Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

Article abstract of DOI:10.3762/bjoc.14.160

Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of water soluble cationic Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic activity in Suzuki–Miyaura coupling reactions. By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were found to be reusable for three cycles without a significant loss of activity. The investigation of the mechanism of the reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies.

Full text of DOI:10.3762/bjoc.14.160

Water-soluble SNS cationic palladium(II) complexes and their
Suzuki–Miyaura cross-coupling reactions in aqueous medium
Alphonse Fiebor1, Richard Tia2, Banothile C. E. Makhubela*1 and Henok H. Kinfe*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2018, 14, 1859–1870.
1Department of Chemistry, University of Johannesburg, PO Box 524,
Auckland Park 2006, South Africa and 2Department of Chemistry,
Kwame Nkrumah University of Science and Technology, Kumasi,
Ghana
doi:10.3762/bjoc.14.160
Received: 11 May 2018
Accepted: 26 June 2018
Published: 23 July 2018
Email:
Banothile C. E. Makhubela* - bmakhubela@uj.ac.za;
Henok H. Kinfe* - hhkinfe@uj.ac.za
Associate Editor: L. Ackermann
© 2018 Fiebor et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
cationic palladium(II) complexes; Pd(II)/Pd(IV) complexes; SNS pincer
complexes; Suzuki–Miyaura
Abstract
Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of
water soluble cationic Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic
activity in Suzuki–Miyaura coupling reactions. By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl
bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were
found to be reusable for three cycles without a significant loss of activity. The investigation of the mechanism of the reaction
revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies.
Introduction
The Suzuki–Miyaura C–C coupling reaction is a powerful ligand-free methodologies [19-25] and the use of water-soluble
method for the synthesis of ubiquitous biaryls and has been ex- palladium pre-catalysts/catalysts [26-30]. The latter is the
tensively employed in the synthesis of natural products, phar- preferred choice since it allows for the reusability of the cata-
maceuticals, agrochemicals, and polymers. The reaction usually lyst for subsequent reactions after simple phase separation [31].
involves a palladium-catalysed coupling of aryl boronates with However, the commonly employed phosphorous and carbene
aryl halides in organic solvents in the presence of an excess of ligand-based palladium(II) complexes are found to be in most
base [1-3]. With the drive for the development of environmen- cases sensitive to moisture and air limiting the scope of their
tally friendly and low cost protocols, a number of methodolo- catalytic application in aqueous reactions [32,33]. This limita-
gies for the Suzuki–Miyaura reaction under aqueous conditions tion encouraged for the development of organosulfur ligand
or in neat water have been reported [4-6]. This has been based palladium(II) complexes by exploiting the strong donor
achieved via microwave heating [7-15], ultrasonication [16-18], properties of sulfur. Such complexes are found to be resistant
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to moisture, air and thermal stress/elevated temperatures and To the best of our knowledge, the only examples reported in the
have been applied in catalysing Suzuki–Miyaura coupling reac- literature are the water-soluble pincer complexes 14, 15 and 16
tions [32,33]. As it was elegantly reviewed by Singh and (Figure 2a). While pincer complex 14 provided moderate
co-workers [33], these organosulfur ligands can be classified (38–68%) GC yields over 6 h at 75 °C using 2 mol % catalyst
into pincer type (symmetrical and unsymmetrical), thioethers, loading with inactivated aryl bromides, pincer complex 15 was
thiourea-based ligands, sulfur-substituted NHCs, thiosemicar- found to be incompatible with both activated and inactivated
bazones and sulfated Schiff bases. Of the pincer ligands, aryl bromides according to the study conducted by Bai and Hor
there are several examples of SCS-based palladium(II) [34]. Similarly, Kumar et al. studied the catalytic activity of
complexes (1–13, Figure 1) which were reported to catalyse the pincer complex 16 and reported that the catalyst was compati-
Suzuki–Miyaura coupling reaction but the corresponding easy- ble with activated aryl bromides to provide reasonable yields
to-synthesise SNS pincer complexes are well underrepresented over 12 h at 100 °C using 2 mol % catalyst loading; but re-
[33].
quired stoichiometric amounts of tetra-n-butylammonium bro-
Figure 1: Examples of reported SCS palladium(II) pincer complexes 1–13.
Figure 2: a) Reported SNS palladium(II) pincer complexes 14–16 as catalysts for Suzuki–Miyaura cross coupling [34]; b) Proposed SNS palladium(II)
pincer complexes 17.
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Beilstein J. Org. Chem. 2018, 14, 1859–1870.
mide (TBAB) to effect the reaction of inactivated aryl bro- the downfield shift of all the protons in the complex, when com-
mides [35]. A further limitation of these catalysts is their inca- pared to the corresponding protons of the ligand, by a differ-
pability to catalyse the coupling reaction when either activated ence of ΔδH 0.5 to 1.3 suggests the deshielding of the nuclei
or inactivated aryl chlorides are employed as coupling partners. due to coordination with the palladium. The downfield shift of
Encouraged by the high hydrophilicity and the potential activi- the protons is in accordance with other previously reported
ty of such complexes, we are interested in the synthesis of palladium(II) complexes [37]. The symmetry of the complex
cationic palladium(II) SNS pincer complexes of the general was supported by the appearance of the two protons of the pyri-
structure 17 (Figure 2b) having rigid fused cyclic rings imparted dine moiety as a doublet at δH 7.76. Furthermore, the formation
by a pyridine backbone; and systematic investigation of their of the two fused five-membered rings was confirmed by the ap-
catalytic activity in the aqueous Suzuki–Miyaura coupling pearance of the axial and equatorial protons of the bridging
reaction. Herein, we report the synthesis of the SNS Pd(II) methylene groups as two broad singlets at δH 5.59 and δH 5.16
pincer complexes and their interesting catalytic activities in the each integrating for two protons as opposed to the appearance
Suzuki–Miyaura cross coupling reactions in neat water.
of the corresponding protons in the ligand as a singlet at δH 4.29
integrating for four protons. In a similar fashion, complex 17b
was synthesised and characterised successfully while ligands
Results and Discussion
Our study commenced with the preparation of the SNS pincer 19c and 19d possessing the electron-donating thioether side
ligand 19a using literature reported protocols [36] as shown in groups favoured the formation of the corresponding pincer com-
Scheme 1. Treatment of in situ-generated thiophenolate with plexes 17c and 17d directly without formation of an isolable
2,6-bis(chloromethyl)pyridine (18) afforded pincer ligand 19a bidentate intermediate observed during the synthesis of com-
in 73% yield. Initial attempts for the synthesis of SNS-Pd(II) plexes 17a and 17b. Furthermore, the successful synthesis of
complex 17a (with Cl− counter ion) were unsuccessful since the the pincer complexes was confirmed by X-ray crystallography
reaction of the SNS pincer ligand 19a with PdCl2(MeCN)2 led and the representative X-ray crystal structure of 17d is shown in
to the formation of N,S-Pd(II) 20a presumably due to the weak Figure 3 [38].
basicity of the sulfur atom. Gratifyingly, the problem was
solved by treatment of the reaction mixture with the halide Single crystals suitable for X-ray analysis of complexes 17d
abstractor AgOTf to provide the desired SNS-Pd(II) complex were obtained by slow evaporation of a mixture of dichloro-
17a in quantitative yield (Scheme 1).
methane and diethyl ether at about −4 °C. Crystallographic data
and structure refinement parameters for 17d are summarised in
The structure of the complex was established using NMR spec- Table 1. Formation of the tridentate pincer complex was con-
troscopy and high-resolution mass spectrometry. Among others, firmed by the crystal structure of 17d. The structure is
Scheme 1: Synthesis of pincer ligands 19a–d and complexes 17a–d.
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Beilstein J. Org. Chem. 2018, 14, 1859–1870.
Figure 3: Molecular structure of 17d. Selected bond distances (Å) and bond angles (°); S(1)–Pd(1)–Cl(1) 93.27(4), S(2)–Pd(1)–Cl(1) 93.34(4),
N(1)–Pd(1)–S(1) 86.70(9), N(1)–Pd(1)–S(2) 86.71(9), C(6)–S(1)–C(9) 100.2(2), C(7)–S(2)–C(13) 102.72(2), S(1)–C(6) 1.808(4), S(2)–C(7) 1.816(4),
Pd(1)–Cl(1) 2.3044(10).
S(1)–Pd(1)–Cl(1), S(2)–Pd(1)–Cl(1), N(1)–Pd(1)–S(1) and
Table 1: Crystal data and structure refinement parameters for 17d.
N(1)–Pd(1)–S(2), respectively. It is observed that the sec-butyl
identification code
Complex 17d
groups attached to the sulfur atom are pointing away from the
plane of the metal centre such that the thioether angles are
100.2(2)° and 102.72(2)° corresponding to C(6)–S(1)–C(9) and
C(7)–S(2)–C(13), respectively. The thioether C–S bond lengths
obtained are 1.808(4) Å and 1.816(4) Å for S(1)–C(6) and
S(2)–C(7), respectively.
empirical formula
formula weight
temperature/K
crystal system
space group
a/Å
C15H24Cl2NPdS2, 2(H2O)
124.20
100.01
triclinic
P-1
7.7438(12)
7.8801(12)
17.140(3)
76.788(2)
89.363(2)
82.357(2)
1009.0(3)
8
b/Å
The thioether bond lengths and angles were found to be consis-
tent to the reported data of 1.816 Å and 100.75°, respectively,
by Sogukomerogullari et al. [39]. Similarly, the Pd–Cl bond
length of 17d (2.3044(10) Å) also corresponds to that of square
planar complexes with a chlorine ligand reported in literature
[40]. The crystal structure of 17d also shows a static disorder of
a CH2 carbon of one of the sec-butyl groups (C14). The atom
site occupancy factors of the two positions of the CH2 carbon
atom was refined to 0.571(11) and 0.429(11). This shows that
the carbon atom has equal probability of being oriented in the
two positions.
c/Å
α/°
β/°
γ/°
volume/Å3
Z
ρcalcg/cm3
μ/mm−1
F(000)
1.635
1.398
508.0
crystal size/mm3
radiation
0.7 × 0.27 × 0.2
Mo Kα (λ = 0.71073)
2Θ range for data collection/° 4.884 to 52.232
index ranges
−9 ≤ h ≤ 9, −9 ≤ k ≤ 9,
−21 ≤ l ≤ 21
With the desired pincer complexes in hand, we then moved on
to investigate their potential as catalysts for Suzuki–Miyaura
coupling reactions. In our first attempt, the electronically deacti-
vated 4-bromoanisole (21a) along with phenylboronic acid
(22a) as coupling partner and pincer complex 17a as catalyst
were selected, in order to identify the optimum catalyst and
reaction conditions (Table 2). Carrying out the reaction with
equimolar amounts of the coupling partners in water at 140 °C
for 4 hours in the presence of 1 mol % pincer complex 17a and
K3PO4 (2 equiv) led to the formation of the biaryl 23a in
reflections collected
17514
independent reflections
4019 [Rint = 0.0199,
Rsigma = 0.0159]
data/restraints/parameters
goodness-of-fit on F2
4019/0/228
1.101
final R indexes [I>=2σ (I)]
final R indexes [all data]
R1 = 0.0393, wR2 = 0.0836
R1 = 0.0410, wR2 = 0.0845
largest diff. peak/hole / e Å−3 1.83/−1.47
accompanied by two lattice water molecules interacting with 92% yield (Table 2, entry 1). The colour of the reaction mix-
each other and an uncoordinated chloride ion through ture remained yellow. The use of solvents other than water gave
hydrogen bonding. The expected square planar geometry of inferior yields (Table 2, entries 2 and 3) which could be attri-
palladium(II) complexes can be observed in the crystal struc- buted to the high hydrophilicity of the pincer complex 17a.
ture of 17d where the bond angles around the palladium metal Several bases including pyridine, Et3N, KOH, K2CO3 and
centre are 93.27(4)°, 93.34(4)°, 86.70(9)° and 86.71(9)° for Cs2CO3 were then evaluated. All except Et3N provided the ex-
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Table 2: Optimization of the Suzuki–Miyaura cross coupling reaction of 4-bromoanisole (21a) and phenylboronic acid (22a).
Entry
Base
Solvent
Cat.
Cat. loading Temp.
Additive
Time (h)
Yield (%)a
1
K3PO4
K3PO4
K3PO4
Pyr
H2O
DMF
toluene
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17a
17c
17c
17d
17d
17b
17b
1
140
140
140
140
140
140
140
140
120
100
80
–
4
4
4
4
4
4
4
4
4
4
4
4
0.5
1
2
4
4
4
1
4
2
2
2
2
2
2
2
2
2
2
92
67
0
2
1
–
3
1
–
4
1
–
90
51
90
95
92
93
84
79
41
77
80
82
86
46
0
5
Et3N
KOH
K2CO3
Cs2CO3
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
1
–
6
1
–
7
1
–
8
1
–
9
1
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
1
–
1
–
1
20 (rt)
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
–
1
–
1
–
1
–
0.5
0.25
0.06
1
–
–
–
TBAB
TBAB
–
91
94
80
85
73
90
72
93
75
85
72
92
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
TBAB
–
TBAB
–
TBAB
–
TBAB
H2O and Hg 17a
H2O and Hg 17a
TBAB
aGC yield.
pected biaryl 23a in comparable and excellent yields (Table 2, er, stirring the reaction mixture beyond 4 hours did not lead to
entries 4–8). The poor performance of Et3N as base in the reac- improved yields. Investigation on the loading of the catalyst in-
tion could be due to its low water solubility. KOH as a common dicated that 1 mol % was sufficient to drive the reaction to near
laboratory reagent gave a comparable yield to the other bases. completion (93% yield, Table 2, entry 9) considering the minor
Therefore, we opted to use KOH as our preferred base for the byproduct formed via homocoupling of the phenylboronic acid
reaction. An improved 93% yield was obtained when the reac- coupling partner. Reducing the catalyst loading by half yielded
tion was carried out at 120 °C (Table 2, entry 9). However, a competitive yield of 86% (a 7% decreased yield, Table 2,
lowering the reaction temperature to less than 120 °C resulted in entry 16). Catalyst loading of less than 0.5 mol % provided
comparatively poorer yields (Table 2, entries 10–12). Monitor- inferior yields (Table 2, entries 17 and 18). In agreement with a
ing of the reaction at different time intervals under otherwise literature report [27], the addition of TBAB (0.5 equiv) im-
identical conditions showed slightly progressive increase in the proved the performance of the reaction (Table 2, entries 14 vs
yield of the product formed (Table 2, entries 13–15) with a 19 and 16 vs 20) but the colour of the reaction mixture turned
maximum yield of 93% after 4 hours (Table 2, entry 9). Howev- black.
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Among the set of SNS pincer complexes investigated in this tained theoretically could support the experimental results. The
study, pincer complex 17a was found to be the most active cata- oxidative addition stage was selected because it is also the rate-
lyst in the absence of TBAB as an additive (Table 2, entry 21 vs determining step for the catalytic cycle, and thus it can be used
23, 25 and 27). Such an outcome suggests that the sterically less to compare the rate of conversions. The PM3 method has been
demanding planar phenyl group renders greater access to the parameterised for transition metal systems and has been found
metal centre for the substrates than the bulkier side groups (both to give geometries, relative energies and activation energy
with electron-donating and electron-withdrawing substituents) trends in good agreement with high-level density functional
and leads to the enhanced catalytic activity observed for 17a, theory (DFT) results at a fraction of the computational cost
which thus implies that the catalytic activity is influenced by [45,46]. It is therefore adequate for studies in which the prime
steric as opposed to electronic effects. On the contrary, carrying purpose is to determine or verify preferred reaction pathways.
out the reactions under otherwise identical conditions but with
the presence of TBAB, the activity of the catalysts was Oxidative addition of 4-bromoanisole to complex 17d proceeds
reversed. The electron rich and sterically demanding tert- by the C–Br bond activation to form a weakened Pd···Br bond,
butylphenyl and isobutyl thioether possessing SNS pincer com- of 3.104 Å length in transition state (TS1), which ultimately
plexes resulted in higher yields (Table 2, entry 24 and 26) than results in a new Pd–Br bond, of 2.605 Å length (IM1)
the electronically poor and sterically less demanding phenyl (Figure 4). The Pd–Br distance is calculated to be 2.60 Å and is
group (Table 2, entry 22) as well as the electronically poor but consistent with similar Pd–Br bond lengths found in the litera-
sterically demanding 4-bromophenyl thioether (Table 1, entry ture for single crystal X-ray structures [47,48]. This oxidative
28) possessing SNS pincer complexes. These results suggest addition step involves a low activation energy barrier of
that in the presence of TBAB the mechanism of the reaction −43.9 kcal/mol. This negative energy implies that there is a
changes and the catalytic activity seems to be under the influ- stable intermediate between the reactants and the transition state
ence of electronic as opposed to steric effects. When the reac- (TS1). Thus, when the energy of the transition state is lower
tion mixture turned black in the presence of TBAB, we were than the energy of the reactants or intermediates from which the
under the impression that the reaction could have proceeded via transition state is formed it means there is a stable intermediate
formation of palladium nanoparticles as it is common with most between them.
palladium catalysed coupling reactions. However, mercury drop
experiments provided comparable yields (Table 2, entry 29 and Nonetheless, such a relatively low energy barrier indicates that
30) under the same reaction conditions ruling out the possibili- the reaction proceeds at a fast rate in getting to the intermediate
ty of a coupling reaction catalysed by palladium nanoparticles (IM1), thus it is kinetically favoured. The reaction then
[37].
proceeds via transition state TS2, leading to the cleavage of the
C(sp2)–Br bond and the formation of a new Pd–C(sp2) bond, to
The fact that the reaction mixture remained yellowish in the form a cis intermediate of energy −93.0 kcal/mol. The new
absence of TBAB and the mercury drop experiments did not Pd–C(sp2) bond distance of 2.00 Å falls within the reported
lead to an appreciable decrease in yield, the reaction was pro- Pd–C(sp2) bond distances [47,48]. Since the bromo ligand is
posed to proceed via a Pd(II) to Pd(IV) mechanism contrary to larger in atomic radius than the chloro ligands the more stable
the previously reported SNS pincer Pd(II) complexes which form of the oxidative addition product is the trans form. As
proceeded via formation of Pd nanoparticles [35] (Pd(II) to such, the cis product can isomerise to a more stable trans inter-
Pd(0) type of mechanism). Literature suggestions on a Pd(II) to mediate of energy −93.6 kcal/mol having a Pd–C(sp2) bond
Pd(IV) mechanism are known for biscarbene (CNC), alkylphos- length of 1.99 Å.
phine (PCP) and aminophosphine (PCP) pincer complexes, and
in each of these cases, catalysis was unaffected by metallic Next, under the optimal conditions with 17d as a catalyst (since
mercury during the cross-coupling reactions [41-43]. In addi- it provided the highest yield in the presence of TBAB, Table 2,
tion, stable Pd(IV) complexes have been widely prepared and entry 26), we examined the substrate scope with different sub-
characterised, thus for the catalysis of the pincer complexes in stituents on the aromatic rings of the bromobenzene and phenyl-
the current study, the Pd(II) to Pd(IV) mechanism was pro- boronic acid. The results are summarised in Table 3 and the
posed as shown in Scheme 2 [44].
scope and yields compare favourably well with reported
methods. First, the substrate scope of the phenylboronic acid
In order to verify the viability of the Pd(II) to Pd(IV) mecha- coupling partner was investigated. Under the optimised reac-
nism proposed, an exploratory computational study using the tion conditions, the presence of electron-donating and moder-
semi-empirical PM3 method was performed on the oxidative ately deactivating groups provided slightly better yields and
addition stage of the mechanism to determine if the results ob- faster reactions than those possessing strongly deactivating sub-
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Beilstein J. Org. Chem. 2018, 14, 1859–1870.
Scheme 2: Proposed mechanism of the Suzuki–Miyaura coupling reaction using pincer complex 17d.
stituents (Table 3, entries 2–4 vs 5). Next, the substrate scope of provide the corresponding biaryls in reasonable yields, to our
the aryl bromides was studied. Interestingly, the reaction provi- dismay the reaction of inactivated aryl chlorides led to the
ded excellent yields with both activated and deactivated aryl recovery of starting materials (Table 3, entries 12 and 13).
bromides, though the presence of a strongly electron-with-
drawing substituent gave marginally better yields than those Finally, the investigation of the reusability of the catalyst was
possessing electron-donating groups (Table 3, entries 6–11) carried out using the model cross-coupling reaction of
without much influence on the rate of the reaction. The slightly 4-bromoanisole (21a) and phenylboronic acid (22a) under the
lower yield of the reaction in the preparation of 23i could be optimised conditions (Scheme 3 and Figure 5). After comple-
ascribed to steric encumbrance exerted by the NO2-substituent tion of the reaction, the products were extracted with toluene
located at the ortho-position of the aryl bromide.
and to the remaining aqueous layer, which contains the catalyst
system, fresh 4-bromoanisole (21a) and phenylboronic acid
Encouraged by these results, the reactivities of aryl chlorides (22a) were added for the second and third cycles of the reaction.
were investigated under the optimised conditions. While acti- To our delight, the catalyst could be reused at least three times
vated aryl chloride 21f reacted with boronic acids possessing without significant loss of activity (93%, 80% and 75% for the
either electron-donating or electron-withdrawing groups to 1st, 2nd and 3rd run, respectively) considering the fact that
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Figure 4: Energy profile for the oxidative addition reaction involving 4-bromoanisole and Pd(II) catalyst precursor 17d. The change in energy for 17d
was calculated by computing it in kcal/mol as a cation at 298.15 K and 1 atm.
Scheme 3: Investigation on the reusability of the catalyst.
some of it could have been extracted along with the product and Conclusion
the results are summarised in Figure 5.
A series of novel cationic Pd(II) complexes have been success-
fully synthesised using easy to prepare SNS pincer ligands. A
Since the bidentate complexes 20a and 20b are also potential detailed investigation into the application of these complexes in
catalysts in their own right, the catalytic activity of 20a was the Suzuki–Miyaura coupling reaction was conducted using
investigated in the Suzuki–Miyaura coupling reaction of various aryl bromides and boronic acids as coupling partners in
4-bromoanisole (21a) and phenylboronic acid (22a) as a proof aqueous medium. All the complexes could catalyse the
of concept. As expected, it catalysed the reaction and provided Suzuki–Miyaura coupling reaction to provide the correspond-
biaryl 23a in moderate yield demonstrating the potential of such ing biaryls in excellent yields with only 0.5 mol % catalyst
complexes in coupling reactions (Scheme 4).
loading. Furthermore, unlike the previously reported SNS
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Beilstein J. Org. Chem. 2018, 14, 1859–1870.
pincer Pd(II) complexes, the catalysts in the current study were
compatible with both electron-donating and electron-with-
drawing substituents on the aryl bromides and boronic acid sub-
strates as well as activated aryl chlorides. Depending on the
presence or absence of the TBAB additive, the reaction may be
fine-tuned to either proceed via steric or electronic control. The
advantage of using these water-soluble catalysts for the cou-
pling reaction was their reusability for up to three times with-
out significant loss in activity. Moreover, the mechanism of the
coupling reaction was probed by a theoretical study that sup-
ported the experimental results. Contrary to the previously re-
ported SNS pincer Pd(II) complexes that were proposed to
proceed via a Pd(II) to Pd(0) type of mechanism, on the basis of
Figure 5: Reusability of pincer complex 17d as a catalyst for the
Suzuki–Miyaura cross coupling reaction.
Table 3: Results from the Suzuki–Miyaura cross-coupling reactions of various aryl bromides and boronic acids using pincer complex 17d as catalyst.a
Entry
ArBr
ArB(OH)2
Product
Yield (%)
Isolated
Time (h)
2
GC
93
1
88
90
86
86
23a
21a
21a
21a
21a
22a
2
3
4
96
94
92
1.5
23b
22b
22c
2
23c
23d
2
22d
22e
5
87
81
3
23e
21a
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Table 3: Results from the Suzuki–Miyaura cross-coupling reactions of various aryl bromides and boronic acids using pincer complex 17d as catalyst.a
(continued)
6
98
96
91
82
2
2
23f
22a
22a
21b
7
23g
23h
21c
21d
8
9
96
94
88
81
1.5
22a
22a
2
23i
23j
21e
21a
21a
10
11
96
95
89
86
2
2
22f
23k
22g
22a
12
13
83
89
77
81
3
3
23l
21f
21f
23m
22f
aCatalyst loading (0.5 mol %), ArX (1.63 mmol), ArB(OH)2 (2.61 mmol), H2O (2 mL), KOH (3.26 mmol), 120 °C, 2 h, TBAB (0.5 equiv relative to ArX).
the study described in this article the coupling reaction is pro- of the backbone on the catalytic activity of the SNS pincer
posed to proceed via a Pd(II) to Pd(IV) mechanism. This sug- Pd(II) complexes. In the future, efforts to fine tune the elec-
gests the effect of the chain length of the linker and the nature tronic and structural features of the thiophenyl and pyridinyl
1868

Beilstein J. Org. Chem. 2018, 14, 1859–1870.
Scheme 4: Suzuki–Miyaura coupling reaction catalysed by the SN-bidentate complex 20a.
8. Yan, J.; Hu, W.; Zhou, W. Synth. Commun. 2006, 36, 2097–2102.
doi:10.1080/00397910600636477
groups will be carried out in order to enable the catalysts to acti-
vate aryl chlorides, possessing electron-donating substituents, in
the coupling reaction.
9. Cohen, A.; Crozet, M. D.; Rathelot, P.; Vanelle, P. Green Chem. 2009,
11, 1736–1742. doi:10.1039/b916123f
10.Dawood, K. M.; El-Deftar, M. M. ARKIVOC 2010, 319–330.
doi:10.3998/ark.5550190.0011.930
Supporting Information
11.Tairai, A.; Sarmah, C.; Das, P. Indian J. Chem. 2012, 51B, 843–848.
12.Shen, L.; Huang, S.; Nie, Y.; Lei, F. Molecules 2013, 18, 1602–1612.
doi:10.3390/molecules18021602
Supporting Information File 1
Experimental part.
13.Massaro, M.; Riela, S.; Lazzara, G.; Gruttadauria, M.; Milioto, S.;
Noto, R. Appl. Organomet. Chem. 2014, 28, 234–238.
doi:10.1002/aoc.3114
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-160-S1.pdf]
14.Hervé, G.; Len, C. Front. Chem. (Lausanne, Switz.) 2015, 3, No. 10.
doi:10.3389/fchem.2015.00010
Supporting Information File 2
NMR spectra.
15.Li, Q. H.; Ding, Y.; Zhang, G.; Zhang, Z.; Mo, S. Curr. Org. Synth.
2017, 14, 462–476. doi:10.2174/1570179413666160624092044
16.Zhang, J.; Yang, F.; Ren, G.; Mak, T. C.; Song, M.; Wu, Y.
Ultrason. Sonochem. 2008, 15, 115–118.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-14-160-S2.pdf]
doi:10.1016/j.ultsonch.2007.02.002
17.de Souza, A. L. F.; da Silva, L. C.; Oliveira, B. L.; Antunes, O.
Tetrahedron Lett. 2008, 49, 3895–3898.
Acknowledgements
doi:10.1016/j.tetlet.2008.04.061
We thank the University of Johannesburg (UJ), the Research
Centre for Synthesis and Catalysis of the Department of Chem-
istry at UJ, Sasol Ltd and the National Research Foundation
(NRF) for funding. The use of UJ Spectrum’s NMR facilities is
also acknowledged. We would also like to thank Mr. Novisi
Oklu for his help in solving of the crystal structure.
18.Said, K.; Salem, R. B. Adv. Chem. Eng. Sci. 2016, 06, 111–123.
doi:10.4236/aces.2016.62013
19.Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4, 2973–2976.
doi:10.1021/ol0263907
20.Liu, L.; Zhang, Y.; Xin, B. J. Org. Chem. 2006, 71, 3994–3997.
doi:10.1021/jo060122v
21.Liu, C.; Ni, Q.; Hu, P.; Qiu, J. Org. Biomol. Chem. 2011, 9, 1054–1060.
doi:10.1039/c0ob00524j
ORCID® iDs
22.Liang, Q.; Xing, P.; Huang, Z.; Dong, J.; Sharpless, K. B.; Li, X.;
Jiang, B. Org. Lett. 2015, 17, 1942–1945.
Alphonse Fiebor - https://orcid.org/0000-0003-0836-0943
Banothile C. E. Makhubela - https://orcid.org/0000-0002-2292-7400
Henok H. Kinfe - https://orcid.org/0000-0002-4958-2836
doi:10.1021/acs.orglett.5b00654
23.Massaro, M.; Riela, S.; Cavallaro, G.; Colletti, C. G.; Milioto, S.;
Noto, R.; Parisi, F.; Lazzara, G. J. Mol. Catal. A: Chem. 2015, 408,
12–19. doi:10.1016/j.molcata.2015.07.008
References
1. Suzuki, A. Pure Appl. Chem. 1991, 63, 419–422.
24.Liu, C.; Li, X.; Wang, X.; Qiu, J. Turk. J. Chem. 2015, 39, 1208–1215.
doi:10.3906/kim-1505-97
doi:10.1351/pac199163030419
25.Hussain, I.; Capricho, J.; Yawer, M. A. Adv. Synth. Catal. 2016, 358,
3320–3349. doi:10.1002/adsc.201600354
2. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
doi:10.1021/cr00039a007
26.DeVasher, R. B.; Moore, L. R.; Shaughnessy, K. H. J. Org. Chem.
2004, 69, 7919–7927. doi:10.1021/jo048910c
3. Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168.
doi:10.1016/S0022-328X(98)01055-9
27.Zhou, J.; Guo, X.; Tu, C.; Li, X.; Sun, H. J. Organomet. Chem. 2009,
694, 697–702. doi:10.1016/j.jorganchem.2008.11.060
28.Garrido, R.; Hernández-Montes, P. S.; Gordillo, Á.; Gómez-Sal, P.;
López-Mardomingo, C.; de Jesús, E. Organometallics 2015, 34,
1855–1863. doi:10.1021/om501295b
4. Chatterjee, A.; Ward, T. R. Catal. Lett. 2016, 146, 820–840.
doi:10.1007/s10562-016-1707-8
5. Polshettiwar, V.; Decottignies, A.; Len, C.; Fihri, A. ChemSusChem
2010, 3, 502–522. doi:10.1002/cssc.200900221
6. Röhlich, C.; Wirth, A. S.; Köhler, K. Chem. – Eur. J. 2012, 18,
15485–15494. doi:10.1002/chem.201201266
29.Matsinha, L. C.; Mao, J.; Mapolie, S. F.; Smith, G. S.
Eur. J. Inorg. Chem. 2015, 4088–4094. doi:10.1002/ejic.201500588
7. Baxendale, I. R.; Griffiths-Jones, C. M.; Ley, S. V.; Tranmer, G. K.
Chem. – Eur. J. 2006, 12, 4407–4416. doi:10.1002/chem.200501400
1869

Beilstein J. Org. Chem. 2018, 14, 1859–1870.
30.Qiu, P.; Zhao, J. Y.; Shi, X.; Duan, X. H. New J. Chem. 2016, 40,
6568–6572. doi:10.1039/c6nj00377j
License and Terms
31.Sun, N.; Chen, M.; Jin, L.; Zhao, W.; Hu, B.; Shen, Z.; Hu, X.
Beilstein J. Org. Chem. 2017, 13, 1735–1744. doi:10.3762/bjoc.13.168
32.Kumar, A.; Rao, G. K.; Kumar, S.; Singh, A. K. Organometallics 2014,
33, 2921–2943. doi:10.1021/om4007196
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0). Please note
that the reuse, redistribution and reproduction in particular
requires that the authors and source are credited.
33.Kumar, A.; Rao, G. K.; Kumar, S.; Singh, A. K. Dalton Trans. 2013, 42,
5200–5223. doi:10.1039/c2dt32432f
34.Bai, S.-Q.; Hor, T. S. A. Chem. Commun. 2008, 3172–3174.
doi:10.1039/b802043d
35.Kumar, S.; Rao, G. K.; Kumar, A.; Singh, M. P.; Singh, A. K.
Dalton Trans. 2013, 42, 16939–16948. doi:10.1039/c3dt51658j
36.Soobramoney, L.; Bala, M. D.; Friedrich, H. B. Dalton Trans. 2014, 43,
15968–15978. doi:10.1039/C4DT01750A
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(https://www.beilstein-journals.org/bjoc)
37.Pioquinto-Mendoza, J. R.; Conelly-Espinosa, P.; Reyes-Martínez, R.;
Toscano, R. A.; Germán-Acacio, J. M.; Avila-Sorrosa, A.;
Baldovino-Pantaleón, O.; Morales-Morales, D. J. Organomet. Chem.
2015, 797, 153–158. doi:10.1016/j.jorganchem.2015.08.024
38.The crystallographic data is deposited at the Cambridge
Crystallographic Data Centre and the CCDC # of 17d is 1839866.
39.Sogukomerogullari, H. G.; Şen, F.; Dinçer, M.; Özdemir, N.;
Sönmez, M. J. Mol. Struct. 2017, 1136, 271–280.
doi:10.1016/j.molstruc.2017.02.015
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.14.160
40.Ocansey, E.; Darkwa, J.; Makhubela, B. C. E. RSC Adv. 2018, 8,
13826–13834. doi:10.1039/C8RA01430B
41.Peris, E.; Loch, J. A.; Mata, J.; Crabtree, R. H. Chem. Commun. 2001,
201–202. doi:10.1039/b008038l
42.Olsson, D.; Wendt, O. F. J. Organomet. Chem. 2009, 694, 3112–3115.
doi:10.1016/j.jorganchem.2009.05.025
43.Bolliger, J.; Blacque, O.; Frech, C. Angew. Chem., Int. Ed. 2007, 46,
6514–6517. doi:10.1002/anie.200701804
44.Canty, A. J. Acc. Chem. Res. 1992, 25, 83–90.
doi:10.1021/ar00014a005
45.Cundari, T. R.; Deng, J. J. Chem. Inf. Comput. Sci. 1999, 39, 376–381.
doi:10.1021/ci980145d
46.Bosque, R.; Maseras, F. J. Comput. Chem. 2000, 21, 562–571.
doi:10.1002/(SICI)1096-987X(200005)21:7<562::AID-JCC5>3.0.CO;2-
0
47.Monteiro, A. L.; Davis, W. M. J. Braz. Chem. Soc. 2004, 15, 83–95.
doi:10.1590/S0103-50532004000100014
48.Nicasio-Collazo, J.; Álvarez, E.; Alvarado-Monzón, J. C.;
Andreu-de-Riquer, G.; Jimenez-Halla, J. O. C.;
De León-Rodríguez, L. M.; Merino, G.; Morales, U.; Serrano, O.;
López, J. A. Dalton Trans. 2011, 40, 12450–12453.
doi:10.1039/c1dt11451d
1870