Kumada-tamaocorriu-coupling using N-heterocyclic carbene ligands bearing pyridyl and ethylenedioxyl moieties

Article abstract of DOI:10.1246/cl.2011.936

Carbene ligands bearing a pyridyl group and an ethylenedioxyl moiety were developed, and utilized as efficient ligands for the nickel-catalyzed KumadaTamaoCorriu coupling. A wide variety of aryl chlorides could be used for the cross-coupling reaction with aryl Grignard reagents to afford the corresponding products in high yields in short time.

Full text of DOI:10.1246/cl.2011.936

doi:10.1246/cl.2011.936
936
Published on the web September 5, 2011
Kumada-Tamao-Corriu Coupling Using N-Heterocyclic Carbene Ligands Bearing Pyridyl
and Ethylenedioxyl Moieties
Koichi Mitsudo,* Yuta Doi, Syunsuke Sakamoto, Hiroki Murakami, Hiroki Mandai, and Seiji Suga*
Graduate School of Natural Science and Technology, Okayama University,
3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530
(Received April 18, 2011; CL-110322; E-mail: suga@cc.okayama-u.ac.jp)
Carbene ligands bearing a pyridyl group and an ethyl-
Carbene precursor 1a, bearing a 2-pyridylmethyl group, was
readily prepared from the reaction of 2-pyridylmethyl-1-imi-
dazole with 1-bromo-2-(2-methoxyethoxy)ethane in high yield
(Scheme 1).7 Precursor 1b, which has a pyridyl group, was also
obtained in a similar manner.
enedioxyl moiety were developed, and utilized as efficient
ligands for the nickel-catalyzed Kumada-Tamao-Corriu cou-
pling. A wide variety of aryl chlorides could be used for the
cross-coupling reaction with aryl Grignard reagents to afford the
corresponding products in high yields in short time.
Thus obtained carbene precursors 1a and 1b were applied to
the nickel-catalyzed coupling reaction between chlorobenzene
and p-tolyl Grignard reagent (Table 1). In the presence of a
catalytic amount of [Ni(acac)2]¢H2O (1.5 mol %) and 1a (1.8
mol %), the cross-coupling of chlorobenzene (2a) and p-
tolylmagnesium bromide (2.5 equiv) proceeded smoothly and
terminated in 20 min to afford 4-methylbiphenyl (3a) in 94%
yield (Entry 1). Using 1b, 3a was obtained in 84% yield
(Entry 2). To compare the efficiency of the ligands, we next
applied typical NHC ligands (IPr, SIPr, and SIMes) to the
reaction (Entries 3-5). In each case, the reaction was slower than
that with 1a or 1b, and the yields of 3a were quite low (18-24%)
and 60-69% of chlorobenzene (2a) was recovered. Using 1,1¤-
Since the synthesis by Arduengo and co-workers in 1991,1
N-heterocyclic carbenes (NHCs) have received considerable
attentions because of their unique characters as ligands2 and
organocatalysts.3
The most commonly used NHC ligands are imidazolium
derivatives bearing sterically hindered arenes, such as IPr, SIPr,
and SIMes (Figure 1). While the steric hindrance should
decrease the catalytic activity, the bulkiness prevents the
aggregation of catalysts, which as a whole leads to the high
activity of NHC catalysts.2h If the aggregation of a less hindered
NHC catalyst can be suppressed by another method, the catalyst
would be more efficient than the existing catalysts. We assumed
that the introduction of coordinating groups, which coordinate to
the metal center of the catalyst, would suppress the aggregation.
We considered the introduction of two different coordinat-
ing groups. One of them strongly coordinates to the metal center
of the catalyst, which suppresses the aggregation of the catalyst,
and the other weakly coordinates to the metal center, which
would act as a liberal coordination site. Thus, appropriate
stability and high activity of the complex would be expected.
According to our hypothesis, we designed novel NHC
ligands bearing a 2-pyridyl group4 and an ethylenedioxy moiety5
as coordinating groups, and found that they were efficient
ligands for the Ni-catalyzed Kumada-Tamao-Corriu coupling.6
N
N
N
Br
Br
O
(1.2 equiv)
O
N
N
N
O
O
CH2Cl2, 40 °C, 24 h
1a
89%
N
N
Br
Br
O
O
(3 equiv)
N
N
O
N
O
neat, 70 °C, 26 h
N
1b
98%
Scheme 1. Synthesis of ligand precursors 1a and 1b.
Table 1. Ni-Catalyzed cross-coupling between chlorobenzene
(2a) and p-tolylmagnesium bromide with several ligandsa
[Ni(acac)2]•H2O (1.5 mol%)
ligand (1.8 mol%)
Typical NHC
p-TolMgBr (2.5 equiv)
Cl
+
biphenyl
THF
N
N
N
N
N
N
60 °C, 20 min
2a
3a
4
Entry
Ligand
3a/%
4/%
Recov. 2a/%
1
2
3
4
5
6
7
8
9
1a
1b
94
84
24
22
18
49
41
69
68
78
6
6
2
3
2
6
4
4
15
4
0
0
IPr
This work
SIPr
SIMes
IPr¢HCl
SIPr¢HCl
SIMes¢HCl
dppf
60
60
69
39
46
22
7
N
n
N
stabilized metal center
by coordinating group
N
O
O
n = 0,1
1c
1d
1e
1f
less hindered
than typical NHC
(e.g. IPr, SIPr, SIMes)
strong
coordinating group
weak
coordinating group
10
17
aGC yield.
Figure 1. Typical and novel designed N-heterocyclic carbenes.
Chem. Lett. 2011, 40, 936-938
© 2011 The Chemical Society of Japan
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937
Br
Br
Table 3. [Ni(acac)2]¢H2O/1a-catalyzed
Corriu coupling of several haloarenesa
[Ni(acac)2]•H2O (1 mol%)
Kumada-Tamao-
N
N
N
N
N
N
1a
(1.2 mol%)
1c
1d
PhMgBr (2.5 equiv)
Ar
X
Ar
THF
Br
60 °C, 20 min
Br
2
3
N
N
O
N
N
O
Entry
1
2
3
Yield/%
86
Recov. 2/%
N
1f
1e
Me
Me
Cl 2e
0
3a
Figure 2. Other ligand precursors used in this work.
2
3
91
86
0
0
3f
Cl
Table 2. [Ni(acac)2]¢H2O/1a-catalyzed
Kumada-Tamao-
2f
Me
Corriu coupling of halobenzenes and p-tolylmagnesium bro-
midea
3g
Cl
[Ni(acac)2]•H2O (0.4–1.5 mol%)
2g
2h
1a
(1.2 equiv to Ni)
Bu
Cl
p-TolMgBr (2.5 equiv)
4
5
6
80
77
81
0
0
0
3h
3i
X
+
biphenyl
THF
60 °C, 20 min
C2l i
MeO
NC
2
3a
4
2a: X = Cl 2b: X = F
2c: X = Br 2d: X = I
Cl 2j
3j
[Ni(acac)2]¢H2O
/mol %
3a
/%
4
/%
Recov. 2a
/%
N
Entry
2
7
8
9
Cl
Br
Cl
42 (53)b
71 (78)c
64
26 (27)b
0 (0)c
0
3k
3l
2k
1
2
3
4
5
6
7
2a
2a
2a
2a
2b
2c
2d
1.5
1.0
0.8
0.4
1.0
1.0
1.0
94
92
88
6
5
7
0
0
0
N
2l
N
31 (93)b 1 (6)b
62 (0)b
99 (0)c
0
3m
2m
0 (75)c 0.2 (10)c
aGC yield. Performed at 80 °C. Performed at 40 °C.
b
c
61
7
70 (77)d 3 (3)d
0 (0)d
b
c
aGC yield. Reaction time was extended to 60 min. Reaction
[Ni(acac)2]¢H2O, 3a was obtained in only 31% yield in
20 min, but the reaction was finished within 1 h to afford
coupling product 3a in 93% yield (Entry 4). These results
suggest that a highly active and relatively stable species was
generated in situ from [Ni(acac)2]¢H2O and 1a. We next applied
other halobenzenes to the reaction. Even fluorobenzene can be
used under these conditions. The reaction was slower than that
with chlorobenzene but was finished within 12 h to afford 3a in
75% yield (Entry 5). Bromobenzene and iodobenzene could also
be used for the reaction to afford 3a in 61% and 77% yields,
respectively (Entries 6 and 7).
To study the scope of the reaction, we next conducted
[Ni(acac)2]¢H2O/1a-catalyzed coupling of several haloarenes
(Table 3). First, chloroarenes bearing electron-donating groups
were carried out. The coupling reaction of o-, m-, and p-
chlorotoluene (2e-2g) proceeded smoothly and corresponding
coupling adducts 3e-3g were obtained in respective yields of
86%, 91%, and 86% (Entries 1-3). In the case of p-butylchloro-
benzene (2h) and p-chloromethoxybenzene (2i), the correspond-
ing coupling products were also obtained in good yields (Entries
4 and 5). We next carried out the coupling reaction of 2j,
possessing an electron-withdrawing cyano group, and found that
desired product 3j was obtained in good yield (81%, Entry 6).
The coupling reactions of 2- and 3-halopyridines also proceeded
under similar conditions, and corresponding coupling products
3k, 3l, and 3m were obtained in moderate to good yields
(Entries 7-9). In the Kumada-Tamao-Corriu coupling of halo-
pyridines, the use of typical NHC such as IPr gave better
results.6n It is probably because steric hindered NHC ligands
would suppress the coordination of a halopyridine to the metal
center and prevent the deactivation of the catalyst.
d
time was extended to 12 h. Performed at 0 °C.
bis(diphenylphosphano)ferrocene (dppf), which has been known
to be an efficient ligand for the Kumada-Tamao-Corriu
coupling, 49% yield of 3a was afforded under similar conditions
(Entry 6). To clarify the role of 2-pyridyl and ethylenedioxy
groups, we next carried out the Ni-catalyzed coupling with
carbene ligand precursors 1c-1f shown in Figure 2, which have
one pyridyl moiety or ethylenedioxy group. Using imidazolium
salt 1c or 1d, which possesses a 2-pyridylmethyl group,
coupling product 3a was obtained in 41% and 69% yields,
respectively (Entries 7 and 8). With 1-mesityl-3-pyridylimida-
zolium salt (1e), 3a was obtained in moderate yield (68%,
Entry 9). 1f bearing an ethylenedioxy moiety, which would have
relatively weak coordination ability, showed better catalytic
activity to afford 3a in 78% (Entry 10). These results suggest
that both a pyridyl group and an ethylenedioxy moiety, which
could coordinate to the nickel metal center, may suppress the
aggregation and make the complexes active. The ethylenedioxy
moiety seems to be more easily liberated, and hence the reaction
using 1f might be slightly faster than others, although further
investigation is necessary to understand the role of the
coordination moieties.
We next optimized the conditions of the [Ni(acac)2]¢H2O/
1a-catalyzed coupling reactions, and several halobenzenes were
applied under the conditions (Table 2). As mentioned above,
coupling product 3a was obtained in 94% yield from chloro-
benzene with 1.5 mol % of [Ni(acac)2]¢H2O (Entry 1). Reducing
the amount of nickel source to 0.8-1.0 mol %, 3a was obtained
in similar yields (Entries 2 and 3). Using 0.4 mol % of
Chem. Lett. 2011, 40, 936-938
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

938
In conclusion, we synthesized novel NHC carbene ligand
J. Chem. Soc., Dalton Trans. 2000, 4499.
precursors 1a and 1b, bearing a pyridyl group and an ethyl-
enedioxy moiety, and found that they were efficient for the Ni-
catalyzed Kumada-Tamao-Corriu coupling. Further scope of the
ligands is under investigation.
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Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and by Okayama
Foundation for Science and Technology. The authors are
grateful to the SC-NMR Laboratory of Okayama University
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This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
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7
Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2011, 40, 936-938
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/