Communications
DOI: 10.1002/anie.200906996
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C H Functionalization
À
Nickel-Catalyzed Direct C H Arylation and Alkenylation of
Heteroarenes with Organosilicon Reagents**
Hitoshi Hachiya, Koji Hirano, Tetsuya Satoh, and Masahiro Miura*
Organosilicon compounds are useful and ubiquitous synthetic
reagents in modern organic chemistry. Among the versatile
transformations involving them, transition metal catalyzed
cross-coupling reactions of organic halides or pseudohalides,
that is Hiyama cross-coupling, ranks as one of the most
provided 2-phenylbenzoxazole (3aa) in 8% yield (GC)
(Table 1, entry 1). Apparently, arylsilane 2a participated in
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the reaction, and the desired cross-coupling involving C H
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Table 1: Optimization studies for nickel-catalyzed direct C H phenyl-
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powerful and reliable C C bond-forming reactions in organic
ation of benzoxazole (1a) with trimethoxyphenylsilane (2a).[a]
synthesis.[1] Recent efforts by Nakao, Hiyama, and co-work-
ers,[2] and Denmark et al.[3] introduce new types of stable and
easy-to-handle silicon-based coupling reagents to enhance the
generality of the reaction. In contrast, the development of
new catalyst systems by Fu and co-workers[4] and Wu and co-
workers[5] has expanded the scope of organic electrophiles
into unactivated alkyl halides and arenesulfonates, respec-
tively. In addition, the Hiyama coupling has significant
benefits involving tractability, low toxicity, and environmen-
tally benignity associated with organosilicon compounds, as
well as organoboron reagents in the Suzuki–Miyaura cou-
pling.
Entry Ligand Additives (equiv)
Solvent Yield of
3aa [%][b]
1[c]
2
3
4
5
phen
phen
phen
phen
bpy
CsF (4.0)
DMAc
8
CsF (2.0) and AgF (2.0)
CsF (2.0) and CuF2 (2.0)
CuF2 (2.0)
DMAc 16
DMAc 60
DMAc 15
DMAc 70
DMAc 24
DMAc 36
CsF (2.0) and CuF2 (2.0)
6
dmphen CsF (2.0) and CuF2 (2.0)
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Meanwhile, metal-mediated C C bond formation through
7
8
9
dtbpy
bpy
bpy
CsF (2.0) and CuF2 (2.0)
CsF (2.0) and CuF2 (2.0)
CsF (2.0) and CuF2 (2.0)
CsF (2.0) and CuF2 (2.0)
CsF (2.0) and CuF2 (2.0)
CsF (3.0) and CuF2 (2.0)
CsF (3.0) and CuCl2 (2.0)
direct C H functionalization[6] has received much attention as
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DMF
67
diglyme 29
DMAc 31
DMAc 54
DMAc 80[g]
a potentially more efficient and complementary process to the
conventional cross-coupling methodology. Although the
direct arylation of a variety of arenes and heteroarenes with
arylboronic acids derivatives has been achieved,[7,8] the
corresponding direct coupling with organosilanes still remains
elusive. To the best of our knowledge, only two successful
examples have been reported to date.[9] Moreover, these
processes rely on the palladium catalysis, and substrates are
limited to those containing an acetamide moiety as the
chelation-assisted cyclopalladation step is crucial in the
catalytic reaction. Herein we report a new nickel-based
10[d] bpy
11[e] bpy
12[f] bpy
13
14
bpy
bpy
DMAc
2
5
CsF (3.0) and Cu(OAc)2·OH2 (2.0) DMAc
[a] A mixture of NiBr2·diglyme (0.050 mmol), ligand (0.050 mmol),
additives, 1a (0.50 mmol), and 2a (1.0 mmol) in solvent (3.0 mL) was
heated at 1508C for 2.5 h under N2. [b] Yield determined by GC methods.
[c] Under air. [d] Used NiBr2 instead of NiBr2·diglyme. [e] Used [Ni-
(acac)2] instead of NiBr2·diglyme. [f] Used 1.0 mmol of H2O. [g] Yield of
isolated product.
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catalyst system for the direct C H arylation and alkenylation
of various heteroarenes with organosilanes.[10]
As an initial experiment, treatment of benzoxazole (1a,
0.50 mmol) with trimethoxyphenylsilane (2a, 1.0 mmol) in
the presence of 10 mol% of NiBr2·diglyme, 10 mol% of 1,10-
phenanthroline (phen), and CsF in 3.0 mL of N,N-dimethyl-
acetamide (DMAc) at 1508C under air (O2 as an oxidant)
bond cleavage took place albeit in low yield. The interesting
preliminary result encouraged us to optimize the reaction
conditions based on the nickel catalyst. The replacement of
air by a metal oxidant such as AgF or CuF2 improved the
reaction efficiency, with CuF2 proving to be superior (Table 1,
entries 2 and 3). Notably, the combination of CsF and CuF2
was necessary for the satisfactory yield (Table 1, entry 4). The
ligand effect was critical in this transformation. Whereas 2,2’-
bipyridine (bpy) increased the yield to 70% (Table 1, entry 5),
2,9-dimethylphenanthroline (dmphen) and 4,4’-di(tert-butyl)-
2,2’-bipyridine (dtbpy) resulted in a lower yield (Table 1,
entries 6 and 7). Some investigations into the solvent revealed
that other amide solvents such as N,N-dimethylformamide
(DMF) resulted in a comparable yield, whereas the use of
diglyme decreased the yield (Table 1, entries 8 and 9). As the
nickel source, NiBr2 or [Ni(acac)2] instead of NiBr2·diglyme
showed lower performance (Table 1, entries 10 and 11).
[*] H. Hachiya, Dr. K. Hirano, Prof. Dr. T. Satoh, Prof. Dr. M. Miura
Department of Applied Chemistry, Faculty of Engineering
Osaka University
Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7362
E-mail: miura@chem.eng.osaka-u.ac.jp
[**] This work was partly supported by the Grants-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technology
(Japan).
Supporting information for this article is available on the WWW
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 2202 –2205