Improved ruthenium catalysts for Z-selective olefin metathesis

Article abstract of DOI:10.1021/ja210225e

Several new C-H-activated ruthenium catalysts for Z-selective olefin metathesis have been synthesized. Both the carboxylate ligand and the aryl group of the N-heterocyclic carbene have been altered and the resulting catalysts evaluated using a range of metathesis reactions. Substitution of bidentate with monodentate X-type ligands led to a severe attenuation of metathesis activity and selectivity, while minor differences were observed between bidentate ligands within the same family (e.g., carboxylates). The use of nitrato-type ligands in place of carboxylates afforded a significant improvement in metathesis activity and selectivity. With these catalysts, turnover numbers approaching 1000 were possible for a variety of cross-metathesis reactions, including the synthesis of industrially relevant products.

Full text of DOI:10.1021/ja210225e

Article
pubs.acs.org/JACS
Improved Ruthenium Catalysts for Z-Selective Olefin Metathesis
Benjamin K. Keitz,‡ Koji Endo,‡ Paresma R. Patel, Myles B. Herbert, and Robert H. Grubbs*
Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125, United States
S
* Supporting Information
ABSTRACT: Several new C−H-activated ruthenium catalysts
for Z-selective olefin metathesis have been synthesized. Both
the carboxylate ligand and the aryl group of the N-heterocyclic
carbene have been altered and the resulting catalysts evaluated
using a range of metathesis reactions. Substitution of bidentate
with monodentate X-type ligands led to a severe attenuation of
metathesis activity and selectivity, while minor differences were
observed between bidentate ligands within the same family
(e.g., carboxylates). The use of nitrato-type ligands in place of
carboxylates afforded a significant improvement in metathesis
activity and selectivity. With these catalysts, turnover numbers
approaching 1000 were possible for a variety of cross-metathesis reactions, including the synthesis of industrially relevant
products.
INTRODUCTION
■
Olefin metathesis is a powerful tool for the construction of new
carbon−carbon bonds.1 The development of robust metathesis
catalysts,2 which carry out this transformation, has facilitated
the adoption of this methodology by a variety of fields
including polymer chemistry,3 organic synthesis,4 biochemis-
try,5 and green chemistry.6 However, the synthesis of cis- or Z-
olefins via olefin metathesis has persisted as a significant
challenge. The attempts to address this problem can generally
be divided into two areas, catalyst control and substrate control,
with examples of the latter recently achieving notable
Figure 1. Catalysts 1−11: Ar = 2,4,6-trimethylbenzene (7), 2,6-
diethyl-4-methylbenzene (8), 2,6-dimethyl-4-methoxybenzene (9),
successes.7 Selectivity via catalyst design, on the other hand,
is much more challenging since the majority of catalysts prefer
the thermodynamically favored E-olefin. It was not until the
pioneering work of Schrock and Hoveyda that a catalyst-
controlled system for the synthesis of Z-olefins via metathesis
was finally realized.8 As a complement to their work, we sought
to develop a functional group tolerant, ruthenium-based
catalyst with similar levels of activity and selectivity.
2,6-dimethyl-4-chlorobenzene (10); Mes = 2,4,6-trimethylbenzene;
DIPP = 2,6-di-isopropylbenzene.
group is critical for achieving high levels of Z-selectivity.9a
Unfortunately, our attempts to make more drastic alterations
have mostly led to decomposition during the C−H activation
step.12 As a consequence of attempting to change the
adamantyl group in 2 with little success, we turned our
attention to the carboxylate ligand and to the aryl group on the
N-heterocyclic carbene (NHC). Thus, exchanging the pivalate
group in 2 for other bi- (κ2) and monodentate (κ1) ligands, and
the mesityl for various aryl groups, has resulted in several new
derivatives that yield important insight into the reactivity and
selectivity of this class of catalysts (Figure 1). Here, we report
on the synthesis and selectivity of these new catalysts and
demonstrate that several are capable of turnover numbers
Recently, we reported on the synthesis and activity of a
ruthenium metathesis catalyst containing a Ru−C bond formed
via carboxylate-induced intramolecular C−H activation (2).9
Structurally similar complexes have previously been isolated as
metathesis decomposition products, but none were metathesis
active.10 Thus, we were surprised to discover that 2 not only
was metathesis active but also showed unprecedented
selectively for Z-olefins in a variety of cross-metathesis
reactions.
Due to the dynamic nature of ruthenacyclobutanes,11
particularly when compared to molybdacycles and tungsta-
cycles, the origin of the Z-selectivity in 2 has remained unclear.
Nonetheless, structure−function relationships derived from
systematic changes of 2 have demonstrated that the adamantyl
Received: October 31, 2011
Published: November 19, 2011
© 2011 American Chemical Society
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Journal of the American Chemical Society
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(TONs) approaching 1000 in cross-metathesis reactions while
maintaining excellent Z-selectivity.
RESULTS
■
We initiated our studies by examining a range of ligands in
place of the previously reported carboxylate 2. However, bulky
carboxylates, such as pivalate, appear to be the only
carboxylates capable of inducing the intramolecular C−H
activation event necessary to form 2. As such, a new synthetic
route was developed in order to access analogues of 2
possessing different X-type ligands. We found that reacting 2
with NaI in THF cleanly afforded the iodo complex 3 that
could then be used to prepare a wide range of catalysts via
transmetalation with various silver salts (Scheme 1). Catalysts
Figure 2. Solid-state structure of 7, with thermal ellipsoids drawn at
50% probability. Selected bond lengths (Å) for 7: C1−Ru 1.961,
C13−Ru 2.057, C23−Ru 1.838, O1−Ru 2.320, O2−Ru 2.367, O3−Ru
2.209.
Scheme 1. Preparation of Catalysts 3−6
a
Table 1. Initiation Rates for Catalysts 1−11
catalyst
temp, °C
initiation rate constant, 10−3 s−1
1
30
30
50
30
30
30
30
30
30
30
70
7.2 0.2
0.87 0.02
0.17 0.01
6.9 0.3
2
3
with monodentate X-ligands were obtained in a similar manner.
Notably, the nitrato complex 7 could be formed either by
reaction of 3 with AgNO3 or by direct reaction of 2 with
NH4NO3, with the latter route being preferred (Scheme 2).
4
5
0.17 0.04
2.5 0.1
6
7
0.84 0.03
0.77 0.05
0.76 0.02
0.24 0.05
8
Scheme 2. Preparation of Catalysts 7 and 11
9
10
11
b
<0.39
a
Initiation rate constants were determined by measuring the decrease
1
in the benzylidene resonance using H NMR spectroscopy following
addition of BVE. Conditions were catalyst (0.003 mmol) and BVE
b
(0.09 mmol) in C6D6 (0.6 mL) at given temperature. Value based on
single half-life of 11.
or more orders of magnitude for the examined catalysts! The
most striking difference was observed between the catalysts
containing bidentate (2, 4−10) and monodentate (3, 11)
ligands. Whereas the bidentate complexes possessed initiation
rates comparable to that of 1, complexes 3 and 11 initiated at
significantly slower rates, even at higher temperatures. In
particular, 11 showed almost no reactivity with BVE, even at
temperatures as high as 70 °C. From these data, we anticipated
that the catalysts with monodentate ligands would be essentially
metathesis inactive (vide infra).
Single-crystal X-ray diffraction revealed that the nitrato ligand
of 7 is coordinated in a bidentate fashion analogous to 2
(Figure 2). Structural parameters, including bond lengths and
angles, were also consistent between 2 and 7.
The aryl substituent on the NHC (8−10) was varied through
straightforward ligand synthesis, followed by metalation and
C−H activation effected by silver pivalate (see the Supporting
Information). In all cases, the pivalate was immediately
exchanged for nitrate, since the nitrato complexes were
generally more stable and easier to isolate. Only subtle steric
and electronic modifications were introduced in the aryl group,
as we found that the C−H activation reaction is sensitive to
more drastic changes, mainly resulting in decomposition.13
Initiation Rates. With a relatively diverse library of
catalysts in hand, we began examining their reactivity in a
range of olefin metathesis reactions. Reaction with butyl vinyl
ether (BVE) was chosen as the first probe of catalyst activity
since this reaction is commonly used to measure the initiation
rate of ruthenium catalysts.14 As shown in Table 1, the
initiation rate, measured by 1H NMR spectroscopy, varied by 2
Besides the differences between κ1 and κ2 ligands, several
significant changes in initiation rate constant were observed
between various bidentate ligands. For instance, exchanging
pivalate (2) for the more electron donating 2,2-dimethox-
ypropanoate (6) led to a small increase in the rate constant.
When the steric bulk of the carboxylate was increased (4) or
decreased (5), initiation rate constants increased and decreased,
respectively. This last result was surprising since, in general,
complexes with Hoveyda-type chelates are thought to initiate
through an associative or associative-interchange mecha-
nism.14c,d Thus, increasing the steric bulk of the carboxylate
should have resulted in a decrease in the initiation rate con-
stant due to the less favorable steric environment around
the metal. The exact opposite was observed with the larger
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2,2-dicyclohexylacetate (4), possessing a higher initiation rate
than smaller carboxylate ligands (2, 5, and 6). Notably, electro-
nic effects play an important role, as evidenced by the dif-
ferences between 6 and 2; thus, complexes of this type likely
initiate through a different mechanism. Finally, the nitrato
complexes 7−9 had approximately the same initiation rate as 2,
while that of 10 was slightly smaller. These results indicate that
minor changes to the aryl group do not have a substantial effect
on the rate of initiation of these catalysts.
Table 3. Homodimerization of Methyl 10-Undenenoate
a
(15)
b
b
catalyst
loading, mol %
time, h
conv,
%
Z, %
Cross-Metathesis. We next turned to evaluating these
complexes in the homodimerization of allyl benzene (12).
While this reaction is relatively facile for most metathesis
catalysts, it provided a useful benchmark to assess the
performance of our catalyst library (Table 2). Reactions were
2
4
5
6
0.1
2
12
6
16
67
3
90
81
0.1
0.1
12
12
>95
>95
8.4
a
Conditions were catalyst (0.1−2 mol %) in THF (3 M in 15) at 35
b
1
°C. Determined by H NMR spectroscopy.
a
Table 2. Homodimerization of Allyl Benzene (12)
b
b
b
catalyst
time, h
conv,
%
Z-13,
%
13/14
2
3
12
12
12
12
3
79
59
7
>95
−
>95
42
c
3
0
4
0.5
1.4
5
65
26
90
90
91
90
>95
92
6
>95
91
3.8
7
18.4
18.1
16.9
33.6
8
3
93
9
3
93
10
11
3
94
c
12
−
0
a
Conditions were catalyst (1 μmol) and 12 (1 mmol) in THF (0.2
b
c
1
mL) at 35 °C. Measured by H NMR spectroscopy. No detectable
amount of 13.
Figure 3. Time-course plot for the conversion (A) and selectivity (B)
of homodimerization of 15 to 16 using catalysts 7−10. Conditions
were 15 (1 mmol) and catalyst (1 μmol) in THF (0.1 mL) at 35 °C.
Data points and error bars were calculated from the average and
standard deviation of three separate runs.
run in THF at 35 °C with a relatively high substrate
concentration (ca. 3 M in 12) and 0.1 mol % catalyst loading
for a set amount of time, at which point the conversion and
1
percentage of Z-olefin were measured by H NMR spectros-
performed well in the reaction with 12 were examined, namely
the carboxylate and nitrato catalysts. Similar to the homodime-
rization of 12, low loadings were used to differentiate the
catalysts. We were pleased to discover that even at 0.1 mol %
loading, most of the catalysts were able to achieve an
appreciable degree of conversion. The exception was catalyst
4, which showed no conversion until the catalyst loading was
increased to 2 mol %. Similar to the reaction with 12, catalysts
4−6 performed relatively poorly, while 2 and 7−10 furnished
the best results. In fact, catalysts 7−10 showed excellent
conversion (>90%) at short reaction times and low catalyst
loading (0.1 mol %) with good selectivity for the Z-olefin (90−
95%, Figure 3). This is a clear demonstration of their superior
activity and selectivity. A time-course monitoring of the
reaction of 15 with catalysts 7−10 revealed some subtle
differences between the nitrato catalysts (Figure 3). Specifically,
there were only slight variations in both conversion and Z-
selectivity for catalysts 7−9, which is consistent with the
initiation rate constants measured for these catalysts and their
reactivity with 12. At shorter reaction times, 10 showed slightly
reduced reaction conversion compared to its analogues, which
is likely a consequence of its slower initiation rate. Nonetheless,
given enough time, 10 was able to reach similar levels of
copy. Low catalyst loadings were used to emphasize the
differences between catalysts. In most cases, a detectable
amount of olefin isomerization byproduct 14 was observed, but
the amount of this undesired product and the total conversion
of 12 varied significantly between catalysts. Catalysts 3 and 11
yielded the largest amount of 14; moreover, this was the only
detectable product for these catalysts. Among the carboxylate-
based catalysts, 4 was the least active, giving low conversion of
12 and poor selectivity for 13. Furthermore, no notable
improvement was observed with complexes 5 and 6. Both 2
and 7−10 showed excellent conversion of 12 and good
selectivity for 13, with catalysts 7−10 taking only 3 h to reach
∼90% conversion. In addition, these catalysts were able to
maintain very high Z-selectivity, even at high levels of
conversion. Catalysts 7−10 afford similar conversions of 12
compared to 2 and are clearly the most efficient of the catalysts
examined, as they are able to achieve high conversion with good
selectivity for the Z-isomer of 13 while forming only a marginal
amount of the undesired product 14.
In order to further differentiate the performance of the
catalysts, the more challenging substrate methyl 10-undece-
noate (15) was examined in the homodimerization reaction
(Table 3, Figure 3). For this reaction, only the catalysts that
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conversion as 7−9. Finally, the time-course study demonstrates
that, at least for this substrate, secondary metathesis events are
relatively slow, as Z-selectivity remains high even after extended
periods of time at ca. 90% conversion.15
The two aforementioned metathesis assays clearly demon-
strated the superior activity of the nitrato catalysts 7−10 over
the carboxylate analogues. However, it was still unclear if this
effect was specific to the chosen substrates. To fully evaluate
the effectiveness of 7−10, several other substrates, including
alcohols, were examined (Table 4). For the majority of these
reaction between 12 and cis-1,4-diacetoxybutene (24).16 Similar
to the case of olefin homodimerization, lowering the temper-
ature and increasing the substrate concentration resulted in
higher conversion to the desired product (25) with comparable
selectivity for the Z-olefin (Table 5). For this assay, all of the
carboxylate catalysts performed roughly the same, reaching
TON ≈ 15; however, significant amounts of 13 were also
formed in each reaction. In contrast, 7 was able to achieve
similar levels of conversion at catalyst loadings as low as 1 mol
%. Furthermore, since 24 possibly interferes with 7, as shown
by the low TONs achieved in the homodimerization of 19, we
suspected that a judicious choice of substrates would allow for
the catalyst loading to be lowered even further.
a
Table 4. Homodimerization of Terminal Olefin Substrates
Subsequently, we selected 28 (Scheme 3) as a synthetic
target because of its industrial relevance in insect pest control
and the fact that the functionality is far removed from the
olefin. Insect pheromones similar to 28 have been prepared via
olefin metathesis before, but those containing Z-olefins have
largely eluded this methodology.17 Thus, the preparation of 28
represented an opportunity to demonstrate the high activity
and selectivity of 7 in an industrially relevant reaction.
Gratifyingly, reaction of 26 with 27 to form 28 proceeded in
high yield (77%) with catalyst loadings as low as 0.5 mol % and
with excellent selectivity (>90%) for the Z-product (Scheme
3).18 More importantly, the use of 7 in this reaction allows for
the preparation of 28 in one step, as opposed to the previously
reported six-step synthesis.19 Thus, catalysts such as 7 should
allow for the efficient synthesis of Z-olefin-containing
pheromones and other natural products via metathesis with
minimal catalyst loadings.
b
c
substrate
catalyst
time, h
Z,
%
yield, %
12
2
3
3
3
3
3
86
73
91
91
83
89
7
92
94
95
95
8
9
10
15
2
12
12
12
12
12
90
91
92
92
94
13
85
94
92
75
7
8
9
10
17 1-octene
2
7
12
12
94
92
30
83
DISCUSSION
■
18 4-penten-1-ol
2
12
12
8
43
81
73
78
85
81
67
78
76
75
As mentioned above, we have previously established that the
adamantyl group in catalysts 2−11 is critical for achieving high
levels of Z-selectivity.9a The results presented here clearly
demonstrate that the other X-type ligand plays an important
role in reactivity, stability, and selectivity as well. The best
demonstration of the significance of this ligand is the observed
difference in initiation rates, where catalysts containing
monodentate ligands (3 and 11) were essentially unreactive.
This result implies that bidentate ligands are unique in their
ability to induce catalyst initiation. Although ruthenium
catalysts containing carboxylate20 or nitrato21 ligands are well-
known, to the best of our knowledge, there has been no report
on their initiation behavior, at least for Hoveyda-type systems.
However, analogues of 1 containing carboxylate or other
bidentate ligands are generally metathesis active,22 which is an
indication that special ligands are not required for standard
catalysts to initiate. It is also worth noting that the replacement
of chlorides or carboxylates with nitrate in other ruthenium
complexes generally resulted in less active and less selective
metathesis catalysts. Thus, the C−H-activated catalysts, which
show the opposite trend, appear to be unique in this regard.
A more general understanding of catalyst initiation can be
gained by considering the differences in rates between
complexes within the same family (e.g., carboxylates). For
instance, electron-donating and bulky groups resulted in an
increase in initiation rate, while smaller groups led to a
decrease. Considering these results, it would have been
interesting to probe the effect of electron-withdrawing
carboxylates (e.g., trifluoroacetate); however, we found that
such complexes were unstable and immediately decomposed
upon anion exchange.23 Overall, the differences in initiation
7
8
9
8
10
8
d
19 Allyl acetate
20 N-allylaniline
7
7
7
7
7
12
12
12
3
>95
90
8
12
30
36
14
21 2-(allyloxy)ethanol
22 Allyl pinacol borane
23 Allyl TMS
67
>95
>95
9
a
Conditions were catalyst (5 μmol) and substrate (5 mmol) in THF (ca.
1.7 mL) at 35 °C. Determined by H NMR spectroscopy. Isolated
yield after chromatography. Conversion, yield not determined.
b
c
1
d
reactions, catalysts 7−10 were easily capable of reaching TON
> 500, in some cases coming close to 1000. Notably, the yields
presented in Table 4 are calculated on the basis of isolated yield,
meaning that the actual TONs are likely to be higher. Certain
substrates, such as 19 and 20, were less reactive and resulted in
reduced TONs. At this time, we believe this attenuation is not a
result of the functional group itself but of its proximity to the
reacting olefin. Nevertheless, the TONs for these substrates are
still respectable. The nitrato complexes 7−10 showed almost
no significant differences in either conversion or Z-selectivity
for the substrates where they were directly compared.15 Finally,
the selectivity for the Z-olefin was excellent in almost every
case, demonstrating the superiority of these catalysts.
Having established the effectiveness of 7 in several
homodimerization reactions, we turned our attention to more
complex reactions including the “standard” cross-metathesis
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a
Table 5. Cross-Metathesis of 12 and 24
b
b
b
b
catalyst
loading, mol %
5
time, h
temp, °C
conv to 25,
%
Z-25,
%
conv to 13,
%
Z-13,
%
2
9
6
70
35
37
50
89
86
26
19
96
>95
4
6
5
5
6
9
70
35
48
45
82
87
33
23
91
>95
3
6
70
35
57
64
75
79
42
22
94
>95
5
7
5
1
7
9
35
35
54
58
83
91
17
28
>95
>95
a
b
Conditions were catalyst, 12 (1 equiv), and 24 (2 equiv) in THF (0.5 M in 12). Determined by gas chromatography with tridecane as internal
standard.
Scheme 3. Synthesis of 28 Using Catalyst 7
In contrast to the various carboxylate ligands, changes to the
aryl group on the NHC had little to no effect on catalyst
initiation and activity. One exception was the replacement of
mesityl (7) with 2,6-dimethyl-4-chlorobenzene (10), which
results in a marginal attenuation of initiation rate. Nonetheless,
this only slightly affects catalytic activity, as evidenced by the
small differences in turnover frequency between 7 and 10. As
mentioned earlier, we have been unable to access aryl groups
significantly different from mesityl due to decomposition upon
attempted C−H activation. For instance, we have demonstrated
that ortho substitution of the aryl ring is required to prevent
undesired C−H activation and subsequent decomposition.12
The remote nature of this part of the NHC ligand makes the
predictability of structural effects on catalyst activity and
selectivity difficult.25 Additionally, the unpredictability asso-
ciated with the synthesis of C−H-activated catalysts with
different N-aryl groups renders such modifications less
convenient for catalyst optimization.
In actual cross-metathesis reactions, the nitrato catalysts 7−
10 were the best catalysts in terms of both activity and
selectivity. At this time, we believe this is a result of the nitrato
ligand imparting greater stability to the complex compared with
carboxylates. Qualitatively, 7−10 were far more tolerant to
oxygen than the carboxylate analogues and also easier to
purify.26 The reasons for this enhanced stability are unclear at
this time, but there are clearly substantial steric and electronic
effects at play. The enhanced stability of the nitrato catalysts
also influences the balance between conversion and Z-
selectivity over the course of the reaction.
As with Mo- and W-based catalysts, the relationship between
conversion and Z-selectivity is critical and warrants further
discussion.8c At low reaction conversions, 7 is almost perfectly
selective for the Z-olefin. Unfortunately, as conversion
increases, Z-selectivity decreases at a rate dependent on the
nature of the substrate and the catalyst, although it typically
stays above 70%.15 An illustration of this phenomenon was
presented in Table 4, specifically, the homodimerization of 18
with 2 and 7. The observed decrease in selectivity may be due
to secondary metathesis events or hydride-induced olefin
isomerization.27 A secondary metathesis mechanism would
require the generation of a nonselective metathesis-active
decomposition product, since the initial catalyst is very
rates between catalysts with different carboxylates imply that a
simple associative or associative-interchange mechanism is not
occurring and that catalysts such as 2 likely undergo multiple
pre-equilibrium steps (e.g., an equilibrium between κ2 and κ1
coordination, and an equilibrium between association and
dissociation of the chelated oxygen) prior to reaction with
olefin.
Unfortunately, while our initiation rate studies allowed us to
identify poor or unreactive catalysts (e.g., with monodentate
ligands), they have not correlated well with actual metathesis
reactivity. Consider, for instance, the negligible difference in
initiation rates between 1 and 4. From this result, we predicted
that these two complexes might have similar reactivity. A time-
course plot for the conversion of cyclooctadiene during ring-
opening metathesis polymerization revealed that this is clearly
not the case (Figure S4). Catalyst 1 is able to complete this
reaction within minutes, while 4 reacts over a period of hours
and never reaches full conversion. Furthermore, when
compared with 2 and 7, 4 is clearly inferior in both activity
and selectivity, despite its greater initiation rate.
Therefore, simply increasing the initiation rate of this class of
catalysts will not necessarily result in increased activity. On the
other hand, decreasing the initiation rate does not result in an
improved catalyst either. In the extreme case, this was shown by
the inactivity of monodentate ligands, but it was also
demonstrated by the lower activity of 5. These observations
parallel the behavior of previous generations of ruthenium
metathesis catalysts.14a Although a complete mechanistic
understanding of initiation for C−H-activated catalysts remains
unclear, the observed discrepancies between initiation rates and
actual metathesis activity can most likely be explained by the
fact that the method used to measure initiation does not take
into account either the reversibility of metathesis reactions or
degenerate metathesis events.24 Both of these factors likely have
a significant effect on the reactivity of C−H-activated catalysts,
particularly in cross-metathesis reactions.
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109, 3708. (c) Vougioukalakis, G. C.; Grubbs, R. H. Chem. Rev. 2010,
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selective. Several possible structures can be envisioned, the
most likely of which would be a catalyst resulting from cleavage
of the Ru−C (adamantyl) bond. Thus far, we have been unable
to detect or isolate any species which may be responsible for
secondary metathesis. On the other hand, the existence of
ruthenium hydrides can be inferred by the observation of olefin
migration in the reaction of 12. Moreover, these species can
(3) (a) Leitgeb, A.; Wappel, J.; Slugovc, C. Polymer 2010, 51, 2927.
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1
also be detected by H NMR spectroscopy under specific
conditions.28 We have attempted to suppress the generation of
hydride species with various chemical quenchers but have been
unable to achieve this thus far.29 Consequently, the design of
new catalysts that are less susceptible to either secondary
metathesis or hydride formation is of paramount importance.
For now, individual researchers must prioritize either
conversion or Z-selectivity with substrates that are more
susceptible to isomerization.
(7) (a) Wang, Y.; Jimenez, M.; Hansen, A. S.; Raiber, E.-A.;
Schreiber, S. L.; Young, D. W. J. Am. Chem. Soc. 2011, 133, 9196.
(b) Gallenkamp, D.; Furstner, A. J. Am. Chem. Soc. 2011, 133, 9232.
̈
(8) (a) Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am.
Chem. Soc. 2009, 131, 16630. (b) Marinescu, S. C.; Schrock, R. R.;
Muller, P.; Takase, M. K.; Hoveyda, A. H. Organometallics 2011, 30,
̈
In summary, we have prepared a variety of new C−H-
activated ruthenium catalysts for Z-selective olefin metathesis.
Adjusting the ligand environment around the metal center has
yielded significant insight into the initiation behavior, activity,
and selectivity of this class of catalysts and has facilitated the
development of improved catalysts (7−10) that are capable of
ca. 1000 turnovers in several cross-metathesis reactions. We
note that these catalysts can be used with very low loadings and
do not require reduced pressures, high temperatures, or
rigorous exclusion of protic solvents in order to operate
effectively. Secondary metathesis events are also relatively slow
for the majority of substrates, meaning that significant reaction
optimization should not be required. On the basis of these
attributes, we anticipate that catalysts such as 7 will be swiftly
adopted by both industrial and academic researchers interested
in the construction of Z-olefins using metathesis methodology.
1780. (c) Meek, S. J.; O’Brien, R. V.; Llaveria, J.; Schrock, R. R.;
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D. S.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2011,
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ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental and synthetic details as well as NMR spectra and
a CIF file. This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) A more thorough analysis of decomposition structures related to
2 will be reported in a subsequent communication.
AUTHOR INFORMATION
■
(13) For instance, both Ar = 2,6-di-isopropylphenyl and 3,5-tert-
butylphenyl formed unstable complexes upon exposure of the
precursors to silver pivalate.
(14) (a) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc.
2001, 123, 6543. (b) Hejl, A. Ph.D. Dissertation, California Institute of
Technology, 2007. (c) Vorfalt, T.; Wannowius, K.-J.; Plenio, H. Agnew.
Chem., Int. Ed. 2010, 1, 5533. (d) Ashworth, I. W.; Hillier, I. H.;
Nelson, D. J.; Percy, J. M.; Vincent, M. A. Chem. Commun. 2011, 47,
5428.
(15) Time-course plots for substrates 12 and 18 can be found in the
Supporting Information.
(16) Ritter, T.; Hejl, A.; Wenzel, A. G.; Funk, T. W.; Grubbs, R. H.
Organometallics 2006, 25, 5740.
Corresponding Author
rhg@caltech.edu
Author Contributions
‡These authors contributed equally.
ACKNOWLEDGMENTS
■
Lawrence Henling and Dr. Michael Day are acknowledged for
X-ray crystallographic analysis. Dr. David VanderVelde is
thanked for assistance with NMR experimentation and analysis.
This work was financially supported by the NIH (NIH
5R01GM031332-27), the NSF (CHE-1048404), Mitsui
Chemicals, Inc. (K.E.), and the NDSEG (fellowship to
B.K.K.). Instrumentation on which this work was carried out
were supported by the NSF (X-ray diffractometer, CHE-
0639094) and the NIH (NMR spectrometer, RR027690).
Materia, Inc. is thanked for its donation of metathesis catalysts.
(17) (a) Banasiak, D. S. J. Mol. Catal. 1985, 28, 107. (b) Pederson, R.
L.; Fellows, I. M.; Ung, T. A.; Ishihara, H.; Hajela, S. P. Adv. Synth.
Catal. 2002, 344, 728. (c) Mol, J. J. Mol. Catal. A: Chem. 2004, 213, 39.
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El-Sayed, A. M. Tetrahedron 2010, 66, 2642.
(18) The stereochemistry of 28 was confirmed by 1H and 13C NMR
spectroscopy in conjunction with 2D techniques including COSY and
HSQC. Further confirmation was obtained using IR spectroscopy. See
the Supporting Information for details.
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