A ruthenium-based catalytic system with switchable selectivity between cyclotrimerization and enyne metathesis/Diels-Alder reactions of terminal alkynes

Article abstract of DOI:10.1016/j.catcom.2013.06.023

In this study, we report a practical catalytic system, [RuCl ₂(p-cymene)]₂/IPr (IPr: 1,3-bis(2,6 diisopropylphenyl) imidazol-2-ylidene), that can switch between cyclotrimerization and cross enyne metathesis. The cyclotrimerization reaction of phenylacetylene catalyzed by [RuCl₂(p-cymene)]₂ can be switched to enyne metathesis by the introduction of a sterically hindered N-heterocyclic carbene. The 1,3-diene formed during this reaction reacts with dienophiles to form the Diels-Alder adduct. A practical one-pot synthesis method, utilizing enyne metathesis/Diels-Alder reactions, was used to construct cyclic compounds in an efficient manner.

Full text of DOI:10.1016/j.catcom.2013.06.023

Catalysis Communications 41 (2013) 12–16
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
A ruthenium-based catalytic system with switchable selectivity
between cyclotrimerization and enyne metathesis/Diels–Alder
☆
reactions of terminal alkynes
⁎
Solmaz Karabulut , Begüm Sariaslan, Bengi Özgün Öztürk
Hacettepe University, Department of Chemistry, 06800, Beytepe-Ankara, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
In this study, we report a practical catalytic system, [RuCl2(p-cymene)]2/IPr (IPr: 1,3-bis(2,6 diisopropylphenyl)
imidazol-2-ylidene), that can switch between cyclotrimerization and cross enyne metathesis. The
cyclotrimerization reaction of phenylacetylene catalyzed by [RuCl2(p-cymene)]2 can be switched to enyne me-
tathesis by the introduction of a sterically hindered N-heterocyclic carbene. The 1,3-diene formed during this re-
action reacts with dienophiles to form the Diels–Alder adduct. A practical one-pot synthesis method, utilizing
enyne metathesis/Diels–Alder reactions, was used to construct cyclic compounds in an efficient manner.
© 2013 The Authors. Published by Elsevier B.V. All rights reserved.
Received 19 March 2013
Received in revised form 14 June 2013
Accepted 14 June 2013
Available online 27 June 2013
Keywords:
Enyne metathesis
Diels–Alder reactions
One-pot synthesis
Switchable catalysis
1. Introduction
al. reported a novel method that utilizes ring closing metathesis
of 1,7-octadiene as an in situ source of ethylene in tandem enyne
Olefin metathesis is a useful synthetic tool for the creation of
carbon–carbon bonds [1]. Numerous applications of metathesis
have been developed to construct a wide variety of organic materials
containing double bonds [2]. Among these applications, enyne me-
tathesis is a unique approach that results in different functionality
in the product compared to other metathesis reactions [3,4]. The
first enyne metathesis reaction that reorganized an alkene and alkyne
to produce 1,3-diene was reported in 1985 [5]. Later, the beneficial ef-
fect of ethylene in enyne metathesis was reported by Mori et al. [6,7].
This progress in enyne metathesis has resulted in novel approaches in
metathesis chemistry, such as a tandem enyne metathesis/Diels–Alder
reaction [8,9]. Using this approach, polycyclic compounds with high
molecular complexity were synthesized in an efficient and selective
manner [10,11]. Consequently, there is a continuing interest in the
production of active metathesis catalysts via practical and simplified
routes as exemplified by the in situ generation of catalytic ruthenium
species [12–14]. In this context, imidazolium salts are employed as the
carbene source along with [RuCl2(p-cymene)]2 to produce an in situ
ruthenium arene system that is an efficient catalyst for the tandem
enyne metathesis/Diels–Alder reactions [15,16]. Recently, Fustero et
metathesis/Diels–Alder reactions [17]. A switchable catalytic system
based on exchange of the active sites of the Grubbs second generation
catalyst was reported to promote two distinct annulation reactions to
construct two different tetrasubstituted benzene derivatives via enyne
metathesis or oxidative cyclometallation [18].
In the course of our continuing studies on the development of
ruthenium-based switchable catalytic systems [19], we discovered that
cyclotrimerization of phenylacetylene catalyzed by [RuCl2(p-cymene)]2
can be switched to enyne metathesis by the introduction of the bulky
IPr ligand under an ethylene atmosphere. In this contribution, we report
a switchable catalytic system that can switch from cyclotrimerization to
enyne metathesis/Diels–Alder reaction of terminal alkynes.
2. Experimental
All manipulations were carried out under an atmosphere of nitrogen
using Schlenk techniques. 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-
2H-imidazol-2-ylidene (IPr) were purchased from Sigma–Aldrich and
used as received. [RuCl2(=CHPh)(IPr)(PCy3)] [20], [(p-cymene)
Ru(Cl)(μ-Cl)2Ru(Cl)(=CHPh)(IPr)] [21], and [RuCl2(IPr)(p-cymene)]
[22] were synthesized according to literature procedures.
☆
This is an open-access article distributed under the terms of the Creative Commons
2.1. Instrumentation
Attribution-NonCommercial-No Derivative Works License, which permits non-commercial
use, distribution, and reproduction in any medium, provided the original author and source
are credited.
1H NMR spectra were recorded at 25 °C with a Bruker GmbH
400 MHz FT-NMR spectrometer. Tetramethylsilane was used as the ref-
erence for 1H and 13C NMR. GC-MS analyses were performed with a
⁎
Corresponding author. Tel.: +90 3122976082.
E-mail address: solmazk@hacettepe.edu.tr (S. Karabulut).
1566-7367/$ – see front matter © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.06.023

S. Karabulut et al. / Catalysis Communications 41 (2013) 12–16
13
Shimadzu GC-MS QP5050A using an Optima column, 5–1.0 μm (50 m ×
0.32 mm) at a temperature range of 50–320 °C (10 °C/min).
an ethylene atmosphere (1 atm). Aliquots taken periodically from the
reaction mixture were analyzed by GC-MS.
2.2. Tandem enyne metathesis/Diels–Alder reactions of arylalkynes
3. Results & discussion
A reactor was charged with [RuCl2(p-cymene)]2 (0.033 mmol),
IPr, (0.066 mmol), and alkyne (0.66 mmol) in 3 ml of toluene and
heated to 80 °C under an ethylene atmosphere (1 atm) for 1 h.
After complete conversion to the 1,3-diene product was observed,
dienophile (0.154 mmol) was added under a nitrogen atmosphere,
and the reaction was stirred at 80 °C for 8 h. The reaction mixture
was analyzed by GC-MS. The solvents were evaporated under re-
duced pressure, and the crude product mixture was purified by col-
umn chromatography, resulting product was analyzed by 1H and
13C NMR analysis.
In this study, we evaluate [RuCl2(p-cymene)]2/IPr as a catalytic sys-
tem to switch selectivity between cyclotrimerization reactions and
enyne metathesis. [RuCl2(p-cymene)]2 catalyzes the cyclotrimerization
reaction of phenylacetylene, which proceeds through the forma-
tion of a ruthenocyclopentadiene intermediate. After introduc-
tion of N-heterocyclic carbene (NHC) ligands in an ethylene
atmosphere, this catalytic intermediate forms
a ruthenium
methylidene species, which catalyzes the enyne metathesis of
phenylacetylene with ethylene to selectively form a 1,3-diene
(Scheme 1).
Our first attempts to obtain a switchable catalytic system were
based on the introduction of phenylacetylene and PCy3 to a solution
of [RuCl2(p-cymene)]2. We envisioned the formation of a vinylidene
intermediate that is converted to a ruthenium methylidene species
in the presence of excess ethylene. For this purpose, several catalytic
systems were tested in the enyne metathesis/Diels–Alder reaction of
phenylacetylene with varying ligand (PCy3 or IPr)/Ru ratios under
an atmosphere of ethylene (Table 1).
2.3. General procedure for the in situ switching between cyclotrimerization
and enyne metathesis reactions
A reactor was charged with [RuCl2(p-cymene)]2 (0.033 mmol,
0.020 g) and phenylacetylene (0.66 mmol, 72 μl) in 3 ml toluene and
heated at 80 °C. After 10 min, 2.0 mol equivalent of IPr (0.066 mmol,
0.026 g) was added to the reaction medium and stirred at 80 °C under
Scheme 1. Ruthenium-catalyzed enyne metathesis/Diels–Alder reactions of aromatic alkynes.

14
S. Karabulut et al. / Catalysis Communications 41 (2013) 12–16
Table 1
Enyne metathesis/Diels–Alders reactions of phenylacetyene.
Productb
Runa
%
Alkyne
Ligand
Ligand/Ru
Time
(h)
Dimerization
(4a-e: 5a-e: 6a-e)
Cyclotrimerization
(7a: 8a)
Diene
(2a-e)
Diels–Alder adductc
(3a-e)
1
2
3
5
6
7
8
9
1a
1a
1a
1a
1a
1b
1c
1d
1e
PCy3
PCy3
IPr
IPr
IPr
IPr
IPr
IPr
IPr
2
4
2
8
10
2
2
2
2
24
24
1
1
1
1
1
1
1
35 (6: 94: 0)
43 (7: 90: 3)
2 (17: 83: 0)
3 (14: 85: 1)
3 (14: 85: 1)
5(19: 81: 0)
0
65(80: 20)
57(79: 19)
3(80: 20)
5(80: 20)
5(80: 20)
5(90: 10)
20 (81: 19)
4(87: 13)
10(84: 16)
–
–
–
–
93
80
76
90
80
90
79
80 (75)
70
70
85 (80)
75 (72)
81 (78)
66 (62)
4 (13: 87: 0)
0
10
a: All reactions were carried out in the presence 4% [RuCl2(p-cymene)]2 (0.033 mmol) with phenylacetylene (0.66 mmol) and varying IPr-PCy3/Ru (mol/mol) ratios in 3 ml of tol-
uene at 80 °C under an ethylene atmosphere (1 atm).
b: Determined by GC-MS
c: The mixture was reacted for 8 h after the addition of dimethylacetylenedicarboxylate (0.77 mmol) at 80 °C. Isolated yields are in parenthesis.
Phenylacetylene was reacted in the presence of 4% [RuCl2(p-
cymene)]2 in toluene at 80 °C under ethylene atmosphere with 4:1 or
2:1 PCy3/Ru ratios. The reactions were monitored by GC-MS analysis.
After 24 h, a significant amount of cyclotrimerization products, 65%
(7a:8a; 80:20), and dimerization products, 35% (4a:5a:6a; 6:94:0),
were observed with a 2:1 PCy3/Ru ratio. Increasing the PCy3/Ru ratio
Table 2
Enyne metathesis/Diels–Alder reaction of phenylacetylene with various dienophiles.
Runa
1
Alkyne
Dienophile
Productb,c ( %)
1a
1b
1c
3a 80 (75)
3b 85 (80)
3c 75 (72)
2
3
4
5
1d
1e
3d 81 (78)
3e 66 (62)
3a-e
6
7
1f
3f 83 (79)
3g 70 (66)
1g
a: All reactions were carried out in the presence 4% [RuCl2(p-cymene)]2 (0.033 mmol) with phenylacetylene (0.66 mmol) and IPr (0.066 mmol) in 3 ml of toluene at 80 °C under an
ethylene atmosphere (1 atm).
b: Determined by GC-MS. Isolated yields are in parenthesis.
c: The mixture was reacted for 8 h after the addition of dienophile (0.77 mmol) at 80 °C.

S. Karabulut et al. / Catalysis Communications 41 (2013) 12–16
15
Table 3
optimum IPr/Ru ratio was 2:1. Methyl and methoxy substituted aro-
matic alkynes, 1b–e, were tested under same reaction conditions
and results were listed on Table 1. 4-methyl (1b) and 4-methoxy
(1d) substituted phenylacetylenes show high selectivity towards
enyne metathesis reactions and gave corresponding Diels–Alder ad-
ducts 3b (85%) and 3d (81%). On the other hand, 2-methyl (1c) and
2-methoxy (1e) substituted phenylacetylenes show relatively poor
selectivity towards enyne metathesis reaction and gave Diels–Alder
adducts, 3c (75%) and 3e (66%) in moderate yields. 4-octyne and
1-octyne were tested under the same reaction conditions. Although
the catalytic system worked efficiently for arylacetylenes, all attempts
to produce 1,3-dienes from 1-octyne and 4-octyne failed. Only a 2–3%
of diene product was observed for 1-octyne and 4-octyne. To expand
the scope of the process, different dienophiles were reacted with 2a
and results were given in Table 2. Maleic anhydride and N-phenyl
maleimide gave Diels–Alder adducts in 83% (3f) and 70% (3 g) yields
under pre-determined reaction conditions.
To expand the scope of this study, the activity of [RuCl2(p-
cymene)]2/IPr was compared to that of other types of ruthenium cata-
lysts for the enyne metathesis reaction between phenylacetylene and
ethylene. For this purpose, several different classes of ruthenium cata-
lysts bearing IPr ligands were synthesized and their activity was tested
in tandem enyne metathesis/Diels–Alder reactions of phenylacetylene
(Table 3). For this purpose, a reactor was charged with the correspond-
ing ruthenium complexes (8% for Ru-I and II and 4% for Ru-III and IV)
and phenylacetylene in toluene and reacted under a slow stream of eth-
ylene at 80 °C for 2 h. Ru-I catalyzed the enyne metathesis reaction to
provide a 95% yield of 2a. Ru-II, a well-known ruthenium alkylidene
complex, catalyzed this reaction to give a 99% yield, whereas Ru-III,
the homobimetallic analog of Ru-II, provided a 96% yield. Our catalytic
system, Ru-IV, displayed comparable activity (93% yield) to the Ru-I,
II and III catalytic systems.
Tandem enyne metathesis/Diels–Alder reactions of phenylacetylene with various ru-
thenium catalysts.
Runa
Catalyst
Diene (2a) Diels-Alder Adduct
(3a) % b
b
%
1
95
83
2
3
99
96
90
88
4
93
80
a: All reactions were carried out in the presence of 8% [Ru-I] or [Ru-II] (0.066 mmol) or
4% [Ru-III] or [Ru-IV] (0.033 mmol) with phenylacetylene (0.66 mmol) in 3 ml of
toluene at 80 °C under an ethylene atmosphere (1 atm) and reacted for 2 h.
b: GC yield
After all of the reaction parameters were determined, the
switching ability of the catalytic system was investigated in detail.
First, phenylacetylene was allowed to react in the presence of 4%
[RuCl2(p-cymene)]2 in toluene at 80 °C under a nitrogen atmosphere
to form the cyclotrimerization products 7a and 8a; then, IPr ligand
was added at different time intervals to switch the reaction to
enyne metathesis under an atmosphere of ethylene. The results are
listed in Table 3. When phenylacetylene was reacted for 5 min in
the presence of only [RuCl2(p-cymene)]2, the cyclotrimerization
product was formed in 3% (7a:8a; 90:10) yield. The addition of
2.0 mol equivalent of IPr ligand after 5 min shifted the product for-
mation towards 2a to give a 90% yield after 2 h; the amount of
cyclotrimerization product increased to 6% (7a:8a; 84:16). In addi-
tion, trace amounts of the dimerization product (2%) were also ob-
served in the GC-MS analysis. The IPr ligand was introduced into
the reaction medium at different time intervals to prove that our cat-
alytic system can be switched in situ from the cyclotrimerization
to 4:
1 didn’t have a beneficial effect on the reaction; only
cyclotrimerization (57%) and dimerization (43%) product distributions
were changed.
These observations indicated the need for ligands that are better σ
donors and sterically more hindered then PCy3 to stabilize the
14-electron ruthenium methylidene species. In this context, IPr, a
bulky NHC ligand was the best candidate with these characteristics.
Upon the addition of 2.0 equivalents of IPr relative to [RuCl2(p-
cymene)]2 and phenylacetylene in toluene at 80 °C, the product
distribution dramatically changed to provide a 93% yield of 2a. In-
creasing the IPr/Ru ratio to 4:1, 8:1 and 10:1 decreased the amount
of 2a to 89%, 80% and 76%, respectively. Upon the addition of 3 mole
equivalents of dimethylacetylenedicarboxylate, the corresponding
Diels–Alder adduct 3a was formed in 80% and 77% yield at the 2:1
and 4:1 IPr:Ru ratios, respectively, after 8 h at 80 °C. Thus, the
Table 4
In situ switchable selectivity of the [RuCl2(p-cymene)]2/IPr catalytic system between cyclotrimerization and enyne metathesis.
Before addition of IPr After addition of IPr
Runa
Timeb
(min.)
Dimer %c
(4a: 5a: 6a)
Cyclo %c
(7a: 8a)
Diene %c
Timed
(h)
Dimer %c
Diene %c
–
(4a: 5a: 6a)
(7a: 8a)
1
2
3
4
5
5
3 (90: 10)
6 (91: 9)
10 (89:11)
14 (90:10)
65 (90:10)
–
–
–
–
–
2
2
2
2
2
2
2
3
3
4
6 (84:16)
90
88
85
80
27
10
15
20
60
10 (83: 17)
12 (88:12)
17 (90: 10)
69 (90:10)
1
a: All reactions were carried out in the presence 4% [RuCl2(p-cymene)]2 (0.033 mmol) with phenylacetylene (72 μl, 0.66 mmol) in 3 ml of toluene at 80 °C under a nitrogen
atmosphere. IPr (0.026 g, 0.066 mmol) was added indicated times under an ethylene atmosphere (1 atm) to switch the reaction to enyne metathesis.
b: Represents the addition time of IPr
c: Determined by GC-MS
d: Represents the time when maximum conversion values were observed

16
S. Karabulut et al. / Catalysis Communications 41 (2013) 12–16
Cyclotrimerization of phenylacetylene
reaction of phenylacetylene to the enyne metathesis at any time
during the cyclotrimerization reaction of phenylacetylene (Table 4).
As expected, runs 1–4 are in sharp contrast with each other. When
phenylacetylene was reacted for 20 min in the presence of 4%
[RuCl2(p-cymene)]2, the cyclotrimerization product was observed in
14% (7a:8a; 90:10) yield. On addition of IPr under an ethylene atmo-
sphere, 2a formed in 88% yield after 2 h. A remarkable change in the
isomer distribution of cyclotrimerization products was observed after
addition of IPr to the reaction medium. This change can be clearly
seen in run 1 and run 4. In run 1, phenylacetylene was reacted for
5 min before the introduction of IPr. At the early stages of the reac-
tion, [RuCl2(p-cymene)]2 is responsible for the cyclotrimerization re-
action via the formation of ruthenocyclopentadiene intermediates.
Upon addition of IPr to the reaction medium, [RuCl2IPr(p-cymene)]
forms as an intermediate, and at this stage, two complexes,
[RuCl2(p-cymene)]2 and [RuCl2IPr(p-cymene)] are responsible for
the cyclotrimerization reaction of phenylacetylene. However, the lat-
ter complex is less selective for the cyclotrimerization reaction and is
responsible for the change in the isomer distribution.
100
90
80
70
60
50
40
30
20
10
0
Nitrogen atmosphere
Ethylene atmosphere
-10
40
90
140
190
240
Time (min.)
Graphic 1. Cyclotrimerization reaction of phenylacetylene under nitrogen and ethylene
atmosphere.
As a final remark, the effect of ethylene on cyclotrimerization reac-
tion rate was investigated in details with 4% [RuCl2(p-cymene)]2 in
toluene at 80 °C (Graphic 1). While cyclotrimerization products
formed in 65% yield (7a + 8a) in 1 h under nitrogen atmosphere,
this value was decreased to 44% under ethylene atmosphere. It is
clear that ethylene slows down the cyclotrimerization reaction and
these results were in great coherence with the given data in Table 3.
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All experimental details and spectroscopic data can found in
supporting information file. Supplementary data to this article can
be found online at http://dx.doi.org/10.1016/j.catcom.2013.06.023.