Arylation of non-activated C-Cl bond with Grignard reagents catalyzed by pincer [PCP]-nickel complexes

Article abstract of DOI:10.1016/j.ica.2014.02.030

A series of pincer Ni(II) complexes were prepared and utilized in the cross-coupling reaction of non-activated aryl chlorides with Grignard reagents (The Kumada reaction). Catalytic studies revealed that complex 5 ([Ph-PNCNP-Ph]-Ni-Cl) showed the highest catalytic activity for the cross-coupling reaction in the presence of 2 mol% catalyst under mild reaction condition.

Full text of DOI:10.1016/j.ica.2014.02.030

Inorganica Chimica Acta 415 (2014) 95–97
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Arylation of non-activated C–Cl bond with Grignard reagents catalyzed
by pincer [PCP]-nickel complexes
⇑
Yunqiang Sun, Xiaoyan Li, Hongjian Sun
School of Chemistry and Chemical Engineering, Key Laboratory of Special Functional Aggregated Materials, Ministry of Education, Shandong University,
Shanda Nanlu 27, 250199 Jinan, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of pincer Ni(II) complexes were prepared and utilized in the cross-coupling reaction of non-
activated aryl chlorides with Grignard reagents (The Kumada reaction). Catalytic studies revealed that
complex 5 ([Ph-PNCNP-Ph]-Ni-Cl) showed the highest catalytic activity for the cross-coupling reaction
in the presence of 2 mol% catalyst under mild reaction condition.
Received 13 January 2014
Received in revised form 23 February 2014
Accepted 26 February 2014
Available online 6 March 2014
Ó 2014 Elsevier B.V. All rights reserved.
Keywords:
Pincer Ni(II) complexes
Kumada cross-coupling reaction
Non-activated C–Cl bond
1. Introduction
gands were studied because they can be directly prepared and
their structures are easily modified [25,26]. Some of the PCP-type
Biaryls are important building blocks for the synthesis of func-
tional materials [1,2], natural products [3] and liquid crystals [4,5].
Transition-metal-catalyzed cross-coupling reactions are versatile
and powerful tools to construct biaryls [6]. Among the cross-
coupling reactions, Suzuki [7], Negishi [8,9] and Stille [10,11] reac-
tions have been extensively studied due to their better functional
group tolerance. However, organoboronic acids, organostannanes,
and organozinc reagents are generally prepared from either
Grignard or Lithium reagents [12]. Therefore, the direct application
of Grignard reagents in cross-coupling reactions could efficiently
reduce an unnecessary synthetic step and makes the synthetic
route less expensive [13]. For a long time, electrophilic substrates
are predominately iodides and bromides in the Kumada reactions.
Recently, much more research work is focused on the usage of low-
reactive organic chlorides due to their low prices and plenty of
industrial sources [14,15].
pincer-metal complexes have been utilized in different kinds of
reactions, such as Heck [27], Suzuki [28] and C–S cross-coupling
reactions [29]. However, for those coupling reactions the electro-
philic substrates were mainly iodides and bromides. Aryl chlorides
as electrophilic substrates have been rarely reported. This observa-
tion led us to broaden the application scope of pincer [PCP]-metal
complexes as catalysts in the Kumada reactions of non-activated
aryl chlorides with Grignard reagents.
In the family of [PCP]-ligands, one of their outstanding features
is the fact that their ligand skeleton could be easily changed in the
benzylic positions and phosphino-R groups [30]. In this work, we
studied the catalytic activity of several [PCP]-nickel pincer com-
plexes for the cross-coupling reactions of the non-activated aryl
chlorides with Grignard reagents by changing the ligand skeletons
and phosphino substituents so as to find the effective [PCP]-nickel
pincer complex as catalyst in the Kumada reactions.
In the last two decades, both palladium and nickel complexes
have been reported and turned out to be excellent catalysts for
the Kumada reactions [16–20]. Due to the formation of two chelate
rings, pincer ligands can not only stabilize transition metal com-
plexes, but also control and adjust their catalytic activity and even
their selectivity in catalytic processes [21,22]. Some catalytically
efficient pincer metal complexes have been employed in coupling,
reduction, and dehydrogenation reactions [23,24]. Pincer [PCP]-li-
2. Experimental
2.1. Materials and methods
All reactions were carried out under N2 atmosphere and all sol-
vents were freshly distilled before use. Aryl chlorides were pur-
chased from commercial sources and the Grignard reagents were
prepared from corresponding bromide and magnesium turnings
in anhydrous tetrahydrofuran (THF) according to known proce-
dures [31]. The concentrations of the Grignard reagents were
⇑
Corresponding author. Tel.: +86 531 88361350; fax: +86 531 88564464.
E-mail address: hjsun@sdu.edu.cn (H. Sun).
http://dx.doi.org/10.1016/j.ica.2014.02.030
0020-1693/Ó 2014 Elsevier B.V. All rights reserved.

96
Y. Sun et al. / Inorganica Chimica Acta 415 (2014) 95–97
Table 2
E
E
E
PR2
Optimization the solvent and reaction time for Eq. (1).a
CH2 NH
O
R
Entry
Solvent
Time (h)
Yield (%)b
Ni Cl
PR2
Ph
iPr
1
5
4
3
2
1
2
3
4
5
6
7
8
Et2O
Toluene
THF
NMP
DMF
DMSO
THF
12
12
12
12
12
12
3
77
88
98
70
47
68
41
81
Fig. 1. [PCP]-nickel complexes with different ligand skeletons and phosphino R
groups.
THF
6
a
Reaction condition: aryl chloride (1.0 mmol), Grignard reagent (1.5 mmol),
Complex 5 (2.0 mol%), THF (2 mL).
GC yield with n-dodecane as an internal standard.
Table 1
b
Cross-coupling of 4-chlorobenzene with 4-methylbenzenemagnesium bromide cat-
alyzed by nickel catalyst.a
Cl
Me
Table 3
Kumada cross-coupling reaction of aryl chlorides with Grignard reagents catalyzed by
[PCP]-Ni Complex
THF, 12 h
(1)
complex 5 catalyst.a
Me
+
Cl
MgBr
R2
MgBr
Complex 5 (2 mol%)
THF, 40 oC
(2)
+
R1
R2
Entry
Catalyst
mol%
Theta (°C)
Yield (%)b
R1
1
2
3
4
5
6
7
8
9
1
2
3
4
2
2
2
2
2
2
2
1
2
2
40
40
40
40
40
40
40
40
23
60
40
96
68
56
97
60
73
65
72
96
Entry
R1
R2
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
H
H
p-Me
p-MeO
H
p-Me
p-MeO
p-MeO
H
p-Me
p-MeO
H
12
12
12
12
12
12
18
18
18
18
18
95.3c
89.7
90.7
92.3
94.0
5
NiCl2
Ni(acac)2
5
5
5
p-Me
p-Me
p-Me
p-MeO
m-Cl
m-Cl
m-Cl
p-Cl
96.0
10
95.7d
89.1d
82.8d
91.3d
87.2d
a
Reaction condition: aryl chloride (1.0 mmol), Grignard reagent (1.5 mmol), THF
(2 mL).
GC yield with n-dodecane as an internal standard.
b
10
11
p-Cl
p-Me
a
Reaction condition: aryl chloride (1.0 mmol), Grignard reagent (1.5 mmol),
pincer Ni catalyst (2.0 mol%), THF (2 mL).
Isolated yield.
GC yield with n-dodecane as an internal standard.
Reaction condition: aryl chloride (1.0 mmol), Grignard reagent (3.0 mmol),
pincer Ni catalyst (2.0 mol%), THF (2 mL).
determined by titration prior to use. NMR spectra were recorded
on a Bruker 300 AV spectrometer. GC–MS was performed on Ther-
mo Trace GC Ultra-DSQ. GC was performed on GC-9790.
b
c
d
2.2. Procedures for Synthesis of [PCP]-nickel Pincer Complexes
The synthesis of [PCP]-nickel pincer complexes (Fig. 1) was car-
ried out according to the literature procedures [32,33,28].
bridged pincer complex 2 while Ph substitution is preferred for NH
bridged ligand (complex 5). From the catalytic activity and eco-
nomical perspective, complex 5 was chosen as the best catalyst.
When the catalyst loading was reduced to 1 mol%, only moderate
yield was obtained (Table 1, entry 8). Operating at a lower temper-
ature led to significantly lower activitity (Table 1, entry 9). The
yield was excellent as the reaction temperature was increased to
60 °C (Table 1, entry 10), but a large amount of homo-coupling
product of the Grignard reagent was formed according to GC–MS
analysis.
2.3. Typical procedure for the Kumada coupling reaction
Aryl chloride (1.0 mmol), ArMgBr (1.5 mmol) in THF (2.0 mL),
catalysts (2.0 mol%), were added to a Schlenk tube under an N2
atmosphere. The reaction was stirred at 40 °C for 12 h.
3. Results and discussion
The influence of solvents and reaction time on the yields with 5
as catalyst was investigated (Table 2). The solvent effect study
showed that THF is the best reaction medium among the tested
solvents for this reaction (Table 2, entries 1–6). The chemical reac-
tion in a shorter reaction time is not complete (Table 2, entries 7
and 8). It was observed that 12 h are needed for the reaction to
be completed (Table 2, entry 3).
Under the optimized condition, a variety of aryl chlorides were
coupled with aryl Grignard reagents (Eq. (2)). The results are listed
in Table 3. It is worth mentioning that for the double couplings of
aryl dichlorides, complex 5 also showed excellent catalytic activity
(Table 3, entries 7–11). m- and p-Dichlorobenzene could be con-
verted to corresponding terphenyls in very high yields using 3.0
equiv. of Grignard reagents for 18 h.
The [PCP]-nickel complexes 1–5 (Fig. 1) were synthesized
according to the literature methods [29–31]. The variation among
the five complexes is either in the position-E or in the R group.
With the [PCP]-nickel complexes 1–5 as catalysts, the cross-
coupling reaction of 4-chlorobenzene with 4-methylphenylmagne-
sium bromide was chosen as a probe reaction to evaluate the
catalytic activities of complexes 1–5 (Eq. (1)). As shown in Table 1,
compared to the pincer nickel complexes 2 and 5, lower yields
were obtained with the simple nickel complexes (NiCl2 and
Ni(acac)2) as catalysts (Table 1, entries 6 and 7). By changing the
pincer spacer from C, O to N, the catalytic activities changed
remarkably (Table 1, entries 1–5) in the presence of 2 mol% of pin-
cer complexes. The best yields were obtained for iPr substituted O

Y. Sun et al. / Inorganica Chimica Acta 415 (2014) 95–97
97
Ar1
Appendix A. Supplementary material
MgBrCl
MgBr
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ica.2014.02.030.
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We gratefully acknowledge the financial support by NSF China
No. 21072113 and Shandong Province Natural Science Foundation
ZR2010BZ002.