Ruthenium-Catalyzed Cross Metathesis of β-Myrcene and its Derivatives with Methyl Acrylate

Article abstract of DOI:10.1002/cctc.201500993

The reaction of β-myrcene with methyl acrylate produces 3-methylenecyclopent-1-ene in the presence of the Ru catalyst Neolyst M2 by ring-closing metathesis in the first step. In the second step, the generated methylidene unit reacts with methyl acrylate to give the corresponding unsaturated cyclic ester by cross metathesis. Under the optimized reaction conditions (80 °C, Neolyst M2, 16 equivalents of methyl acrylate), derivatives of β-myrcene, myrcenol, myrcenyl acetate, and β-ocimene, react to yield functionalized acyclic esters.

Full text of DOI:10.1002/cctc.201500993

DOI: 10.1002/cctc.201500993
Communications
Ruthenium-Catalyzed Cross Metathesis of b-Myrcene and
its Derivatives with Methyl Acrylate
Arno Behr,* Leif Johnen, Andreas Wintzer, Arzu Gümüs¸ C¸etin, Peter Neubert, and
Lutz Domke[a]
The reaction of b-myrcene with methyl acrylate produces 3-
methylenecyclopent-1-ene in the presence of the Ru catalyst
Neolyst M2 by ring-closing metathesis in the first step. In the
second step, the generated methylidene unit reacts with
methyl acrylate to give the corresponding unsaturated cyclic
ester by cross metathesis. Under the optimized reaction condi-
tions (808C, Neolyst M2, 16 equivalents of methyl acrylate), de-
rivatives of b-myrcene, myrcenol, myrcenyl acetate, and b-oci-
mene, react to yield functionalized acyclic esters.
Since its discovery by Banks and Bailey in 1964 when they re-
acted propylene with ethylene and 2-butene,[1] metathesis has
become powerful for both industrial applications[2] and aca-
demic research.[3] It constitutes an elegant route for direct CÀC
bond formation in organic chemistry,[3a,b] has a spectacular
Scheme 1. Metathesis of b-myrcene with methyl acrylate.
functional group tolerance, and Ru-catalyzed metathesis is
often a key step in the total synthesis of natural[4] and biologi-
cally active compounds.[5]
cyclic pentenes.[10] Bilel and co-workers examined the cross
metathesis of several terpenes[11] such as citronellal, citronellol,
and citral with methyl acrylate to form terpenoids using a Hov-
eyda catalyst.[12] The range of substrates was expanded by
Mauduit to other terpenes, which included citronellene.[13]
However, for this substrate, which is similar to myrcene, an
only moderate yield (<25%) could be realized. Quite recently,
Fomine et al. examined the metathesis of a- and b-pinene by
computational modeling.[14] Nevertheless, to the best of our
knowledge, a cross metathesis of b-myrcene has not been de-
scribed so far.
Furthermore, because of its convenient reaction regime, it is
of great importance for industrial applications, and thus indus-
trially relevant compounds can be attained easily from bulk
chemicals in a single step.[6] The production of cyclohexadece-
none by Symrise, a flavor better known as Globanone, is an ex-
ample of the successful application of metathesis.
To date, the metathesis of 1,3-dienes has been rarely report-
ed in the literature. Cossy and co-workers attained high che-
moselectivities and yields in the cross metathesis of methyl
sorbate with 1-octene using a Hoveyda catalyst.[7] Additionally,
a structurally related substrate was reacted with styrene in the
presence of the Grubbs II catalyst.[8] With the use of this cata-
lyst, the scope could be expanded to other functionalized
dienes and reactants.[9] However, all of these examples have in
common that either high catalyst loadings (up to 5 mol%) or
long reaction times were required to achieve satisfactory
yields.
The demand for an easy access to unsaturated ester deriva-
tives, which show potential features as flavors and fragran-
ces,[15] has prompted us to undertake investigations in the field
of terpene functionalization. Herein, we present a hitherto un-
known derivatization of renewable b-myrcene with methyl ac-
rylate by a cross-metathesis reaction.
Our initial studies were focused on the cross metathesis of
b-myrcene with methyl acrylate (Scheme 1). Both C11-ester 1a
and 1b, respectively, derived from the direct cross metathesis,
were not formed in the presence of all tested Ru catalysts
(Table 1).
Previously, the 1,3-diene b-myrcene (Scheme 1) has been ex-
amined exclusively in homometathesis to give functionalized
[a] Prof. Dr. A. Behr, Dr. L. Johnen, Dr. A. Wintzer, A. Gümüs¸ C¸etin, P. Neubert,
Dr. L. Domke
Instead, b-myrcene undergoes homometathesis to yield the
ring-closed product (RCP), 3-methylenecyclopent-1-ene (2),[10,16]
which is ready to react with methyl acrylate to yield the corre-
sponding cross-metathesis product, methyl 2-(cyclopent-2-en-
1-ylidene)acetate (3). Although its synthesis has already been
suggested in a Horner–Wadsworth–Emmons reaction by Shiba-
saki et al.,[17] this compound has not been described so far. It
Department of Biochemical and Chemical Engineering
Technische Universität Dortmund
Emil-Figge Strasse 66, 44227 Dortmund (Germany)
E-mail: behr@bci.tu-dortmund.de
Supporting Information and ORCID(s) from the author(s) for this article
are available on the WWW under http://dx.doi.org/10.1002/
cctc.201500993.
ChemCatChem 2016, 8, 515 – 522
515
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
Table 1. Precatalyst screening of the cross metathesis of b-myrcene and methyl acrylate at different temperatures.[a]
Entry
Precatalyst
Temperature
808C
608C
908C
X [%]
Y(2) [%]
Y(3) [%]
X [%]
Y(2) [%]
Y(3) [%]
X [%]
Y(2) [%]
Y(3) [%]
1
2
3
4
–
–
2
68
8
29
37
9
–
2
56
7
28
2
9
–
–
1
-
-
2
–
–
3
–
3
62
67
66
1
–
–
13
14
6
–
7
–
2
63
65
61
2
–
–
13
10
4
Grubbs I
Grubbs II
Neolyst M2
Neolyst M2py
Neolyst M31
Neolyst M51
98
95
82
17
21
97
94
77
55
28
5
6[b]
7[c]
8
–
3
–
17
23
[a] 0.5 mol% precatalyst, c(b-myrcene)=0.1 molLÀ1, b-myrcene/methyl acrylate=1:4, t=1 h, toluene; conversion and yields were detected by GC (Abbrevi-
ations of the precatalysts: see Figure 1). [b] Addition of 50.0 mol% PhSiCl3. [c] Addition of 0.5 mol% 0.1m HCl. Abbreviations: X=conversion, Y=yield.
possesses a characteristic odor that can be described as
“green”, “buttery”, or “plastic”.
Grubbs II catalyst. This observation was discussed previously
by Grela et al. and is attributed to an easier dissociation of the
benzylidene in Grubbs II than the indenylidene in Neolyst
M2.[19]
Among the various Ru precatalysts tested were those dem-
onstrated previously to be successful in metathesis, such as
first- and second-generation Grubbs catalysts and representa-
tives of the Neolyst family (Figure 1). The main results of the
screening of different precatalysts are presented in Table 1.
The structurally related catalyst, Neolyst M2py, which has
one chlorine and the phosphine ligand is substituted by pyri-
dine, also demonstrated a good activity for the homometathe-
sis to yield 2 in 66%, but less of product 3 was ob-
tained (entry 5). Surprisingly, a reaction performed
with Neolyst M31 resulted in low amounts of the de-
sired products at all temperatures (entry 6). Signifi-
cant differences between the conversion and yield in-
dicated polymeric side reactions, for example, the
ring-opening polymerization of cyclic diene 2. This
phenomenon was described by Sita in the polymeri-
zation of citronellene.[10a] Products derived from an
acyclic diene metathesis of the substrate were not
observed in all runs is in accordance with the results
of Fogg et al. for highly dilute solutions.[20] The results
from experiments in which Neolyst M51 was used as
the precatalyst are in line with the work of Grela
et al.,[21] as it is not thermally stable enough to per-
form ring-closing metathesis efficiently.
Figure 1. Selected Ru precatalysts for the cross metathesis of b-myrcene (Cy=cyclohexyl,
Mes=mesityl).
Encouraged by the results with Neolyst M2, differ-
ent solvents were screened. With regard to the econ-
omy and eco-friendly credentials of metathesis,
The experiments were started at 608C, and only the reaction
with the Grubbs II catalyst gave a satisfactory conversion (X) of
b-myrcene with a good yield (Y) to the cyclic homometathesis
product 2 of 56%, whereas only traces of the cyclic C7-ester 3
could be detected in the final mixture (entry 3). However, a re-
action with the structurally similar precatalyst Neolyst M2,[18]
which bears an indenylidene at the metal center instead of
benzylidene, gave the diene 2 only in poor yield (7%, entry 4).
If the reaction temperature was increased to 808C, an en-
hanced conversion was noted in all cases. Using Grubbs II and
Neolyst M2 catalysts led to similar results with almost full con-
version after 1 h and a yield of the diene 2 of 62 and 67%, re-
spectively. Fortunately, in addition to the homometathesis
product, the ester 3 could be detected in up to 14% yield. A
comparison of both runs showed that Neolyst M2 required
higher temperatures to attain a similar activity to that of the
which usually works with expensive transition-metal catalysts
synthesized in multistep reactions, the choice of the right sol-
vent is essential. In particular, a suitable solvent could facilitate
the recovery of the catalyst and would offer a better product
separation. The results for the solvent screening are shown in
Figure 2.
Among a number of solvents, the catalyst showed a compa-
rable activity and selectivity for the desired products in tolu-
ene, heptane, and 1,4-dioxane. More polar solvents such as
methyl tert-butyl ether (MTBE) and THF have worse characteris-
tics towards the reaction, and only traces of the cyclic ester
were formed. In contrast to the low-boiling-point solvents,
only propylene carbonate (PC, high boiling) has the ability to
give 2 and its consecutive product 3 in promising yields. With
regard to a beneficial product separation by distillation, this
solvent has to be considered.[22] Furthermore, no reaction took
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
516
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
Furthermore, the dependence on the amount of methyl ac-
rylate was examined in the hope to promote the reaction in
favor of either diene 2 or cyclic ester 3. The results are illustrat-
ed in Figure 4.
Figure 2. Optimization of the solvent in the cross metathesis of b-myrcene
with methyl acrylate. Conditions: 0.5 mol% Neolyst M2, c(b-myrcene)=0.1
molLÀ1, b-myrcene/methyl acrylate=1:4, T=808C or reflux, t=1 h; conver-
sions and yields were detected by GC (MTBE=methyl tert-butyl ether,
NMP=N-methyl-2-pyrrolidone, PC=propylene carbonate). Abbreviations:
X=conversion, Y=yield.
place in solvents such as dichloromethane, methanol, DMSO,
and ethylene glycol.
Figure 4. Optimization of the b-myrcene/methyl acrylate molar ratio in the
cross metathesis of b-myrcene with methyl acrylate. Conditions: 0.5 mol%
Neolyst M2, c(b-myrcene)=0.1 molLÀ1, T=808C, t=1 h, toluene; conversion
and yields were detected by GC. Abbreviations: X=conversion, Y=yield.
Our attention was then focused on the variation of the cata-
lyst loading to minimize side reactions and thus to force the
final cross metathesis to give 3 using toluene as the solvent
(Figure 3). It may be assumed that an enhanced concentration
of the active catalyst will promote the second reaction step of
the cross metathesis with methyl acrylate.
An increase of the ratio of b-myrcene to methyl acrylate
from 1:4 to 1:8 and finally to 1:16 gave an improved yield for
the consecutive product 3 of up to 20%, as expected. The use
of methyl acrylate in a great excess, such as 1:32 or even 1:64,
seems to inhibit the reaction and both the homo- and cross-
metathesis products were detected in lower amounts. At
a lower ratio of only 1:2, more diene 2 (74%) and less C7-ester
3 (5%) were formed. Consequently, if no methyl acrylate is
added to the reaction, a maximum yield of 86% of 2 was de-
tected.
Indeed, with the application of a combination of both steer-
ing effects, a catalyst concentration of 1.5 mol% and an excess
of methyl acrylate of 16:1 gave a 22% yield of the ring-closing
metathesis product and a maximum of 42% for the corre-
sponding cyclic ester 3.
With regard to the economy of this reaction, we tried to op-
timize the space time yield by increasing the substrate concen-
tration (Figure 5).
An enhanced b-myrcene concentration (up to 0.5 molLÀ1)
has no significant influence on reactivity and selectivity. How-
ever, if the reaction mixture is more concentrated, the conver-
Figure 3. Optimization of the catalyst loading in the cross metathesis of b-
myrcene with methyl acrylate. Conditions: Neolyst M2, c(b-myrcene)=0.1
molLÀ1, b-myrcene/methyl acrylate=1:4, T=808C, t=1 h, toluene; conver-
sion and yields were detected by GC. Abbreviations: X=conversion,
Y=yield.
If the concentration of the precatalyst is doubled to 1 mol%,
the detected amount of 3-methylenecyclopent-1-ene (2) in the
final mixture decreased, whereas the yield of the cyclic ester 3
increased. A further increase of the catalyst concentration to
1.5 mol% affected the homometathesis but generated the
consecutive product in up to 35% yield. Unfortunately, this
trend was not observed using 2 mol% of Neolyst M2. Indeed,
despite the full conversion, less of the ring-closing metathesis
product 2 and less of the cross-metathesis product 3 were
generated. It can be supposed that Neolyst M2 catalyzes the
ring-opening metathesis polymerization (ROMP)[23] of 2 in addi-
tion to the ring-closing metathesis of b-myrcene to give 3. If
0.25 mol% of the catalyst was employed, the conversion de-
creased, but a higher selectivity for the diene (54%) was ach-
ieved. Unfortunately, no cyclic ester could be detected.
Figure 5. Optimization of the b-myrcene concentration in the cross metathe-
sis of b-myrcene with methyl acrylate. Conditions: 0.5 mol% Neolyst M2, b-
myrcene/methyl acrylate=1:4, T=808C, t=1 h, toluene; conversion and
yields were detected by GC. Abbreviations: X=conversion, Y=yield.
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
517
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
sion and thus the yield for both products decreased. Possibly,
at higher concentrations, a catalyst deactivation occurs caused
by substrate inhibition. At a low concentration of 0.05 molLÀ1,
the yield for the homometathesis product could be slightly im-
proved (70%), but surprisingly, no ring-closed product was ob-
tained.
myrcene. Indeed, the direct cross-metathesis product is gener-
ated in all cases, however, the formation of Diels–Alder ad-
ducts (DAA) was also detected. An increase of the catalyst
loading from 0.5 to 3 mol% led to an increased conversion to
23% to give the ester 4 in a maximum 4% yield (entries 1–3).
If the excess of methyl acrylate was increased to 1:16, 14% of
the desired product could be detected (entry 4). Remarkably,
a further enhancement of the acrylate and an increased reac-
tion time (entries 5 and 6, respectively) promoted the unde-
sired Diels–Alder reaction.
These results illustrated that the reaction path of an intra-
molecular homometathesis (to give 2) is much faster than the
direct cross metathesis of b-myrcene itself (to give 1a,b). To
prevent the ring-closing reaction, the (isolated) threefold sub-
stituted double bond was functionalized so that the remaining
diene unit of the molecule can react exclusively with the reac-
tant. Therefore, myrcenol as well as its O-acetylated derivative,
myrcenyl acetate, were applied to the reaction. The latter was
synthesized by treatment of the alcohol with acetyl chloride in
the presence of pyridine. Moreover, the reaction of isomeric b-
ocimene was examined (Figure 6).
Additionally, myrcenyl acetate was used in the reaction, and
the results are given in Table 3.
Table 3. Cross metathesis of myrcenyl acetate with methyl acrylate with
Neolyst M2 in toluene.[a]
Entry
Precatalyst
[mol%]
Myrcenyl acetate/
methyl acrylate
X
[%]
Y(5)
[%]
Y(DAA)
[%]
1
2
3
0.5
0.5
1.5
1:4
1:16
1:4
30
37
29
1
4
4
1
6
2
[a] Neolyst M2, c(myrcenyl acetate)=0.1 molLÀ1, T=808C, t=3 h, tolu-
ene; conversion and yields were detected by GC. Abbreviations: X=con-
version, Y=yield.
Under the optimized reaction conditions, only traces of
product 5 were detected (entry 1). Although the catalyst load-
ing and/or amount of methyl acrylate were increased, only
a negligible yield for the cross-metathesis product was ob-
tained (entries 2 and 3). Clearly, the substituent of the sub-
strate seems to have a dramatic influence on the reaction. Pre-
vious investigations by Hoye and Zhao[10b] on linalool showed
that a nucleophilic hydroxyl group is able to coordinate to the
metal center of the catalyst by substitution of a chlorine or
phosphine to lead to an increased reaction rate. A non-nucleo-
philic acetyl function, which is present in myrcenyl acetate,
does not have these characteristics, which explains the low
conversion rates in a reaction with methyl acrylate.
Figure 6. Applied structurally related dienes for the cross metathesis with
methyl acrylate (double arrow: possible ring-closing metathesis reaction).
The first investigations were undertaken with myrcenol, and
the results of the reaction with methyl acrylate in the presence
of Neolyst M2 are shown in Table 2.
All experiments were performed with Neolyst M2 in toluene
by adapting the reaction conditions from the reaction of b-
Table 2. Cross metathesis of myrcenol with methyl acrylate with Neolyst
M2 in toluene.[a]
As b-myrcene seemed to be highly reactive in ring-closing
metathesis, the isomer b-ocimene was taken into consideration
for direct cross metathesis with methyl acrylate. A mixture of
both the cis and trans isomers (cis/trans=33:67) was first react-
ed in the presence of Neolyst M2 without any additional acry-
late to give the corresponding methyl cyclopentadiene (6;
Scheme 2). The results of the temperature dependence of the
reaction are shown in Figure 7.
Entry
Precatalyst
[mol%]
Myrcenol/
methyl acrylate
X
[%]
Y(4)
[%]
Y(DAA)
[%]
1
2
3
4
5[b]
6
0.5
1.0
3.0
3.0
3.0
3.0
1:4
1:4
1:4
1:16
1:16
1:32
5
8
23
44
72
59
1
1
4
14
11
9
1
4
3
8
15
13
In accordance with the results for the cross metathesis of b-
myrcene (see above), the highest activity for Neolyst M2 was
achieved at reaction temperatures above 808C, which yielded
up to 25% of 6. In addition, it also indicated that a ring-closing
reaction takes place for the cis rather than for the trans isomer,
which might be caused by the physical configuration/distance
between the double bonds (Scheme 3). As a result, a maximum
[a] Neolyst M2, c(myrcenol)=0.1 molLÀ1, T=808C, t=1 h, toluene; con-
version and yields were detected by GC. [b] t=8 h. Abbreviations: X=
conversion, Y=yield.
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
518
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
Table 4. Ring-closing metathesis of a cis/trans mixture of b-ocimene with
Neolyst M2 in toluene.[a]
Entry
Precatalyst
[%][mol%]
X(cis-ocimene)
[%][%]
X(trans-ocimene)
[%][%]
Y(6)
[%][%]
1
2
3
4
5
6[b]
0.1
0.3
0.5
1.0
1.5
0.5
36
62
94
99
99
98
24
27
33
49
59
70
4
13
24
25
24
4
Scheme 2. Ring-closing metathesis of a cis/trans mixture of b-ocimene.
[a] Neolyst M2, c(b-ocimene)=0.1 molLÀ1, T=808C, t=1 h, toluene; con-
versions and yield were detected by GC. [b] t=16 h. Abbreviations: X=
conversion, Y=yield.
ing was examined (Table 4). An increased amount of Neolyst
M2 caused an increased conversion of both cis- and trans-oci-
mene. Simultaneously, the yield of 6 was increased to 25%
using 1 mol% of the precatalyst (entry 4). Surprisingly, a pro-
longed reaction time improved the conversion but affected
the amount of product (4%; entry 6). This observation can be
explained by the fact that methyl cyclopentadiene might fur-
ther react in consecutive metathesis reactions (e.g., ROMP).
The special electronic situation of the double bond in b-oci-
mene (see above) allows a direct cross metathesis with methyl
acrylate to give the expected unsaturated acyclic ester 7.
Moreover, the threefold substituted double bond reacts too to
give the corresponding product 8 with the dissociation of iso-
butene. As a result of their configurations, several diastereo-
mers of 7 and 8 are possible. The results are summarized in
Table 5.
Figure 7. Optimization of the temperature in the homometathesis of b-oci-
mene. Conditions: 0.5 mol% Neolyst M2, c(b-ocimene)=0.1 molLÀ1, t=1 h,
toluene; conversions and yield were detected by GC. Abbreviations: X=con-
version, Y=yield.
of 41% conversion was achieved for the trans isomer, whereas
a conversion of more than 94% cis-ocimene was observed.
Furthermore, the conversion of b-ocimene is significantly
higher than the yield of the cyclic product. It is supposed that
this is caused by the modified 1,3-diene unit in b-ocimene: the
diene unit of b-myrcene contains two terminal double bonds.
However, in b-ocimene an internal double bond is present
next to the terminal one, which seems to affect the activity of
the entire 1,3-diene unit towards homometathesis. Finally, b-
ocimene is more able to react in an acyclic diene metathesis
(ADMET), which is in agreement with the ring-closing metathe-
sis and is one of the possible side reactions.
An increase of the reaction temperature from 60 to 908C
promoted the conversion, and a maximum yield of the acyclic
esters 7 and 8 of 10 and 18%, respectively, could be attained
(entries 1–3). If 1.5 mol% of the precatalyst was applied, the
amounts of the desired products could only be improved
slightly (entry 4).
Furthermore, the influence of an excess of methyl acrylate
was examined (Figure 8). With a b-ocimene/methyl acrylate
ratio of 1:8 and 1:16, respectively, the highest yields of both
To counteract those unintended reactions and simultaneous-
ly increase the yield of 6, the dependence of the catalyst load-
Scheme 3. Visualization of the reactivity of cis- and trans-ocimene in ring-closing metathesis.
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
519
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
Experimental Section
Table 5. Cross metathesis of
a cis/trans mixture of b-ocimene with
methyl acrylate with Neolyst M2 in toluene.[a]
Laboratory experiments
All experiments in this work were performed in an oxygen-free en-
vironment using standard Schlenk techniques. Typically, Neolyst
M2 (10.7 mg, 0.011 mmol, 1.5 mol%) and dry toluene (7.5 mL) were
placed in a 100 mL two-necked round-bottomed flask equipped
with a reflux condenser fitted with a bubble counter on top. The
mixture was then placed into an ultrasonic bath for 2 min until the
solid was dissolved completely. Subsequently, b-myrcene
(102.2 mg, 0.75 mmol, 1.0 equiv.) and methyl acrylate (1033.1 mg,
12.0 mmol, 16.0 equiv.) were added, and the flask was immersed in
a preheated oil bath at the desired temperature (e.g., 808C). After
stirring for 1 h, the reaction was stopped by cooling to RT using an
ice bath, and the mixture was analyzed by GC using di-n-butyl
ether as the internal standard and isopropanol as an additional sol-
vent.
Entry
T [8C]
X [%]
Y(6) [%]
Y(7) [%]
Y(8) [%]
1
2
3
4[b]
60
80
90
80
49
74
71
84
4
3
1
2
2
8
10
13
6
14
18
17
[a] 0.5 mol% Neolyst M2, c(b-ocimene)=0.1 molLÀ1, t=1 h, toluene; con-
version and yields were detected by GC. [b] 1.5 mol% Neolyst M2. Abbre-
viations: X=conversion, Y=yield.
Chemicals
All nonaqueous solvents used in this work were purchased dry
from Acros Organics (Geel, Belgium) with a purity of 99% or
higher. b-Myrcene was purchased from Acros Organics with
a purity of 90%. Myrcenol and a cis/trans mixture of b-ocimene
(cis/trans=33:67) were used in a purity of 98% and were donated
by Givaudan (Vernier, Switzerland). Other chemicals were pur-
chased from commercial suppliers and were of the highest purity
available. They were used as received without further purification.
The Ru precatalysts denoted as “Neolyst” were donated by Umi-
core AG & Co. KG (Hanau, Germany). The Grubbs I and II precata-
lysts were purchased from Sigma Aldrich (St. Louis, Missouri, USA).
Ar gas (99.998%) was purchased from Air Liquide Deutschland
GmbH (Düsseldorf, Germany) and was used as received.
Figure 8. Optimization of the b-ocimene/methyl acrylate molar ratio in the
cross metathesis of b-ocimene with methyl acrylate. Conditions: 0.5 mol%
Neolyst M2, c(b-ocimene)=0.1 molLÀ1, t=1 h, toluene; yields were detected
by GC. Abbreviations: X=conversion, Y=yield.
Analysis
Standard gas chromatographic analyses were performed by using
a HP 6890 instrument (Hewlett–Packard GmbH, Waldbronn, Germa-
ny) equipped with a flame ionization detector (FID, 3008C) and
a HP5 capillary column (30 m, diameter 0.32 mm, film thickness
0.25 mm) connected to an autosampler. N2 was used as the carrier
gas. The injection volume of a sample was 1 mL.
cross-metathesis products were attained. Interestingly, no
cyclic diene was produced. Moreover, an excess of 1:32 seems
to inhibit the reaction as already confirmed for the reaction of
b-myrcene (see above). A slight excess of methyl acrylate (1:2)
affects the yields of the direct cross-metathesis products but
also promotes the ring-closing reaction.
GC–MS was performed by using a Hewlett–Packard 5973 instru-
ment (70 eV).
In conclusion, we report the first access to methyl 2-(cyclo-
pent-2-en-1-ylidene)acetate from the reaction of renewable b-
myrcene with methyl acrylate. This Ru-catalyzed tandem reac-
tion consists of a ring-closing metathesis of b-myrcene and
a subsequent cross metathesis with methyl acrylate and gives
a convenient access to cyclic C7-esters. Under the optimized re-
action conditions, a temperature of 808C, a catalyst loading
(Neolyst M2) of 1.5 mol%, and a methyl acrylate ratio of 1:16,
the desired product was yielded in 42%. Further systematic ex-
aminations with other functionalized myrcene derivatives gave
a detailed insight into the reaction pattern of the terpenyl scaf-
fold. As a result of their modified structures, myrcenol and
myrcenyl acetate were able to react directly in a cross meta-
thesis with methyl acrylate to give the corresponding acyclic
esters in up to 14%. In the reaction of b-ocimene, both the
cyclic diene and acyclic esters could be achieved with yields of
25 and 18%, respectively.
All pure components were calibrated to determine the conversion
(X) of the reaction and yield (Y) of the products.
1H and 13C NMR spectra were recorded by using a Bruker DRX400
(400 MHz for 1H and 101 MHz for 13C) and a Bruker DRX500
1
(500 MHz for H and 126 MHz for 13C) at RT (Bruker Corp., Billerica,
Massachusetts, USA). All chemical shifts d are given in ppm. Cou-
pling constants are indicated as J and given in Hz. References: TMS
(d=0.00 ppm) was taken as internal standard. The chemical shift
for deuterated chloroform CDCl3 is d=7.26 ppm. Peak characteriza-
tion: s=singlet, d=doublet, dd=double doublet, t=triplet, dt=
double triplet, m=multiplet.
Product isolation and characterization
3-Methylenecyclopent-1-ene (2): The reaction mixture was puri-
fied by distillation to yield the desired product (bp=828C) accord-
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
520
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
ing to Hoye et al.[10c] 1H NMR (500 MHz, CDCl3): d=2.53 (m, 4H,
2CH2), 4.77 (s, 1H, CH2ÀHA), 4.86 (s, 1H, CH2ÀHB), 6.15 ppm (m, 2H,
CH=CH); 13C NMR (126 MHz, CDCl3): d=29.1 (CH2), 32.4 (CH2), 102.3
(=CH2), 134.6 (CH), 139.6 (CH), 155.2 ppm (C).
136 (7), 121 (12), 105 (19), 91 (52), 79 (100), 77 (32), 67 (35), 65 (17),
63 (7), 55 (33), 53 (20), 51 (16).
Acknowledgements
(E/Z)-Methyl 2-(cyclopent-2-en-1-ylidene)acetate ((E/Z)-3): The re-
action mixture was purified by column chromatography (silica
40 Š, cyclohexane/ethyl acetate 4:1) to yield the desired product
This work was financially supported by the German Research
Foundation (Deutsche Forschungsgemeinschaft DFG). The au-
thors would like to thank Umicore AG&Co. KG for the donation
of the ruthenium catalysts. We also thank Givaudan S.A. for the
donation of myrcenol and b-ocimene.
1
as a cis/trans mixture (bp=1938C). H NMR (500 MHz, CDCl3): d=
2.56 (m, 2H, CH2), 2.95 (m, 2H, CH2), 3.64 (s, 3H, OCH3), 5.55 (s, 1H,
CHCO2CH3 of the E isomer), 5.70 (s, 1H, CHCO2CH3 of the Z isomer),
6.23 (m, 1H, CH), 6.55 ppm (m, 1H, CH); 13C NMR (126 MHz, CDCl3):
d=31.3 (CH2), 34.8 (CH2), 52.3 (OCH3), 109.7 (=CH2), 136.1 (CH),
149.7 (CH), 154.4 (C), 169.6 ppm (C=O); MS (EI, 70 eV): m/z (%): 139
(7), 138 (M+, 76), 123 (14), 108 (8), 107 (96), 106 (39), 105 (24), 95
(26), 80 (8), 79 (77), 78 (48), 77 (100), 67 (20), 53 (14), 52 (14), 51
(29), 50 (18).
Keywords: alkenes · CÀC coupling · homogeneous catalysis ·
metathesis · ruthenium
[1] R. L. Banks, G. C. Bailey, Ind. Eng. Chem. Prod. Res. Dev. 1964, 3, 170–
173.
Methyl-8-hydroxy-8-methyl-4-methylennon-2-enoate (4): MS (EI,
70 eV): m/z (%): 212 (M+, 76), 194 (5), 179 (5), 165 (14), 151 (26),
135 (11), 125 (14), 119 (5), 107 (28), 95 (29), 91 (15), 79 (63), 66 (20),
63 (3), 59 (100), 55 (18).
[2] J. C. Mol, J. Mol. Catal. A 2004, 213, 39–45.
[3] a) M. Schuster, S. Blechert, Angew. Chem. Int. Ed. Engl. 1997, 36, 2036–
2056; Angew. Chem. 1997, 109, 2124–2144; b) R. H. Grubbs, S. Chang,
Tetrahedron 1998, 54, 4413–4450; c) A. Fürstner, Angew. Chem. Int. Ed.
2000, 39, 3012–3043; Angew. Chem. 2000, 112, 3140–3172; d) T. M.
Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18–29; e) R. R. Schrock,
A. H. Hoveyda, Angew. Chem. Int. Ed. 2003, 42, 4592–4633; Angew.
Chem. 2003, 115, 4740–4782; f) D. Astruc, New J. Chem. 2005, 29, 42–
56; g) A. H. Hoveyda, A. R. Zhugralin, Nature 2007, 450, 243–251;
h) C. E. Diesendruck, E. Tzur, N. G. Lemcoff, Eur. J. Inorg. Chem. 2009,
4185–4203; i) C. Deraedt, M. d’Halluin, D. Astruc, Eur. J. Inorg. Chem.
2013, 4881–4909.
[4] a) A. Fürstner, F. Jeanjean, P. Razon, Angew. Chem. Int. Ed. 2002, 41,
2097–2101; Angew. Chem. 2002, 114, 2203–2206; b) A. Fürstner, F.
Jeanjean, P. Razon, C. Wirtz, R. Mynott, Chem. Eur. J. 2003, 9, 320–326;
c) For a review article, see S. Bose, S. Ghosh, Proc. Indian Natl. Sci. Acad.
2014, 80, 37–54.
[5] a) A.-M. Faucher, M. D. Bailey, P. L. Beaulieu, C. Brochu, J.-S. Duceppe, J.-
M. Ferland, E. Ghiro, V. Gorys, T. Halmos, S. H. Kawai, M. Poirier, B. Simo-
neau, Y. S. Tsantrizos, M. Llinàs-Brunet, Org. Lett. 2004, 6, 2901–2904;
b) T. Nicola, M. Brenner, K. Donsbach, P. Kreye, Org. Process Res. Dev.
2005, 9, 513–515; c) A. Fürstner, Chem. Commun. 2011, 47, 6505–6511.
[6] a) A. Rybak, M. A. Meier, Green Chem. 2007, 9, 1356–1361; b) A. Behr, J.
PØrez Gomes, Z. Bayrak, Eur. J. Lipid Sci. Technol. 2011, 113, 189–196;
c) A. Behr, J. PØrez Gomes, Beilstein J. Org. Chem. 2011, 7, 1–8; d) A.
Behr, J. Gomes-Jelonek, H. Witte, Chem. Ing. Tech. 2012, 84, 2174–2181;
e) X. Miao, C. Fischmeister, C. Bruneau, P. H. Dixneuf, J.-L. Dubois, J.-L.
Couturier, ChemSusChem 2012, 5, 1410–1414; f) A. DupØ, M. Achard, C.
Fischmeister, C. Bruneau, ChemSusChem 2012, 5, 2249–2254; g) Y. Vysh-
navi, R. B. N. Prasad, M. S. L. Karuna, Ind. Crops Prod. 2013, 50, 701–706;
h) A. Behr, S. Toepell, S. Harmuth, RSC Adv. 2014, 4, 16320–16326; i) A.
Behr, S. Toepell, J. Am. Oil Chem. Soc. 2015, 92, 603–611; For good
review articles, see j) L. M. de Espinosa, M. A. R. Meier, Top. Organomet.
Chem. 2012, 39, 1–44; k) S. Chikkali, S. Mecking, Angew. Chem. Int. Ed.
2012, 51, 5802–5808; Angew. Chem. 2012, 124, 5902–5909.
[7] L. FerriØ, D. Amans, S. Reymond, V. Bellosta, P. Capdevielle, J. Cossy, J.
Organomet. Chem. 2006, 691, 5456–5465.
Methyl-8-acetoxy-8-methyl-4-methylennon-2-enoate (5): MS (EI,
70 eV): m/z (%): 254 (M+, 2), 194 (14), 179 (18), 165 (15), 151 (59),
135 (35), 125 (18), 119 (26), 107 (30), 95 (47), 79 (100), 69 (27), 59
(56), 55 (35), 52 (10).
2-Methyl-cyclopenta-1,3-diene (6): A typical experiment was per-
formed in dichloromethane at 808C for 18 h. The mixture was
cooled to RT, concentrated in vacuo, and purified by Kugelrohr dis-
tillation to yield the desired product as a colorless oil according to
Korenevskii and Sergeyev[24] and Nicole et al.[25] 1H NMR (500 MHz,
4
4
CDCl3): d=2.02 (dt, JHÀH =1.9 Hz, JHÀH =1.5 Hz, 3H, CH3), 2.95 (m,
2H, CH2), 6.00 (m, 1H, CH), 6.41 ppm (m, 2H, CH=CH); 13C NMR
(126 MHz, CDCl3): d=15.2 (CH3), 41.4 (CH2), 126.8 (CH), 133.7 (CH=
CH), 135.8 (CH=CH), 142.2 ppm (C).
Methyl 4,8-dimethylnona-2,4,7-trienoate (7): MS (EI, 70 eV): m/z
(%): 194 (M+, 4), 179 (18), 147 (13), 135 (29), 125 (54), 119 (61), 112
(41), 105 (39), 91 (100), 77 (63), 69 (19), 65 (31), 59 (24), 53 (39).
Methyl 6-methylocta-2,5,7-trienoate (8): MS (EI, 70 eV): m/z (%):
166 (M+, 3), 135 (2), 107 (4), 103 (1), 91 (12), 87 (3), 80 (100), 79
(42), 77 (10), 65 (6), 59 (2), 55 (12), 51 (5).
2-Methyl-6-methyleneoct-7-en-2-ylacetate (myrcenyl acetate):
Myrcenol (1.00 g, 6.48 mmol, 1.0 equiv.) was dissolved in dichloro-
methane (25 mL), and pyridine (2.05 g, 25.92 mmol, 4.0 equiv.) was
added. The mixture was cooled to 08C, and acetyl chloride (1.53 g,
19.44 mmol, 3.0 equiv.) was added dropwise. The solution was
stirred at RT for 2 h before it was concentrated in vacuo, and the
residue was purified by column chromatography (silica 40 Š, cyclo-
hexane/ethyl acetate 8:1) to yield the desired product (0.71 g,
[8] T. W. Funk, J. Efskind, R. H. Grubbs, Org. Lett. 2005, 7, 187–190.
[9] G. Moura-Letts, D. P. Curran, Org. Lett. 2007, 9, 5–8.
[10] a) L. R. Sita, Macromolecules 1995, 28, 656–657; b) T. R. Hoye, H. Zhao,
Org. Lett. 1999, 1, 1123–1125; c) S. Kobayashi, C. Lu, T. R. Hoye, M. A.
Hillmyer, J. Am. Chem. Soc. 2009, 131, 7960–7961.
[11] For further metathesis reactions of various terpenes, see a) R. T. Mathers,
K. C. McMahon, K. Damodaran, C. J. Retarides, D. J. Kelley, Macromole-
cules 2006, 39, 8982–8986; b) R. T. Mathers, K. Damodaran, M. G.
Rendos, M. S. Lavrich, Macromolecules 2009, 42, 1512–1518; c) A. Martí-
nez, S. GutiØrrez, M. A. Tlenkopatchev, Molecules 2012, 17, 6001–6010;
d) E. Grau, S. Mecking, Green Chem. 2013, 15, 1112.
1
71%). H NMR (400 MHz, CDCl3): d=1.42 (s, 6H, 3CH3), 1.51 (m, 2H,
3
CH2), 1.77 (m, 2H, CH2), 1.96 (s, 3H, C(=O)CH3), 2.20 (t, JHÀH
=
7.6 Hz, 2H, CCH2CH2), 4.99 (s, 1H, C(=CH2ÀHA)), 5.02 (s, 1H, C(=
3
CH2ÀHB)), 5.06 (d, JHÀH =17.6 Hz, 1H, CH=CH2ÀHA)), 5.21 (d,
A
3
3JHÀH =10.9 Hz, 1H, CH=CH2ÀHB)), 6.37 ppm (dd, JHÀH =17.6 Hz,
B
A
3JHÀH =10.8 Hz, 1H, CH=CH2); 13C NMR (101 MHz, CDCl3): d=22.5
B
(CH2), 22.6 (CH3), 22.6 (2C, C(CH3)2), 31.6 (CH2), 40.7 (CH2), 82.4
(C(CH3)2), 113.3 (CH=CH2), 115.9 (C=CH2), 138.9 (CH), 146.2 (C=CH2),
154.4 (C), 170.6 ppm (C=O); MS (EI, 70 eV): m/z (%): 196 (M+, 4),
[12] H. Bilel, N. Hamdi, F. Zagrouba, C. Fischmeister, C. Bruneau, Green Chem.
2011, 13, 1448–1452.
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
521
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
´
´
[13] E. BorrØ, T. H. Dinh, F. Caijo, C. CrØvisy, M. Mauduit, Synthesis 2011, 13,
2125–2130.
[21] a) M. Bieniek, C. Samojłowicz, V. Sashuk, R. Bujok, P. Sledz, N. Lugan, G.
Lavigne, D. Arlt, K. Grela, Organometallics 2011, 30, 4144–4158; b) S.
Guidone, E. Blondiaux, C. Samojłowicz, Ł. Gułajski, M. Ke˛dziorek, M. Ma-
[14] a) S. Fomine, M. A. Tlenkopatchev, J. Organomet. Chem. 2012, 701, 68–
74; b) A. Acevedo, S. Fomine, S. GutiØrrez, M. A. Tlenkopatchev, J. Orga-
nomet. Chem. 2014, 765, 17–22.
´
´
linska, A. Pazio, K. Wozniak, K. Grela, A. Doppiu, C. S. J. Cazina, Adv.
Synth. Catal. 2012, 354, 2734–2742.
[22] For more details, see the Supporting Information.
[23] a) J.-L. HØrisson, Y. Chauvin, Makromol. Chem. 1970, 141, 161–176;
b) R. H. Grubbs, W. Tumas, Science 1989, 243, 907–915; c) S. Sutthasupa,
M. Shiotsuki, F. Sanda, Polym. J. 2010, 42, 905–915.
[24] V. A. Korenevskii, N. M. Sergeyev, J. Am. Chem. Soc. 1972, 94, 8586–
8587.
[15] a) A. Goeke, K. Berg-Schulz, J. Bajgrowicz, WO 0216307, 2002; b) D. J.
Rowe, Chemistry and Technology of Flavours and Fragrances, Wiley-
Blackwell, Bodmin, 2009.
[16] D. Yamamoto, A. Matsumoto, Macromolecules 2013, 46, 9526–9536.
[17] T. Arai, H. Sasai, K. Yamaguchi, M. Shibasaki, J. Am. Chem. Soc. 1998,
120, 441–442.
[25] T. Laurens, D. Nicole, P. Rubini, J. C. Lauer, M. Matlengiewicz, N. Henzel,
Magn. Reson. Chem. 1991, 29, 1119–1129.
[18] F. Boeda, H. Clavier, S. P. Nolan, Chem. Commun. 2008, 2726–2740.
´
[19] R. Gawin, A. Makal, K. Wozniak, M. Mauduit, K. Grela, Angew. Chem. Int.
Ed. 2007, 46, 7206–7209; Angew. Chem. 2007, 119, 7344–7347.
[20] J. C. Conrad, M. D. Eelman, J. A. Duarte Silva, S. Monfette, H. H. Parnas,
J. L. Snelgrove, D. E. Fogg, J. Am. Chem. Soc. 2007, 129, 1024–1025.
Received: September 8, 2015
Published online on December 8, 2015
ChemCatChem 2016, 8, 515 – 522
www.chemcatchem.org
522
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim