Fast-initiating, ruthenium-based catalysts for improved activity in highly E-selective cross metathesis

Article abstract of DOI:10.1021/jacs.6b11330

Ruthenium-based olefin metathesis catalysts bearing dithiolate ligands have been recently employed to generate olefins with high E-selectivity (>99% E) but have been limited by low to moderate yields. In this report, ¹H NMR studies reveal that a major contributing factor to this low activity is the extremely low initiation rates of these catalysts with trans olefins. Introducing a 2-isopropoxy-3-phenylbenzylidene ligand in place of the conventional 2-isopropoxybenzylidene ligand resulted in catalysts that initiate rapidly under reaction conditions. As a result, reactions were completed in significantly less time and delivered higher yields than those in previous reports while maintaining high stereoselectivity (>99% E).

Full text of DOI:10.1021/jacs.6b11330

Article
pubs.acs.org/JACS
Fast-Initiating, Ruthenium-based Catalysts for Improved Activity
in Highly E‑Selective Cross Metathesis
Tonia S. Ahmed and Robert H. Grubbs*
The Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and Chemical Engineering. California
Institute of Technology, Pasadena, California 91125, United States
S
* Supporting Information
ABSTRACT: Ruthenium-based olefin metathesis catalysts bearing dithiolate ligands have been
recently employed to generate olefins with high E-selectivity (>99% E) but have been limited
by low to moderate yields. In this report, 1H NMR studies reveal that a major contributing factor
to this low activity is the extremely low initiation rates of these catalysts with trans
olefins. Introducing a 2-isopropoxy-3-phenylbenzylidene ligand in place of the conventional
2-isopropoxybenzylidene ligand resulted in catalysts that initiate rapidly under reaction conditions.
As a result, reactions were completed in significantly less time and delivered higher yields than
those in previous reports while maintaining high stereoselectivity (>99% E).
catalytic trans-hydrosilylation/protodesilylation,12 or semihy-
BACKGROUND
■
drogenation13 can also furnish trans olefins. These methods,
Given its robustness and general ease of implementation,
transition metal-catalyzed olefin metathesis has become an
however, are either harsh or require multiple steps to reach the
desired trans product.
The first demonstration of highly kinetically trans-selective
transition metal-catalyzed olefin cross metathesis was reported
increasingly ubiquitous method for generating C−C double
bonds in a wide variety of fields including organic synthesis,
green chemistry, and biochemistry.1 Over the last several years,
this year with the unexpected discovery that ruthenium-based
catalysts bearing chelated dithiolate ligands are able to perform
cross metathesis between two trans olefins or between a trans
olefin and a terminal olefin to generate products with high trans
selectivity (>98% E).3l These catalysts had been previously
demonstrated to react with cis starting materials to form
highly cis products.3k Hence, these catalysts are stereoretentive,
preserving the stereochemical purity of the starting olefins
in the product olefins. The E-selectivity of the catalysts is
proposed to arise from the two N-aryl groups of the NHC
forcing the α substituents of a side-bound metallacycle to point
down while the β substituent can point into the open space in
front of the plane containing the N−C−N bonds of the NHC
and between the two N-aryl groups (Figure 1). This proposed
model was supported by the observation that reducing the size
of the ortho substituents of the N-aryl groups of the NHC led to
increased catalyst activity in this transformation. A subsequent
report from the Hoveyda and Schrock groups demonstrated a
similar approach to achieving trans-selective cross metathesis
using Mo-based catalysts.3m Steric interactions of the sub-
stituents of the metallacycle with surrounding ligands in
combination with minimizing unfavorable eclipsing interactions
olefin metathesis has been significantly advanced through the
synthesis of well-defined catalysts, where methodical tuning of
catalyst architecture has allowed for the development of different
catalysts that can each achieve a specific purpose including
enantioselectivity,2 stereoselectivity,3 or increased activity.4
Achieving high selectivity for 1,2-disubstituted olefinic
products with a particular stereochemistry (E or Z) was a
longstanding challenge in olefin metathesis until discrete
Ru-,3e−h Mo-, and W-based3b−d catalysts were developed in
recent years for the metathesis of terminal olefins to produce
high levels of cis olefins. Each of these catalysts exploits steric
impedances within the catalyst structure to favor the syn over
the anti metallacyclobutane pathway.5
Until very recently, methods of achieving high kinetic trans
selectivity through olefin metathesis had remained elusive.
Selectivity for trans product in olefin metathesis can often be
achieved by allowing the reaction to reach equilibrium so that
the thermodynamically favored product, often trans, is present
in higher quantities.6 However, the difference in energy
between some cis and trans isomers may be insignificant;
hence, this method is not reliable for obtaining all trans
products in high selectivity. Other methods for preparing trans
olefins with high stereoselectivity include Z-selective ethenol-
ysis of E-/Z-olefin mixtures,7 Wittig reactions of stabilized
ylides,8 Julia olefinations,9 and Peterson olefinations.10 In
addition, alkyne metathesis followed by Na/NH3 reduction,11
Received: October 31, 2016
© XXXX American Chemical Society
A
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Figure 1. Proposed models for high kinetic trans and cis selectivity in cross metathesis with ruthenium catalysts3l (left) and high trans selectivity with
molybdenum catalysts3m (right).
of new catalysts with improved initiation efficiency that demon-
strate significantly improved conversions and reaction times in
comparison to previous catalysts.
RESULTS AND DISCUSSION
■
When examining the self-metathesis of trans-2-hexenyl acetate
catalyzed by 1 mol % 1, uninitiated catalyst was evident in
1
the H NMR after 24 h at 45 °C, at which time only 85% of
the catalyst had initiated (Figure 2). Based on this result, new
catalyst 2, bearing a chelating 2-isopropoxy-3-phenylbenzylidene
ligand in place of the 2-isopropoxybenzylidene of catalyst 1,
was synthesized. This alteration has been shown to drastically
increase rates of initiation in other ruthenium-based metathesis
catalysts.4c−f Under the same aforementioned reaction con-
ditions with trans-2-hexenyl acetate, 93% of 2 initiated after only
3 h, and 2 was fully initiated within 6 h. For each catalyst, loss of
the chelated benzylidene ligand is required prior to entrance
into the catalytic cycle of olefin metathesis. Given the poor
initiation of 1 even under relatively forcing conditions of
elevated temperatures and high trans-substrate concentration,
the concentration of active catalyst is significantly lower than
that expected from the catalyst loading. As a result, the yields
of products are diminished, limiting the use of this catalyst. This
issue is resolved with catalyst 2.
Initiation rate constants (kinit) were calculated for 1 and 2
under these reactions conditions and were determined to
be 2.52 × 10−5 and 1.75 × 10−4 s−1, respectively (Figure 3).
Figure 2. Signals corresponding to the benzylidene protons of each
1 and 2 over the course of the reaction with trans-2-hexenyl acetate
(0.5 M) in THF-d8 at 45 °C. Percentages shown are percentages of
Figure 3. Plot of ln([Ru]/[Ru]0) versus time. Plots remain
catalyst initiated as determined by the decrease in the benzylidene
approximately linear over the course of three half-lives of the reaction.
signal over time upon reaction with substrate.
of these substituents was their proposed rationale for the
favorable formation of anti metallacycles.
The relative rate constant (krel) hence has a value of ∼7. Thus,
one-seventh of the catalyst loading of 1 can be used to achieve
the same active catalyst concentration with catalyst 2. Given the
low activity seen in previous studies of 1 in cross metathesis
reactions involving trans olefins and the inability of this catalyst
to initiate efficiently even under forcing conditions, the dif-
ference in the ability between 1 and 2 to initiate under normal
reaction conditions can make a significant difference in the
ability to provide meaningful yields of products.
In many instances, the trans-selective, Ru dithiolate catalysts
generated low yields of products. Two possible reasons for the
low activity can be envisioned: slow catalyst initiation and the
inherently small “open space” in which the β substituent can
place itself. Herein, we establish that poor initiation is indeed a
significant factor in the low conversions observed with previous
dithiolate catalysts. We address this through the development
B
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Scheme 1
Figure 4. Catalysts examined in this study.
a
Table 1. Self-Metathesis of Methyl 9-octadeceonate
entry
1
starting material
Ru (mol %)
time
1 h
% MO (E/Z)
% DE (E/Z)
% 9C18 (E/Z)
E
1 (1.0)
99 (>99/1)
92 (>99/1)
54 (>99/1)
50 (>99/1)
80 (>99/1)
50 (>99/1)
88 (>99/1)
50 (>99/1)
84 (>99/1)
60 (>99/1)
50 (>99/1)
50 (>99/1)
62 (>99/1)
50 (>99/1)
50 (>99/1)
98 (<1/99)
92 (<1/99)
54 (<1/99)
50 (<1/99)
80 (<1/99)
50 (<1/99)
70 (<1/99)
60 (<1/99)
50 (<1/99)
50 (<1/99)
76 (<1/99)
50 (<1/99)
62 (<1/99)
50 (<1/99)
0.5 (>99/1)
4 (>99/1)
0.5 (>99/1)
4 (>99/1)
23 (>99/1)
25 (>99/1)
10 (>99/1)
25 (>99/1)
6 (>99/1)
25 (>99/1)
8 (>99/1)
20 (>99/1)
25 (>99/1)
25 (>99/1)
19 (>99/1)
25 (>99/1)
25 (>99/1)
1 (<1/99)
4 (<1/99)
23 (<1/99)
25 (<1/99)
10 (<1/99)
25 (<1/99)
15 (<1/99)
20 (<1/99)
25 (<1/99)
25 (<1/99)
12 (<1/99)
25 (<1/99)
19 (<1/99)
25 (<1/99)
3 h
11 h
23 (>99/1)
25 (>99/1)
10 (>99/1)
25 (>99/1)
6 (>99/1)
15 h
2
3
4
E
E
E
2 (1.0)
3 (1.0)
4 (1.0)
1 h
3 h
30 min
2.5 h
25 (>99/1)
8 (>99/1)
10 min
20 min
30 min
1 h
20 (>99/1)
25 (>99/1)
25 (>99/1)
19 (>99/1)
25 (>99/1)
25 (>99/1)
1 (<1/99)
5
6
E
E
4 (0.5)
5 (1.0)
10 min
20 min
40 min
30 min
1 h
7
8
E
Z
5 (0.5)
1 (0.1)
4 (<1/99)
3 h
23 (<1/99)
25 (<1/99)
10 (<1/99)
25 (<1/99)
15 (<1/99)
20 (<1/99)
25 (<1/99)
25 (<1/99)
12 (<1/99)
25 (<1/99)
19 (<1/99)
25 (<1/99)
5 h
9
Z
Z
2 (0.1)
3 (0.5)
15 min
30 min
30 s
10
60 s
90 s
11
12
Z
Z
3 (0.05)
4 (0.1)
15 min
15 min
40 min
25 min
50 min
13
Z
5 (0.1)
a
Product distribution and selectivity analyzed by GC using tridecane as an internal standard.
C
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By varying the size of the ortho substituents of the N-aryl
groups of the NHC, a series of other fast-initiating catalysts
(3−5) were synthesized (Scheme 1). 2−5 were synthesized
from phosphine-bound catalysts 2a−5a. The chelating
2-isopropoxy-3-phenylbenzylidene ligand is installed by reac-
tion of 2a−5a with CuCl and (E/Z)-2-isopropoxy-3-(prop-1-
en-1-yl)-1,1′-biphenyl to generate 2b−5b. This is followed
by the exchange of the two chloride X-ligands with a dithiolate
ligand using a zinc transmetallating agent to produce 2−5
(Figure 4).
Scheme 2. Cross Metathesis of trans-1,4-Diacetoxy-2-butene
with trans-4-Octene
a
To observe differences in reactivity of catalysts 1−5, the
self-metathesis of the trans isomer of the substrate methyl
9-octadecenoate (MO) to produce dimethyl 9-octadecenedioate
(DE) and 9-octadecene (9C18) was examined (Table 1, entries
1−7). With 1 mol % 1, this reaction requires 15 h to reach
equilibrium, whereas the same reaction with 2 reaches equili-
brium in 3 h while maintaining the same high stereoselectivity
(>99% E). To examine the relationship between the size of the
ortho substituents of the N-aryl group of the NHC and catalyst
activity, 3−5 were then studied in this reaction. 3 reaches
equilibrium in 2.5 h, whereas it only takes 30 min for 4 and
20 min for 5 to achieve the same distribution while high trans
selectivity is conserved (>99% E). The catalyst loading of 4 and
5 can be dropped to 0.5 mol %, and the reaction still reaches
equilibrium within 1 h and 40 min, respectively.
The self-metathesis of the cis analogue of this substrate,
Z-methyl 9-octadecenoate, was also analyzed (Table 1, entries
8−13). These catalysts were markedly more active in this
reaction than that of the E-isomer. Catalyst 3 (0.5 mol %)
is strikingly fast and reaches equilibrium in 90 s, while the
products retain the stereochemistry of the starting material
(>99% Z). The catalyst loading can be reduced 10-fold to
0.05 mol %, and the reaction reaches equilibrium in 15 min.
With 0.1 mol % catalyst, the reaction reaches equilibrium in
30 min with 2, 40 min with 4, and 50 min with 5. Catalyst 1,
however, requires 5 h at the same loading to achieve
equilibrium.
a
Conversions determined using 1H NMR. Stereoselectivity determined
by GC. Inset shows early time points.
substrates in comparison to that of 2, but is more active than 1
in this transformation. Catalyst 4 is remarkably fast in this
reaction, achieving 80% conversion to the product (>99% E) in
only 25 min. Also in agreement with the proposed model that
suggests increased activity with decreasing ortho substituent size
of the N-aryl groups, 5 demonstrated high initial conversion
early in the reaction, but was found to decompose under reaction
conditions, only reaching 36% overall conversion.
As seen in the reaction with methyl 9-octadecenoate, the
reaction of the cis isomers of these substrates, cis-4-octene and
cis-1,4-diacetoxy-2-butene (4:1 molar ratio), was significantly
more facile than that of the corresponding trans isomers with
the catalysts (Scheme 3). 3 was the most active catalyst in
this reaction, reaching 86% conversion in 11 min. 2 and 4
To examine the disparity of the rates of reaction of each of
these catalysts with the E- and Z-isomers of methyl 9-octa-
decenoate, a relative rate constant (kZ/kE) was calculated using
the times needed for the reactions to reach equilibrium (tE and
tZ), assuming first-order kinetics with respect to initial catalyst
concentration ([Ru]E and [Ru]Z).14
Scheme 3. Cross Metathesis of cis-1,4-Diacetoxy-2-butene
with cis-4-Octene
a
kZ/kE = [Ru]EtE/([Ru]Z tZ)
(1)
For catalysts 2−5, kZ/kE values were determined to be 200,
60, 7.5, and 4. This is in accordance with our proposed model
for selectivity, where E-olefin formation proceeds through
a metallacycle in which the β substituent points into the “open
space” between the two N-aryl groups. Thus, reducing the
size of the ortho substituents of the N-aryl groups increases the
ability of the E-olefin to react with the catalysts.
In order to examine the reactivity of these catalysts with
substrates bearing functional groups closer to the double bond,
cross metathesis between trans-4-octene and trans-1,4-diac-
etoxy-2-butene (4:1 mol ratio) was examined (Scheme 2).
Using 1 (7.5 mol %), this reaction reaches a conversion of only
4% in 1 h to trans-2-hexenyl acetate (>99% E). Under identical
conditions, 2 achieves 24% conversion in 1 h. After 7 h, the
reaction reaches 80% conversion with 2, while parent catalyst 1
requires 3 days to reach 65% conversion. Consistent with the
proposed model for selectivity, 3, with bulky N-diisopropyl-
phenyl groups of the NHC, has lower activity for these trans
a
Conversions determined using 1H NMR. Stereoselectivity determined
by GC.
D
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a
performed similarly, both reaching 81% conversion in 15 min. 1
reached 80% conversion in this reaction in 20 min. Catalyst 5
again decomposed under reaction conditions, reaching an
overall yield of 28%. At the start of the reaction, however, it
displayed reactivity less than that of catalysts 2−4 but greater
than that of parent catalyst 1. In this set of reactions, the
opposite trend is seen with respect to changing the identity of
the ortho substituents: As the NHC substituents get smaller,
the reactivity with this substrate decreases. Because degradation
is seen in both the reaction with the cis and trans isomers,
the decomposition of 5 is likely due to a side reaction with
1,4-diacetoxy-2-butene.
Table 3. Cross Metathesis of 1-Decene and cis-4-Octene
entry
1
[Ru]
time (h)
yield
E/Z
1
0.25
73
74
74
75
75
75
76
77
77
77
77
78
75
75
75
74
65
70
70
70
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
2/98
1
2
4
2
3
4
5
2
3
4
5
0.25
1
2
The more challenging reaction of the cross metathesis of
a disubstituted olefin, trans-4-octene, and a terminal olefin,
1-decene, to generate 4-tridecene was then attempted (Table 2).
4
0.25
1
a
2
2/98
Table 2. Cross Metathesis of 1-Decene and trans-4-Octene
4
5/95
0.25
1
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
<1/99
2
entry
1
[Ru]
time (h)
yield
E/Z
4
1
0.25
17
20
20
21
24
25
26
27
16
17
17
19
47
49
50
49
51
52
52
52
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
90/10
90/10
90/10
90/10
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
0.25
1
1
2
2
4
4
a
2
3
4
5
2
3
4
5
0.25
Product distribution and selectivity analyzed by GC using tetradecane
1
as an internal standard.
2
4
0.25
CONCLUSIONS
■
1
1H NMR studies were used to determine that recently reported
highly stereoretentive ruthenium-based catalysts bearing
dithiolate ligands suffer from poor catalyst initiation in reac-
tions with trans olefins. In order to improve initiation
characteristics, a series of fast-initiating catalysts 2−5 possessing
a 2-isopropoxy-3-phenylbenzylidene ligand in place of the
2-isopropoxybenzylidene ligand were synthesized. These
catalysts demonstrate significantly improved initiation com-
pared to that of 1, resulting in considerably increased activity of
these catalysts in reactions of trans olefins and demonstrating
higher yields at shorter reaction times, while maintaining high
stereoselectivity of products (>99% E). Some improvement was
also observed in reactions with cis olefins compared to pre-
viously reported catalysts, although the difference was more
marginal as the previous catalysts were efficient at catalyz-
ing reactions involving cis olefins with high stereoselectivity
(>99% Z).
2
4
0.25
1
2
4
0.25
1
2
4
a
Product distribution and selectivity analyzed by GC using tetradecane
as an internal standard.
This reaction proved difficult for all catalysts due to rapid
decomposition of these catalysts, likely due to the formation of
the unstable ruthenium methylidenes under these conditions. As
a result, yields of the product in this reaction for each of these
catalysts did not change significantly after 15 min. Catalyst 3
(6 mol %) was the least active, reaching a maximum of 19%
yield (90% E).15 2 generated the product in 27% yield, slightly
higher than that of 1 at 21% yield. 4 and 5, however, were
efficient at reaching moderate yields of products with yields of
50 and 52%, respectively, again in agreement with the proposed
model by which reducing ortho substituent size of N-aryl groups
is proposed to increase catalytic activity.16 Catalysts 1, 2, 4, and
5 all delivered high selectivity of the trans product (>99% E).
In the cross metathesis of cis-4-octene and 1-decene, yields
were consistent across catalysts 1−4, ranging from 75−78%
with high stereoretention (>95% Z) throughout the reaction
(Table 3).17 Catalyst 5 generated the product in a slightly lower
70% yield.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.6b11330.
Characterization data, and experimental data (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: rhg@caltech.edu.
■
ORCID
Robert H. Grubbs: 0000-0002-0057-7817
Notes
The authors declare no competing financial interest.
E
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Sci. 1980, 333, 165. (d) Ritter, T.; Hejl, A.; Wenzel, A. J.; Funk, T. W.;
Grubbs, R. H. Organometallics 2006, 25 (24), 5740.
ACKNOWLEDGMENTS
■
We acknowledge funding from the Office of Naval Research
(N00014-14-1-0650) and the NSF (CHE-1502616). T.S.A. is
grateful for support from the National Science Foundation
through a Graduate Research Fellowship. Any opinion,
findings, and conclusions or recommendations expressed in
this material are those of the authors and do not necessarily
reflect the views of the National Science Foundation. Materia,
Inc. is thanked for generous donations of catalysts 2a and 3a.
M. A. Pribisko, B. L. Quigley, and R. M. B. Silva are thanked for
their input on this manuscript. J. R. Sampson, W. J. Wolf, N. F.
Nathel, and T. P. Montgomery are thanked for helpful
discussions.
(7) (a) Marinescu, S. C.; Levine, D. S.; Zhao, Y.; Schrock, R. R.;
Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 11512. (b) Miyazaki, H.;
Herbert, M. B.; Liu, P.; Dong, X.; Xu, X.; Keitz, B. K.; Ung, T.;
Mkrtumyan, G.; Houk, K. N.; Grubbs, R. H. J. Am. Chem. Soc. 2013,
135, 5848.
(8) Vedejs, E.; Peterson, M. J. Top. Stereochem. 1994, 21, 1.
(9) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563.
(10) van Staden, L. F.; Gravestock, D.; Ager, D. J. Chem. Soc. Rev.
2002, 31, 195.
(11) Pasto, D. J. In Comprehensive Organic Synthesis, Vol. 8; Trost, B.
M., Fleming, I., Ed.; Pergamon Press: Oxford, 1991; Chapter 3.3.
(12) Trost, B. M.; Ball, Z. T.; Joge, T. J. Am. Chem. Soc. 2002, 124,
̈
7922.
(13) (a) Srimani, D.; Diskin-Posner, Y.; Ben-David, Y.; Milstein, D.
Angew. Chem., Int. Ed. 2013, 52, 14131. (b) Radkowski, K.;
REFERENCES
■
Sundararaju, B.; Furstner, A. Angew. Chem., Int. Ed. 2013, 52, 355.
̈
(1) Grubbs, R. H., Wenzel, A. G., O’Leary, D. J., Khosravi, E., Eds.
Handbook of Metathesis; Wiley−VCH: Weinheim, 2015.
(2) (a) Hoveyda, A. H.; Schrock, R. R. Chem. - Eur. J. 2001, 7, 945.
(b) Van Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A.
H. J. Am. Chem. Soc. 2005, 127, 6877. (c) Funk, T. W.; Berlin, J. M.;
Grubbs, R. H. J. Am. Chem. Soc. 2006, 128 (6), 1840. (d) Berlin, J. M.;
Goldberg, S. D.; Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 7591.
(e) Tiede, S.; Berger, A.; Schlesiger, D.; Rost, D.; Luhl, A.; Blechert, S.
Angew. Chem., Int. Ed. 2010, 49, 3972. (f) Furstner, A.; Ackermann, L.;
Gabor, B.; Goddard, R.; Lehmann, C. W.; Mynott, R.; Stelzer, F.;
(c) Liu, Y.; Hu, L.; Chen, H.; Du, H. Chem. - Eur. J. 2015, 21, 3495.
(14) By increasing catalyst concentration by a certain factor, reaction
rate was increased by the same factor. See Table S1 for data.
(15) In this case, conversion of 1-decene to a variety of isomers was
also seen, and this isomerization process might be responsible for the
degraded level of E-selectivity.
(16) Previous studies have shown that Ru---F interactions sometimes
occur in particular olefin metathesis systems.18 Although there is no
evidence of this in this system, this type of interaction might play a role
in this reaction.
̈
̈
(17) Lower yields than expected in this reaction could be attributed
to the self-metathesis of the product, 4-tridecene, to form 4-octene and
9-octadecene as detected by GC. Degradation of Z-content with 3 is
likely due to secondary metathesis processes promoted by this very
active catalyst.
Thiel, O. R. Chem. - Eur. J. 2001, 7 (15), 3236−3253.
(3) (a) Flook, M. M.; Jiang, A. J.; Schrock, R. R.; Muller, P.;
̈
Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7962. (b) Jiang, A. J.;
Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131,
16630. (c) Meek, S. J.; O’Brien, R. V.; Llaveria, J.; Schrock, R. R.;
Hoveyda, A. H. Nature 2011, 471, 461. (d) Yu, M.; Wang, C.; Kyle, A.
F.; Jakubec, P.; Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature
2011, 479, 88. (e) Endo, K.; Grubbs, R. H. J. Am. Chem. Soc. 2011,
133, 8525. (f) Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. J.
Am. Chem. Soc. 2011, 133, 9686. (g) Keitz, B. K.; Endo, K.; Patel, P.
R.; Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2012, 134, 693.
(18) Ritter, T.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2006,
128, 11768.
(h) Occhipinti, G.; Hansen, F. R.; Tornroos, K. W.; Jensen, V. R. J.
̈
Am. Chem. Soc. 2013, 135, 3331. (i) Khan, R. K. M.; Torker, S.;
Hoveyda, A. H. J. Am. Chem. Soc. 2013, 135, 10258. (j) Koh, M. J.;
Khan, R. K. M.; Torker, S.; Hoveyda, A. H. Angew. Chem., Int. Ed.
2014, 53, 1968. (k) Koh, M. J.; Khan, R. K. M.; Torker, S.; Yu, M.;
Mikus, M. S.; Hoveyda, A. H. Nature 2015, 517, 181. (l) Johns, A. M.;
Ahmed, T. S.; Jackson, B. W.; Grubbs, R. H.; Pederson, R. L. Org. Lett.
2016, 18 (4), 772. (m) Nguyen, T. T.; Koh, M. J.; Shen, X.; Romiti, F.;
Schrock, R. R.; Hoveyda, A. H. Science 2016, 352, 569.
(4) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953. (b) Furstner, A.; Ackermann, L.; Gabor, B.; Goddard, R.;
̈
Lehmann, C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R. Chem. - Eur. J.
2001, 7 (15), 3236−3253. (c) Wakamatsu, H.; Blechert, S. Angew.
Chem., Int. Ed. 2002, 41, 2403. (d) Bujok, R.; Bieniek, M.; Masnyk, M.;
Michrowska, A.; Sarosiek, A.; Stępowska, H.; Arlt, D.; Grela, K. J. Org.
Chem. 2004, 69, 6894. (e) Nelson, D. J.; Queval, P.; Rouen, M.;
Magrez, M.; Toupet, L.; Caijo, F.; Borre, E.; Laurent, I.; Crev
́
isy, C.;
Basle, O.; Mauduit, M.; Percy, J. M. ACS Catal. 2013, 3, 259. (f) Engle,
́
K. M.; Lu, G.; Luo, S.; Henling, L. M.; Takase, M. K.; Liu, P.; Houk, K.
N.; Grubbs, R. H. J. Am. Chem. Soc. 2015, 137, 5782.
(5) (a) Liu, P.; Xu, X.; Dong, X.; Keitz, B. K.; Herbert, M. B.; Grubbs,
R. H.; Houk, K. N. J. Am. Chem. Soc. 2012, 134, 1464. (b) Dang, Y.;
Wang, Z. X.; Wang, X. Organometallics 2012, 31, 7222. (c) Dang, Y.;
Wang, Z. X.; Wang, X. Organometallics 2012, 31, 8654. (d) Occhipinti,
G.; Koudriavtsev, V.; Tornroos, K. W.; Jensen, V. R. Dalton Trans.
̈
2014, 43, 11106. (e) Torker, S.; Khan, R. K. M.; Hoveyda, A. H. J. Am.
Chem. Soc. 2014, 136, 3439.
(6) (a) Bilhou, J. L.; Basset, J. M.; Mutin, R.; Graydon, W. F. J. Am.
Chem. Soc. 1977, 99, 4083. (b) Leconte, M.; Basset, J. M. J. Am. Chem.
Soc. 1979, 101, 7296. (c) Leconte, M.; Basset, J. M. Ann. N. Y. Acad.
F
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