Microwave assisted Suzuki-Miyaura and Mizoroki-Heck cross-couplings catalyzed by non-symmetric Pd(II) CNS pincers supported by iminophosphorane ligands

Article abstract of DOI:10.1016/j.ica.2017.03.044

Two new Pd^II non-symmetrical CNS pincer type complexes [PdCl{C₆H₄(Ph₂P?=?NC₆H₄SR-κ³-C,N,S)}] [R?=?Bn (3) and 4-C₆H₅NO₂ (4)], supported by iminophosphorane ligands functionalized with a thioether moiety, were prepared and fully characterized. These compounds and the already known complexes 1 (R?=?Me) and 2 (R?=?Ph) were evaluated as catalysts in microwave assisted Suzuki-Miyaura and Mizoroki-Heck coupling reactions. Whereas compound 1 instantaneously decomposed under MW irradiation, as visible black Pd⁰ precipitated in both processes, compounds 2–4 showed good conversions without apparent decomposition. The coupling reactions were dramatically accelerated under MW radiation when compared to conventional heating, with 3 (R?=?4-C₆H₄NO₂) showing the highest catalytic efficiency of all in both processes. The catalytic activity of complex 2 was further examined in the two cross-couplings with a series of para-substituted bromo-benzenes. Both catalyses proceeded under normal aerobic conditions and were not affected by an excess of elemental Hg. The Mizoroki-Heck reaction operated with high regioselectivity, yielding only the linear 1,2-products.

Full text of DOI:10.1016/j.ica.2017.03.044

Inorganica Chimica Acta 462 (2017) 249–255
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Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Research paper
Microwave assisted Suzuki-Miyaura and Mizoroki-Heck cross-couplings
catalyzed by non-symmetric Pd(II) CNS pincers supported by
iminophosphorane ligands
a
b
c,
⇑
Sandra Ramírez-Rave , David Morales-Morales , Jean-Michel Grévy
a
Departamento de Química, Área de Catálisis, Grupo ECOCATAL, Universidad Autónoma Metropolitana-Iztapalapa, Avenida San Rafael Atlixco # 189, 09340 Ciudad de México, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Cd. Universitaria, Circuito Exterior, Coyoacán, 04510 Ciudad de México, Mexico
Centro de Investigaciones Químicas, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Avenida Universidad # 1001,
b
c
Chamilpa, CP 62209 Cuernavaca, Morelos, Mexico
a r t i c l e i n f o
a b s t r a c t
Two new PdII non-symmetrical CNS pincer type complexes [PdCl{C H (Ph P = NC H SR- 3-C,N,S)}]
j
Article history:
6
4
2
6
4
Received 28 February 2017
Received in revised form 30 March 2017
Accepted 31 March 2017
Available online 3 April 2017
[
R = Bn (3) and 4-C
moiety, were prepared and fully characterized. These compounds and the already known complexes 1
R = Me) and 2 (R = Ph) were evaluated as catalysts in microwave assisted Suzuki-Miyaura and
6 5 2
H NO (4)], supported by iminophosphorane ligands functionalized with a thioether
(
Mizoroki-Heck coupling reactions. Whereas compound 1 instantaneously decomposed under MW irradi-
0
ation, as visible black Pd precipitated in both processes, compounds 2–4 showed good conversions with-
Keywords:
out apparent decomposition. The coupling reactions were dramatically accelerated under MW radiation
when compared to conventional heating, with 3 (R = 4-C H NO ) showing the highest catalytic efficiency
6 4 2
of all in both processes. The catalytic activity of complex 2 was further examined in the two cross-cou-
plings with a series of para-substituted bromo-benzenes. Both catalyses proceeded under normal aerobic
conditions and were not affected by an excess of elemental Hg. The Mizoroki-Heck reaction operated
with high regioselectivity, yielding only the linear 1,2-products.
Iminophosphorane
Non-symmetrical pincer
Palladium
Suzuki-Miyaura
Mizoroki-Heck
Microwave
Ó 2017 Elsevier B.V. All rights reserved.
1
. Introduction
Transition metal catalysts have played a very important part in
Actually, the Suzuki-Miyaura coupling between organic halides
and phenylboronic acids is one of the most powerful methods for
the synthesis of biaryl compounds. These are intermediates in
the organic synthesis of performance materials and pharmaceuti-
cals under mild reaction conditions [9]. The Mizoroki-Heck cou-
pling between organic halides or pseudohalides (diazonium salts
and triflates) and alkenes is also really attractive, as it allows the
substitution of alkenes with high stereoselectivity for trans cou-
pling [10]. Finding efficient and selective catalytic systems for
these specific transformations using transition metal complexes
is still an active subject in organic synthesis. For instance, as a
result of their high thermal and oxidative stabilities, palladium-
pincer complexes have been widely studied to promote very effi-
ciently different CAC cross-couplings [11–14]. During the past
two decades, the vast majority of the studies reported on this sub-
ject referred to pincer complexes of typical XYX structure with C2v
symmetry, were the central atom in the ligand is commonly a N or
a C atom usually carrying a negative charge, and the side arms
donor atoms are identical and usually a heteroatom from the
non-exhaustive list: N, P, O, S, Se or a carbene (Fig. 1A). Nonethe-
less, it has been shown lately that non-symmetrical pincer com-
chemistry since the beginning of the 20th Century. Nevertheless,
their role became invaluable for synthetic chemists with the
apparition of cross-coupling reactions catalyzed by palladium,
which allowed the design of new organic compounds with a wide
spectrum of different applications (new materials, optical devises,
0
drugs, etc.) [1]. They were developed in the 70 s independently by
Mizoroki [2] and Heck [3], Stille [4], Negishi [5], Sonogashira [6]
and Suzuki [7], with some differences in their starting reagents
and the nature of the newly formed compound during the catalytic
process. These reactions have in common that two organic mole-
cules bond to Pd in different steps of the catalytic cycle through
the formation of a carbon–metal
r bond and subsequently these
carbon atoms migrate to form a new CAC bond, which would be
difficult to obtain otherwise [8].
⇑
Corresponding author.
E-mail address: jeanmichelg@gmail.com (J.-M. Grévy).
http://dx.doi.org/10.1016/j.ica.2017.03.044
020-1693/Ó 2017 Elsevier B.V. All rights reserved.
0

2
50
S. Ramírez-Rave et al. / Inorganica Chimica Acta 462 (2017) 249–255
Fig. 1. General formula of pincer complexes: symmetrical (A), non-symmetrical (B) and non-symmetrical CNS (C), based on mixed iminophosphorane-thioether ligands (this
work).
0
plexes (XYX ), were the side arm donor atoms are different
(
[
using standard procedures [26]. Infrared spectra were acquired in
KBr using a Bruker Vector 22 instrument. NMR spectra were
recorded on a Varian Gemini 200 MHz and a Varian Unity Inova
0
X – X ), can bring some benefits to catalytic applications (Fig. 1B)
15]. In particular this ligand family provide an easiest access to
hemilabile coordination with potentially increased catalyst activ-
ity, and facilitate the introduction of chirality.
400 MHz instruments in CDCl
3
, which was used as internal refer-
ence. P{ H} NMR spectra were acquired with complete proton
decoupling and are reported in ppm using 85% H PO as external
3
1
1
In an earlier paper we have reported a rare model of non-sym-
3
4
II
metrical CNS Pd pincer complexes derived from iminophospho-
standard. Mass measurements (FAB+) were obtained at a resolu-
tion of 3000 using magnetic field scans and the matrix ions as
the reference material or, alternatively, by electric field scans with
the sample peak bracketed by two (polyethylene glycol or cesium
iodide) reference ions. Melting points were measured in a Mel
Temp II device using sealed capillaries and are reported without
correction.
3
rane [PdCl{C H
6 4
2
(Ph P = NC
6 4
H SR-
j
-C,N,S)} (R = Me, Ph)] were
the anionic C atom occupies a lateral position instead of the typical
central position in common pincer complexes (Fig. 1C) [16]. Pre-
liminary experiments showed that the methyl substituted complex
(
R = Me) was an efficient catalyst in the Suzuki-Miyaura CAC cross-
coupling reactions of a series of para-substituted bromobenzenes
under conventional heating (110 °C).
In the search for more eco-friendly, economical and sustainable
protocols than conventional laboratory heating techniques, it has
been established that microwave (MW) assisted methods have
undeniable advantages and benefit a wide range of metal-cat-
alyzed processes and cross-coupling reactions, exhibiting faster
reaction kinetics, shorter reaction times and cleaner products
3
2
.1. Synthesis of [PdCl{C
6
H
4
(Ph
2
P = NC
6
H
4
SPhNO
2
-
j
-C,N,S)}](3)
ꢁ5
[
Na
2
PdCl
4
] (0.013 g, 4.38 ꢀ 10 mol) was added to a mixture of
iminophosphorane
4
ligand
[Ph
3
P = NC
PO
H
6 4
SPhNO
2
]
(0.022 g,
ꢁ5
ꢁ5
.38 ꢀ 10 mol) and excess of Na
3
4
(0.0123 g, 7.5 ꢀ 10 mol)
2
in toluene (20 ml), under N atmosphere. The resulting solution
[
17]. For instance, Larhed first reported the use of this energy
was refluxed for 1.5 h. After this time, the solution was filtered
on silica gel and the solvent was removed under vacuum leading
to the isolation of an orange powder. Yield (0.002 g, 20%). Mp.:
H22ClN O P Pd S (647.42): C, 55.66; H,
2 2 1 1 1
.43; N, 4.33. Found: C, 55.93; H, 3.58; N, 4.03. MS FAB+: 468
source to promote CAC cross-coupling reactions in both homoge-
nous and solid phase processes [18] obtaining high yields of con-
versions within 5 min of irradiation at low potencies. Since then,
many reports have shown that microwave assisted methodology
can be used to improve CAC cross-coupling protocols in different
solvents for a wide variety of Pd compounds [19–21], including
few palladacycles [22] and pincer complexes [23]. In this context,
a review on the subject of MW assisted synthesis in aqueous media
has recently been published and is dedicated in part to CAC cross-
couplings [24]. We report here the catalytic behavior of non-sym-
metrical CNS pincer Pd complexes 1, 2, 3, and 4 (Scheme 1) as cat-
alysts in the Suzuki-Miyaura and Mizoroki-Heck cross-coupling
reactions under MW activation.
1
3
55 °C. Anal. Calc. for C30
ꢁ1
1
(
60%). IR (
m
, cm ): 1255 (
), 6.87 (dd, 1H, SC
N), 7.25 (dd, 1H, SC
PPh ), 7.66 (m, 4H PPh
00 MHz) d: 15.31 (-SCH ), 156.93 (d,
52.86 (C -N, SC N), 129.13 (C , SC
26.74 (C , SC N), 135.92 (C , SC
PPh ), 132.80 (d, P,C = 10.0 Hz,
= 11.0 Hz, C PPh ), 133.77 (d, JP,C = 2.0 Hz, C
P,C = 142.1 Hz, C -P, PC
Pd). P{ H} NMR (CDCl
m
PN). H NMR (CDCl
N), 7.02 (t, 1H, SC
N), 8.17 (m, 4H
3
, 400 MHz):
N),
PPh ),
). C{ H}NMR (CDCl
d = 2.83 (s, 3H, -SCH
3
6
H
4
6 4
H
8
7
1
1
1
C
.17 (d, 1H, SC
6
H
4
6
H
4
o
3
1
3
1
.61 (m, 4H
m
3
p
3
3
,
N),
N),
3
3
J
PC = 31.9, C
N), 128.82 (C
H N), 125.82 (d, JPC = 113.02,
6 4
i
-S, SC
, SC
6
H
H
4
i
6
H
4
3
6
H
4
4
6
4
1
5
H
6 4
6
2
3
i
3
J
C
o
PPh
3
), 129.56 (d,
PPh ), 141.00 (d,
Pd), 155.62 (d, JP,C = 19.1 Hz, C -Pd, PC
3
, 161 MHz): d = 47.3.
J
P,
4
C
m
3
p
3
1
2
J
i
6
H
4
i
6
-
3
1
1
H
4
2
. Experimental
3
The ligands used in this work, as well as catalysts 1 and 2, were
6 4 2 6 4 2 6 5
2.2. Synthesis of [PdCl{C H (Ph P = NC H SCH C H -j -C,N,S)}] (4)
previously reported by our laboratory [16,25]. The synthesis of
complexes 3 and 4 was carried out under nitrogen atmosphere
using conventional Schlenk techniques, and solvents were dried
ꢁ5
Under N
2
atmosphere, [Na
2
PdCl
4
] (0.013 g, 4.38 ꢀ 10 mol)
P = NC
was added to a mixture of iminophosphorane ligand [Ph
2
6
-
Scheme 1. Synthesis of non-symmetric CNS pincer complexes 1–4.

S. Ramírez-Rave et al. / Inorganica Chimica Acta 462 (2017) 249–255
251
ꢁ
5
H
(
4
SCH
C H
2 6 5
] (0.021 g, 4.38 ꢀ 10 mol) and an excess of Na
3
PO
4
3. Results and discussion
ꢁ5
0.0123 g, 7.5 ꢀ 10 mol) in 20 ml of 1,2-dichloroethane. The
resulting solution was refluxed for 1.5 h. After this time, the solu-
tion was filtered on silica gel and the solvent was removed under
vacuum leading to the isolation of a yellow powder. Yield
The iminophosphorane ligands were synthesized following a
procedure previously reported by our group [1,2] (Scheme 1).
Following the method reported for the synthesis of complexes 1
and 2, [Na PdCl ] and an excess of base (Na PO in this case) were
(
0.022 g, 81%). Mp.: 157 °C. Anal. Calc. for C31
1 1 1 1 1
H25Cl N P Pd S
2
4
3
4
(
616.45): C, 60.40; H, 4.09; N, 2.27. Found: C, 60.19; H, 4.44; N,
reacted with the corresponding iminophosphorane ligand under
reflux in toluene or 1,2-dichloroethane, yielding the new non-sym-
metric CNS pincer complexes 3 and 4, respectively (Scheme 1). The
formation of 3 was very slow as compared to that of 4, and only
20% yield of 3 was obtained during the time required to obtained
80% yield of the other complexes (1 82%, 2 81%, 4 81%). Some
efforts have been made to improve the yield of formation of pincer
3, but longer reaction times and higher temperatures just lead to
the formation of complex mixtures difficult to purify. Both com-
plexes were obtained as air- and moisture-stable orange to yellow
solids, soluble in organic chlorinated and polar solvents. Spectro-
scopic and analytical data were consistent with the proposed
structures.
ꢁ1
2
4
1
.55. IR (
00 MHz):d = 2.83 (s, 3H, -SCH
SC N), 8.17 (d, 1H SC
, PPh ), 7.48 (m, 4H , PPh
NMR (CDCl
-S, SC N), 152.85 (C
, SC N), 126.74 (C , SC
P,C = 106.0 Hz, PPh ), 132.86 (d,
P,C = 13.2 Hz, C PPh ), 133.25 (d,
), 140.59 (d, JP,C = 150.2 Hz, C -P, PC Pd), 154.01 (d,
P{ H} NMR (CDCl
3
m, cm ): 1257 (mPN). MS FAB+: 616 (40%). NMR (CDCl ,
3
), 6.87 (dd, 1H
,
SC
6
4
H N), 7.02 (t,
H
m, 4H
,
6
H
4
,
6
H
4
N), 7.25 (dd, 1H
,
SC
, PPh
6
H
4
N), 7.60
1
3
1
(
o
3
m
3
), 7.39 (m, 4H
p
3
). C{ H}
J
4
3
, 100 MHz) d: 15.31 (-SCH
-N, SC N), 129.13 (C
N), 135.92 (C , SC
P,C = 10.0 Hz,
2
), 156.93 (d,
PC = 31.90,
N), 128.82
N), 128.45 (d,
PPh ),
P,C = 1.1 Hz, C
C
i
6
H
4
i
6
H
4
3
, SC H
6 4
(
C
4
6
H
4
5
6
H
4
6
6 4
H
1
2
J
C
i
3
J
C
o
3
3
4
1
PPh
29.26 (d,
J
m
3
J
p
2
3
i
1
H
6 4
J
P,
31
C
= 16.1 Hz, C
d = 47.9.
i
-Pd, PC
6
H
4
Pd).
3
, 161 MHz):
IR spectroscopy shows that iminophosphorane ligands coordi-
nate the metal center through the iminic N, since the
m
(P = N)
absorption (3: 1251 cm ; 4: 1249 cm ) has been shifted to lower
frequencies when compared to the corresponding free ligand (Ph
ꢁ1
ꢁ1
2
.3. General procedure for the suzuki–miyaura cross-coupling
3
-
ꢁ
1
Suzuki–Miyaura couplings were done in glass tubes suitable for
P = NC H SPhNO :
1330 cm
;
2 6 4 2 6 5
Ph P = NC H SCH C H :
6
4
2
ꢁ
1
use in a microwave apparatus. 5 mL of a DMF solution containing
1332 cm ), as observed for similar compounds before [1,2,27].
ꢁ4
ꢁ4
31
1
1
13
1
an halobenzene (4.3 ꢀ 10 mol), phenyl boronic acid (4.7 ꢀ 10
-
Multinuclear NMR experiments, P{ H}, H and C{ H}, also con-
ꢁ
4
ꢁ3
mol), Na
.1 mol%) were stirred and heated at 110 °C under microwave irra-
diation during 5 min in a CEM Discover reactor. Then, the reaction
mixture was cooled at room temperature and extracted with CH
Cl . The organic phase was collected and dried with anhydrous
Na SO , filtered through Celite and analyzed by Gas Chromatogra-
3
PO
4
(9.5 ꢀ 10 mol) and Pd catalyst (4.31 ꢀ 10 mmol,
firm the suggested structures for complexes 3 and 4. For instance,
3
1
1
0
the P{ H} NMR spectra shows only one single signal and when
compared with the respective free ligand this signal shows the
expected 50 ppm shift due to the endo orthometallation (3, d
47.3 ppm; 4, d 47.9 ppm). The similarity of chemical shift between
3 and 4 suggests that the nature of S substituents in Pd complexes
2
-
2
2
4
1
phy (GC–MS) on an Agilent 6890 N GC with a 30.0 m DB-1MS cap-
illary column coupled to an Agilent 5973 Inert Mass Selective
detector.
has no significant electronic effect on the P atom. In H NMR spec-
tra, the new orthometallated ring gives place to four signals in the
aromatic region between d 7 and 8 ppm for both non-symmetric
1
3
1
CNS pincer compounds. The C{ H} NMR spectra also validates
the formation of pincer complexes 3 and 4 through orthometalla-
1
3
2
.4. General procedure for the Mizoroki-Heck cross-coupling reactions
tion due to the presence of a new quaternary C coupled to P, cor-
2
responding to the metallocycled Cipso, at d 155.62 ppm (d, JP,
2
Mizoroki-Heck couplings were carried out in glass tubes appro-
C = 19.1 Hz) for 3 and 154.01 ppm (d, JP,C = 16.1 Hz) for 4. Compa-
priate for use in a microwave reactor. Different p-substituted bro-
rable chemical shifts and spin systems were already described for
related iminophosphorane pincer compounds [1,2,28].
ꢁ4
ꢁ4
mobenzenes (4.317 ꢀ 10 mol), styrene (4.749 ꢀ 10 mol),
ꢁ
4
ꢁ3
Na
.1 mol%) were mixed in 5 mL of DMF under vigorous stirring
and also heated at 110 °C under microwave irradiation during
5 min in a CEM Discover apparatus. Subsequently, the reaction
mixture was cooled at RT and treated with CH Cl , the organic
phase was collected, dried with anhydrous Na SO and filtered
3
PO
4
(9.498 ꢀ 10 mol) and Pd catalyst (4.31 ꢀ 10 mmol,
0
1
3.1. MW assisted Suzuki-Miyaura cross-coupling
2
2
2
4
The Suzuki-Miyaura reaction is an efficient Pd catalyzed CAC
coupling reaction between organohalides and phenylboronic acids
that is widely used to synthesize poly-olefins, styrene and biphenyl
compounds both in laboratory and industrial scales. Thus, we
chose to evaluate the activity of compounds 1–4 in the Suzuki-
Miyaura reaction between an aryl-halide and phenylboronic acid.
It is well known that CAC cross-couplings are influenced by a ser-
ies of parameters, so in order to evaluate the effect of the reaction
temperature, solvent, base and catalyst loading we performed
experiments to define the optimal conditions. Preliminary runs of
Suzuki-Miyaura coupling were carried out reacting phenylboronic
acid and bromobenzene in the presence of different catalyst
charges and 2.2 equivalents of base. In a previous evaluation of
the catalyst activity of 1 in the same cross-coupling under conven-
through Celite. Finally, extracted samples were analyzed by Gas
Chromatography (GC–MS) on an Agilent 6890 N GC with a
3
0.0 m DB-1MS capillary column coupled to an Agilent 5973 Inert
Mass Selective detector.
Complementary catalytic experiments were done under the
same reaction conditions using different bases [Na
Rb CO , Cs CO , NaOH].
2 3 2 3
CO , K CO ,
2
3
2
3
2.5. Mercury drop experiments
Following the catalytic procedures 1.3 and 1.4, two drops of ele-
mental Hg were added to the reaction media before microwave
irradiation. The CH Cl extract samples were obtained and ana-
2
2
3 4
tional heating we observed better results using the base Na PO , so
lyzed by GC-MS in the same way. No significant difference in the
conversion was observed between these experiments and those
in the absence of mercury, indicating that heterogeneous Pd(0) is
not involved in the reaction.
we selected that same base in those preliminary runs. The results
showed that a 0.1% molar catalyst load was optimal, and allowed
a comparison of the catalytic efficiency of 1, 2, 3 and 4 (Scheme 2)
(Table 1).

2
52
S. Ramírez-Rave et al. / Inorganica Chimica Acta 462 (2017) 249–255
Scheme 2. Evaluation of the catalytic activity of complexes 1–4 in Suzuki-Miyaura reaction.
Table 1
MW assisted Suzuki Miyaura coupling between phenyl bromide and
phenylboronic acid using catalysts 1–4 in the presence of Na PO as base.
5 min, fair to good conversions were observed with electron donat-
ing (EDG) para substituents (entries 1–4 Table 3) and excellent
yields were obtained with electron-withdrawing groups (EWG)
(entries 5–9 Table 3). Comparing these results with our prelimi-
nary evaluation of 1 and 2 as catalysts for the same cross-coupling
process but under conventional heating, the benefits of microwave
irradiation are evident. While 2 was almost inactive under conven-
tional heating, now, under microwave assistance, 2 became a bet-
ter catalyst than 1 which decomposed promptly, i.e. with 10 times
lower catalyst charge (0.1% vs. 1%) 2 performed the coupling with
better (entries 1–5, para-EDG) or equal (entries 6–9, para-EWG)
conversions in shorter times (5 min vs. 5 h) and at the same tem-
perature. The high yield of 4-chlorobiphenyl (93%) in the coupling
of 1-bromo-4-chloro benzene (entry 5) indicated that 2 selectively
reacted with the more activated C-Br bond and that the C-Cl bond
was almost unreactive in those conditions.
3
4
L
Conversion (%)
0*
72
90
66
1
2
3
4
Reaction conditions: DMF (5 mL), phenyl bromide (0.43 mmol), Na
3
PO
4
ꢁ
3
(
(
0.95 mmol), [Pd] 0.1% mol (4.31 ꢀ 10 mmol), and phenylboronic acid
*
0.47 mmol). Temperature 110 °C (60 W), reaction time 5 min,
1
decomposes instantaneously under microwave irradiation.
In the reaction between bromobenzene and phenylboronic acid
0
catalyzed by compound 1, the formation of visible black Pd indi-
cated the decomposition of the complex. Consequently the conver-
sion of the expected biphenyl product was not detected, suggesting
that the palladacycle in this pincer compound suffers some kind of
destruction under microwave irradiation. On the other hand, com-
pounds 2, 3 and 4 showed high yields of the expected coupled pro-
duct, 72%, 90% and 66% respectively. This was quite unexpected for
us, knowing that in our previous study of 1 and 2 as potential cat-
alysts in the same cross-coupling process but under conventional
heating, 1 was found to perform better than 2 who showed almost
no catalytic activity (5% conversion). In the present case, it
appeared that a phenyl or benzyl substituent on the S atom pro-
vided some stability to the CNS pincer under microwave irradia-
tion without hampering the catalytic performance, because no
decomposition was observed for 2, 3 and 4. A comparison of the
Apart from the Suzuki-Miyaura coupling reaction with complex
1, under these conditions no decomposition of the catalyst was
observed during catalysis and the performance of catalysts 2, 3,
and 4 were not affected by the presence of excess elemental Mer-
cury. These results suggest that the reaction may not proceed
through the formation of soluble palladium nanoparticles. This is
worth mentioning because there is still some discussion in the lit-
erature concerning the oxidation states of the metal center
involved in the catalytic cycle with palladacycles. Depending on
the structure of the complex and the conditions used, two principal
mechanistic schemes are possible: a Pd(0)/Pd(II) redox cycle with
destruction of the palladacycle and a Pd(II)/Pd(IV) cycle maintain-
ing the palladacycle intact. In the present study the Pd(II)/Pd(IV)
scheme is more preferred because of the stabilizing effect present
in the electron-donating ligand, also elemental Hg makes no differ-
ence in the isolated yields of coupling products and the catalysis
operate under normal aerobic conditions. However, an earlier
report from Urriolabeltia et al. [30] unveiled the hemilabile charac-
activity of 2 (-SPh) and 3 (-SC
steric bulk, indicated that the electron-withdrawing group NO
6
H
4
pNO
2
), two compounds of similar
in
2
para position has a positive outcome on the catalytic activity that
can be related to electronic factors. This notable effect is probably
not related to an expected decrease of electron density on the Pd
2
center due to the strong electron withdrawing property of NO ,
because that would work against the oxidative addition step of
the catalytic cycle. We rather believe that it is related to an
improved hemilability of the coordination between S and Pd,
II
II
ter of the thioether coordination to Pd in a related CNS complex,
so that we cannot rule out here the other possibility that the S
atom would be displaced from the metal during the catalysis with-
out forming high valent Pd species [1,31].
related to a decrease of the
r donor character of S. However, even
if the highest yield of conversion was obtained with 3 (90%), we
chose to complete the catalytic study with complex 2 (72%), which
is significantly easier to synthesize than 3 (yield of synthesis for 2
3.2. MW assisted Mizoroki-Heck cross-coupling
The Pd catalyzed arylation of olefins is a powerful tool for the
construction of CAC bonds and it is widely used in the synthesis
of polymers, pharmaceuticals and natural products. So, the
8
0% vs. 20% for 3) but still displays a satisfactory catalytic perfor-
mance when compared to that of 3 (yield of conversion: 72% for
2
vs. 90% for 3).
Due to the essential role played by the base in the Suzuki-
Table 2
Miyaura coupling, we kept on studying the effect of different bases
using 2 as catalyst under the aforementioned conditions, but with
a limited reaction time of 2.5 min of MW irradiation. As expected
MW assisted Suzuki-Miyaura coupling between bromobenzene and phenyl-
boronic acid using 2 as catalyst and different bases.
Base
Na CO
CO
Conversion (%)
from our previous report, the best results were obtained when Na
2
-
CO or Na PO were used, giving conversions of 40% and 50%
3
3
4
2
3
40
30
20
38
15
50
K
2
3
respectively. Any other base tested appeared to reduce the yield
of coupling product (Table 2).
Rb
Cs
NaOH
Na PO
2
CO
3
2
CO
3
3 4
Under optimized conditions (Na PO , DMF, 110 °C, 5 min), 2
was evaluated as catalyst toward different para-substituted bro-
mobenzenes. The results showed a clear correlation between the
yield of transformation and the nature of the aromatic substituent
para to Br, or its Hammett substituent constant [29]. Thus, in only
3
4
Reaction conditions: DMF (5 mL), phenyl bromide (0.43 mmol), base
(0.95 mmol),
(0.47 mmol). Temperature 110 °C (60 W), reaction time 2.5 min.
0.1 mol% (4.31 ꢀ 10ꢁ3 mmol), and phenylboronic acid
2

S. Ramírez-Rave et al. / Inorganica Chimica Acta 462 (2017) 249–255
253
Table 3
Table 4
MW assisted Suzuki-Miyaura coupling between phenylboronic acid and different para
substituted phenyl bromide using 2 as catalyst.
MW assisted Mizoroki-Heck coupling between phenyl bromide and styrene using
catalysts 1–4 in the presence of Na
3
PO
4
as base.
Entry Bromobenzene
1
Product
% Conversion
63
L
cis-Stilbene
trans-Stilbene
Conversion (%)
1*
2
3
0
6
6
5
0
0
46
45
38
52
51
43
4
2
3
4
5
6
7
8
9
74
3 4
Reaction conditions: DMF (5 mL), phenyl bromide (0.43 mmol), Na PO
3
(
1
0.95 mmol), [Pd] (4.31 ꢀ 10ꢁ mmol), and styrene (0.47 mmol). Temperature
*
10 °C (100 W), reaction time 15 min, 1 decomposes instantaneously under
64
microwave irradiation.
First, it is worth mentioning here that this catalysis occurs with
high regioselectivity and only the linear, or 1,2-products, are
obtained. In a study regarding the regiochemistry of the Heck reac-
tion with Pd complexes supported by diphosphine ligands, Cabri
et al. [32] proposed that differences in regioselectivity depend on
the alkene substituent and the reaction pathway taken for the
alkene coordination-insertion event, i.e. a neutral pathway vs. a
cationic pathway. With styrene, the neutral pathway would lead
to a 100% conversion in 1,2-product as in our case, while the catio-
nic pathway would give rise to a mixture of 1,2- and 1,1-product in
a 60%/40% proportion. Even when our non-symmetrical CNS pincer
complexes are structurally radically different from the diphos-
phine complexes studied by Cabri and so we cannot formally refer
to a neutral pathway, it is clear that these non-symmetrical pincers
influence the carbopalladation step in such a way that a high 1,2-
regioselectivity is observed here.
72
93
>99
92
96
>99
As observed in the Suzuki Miyaura cross-coupling study, the
results collected in Table 5 show a net correlation between the
yield of transformation and the nature of the aromatic substituent
para to Br, or its Hammett substituent constant [29]. We observed
a complete conversion with 1-bromo-4-nitrobenzene (99%, entry
9) and high yield conversions with other electron-withdrawing
group (64 to 95%, entries 6–8). Lower conversions and yields were
achieved with aryl bromides substituted with electron-donating
groups (10–50%, entries 1–5). Altogether, there is a good correla-
tion between the Hammett constant of the para-substituent and
the conversion yield. This electronic effect is not surprising, since
electron-withdrawing substituents on the aromatic ring are
expected to facilitate the coupling reaction considering that an
essential oxidative addition step of the aryl bromide to the metal
center occurs during the catalytic cycle.
Yields obtained by GC are based on remaining bromobenzene and are the average of
two runs. Reaction conditions: DMF (5 mL), phenyl bromide (0.43 mmol), Na PO
3
4
ꢁ
3
(
0.95 mmol), 2 0.1 mol% (4.31 ꢀ 10 mmol), and phenylboronic acid (0.47 mmol).
Temperature 110 °C (60 W), reaction time 5 min.
catalytic activity of complexes 1, 2, 3 and 4 was also estimated in a
model Mizoroki-Heck cross-coupling reaction between bromoben-
zene and styrene, using the generic conditions displayed in
Scheme 3, with the base Na
3 4
PO and a 0.1% mol. catalyst load
(Table 4). As predictable from its aforementioned behavior in the
Suzuki-Miyaura coupling, complex 1 decomposed before any cou-
pled product could be formed and detected. The instantaneous for-
0
mation of visible Pd black precipitate indicated that the
The exact mechanism of the Heck reaction is not completely
understood, with the exact mechanistic pathways depending on
reaction conditions and substrates employed. However, for the
same reasons exposed in the Suzuki-Miyaura study, i.e high ther-
mal and aerobic stability of the catalytic system and no effect of
the Mercury drop on the yields of conversion, a Pd(0)/Pd(II) redox
cycle with destruction of the palladacycle is not likely in this
catalysis.
palladacycle was quickly destroyed under microwave irradiation.
However, in the same conditions complexes 2, 3 and 4 proved
again to be efficient catalysts with fairly good conversions [(2)
5
2%; (3) 51%; and (4) 43%] with the usual, although remarkable,
trans-selectivity of the Mizoroki-Heck coupling. Compounds 2
and 3 performed as roughly equally efficient catalysts, thus, for
practical reasons we preferred the easiest to synthesize pincer 2
to continue with the catalytic study.
In summary, the microwave assisted catalytic activity of non-
3 4
Under optimized conditions (Na PO , DMF, 110 °C, 15 min, 0.1%
II
symmetrical pincer Pd complexes [PdCl{C
6
H
4
(Ph
PhNO
Ph)] was evaluated in the Suzuki-Miyaura and Mizoroki-
Heck cross-coupling reactions. Apart from compound 1 which
2
P = NC
6 4
H SR–
mol. catalyst load), the catalytic activity of 2 was assessed in the
Mizoroki-Heck cross-coupling process between styrene and differ-
ent para-substituted bromobenzenes.
j
–C,N,S)}, 1 (R = CH
3
), 2 (R = Ph), 3 (R = p-NO
2
2
) and 4
(
R = CH
2
Scheme 3. Evaluation of the catalytic activity of complexes 1–4 in Mizoroki-Heck reaction.

2
54
S. Ramírez-Rave et al. / Inorganica Chimica Acta 462 (2017) 249–255
Table 5
MW assisted Mizoroki-Heck coupling between styrene and different para substituted phenyl bromide using 2 as catalyst.
Entry
1
Bromobenzene
Cis
%
Trans
%
Conv. Total %
11
>1
10
2
3
4
5
6
7
8
9
>1
>1
6
18
25
46
50
95
64
85
>99
19
26
52
51
99
73
88
>99
>1
4
7
3
<1
3 4
Yields obtained by GC are based on remaining bromobenzene and are the average of two runs. Reaction conditions: DMF (5 mL), phenyl bromide (0.43 mmol), Na PO
ꢁ
3
(
0.95 mmol), 2 0.1 mol% (4.31 ꢀ 10 mmol), and styrene (0.47 mmol). Temperature 110 °C (100 W), reaction time 15 min.
decomposes under the reaction conditions, they all prove efficient
catalysts for these reactions, with complexes 2 and 3 displaying the
highest yields of transformation in both reactions. The use of MW
heating lead to a considerable diminution in reaction times when
compared to conventional heating. Neither coupling reaction may
involve the formation of soluble palladium nanoparticles because
the new catalytic system is very thermally and air stable, and is
not affected by elemental mercury. The highest activity of 3 in
the Suzuki-Miyaura reaction may be an indication that hemilabil-
ity of S coordination is involved during the catalytic process. Com-
(CB2009/134528 and CB2010/154732) and Ph. D. scholarships for
S.R.-R.
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