Isomerizing olefin metathesis as a strategy to access defined distributions of unsaturated compounds from fatty acids

Article abstract of DOI:10.1021/ja303822c

The dimeric palladium(I) complex [Pd(μ-Br)^tBu ₃P]₂ was found to possess unique activity for the catalytic double-bond migration within unsaturated compounds. This isomerization catalyst is fully compatible with state-of-the-art olefin metathesis catalysts. In the presence of bifunctional catalyst systems consisting of [Pd(μ-Br)^tBu₃P]₂ and NHC-indylidene ruthenium complexes, unsaturated compounds are continuously converted into equilibrium mixtures of double-bond isomers, which concurrently undergo catalytic olefin metathesis. Using such highly active catalyst systems, the isomerizing olefin metathesis becomes an efficient way to access defined distributions of unsaturated compounds from olefinic substrates. Computational models were designed to predict the outcome of such reactions. The synthetic utility of isomerizing metatheses is demonstrated by various new applications. Thus, the isomerizing self-metathesis of oleic and other fatty acids and esters provides olefins along with unsaturated mono- and dicarboxylates in distributions with adjustable widths. The cross-metathesis of two olefins with different chain lengths leads to regular distributions with a mean chain length that depends on the chain length of both starting materials and their ratio. The cross-metathesis of oleic acid with ethylene serves to access olefin blends with mean chain lengths below 18 carbons, while its analogous reaction with hex-3-enedioic acid gives unsaturated dicarboxylic acids with adjustable mean chain lengths as major products. Overall, the concept of isomerizing metatheses promises to open up new synthetic opportunities for the incorporation of oleochemicals as renewable feedstocks into the chemical value chain.

Full text of DOI:10.1021/ja303822c

Article
pubs.acs.org/JACS
Isomerizing Olefin Metathesis as a Strategy To Access Defined
Distributions of Unsaturated Compounds from Fatty Acids
Dominik M. Ohlmann,† Nicole Tschauder,‡ Jean-Pierre Stockis,‡ Kathe Gooßen,† Markus Dierker,§
̈
and Lukas J. Gooßen*,†
†Fachbereich Chemie, Technische Universitat Kaiserslautern, Erwin-Schrodinger-Straße 54, 67663 Kaiserslautern, Germany
̈
̈
‡Fachbereich Mathematik, Technische Universitat Kaiserslautern, Erwin-Schrodinger-Straße 54, 67663 Kaiserslautern, Germany
̈
̈
§BASF Personal Care and Nutrition GmbH, Henkelstraße 67, 40551 Dusseldorf, Germany
̈
S
* Supporting Information
ABSTRACT: The dimeric palladium(I) complex [Pd(μ-Br)
tBu3P]2 was found to possess unique activity for the catalytic
double-bond migration within unsaturated compounds. This
isomerization catalyst is fully compatible with state-of-the-art
olefin metathesis catalysts. In the presence of bifunctional
catalyst systems consisting of [Pd(μ-Br)tBu3P]2 and NHC−
indylidene ruthenium complexes, unsaturated compounds are
continuously converted into equilibrium mixtures of double-
bond isomers, which concurrently undergo catalytic olefin metathesis. Using such highly active catalyst systems, the isomerizing
olefin metathesis becomes an efficient way to access defined distributions of unsaturated compounds from olefinic substrates.
Computational models were designed to predict the outcome of such reactions. The synthetic utility of isomerizing metatheses is
demonstrated by various new applications. Thus, the isomerizing self-metathesis of oleic and other fatty acids and esters provides
olefins along with unsaturated mono- and dicarboxylates in distributions with adjustable widths. The cross-metathesis of two
olefins with different chain lengths leads to regular distributions with a mean chain length that depends on the chain length of
both starting materials and their ratio. The cross-metathesis of oleic acid with ethylene serves to access olefin blends with mean
chain lengths below 18 carbons, while its analogous reaction with hex-3-enedioic acid gives unsaturated dicarboxylic acids with
adjustable mean chain lengths as major products. Overall, the concept of isomerizing metatheses promises to open up new
synthetic opportunities for the incorporation of oleochemicals as renewable feedstocks into the chemical value chain.
they provide long carbon chains (C16−C20) and are widely
available on large scales. Current synthetic transformations
include their ozonolysis, epoxidation, reduction, olefin meta-
thesis, and enzymatic transformations.2 Plant oil-derived pro-
ducts are already extensively used as surfactants, resins, lubri-
cants, functionalized polymers, and coatings.3
A key factor that complicates a broader incorporation of fatty
acids into the current chemical value chain is that only a few
chain lengths are available from plant oils in sufficient abun-
dance, oleic acid (1b) with its 18 carbon atoms being the most
widely available. It can efficiently be functionalized at both its
carboxylate group and its double bond, giving access to a
variety of building blocks. The discovery of isomerizing func-
tionalizations has further widened the spectrum of products
accessible from this raw material. Isomerizing hydroformyla-
tions,4 alkoxycarbonylations,5 and hydroborations6 allow its
functionalization selectively in the ω-position. Five-membered
ring lactones are obtained by isomerizing lactonizations,7 while
isomerizing 1,4-additions give rise to β-arylated and β-amino
acids.8
INTRODUCTION
■
Most of the present chemical value chain has evolved based
primarily on petrochemical feedstocks. During steam cracking,
crude oil is converted to olefin mixtures, which are then
separated into fractions of similar chain lengths by distillation.
Olefin blends with longer carbon chains are accessed on a
hundred kiloton scale through the Shell Higher Olefin Process
(SHOP), in which ethylene is converted into C10−C18 olefins
in a sequence of oligomerization, isomerization, and meta-
thesis.1 Due to their better availability, blends rather than single
compounds are promising building blocks for polymers,
surfactants, and plasticizers. The use of such defined mixtures
of compounds with similar chain lengths potentially leads to
better properties of the final bulk product than would be
achievable for products derived from single compounds. For
example, polymers resulting from mixed chain-length mono-
mers would have reduced melting ranges and an improved
processability, and detergents may display improved surface
activity.
Due to the progressive depletion of crude oil, it is of high
interest to increase the fraction of renewable feedstocks in the
production of the above-mentioned commodities. In this con-
text, plant oils are particularly attractive raw materials, because
Received: April 20, 2012
Published: July 20, 2012
© 2012 American Chemical Society
13716
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
However, in all the above transformations, the entire ali-
phatic carbon backbone remains intact. It is not yet possible to
convert oleic acid (1b) into compound mixtures with a chain-
length distribution that is adjustable both with regard to its
mean and span, in analogy to the olefin blends available from
petrochemical sources.
We envisioned that isomerizing metatheses might present a
solution to this challenge. If an effective catalyst system could
be found that would continuously equilibrate the position of
the double bond in olefinic substrates, such as oleic acid (1b),
and at the same time continuously metathesize the olefin
mixture, defined distributions of functionalized products should
become available.
Figure 1. Expected product distribution in the isomerizing self-
metathesis of oleic acid derivatives 1.
The product fractions would cover a range of chain lengths, but
the average chain length would remain at 18 carbon atoms.
Since the carbon chain lengths of the olefins would have to
be equal at least to two, the unsaturated monocarboxylates to
three, and the unsaturated dicarboxylates to four, the chain-
length distributions of the three product classes would be
slightly different from each other. With an ideal catalyst system,
it should be possible to influence the widths of these
distributions by stopping the reaction at various time points
before complete conversion. When using bimetallic catalysts
composed of one metal mediating the isomerization and the
other the olefin metathesis, variation of their ratio would allow
individually tuning the reaction rates and thus the composition
of the product cuts.
However, while the principal feasibility of isomerizing metatheses
has been demonstrated (Scheme 1), substantial improvements in
Scheme 1. Pioneering Work in Isomerizing Self-Metatheses
The product and chain-length distributions obtained in
isomerizing metatheses would also be affected by the addition
of a second olefinic substrate such as ethylene or acrylic (14b)
or maleic acid (14c). As in nonisomerizing metatheses, the
selective removal of one of the products by evaporation or
crystallization should allow shifting of the equilibrium toward
one desired product class. The olefin fractions would be of
interest as substitutes for intermediates otherwise obtained by
the SHOP process, and the dicarboxylates, which are not easily
accessible from petrochemical resources, should be useful pre-
cursors for novel bio-based polyesters, polyamides, and polyur-
ethanes, as well as resins, fibers, coatings, and adhesives.12
However, several challenges needed to be overcome before
such isomerizing metatheses could be achieved. The metathesis
of 1b itself is far from trivial, and only few catalysts are known
to convert this substrate, which is available on scale only in
moderate purity, contaminated with other fatty acids, terpenes,
and further impurities. Moreover, both the isomerization and
the metathesis catalysts would have to tolerate the presence of
esters or even acidic carboxylate groups, and should have
no detrimental effect on each other. This is hard to achieve
because most known isomerization catalysts require activation
with aggressive reagents such as metal hydrides, acids, or acid
chlorides.13 It is also likely that ligands would exchange
between the two metal centers, resulting in the deactivation of
both. Ru-based metathesis catalysts are well-known not to
tolerate the presence of phosphine ligands. Another hurdle for
the development of isomerizing metatheses of free fatty acids is
that the latter tend to cyclize to the corresponding lactones in
the presence of double-bond isomerization catalysts at elevated
temperatures.7 The entire process would thus have to be
performed under very mild conditions and at low temperatures.
In the present work, we describe how these challenges were
overcome with catalyst systems consisting of [Pd(μ-Br)tBu3P]2
as the isomerization catalyst and Hoveyda−Grubbs-type metathe-
sis catalysts. They mediate the isomerizing self-metathesis of alkyl
oleates and oleic acid (1b) at loadings below 1 mol %, as well as
the isomerizing cross-metathesis with several short-chain olefins.
catalytic activity and functional group tolerance are needed
before an application of this transformation to the valorization
of 1b becomes realistic. The first observation of a double-bond
isomerization/cross-metathesis process dates back to 1975,
when Porri et al. observed the formation of olefin mixtures
rather than the expected polyolefins in the metathesis
polymerization of olefins with iridium/silver systems.9 Grubbs
et al. demonstrated that the same catalyst can be used to
convert 1-octadecene into an olefin mixture with a broad chain-
length distribution.10 Moreover, they showed that methyl oleate
(1a) can be transformed into a mixture of olefins, unsaturated
monoesters and α,ω-diesters, each with a range of chain
lengths. However, despite high loadings of an expen-
sive iridium/silver catalyst, the conversion remained incom-
plete, and the product distribution never reached its
equilibrium state.
Recently, Consorti and Dupont have reevaluated the
isomerizing metathesis of (E)-3-hexene (9) with a combination
of 0.5 mol % modified Hoveyda−Grubbs metathesis catalyst
and 1 mol % ruthenium hydride isomerization catalyst in an
ionic liquid and obtained a mixture of olefins with up to 17
carbons.11
The valorization of fatty acids and esters, in particular, would
benefit from isomerizing olefin metathesis processes.10,11 Figure 1
illustrates the expected outcome of an isomerizing self-
metathesis of oleic acid (1b) with an ideal catalyst system. In
the course of the reaction, statistical mixtures of olefins, un-
saturated monocarboxylates and dicarboxylates would form.
13717
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
a
Table 1. Catalytic Double-Bond Isomerization of Methyl Oleate and Oleic Acid
no.
R
catalyst (mol %)
solvent, T (°C)
result
1
Me
Me
Me
Me
Me
Me
Me
H
PdCl2 (5)
EtOH, 80
EtOH, 80
octane, 125
toluene, 90
toluene, 90
neat, 70
double-bond shifted by up to 5 positions
2
RhCl3·3 H2O (2)
Fe(CO)5 (20)
IC1 (1.5)
equilibrium distribution of double-bond isomers
equilibrium distribution of double-bond isomers
equilibrium distribution of double-bond isomers
equilibrium distribution of double-bond isomers
no isomerization
3
4
5
IC2 (1.5)
6
IC3 (0.5)
7
IC4 (0.25)
Rh(OTf)(cod) (1)
IC1 (1.5)
neat, 70
equilibrium distribution of double-bond isomers
no isomerization
8
neat, 70
9
H
toluene, 70
toluene, 70
neat, 70
no isomerization
10
11
12
H
IC2 (1.5)
no isomerization
H
IC3 (0.5)
double-bond shifted by up to 5 positions
equilibrium distribution of double-bond isomers
H
IC4 (0.25)
neat, 70
a
cod = 1,4-octadienyl. Reaction conditions: 0.5 mmol 1a or 1b, catalyst, solvent 1.0 mL (if appropriate), temperature given, 16 h, argon atmosphere.
GC results after esterification with MeOH/H2SO4.
instability of metathesis catalysts, which precludes running the
targeted isomerizing metathesis reactions above 70 °C. Another
reason for avoiding high temperatures is the known cyclization
of unsaturated carboxylic acids to the corresponding lactones in
the presence of isomerization catalysts above 100 °C.7a
A control experiment revealed that the acidic conditions of
the esterification do not lead to double-bond migration (see
Supporting Information).
Since none of the established isomerization catalysts dis-
played the desired level of activity, we explored other metal
complexes that we believed to have promising structural
features that had not previously been described as isomerization
catalysts.
RESULTS AND DISCUSSION
■
Isomerization of Oleic Acid and Derivatives. The first
step toward achieving an effective catalytic isomerizing metath-
esis was to identify an isomerization catalyst that would be
active under the typical conditions of a double-bond metathesis.
Oleic acid (1b) and its esters were expected to be more
challenging substrates than simple olefins, so these were chosen
as our initial model substrates.
In the context of our research on isomerizing functionaliza-
tions of fatty acids, we had extensively evaluated the activity of
known isomerization catalysts.8a In continuation of these studies,
we treated oleic acid (1b) with various known isomerization
catalysts under literature conditions and investigated the progress
of the isomerization by gas chromatography. Selected results are
summarized in Table 1.
The results confirmed that few catalysts are capable of
converting both methyl oleate (1a) and oleic acid (1b) into an
equilibrium mixture of all 31 possible isomers, within less than
1 h, at below 1 mol % loading, and under neutral conditions.
We considered this level of catalyst activity a prerequisite for
the targeted process. Simple metal complexes were only found
to promote the double-bond migration in 1a and 1b at high
loadings and often required protic solvents (entries 1 to 3, 8).
Solely rhodium bisphosphite complexes,4,8a such as IC1 and
IC2, displayed a high catalytic activity for the isomerization of
methyl oleate (1a) even at low loadings (entries 4 to 5). Unfor-
tunately, they did not promote the double-bond migration in
oleic acid (1b) (entries 9 to 10). In contrast, palladium
bisalkylphosphine complexes such as IC35 were active for the
isomerization only of the acid but not of the ester (entry 11).
According to the literature, such complexes require activation
with strong acids,5 which would, however, be incompatible with
the metathesis catalyst.
The dimeric palladium complex [Pd(μ-Br)(tBu3P)]2 (IC4)
caught our attention in this context. This complex was first
reported by Mingos et al.15 and has since been applied by
Hartwig and others to various catalytic cross-coupling reactions,
because of its pronounced ability toward aryl halide activa-
tion.16 Although it had never been reported to display activity
in double-bond isomerizations, we believed that it might be a
good catalyst for this reaction because mechanistic studies have
revealed that this unusual dimeric Pd(I) complex forms hydri-
dopalladium(II) species under remarkably mild conditions. The
addition of such Pd−H species across C−C double-bonds is
believed to be the initiating step in olefin isomerization.17
The level of activity that IC4 displayed in the isomerization
of both oleic acid (1b) and methyl oleate (1a) surpassed all our
expectations. A loading of only 0.25 mol % of this dimeric
complex was sufficient to reach an equilibrium distribution
of double-bond isomers for 1a and 1b within a few hours
(entries 7 and 12, Table 1). Under these mild conditions,
undesired side reactions, such as the formation of lactones7 or
of estolide oligomers,18 were never observed.
The mechanism of the IC4-catalyzed isomerization could
not yet be elucidated in full. In low-temperature NMR studies
of the reaction solution in CD2Cl2, signals at −15.8 ppm
Other catalysts described for isomerization processes were
reported to be active only at higher temperatures.14 They were
neglected in this catalyst screening because of the thermal
13718
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
2
(t, JH−P = 6.9 Hz) were detected that likely pertain to mono-
meric palladium-hydride species.19 Based on preliminary
mechanistic studies and the work by Hartwig et al.,20 we propose
that the active catalyst is a PtBu3Pd(H)Br species generated from
the palladium dimer IC4 along with a cyclometalated Pd(II)Br
species.21 We further assume that the catalytic cycle proceeds via
the insertion of olefins into the Pd−H bond (Scheme 2).
Scheme 2. Postulated Mechanism of the Palladium-
Catalyzed Double-Bond Migration
Figure 2. Metathesis catalysts investigated in this study.
Scheme 3. Self-Metathesis of Methyl Oleate and Oleic Acid
For methyl oleate (1a), the previously effective rhodium/
bisphosphite complexes IC1 and IC2 turned out to be
incompatible with the metathesis catalyst. Both lost their
isomerization activity in the presence of the ruthenium
complex. The metathesis reaction was also affected, leading to
substantially reduced amounts of the self-metathesis products
(entries 1 and 2). The palladium complex IC3 showed no
isomerization activity under neutral conditions but had a less
detrimental effect on the metathesis catalyst, so that higher
conversions were reached in the self-metathesis (entry 3).
In sharp contrast, the palladium dimer IC4 retained its full
isomerization activity and did not interfere with the metathesis
of methyl oleate (1a). Within 20 h, 1a was thus converted into
an equilibrium mixture of olefins, monoesters, and diesters,
each with a broad chain-length distribution (entry 4). Similar
results were also obtained with catalyst MC3 and the first
generation Hoveyda−Grubbs catalyst MC1 (entries 5 and 6).
The great advantage of IC4 as a catalyst precursor is that
it bears only one phosphine per palladium. Release of
phosphine ligands, which would inhibit the catalytic activity of
the metathesis catalyst, is thus unlikely. Moreover, its activa-
tion does not require hydride or acid reagents, which could
also be expected to have a negative impact on the metathesis
catalyst.
With the discovery of this uniquely active isomerization
catalyst, a decisive first milestone was reached en route to the
desired isomerizing metathesis.
Self-Metathesis of Oleic Acid and Derivatives. The
logical next step was to identify a suitable metathesis catalyst.
We examined the catalytic activity of various ruthenium com-
plexes for the self-metathesis of methyl oleate (1a) and oleic
acid (1b), among them a Hoveyda−Grubbs first generation
catalyst (MC1),22 the Umicore-M42 (MC2)23 and M31
catalysts (MC3),24 a Hoveyda−Grubbs second generation
Furstner’s metathesis catalyst MC5 completely shut down the
̈
isomerization activity of the palladium dimer IC4, which can be
rationalized by the release of a phosphine during catalyst
initiation, which then coordinates to the isomerization catalyst
(entry 7). A similar observation was made for the Umicore-M11
catalyst (MC6).
catalyst (MC4),25 Furstner’s catalyst (MC5),26 the Umicore-
In the isomerizing self-metathesis of oleic acid (1b) using the
Umicore-M42 metathesis catalyst MC2, the rhodium/bisphos-
phite complexes IC1 and IC2 were unsuitable as cocatalysts,
as anticipated from the isomerization studies above (entries 8
and 9). The palladium complex IC3 and the metathesis catalyst
MC2 were reasonably compatible with each other, but the
conversion remained incomplete (entry 10). Once again, the
palladium dimer IC4 performed best by far. In combination
both with MC2 and with MC3, full conversions of oleic acid
(1b) were achieved (entries 11 and 12). Interestingly, the first
generation Hoveyda−Grubbs catalyst MC1 lost its catalytic
activity in the presence of the palladium dimer IC4 without
negatively impacting the isomerization activity of the latter
(entry 13). Since the other ruthenium catalysts had shown
insufficient activity for the free acid even in the absence of an
isomerization catalyst, they were not further considered in this
study.
̈
M11 catalyst (MC6),27 and the Umicore-M41 catalyst (MC7)
(Figure 2).23
All of the depicted complexes displayed metathesis activity
for methyl oleate (1a). However, only the catalysts Umicore-
M42 (MC2) and Umicore-M31 (MC3) showed high catalytic
activity also for the self-metathesis of oleic acid (1b)
(Scheme 3).
The best results were achieved with MC2, which even at a
0.2% loading, led to 80% conversion of 1b after 20 h at 45 °C in
the absence of added solvent. This finding is in good agreement
with reports by the groups of Dierker and Foglia.28
Isomerizing Self-Metathesis of Oleic Acid and
Derivatives. With active catalysts in hand for both the iso-
merization and the metathesis reactions, we went on to evaluate
their combination into a single process. The results obtained
are summarized in Table 2.
13719
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
a
Table 2. Isomerizing Self-Metathesis of Methyl Oleate and Oleic Acid
no.
R
met. cat.
isom. cat.
conv. (%)
comments
1
Me
Me
Me
Me
Me
Me
Me
H
MC2
MC2
MC2
MC2
MC3
MC1
MC5
MC2
MC2
MC2
MC2
MC3
MC1
IC1
IC2
IC3
IC4
IC4
IC4
IC4
IC1
IC2
IC3
IC4
IC4
IC4
10
no isomerization, ca. 10% self-metathesis products
no isomerization, ca. 50% self-metathesis products
no isomerization, ca. 65% self-metathesis products
isomerizing self-metathesis close to equilibrium
isomerizing self-metathesis close to equilibrium
isomerizing self-metathesis close to equilibrium
2
50
3
70
4
full
full
full
50
5
6
7
<20% isomerizing self-metathesis, ca. 40% self-metathesis products
<10% isomerizing self-metathesis, ca. 40% self-metathesis products
no isomerization, traces of self-metathesis products
8
55
9
H
<5
55
10
11
12
13
H
<10% isomerizing self-metathesis, ca. 40% self-metathesis products
isomerizing self-metathesis close to equilibrium
H
full
full
full
H
isomerizing self-metathesis close to equilibrium
H
isomerization into equilibrium distribution, no self-metathesis products
a
Reaction conditions: 3.0 mmol of substrate 1a or 1b (90% purity), 0.5 mol % isomerization catalyst, 0.2 mol % metathesis catalyst, neat, 45 °C for
Rh catalyzed reactions or 70 °C for Pd catalyzed reactions, 20 h, argon atmosphere. The reaction mixtures were analyzed by GC after esterification
with H2SO4/MeOH.
Figure 3. Product distributions obtained in the isomerizing self-
Figure 4. Reaction progress of the isomerizing self-metathesis of oleic
acid (1b) visualized through the olefin chain-length distribution.
Reaction conditions: 0.5 mmol of 1b, 0.6 mol % IC4, 0.5 mol % MC2,
2.0 mL of hexane, 60 °C, argon atmosphere.
metathesis of oleic acid (1b). Reaction conditions: 1.0 mmol of 1b,
0.6 mol % IC4, 0.5 mol % MC2, hexane 3.0 mL, 70 °C, 20 h, argon
atmosphere. GC results after esterification with MeOH/H2SO4.
The results of the isomerizing self-metathesis of 1b in
the presence of 0.5 mol % MC2 and 0.6 mol % palladium dimer
IC4 in hexane are visualized in Figure 3. The individual gas-
chromatographic signals were assigned to olefins, monocarbox-
ylates, and dicarboxylates based on mass spectral data. Since
the peak shapes vary strongly for the product classes, a
histogram was generated in which the integrals of the GC peaks
are plotted against the retention times. Idealized curves were
superimposed on this processed GC to visualize the dis-
tributions for each product class. When interpreting the plots,
one must take into account that the areas below these curves do
not represent the relative occurrence of each product class,
because the signal spacing increases from left to right and
because the individual integrals are uncorrected for response
factors.
Uniform, broad chain-length distributions for all product
fractions were obtained under the conditions described above.
The chain-length distribution of the olefin fraction reaches up
to at least C26. Unsaturated monocarboxylates were detected
from C13 to C25, dicarboxylates from C13 to C22.
The progress of the isomerizing self-metathesis of oleic acid
(1b) was monitored over time to confirm that the product
distribution indeed reached its maximum width under these
conditions. To simplify product analysis and maximize the
detection sensitivity, the unfunctionalized olefin fraction was
selectively extracted from the reaction mixture and analyzed by
GC/GC-MS. The histograms in Figure 4 reveal that after 2 h at
60 °C, the product distribution is still relatively sharp. It
continuously broadens over the subsequent 6 h, but is not
further impacted beyond that point in time. This confirms that
after 8 h, an equilibrium composed mainly of olefins ranging
from C8 to C32 is reached.
We next probed whether the product distribution of the
isomerizing self-metathesis can be tuned by adjusting the
reaction conditions. Upon reduction of the reaction temper-
ature to 25 °C under otherwise identical conditions, double-
bond migration is completely shut down, while the olefin
metathesis still reaches its equilibrium. Thus, in the presence of
0.6 mol % IC4 and 0.5 mol % MC2 at 25 °C in hexane, a 1:1:1
mixture of oleic acid (1b), 1,18-octadec-9-enedioic acid (3b),
and 9-octadecene (4) is formed. The observed influence of the
reaction temperature on the rate of the isomerization but not
on the metathesis should allow tuning the width of the product
distribution simply by choosing the appropriate temperature
within a range of 25 to 70 °C.
At 40 °C, equal amounts of olefins and mono- and dicar-
boxylates were indeed formed, each with a very narrow
13720
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
chain-length distribution around the C18 self-metathesis pro-
ducts 1, 5, and 6 (Figure 5).
Figure 7. Product distribution resulting from the isomerizing self-
metathesis of oleic acid (1b). Reaction conditions: 1.0 mmol of 1b,
0.3 mol % IC4, 0.5 mol % MC3, hexane 3.0 mL, 50 °C, 20 h, argon
atmosphere.
Figure 5. Product distribution resulting from the isomerizing self-
metathesis of oleic acid (1b). Reaction conditions: 1.00 mmol of 1b,
0.6 mol % IC4, 0.5 mol % MC2, hexane 3.0 mL, 40 °C, 20 h, argon
atmosphere.
Scheme 4. Isomerizing Self-Metathesis of 10-Undecenoic
and Linoleic Acids
successfully converted, among them 10-undecenoic acid (7)
and linoleic acid (8, Scheme 4).
Figure 6. Product distribution resulting from the isomerizing self-
metathesis of oleic acid (1b). Reaction conditions: 1.0 mmol of 1b,
1.2 mol % IC4, 0.5 mol % MC2, neat, 60 °C, 8 h, argon atmosphere.
Compound 7 is a particularly interesting example since at the
outset, the double bond is in the terminal position. Thus, the
product distribution initially has additional maxima for long-
and short-chain products. However, due to the high efficiency
of the isomerization catalyst, it converges toward the usual
equilibrium distributions for all three product classes within
20 h, even at low catalyst loadings.
Linoleic acid (8) is another challenging substrate, as it
contains two double-bonds that may be moved into
conjugation. Although conjugated dienes are known to
interfere with transition metal-based isomerization cata-
lysts,29 the standard conditions still led to full conversion of
this substrate.
The isomerizing metathesis of oleic acid (1b) can also be
performed under solvent-free conditions. Since this somewhat
reduces the activity of the isomerization catalyst, its loading
needs to be increased to 1.2 mol %. Figure 6 visualizes the
outcome of an isomerizing self-metathesis of neat oleic acid
(1b). The reaction mixture was stirred for 8 h using 1.2 mol %
of IC4 and 0.5 mol % of MC2 as the catalyst system. After this
short reaction time, the product distributions are still relatively
narrow and consist of C12−C24-olefins, C12−C25-monocarbox-
ylates, and C14−C22-dicarboxylates.
Isomerizing Metathesis of Simple Olefins. The
performance of the new bimetallic catalyst system was
benchmarked also for simple olefins such as (E)-3-hexene
(9). Consorti and Dupont had found that the isomerizing olefin
metathesis of this substrate requires 2 days using 0.5 mol % of a
ruthenium-hydride isomerization catalyst and 1 mol % of a
modified Hoveyda−Grubbs metathesis catalyst in an ionic
liquid solvent.11 Our catalyst system promoted this reaction
with substantially higher efficiency. Already at loadings of
0.1 mol % of the palladium dimer IC4 and 0.2 mol % of the
second generation Hoveyda−Grubbs catalyst MC4, the reac-
tion reached its equilibrium within only 16 h (Scheme 5).
The metathesis catalyst MC3 combined with IC4 promotes
the isomerizing self-metathesis of 1b at lower temperatures
than MC2. Even after reducing the IC4-loading to 0.3 mol %,
full equilibrium was still reached using 0.5 mol % MC3 at 50 °C
in hexane (Figure 7, see Figure 3 for comparison).
In order to reach fully equilibrated product distributions as in
Figures 3 and 7, both the isomerization and metathesis catalysts
must react with each double bond in the reaction mixture not
only once but several times. Turnover numbers (TON) cal-
culated using the conversion of the olefin starting material are
thus not very meaningful to map out the reaction progress. Still,
a rough impression of the high efficiency of the catalyst system
may be obtained when one considers that for combinations of
0.01 mol % IC4 and 0.025 mol % of either MC2 or MC3, more
than 50% of the products have chain lengths other than 18,
corresponding to a TON > 2000 for both the isomerization and
the olefin metathesis.
Scheme 5. Isomerizing Self-Metathesis of (E)-3-Hexene
Isomerizing Self-Metathesis of Other Fatty Acids. With
a catalyst system consisting of 0.5 mol % IC4 and 0.6 mol %
MC2, other fatty acids beside oleic acid derivatives were
13721
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
The resulting olefin mixture shows the expected chain-length
distribution with a maximum at C6 and a shallow downward
slope toward higher olefins (Figure 8, red bars). Chains with
Figure 9. Cooperative (red) and sequential (blue) processes for the
isomerizing cross-metathesis of (E)-3-hexene (9) and 1-octadecene
(11). *C5 fraction may contain unresolved C4 and C3 olefins.
on the other. For the sequential reaction, both olefins were
initially converted into an equilibrium mixture of positional
isomers by reaction with the isomerization catalyst IC4. The
catalyst was then separated from the olefin mixture by filtration
through basic alumina. Subsequently, the olefin mixture was
allowed to react in the presence of the metathesis catalyst MC4.
The sequential process leads to an entirely different chain-
length distribution, with maxima around C6, the initial chain
length of the hexene, and C18, the most likely chain length of a
self-metathesis product of octadecene (Figure 9, blue bars).
This experiment confirmed that cooperative action of the
isomerization and metathesis catalysts leads to a smooth chain-
length distribution even under challenging conditions. Such
product mixtures not only are useful as monomers but also can
be functionalized further, for example, via isomerizing
alkoxycarbonylations, hydroborations, or hydroformylations.4−6
The overall processes would open up additional opportunities
for the incorporation of carbon atoms derived from
oleochemical sources into the chemical value chain.
Figure 8. Chain-length distribution obtained in the cooperative
isomerizing self-metathesis of 9 (red) and in the analogous sequential
process (blue). *C5 fraction may contain unresolved C4 and C3 olefins.
more than 17 carbon atoms were detectable in trace quantities.
In contrast, chains with only up to 10 carbon atoms are
accessible via a consecutive isomerization and metathesis of
(E)-3-hexene (9, Figure 8, blue bars).
Beyond the isomerizing self-metathesis of olefins, in which
the mean chain length always remains unchanged, one could
imagine related processes in which not only the distribution
shapes but also the mean chain lengths of the olefin mixtures
are tunable. Thus, the isomerizing cross-metathesis of a mix-
ture of two olefins with different chain lengths should, in
principle, allow the synthesis of olefin blends with mean chain
lengths ranging anywhere between the lengths of the two
starting materials. Adjustment of the mean chain length should
be possible simply by changing the ratio between the two
starting materials. This concept is illustrated in Scheme 6 using
We next probed whether the mean chain length can indeed
be controlled by varying the ratio of olefin starting materials.
We thus mixed (E)-3-hexene (9) with 1-octadecene (11) in
three different ratios and subjected them to isomerizing olefin
metathesis using 0.5 mol % IC4 and 0.6 mol % MC4 as the
catalyst system (see Scheme 6). Regular chain-length
distributions were obtained in all cases (Figure 10). The
Scheme 6. Isomerizing Cross-Metathesis of (E)-3-Hexene
and 1-Octadecene
the example of an isomerizing cross-metathesis of 1-octadecene
(11), available from oleochemical sources, with a short-
chain olefin.
Indeed, the isomerizing metathesis of a 1:1 mixture of
1-octadecene (11) with (E)-3-hexene (9) in the presence of
0.6 mol % Pd-dimer IC4 and 0.5 mol % metathesis catalyst MC4
led to a uniform product distribution with the expected mean
chain length of 12 carbon atoms. The use of a long-chain olefin
unsaturated at the terminal position poses a particular challenge
for the isomerization catalyst. During the first hours of the
reaction, an irregular distribution with local maxima at chain
lengths of 34 and 6 carbon atoms were observed. However,
after 20 h, an almost ideal distribution was reached, further
demonstrating the high activity of the catalyst system (Figure 9,
red bars).
Figure 10. Product distributions resulting from cross-metathesis of 9
and 11 with different ratios. *C5 fraction may contain unresolved C4
and C3 olefins.
maxima of the distributions reflect the expected shift in the
mean chain length resulting from changing the ratio of the two
starting materials. With 0.5 equiv of 1-octadecene (11), the
calculated mean is C10 (red bars), with 1 equiv of 11 it is C12
(blue bars), and with 2 equiv of 11 it is C14 (green bars).
Figure 9 also illustrates the fundamental difference between
an isomerizing olefin metathesis on one hand, and a sequential
process of double-bond isomerization followed by metathesis
13722
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
Mathematical Prediction of the Product Distributions.
The overall trends in the product distributions are clearly visi-
ble from the experimental data. However, there are several fac-
tors that may cause experimental deviations from the
theoretical reaction outcome. One has to take into account
that short-chain olefins with chain lengths below C5 partially
evaporate during the reactions, resulting in a shift of the
detected chain-length distribution toward longer chains. Due to
their volatility, these olefins are not detected quantitatively in
the gas chromatograms, preventing an exact quantification of
the product fractions. Moreover, the GC response factors can
be expected to vary slightly for each olefin. Because of these
analytical issues, it was desirable to develop a method to
calculate ideal product distributions for isomerizing metatheses.
In order to predict equilibrium distributions of the product
fractions, we designed a mathematical simulation of the
reaction using the statistics software R.30 The following base
assumptions were made: (1) All reaction products remain in
the reaction solution; (2) all double-bond isomers have the
same stability, which means that the double-bond will be in any
position of the carbon chain with the same probability; (3) the
isomerization proceeds substantially faster than the metathesis,
so that full equilibration of the double-bond position occurs
between each metathesis step. For the calculations discussed
below, the program was parametrized such that the metathesis
proceeds with a similar reaction rate for each double-bond
isomer.
Figure 11. Calculated distributions for the self-metathesis of
dodecene.
are observed, rather than narrow distributions that gradually
broaden (see Figure 5). The simulation gets sufficiently close to
the equilibrium distribution at a TON of 2000 or above (on
average 10 metathesis steps per olefin molecule). These
calculations demonstrate that the TONs for the metathesis
catalyst are at least 10 times higher than the substrate-to-
catalyst ratio would suggest (see the discussion of experimental
TONs, above).
Figure 12 depicts the overlaid histograms calculated for 200
dodecene molecules versus 100 hexene and 100 octadecene
The program is based on a Markov process using a modified
sample-with-replacement method to simulate the progress of
the chemical reaction. The situation at the onset of the reaction
is described by a vector containing the chain length of all
individual molecules that are available for reaction with a single
molecule of the metathesis catalyst. In the first step, the
initiation of the metathesis catalyst molecule is simulated by
randomly selecting one olefin molecule, cleaving it at a random
position and attaching one part to the metathesis catalyst. In
each subsequent step, this residue is combined with one part of
another randomly selected olefin, while the other part of the
olefin remains at the catalyst. The vector of olefin molecules is
then updated, and the process is repeated until the desired
number of iterations is reached.
Using this simulation program, the chain-length distributions
were predicted for isomerizing metatheses of 200 olefin mole-
cules, which corresponds to isomerizing metatheses using
0.5 mol % metathesis catalyst. Fluctuation of the results can be
reduced to a more realistic degree when averaging 100 runs.
This roughly approximates an experimental situation in which
100 catalyst molecules react with 20 000 olefin molecules. In
the chemical experiments, 1018 catalyst molecules convert 1020
olefin molecules, which reduces fluctuation to a negligible
amount.
Figure 12. Calculated distributions for the metatheses of dodecene
and a 1:1 octadecene/hexene mixture.
molecules; each as an average of 100 runs with 2000 steps.
Their congruence demonstrates that after each molecule has
been metathesized on average ten or more times, the reaction
outcome of isomerizing metatheses is dependent only on the
mean chain length and not on the starting material
composition. This corresponds well with the experimental
observations discussed below Scheme 6.
We first investigated how many turnovers of the metathesis
catalyst are required to fully convert the olefin starting materials
and to achieve the experimentally observed regular distribu-
tions. This was performed using dodecene (Figure 11).
Using up to 1000 steps, which correspond to an average of
five metathesis steps per molecule, an overproportional amount
of C12 molecules is still seen in the simulation. The distribution
shape is a result of the parametrization of the program, in which
the double-bond migration is simulated to be substantially
faster than the olefin metathesis. Thus, at incomplete con-
version, left-over C12 starting material isomers along with
products spanning the full width of the equilibrium distribution
Figure 13 shows superimposed histograms corresponding to
simulations with 200 olefins with 3, 6, and 12 carbons, each as
an average over 100 runs, to demonstrate the influence of the
mean chain length on the shape of the product distribution.
The shapes of the histograms change from being exponential-
like (C3) to being Boltzmann-like with sharp (C6) and finally
broad maxima (C12) (Figure 13). These shapes are as expected
for an array of molecules with a defined mean, a defined left-
hand chain length limit at C2, and a right-hand chain length that
is unlimited.
Overall, the simulation program allows prediction of the
experimental outcomes of isomerizing metatheses based on the
13723
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
Neither MC2 nor MC1 displayed any activity for the cross-
metathesis of 1a or 1b with ethylene (entries 1, 2, 6, and 7).
Moreover, in their presence and under an ethylene atmosphere,
IC4 appeared to lose its isomerization activity (entries 1, 2, 6,
and 7). In contrast, both the MC3/IC4 and the MC7/IC4
combinations remained active in the presence of ethylene
(entries 3−5, 8). With a catalyst system consisting of 0.6 mol %
MC3 and 0.6 mol % IC4, 85% conversion was reached in the
isomerizing ethenolysis of methyl oleate (1a) (entry 4). Similarly,
a catalyst system consisting of 0.6 mol % MC7 and 0.5 mol %
IC4 led to full conversion in the isomerizing ethenolysis of
oleic acid (1b) (entry 8).
Further investigations revealed that the desired regular
product distribution with a single maximum, indicative of full
equilibration, could be reached with loadings above 1.5 mol %
of the metathesis catalyst and 0.75 mol % of the isomeriza-
tion catalyst (entries 9 to 12). Any additional increase in the
loadings of both catalysts no longer influenced the shape of
the product distribution. This is illustrated in Figure 14,
which shows histograms of the olefin product fractions
obtained by hexane extraction of the basified reaction mix-
tures. The mono- and diacids displayed similar distribution
patterns.
Figure 13. Calculated distributions for the metatheses of propene,
hexene, and dodecene.
mean carbon-chain length of the olefin starting materials. It
represents an important first step toward finding an analytical
formula to describe the relative abundance of each carbon chain
based only on the mean chain length. This is the subject of
ongoing research.
Isomerizing Ethenolysis of Fatty Acids. In continuation
of the experimental studies, we next evaluated whether it is also
possible to adjust the chain lengths of fatty acid-derived
products by adding defined amounts of a cross-metathesis
partner. Thus, the use of a suitable metathesis catalyst and
an ethylene atmosphere would allow incorporation of this
C2-building block into the product fractions obtained by
isomerizing cross-metathesis of oleic acid derivatives. This
would result in a considerable shift of the mean chain length
toward lower carbon-chain lengths. At the same time, the ratio
of olefins and mono- and dicarboxylates will shift toward the
olefin fraction because of the additional unfunctionalized chain
ends.
In order to make this cross-metathesis work, the metathesis
catalyst needed to activate ethylene and oleic acid derivatives at
comparable rates. We searched for a suitable bimetallic catalyst
system using the isomerizing ethenolysis of methyl oleate (1a)
and oleic acid (1b), starting from the reaction conditions
optimized for their isomerizing self-metathesis (Table 3).
Figure 14. Chain-length distributions of the olefin fraction from the
isomerizing ethenolysis of oleic acid (1b).
a
Table 3. Optimization of the Isomerizing Ethenolysis of Oleic Acid Derivatives
b
no.
IC4 (mol %)
metath. cat. (mol %)
R
conv. (%)
comment
1
0.5
MC2 (0.6)
MC1 (0.6)
MC7 (0.6)
MC3 (0.6)
MC3(0.6)
MC2(0.6)
MC1 (0.6)
MC7 (0.6)
MC7 (0.5)
MC7 (1.5)
MC7 (2.5)
MC7 (5.0)
Me
Me
Me
Me
H
35
no isomerization, ca. 20% self-metathesis, ca. 15% ethenolysis
2
0.5
<5
59
3
0.5
ca. 25% nonisomerizing self-metathesis, ethenolysis detectable
isomerizing ethenolysis, distribution is far from equilibrium
isomerizing ethenolysis, distribution is far from equilibrium
no isomerization, 54% self-metathesis, no ethenolysis
4
0.5
85
5
0.5
65
6
0.5
H
60
7
0.5
H
<5
full
full
full
full
full
8
0.5
H
isomerizing ethenolysis, distribution is far from equilibrium
isomerizing ethenolysis, distribution is far from equilibrium
isomerizing ethenolysis, distribution is close to equilibrium
isomerizing ethenolysis, distribution is far from equilibrium
isomerizing ethenolysis, distribution is close to equilibrium
9
0.25
0.75
0.25
0.5
H
10
11
12
H
H
H
a
Reaction conditions: 0.5−1.0 mmol of substrate 1a or 1b, isomerization catalyst IC4, metathesis catalyst, 6.0 mL of hexane/mmol substrate, 50 °C,
b
ethylene atmosphere, 16 h. Conversion of the substrate 1a or 1b, analysis of the product mixtures by GC after esterification with MeOH/H2SO4.
13724
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
a
Table 4. Optimization of the Isomerizing Cross-Metathesis of 1a and 1b with Different Olefins
IC4
(mol %)
metath. cat.
(mol %)
conv.
b
no.
R
X, Y
solvent
(%)
comment
1
2
3
4
5
6
7
Me H, COOMe
Me H, COOH
1
MC2 (1.5)
MC2 (1.5)
MC2 (1.5)
MC2 (1.5)
MC2 (1.5)
MC2 (1.5)
MC2 (1.5)
neat
25
20
31
39
80
85
full
predominantly self-metathesis, no cross-metathesis products
predominantly self-metathesis, no cross-metathesis products
predominantly self-metathesis, no cross-metathesis products
predominantly self-metathesis, no cross-metathesis products
isomerizing self-metathesis, no cross-metathesis products
isomerizing self-metathesis, no cross-metathesis products
1
neat
H
H
H
H
H, COOMe
1
neat
H, COOH
1
neat
COOH, (Z)-COOH
COOH, (Z)-COOH
0.75
0.75
2.5
neat
hexane
THF
Me COOH, (Z)-COOH
isomerizing cross-metathesis far from equilibrium, no shift of mean
chain length
8
9
Me COOH, (Z)-COOH
2.5
2.5
MC2 (1.5)
MC7 (5.0)
toluene
THF
full
full
isomerizing cross-metathesis far from equilibrium, no shift of mean
chain length
H
CH2COOH, (E)-
CH2COOH
isomerizing cross-metathesis close to equilibrium, significant shift of
mean chain length
a
Reaction conditions: 0.25 mmol of substrate 1a or 1b, 0.25−1.25 mmol of coupling partner 14a−d, isomerization catalyst IC4, metathesis catalyst,
b
1.5 mL of solvent, if appropriate, 70 °C, 16 h, argon atmosphere. Conversion of the substrate 1a or 1b, analysis of the product mixtures by GC after
esterification with MeOH/H2SO4.
Isomerizing Cross-Metathesis of Fatty Acids with
Dicarboxylic Acids. The isomerizing cross-metathesis of
oleic acid (1b) with a short-chain unsaturated mono- or
dicarboxylic acid should lead to the formation of predominantly
mono- or dicarboxylic acids with medium chain lengths. To
probe the feasibility of this approach, we investigated various
carboxylate-containing substrates in isomerizing cross-metatheses
with oleic acid (1b) or methyl oleate (1a). As can be seen in
Table 4, neither acrylic acid (14b) nor methyl acrylate (14a) gave
satisfactory results with a catalyst system consisting of IC4 and
Figure 15. Product distribution of cross-metathesis of oleic acid (1b)
MC2. Even at relatively high loadings of MC2, the rate of cross-
with 2 equiv of (E)-3-hexenedioic acid (14d). Reaction conditions:
metathesis was insufficient. More importantly, the acrylate moiety
0.5 mmol of oleic acid (1b), 1.0 mmol of (E)-3-hexenedioic acid
(14d), 2.5 mol % IC4, 5.0 mol % MC7, 2.0 mL THF, 60 °C, 16 h,
argon atmosphere.
inhibited the isomerization catalyst (entries 1−4). The inhibition
of double-bond migration in the presence of acrylates has been
reported also for Ru−H catalyzed isomerizations concurrently
or subsequently to metathesis reactions.31
quantitatively. The mean chain length of all product fractions
was substantially lower than in the self-metathesis of 1b, and
the dicarboxylic acid fraction became dominant.
With maleic acid (14c), the results were more encouraging,
but the rate of cross-metathesis was still substantially lower than
that of the self-metathesis of oleic acid (1b) (entries 5 and 6).
When starting from methyl oleate (1a) rather than oleic acid
(1b), the isomerizing cross-metathesis was successful, but due
to the low reactivity of maleic acid, no more than one
equivalent of it could be incorporated into the product mixture
(entries 7 and 8). When excess maleic acid (14c) was used,
most of it remained unchanged, thus precluding a tuning of the
mean chain length by varying the stoichiometry. These results
are encouraging, and it may well be possible to perform
effective isomerizing cross-metatheses with this substrate
combination using specially adapted metathesis catalysts.
In order to prove the concept using the catalysts systems
available to us, we switched to (E)-3-hexenedioic acid (14d) as
the coupling partner (entry 9). With 2 equiv of this non-
conjugated dicarboxylic acid, the cross-metathesis proceeded
at the same rate as the self-metathesis, and the isomerization
was unaffected by the presence of the short-chain substrate
(Table 4). The product distribution obtained in this cross-
metathesis experiment is depicted in Figure 15. Both oleic acid
(1b) and (E)-3-hexenedioic acid (14d) were converted
In order to obtain a more precise picture of the relative
chain-length distribution, the olefin fractions of several
reactions between (E)-3-hexenedioic acid (14d) and oleic
acid (1b) with different stoichiometries were selectively
extracted and analyzed by GC and GC-MS. Figure 16 shows
how the distribution maxima shift from 18 carbons for pure
oleic acid (1b) to lower numbers. This would be expected for
distributions with mean chain lengths of 10 for a 2:1 and 8 for a
5:1 ratio of (E)-3-hexenedioic acid (14d) to oleic acid (1b).
These studies confirm that the catalyst system remains active
in the presence of (E)-3-hexenedioic acid (14d). The optimal
solvent for this reaction type is THF, because it efficiently
solubilizes even dicarboxylic acids.
For processes in which the low-boiling olefin fraction is
continually removed by distillation to drive the equilibrium
further toward the dicarboxylic acid products, this low-boiling
solvent is unsuitable. We evaluated several high-boiling solvents
in its place and found that Dowtherm A, a eutectic mixture of
diphenyl ether and biphenyl, is also a suitable reaction solvent,
although the reaction does not proceed quite as fast (Table 5).
13725
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
Figure 17. Product distribution of cross-metathesis of oleic acid (1b)
with 2 equiv of (E)-3-hexenedioic acid (14d) under vacuum. Reaction
conditions: 0.5 mmol of oleic acid (1b), 1.0 mmol of (E)-3-
hexenedioic acid (14d), 2.5 mol % IC4, 5.0 mol % MC7, 60 °C, 16 h,
0.01 mbar.
Figure 16. Chain-length distribution of the olefin fraction from
isomerizing cross-metathesis of 1b with 14d, compared with the
isomerizing self-metathesis of 1b. Reaction conditions as given in
Table 5, entry 7. Chains shorter than C7 are unresolved due to
overlapping peaks.
can be expected to lead to “metathesized biodiesel” with further
improved properties.
The new catalyst system is also sufficiently effective to
allow conversion of mixtures of olefins with two different
chain lengths into regular product distributions with mean
chain lengths that can be influenced by the chain lengths
of the starting materials and their ratio. The olefin blends
thus obtained can be used as monomers in polymerization
reactions.33 They can also be functionalized via isomerizing
hydroformylations, alkoxycarbonylations, or hydroborations,
thereby providing building blocks that would otherwise only
be accessible from petrochemical sources, for example, via
the SHOP process.
Unsaturated dicarboxylic acids with defined chain-length dis-
tributions can be obtained via the isomerizing cross-metathesis
of oleic acid with short-chain unsaturated dicarboxylic acids.
Low-melting dicarboxylate mixtures are of interest, for example,
for resins, coatings, or adhesives and as building blocks for
polyesters and polyurethanes.34
In all cases, the shape of the product distributions can be
influenced by the choice of the metathesis catalyst and its
amount relative to that of the isomerization catalyst. A com-
putational approach was devised that allows simulating the
outcome of isomerizing self- and cross-metathesis reactions and
interpreting the results obtained in the chemical reactions.
The discovery of a catalyst system with a new level of activity
along with the progress made in methodically understanding
isomerizing metatheses may serve as a starting point for trans-
forming this process from a laboratory curiosity into a syn-
thetically valuable technology.
Using this solvent, the olefin fraction can continuously be
removed by distillation during the isomerizing metathesis. This
results in a shift of the equilibrium toward the dicarboxylic
acids, as illustrated by the histogram in Figure 17.
A full shift of the equilibrium toward the dicarboxylic acids
should be possible using specialized equipment, such as thin-
film evaporation reactors.
CONCLUSION
■
Our results demonstrate that isomerizing olefin metathesis is a
powerful synthetic tool. Its potential applications by far surpass
those of consecutive double-bond isomerization and metathesis
sequences.
The discovery of the dimeric palladium(I) complex [Pd(μ-
Br)tBu3P]2 as a uniquely active isomerization catalyst, which
retains its activity in the presence of state-of-the-art olefin
metathesis catalysts without lessening their own activity, set the
stage for the development of an array of synthetic trans-
formations involving isomerizing olefin metatheses. A particular
focus was set on the utilization of long-chain unsaturated
compounds derived from renewable plant-based resources.
The isomerizing self-metatheses of oleic acid and methyl
oleate proceeded with impressive efficiency and turnover num-
bers well above 103. At present, metathesized fatty acid esters
are tested as additives to lower the crystallization temperature
of biodiesel.32 The use of isomerizing metatheses for the same
purpose would provide a broad chain-length distribution that
a
Table 5. Optimization of the Isomerizing Cross-Metathesis of Oleic with Hexenedioic Acid
b
no.
IC4 (mol %)
MC7 (mol %)
14d (equiv)
solvent
THF
conv. 1b (%)
conv. 14d (%)
1
2
3
4
2.5
2.5
2.5
2.0
5.0
5.0
5.0
3.0
2
3
5
2
98
98
98
98
98
97
97
85
THF
THF
Dowtherm A
a
Reaction conditions: 0.50 mmol of oleic acid (1b), (E)-3-hexenedioic acid (14d), isomerization catalyst IC4, metathesis catalyst MC7,
b
2.0 mL of solvent, 60 °C, 16 h, argon atmosphere. Conversion of 1b, analysis of the product mixtures by GC after esterification with
MeOH/H2SO4.
13726
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
9-octadecene (5) and 42% of 1,18-octadec-9-enedioic acid dimethyl
ester (6a).
EXPERIMENTAL SECTION
■
General Methods. Reactions were performed under an argon
atmosphere in oven-dried glassware containing a Teflon-coated stirrer
bar and dry septum. For the exclusion of atmospheric oxygen from the
reaction media, solvents were degassed and purged with argon before
the reagents were mixed. Solvents were purified by standard
procedures prior to use. GC analyses of isomerizing metathesis
reactions of olefins were carried out using a HP-5 column, 30 m ×
320 μm × 0.25 μm, split 50:1, injector temperature of 220 °C, detector
temperature of 330 °C, helium carrier gas; temperature program,
starting from 40 °C, hold for 5 min, heating to 250 °C at a rate of
10°/min, hold for 2 min, heating to 300 °C at a rate of 40°/min, hold
for 15 min. GC analyses of isomerizing metathesis reactions of fatty
acid derivatives were carried out using a HP-5 column, 30 m × 320 μm ×
0.25 μm, split 50:1, injector temperature of 260 °C, detector
temperature of 330 °C, helium carrier gas; temperature program,
starting from 50 °C, hold for 3 min, heating to 300 °C at a rate of
8°/min, hold for 10 min. GC analyses of fatty acid isomerization studies
were carried out using a crossbond PEG column, 60 m × 320 μm ×
0.25 μm, split 10:1, injector temperature of 250 °C, nitrogen carrier
gas; temperature program, starting from 50 °C, hold for 1 min, heating
to 220 °C at a rate of 15°/min, hold for 10 min, heating to 250 °C at a
rate of 15°/min, hold for 15 min. Commercial substrates were used as
received unless otherwise stated. The metathesis catalysts used herein
are available commercially, for example, from Sigma-Aldrich or
Umicore: MC1, dichloro-(o-iso-propoxyphenylmethylene)-
(tricyclohexylphosphino)ruthenium(II), CAS-no. 203714-71-0; MC2,
1,3-bis(mesityl)-2-imidazolidinylidene]-[2-[[(2-methylphenyl)imino]-
methyl]-phenolyl]-[3-phenyl-indenyliden]-ruthenium(II)chloride,
CAS-no. 934538-12-2; MC3, 1,3-bis(2,4,6-trimethylphenyl)-2-
imidazolidinylidene]dichloro-(3-phenyl-1H-inden-1-ylidene)(pyridyl)-
ruthenium(II), CAS-no. 1031262-76-6; MC4, 1,3-bis-(2,4,6-trimethyl-
phenyl)-2-imidazolidinylidene)dichloro(o-iso-propoxyphenyl-
methylene)ruthenium(II), CAS-no. 301224-40-8; MC5, dichloro-(3-
phenyl-1H-inden-1-ylidene)bis(tricyclo-hexylphosphino)ruthenium(II),
CAS-no. 250220-36-1; MC6, dichloro-(3-phenyl-1H-inden-1-ylidene)-
bis(iso-butylphoban)ruthenium(II), CAS-no. 894423-99-5; MC7, 1,
3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene-[2-[[(4-
methylphenyl)imino]-methyl]-4-nitrophenolyl]-[3-phenyl-1H-inden-
1-ylid-ene]ruthenium(II)chloride, CAS-no. 934538-04-2. The isomer-
ization catalyst IC4 can be obtained, for example, from Strem: dis
(tri-tert-butylphosphino)palladiumdibromide, CAS-no. 185812-86-6.
Experimental Procedures. Isomerization of Oleic Acid (1b)
with Palladium Dimer IC4 (See Table 1). A 20 mL headspace vial
with septum cap and stirring bar was charged with isomerization
catalyst IC4 (5.8 mg, 7.5 μmol). Oleic acid (1b) (90% purity, 942 mg,
3.0 mmol, 1.06 mL) was added via syringe, and the mixture was stirred
at 70 °C for 16 h. For workup, methanol (2 mL) and 4 drops of
sulfuric acid were added, and the mixture was stirred at 65 °C for 2 h.
The resulting mixture was washed with aqueous bicarbonate solution
(2 mL), extracted with ethyl acetate (2 mL), filtered through MgSO4,
and analyzed by GC. The gas chromatogram showed a distribution of
double-bond isomers of methyl octadecenoates that was in good
agreement with literature data on the equilibrium distribution of C18
methyl ester double-bond isomers. The concentration of the α,β-
unsaturated isomer was determined to be 3.5%, which is an indicator
that the equilibrium had been reached.6 For full data, see Supporting
Information, Figure S1.
Isomerizing Self-Metathesis of Oleic Acid (1b). Catalyst Screening
for Table 2. A 20 mL headspace vial with septum cap and stirring bar
was charged with isomerization catalyst IC1−4 (0.5 mol %) and
metathesis catalyst MC1−MC5 (0.2 mol %). Oleic acid (1b) and
solvent (if appropriate) were added via syringe, and the mixture was
stirred at 40−70 °C for 2−16 h. For workup, methanol (2 mL) and 4
drops of sulfuric acid were added, and the mixture was stirred at 65 °C
for 2 h. The resulting mixture was washed with aqueous bicarbonate
solution (2 mL), extracted with ethyl acetate (2 mL), filtered through
MgSO4, and analyzed by GC. The resulting distributions are provided
in Figures 4 and 6−8.
Procedure To Obtain the Distribution Given in Figure 3.
Following the above procedure, 1b (90% purity, 354 mg, 1.0 mmol),
catalyst IC4 (4.9 mg, 6 μmol), catalyst MC2 (4.2 mg, 5 μmol), and
hexane (3.0 mL) were stirred for 20 h at 70 °C. The gas
chromatographic signals were assigned to olefins and mono- and
diesters via GC-MS and comparison to authentic samples. To generate
the histograms, the relative areas for the individual compounds were
plotted against their retention time, and overlapping peaks were marked
with dashed lines.
Procedure To Obtain the Distribution Given in Figure 4. Following
the above procedure, 1b (90% purity, 157 mg, 0.5 mmol), catalyst IC4
(2.1 mg, 2.5 μmol), catalyst MC2 (2.5 mg, 3 μmol), and hexane
(2.0 mL) were stirred for 2, 8, or 16 h at 60 °C. The olefins were
separated as follows: NaOH solution (200 mg in methanol/water, 2.0/
6.0 mL) was added to the reaction mixture. The mixture was stirred at
80 °C for 4 h to saponify the carboxylates. After cooling to 20 °C, it
was extracted with hexane. The organic phase was separated, filtered
through MgSO4, and analyzed by GC. To generate the histograms in
Figure 5, the relative areas for the individual compounds were plotted
against their chain length.
Procedure To Obtain the Distribution Given in Figure 5. Following
the above procedure, 1b (90% purity, 354 mg, 1.0 mmol), catalyst IC4
(4.9 mg, 6 μmol), catalyst MC2 (4.2 mg, 5 μmol), and hexane
(3.0 mL) were stirred for 20 h at 40 °C. The gas chromatographic
signals were assigned to olefins and mono- and diesters via GC-MS
and comparison to authentic samples. To generate the histograms, the
relative areas for the individual compounds were plotted against their
retention time, and overlapping peaks were marked with dashed lines.
Procedure to Obtain the Distribution Given in Figure 6. Following
the above procedure, 1b (90% purity, 354 mg, 1.0 mmol), catalyst IC4
(4.9 mg, 6 μmol), and catalyst MC2 (4.2 mg, 5 μmol) were stirred for
8 h at 60 °C. The gas chromatographic signals were assigned to olefins
and mono- and diesters via GC-MS and comparison to authentic
samples. To generate the histograms, the relative areas for the
individual compounds were plotted against their retention time, and
overlapping peaks were marked with dashed lines.
Procedure To Obtain the Distribution Given in Figure 7. Following
the above procedure, 1b (90% purity, 354 mg, 1.0 mmol), catalyst IC4
(2.5 mg, 3 μmol), catalyst MC3 (3.7 mg, 5 μmol), and hexane
(3.0 mL) were stirred for 20 h at 50 °C. The gas chromatographic
signals were assigned to olefins and mono- and diesters via GC-MS
and comparison to authentic samples. To generate the histograms, the
relative areas for the individual compounds were plotted against their
retention time, and overlapping peaks were marked with dashed lines.
Isomerizing Self-Metathesis of 10-Undecenoic Acid (7)
(Scheme 4). A 20 mL headspace vial with septum cap and stirring
bar was charged with isomerization catalyst IC4 (3.9 mg, 2.5 μmol)
and metathesis catalyst MC2 (2.5 mg, 3 μmol). 10-Undecenoic acid
(7) (98% purity, 94 mg, 0.5 mmol) and hexane (3 mL) were added via
syringe, and the mixture was stirred at 70 °C for 20 h. For workup,
methanol (2 mL) and 4 drops of sulfuric acid were added, and the
mixture was stirred at 65 °C for 2 h. The resulting mixture was washed
with aqueous bicarbonate solution (2 mL), extracted with ethyl acetate
(2 mL), filtered through MgSO4, and analyzed by GC and GC-MS.
The gas chromatograms showed a mixture of C11−C16 olefins, C7−C24
unsaturated monoesters, and C11−C24 unsaturated diesters.
Self-Metathesis of Oleic Acid (1b) (Scheme 3). A 20 mL headspace
vial with septum cap and stirring bar was charged with metathesis
catalyst MC2 (4.2 mg, 5 μmol). Oleic acid (1b) (90% purity, 785 mg,
2.5 mmol, 885 μL) was added via syringe, and the mixture was stirred
at 45 °C for 20 h. For workup, methanol (2 mL) and 4 drops of
sulfuric acid were added, and the mixture was stirred at 65 °C for 2 h.
The resulting mixture was washed with aqueous bicarbonate solution
(2 mL), extracted with ethyl acetate (2 mL), filtered through MgSO4,
and analyzed by GC. The gas chromatogram displayed 20% methyl
oleate (1a) corresponding to 80% conversion of 1b into 43% of
13727
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
Isomerizing Self-Metathesis of Linoleic Acid (8) (Scheme 4).
In an analogous procedure, linoleic acid (90% purity, 140 mg,
0.5 mmol) was converted into a mixture of C11−C22 diolefins, C9−C24
diunsaturated monoesters, and C8−C22 diunsaturated diesters.
Isomerizing Self-Metathesis of (E)-3-Hexene (9) (Figure 8,
Red Bars). A 20 mL headspace vial with septum cap and stirring bar
was charged with isomerization catalyst IC4 (4.1 mg, 5.0 μmol) and
metathesis catalyst MC4 (3.8 mg, 6.0 μmol). (E)-3-Hexene (9)
(86 mg, 127 μL, 1.00 mmol) and toluene (1.0 mL) were added via
syringe, and the mixture was stirred at 45 °C for 16 h. After cooling to
20 °C, the mixture was diluted with toluene (3 mL), filtered through a
basic alumina plug and analyzed by GC and GC-MS. The gas
chromatogram of the mixture displayed olefins with the chain-length
distribution provided in the Supporting Information, Table S2.
Sequential Isomerization and Self-Metathesis of (E)-3-
Hexene (9) (Figure 8, Blue Bars). A 20 mL headspace vial with
septum cap and stirring bar was charged with isomerization catalyst
IC4 (10 mg, 12.5 μmol). Via syringe, toluene (1.0 mL) and (E)-3-
hexene (9) (43 mg, 63 μL, 0.50 mmol) were added, and the mixture
was stirred at 45 °C for 16 h. After cooling to 20 °C, the mixture was
filtered through a basic alumina plug into another reaction vial to
remove the palladium catalyst. A solution of metathesis catalyst MC4
(7.72 mg, 12.3 μmol) in degassed toluene (0.5 mL) was added, and
the mixture was stirred for 16 h at 45 °C. After cooling to 20 °C, the
mixture was diluted with toluene (3 mL), filtered through a basic
alumina plug, and analyzed by GC. The gas chromatogram of the
mixture showed olefins with the chain-length distribution provided in
the Supporting Information, Table S3.
Sequential Isomerization and Cross-Metathesis of (E)-3-
Hexene (9) and 1-Octadecene (11) (Figure 9, Red Bars). A
20 mL headspace vial with septum cap and stirring bar was charged
with isomerization catalyst IC4 (10 mg, 12.5 μmol). Via syringe,
toluene (1.0 mL), (E)-3-hexene (9) (43 mg, 63 μL, 0.50 mmol), and
1-octadecene (11) (66 mg, 84 μL, 0.25 mmol) were added, and the
mixture was stirred at 45 °C for 16 h. After cooling to 20 °C, the
mixture was filtered through a basic alumina plug into another reaction
vial to remove the palladium catalyst. A solution of metathesis catalyst
MC4 (7.72 mg, 12.3 μmol) in degassed toluene (0.5 mL) was added,
and the mixture was stirred for 16 h at 45 °C. After cooling to 20 °C,
the mixture was diluted with toluene (3 mL), filtered through a basic
alumina plug, and analyzed by GC. The gas chromatogram of the
mixture showed olefins with the chain-length distribution provided in
the Supporting Information, Table S5.
Isomerizing Cross-Metathesis of (E)-3-Hexene (9) with 1-
Octadecene (11) Leading to the Dishtributions Given in Figure
10. A 20 mL headspace vial with septum cap and stirring bar was
charged with isomerization catalyst IC4 (4.1 mg, 5 μmol) and
metathesis catalyst MC4 (3.8 mg, 6 μmol). (E)-3-Hexene (9) (43 mg,
63 μL, 0.5 mmol), 1-octadecene (11) (0.5−2 equiv), and toluene
(1.0 mL) were added via syringe, and the mixture was stirred at 45 °C
for 16 h. The gas chromatogram of the reaction mixture showed
olefins with the chain-length distribution displayed in Figure 10. For
the reaction in the presence of 0.5 equiv of 11 (66.4 mg, 84 μL,
0.25 mmol), the chain-length distribution is provided in the
Supporting Information, Table S4.
Isomerizing Ethenolysis of Oleic Acid (1b) (Figure 14). A
20 mL headspace vial with septum cap and stirring bar was charged
with isomerization catalyst IC4 (3.1 mg, 3.8 μmol) and metathesis
catalyst MC7 (6.7 mg, 7.5 μmol), and purged three times with
ethylene (purity N30, atmospheric pressure). Oleic acid (1b) (99%,
143 mg, 161 μL, 0.50 mmol) and hexane (3.0 mL) were added via
syringe, and the mixture was stirred at 50 °C for 16 h. In order to
analyze the olefin fraction in detail, separation of the olefins was
accomplished as follows: To the reaction mixture was added NaOH
solution (200 mg in methanol/water, 2.0/6.0 mL). The mixture was
stirred at 80 °C for 4 h, and after cooling to 20 °C, it was extracted
with hexane. The organic phase was separated, filtered through
MgSO4, and analyzed by GC. The olefin fraction displayed the chain-
length distribution provided in the Supporting Information, Table S6.
Isomerizing Cross-Metathesis of Oleic Acid (1b) and (E)-3-
Hexenedioic Acid (14d) (Figure 16). A 20 mL headspace vial with
septum cap and stirring bar was charged with isomerization catalyst
IC4 (5.1 mg, 6.3 μmol), metathesis catalyst MC7 (7.9 mg, 12.5 μmol),
and (E)-3-hexenedioic acid 14d (74 mg, 0.5 mmol, 2.0 equiv.). Oleic
acid (1b) (99% purity, 71 mg, 80 μL, 0.25 mmol) and THF (1.0 mL)
were added via syringe, and the mixture was stirred at 60 °C for 16 h.
The olefins were separated as follows: NaOH solution (200 mg in
methanol/water, 2.0/6.0 mL) was added to the reaction mixture. The
mixture was stirred at 80 °C for 4 h to saponify the carboxylates. After
cooling to 20 °C, it was extracted with hexane. The organic phase was
separated, filtered through MgSO4, and analyzed by GC and GC-MS.
The olefin fraction displayed the chain-length distribution provided in
the Supporting Information, Table S7.
Simulations of Olefin Product Distributions. All computations
were carried out using the R statistics software.30 The input text for all
simulations is detailed in the Supporting Information. The output was
generated in the form of .txt files that were then imported into MS
Excel for generation of histograms.
ASSOCIATED CONTENT
* Supporting Information
■
S
Gas chromatographic data and the simulation program code.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
goossen@chemie.uni-kl.de
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank NanoKat, the Collaborative Research Centre SFB/
TRR 88 “3MET”, the Stiftung der Deutschen Wirtschaft
(fellowship to D.M.O.), and the Carl Zeiss Foundation (Center
for Mathematical and Computational Modeling (CM)2 fellow-
ship to N.T.) for financial support, and Umicore AG for the
donation of chemicals.
REFERENCES
■
(1) Arpe, H.-J. Industrielle organische Chemie: bedeutende Vor- und
Zwischenprodukte, 6th ed.; Wiley-VCH: Weinheim, Germany, 2007, pp
94−95.
(2) Biermann, U.; Bornscheuer, U.; Meier, M. A. R.; Metzger, J. O.;
Schafer, H. J. Angew. Chem. 2011, 123, 3938−3956; Angew. Chem., Int.
̈
Ed. 2011, 50, 3854−3871.
(3) (a) Carlsson, A. S.; Lindberg Yilmaz, J.; Green, A. G.; Stymne, S.;
Hofvander, P. Eur. J. Lipid Sci. Technol. 2011, 113, 812−831. (b) Hill,
K. Pure Appl. Chem. 2007, 79, 1999−2011. (c) Ronda, J. C.; Lligadas,
̀ ́
G.; Galia, M.; Cadiz, V. Eur. J. Lipid Sci. Technol. 2011, 113, 46−58.
(d) Meier, M. A. R.; Metzger, J. O.; Schubert, U. S. Chem. Soc. Rev.
2007, 36, 1788−1802. (e) Xia, Y.; Larock, R. C. Green Chem. 2010, 12,
1893−1909.
(4) Behr, A.; Obst, D.; Westfechtel, A. Eur. J. Lipid Sci. Technol. 2005,
107, 213−219.
́
(5) (a) Jimenez-Rodriguez, C.; Eastham, G. R.; Cole-Hamilton, D. J.
́
Inorg. Chem. Commun. 2005, 8, 878−881. (b) Jimenez-Rodriguez, C.;
Eastham, G. R.; Cole-Hamilton, D. J. Chem. Commun. 2004, 1720−
1721. (c) Quinzler, D.; Mecking, S. Angew. Chem. 2010, 122, 4402−
4404;(d) Angew. Chem., Int. Ed. 2010, 49, 4306−4308.
(6) Ghebreyessus, K. Y.; Angelici, R. J. Organometallics 2006, 25,
3040−3044.
(7) (a) Gooßen, L. J.; Ohlmann, D. M.; Dierker, M. Green Chem.
2010, 12, 197−200. (b) Gooßen, L. J.; Ohlmann, D. M.; Dierker, M.;
Lohl, T. European Patent EP 22411562, 2009.
̈
13728
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729

Journal of the American Chemical Society
Article
(8) (a) Ohlmann, D. M.; Gooßen, L. J.; Dierker, M. Chem.Eur. J.
2011, 17, 9508−3519. (b) Gooßen, L. J.; Ohlmann, D. M.; Dierker, M.
European Patent EP 10189314, 2010.
(23) Verpoort, F. W. C.; De Clercq, B. International Patent
WO2003062253, 2003.
(24) (a) Clavier, H.; Nolan, S. P. Chem.Eur. J. 2007, 13, 8029−
8036. (b) Monsaert, S.; Drozdzak, R.; Dragutan, V.; Dragutan, I.;
Verpoort, F. Eur. J. Inorg. Chem. 2008, 432−440.
(9) Porri, L.; Diversi., P.; Lucherini, A.; Rossi, R. Makromol. Chem.
1975, 176, 3121−3125.
(25) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J.
Am. Chem. Soc. 2000, 122, 8168−8179. (b) Gessler, S.; Randl, S.;
Blechert, S. Tetrahedron Lett. 2000, 41, 9973−9976.
(10) France, M. B.; Feldman, J.; Grubbs, R. H. J. Chem. Soc., Chem.
Commun. 1994, 1307−1308.
(11) Consorti, C. S.; Aydos, G. L. P.; Dupont, J. Chem. Commun.
2010, 46, 9058−9060.
(26) (a) Furstner, A.; Guth, O.; Duffels, A.; Seidel, G.; Liebl, M.;
̈
̈
Gabor, B.; Mynott, R. Chem.Eur. J. 2001, 7, 4811−4820. (b) Mierde,
H. V.; Van Der Voort, P.; De Vos, D.; Verpoort, F. Eur. J. Org. Chem.
2008, 1625−1631. (c) Boeda, F.; Clavier, H.; Nolan, S. P. Chem.
Commun. 2008, 2726−2740.
(12) (a) Johnson, R. W. Fatty Acids in Industry: Processes, Properties,
Derivatives, Applications. Marcel Dekker Inc.: New York, 1989.
(b) Huf, S.; Krugener, S.; Hirth, T.; Rupp, S.; Zibek, S. Eur. J. Lipid
̈
Sci. Technol. 2011, 113, 548−561. (c) Schindler, J.; Meussdoerffer, F.;
Giesel-Buehler, H. Forum Mikrobiol. 1990, 13, 274−281. (d) Pic-
ataggio, S.; Rohrer, T.; Deanda, K.; Lanning, D.; Reynolds, R.;
Mielenz, J.; Eirich, L. D. Nat. Biotechnol. 1992, 10, 894−898.
(13) (a) Schmidt, B. Eur. J. Org. Chem. 2003, 816−819. (b) Schmidt,
B. J. Org. Chem. 2004, 69, 7672−7687. (c) Gauthier, D.; Lindhardt, A.
T.; Olsen, E. P. K.; Overgaard, J.; Skrydstrup, T. J. Am. Chem. Soc.
2010, 132, 7998−8009.
(27) Sasol Technology UK and Umicore AG and Co KG.
International Patent WO 2007/010453 A2, 2007.
(28) (a) Ngo, H. L.; Jones, K.; Foglia, T. A. J. Am. Oil Chem. Soc.
2006, 83, 629−634. (b) Samorski, M.; Dierker, M. European Patent
EP 2157076, 2008.
(29) For the reaction of 1,3-dienes with iron carbonyl, see:
(a) Knolker, H.-J. Chem. Soc. Rev. 1999, 28, 151−157. For
̈
coordination modes of 1,3-dienes, see: (b) Mashima, K.; Nakamura,
A. J. Organomet. Chem. 2002, 663, 5−12. For the synthesis of
conjugated plant oils, see: (c) Quirino, R. L.; Larock, R. C. J. Am. Oil
Chem. Soc. 2012, 89, 1113−1124.
(14) (a) Barton, D. H. R.; Davies, S. G.; Motherwell, W. B. Synthesis
1979, 265−266. (b) Wakamatsu, H.; Nishida, M.; Adachi, N.; Mori,
M. J. Org. Chem. 2000, 65, 3966−3970. (c) Singer, H.; Stein, W.;
Lepper, H. Fette, Seifen, Anstrichm. 1972, 74, 193−198. (d) Salvini, S.;
Piacenti, F.; Frediani., P.; Devescovi, A.; Caporali, M. J. Organomet.
Chem. 2001, 625, 255−267. (e) Laï, R.; Ucciani, E.; Naudet, M. Bull.
Soc. Chim. Fr. 1969, 3, 793−797. (f) Rhoads, S. J.; Chattopadhyay, J.
K.; Waali, E. E. J. Org. Chem. 1970, 35, 3352−3358.
(30) R Development Core Team R: A language and environment for
statistical computing; R Foundation for Statistical Computing, Vienna,
Austria, 2010. ISBN 3-900051-07-0, URL http://www.R-project.org/.
(31) (a) Djigoue, G. B.; Meier, M. A. R. Appl. Catal., A 2009, 368,
́
158−162. (b) Schmidt, B.; Geißler, D. ChemCatChem 2010, 2, 423−
429.
(15) For the synthesis and properties of IC4, see: (a) Vilar, R.;
Mingos, D. M. P.; Cardin, C. J. J. Chem. Soc., Dalton Trans. 1996, 23,
4313−4314. (b) Colacot, T. J. Platinum Metals Rev. 2009, 53, 183−
(32) (a) Marvey, B. B. Int. J. Mol. Sci 2008, 9, 1393−1406.
(b) Montenegro, R. E.; Meier, M. A. R. Eur. J. Lipid Sci. Technol. 2012,
114, 55−62.
́ ́
188. (c) Dura-Vila, V.; Mingos, D. M. P.; Vilar, R.; White, A. J. P.;
Williams, D. J. J. Organomet. Chem. 2000, 600, 198−205. (d) Colacot,
(33) Heublein, G.; Hartung, H.; Helbig, M.; Stadermann, D. J.
Macromol. Sci., Chem. 1982, 17, 821−845.
T. J.; Hooper, M. W.; Grasa, G. A. International Patent WO 2011/
012889A1, 2011. (e) Gooßen, L. J.; Mamone, P.; Grunberg, M. F.;
̈
(34) (a) Johnson, R. W. Fatty Acids in Industry: Processes, Properties,
Derivatives, Applications. Marcel Dekker Inc.: New York, 1989.
Arndt, M. European Patent EP 11005326, 2011.
(16) For examples of C−C couplings, see: (a) Huang, J.; Bunel, E.;
Faul, M. M. Org. Lett. 2007, 9, 4343−4346. (b) Stambuli, J. P.;
Kuwano, R.; Hartwig, J. F. Angew. Chem., Int. Ed. 2002, 41, 4746−
4748. (c) Hama, T.; Liu, X.; Culkin, D. A.; Hartwig, J. F. J. Am. Chem.
Soc. 2003, 125, 11176−11177. (d) Hama, T.; Hartwig, J. F. Org. Lett.
2008, 10, 1545−1548. (e) Hama, T.; Hartwig, J. F. Org. Lett. 2008, 10,
1549−1552. For examples of C−N and C−S couplings, see:
(f) Ryberg, P. Org. Process Res. Dev. 2008, 12, 540−543. (g) Prashad,
M.; Mak, X. Y.; Liu, Y.; Repic, O. J. Org. Chem. 2003, 68, 11C63−
1164. (h) Eichmann, C. C.; Stambuli, J. P. J. Org. Chem. 2009, 74,
4005−4008. For recently developed C−Si couplings, see:
(i) Hemgesberg, M.; Ohlmann, D. M.; Schmitt, Y.; Wolfe, M.;
(b) Huf, S.; Krugener, S.; Hirth, T.; Rupp, S.; Zibek, S. Eur. J. Lipid
̈
Sci. Technol. 2011, 113, 548−561. (c) Schindler, J.; Meussdoerffer, F.;
Giesel-Buehler, H. Forum Mikrobiol. 1990, 13, 274−281. (d) Pic-
ataggio, S.; Rohrer, T.; Deanda, K.; Lanning, D.; Reynolds, R.;
Mielenz, J.; Eirich, L. D. Nat. Biotechnol. 1992, 10, 894−898.
NOTE ADDED AFTER ASAP PUBLICATION
■
This paper was published ASAP on August 9, 2012. The
captions to Tables 4 and 5 have been updated. The revised
version was posted on August 13, 2012.
Muller, M. K.; Erb, B.; Sun, Y.; Gooßen, L. J.; Gerhards, M.; Thiel, W.
̈
R. Eur. J. Org. Chem. 2012, 11, 2142−2151.
(17) For reviews on double-bond migration of olefins, see: (a) Smith,
M. B.; March, J. March’s Advanced Organic Chemistry, 6th Ed.; John
Wiley & Sons, Inc.: Hoboken, NJ, 2007; pp 767−772, and references
therein. (b) Rodriguez, J.; Brun, P.; Waegell, B. Bull. Soc. Chim. Fr.
1989, 799−823. (c) Jardine, F. R. In The Chemistry of the Metal-Carbon
Bond; Hartley, F. R., Patai, S., Eds.; Wiley: New York, 1987; Vol. 4, pp
733−818. (d) Schunn, R. A. Inorg. Chem. 1970, 9, 2567−2572.
(18) (a) Cermak, S. C.; Isbell, T. A. J. Am. Oil Chem. Soc. 2001, 78,
557−565. (b) Isbell, T. A.; Frykman, H. B.; Abbott, T. P.; Lohr, J. E.;
Drozd, J. C. J. Am. Oil Chem. Soc. 1997, 74, 473−477.
(19) Yoshida, T.; Otsuka, S. J. Am. Chem. Soc. 1977, 99, 2134−2140.
(20) Barrios-Landeros, F.; Carrow, B. P.; Hartwig, J. F. J. Am. Chem.
Soc. 2008, 130, 5842−5843.
(21) Mamone, P.; Grunberg, M. F.; Fromm, A.; Khan, B. A.; Gooßen,
̈
L. J. Org. Lett. 2012, 14, 3716−3719.
(22) (a) Harrity, J. P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.;
Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 2343−2351.
(b) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A.
H. J. Am. Chem. Soc. 1999, 121, 791−799.
13729
dx.doi.org/10.1021/ja303822c | J. Am. Chem. Soc. 2012, 134, 13716−13729