MIDA as a simple and highly efficient ligand for palladium-catalyzed Hiyama cross-coupling of aryl halides

Article abstract of DOI:10.1039/c4ob01056f

N-Methyliminodiacetic acid (MIDA) as a simple, air stable and water-soluble ligand has been used in the palladium-catalyzed Hiyama cross-coupling reaction of trimethoxyphenylsilane with aryl halides. The yield of the corresponding Hiyama coupling products is high up to around 90% in water and isopropanol under an ambient atmosphere in the presence of KOH and NaF. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob01056f

Organic &
Biomolecular Chemistry
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MIDA as a simple and highly efficient ligand for
palladium-catalyzed Hiyama cross-coupling of aryl
halides†
Cite this: Org. Biomol. Chem., 2014,
12, 7136
Mengping Guo,*a,b Liang Qi,a,b Qiaochu Zhang,a,b Zhiyong Zhu,a Wei Lia and
Xiaogang Lia,b
Received 22nd May 2014,
Accepted 24th July 2014
N-Methyliminodiacetic acid (MIDA) as a simple, air stable and water-soluble ligand has been used in the
palladium-catalyzed Hiyama cross-coupling reaction of trimethoxyphenylsilane with aryl halides. The
yield of the corresponding Hiyama coupling products is high up to around 90% in water and isopropanol
under an ambient atmosphere in the presence of KOH and NaF.
DOI: 10.1039/c4ob01056f
www.rsc.org/obc
these simple ligands could make the reaction occur smoothly. It
is necessary to try, assuming that N-methyliminodiacetic acid
Introduction
The synthesis of carbon–carbon bonds by transition metal (MIDA) is a good candidate. It is a simple, air stable, low cost
catalyzed cross-coupling has developed into one of the most and highly active ligand. To the best of our knowledge, MIDA
useful and important classes of reactions in modern synthetic has not been used as a ligand in the transition-metal-catalyzed
organic chemistry over the past 40 years.1 Among these cross- Hiyama cross-coupling reaction. It not only can be dissolved in
coupling reactions, the palladium-catalyzed Hiyama reaction water but also can be obtained easily and cheaply. Meanwhile,
of organosilane with aryl halides has attracted much attention this ligand is stable in air, moisture and heat treatment, and it
in organic synthesis.2 In the last two decades many efforts can be used to activate the Hiyama cross-coupling reaction in
have been made to develop more active catalysts for the aqueous media under an ambient atmosphere. Moreover, such
Hiyama coupling reaction.3–8 In catalytic systems, a very impor- a catalyst shows potential applications in industry.
tant role was played by the appropriate selection of the catalyst
which should show high activity, selectivity and stability under
the reaction conditions.9 Soluble palladium compounds con-
Results and discussion
Optimization of reaction conditions
taining phosphorus ligands have been widely used in C–C
cross-coupling reactions because of their facile synthesis and
structural versatility.10,11 Although most of the phosphorus
Initially the cross-coupling reaction of phenyltrimethoxysilane
catalysts have exhibited excellent activity, the increasing
with bromobenzene was carried out in the system of 3 ml
environmental concerns12–15 oblige us to develop environ-
ethanol, 3 ml H2O and 3 mmol NaOH without any protective
mental benign catalysts for the organic transformation.
atmosphere. After stirring for 4 h in an 80 °C oil bath, a yield
Since the successful isolation of the first stable carbene by
of 41% biphenyl was obtained. The yields were different in
Arguengo in 1991, N-heterocyclic carbenes (NHCs) have been
various solvents. So the cross-coupling reaction of phenyl-
extensively studied in the field of organometallics as ligands
trimethoxysilane with bromobenzene was chosen as a model
comparable to the conventional phosphine ligands.16–19 Some
reaction to optimize the reaction conditions. The results are
highly active palladium systems with carbene ligands for the
summarized in Table 1. Subsequently a series of alcohols were
Hiyama reaction have been developed.20–22 However, NHCs
altered to examine the different activities in the base NaOH.
always have bulky structures, and few studies on simple struc-
Methanol, n-propanol, 1-butanol and PEG400 (Table 1, entries
tures and electron-rich N-ligands have been conducted. Maybe,
1, 3, 5 and 6) provided general results of the cross-coupling reac-
tion. Isopropanol showed higher activity than other alcohols
with a good yield (Table 1, entry 4). Then some other common
aInstitute of Coordination Catalysis, College of Chemistry and Bio-engineering,
Yichun University, Yichun 336000, PR China. E-mail: guomengping65@163.com
organic solvents were tested to choose the best one. Unfortu-
bEngineering Center of Jiangxi University for Lithium Energy, Yichun University,
nately THF, acetone, acetonitrile and 1,4-dioxane (Table 1,
Yichun 336000, PR China
entries 8–11) all expressed poor vitality except DMSO (Table 1,
†Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4ob01056f
entry 7). It is clear that isopropanol was the best solvent in the
7136 | Org. Biomol. Chem., 2014, 12, 7136–7139
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used in the reaction. The results are summarized in Table 2.
Both NaOH and KOH (Table 2, entries 1 and 2) provided better
yields than other bases, but KOH was a little better than
NaOH. According to the results, strong bases show higher
activities than weak ones. Although KOH was the best base in
the cross-coupling reaction, the yield of the product was not
ideal. Fluorion is a critical additive in the reaction of organo-
silicon. Silicane need to be activated by fluorion because of its
low reaction activity. Generally fluorion is from TBAF, TASF,
NaF, KF and so on, but TBAF and TASF cost much higher than
inorganic salts. So we try to add NaF to provide fluorion to
promote the cross-coupling reaction. The results are summar-
ized in Table 3. It is clear that the yield of the cross-coupling
reaction was better while both 3 mmol KOH and 3 mmol NaF
were added (Table 3, entry 3). If only NaF was added as a base,
the yield was not ideal even after increasing the amount of
NaF (Table 2, entry 5, Table 3, entry 5). What is more, in order
to confirm that MIDA serves as a ligand in the reaction, a reac-
tion was carried out in the optimized system (Table 4, entry
15). It is obvious that the palladium-catalyzed ligand-free
Hiyama reaction could not occur smoothly. So MIDA serves as
a ligand in this reaction.
Table 1 Effect of the solvent on the Hiyama reaction of phenyl-
trimethoxysilane with bromobenzene
Entry
Solvent–H2O (v : v = 1 : 1)
Yield (%)
1
2
Methanol
Ethanol
44
41
3
4
PEG400
IPA
52
75
5
6
7
N-Propanol
1-Butanol
DMSO
46
54
64
8
9
THF
1,4-Dioxane
Acetone
Acetonitrile
IPA–H2O (6 : 0)
IPA–H2O (5 : 1)
IPA–H2O (4 : 2)
IPA–H2O (2 : 4)
IPA–H2O (1 : 5)
IPA–H2O (0 : 6)
48
21
24
29
Trace
Trace
52
48
31
10
11
12
13
14
15
16
17
Trace
Scope and limitations of substrates
Reaction conditions: phenyltrimethoxysilane 1.2 mmol, bromo-
benzene 1 mmol, NaOH 3 mmol, PdCl2 0.02 mmol, ligand (MIDA)
0.02 mmol, solvent 3 ml, H2O 3 ml, 80 °C, stirred for 4 h. In situ
reaction. Isolated yield.
With the optimized conditions in hand, we further studied the
generality of the cross-coupling reactions of aryl halides with
aryltrimethoxysilane in the presence of 2 mol% PdCl2 per
ligand (MIDA) and 3 mmol of KOH at 80 °C in water and iso-
propanol (v : v = 1 : 1). The results are shown in Table 4.
Various 4-substituted aryl bromides and aryl chlorides,
bearing either electron-donating or electron-withdrawing
groups, such as –OMe, –CH3, –CF3 and –NO2, provided the
corresponding products in moderate to good yields. Regardless
of the reactants with electron-withdrawing groups or electron-
donating groups, the additive NaF could promote the cross-
coupling reactions. Besides, the aryl halides with electron-with-
drawing groups commonly have a positive activity than elec-
tron-donating groups, even if aryl halides are substituted by
chlorine (Table 4, entries 4 and 5). For example, 4-nitroben-
zene chloride and 4-trifluoromethyl chlorobenzene, afforded
system, but the reaction could not occur smoothly due to the
lack of adequate water (Table 1, entries 12–17).
As we know, the base in the Hiyama reaction was a signifi-
cant element especially NaOH and KOH, which were the
common bases in the Hiyama cross-coupling reaction. So
some common inorganic bases and some organic bases were
Table 2 Effect of the base on the Hiyama reaction of phenyltrimethoxy-
silane with bromobenzene
Entry
Base
Yield (%)
Table 3 Effect of F− on the Hiyama reaction of aryltrimethoxysilane
with bromobenzene
1
NaOH
72
2
3
4
KOH
Na2CO3
K2CO3
81
25
25
5
6
7
8
NaF
20
Entry
NaF
Yield (%)
KH2PO4
K3PO4·3H2O
Na3PO4
DMF
DMA
Cs2CO3
Morpholine
Trace
Trace
Trace
Trace
27
30
Trace
1
2
3
1 mmol
3 mmol
5 mmol
Free
88
92
65
81
25
9
10
11
12
4
5a
5 mmol
Reaction conditions: phenyltrimethoxysilane 1.2 mmol, bromo- Reaction conditions: phenyltrimethoxysilane 1.2 mmol, bromo-
benzene 1 mmol, base 3 mmol, PdCl2 0.02 mmol, Ligand (MIDA) benzene 1 mmol, KOH 3 mmol, PdCl2 0.02 mmol, ligand (MIDA)
0.02 mmol, IPA 3 ml, H2O 3 ml, 80 °C, stirred for 4 h. In situ reaction. 0.02 mmol, IPA 3 ml, H2O 3 ml, 80 °C, stirred for 4 h. a Without
Isolated yield.
3 mmol KOH. In situ reaction. Isolated yield.
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and trimethoxy (4-methoxyphenyl)silane were purchased from
TCI. Other chemicals were obtained commercially and used
without any prior purification. All products were isolated by
thin layer chromatography on a silica gel using n-hexane and
ethyl acetate unless otherwise noted. Compounds described in
the literature were characterized by 1H NMR and 13C NMR
spectra compared with reported data. 1H NMR spectra were
recorded on a Bruker Avance II 400 spectrometer using TMS as
the internal standard. All the Hiyama reactions were carried
out under air. A mixture of aryl halide (1.0 mmol), aryltri-
methoxysilane (1.2 mmol), base (3.0 mmol), PdCl2 (0.02 mol%,
0.0036 g), ligand MIDA (0.02 mol%, 0.0029 g), H2O (3.0 ml),
and IPA (3.0 ml) were stirred at 80 °C for the indicated
time. The reaction mixtures were extracted with ethyl acetate
(3 × 10 ml). The solvent was concentrated under vacuum.
Table 4 Hiyama coupling-reaction of aryl bromides with phenyl
trimethoxysilane
No. Entry
1
Aryl bromide
Yielda (%) Yieldb (%)
81
63
92
84
2
3
53
89
58
42
40
81
78
97
76
65
63
94
4
5
6c
7d
8
Conclusions
In conclusion, MIDA, a simple, easily obtained and air stable
ligand could activate the aryl halides in the palladium-cata-
lyzed Hiyama reaction in water and isopropanol. Simple
ligands may have the same function with bulky electron-rich
ones, when used in a suitable system.
9
72
85
10e
11
64
77
80
93
Acknowledgements
12f
13
39
57
We are grateful to the National Natural Science Foundation of
China (no. 21063015) and the Scientific Research Fund of
Jiangxi Provincial Education Department (no. GJJ 12597) for
their financial support.
84
96
14g
15h
51
62
Trace
Trace
Notes and references
Reaction conditions: phenyltrimethoxysilane 1.2 mmol, bromo-
benzene 1 mmol, KOH 3 mmol, PdCl2 0.02 mmol, ligand (MIDA)
0.02 mmol, IPA 3 ml, H2O 3 ml, 80 °C, stirred for 6 h. In situ
reaction. Isolated yield. a Without NaF. b 3 mmol NaF was used.
c–g 80 °C, stirred for 12 h. h Without the ligand.
1 F. S. Hannah, R. J. D. Warren Galloway and D. R. Spring,
Chem. Soc. Rev., 2012, 41, 1845.
2 S. E. Denmark and C. S. Regens, Acc. Chem. Res., 2008, 41,
1486.
3 Y. Hatanaka and T. Hiyama, J. Org. Chem., 1988, 53, 918.
4 J.-Y. Lee and G. C. Fu, J. Am. Chem. Soc., 2003, 125, 5616.
5 D. A. Powell and G. C. Fu, J. Am. Chem. Soc., 2004, 126,
7788.
6 S. E. Denmark, J. Am. Chem. Soc., 1999, 121, 5821.
7 X. Dai, N. A. Strotman and G. C. Fu, J. Am. Chem. Soc.,
2008, 130, 3302.
8 T. Yanase, Y. Monguchi and H. Sajiki, RSC Adv., 2012, 2,
590.
9 I. B1aszczyk and A. M. Trzeciak, Tetrahedron, 2010, 66, 9502.
10 A. M. Trzeciak and J. J. Ziólkowski, Coord. Chem. Rev., 2005,
249, 2308.
excellent yields in the system in which NaF participated. Mean-
while 4-bromine toluene and 4-bromoanisole reacted with
trimethoxyphenylsilane, trimethoxy(p-toly)silane or trimethoxy
(4-methoxyphenyl)silane all provided moderate cross-coupling
yields without the additive, despite delayed reaction time
(Table 4, entries 6, 7, 12 and 14). Under the same conditions
the yields of these cross-coupling products were improved
while using NaF. Heterocyclic compounds,pyridine and thio-
phene (Table 4, entries 8 and 9), provided good yields when
reacted with trimethoxyphenylsilane.
11 A. M. Trzeciak and J. J. Ziólkowski, Coord. Chem. Rev., 2007,
251, 1281.
12 T. Matsumoto, M. Ueno, N. Wang and S. Kobayashi, Chem.
– Asian J., 2008, 3, 196.
Experimental
Aryl chlorides, aryl bromides and MIDA were purchased from
Alfa Aesar. Trimethoxyphenylsilane, trimethoxy(p-toly)silane 13 T. Mallat and A. Baiker, Chem. Rev., 2004, 104, 3037.
7138 | Org. Biomol. Chem., 2014, 12, 7136–7139
This journal is © The Royal Society of Chemistry 2014

View Article Online
Organic & Biomolecular Chemistry
Paper
14 N. Jamwal, M. Gupta and S. Paul, Green Chem., 2008, 10, 18 D. Pugh and A. A. Danopoulos, Coord. Chem. Rev., 2007,
999. 251, 610.
15 S. F. J. Hackett, R. M. Brydson, M. H. Gass, I. Harvey, 19 P. L. Arnold and I. J. Casely, Chem. Rev., 2009, 109,
A. D. Newman, K. Wilson and A. F. Lee, Angew. Chem., Int.
Ed., 2007, 46, 8593.
3599.
20 S. Roy and H. Plenio, Adv. Synth. Catal., 2010, 352, 1014.
16 A. J. Arduengo III, R. L. Harlow and M. Kline, J. Am. Chem. 21 X.-Y. Xu, B.-C. Xu, Y.-X. Li and S. H. Hong, Organometallics,
Soc., 1991, 113, 361. 2010, 29, 6343.
17 S. Díez-González, N. Marion and S. P. Nolan, Chem. Rev., 22 D. R. Snead, S. Inagaki, K. A. Abboud and S. H. Hong,
2009, 109, 3612.
Organometallics, 2010, 29, 1729.
This journal is © The Royal Society of Chemistry 2014
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