Fishing for the right catalyst for the cross-metathesis reaction of methyl oleate with 2-methyl-2-butene

Article abstract of DOI:10.1039/c6cy02623k

The activity of various Ru-alkylidene olefin metathesis catalyst types on the outcome of cross-metathesis of methyl oleate with 2-methyl-2-butene was studied.

Full text of DOI:10.1039/c6cy02623k

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Fishing for the right catalyst for the cross-
metathesis reaction of methyl oleate with
Cite this: DOI: 10.1039/c6cy02623k
2-methyl-2-butene†
Received 15th December 2016,
Accepted 25th January 2017
a
b
a
*
*
A. Sytniczuk, A. Kajetanowicz and K. Grela
DOI: 10.1039/c6cy02623k
The activity of various Ru-alkylidene olefin metathesis catalyst types on the outcome of cross-metathesis
of methyl oleate with 2-methyl-2-butene was studied.
rsc.li/catalysis
cants,25,26 and coatings,27 or even oil based paints, printing
inks, and synthetic resins.
1. Introduction
With the discovery of well-defined ruthenium catalysts, olefin
metathesis has become an irreplaceable tool in the synthesis
of carbon–carbon double bonds.1,2 Ring closing metathesis
(RCM)3,4 and ring opening metathesis polymerisation
(ROMP)5–7 are widely used in the large scale production of
new materials,8,9 complex polymeric compounds,10,11 and
various natural products, such as macrocyclic lactones with
musk odor12 or antibiotics.13 Nonetheless, the greatest poten-
tial for the synthesis of the new compounds is related to utili-
zation of the cross-metathesis (CM) reaction. Recent develop-
ments leading to metathesis catalysts with increased
stability1,2 and thus greater tolerance to functional groups
enabled easy functionalization of organic compounds.1,2 It
has been proved that CM proceeds well not only with the
unfunctionalised olefins but also with alkenes containing
various functional groups such as vinyl sulfones,14 acryloni-
trile,15,16 acrylic esters,17,18 or even vinyl halides,19,20 which
were believed to be quite demanding substrates.
Agenda 21, the comprehensive economic plan adopted by
more than 180 governments, is encouraging the use of renew-
able natural resources21 like, inter alia, oils and fats of both
plant and animal origin. The total market based on these
valuable resources amounts to more than 140 million tons
per year which is 5% of the total biomass produced every
year. These oleochemicals are used for the production of
important product groups22,23 such as surfactants,24,25 lubri-
Plant oils and fats, due to their diverse construction and
multiplicity of double bonds, are perfect substrates to various
organic transformations such as oxidation,28 epoxidation,29
or transition-metal catalysed addition.30 As previously
proved,31 olefin metathesis can also be a perfect tool to con-
vert plant oils into valuable commodity chemicals; however,
in the context of industrial use of this methodology the
appropriate choice of the catalyst is crucial in order to
achieve the most economical process characterised by the
highest selectivity and conversion possible.32–37 Following the
studies on acetate functionalisation,35–37 in the present arti-
cle the influence of N-heterocyclic carbenes (NHCs), phos-
phorous ligands and alkylidene moieties present in the
Hoveyda–Grubbs, Grubbs and indenylidene type ruthenium
catalysts on cross-metathesis of methyl oleate with 2-methyl-
2-butene was studied.
The CM reaction of olefins with an excess of 2-methyl-2-
butene was described for the first time by Grubbs38 and can
be seen as an effective and direct method for the conversion
of a terminal mono-substituted C–C double bond into a tri-
substituted “prenyl-type” one (–CHCH2 → –CHCMe2).
Such a formed trisubstituted prenyl double bond undergoes
a number of useful synthetic transformations, including
electrophilic addition39 as well as recently intensively studied
metal- and organo-catalysed reactions.40–44 In addition, the
prenyl fragment has been shown to be important for
protein–protein binding through specialized prenyl-binding
domains.45
a Faculty of Chemistry, Biological and Chemical Research Centre, University of
Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland.
E-mail: prof.grela@gmail.com
b Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52,
01-224 Warsaw, Poland. E-mail: anna.kajetanowicz@gmail.com
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c6cy02623k
Although it was observed that the CM reaction with
2-methyl-2-butene is sometimes less selective38,46 than the
analogous transformation with 2-methyl-propene47 the use of
higher boiling 2-methyl-2-butene is more convenient from the
practical point of view than working with gaseous and more
expensive 2-methylpropene.
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2. Results and discussion
in pairs can be different (i.e. 3 vs. 4 and 5 vs. 6), as the con-
secutive metathesis events are independent.
The cross metathesis transformation of methyl oleate (1)
with 2-methyl-2-butene (2, Scheme 1) was chosen to obtain
potentially valuable commodity chemicals containing prenyl-
type double bonds: methyl 10-methylundec-9-enoate (3) and
2-methylundec-2-ene (4).44,48–51 In addition to these expected
CM products, the linear by-products of the CM reaction with
2 can also be formed,38 namely, methyl undec-9-enoate (5)
and undec-2-ene (6). To make the picture complete, products
formed via self-cross metathesis of methyl oleate (1), octadec-
9-ene (7) and dimethyl octadec-9-enedioate (8) can also be
expected (Scheme 1). The undesired products 5 and 6,
created in some amount, can lead in a series of secondary
metathesis and isomerisation52,53 events to form even more
complicated reaction mixtures. At the same time, because
2-methyl-2-butene (2) is used in excess, we hoped that the less
sterically hindered and therefore more metathetically accessi-
ble compounds 5 and 6 as well as 7 and 8 can react further
with another molecule of 2, thus increasing the amount of
the expected products 3 and 4 in the reaction mixture
(Scheme 1). Finally, we assumed that the proportion of the
possible products obtained from either the alkyl-terminus or
the ester-terminus of the methyl oleate molecule considered
Because the “prenylated” 3 and 4 are the most interesting
products from those possible to be found in the reaction
mixture,39–45 we assumed that not only the conversion of 1
but also the selectivity towards these two compounds shall be
the key factor in our optimisation. To do so, having in hand
a large collection of assorted ruthenium metathesis catalysts,
we attempted a number of experiments varying the reaction
conditions and the catalyst used (Fig. 3 and 11).
2.1 Preliminary study
The first objective of this study was to find the most suitable
conditions for the metathesis reaction leading to the highest
conversion of 1 and the highest selectivity towards the prod-
ucts 3 and 4. The selection of the best reaction parameters,
namely, a solvent, temperature and time, as well as an excess
of 2-methyl-2-butene (2), was performed using two very popu-
lar and commercially available catalysts: Hoveyda–Grubbs
second generation (Hov-II) and Umicore™ M2 (Ind-II)
(Fig. 1). The solvents tested were toluene, dichloromethane
and dichloroethane; the reaction was also conducted without
any solvent. Despite a great interest in carrying out metathe-
Scheme 1 Self-metathesis reaction of methyl oleate (1) and cross-metathesis reaction of methyl oleate (1) with 2-methyl-2-butene (2).
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amount of 2 (Table 1, entries 1–4). It was found that under
these conditions Hov-II exhibited in general similar effective-
ness regardless of the quantity of 2-methyl-2-butene (2); how-
ever, slightly better conversion and selectivity were observed
when the substrate ratio was 1 : 10. When either dichloro-
methane or 1,2-dichloroethane was used in the CM reaction
instead of toluene under otherwise identical conditions, a
significant drop of conversion was observed while selectivity
stayed at a similar level (Table 1, entries 5–6). The result of
the reaction in which the substrate 2 was also the solvent
(Table 1, entry 7) was almost identical to those obtained for
the substrate ratio of 1 : 10 (Table 1, entry 2), but for eco-
nomic reasons such conditions were not considered further.
Since it was proved52 that addition of quinones may improve
the selectivity of the metathesis reaction, 2-chlorobenzo-
quinone was examined (Table 1, entries 8 and 9). The first
reaction was performed in toluene at room temperature for
5 h with ten equivalents of 2 relative to 1. An increase in
selectivity of the process towards the products 3 and 4 was
observed; however, the conversion was more than 20% lower
than that observed in the reaction without quinone (Table 1,
entry 2). When the reaction time was extended to 24 h the
conversion increased, but at the same time the selectivity
decreased. Because in our opinion the benefits achieved by
the introduction of an additional reagent to the examined
system did not compensate for its additional complication,
studies utilizing quinones were not continued. Next, the
influence of temperature was examined (Table 1, entries 2,
10–12). It was found that increasing the temperature from rt
to 40 °C resulted in an improvement both in conversion and
in selectivity. A further increase of the temperature to 60 and
80 °C resulted in almost full conversion and good selectivity.
Interestingly, when the indenylidene catalyst Umicore™
M2 (Ind-II) was applied under the conditions optimized for
the Hoveyda–Grubbs complex (10 equivalents of 2, toluene,
Fig.
1 The most popular commercially available ruthenium olefin
metathesis catalysts, belonging to the first (L = PCy3) and the second
generation (L = SIMes).
sis in aqueous media or in water-based emulsions,54,55 such
systems have not been included in the present study. A wide
range of temperatures was examined, starting at 20 °C and
increasing up to 80 °C with 20° intervals.
During the selection of the most desirable conditions for
the metathesis reaction two parameters were considered to
be of key importance: the substrate conversion and the molar
composition of the resulting reaction mixture. The outcome
of the optimization study is presented in Table 1. The conver-
sion of methyl oleate (1) and the proportion of the products
in the reaction mixture (presented in mole fractions) were
determined by gas chromatography with dodecane as an
internal standard, wherein both geometrical isomers E and Z
were counted together. To identify the components of the
post reaction mixture, the samples were examined by GC-MS
(using the same column), and retention times were compared
with the independently obtained samples.56 The structure
and configuration of the isolated main products were addi-
tionally confirmed by 1H and 13C NMR spectroscopy.
An initial study on the cross-metathesis of methyl oleate
(1) in the presence of the Hoveyda–Grubbs catalyst Hov-II
was performed in toluene at room temperature with varying
amounts of the cross-partner 2. During these experiments, in
order to maintain the concentration of 1 at a constant level,
the amount of solvent was decreased to match the increasing
Table 1 Cross-metathesis reactions in the presence of the ruthenium catalysts Hov-II and Ind-IIa
Equiv.
Temp [°C] Time [h] of 2
Molar fraction Molar fraction Molar fraction Molar fraction
Entry Cat.
Solvent
Conversion% of 3b
of 4b
of 5b
of 6b
1
2
3
4
5
6
7
Hov-II Toluene Rt
Hov-II Toluene Rt
Hov-II Toluene Rt
Hov-II Toluene Rt
5
5
5
5
5
5
5
5
24
5
5
5
5
5
24
48
2
10
19
38
10
10
38
10
10
10
10
10
10
10
10
10
64
75
69
67
40
41
77
52
79
94
92
97
5
0.19
0.22
0.22
0.23
0.19
0.19
0.24
0.37
0.28
0.33
0.38
0.36
0.12
—
0.25
0.31
0.28
0.32
0.29
0.30
0.32
0.36
0.39
0.35
0.28
0.39
0.25
—
0.15
0.15
0.18
0.17
0.17
0.17
0.17
0.06
0.14
0.10
0.06
0.08
0.30
—
0.16
0.11
0.13
0.15
0.08
0.05
0.12
0.09
0.08
0.11
0.18
0.16
0.12
—
Hov-II DCM
Rt
Rt
Rt
Hov-II DCE
d
Hov-II
—
8c
9c
10
11
12
13
14
15
16
Hov II Toluene Rt
Hov-II Toluene Rt
Hov-II Toluene 40
Hov-II Toluene 60
Hov-II Toluene 80
Ind-II
Ind-II
Ind-II
Ind-II
Toluene 80
Toluene 40
Toluene 40
Toluene 40
0
65
86
0.28
0.30
0.40
0.43
0.13
0.14
0.06
0.07
a
b
Reaction conditions: 1 mol% cat., [M](1) = 0.17 M, 0.6 equiv. dodecane (internal standard for GC). Determined by GC, calculated for both
E/Z isomers. c 2 mol% 2-chloroquinone was added. 2-Methyl-2-butene (2) served as a solvent.
d
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80 °C, 5 h), almost no conversion of substrate was observed
(Table 1, entry 14). This forced us to re-investigate the opti-
mal conditions for the indenylidene system57 in an indepen-
dent way. Since toluene appeared to be the best solvent for
the CM reaction of 1, and the ratio between substrates 1 and
2 seemed to be optimal as well, only the temperature, the
reaction time and the amount of catalyst were re-examined
during this optimization. As was found previously, when the
reaction was performed for 5 hours at 80 °C, only 5% conver-
sion was observed and, as expected, decreasing the tempera-
ture to 40 °C gave an even worse result—practically no con-
version. However, when the reaction time was extended to
24 and 48 h the level of conversion increased significantly to
65% and 86% (Table 1, entries 15 and 16). Based on these
results the optimal conditions for further research were
selected, namely, 10 equivalents of 2, toluene as a solvent, 5
hours at 80 °C for Hoveyda–Grubbs type complexes and 48
hours at 40 °C for indenylidene. The latter was also applied
for Grubbs type catalysts since it is known that most
complexes of this type exhibit limited stability at elevated
temperature.
were much less active than the previously examined second
generations catalysts (see Table 1, entry 12 for Hov-II and
entry 16 for Ind-II) and did not even reach 20% conversion
(15, 12 and 9% for Hov-I, Ind-I, and Gr-I, respectively).
2.3 Phosphine-free second generation complexes
Since the first generation complexes were found to be useless
catalysts in the studied transformation, we decided to con-
centrate our efforts on finding the optimal Ru-compound
promoting the CM reaction among second-generation cata-
lysts, both the commercially available ones and those recently
obtained in our laboratory. The goal behind testing a so large
and heterogeneous collection of catalysts was to find the cor-
relation between the catalyst structure and their activity and
selectivity in the studied CM reaction between 1 and 2. Partic-
ular emphasis was put on the impact of different NHC and
benzylidene ligands present in ruthenium complexes (Fig. 3).
In a series of cross-metathesis reactions of methyl oleate
(1) with 2-methyl-2-butene (2) utilizing Hoveyda-Grubbs type
complexes mixed results were observed (Fig. 4). There were
catalysts that exhibited very high activity, namely, Hov-II,
[Ru]-4, [Ru]-6, [Ru]-7, [Ru]-12, [Ru]-14, [Ru]-15, [Ru]-16, [Ru]-
21, and [Ru]-23 (Fig. 4), but at the same time complexes that
converted only a small fraction of 1 into products were
found: [Ru]-2, [Ru]-8, and [Ru]-11. These experiments pro-
vided the first input for a detailed study on the influence of
the structure of both neutral and benzylidene-type ligands on
the catalyst activity and selectivity.
Interestingly, migration of the double bond was not
observed in the examined reactions.
2.2 First generation complexes
With the optimized reaction conditions in hand, the system-
atic search for the best catalyst for the cross-metathesis reac-
tion between methyl oleate (1) and 2-methyl-2-butene (2) was
started. First, the reaction catalysed by first generation com-
plexes (Fig. 2) was studied.
In comparison to previously utilized second generation
complexes, the first generation catalysts Hov-I, Ind-I, and Gr-I
were found to be selective mostly towards the undesired
self-metathesis reaction, as the “dimerization” products 7
and 8 comprised around 80% of all products present in the
reaction mixture. What is more, first generation complexes
First, the influence of different NHC ligands on the activity
of Hoveyda–Grubbs type catalysts bearing the same
benzylidene part was examined (Fig. 5). Compared to the
commercially available Hoveyda–Grubbs catalyst Hov-II bear-
ing the SIMes ligand (1,3-bisIJ2,4,6-trimethylphenyl)imidazolin-
2-ylidene),
its
analogue
with
SIPr
(1,3-bisIJ2,6-
diisopropylphenyl)imidazolin-2-ylidene), [Ru]-1, exhibited
lower activity and selectivity, as the undesired products 5, 7,
and 8 accounted for around 50% of all products. A rather
similar result was obtained for [Ru]-3 bearing a methyl
2,3,4,5,6-pentafluorobenzoate substituent in the backbone of
4,5-dihydro-1H-imidazole, which was a small disenchant-
ment.58 Exchanging SIMes with Me2IMes (1,3-bisIJ2,4,6-
trimethylphenyl)imidazol-2-ylidene) ([Ru]-2)59 also led to a
significant decrease in both conversion and selectivity of the
cross-metathesis reaction.
The next vital structural feature checked by us was the
influence of an alkoxy fragment in the benzylidene ligand of
the Hoveyda–Grubbs catalyst. To do so, complexes [Ru]-10,
[Ru]-16, [Ru]-17, [Ru]-18, and [Ru]-19 were compared in the
CM of 1 with 2 with Hov-II (Fig. 6). Unfortunately, replacing
the isopropoxy fragment of the original Hoveyda catalyst with
other alkoxy groups led to catalysts of decreased activity and
selectivity (Fig. 6). In almost each case significant amounts
of the homo-dimerization products 7 and 8 or undesired
cross-metathesis products 5 and 6 were formed. In terms
of catalytic activity the most advantageous change was the
Fig. 2 Comparison of 1st generation catalysts (conditions: 2 – 10
equiv., [Ru] – 1 mol%, toluene, 5 h, 80 °C for Hov I and 48 h at 40 °C
for Gr I and Ind I).
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Fig. 3 Hoveyda–Grubbs type catalysts used in this study.
replacement of isopropyl by the cyclopentane group in the
ethereal fragment, as demonstrated by complex [Ru]-16.60,61
Application of this catalyst resulted in 96% conversion of 1;
however the selectivity of the studied CM process was lower
than in the case of iPrO-substituted Hov-II. Interestingly, use
of this catalyst led to larger quantities of cross-metathesis
products 5 and 6 bearing disubstituted double bonds. When
a higher “homologue” of [Ru]-16, namely [Ru]-17, was uti-
lized, both conversion and selectivity slightly dropped,
although they still remained at an acceptable level. Finally, in
the model reaction between 1 and 2 catalysed by the commer-
cially available Umicore™ M51 ([Ru]-18),62 the observed con-
version was comparable to the result obtained with [Ru]-16
(86 versus 94%) while selectivity towards the desired CM
products was slightly higher. On the other hand, Umicore™
M52 ([Ru]-19),62 which differs from M51 only by the lack of a
methyl group, was less effective and exhibited both lower
conversion and selectivity. The least effective complex in this
series was [Ru]-10,63 which at about 45% conversion gave an
almost equimolar mixture of 3–5, 7 and 8.
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Fig. 4 Comparison of various Hoveyda–Grubbs type catalysts (conditions: 2 – 10 equiv., [Ru] – 1 mol%, toluene, 5 h, 80°).
Until now the SIMes bearing Hov-II has been the most ac-
tive and selective among the tested catalysts, transforming 1
very effectively to the desired products 3 and 4. In the
next step, the influence of electronic modification64 of the
benzylidene ligand by introducing electron withdrawing
groups (EWGs) in the para position to the isopropoxy group
was examined (Fig. 7). It is known that EWGs could improve
the catalytic activity of the Hoveyda–Grubbs complex due to
the weakening of the oxygen–ruthenium bond and facilita-
tion of dissociation of benzylidene ligands.64 The first
member of this family of EWG-activated metathesis catalysts,
[Ru]-4 with a nitro substituent,65 exhibited indeed a visibly
higher activity than that observed for Hov-II (Fig. 7). Further-
more, only a very small amount of side products was
formed. Slightly lower but still fairly satisfactory activity and
selectivity were exhibited by the commercially available
Umicore™ M71 SIMes ([Ru]-12) with the 2,2,2-trifluoro-N-
methylacetamide substituent as well as by Umicore™ M73
SIMes ([Ru]-14) with the carbamate substituent.62 When M73
SIMes was utilized in the studied reaction, good conversion
of 1 (92%) as well as good selectivity was observed; in the
reaction mixture mainly cross-metathesis products were
present with a small amount of dimeric products. An even
better result was found for the structural analogue [Ru]-12
Fig.
5
Comparison of Hoveyda–Grubbs type catalysts bearing
Fig. 6 Comparison of Hoveyda–Grubbs type catalysts with different
different NHC ligands (conditions as in Fig. 4).
ethereal substituents in the benzylidene moiety (conditions as in Fig. 4).
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Fig. 7 Comparison of Hoveyda–Grubbs analogues with SIMes ligand
Fig. 8 Comparison of [Ru]-4 analogues bearing different NHC ligands
bearing different benzylidene moieties (conditions as in Fig. 4).
(conditions as in Fig. 4).
(Umicore™ M71 SIMes); the selectivity slightly increased and
the conversion of 1 was higher by a few percent. The Zannan
catalyst [Ru]-23,66 with a dimethylsulfonamide substituent,
was one of the most active among the tested complexes,
giving 96% conversion; however in terms of selectivity it
exhibited worse properties than those of its competitors, as a
significant amount of dimerization products were formed
during the reaction (Fig. 7). The last members of the group
of EWG substituted Hoveyda–Grubbs analogues were com-
plexes bearing benzenesulfonic esters, [Ru]-20, [Ru]-21 and
[Ru]-22 (in Fig. 7 only the best one is shown).67 In accordance
with the literature notion, we observed that the substituent
in the para position of benzenesulfonic acid has a significant
influence on the catalyst activity (Fig. 7). Complex [Ru]-20
was found to be the least active and selective one in this
group, while both [Ru]-21 and [Ru]-22, where the phenyl sul-
fone fragment was modified either with a methoxy or a nitro
group, show substantially better results in terms of conver-
sion (92 and 86%, respectively, in comparison to 58% for
[Ru]-20) and selectivity.
As could be expected from the preliminary screening (cf.
Fig. 5) most of the substituted Hoveyda–Grubbs type catalysts
bearing the SIPr ligand showed average activity in CM of
methyl oleate (1) and 2-methyl-2-butene (2) (Fig. 9). Only com-
mercially available [Ru]-13 (Umicore™ M71-SIPr) and [Ru]-15
(Umicore™ M73-SIPr)62 led to satisfactory results. However,
the activity and selectivity exhibited by these complexes were
still lower than those of SIMes containing [Ru]-4.
In the next step of our study, the influence of anionic
ligands on the model CM reaction was tested (Fig. 10). When
chloride ligands in Hov-II were changed to trifluoroacetic
ones, producing the modified Hoveyda–Grubbs type catalyst
[Ru]-8,70 a significant reduction of the usefulness of such an
obtained complex in the cross-metathesis reaction between
methyl oleate (1) and 2-methyl-2-butene (2) was observed.
As the nitro-substituted Hoveyda catalyst [Ru]-4 was
found to exhibit the highest conversion and selectivity in
the studied CM of 1, we decided to use it as the platform to
investigate the influence of various NHC ligands in more
detail (Fig. 8). The first alteration of the nitro-Hoveyda cata-
lyst was complex [Ru]-5 with a sterically enlarged NHC
ligand (SIPr). This modification, however, exhibited rather
moderate activity, with 60% substrate conversion, and
moderate selectivity. On the other hand,
a designer
imidazolinium NHC ligand, introduced by Dorta68,69 (as in
complex [Ru]-7) led to more satisfactory results. Application
of [Ru]-7 gave an almost quantitative conversion together
with high selectivity towards the desired products 3 and 4.
The dimethylimidazolium NHC ligand,59 placed on the same
platform ([Ru]-6) gave still satisfactory results, but its perfor-
mance was visibly lesser.
Fig. 9 Comparison of Hoveyda–Grubbs type catalysts with different
benzylidene moieties and SIPr NHCs (conditions as in Fig. 4).
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Analysis of the reaction mixtures presented in Fig. 13
clearly shows that commercial Umicore™ M2 catalyst Ind-II
is the most active complex in the tested transformation,
while its structural modification caused a decrease in the
conversion of substrate 1. Importantly, Ind-II was also one of
the most selective in its class (Fig. 13). When Ind-II bearing
the saturated SIMes ligand was substituted with IMes
containing [Ru]-25, a significant decrease in activity of the
latter was observed, resulting in a much lower conversion
and yield of the desired products. Application of Me2IMes-
containing [Ru]-2459 allows for a twofold increase in conver-
sion as compared with [Ru]-25; however, it was still only half
of the number obtained for Ind-II. Both ruthenium com-
plexes bearing unsaturated ligands reached very similar selec-
tivity and gave a mixture of cross- and self-metathesis prod-
ucts. Introduction of a substituent into the backbone of 4,5-
dihydro-1H-imidazole ligand, as in [Ru]-33,71 resulted in
higher conversion of 1 and higher selectivity towards 3 and 4,
but still gave worse results as compared to unmodified Ind-II.
Complex [Ru]-2672 was the least active one in this series;
however, it was also among the most selective ones.
Fig. 10 Hoveyda–Grubbs type catalysts bearing different anionic
ligands (conditions as in Fig. 4).
Not only did the conversion decrease by almost two thirds,
but also a significant decrease of the selectivity towards the
desired compounds 3 and 4 was detected, while 7 and 8 were
the main components of the reaction mixture. In contrast to
complexes bearing the SIMes ligand, in the case of their SIPr
analogues, the modification of the anionic ligands affected
neither the activity nor the selectivity, as the results obtained
for [Ru]-1 and [Ru]-9 were almost the same.
In Fig. 14 we present in greater detail a subset of
indenylidene catalysts bearing unsymmetrical NHC ligands.
It is easy to see that modification of the N-substituent in the
imidazolinium ring of a NHC ligand has a huge influence on
the effectivity of such derived catalysts in cross-metathesis re-
actions between 1 and 2 (Fig. 14). For example, replacement
of one mesitylene ring with a benzyl group possessing a sub-
stituent in the ortho position, such as the N,N-dimethylamino
group in [Ru]-2773 or the methoxy group in [Ru]-28,73 reduced
the conversion of the methyl oleate (1) to 71 and 41%, respec-
tively, in comparison to 86% obtained when unmodified
Umicore M2 was applied. The same trend was even more visi-
ble for the complexes containing thiophene or furane moie-
ties, [Ru]-2973 and [Ru]-30,73 respectively, where the conver-
sion was as little as 22 and 12%. The changes in the
structure of the NHC ligand also affected the selectivity of
the process. When complexes with N-benzyl NHC ligands
were applied, a mixture of cross- and self-metathesis prod-
ucts was obtained; however, in both cases 3 and 4 were
formed predominantly. Interestingly, application of catalyst
[Ru]-29 bearing the NHC ligand with a furane moiety gave in
large proportion products of self-CM of 1 (however with low
conversion). Having in hand two mass-enlarged complexes
designed for application in nanofiltration,74,75 we decided to
include them in our tests. Unfortunately, when [Ru]-31 and
[Ru]-32 bearing NHC ligands decorated with polyhedral oligo-
meric silsesquioxane (POSS) were applied, the conversion of
substrate 1 reached 40–60% only, and the selectivity was
rather low.
2.4 Second generation complexes with phosphine ligand
In the second part of the study, we attempted to test in more
detail complexes other than phosphine-free Hoveyda–Grubbs
catalysts (Fig. 11). Since in the preliminary study we noted
that the cross-metathesis reaction of methyl oleate (1) and
2-methyl-2-butene (2) in the presence of indenylidene catalyst
Ind-II was significantly slower as compared to the same
transformation catalysed by Hoveyda–Grubbs complex, in
this part of the research the reaction time was extended to 48
hours and the temperature was maintained at 40 °C.
After some preliminary experiments, we decided to apply
the same conditions also to reactions promoted by Grubbs
type catalysts. The results of testing of the small library of 18
Grubbs and indenylidene type of complexes require some
comments. There were not only catalysts with relatively high
activity, which resulted in a high level of conversion of
methyl oleate (1), viz. Ind-II, [Ru]-27, [Ru]-32, [Ru]-33, [Ru]-37,
and [Ru]-38, but also catalysts characterized by very low activ-
ity with the conversion of 1 below 20%, viz. [Ru]-25, [Ru]-26,
[Ru]-30, [Ru]-34, and [Ru]-35 (Fig. 12). Disappointingly, most
of the indenylidene and Grubbs type complexes exhibited low
selectivity and in most cases the percentage of the desired
products in the reaction mixture was less than 50%. Only two
complexes produced a high yield of the products 3 and 4,
namely Ind-II and [Ru]-37.
The next factor which strongly affected the results of
cross-metathesis reactions between methyl oleate (1) and
2-methyl-2-butene (2) catalysed by indenylidene type com-
plexes was the kind of P-ligand used (Fig. 15). The highest
conversion (86%) and selectivity towards the desired products
3 and 4 were exhibited by Ind-II, the catalyst bearing a
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Fig. 11 Indenylidene and Grubbs type catalysts used in this study.
tricyclohexylphosphine ligand. Exchange of tricyclohexyl-
phosphine with triphenylphosphine (in [Ru]-35) or triiso-
propylphosphite (in [Ru]-36) caused a significant drop in con-
version to 15% and 27%, respectively. In contrast to Ind-II
which gave predominantly a mixture of both cross-metathesis
products, [Ru]-35 was selective towards only one of them,
namely 2-methylundec-2-ene (4). This product represents ap-
proximately 50% of all products obtained during the reac-
tion. [Ru]-36 provided an almost equimolar mixture of
“prenylated” (3 and 4) and linear (5 and 6) products of cross-
metathesis reaction together with around 10% self-products,
7 and 8. The somewhat disappointing result obtained with
[Ru]-36, which previously was proved to be an effective cata-
lyst for challenging reactions operating at high temperatures
(80° or higher),76 is due to the utilization of this complex
below the optimal temperature for its activity. Although we
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Fig. 12 Comparison of the indenylidene and Grubbs type catalysts (conditions: 2 – 10 equiv., [Ru] – 1 mol%, toluene, 48 h at 40 °C).
are convinced that an increase in temperature to 80 or even
120 °C would considerably improve the result, for the sake of
an easier comparison with other complexes we kept the con-
ditions fixed. It should also be mentioned that the studied
complex [Ru]-36 is in the cis form while the other coupled
catalysts are in the trans form. [Ru]-35, in which the only
structural modification in comparison to [Ru]-34 was the
replacement of the SIMes ligand by the SIPr one, exhibited
slightly lower activity and selectivity than its analogue.
2-methyl-2-butene (2) in comparison to Hoveyda–Grubbs cata-
lysts even if the reaction time was almost ten times longer.
The first generation catalyst Gr-I, as shown previously in
Fig. 2, exhibited low activity and formed predominantly self-
metathesis products. In comparison, the second generation
complexes were more reactive and transformed 1 with moder-
ate efficiency; however they favoured the formation of the
self-metathesis products 7 and 8 at the expense of the desired
products. The only exception was [Ru]-37 bearing a Me2IMes
ligand which not only was the most active (conversion 78%)
but also was the most selective catalyst in the tested group.
The Grubbs type complexes (Fig. 16) were found to be rela-
tively ineffective in the reaction of methyl oleate (1) and
Fig. 13 Comparison of Ind-II analogues bearing different NHC ligands
(both N-substituents in the imidazole/imidazoline ring are aromatic)
(conditions as in Fig. 12).
Fig. 14 Comparison of Umicore™ M2 analogues bearing different
NHC ligands (one arm of the imidazole/imidazoline ring is aliphatic)
(conditions as in Fig. 12).
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Fig. 17 Cross metathesis reaction with different loadings of [Ru]-4
(conditions: 2 – 10 equiv., toluene, 5 h, 80 °C). At 500 and 100 ppm
loading no conversion was observed.
Fig. 15 Indenylidene type catalysts bearing other neutral ligands
(conditions as in Fig. 12).
reducing the amount of complex failed—no products of the
metathesis reaction were observed. Another interesting obser-
vation was a drop in selectivity caused by diminishing cata-
lyst loading. This can be related to the fact that during the
metathesis process 1 and 2 reacted with each other, yielding
both main and side products (see Scheme 1). The main prod-
ucts 3 and 4, having triple-substituted double bonds, did not
undergo further reaction but at the same time by-products
5–8 with double-substituted double bonds could still react.
The conditions selected for the examined transformation
with excess 2-methyl-2-butene (2) and a sufficient amount of
the catalyst allowed for further reaction of the side-products
that were created at the beginning of the reaction with an
excess of 2 while the metathesis catalyst was still active.
When a smaller loading of the complex was used, not all
products had “enough time” to react, with an excess of 2
leading to major CM products.
Conclusions
Fig. 16 Grubbs type complexes (conditions as in Fig. 12).
Screening a large set of various Ru metathesis catalysts in a
cross-metathesis reaction of methyl oleate (1) with 2-methyl-
2-butene (2) allowed for selecting complexes that exhibited
the most advantageous properties in this transformation,
leading to high selectivity toward the desired cross-
metathesis products 3 and 4 bearing a trisubstituted double
bond. Although no simple relationships between the struc-
ture of the complexes and their effectiveness in CM of 1 was
found, some trends however were noticed. First of all, it was
found that the CM reaction could be effectively performed
only with second generation Ru catalysts. When the first
generation complexes were applied, a significant decrease in
activity was observed together with an increase in selectivity
towards unwanted self-metathesis products. In comparison
to indenylidene and Grubbs systems, Hoveyda–Grubbs cata-
lysts were found to be, in general, more active, reaching
higher conversion in a shorter time with only just a few
exceptions. When the reaction was carried out with less active
complexes, the self-metathesis products 7 and 8 were predom-
inantly formed, which is particularly true for the majority of
Mainly the cross-metathesis products 3 and 4 were obtained
with only traces of dimerization products in this case; how-
ever, the conversion was lower than in the case of the
Hoveyda–Grubbs system.
After a thorough and meticulous testing of numerous cata-
lysts the best ruthenium complex for cross-metathesis reac-
tion of methyl oleate (1) with 2-methyl-2-butene (2) was
selected—[Ru]-4. Not only did it give very good results—
almost quantitative conversion and very good selectivity—but
it is also commercially available (comparable results were
obtained for [Ru]-7, but since it was a “homemade” catalyst it
has limited availability). That is why [Ru]-4 was selected for
further study with decreased catalyst loading (0.5 and 0.1
mol% and then 500 and 100 ppm, Fig. 17). When 0.5 mol%
[Ru]-4 was used, the conversion of the starting material was
very similar to the result obtained in the presence of 1 mol%
catalysts. Also, decreasing the catalysts loading to 0.1%
resulted in relatively good conversion of 1 (81%) but further
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Grubbs and indenylidene type catalysts. Under standard con-
ditions (2 – 10 equiv., [Ru] – 1 mol%, toluene, 5 h, 80°) the
catalyst of choice for this transformation is [Ru]-4 which not
only gave one of the best results (together with [Ru]-7) but is
also commercially available. Decreasing the catalyst loading
to 1000 ppm allowed for synthesis of the desired products
with a high yield and acceptable selectivity. Further reduction
of the amount of catalysts failed, and only substrates were
observed in the reaction mixture.
The obtained results clearly demonstrate that one can
effectively synthesize olefins with a prenylated double bond;
however, the transformation is challenging because the reac-
tion mixture obtained is a complex one. On the other hand,
in the present study the suitable conditions and a high-
performing catalyst for this reaction were identified.
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Acknowledgements
AK would like to thank The National Science Centre – Poland,
Program SONATA, NCN/2011/03/D/ST5/06079, for financial
support. KG and AS wish to thank the Foundation for Polish
Science for the “Team” Programme co-financed by the EU
European Regional Development Fund-Operational Program
Innovative Economy 2009/2013.
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