 3. Rate constants obtained from the combined fit of the conver-
sion–time data of complexes 1
ACHTUNGTERNNUG(NEt2), 1(H), and 1HCATUNGTREN(NUGN NO2) at different con-
centrations (c0(Pcat)=2.5ꢂ10ꢀ5–3.0ꢂ10ꢀ4 molLꢀ1, R2 =0.92–0.98).
AHCTUNGTRENNUNG
Complex kdec2 [mꢀ1 sꢀ1
]
kact (NMR) [sꢀ1] and
kini (UV/Vis) [sꢀ1
kS [mꢀ1 sꢀ1
]
]
15ꢂ3[a]
(0.54ꢂ0.04)ꢂ10ꢀ4 (NMR)[a]
1
G
74ꢂ4
89ꢂ22
89.4[d]
ꢃ4[b]
0.69ꢂ10ꢀ4 (UV/Vis)[c]
23ꢂ7
(6.6ꢂ0.3)ꢂ10ꢀ4 (NMR)
32ꢂ8[b]
87ꢂ16
AHCTUNGTRENNUNG
1ACHTUNGTRENNUNG
246ꢂ15[b]
132ꢂ10ꢀ4 (UV/Vis)[c]
shared parameter: kdec1 =0.0041 sꢀ1[e]
[a] Determined from a combined fit of the 1ACTHNUTRGENUNG(NEt2) data. [b] From two-
step data analysis. [c] UV/Vis measurements; the initiation rate constant,
kini, as calculated for 0.1m DEDAM from data given in reference [14].
[d] Fixed value; mean kS value: (84ꢂ5) mꢀ1 sꢀ1. [e] Fixed value; deter-
mined from combined fit of 1(H) data; error: ꢂ0.001 sꢀ1
.
(Table 3).[40] The linear fits in Figure 6 share a common in-
Activation of Pcat: Following the analysis of the conver-
sion–time data by utilizing model II, the validity of this ap-
proach must be tested by evaluating the dependence of the
obtained rate constants on the concentration of Pcat. In
Figure 5, the activation rate, kact, is plotted against the initial
tercept at 0.0030 sꢀ1. An alternative plot of kdec versus
cmax
ACTHNUTRGNE(NUG Acat) (Figure S44 in the Supporting Information) also
shows a linear relationship, with nearly the same intercept
at kdec1 =0.0029 sꢀ1. This unimolecular deactivation reaction,
which is first order with respect to ruthenium, can be due to
the reaction of Acat with adventitious impurities in the re-
concentration, c0
ACHTUNGTRENNUNG(Pcat). For the RCM of DEDAM, the acti-
Figure 5. Semilogarithmic plot of the activation rate constant versus the
Figure 6. Plot of kdec versus the initial precatalyst concentration, c0
ACHTUNGTRENNUNG
~
~
&
&
*
*
initial concentration of Pcat for 1(H) ( ), 1
(NO2) ( ), and 1
(NEt2) ( )
for 1
ACHTUGNTRENNU(NG NO2) ( ), 1(H), 1(H) ( ), and 1ACHTUNRTEGG(NNUN NEt2) ( ) with cACTHUNGTRENNUNG
and DEDAM (c=0.1 molLꢀ1) at 303 K.
0.1 molLꢀ1 at 303 K.
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Kinetics of Ring-Closing Metathesis Reactions
FULL PAPER
agents and solvents and/or due to other processes such as
the known reaction of ruthenium with the NHC ligand or
hydride formation.[16b] A significant ethene contribution to
this reaction is less likely, because the ethene concentration
changes in the different experiments.[16b]
time-dependent concentrations of the various precatalysts
and the active species is possible. This is illustrated in
Figure 7 for the RCM reaction of DEDAM catalyzed by
three different precatalysts 1
ACHTUGTNRENGUN(NO2), 1(H), and 1ACHTUNGTERN(NUGN NEt2). 1-
AHCTUNGTRENNUNG
The slopes of the linear fits in Figure 6 provide the bimo-
lecular rate constants, kdec2 (Table 3), in accordance with
Equation (9).
kdec ¼ kdec1 þ kdec2 ꢁ c0ðPcatÞ
ð9Þ
The rate of Acat deactivation as given by kdec also depends
on c0
(Pcat) (Figure 6). This pathway will be called the bimo-
ACHTUNGTRENNUNG
lecular deactivation pathway. There is evidence in the litera-
ture for bimolecular deactivation reactions of Grubbs type
catalysts: 1) It has been suggested that the increase in the
catalytic performance of solid-supported olefin metathesis
catalysts can result from a lower number of bimolecular de-
activation events,[41] 2) for Grubbs II complexes, the prod-
ucts resulting from bimolecular deactivation reactions have
been isolated and characterized,[16b] as well as dimeric spe-
cies;[15,42] and 3) the turnover number of olefin metathesis
reactions decreases upon an increase in the concentration of
the precatalyst.
Figure 7. Calculated time-dependent concentration of the three precata-
lysts 1(NO2), 1(H), and 1
(NEt2) (c0(Pcat)=0.1 mmolLꢀ1) and of Acat ob-
tained from the respective precatalysts during the three RCM reactions
with DEDAM at 303 K during the first 3000 s of the reactions (Pcat:
solid lines, Acat: dashed lines).
N
G
ACHTUNGTRENNUNG
We show here that the rate constant for the bimolecular
deactivation, kdec2, depends on the nature of the precatalysts;
the kdec2 value is much higher for the electron-deficient pre-
catalysts than it is for the electron-rich ones (Table 3). Con-
sequently, different precatalysts are characterized by differ-
ent rates of deactivation. This explains why different preca-
talysts produce different conversions in olefin metathesis re-
actions. Rapidly initiating precatalysts generate a high con-
centration of Acat, which falls victim to bimolecular
deactivation reactions much faster than Acat derived from
slowly initiating precatalysts, for which the bimolecular de-
activation pathway is less important. On the other hand, due
to the bimolecular nature of the catalytic transformation,
the low stationary concentration of Acat derived from
decay of c(1
Based on an initial c(1
tion of Acat reaches a maximum of about 0.05 mmolLꢀ1
after approximately 120 s, which is higher than c(1(NO2)) at
this time. Due to the short life times, the concentrations of
Pcat and Acat decrease rapidly, and after approximately
1000 s, both species are almost gone. In contrast, the concen-
G
ACHTUNGTRENNUNG(Acat).
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
tration of Acat derived from 1ACHTNUTRGENNG(U NEt2) reaches quasistationar-
ity within the same timeframe and remains negligible (<
0.001 mmolLꢀ1) to the end of the RCM reaction.
The high intermediate concentration of Acat derived
from 1
a rapid decrease in the amount of active species; this is not
the case when Acat is slowly generated from 1(NEt2). Con-
ACHTUNGTRENUN(GN NO2) favors bimolecular reactions, which lead to
1
N
ACHTUNGTRENNUNG
A
sequently, better RCM yields are observed for slowly initiat-
ing precatalysts. Avoidance of high concentrations of Acat
clearly leads to higher yields. This also explains why the ad-
dition of Pcat in several portions can produce higher conver-
sions in olefin metathesis reactions than the addition of all
of the Pcat in a single batch.[44]
Under the chosen reaction conditions, the relative contri-
bution of uni- and bimolecular deactivation is different for
the various precatalysts. For the rapidly initiating precatalyst
1ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
The role of ethene: So far, the potential role of ethene in
the present scenario has not been dealt with. Ethene has
been claimed to play an important role in deactivation reac-
tions, because it forms the respective ruthenium methyli-
dene complex from the precatalyst, which appears to be
a key species in catalyst decomposition.[16b,45] However,
cross-metathesis reactions with ethene (ethenolysis) can be
efficiently done at low catalyst loadings,[46] which could indi-
cate that ethene-induced catalyst decomposition is not domi-
nant. The NMR data obtained in the present study provide
the time-dependent ethene concentration in the reaction
plain the systematic errors seen in the data analysis with
model I, which assumes unimolecular catalyst deactivation.
Acat can be deactivated by any ruthenium species present
in solution; the most likely candidates are the reaction of
Acat with Acat or the reaction of Acat with Pcat.[43] The
good fit of the experimental data to a sum of two exponen-
tials favors the reaction of Acat with Pcat.
Time-dependent concentration of Pcat and Acat: Based on
the respective conversion–time plots, the calculation of the
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16409

H. Plenio et al.
Figure 9. Double logarithmic plot of AmpRmax/c0(Pcat) versus kR
ACHTUNGTRNENUG /
act
Figure 8. Experimental time-dependent ethene concentration in an NMR
tube with a punctured cap during the RCM of DEDAM by using preca-
(kRdecꢀkRact) for the precatalysts 1
ACHTUGNTERNN(UGN NO2), 1(H), 1ACHTUNGTRENG(NU OiPr), 1ACHTUNGERTG(NUNN NEt2), 2ACHTUNGTRENNUNG(NO2),
talysts
1
G
1
E
1ACTHNGUTERNNU(G OiPr) with DEDAM (c=
&
2(F), 2ACTHUNGTRNENUG(OiPr), and 2ACHTUGNTREN(NUGN NEt2) in the RCM of DEDAM ( ), NTs5 (3), or
0.1 molLꢀ1
)
ACHTUNGTRENNUNG
NBoc6 ( ) (c(substrate)=0.1 molLꢀ1) at 303 K. The kS (L molꢀ1 sꢀ1
)
*
precatalyst loading) at 303 K in [D8]toluene.
values for the substrates from the two-step data analysis: DEDAM: 65ꢂ
1 (R2 =0.998); NTs5: 417ꢂ10 (R2 =0.991); NBoc6: 855ꢂ60 (R2 =0.965).
mixture during the RCM reaction. Due to the use of a punc-
tured NMR cap, the evaporation of ethene was allowed, so
it does not accumulate during the reaction. In Figure 8, the
versus kRact/(kRdecꢀkRact) should result in a straight line
through the origin, with the slope kS. The plots of AmpR/c0-
experimental time-dependent
c
N
A
played.[47] The maximum concentration of ethene in the re-
action mixture is much smaller for slowly activating precata-
lysts than it is for rapidly activating ones (which can also be
limited by the solubility of ethene in toluene),[48] and it is
always much smaller than the (initial) substrate concentra-
tion. However, in the course of the reaction, substrate is
consumed and ethene is generated. Nonetheless, in the ma-
jority of the experiments done here, the substrate conver-
NBoc6 are characterized by excellent correlation coeffi-
cients.
kRact
kRdec ꢀ kRact
AmpR ¼ kS ꢁ c0ðPcatÞ ꢁ
ð8cÞ
Figure 9 provides clear proof of the validity of Equa-
tion (8b) for the DEDAM, NTs5, and NBoc6 reactions. The
straight lines with slopes close to unity show that the same
catalytically active species (Acat) is formed from the differ-
ent precatalysts. The second-order rate constants, kS
(Lmolꢀ1 sꢀ1), at 303 K for the different substrates were cal-
culated (Figure 9). NBoc6 and NTs5 are excellent RCM sub-
strates, which react much faster than DEDAM. The reluc-
tance of DEDAM to undergo olefin metathesis reactions is
also reflected in the slow initiation rates relative to those of
the other olefins with the same Pcat.[14,51] The interchange
pathway requires better attacking ability of the olefin and is
much less important for this sterically demanding substrate.
sion is less than 50%, so c(S) is larger than cACHTNUTRGNE(NUG ethene). It
cannot be ruled out that ethene-induced deactivation can be
significant in olefin metathesis reactions that are character-
ized by almost complete consumption of the reactants and/
or that are carried out with extremely small concentrations
of ruthenium. With regard to catalyst decomposition, ethene
does not seem to play a major role in the present study: The
bimolecular deactivation involves two ruthenium complexes
and the rate of the unimolecular (or pseudo-first-order) de-
activation experiences no major influence at different c-
ACHTUNGTRENNUNG
(ethene) values.[16b] However, the role of ethene in olefin
metathesis is far from being fully resolved, and more de-
tailed studies are warranted.[49]
Combined data analysis: In order to further establish the
validity of mod
the RCM reactions of DEDAM catalyzed by 1(H), 1
and 1
(NO2) at various values of c0(Pcat)=0.01–0.3 mmolLꢀ1
and c
(DEDAM)=0.1 mmolLꢀ1 were fitted together by
using x=time and z=c0
(Pcat) as independent variables (for
ACHTUNGTRENNUNG
The bimolecular rate constant of catalysis (kS) for the RCM
substrates DEDAM, NBoc6, and NTs5: A highly relevant
parameter, which can be derived from the experimental
data presented in this work, is the second-order rate con-
stant for catalysis, kS. It describes the reaction between the
active species and substrate. The conversion data for the
RCM reactions with DEDAM, NTs5, or NBoc6 illustrate
the different abilities of those substrates to undergo RCM
transformations with Acat (Figure 9). For the series of pre-
catalysts bearing different aromatic ring substituents
(Scheme 2), Equation (8b) will hold for any substitution pat-
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
fitting function, see the Supporting Information).
However, in attempting the combined fits, several as-
sumptions have to be made: 1) which of the two observed
steps is the fast and which is the slow one (=>kact <kdec);
2) all combined experiments lead to a unique catalytically
active species; 3) which of the constants are dependent on z
(=>kact ¼ f(z); kdec =f(z)); and 4) in which way (function)
the constants depend on z (=>kdec =kdec1 +kdec2·z).
tern [Eq. (8c)]. Accordingly, a linear plot of AmpR/c0
ACTHNUTRGNE(NUG Pcat)
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Kinetics of Ring-Closing Metathesis Reactions
FULL PAPER
The decisions on how to deal with those assumptions
were made based on the results of the two-step data evalua-
tion described before. For the crucial assignment of the re-
action order of the deactivation reaction, we have also used
the full set of DEDAM conversion–time data for 1(H) at
different concentrations in a combined fit based on mod-
precatalysts. This could mean that the changes in the UV/
Vis absorbance, which were used to determine the initiation
rates, are diagnostic for the first steps of a multistep scenario
in converting Pcat into Acat,[53] as has been suggested re-
cently.[54]
The values for kdec2 are listed in Table 3. There is good
agreement of the rates obtained from the two-step analysis
and the combined fit.[55] Most importantly, with regard to
the interpretation of the rate constants kdec1 and kdec2, we
came to the same conclusions as before (see the Deactiva-
tion of Acat section).
ACHTUNGTRENNUNGel II. The three potential pathways (exclusively unimolecular
or exclusively bimolecular or uni- and bimolecular) were
modeled. It was found that the best fit of experimental and
calculated data was obtained for a combination of uni- and
bimolecular deactivation reactions (Figure 10; Figures S49
A diagram of the determined rate constants versus Ham-
mett constants[56] in Figure 11 illustrates the relative rates of
precatalyst activation, catalytic transformation, and deacti-
vation of the catalytically active species.
Figure 10. Combined fit (R2 =0.92) for the RCM of DEDAM by using
1(H) at different concentrations of Pcat (cACTHNUTRGNEUNG
(DEDAM)=0.1 molLꢀ1) and
assuming uni- and bimolecular catalyst deactivation. The different traces
correspond to five concentrations in the range c(1(H))=0.025, 0.05, 0.1,
0.2 and 0.3 mmolLꢀ1 (bottom trace to top trace).
and S50 in the Supporting Information). The combined fit
gave kdec1 =0.0041 sꢀ1, which is in very good agreement with
the value of kdec1 =0.0030 sꢀ1 that was obtained in the two-
step data analysis. This confirms that deactivation takes
place through two parallel pathways.
Figure 11. Hammett plot of the rate constants kact, kcat, kdec1, and kdec at c-
ACHUTNGRENNUG CAHTUNGTRENNUGN
(DEDAM)=0.1 molLꢀ1 and c0(Pcat)=10ꢀ4 molLꢀ1. The kcat and kdec1
values are the same for all complexes.
Based on this result, the combined fitting for the full
DEDAM conversion data for three precatalysts and
RCM reactions at different temperatures: The yields ob-
served for the RCM reactions are temperature dependent.
This was demonstrated for the RCM reactions of DEDAM
catalyzed by 1(H) and 1ACHTNUTRGNEUGN(NO2) (Figure 12), which were done
over a large temperature range. In general, higher reaction
temperatures led to enhanced product formation. For the
DEDAM at various concentrations was done to obtain kdec2
,
kact for the individual precatalysts, and a single kS value for
the DEDAM conversion (Table 3; Figure S47 in the Sup-
porting Information).[52]
The data in Table 3 provide convincing evidence for the
applicability of the conversion–time data analysis according
to model II. On comparison of the various rate constants ob-
tained by different methods, good agreement is observed.
The initiation rates (kini) obtained from our previous UV/
Vis studies[14] were compared with the activation rates (kact)
calculated from the conversion–time data (Table 3). Both
rate constants increase with increasing electron deficiency at
the Ru center. Despite the fact that two very different ex-
perimental methods were employed, there is good agree-
ment between the kini and kact values. However, we note that
the respective kini values are consistently larger than kact and
that this difference increases for the more rapidly initiating
RCM reactions of 1ACTHNUTRGNEUNG(NO2) and DEDAM, product formation
improves from F=0.18 at 283 K to F=0.41 at 343 K. This is
indicative of different activation barriers for catalyst deacti-
vation and catalytic conversion. The temperature depend-
ence of the three rate constants (kact, kcat, and kdec) for the
1(H) catalyzed reactions was analyzed by using Arrhenius
plots. The data obtained from the respective Arrhenius plots
for the RCM of DEDAM with 1(H) are: EA [kJmolꢀ1], k
(T=303 K) [sꢀ1 ꢂ103]=66.2ꢂ1.4, 0.87ꢂ0.07 (act), 100.3ꢂ
3.4, 1.41ꢂ0.27 (cat), and 82.6ꢂ3.2, 6.66ꢂ1.10 (dec). This
explains the better substrate conversion at elevated temper-
atures.
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16411

H. Plenio et al.
kdec2, for the bimolecular deactivation for electron-defi-
cient precatalysts are higher than those for electron-rich
precatalysts. The rapidly activating precatalyst 1ACHTUNGTRENNUNG(NO2)
produces high concentration of Acat, which rapidly falls
victim to bimolecular deactivation reactions. There is evi-
dence that this deactivation is a reaction of the respec-
tive Pcat and Acat complexes. The slowly activating pre-
catalyst 1ACTHNUGTRENUNG(NEt2) acts as a reservoir and maintains a very
small concentration of Acat over a long period of time,
the deactivation reaction of which is predominantly uni-
AHCTUNGTREGmNNNU olecular. These results can explain the different per-
formances (substrate conversions) of the various precata-
lysts in RCM reactions.
5) The different activation energies of deactivation and cat-
alytic reactions lead to increasing substrate conversions
at elevated temperatures. It follows that the most effi-
cient RCM transformations will occur at the highest
practical reaction temperatures with slowly initiating pre-
catalysts.
Figure 12. Experimental conversion–time curves for the RCM of
DEDAM catalyzed by (NO2) at
(DEDAM)=0.1 molLꢀ1 and
c0(1(NO2))=2ꢂ10ꢀ5 molLꢀ1 (200 ppm catalyst loading) in the tempera-
ture range of 283–343 K.
1
G
cACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Conclusion
The systematic analysis of a large number of electronically
and sterically modified precatalysts in various RCM reac-
tions by using the methodology reported here has led to
a more detailed understanding of the factors contributing to
the success of ring-closing metathesis reactions. This en-
hanced understanding should aid the quest for more power-
ful catalysts for such reactions.[57]
We propose a kinetic model that utilizes conversion–time
data to determine the concentration of active catalyst
(Acat) as a function of time. The rate of the catalytic trans-
formation is used as a monitor. This approach is based on
the detailed analysis of the conversion–time data of repre-
sentative ring-closing metathesis reactions under a variety of
reaction conditions, by employing a range of different Hov-
eyda type precatalysts. Based on this, we come to the follow-
ing conclusions:
Acknowledgements
1) Slowly initiating precatalysts lead to more efficient prod-
uct formation in RCM reactions than rapidly initiating
precatalysts. However, the superior substrate conversion
of the slowly initiating precatalysts comes at the price of
(much) longer reactions times.
This work was supported by the TU Darmstadt and by the DFG (in part)
through grant Pl 178/8-3 and the European Research Council (ERC start-
ing grant no. 257041 to C.M.T.). We wish to thank Dr. R. Kadyrov for
valuable discussions and L. Kaltschnee for programming the automatic
acquisition macro. We wish to thank the referees for their valuable com-
ments.
2) Based on the kinetic model reported here, the analysis of
RCM conversion–time data yields the rates of the activa-
tion reaction (kact), of the catalytic reaction (kcat), and of
the deactivation reaction (kdec). In most of the reactions
studied, deactivation of Acat is faster than its formation
by activation (kdec >kact), which leads to stationary state
conditions for Acat.
[1] O. N. Temkin, Homogeneous Catalysis with Metal Complexes: Kinet-
ic Aspects and Mechanisms, 2nd ed., Wiley, Chichester, 2012.
[2] However, the transfer of a gaseous reactant (hydrogen, propene)
into the solvent of a homogeneously catalyzed reaction can be limit-
ing for the overall reaction rate.
[3] a) R. H. Grubbs, Angew. Chem. 2006, 118, 3845–3850; Angew.
Chem. Int. Ed. 2006, 45, 3760–3765; b) R. R. Schrock, Angew.
Chem. 2006, 118, 3832–3844; Angew. Chem. Int. Ed. 2006, 45, 3748–
3759; c) Y. Chauvin, Angew. Chem. 2006, 118, 3824–3831; Angew.
Chem. Int. Ed. 2006, 45, 3740–3747.
[4] a) A. H. Hoveyda, A. R. Zhugralin, Nature 2007, 450, 243–251;
b) M. J. Krische, Proc. Natl. Acad. Sci. USA 2010, 107, 3279–3280;
c) S. Chikkali, S. Mecking, Angew. Chem. 2012, 124, 5902–5909;
Angew. Chem. Int. Ed. 2012, 51, 5802–5808; d) A. H. Hoveyda, S. J.
Malcolmson, S. J. Meek, A. R. Zhugralin, Angew. Chem. 2010, 122,
38–49; Angew. Chem. Int. Ed. 2010, 49, 34–44; e) A. Fꢀrstner,
Chem. Commun. 2011, 47, 6505–6511; f) Y. A. Lin, J. M. Chalker,
B. G. Davis, ChemBioChem 2009, 10, 959–969; g) V. Sashuk, L. H.
Peeck, H. Plenio, Chem. Eur. J. 2010, 16, 3983–3993; h) S. P. Nolan,
H. Clavier, Chem. Soc. Rev. 2010, 39, 3305–3316; i) S. J. Meek, R. V.
OꢃBrien, J. Llaveria, R. R. Schrock, A. H. Hoveyda, Nature 2011,
471, 461–466; j) M. Yu, C. Wang, A. F. Kyle, P. Jakubec, D. J. Dixon,
R. R. Schrock, A. H. Hoveyda, Nature 2011, 479, 88–93; k) S.
3) The bimolecular catalytic rate constants kS (Lmolꢀ1 sꢀ1)
for three substrates were determined as 65ꢂ
1 (DEDAM), 417ꢂ10 (NTs5), and 855ꢂ60 (NBoc6).
The kS value illustrates the ability of the respective sub-
strates to undergo RCM reactions, and it shows that the
RCM reaction itself is a very fast process. The rate con-
stants for the catalytic conversions are independent of
the nature of the precatalysts, which demonstrates that
all precatalysts generate the same catalytically active spe-
cies Acat upon activation.
4) Within the concentration range employed in the present
study, the deactivation of Acat occurs along two parallel
pathways: a unimolecular and a bimolecular reaction in-
volving two ruthenium complexes. The rate constants,
16412
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Chem. Eur. J. 2013, 19, 16403 – 16414

Kinetics of Ring-Closing Metathesis Reactions
FULL PAPER
Kotha, M. K. Dipak, Tetrahedron 2012, 68, 397–421; l) M. Bieniek,
Advanced Materials (NATO Science Series II: Mathematics, Physics
´
˙
´
˘
C. Samojłowicz, V. Sashuk, R. Bujok, P. Sledz, N. L. Lugan, G. Lav-
and Chemistry, Vol. 243) (Eds.: Y. Imamoglu, V. Dragutan), Spring-
igne, D. Arlt, K. Grela, Organometallics 2011, 30, 4144–4158; m) M.
er, Dordrecht, 2007, pp. 125–135.
´
Barbasiewicz, K. Grudzien, M. Malinska, Organometallics 2012, 31,
3171–3177.
[22] a) B. R. Galan, M. Pitak, M. Gembicky, J. B. Keister, S. T. Diver, J.
Am. Chem. Soc. 2009, 131, 6822–6832; b) L. H. Peeck, R. Savka, H.
Plenio, Chem. Eur. J. 2012, 18, 12845–12853; c) M. B. Dinger, J. C.
Mol, Eur. J. Inorg. Chem. 2003, 2003, 2827–2833; d) D. Banti, J. C.
Mol, J. Organomet. Chem. 2004, 689, 3113–3116.
[5] a) C. A. Busacca, D. R. Fandrick, J. J. Song, C. H. Senanayake, Adv.
Synth. Catal. 2011, 353, 1825–1864; b) J. W. Morzycki, Steroids 2011,
76, 949–966.
[6] a) H. Mutlu, L. M. de Espinosa, M. A. R. Meier, Chem. Soc. Rev.
2011, 40, 1404–1445; b) A. Leitgeb, J. Wappel, C. Slugovc, Polymer
2010, 51, 2927–2946; c) Y.-X. Lu, F. Tournilhac, L. Leibler, Z.
Guan, J. Am. Chem. Soc. 2012, 134, 8424–8427.
[7] a) G. C. Vougioukalakis, R. H. Grubbs, Chem. Rev. 2010, 110, 1746–
1787; b) C. Samojłowicz, M. Bieniek, K. Grela, Chem. Rev. 2009,
109, 3708–3742.
[23] S. Monfette, D. E. Fogg, Chem. Rev. 2009, 109, 3783–3816.
[24] I. W. Ashworth, D. Carboni, I. H. Hillier, D. J. Nelson, J. M. Percy,
G. Rinaudo, M. A. Vincent, Chem. Commun. 2010, 46, 7145.
[25] a) I. C. Stewart, B. K. Keitz, K. M. Kuhn, R. M. Thomas, R. H.
Grubbs, J. Am. Chem. Soc. 2010, 132, 8534–8535; b) B. K. Keitz,
R. H. Grubbs, J. Am. Chem. Soc. 2011, 133, 16277–16284.
[26] M. Bieniek, A. Michrowska, D. L. Usanov, K. Grela, Chem. Eur. J.
2008, 14, 806–818.
[27] P. Kos, R. Savka, H. Plenio, Adv. Synth. Catal. 2013, 355, 439–447.
[28] a) X. Luan, R. Mariz, M. Gatti, C. Costabile, A. Poater, L. Cavallo,
A. Linden, R. Dorta, J. Am. Chem. Soc. 2008, 130, 6848–6858;
b) R. T. M. Jakobs, R. P. Sijbesma, Organometallics 2012, 31, 2476–
2481.
[8] E. L. Dias, S. T. Nguyen, R. H. Grubbs, J. Am. Chem. Soc. 1997, 119,
3887–3897.
[9] a) M. S. Sanford, J. A. Love, R. H. Grubbs, J. Am. Chem. Soc. 2001,
123, 6543–6554; b) T. M. Trnka, J. P. Morgan, M. S. Sanford, T. E.
Wilhelm, M. Scholl, T.-L. Choi, S. Ding, M. W. Day, R. H. Grubbs, J.
Am. Chem. Soc. 2003, 125, 2546–2558; c) C. A. Urbina-Blanco, A.
Poater, T. Lebl, S. Manzini, A. M. Z. Slawin, L. Cavallo, S. P. Nolan,
J. Am. Chem. Soc. 2013, 135, 7073–7079.
[29] C. S. Adjiman, A. J. Clarke, G. Cooper, P. C. Taylor, Chem.
Commun. 2008, 2806.
[10] a) G. C. Vougioukalakis, R. H. Grubbs, Chem. Eur. J. 2008, 14,
7545–7556; b) T. Vorfalt, K. J. Wannowius, H. Plenio, Angew. Chem.
2010, 122, 5665–5668; Angew. Chem. Int. Ed. 2010, 49, 5533–5536;
c) I. W. Ashworth, I. H. Hillier, D. J. Nelson, J. M. Percy, M. A. Vin-
cent, Chem. Commun. 2011, 47, 5428–5430.
[11] a) E. F. van der Eide, W. E. Piers, Nat. Chem. 2010, 2, 571–576;
b) E. M. Leitao, E. F. van der Eide, P. E. Romero, W. E. Piers, R.
McDonald, J. Am. Chem. Soc. 2010, 132, 2784–2794; c) E. F. van der
Eide, P. E. Romero, W. E. Piers, J. Am. Chem. Soc. 2008, 130, 4485–
4491.
[30] D. J. Nelson, D. Carboni, I. W. Ashworth, J. M. Percy, J. Org. Chem.
2011, 76, 8386–8393.
[31] This assumption is reasonable, because it is well known that solu-
tions of Pcat in toluene are very stable in the absence of olefin.
[32] M. Gatti, E. Drinkel, L. Wu, I. Pusterla, F. Gaggia, R. Dorta, J. Am.
Chem. Soc. 2010, 132, 15179–15181.
[33] L. H. Peeck, H. Plenio, Organometallics 2010, 29, 2761–2768.
[34] K. J. Laidler, Chemical Kinetics, Harper and Row, New York, 1987.
[35] It will later be seen that this assignment can depend on the nature
of the precatalyst and specific reactions.
[36] a) K. J. Wannowius, GIT Fachz. Lab. 1990, 643–651; b) J. Andraos,
Can. J. Chem. 1999, 90, 565–576.
[12] a) S. Torker, D. Merki, P. Chen, J. Am. Chem. Soc. 2008, 130, 4808–
4814; b) K. Getty, M. U. Delgado-Jaime, P. Kennepohl, J. Am.
Chem. Soc. 2007, 129, 15774–15776.
[37] T. Vorfalt, K.-J. Wannowius, V. Thiel, H. Plenio, Chem. Eur. J. 2010,
16, 12312–12315.
[38] A. Piermattei, S. Karthikeyan, R. P. Sijbesma, Nat. Chem. 2009, 1,
133–137.
[13] a) F. NuÇez-Zarur, X. Solans-Monfort, L. Rodriguez-Santiago, M.
Sodupe, Organometallics 2012, 31, 4203–4215; b) F. Nunez-Zarur,
X. Solans-Monfort, L. Rodriguez-Santiago, R. Pleixats, M. Sodupe,
Chem. Eur. J. 2011, 17, 7506–7520; c) X. Solans-Monfort, R. Pleix-
ats, M. Sodupe, Chem. Eur. J. 2010, 16, 7331–7343; d) C. Adlhart, P.
Chen, J. Am. Chem. Soc. 2004, 126, 3496–3510; e) L. Cavallo, J.
Am. Chem. Soc. 2002, 124, 8965–8973; f) A. Poater, F. Ragone, A.
Correa, L. Cavallo, Dalton Trans. 2011, 40, 11066–11069; g) R. Cre-
dendino, A. Poater, F. Ragone, L. Cavallo, Catal. Sci. Technol. 2011,
1, 1287.
[14] V. Thiel, M. Hendann, K. J. Wannowius, H. Plenio, J. Am. Chem.
Soc. 2012, 134, 1104–1114.
[15] E. M. Leitao, S. R. Dubberley, W. E. Piers, Q. Wu, R. McDonald,
Chem. Eur. J. 2008, 14, 11565–11572.
[16] a) M. Ulman, R. H. Grubbs, J. Org. Chem. 1999, 64, 7202–7207;
b) S. H. Hong, A. G. Wenzel, T. T. Salguero, M. W. Day, R. H.
Grubbs, J. Am. Chem. Soc. 2007, 129, 7961–7968.
[17] a) J. Mathew, N. Koga, C. H. Suresh, Organometallics 2008, 27,
4666–4670; b) A. Poater, L. Cavallo, J. Mol. Catal. A Chem. 2010,
324, 75–79; c) F. C. Courchay, J. C. Sworen, I. Ghiviriga, K. A.
Abboud, K. B. Wagener, Organometallics 2006, 25, 6074–6086.
[18] W. J. van Rensburg, P. J. Steynberg, W. H. Meyer, M. M. Kirk, G. S.
Forman, J. Am. Chem. Soc. 2004, 126, 14332–14333.
[19] a) K. M. Kuhn, J.-B. Bourg, C. K. Chung, S. C. Virgil, R. H. Grubbs,
J. Am. Chem. Soc. 2009, 131, 5313–5320; b) R. D. Savka, H. Plenio,
J. Organomet. Chem. 2012, 710, 68–74; c) T. Ritter, M. W. Day,
R. H. Grubbs, J. Am. Chem. Soc. 2006, 128, 11768–11769; d) G. Oc-
chipinti, H.-R. Bjørsvik, V. R. Jensen, J. Am. Chem. Soc. 2006, 128,
6952–6964.
[20] K. Vehlow, S. Gessler, S. Blechert, Angew. Chem. 2007, 119, 8228–
8231; Angew. Chem. Int. Ed. 2007, 46, 8082–8085.
[21] A. V. Nizovtsev; V. V. Afanasiev, E. V. Shutko, N. B. Bespalova in
Metathesis Chemistry: From Nanostructure Design to Synthesis of
[39] a) A. Ben-Asuly, A. Aharoni, C. E. Diesendruck, Y. Vidavsky, I.
Goldberg, B. F. Straub, N. G. Lemcoff, Organometallics 2009, 28,
4652–4655; b) A. Ben-Asuly, E. Tzur, C. E. Diesendruck, M. Siga-
lov, I. Goldberg, N. G. Lemcoff, Organometallics 2008, 27, 6422–
6425.
[40] An alternative interpretation of the intercept is that of an equilibri-
um reaction, in which the intercept stands for the back reaction.
However, we consider this explanantion to be less likely, because
the unimolecular (or pseudo-first-order) deactivation is well known.
[41] M. R. Buchmeiser, Chem. Rev. 2009, 109, 303–321.
[42] M. L. Macnaughtan, J. B. Gary, D. L. Gerlach, M. J. A. Johnson,
J. W. Kampf, Organometallics 2009, 28, 2880–2887.
[43] E. Kamke, Differentialgleichungen—Lçsungsmethoden und Lçsun-
gen, Akademische Verlagsgesellschaft Geest/Portig KG, Leipzig
1967. To the best of our knowledge, no closed-form solution for the
respective differential equations exists for either of the deactivation
mechanisms.
[44] a) V. Sashuk, C. Samojlowicz, A. Szadkowska, K. Grela, Chem.
Commun. 2008, 2468–2470; b) T. Vorfalt, S. Leuthꢄußer, H. Plenio,
Angew. Chem. 2009, 121, 5293–5296; Angew. Chem. Int. Ed. 2009,
48, 5191–5194; c) V. Farina, C. Shu, X. Zeng, X. Wei, Z. Han, N. K.
Yee, C. H. Senanayake, Org. Process Res. Dev. 2009, 13, 250–254.
[45] J. A. M. Lummiss, N. J. Beach, J. C. Smith, D. E. Fogg, Catal. Sci.
Technol. 2012, 2, 1630–1632.
[46] a) R. M. Thomas, B. K. Keitz, T. M. Champagne, R. H. Grubbs, J.
Am. Chem. Soc. 2011, 133, 7490–7496; b) S. Wolf, H. Plenio, Green
Chem. 2011, 13, 2008–2012; c) C. P. Park, M. M. Van Wingerden, S.-
Y. Han, D.-P. Kim, R. H. Grubbs, Org. Lett. 2011, 13, 2398–2401;
d) K. A. Burdett, L. D. Harris, P. Margl, B. R. Maughon, T. Mokh-
Chem. Eur. J. 2013, 19, 16403 – 16414
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16413

H. Plenio et al.
tar-Zadeh, P. C. Saucier, E. P. Wasserman, Organometallics 2004, 23,
2027–2047.
[52] The mathematical background for this approach is detailed in the
Supporting Information.
[47] The curves are characterized by a fast increase in ethene concentra-
tion due to product formation and by a slower “evaporation” of
ethene from the toluene solution.
[53] This is based on a multi-wavelength analysis of UV/Vis data for pre-
catalyst initiation: P. Kos, G. Hoffmann, K.-J. Wannowius, H. Plenio,
unpublished results.
[48] L.-S. Lee, H.-J. Ou, H.-L. Hsu, Fluid Phase Equilib. 2005, 231, 221–
230.
[54] I. W. Ashworth, I. H. Hillier, D. J. Nelson, J. M. Percy, M. A. Vin-
cent, ACS Catal. 2013, 3, 1929–1939.
[49] a) A. G. D. Grotevendt, J. A. M. Lummiss, M. L. Mastronardi, D. E.
Fogg, J. Am. Chem. Soc. 2011, 133, 15918–15921; b) S. T. Diver,
A. J. Giessert, Chem. Rev. 2004, 104, 1317–1382.
[55] In the combined fit for all precatalysts, the errors for 1
larger than the values themselves. Therefore, the combined fit of all
of the 1(NEt2) data was done separately.
ACHTUNGTRENNUNG(NEt2) are
AHCTUNGTRENNUNG
[50] Based on the special properties of DEDAM (poor RCM substrate)
and of 1(NO2; fast initiation), it appears justified to interconvert the
assignment of slow and fast reactions for this substrate/precatalyst
combination only. Upon recalculation of the abscissa data in
Figure 9, the data points now fit the linear relationship perfectly.
[51] D. R. Lane, C. M. Beavers, M. M. Olmstead, N. E. Schore, Organo-
metallics 2009, 28, 6789–6797.
[56] C. Hansch, A. Leo, R. W. Taft, Chem. Rev. 1991, 91, 165–195.
[57] Y. Chu, W. Heyndrickx, G. Occhipinti, V. R. Jensen, B. K. Alsberg,
J. Am. Chem. Soc. 2012, 134, 8885–8895.
Received: November 20, 2012
Revised: August 7, 2013
Published online: October 14, 2013
16414
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