Pd/C-catalyzed and water-mediated hiyama cross-coupling reaction using an electron-deficient phosphine ligand

Article abstract of DOI:10.1246/cl.2011.910

The Pd/C-catalyzed Hiyama cross-coupling reaction between a variety of aryl halides and aryltriethoxysilanes was developed. Since only small amounts of the 10% Pd/C (0.5 mol%) and phosphine ligand (1.0 mol%) are required for efficient reaction, the protocol would be practical for the construction of biphenyl derivatives.

Full text of DOI:10.1246/cl.2011.910

doi:10.1246/cl.2011.910
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Published on the web September 5, 2011
Pd/C-catalyzed and Water-mediated Hiyama Cross-coupling Reaction
Using an Electron-deficient Phosphine Ligand
Takayoshi Yanase, Shigeki Mori, Yasunari Monguchi, and Hironao Sajiki*
Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196
(
Received March 25, 2011; CL-110252; E-mail: sajiki@gifu-pu.ac.jp)
The Pd/C-catalyzed Hiyama cross-coupling reaction be-
tween a variety of aryl halides and aryltriethoxysilanes was
developed. Since only small amounts of the 10% Pd/C
ogen atom on the benzene ring, significantly improved the
reaction rate, and the reaction was completed within 6 h (Entries
11 and 12). Particularly, in the case of (4-FC6H4)3P, a favorable
11,12
(
0.5 mol %) and phosphine ligand (1.0 mol %) are required for
isolated yield of 3 (83%) was obtained.
efficient reaction, the protocol would be practical for the
construction of biphenyl derivatives.
Although TBAF is highly hygroscopic, and absorbed water
usually poses a potential risk of deactivating the fluoride ion
by the formation of hydrogen bonds, the yield of 3 decreased
1
3
to 70% when using dried TBAF, which might indicate the
importance of water in the reaction (Entry 13). The addition of
50 or 100 ¯L of water to 1 mL of anhydrous toluene in the
0.5 mmol scale cross-coupling of 1 significantly enhanced the
reaction efficiency, while the further addition of water (200 ¯L)
rather delayed the reaction (Entries 14­16). The amounts of 10%
Pd/C and (4-FC H ) P could be reduced to 0.5 and 1 mol %,
The palladium-catalyzed cross-coupling reactions of aryl
halides or halide equivalents with organometallic compounds
1
are widely used for the construction of carbon­carbon bonds.
2,3
The use of organosilanes as organometallic compounds, which
was initially explored by Hiyama,3 is drawing increasing
attention as one of the most attractive approaches, since
organosilanes are easy to handle and environmentally friendly
due to their air-stability and low toxicity. The Hiyama coupling
has generally been catalyzed by homogeneous palladium
complexes. Heterogeneous catalysts have been recently recog-
nized as alternatives in a variety of organic synthetic fields due
6
4 3
respectively, and the yield was eventually improved to 90% due
1
4,15
to the suppression of the homocoupling reaction (Entry 17).
The reaction was obviously impeded by a decrease in the
reaction temperature (80 °C), and a significant amount (24%)
of the unchanged starting material 1 remained (Entry 18).
Furthermore, the reaction was depressed by using 0.5 mol %
4
to their air-stability and recoverability. In particular, palladium
on carbon (Pd/C), which is a commercially available heteroge-
neous catalyst widely employed for hydrogenation, has been
Pd(OAc) in place of 10% Pd/C owing to the formation of
2
5
nitrobenzene by the deiodination of 1 and 4,4¤-dinitrobiphenyl
1
6
in use for various kinds of cross-coupling reactions, such as
(Entry 19).
6
carbon­carbon and carbon­nitrogen bond formations. During
We next applied the optimized conditions indicated in
Table 1, Entry 17, to the cross-coupling reaction between a
wide range of substituted aryl halides and aryltriethoxysilanes
(Table 2). Both 4-iodonitrobenzene (Entries 1­3) and 4-iodo-
anisole (Entries 4­6) were effectively cross-coupled with either
the phenyl- (Entries 1 and 4), p-tolyl- (Entries 2 and 5), or
4-chlorophenyltriethoxysilane (Entries 3 and 6), to give the
the preparation of this manuscript, a comparative study on the
activity of Pd/Cs from various vendors regarding the cross-
coupling reactions, including the Hiyama coupling, was report-
7
ed. However, the conditions for the Hiyama coupling, such as
solvents and ligands, were not well investigated and were only
for the nonsubstituted phenylation of bromoarenes. In this paper,
we describe efficient conditions for the Pd/C-catalyzed Hiyama
cross-coupling reaction between a variety of aryltrialkoxysilanes
and aryl halides as well as the role of a small amount of water
for effective reaction.
1
7
corresponding biphenyl derivatives in good to excellent yields.
Aryl bromides possessing an electron-withdrawing nitro, acetyl,
formyl, or cyano functionality on the benzene ring were also
found to be good substrates for the cross-coupling (Entries
8­11). 4-Bromoanisole as well as the 3- and 2-bromoanisoles
could also react with phenyl- or p-tolyltriethoxysilane to give the
desired biaryl derivatives in good yields (Entries 12­15). These
results indicated that the present Pd/C-catalyzed Hiyama
coupling reaction is not affected by the substitution position
and electron-withdrawing or -donating nature of the substituents
on the benzene nuclei of the aryl halides. 3-Iodopyridine and
3-bromopyridine were also good substrates, and the desired
3-phenylpyridine could be smoothly obtained (Entries 7 and 16).
It should be noted that the present conditions could be applied to
the cross-coupling of 4-chloronitrobenzene with phenyltrieth-
oxysilane, while the reaction efficiency obviously decreased
(Entry 17) compared to the reaction of the 4-iodo- and
4-bromonitrobenzene (Entries 1 and 8).
The cross-coupling between 4-iodonitrobenzene (1) and
phenyltriethoxysilane (2, 1.5 equiv) in boiling toluene in the
presence of 10% Pd/C7 (5 mol %) and tetrabutylammonium
fluoride (TBAF, 2 equiv) was accelerated by the addition
of 1,1-bis(diphenylphosphino)ferrocene (DPPF, 10 mol %)
­9
(Table 1, Entries 1 vs. 2). However, the use of DMF, dioxane,
or THF as a solvent (Entries 3­5) or metal fluorides, such as
21
sodium fluoride (see Supporting Information ) instead of
TBAF, impeded the cross-coupling reaction, and significant
quantities of the homocoupling products (4,4¤-dinitrobiphenyl
and biphenyl) were observed by TLC analysis.10 Triphenyl-
phosphine (Entry 6) and tris(4-tolyl)phosphine (Entry 7) were
effectively employed as a ligand (20 mol %), while the addition
of tris(4-methoxyphenyl)phosphine (Entry 8) or trialkylphos-
phines (Entries 9 and 10) indicated only a slight enhancing
effect. Furthermore, the use of tris(4-chlorophenyl)phosphine or
tris(4-fluorophenyl)phosphine [(4-FC6H4)3P], possessing a hal-
The low level of Pd-leaching (3.8% of total Pd amount) in
the filtered reaction media of the 10% Pd/C-catalyzed cross-
coupling reaction between 4-bromonitrobenzene and phenyl-
Chem. Lett. 2011, 40, 910­912
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

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Table 1. Effect of phosphine ligands on the Pd/C-catalyzed Hiyama cross-coupling reaction
1
0% Pd/C (5 mol%)
TBAF·3H O (2 equiv)
2
O N
I
Si(OEt)3
O N
2
2
1
2
3
0
.5 mmol
1.5 equiv
Entry
1
Solvent/1 mL
Ligand/20 mol %
Water additive/¯L
Bath temp/°C
Time/h
Yield/%a
toluene
toluene
DMF
dioxane
THF
®
DPPF
DPPF
DPPF
DPPF
®
®
®
®
®
®
®
®
®
®
®
®
®
120
120
120
130
90
24
14
1
2
1
20
20
24
12
24
6
6
17
4
52
64
16
5
b
2
3
4
5
b
b
b
7
6
7
8
9
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1
PPh3
120
120
120
120
120
120
120
120
120
120
120
120
80
63
66
50
58
41
69
83
70
83
80
64
90
66
72
tris(4-tolyl)phosphine
tris(4-methoxyphenyl)phosphine
tricyclohexylphosphine
10
2-(di-t-butylphosphino)biphenyl
tris(4-chlorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
tris(4-fluorophenyl)phosphine
1
1
12
13
14
15
16
17
18
19
c
50 (4.8% aq. toluene)
100 (9.1% aq. toluene)
200 (17% aq. toluene)
50 (4.8% aq. toluene)
50 (4.8% aq. toluene)
50 (4.8% aq. toluene)
b
4
24
6
24
2
d
d,e
f
120
c
a
Determined by H NMR using 1,4-dioxane as an internal standard. 10 mol % of DPPF was employed. TBAF was dried under vacuum
d
e
at 90 °C for 0.5 h prior to use. 0.5 mol % of 10% Pd/C and 1 mol % of (4-FC6H4)3P were employed. 4,4¤-Dinitrobiphenyl was obtained
as a by-product in 8% yield together with the recovered 1 in 24% yield. 0.5 mol % of Pd(OAc)2 instead of 10% Pd/C and 1 mol % (4-
f
FC6H4)3P were used. 4,4¤-Dinitrobiphenyl was obtained in 5% yield.
Table 2. The Hiyama cross-coupling of various aryl halides
and aryltriethoxysilanesa
triethoxysilane in the presence of (4-FC H ) P was confirmed
6 4 3
based on an inductively coupled plasma-atomic emission
1
0% Pd/C, (4-FC H ) P
18
6
4 3
spectrometric analysis. This suggests that the leached Pd
R
TBAF·3H O
R
2
species could be actual catalysts and the Pd/C may act as a
Aryl
X
Si(OEt)3
Aryl
4
1
.8% aq. toluene
20 °C (bath temp)
19
reservoir of the leached and soluble active Pd species. The
1
mmol
1.5 equiv
obtained 4-nitrobiphenyl was not contaminated with Pd species
after the simple purification using silica gel column chromatog-
Entry
Aryl­X
R
Time/h Yield/%b
1
8
raphy.
1
2
3
4
5
6
7
8
9
4-NO2-C6H4I
4-NO -C H I
H
6
12
6
6
12
9
88
80
75
85
79
83
85
81
86
86
85
83
77
90
80
81
47
A plausible mechanism is illustrated in Figure 1. Denmark
et al. reported that arylsilanol derivatives are likely to be more
reactive than arylalkoxysilanes for the Hiyama coupling reac-
4-Me
4-Cl
H
4-Me
4-Cl
H
H
H
H
H
H
4-Me
H
H
H
2
6
4
4-NO2-C6H4I
4-MeO-C6H4I
4-MeO-C6H4I
4-MeO-C6H4I
3-iodopyridine
4-NO2-C6H4Br
4-Ac-C H Br
2
,3
tion.
The aryltriethoxysilanes (A) in Figure 1 would be
partially hydrolyzed by a small amount of water to give a
mixture of the corresponding arylsilanol derivatives (B). The
electrophilicity of the silicon atoms would be enhanced by the
hydrolysis of A presumably due to the decrease in both the
electron density and steric hindrance around the silicon atom,
leading to the easy generation of the active silicate complex (C)
by the fluoride attack derived from TBAF. On the contrary, the
addition of an excess amount of water would accelerate the
formation of the inactive cage-shaped silanol polymer (D) that
12
6
12
12
12
24
24
12
17
18
18
6
4
1
0
4-CHO-C6H4Br
4-CN-C6H4Br
4-MeO-C6H4Br
4-MeO-C6H4Br
3-MeO-C H Br
1
1
1
1
1
1
1
1
2
3
4
5
6
7
6
4
causes the low efficiencies of the Hiyama coupling reaction
2-MeO-C6H4Br
3-bromopyridine
4-NO2-C6H4Cl
20
(
Table 1, Entry 16).
In summary, we have developed a Pd/C­(4-FC H ) P-
6
4 3
H
catalyzed and water-mediated Hiyama cross-coupling reaction as
an effective method for the preparation of biaryls. This reaction
system can be easily performed by the use of only 0.5 mol % of
10% Pd/C, is applicable to the cross-coupling of various aryl
aThe reactions were carried out in the presence of 0.5 mol %
of 10% Pd/C, 1.0 mol % of (4-FC6H4)3P, and 2 equiv of
b
TBAF¢3H2O. Isolated yield.
Chem. Lett. 2011, 40, 910­912
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

9
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Ar2
Si
14, 6994; T. Kurita, M. Abe, T. Maegawa, Y. Monguchi, H. Sajiki,
Synlett 2007, 2521; Y. Monguchi, K. Kitamoto, T. Ikawa, T.
Maegawa, H. Sajiki, Adv. Synth. Catal. 2008, 350, 2767.
Ar2 Si(OEt)2
Ar2
Si
O
O
O
O
OH
Ar2
Si
2
Ar2 Si(OEt)3
A
Ar Si
O
7
8
A. Komáromi, F. Szabó, Z. Novák, Tetrahedron Lett. 2010, 51, 5411.
The Pd/C used in the present study was commercially available from
the N.E. Chemcat Corporation in Japan and was effectively
employed for the Suzuki­Miyaura, Sonogashira, and Buchwald­
Hartwig reactions, see ref. 6. The Pd particle size and carbon surface
O
Ar2 Si(OH)2
OEt
Ar2
O
Ar2
O
O
Si
Si
small amount excess
O
O
Si
Ar2
of H O
of H O
2
2
Si
Ar2 Si(OH)3
2
O
D
Ar
Ar1
L2Pd
2
¹1
area are approximately 5 nm and 1100 m g , respectively.
Köhler et al. demonstrated the effect of the properties of the Pd/Cs,
such as Pd particle size and surface area, on the reaction progress,
see: K. Köhler, R. G. Heidenreich, J. G. E. Krauter, U. Pietsch,
Chem.®Eur. J. 2002, 8, 622.
B
F
1
9
Ar –X
F
RO) Si Ar2
oxidative
addition
(
3
X
R = H or Et
10 When CsF (2 equiv) was used as the base together with
tetrabutylammonium bromide (TBAB, 2 equiv), the desired 3 was
obtained only in 17% yield after 24 h, although the addition of
TBAB increased the CsF solubility.
Pd(0)
C
transmetallation
Ar1
reductive
elimination
F
L2Pd
1
1 The electron-deficient phosphine ligands, which make the Pd(II)
(
RO) Si
X
Ar2 Ar –Ar2
1
3
intermediate more electrophilic, would accelerate the reaction rate of
the transmetallation or reductive elimination step. Denmark recently
showed that, in most cases, the transmetallation step in the Hiyama
coupling reactions is rate-limiting, see ref. 2.
2 Buchwald reported that the electron-deficient nature of the ligand is
important in facilitating the transmetallation during the palladium-
catalyzed N-arylation of secondary acyclic amides, see: J. D. Hicks,
A. M. Hyde, A. M. Cuezva, S. L. Buchwald, J. Am. Chem. Soc.
Figure 1. Plausible mechanism of the Pd/C-catalyzed Hiyama
cross-coupling reaction.
1
halides and arylalkoxysilanes, and is readily applicable to the
large-scale synthesis of asymmetric biaryls derivatives.
2009, 131, 16720.
1
3 The procedure for the preparation of dried TBAF: D. W. Kim, H.-J.
Jeong, S. T. Lim, M.-H. Sohn, Angew. Chem., Int. Ed. 2008, 47,
8404; R. K. Sharma, J. L. Fry, J. Org. Chem. 1983, 48, 2112; D. P.
Cox, J. Terpinski, W. Lawrynowicz, J. Org. Chem. 1984, 49, 3216.
4 Recently, a very low catalyst loading Hiyama cross-coupling
reaction using oxime-derived palldacycles as catalysts in 50%
NaOH solution was reported by C. Nájera et al. although only the
homocoupled product derived from 4-bromoanisole was obtained
using 0.5 mol % of Pd/C as a catalyst: see: E. Alacid, C. Nájera,
J. Org. Chem. 2008, 73, 2315; E. Alacid, C. Nájera, Adv. Synth.
Catal. 2006, 348, 945.
We thank the N.E. Chemcat Corporation for the gift of the
0% Pd/C.
1
1
This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
References and Notes
1
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15 The progress of the coupling between 1 and 2 under our optimal
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16 When Pd(OAc)2 or PdCl2 was used for the reaction of phenyl-
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2
2
1
Supporting Information.
17 The electron-deficient arylsilanes bearing an electron-withdrawing
chloro group required a shorter time to complete the reaction,
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Chem. Lett. 2011, 40, 910­912
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/