Ruthenium-catalyzed oxidative homocoupling of arylboronic acids in water: Ligand tuned reactivity and mechanistic study

Article abstract of DOI:10.1021/acs.inorgchem.6b01115

Molecular catalysts based on water-soluble arene-Ru(II) complexes ([Ru]-1-[Ru]-5) containing aniline (L1), 2-methylaniline (L2), 2,6-dimethylaniline (L3), 4-methylaniline (L4), and 4-chloroaniline (L5) were designed for the homocoupling of arylboronic acids in water. These complexes were fully characterized by ¹H, ¹³C NMR, mass spectrometry, and elemental analyses. Structural geometry for two of the representative arene-Ru(II) complexes [Ru]-3 and [Ru]-4 was established by single-crystal X-ray diffraction studies. Our studies showed that the selectivity toward biaryls products is influenced by the position and the electronic behavior of various substituents of aniline ligand coordinated to ruthenium. Extensive investigations using ¹H NMR, ¹⁹F NMR, and mass spectral studies provided insights into the mechanistic pathway of homocoupling of arylboronic acids, where the identification of important organometallic intermediates, such as σ-aryl/di(σ-aryl) coordinated arene-Ru(II) species, suggested that the reaction proceeds through the formation of crucial di(σ-aryl)-Ru intermediates by the interaction of arylboronic acid with Ru-catalyst to yield biaryl products.

Full text of DOI:10.1021/acs.inorgchem.6b01115

Article
pubs.acs.org/IC
Ruthenium-Catalyzed Oxidative Homocoupling of Arylboronic Acids
in Water: Ligand Tuned Reactivity and Mechanistic Study
Deepika Tyagi,† Chinky Binnani,† Rohit K. Rai,† Ambikesh D. Dwivedi,† Kavita Gupta,† Pei-Zhou Li,§
Yanli Zhao,§ and Sanjay K. Singh*,†,‡
†Discipline of Chemistry, School of Basic Sciences, and ‡Centre of Material Science and Engineering, Indian Institute of Technology
(IIT) Indore, Indore 453552, Madhya Pradesh, India
§Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: Molecular catalysts based on water-soluble arene-Ru(II)
complexes ([Ru]-1−[Ru]-5) containing aniline (L1), 2-methylaniline (L2),
2,6-dimethylaniline (L3), 4-methylaniline (L4), and 4-chloroaniline (L5) were
designed for the homocoupling of arylboronic acids in water. These complexes
1
were fully characterized by H, 13C NMR, mass spectrometry, and elemental
analyses. Structural geometry for two of the representative arene-Ru(II)
complexes [Ru]-3 and [Ru]-4 was established by single-crystal X-ray diffraction
studies. Our studies showed that the selectivity toward biaryls products is
influenced by the position and the electronic behavior of various substituents of
1
aniline ligand coordinated to ruthenium. Extensive investigations using H
NMR, 19F NMR, and mass spectral studies provided insights into the
mechanistic pathway of homocoupling of arylboronic acids, where the
identification of important organometallic intermediates, such as σ-aryl/di(σ-
aryl) coordinated arene-Ru(II) species, suggested that the reaction proceeds through the formation of crucial di(σ-aryl)-Ru
intermediates by the interaction of arylboronic acid with Ru-catalyst to yield biaryl products.
(∼130 °C)10 and in a few cases with additives like p-
INTRODUCTION
■
toluenesulfonyl chloride under N2 atmosphere.12
The synthesis of biaryls is important as they are abundantly
present in natural products, and extensively applied in
Moreover, arene-Ru(II) complexes represent an active class
of catalysts for several catalytic reactions, such as hydrogenation
reactions of unsaturated bonds of carbonyl, imines and alkene
pharmaceuticals, polymers, optically active ligands, and various
fine chemicals.1 Several methodologies have been developed to
bonds, C−N coupling (amidation and hydroamination), C−H
synthesize both symmetrical and asymmetrical biaryls.2 Among
bond activation, and oxidative Heck reactions.13,14 Brown et al.
these, transition metal-catalyzed C−C bond formation for the
reported arene-Ru(II)-catalyzed oxidative Heck reaction using
synthesis of symmetrical biaryls has emerged as an important
PhB(OH)2 and butyl acrylate for the formation of methyl-
synthetic methodology.3 Typically, the bottleneck in this
process is the key step involving the formation of metal−
carbon bond; to overcome this, several nucleophiles such as
PhN2BF4, SnBu3Ph, PhMgBr, ArBF3K, and ArB(OH)2 are
being widely used as a source of aryl group.4 Among these
nucleophiles, arylboronic acid offers several advantages, such as
its ready availability, easiness to handle, and less toxicity
(particularly over Sn-based reagents).4 For homocoupling of
arylboronic acids to biaryls, several catalytic systems based on
Cu, Au, Pd, Ni, Cr, Rh, etc., were reported in the past (Scheme
1).5−10 There are several reports using transition metal salts for
homocoupling reaction of arylboronic acids under mild
conditions, but reports based on homogeneous complex-
catalyzed homocoupling reactions are very few (Scheme 1
and Table S1).5−10 Moreover, most of these homogeneous
complex-catalyzed reactions were performed in organic solvents
(toluene, xylene, DMF, THF)6c,f,11 or at high temperature
cinnamate in THF with [(η6-p-cymene)Ru(PPh3)Cl2] catalyst
and CuCl2 as reoxidant.14a Interestingly, phosphine-free
dichloro ruthenium dimer catalyst, [(η6-p-cymene)RuCl2]2
was found to be more active than the [(η6-p-cymene)Ru-
(PPh3)Cl2], suggesting the inhibitory role of PPh3 in [(η6-p-
cymene)Ru(PPh3)Cl2] catalyst.14a Studies suggested that the
dissociation of ligands (PPh3), chloro-bridge breaking, and
coordination properties of the solvents used for the catalytic
reactions are few of the several crucial factors influencing these
catalytic reactions.14a We have also reported arene-Ru(II)
catalysts containing simple nitrogen bound ligand as active
catalysts for C−N coupling reaction and hydrogenation/ring-
opening reaction in water and observed that arene-Ru(II)
complexes remain highly active even under aqueous−aerobic
Received: May 6, 2016
© XXXX American Chemical Society
A
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Scheme 1. Catalytic Homocoupling Reaction of Arylboronic Acids Using Various Metal Catalysts
Scheme 2. Synthesis of Arene-Ru(II) Complexes ([Ru]-1−[Ru]-5) with Several Aniline-Based Ligands (L1−L5) Investigated for
Homocoupling of Arylboronic Acid
conditions.15 In particular, [(η6-benzene)Ru(aniline)Cl2] com-
plex, [Ru]-1, employed for C−N coupling reaction, displayed
superior catalytic reaction than the corresponding dichloro
bridged arene-ruthenium precursor dimer catalyst, [(η6-
benzene)RuCl2]2, under analogous reaction conditions.15a We
revealed that being a simple σ-donor ligand, aniline ligands can
form a stable mononuclear ruthenium complex, which is a
structural analogue of [(η6-arene)Ru(PPh3)Cl2], but in
contrary to PPh3, aniline can be easily displaced by incoming
coordinating reactant molecule under catalytic reaction
conditions.15a These findings were indeed interesting, as
electronic and steric properties of the aniline ligand can be
easily fine-tuned by applying several substituents on the phenyl
ring. Moreover, [Ru]-1 complex advantageously showed high
aqueous solubility, and therefore offered opportunity to
perform water-based catalytic reaction.
Inspired by the high activity of arene-Ru(II) complexes for
various C−C coupling reactions, where the reaction of
ArB(OH)2 with Ru(II) precursor readily formed Ru−C bond
via transmetalation,14 we herein systematically investigated
highly active water-soluble arene-Ru(II) catalysts, [(η6-
benzene)Ru(L)Cl2] (L = aniline or substituted aniline), for
catalytic homocoupling of ArB(OH)2 to symmetrical biaryls in
water, considering that di(σ-aryl)-Ru species may also form
during the catalytic reaction. While establishing the solid-state
structure of the catalyst by single-crystal X-ray diffraction, we
have extensively investigated the mode of interaction of the (η6-
benzene)-Ru(II)aniline catalyst ([Ru]-1) with ArB(OH)2 using
1
mass spectrometry and H and 19F NMR. On the basis of the
identification of a few of the important intermediates including
σ-aryl/di(σ-aryl)-Ru(II) species by mass spectrometry and 19F
NMR, we also proposed a considerable mechanistic approach
for the catalytic homocoupling of ArB(OH)2 to symmetrical
biaryls in water.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Water-Soluble
Arene-Ru(II)-Based Molecular Catalysts Containing Sim-
ple Aniline Ligands. At the outset, we synthesized arene-
Ru(II) complexes with aniline-based ligands in methanol using
our previously reported procedure.15a We chose aniline (L1), o-
methylaniline (L2), 2,6-dimethylaniline (L3), p-methylaniline
(L4), and p-chloroaniline (L5) as model ligands, considering
the electronic and steric effects due to the different substituents.
These ligands (L1−L5) were reacted with [(η6-benzene)-
RuCl2]2 in methanol under refluxing condition to obtain the
corresponding neutral mononuclear arene-Ru(II) complexes,
[(η6-benzene)Ru(L)Cl2] (L = L1 ([Ru]-1), L2 ([Ru]-2), L3
B
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Figure 1. Crystal structure of the complex [Ru-3]. Ellipsoids are set at 30% probability. All hydrogen atoms, except those on nitrogen, are omitted
for clarity. Selected bond lengths [Å] and angles [deg]: Ru1−N1 2.181(3), Ru1−Cl1 2.402(11), Ru1−Cl2 2.421(10), Ru1−Cav 1.174, Cl1−Ru1−
Cl2 88.91(4), N1−Ru1−Cl1 81.93(9), N1−Ru1−Cl2 82.03(8), C7−N1−Ru1 120.3(2).
([Ru]-3), L4 ([Ru]-4), and L5 ([Ru]-5), in excellent yields
(Scheme 2, please see Experimental Section and Supporting
Information for details). The obtained orange to brown colored
the η6-benzene ring. The Ru−nitrogen bond distance (Ru1−
N1) for the sterically crowded ligand (L3) is 2.181 Å, which is
slightly higher than the Ru−N bond distance (2.158 Å) for our
previously reported complex with L1 ligand ([Ru]-1). Ru−
chlorine bond distances for Ru1−Cl1 and Ru1−Cl2 are 2.402
and 2.421 Å, respectively. The N1−Ru1−C7 angle (120.3°)
indicates the away placement of phenyl ring of ligand (L3)
from the metal center. Angles between the legs, Cl1−Ru1−Cl2
(88.91°), N1−Ru1−Cl1 (81.93°), and N1−Ru1−Cl2 (82.03°),
and those between the legs and the centroid of η6−benzene
ring (Cct) (126.97°−133.26°) for the complex [Ru]-3 are close
to those reported earlier.15,16 Detailed crystal refinement data
are provided in Table 1, and selected bond lengths and bond
angles are given in Tables S2 and S3. We also confirmed the
molecular structure of the complex [Ru]-4 by single-crystal X-
ray diffraction studies, but, unfortunately, we could not retrieve
the refined data due to the distortion observed in the structure
(Figure S1).
Arene-Ru(II)-Catalyzed Homocoupling of Arylboronic
Acids to Symmetrical Biaryls. At the outset of our
investigations, we chose water as a solvent due to the high
aqueous solubility of these complexes, and then examined the
effect of various bases on the desired homocoupling reaction
using phenylboronic acid (1a) as model substrate in the
presence of [Ru]-1 (2.5 mol %) in water at 70 °C (Table 2).
Preliminary results indicated that Na2CO3 outperforms with
respect to the selectivity (47%) toward the homocoupled
product, biphenyl (2a), with >99% conversion of 1a (Table 2,
entry 1), among a variety of bases (NaOH, KOH, Na3PO4,
K3PO4, NaHCO3, and K2CO3) used for the reaction (Table
S4). Notably, in the absence of base, the conversion of 1a
decreases drastically to a mere 16% under analogous reaction
conditions (Table 2, entry 2), as generally base facilitates the
C−B bond scission and assists in subsequent transmetalation
step for the aryl insertion into the metal of catalyst.
Interestingly, addition of a slight amount of methanol was
found to be beneficial, as presumably it enhances the solubility
of the substrate for the homocoupling reaction of 1a (Table 2,
entry 3). It is worth noting that the reaction could not proceed
in the absence of the catalyst (Table 2, entry 4). Further,
decreasing the reaction temperature to 60 °C resulted in a
decrease in conversion (91%), and at room temperature only
1
complexes, [Ru]-2−[Ru]-5 were characterized by H NMR,
13C NMR, elemental analyses, and ESI-mass spectrometry.
1H NMR spectra of the complexes [Ru]-2−[Ru]-5 displayed
that upon coordination to ruthenium, the protons of aniline-
based ligands shifted to the downfield region, in comparison to
the free ligands.15,16 In complex [Ru]-2, aromatic protons of
ligand L2 resonated in the range of 7.17−7.36 ppm in
comparison to the resonance observed at 6.72−7.08 ppm for
the free ligand L2. Significant downfield shifting in the singlet
for methyl protons (o-CH3 2.45 ppm) of Ru coordinated L2 in
[Ru]-2 was observed, in comparison to that for free ligand L2
(o-CH3 2.19 ppm). Analogously, for [Ru]-3, aromatic protons
corresponding to the ligand L3 resonated in the downfield
region (at 6.98(t), 6.77(d), and 2.21(s) ppm) in comparison to
those for free ligand L3. For [Ru]-4, two doublets were
observed, respectively, at 7.34 and 7.18 ppm. The p-CH3
protons of the ligand L4 in [Ru]-4 appeared as a sharp singlet
at 2.36 ppm, in comparison to 2.21 ppm in free ligand L4.
Moreover, the Ru bound η6-benezene ring resonated in the
range of 5.31−5.95 ppm for the complexes [Ru]-2−[Ru]-5. 1H
NMR results clearly inferred a significant downfield shift in the
protons corresponding to the coordinated ligands in compar-
ison to the free ligands that further supports the proposed
molecular identity of the complexes [Ru]-2−[Ru]-5.
The molecular structure of the representative arene-Ru(II)
complex, [Ru]-3, was confirmed by the single-crystal X-ray
diffraction study using the most appropriate crystals grown
from the slow evaporation of methanol−dichloromethane
solution of the complex [Ru]-3. The complex [Ru]-3
crystallizes in the trigonal crystal system with R3 space group.
̅
The solid-state structure of the complex [Ru]-3, as shown in
Figure 1, clearly demonstrated that 2,6-dimethylaniline (L3)
coordinated to the metal center through the nitrogen atom.
Analogous to our previously reported X-ray diffraction study of
the complex [Ru]-1,15a the ruthenium center in the complex
[Ru]-3 also adopted the pseudo-octahedral geometry, where
the η6-benzene ring remains planar as a top and the coordinated
ligand (L3) along with two chloro ligands as three legs. The
ruthenium center is displaced by 1.661 Å from the centroid of
C
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Table 1. Crystal Data and Structure Refinement for Complex
[Ru]-3
Table 2. Optimization of Reaction Conditions for the
Ruthenium-Catalyzed Aqueous−Aerobic Homocoupling of
a
Phenylboronic Acid
crystal parameter
empirical formula
crystal data
C14H17Cl2NRu
formula weight
temperature (K)
wavelength (Å)
crystal system, space group
a (Å)
371.26
293(2)
1.54184
jl
sel. (%) ,
trigonal, R3
̅
31.3000(16)
31.3000(16)
8.6405(4)
temp/time
(oC/h)
conv
j
entry
base
(%)
2a
3a
b (Å)
1
Na2CO3
without base
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
70/4
70/4
70/4
70/4
60/4
rt/4
99
16
99
47
53
c (Å)
k
2
traces
63
−
α (deg)
90
b
3
37
β (deg)
90
bc
,
i
4
−
γ (deg)
volume (Å3)
Z, calculated density (mg/m3)
adsorption coefficient (μ) (mm−1
F (000)
crystal size (mm3)
θ range for data collection (deg)
index ranges
120
b
5
91
30
70
7330.9(10)
b
k
6
bd
6
traces
−
18, 1.514
i
,
7
8
9
70/4
70/4
70/4
70/4
70/4
−
)
10.662
be
k
,
3
99
99
99
traces
35
−
3348
bf
,
65
20
20
0.32 × 0.08 × 0.07
4.89−73.12
−38 ≤ h ≤ 26
−38 ≤ k ≤ 36
−10 ≤ l ≤ 3
5757
bg
,
10
bgh
80 (41)
80 (67)
,
,
11
a
Reaction conditions: 1a (1.0 mmol), base (2.0 mmol), cat. [Ru]-1
b
(2.5 mol %), water (5 mL). Water (4.7 mL) with added methanol
c
d
e
(0.3 mL). Without catalyst. With N2 atmosphere. Cat. [(η6-
reflns collected
f
benzene)Ru(PPh3)Cl2] (2.5 mol %). Cat. [{(η6-benzene)RuCl2}2]
indep reflns
3272 [R(int) = 0.0292]
99.7%
g
h
(1.25 mol %). With additive Cu(OAc)2 (1.5 mmol). Cat. [Ru]-1 (5
mol %). No reaction. Conversion of phenylboronic acid and
selectivity on the basis of H NMR and isolated yield in parentheses.
Not detected. Isolated yield of purified products obtained from
completeness to θ = 67.684°
absorption correction
max and min transmission
refinement method
data/restraints/parameters
GOF on F2
i
j
semiempirical from equivalents
0.474 and 0.413
full-matrix least-squares on F2
3272/0/165
1
k
l
column chromatography is given in parentheses.
1.039
(67% for biphenyl 2a, Table 2, entry 11). This is presumably at
higher catalyst loading when unwanted side reactions (e.g.,
protodeboronation or polymerization reaction or decomposi-
tion of arylboronic acid) considerably subside.5b,18−20 Further,
the amount of Cu(OAc)2 was also optimized by evaluating the
catalytic reaction carried out with varying amounts of
Cu(OAc)2 (0.1−1.5 equiv) (Table S5). Results inferred that
a lower content of Cu(OAc)2 resulted in poor yields of
biphenyl. Notably, reactions performed without using Cu-
(OAc)2 or the base (Na2CO3) resulted in very poor yield, 20%
and 10%, respectively. Hence, with the best optimized
conditions, further experiments were performed in air using 5
mol % Ru catalysts in the presence of 2 equiv of Na2CO3 and
1.5 equiv of Cu(OAc)2.
Further, [Ru]-1 catalyst also showed good tolerance for
various substituted arylboronic acids (Table 3, entries 1−7).
The initial substrate screening experiments indicated that
electron-rich p-CH3 (1b)- and p-OCH3 (1c)-substituted
phenylboronic acid resulted in higher isolated yield (55% and
68%) for corresponding biaryl products, 2b and 2c,
respectively, and thereby presumably suggesting an electroni-
cally influenced catalytic reaction where the electron-rich
arylboronic acid generates better nucleophiles (Table 3, entries
2 and 3). Conversely, electron-withdrawing substitutes, p-Cl-
(1d) and p-F- (1e), on phenylboronic acid resulted in relatively
lower isolated yield (54% and 36%) for biaryl products, 2d and
2e, respectively (Table 3, entries 4 and 5). Structural analogues
of 1b and 1c, but with electron-withdrawing substituents,
showed complete conversion with higher yields for correspond-
ing homocoupled products. With p-OCF3-substituted phenyl-
boronic acid (1f), 68% yield for 4,4′-(trifluoromethoxy)-
biphenyl (2f) was achieved (Table 3, entry 6). Analogously,
final R indices [I > 2σ(I)]
R indices (all data)
R1 = 0.0355, wR2 = 0.0840
R1 = 0.0455, wR2 = 0.0883
0.438 and −0.760
largest diff. peak and hole (e Å−3
)
6% conversion was observed (Table 2, entries 5 and 6).
Moreover, the role of aerobic condition was also found to be
essential for the catalytic reaction, as no conversion of 1a was
observed for the reaction performed under N2 atmosphere
(Table 2, entry 7, and Table S5).17 It is worth mentioning that
[(η6-benzene)Ru(PPh3)Cl2] was found to be poorly active
(Table 2, entry 8), suggesting the inhibitory role of PPh3.14a
Moreover, [{(η6-benzene)RuCl2}2] also resulted in low
selectivity for biphenyl (Table 2, entry 9), indicating the
crucial role of the aniline ligand to control the selectivity of the
products. Please refer to later sections for further discussion on
the effect of aniline ligands on the catalytic homocoupling
reactions. In our further investigation, we also performed
experiments in the optimized reaction condition with an
additive, Cu(OAc)2 (Table 2, entry 10). Advantageously, the
selectivity toward biphenyl was significantly enhanced to 80%,
suggesting the crucial role of Cu(OAc)2 as an oxidant to
regenerate the Ru(II) species and retard catalyst decomposition
during the catalytic cycle (Scheme S1).4e,5,17 However,
complete selectivity for biphenyl could not be achieved,
presumably because the protic solvents facilitate phenol
formation.5e,6b Despite high conversion of phenylboronic acid
with good selectivity for homocoupled product observed with
2.5 mol % Ru catalyst, low isolated yields (41%) were obtained
for biphenyl 2a (Table 2, entry 10). However, reaction
performed with 5 mol % Ru catalyst resulted in the
enhancement of isolated yield of the homocoupled product
D
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Table 3. Catalytic Conversion of Various Substituted Arylboronic Acids to Corresponding Symmetrical Biaryls in the Presence
a
of [Ru]-1 Catalyst
a
Reaction conditions: 1 (1.0 mmol), Na2CO3 (2.0 mmol), [Ru]-1 (5 mol %), additive Cu(OAc)2 (1.5 mmol), water (4.7 mL) with added methanol
b
c
1
(0.3 mL), T = 70 °C. Conversion of 1a−1g and selectivity for 2a−2g and 3a−3g, respectively, as determined by H NMR. Isolated yield of
purified biaryl (2a−2g) products obtained from column chromatography is given in parentheses.
with p-CF3-phenylboronic acid (1g), corresponding homo-
coupled product, 4,4′-(trifluoromethyl)biphenyl (2g), was
achieved in 60% yield (Table 3, entry 7). In contrary to the
above, protodeboronation was observed for the reactions with
4-hydroxyphenylboronic acid, 1-naphthylboronic acid, and 2-
biphenylboronic acid.18−20
Figure 2 displayed biaryl (2a−2e) yields for the catalytic
conversion of 1a−1e in the presence of [Ru]-1−[Ru]-5
catalysts. As inferred from Figure 2, [Ru]-3 catalyst containing
sterically hindered 2,6-dimethylaniline ligand resulted in lower
selectivity for biaryls in comparison to [Ru]-1. Presumably, the
sterically hindered 2,6-dimethylaniline retarded the formation
of crucial di(σ-aryl)-Ru species. Moreover, reaction with [Ru]-
5, containing electron-withdrawing p-chloro-substituted aniline
ligand, also displayed lower selectivity for biaryls. Catalytic
reaction with [Ru]-2−[Ru]-5 also displayed moderately higher
yields (36−66%) toward respective biaryl products (2b−2c) of
the arylboronic acids with p-substituted electron-donating
groups −CH3 (1b) and −OCH3 (1c), in comparison to
those with electron-withdrawing substituents, p-Cl (1d) and p-
F (1e) (25−47%) (Table S7).
Encouraged by the results for facile homocoupling reaction
of a wide range of arylboronic acids catalyzed by ruthenium
catalysts, we further intended to find out the chemoselectivity
of coupled products between two different arylboronic acids.
Under optimized reaction conditions, reactions were performed
using an equimolar ratio of two distinct arylboronic acids
(Scheme 3), and selectivities toward the homo- and cross-
coupled biaryls were determined by GC−MS (Figures S2−S4).
Results inferred that the reaction of 4-methylphenylboronic
acid (1b) with 4-methoxyphenylboronic acid (1c) showed
higher selectivity for the formation of cross-coupled product
(50% for 4-methyl-4′-methoxy-1,1′-biphenyl, 2bc) along with
the homocoupled products of both of the arylboronic acids
After having the best optimized reaction conditions, we
investigated the effect of the substituents at the aniline ligands
(L1−L5) on the catalytic performance of the resulting arene-
Ru(II) catalysts, [Ru]-1−[Ru]-5, for the homocoupling of 1a
to obtain 2a. Among the studied arene-Ru(II) catalysts, aniline-
coordinating ruthenium catalyst, [Ru]-1, was found to be
highly active, as illustrated by the observed high conversion and
yield for 2a (67%). Conversely, arene-Ru(II) catalysts, [Ru]-2,
[Ru]-4, and [Ru]-5, bearing ortho-/para-substituted CH3- or
Cl-anilines, could not furnish any improvement in the
selectivity of the desired biphenyl product (2a). Moreover,
[Ru]-3 catalyst, containing sterically hindered 2,6-dimethylani-
line ligand, also resulted in lower selectivity for 2a (Figure 2
and Table S6). To investigate further the effect of [Ru]-1−
[Ru]-5 catalysts, experiments were performed with all of the
arene-Ru(II) catalysts for a range of p-substituted phenyl-
boronic acids containing electron-donating groups, −CH3 (1b)
and −OCH3 (1c), and electron-withdrawing groups, −Cl (1d)
and −F (1e) (Figure 2 and Table S7). The trend of relative
catalytic performance of all of the catalysts observed with 1a
also persists for the catalytic homocoupling of p-substituted
phenylboronic acid (1b−1e).
E
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Figure 2. Influence of (5 mol %) arene-Ru(II) catalysts, [Ru]-1−[Ru]-5, on the yield of biaryls (2a−2e) for the catalytic homocoupling of
arylboronic acids (1a−1e) at 70 °C.
Scheme 3. Competitive C−C Coupling Reactions of Different Arylboronic Acids As Catalyzed by [Ru]-1 Catalyst
F
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Figure 3. Mass spectral analysis for the identification of σ-aryl-Ru intermediate species of the [Ru]-catalyzed homocoupling reaction of (a) p-
methylphenylboronic acid (1b) and (b) p-chlorophenylboronic acid (1d).
(41% for 4,4′-dimethylbiphenyl (2b) and 9% for 4,4′-
methoxybiphenyl (2c)). Analogously, selectivity toward the
cross-coupled product, 4-methyl-4′-methoxybiphenyl (2bd),
was found to be higher (47%) for the reaction of 4-
methylphenylboronic acid (1b) and 4-chlorophenylboronic
acid (1d). Relative selectivities for corresponding homocoupled
products, 4,4′-dimethylbiphenyl (2b) and 4,4′-dichlorobiphenyl
(2d), were 25% and 27%, respectively. Moreover, for the
reaction between 4-methylphenylboronic acid (1b) and 4-
trifluoromethylphenylboronic acid (1g), 43% selectivity for
cross-coupled product 4-methyl-4′-(trifluoromethyl)-1,1′-bi-
phenyl (2bg) was achieved along with the respective
homocoupled products, 2b and 2g.
Stability checks of the catalysts [Ru]-1−[Ru]-5 were
performed by thermal gravimetric analysis (TGA) and 1H
NMR experiments. TGA results inferred that all of the catalysts
exhibit good thermal stability up to ca. 160 °C (Figure S5).
Moreover, remarkable stability of these catalysts toward air and
water was also observed during the course of the catalytic
reactions. To further examine the stability of the active
catalysts, [Ru]-1 catalyst heated at 70 °C for an extended
period of time (4, 12, and 24 h) was analyzed by 1H NMR. 1H
NMR results inferred that the catalyst remains stable even after
24 h of heating at 70 °C in water with no significant
decomposition of the catalyst (Figure S6).
after 30 min by ESI−mass spectrometry. In the mass spectra of
[Ru]-2 catalyst with p-methylphenylboronic acid (1b), several
new species corresponding to the σ-aryl-Ru moieties, [(η6-
benzene)Ru(σ-C6H4CH3)(CH3CN)2]+ (m/z 353.04), [(η6-
benzene)Ru(σ-C6H4CH3)(CH3CN)]+ (m/z 312.02), [(η6-
benzene)Ru(σ-C6H4CH3)]+ (m/z 270.99), were observed in
positive mode (Figure 3). The observed mass spectral patterns
of various σ-aryl-Ru moieties match well with their simulated
mass patterns (Figure S7). A similar mass spectral pattern with
σ-aryl-Ru moieties, [(η6-benzene)Ru(σ-C6H4Cl)(CH3CN)2]
(m/z 372.99), [(η6-benzene)Ru(σ-C6H4Cl)(CH3CN)]+ (m/z
331.97), [(η6-benzene)Ru(σ-C6H4Cl)]+ (m/z 290.94), was also
observed for the reaction of [Ru-2] with p-chlorophenylbor-
onic acid (1d) (Figure 3 and Figure S7).
Moreover, in the course of reaction, it was observed that
ligand effect significantly controls the selectivity of the
homocoupled product. Evidence for the presence of ligand
bound σ-aryl-Ru intermediates was further confirmed by mass
spectrometry while analyzing the negative mode mass spectra
of the above reaction mixture (Figure 4 and Figure S8). For p-
methylphenylboronic acid, a fragment observed at m/z =
489.55 was assigned to a ligand bound di(σ-aryl)-Ru species,
Mechanistic Studies. Encouraged by the unique catalytic
activity of arene-Ru(II)-catalyzed homocoupling of arylboronic
acids, we attempted to systematically investigate and identify
possible reaction pathway. The identification and character-
ization of key intermediates of the homocoupling reaction is
crucial to gain more understanding for the development of
active catalysts. Therefore, the evidence for the formation of σ-
aryl-Ru/di(σ-aryl)-Ru intermediates was confirmed by mass
spectrometry and NMR spectroscopy. These σ-aryl organo-
metallic species are regarded as key intermediates in the
homocoupling reaction.7f,14 [Ru]-2 catalyst was mixed with
arylboronic acid (p-methylphenylboronic acid (1b) or 4-
chlorobnzeneboronic acid (1d)) in varying catalyst to substrate
(C:S) molar ratios of 1:1, 1:2, and 2:1 in acetonitrile with
triethylamine added, and the reaction mixture was analyzed
Figure 4. Mass spectral analysis of di(σ-aryl)-Ru species, key
intermediates in the catalytic homocoupling of arylboronic acids,
with the [Ru]-2 catalyst, obtained in the presence of 2.0 equiv excess
of (a) p-methylphenylboronic acid (1b) and (b) p-chlorophenylbor-
onic acid (1d) in acetonitrile.
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[{(η6-benzene)Ru(σ-C6H4CH3)2(L2)} + Na − 2H]− (L2 = o-
methylaniline). Reaction with p-chlorophenylboronic acid also
showed analogous di(σ-aryl)-Ru species at m/z = 571.36
corresponding to [{(η6-benzene)Ru(σ-C6H4Cl)2(L2)} +
CH3CN + Na − 2H]−.
To further extend our study on identification of the possible
reaction intermediates, we also performed mass spectral
analysis under the optimized catalytic reaction condition in
water. Analogous to that observed with the stoichiometric
reactions of catalyst with arylboronic acid in acetonitrile (as
discussed above), interestingly, we also observed several
important σ-aryl-Ru and di(σ-aryl)-Ru intermediate species
during the course of the catalytic reaction. As shown in Figure
5, mass spectral analysis of the homocoupling of phenylboronic
with the respective species generated after the loss of the ligand,
[(η6-benzene)Ru(σ-C6H4CH3)2] (m/z = 363.09), and, more-
over, ligand bound mono σ-aryl-Ru intermediate, [(η6-
benzene)Ru(σ-C6H4CH3)(L1)(CH3CN)]+ (m/z = 407.11).
The observed mass spectral patterns for these intermediate
species are in good agreement with their simulated mass
spectral patterns (Figure S9).
We further explored the mass spectral analysis of the
homocoupling of phenylboronic acid (1a) and p-methylphe-
nylboronic acid (1b) in the presence of [Ru]-4 and [Ru]-5
catalysts, to investigate if the analogous ligand bound
intermediates were generated during the catalytic reaction,
also with these catalysts. Analogous to the mass spectral
analysis of [Ru]-1-catalyzed reaction, we also observed similar
ligand coordinated di(σ-aryl)-Ru species, [(η6-benzene)Ru(σ−
C6H5)2(L4)] (m/z = 441.10) (L4 = p-methylaniline) and
mono(σ-aryl)-Ru species [(η6-benzene)Ru(σ-C6H5)(L4)-
(CH3CN)]+ (m/z = 404.97), for homocoupling reaction of
phenylboronic acid (1a) and [(η6-benzene)Ru(σ-
C6H5CH3)2(L4)] (m/z = 469.15) and mono(σ-aryl)-Ru
species [(η6-benzene)Ru(σ-C6H5CH3)(L4)(CH3CN)]+ (m/z
= 419.01), for homocoupling reaction of p-methylphenylbor-
onic acid (1b) with [Ru]-4 catalyst (Figure S10). Analogous
intermediates were also observed during the mass spectral
analysis for the catalytic homocoupling of 1a and 1b in the
presence of [Ru]-5 catalyst (Figure S11).
To further strengthen our understanding based on the
identification of several σ-aryl-Ru species by mass spectrometry,
we aimed to obtain similar σ-aryl-Ru intermediates by 19F NMR
spectroscopy using 4-fluorophenylboronic acid (1e) and 4-
trifluoromethylphenylboronic acid (1g) substrates with the
ruthenium catalyst [Ru]-2 in a C:S ratio of 1:2 in CDCl3
solvent. The 19F NMR spectra revealed that peaks correspond-
ing to both reactants were missing, but some new peaks were
observed in the range of corresponding σ-aryl Ru species. In the
19F NMR spectrum for [Ru]-2 catalyst with 4-fluorophenylbor-
onic acid (1e), a new peak observed at δ = −115.799 ppm was
attributed to σ-4-fluorophenyl coordinated Ru species, [(η6-
benzene)Ru(σ-C6H4F)], along with the two resonances that
appeared at δ = −123.430 and −125.931 ppm assigned to 4,4′-
difluorobiphenyl (2e) and 4-fluorophenol (3e), respectively
(Figure S12). For [Ru]-2 catalyst with 4-trifluoromethylphe-
nylboronic acid (1g), the 19F NMR spectrum analogously
showed a resonance corresponding to σ-4-trifluoromethylphen-
yl coordinated Ru species, [(η6-benzene)Ru(σ-C6H4CF3)] at δ
= −61.859 ppm (Figure 6). The other two resonances at
−62.597 and −62.761 ppm were attributed to 4,4′-trifluor-
omethylbiphenyl and 4-trifluoromethylphenyl, respectively
(Figure S13).21 Moreover, we also observed ligand bound σ-
aryl-Ru intermediate, [{(η6-benzene)Ru(σ-C6H4CF3)(Et3N)} +
Na]+ (m/z 450.1) in the mass spectral analyses of the
acetonitrile solution of [Ru]-2 catalyst and 4-trifluoromethyl-
phenylboronic acid in the presence of trimethylamine (Figure
6).
Figure 5. Mass spectral analysis for the identification of σ-aryl-Ru
intermediate species generated for the homocoupling of p-methyl-
phenylboronic acid (1b) in the presence of [Ru]-1 catalyst under
catalytic reaction condition.
acid (1a) in the presence of [Ru]-1 catalyst displayed the
formation of key di(σ-ryl)-Ru intermediates, [(η6-benzene)Ru-
(σ-C6H5)2(L1)] (m/z = 427.05), (L1 = aniline) where the
aniline ligand remains intact. Appearance of such ligand bound
di(σ-aryl)-Ru species during the catalytic reaction (analyzed at
0.5, 1.5, and 3.0 h) further supports the decisive role of the
aniline-based ligand to tune the selectivity of biaryls. However,
along with the above, ligand bound mono σ-aryl-Ru species,
[(η6-benzene)Ru(σ-C6H5)(L1) (CH3CN)]+ (m/z = 390.97)
and their respective di(σ-aryl)-Ru species formed by the loss of
ligand, [(η6-benzene)Ru(σ-C6H5)2] (m/z = 335.03), were also
observed during the mass spectral analysis of the catalytic
reaction. We also analyzed the catalytic homocoupling reaction
of p-methylphenylboronic acid (1b) by mass spectrometry to
identify analogous ligand bound di(σ-aryl)-Ru species during
the course of the catalytic reaction. Interestingly, the respective
ligand bound di(σ-aryl)-Ru intermediate, [(η6-benzene)Ru(σ-
C6H4CH3)2(L1)] (m/z = 455.23), was also identified, along
Catalytic reaction of various ruthenium catalysts [Ru]-1−
[Ru]-5 studied inferred that there is a significant ligand effect to
influence the selectivity of the homocoupled product. More-
over, several ligands coordinated mono/di(σ-aryl)-Ru inter-
mediates have been observed during mass spectral analysis,
suggesting that presumably aniline ligands remain coordinated
with the ruthenium metal during the catalytic reaction.
Comparing the catalytic performance of the (η6-arene)-
Ru(II)-aniline catalyst ([Ru]-1) to those of the arene-
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effect of the coordinating aniline ligands was observed on the
selectivity toward biaryls, where [Ru]-2 containing o-methyl
substitution, [Ru]-3 containing sterically hindered 2,6-dimethyl
aniline, or [Ru]-5 containing electron-withdrawing p-chloroani-
line resulted in the lower selectivity for biaryls, while other
complexes containing aniline ([Ru]-1) and 4-methylaniline
([Ru]-4) showed higher selectivity for biaryls. This was further
supported by the identification of several ligand bound σ-aryl-
Ru and di(σ-aryl)-Ru intermediates by mass spectral and 19F
NMR studies of the catalytic reaction. The formation of di(σ-
aryl)-Ru species during the catalytic reaction is crucial and is
expected to be a key intermediate of the formation of biaryl by
Ru-catalyzed homocoupling of arylboronic acids. We believe
that the present study will subsequently contribute in
enhancing the mechanistic understanding of Ru-catalyzed
homocoupling and other related reactions.
Figure 6. (a)19F NMR and (b) mass spectral evidence for σ-aryl-Ru
species generated during the homocoupling reaction of p-trifluor-
omethylphenylboronic acid in the presence of [Ru]-2 catalyst.
EXPERIMENTAL SECTION
■
Materials and Instrumentation. All reactions were performed in
aerobic conditions using the high-purity chemicals procured from
Sigma-Aldrich and Alfa Aesar. Ruthenium arene precursor, [{(η6-
benzene)RuCl2}2], was synthesized as per the reported procedure.23
Aniline-based ligands were purchased from Alfa Aesar and used as
received for the catalysts synthesis without further purification.
Progress of catalytic reactions was monitored using thin layer
chromatography (TLC). 1H NMR (400 MHz), 13C NMR (100
MHz), and 19F NMR (376.5 MHz) spectra were recorded at 298 K
using CDCl3 and DMSO-d6 as solvents on a Bruker Avance 400
spectrometer. Tetramethylsilane (TMS) was used as an external
standard for measuring the chemical shifts (in ppm), which are relative
to the center of the singlet at 7.26 ppm for CDCl3 and 2.49 ppm for
DMSO-d6 in 1H NMR and to the center of the triplet at 77.0 ppm for
CDCl3 and 39.50 ppm for DMSO-d6 in 13C NMR, respectively.
Coupling constant (J) values are reported in hertz (Hz), and the
splitting patterns are designated as follows: s (singlet); d (doublet); t
(triplet); m (multiplet); br (broad). Thermo Scientific FLASH 2000
elemental analyzer aided the elemental analysis of the complex. ESI−
mass spectra were recorded on a micrOTF-Q II mass spectrometer.
GC−MS analysis was performed on a Shimadzu GCMS-QP2010 Ultra
and GC-2010 Plus system in EI (electron impact) mode using Rtx-
5MS column. Thermal gravimetric analyses (TGA) were performed
on the Mettler Toledo thermal analysis system.
Single-Crystal X-ray Diffraction Studies. Single-crystal X-ray
structure studies of [Ru]-3 and [Ru]-4 were executed on a CCD
Agilent Technologies (Oxford Diffraction) SUPER NOVA diffrac-
tometer. Using graphite-monochromated Cu Kα radiation (λ =
1.54184 Å)-based diffraction, data were collected at 293(2) K by the
standard “phi-omega” scan techniques, and were scaled and reduced
using CrysAlisPro RED software. The extracted data were evaluated
using the CrysAlisPro CCD software. The structures were solved by
direct methods using SHELXS-97, and refined by full matrix least-
squares with SHELXL-97, refining on F2.24 The positions of all of the
atoms were determined by direct methods. X-ray data for [Ru]-4
complex were found to be abnormal and could not be refined to attain
suitable parameters to report. However, the X-ray data give a clear
indication for Ru-coordinated p-methylaniline. All non-hydrogen
atoms were refined anisotropically. The remaining hydrogen atoms
were placed in geometrically constrained positions, and refined with
isotropic temperature factors, generally 1.2Ueq of their parent atoms.
The CCDC number 1442036 contains the supplementary crystallo-
graphic data for [Ru]-3. These data are freely available at www.ccdc.
cam.ac.uk (or can be procured from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB21 EZ, UK; fax: (+44)
1223-336-033; or deposit@ccdc.cam.ac.uk).
ruthenium dimer, the positive effect of the ruthenium
coordinated aniline ligand on the observed high selectivity for
the homocoupled product is apparently visible. Results inferred
a significant enhancement in the selectivity of biphenyl product
while performing the catalytic reaction with arene-ruthenium
dimer with added aniline ligand (Table S8). However, the
enhancement was not as par with the corresponding
ruthenium-aniline catalyst, further indicating that the pre-
formed ruthenium−aniline bond is a crucial structural require-
ment in the catalyst to achieve high activity. The catalytic
reactions were also performed with ruthenium benzene dimer
with added p-methylaniline (L4) and p-chloroaniline (L5),
respectively, and the results show the superiority of the
respective arene-Ru(II) complexes with coordinated aniline-
based ligands, [Ru]-4 and [Ru]-5, over the reaction using
arene-ruthenium dimer precursors with added free aniline for
synthesis of biaryls.
A tentative mechanism for the homocoupling of arylboronic
acids to biaryls can therefore be proposed on the basis of
several important intermediates, particularly ligand bound di(σ-
aryl)-Ru species (Figures 3−6, and Figures S7 and S9) of the
catalytic cycle identified in the reaction mixture using ESI−MS
and 19F NMR spectral analysis (Scheme S2). The reactive
ruthenium catalysts ([Ru]) reacted with arylboronic acid (1) to
form a transmetalated σ-aryl-Ru(II) intermediate ([Ru]-x′).
Subsequently, the second molecule of arylboronic acid (1) also
reacted with the intermediate ([Ru]-x′) to form another
transmetalated di(σ-aryl)-Ru(II) intermediate ([Ru]-xx′).7f
Finally, the oxidatively coupled product, biaryl (2), was
released by reductive elimination and resulted in the formation
of Ru(0) species. This species is further oxidized by an oxidant
(aerial O2 and Cu(OAc)2) to regenerate the active ruthenium
species Ru(II) (Scheme S1).4e,17,22
CONCLUSION
■
In summary, we have developed a highly water-soluble
molecular catalyst based on arene-Ru(II) complexes, [Ru]-1−
[Ru]-5, containing readily available aniline ligands, L1−L5.
High aqueous solubility and aqueous−aerobic stability of these
molecular catalysts led us to explore their catalytic activity for
the homocoupling of arylboronic acids to corresponding biaryls
in water under moderate reaction conditions. A remarkable
General Procedure for the Synthesis of Complexes [Ru]-2−
[Ru]-5. Treatment of dichloro bridged arene-ruthenium dimer (0.5
mmol) and suitable substituted aniline as a ligand (1.05 mmol) in
methanol (100 mL) under refluxing condition for 24 h resulted in the
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formation of the orange to brown color solution.15a The solution was
filtered through the crucible, and then the solution was dried over a
rotary evaporator to obtain brown precipitate. Further, the precipitate
was dissolved in a mixture of methanol and dichloromethane (1:1 v/v,
10 mL), and kept at room temperature overnight to obtain the
crystalline form of the complex. The obtained crystalline complex was
separated from the mother liquor and washed again with hexane and
diethyl ether 4−5 times. The identity of resulting complex was
assessed using 1H NMR, 13C NMR, mass spectroscopy, CHN
elemental analysis, and single-crystal XRD study.
layer chromatography (TLC). After the reaction, the reaction mixture
was quenched with 1 M solution of HCl (5 mL), and then extracted
with ethyl acetate (4 × 10 mL), the organic layer was dried over
anhydrous Na2SO4, and further the solvent was evaporated under
reduced pressure to get the desired product. The reaction
1
intermediates and products were identified by H NMR, 13C NMR,
ESI−MS, and GC−MS. The conversion and selectivities of the
1
products were obtained by H NMR. Isolated yield was calculated by
using column chromatography with n-hexane:ethyl acetate (99:1 or
95:5 v/v on the basis of polarity of desired product) as eluent.
General Procedure for the Competitive C−C Coupling
Reactions of Different Arylboronic Acids To Form Symmetrical
and Asymmetrical Biaryls. The competitive C−C coupling
reactions of different arylboronic acids to obtain homocoupled and
cross-coupled biaryls were carried out in open atmospheric conditions
with a procedure identical to that used for the homocoupling of
arylboronic acids. For this, two different arylboronic acids (0.5 mmol
each) with sodium carbonate (0.210 g, 2 mmol) and Cu(OAc)2 (0.300
g, 1.5 mmol) were added to a reaction tube containing water (4.7 mL)
with methanol (0.3 mL) solution of the [Ru]-1 catalyst (0.017 g, 5
mol %). The reaction mixture was stirred for the desired reaction time
at 70 °C in an oil bath. After the reaction, reaction mixture was
quenched with 1 M solution of HCl (5 mL), and then extracted with
ethyl acetate (4 × 10 mL), organic layer was dried over anhydrous
Na2SO4, and further the solvent was evaporated under reduced
pressure to get the desired product. The ratio of homo- and cross-
coupled products was calculated with the aid of GC−MS analysis.
Mass Spectrometric Analysis of Catalytic Homocoupling of
a 2 equiv Excess of p-Methylphenylboronic acid (1b) and p-
Chlorophenylboronic Acid (1d) in Acetonitrile. [Ru]-2 was
added to p-methylphenylboronic acid (1b) or p-chlorophenylboronic
acid (1d) (C:S ratio 1:1, 1:2, and 2:1) in acetonitrile (10 mL) followed
by Et3N (2 μL). The reaction mixture was then sonicated for 5 min
and analyzed by mass spectrometry.
Mass Spectrometric Analysis of Catalytic Homocoupling
Reaction of Phenylboronic Acid (1a) and p-Methylphenylbor-
onic Acid (1b), Respectively, in the Presence of [Ru]-1, [Ru]-4,
and [Ru]-5 Catalysts under Optimized Reaction Conditions.
For this experiment, a 100 μL aliquot was taken out of reaction
mixture at the intervals of 0.5, 1.5, and 3 h, for 1a, and 2, 4, and 6 h, for
1b, during the catalytic homocoupling reaction of arylboronicacids
with C:S ratio 1:40 in the presence of complexes [Ru]-1, [Ru]-4, and
[Ru]-5, respectively, under the optimized reaction conditions. To the
aliquot of the reaction mixture was added 2 mL of acetonitrile, and the
mixture was centrifuged to obtain the clear solution, which was
analyzed by mass spectrometry.
Synthesis of [(η6-Benzene)RuCl2(2-methylaniline)] ([Ru]-2). The
complex [Ru]-2 was synthesized following the above general
procedure, using [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol) as
ruthenium precursor, and the ligand 2-methylaniline (112 μL, 1.05
mmol) with 100 mL of methanol as solvent. Orange-brown color,
yield: 87% (0.279 g). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.36−
7.28 (m, 3H), 7.17 (t, 1H, J = 8 Hz), 5.31 (s, 6H), 4.79 (br, 2H), 2.45
(s, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm) = 143.78, 131.52,
127.51, 125.93, 120.17, 83.06, 17.74. MS (ESI) m/z calculated for
[(η6-benzene)RuCl2(2-methylaniline)]: 321.79 [M − Cl]+, found
322.00 [M − Cl]+. Anal. Calcd for [Ru]-2: C, 43.71; H, 4.23; N, 3.92.
Found: C, 43.89; H, 3.99; N, 3.44.
Synthesis of Complex [(η6-Benzene)RuCl2(2,6-dimethylaniline)]
([Ru]-3). The complex [Ru]-3 was synthesized following the above
general procedure, using [{(η6-benzene)RuCl2}2] (0.250 g, 0.5 mmol)
as ruthenium precursor, and the ligand 2,6-dimethylaniline (130 μL,
1.05 mmol) with 100 mL of methanol as solvent. Orange color, yield:
89% (0.267 g). X-ray quality orange colored crystals were grown from
the slow evaporation of the solution of [Ru]-3 complex in a mixture of
1
methanol−dichloromethane (1:1 v/v) with diethyl ether added. H
NMR (400 MHz, DMSO-d6): δ (ppm) = 6.77 (d, 2H, J = 8 Hz), 6.38
(t, 1H, J = 8 Hz), 5.95 (s, 6H), 4.44 (br., 2H), 2.05 (s, 6H). 13C NMR
(100 MHz, DMSO-d6): δ (ppm) = 127.71, 120.52, 115.78, 87.64,
30.68, 17.77. MS (ESI) m/z calculated for [(η6-benzene)RuCl2(2,6-
dimethylaniline)]: 301.04 [M − 2Cl]2+, found 301.14 [M − 2Cl]2+.
Anal. Calcd for [Ru]-3: C, 45.29; H, 4.62; N, 3.77. Found: C, 45.47;
H, 4.46; N, 3.50.
Synthesis of Complex [(η6-Benzene)RuCl2(4-methylaniline)]([Ru]-
4). The complex [Ru]-4 was synthesized following the above general
procedure, using [{(η6-C6H6)RuCl2}2] (0.250 g, 0.5 mmol) as
ruthenium precursor, and the ligand 4-methylaniline (112 μL, 1.05
mmol) with 100 mL of methanol as solvent. Orange color, yield: 86%
(0.276 g). X-ray quality orange colored crystals were grown from the
slow evaporation of the solution of [Ru]-4 complex in a mixture of
1
methanol−dichloromethane (1:1 v/v) with diethyl ether added. H
19F NMR Spectral Analysis of the Catalytic Homocoupling
Reaction of 4-Trifluoromethylphenylboronic Acid (1f). [Ru]-2
and 4-trifluoromethylphenylboronic acid (1f) (C:S ratio = 1:2) were
added in CDCl3 (500 μL) followed by Et3N (2 μL). The 19F NMR
spectrum was recorded for the solution to observe the σ-aryl-Ru
intermediate.
Mass Spectral Analysis of Catalytic Homocoupling Reaction
of 4-Trifluoromethylphenylboronic Acid (1f). [Ru]-2 and 4-
trifluoromethylphenylboronic acid (1f) (C:S ratio = 1:5) were added
in THF (5 mL) followed by Et3N (5 mL), and then stirred for 2 h at
50 °C. The reaction mixture was filtered through a crucible, then the
solvent was evaporated, and the obtained solid was analyzed by mass
spectrometry.
NMR (400 MHz, CDCl3): δ (ppm) = 7.34 (d, 2H, J = 8 Hz), 7.18 (d,
2H, J = 8 Hz), 5.35 (s, 6H), 4.95 (br, 2H), 2.36 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ (ppm) = 143.10, 135.46, 130.19, 119.90, 83.14,
20.91. MS (ESI) m/z calculated for [(η6-benzene)RuCl2(4-methylani-
line)]: 321.79 [M − Cl]+, found 322.00 [M − Cl]+. Anal. Calcd for
[Ru]-4: C, 43.71; H, 4.23; N, 3.92. Found: C, 43.89; H, 3.99; N, 3.44.
Preparation of Complex [(η6-Benzene)RuCl2(4-chloroaniline)]
([Ru]-5). The complex [Ru]-5 was synthesized following the above
general procedure, using [{(η6-C6H6)RuCl2}2] (0.250 g, 0.5 mmol) as
ruthenium precursor, and the ligand 4-chloroaniline (0.134 g, 1.05
mmol) with 100 mL of methanol as solvent. Orange-brown color,
yield: 84% (0.287 g). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.40−
7.32 (m, 4H), 5.38 (s, 6H), 4.83 (br, 2H). MS (ESI) m/z calculated
for [(η6-benzene)RuCl2(4-chloroaniline)]: 341.94 [M − Cl]+, found
340.12 [M − Cl]+. Anal. Calcd for [Ru]-5: C, 38.16; H, 3.20; N, 3.71.
Found: C, 38.22; H, 3.09; N, 3.49.
ASSOCIATED CONTENT
■
General Procedure for the Homocoupling of Arylboronic
Acids To Form Biaryls. The ruthenium-catalyzed homocoupling of
arylboronic acids to obtain symmetrical biaryls was carried out in open
atmospheric conditions. For this, arylboronic acid (1 mmol) with
sodium carbonate (0.210 g, 2 mmol) and Cu(OAc)2 (0.300 g, 1.5
mmol) was added to a reaction tube containing water (4.7 mL) with
methanol (0.3 mL) solution of the [Ru]-catalyst (0.017 g, 5 mol %).
The reaction mixture was stirred for the desired reaction time at 70 °C
in an oil bath. The progress of the reaction was monitored by thin
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.6b01115.
Additional tables, figures, schemes, NMR spectra and
data, GC−MS spectra, and references (PDF)
X-ray data for compound [Ru]-3 (CIF)
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lez-Arellano, C.; Corma, A.; Iglesias, M.; San
́
chez, F. Chem. Commun.
AUTHOR INFORMATION
Corresponding Author
*E-mail: sksingh@iiti.ac.in.
Notes
■
2005, 1990−1992. (d) Wang, L.; Zhang, W.; Su, D. S.; Meng, X.; Xiao,
F.-S. Chem. Commun. 2012, 48, 5476−5478. (e) Wang, L.; Wang, H.;
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ACKNOWLEDGMENTS
■
Financial support from IIT Indore, CSIR, New Delhi
(01(2722)/13/EMR-II), and SERB-DST (SB/FT/CS-028/
2014), New Delhi, is acknowledged. SIC, IIT Indore, and
NTU Singapore are acknowledged for instrumentation
facilities. D.T. thanks UGC, New Delhi, and R.K.R. and K.G.
thank CSIR, New Delhi, for their SRF grants. C.B. thanks
MHRD and A.D.D. thanks CSIR, New Delhi [01(2722)/13/
EMR-II], for their fellowships.
̀
Serrano, J. L.; Perez, J.; García, L.; Fairlamb, I. J. S. Chem. Commun.
2014, 50, 9859−9861. (g) Fu, W. C.; Zhou, Z.; Kwong, F. Y. Org.
Chem. Front. 2016, 3, 273−276.
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