Cyclometalated Z-Selective Ruthenium Metathesis Catalysts with Modified N-Chelating Groups

Article abstract of DOI:10.1021/acs.organomet.5b00185

In order to design improved ruthenium catalysts for Z-selective olefin metathesis reactions, four cyclometalated catalysts with new chelated architectures were synthesized, structurally characterized, and tested in metathesis assays. The mechanism of formation of each was explored using DFT calculations. Of note, two complexes are derived from activation of a tertiary C-H bond, and one features a four-membered chelating architecture. In addition, two dipivalate complexes that did not undergo further C-H activation were isolated and studied to elucidate information about the factors affecting cyclometalation.

Full text of DOI:10.1021/acs.organomet.5b00185

Article
pubs.acs.org/Organometallics
Cyclometalated Z‑Selective Ruthenium Metathesis Catalysts with
Modified N‑Chelating Groups
Myles B. Herbert,†,§ Benjamin A. Suslick, Peng Liu, Lufeng Zou, Peter K. Dornan, 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, United States
*
S Supporting Information
ABSTRACT: In order to design improved ruthenium catalysts for Z-
selective olefin metathesis reactions, four cyclometalated catalysts with
new chelated architectures were synthesized, structurally characterized,
and tested in metathesis assays. The mechanism of formation of each
was explored using DFT calculations. Of note, two complexes are
derived from activation of a tertiary C−H bond, and one features a four-
membered chelating architecture. In addition, two dipivalate complexes
that did not undergo further C−H activation were isolated and studied
to elucidate information about the factors affecting cyclometalation.
INTRODUCTION
Scheme 1. Salt Metathesis and Carboxylate Assisted C−H
Activation To Produce Cyclometalated Catalyst 2
■
Since its discovery in the 1950s, olefin metathesis has become a
premier reaction for the construction of carbon−carbon double
1
bonds. The continued development of well-defined transition
metal alkylidene catalysts has allowed metathesis to become
highly prevalent in a wide variety of fields, including chemical
2
3
4
biology, materials science, and green chemistry. Controlling
stereoselectivity in cross-metathesis (CM) reactions has long
been a goal of research, as there is a pressing need to develop
reliable routes to stereopure internal olefin products. Since the
reaction is typically performed under thermodynamic control
and traditional catalysts generally favor formation of the more
stable E-isomer, the discovery and development of catalysts
capable of preferentially producing the Z-olefin isomer was
highly desired. The laboratories of Schrock and Hoveyda
provided the first examples of Z-selective catalysts with
monoaryloxide pyrrolidine (MAP) complexes of molybdenum
contain one chloride and one pivalate ligand, however, have
been independently prepared and do not undergo C−H
8
activation even upon heating. These studies suggest that C−H
activation occurs only from the dipivalate complex and not
from the monochloride, monopivalate complex. Silver(I)
pivalate (AgOPiv) was originally used as a ligand exchange
and C−H activation reagent, though it was later found to
induce the decomposition of the desired cyclometalated
9
catalysts. For some ruthenium complexes, the salt metathesis
5
and tungsten.
steps are slow and the resulting cyclometalated species
decompose prior to isolation. We thus desired to find
conditions using a less reactive metal pivalate to promote the
ligand exchange. It was discovered that exposing certain
ruthenium alkylidene complexes to sodium pivalate (NaOPiv)
in a 1:1 mixture of MeOH and THF led to clean formation of
the desired cyclometalated catalysts without accompanying
More recently, our group has developed a class of Z-selective
ruthenium-based catalysts that contain a cyclometalated N-
heterocyclic carbene (NHC) ligand derived from C−H
6
,7
activation of an N-1-adamantyl substituent (Scheme 1).
The treatment of ruthenium dichloride complexes with an
excess of a metal pivalate causes the exchange of the chloride
ligands for pivalates, leading to the formation of a dipivalate-
substituted complex. This species can then rapidly undergo a
carboxylate-assisted C−H bond activation to yield the desired
cyclometalated complex along with one equivalent of pivalic
1
0,11
decomposition.
With this mild method in hand and with the aid of DFT
12
calculations, we were able to develop a family of ruthenium
6
acid. Thus far, no stable dipivalate-substituted ruthenium
Received: March 5, 2015
alkylidene complexes have been reported. Complexes that
©
XXXX American Chemical Society
A
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catalysts with five-membered, N-1-adamantyl chelates that have
exhibited remarkably high Z-selectivity and activity (Figure 1).
zation reactions. Additionally, two stable dipivalate complexes
were isolated and studied for the development of improved
cyclometalated catalysts.
RESULTS AND DISCUSSION
■
Synthesis of New Cyclometalated Architectures. Due
to the unpredictable stability of cyclometalated architectures,
we first sought to screen various ruthenium dichloride
alkylidene complexes to determine whether a stable cyclo-
metalated species could form after a carboxylate-assisted C−H
bond insertion event. A number of complexes were prepared
with varying N-substituents. These complexes were subse-
quently exposed to a metal pivalate to determine if they could
form a stable chelating ruthenium−carbon bond in the
Figure 1. Prominent cyclometalated ruthenium catalysts for Z-
selective olefin metathesis.
Our first highly Z-selective catalyst (2) features a pivalate X-
type ligand and an N-mesityl group as the nonchelated NHC
1
1
3
presence of an alkylidene, which was monitored using H
substituent. This complex was able to catalyze the
homodimerization of terminal olefins with ∼90% selectivity
for the Z-olefin at 1 mol % catalyst loading. It was subsequently
found that substitution of the pivalate ligand of 2 with a nitrate
ligand led to formation of catalyst 3, which now exhibited
NMR spectroscopy. Ten equivalents of NaOPiv were added to
a solution of each complex in a 1:1 mixture of CD OD and
3
THF-d . With species that were able to form a stable complex,
8
the starting material was readily converted to a cyclometalated
species with concurrent generation of pivalic acid. Alternatively,
with some species, a dipivalate complex resulting from salt
metathesis of the starting material was observed before C−H
activation occurred. If pivalic acid was generated with
disappearance of the starting material dichloride complex or
the analogous dicarboxylate adduct, and formation of a
ruthenium hydride was observed, the complex was deemed
unstable and not relevant for further study.
1
4
∼
95% Z-selectivity in homodimerization reactions. When the
nonchelating N-aryl NHC substituent was changed to an N-2,6-
diisopropylphenyl (DIPP) group, the selectivity increased
further, as catalyst 4 exhibited >98% selectivity in analogous
10
homodimerization reactions. Catalysts 3 and 4 also proved to
be more active than 2 and could be used at catalyst loadings as
low as 0.01 mol %. These three cyclometalated catalysts have
proven effective in more complicated cross metathesis,
macrocyclic ring-closing metathesis (mRCM), asymmetric
15
16
We first attempted to form a cyclometalated complex with a
five-membered chelate derived from activation of the N-bornyl
substituent of previously reported complex 10 (Scheme 2).
17
18
ring-opening cross metathesis (AROCM), ethenolysis, and
19
ring-opening metathesis polymerization (ROMP) reactions.
Although significant advancements in the design of cyclo-
metalated complexes have been made, one area that has yet to
be thoroughly investigated is the effect of the N-chelating group
on activity and selectivity. Five catalysts bearing chelating
groups other than an N-1-adamantyl group have been reported
by our group and are depicted in Figure 2. Catalyst 5 features a
Scheme 2. C−H Activation To Form Cyclometalated
Complex 11
This carbocyclic group is markedly different in terms of
structure and connectivity when compared to the previously
reported N-1-adamantyl group. An N-DIPP group was chosen
as the nonchelating substituent because it imparts improved
activity and selectivity to this family of catalysts (vide supra). N-
Bornyl complex 10 was treated with NaOPiv and formed the
depicted cyclometalated complex according to two-dimensional
NMR analysis (see Supporting Information). Despite contain-
ing multiple accessible C−H bonds, only one complex was
stably formed. In order to explain the experimentally observed
formation of product 11, DFT calculations were performed.
Our previous mechanistic and computational studies
indicated that the carboxylate-assisted C−H activation of the
ruthenium dipivalate to form the N-1-adamantyl cyclometalated
complex 2 occurs via a concerted metalation−deprotonation
Figure 2. Previously reported catalysts bearing modified N-chelating
groups. MIPP = 2-methyl-6-isopropylphenyl.
modified N-1-adamantyl group substituted with two bridgehead
10
methyl groups and exhibits similar activity to catalyst 2, while
t
catalysts 6 and 7 contain N- Bu chelates and exhibit no CM
1
9b
reactivity. Alternatively, catalysts 8 and 9 bear six-membered
chelates and exhibit significantly reduced Z-selectivity in CM
8
,13a
reactions.
In this report, several new chelating architectures
were synthesized in an effort to understand how chelate size
and geometry affect both catalyst activity and selectivity. The
barriers to C−H activation of each species were determined by
DFT calculations, which aided in the prediction of which
isomer would preferentially form when the chelating
substituent contained multiple, accessible C−H bonds. The
metathesis activity of these new cyclometalated catalysts was
subsequently probed in standard terminal olefin homodimeri-
20a,b
(CMD) mechanism.
In the C−H activation transition state,
the deprotonating pivalate adopts a pseudoapical geometry,
displacing the aryl ether chelate. On the basis of this
mechanism, we calculated the C−H activation pathways
involving different C−H bonds of the N-bornyl group in the
dipivalate-substituted complex 12 (Figure 3). The calculations
were performed at the same level of theory in our recent
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only the five-membered cyclometalated 11 complex is formed.
The DFT calculations have allowed us to predict which isomer
of a cyclometalated catalyst will preferentially form based on
25
the relative barriers of C−H activation.
Cyclometalated complexes derived from C−H activation of
N-2-adamantyl NHC substituents were next investigated to
elucidate the effect of a subtle change in the connectivity of the
N-chelating group. The N-1-adamantyl group of dichloride
complex 1 is unique in that the carbon atom that undergoes
C−H activation sits quite close to the ruthenium center (2.80
13a
Å) (Figure 4). The resulting cyclometalated complex (2) is
Figure 4. Previously reported crystal structure of dichloride complex 1.
Displacement ellipsoids are drawn at 50% probability. For clarity,
hydrogen atoms have been omitted. Selected bond lengths (Å) for 1:
C1−Ru: 1.99, C23−Ru: 1.84; distance between C12 and Ru: 2.80.
seemingly less susceptible to insertion of the chelating
ruthenium−carbon bond into the alkylidene and subsequent
decomposition. Unlike the N-1-adamantyl-substituted complex
1
however, the solid-state structure of the N-2-adamantyl
dichloride complex 15 does not feature any carbon atoms in
close proximity to the ruthenium center (Figure 5). Never-
theless, complexes 15 and 17, bearing an N-Mes and N-DIPP
group, respectively, were exposed to NaOPiv and formed stable
complexes 16 and 18 (Scheme 3). Single crystals of both were
grown and the structures were determined by X-ray
crystallography (Figures 6 and 7). These structures are derived
from activation of a tertiary C−H bond to form a five-
Figure 3. Transition states of C−H bond activation at different sites of
dipivalate complex 12 and corresponding cyclometalated products.
The Gibbs free energies are with respect to the dipivalate complex 12.
6
computational studies of ruthenium metathesis catalysts.
21
Geometries were optimized with B3LYP and the LANL2DZ
basis set for Ru and 6-31G(d) for other atoms. Single-point
energies were calculated with M06 and the SDD basis set for
Ru and 6-311+G(d,p) for other atoms. The SMD solvation
model in THF solvent was employed in the single-point energy
calculations. All calculations were performed with Gaussian
22
2
3
2
4
09.
The computed Gibbs free energies of the rate- and
selectivity-determining C−H activation transition states and
the corresponding cyclometalated products are shown in Figure
3
. Formation of the five-membered chelate (11) is predicted to
be favored both kinetically and thermodynamically. The
corresponding six-membered chelating complexes (13 and
Figure 5. Crystal structure of ruthenium dichloride complex 15.
Displacement ellipsoids are drawn at 50% probability. For clarity,
hydrogen atoms have been omitted. Selected bond lengths (Å) for 15:
C1−Ru: 1.97, C23−Ru: 1.84; distance between C5 and Ru: 3.99;
distance between C9 and Ru: 4.28.
1
4) are 2−3 kcal/mol less stable than 11, and the barriers for
C−H activation to form these complexes are more than 5 kcal/
mol higher than that to form the five-membered chelate. These
calculations are consistent with the experimental results that
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Scheme 3. C−H Activation To Form Cyclometalated
Complexes 16 and 18
Scheme 4. C−H Activation To Form Cyclometalated
Complex 20
We initially thought that C−H activation of the N-methyl
group would be unfavorable due to formation of a strained
four-membered chelate, and therefore C−H activation would
occur on the N-mesityl group to form a six-membered chelate.
In the reported crystal structure of ruthenium dichloride
complex 19, however, the N-methyl group sits close to the
ruthenium center (2.83 Å), while the N-mesityl ortho-methyl
group is much farther away (Figure 8). Similarly to the N-1-
Figure 6. X-ray crystal structure of cyclometalated complex 16.
Displacement ellipsoids are drawn at 50% probability. For clarity,
hydrogen atoms have been omitted. Selected bond lengths (Å) for 16:
C1−Ru: 1.95, C21−Ru: 2.08, C31−Ru: 1.85.
Figure 8. Previously reported crystal structure of dichloride complex
1
9. Displacement ellipsoids are drawn at 50% probability. For clarity,
hydrogen atoms have been omitted. Selected bond lengths (Å) and
angles (deg) for 19: C1−Ru: 2.01, C7A−Ru: 1.84, N−C1−N: 119.6;
2
6a
distance between C3 and Ru: 2.83.
adamantyl complex 1, upon treatment with NaOPiv, the C−H
bond proximal to the ruthenium center, on the N-methyl group
in this case, underwent C−H activation to form complex 20,
containing a stable four-membered chelate. The structure was
confirmed by X-ray crystallographic analysis (Figure 9). It
seems that the flexibility of the acyclic carbene ligand allows the
smaller and more strained chelate to form as a stable complex.
DFT calculations indicated that formation of the four-
membered chelate from 19 has a much lower activation barrier
and leads to a more stable cyclometalated complex compared to
formation of the six-membered chelate via activation of the
mesityl C−H bond (Figure 10). This selectivity is attributed to
two effects. First, the greater N−C−N angle of the acyclic
diamino carbene promotes formation of the four-membered
chelate. The N−C−N angle increases from 117° in 21 to 124°
in TS-20 and 125° in 20 in the four-membered pathway, while
it remains unchanged in the corresponding six-membered
chelated structures (Figure 10). Additionally, in the transition
state to form the planar four-membered chelate (TS-20), the
C−H bond being deprotonated is oriented toward the bottom-
bound carboxylate (see Figure 11 for a Newman projection
Figure 7. X-ray crystal structure of complex 18. Displacement
ellipsoids are drawn at 50% probability. For clarity, hydrogen atoms
have been omitted. Selected bond lengths (Å) for 18: C1−Ru: 1.95,
C31−Ru: 2.08, C41−Ru: 1.85.
membered chelating architecture. DFT calculations were
performed and revealed that the barriers of C−H activation
to form 16 and 18 are 28.8 and 28.2 kcal/mol, respectively.
These barriers are about 5 kcal/mol higher than those for the
activation of the less hindered methylene C−H bonds to form
the five-membered chelates 2 and 11 and are closer to those for
six-membered chelates such as complex 8.
Finally, we sought to determine if a previously reported
ruthenium alkylidene complex (19) bearing an acyclic diamino
26
carbene ligand could undergo cyclometalation (Scheme 4).
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Figure 11. Newman projections along the forming Ru−C bond in
transition states TS-20 and TS-22.
along the forming Ru−C bond). In contrast, to form a
puckered six-membered chelate in TS-22, significant distortion
of the cleaving C−H bond is required to approach the bottom-
bound carboxylate (Figure 11).
Figure 9. X-ray crystal structure of complex 20. Displacement
ellipsoids are drawn at 50% probability. For clarity, hydrogen atoms
have been omitted. Selected bond lengths (Å) and angles (deg) for 20:
C1−Ru: 1.96, C21−Ru: 2.07, C22−Ru: 1.85, N−C1−N: 124.7.
It has been shown experimentally that formation of planar
four- or five-membered) chelates is often more favorable than
(
formation of puckered six-membered chelates. This selectivity
trend is supported by the computed C−H activation barriers
for various ruthenium NHC complexes shown in Table 1.
Formation of smaller-ring chelates via activation of primary and
secondary C−H bonds (entries 1−3) is predicted to be facile
and always more favorable than forming a six-membered
chelate with either N-mesityl or N-bornyl groups. Notably,
formation of the sterically hindered five-membered chelates 16
and 18 (entries 4 and 5) requires higher barriers, which are still
comparable to those for six-membered chelates resulting from
activation of sterically more accessible primary or secondary
C−H bonds (entry 6).
Metathesis Activity and Selectivity of New Cyclo-
metalated Catalysts. The metathesis activities of the stable
cyclometalated ruthenium complexes were evaluated using
standard terminal olefin homodimerization reactions of
allylbenzene (24), 4-penten-1-ol (25), and methyl-10-undece-
1
3b
noate (26).
Allylbenzene is easily isomerized to β-
methylstyrene by catalyst decomposition products. As such, it
can act as an indicator of the stability of the active catalyst
based on the ratio of isomerized product to the desired
homocoupled product. 4-Penten-1-ol was chosen as a substrate
because the homodimerized product undergoes undesired and
rapid Z to E isomerization with previously reported Z-selective
catalysts, and we had hoped we could find new cyclometalated
complexes that would be improved in this regard. Discovery of
new catalysts that maintain high Z-selectivity at high
conversions is desired. Finally, methyl-10-undecenoate contains
a functional group that is far removed from the olefin and does
not typically undergo undesired side-reactions, making it a
good test of the inherent metathesis reactivity of a catalyst.
Cyclometalated catalysts 11, 16, and 18 exhibited generally
high Z-selectivity at early reaction times in the homodimeriza-
tion assays tested, providing >75% of the Z-olefin product in
most cases (Table 2). Unfortunately, these catalysts produced a
significant amount of undesired olefin walking product in
allylbenzene and 4-pentenol homodimerization assays. Addi-
tionally, for all substrates, but especially 4-pentenol, Z to E
27
isomerization occurred readily. Catalyst 20, bearing a four-
membered chelate, was metathesis inactive in all of the assays
tested. This is not surprising, however, given that this catalyst
contains the highly strained four-membered chelate, likely
Figure 10. Transition states of C−H bond activation at different sites
of dipivalate complex 21 and corresponding cyclometalated products.
The Gibbs free energies are with respect to the dipivalate complex 21.
9
leading to facile decomposition.
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Table 1. Computed Activation Barriers of C−H Activation To Form Four-, Five-, and Six-Membered Chelates
a
b
c
See ref 6. See Figure 3. See Figure 10.
Catalysts 11 and 18, bearing bulky N-DIPP groups, emerged
as the best catalysts of those tested in terms of Z-selectivity. For
allylbenzene and methyl-10-undecenoate homodimerization
reactions, the Z-selectivity was generally >95% at early reaction
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Table 2. Homodimerization of Allylbenzene (24), 4-Penten-
while others cannot. As previously mentioned, monochloride,
monocarboxylate adducts have been independently prepared
1
-ol (25), and Methyl-10-undecenoate (26)
8
and do not undergo C−H activation even upon heating.
We originally intended to C−H activate the benzylic carbon
of an N-mesityl group of thiazole NHC-substituted 27 to form
a six-membered chelating complex similar to complexes 8 and
28
9
.
However, a stable dipivalate-substituted complex (28) was
substrate
catalyst
time (h)
conv (%)
%Z-A
A/B
formed instead, and even upon heating, C−H activation did not
occur (Scheme 5). An X-ray crystal structure of 28 was
24
25
26
11
1
2
4
1
2
4
1
2
4
1
2
4
1
2
4
1
2
4
1
2
4
1
2
4
1
2
4
54
86
>95
>95
90
2.7
1.0
>95
19
0.8
Scheme 5. Salt Metathesis Reaction To Form Dipivalate
Complex 28
1
1
6
8
95
1.9
34
94
0.7
86
79
0.2
10
>95
>95
>95
74
2.1
16
1.0
31
0.6
11
>95
>95
>95
94
3.4
63
2.6
55
2.2
1
1
6
8
58
4.5
>95
>95
31
54
3.1
52
2.4
83
3.8
82
88
1.6
>95
83
81
1.4
11
>95
93
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
92
>95
31
74
1
1
6
8
51
63
30
91
21
19
93
28
90
39
75
times and did not fall below 74% after 4 h. N-Bornyl
cyclometalated catalyst 11 proved to be slightly more active
than N-2-adamantyl cyclometalated catalyst 18, generally
reaching higher conversions for all substrates. Catalyst 16,
bearing an N-2-adamantyl chelate and N-mesityl group, was
inherently less Z-selective in the allylbenzene and methyl-10-
undecenoate homodimerization reactions and exhibited more
rapid Z-degradation. As expected, the 4-penten-1-ol homo-
dimerization reactions exhibited significant Z/E isomerization
for catalysts 11, 16, and 18 even after 1 h. Current efforts are
aimed at understanding the complex and nuanced factors
affecting Z-content degradation processes and will be reported
in due time. Overall, these catalysts still showed reduced Z-
selectivity, higher Z/E isomerization, and increased olefin
walking compared to N-1-adamantyl chelated catalysts 2−4.
Thus, we believe that the N-1-adamantyl substituent is an ideal
chelating group. Due to the unsatisfactory activity and
selectivity of these newly reported catalysts, further catalyst
development and optimization were not carried out.
Isolation of Dipivalate Complexes. During our inves-
tigations into forming new chelating architectures, we were able
to isolate stable dipivalate complexes that unexpectedly did not
undergo C−H activation; prior to this work, no ruthenium
alkylidene dipivalate complexes had been reported. Since it has
been shown that C−H activation occurs from dipivalate
intermediates, studying these isolable complexes could provide
important insight into why certain N-groups can be activated
Figure 12. Crystal structure of complex 27. Displacement ellipsoids
are drawn at 50% probability. For clarity, hydrogen atoms have been
omitted. Selected bond lengths (Å) for 27: C1−Ru: 1.95, C15−Ru:
2
8
1
.83.
obtained and provided insight into why this complex did not
undergo C−H activation (Figure 13). In the crystal structure of
the starting complex 27, the N-mesityl group resides over the
chloride X-type ligands (Figure 12). In the structure of 28,
however, the NHC has rotated such that the N-mesityl group
resides over the ruthenium alkylidene, most likely due to the
increased steric bulk of the pivalate X-type ligands. As a result,
the distance between the pivalate ligands and the ortho-methyl
group of the N-mesityl substituent is too large to undergo a
carboxylate-assisted activation event. The structure also features
one monodentate pivalate ligand and one bidentate pivalate
ligand. DFT calculations revealed that the barrier to C−H
activation of this dipivalate complex was prohibitively high at
35.4 kcal/mol (Table 1, entry 7). This is in line with the high
barriers to form six-membered chelates. In addition, replacing
one of the N-mesityl groups with a S atom diminishes the steric
strain in the dipivalate complex and thus leads to an even
higher barrier than the cyclometalation of the N,N′-dimesityl
NHC complex 23. The agreement between computed and
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Figure 14. X-ray crystal structure of dichloride complex 29.
Displacement ellipsoids are drawn at 50% probability. For clarity,
hydrogen atoms have been omitted. Selected bond lengths (Å) for 29:
C1−Ru: 1.98, C23−Ru: 1.83.
Figure 13. X-ray crystal structure of complex 28. Displacement
ellipsoids are drawn at 50% probability. For clarity, hydrogen atoms
have been omitted. Selected bond lengths (Å) for 28: C1−Ru: 1.97,
C15−Ru: 1.84.
for the preparation of previously not accessible catalysts with
chelating N-substituents other than N-1-adamantyl. New
complexes containing multiple potential sites for C−H
activation and tertiary C−H bonds were explored. Using
DFT calculations, we were able to correctly predict which
isomer of a cyclometalated complex will form by comparing the
relative barriers of C−H activation. Formation of planar four-
and five-membered chelates is found to be more favorable than
formation of six-membered chelates. The metathesis activities
of the resulting stable complexes were evaluated, and they
unfortunately proved to be less active and Z-selective when
compared to previously reported cyclometalated catalysts
substituted with an N-1-adamantyl group. These studies have
provided information about how chelating substituents affect
the stability, activity, and selectivity of the resulting catalysts. In
addition to studying new chelated architectures, two stable
dipivalate complexes were isolated. It has been shown that for
cyclometalation to occur ruthenium dichloride complexes must
first undergo two salt metathesis steps to form a dipivalate
intermediate, which then undergoes rapid C−H activation to
form a cyclometalated catalyst. However, we have shown here
that for some complexes a stable dipivalate complex can form
that cannot undergo activation. With these complexes, we were
able to probe some of the factors affecting carboxylate-assisted
C−H bond activations and determined that flexibility of the N-
substituents could prevent cyclometalation.
experimentally observed reactivities indicates that it is now
becoming possible to predict whether a cyclometalated
architecture can be formed by investigating the barriers of
C−H activation of the corresponding dipivalate complex.
Similarly, when complex 29, bearing an N-myrtanyl group,
was treated with NaOPiv, dipivalate complex 30 was formed;
however no C−H activation occurred even upon heating
(
Scheme 6). Unfortunately we were unable to obtain a crystal
Scheme 6. Salt Metathesis Reaction To Form Dipivalate
Complex 30
structure of the dipivalate complex; however instead we were
able to obtain a crystal structure of the dichloride starting
complex 29 (Figure 14). The methylene linker of this N-
substituent seemingly gives the group added flexibility, allowing
it to rotate away from the ruthenium center. Substitution of the
chlorides with the bulky pivalates would likely increase the
steric bulk of the congested ruthenium center and further push
the N-myrtanyl group away, preventing C−H activation from
occurring. It is also possible that the NHC ligand would rotate
away from the pivalate-substituted metal center similar to what
was observed for complex 28. The information gained from the
isolation and characterization of dipivalate-substituted com-
plexes 28 and 30 will be important for the future design of
more stable and improved Z-selective olefin metathesis
catalysts.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out in dry
glassware under an argon atmosphere using standard Schlenk
techniques or in a Vacuum Atmospheres glovebox under a nitrogen
atmosphere unless otherwise specified. All solvents were purified by
passage through solvent purification columns and further degassed by
bubbling argon. Hexane was dried over CaH and distilled into a dry
2
Schlenk flask and subsequently degassed with argon. THF was purified
by passage through solvent purification columns and further degassed
with argon. NMR solvents were dried over CaH and vacuum
2
transferred to a dry Schlenk flask and subsequently degassed with
bubbling argon. C D6 was purified by passage through a solvent
6
purification column. CDCl3 was used as received. Potassium tert-
amyloxide was purchased as a toluene solution and concentrated
before use. Dichloro(o-isopropoxyphenylmethylene)-
CONCLUSIONS
■
Four new cyclometalated ruthenium alkylidene complexes were
synthesized, and the mechanism of their formation was
investigated using DFT calculations. The use of a milder salt
metathesis and C−H activation reagent, NaOPiv, has allowed
(
tricyclohexylphosphine)ruthenium [Ru(PCy )(CH-o-iPrO-Ph)-
3
Cl ] was obtained from Materia, Inc. Other commercially available
2
reagents and silica gel were used as received.
H
DOI: 10.1021/acs.organomet.5b00185
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1
13
Purity was established by H and C NMR analysis, and identity
solvent was removed under reduced pressure. The resulting residue
1
was demonstrated using high-resolution mass spectrometry. H and
C{ H} NMR spectra were recorded on a Varian 600 MHz
was dissolved in C H , filtered through Celite, and concentrated under
6
6
1
3
1
reduced pressure. The residue was dissolved in 5:1 pentane/Et O (ca.
2
spectrometer, a Varian 500 MHz spectrometer, or a Varian 400
MHz spectrometer. High-resolution mass spectra were provided by
the California Institute of Technology Mass Spectrometry Facility
using a JEOL JMS-600H high-resolution mass spectrometer. X-ray
crystallographic data were collected by the California Institute of
Technology Beckman Institute X-ray Crystallographic Facility using a
Bruker KAPPA APEXII X-ray diffractometer.
3 mL) and let slowly evaporate to yield large blue crystals. The mother
liquor was removed and the crystals were washed with pentane (4 × 5
mL) and then Et O (2 × 4 mL), yielding pure blue crystals after
2
drying under reduced pressure (19 mg, 13%). The crystals were used
1
for X-ray crystallography to obtain a crystal structure. H NMR (500
MHz, C D ): δ 14.84 (s, 1H), 7.46 (dd, J = 7.5, 1.6 Hz, 1H), 7.37
6 6
(ddd, J = 8.3, 7.4, 1.7 Hz, 1H), 6.89 (td, J = 7.4, 0.8 Hz, 1H), 6.81 (d, J
= 6.2 Hz, 2H), 6.69 (d, J = 8.4 Hz, 1H), 4.81 (hept, J = 6.4 Hz, 1H),
3.63−3.43 (m, 1H), 3.39−3.24 (m, 1H), 2.96 (qd, J = 12.0, 11.4, 3.9
Hz, 1H), 2.39−2.36 (m, 1H), 2.33 (s, 3H), 2.31 (td, J = 75.4, 1.9 Hz,
1H), 2.29 (s, 3H), 2.22 (s, 3H), 2.14 (s, 1H), 2.07 (s, 1H), 1.96−1.87
(m, 3H), 1.80 (d, J = 12.1 Hz, 2H), 1.74 (s, 1H), 1.64 (d, J = 6.5 Hz,
Synthesis of 11. In a glovebox, a 20 mL scintillation vial with a
magnetic stir bar was charged with 10 (102 mg, 0.148 mmol, 1 equiv)
and NaOPiv (184 mg, 1.48 mmol, 10 equiv). Rigorously deoxygenated
THF (ca. 5 mL) and MeOH (ca. 5 mL) were added, and the reaction
was heated to 35 °C and stirred for 1 day. During the reaction, the
color of the solution changed from green to brown. Upon completion,
solvent was removed under reduced pressure. The resulting residue
was dissolved in C H , filtered through Celite, and concentrated under
3H), 1.54 (d, J = 12.4 Hz, 1H), 1.23 (s, 9H), 1.17 (d, J = 6.2 Hz, 3H),
1.09 (dd, J = 12.4, 2.4 Hz, 1H). 13C{ H} NMR (126 MHz, C
1
D
6
): δ
6
263.52, 219.40, 187.10, 154.02, 144.03, 137.93, 137.14, 136.66, 136.60,
130.05, 129.48, 128.59, 125.79, 123.29, 123.19, 113.77, 80.92, 74.41,
52.17, 50.14, 48.72, 46.04, 39.43, 39.22, 38.67, 38.12, 32.53, 32.37,
6
6
reduced pressure. The desired product was purified by column
chromatography (5:1 pentane/Et O to 1:1 pentane/Et O to Et O),
2
2
2
separating away a yellow and green band, yielding a purple solid (13
31.50, 30.48, 28.50, 21.84, 21.14, 21.03, 18.68. HRMS-FAB (m/z)”
1
+
mg, 12%). H NMR (600 MHz, C D ): δ 15.06 (s, 1H), 7.54 (dd, J =
[M] calcd for C37
H
50
N
2
O
3
Ru, 672.2866; found, 672.2868.
6
6
7
.5, 1.6 Hz, 1 Hz), 7.20 (td, J = 8.0, 1.7 Hz, 1H), 7.13 (t, J = 7.7 Hz,
Synthesis of 17. In a glovebox, S2 (300 mg, 0.75 mmol, 1 equiv)
and sodium bis(trimethylsilyl)amide (152 mg, 0.83 mmol, 1.1 equiv)
were dissolved in benzene (ca. 10 mL) in a 20 mL scintillation vial
with a magnetic stir bar. The solution was stirred for 3 h at room
temperature and then filtered with a PTFE membrane syringe filter
1H), 7.04 (dd, J = 7.8, 1.5 Hz, 1H), 7.00 (dd, J = 7.6, 1.5 Hz, 1H), 6.88
(
td, J = 7.4, 0.8 Hz, 1H), 6.57 (d, J = 8.3 Hz, 1H), 5.02 (dd, J = 9.9, 4.0
Hz, 1H), 4.56 (hept, J = 6.2 Hz, 1H), 3.92 (hept, J = 7.2 Hz, 1H), 3.76
dt, J = 12.4, 10.2 Hz, 1H), 3.70 (dd, J = 9.9, 2.0 Hz, 1H), 3.34 (td, J =
(
1
1
3
0.0, 2.4 Hz, 1H), 3.29−3.18 (m, 2H), 2.93 (hept, J = 5.9 Hz, 1H),
.50 (t, J = 4.2 Hz, 1H), 1.47 (d, J = 6.8 Hz, 3H), 1.40 (d, J = 6.2 Hz,
H), 1.35 (d, J = 6.1 Hz, 4H), 1.28 (d, J = 6.9 Hz, 4H), 1.24 (d, J = 6.8
(pore size 0.2 μm) into a new 20 mL scintillation vial containing
i
Ru(PCy
)(CH-o- PrO-Ph)Cl
(451 mg, 0.75 mmol, 1.1 equiv) and
3
2
a magnetic stir bar. The vial was sealed and removed from the
glovebox. It was allowed to stir at 50 °C for 4 h. Over the course of the
reaction, the solution changed from brown to brown-green. After
cooling to room temperature, the solvent was removed under reduced
pressure, yielding a green-brown solid. The solid was washed with
hexane and filtered over Celite until the washes were colorless. This
yielded a green solid. The green solid was collected by dissolving in
DCM and concentrating under reduced pressure. The desired product
Hz, 4H), 1.16 (d, J = 6.9 Hz, 3H), 1.15 (s, 3H), 1.04 (s, 9H), 0.94 (s,
13
1
3H), 0.91 (s, 3H), 0.12 (ddd, J = 12.3, 9.5, 3.2 Hz, 1H). C{ H}
NMR (126 MHz, C D ): δ 262.65, 219.23, 187.16, 154.52, 148.35,
6
6
1
1
3
2
45.76, 143.07, 137.85, 128.16, 125.62, 123.91, 123.60, 123.04, 122.60,
13.58, 77.29, 73.87, 60.74, 55.21, 52.85, 49.68, 48.95, 47.19, 39.06,
7.44, 29.81, 28.49, 28.21, 27.99, 27.55, 27.07, 26.31, 25.03, 24.49,
+
3.23, 22.19, 21.88, 21.10, 19.18, 15.71; HRMS-FAB (m/z) [M]
calcd for C H N O Ru, 716.3492; found, 716.3508.
was purified by column chromatography (4:1 pentane/Et
2
O to Et
yielding a green solid (243 mg, 47%). H NMR (500 MHz, C D
6 6
2
O),
): δ
40
58
2
3
1
Synthesis of 15. In a glovebox, S1 (300 mg, 0.836 mmol, 1.1 equiv)
and potassium tert-amyloxide (96 mg, 0.76 mmol, 1 equiv) were
dissolved in hexane (ca. 15 mL) in a 20 mL scintillation vial with a
magnetic stir bar. The solution was stirred for 2 h at room temperature
and then filtered with a PTFE membrane syringe filter (pore size 0.2
16.46 (s, 1H), 7.33 (t, J = 7.7 Hz, 1H), 7.18 (s, 1H), 7.11−7.01 (m,
3H), 6.64 (td, J = 7.5, 0.8 Hz, 1H), 6.38 (d, J = 8.4 Hz, 1H), 5.57 (s,
1H), 4.53 (hept, J = 6.0 Hz, 1H), 3.61−3.53 (m, 2H), 3.52−3.43 (m,
2H), 3.33 (hept, J = 6.8 Hz, 2H), 2.93 (s, 2H), 2.44 (d, J = 12.0 Hz,
2H), 1.94 (t, J = 12.5 Hz, 5H), 1.80 (s, 1H), 1.65 (d, J = 6.1 Hz, 6H),
1.68−1.60 (m, 4H), 1.07 (d, J = 7.0 Hz, 6H), 1.02 (d, J = 6.6 Hz, 6H).
μm) into a new 20 mL scintillation vial containing Ru(PCy )(CH-
3
i
o- PrO-Ph)Cl (457 mg, 0.76 mmol, 1 equiv) and a magnetic stir bar.
2
13
1
The vial was sealed and removed from the glovebox. It was allowed to
stir at 65 °C for 4 h. Over the course of the reaction, a green solid
precipitated out from the red-brown solution. After cooling to room
temperature, the solution was filtered over Celite and the green solid
was washed thoroughly with hexane until the washes were colorless.
The green solid was collected by dissolving in DCM and concentrating
under reduced pressure. The desired product was purified by column
chromatography (4:1 pentane/Et O to Et O), yielding a green solid
C{ H} NMR (126 MHz, C D ): δ 287.50, 213.15, 182.87, 153.18,
6 6
149.00, 144.43, 139.01, 129.71, 129.07, 125.17, 122.48, 113.29, 74.69,
66.11, 55.84, 53.33, 49.19, 39.62, 38.59, 34.34, 33.66, 28.52, 28.30,
27.72, 25.78, 24.29, 22.61. HRMS-FAB (m/z): [M]+ calcd for
C H Cl N ORu, 684.2188; found, 684.2179.
35
48
2
2
Synthesis of 18. In a glovebox, a 20 mL scintillation vial with a
magnetic stir bar was charged with 17 (100 mg, 0.146 mmol, 1 equiv)
and NaOPiv (181 mg, 1.46 mmol, 10 equiv). Rigorously deoxygenated
THF (ca. 5 mL) and MeOH (ca. 5 mL) were added, and the reaction
was heated to 35 °C and stirred for 5 days. During the reaction, the
color of the solution changed from green to brown. Upon completion,
solvent was removed under reduced pressure. The resulting residue
was dissolved in C H , filtered through Celite, and concentrated under
2
2
1
(
(
164 mg, 34%). H NMR (500 MHz, CDCl ): δ 16.47 (s, 1H), 7.51
ddd, J = 8.8, 6.4, 2.6 Hz, 1H), 7.06 (s, 2H), 6.93 (d, J = 8.7 Hz, 1H),
3
6
.90−6.87 (m, 2H), 5.18 (s, 1H), 5.12 (hept, J = 6.1 Hz, 1H), 4.20 (t, J
8.9 Hz, 2H), 3.94 (t, J = 8.9 Hz, 2H), 2.87 (s, 2H), 2.45 (s, 3H), 2.25
s, 6H), 2.30−2.17 (m, 4H), 2.08−2.05 (m, 4H), 2.02 (s, 1H), 1.99 (s,
=
(
1
6
6
H), 1.89 (s, 1H), 1.85 (s, 2H), 1.73 (d, J = 6.1 Hz, 6H). 13C{ H}
1
reduced pressure. The residue was dissolved in 5:1 pentane/Et O (ca.
2
NMR (126 MHz, CDCl ): δ 296.61, 211.38, 182.62, 152.47, 144.89,
3 mL) and let slowly evaporate to yield large blue crystals. The mother
3
1
6
2
6
38.75, 138.63, 138.22, 129.85, 129.71, 123.16, 122.61, 113.13, 74.58,
liquor was removed, and the crystals were washed with pentane (4 × 5
5.34, 52.43, 49.37, 38.92, 38.20, 34.44, 33.40, 28.07, 27.49, 22.56,
mL) and then Et O (2 × 4 mL), yielding pure blue crystals after
2
+
1.32, 18.40. HRMS-FAB (m/z): [M] calcd for C H Cl N ORu,
drying under reduced pressure (10 mg, 10%). The crystals were used
32
42
2
2
1
42.1718; found, 642.1746.
Synthesis of 16. In a glovebox, a 20 mL scintillation vial with a
for X-ray crystallography to obtain a crystal structure. H NMR (500
MHz, C D ): δ 15.01 (s, 1H), 7.50 (dd, J = 7.5, 1.6 Hz, 1H), 7.33
6
6
magnetic stir bar was charged with 15 (140 mg, 0.218 mmol, 1 equiv)
and NaOPiv (270 mg, 2.18 mmol, 10 equiv). Rigorously deoxygenated
THF (ca. 5 mL) and MeOH (ca. 5 mL) were added, and the reaction
was heated to 35 °C and stirred for 1 day. During the reaction, the
color of the solution changed from green to brown. Upon completion,
(ddd, J = 8.4, 7.4, 1.7 Hz, 1H), 7.19 (t, J = 7.7 Hz, 1H), 7.11 (dd, J =
7.7, 1.6 Hz, 1H), 7.05 (dd, J = 7.6, 1.6 Hz, 1H), 6.88 (td, J = 7.4, 0.7
Hz, 1H), 6.62 (d, J = 8.3 Hz, 1H), 4.72 (hept, J = 6.4 Hz, 1H), 3.98
(hept, J = 6.8 Hz, 1H), 3.69 (ddd, J = 11.9, 10.4, 6.2 Hz, 1H), 3.58 (q,
J = 10.5 Hz, 1H), 3.36 (td, J = 10.0, 6.4 Hz, 1H), 3.05−2.93 (m, 2H),
I
DOI: 10.1021/acs.organomet.5b00185
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
2
2
3
2
.39 (dt, J = 12.5, 2.3 Hz, 1H), 2.29−2.15 (m, 2H), 2.12−2.03 (m,
H), 1.93−1.85 (m, 2H), 1.83−1.73 (m, 4H), 1.64 (d, J = 6.5 Hz,
H), 1.59 (d, J = 6.8 Hz, 3H), 1.54−1.46 (m, 1H), 1.44−1.35 (m,
H), 1.30 (d, J = 2.9 Hz, 3H), 1.29 (d, J = 2.8 Hz, 3H), 1.24 (d, J = 6.9
1H), 7.14−7.09 (m, 2H), 6.86−6.81 (m, 2H), 6.70 (td, J = 7.5, 0.8 Hz,
1H), 6.45 (d, J = 8.2 Hz, 1H), 4.86 (dd, J = 12.9, 9.0 Hz, 1H), 4.66
(hept, J = 6.2 Hz, 1H), 4.44 (dd, J = 12.9, 5.1 Hz, 1H), 3.36−3.25 (m,
2H), 3.22−3.08 (m, 2H), 2.66−2.58 (m, 1H), 2.45 (dtd, J = 9.6, 6.3,
1.8 Hz, 1H), 2.30−2.26 (m, 1H), 2.29 (s, 3H), 2.27 (s, 3H), 2.23 (s,
3H), 2.21−2.07 (m, 2H), 1.99−1.95 (m, 1H), 1.94−1.85 (m, 2H),
1.75 (d, J = 6.1 Hz, 3H), 1.71 (d, J = 6.1 Hz, 3H), 1.44 (s, 3H), 1.35
(s, 3H), 1.02 (d, J = 9.6 Hz, 1H). 13C{ H} NMR (126 MHz, C D ): δ
13
1
Hz, 3H), 1.20 (d, J = 6.2 Hz, 3H), 1.08 (s, 9H). C{ H} NMR (126
MHz, C D ): δ 263.12, 217.48, 167.88, 154.04, 149.08, 147.17, 144.12,
6
6
1
8
3
2
37.59, 128.58, 128.50, 125.80, 124.82, 124.11, 123.21, 123.06, 114.13,
0.54, 74.51, 55.49, 50.04, 48.03, 44.91, 39.36, 39.24, 38.18, 38.06,
4.46, 32.30, 31.30, 30.28, 28.93, 28.81, 28.71, 26.22, 25.31, 23.10,
2.70, 21.90, 21.60 (note: signal at 263.12 ppm detected as cross-peak
1
6
6
288.2, 212.0, 152.8, 144.8, 138.9, 138.6, 138.6, 138.5, 129.9, 129.8,
128.9, 122.4, 122.3, 113.2, 75.0, 58.8, 51.8, 48.5, 45.7, 42.0, 41.3, 39.0,
34.0, 28.4, 26.5, 24.1, 22.4, 22.3, 21.1, 20.2, 18.4, 18.3. HRMS-FAB
in HSQC that we are assigning to a benzylidene carbon). HRMS-FAB
+
+
(
7
m/z): [M + H] calcd for C H N O Ru, 715.3413; found,
15.3383.
(m/z): [M] calcd for C H Cl N ORu, 644.1875; found, 644.1889.
4
0
56
2
3
32
44
2
2
Synthesis of 30. In a glovebox, 29 (98 mg, 0.152 mmol, 1 equiv)
was dissolved in THF (1.5 mL). A solution of NaOPiv (188 mg, 1.52
mmol, 10 equiv) in MeOH (1.5 mL) was then added. The vessel was
sealed and heated to 50 °C for 7.5 h. A crude aliquot was analyzed by
Synthesis of 20. In a glovebox, a 20 mL scintillation vial with a
magnetic stir bar was charged with 19 (36 mg, 0.057 mmol, 1 equiv)
and NaOPiv (72 mg, 0.57 mmol, 10 equiv). Rigorously deoxygenated
THF (ca. 1 mL) and MeOH (ca. 1 mL) were added, and the reaction
was heated to 35 °C and stirred for 1 h. During the reaction, the color
of the solution changed from green to dark blue. Upon completion,
solvent was removed under reduced pressure. The resulting residue
was dissolved in C H , filtered through Celite, and concentrated under
1
H NMR, and full conversion to the bispivalate was observed. The
crude mixture was then concentrated in vacuo, taken up in ether, and
filtered through Celite to give 112 mg (95%) of a dark blue solid. A
sample was purified by silica gel column chromatography in the
1
6
6
glovebox (25−50% ether in hexanes) to give a bright blue solid. H
reduced pressure. The desired product was purified by column
chromatography (4:1 pentane/Et O), yielding the dark blue solid 20
NMR (500 MHz, C D ): δ 18.28 (s, 1H), 7.2−7.15 (m, 1H), 7.05
6
6
2
(ddd, J = 8.2, 7.3, 1.7 Hz, 1H), 6.94 (s, 1H), 6.70 (s, 1H), 6.68 (dd, J =
(
4
9 mg, 24%). Crystals suitable for X-ray diffraction were grown from
:1 pentane/Et O. H NMR (500 MHz, C D ): δ 16.19 (s, 1H), 7.74
8
4
3
2
.3, 7.4 Hz, 1H), 6.42 (d, J = 8.3 Hz, 1H), 5.19 (t, J = 11.3 Hz, 1H),
.53 (hept, J = 6.3 Hz, 1H), 3.44−3.38 (m, 2H), 3.28−3.18 (m, 2H),
.16−3.08 (m, 1H), 2.90 (s, 3H), 2.60−2.50 (m, 2H), 2.48−2.33 (m,
H), 2.21 (t, J = 5.4 Hz, 1H), 2.14 (s, 3H), 2.13 (s, 3H), 2.15−2.09
1
2
6
6
(
6
d, J = 7.8 Hz, 1H), 7.33 (t, J = 7.8 Hz, 1H), 6.94 (t, J = 7.3 Hz, 1H),
.70 (d, J = 8.3 Hz, 1H), 6.44 (s, 1H), 6.37 (s, 1H), 6.31 (d, J = 3.4
Hz, 2H), 4.67 (hept, J = 6.5 Hz, 1H), 4.09 (d, J = 5.2 Hz, 1H), 3.75 (d,
J = 5.2 Hz, 1H), 3.28 (s, 3H), 2.62 (s, 3H), 2.43 (s, 3H), 2.21 (s, 3H),
(
(
9
m, 1H), 2.09−2.03 (m, 1H), 1.90−1.81 (m, 1H), 1.75 (s, 3H), 1.61
d, J = 6.2 Hz, 3H), 1.41 (s, 3H), 1.31 (d, J = 6.3 Hz, 3H), 1.30 (s,
2
.04 (s, 3H), 1.95 (s, 3H), 1.92 (s, 3H), 1.50 (s, 9H), 1.43 (d, J = 6.2
13
1
H), 1.22 (s, 9H), 1.14 (d, J = 9.4 Hz, 1H). C{ H} NMR (126 MHz,
13
1
Hz, 3H), 1.24 (d, J = 6.2 Hz, 3H). C{ H} NMR (126 MHz, C D ):
δ 263.73, 197.24, 156.15, 145.39, 142.19, 140.40, 136.29, 135.90,
6
6
C D ): δ 305.5, 212.1, 187.9, 183.8, 154.3, 144.6, 139.8, 139.1, 138.0,
6
6
1
4
2
37.3, 129.7, 129.2, 128.5, 123.2, 122.9, 112.7, 75.2, 57.5, 52.1, 48.4,
6.7, 42.4, 41.1, 39.3, 39.2, 39.1, 34.4, 29.0, 28.8, 28.1, 26.8, 23.8, 21.6,
1.3, 21.0, 19.4, 19.1, 18.6 (note: signal at 305.5 ppm detected as
1
1
2
35.21, 135.06, 134.64, 133.81, 128.68, 128.59, 128.42, 128.35, 127.97,
27.71, 125.84, 123.62, 122.68, 113.68, 75.94, 44.54, 31.81, 28.22,
2.75, 22.06, 21.50, 20.86, 20.74, 19.74, 19.47, 18.97, 18.92, 14.31
cross-peak in HSQC that we are assigning to a benzylidene carbon).
(note: signal at 263.73 ppm detected as cross-peak in HSQC that we
+
+
HRMS-FAB (m/z): [M] calcd for C42
77.3800.
General Cross Metathesis Assay Methods. Each cross
H N O Ru], 777.3781; found,
63 2 5
are assigning to a benzylidene carbon); HRMS-FAB (m/z): [M + H]
H calcd for C H N O Ru, 657.2631; found, 657.2620.
7
−
2
36 47
2
3
Synthesis of 28. In a glovebox, a 20 mL scintillation vial with a
experiment using catalysts 11, 16, 18, and 20 was run in a glovebox
at 35 °C with 1 mol % catalyst loading in 3 M THF. Since cross
metathesis is an equilibrium reaction, the experiments were left open
to the glovebox atmosphere to remove any produced ethylene from
the reaction vial. Time points were taken at 1, 2, and 4 h by taking a
magnetic stir bar was charged with 27 (50 mg, 0.097 mmol, 1 equiv)
and NaOPiv (120 mg, 0.97 mmol, 10 equiv). Rigorously deoxygenated
THF (ca. 2 mL) and MeOH (ca. 2 mL) were added, and the reaction
was stirred at room temperature for 3 h. Upon completion, solvent was
removed under reduced pressure. The resulting residue was dissolved
small aliquot and dissolving in CDCl . The overall conversion of
3
in C H , filtered through Celite, and concentrated under reduced
6
6
1
starting olefin to products was determined by H NMR in CDCl
pressure, yielding a brown solid. The solid was dissolved in pentane
and then stored in a freezer for 1 h. After cooling, a brown solid had
precipitated out of solution and was isolated by filtering over Celite. It
was then washed with cold pentane (1 mL × 2) and then washed
through with room-temperature pentane. Solvent was removed under
reduced pressure, yielding a brown solid (28 mg, 42%). A crystal for X-
3
comparing isomerized product and cross products to the starting
material. Additionally, the Z-selectivity was determined by comparing
the diagnostic peaks for the E- and Z-olefins of each substrate.
Specifically, the diagnostic peaks for Z-olefins in CDCl are as follows:
3
allyl benzene at 5.78 ppm, 4-pentenol at 5.38−5.19 ppm, and methyl-
1
0-undecenoate at 5.30 ppm. The diagnostic peaks for the E-olefins
ray crystallography was made by slow evaporation recrystallization in
1
are as follows: allyl benzene at 5.74 ppm, 4-pentenol at 5.45 ppm, and
methyl-10-undecenoate at 5.33 ppm. Finally, the ratio of cross product
to isomerized material was determined for allyl benzene and 4-
pentenol substrates. No isomerized product was noted for the 10-
methylundecenoate substrate.
5:1 pentane/Et O. H NMR (500 MHz, C D ): δ 17.52 (s, 1H), 7.33
2
6
6
(
6
dd, J = 7.5, 1.5 Hz, 1H), 7.05 (ddd, J = 8.9, 7.5, 1.6 Hz, 1H), 6.84−
.76 (m, 3H), 6.47 (d, J = 8.4 Hz, 1H), 4.62 (hept, J = 6.2 Hz, 1H),
2
(
.20 (s, 3H), 2.14 (s, 6H), 1.70 (s, 3H), 1.46 (d, J = 6.3 Hz, 6H), 1.35
s, 3H), 1.28 (s, 18H). 13C{ H} NMR (126 MHz, C D ): δ 251.86,
1
6
6
Several experiments were performed to probe the metathesis
activity of the dipivalate species 28 and 30. A simple cross metathesis
of allyl benzene with cis-1,4-diacetoxy-2-butene at a catalyst loading of
5 mol % catalyst loading in DCM was performed. This reaction was
monitored by GC-MS to determine if any new species (i.e., cross
products) were formed. After 1 day at 35 °C, no new products were
noted by GC, indicating that a simple cross did not occur even to a
minimal extent. A simple RCM of diethyl diallylmalonate was
performed in deuterated benzene with a catalyst loading of 1 mol %
catalyst loading at 50 °C. After 1 day, no ring-closed product was
noted by NMR (i.e., no new olefinic peaks were observed). These two
reactions, therefore, indicate that this complex does not catalyze RCM
or CM reactions.
2
1
1
15.59, 186.23, 155.19, 144.21, 139.51, 139.17, 138.76, 137.42, 129.54,
29.27, 124.03, 122.96, 112.92, 75.54, 39.25, 28.43, 21.49, 21.14,
8.19, 11.97, 11.73. HRMS-FAB (m/z): [M + H]+ calcd for
C H NO RuS, 684.2297; found, 684.3880.
34
48
5
Synthesis of 29. In an inert atmosphere glovebox, a vial was
charged with imidazolinium salt S4 (103.1 mg, 0.25 mmol, 1 equiv)
and NaO Bu (24 mg, 0.25 mmol, 1 equiv). Toluene (5 mL) was
t
added, and the mixture was stirred at room temperature for 5 min.
Grubbs−Hoveyda 1 (150.3 mg, 0.25 mmol, 1 equiv) was then added,
and the mixture was heated to 60 °C for 8 h. The solvent was removed
in vacuo, and the title compound was purified by silica gel
chromatography (5−20% ethyl acetate in hexanes) to give a green-
1
brown solid (161 mg, 67%). H NMR (500 MHz, C D ): δ 16.49 (s,
6
6
J
DOI: 10.1021/acs.organomet.5b00185
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
2
013, 135, 10258−10261. (b) Koh, M. J.; Khan, R. K. M.; Torker, S.;
ASSOCIATED CONTENT
■
Hoveyda, A. H. Angew. Chem., Int. Ed. 2014, 53, 1968−1972. (c) Khan,
R. K. M.; Torker, S.; Hoveyda, A. H. J. Am. Chem. Soc. 2014, 136,
*
S
Supporting Information
1
13
Experimental details, H and C NMR spectra, crystallographic
data, and a text file of all computed molecule Cartesian
coordinates in a format for convenient visualization. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.organomet.5b00185.
1
̈
4337−14340. (d) Occhipinti, G.; Hansen, F. R.; Tornroos, K. W.;
Jensen, V. R. J. Am. Chem. Soc. 2013, 135, 3331−3334. (e) Occhipinti,
G.; Koudriavtsev, V.; Tornroos, K. W.; Jensen, V. R. Dalton Trans.
2
014, 43, 11106−11117.
(8) Endo, K.; Herbert, M. B.; Grubbs, R. H. Organometallics 2013,
2, 5128−5135.
3
AUTHOR INFORMATION
Corresponding Authors
E-mail: houk@chem.ucla.edu.
E-mail: rhg@caltech.edu.
Author Contributions
(9) Herbert, M. B.; Lan, Y.; Keitz, B. K.; Liu, P.; Endo, K.; Day, M.
■
W.; Houk, K. N.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 7861−
866.
10) Rosebrugh, L. E.; Herbert, M. B.; Marx, V. M.; Keitz, B. K.;
Grubbs, R. H. J. Am. Chem. Soc. 2013, 135, 1276−1279.
11) MeOH is needed to solubilize the sodium carboxylate starting
material.
7
(
*
*
(
§
M. B. Herbert and B. A. Suslick contributed equally.
(
12) (a) Liu, P.; Xu, X.; Dong, X.; Keitz, B. K.; Herbert, M. B.;
Notes
Grubbs, R. H.; Houk, K. N. J. Am. Chem. Soc. 2012, 134, 1464−1467.
b) Dang, Y.; Wang, Z.-X.; Wang, X. Organometallics 2012, 31, 7222−
The authors declare no competing financial interest.
(
7
8
(
234. (c) Dang, Y.; Wang, Z.-X.; Wang, X. Organometallics 2012, 31,
654−8657.
ACKNOWLEDGMENTS
■
Dr. David VanderVelde is thanked for his assistance with NMR
characterization and experiments. Lawrence Henling and Dr.
Michael K. Takase are acknowledged for X-ray crystallographic
analysis. This work was financially supported by the NIH (NIH
13) (a) Endo, K.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133, 8525−
8
527. (b) Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. J. Am.
Chem. Soc. 2011, 133, 9686−9688.
(14) Keitz, B. K.; Endo, K.; Patel, P. R.; Herbert, M. B.; Grubbs, R. H.
J. Am. Chem. Soc. 2012, 134, 693−699.
5
R01GM031332, R.H.G.) and the NSF (CHE-1212767,
(15) (a) Herbert, M. B.; Marx, V. M.; Pederson, R. L.; Grubbs, R. H.
R.H.G. and CHE-1361104, K.N.H.). The Bruker KAPPA
APEXII X-ray diffractometer was purchased via an NSF
CRIF:MU award to the California Institute of Technology
Angew. Chem., Int. Ed. 2013, 52, 310−314. (b) Cannon, J. S.; Grubbs,
R. H. Angew. Chem., Int. Ed. 2013, 52, 9001−9004. (c) Quigley, B.;
Grubbs, R. H. Chem. Sci. 2014, 5, 501−506. (d) Mangold, S. L.;
O’Leary, D. J.; Grubbs, R. H. J. Am. Chem. Soc. 2014, 136, 12469−
(
CHE-0639094). 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-
1
(
2478.
16) Marx, V. M.; Herbert, M. B.; Keitz, B. K.; Grubbs, R. H. J. Am.
Chem. Soc. 2013, 135, 94−97.
17) (a) Hartung, J.; Grubbs, R. H. J. Am. Chem. Soc. 2013, 135,
10183−10185. (b) Hartung, J.; Grubbs, R. H. Angew. Chem., Int. Ed.
014, 53, 3885−3888. (c) Hartung, J.; Dornan, P. K.; Grubbs, R. H. J.
Am. Chem. Soc. 2014, 136, 13029−13037.
18) Miyazaki, H.; Herbert, M. B.; Liu, P.; Dong, X.; Xu, X.; Keitz, B.
(
1053575).
2
REFERENCES
■
(
(
̈
1) (a) Furstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012−3043.
K.; Ung, T.; Mkrtumyan, G.; Houk, K. N.; Grubbs, R. H. J. Am. Chem.
Soc. 2013, 135, 5848−5858.
(
b) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18−29.
(
c) Schrock, R. R. Chem. Rev. 2002, 102, 145−180. (d) Schrock, R. R.;
(19) (a) Keitz, B. K.; Fedorov, A.; Grubbs, R. H. J. Am. Chem. Soc.
Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592−4633.
2
012, 134, 2040−2043. (b) Rosebrugh, L. E.; Marx, V. M.; Keitz, B.
K.; Grubbs, R. H. J. Am. Chem. Soc. 2013, 135, 10032−10035.
20) (a) These results suggest that oxidative addition of C−H bonds
(
1
e) Vougioukalakis, G.; Grubbs, R. H. Chem. Rev. 2009, 110, 1746−
787. (f) Samojłowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009,
(
1
(
09, 3708−3742.
to form these cyclometalated architectures is not occurring.. (b) For
mechanistic studies on ruthenium-catalyzed C−H bond activation via
the CMD mechanism: Ackermann, L.; Vicente, R.; Althammer, A.
Org. Lett. 2008, 10, 2299−2302.
2) Lin, Y. A.; Chalker, J. M.; Davis, B. G. ChemBioChem 2009, 10,
9
(
(
59−969.
3) (a) Slugovc, C. Macromol. Rapid Commun. 2004, 25, 1283−1297.
b) Miyake, G. M.; Piunova, V. A.; Weitekamp, R. A.; Grubbs, R. H.
(
21) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785−
89. (b) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J.
J. Phys. Chem. 1994, 98, 11623−11627.
22) (a) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215−
41. (b) Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157−167.
23) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B
Angew. Chem., Int. Ed. 2012, 51, 11246−11248. (c) Miyake, G. M.;
Weitekamp, R. A.; Piunova, V. A.; Grubbs, R. H. J. Am. Chem. Soc.
7
2
(
012, 134, 14249−14254.
4) Schrodi, Y.; Ung, T.; Vargas, A.; Mkrtumyan, G.; Lee, C. W.;
(
2
(
Champagne, T. M.; Pederson, R. L.; Hong, S. H. Clean: Soil, Air,
Water. 2008, 36, 669−673.
(
5) (a) Flook, M. M.; Jiang, A. J.; Schrock, R. R.; Mu
̈
ller, P.;
2009, 113, 6378−6396.
Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7962−7963. (b) Jiang, A.
J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009,
(24) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, M. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
1
31, 16630−16631. (c) Yu, M.; Wang, C.; Kyle, A. F.; Jukubec, P.;
Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 479, 88−93.
d) Meek, S. J.; O’Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda, A.
(
H. Nature 2011, 471, 461−466. (e) Speed, A. W. H.; Mann, T. J.;
O’Brien, R. V.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2014,
1
(
36, 16136−16139.
6) For a study on the mechanism of the C−H activation reaction,
see: Cannon, J. S.; Zou, L.; Liu, P.; Lan, Y.; O’Leary, D. J.; Houk, K.
N.; Grubbs, R. H. J. Am. Chem. Soc. 2014, 136, 6733−6743.
(
7) For examples of other reported Z-selective ruthenium catalysts,
see: (a) Khan, R. K. M.; Torker, S.; Hoveyda, A. H. J. Am. Chem. Soc.
K
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Article
̈
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J.
B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision D.01;
Gaussian, Inc.: Wallingford, CT, 2009.
(
25) For computational studies on the selectivity in palladium-
catalyzed carboxylate-assisted C−H activations: (a) Gorelsky, S. I.;
Lapointe, D.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848−10849.
(
2
́
b) Guihaume, J.; Clot, E.; Eisenstein, O.; Perutz, R. N. Dalton Trans.
010, 39, 10510−10519. (c) Gorelsky, S. I.; Lapointe, D.; Fagnou, K.
J. Org. Chem. 2012, 77, 658−668. (d) Petit, A.; Flygare, J.; Miller, A.
T.; Winkel, G.; Ess, D. H. Org. Lett. 2012, 14, 3680−3683.
(
26) (a) Rosen, E. L.; Sung, D. H.; Chen, Z.; Lynch, V. M.; Bielawski,
C. W. Organometallics 2010, 29, 250−256. (b) Pazio, A.; Wozniak, K.;
Grela, K.; Trzaskowski, B. Organometallics 2015, 34, 563−570.
(
27) Z-Content degradation is an issue for this family of
cyclometalated catalysts, and current investigations are aimed at
elucidating its origins.
(
28) Vougiokalakis, G. C.; Grubbs, R. H. J. Am. Chem. Soc. 2008, 130,
2234−2245.
L
DOI: 10.1021/acs.organomet.5b00185
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