Homogeneous ruthenium precatalyst for suzuki-miyaura coupling reaction

Article abstract of DOI:10.1246/cl.2010.1050

Ru(cod)(2-methylallyl)₂ was found to catalyze the SuzukiMiyaura cross-coupling reaction of aryl bromides and aryl iodides with arylboronic acids. The reaction was catalyzed by 10 mol% Ru(cod)(2-methylallyl)₂ at 60°C, and afforded the biaryls in moderate to good yields.

Full text of DOI:10.1246/cl.2010.1050

doi:10.1246/cl.2010.1050
1050
Published on the web August 21, 2010
Homogeneous Ruthenium Precatalyst for Suzuki-Miyaura Coupling Reaction
Motoi Kawatsura,* Kosuke Kamesaki, Mitsuaki Yamamoto, Shuichi Hayase, and Toshiyuki Itoh*
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Koyama, Tottori 680-8552
(Received July 9, 2010; CL-100620; E-mail: kawatsur@chem.tottori-u.ac.jp)
Table 1. Optimization of the ruthenium-catalyzed Suzuki-
Ru(cod)(2-methylallyl)2 was found to catalyze the Suzuki-
Miyaura cross-coupling reaction of aryl bromides and aryl
iodides with arylboronic acids. The reaction was catalyzed by
10 mol % Ru(cod)(2-methylallyl)2 at 60 °C, and afforded the
biaryls in moderate to good yields.
Miyaura coupling of 1a with 2aa
[Ru]
+
Me
I
PhB(OH)2
Me
Ph
base
1a
2a
3a
Yield
/%c
Entry
[Ru]b
Base
Solvent
The Suzuki-Miyaura cross-coupling reaction is one of the
most versatile synthetic methods for the construction of carbon-
carbon bonds and has been used for the synthesis of biaryls.1
Originally, the reaction used a palladium catalyst, and several
highly active palladium-ligand catalysts have been developed in
the last decade.2 Alternatively, the cross-coupling of aryl halides
with arylboronic acids has also been accomplished using other
metal catalysts such as nickel,3 copper,4 platinum,5 or rhodium.6
Ruthenium is also known to catalyze the coupling reaction, but
its use is limited to heterogeneous systems.7,8 For example,
Rothenberg reported in 2002 that ruthenium nanocolloid
catalyzed the Suzuki-Miyaura cross-coupling.7 Two years later,
Chang et al. succeeded in demonstrating that supported
ruthenium on alumina (Ru/Al2O3) effectively catalyzed the
coupling reaction, and they also mentioned that a homogeneous
ruthenium precursor is much less effective.8 However, we
understand they suggested that the homogeneous ruthenium
catalyst system is potentially capable of promoting cross-
coupling, therefore, we initiated a study to realize a practical
homogeneous ruthenium-catalyzed Suzuki-Miyaura cross-cou-
pling reaction. We now report the homogeneous ruthenium
precatalyst [Ru(cod)(2-methylallyl)2] catalyzed Suzuki-Miyaura
reaction of aryl iodides and bromides with arylboronic acid.
As shown in Table 1, a series of commercially available
ruthenium precursors were screened for the reaction of 4-
iodotoluene (1a) with phenylboronic acid (2a). The reaction
using RuCl3, Ru3(CO)12, and [RuCl2(p-cymene)]2 ([Ru-1])
resulted in less than 5% yield (Entries 1-3). The reaction with
RuCl2(cod) gave the desired biaryl compound in moderate yield
(Entry 4). To our delight, Ru(cod)(2-methylallyl)2 ([Ru-2])
effectively catalyzed the reaction at 60 °C in THF/H2O solvent,
and a 71% yield of 3a was obtained (Entry 5). Optimization of
the reaction conditions for the Ru(cod)(2-methylallyl)2 catalyzed
reaction of 1a with 2a revealed that the cyclopentyl methyl ether
(CPME) is the best solvent for the reaction (Entries 5-7). The
choice of base is also important in order to realize a high yield,
and we concluded that NaOtBu or CsOH is a promising base to
produce a good yield (Entries 7-10).
THF/H2O
(10/1)
THF/H2O
(10/1)
THF/H2O
(10/1)
THF/H2O
(10/1)
THF/H2O
(10/1)
dioxane/H2O
(10/1)
CPME/H2O
(10/1)
CPME/H2O
(10/1)
1
2
RuCl3•xH2O
Ru3(CO)12
[Ru-1]
KOH
KOH
KOH
KOH
KOH
KOH
KOH
NaOH
CsOH
0
0
3
5
4
[RuCl2(cod)]n
[Ru-2]
56
71
11
79
52
86
90
5
6
[Ru-2]
7
[Ru-2]
8
[Ru-2]
CPME/H2O
(10/1)
CPME/H2O
(10/1)
9
[Ru-2]
10
[Ru-2]
NaOtBu
aAll reactions were carried out with 1a (0.35 mmol), 2a
(1.06 mmol), ruthenium (0.035 mmol for RuCl3, RuCl2(cod),
and [Ru-2]. 0.018 mmol for [Ru-1]. 0.012 mmol for Ru3-
(CO)12), and base (0.88 mmol) in solvent (2.0 mL) under
nitrogen at 60 °C for 12 h. b[Ru-1]: [RuCl2(p-cymeme)]2.
c
[Ru-2]: Ru(cod)(2-methylallyl)2. Determined by HPLC anal-
ysis.
10 mol%
Ru(cod)(2-methylallyl)2
+
ArB(OH)2
X
Ar
base
R
R
1a-k
2a-e
3
CPME/H2O (10/1)
60 °C, 12 h
1: X = I
4: X = Br
Scheme 1.
The coupling reactions of several aryl iodides 1a-1k with
arylboronic acids 2a-2e were examined using an optimized
catalytic system (Scheme 1).9 Typically, the reaction was carried
out as follows: 10 mol % Ru(cod)(2-methylallyl)2, NaOt-Bu or
CsOH (2.5 equiv), the aryl iodide and arylboronic acid (3 equiv)
were mixed in CPME/H2O (10/1) at 60 °C for 12 h. The results
are summarized in Table 2. Aryl iodides 1b-1d were coupled
with phenylboronic acid (2a) to give the corresponding biaryls
in good yields (88-95% isolated yield) (Entries 1-5). For the
reaction of 1b and 1c, NaOt-Bu produced a better result than
CsOH. On the other hand, CsOH realized higher yields than
NaOt-Bu for the reactions of 1e-1h, which contained electron-
donating or electron-withdrawing groups at the para-position
Chem. Lett. 2010, 39, 1050-1051
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1051
Table 2. Ru(cod)(2-methylallyl)2-catalyzed Suzuki-Miyaura
coupling of aryl iodides 1a-1ka
Table 3. Ruthenium-catalyzed Suzuki-Miyaura coupling of
aryl bromides 4a-4da
Entry R
Ar
Base
NaOtBu 89
CsOH 86
NaOtBu 95
Yield/%b,c
Yield
Entry
R
2
Base
/%b,c
1
2
3
4
5
6
7
8
9
H (1b)
H (1b)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
1
2
3
4
5
H (4a)
2a
2a
2a
2a
2b
NaOtBu
NaOtBu
CsOH
CsOH
NaOtBu
73
88
79
86
64
4-t-Bu (1c)
4-t-Bu (1c)
4-Ph (1d)
4-OMe (1e)
4-OMe (1e)
4-F (1f)
4-Me (4b)
4-Cl (4c)
4-OMe (4d)
4-Me (4b)
CsOH
88
NaOtBu 88
NaOtBu 68
CsOH
75 (82)d
aReaction conditions: 1 (0.35 mmol), 2 (1.06 mmol), [Ru-2]
(0.035 mmol), and base (1.05 mmol) in CPME/H2O (10/1)
(2.0 mL) under nitrogen at 60 °C for 12 h. Isolated yield by
silica gel column chromatography. cAn average of at least two
NaOtBu 23
4-F (1f)
CsOH
CsOH
CsOH
60
70
53
b
10 4-Br (1g)
11 4-CO2Me (1h) Ph (2a)
runs.
12 2-Me (1i)
13 2-OMe (1j)
14 4-Ac (1k)
15 4-Ac (1k)
16 4-Me (1a)
17 4-Me (1a)
18 4-Me (1a)
19 4-Me (1a)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
NaOtBu 44
NaOtBu 72
NaOtBu (8)d
References and Notes
1
a) A. Suzuki, Pure Appl. Chem. 1991, 63, 419. b) N.
Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457. c) A.
Suzuki, J. Organomet. Chem. 1999, 576, 147. d) N.
Miyaura, Top. Curr. Chem. 2002, 219, 11. e) G. A.
Molander, B. Canturk, Angew. Chem., Int. Ed. 2009, 48,
9240, and references cited therein.
CsOH
(8)d
4-MeOC6H4 (2b) NaOtBu 52
4-FC6H4 (2c)
4-PhC6H4 (2d)
4-MeC6H4 (2e)
NaOtBu 55
NaOtBu 54
NaOtBu 59
2
For selected papers on the palladium-catalyzed Suzuki-
Miyaura cross-coupling reaction, see: a) A. F. Littke, C. Dai,
G. C. Fu, J. Am. Chem. Soc. 2000, 122, 4020. b) J. P.
Stambuli, R. Kuwano, J. F. Hartwig, Angew. Chem., Int. Ed.
2002, 41, 4746. c) K. W. Anderson, S. L. Buchwald, Angew.
Chem., Int. Ed. 2005, 44, 6173. d) C. M. So, C. P. Lau, F. Y.
Kwong, Angew. Chem., Int. Ed. 2008, 47, 8059, and
references cited therein.
aReaction conditions: 1 (0.35 mmol), 2 (1.06 mmol), [Ru-2]
(0.035 mmol), and base (0.88 mmol) in CPME/H2O (10/1)
b
(2.0 mL) under nitrogen at 60 °C for 12 h. Isolated yield by
silica gel column chromatography. cAn average of at least two
d
runs. HPLC yields in parentheses.
3
Recent examples of the nickel-catalyzed Suzuki-Miyaura
cross-coupling reaction, see: a) K. W. Quasdorf, M. Riener,
K. V. Petrova, N. K. Garg, J. Am. Chem. Soc. 2009, 131,
17748. b) A. Antoft-Finch, T. Blackburn, V. Snieckus, J. Am.
Chem. Soc. 2009, 131, 17750. c) D.-G. Yu, M. Yu, B.-T.
Guan, B.-J. Li, Y. Zheng, Z.-H. Wu, Z.-J. Shi, Org. Lett.
2009, 11, 3374. d) K. Inamoto, J. Kuroda, E. Kwon, K.
Hiroya, T. Doi, J. Organomet. Chem. 2009, 694, 389. e) L.
Xu, B.-J. Li, Z.-H. Wu, X.-Y. Lu, B.-T. Guan, B.-Q. Wang,
K.-Q. Zhao, Z.-J. Shi, Org. Lett. 2010, 12, 884.
a) J.-H. Li, D.-P. Wang, Eur. J. Org. Chem. 2006, 2063. b) J.
Mao, J. Guo, F. Fang, S.-J. Ji, Tetrahedron 2008, 64, 3905.
a) R. B. Bedford, S. L. Hazelwood, D. A. Albisson,
Organometallics 2002, 21, 2599. b) C. H. Oh, Y. M. Lim,
C. H. You, Tetrahedron Lett. 2002, 43, 4645.
(Entries 6-11). For example, when NaOt-Bu was used for the
reaction of 1-fluoro-4-iodobenzene (1f), a biaryl was produced
in only 23% yield, but when using CsOH, the yield increased to
60% (Entries 8 and 9). Furthermore, the reaction of 1-bromo-4-
iodobenzene (1g) proceeded with perfect chemoselectivity, and
we observed no trace amounts of p-terphenyl and 4-iodobi-
phenyl (Entry 10). The sterically hindered ortho-substituted aryl
iodides, such as 1i and 1j, also produced the desired biaryls by
the combination of Ru(cod)(2-methylallyl)2 and NaOt-Bu
(Entries 12 and 13). Unfortunately, the reactions of 1k with 2a
resulted in very poor yields (Entries 14 and 15). We further
examined the reactions with other arylboronic acids. Several
para-substituted arylboronic acids 2b-2e reacted with 1a under
the optimized reaction conditions, producing the desired
products in moderate isolated yields (52-59%) (Entries 16-19).
We next attempted the Ru(cod)(2-methylallyl)2 catalyzed
Suzuki-Miyaura coupling of aryl bromides 4a-4d. The results
are summarized in Table 3. After a small modification10 of the
reaction conditions, the desired coupling reactions of the aryl
bromides 4a-4d with arylboronic acids 2a and 2b were
effectively promoted by the Ru(cod)(2-methylallyl)2 at 60 °C,
and the corresponding biaryls were obtained in good yield.
In conclusion, we succeeded in demonstrating the Ru-
(cod)(2-methylallyl)2-catalyzed Suzuki-Miyaura cross-coupling
reaction of aryl iodides and aryl bromides.
4
5
6
7
L. Zhang, J. Wu, Adv. Synth. Catal. 2008, 350, 2409.
a) M. B. Thathagar, J. Beckers, G. Rothenberg, J. Am. Chem.
Soc. 2002, 124, 11858. b) M. B. Thathagar, J. Beckers, G.
Rothenberg, Adv. Synth. Catal. 2003, 345, 979.
Y. Na, S. Park, S. B. Han, H. Han, S. Ko, S. Chang, J. Am.
Chem. Soc. 2004, 126, 250.
8
9
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett.
10 The amount of base was changed from 2.5 equiv to
3.0 equiv.
Chem. Lett. 2010, 39, 1050-1051
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/