Bis(NHC)-Pd-catalyzed one-pot competitive C-C*C-C, C-C*C-O, C-C*C-N, and C-O*C-N cross-coupling reactions on an aryl di-halide catalyzed by a homogenous basic ionic liquid (TAIm[OH]) under base-free, ligand-free, and solvent-free conditions

Article abstract of DOI:10.1039/d1nj00067e

Bis(NHC)-Pd-catalyzed competitive asymmetrical C-C*C-C, C-C*C-O, C-C*C-N, and O-C*C-N cross-coupling reactions were performedviathe one-pot strategy in the presence of a new ionic liquid, which played the roles of solvent, base, and ligand simultaneously. The ionic liquid was prepared based on a methyl imidazolium moiety with hydroxyl counter anionsviaa Hofmann elimination on a 1,3,5-triazine framework (TAIm[OH]). Pd ions could be efficiently coordinated through the bis(NHC)-ligand moiety in the ionic liquid. Based on differences in the competitive kinetics of C-C cross-coupling reactions (Heck, Suzuki, and Sonogashira) with C-N and C-O cross-coupling reactions, and also differences in the kinetics of aryl halides, the coupling reactions could be selectively performed with a low amount of by-products. The competitive cross-coupling reactions were thus performed with high selectivity under mild reaction conditions.

Full text of DOI:10.1039/d1nj00067e

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Bis(NHC)-Pd-catalyzed one-pot competitive
C–C*C–C, C–C*C–O, C–C*C–N, and C–O*C–N
cross-coupling reactions on an aryl di-halide
catalyzed by a homogenous basic ionic liquid
(TAIm[OH]) under base-free, ligand-free, and
solvent-free conditions†
Cite this: New J. Chem., 2021,
45, 11662
c
Yanfang Zhu,a Guiyang Xu*b and Milad Kazemnejadi
*
Bis(NHC)-Pd-catalyzed competitive asymmetrical C–C*C–C, C–C*C–O, C–C*C–N, and O–C*C–N
cross-coupling reactions were performed via the one-pot strategy in the presence of a new ionic liquid,
which played the roles of solvent, base, and ligand simultaneously. The ionic liquid was prepared based
on a methyl imidazolium moiety with hydroxyl counter anions via a Hofmann elimination on a 1,3,5-
triazine framework (TAIm[OH]). Pd ions could be efficiently coordinated through the bis(NHC)-ligand
moiety in the ionic liquid. Based on differences in the competitive kinetics of C–C cross-coupling
reactions (Heck, Suzuki, and Sonogashira) with C–N and C–O cross-coupling reactions, and also
differences in the kinetics of aryl halides, the coupling reactions could be selectively performed with a
low amount of by-products. The competitive cross-coupling reactions were thus performed with high
selectivity under mild reaction conditions.
Received 5th January 2021,
Accepted 23rd May 2021
DOI: 10.1039/d1nj00067e
rsc.li/njc
for the direct arylation reaction,4 (3) [[(PDCR)Pd(MeCN)](PF6)2]
for the electrochemical activation of CO2,5 (4) SPIONs-bis(NHC)–
Introduction
Palladium complexes of bis-N-heterocyclic carbene (NHC) palladium(II) for C–C cross-coupling reactions,2 and (5) binuclear
ligands, as a powerful ligand in transition metal organometallic NHC–palladium(II) complexes for Suzuki–Miyaura cross-coupling
chemistry, has been successfully employed for a wide variety of reactions.3
organic reactions, especially cross-coupling reactions due to
Cross-coupling reactions represent one of the most fundamental
their strong s-donor and weak p-acceptor properties.1 Their routes for the construction of C–C, C–O, and C–N bonds in
good catalytic activity, stability, functionality tolerance, and organic molecules and materials. Cross-coupling reactions
ease of preparation with cheap and accessible materials, and ease allow the formation of various cross bonds with different
of modification are some of the advantages of N-heterocyclic hybridizations (sp2–sp2, sp2–sp, sp3–sp3) as well as with different
carbene (NHC) compounds, which make them promising ligands atoms (S, P, N, O, C, etc.). Over the last three decades,
for Pd-based catalytic systems.2,3 The efficient application of palladium(0)-based catalytic systems have been recognized as a
Pd–NHC complexes is well known in organometallic chemistry reliable, compatible, and powerful tool for the construction of a
and catalysts, especially over the last decade, and various variety of cross-coupling reactions.6,7 In addition, there are several
modifications have been reported for Pd–NHC ligands, including: reports of palladium’s capability in asymmetric cross-coupling
(1) N,N0-bridged binuclear NHC palladium complex for the Suzuki reactions. In the meantime, coupling reactions with sp3 and sp2
reaction,1 (2) 2-hydroxyethyl substituted N-coordinate-Pd(II)(NHC) hybridization have greatly outcompeted Kumada couplings,
possibly because of the higher geometric versatility and stability
of sp3 and sp2 than sp carbons.8 Moreover, these carbons are
predominant in the framework of applicable molecules in
medicine, agrochemicals, and natural organic molecules.9,10
The C–N and C–O cross-coupling reactions should also be added
to this class, mainly due to their inevitable importance and
application to construct important molecules used in medicine,
agrochemicals, petrochemicals, and pharmaceuticals.11
a Xi’an Key Laboratory of Advanced Photo-electronics Materials and Energy
Conversion Device, School of Science, Xijing University, Xi’an, 710123, P. R. China
b Xi’an Modern Chemistry Research Institute, Xi’an, 710065, P. R. China.
E-mail: xuguiyang90@163.com
c Department of Chemistry, College of Science, Shiraz University, Shiraz,
7194684795, Iran. E-mail: miladkazemnejad@yahoo.com
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1nj00067e
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Cammidge et al. reported the first series of asymmetric anion of hydroxyl anions and imidazole cations on a triazine
Suzuki cross-coupling reactions to prepare chiral binaphthalenes framework was prepared and characterized. The basic ionic liquid
with ee’s of up to 85%.12 Castanet et al. reported a Pd-catalyzed could play the role of a ligand, and effective solvent and base. Pd
asymmetric Suzuki coupling with 2-methoxy-1-naphthylboronic ions could be coordinated via the bis-NHC moiety of the ionic liquid
acid and 1-iodo-2-methoxynaphthalene using chiral phosphine and used as an efficient catalyst for C–C cross-coupling reactions.
ligands.13
Recently, Rokade et al. reviewed recent advances in asymmetric
A3 coupling.14 Varenikov et al. used organotitanium nucleophiles in
an asymmetric cross-coupling reaction in order to synthesize chiral
a-CF3 thioethers.15 Dong et al. reported a general asymmetric Cu-
catalyzed enantioconvergent Sonogashira C(sp3)–C(sp) coupling.8
However, to the best of our knowledge, there is no report
applying different cross-coupling reaction on an aryl di-halide
simultaneously using traditional C–C, C–N, and C–O cross-
coupling reactions as a popular and reliable route.
Results and discussion
Catalyst characterization
According to the acid titration assay, there was 12.0 mmol
hydroxyl groups in 1.0 mmol of the ionic liquid. This gives a
density equal to 1.55 g cmꢀ3 for the ionic liquid, which is
completely in agreement with the density measured by a
standard instrument (1.52 g cmꢀ3). Also, the viscosity of
TAIm[OH] was found to be 1194 cP. Table 1 shows the general
The ligand, base, and solvent are the three critical parameters
for the coupling reactions, especially with palladium-based
catalysts. However, in many cases, the use of catalysts in
industrial and medical fields is limited due to environmental
and cost limitations. For example, although phosphine ligands
are highly active for palladium coordination, they are toxic and
not economically viable at all.7,9
Despite extensive progress in this area, there has been a
continuous development in the ligand design, base, and solvent
to overcome the shortcomings in this field, such as the environ-
mental concerns, efficiency, selectivity, and cost.10,12
1
physical properties of TAIm[OH]. H-NMR, 13C-NMR and EDX
analyses were performed and completely confirmed the
chemical structures of compounds 2 and 3 (ESI,† Fig. S1–S4,
and Scheme 1), in which all three Cl sites in TCT were
functionalized with iodide, and subsequently methyl imidazole.
In addition, the complete elimination of iodide in the EDX
spectrum of 3 confirmed the successfull Hofmann elimination
reaction. Scheme 1 shows a mechanistic view of this transformation,
where iodide counter ions attack Ag2O to give the TAIm[OAg]
intermediate. Then, in the presence of a water molecule, AgOH
is formed and provides the desire product. Another proof of this
process was the formation of AgI sediments, which were char-
acterized by FTIR analysis. It is worth noting that the reaction
failed with TCT and no products of 4 were found (Scheme 2).
This could be directly related to the difference in the atomic
radius of Cl (175 pm) and iodide (198 pm), wherein Iodine binds
more weakly to the imidazole cation than chlorine. However,
with cyanuric iodide, the reaction proceeded efficiently.
The high-resolution XPS 3d-Pd analysis of TAIm[OH]–Pd
complex confirmed the presence of both Pd(0) and Pd(2+)
simultaneously in the catalyst (Fig. 1). As shown in Fig. 1, the
peaks at 337.20 and 342.55 eV were assigned to the binding
energies of 3d5/2 and 3d3/2, corresponding to the 2+ oxidation
state of Pd.24 Also, the two peaks with smaller intensities at
335.30 and 340.33 eV demonstrated that a small amount of Pd
was in the zero oxidation state.24,25 This is a positive point in a
cross-coupling reaction with possible oxidative–addition and
reductive-elimination stages, as has been seen for Pd-catalyzed
C–C cross-coupling reactions.
Ionic liquids or molten salts are an interesting group of
chemical compounds that are composed of organic cations and
organic or mineral anions, but have completely different
properties from the ionic salts.16 The properties of ionic liquids
are highly dependent on the selection of the cations and
anions, and by changing them, a range of application of ionic
liquids can be provided.17 A wide liquid range is one of the
most important features that determines their use as an
effective solvent.17 Most ionic liquids have good thermal and
chemical stability and have
a
low vapor pressure.16,18
Non-flammability and non-corrosive properties are also among
the most common properties of ionic liquids.17 For this reason,
they have been used as green solvents in most organic reactions,
including hydrogenation, oxidation, coupling reactions, Diels–
Alder reaction, etc.19 Their application in extraction and
separation (distillation extraction, gas separation),20 energy and
clean technologies (color-sensitive solar cells, supercapacitors, as
electrolytes for batteries, etc.), recovery of useful substances in
biomass, application in industries (as lubricants and additives, as
surfactants, fuels, additives to paints and coatings), spectroscopy,
electrochemistry (modification of the electrode), chromatography
(preparation of a stationary phase),21 stability and protein and
enzymes activity in the presence of ionic liquids, etc. are among
the other uses of ionic liquids.16–20,22,23
Kinetics of the cross-coupling reactions
In order to perform the asymmetric cross-coupling reactions, the
kinetics of C–C, C–O, and C–N coupling reactions were studied.
In this work, an ionic liquid with a high basicity, suitable
ligand (toward the coordination of Pd ions), and good solvent
property was developed for traditional as well as competitive
cross-coupling reactions with a combination of two different
coupling reaction simultaneously, for the first time. In this way, a
homogeneous water-soluble ionic liquid consisting of a counter
Table 1 Physical properties of the TAIm[OH] ionic liquid
Mw
Density Viscosity
Physical properties (g molꢀ1
)
Color/appearance (g cmꢀ3
Yellow oil
1.52a
)
(cP)
Value
375.4
1194
a
Based on the apparatus. 1.55 g cmꢀ3 from the acid titration assay.
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4 Heck 4 Sonogashira 4 CO 4 C–N. In addition, the kinetics
were different for each of the aryl halides. As a comparison
and for a better understanding, the kinetics of the coupling
reactions for each of the aryl halides were plotted separately
(Fig. S6, ESI†). The curves again showed a significant kinetic
difference for each reaction (for the same halide).
In the next step, the coupling reaction kinetics of the different
aryl halides for each reaction were studied. We used significant and
tangible differences in the kinetics of the catalytic coupling reac-
tions using TAIm[OH]–Pd to perform the asymmetric couplings.
Initially, the optimization study over the Heck model reaction
of styrene with iodobenzene revealed that 1,2-diphenylethene
could be obtained at 120 1C in 2.0 mL of TAIm[OH] ionic liquid
(as a solvent, ligand, and base) in the presence of 1.0 mol%
Pd(OAc)2 (ESI,† Fig. S7).
The catalytic activity of TAIm[OH]–Pd was first evaluated for
the traditional one-sided C–C, C–O, and C–N cross-coupling
reactions under optimized conditions. Initially, the traditional
coupling (coupling from one-halide substituted aryl halide)
Heck, Suzuki, and Sonogashira reactions were performed in
the presence of TAIm[OH]–Pd. In addition, the C–N and C–O
coupling reactions were performed with imidazole and phenol,
respectively. The results are summarized in Table 2. According
to the results of the kinetics studies, the efficiency of the
coupling reactions was as follows: Suzuki 4 Heck 4 Sonoga-
shira 4 C–O 4 C–N.
Scheme 1 Preparation of TAIm[OH] (3) and imidazolium hydroxide–
triazine TAIm[OH]-Pd (4).
Next, the competitive coupling reactions of Heck–Sonogashira
(Table 3), Heck–Suzuki (Table 4), Sonogashira–Suzuki (Table 5),
C–N (Table 6), C–O (Table 7), and N–O (Table 8) with asymmetrical
structures was done with TAIm[OH]–Pd. As shown in the tables,
each reaction was performed with different combinations of
1,4-di-aryl halides. The synthetic behaviors for the asymmetric
coupling reactions were similar to in the traditional coupling
reactions (Table 2) and followed the order: Suzuki 4 Heck 4
Sonogashira 4 C–O 4 C–N. Notably, there was a higher and more
noticeable efficiency for these reactions than for the one-halide
substituted aryl halides (for almost all the reactions).
Scheme 2 Mechanistic view of the Hofmann elimination during the
preparation of TAIm[OH] ionic liquid.
Overall, the results showed that a slower coupling reaction
controls the efficiency of the competitive coupling reaction.
When 1-ethynyl-4-vinylbenzene was used as the starting
material, the time and efficiency were significantly improved
(ex. Table 3, entries 7–9). The reaction of 1-ethynyl-4-
vinylbenzene in the presence of two mmols of iodobenzene gave
the product 11 quantitatively in 80 min (compare with entry 4,
Table 3). Chlorobenzene and bromobenzene performed similarly
at 120 and 100 min, respectively (Table 3, entries 8 and 9).
In general, it can be concluded that the reactivity of
1-ethynyl-4-vinylbenzene was higher than that of 1,4-aryl
halides with the same and non-uniform halides (Scheme 3).
Also, 1,4-aryl halide with the same halide showed higher
reactivity than the non-uniform type (for a specific reaction).
Fig. 1 High-resolution (normalized, energy-corrected) XPS analysis of
TAIm[OH]–Pd.
The reactions were continuously monitored by GC using
valid and pure samples as the standards. The results are
Control experiments and evidence of the mechanism
shown by diagrams as a function of time in Fig. S5 (ESI†). In order to investigate the mechanism of the asymmetric
As shown in the diagrams, all five reactions had different coupling reactions and to determine which halide participates
kinetics, and in this respect they followed the order: Suzuki first in the coupling reaction, the asymmetric coupling reaction
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Table 2 C–C, C–N, and C–O cross-coupling reactions catalyzed by
TAIm[OH]–Pda
Table 4 Asymmetric cross-coupling in the Heck and Suzuki reactions
catalyzed by the TAIm[OH]–Pd ionic liquida
Entry X, Y
Aryl halide Time (min) Yieldb (%)
Entry Coupling reaction
X
Product Time (min) Yieldb (%)
1
2
3
4
X = I, Y = Cl
—
—
—
—
—
—
210
75
220
60
200
70
50
75
86
72
95
80
90
95
93
85
X = I, Y = Br
X = Br, Y = Cl
X = I, Y = I
1
Sonogashira
I
6
100
145
160
60
97
94
90
90
86
75
96
96
90
96
85
80
95
90
85
2
Br
Cl
I
Br
Cl
I
Br
Cl
I
Br
Cl
I
3
4
5
X = Cl, Y = Cl
X = Br, Y = Br
X = vinyl, Y = B(OH)2 Ph–I
Heck
7
6
5
80
7c
8c
9c
6
7
8
9
10
11
12
13
14
15
220
30
Ph–Br
Ph–Cl
60
120
Suzuki
C–N
8
40
160
3.5 h
5.5 h
8.0 h
2.5 h
3.5 h
6.0 h
a
Reaction conditions: phenylboronic acid (1.0 mmol), styrene (1.3 mmol),
aryl halide (1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH] (2.0 mL), H2O
9
b
c
(2.0 mL), ref., sealed tube. Isolated yield. Aryl halide (2.0 mmol).
C–O
10
Br
Cl
Table 5 Asymmetric cross-coupling in the Sonogashira and Suzuki reactions
catalyzed by the TAIm[OH]–Pd ionic liquida
a
General reaction conditions: phenyl acetylene (imidazole, phenol,
phenylboronic acid, 1.0 mmol, styrene, 1.3 mmol), aryl halide
(1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH] (2.0 mL), H2O (2.0 mL),
b
ref., sealed tube. Isolated yield.
Entry X, Y
Aryl halide Time (min) Yieldb (%)
1
2
3
4
5
6
7
8
9
X = I, Y = Cl
X = I, Y = Br
X = Br, Y = Cl
X = I, Y = I
X = Cl, Y = Cl
X = Br, Y = Br
X = B(OH)2, Y = acetyl
—
—
—
155
140
165
90
150
130
85
90
92
86
98
92
95
98
96
92
Table
3
Asymmetric cross-coupling in the Heck and Sonogashira
reactions catalyzed by the TAIm[OH]–Pd ionic liquida
Ph–I
Ph–Br
Ph–Cl
120
150
a
Reaction conditions: phenyl acetylene (1.0 mmol), phenylboronic acid
Entry X, Y
Aryl halide Time (min) Yieldb (%)
(1.0 mmol), aryl halide (1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH]
(2.0 mL), H2O (2.0 mL), ref., sealed tube. Isolated yield.
b
1
2
3
4
X = I, Y = Cl
—
—
—
—
—
—
150
140
160
110
150
130
80
94
95
90
96
94
94
98
94
94
X = I, Y = Br
X = Br, Y = Cl
X = I, Y = I
prepared using 1-chloro-4-iodobenzene with a stoichiometric
ratio equal to styrene in the presence of TAIm[OH]–Pd
(Scheme 4, experiment 2). The results showed that the efficiency
in this case was much better in terms of the time and efficiency
than when chlorobenzene was used as a starting material
(Scheme 4, experiment 2). These results are in complete
agreement with the results of the coupling reactions on
1-ethynyl-4-vinylbenzene (Table 3, entries 7–9).
5
X = Cl, Y = Cl
X = Br, Y = Br
X = Vinyl, Y = acetyl Ph–I
6
7c
8c
9c
Ph–Br
Ph–Cl
100
120
a
Reaction conditions: phenyl acetylene (1.0 mmol), styrene (1.3 mmol),
aryl halide (1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH] (2.0 mL), H2O
b
c
(2.0 mL), ref., sealed tube. Isolated yield. Aryl halide (2.0 mmol).
The results showed that the asymmetric coupling reaction
initially begins with the coupling reaction with the faster
kinetics, which gives a more active intermediate for the
subsequent coupling reaction, with the slower kinetics.
The selectivity of the catalyst can also be justified by these
results, so that due to the higher activity of 21 over that of
1-chloro-4-iodobenzene as a starting material, the second
coupling reaction (i.e., Sonogashira reaction) occurred when
the Heck reaction was done inevitably, which was itself a
driving force for the Heck reaction (according to the principle
of Le Chatelier’s principle).
of Heck and Sonogashira with 1-chloro-4-iodobenzene in the
presence of TAIm[OH]–Pd was performed under optimized
conditions (Table 2). The reaction was worked up after 20 min
and the major product was immediately separated by flash
chromatography. Scheme 4 shows the major product as
1-chloro-4-styrylbenzene with a 25% isolated yield, as confirmed
and characterized by NMR, MS, and flame testing (Scheme 4,
experiment 1). The results suggest that that the reaction initially
begins with a coupling with faster kinetics and with a more
reactive halide. In a separate experiment, compound 21 was
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Table 6 Asymmetric C–N cross-coupling of imidazole with styrene,
phenylacetylene, and phenylboronic acid catalyzed by the TAIm[OH]–Pd
ionic liquida
Table 8 Asymmetric C–N, C–O cross-coupling of imidazole and phenol
with aryl halide catalyzed by the TAIm[OH]–Pd ionic liquida
Entry
X, Y
Time (min)
Yieldb (%)
1
2
3
4
5
6
X = I, Y = Cl
X = I, Y = Br
X = Br, Y = Cl
X = I, Y = I
X = Cl, Y = Cl
X = Br, Y = Br
7.0
5.0
7.2
3.0
6.5
4.8
85
88
85
98
85
85
Entry X, Y
Applied reaction Product Time (h) Yieldb (%)
1
X = I, Y = Cl Heck
14
15
16
14
15
16
14
15
16
14
15
16
8.0
7
82
85
80
80
86
83
77
85
83
85
88
80
2
Suzuki
Sonogashira
3
4
7.5
8.2
7.2
7.5
8.5
7.0
7.5
75
7.0
7.0
a
Reaction conditions: phenol (1.3 mmol), imidazole (1.0 mmol), aryl
halide (1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH] (2.0 mL), H2O
X = I, Y = Br Heck
5
Suzuki
Sonogashira
b
(2.0 mL), ref., sealed tube. Isolated yield.
6
7
X = Br, Y = Cl Heck
8
Suzuki
Sonogashira
Heck
9
10
11
12
X = I, Y = I
X = Cl, Y = Cl Suzuki
X = Br, Y = Br Sonogashira
a
Reaction conditions: phenylboronic acid (phenylacetylene)
(1.0 mmol), (styrene (1.3 mmol)), imidazole (1.3 mmol), aryl halide
(1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH] (2.0 mL), H2O (2.0 mL),
Scheme 3 Reactivity order of 1-ethynyl-4-vinylbenzene with 1,4-aryl
halides.
b
ref., sealed tube. Isolated yield.
Table 7 Asymmetric C–N cross-coupling of phenol with styrene, phe-
nylacetylene, and phenylboronic acid catalyzed by the TAIm[OH]–Pd ionic
liquida
Entry X, Y
Applied reaction Product Time (h) Yield (%)
Scheme 4 Control experiments for the evaluation of the asymmetric
cross-coupling reactions.
1
2
3
4
5
6
7
8
X = I, Y = Cl
Heck
Suzuki
Sonogashira
17
18
19
17
18
19
17
18
19
17
18
19
6.2
5.5
6.0
6.5
6.0
6.5
6.5
5.8
6.5
6.0
5.3
5.8
80
88
80
90
92
86
88
92
84
84
90
82
X = I, Y = Br Heck
complex, were studied. For this goal, the following three control
experiments were performed:
Suzuki
Sonogashira
X = Br, Y = Cl Heck
(i) The catalyst was extracted from the aqueous phase with
n-BuOH after completion of the reaction between iodobenzene
(1.0 mmol) and styrene (1.3 mmol) (catalyzed by TAIm[OH]–Pd
for 60 min), then characterized by high-resolution XPS 3d-Pd
analysis.
Typically, in the ‘‘cocktail’’ of catalyst systems, the Pd
separation/detachment from the catalysts via the catalytic
interaction, like the oxidative–addition of aryl halides (Ar–X)
to the Pd(0) species, initiates the C–C bond formation reaction in
solution.26,27 Then, by the re-deposition of the regenerated Pd(0),
it backs onto the support through a reductive elimination step at
the end of the reaction.28
Suzuki
Sonogashira
Heck
9
10
11
12
X = I, Y = I
X = Cl, Y = Cl Suzuki
X = Br, Y = Br Sonogashira
a
Reaction conditions: phenylboronic acid (phenylacetylene)
(1.0 mmol), (styrene (1.3 mmol)), phenol (1.3 mmol), aryl halide
(1.0 mmol), Pd(OAc)2 (1.0 mol%), TAIm[OH] (2.0 mL), H2O (2.0 mL),
ref., sealed tube.
Catalyst type
Due to the homogeneous nature of the catalyst and its NHC–Pd
complex structure, the type of catalyst from the viewpoints of a
‘‘cocktail’’ of catalysts system and homogeneous palladium
However, the regenerated Pd(0) species are highly unstable
and tend to accumulate in the re-deposition process or in the
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reaction solution to obtain a completely different catalyst from than 1.0 h, while the reaction conversion was screened by TLC.
the freshly prepared one, and so lead to a decreases in the The results indicated there was no change in the yield of the
catalytic and potential activity and adverse recycling, which reaction, for which a 91% isolated yield was found at the end of
poses an important issue for the practical application of Pd the reactions as seen in the absence of Hg(0) (Table 2, entry 4,
catalysts supported on solid–liquid catalytic systems.29,30 In product 7). The results were in agreement with those for homo-
this way, the homogeneous catalyst was extracted to n-BuOH geneous molecular complexes of palladium for TAlm[OH]–Pd
after completion of the Heck model reaction (cross-coupling and there was no evidence of Pd transformation as Pd dissolu-
of styrene with iodobenzene), and then characterized by high- tion and re-deposition processes characteristic of the ‘‘cocktail’’
resolution XPS analysis. As shown in Fig. 2, there was no of catalysts systems. In conclusion, the present catalytic system
considerable change in the oxidation states and the intensities comprises molecular complexes of palladium, for which the
of the Pd (3d-Pd) centers in the recovered catalyst. However, ligand (TAlm[OH]) also plays the role of a solvent. Coordination
some decrease in the intensity of all the peaks was observed, of the Pd ions to TAlm[OH] causes a heterogeneous but water-
which could be attributed to the loss of some of the catalyst soluble molecular complex to form. In this way, a traditional
during the recovery process. Nevertheless, the results well Pd-catalyzed catalytic system is proposed for the C–C, C–N, and
confirmed the intact structure of the recovered catalyst after C–O cross-coupling reactions.
the coupling reaction, as in the freshly prepared catalyst.
Mechanism studies
(ii) In order to study the leaching of Pd metal in the reaction
mixture, the reaction mixture was characterized by ICP-MS According to the evidence obtained and the mechanisms
analysis after catalyst extraction over the model Heck coupling reported for Heck and Sonogashira reactions,10,33 a mechanism
reaction. For this purpose, the catalyst was extracted by n-BuOH was proposed for the asymmetric reaction of the Heck–Sonogashira
by separating the aqueous phase from the organic phase and coupling catalyzed by TAIm[OH]–Pd selectively. However, the
then, ICP-MS analysis was performed from the organic phase. mechanism can be generalized to other coupling reactions. It is
The results did not show any trace of Pd in the reaction also important to note that no mechanism for such reactions
mixture, which clearly indicated the homogeneity of the has been reported so far. The results of XPS analysis showed
reaction medium and the homogeneous performance of the that the coordinated Pd ions in TAIm[OH]–Pd had a mixture of
catalyst. In the ‘‘cocktail’’ of catalyst systems, the phenomena 0 and 2+ oxidation states. Therefore, according to the expecta-
of aggregation and re-deposition cause some metal leaching tions and mechanisms reported for catalytic coupling reactions
into the solution, which the results of this study did not show.29 with Pd, the coupling reaction included oxidative–addition and
(iii) In order to manifest the Pd aggregation (in situ preparation reductive-elimination steps. On the other hand, the results
of Pd NPs) over the catalyst surface, metallic mercury was added to showed that the asymmetric competitive coupling reaction
the reaction mixture as a heterogeneous catalyst poisoner.
began with a faster coupling reaction kinetically and with a
The mercury-poisoning test is a reliable and common assay more reactive halide. Therefore, according to the results
to manifest the presence of nanoparticles and clusters in a obtained in Table 2, the asymmetric coupling reaction began
reaction mixture. Although the formation of metal NPs is with the Heck reaction and from the iodide side. The proposed
usually easy to see under a microscope, clusters are much more mechanism is shown in Scheme 5, cycle a. According to the
difficult to detect.31,32 Nevertheless, Hg-poisoning of the proposed mechanism, the reaction initially begins with an
heterogeneous complex-catalyzed Heck reaction stopped the oxidative–addition in iodide and the formation of the inter-
conversion. For this goal, in the Heck model reaction between mediate I. In the presence of an alkene, a p-complex II is
iodobenzene with styrene, 320 molar equivalents of formed and then insertion is performed (Intermediate III).
mercury (Hg(0)) vs. Pd catalyst was added to the reaction With a b-H elimination, a double bond is formed, followed by
mixture (at t = 0). The reaction medium was stirred for more the formation of p-complex IV. The role of hydroxyl groups in
the ionic liquid as a base at this stage was proved by the roles
of: (i) reductive elimination, (ii) formation of the Heck product,
and (iii) the return of the catalyst to the cycle. Then, the
coupling reaction of the Sonogashira with the Cl leaving group
continues. The Sonogashira reaction was also performed
according to the traditional mechanisms reported for the
Pd-catalyzed Sonogashira reaction, including oxidative–addition
and reductive-elimination steps (Scheme 5, cycle b).7,9,10,33 The
control reaction in the previous section showed that the initial
product of the Heck coupling reaction was much more active
than its un-coupled type, and it seemed to have less activation
energy for the oxidative–addition and reductive-elimination
steps. Thus, the activated aryl halide was triggered by a slower
reaction (here, Sonogashira). Finally, the product 11 was formed
Fig. 2 Recovered TAIm[OH]–Pd after the C–C cross-coupling reaction
of styrene with iodobenzene.
by a reductive-elimination.
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Scheme 5 Proposed reaction mechanism for the TAIm[OH]–Pd-catalyzed asymmetric cross-coupling of Heck and Sonogashira reactions.
(X is supposed to be a more reactive halide.)
In order to investigate the absence of any radical species As shown in Scheme 6, given the superior p kinetics for the
involved in the mechanism, the reaction of the Heck model was Suzuki reaction, the Suzuki reaction initially reacts with a more
performed in the presence of DPPH radical. For this purpose, in reactive halide (here X). The oxidation-addition reaction leads
two separate reactions, DPPH was first added, and for another to the preparation of intermediate I (Scheme 6). The basicity
it was added after 30 min, to a reaction mixture including nature of the catalyst creates stable R–B(OH)3ꢀ—Cat. species
styrene, iodobenzene, Pd(OAc)2, and TAIm[OH] (Fig. S8, ESI†). (Int. II) in the presence of phenylboronic acid (Scheme 6).
The results showed no significant change in the kinetics of the The cationic nature of the catalyst ensures the intermediate
reactions and also that the kinetics were quite similar to the II’s stability. In the next step, the transmetalation leads to the
normal reaction kinetics, which ruled out the presence of any bond formation of the aryl ring to the palladium sites and the
radical in the reaction mechanism. Subsequently, a similar removal of B(OH)4ꢀ species. The reductive-elimination leads to
mechanism was proposed for the competitive cross-coupling the formation of the Suzuki product, which subsequently
of Suzuki with C–Z (Z = O, N) according to the literature.11,33 undergoes another oxidative–addition reaction to create the
Scheme 6 Proposed reaction mechanism for the TAIm[OH]–Pd-catalyzed asymmetric cross-coupling of C–Z (Z = O, N) and Suzuki reactions.
(X is supposed to be a more reactive halide.)
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intermediate IV. The heteroatom compound is added to the catalyst, Preparation of 1,10,100-(1,3,5-triazine-2,4,6-triyl)tris(3-methyl-
and then the basicity nature of the catalyst eliminates HX. The 1H-imidazol-3-ium)hydroxide (TAIm[OH]) (3), and TAIm[OH]–Pd
asymmetric product of the coupling is created by the reductive-
elimination reaction and the catalyst is returned to the cycle.
First, for the preparation of cyanuric iodide (1), TCT (0.37 g,
2.0 mmol) was added to 20 mL of dry acetone at room
temperature. Then, NaI (1.5 g, 10 mmol) was added to the
mixture. The flask was sealed and the mixture was stirred for
12 h. The color of the solution gradually turned yellow. Then,
Conclusion
1-methylimidazole (15.0 mmol) was added to the mixture,
which was then refluxed for 24 h. [TAIm]OH (2) was extracted
to n-BuOH (3 ꢁ 10 mL). The resulting organic phases were
placed in a vacuum oven (65 1C) for 24 h. Exchange of the
iodide counter ions with hydroxide was preformed via the
Hofmann elimination using Ag2O. Ag2O was also prepared in
In this work, a general, and versatile protocol was developed for
the competitive cross-couplings of C–C*C–C (including Heck,
Suzuki, and Sonogashira coupling reactions), C–C*C–O,
C–C*C–N, and O–C*C–N cross-coupling reactions. The reactions
were catalyzed in the presence of an ionic liquid with the
intrinsic basicity that could allow coordination with Pd ions
through bis(NHC) atoms and acted as a solvent. So, the reactions
were performed under solvent-, base-, and ligand-free conditions,
and good to high selectivity and efficiency were obtained. The
kinetics of the reactions showed a significant difference toward all
coupling reactions as well as the aryl halides, which could be
responsible for the high selectivity observed for the asymmetric
coupling products. There was a low by-product yield or one-sided
coupling for the reactions. An insight into mechanism revealed that
the asymmetric coupling reactions start with the more reactive
reaction kinetically and then, the slower coupling reaction.
this study according to
a simple procedure described
elsewhere.35 [TAIm]OH (2, 1.0 mL) was added to 20 mL distilled
water, then Ag2O (8.0 mmol, 1.8 g) was added to the mixture in
one step. The reaction was performed under reflux conditions
for 8 h. The sediment (AgI) was filtered and the product was
extracted to n-BuOH (3 ꢁ 10 mL). The resulting organic phases
were dried in a vacuum oven (65 1C).
1
Characterization data for 2. Yellow oil, H-NMR (250 MHz,
D2O) d (ppm): 4.50 (s, 9H, CH3), 7.32 (d, 3H, J = 6.25 Hz, Im-H),
7.96 (d, 3H, J = 6.25 Hz, Im-H), 8.98 (s, 3H, Im-H) (Fig. S2a,
ESI†); 13C-NMR (62.9 MHz, D2O) d (ppm): 38.0, 117.7, 126.2,
144.6 (Fig. S2b, ESI†); EDX (wt%) = C 26.55, N 18.88, I 44.57
(Fig. S4a, ESI†).
Experimental
Materials and instrumentation
1
Characterization data for 3. Yellow oil, H-NMR (250 MHz,
D2O) d (ppm): 4.14 (s, 9H, CH3), 7.86 (d, 3H, J = 7.00 Hz, Im-H),
8.10 (d, 3H, J = 7.00 Hz, Im-H), 8.98 (s, 3H, Im-H) (Fig. S2c,
ESI†); 13C-NMR (62.9 MHz, D2O) d (ppm): 38.7, 118.8, 126.6,
145.6 (Fig. S2d, ESI†); EDX (wt%) = C 49.33, N 35.76, O 14.91
(Fig. S4b, ESI†).
TAIm[OH]–Pd was separately prepared to manifest the oxidation
state of the coordinated Pd. For this goal, TAIm[OH] (2.0 mmol) as
a ligand was added to 15 mL EtOH, and then 2.0 mmol Pd(OAc)2
was added to the mixture at room temperature. Immediately
after the addition of Pd salt, the color of the solution turned brown.
The mixture was refluxed for 1 h. Then, after cooling to room
temperature, the dark gray powder was filtered from the mixture,
followed by drying in an oven. TAIm[OH]–Pd complex was
successfully characterized by 1H-NMR, 13C-NMR, EDX, and HR-
MS spectra (Fig. S3 and S4, ESI†).
All the chemicals were obtained from Sigma Aldrich or Merck
and used as received without further purification. All the
solvents were distilled (under an Ar atmosphere) before use.
All the other reagents were of analytical grade. Progress of the
coupling reactions were monitored by thin layer chromatography
(TLC) on silica gel or gas chromatography (GC) on a Shimadzu-
14B gas chromatograph with N2 flow as a carrier gas and
equipped with an HP-1 capillary column. Anisole was used as
an internal standard for the quantitative analyses. FTIR analyses
were recorded on a JASCO FT/IR 4600 spectrophotometer using
KBr disk. The NMR spectra, 1H- and 13C-(62.9 MHz), were
obtained using a Bruker Avance DPX-250: 1H (250 MHz), 13C
(62.9 MHz) and Bruker Avance II 400 MHz spectrometer in
deuterated solvents of DMSO-d6 or CDCl3, and TMS as an
internal standard. XPS analyses were conducted on a XR3E2
(VG Microtech) with an anode X-ray source using Al Ka =
1486.6 eV. Energy-dispersive X-ray spectroscopy (EDX) analysis
was conducted on a field emission scanning electron micro-
scope, FESEM JOET 7600F, equipped with a spectrometer for
energy dispersion of the X-rays from Oxford instruments.
Elemental analysis (C, H, N, S) was performed using a
PerkinElmer-2004 apparatus. ICP-MS analysis was conducted
Characterization data for 4. Brown powder, 1H-NMR
(250 MHz, CDCl3) d (ppm): 1.96 (s, 3H), 3.04 (s, 6H), 4.00 (s,
3H), 6.69 (d, j = 7.50, 2H), 6.95 (d, j = 7.50, 2H); 8.63 (s, 1H);
13C-NMR (62.9 MHz, D2O) d (ppm): 24.8, 36.4, 41.7, 112.8, 114,
119.9, 121.4, 137.6, 162.3, 166.2, 170.2, 173.2; EDX (wt%) =
C 40.12, N 25.06, O 13.12, Pd 21.57. HR-MS (FTMS ESI+):
calculated for [TAIm–Pd]+ (C17H21N9O2Pd) (cation) [M]+,
244.54345; found, 244.54340.
on
a PerkinElmer ELAN 6100 DRC-e instrument. High-
resolution mass spectroscopy (HR-MS) was performed using a
previously reported protocol34 on a Thermo Scientific Q Exactive
Determination of the hydroxyl groups in TAIm[OH]
plus (QE+). An on-board syringe pump at 5 mL minꢀ1 was used The hydroxyl content in TAIm[OH] was measured by an acid
for this analysis. Data were obtained over the QE+ in the positive titration assay. In this test, 1.0 mL of the ionic liquid was added
ion mode at a target resolution of 70000 at 200 m/z.
to 50 mL of distilled water and the mixture was stirred
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vigorously for 10 min (pH = 13.88). The resulting solution Acknowledgements
was titrated with 1.0 M acetic acid in the presence of
This work was supported by the Special Scientific Research
Project of Shaanxi Education Department (No. 19JK0904) and
the Science Research Foundation of Xijing University
(No. XJ18T03 and XJ18B05). The authors acknowledge the
support given by the Youth Innovation Team of Shaanxi
Universities.
phenolphthalein indicator at room temperature under air
conditions. About 11.96 mL acetic acid was consumed at the
end point (pH 7.0). At the same time, a blank was also titrated and
the total volume of acetic acid was recorded. Based on the
experiment, 1.0 mL of ionic liquid contained 12.0 mmol
hydroxyl group. So, with assumption of three equivalent of ꢀOH
ions in a mmol of TAIm[OH], there were 4 mmol TAIm[OH] in 1.0
mL of ionic liquid. Based on the Mw of the ionic liquid, it can be
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