Activity of homobimetallic ruthenium alkylidene complexes on intermolecular [2+2+2] cyclotrimerisation reactions of terminal alkynes

Article abstract of DOI:10.1016/j.ica.2011.09.023

The activity of homobimetallic ruthenium alkylidene complexes, [(p-cymene)Ru(Cl)(μ-Cl)₂Ru(Cl)(CHPh)(PCy₃)] [Ru-I] and [(p-cymene)Ru(Cl)(μ-Cl)₂Ru(Cl)(CHPh)(IPr)] [Ru-II], on intermolecular [2+2+2] cyclotrimerisation reactio

Full text of DOI:10.1016/j.ica.2011.09.023

Inorganica Chimica Acta 378 (2011) 257–263
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Activity of homobimetallic ruthenium alkylidene complexes on intermolecular
[2+2+2] cyclotrimerisation reactions of terminal alkynes
⇑
_
Bengi Özgün Öztürk, Solmaz Karabulut , Yavuz Imamog˘lu
Department of Chemistry, Hacettepe University, 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:
Received 15 April 2011
Received in revised form 22 August 2011
Accepted 10 September 2011
Available online 17 September 2011
The activity of homobimetallic ruthenium alkylidene complexes, [(p-cymene)Ru(Cl)(l-Cl)2Ru(Cl)
(@CHPh)(PCy3)] [Ru-I] and [(p-cymene)Ru(Cl)(l-Cl)2Ru(Cl)(@CHPh)(IPr)] [Ru-II], on intermolecular
[2+2+2] cyclotrimerisation reactions of monoynes has been investigated for the first time. It was found
that these complexes can catalyse the chemo and regioselective cyclotrimerisation reactions of alkynes
at both 25 and 50 °C in polar, aprotic solvents. The catalytic activity of [Ru-I] and [Ru-II] was compared
to other well-known ruthenium catalysts such as Grubbs first generation catalyst [RuCl2(@CHPh)(PCy3)2]
Keywords:
[Ru-III], [RuCl(l-Cl)(p-cymene)]2 [Ru-IV] and [RuCl2(p-cymene)PCy3] [Ru-V] complexes. To examine the
Ruthenium
Cyclotrimerisation
Alkynes
Silicon
Arene ligands
effect of the steric hinderance of substrates on the regioselectivity of the reaction, a series of sterically
hindered silicon containing alkynes (1a, 1b, 1c) were used. It was shown that the isomeric product dis-
tribution of the reaction shifts from 1,2,4-trisubstituted arenes to 1,3,5-trisubstituted arenes as the steric
hinderance on the substrates increases. These homobimetallic ruthenium alkylidene complexes also cat-
alysed regio- and chemo-selective cross-cyclotrimerisation reactions between silicon-containing alkynes
(1a, 1b, 1c) and aliphatic alkynes (1d–g).
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
Ruthenium catalysts such as [RuCl(cod)Cp] [17], are widely used
in the cyclotrimerisation reactions of alkynes as well as the
Compared to conventional strategies, such as electrophilic aro-
matic substitutions or orthometalation techniques [1], the transi-
tion metal catalysed [2+2+2] cyclotrimerisation of alkynes is
considerably advantageous in the synthesis of highly substituted
benzene derivatives due to its atom-economical and convergent
nature [2,3]. Cyclotrimerisation of alkynes is catalysed using a vari-
ety of transition metal catalysts including: Co, Fe, Ni, Pd, Re, Rh, Ru
and Ta [4–10]. Among them, CpCo complexes (Cp: cyclopentadi-
enyl), such as CpCo(CO)2, have been widely used in the pharmaceu-
tical industry, in the preparation of natural products and in the
preparation of functionalised materials [11]. Ni(acac)2/PPh3 [14]
and the Wilkinson catalyst, RhCl2(PPh3)3 [15], have also been used
to catalyse cyclotrimerisation reactions of alkynes. To control the
chemo- and regioselectivity of cyclotrimerisation reactions, a stoi-
[2+2+2] cycloaddition of 1,6-diynes with nitriles, isocyanates and
isothiocyanates to afford pyridines, bicyclic pyridones and thio-
pyridones at good yields [18]. The [RuCl(cod)Cp] catalyst has been
successfully applied to achieve the chemoselective [2+2+2] cyclo-
addition of three different alkynes, through the control of the mo-
lar ratio of the substrates [19]. Lin et al. reported the activity of an
air stable Ru(II) perchloro-cyclobutenonyl complex towards
[2+2+2] cyclotrimerisation reactions [20]. Recently, a homobime-
tallic ruthenium complex, [{Ru(g l-Cl)Cl}2], was shown
3-C10H16)(
to catalyse the cyclotrimerisation reactions of alkynes in aqueous
media [21]. Although, there are several reports on the catalytic
activity of ruthenium complexes towards inter- and intra-cyclotri-
merisation reactions of alkynes, there are few examples using
ruthenium alkylidene complexes to mediate [2+2+2] the cycload-
dition of alkynes in an intra- or intermolecular fashion. Blechert re-
ported, for the first time that Grubbs first generation catalyst can
catalyse the intramolecular [2+2+2] cyclotrimerisation reactions
of triynes at good yields [22]. Roy and Das prepared carbohydrate
derivatives with Grubbs first generation catalyst utilising the inter-
molecular cyclotrimerisation reactions [23]. Additionally, this cat-
alyst was used for cross-cyclotrimerisation of diynes with alkynes
[15], for solid-supported cyclotrimerisation reactions [24] and for
the synthesis of indacenes [25]. More recently, Castells reported
that second generation Grubbs and Hoveyda–Grubbs complexes
chiometric approach was used, which utilised (g
2-propene)Ti(O-i-
Pr)2 [12], and ZrCp2(C4Et4) [13]. A binary metallic system of nickel
and zinc phenoxide was reported by Odashima and co-workers
[16] as a high chemo and regioselective approach to intermolecular
cyclotrimerisation reactions for two different monoynes. Zhou and
colleagues reported an efficient binary metallic system of
Y[N(TMS)2]3/FeCl3 for the cyclotrimerisation of terminal alkynes.
⇑
Corresponding author. Tel.: +90 3122976082; fax: +90 3122992163.
E-mail address: solmazk@hacettepe.edu.tr (S. Karabulut).
0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2011.09.023

258
B.Özgün Öztürk et al. / Inorganica Chimica Acta 378 (2011) 257–263
are efficient catalysts for the cross [2+2+2] cyclotrimerisation of
diynes with alkynes and demonstrated that the process was still
selective when applied to non-symmetric diynes [26].
To date, no examples of intermolecular cyclotrimerisation reac-
tions of monoynes catalysed using homobimetallic ruthenium
alkylidene complexes have been reported. In this study, we report
the activity of homobimetallic ruthenium alkylidene complexes
(Scheme 1) on the intermolecular [2+2+2] cyclotrimerisation
reactions of monoynes and the chemo- and regio-selective cross-
intermolecular cyclotrimerisation reactions of two different
alkynes.
2.3. Procedure for intermolecular [2+2+2] cyclotrimerisation reactions
of silicon containing terminal alkynes
2.3.1. Representative procedure for the preparation of 1,3,5-
tris((trimethylsilyloxy)methyl)benzene (2a) and 1,2,4-
tris((trimethylsilyloxy)methyl)benzene (3a)
A reactor was charged with [Ru-II] (0.030 mmol) and 1a
(0.75 mmol) in 1 ml of dry THF under a nitrogen atmosphere.
The reaction mixture was stirred at 50 °C for 15 h. Aliquots taken
periodically from the reaction mixture were analysed by GC–MS.
The solvent was evaporated and crude product mixture was passed
through a plug of silica gel to remove catalytic impurities. The final
product was a mixture of 1,3,5-trisubstitued (2a) and 1,2,4-trisub-
stitued (3a) arene isomers (Scheme 2). The mixtures were analysed
by 1H and 13C NMR.
2. Experimental
2.1. Materials
All manipulations were carried out under an inert atmosphere of
nitrogen using Schlenk techniques. 3-Trimethylsiloxy-1-propyne
(1a), 3-(trimethylsilyloxy)-1-butyne (1b), [(1,1-dimethyl-2-propy-
nyl)-oxy]trimethylsilane (1c), 1-heptyne (1d), 1-octyne (1e),
1-dodecyne (1f) and 1-tetradecyne (1g) were purchased from Sig-
ma–Aldrich and used as received. Grubbs first generation catalyst
[RuCl2(@CHPh)(PCy3)2] [Ru-III] and [RuCl2(p-cymene)]2 [Ru-IV]
were purchased from Sigma–Aldrich and used as received, [(p-cym-
2.3.2. 1,3,5-tris((Trimethylsilyloxy)methyl)benzene (2a)
1H NMR (CDCl3; ppm): 7.32 (s, 3H), 4.73 (s, 6H), 0.12 (s, 27H).
13C NMR (CDCl3; ppm): 141.67, 123.30, 68.10, 0.41, MS [EI 70 eV]
m/z 384 [M+].
2.3.3. 1,2,4-tris((Trimethylsilyloxy)methyl)benzene (3a)
1H NMR (CDCl3; ppm): 7.28 (s, 1H), 7.20 (d, J = 7.40 Hz, 1H), 7.10
(d, J = 7.40 Hz, 1H), 4.75 (s, 2H), 4.70 (s, 2H), 4.51 (d, J = 6.5 Hz, 2H),
0.14 (s, 9H), 0.12 (s, 18H). 13C NMR (CDCl3; ppm): 140.0, 138.10,
136.72, 127.34, 125.90, 125.40, 65.10, 63.20, 62.0, 1.93, MS [EI
70 eV] m/z 384 [M+].
ene)Ru(Cl)(l-Cl)2Ru(Cl)(@CHPh)(PCy3)] [Ru-I] [(p-cymene)Ru(Cl)
(l-Cl)2Ru(Cl)(@CHPh)(IPr)] [Ru-II] (IPr: 1,3-bis(2,6-diisopropyl-
phenyl)-imidazoline) and [RuCl2(p-cymene)PCy3] [Ru-V] were syn-
thesised according to the literature [27,28]. Toluene, THF,
dichloromethane and acetone were purchased from Sigma–Aldrich
and distilled under Na/benzophenone, P2O5 and CaCl2, respectively
and stored under an inert atmosphere of nitrogen.
2.3.4. 1,3,5-tris(1-(Trimethylsilyloxy)ethyl)benzene (2b)
1H NMR (CDCl3; ppm): 7.29 (s, 3H), 4.50 (q, 3H), 1.50 (d,
J = 6.8 Hz, 9H), 0.12 (s, 27 H). 13C NMR (CDCl3; ppm): 145.0,
121.0, 72.10, 25.20, 1.93. MS [EI 70 eV] m/z 426 [M+].
2.2. Instrumentation
1H and 13C NMR spectra were recorded at 25 °C with a Bruker
GmbH 400 MHz high performance digital FT NMR spectrometer
using CDCl3 as a solvent. Tetramethylsilane was used for the 1H
and 13C NMR reference. GC–MS analyses were performed with a
2.3.5. 1,2,4-tris(1-(Trimethylsilyloxy)ethyl)benzene (3b)
1H NMR (CDCl3; ppm): 7.25 (s, 1H), 7.21 (d, J = 7.44 Hz, 1H), 7.05
(d, J = 7.44 Hz, 1H), 4.51(q, 1H), 4.40 (q, 2H), 4.30 (m, 2H), 0.14 (s,
9H), 0.12 (s, 18H). 13C NMR (CDCl3; ppm): 143.0, 140.20, 137.55,
126.0, 122.85, 122.30, 69.84, 68.30, 68.14, 23.40, 23.06, 1.93. MS
[EI 70 eV] m/z 426 [M+].
Shimadzu GC–MS QP5050A using an Optima column, 5–1.0 lm
(50 m  0.32 mm) and a temperature range of 50–300 °C (10 °C/
min). The carrier gas was helium with a flow rate of 1 mL/min.
IPr
PCy3
Cl
PCy3
Ru
Cl
Cl
Cl
Ph
Ph
Ph
Cl
Cl
Ru
Cl
Ru
Ru
Ru
Cl
Cl
Cl
PCy3
[Ru-III]
[Ru-II]
[Ru-I]
Cl
Cl
Cl
Cl
Cl
Ru
Cl
Ru
Ru
PCy3
[Ru-V]
[Ru-IV]
IPr:1,3-bis(2,6-diisopropylphenyl)-imidazoline
Scheme 1. Various ruthenium complexes, which were used in intermolecular [2+2+2] cyclotrimerisation reactions of monoynes.

B.Özgün Öztürk et al. / Inorganica Chimica Acta 378 (2011) 257–263
259
Si(CH3)3
Si(CH3)3
O
Si(CH3)3
O
O
4mol%Ru
RT,15h,THF
O
Si
O
Si(CH3)3
O
O
(H3C)3Si
Si(CH3)3
2a
1a
3a
Scheme 2. Representative cyclotrimerisation reaction of 1a.
2.3.6. 1,3,5-tris(2-(Trimethylsilyloxy)propan-2-yl)benzene (2c)
1H NMR (CDCl3; ppm): 7.20 (s, 1H), 1.45 (s, 18H), 0.12 (s, 27H).
13C NMR (CDCl3; ppm): 148.40, 123.0, 76.64, 30.10, 1.94. MS [EI
70 eV] m/z 468 [M+].
2.4.5. 1,3-bis(trimethylosiloxyl methyl)-4-heptyl-benzene (3e)
1H NMR (CDCl3; ppm): 7.23 (d, J = 7.70 Hz, 1H), 7.19 (s, 1H), 6.94
(d, J = 7.71 Hz, 1H), 4.59(d, 2H), 4.40 (d, J = 6.42 Hz, 2H), 2.69
(m,2H), 1.58 (m, 2H), 1.33–1.25 (m, 6H), 0.89 (t, 3H), 0.14 (s, 9H),
0.12 (s, 9H). 13C NMR (CDCl3; ppm): 141.66, 139.95, 137.14,
128.96, 127.30, 127.11, 64.21, 62.55, 33.66, 31.30, 30.92, 29.42,
22.62, 14.09, 1.93. MS [EI 70 eV] m/z 366 [M+].
2.3.7. 1,2,4-tris(2-(Trimethylsilyloxy)propan-2-yl)benzene (3c)
This compound could only be detected by GC–MS. Amount of
the isomer was too low to detect by 13C and 1H NMR. MS [EI
70 eV] m/z 468 [M+].
2.4.6. 1,2-bis(Trimethylosiloxyl methyl)-4-decyl-benzene (2f)
This compound could only be detected by GC–MS. Amount of
the isomer was too low to detect by 13C and 1H NMR. MS [EI
70 eV] m/z 422 [M+].
2.4. Procedure for intermolecular [2+2+2] cross-cyclotrimerisation
reactions of alkyne 1a with 1-heptyne (1d), 1-octyne (1e), 1-dodecyne
(1f) and 1-tetradecyne (1g)
2.4.1. Representative procedure for the preparation of 1,2-bis(trimeth
ylosiloxyl methyl)-4-heptyl-benzene (2e) and 1,3-bis(trimethylosil
oxylmethyl)-4-heptyl-benzene (3e)
2.4.7. 1,3-bis(Trimethylosiloxyl methyl)-4-decyl-benzene (3f)
1H NMR (CDCl3; ppm): 7.24 (d, J = 7.68 Hz, 1H), 7.18 (s, 1H),
6.93 (d, J = 7.67 Hz, 1H), 4.60(d, 2H), 4.40 (d, J = 6.40 Hz, 2H), 2.70
(m, 2H), 1.58 (m, 2H), 1.42–1.22 (m, 15H), 0.89 (t, 3H), 0.14 (s,
9H), 0.12 (s, 9H). 13C NMR (CDCl3; ppm): 142.0, 140.61, 137.63,
129.05, 127.72, 127.88, 64.25, 62.59, 33.70, 31.30, 30.92, 29.42,
29.10, 29.0, 28.75, 23.40, 22.62, 14.09, 1.93. MS [EI 70 eV] m/z
422 [M+].
To a mixture of [Ru-IV] (0.039 mmol) and 1a (1.625 mmol) in
1.5 ml dry THF, 450
lL of a THF solution of 1-octyne (0.325 mmol)
was added in nine aliquots of 50
lL over a period of 30 min. The
reaction mixture was stirred for 48 h at 50 °C. Aliquots were taken
periodically from the reaction mixture and analysed by GC–MS.
The solvent was evaporated and the crude product mixture was
passed through a plug of silica gel to remove catalytic impurities.
The mixture was then analysed by 1H and 13C NMR. The final prod-
uct was determined to be a mixture of 2e, 3e and 2a.
2.4.8. 1,2-bis(Trimethylosiloxyl methyl)-4-dodecyl-benzene (2g)
This compound could only be detected by GC–MS. Amount of
the isomer was too low to detect by 13C and 1H NMR. MS [EI
70 eV] m/z 450 [M+].
2.4.2. 1,2-bis(Trimethylosiloxyl methyl)-4-pentyl-benzene (2d)
1H NMR (CDCl3; ppm): 7.26 (s, 1H), 7.16 (d, J = 7.55 Hz, 1H),
7.12 (d, J = 7.55 Hz, 1H), 4.62 (s, 2H), 4.48 (d, J = 6.40 Hz, 2H),
2.67 (m, 2H), 1.58 (m, 2H), 1.34–1.25 (m, 4H), 0.89 (t, 3H), 0.14
(s, 9H), 0.12 (s, 9H). 13C NMR (CDCl3; ppm): 141.0, 137.0, 133.2,
129.84, 125.87, 125.49, 64.21, 62.55, 33.63, 31.31, 29.35, 22.57,
14.10, 1.94. MS [EI 70 eV] m/z 352 [M+].
2.4.9. 1,3-bis(Trimethylosiloxyl methyl)-4-dodecyl-benzene (3g)
1H NMR (CDCl3; ppm): 7.24 (d, J = 7.66 Hz, 1H), 7.18 (s, 1H),
6.94 (d, J = 7.66 Hz, 1H), 4.61 (d, 2H), 4.39 (d, J = 6.45 Hz, 2H),
2.70 (m, 2H), 1.58 (m, 2H), 1.42–1.20 (m, 19H), 0.89 (t, 3H), 0.14
(s, 9H), 0.12 (s, 9H). 13C NMR (CDCl3; ppm): 142.1, 140.65,
137.69, 129.15, 127.80, 127.80, 64.24, 62.57, 33.70, 31.30, 30.92,
29.80 29.42, 29.30, 29.10, 29.0, 28.75, 23.40, 22.62, 14.09, 1.93.
MS [EI 70 eV] m/z 450 [M+].
2.4.3. 1,3-bis(Trimethylosiloxyl methyl)-4-pentyl-benzene (3d)
1H NMR (CDCl3; ppm): 7.22 (d, J = 7.81 Hz, 1H), 7.19 (s, 1H),
6.94 (d, J = 7.84 Hz, 1H), 4.59 (d, 2H), 4.40 (d, J = 6.50 Hz, 2H),
2.69 (m, 2H), 1.58 (m, 2H), 1.33–1.25 (m, 4H), 0.89 (t, 3H), 0.14
(s, 9H), 0.12 (s, 9H). 13C NMR (CDCl3; ppm): 141.54, 139.70,
137.10, 129.10, 127.30, 127.21, 64.24, 62.45, 33.67, 31.32, 29.40,
22.59, 14.11, 1.93. MS [EI 70 eV] m/z 352 [M+].
3. Results and discussion
In this study, several ruthenium complexes (Scheme 1), Grubbs
first generation catalysts [Ru-III], [(p-cymene)Ru(Cl)(
l-Cl)2
2.4.4. 1,2 -bis (trimethylosiloxyl methyl) -4-heptyl-benzene (2e)
1H NMR (CDCl3; ppm): 7.25 (s, 1H), 7.16 (d, J = 7.51 Hz, 1H), 7.10
(d, J = 7.51 Hz, 1H), 4.62 (s, 2H), 4.48 (d, J = 6.40 Hz, 2H), 2.69
(m, 2H), 1.58 (m, 2H), 1.33–1.25 (m, 6H), 0.89 (t, 3H), 0.14
(s, 9H), 0.12 (s, 9H). 13C NMR (CDCl3; ppm): 141.3, 137.2, 133.1,
129.85, 125.90, 125.49, 64.21, 62.55, 33.66, 31.30, 30.92, 29.42,
22.62, 14.09, 1.93. MS [EI 70 eV] m/z 366 [M+].
Ru(Cl)(@CHPh)(PCy3)] [Ru-I], ([(p-cymene)(Cl)Ru( -Cl)2Ru(Cl)
l
(IPr)-(CHPh) [Ru-III], [(p-cymene)RuCl2]2 [Ru-IV] and [(p-cyme-
ne)RuCl2PCy3] [Ru-V] were tested onintermolecularcyclotrimerisa-
tion reactions of terminal alkynes. The activity of homobimetallic
ruthenium complexes [Ru-II] and [Ru-III] towards cyclotrimerisa-
tion reactions of monoynes were compared to other well-known
ruthenium complexes, such as [Ru-I] and [Ru-IV].

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B.Özgün Öztürk et al. / Inorganica Chimica Acta 378 (2011) 257–263
3.1. Intermolecular [2+2+2] cyclotrimerisation reactions of silicon
containing alkynes
catalyst was not used in any further studies because of its low cat-
alytic activity and regioselectivity towards intermolecular cyclotri-
merisation reactions of 1a. The catalytic activity difference
between [Ru]-I, II, III and [Ru]-IV, V can possibly be explained
by the presence of the alkylidene group on [Ru-I], [Ru-II] and [
Ru-III]. It has been reported in literature that ruthenium arene
fragments are capable of forming mono or bis-alkylidene com-
plexes in polar solvents at relatively high temperatures [29]. Con-
sidering this fact, it is possible that at room temperature the
metathetic cascade route, compared to the metallacycle pathway,
would be the predominant reaction pathway for the ruthenium
alkylidene complexes.
The second tests were carried out at 50 °C. The activity of
[Ru-III] stayed nearly the same, but regioselectivity of the reaction
decreased from (2a:3a) 16:84 to 25:75. When catalysed by [Ru-I]
and [Ru-II], the cyclotrimerisation reaction of 1a proceeded with
95% (2a:3a; 21:79) and 98% (2a:3a; 21:79) yields of the trisubsti-
tuted arene isomers 2a:3a, respectively. The reaction carried out
with [Ru-IV] at 50 °C yielded 100% (2a:3a; 20:80) within 4 h. The
homobimetallic alkylidene complexes [Ru-I] and [Ru-II] and
monometallic alkylidene complexes [Ru-III] can catalyse the inter-
molecular cyclotrimerisation reactions at room temperature with
high regioselectivity. However at 50 °C, a slight decrease in regi-
oselectivity, but an increment in yield was observed.
Next, a study was performed to determine the effect of the sub-
strate on the cyclotrimerisation reactions. For this purpose a set of
three silicon containing alkynes, 1a, 1b and 1c were selected and
their effect on the reaction yield and regioselectivity was investi-
gated (Table 2). Alkyne 1b, a more sterically hindered alkyne than
1a, was reacted with 4% mol catalysts in THF at room temperature.
The best conversion value of 53% ( 2b:3b; 76:24) was obtained
using [Ru-II]. The [Ru-IV] catalysed reaction showed the best reg-
ioselectivity with a relatively lower yield of both 2b and 3b, (32%
2b:3b; 80:20) at room temperature. At 50 °C, the [Ru-II] catalysed
cyclotrimerisation reaction was completed within 22 h with a
small increase in yield (65%;2b:3b; 76:24). Under these conditions,
[Ru-IV] demonstrated the best results for both regioselectivity
(2b:3b; 84:16) and yield (70%). Next, alkyne 1c was reacted with
various ruthenium catalysts under pre-determined reaction condi-
tions. None of our Ru-complexes catalysed this reaction at room
temperature. However at 50 °C, [Ru-I], [Ru-II] and [Ru-IV] yielded
corresponding arenes 2c and 3c with 20% (2c:3c; 80:20), 30% (
2c:3c; 90:10) and 24% (2c:3c; 83:17) yields, respectively.
Considering these results, the regioselectivity of the reaction
shifts from a 1,2,4-(3a–c) to a 1,3,5-(2a–c) trisubstituted arene iso-
mer formation based on the increasing steric hinderance of the
substrate. The reaction of 1b and 1c demonstrated that the meta-
thetic cascade route produces the less hindered corresponding are-
nes 2b and 2c as the major products. Additionally, traces of
dimerisation and acyclic trimerisation products were observed by
GC–MS during the cyclotrimerisation reactions of 1b and 1c with
our catalytic system. Comparing these observed manifolds, we
can conclude that the steric effect of the substrate has a direct ef-
fect on product distribution and yield.
To optimise the reaction conditions, alkyne 1a was reacted with
[Ru-II] and [Ru-IV] under a variety of reaction conditions (Scheme
2). The first tests were carried out in THF with 4% mol of [Ru-II] at
room temperature. The reaction was monitored by GC–MS by tak-
ing aliquots from the reaction mixture. After no improvement in
yield was observed, the solvent was evaporated and the organic
products were purified by passing the reaction mixture through a
silica column using ethyl acetate as the eluent. The resulting prod-
uct mixture was found to be an isomeric mixture of 1,2,4- and
1,3,5-substituted benzene derivatives confirmed by both GC–MS
and NMR analyses.
Using the [Ru-II] catalyst, the reaction proceeded smoothly and
within 15 h, a yield of 94% (2a:3a; 20:80) cyclotrimerisation prod-
ucts, 2a and 3a, was achieved. Using the [Ru-IV] catalyst only 43%
yield was obtained, (2a:3a; 19:81) and the [Ru-V] catalyst yielded
30% (2a:3a; 35:65). To increase the yields using the [Ru-IV] and [
Ru-V] catalysts, the respective reaction mixtures were heated. At
50 °C, a sharp increase in the activity of the reaction mixture con-
taining [Ru-IV] was observed. Compound 1a was completely trans-
formed into 2a and 3a with a 4% catalytic loading of [Ru-IV] in THF.
[Ru-IV] demonstrated the best catalytic performance at 50 °C, with
a yield of 100% of the cyclotrimerisation product within 4 h. No
improvement in the yield was obtained when the reaction was car-
ried out at higher temperatures, such as 60, 70 and 80 °C.
Toluene, dichloromethane, acetone and THF were tested to
determine the best reaction solvent and the results are listed on
Table 1. Among these solvents, toluene gave relatively poor results,
considering both the time and regioselectivity of the reaction.
Homobimetallic complexes are also sparingly soluble in toluene.
The use of polar solvents demonstrated slightly better perfor-
mances. The results on Table 1 indicate that acetone and THF are
comparable solvents when considering regioselectivity and yield
values. However, in addition to higher regioselectivity, THF dem-
onstrated slightly better catalytic activity compared to the other
solvents. It was observed that the reaction times for the cyclotri-
merisation of 1a could be reduced from 72 to 15 h with a slight in-
crease in yield and regioselectivity when using THF as the solvent.
After the best reaction conditions were determined, the cata-
lytic activity of [Ru-I], [Ru-II], [Ru-III], [Ru-IV] and [Ru-V] were
tested on the intermolecular [2+2+2] cyclotrimerisation reactions
of the silicon containing substrate 1a. The results are summarised
on Table 2. First, the tests were carried out at room temperature
with a catalytic loading of 4% mol catalyst in THF using 1a as the
substrate. Grubbs first generation catalyst [Ru-III], which is a
well-known alkylidene complex, was used to catalyse this reaction.
The reaction was completed within 15 h with a yield of 90% (2a:3a;
16:84). Homobimetallic ruthenium alkylidene complexes [Ru-I]
and [Ru-II] gave a yield of 94% (2a:3a; 20:80) and 92% (2a:3a;
18:82), respectively. [Ru-IV] and [Ru-V] demonstrated poor cata-
lytic activity at room temperature where yields of only 43%
(2a:3a; 19:81) and 23% (2a:3a; 40:60), respectively, were achieved.
No improvement in yield was observed after 20 h. The [Ru-V]
3.2. Intermolecular [2+2+2] cross cyclotrimerisation reactions of two
alkynes
Table 1
Solvent effect on cyclotrimerisation reactions of terminal alkynes.
To obtain chemo- and regioselective cross-cyclotrimerisation
products, 1a was reacted with various alkynes. To date, a few suc-
cessful strategies have been employed to overcome the poor che-
mo- and regio-selectivity of intermolecular cyclotrimerisation
reactions between two or three alkynes. Odashima and co-workers
employed a binary metal system to obtain a chemoselective
process for the intermolecular cross-cyclotrimerisation reactions
between two or three alkynes with the slow addition of one of
Solvent
Yielda (%)
Time (h)
Isomer ratio (2a:3a)
Toluene
Dichloromethane
Acetone
80
90
93
94
72
24
18
15
28:72
23:77
20:80
20:80
THF
a
0.030 mmol [Ru-I] was added to a 1 ml THF solution of alkyne 1a (0.724 mmol)
at room temperature. The reaction mixture was periodically analysed by GC–MS.

B.Özgün Öztürk et al. / Inorganica Chimica Acta 378 (2011) 257–263
261
Table 2
Cyclotrimerisation reactions of alkynes 1a, 1b and 1c with various ruthenium catalysts.
Alkyne
Temperature (°C)
Catalyst
Time (h)
Yielda(%)
Products
R
R
R
R
R
R
2a-c
3a-c
25
50
[Ru-I]
15
15
15
15
20
12
10
8
94
92
90
43
30
90
95
98
100
20
18
16
19
35
25
21
21
20
80
82
84
81
65
75
79
79
80
[Ru-II]
[Ru-III]
[Ru-IV]
[Ru-V]
[Ru-I]
[Ru-II]
[Ru-III]
[Ru-IV]
Si
O
(1a)
4
25
50
[Ru-I]
15
15
15
15
28
20
22
24
45
53
42
32
50
55
65
70
77
76
74
80
76
78
76
84
23
24
26
20
24
22
24
16
[Ru-II]
[Ru-III]
[Ru-IV]
[Ru-I]
[Ru-II]
[Ru-III]
[Ru-IV]
Si
O
(1b)
25
50
[Ru-I]
48
48
48
48
72
72
72
72
0
0
0
0
6
20
30
24
0
0
0
0
0
0
[Ru-II]
[Ru-III]
[Ru-IV]
[Ru-I]
[Ru-II]
[Ru-III]
[Ru-IV]
Si
O
0
0
59
80
90
83
41
20
10
17
(1c)
a
0.030 mmol [Ru] was added to a 1 ml THF solution of alkyne 1a–c (0.724 mmol). The reaction mixture was periodically analysed by GC–MS.
the alkynes to the reaction medium. An intramolecular version of
this process has been successfully employed using a diyne and ex-
cess of an alkyne.
To determine the best reaction conditions for the cross-cyclotri-
merisation of monoynes, 1a and 1d (1-heptyne) were reacted with
Ru catalysis under various reaction conditions to achieve a high
chemo- and regioselective process. The effect of the 1a/1d–g ratio
on chemoselectivity of the reaction was initially investigated. One
molar equivalent of alkyne 1a was reacted with 1 M equivalent of
1d in THF at room temperature using a 4% mol of [Ru-II]. After
72 h, GC–MS analysis revealed that only trace amounts of the
cyclotrimerisation products were formed under these conditions.
+
R2
R1
R1:CH2OSi(CH3)3
(1 equivalent)
R2:C5H9
(5 equivalent)
4
m o l % [ R u - I I ]
R1
R1
R1
R2
R2
R2
R1
R2
R1
R1
R2
R2
R2
+
+
+
+
+
R2
+
R2
R1
R1
R2
R2
R1
3a
5
3d
6
7
4d-g
2d
Scheme 3. Representative cross-cyclotrimerisation reactions of excess 1d (5 mol equivalent) and 1a (1 mol equivalent).

262
B.Özgün Öztürk et al. / Inorganica Chimica Acta 378 (2011) 257–263
R1
R1
R1
R1
R2
R1
4 mol%Ru
+
R1
(5 equivalent)
+
R2
+
THF,50o C,48h
(1 equivalent)
R1
R1
R2
R2: C5H9
C6H11
(1d)
(1e)
R1:CH2OSi(CH3)3
2a
2d-g
1a
C10H19 (1f )
3d-g
C12H23
(1g)
Scheme 4. Representative cross-cyclotrimerisation reactions of excess 1a (5 mol equivalent) and 1d–g (1 mol equivalent).
The reaction was also carried out at 50 °C and resulted in no cross-
cyclotrimerisation products; however, 2a, 3a and 4d were formed.
When a mixture of a mol equivalent of 1a and a 5 mol equivalent of
1d were reacted under the same conditions, chemoselectivity of
the reaction was completely lost, resulting in a mixture of trisub-
stituted arenes (Scheme 3). The products of the reaction between
1a and 1d in a 1:5 ratio demonstrated that the homodimerisation
of 1d and the homo cyclotrimerisation of 1a and 1d are the major
competitive reactions. The preceding experiments revealed that an
excess amount of alkyne 1d–g present in the reaction media has a
negative impact on the regio- and chemoselectivity of the cross-
cyclotrimerisation reaction.
1a and 1d was catalysed by [Ru-III] under the optimum reaction
conditions resulting in a 28% yield of 2d and 3d (2d:3d; 88:12).
A sharp increase to a 75% yield of in 2d and 3d (2d:3d; 86:14)
was observed when [Ru-I], the homobimetallic analog of [Ru-III],
was employed as a catalyst. Another slight increase in yield (77%,
2d:3d; 87:13) was observed when [Ru-II] was employed as a cat-
alyst. However, among these catalysts, [Ru-IV] demonstrated the
best catalytic activity towards cross cyclotrimerisation reactions.
The [Ru-IV] catalysed reactions provided a high yield of 2d and
3d (81%, 2d:3d; 81:19).
3.3. Activity of ruthenium complexes
The slow addition of 1d to the reaction media may offer a pos-
sible solution to the chemoselectivity problem. To demonstrate
this, 1d was added slowly to a solution containing a 5 mol equiva-
lent of 1a (1a:1d; 5:1) and [Ru-II] (4% mol). The mixture was then
stirred at 50 °C for 48 h (Scheme 4). GC–MS analysis revealed a
mixture of the regioisomeric cycloadducts 2d and 3d, which were
formed by the chemoselective coupling of two molecules of 1a and
one molecule of 1d (77% yield; 2d:3d; 87:13).
After the best reaction conditions were determined, the cata-
lytic activity of [Ru-I], [Ru-II], [Ru-III] and [Ru-IV] were tested
on cross-intermolecular cyclotrimerisation reactions of 1a and
1d–g (Table 3). [Ru-III], a monometallic ruthenium alkylidene
complex, demonstrated poor catalytic activity on the cross-cyclo-
trimerisation reactions that take places between 1a and the ali-
phatic alkynes 1d–g, which follow a metathetic cascade route. [
Ru-I], which is a homobimetallic analog of [Ru-III] that combines
a ruthenium-arene fragment bridged by chlorine atoms, revealed
relatively high activity for regio- and chemoselective cross-cyclo-
trimerisation reactions of two different alkynes. The reaction of
[Ru-I], which consists of two ruthenium fragments, can be syn-
thesised by reacting [Ru-III] and [Ru-IV] in dichloromethane at
room temperature for 2 h. In our study, we demonstrated that both
[Ru-III] and [Ru-IV] can be used to catalyse the intermolecular
cyclotrimerisation reactions of 1a in quantitative yields. Although
no mechanistic studies have been performed, it is possible that
the mechanism for this intermolecular cyclotrimerisation reactions
may be originating from both metathesis cascade route and metal-
lacycle route considering the nature of the homobimetallic cata-
lysts. Additionally, it has been reported in literature that the
reactions catalysed with [Ru-III] follows a metathetic cascade
route which is favourable at both 25 °C and higher temperatures
[23,15]. Similar studies have reported that ruthenium arene com-
plexes such as [Ru-IV] catalyse the cyclotrimerisation reactions
of alkynes following a metallacycle route [18,21,22]. It has been re-
ported in literature that ruthenium arene fragments can also form
bis-alkylidene complexes which are active as expected [29]. There-
fore, Ru-arene fragment of [Ru-I], [Ru-II] and [Ru-IV] may react
Table 3
Cross-cyclotrimerisation reactions of 1a and 1d–g with various ruthenium catalysts.
R1
R2
R1/R2
Yielda,b (%)
Catalyst
Product (%)
2d–g
3d–g
4
5
6
7c
8
10
75
77
28
81
61
63
22
65
25
27
11
30
25
27
8
[Ru-I]
86
87
88
81
90
90
92
88
89
89
90
88
88
88
90
89
14
13
12
19
10
10
8
12
11
11
10
12
12
12
10
11
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
30
30
32
33
32
25
33
25
34
30
32
30
39
40
36
40
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
O
O
O
O
Si(CH3)3
Si(CH3)3
Si(CH3)3
Si(CH3)3
C5H11
[Ru-II]
[Ru-III]
[Ru-IV]
[Ru-I]
[Ru-II]
[Ru-III]
[Ru-IV]
[Ru-I]
[Ru-II]
[Ru-III]
[Ru-IV]
[Ru-I]
[Ru-II]
[Ru-III]
[Ru-IV]
(1d)
10
10
10
C6H13
(1e)
C10H22
(1f)
C12H26
(1g)
28
a
b
c
Yield was based on aliphatic alkynes (1d–g).
0.030 mmol [Ru] was added to a 1 ml THF solution of alkyne 1a–c (0.724 mmol) and stirred for 48 h at 50 °C. The reaction mixture was periodically analysed by GC–MS.
Yield was based on 1a.

B.Özgün Öztürk et al. / Inorganica Chimica Acta 378 (2011) 257–263
263
[4] (a) A. Goswami, T. Ito, S. Okamoto, Adv. Synth. Catal. 349 (2007) 2368;
with a terminal alkyne in highly polar solvents at relatively high
temperatures to form an active bis-alkylidene complex. Thus mak-
ing two mechanisms, metathesis cascade and metallacycle route
are difficult to distinguish from each other at 50 °C.
The comparable high activity of [Ru-III] with our homobimetal-
lic ruthenium systems [Ru-I], [Ru-II] and [Ru-IV] towards the
cyclotrimerisation reaction of 1a indicated that this reaction pro-
ceeded through both a metathetic cascade, considering the rela-
(b) G. Hilt, W. Hess, T. Vogler, C. Hengst, J. Organomet. Chem. 690 (2005) 5170;
(c) M. Lautens, W. Klute, W. Tam, Chem. Rev. 96 (1996) 49;
(d) K. Peter, C. Vollhardt, Angew. Chem., Int. Ed. 23 (1984) 539;
(e) L.V.R. Bonaga, H.C. Zhang, A.F. Moretto, H. Ye, D.A. Gauthier, J. Li, G.C. Leo,
B.E. Maryanoff, J. Am. Chem. Soc. 127 (2005) 3473.
[5] (a) K. Tanaka, K. Shirasaka, Org. Lett. 5 (2003) 4697;
(b) K. Tanaka, K. Toyoda, A. Wada, K. Shirasaka, M. Hirano, Chem. Eur. J. 11
(2005) 1145;
(c) R. Grigg, R. Scott, P. Stevenson, Tetrahedron Lett. 23 (1982) 2691.
[6] C. Breschi, L. Piparo, P. Pertici, A.M. Caporusso, G. Vitulli, J. Organomet. Chem.
607 (2000) 57.
tively similar activity of [Ru-III], [Ru-I] and [Ru-II] and
a
metallacycle route [Ru-IV]. Combining these manifolds observa-
tions, we can conclude that it is possible for two ruthenium centres
(ruthenium alkylidene and the ruthenium arene [Ru-I] and [Ru-II])
to be active towards cyclotrimerisation reactions.
[7] N. Saino, D. Kogure, S. Okamoto, Org. Lett. 7 (2005) 3065.
[8] (a) S. Saito, T. Kawasaki, N. Tsuboya, Y. Yamamoto, J. Org. Chem. 66 (2001) 796;
(b) Y. Sato, T. Nishimata, M. Mori, J. Org. Chem. 59 (1994) 6133.
[9] (a) P.M. Maitles, Acc. Chem. Res. 9 (1976) 93;
(b) B.M. Trost, G.J. Tanoury, J. Am. Chem. Soc. 109 (1987) 4753.
[10] J.R. Strickler, M.A. Bruck, D.E. Wigley, J. Am. Chem. Soc. 112 (1990) 2814.
[11] (a) J.A. Teske, A. Deiters, J. Org. Chem. 73 (2008) 342;
(b) S.J. Neeson, P.J. Stevenson, Tetrahedron 45 (1989) 6239;
(c) E.A. Anderson, E.J. Alexanian, E.J. Sorensen, Angew. Chem., Int. Ed. 43 (2004)
1998;
4. Conclusion
In conclusion, we have shown that homobimetallic ruthenium
alkylidene complexes [Ru-I] and [Ru-II] are efficient catalysts for
the transformation of alkynes to substituted arenes by chemo-
and regio-selective intermolecular-[2+2+2] cyclotrimerisation
reactions. These ruthenium complexes promote the catalytic cyclo-
trimerisation of less sterically hindered alkynes in a selective man-
ner with 1,2,4-trisubstituted arenes. Conversely, the processes
favours the formation of 1,3,5-trisubstituted arenes with sterically
hindered alkynes. The catalytic systems were also capable of form-
ing substituted arenes through the cross-intermolecular cyclotri-
merisation of two monoynes. Considering the nature of the
homobimetallic alkylidene complexes, it is possible that these
transformations can follow both cascade metathetic and metalla-
cycle routes depending upon the reaction conditions.
(d) C.A. Chang, C.G. Francisco, T.R. Gadek, J.J.A. King, E.D. Sternberg, K.P.C.
Vollhardt, in: B.M. Trost, C.R. Hutchinson (Eds.), Organic Synthesis Today and
Tomorrow, Pergamon Press, Oxford, 1981. p. 71;
(e) K.P.C. Vollhardt, Pure Appl. Chem. 57 (1985) 1819;
(f) K.P.C. Vollhardt, Pure Appl. Chem. 65 (1993) 153;
(g) C. Eickmeier, D. Holmes, H. Junga, A.J. Matzger, F. Scherhag, M. Shim, K.P.C.
Vollhardt, Angew. Chem., Int. Ed. 38 (1999) 800;
(h) C. Aubert, O. Buisine, M. Petit, F. Slowinski, M. Malacria, Pure Appl. Chem.
71 (1999) 1463;
(i) F. Slowinski, C. Aubert, M. Malacria, J. Org. Chem. 68 (2003) 378.
[12] D. Suzuki, H. Urabe, F. Sato, J. Am. Chem. Soc. 123 (2001) 7925.
[13] T. Takahashi, Z. Xi, A. Yamazaki, Y. Liu, K. Nakajima, M. Kotora, J. Mol. Catal. A:
Chem. 239 (2005) 166.
[14] Y. Sato, K. Ohashi, M. Mori, Tetrahedron Lett. 40 (1999) 5231.
[15] B. Witulski, T. Stengel, J.M. Fernández-Hernández, Chem. Commun. (2000)
1965.
[16] N. Mori, S. Ikeda, K. Odashima, Chem. Commun. (2001) 181.
[17] (a) Y. Yamamoto, T. Arakawa, R. Ogawa, K. Itoh, J. Am. Chem. Soc. 125 (2003)
12143;
(b) Y. Yamamoto, K. Hata, T. Arakawa, K. Itoh, Chem. Commun. (2003) 1290–
1291;
Acknowledgments
Y. Yamamoto, J. Ishii, H. Nishiyama, K. Itoh, J. Am. Chem. Soc. 126 (2004)
3712.
[18] (a) Y. Yamamoto, R. Ogawa, K. Itoh, J. Am. Chem. Soc. 123 (2001) 6189;
(b) Y. Yamamoto, H. Takagishi, K. Itoh, Org. Lett. 3 (2001) 2117;
(c) Y. Yamamoto, K. Kinpara, T. Saigoku, H. Takagishi, S. Okuda, H. Nishiyama,
K. Itoh, J. Am. Chem. Soc. 127 (2005) 605.
We thank the Scientific and Technological Research Council of
Turkey (TUBITAK, 107T084) and Hacettepe University (080160
1008) for research support.
References
[19] Y. Ura, Y. Sato, H. Tsujita, T. Kondo, M. Imachi, T. Mitsudo, J. Mol. Catal. A:
Chem. 239 (2005) 166.
[20] C.Y. Wu, Y.C. Lin, P.T. Chou, Y. Wang, Y.H. Liu, Dalton Trans. 40 (2011) 3748.
[21] (a) V. Cadierno, S.E. García-Garrido, J. Gimeno, J. Am. Chem. Soc. 128 (2006)
15094;
[1] F.A. Carey, R.J. Sundberg, Advanced Organic Chemistry, third ed., Plenum Press,
New York, 1990 (Part B, Chapter 11, 571).
[2] (a) B.M. Trost, Science 254 (1991) 1471;
(b) V. Cadierno, J. Francos, S.E. García-Garrido, Green Chem. Lett. Rev. 4 (2011)
55.
(b) B.M. Trost, Angew. Chem., Int. Ed. Engl. 34 (1995) 259;
(c) B.M. Trost, Acc. Chem. Res. 35 (2002) 695;
[22] J. Peters, S. Blechert, Chem. Commun. (1997) 1983.
[23] S.K. Das, R. Roy, Tetrahedron Lett. 40 (1999) 4015.
[24] D.D. Young, R.S. Senaiar, A. Deiters, Chem. Eur. J. 12 (2006) 5563.
[25] G.B. Hoven, J. Efskind, C. Romming, K. Undheim, J. Org. Chem. 67 (2002)
2459.
[26] Á. Mallagaray, S. Medina, G. Domínguez, J. Pérez-Castells, Synlett 14 (2010)
2114.
[27] A. Fürstner, L. Ackermann, B. Gabor, R. Goddard, C.W. Lehmann, R. Mynott, F.
Stelzer, O.R. Thiel, Chem. Eur. J. 7 (2001) 3236.
(d) N. Saino, F. Amemiya, E. Tanabe, K. Kase, S. Okamoto, Org. Lett. 8 (2006)
1439;
(e) T. Shibata, K. Tsuchikama, Org. Biomol. Chem. 6 (2008) 1317.
[3] (a) B.R. Galan, T. Rovis, Angew. Chem., Int. Ed. 48 (2009) 2830;
(b) B. Heller, M. Hapke, Chem. Soc. Rev. 36 (2007) 1085;
(c) P.R. Chopade, J. Louie, Adv. Synth. Catal. 348 (2006) 2307;
(d) S. Kotha, E. Brahmachary, K. Lahiri, Eur. J. Org. Chem. 2005 (2005) 4741;
(e) J.A. Varela, C. Saa, Chem. Rev. 103 (2003) 3787;
(f) S. Saito, Y. Yamamoto, Chem. Rev. 100 (2000) 2901;
(g) N.E. Schore, Chem. Rev. 88 (1988) 1081;
(h) G. Domínguez, J. Pérez-Castells, Chem. Soc. Rev. 40 (2011) 3430.
[28] E.L. Dias, R.H. Grubbs, Organometallics 17 (1998) 2758.
[29] V. Cadierno, M.P. Gamasa, J. Gimeno, Coord. Chem. Rev. 248 (2004) 1627.