A well-defined {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2}2 2P(CH3 )2 CHNCH(CH3 )2 2 PdCl2 Complex } complex catalyzed catalyzed hiyama coupling hiyama coupling of aryl bromides of aryl bromides with arylsilanes with arylsilanes

Article abstract of DOI:10.3390/molecules21080987

palladium (II) complex {[(PhCH2 O)2 P(CH3 )2 CHNCH(CH3 )2 ]2 PdCl2 } catalyzed Hiyama Abstract: A palladium (II) complex {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} catalyzed Hiyama crosscoupling reaction between aryl bromides and arylsilanes has been developed. The substituted biaryls cross-coupling reaction between aryl bromides and arylsilanes has been developed. The substituted biaryls were produced in moderate to high yields, regardless of electron-withdrawing or electron-donating. were produced in moderate to high yields, regardless of electron-withdrawing or electron-donating.

Full text of DOI:10.3390/molecules21080987

molecules
Article
A Well-Defined
{[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2}
Complex Catalyzed Hiyama Coupling of Aryl
Bromides with Arylsilanes
Mengping Guo 1,2,*, Leiqing Fu 1,2, Jiamin Li 1, Lanjiang Zhou 1 and Yanping Kang 1
1
Institute of Coordination Catalysis, College of Chemistry and Bio-Engineering, Yichun University,
Yichun 336000, China; fuleiqing2009@163.com (L.F.); lijiamin@163.com (J.L.);
zhoulanjiang@163.com (L.Z.); kangyanping@163.com (Y.K.)
Engineering Center of Jiangxi University for Lithium Energy, Yichun University, Yichun 336000, China
2
*
Correspondence: guomengping65@163.com; Tel.: +86-795-320-0535
Academic Editors: Diego A. Alonso and Isidro M. Pastor
Received: 27 May 2016; Accepted: 15 July 2016; Published: 29 July 2016
Abstract: A palladium (II) complex {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} catalyzed Hiyama
cross-coupling reaction between aryl bromides and arylsilanes has been developed. The substituted
biaryls were produced in moderate to high yields, regardless of electron-withdrawing or electron-donating.
well-defined catalyst
Br
+
R2
Si(OMe)3
R2
Solvent, Base
R1
R1
Keywords: palladium (II) complex; Hiyama cross-coupling reaction; unsymmetrical biaryls;
synthetic method
1. Introduction
Transition metal-mediated cross-coupling reactions is one of the most powerful and versatile
methods for the generation of unsymmetrical biaryls which are widely found as important structural
units in pharmaceuticals [
polymers [ ], liquid crystal materials [
transformations include organozinc (Negishi) [
1
], natural products [
] and microelectrode arrays [
] reaction, organotin (Stille) [
2
], bioactive products [
3
], herbicides [
]. These cross-coupling
] reaction, organoboron
4], conducting
5
6
7
8
9
(Suzuki-Miyaura) [10] reaction, and organomagnesium (Kumada) reaction [11]. Aryl halides have
been widely used for a variety of cross-coupling reactions to form C-C bond. Recently, “comparatively
unreactive” organosilane (Hiyama) reagents have been proposed as potential coupling partners
due to their low cost and toxicity [12
media [14]. Generally, great successes have been obtained using in situ catalytic systems as
catalysts for Hiyama cross-coupling reactions [15 18]. However, the use of well-defined catalysts
is still rare [14 19 22]. Herein, we have synthesized an air- and moisture-stable Pd (II) complex
,13] ease of handling and stability in various chemical
–
,
–
[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2 (PdCl2L2) containing electron-rich, sterically bulky
phosphane (L), and it has been proved to be a highly efficient catalyst for Suzuki reaction with
low Pd-catalyst loading (0.01%) [23]. Herein, this catalyst (Figure 1) is used for palladium-catalyzed
Hiyama coupling reactions of arylsilanes with aryl bromides under ambient atmosphere.
Molecules 2016, 21, 987; doi:10.3390/molecules21080987
www.mdpi.com/journal/molecules

Molecules 2016, 21, 987
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O
P
N
O
O
THF
rt, 4 h
N
P
2
Pd
Cl
+
Na2PdCl4
P
N
Cl
O
O
O
L
PdCl2L2
Figure 1. Synthesis of catalyst.
2. Results and Discussion
2.1. Optimization of the Hiyama Reaction Condition
The catalyst PdCl2L2, which was inert to air and moisture, was composed of Na2PdCl4 with
2 equiv of the ligand L in THF at room temperature (Figure 1). The X-ray crystal structure of PdCl2L2
was shown as reported in [23]. The model reaction of bromobenzene with phenyltrimethoxysilane was
initiated to optimize the cross-coupling conditions. Solvents used in the reaction were environmentally
friendly and cheap and it avoid the troublesome solvents (NMP, DMF, etc.) that were conventionally
applied in similar Hiyama reactions [14]. Results showed that no cross-coupled product was obtained
when only H2O was used as solvent (Table 1, entry 1). However, it was exciting that a low yield (36%)
was obtained in PEG solvent (Table 1, entry 2). Inspired by this, we explored different proportions
of PEG and H2O (Table 1, entries 3–5), and it was discovered that PEG:H2O = 1:1 (volume ratio) was
the efficient reaction system in this reaction (Table 1, entry 4) while the mixed solvent CH3CH2OH
and H2O was not suitable for this reaction (Table 1, entry 6). Consequently, PEG:H2O = 1:1 (volume
ratio) was chosen as the best solvent. To the best our knowledge, the base TBAF
role in this reaction because TBAF 3H2O may show the function of the activation of arylsilane [24].
In order to avoid the use of TBAF 3H2O, we started to investigate a variety of inorganic salt base
‚
3H2O played a key
‚
‚
which should show the capability to favor the removal of silicon groups. Intriguingly, it gave a high
yield of biphenyls (85%) when NaOH was applied as the base (Table 1, entry 7). Furthermore, the
reaction did not proceed well when carried out with other base such as KOH, Et3N, Na2CO3, K3PO4
and NaOAc 3H2O (Table 1, entries 8–12). According to the above results, PEG:H2O = 1:1 (volume
‚
ratio), as the solvent, and NaOH as the base gave the best results. Since this catalytic system was
not sensitive to oxygen, the reactions were carried out under air atmosphere without the protection
of nitrogen.
Table 1. Optimization of the Hiyama reaction condition a.
PdCl2L2
Br +
Si(OMe)3
Solvent, Base
80 ℃, 2 h, under air
Yield (%) b
Entry
Solvent
Base
1
2
3
4
5
H2O
PEG
PEG:H2O = 1:3
PEG:H2O = 1:1
PEG:H2O = 3:1
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0
36
50
73
64
6
7
8
9
10
11
12
CH3CH2OH:H2O = 1:1
PEG:H2O = 1:1
PEG:H2O = 1:1
PEG:H2O = 1:1
PEG:H2O = 1:1
PEG:H2O = 1:1
PEG:H2O = 1:1
K2CO3
NaOH
KOH
Et3N
Na2CO3
K3PO4
trace
85
75
58
71
62
69
NaOAc‚3H2O
a
Reaction conditions:1.0 mmol bromobenzene, 1.2 mmol arylsilane, 0.02 mmol catalyst, 4.0 mL solvent, volume
ratio, 3.0 mmol base, 80 ˝C under air. All the reactions were carried out for 2 h; b Isolated yield was based on
the bromobenzene.

Molecules 2016, 21, 987
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2.2. Scope of the Substrates
The optimized reaction conditions were used in the Hiyama coupling reaction of various aryl
bromides and arylsilanes with PdCl2L2 as a catalyst. The results were shown in Table 2. As expected,
activated aryl bromide was smoothly converted into the corresponding products in 92% yields and
85% yields (Table 2, entries 2, 5). However, the electron donating group of aryl bromide would slightly
decrease the reaction efficiency (Table 2, entries 3, 6). We also examined the electron donating group of
arylsilane base on the resulting yields of the reactions. Electron donating group of arylsilane could
be afforded biphenyl compounds at a higher temperature for 100 ˝C (Table 2, entries 4–8) but with
lower yields. If aryl bromide and arylsilane both contained an electron donating group, the biphenyl
yield clearly declined (Table 2, entry 6). Importantly, 1-bromonaphthalene was also applicable to
these reaction conditions in moderate to good yield (Table 2, entry 7). The reaction system was also
sufficiently stable for halogenated heterocyclic, so that 2-bromothiophene could be coupled with good
efficiency (Table 2, entry 8).
Table 2. Scope and Limitations of the Substrates a.
Br
PdCl2L2, NaOH
+
R2
Si(OMe)3
R2
PEG/H2O (2/2 mL)
80-100 ℃, 2 h, under air
R1
Product
R1
Ar-Br
Yield (%) b
Entry
Ar-Si(OMe)3
Br
Si(OMe)3
Si(OMe)3
Si(OMe)3
1
88
92
72
74
85
65
O
O
C
2
H3C
H3C
C
Br
H3C
O
Br
H3C
O
3
4 c
5 c
6 c
Br
H3C
H3C
H3C
O
O
O
Si(OMe)3
O
CH3
O
C
O
Si(OMe)3
H3C
C
O
CH3
H3C
Br
H3C
O
Br
Si(OMe)3
H3C
O
O
CH3
O
CH3
7 c
83
74
H3C
O
Si(OMe)3
Br
Br
S
S
8 c
H3C
O
Si(OMe)3
O
CH3
a
Reaction conditions:1.0 mmol aryl bromide, 1.2 mmol arylsilane, 0.02 mmol catalyst, 4.0 mL solvent,
PEG:H2O = 1:1 (volume ratio), 3.0 mmol NaOH, 80 ˝C under air. All the reactions were carried out for
2 h; b Isolated yield was based on the aryl bromide; c The reaction temperature was 100 ˝C.
3. Experimental Section
3.1. Reagents and Equipment
NMR spectra were recorded using 400 MHz in DMSO-d6 solutions at room temperature
(tetramethylsilane (TMS) was used as an internal standard) on a Bruker Avance III spectrometer
(Billerica, MA, USA, see Supplementary Materials). All chemicals employed in the reaction were
analytical grade, obtained commercially from Aldrich or Alfa Aesar and were used as received without
any prior purification.

Molecules 2016, 21, 987
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3.2. Synthesis of the Catalyst
The palladium complex PdCl2L2 was prepared using a method previously reported elsewhere [21].
A solution of 1 mmol (0.345 g) was added dropwise to a suspension of 0.5 mmol Na2PdCl4 (0.147 g)
in THF (20.0 mL) and the reaction mixture was stirred at ambient temperature for 4 h (Figure 1).
The volume was reduced to 5.0 mL and diethyl ether was added to precipitate a yellow powder which
was then filtered off and washed with diethyl ether. The complex PdCl2L2 was obtained in 92% yield.
3.3. General Procedure for the Synthesis
A mixture of aryl bromide (1.0 mmol), arylsilane (1.2 mmol), NaOH (3.0 mmo˝l), 4.0 mL solvent,
PEG:H2O = 1:1 (volume ratio) and catalyst (0.02 mmol) was stirred at 80–100 C for 2 h under
air. The reaction was quenched with brine (15 mL) and extracted three times with ethyl acetate
(3
ˆ
10 mL). The organic phase was dried with MgSO4 for 4 h, filtered and concentrated under reduced
pressure using a rotary evaporator. The crude products were re-crystallized by dichloromethane
(2 mL) at
13C-NMR spectroscopy.
´
10 ˝C for 24 h. Filtered and dried, the purified products were identified by 1H-NMR and
3.4. Analytical Data of Representative Products
˝
Biphenyl Yield 88%: mp: 70–71 C; 1H-NMR (DMSO-d6):
δ 7.66 (d, J = 7.2 Hz, 4H), 7.47 (d, J = 7.6 Hz,
4H), 7.37 (t, J = 7.2 Hz, 2H). 13C-NMR (DMSO-d6): δ 127.1, 127.8, 129.3, 140.7.
˝
4-Acetyl-4’-methoxybiphenyl Yield 85%: mp: 153–154 C; 1H-NMR (DMSO-d6):
δ = 7.99 (d, J = 8.0 Hz,
2H), 7.79(d, J = 7.5 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 7.5 Hz, 2H), 3.81 (s, 3H), 2.59 (s, 3H).
13C-NMR (DMSO-d6): δ 27.1, 55.7, 115.0, 126.6, 128.6, 129.3, 131.5, 135.4, 144.6, 160.1, 197.8.
˝
1
4-Methoxybiphenyl Yield 74% and Yield 72%: mp: 90 C; H-NMR (DMSO-d6):
δ = 7.61 (m, 4H),
7.43 (m, 2H), 7.32 (d, J = 7.2 Hz, 1H), 7.01 (d, J = 8.2 Hz, 2H), 3.79 (s, 3H, CH3). 13C-NMR (DMSO-d6):
δ 55.6, 114.8, 126.6, 127.1, 128.2, 129.3, 133.0, 140.3, 159.3.
˝
1
4-Acetylbiphenyl Yield 92%: mp: 121 C; H-NMR (DMSO-d6):
δ = 8.04 (d, J = 8.0 Hz, 2H), 7.82
(d, J = 8.0 Hz, 2H), 7.75 (d, J = 8.0 Hz, 2H), 7.51 (m, 1H), 7.44 (d, J = 8.0 Hz, 2H), 2.61 (s, 3H).
13C-NMR (DMSO-d6): δ 27.2, 127.3, 127.4, 128.8, 129.3, 129.5, 136.1, 139.3, 145.0, 197.9.
4. Conclusions
In conclusion, complex PdCl2L2 was demonstrated to be a highly active catalyst for the Hiyama
coupling reaction of a range of aryl bromides with arylsilanes, affording the coupling products with
moderate to high yields. This method is consistent with the concept of green chemistry, and further
studies on the applicability of this catalyst system in other coupling reactions such as Sonogashira and
amination are currently under investigation in our laboratory.
Supplementary Materials: Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/
21/8/987/s1.
Acknowledgments: Financial support from the National Natural Science Foundation of China (No. 21063015,
No. 21363026) and the Jiangxi Provincial Natural Science Foundation of China (No. 20114BAB203012), the Key
Science and Technology plan of Yichun City (No. (2010) 24) is gratefully acknowledged.
Author Contributions: M.G. and L.F. conceived and designed research. J.L., L.Z. and Y.K. performed the
experiments. L.F. wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} are available
from the authors.
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2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access
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