Homocoupling of aryl Grignard reagents to form biaryls using ruthenium(III) complex, [RuCl(C3S5)(H2O)(PPh 3)2]

Article abstract of DOI:10.1016/j.molcata.2012.02.013

Ruthenium(III) complex, [RuCl(C₃S₅)(H ₂O)(PPh₃)₂] is an effective catalyst for the homocoupling of the aryl-Grignard reagents (ArMgX) to form biaryl derivatives. The catalytic methodology involves an in situ generation of the Grignard reagents. The method is simpler, economical and of great synthetic utility. The reaction will be environmental friendly due to the involvement of molecular oxygen as oxidant.

Full text of DOI:10.1016/j.molcata.2012.02.013

Journal of Molecular Catalysis A: Chemical 358 (2012) 73–78
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Homocoupling of aryl Grignard reagents to form biaryls using ruthenium(III)
complex, [RuCl(C3S5)(H2O)(PPh3)2]
P.I. Aparna, Badekai Ramachandra Bhat∗
Catalysis and Materials Laboratory, Department of Chemistry, National Institute of Technology Karnataka, Surathkal, Srinivasanagar 575025, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Ruthenium(III) complex, [RuCl(C3S5)(H2O)(PPh3)2] is an effective catalyst for the homocoupling of the
aryl-Grignard reagents (ArMgX) to form biaryl derivatives. The catalytic methodology involves an in situ
generation of the Grignard reagents. The method is simpler, economical and of great synthetic utility.
The reaction will be environmental friendly due to the involvement of molecular oxygen as oxidant.
© 2012 Elsevier B.V. All rights reserved.
Received 13 January 2012
Received in revised form 10 February 2012
Accepted 21 February 2012
Available online 1 March 2012
Keywords:
Homocoupling
Catalytic methodology
Grignard reagent
Biaryl
Molecular oxygen
1. Introduction
a wide range of oxidation states, coordination geometries, toler-
ance towards functional groups, ease of synthesis and versatility
The potential applications of the symmetrical di- or pol-
yaromatic, olefinic or acetylenic conjugated compounds in
pharmaceuticals, optical materials, conductive polymers and liquid
crystals are well recognized [1,2]. Homocoupling reactions of aryl,
alkenyl and alkynyl Grignard reagents provide an easy and efficient
access for the synthesis of such compounds. The transition metal
catalyzed coupling reactions are the popular choice for biaryl syn-
thesis, holding the synthetic advantages such as high selectivity,
broad substrate scopes and mild reaction conditions [3]. Several
kinds of transition metal precursors, CoCl2 [4], MnCl2 [5], FeCl3 [6],
TiCl4 [7], VO(OEt)Cl2 [8], Cu(OAc)2 [9], etc. were used in stoichio-
metric amount or catalytical amount in the presence of a reoxidant
to carry out the oxidative coupling process. Recently iron [10], pal-
ladium [11], etc. catalyzed aerobic homocoupling reactions of aryl
magnesium derivatives have been achieved successfully. Although
transition metal free homocoupling of ArMgX has been reported
[12–15], their urge in stoichiometric amount of organic oxidant
limits its use for large scale applications. The exploration of the
catalytic systems which are greener and more efficient approaches
for this transformation is still challenging. Nevertheless, palladium
and nickel complexes have been the dominant choice to catalyze
the coupling of the Grignard reagents with aryl bromides, iodides
andchlorides[16,17], theabilityof rutheniumcomplexesto assume
provides unique opportunities for catalysis [18,19].
As a part of our ongoing research towards synthesis of biaryls,
herein, we report the efficient catalytic system for the coupling of
Grignard reagents using new ruthenium(III) complex, containing
C3S5 and triphenylphosphine ligands, to afford biaryls in good to
high yields. We have synthesized Grignard reagent in situ and atmo-
spheric molecular oxygen being used as the oxidant, renders the
reaction greener. This procedure is simple, mild and works effi-
ciently without any external oxidants and additives.
2. Experimental
2.1. Materials and methods
All chemicals used were of analytical grade. Solvents were
purified and dried according to the standard procedures [20].
[RuCl2(PPh3)2] was synthesized as per the reported procedure [21].
The C, H, O and S contents of the complex were determined by Ther-
moflash EA1112 series elemental analyzer. Magnetic susceptibility
measurement was recorded on a Sherwood Scientific instrument
(UK). Thermal analysis was carried out (EXSTAR-6000) from room
temperature to 700 ◦C at a heating rate of 10 ◦C/min. The electronic
spectrum of the complex was measured on a GBC Cintra 101 UV–Vis
double beam spectrophotometer using DMF in the 200–800 nm
range. FT-IR spectrum was recorded on a Thermo Nicolet Avatar FT-
∗
IR spectrometer in the frequency range 400–4000 cm−1
.
1H NMR
Corresponding author. Tel.: +91 824 2474000x3204; fax: +91 824 2474033.
E-mail address: chandpoorna@yahoo.com (B.R. Bhat).
and 31P NMR spectra were recorded in Bruker AV 400 instrument
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2012.02.013

74
P.I. Aparna, B.R. Bhat / Journal of Molecular Catalysis A: Chemical 358 (2012) 73–78
Fig. 1. Schematic representation of synthesis of complex (1).
Table 1
FT-IR and UV–Vis spectral results of complex (1).
FT-IR
UV–Vis
Wave number (cm−1
)
Assignment
Wave number (cm−1
)
Assignment
ꢀmax (nm)
Assignment
LM CT
1431, 1226
1053
972.9
ꢁ(C C)
ꢁ(C S)
ꢁ(C S)
619
3383.6
747, 691.7, 511
ꢁ(SC CS)
ꢁ(O H)
Bands due to triphenylphosphine
418
367, 358, 275
ILCT
LMCT, ligand to metal charge transfer transition.
ILCT, intra ligand charge transfer transition.
using TMS and H3PO4 as internal standards respectively. Elec-
trochemical study was performed using Versa STAT-3 in 0.005 M
dichloromethane solutions of [(n-C4H9)4N]ClO4 (TBAP) as a sup-
porting electrolyte. Coupling reactions were monitored by gas
chromatography, Shimadzu 2014.
3. Results and discussion
3.1. Characterization
The elemental analyses (C, H, O, S) are in good agreement with
the molecular formula proposed for the complex (1). Selected IR
bands and electronic spectral results are listed in Table 1. 1H NMR
spectra showed resonance at ı 7.08–7.23 ppm which has been
assigned to the protons of two coordinated triphenylphosphine
2.2. Preparation of complex [RuCl(C3S5)(H2O)(PPh3)2] (1)
1
groups present in the complex (1). 31P{ H} NMR spectrum exhibits
Complex (1) was prepared under strictly anhydrous condi-
tions (Fig. 1). To a methanol (20 ml) solution containing CS2
(0.2 ml, 3 mmol) and sodium metal, was added ruthenium com-
plex, [RuCl2(PPh3)2] (695 mg, 1 mmol) with constant stirring. The
mixture was refluxed for 4 h. The dark brown precipitate obtained
was filtered, washed with methanol, petroleum ether (60–80 ◦C)
and dried in vacuo. Yield: 72%. M.P: 235 ◦C.
a sharp singlet at 50.28 ppm supporting the presence of the mag-
netically equivalent triphenylphosphine groups [23]. The room
temperature magnetic moment 1.81 BM shows that the complex
(1) is one- electron paramagnetic, which confirms its octahedral
geometry [24]. From TG analysis (Fig. 2), the weight loss of the com-
plex (1) was observed at temperature around 150–190, 190–215,
215–305 and 305–371 ◦C which corresponds to the loss of coordi-
nated water, chloride, triphenylphosphine and carbon disulphide
respectively. This further supports the assumed structure of the
ruthenium(III) complex. Cyclic voltammogram of the complex (1)
Anal. Calc. for C39H32ClOP2RuS5, Found (calculated) (%): C, 52.86
(53.50); H, 3.62 (3.68); O, 1.89 (1.83); S, 18.26 (18.31).
2.3. Aryl–aryl coupling reaction
Coupling reaction was carried out according to the reported
procedure [22] with slight modification. Present catalytic reaction
was performed in the presence of atmospheric molecular oxygen.
Magnesium turnings (0.320 g, 0.013 g atom) were placed in a two
necked round bottom flask with a calcium chloride guard tube. A
crystal of iodine was added. Aryl halide (Ar-X, X = Br or Cl) (2 mmol
of total 10 mmol) in 5 ml of anhydrous diethyl ether was added
with stirring at room temperature. The appearance of turbidity after
5 min indicated the initiation of the reaction. The remaining Ar-X
in 5 ml of ether was added drop wise and the reaction mixture was
stirred for 40 min at room temperature. To this reaction mixture,
ruthenium(III) catalyst chosen for investigation was added and stir-
ring was continued for 6 h. The reaction mixture was cooled and
hydrolyzed with a saturated solution of aqueous ammonium chlo-
ride. The ether extract on evaporation of the solvent gave the crude
product which compared well with authentic samples of biphenyl
using gas chromatography.
Fig. 2. TG and DTG curves of complex (1).

P.I. Aparna, B.R. Bhat / Journal of Molecular Catalysis A: Chemical 358 (2012) 73–78
75
Table 2
Electrochemical data of complex (1).
RuIII/RuIV
RuIII/RuII
Epa (V)
Epc (V)
E1/2 (V)
ꢂEp (mV)
Epc (V)
−0.59
0.85
0.92
0.88
70
Supporting electrolyte, [(NBu4)ClO4] (0.005 M); complex, 0.001 M in
dichloromethane.
E1/2 = 0.5(Epa + Epc).
ꢂEp = Epa − Epc
.
exhibits reversible oxidation couple RuIII/RuIV at E1/2 = +0.88 V with
a peak-to-peak separation ꢂEp = 70 mV with respect to Ag/AgCl,
which does not change with a change in the scan rates, supporting
reversibility (Table 2). Further, the complex exhibits an irreversible
reduction in the range −0.59 V. The reason for the irreversibility
observed for the reductive response of the complex may be due to
a short lived reduced state of the metal ion [25] or due to oxidative
degradation of ligands [26].
3.2. Catalytic activity
Fig. 3. Effect of reaction time on the yield of bromobenzene to biphenyl.
In the present methodology, the Grignard reagent which was
synthesized in situ on reaction with a catalytic amount of complex
(1) yields respective biaryl. In order to activate the surface of the
commercial magnesium turnings, iodine was added. Formation of
Grignard reagent was carried out with careful control of the rate of
addition of aryl halide to avoid coupling side products. The reaction
was carried out in the presence of the atmospheric molecular oxy-
gen, which is considered as the greenest and most environmentally
benign protocol [27], without addition of any external oxidants.
The reaction conditions for the coupling of phenylmagnesium bro-
mide (1e) were optimized with respect to solvent, time and catalyst
concentration.
Table 4
Effect of catalyst concentration on the yield of coupling product.a
Entry
Amount of complex (1) (mmol)
Yield (%)b
1
2
No catalyst
0.01
01.12
19.72
32.36
47.36
61.23
75.96
75.62
74.97
75.88
04.23
74.02
3
4
0.015
0.02
5
6
0.025
0.03
7
0.04
8
0.05
9c
10d
11e
0.03
0.03
0.15
a
3.2.1. Solvent effect
Reactions were carried out with 10 mmol of bromobenzene in the presence of
atmospheric molecular oxygen.
Solvents play a crucial role in the coupling reactions. The
activity of the complex (1) was checked in different solvents,
tetrahydrofuran, diethyl ether, benzene, etc., with molecular oxy-
gen as oxidant (Table 3). The best conversion was observed in
diethyl ether as ether molecules actually coordinate with and thus
helps in stabilizing the Grignard reagent (entry 2). The least con-
version was observed in benzene, since the formation of polar
Grignard reagent stops in most non-polar organic solvents as
it forms an insoluble deposit at the metallic surface. The order
of increasing percentage yield in tested solvents follows, ben-
zene < tetrahydrofuran < diethyl ether.
b
GC yield based on the amount of bromobenzene.
In the presence of pure oxygen.
Inert atmosphere (argon).
With 50.0 mmol of bromobenzene in the presence of 0.15 mmol catalyst for 10 h.
c
d
e
regular intervals of time under similar reaction conditions. The
yield increased with reaction time (Fig. 3) and total reaction time
of 6 h at room temperature gave a constant conversion of 76%.
3.2.3. Effect of catalyst loading and influence of air on the reaction
To study the effect of catalyst concentration on the reaction,
substrate to catalyst ratio was varied from total catalyst amount
0.01 mmol to 0.05 mmol (Table 4). It can be observed that even at
very low catalyst loading of 0.025 mmol (entry 5), the moderate
3.2.2. Effect of reaction time
The dependence of product yield on reaction time for the cou-
pling of 1e was studied by analyzing the reaction mixture at
Table 3
Optimization of ruthenium-catalyzed homocoupling of phenylmagnesium bromide (1e)a in different solvents.
0.03 mmol [RuCl(C3S5)H2O(PPh3)2]
temperature, 6 h
air, Mg turnings
Br
MgBr
solvent, temperature, 40 min
2e
1e
Entry
Solvent
Temperature (◦C)
Yield (%)b
1
2
3
Tetrahydrofuran
Diethyl ether
Benzene
60
62
75
36
r.t.c
40
a
Reaction conditions: Mg turnings (0.320 g), bromobenzene (10 mmol), catalyst (0.03 mmol), Et2O (10 ml).
GC yield based on the amount of bromobenzene.
r.t., room temperature.
b
c

76
P.I. Aparna, B.R. Bhat / Journal of Molecular Catalysis A: Chemical 358 (2012) 73–78
Table 5
S
)(H O)(PPh )
2 3
2
Ruthenium-catalyzed homocoupling of Grignard reagents with atmospheric oxygen as an oxidant.a Ar–Mg–Brair, 0.03 mmol [RuC−l→(C
]Ar–Ar.
3
5
Et O, r.t., 6 h
2
Entry
1
RMgBr
Product
Yield (%)b
MgBr
83
1a
2a
MgBr
2
74
1b
2b
MeO
MgBr
MeO
OMe
3
89
1c
2c
OMe
OMe
MgBr
MgBr
4
72
MeO
2d
1d
1e
5
6
7
76
71
70
2e
Cl
N
MgBr
Cl
N
Cl
1f
2f
MgBr
N
1g
1h
2g
8c
65
MgBr
2h

P.I. Aparna, B.R. Bhat / Journal of Molecular Catalysis A: Chemical 358 (2012) 73–78
77
Table 5 (Continued)
Entry
RMgBr
Product
Yield (%)b
NC
MgBr
NC
CN
9
62
1i
2i
O2N
MgBr
NO2
14
10
64
NO2
1j
2j
a
Reaction conditions: Mg turnings (0.320 g), aryl halide (10 mmol), catalyst (0.03 mmol), Et2O (10 ml).
GC yield based on the amount of aryl halide.
b
c
In THF, 60 ◦C, 10 h.
yield was obtained. The yield increased with increase in catalyst
homocoupling product Ar–Ar and Ru(II) is regenerated. In fact, the
best way to favor the reductive elimination is to increase the oxi-
dation state of the metal. Thus, it is very reasonable to think that
the formation of an unstable ruthenium(IV) species (c) is required
to achieve a very quick reductive elimination that gives (d). The
formation of peroxo-ruthenium(IV) intermediate was confirmed
by the UV–Vis spectrophotometer analysis. The absorption peak
of the catalytic reaction mixture appeared at 398 nm that can
be attributed for peroxo-ruthenium(IV) intermediate [31] and its
absence in the reaction mixture carried out under inert condition
further confirms the necessity of molecular oxygen for the present
catalytic system. The formation of such a peroxo complex as cat-
alytic intermediate is very well established for various manganese,
iron and palladium-catalyzed reactions [30,32,33].
loading and reaches to the highest value of 76% with 0.03 mmol
of catalyst (entry 6). It is noteworthy that the use of pure oxygen
instead of atmospheric oxygen has no significant influence on the
yields (entry 9). Also the absence of air results lower yield may
be due to the lack of formation of peroxo-ruthenium(IV) active
species (entry 10). The present coupling can be readily scaled up
to the reaction of 50.0 mmol of the aryl halide using 0.15 mmol of
the catalyst, which yields 74% of biaryl with negligible amount of
byproducts (entry 11). The efficiency of the complex (1) should be
underlined since, in the absence of ruthenium(III) complex, Grig-
nard reagents generally react very quickly with oxygen to give
various products (mainly ROH and RH) but only traces of coupling
product.This promising result encouraged us to extend the scope of
the reaction to various aryl Grignard reagents (Table 5). Thus, sim-
ple and functionalized biaryl compounds were synthesized in good
yields (entries 1–10). Introduction of methyl group at the ortho-
position of the aryl Grignard reagent 1b resulted in somewhat lower
yield of the homocoupling product (entry 2). 4-Methoxy- and 2-
methoxyphenylmagnesium bromide can be efficiently converted
into the corresponding biaryls 2c and 2d, respectively, under sim-
ilar conditions (entries 3 and 4).It is noteworthy that the present
reaction system is tolerant of aryl chloride functionality (entry 6).
Also it allows the coupling of heteroaryl Grignard reagent 1 g suc-
cessfully (entry 7). Although sterically demanding substrate 1 h
required higher reaction temperature and longer reaction time, it
gave the corresponding biaryl 2 h in moderate to good yield (entry
8). The reaction is chemoselective; thus, nitrile, or nitro groups are
tolerated (entries 9 and 10). It is observed that electron donating
group on Grignard reagent enhances the yield of coupling prod-
uct compared to that of electron withdrawing group (entries 1 and
6). In all these experiments, formations of cross-coupling products
were very less.
3.3. Proposed mechanism
The proposed mechanism is depicted in Fig. 4 for complex
(1) catalyzed reaction. The oxidative addition of the molec-
ular oxygen to
a low valent ruthenium complex (a) forms
peroxo-ruthenium(IV) intermediate (b) which is the key step of
this catalytic cycle [28,29]. It is then reacts with two equiva-
lents of RMgX to give biarylruthenium(IV) intermediate (c) and
XMgOOMgX [30]. Thus formed biarylruthenium(IV) intermediate
(c) undergoes rapid reductive elimination which eventually yields
Fig. 4. Proposed mechanism for the complex (1) catalyzed coupling reaction.

78
P.I. Aparna, B.R. Bhat / Journal of Molecular Catalysis A: Chemical 358 (2012) 73–78
4. Conclusions
[8] T. Ishikawa, A. Ogawa, T. Hirao, Organometallics 17 (1998) 5713–5716.
[9] A.S. Demir, O. Reis, M. Emrullahoglu, J. Org. Chem. 68 (2003) 10130–10134.
[10] W. Liu, A. Lei, Tetrahedron Lett. 49 (2008) 610–613.
[11] H. Yoshida, Y. Yamaryo, J. Ohshita, A. Kunai, Tetrahedron Lett. 44 (2003)
1541–1544.
[12] A. Krasovskiy, A. Tishkov, V. Amo, H. Mayr, P. Knochel, Angew. Chem. Int. Ed.
45 (2006) 5010–5014.
[13] M.S. Maji, A. Studer, Synthesis 14 (2009) 2467–2470.
[14] M.S. Maji, T. Pfeifer, A. Studer, Chem. Eur. J. 16 (2010) 5872–5875.
[15] M.S. Maji, T. Pfeifer, A. Studer, Angew. Chem. Int. Ed. 47 (2008) 9547–9550.
[16] S.Y.W. Lau, G. Hughes, P.D. O’Shea, I.W. Davies, Org. Lett. 9 (2007) 2239–
2242.
[17] T. Hatakeyama, S. Hashimoto, K. Ishizuka, M. Nakamura, J. Am. Chem. Soc. 131
(2009) 11949–21196.
[18] V.K. Srivastava, R.S. Shukla, H.C. Bajaj, R.V. Jasra, Appl. Catal. A: Gen. 282 (2005)
31–38.
[19] N. Mizuno, K. Yamaguchi, Catal. Today 132 (2008) 18–26.
[20] A.I. Vogel, Textbook of Practical Organic Chemistry, fifth ed., Longman, London,
1989.
[21] T.A. Stephenson, G. Wilkinson, J. Inorg. Nucl. Chem. 28 (1966) 945–956.
[22] N.P. Priya, S. Arunachalam, A. Manimaran, D. Muthupriya, C. Jayabalakrishnan,
Spectrochim. Acta A 72 (2009) 670–676.
In conclusion, newly synthesized octahedral ruthenium(III)
complex has been effectively applied for the catalytic transfor-
mation of various aryl halides to the corresponding symmetric
biaryl in good to high yields. Present catalytic procedure of an
in situ formation of the Grignard reagent makes the biaryl synthesis
route much simpler, energy efficient, economical and of great syn-
thetic utility. The oxidant atmospheric molecular oxygen makes
the coupling reaction environmental friendly and cost effective.
Peroxo-ruthenium(IV) active species is responsible for the effi-
ciency of present catalytic system. The small amount of catalyst,
chemoselectivity and eco-friendly procedures makes the reaction
system readily amenable to a large-scale synthesis of biaryl com-
pounds.
Acknowledgments
[23] M.W. Schoonover, C.P. Kubiak, R. Eisenberg, Inorg. Chem. 17 (1978) 3050–
3055.
Ms. Aparna, P.I. thanks National Institute of Technology Kar-
nataka, Surathkal for research fellowship. The authors thank Indian
Institute of Science, Bangalore, for NMR analysis.
[24] R. Raveendran, S. Pal, Polyhedron 27 (2008) 655–662.
[25] A.M. Bond, R. Colton, D.R. Mann, Inorg. Chem. 29 (1990) 4665–4671.
[26] A. Basu, T.G. Kasar, N.Y. Sapre, Inorg. Chem. 27 (1988) 4539–4542.
[27] C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 111 (2011) 1780–1824.
[28] A. Hussain, R.S. Shukla, R.B. Thorat, H.J. Padhiyar, K.N. Bhatt, J. Mol. Catal. A:
Chem. 193 (2003) 1–12.
[29] A. Ourari, M. Khelafi, D. Aggoun, G. Bouet, M.A. Khan, Adv. Phys. Chem. 2011
(2011) 1–11.
[30] G. Cahiez, A. Moyeux, J. Buendia, C. Duplais, J. Am. Chem. Soc. 129 (2007)
13788–13789.
[31] T. Joseph, D.P. Sawant, C.S. Gopinath, S.B. Halligudi, J. Mol. Catal. A: Chem. 184
(2002) 289–299.
[32] B.S. Lane, K. Burgess, Chem. Rev. 103 (2003) 2457–2474.
[33] C. Adamo, C. Amatore, I. Ciofini, A. Jutand, H. Lakmini, J. Am. Chem. 128 (2006)
6829–6836.
References
[1] J.P. Corbet, G. Mignani, Chem. Rev. 106 (2006) 2651–2710.
[2] S.S. Zhu, T.M. Swager, Adv. Mater. 8 (1996) 497–500.
[3] D. Alberico, M.E. Scott, M. Lautens, Chem. Rev. 107 (2007) 174–238.
[4] G. Cahiez, A. Moyeux, Chem. Rev. 110 (2010) 1435–1462.
[5] G. Cahiez, O. Gager, F. Lecomte, Org. Lett. 10 (2008) 5255–5256.
[6] M. Nakamura, K. Matsuo, S. Ito, E. Nakamura, J. Am. Chem. Soc. 126 (2004)
3686–3687.
[7] A. Inoue, K. Kitagawa, H. Shinokubo, K. Oshima, Tetrahedron 56 (2000)
9601–9605.