Z -selective ethenolysis with a ruthenium metathesis catalyst: Experiment and theory

Article abstract of DOI:10.1021/ja4010267

The Z-selective ethenolysis activity of chelated ruthenium metathesis catalysts was investigated with experiment and theory. A five-membered chelated catalyst that was successfully employed in Z-selective cross metathesis reactions has now been found to be highly active for Z-selective ethenolysis at low ethylene pressures, while tolerating a wide variety of functional groups. This phenomenon also affects its activity in cross metathesis reactions and prohibits crossover reactions of internal olefins via trisubstituted ruthenacyclobutane intermediates. In contrast, a related catalyst containing a six-membered chelated architecture is not active for ethenolysis and seems to react through different pathways more reminiscent of previous generations of ruthenium catalysts. Computational investigations of the effects of substitution on relevant transition states and ruthenacyclobutane intermediates revealed that the differences of activities are attributed to the steric repulsions of the anionic ligand with the chelating groups.

Full text of DOI:10.1021/ja4010267

Article
pubs.acs.org/JACS
Z‑Selective Ethenolysis with a Ruthenium Metathesis Catalyst:
Experiment and Theory
Hiroshi Miyazaki,†,§ Myles B. Herbert,†,§ Peng Liu,‡ Xiaofei Dong,‡ Xiufang Xu,‡,# Benjamin K. Keitz,†
Thay Ung,⊥ Garik Mkrtumyan,⊥ K. N. Houk,*,‡ and Robert H. Grubbs*,†
†Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute
of Technology, Pasadena, California 91125, United States
‡Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, United States
#Department of Chemistry, Nankai University, Tianjin 300071, P. R. China
⊥Materia Inc., 60 North San Gabriel Boulevard, Pasadena, California 91107, United States
S
* Supporting Information
ABSTRACT: The Z-selective ethenolysis activity of chelated
ruthenium metathesis catalysts was investigated with experi-
ment and theory. A five-membered chelated catalyst that was
successfully employed in Z-selective cross metathesis reactions
has now been found to be highly active for Z-selective
ethenolysis at low ethylene pressures, while tolerating a wide
variety of functional groups. This phenomenon also affects its
activity in cross metathesis reactions and prohibits crossover reactions of internal olefins via trisubstituted ruthenacyclobutane
intermediates. In contrast, a related catalyst containing a six-membered chelated architecture is not active for ethenolysis and
seems to react through different pathways more reminiscent of previous generations of ruthenium catalysts. Computational
investigations of the effects of substitution on relevant transition states and ruthenacyclobutane intermediates revealed that the
differences of activities are attributed to the steric repulsions of the anionic ligand with the chelating groups.
thesis is when a metathesis reaction occurs between two
substrate molecules instead of between a substrate molecule
and ethylene, and secondary metathesis involves the CM of two
terminal olefins to generate an internal olefin and ethylene
(Scheme 1). Industrially, the ethenolysis of seed oil derivatives
affords chemically desirable products with applications in
cosmetics, detergents, polymer additives, and renewable
biofuels.5
The ability to selectively form the kinetically preferred Z-
olefin products in CM reactions is another significant challenge
in metathesis research, as catalysts have generally been
observed to favor formation of the thermodynamic E-isomer.
The Z-olefin motif is prevalent in a variety of small molecules,
including many natural products and pharmaceutical targets.
The first example of a catalyst-controlled system capable of
predominantly forming the Z-isomer in CM reactions was
reported by the Hoveyda and Schrock laboratories. The Z-
selectivity of the reported tungsten and molybdenum catalysts
was attributed to the difference in the size of the two axial
ligands. This size difference influences the orientation of the
substituents on the forming metallacyclobutane intermediate
and leads to productive formation of Z-olefins.6 These catalysts
have shown great utility in the synthesis of complicated natural
products and stereoregular polymers.7 A particular Z-selective
INTRODUCTION
■
The discovery of transition metal alkylidene catalysts has
allowed olefin metathesis to permeate the literature in a wide
variety of fields including green chemistry,1 natural product
synthesis,2 and polymer chemistry,3 since its discovery in the
1950s. The development of catalysts that exhibit preference for
kinetically versus thermodynamically controlled products, such
as the generation of terminal olefins from internal olefins,
termed ethenolysis, and the formation of Z-olefins in cross
metathesis (CM) reactions, is a particular challenge in the field.
For a metathesis catalyst to be active in ethenolysis reactions,
it must exhibit high activity and stability as a propagating
methylidene. However, many known metathesis catalysts are
unstable as methylidene complexes and undergo rapid
decomposition, thus exhibiting poor ethenolysis reactivity.4
The desired ethenolysis catalytic cycle is depicted in Scheme 1.
Initial reaction of an internal olefin with a metal methylidene
proceeds via a 1,2-metallacycle and produces a terminal olefin
and the corresponding substituted metal alkylidene. Further
reaction with ethylene forms a second equivalent of terminal
olefin and regenerates the catalytically active methylidene.
For an ethenolysis catalyst to show high selectivity at
appropriate ethylene pressures, formation of terminal olefin
products must be favored over back reactions and side reactions
that produce internal olefins (Scheme 1). Side reactions that
reduce selectivity for the desired terminal olefin products
include self-metathesis and secondary metathesis. Self-meta-
Received: January 29, 2013
© XXXX American Chemical Society
A
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Scheme 1. Ethenolysis and Related Side Reactions
Figure 1. Prominent ruthenium metathesis catalysts (Mes = 2,4,6-
trimethylphenyl).
C−H activation of an N-adamantyl substituent, and exhibit
activity and Z-selectivity rivaling the aforementioned group IV
systems. The identity of the anionic ligand has been found to
have great consequence on reactivity and selectivity, as
replacement of a carboxylate on 4 for a nitrato-type ligand
(5) results in greater stability, Z-selectivity, and close to 1000
turnovers for homodimerization reactions. Z-selective CM,
macrocyclic ring closing metathesis (RCM), and ring-opening
metathesis polymerization (ROMP) reactions have been
reported using this family of chelated catalysts.10
Our groups and others have used density functional theory
(DFT) calculations to elucidate important information about
the mechanism of action, origin of Z-selectivity, and stability of
chelated ruthenium catalysts 4 and 5.11 The metathesis reaction
occurs via a side-bound mechanism, different from that with
nonchelated ruthenium catalysts. The olefin approaches cis to
the NHC ligand on the catalyst.12 The N-adamantyl chelating
group positions the N-mesityl substituent directly over the
forming metallacyclobutane, thus causing its substituents to be
oriented away to avoid steric repulsions and leading to high Z-
selectivity of the metathesis products.
molybdenum catalyst (1) was shown to be effective for the Z-
selective ethenolysis of internal olefins.8 In this process, the
corresponding molybdenum methylidene reacts preferentially
with cis-olefins to produce two terminal olefins, while trans-
olefins react to a significantly smaller extent (Scheme 2). Since
To design better catalysts for Z-selective metathesis, a more
thorough understanding of this family of chelated ruthenium
catalysts is required. The goal of this study is to explore the Z-
selectivity of these catalysts for ethenolysis reactions and
concurrently investigate how this can help us better understand
their CM reactivity. The stability and structure of metal-
lacyclobutane intermediates greatly influences metathesis
reactivity and selectivity; thus, we sought to study the effects
of substitution on relevant ruthenacyclobutane intermediates
using experimental and theoretical techniques. Both catalysts 3
and 5 were tested so that the effects of chelate size could be
investigated.13 Herein, we report a method for the functional
group tolerant Z-selective ethenolysis of internal olefins and
explore other unique reactivity of chelated ruthenium catalysts,
providing hypotheses of observed behavior based on
ruthenacyclobutane stability and structure.
Scheme 2. Z-Selective Ethenolysis Reaction Using
Molybdenum Catalyst 1
ethenolysis is the reverse of cross metathesis, the same 1,2-
disubstituted metallacyclobutane complex must be formed as an
intermediate in both reactions. Hence, if a catalyst is highly Z-
selective when forming cross products, it is expected to also be
able to selectively degrade cis-olefins by ethenolysis, assuming
that the corresponding metal methylidene complex is stable.
A family of functional group tolerant Z-selective ruthenium-
based catalysts has recently been reported that contain a
chelating N-heterocyclic carbene (NHC) ligand derived from
an intramolecular carboxylate-driven C−H bond insertion of an
N-bound substituent (Figure 1).9 Catalyst 3 is derived from C−
H activation of the benzylic position of the N-mesityl
substituent of complex 2 and thus contains a six-membered
chelated structure that imparts slightly improved Z-selectivity
compared to previous generations of ruthenium catalysts.
Catalysts 4 and 5 contain five-membered chelates derived from
RESULTS AND DISCUSSION
■
Ethenolysis Experimental Investigations. The ethenol-
ysis activity of chelated ruthenium complexes 3 and 5 was
initially investigated in order to directly compare our chelated
catalysts to previously reported catalysts.14 We first explored
their activity and selectivity for the ethenolysis of the
completely cis-olefin substrate, methyl oleate (Table 1). The
ethenolysis of methyl oleate is a standard assay used to compare
ethenolysis reactivity and selectivity of metathesis catalysts. It
should be noted that selectivity here refers to the formation of
the desired ethenolysis products, terminal olefins 7 and 8, and
B
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both internal olefin mixtures (∼80% E) to >95% of the E-
isomer at 5 atm of ethylene and 0.5 mol % catalyst loading for
the two substrates (Scheme 3); the products of both reactions
were recovered by flash column chromatography.16 For 5-
decene, the purely E-isomer (>95% E) was isolated in 90%
yield based upon initial E-content.17 For 12, the purely E-
internal olefin (>95% E) and 8-nonenyl acetate produced by
ethenolysis of the Z-olefins were both quantitatively recovered
(Scheme 3). Exposure of catalyst 3 (0.5 mol %) to a ∼4:1
mixture of the trans- and cis-isomers of 12 at 5 atm of ethylene
led to a very small amount of ethenolysis (<3% conversion)
and no observable selectivity. Additionally, only olefin
migration of the starting material 12 was observed when the
reaction was carried out at 1 atm of ethylene at higher loadings
of catalyst 3 (5 mol %).
Table 1. Ethenolysis Reactions of Methyl Oleate Catalyzed
by Catalysts 3 and 5
a
b
c
d
entry
catalyst
mol %
yield
selectivity
TON
1
2
3
4
3
3
5
5
0.1
0%
0%
-
0
0
0.01
0.1
-
80%
12%
>95%
>95%
800
1160
0.01
a
The reactions were run in a minimal amount of CH2Cl2 for 1 h at 40
b
With the knowledge that 5 was an effective Z-selective
°C and 10.2 atm of ethylene. Yield = (moles of ethenolysis products
7 + 8) × 100%/(initial moles of 6). Selectivity = (moles of
c
ethenolysis catalyst, we sought to investigate its functional
group compatibility in E-isomer enrichment reactions.18
A
ethenolysis products 7 + 8) × 100%/(moles of total products 7 + 8 +
d
9 + 10). TON = yield × [(initial moles of 6)/(moles of catalyst)].
variety of functional groups were tolerated under the reaction
conditions, including acetates, alcohols, esters, amines, and
ketones (Table 2). Reaction performed with 5 atm of ethylene
for all E-dominant substrates (72−82% E) led to enrichment of
the internal olefins with >95% of the E-isomer as monitored by
1H NMR. Although the same reactions performed under 1 atm
of ethylene proceeded with high selectivity, reaction at 5 atm
was necessary to push the ∼80% mixtures to >95% of the E-
isomer.
not to the catalyst’s E/Z selectivity. Although catalyst 3 showed
no reactivity at the catalyst loadings tested, catalyst 5 was able
to catalyze the transformation with high turnovers and high
selectivity at low loadings.15 The fact that 5 is highly active as
an ethenolysis catalyst and previously exhibited high Z-
selectivity in CM reactions strongly suggests that it would
exhibit high selectivity for Z-olefins in ethenolysis reactions.
We tested chelated catalysts 3 and 5 in the ethenolysis of
∼4:1 mixtures of the trans- and cis-isomers of two internal
olefins, 5-decene and the acetate-substituted substrate 12, to
determine if these catalysts exhibited any selectivity for Z-
olefins. We were pleased to find that under the optimized
conditions depicted in Scheme 3, catalyst 5 was able to enrich
We next attempted to quantify the ethenolysis selectivity of
catalyst 5 by investigating the relative rates of degradation of E
1
and Z internal olefins using H NMR spectroscopy. 5-Decene
was chosen as a substrate since the stereopure E- and Z-isomers
are commercially available. The rate of ethenolysis was found to
be first-order in substrate8 and the relative rates of 5-decene
ethenolysis were determined under 1 atm of ethylene (see
Supporting Information). Neither the ethenolysis of Z-5-
decene nor E-5-decene proceeded to completion under the
reaction conditions.19 Nevertheless, log plots of substrate
concentration versus time at early reaction times were found to
be linear (E-5-decene, R2 = 0.93; Z-5-decene, R2 = 0.98). From
Scheme 3. Z-Selective Ethenolysis Reaction of Substrate 12
Table 2. E-Isomer Enrichment by Z-Selective Ethenolysis of Various Functionalized Symmetrical Internal Olefins with the
Formula R(CH2)nCHCH-(CH2)nR Using Catalyst 5
entry
compound
R; n
initial %E
mol % 5
pressure (atm)
time (h)
final %E
1
11
CH3; 3
79
79
52
78
78
82
82
68
80
80
80
80
60
72
72
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.0
0.5
0.5
1
5
5
1
5
1
5
5
1
5
1
5
5
1
5
4
4
4
4
4
4
4
4
6
6
4
4
6
4
4
90
2
>95
90
3
4
12
15
OAc; 7
OH; 4
93
5
>95
92
6
7
>95
90
8
9
16
17
CO2Me; 6
NHPh; 3
88
10
11
12
13
14
15
>95
92
>95
86
18
C(O)Me; 2
90
>95
C
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Figure 2. The most favorable pathway of ethenolysis of cis-2-butene with catalyst 5. Gibbs free energies and enthalpies (in parentheses) are in kcal/
mol and with respect to the most stable ruthenium ethylidene complex 47 (an isomer of 27, see Figure 4). For clarity, the chelating adamantyl group
is not shown in the 3D transition state structures.
Figure 3. The most favorable pathway of ethenolysis of trans-2-butene with catalyst 5. Gibbs free energies and enthalpies (in parentheses) are in
kcal/mol and with respect to the most stable ruthenium ethylidene complex 47 (an isomer of 27, see Figure 4). For clarity, the chelating adamantyl
group is not shown in the 3D transition state structures. In subsequent steps, 27 reacts with ethylene to regenerate 21. This is identical to the second
half of the catalytic cycle in the reaction with cis-2-butene (see Figure 2).
the slopes of these plots, the ratio of the rate constants for
ethenolysis of Z-5-decene and E-5-decene (kZ/kE) was found to
be ca. 4.5. The corresponding kZ/kE value reported for
molybdenum catalyst 1, 30 5, is significantly higher, implying
that catalyst 1 is inherently more selective than 5. However, all
reactions catalyzed by 1 were conducted under high ethylene
pressures not suitable for benchtop reactions (4−20 atm).20
The functional group tolerance of catalyst 5 and the Z-
selectivity at ethylene pressures as low as 1 atm highlights
advantages of this particular ruthenium-based system for the
preparation of terminal olefins from internal olefins and for the
purification of E/Z mixtures.21 The further development of
chelated catalysts with increased Z-selectivity will lead to
ruthenium catalysts with increased kZ/kE values.22
with a theoretical level found to be satisfactory in our previous
computational studies of chelated ruthenium catalysts.11
Geometries were optimized in the gas phase with B3LYP24/
LANL2DZ−6-31G(d). Single point calculations were per-
formed with M0625/SDD-6-311+G(d,p) and the SMD26
solvation model with THF solvent.
Reaction pathways initiated from both ruthenium methyl-
idene and alkylidene complexes were investigated, since these
interconvert during the ethenolysis reaction. The most
favorable pathway of the ethenolysis of cis-2-butene with
catalyst 5 involves the side-bound approach of the internal
olefin to the ruthenium methylidene complex 21 (Figure 2).
Formation of the ruthenacyclobutane intermediate 23 requires
an activation free energy of 8.8 kcal/mol (TS22). In 21, TS22,
and 23, the nitrate is syn to the α-H on the chelating adamantyl
group. Ruthenacyclobutane 23 isomerizes to form a less stable
ruthenacycle 24, in which the nitrate is anti to the adamantyl α-
H.27 Cleavage of the ruthenacycle 24 via TS25 requires a
comparable activation energy as TS22 (ΔG⧧ = 8.6 kcal/mol),
Ethenolysis Computational Investigations. To under-
stand the mechanism of ethenolysis, and the origin of Z-
selectivity with catalyst 5, we computed the ethenolysis reaction
pathways and the Z/E-selectivity with density functional theory
(DFT). The calculations were performed using Gaussian 0923
D
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Table 3. Internal−Terminal Cross Metathesis Reaction of 5-Decene (11) and 8-Nonenyl Acetate (14) Catalyzed by 3 or 5
a
a
b
b
entry
catalyst
mol %
substrate
time (h)
yield of 20
yield of 12
% Z of 20
% Z of 12
1
2
3
4
5
5
3
3
0.2
0.2
2.5
2.5
Z-11
E-11
Z-11
E-11
6
24
2
57%
<1%
69%
53%
21%
19%
14%
17%
91%
-
83%
87%
22%
33%
23%
25%
2
a
b
1
Determined by gas chromatography. Determined by H NMR.
and generates a ruthenium−propene π complex 26. In contrast,
productive cleavage of 23 without isomerization to 24 requires
a much higher barrier (ΔG⧧ = 20.9 kcal/mol) and forms an
unstable ruthenium ethylidene complex in which the ethylidene
is trans to the chelating Ru−C bond. Thus, the isomerization to
24 is necessary before cleaving the ruthenacyclobutane.
Decoordination of propene from 26 yields ruthenium ethyl-
idene 27, which then binds to an ethylene molecule to form π
complex 28. Subsequent steps involve the formation and
cleavage of monosubstituted ruthenacyclobutane intermediates
via TS29 and TS32, respectively, and eventually regeneration of
the ruthenium methylidene complex 21. The monosubstituted
transition states in the second half of the catalytic cycle (TS29
and TS32) are both 3−4 kcal/mol more stable than the
disubstituted transition states TS22 and TS25. Thus, the
reaction of ruthenium methylidene with the internal olefin is
the rate-limiting step in the catalytic cycle (TS22), while the
productive cleavage of the disubstituted metallacycle (TS25)
requires essentially identical activation energy.
The anionic nitrate ligand binds bidentate to the ruthenium
in all four transition states in the catalytic cycle, although the
Ru−O bond trans to the alkylidene is significantly longer than
the Ru−O bond trans to the NHC (∼2.4 versus ∼2.2 Å). The
transition states with monodentate nitrate are five-coordinated
with trigonal bipyramidal geometries and 1−4 kcal/mol less
stable than the corresponding bidentate transition states (see
Supporting Information). The small energy differences between
mono- and bidentate nitrate complexes suggest that the
monodentate transition structures might become favorable
with bulkier olefin substituents and/or bulkier anionic ligands.
Structures containing both mono- and bidentate binding modes
are considered in the following computations and only the
most favorable structures are shown.
In the analogous reaction with trans-2-butene, both transition
states TS33 and TS36 are less stable than the corresponding
transition states TS22 and TS25 in the reaction with cis-2-
butene (Figure 3). In TS33 and TS36, one of the olefin
substituents is pointing toward the N-mesityl group and leads
to significant steric repulsions. The overall activation barrier is
5.2 kcal/mol higher than the ethenolysis of cis-2-butene. This
explains the observed Z-selectivity in ethenolysis reactions.28
Interestingly, the ruthenacyclobutane intermediates 34 and 35
in the reaction with trans-2-butene are slightly more stable than
the corresponding cis-substituted metallacycles 23 and 24.
Unlike the metathesis transition states, in which the olefin and
the Ru-alkylidene are almost in the same plane, the four-
membered metallacycle intermediates are puckered. The
methyl substituents on the metallacycles in 34 and 35 are
not directly pointing toward the N-mesityl group on the ligand
(see Supporting Information for the 3D structures of the
metallacycle intermediates). The ligand−metallacycle repul-
sions in the metallacycle intermediates are smaller than in the
transition states.
Crossover Experimental Studies. Research presented in a
previous report led us to believe that ethenolysis plays a major
role in CM reactions catalyzed by 5.10c The CM reaction
between a cis-internal olefin and a terminal olefin was
monitored over time and revealed that internal olefins must
be broken down by ethenolysis before a heterocross product
can be generated; it was proposed that the required
methylidene complex was generated by homodimerization of
the terminal olefin substrate. In addition to this, no crossover
was observed when two cis-internal olefins were reacted in the
presence of catalyst 5, and it was suggested that this was due to
high steric demands associated with forming trisubstituted
ruthenacycles using this particular catalyst.29 Since CM between
two internal olefins is a common occurrence for previous
generations of metathesis catalysts including molybdenum-
based Z-selective catalysts,6 we desired to further probe this
unique reactivity of catalyst 5. Previously, species 20 was
synthesized by reacting the two terminal olefins 1-hexene and
8-nonenyl acetate in the presence of catalyst 5 (0.5 mol %) and
proceeded with high yield (67%) and cis-selectivity (91% Z-
olefin). We explored whether catalysts 5 and 3 were able to
form substrate 20 from (1) an internal olefin and a terminal
olefin, or (2) two internal olefins. Catalysts 5 and 3 were both
investigated in order to elucidate differences in reactivity,
activity, and selectivity between the complexes with different
chelate sizes.
The reaction of 5-decene (11) and 8-nonenyl acetate (14) to
form compound 20 was initially probed (Table 3). When
catalyst 5 was employed, use of the cis- and trans-isomers of 5-
decene greatly affected its metathesis activity (entries 1 and 2).
Reaction with cis-5-decene led to formation of 20 with 57%
yield and 91% Z-isomer at 0.2 mol % of 5. The analogous
reaction under the same conditions with trans-5-decene led to
only trace amounts of 20. In both cases, the undesired
homodimer of 8-nonenyl acetate (compound 12) was also
formed in similar quantities and Z-selectivities, regardless of the
isomer of 5-decene used. Conversely, catalyst 3 was able to
form compound 20 with both isomers of 5-decene (entries 3
and 4). The % Z values of 20 and 12 were notably low
compared to the reactions catalyzed by 5; however, this is
attributed to extensive Z/E isomerization by secondary
metathesis processes at the long reaction times.
The unique behavior of catalyst 5 gives important insight
into the reactivity of this chelated catalyst.30 Since 5 is effective
for the Z-selective ethenolysis of internal olefins, its inability to
react with trans-olefins in CM reactions further suggests that all
internal olefins must undergo ethenolysis first to generate
E
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Scheme 4. Reaction of a Methylidene with cis-5-Decene To Produce 1-Hexene and the Corresponding Substituted Alkylidene
Table 4. Internal−Internal Cross Metathesis Reaction of 5-Decene (11) with 12 Catalyzed by 3 or 5
a
b
b
c
c
entry
catalyst
mol %
substrate
ethylene exposure
time (h)
yield of 20
yield of 14
% Z of 20
% Z of 12
1
2
3
4
5
6
5
5
5
5
3
3
1.0
1.0
1.0
1.0
2.5
2.5
Z-11
E-11
Z-11
E-11
Z-11
E-11
-
-
24
24
4.5
24
2
<1%
<1%
21%
<1%
37%
30%
<1%
<1%
8%
-
76%
75%
70%
76%
46%
60%
-
+
+
-
95%
-
2%
<1%
31%
31%
-
2
<1%
a
b
+ = 1 atm of ethylene was introduced into the headspace of the reaction vessel for 2 h prior to reaction. Determined by gas chromatography.
c
1
Determined by H NMR.
terminal olefins, and the productive CM reaction occurs
between two terminal olefin molecules. In the reaction shown
in Table 3 catalyzed by 5, it is proposed that a methylidene is
initially formed by homodimerization of 8-nonenyl acetate (14)
to form 12. This methylidene can then react with cis-5-decene
to form 1-hexene and the corresponding substituted alkylidene
(Scheme 4), both of which can react further with the terminal
olefin 8-nonenyl acetate to generate cross product 20. Since 8-
nonenyl acetate must initially be homodimerized for productive
CM to occur, larger amounts of 12 will be generated compared
to other catalysts, as was observed. It is also interesting to note
that because catalyst 3 is not particularly active as an
ethenolysis catalyst, CM reactions catalyzed by 3 seems to
proceed through different pathways that are more similar to
previous generations of ruthenium catalysts, like 2. To further
test these hypotheses, the reactions of two internal olefins in
the presence and absence of ethylene were attempted.
Exposure of catalyst 5 to a mixture of the internal olefins 5-
decene (11) and 12 (75% Z) under the conditions shown in
Table 4 led to no formation of cross product 20 regardless of
which isomer of 5-decene was employed (entries 1 and 2).31,32
However, addition of 1 atm of ethylene into the headspace of
the reaction vessel for 2 h followed by stirring for 4.5 h did lead
to formation of product 20 with cis-5-decene (entry 3). No
crossover was observed under these conditions when the trans-
isomer was used (entry 4). This again supports the hypothesis
that productive CM reactions involving internal olefins first
proceed via Z-selective ethenolysis. In contrast, under the same
conditions depicted in Table 4, catalyst 3 catalyzes the CM of
two internal olefins in the absence of ethylene regardless of
which isomer of 5-decene is employed (entries 5 and 6). Thus,
CM with catalyst 3 proceeds through a completely different
pathway and with this catalyst, trisubstituted ruthenacyclobu-
tane intermediates are accessible. The low E/Z ratio is again
attributed to extensive Z/E isomerization by secondary
metathesis processes as evidenced by the degradation of 12
from 75% to 46% of the Z-isomer.
and cleave the di- and trisubstituted ruthenacycle intermediates
involved in reactions catalyzed by chelated catalysts 5 and 3,
and the nonchelated catalyst 2. We first investigated the
metathesis reactions of two internal cis-olefins with catalysts 2,
3, and 5.33 To simplify the calculations, we used trimethyl
substituted ruthenacyclobutanes (i.e., the reaction of ruthenium
ethylidene with cis-2-butene) in the calculations as a model of
the long conformationally mobile substrates used experimen-
tally. Figure 4 shows the reactions of alkylidenes formed from
catalysts 2, 3, and 5 with cis-2-butene. In these reactions, trans-
2-butene is formed preferentially with catalyst 2, and catalysts 3
and 5 give cis-2-butene product.
Reaction with the unchelated catalyst 2 (Figure 4a) forms
trans-olefin product via the bottom-bound mechanism, i.e., the
olefin approaches trans to the NHC ligand.34,12 In the reactions
with chelated catalysts 3 and 5, the most favorable pathway
involves the side-bound mechanism (Figure 4b,c).11 The
activation barrier of the reaction catalyzed by 5 is 5.6 and 3.7
kcal/mol higher than that with catalysts 2 and 3, respectively.
The activation energy of the rate-determining transition state
TS51 is 14.1 kcal/mol with respect to the ruthenium alkylidene
complex 47. In the reactions with catalysts 2 and 3, the
activation energies are 8.5 and 10.4 kcal/mol, respectively
(TS40 and TS45). The overall barrier of the reaction with
catalyst 5 is likely to be higher than 14.1 kcal/mol, since the
catalyst resting state may be more stable than the energy zero in
the calculations (47). This suggests that formation of
trisubstituted ruthenacyclobutanes with catalyst 5 is much
more difficult than with catalysts 2 and 3, in agreement with the
observed low crossover reactivities of 5 (Table 4).
The low crossover reactivity of catalyst 5 is attributed to one
particular trisubstituted transition state, TS51, which is 4.4
kcal/mol less stable than the other trisubstituted transition state
TS48. In TS51, the ethylidene is syn to the α-hydrogen on the
chelating adamantyl group, while in TS48 the ethylidene is anti
to the α-hydrogen. Interestingly, TS51 is the only transition
state involving a nitrate ligand bound monodentate among all
the transition states investigated in this study. Its bidentate
isomer TS51′ is 0.8 kcal/mol less stable, which is in contrast to
Crossover Computational Studies. We employed
computations to determine the activation energies to form
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Figure 4. Reactions of ruthenium ethylidene complexes with cis-2-butene. These are the rate-determining steps in the metathesis of two cis internal
olefins in the absence of ethylene. Free energies and enthalpies (in parentheses) are given in kcal/mol with respect to the ruthenium alkylidene
complexes (37, 41, and 47, respectively). For clarity, the chelating adamantyl group is not shown in the 3D structures of TS48 and TS51.
other bidentate nitrate transition states that are typically 3 kcal/
mol more stable than corresponding monodentate nitrate TS.
To better illustrate the steric interactions with the nitrate
ligand, “side-views” of the di- and trisubstituted transition states
with catalyst 5 are shown in Figure 5. In the high energy
trisubstituted transition state TS51′, the nitrate is located
between the bulky chelating adamantyl group and one of the
methyl substituents on the olefin. The distances between the
nitrate and the olefin and between the nitrate and the
adamantyl group are both significantly shorter than the sum
of the van der Waals radii (the N−H distances are 2.57 and
2.51 Å, respectively, compared to the sum of van der Waals
radii of N and H, 2.75 Å). The steric repulsions of the anionic
nitrate ligand with the chelating adamantyl group and the
substituent on the olefin clearly destabilize the bidentate
transition state TS51′ and force the trisubstituted reaction to
proceed via a generally less favorable monodentate transition
state (TS51). As described earlier, the isomerization of the
metallacyclobutane intermediate is necessary for a productive
turnover. In the other trisubstituted metathesis transition state
TS48, the nitrate is located on the less crowded side that is syn
to the α-adamantyl hydrogen. In TS48, the nitrate−adamantyl
and nitrate−olefin distances are both longer than correspond-
ing distances in TS51′. With the diminished steric repulsions
with the nitrate, TS48 is 5.4 kcal/mol more stable than TS51′.
Thus, the rate-limiting step in the trisubstituted catalytic cycle is
TS51.
In the presence of ethylene, ruthenium methylidene
complexes are formed by the reaction of ethylene and
ruthenium alkylidenes. The reaction of ruthenium methylidene
21 with cis-2-butene proceeds through disubstituted transition
states TS22 and TS25 (Figure 2). TS22 and TS25 are both
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Figure 5. Side view of the dimethyl substituted transition states (TS22 and TS25) and the trimethyl substituted TS48 and TS51′. TS51′ is
destabilized due to steric repulsions of the nitrate with the chelating adamantyl group and the methyl group on the olefin.
Figure 6. Free energies and enthalpies (in parentheses) of the reaction of ruthenium methylidene complexes with cis-2-butene catalyzed by (a)
catalyst 2 and (b) catalyst 3. These are the rate-determining steps in the ethenolysis of internal olefins. All energies are with respect to the ruthenium
ethylidene complexes (37 and 41, see Figure 4) and are given in kcal/mol. See Figure 2 for the reaction catalyzed by catalyst 5.
more stable than the corresponding trisubstituted transition
states: TS22 is only 0.9 kcal/mol more stable than TS48
because of smaller steric repulsions of the internal olefin with
the methylidene than with the ethylidene (Figure 5). Replacing
the methyl substituent with hydrogen, TS25 is dramatically
stabilized by 6.3 kcal/mol compared to TS51′, due to
H
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alleviation of steric repulsions with the nitrate (see Figure 5 for
direct comparison of the structures of di- and trisubstituted
TS). The activation energy of the reaction of cis-2-butene with
this methylidene is 5.3 kcal/mol lower than the corresponding
pathway to form the trisubstituted ruthenacycle (ΔG⧧ = 8.8
kcal/mol, TS22 compared to 14.1 kcal/mol, TS51). Thus, in
the presence of ethylene, crossover products are formed, as was
observed experimentally, from the reaction of internal olefins
with the methylidene complex of catalyst 5 rather than with
corresponding alkylidene complexes.
The trisubstituted metathesis pathways with catalysts 2 and 3
were also calculated and shown in Figure 4a,b. In contrast to
the high activation barrier of the trisubstituted pathway with
catalyst 5, catalysts 2 and 3 both have lower activation barrier in
the trisubstituted reaction (ΔG⧧ = 8.5 and 10.4 kcal/mol,
respectively, compared to ΔG⧧ = 14.1 kcal/mol with 5). This is
attributed to less steric demand in the trisubstituted transition
states with these catalysts; the chelating mesityl group in
catalyst 3 is less bulky than the chelating adamantyl in 5. With
the unchelated catalyst 2, the olefin approaches from the
bottom, trans to the NHC ligand and thus there are no
unfavorable ligand−substrate steric repulsions in the transition
states.
As a comparison with the disubstituted pathway of catalyst 5
(Figure 2), we also computed the activation barriers of the
reactions of cis-2-butene and the ruthenium methylidenes
derived from catalysts 2 and 3 (Figure 6, panels a and b,
respectively). For the unchelated catalyst 2, the reaction of cis-
2-butene with methylidene 52 requires an activation energy of
8.9 kcal/mol. This is slightly higher than the barrier in the
reaction with corresponding ethylidene 37 (ΔG⧧ = 8.5 kcal/
mol, Figure 4a). This is attributed to fact that ruthenium
methylidene 52 is 5.8 kcal/mol less stable than corresponding
ethylidene 37 as well as the absence of unfavorable ligand-
substrate steric repulsions in the trisubstituted transition states.
The reaction of cis-2-butene with the methylidene complex of
catalyst 3 (56) requires a slightly lower activation energy than
corresponding ethylidene (41) (ΔG⧧ = 8.7 kcal/mol compared
to 10.4 kcal/mol). With both catalysts 2 and 3, the differences
between di- and trisubstituted activation barriers are within 1−2
kcal/mol. This suggests that the rate of crossover of internal
olefins will not be significantly affected by the exposure to
ethylene.
To complete the computational investigations, another two
scenarios involving disubstituted ruthenacyclobutanes, homo-
dimerization and nonproductive metathesis of terminal olefins,
were also computed and the detailed results are provided in the
Supporting Information. The homodimerization pathways of
propene to form E- or Z-2-butene with catalysts 2, 3, and 5 are
shown in Figure S1, and the competing nonproductive
reactions of propene and ruthenium ethylidenes are shown in
Figure S2.35 The computations predicted that the non-
productive equilibration with catalysts 2 and 3 both requires
lower activation barrier than the corresponding productive
homodimerization pathway. In contrast, with catalyst 5, the
nonproductive pathway requires 1.5 kcal/mol higher activation
energy than homodimerization (12.7 kcal/mol compared to
11.2 kcal/mol, see Supporting Information for details). Similar
to the trisubstituted transition state, the 1,3-disubstituted
nonproductive transition state is destabilized by steric
repulsions with the nitrate, which is also located between the
adamantyl and the methyl substituent on the olefin.
CONCLUSION
■
In summary, we have investigated the ethenolysis behavior of a
new class of ruthenium metathesis catalysts, 3 and 5, containing
chelating NHC ligands. Catalyst 5 was found to catalyze Z-
selective ethenolysis reactions at low ethylene pressures (1−5
atm) with substrates containing a wide variety of functional
groups. DFT calculations showed that the Z-selectivity in
ethenolysis reactions catalyzed by 5 is a result of steric effects
that prohibit E-olefins from productively reacting with the
corresponding methylidene. Two internal olefins could not
undergo CM in the presence of 5 to form cross products but
must first react with ethylene to form terminal olefins. In
addition to this, no crossover was observed when trans-internal
olefins were employed as substrates in CM reactions. This
implies that the Z-selective ethenolysis behavior of 5 plays a
large role not only in its ethenolysis reactivity, but also in its
CM reactivity. In contrast, catalyst 3 containing a six-membered
chelate exhibited poor ethenolysis reactivity and was capable of
catalyzing the crossover of two internal olefins in the absence of
ethylene, and thus reacts by a different pathway compared to 5.
DFT calculations revealed the origins of the different
reactivities of catalysts 3 and 5 in the crossover of internal
olefins. The low crossover reactivity of two internal olefins with
catalyst 5 is attributed to the steric repulsions of the nitrate
anionic ligand with the chelating adamantyl group and the
olefin substituent in the trisubstituted metathesis transition
state. In ethenolysis reactions with catalyst 5, similar steric
control also prevents the ruthenium alkylidene from reacting
with internal olefins. In contrast, the most favorable ethenolysis
pathway catalyzed by 5 involves the reaction of an internal
olefin with a ruthenium methylidene to avoid trisubstituted
metathesis transition states. Catalyst 3 has a smaller mesityl
chelating group, and thus the steric repulsions with the anionic
ligand are diminished, making it capable to productively form
and cleave trisubstituted metallacycles.
The elucidation of a functional-group-tolerant ruthenium
metathesis catalyst capable of performing Z-selective ethenol-
ysis at ethylene pressures as low as 1 atm should enable the
widespread use of this technology in academic and industrial
settings. In addition to providing important insight into the
ethenolysis behavior of catalyst 5, a better understanding of its
CM reactivity has been gained and should provide important
information for researchers planning on using this catalyst for a
variety of applications. It is envisioned that the further
development of new Z-selective catalysts should make this Z-
selective ethenolysis methodology even more selective and
efficient.
ASSOCIATED CONTENT
* Supporting Information
Experimental details, NMR spectra, optimized Cartesian
coordinates and energies, details of computational methods,
and complete reference of Gaussian 09. This material is
available free of charge via the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
rhg@caltech.edu; houk@chem.ucla.edu
■
Author Contributions
§H.M. and M.B.H. contributed equally.
Notes
The authors declare no competing financial interest.
I
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ACKNOWLEDGMENTS
■
Dr. David VanderVelde is thanked for his assistance with NMR
characterization and experiments. This work was financially
supported by the NIH (NIH 5R01GM031332-27, R.H.G.), the
NSF (CHE-1048404, R.H.G. and CHE-1059084, K.N.H.), the
NDSEG (fellowship to B.K.K.), and Mitsubishi Tanabe Pharma
Corporation (H.M.). Materia, Inc. is acknowledged for its
generous donation of metathesis catalysts. Calculations were
performed on the Hoffman2 cluster at UCLA and the Extreme
Science and Engineering Discovery Environment (XSEDE),
which is supported by the National Science Foundation (OCI-
1053575).
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(17) It should be noted that the volatility of the generated 1-hexene
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(20) The reactivity differences between 5 and 1 can be partially
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meaning that neat reactions could not be performed as with catalyst 5.
The necessary addition of solvent to these reactions seemingly reduced
the activity of catalyst 5.
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used to purify products from reactions other than metathesis that
produce E-olefins but that are not perfectly selective for their
formation.
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(27) Isomerization of 23 to 24 occurs via monodentate nitrate
complexes. See Supporting Information for details.
(28) Theoretical calculations predicted higher Z-selectivity than what
the observed relative rates of E and Z olefins would suggest.
(29) It should be noted that catalyst 4 was also not able to catalyze
the CM of two internal olefins and, as such, we believe that
trisubstituted metallacycle intermediates are also unfavorable.
(30) For catalyst 4, it is thought that formation of a methylidene is
possible and that the reaction proceeds via the same mechanism as
with 5, but reaction with a large excess of ethylene leads to
decomposition.
(31) Raising the temperature from 35 to 80 °C did not affect
reactivity as formation of 20 was still not observed.
(32) This suggests that the self-metathesis processes outlined in
Scheme 1 are prevented, helping explain the high selectivity observed
in the ethenolysis of methyl oleate by catalyst 5.
(33) To simplify calculations, an analog of catalyst 3 where the
pivalate ligand is replaced by an acetate ligand was used for modeling.
(34) The competing pathway to form cis-2-butene requires a barrier
of 8.7 kcal/mol, only 0.2 kcal/mol higher than the trans pathway,
indicating poor Z/E-selectivity from kinetic control.
(35) Computational studies of olefin homodimerization with
catalysts 2, 4, and 5 have already been reported (see ref 11). Here
we repeated some of the computations to make direct comparisons
between different catalysts and between productive and nonproductive
metathesis.
K
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