Highly active ruthenium metathesis catalysts exhibiting unprecedented activity and Z-selectivity

Article abstract of DOI:10.1021/ja311916m

A novel chelated ruthenium-based metathesis catalyst bearing an N-2,6-diisopropylphenyl group is reported and displays near-perfect selectivity for the Z-olefin (>95%), as well as unparalleled TONs of up to 7400, in a variety of homodimerization and industrially relevant metathesis reactions. This derivative and other new catalytically active species were synthesized using an improved method employing sodium carboxylates to induce the salt metathesis and C-H activation of these chelated complexes. All of these new ruthenium-based catalysts are highly Z-selective in the homodimerization of terminal olefins.

Full text of DOI:10.1021/ja311916m

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Communication
Highly Active Ruthenium Metathesis Catalysts
Exhibiting Unprecedented Activity and Z-Selectivity
Lauren Estelle Rosebrugh, Myles B. Herbert, Vanessa M.
Marx, Benjamin Keith Keitz, and Robert Howard Grubbs
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja311916m • Publication Date (Web): 14 Jan 2013
Downloaded from http://pubs.acs.org on January 15, 2013
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Highly Active Ruthenium Metathesis Catalysts Exhibiting Un-
precedented Activity and Z-Selectivity
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Lauren E. Rosebrugh, Myles B. Herbert, Vanessa M. Marx, Benjamin K. Keitz, Robert H. Grubbs*
Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and Chemical Engineering, Cali-
fornia Institute of Technology, Pasadena, California 91125, United States
Supporting Information Placeholder
tramolecular C-H activation induced by the addition of
ABSTRACT: A novel chelated ruthenium-based me-
silver pivalate (AgOPiv) (Scheme 1). Prior to this re-
tathesis catalyst bearing an N-2,6-diisopropylphenyl
port, nitrato-catalyst 3 was the best Z-selective ruthe-
group is reported and displays near-perfect selectivity
nium-based metathesis catalyst, with turnover num-
for the Z-olefin (>95%), as well as unparalleled TONs
bers (TONs) approaching 1000 and Z-selectivity on
of up to 7400, in a variety of homodimerization and
average around 90%. This catalyst has been shown to
industrially relevant metathesis reactions. This deriva-
be effective for the synthesis of homo- and hetero-
tive and other new catalytically-active species were
cross products, stereoregular polymers, and a variety
synthesized using an improved method employing
of insect pheromones and macrocyclic musks.8c,9
sodium carboxylates to induce the salt metathesis and
C-H activation of these chelated complexes. All of the-
se new ruthenium-based catalysts are highly Z-
Scheme 1. Synthetic Route to Previously Reported
C-H Activated Metathesis Catalysts.
selective in the homodimerization of terminal olefins.
N
N Mes
N
N Mes
N
N Mes
Cl
AgOPiv
NH4NO3
Ru
O
Ru
O
Ru
O
O
N
O
Cl
O
iPr
tBu
O
iPr
O
iPr
The transition-metal catalyzed olefin metathesis re-
action has emerged as an indispensable methodology
for the construction of new carbon-carbon double
bonds.1 Since its discovery in the 1950s, metathesis
has been employed with great success in a number of
fields, including biochemistry,2 materials science,3 and
green chemistry.4 However, an ongoing challenge in
cross metathesis (CM) reactions has been the control
of stereoselectivity, as metathesis catalysts generally
favor formation of the thermodynamically preferred
E-olefin.5 Many natural products and pharmaceutical
targets, on the other hand, contain Z-olefins.6 Recent
groundbreaking work by Schrock and Hoveyda et. al.
resulted in the development of the first Z-selective
metathesis catalysts using molybdenum and tungsten,
allowing for the effective synthesis of Z-olefins via
metathesis for the first time and opening the door to
the development of new and improved Z-selective cat-
alysts.7
1
2
3
Based on computational data, we hypothesized that
increasing the steric bulk of the N-aryl group of 3
would further destabilize the E-selective transition
state, thereby enhancing Z-selectivity.10 However, as
detailed in a previous report, attempts to make signif-
icant alterations to the NHC substituents, both to the
chelating group and to the N-aryl group, mostly re-
sulted in decomposition upon exposure to AgOPiv.11
In order to access stable chelated species with various
modifications to the NHC substituents, we sought to
develop a milder approach to form this ruthenium-
carbon bond. Herein, we report on an improved
method to induce the salt metathesis and C-H activa-
tion of ruthenium alkylidene complexes employing
mild and economically viable sodium carboxylates,
and explore the superior activity and selectivity of
several new chelated metathesis-active catalysts.
Through the use of this improved approach, we have
uncovered the highly active catalyst 9, which on aver-
age gives >95% Z-selectivity and TONs of up to 7400
in the homodimerizations of terminal olefin sub-
strates. In contrast, recently reported molybdenum-
More recently, we reported on the synthesis and
activity of a comparable class of Z-selective ruthenium
metathesis catalysts (2, 3) containing a chelating N-
heterocyclic carbene (NHC) ligand.8 The Ru-
adamantyl bond of the chelate was formed via an in-
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and tungsten-based systems reach TONs of up to 500
the nitrato-complexes would be more stable and show
increased activity.8c,15 While this seemed to be the
case for complexes possessing chelating N-
adamantyl group, catalyst 7 was more stable and
more easily isolated in the pivalate form. Catalysts
successfully synthesized using the NaOPiv method
are depicted in Figure 1.
1
2
3
4
5
6
7
with comparable Z-selectivities for the same reac-
tions.12 As such, the turnover numbers reported here-
in are the highest for any Z-selective metathesis cata-
lyst to date.
a
Scheme 2. Decomposition and C-H Activation
Pathways of 4.
8
9
N
N Mes
N
N
MIPP
N
N DIPP
N
N
DIPP
N
N DIPP
10
11
12
13
14
15
16
17
18
19
20
21
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tBu
Ru
O
Ru
O
O
Ru
O
Cl
AgOPiv
Ru
O
O
O
N
O
N
Ru
O
O
iPr
Cl
O
tBu
O
iPr
O
iPr
O
O
O
O
iPr
tBu
iPr
7
8
9
4
5
Figure 1. Catalysts 7-9: Mes = 2,4,6-trimethylphenyl (7);
MIPP = 2,6-methylisopropylphenyl (8) DIPP = 2,6-
diisopropylphenyl (9).
N
N DIPP
N
N DIPP
NaOPiv
NH4NO3
Ru
O
Ru
O
O
N
O
O
iPr
tBu
O
iPr
O
To look at the efficacy of these new complexes for
metathesis, we first evaluated their performance in
the homodimerization of allyl benzene (10). While a
relatively facile substrate for homodimerization, allyl
benzene is also prone to olefin isomerization to form
12. Importantly, the extent of this side reaction de-
pends heavily on the identity and stability of the cata-
lyst, making 10 a good benchmark substrate.16 Ho-
modimerization reactions were generally run in THF
at 35°C with a high substrate concentration (3.3 M in
10) and a catalyst loading varying between 0.1 and 2
mol%.17 Excellent conversions and near-perfect Z-
6
9
20% yield over two steps
We initiated our studies by first employing sodium
pivalate (NaOPiv) in place of AgOPiv during the C-H
activation step. It was quickly discovered that expos-
ing the unactivated dichloride catalyst 1 to excess
NaOPiv in a 1:1 mixture of THF and MeOH resulted in
the clean formation of the desired chelated catalyst 2
after heating at 40°C for 6 hours.13,14 In order to ex-
plore the utility and mildness of this new approach,
we revisited a number of ruthenium complexes con-
taining a variety of N-aryl and N-carbocyclic groups
that had decomposed when using AgOPiv. Attempts to
replace the N-mesityl group of 3 with a bulkier DIPP
group, as in 4, for example, had resulted in substantial
decomposition to 5 during the C-H activation step.
Using NaOPiv, however, we were able to cleanly form
the stable N-adamantyl, N-DIPP pivalate precursor (6)
of catalyst 9 (Scheme 2).
1
selectivities (>95%) were seen by H NMR spectros-
copy with 7-9, with 8 and 9 being the most selective
for the homodimer 11 over the olefin isomerization
product 12.
Table 1. Homodimerization of Allyl Benzene (10).
We were also able to generate activated N-3,5-
dimethyladamantyl, N-mesityl (7) and N-adamantyl, N-
2,6-methylisopropylphenyl (MIPP) (8) derivatives via
this improved method. More extreme alterations to
the chelating group, however, including exchanging
the N-adamantane for an N-cyclohexyl or N-1-
methylcyclohexyl group, resulted in the formation of
chelated catalysts that were inherently unstable.
When these reactions were monitored by 1H NMR
spectroscopy, these complexes were seen to either
decompose immediately to a ruthenium-hydride spe-
cies upon introduction of NaOPiv or form a meta-
stable activated complex that was unisolable without
noticeable decomposition.
loading,
mol %
conv, Z-11,
catalyst
time, h
11/12a
a
a
%
%
7
2
1.5
2
94
78
>95
>95
>95
16.6
50
8b
0.1
0.1
9
2
>95
50
aDetermined by 1H NMR spectroscopy. bDCE was used in
place of THF.
In order to differentiate between these very active
catalysts, we turned to two more challenging ho-
modimerization substrates, methyl 10-undecenoate
(13) and the primary alcohol 4-pentenol (14), the
latter of which has been indirectly implicated in the
decomposition of previous generations of ruthenium
metathesis catalysts.18 Reactions were run utilizing
the standard conditions described above. Of the three
Complexes observed to form a stable chelated archi-
tecture were subsequently converted to the nitrate
form via ligand exchange with the pivalate (Scheme
2), as past experience with catalyst 3 suggested that
2
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Journal of the American Chemical Society
catalysts, 9 gave the best results, providing the ho- Having established the effectiveness of 9 in ho-
1
modimerization products in high conversions (>95%
and 77% for 13 and 14, respectively) with >95% Z-
selectivity for both substrates. Catalyst 8 also demon-
strated excellent selectivity (>95% Z for both sub-
strates) but low conversions, particularly in the ho-
modimerization of 14 (7%). The almost exclusive se-
lectivity for the Z-olefin observed with 8 and 9 is like-
ly a result of the steric bulk of the N-MIPP or N-DIPP
group positioned over the alkylidene, which ensures
that any approach of the terminal olefin in a manner
that would produce an E-olefin is extremely disfa-
vored.10 Previously, the homodimer of 14 was isolat-
ed in 67% yield with only 81% selectivity for the Z-
olefin using catalyst 3; thus the development of 9 rep-
resents a significant improvement in the field of Z-
selective metathesis.
modimerization reactions, we set about to further
evaluate its activity and Z-selectivity by exploring
more complex transformations. The reaction of 1-
hexene (15) and 8-nonenyl acetate (16) to form the
pheromone derivative 17 was previously described
using catalyst 3, and proceeded in good yield (67%)
with high Z-selectivity (91%) at a low catalyst loading
(0.5 mol %).8c Catalyst 9 was able to catalyze this
transformation with no observable formation of the
E-isomer and in slightly higher yield (71%) at the
same catalyst loading. Additionally, the catalyst load-
ing could be lowered to 0.1 mol % and still provide a
good yield of 17 (60%) while maintaining >95% Z-
selectivity (Scheme 3). The expansion of this method-
ology to produce more complicated cross products
with presumably total Z-selectivity should further en-
able its widespread use in the synthesis of Z-olefin-
containing pheromones and other natural products.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
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Table 2. Homodimerization of 10-Methyl Undecenoate
(13) and 4-Pentenol (14).
Scheme 3. Synthesis of Pheromone 17 Using Cata-
lyst 9.
R
catalyst
R
R
THF (3.3 M)
35°C
R = -(CH2)8CO2Me (13),
-(CH2)3OH (14)
OAc
7
OAc
7
9
+
THF (0.5 M)
35°C
17
15
16
loading, time,
conv,
%
Z,
%
substrate catalyst
a
a
mol %
h
0.1 mol %: 60% yield, >95% Z
0.5 mol %: 71% yield, >95% Z
13
7
8b
2
3
77
65
>95
83
7
91
Table 3. Z-Selective Macrocyclizations Employing Cata-
0.1
0.1
2
6
>95
>95
80
lyst 9.a
9
6
X
X
14
7
8b
1.5
2
Y
Y
9 (7.5 mol%),
20 mtorr
m
m
n
n
0.1
0.1
0.1
>95
>95
92
24 h, 60°C,
DCE (3 mM)
9
9b
2
77
79
2
18-20
18a-20a
aDetermined by 1H NMR spectroscopy. bDCE was used in
place of THF.
O
OH
O
O
In order to further quantify the activity of the high-
ly Z-selective catalyst 9, we assayed its performance at
room temperature and lower concentration (1 M in
substrate). Under these conditions, similar conver-
sions and Z-selectivities were observed compared to
those recorded under standard conditions, although
significantly longer reaction times were necessary.
We additionally tested 9 at 0.01 mol % and were
pleased to discover that it performed exceptionally
well, reaching turnover numbers as high as 5800 and
7400 in the homodimerizations of 14 and 10, respec-
tively, while maintaining >95% Z-selectivity. This is in
comparison to previously reported TONs of up to
1000 for catalyst 3 in conjunction with on average
90% Z-selectivity.8c Finally, isolated yields were ob-
tained for all reactions employing catalyst 9, including
those run using the standard conditions (see Support-
ing Information).
17
17
17
20
19
18
45% yield
(>95% Z)
36% yield
(>95% Z)
64% yield
(>95% Z)
aIsolated yields (E/Z ratios determined by 1H- or 13C-NMR
spectroscopy).
We next evaluated catalyst 9 in macrocyclic ring-
closing metathesis (RCM).5,6,19 Although W- and Mo-
based systems exhibit Z-selectivities as high as 97%
for these reactions,20 the Ru-based systems on aver-
age only result in ca. 85% Z-selectivity.9c Particularly
problematic for the Ru-based system are substrates
containing ketone or alcohol functionality, in which it
is observed that the Z-isomer is readily degraded at
high conversions. Thus, we were delighted to find
that when dienes 18a-20a were exposed to catalyst
9, macrocycles 18-20 were all obtained in modest
3
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lakis, G.; Grubbs, R. H. Chem. Rev. 2009, 110, 1746. (f) Samo-
yields and with only trace amounts of the E-isomer
jłowicz, C.; Bieniek, M.; Grela, K. Chem. Rev. 2009, 109, 3708.
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(5) Grubbs, R. H. Handbook of Metathesis; Wiley-VCH: Wein-
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(6) Cossy, J.; Arseniyadis, S.; Meyer, C. Metathesis in Natural
Product Synthesis: Strategies, Substrates, and Catalysts, 1st ed.;
Wiley-VCH: Weinheim, Germany, 2010.
1
2
3
4
5
6
7
8
1
evident by H and 13C NMR spectroscopy (Table 3). It
is expected that this methodology will have applica-
tion to a variety of natural products and pharmaceuti-
cals, as well as for the synthesis of a unique class of
olfactory compounds, termed macrocyclic musks.
Many of these compounds contain a macrocyclic
backbone either featuring a Z-olefin, or bearing func-
tionality stereospecifically installed using
a Z-
9
olefin.5,6,19,21 In fact, 18 and 19 are both currently in
demand by the perfume industry (marketed as am-
brettolide and civetone, respectively).21
10
11
12
13
14
15
16
17
18
19
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(7) (a) Flook, M. M.; Jiang, A. J.; Schrock, R. R.; Müller, P.; Hov-
eyda, A. H. J. Am. Chem. Soc. 2009, 131, 7962. (b) Marinescu, S. C.;
Schrock, R. R.; Müller, P.; Takase, M. K.; Hoveyda, A. H. Organome-
tallics 2011, 30, 1780. (c) Yu, M.; Wang, C.; Kyle, A. F.; Jukubec, P.;
Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 479, 88.
(d) Meek, S. J.; O’Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda,
A. H. Nature 2011, 471, 461. (e) Flook, M. M.; Ng, V. W. L.;
Schrock, R. R. J. Am. Chem. Soc. 2011, 133, 1784. (f) Jiang, A. J.;
Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009,
131, 16630.
(8) (a) Endo, K.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 133,
8525. b) Keitz, B. K.; Endo, K.; Herbert, M. B.; Grubbs, R. H. J. Am.
Chem. Soc. 2011, 133, 9686. (c) Keitz, B. K.; Endo, K.; Patel, P. R.;
Herbert, M. B.; Grubbs, R. H. J. Am. Chem. Soc. 2011, 134, 693.
(9) (a) Keitz, B. K.; Fedorov, A.; Grubbs, R. H. J. Am. Chem. Soc.
2012, 134, 2040. (b) Herbert, M. B.; Marx, V. M.; Pederson, R. L.;
Grubbs, R. H. Angew. Chem. Int. Ed. 2012, 52, 310. (c) Marx, V. M.;
Herbert, M. B.; Keitz, B. K.; Grubbs, R. H. J. Am. Chem. Soc. 2013,
10.1021/ja311241q.
(10) 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.
(11) 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.
(12) Peryshkov, D. V.; Schrock, R. R.; Takase, M. K.; Muller, P.;
Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 20754.
(13) The two-step synthesis of 3 using AgOPiv proceeded in
48% overall yield, whereas the same sequence using NaOPiv
provided 3 in 60% overall yield.
(14) Reaction of 1 with excess sodium acetate also resulted in
complete conversion to 2, but with some catalysts the C-H activa-
tion failed to reach full conversion. Reducing the steric bulk of the
carboxylate even further by using sodium formate or sodium
bicarbonate results in no discernible conversion to the desired
chelated product.
(15) Complex 6 and the pivalate analogue of catalyst 8 were
isolated and assayed. As expected, they exhibited decreased ac-
tivity and stability compared to the corresponding nitrato-
complexes.
(16) Ritter, T.; Hejl, A.; Wenzel, A. G.; Funk, T. W.; Grubbs, R. H.
Organometallics 2006, 25, 5740.
(17) Catalyst 8 was not soluble in THF, thus all reactions using
8 were run in 1,2-dichloroethane (DCE). Experimentation with
catalyst 9 showed that using DCE in place of THF provided analo-
gous results (see Table 2).
(18) (a) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T.
E.; Scholl, M.; Choi, T. L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am.
Chem. Soc. 2003, 125, 2546. (b) Beach, N. J.; Lummiss, J. A. M.;
Bates, J. M.; Fogg, D. E. Organometallics 2012, 31, 2349.
(19) (a) Gradillas, A.; Pérez-Castells, J. Angew. Chem. Int. Ed.
2006, 45, 6086-6101. (b) Majumdar, K. C.; Rahaman, H.; Roy, B.
Curr. Org. Chem. 2007, 11, 1339-1365. (c) Diederich, F.; Stang, P.
J.; Tykwinski, R. R. Modern Supramolecular Chemistry: Strategies
for Macrocycle Synthesis. Wiley-VCH: Weinhem, 2008.
In summary, we have developed a new method to
effect the salt metathesis and C-H activation of Z-
selective ruthenium-based metathesis catalysts using
sodium carboxylates. This approach has been used to
synthesize several new stable chelated species, all of
which were found to be Z-selective in the homodi-
merizations of terminal olefin substrates. Notably,
installation of an N-2,6-diisopropylphenyl group on
the NHC led to significant improvements in activity
and selectivity in both the homodimerization reac-
tions of terminal olefins and industrially relevant
products. Near-perfect selectivity for the Z-olefin
(>95%) and unmatched TONs of up to 7400 were
observed while retaining the ease of use associated
with the ruthenium family of metathesis catalysts.
ASSOCIATED CONTENT
Experimental details and characterization data for all
compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
rhg@caltech.edu
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
Dr. David VanderVelde is thanked for assistance with
NMR experimentation and analysis. This work was fi-
nancially supported by the NIH (R01-GM031332), the
NSF (CHE-1212767), and the NSERC of Canada (fellow-
ship to V.M.M.). Instrumentation on which this work was
carried out was supported by the NIH (NMR spectrome-
ter, RR027690). Materia, Inc. is thanked for its donation
of metathesis catalysts.
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Schrock, R. R. Chem. Rev. 2002, 102, 145. (d) Schrock, R. R.; Hov-
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Journal of the American Chemical Society
(20) Yu, M.; Wang, C.; Kyle, A. F.; Jakubec, P.; Dixon, D. J.;
Schrock, R. R.; Hoveyda, A. H. Nature. 2011, 479, 88-93.
(21) (a) Rowe, D. J. Chemistry and Technology of Flavors and
Fragrances. Blackwell: Oxford, 2005. (b) Ohloff, G.; Pickenhagen,
W.; Kraft, P. Scent and Chemistry - The Molecular World of Odors.
Verlag Helvectica Acta: Zurich, 2011.
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ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 15
Table of Contents Graphic:
1
Ph
2
3
Ph
OH
N
N DIPP
4
5
6
Ru
O
O
N
O
iPr
O
OAc
7
7
8
>95% Z in all cases
Up to 7400 TONs
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
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60
6
ACS Paragon Plus Environment

N
N Mes
N
N Mes
N
N Mes
Page 7 oJfo1u5rnal of the American Chemical Society
Cl
Cl
AgOPiv
NH4NO3
Ru
O
Ru
Ru
O
N
O
ACS Paragon Plus Environment
O
iPr
tBu
O
O
iPr
O
O
iPr
1
2
1
2
3

N
N
DIPP
N
N DIPP
Journal of the American ChemiPcalgSeo8coiefty15
tBu
O
Cl
Cl
AgOPiv
Ru
Ru
O
iPr
O
O
O
O
tBu
iPr
1
2
3
4
5
4NaOPiv
N
N DIPP
N
N DIPP
5
6
7
8
9
NH4NO3
Ru
Ru
O
N
O
ACS Paragon Plus Environment
O
iPr
tBu
O
O
iPr
O
O
6
9
20% yield over two steps

JPoaugren9aloofMf1et5she American Chemical Society
N DIPP
N
N
N
N
MIPP
N
Ru
Ru
Ru
O
O
N
O
N
ACS Paragon Plus Environment
tBu
O
O
O
O
O
O
O
O
1
iPr
iPr
iPr
2
3
7
8
9

Ph
catalyst
Journal of the American Chemical Society Page 10 of 15
+
ACS Paragon Plus Environment
Ph
Ph
THF (3.3 M)
Ph
35°C
10
12
1
2
11

R
catalyst
PageJo1u1rnoaf l1o5f the American Chemical Society
R
R
ACS Paragon Plus Environment
THF (3.3 M)
35°C
R = -(CH2)8CO2Me (13),
1
-(CH2)3OH (14)
2

OAc
Journal of the American Chemical SocietyPage 12 of 15
7
OAc
7
9
+
THF (0.5 M)
35°C
17
15
16
ACS Paragon Plus Environment
1
2
3
4
0.1 mol %: 60% yield, >95% Z
0.5 mol %: 71% yield, >95% Z

X
X
Page 1J3ooufrn1a5l of the American Chemical Society
Y
Y
9 (7.5 mol%),
20 mtorr
m
m
n
n
1
2
24 h, 60°C,
DCE (3 mM)
3
4
18-20
18a-20a
5
6
7
O
OH
O
O
8
9
17
17
17
10
11
12
13
14
15
16
17
20
45% yield
(>95% Z)
19
36% yield
(>95% Z)
18
64% yield
(>95% Z)
ACS Paragon Plus Environment
aIsolated yields (E/Z ratios determined by 1H- or 13C-NMR
18
spectroscopy).
19
20

Journal of the American Chemical Society
Page 14 of 15
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60
62x35mm (300 x 300 DPI)
ACS Paragon Plus Environment

Ph
urPnaagl eof1t5heofA1m5erican Chemical Socie
Ph
OH
N
N
DIPP
Ru
O
1ON
O
2
3
4
5
O
iPr
ACS Paragon Plus Environment
OAc
>95% Z in all cases
Up to 7400 TONs
7