Ruthenium-catalyzed oxidative alkenylation of arenes via regioselective ch bond cleavage directed by a nitrogen-containing group

Article abstract of DOI:10.1246/cl.2011.1165

Direct alkenylation of 1-phenylpyrazoles with alkenes such as acrylates accompanied by regioselective CH bond cleavage proceeds efficiently under ruthenium catalysis in the presence of a copper oxidant. The procedure is also applicable to 2-phenylbenzothiazole and benzanilide.

Full text of DOI:10.1246/cl.2011.1165

doi:10.1246/cl.2011.1165
Published on the web September 28, 2011
1165
Ruthenium-catalyzed Oxidative Alkenylation of Arenes via Regioselective
C-H Bond Cleavage Directed by a Nitrogen-containing Group
Yuto Hashimoto, Takumi Ueyama, Tatsuya Fukutani, Koji Hirano, Tetsuya Satoh,* and Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871
(Received August 8, 2011; CL-110661; E-mail: satoh@chem.eng.osaka-u.ac.jp, miura@chem.eng.osaka-u.ac.jp)
Table 1. Reaction of 1-phenylpyrazoles 1 with alkenes 2a
Direct alkenylation of 1-phenylpyrazoles with alkenes such
as acrylates accompanied by regioselective C-H bond cleavage
proceeds efficiently under ruthenium catalysis in the presence
of a copper oxidant. The procedure is also applicable to
2-phenylbenzothiazole and benzanilide.
R1
R1
R2
R2
X
N
N
[Ru(p-cymene)Cl2]2
N
N
R4
+
R4
Cu(OAc)2•H2O
DMF
2
R3
R3
Transition-metal-catalyzed regioselective C-H functionali-
zation reactions with the aid of directing groups have been
recognized as synthetically attractive tools from atom- and step-
economic points of view.1 Particularly, the palladium- and
rhodium-catalyzed ortho-alkenylation of aromatic substrates
with readily available alkenes seems to be a useful method
to selectively construct ³-conjugated vinylarene frameworks,
which can be widely seen in organic materials.2 As early
examples, we demonstrated that 2-phenylphenols,3 N-(arylsul-
fonyl)-2-phenylanilines,4 and benzoic acids4,5 undergo directed
alkenylation under Pd- or Rh-catalysis. Since then, a number of
related oxidative alkenylation reactions have been disclosed by
us6 and others.7 Compared to well-developed Pd- and Rh-
catalyzed reactions, the ruthenium-catalyzed version has been
less explored. Recently, we succeeded in finding that hetero-
arene carboxylic acids undergo directed alkenylation under Ru-
catalysis.8a Although the Ru-catalyzed alkenylation9,10 seems to
be attractive due to relatively lower catalyst cost compared to Pd
and Rh, the substrates have so far been limited to carboxylic
acids.8 Therefore, we have investigated the applicability of our
Ru-catalyst system to other substrates and found that phenyl-
azoles and benzanilide are capable of undergoing the regio-
selective alkenylation directed by their nitrogen-containing
groups. In most cases, monoalkenylated products can be
obtained selectively. The results obtained for the reactions are
described herein.
1
3: X = H
4: X = CH=CHR4
Entry
1
2
Product(s), Yieldb/%
N
N
N
N
X
R4
R4
1
2a: R4 = CO2(n-Bu)
2a: R4 = CO2(n-Bu)
2b: R4 = CO2Et
3a: R4 = CO2(n-Bu), 67
3a: R4 = CO2(n-Bu), 65
3b: R4 = CO2Et, 62
3c: R4 = CO2Cy, 42
4c: R4 = CO2Cy, 16
3d: R4 = CN, 43d
1a
2c
3
4
2c: R4 = CO2Cy
5
6
2d: R4 = CN
2e: R4 = Ph
3e: R4 = Ph, 18
Me
Me
R2
R2
X
N
N
N
N
CO2(n-Bu)
7
8
1b: R2 = H
2a
3f: R2 = H, 41
4f: R2 = H, 19
3g: R2 = Me, 78
1c: R2 = Me
N
N
N
N
X
CO2(n-Bu)
In an initial attempt, 1-phenylpyrazole (1a) (0.25 mmol) was
treated with butyl acrylate (2a) (0.5 mmol) in the presence of
[Ru(p-cymene)Cl2]2 (0.013 mmol) and Cu(OAc)2¢H2O (0.5
mmol) as catalyst and oxidant, respectively, in DMF at 100 °C
for 4 h under N2. As a result, a monoalkenylated product, 1-{2-
[(E)-2-(n-butoxycarbonyl)ethenyl]phenyl}pyrazole (3a), was
obtained in 67% yield (Entry 1 in Table 1). Note that even
under conditions using excess 2a, only a minor amount of
dialkenylated product was detected by GC-MS. This is in
contrast to the fact that the selective monoalkenylation could be
achieved by using excess 1a under Rh catalysis.6a The catalyst
loading could be reduced up to 2 mol % to afford 3a in a
comparable yield (Entry 2). The reaction of 1a with ethyl
acrylate (2b) proceeded similarly to give monoalkenylated
product 3b in 62% yield (Entry 3). In the case using cyclohexyl
acrylate (2c), in contrast, a separable mixture of mono- (3c) and
dialkenylated (4c) products was formed and isolated in 46%
and 16% yields, respectively (Entry 4). Acrylonitrile (2d) and
R3
R3
9
1d: R3 = Me
2a
3h: R3 = Me, 74
4h: R3 = Me, 20
3i: R3 = Cl, 53
4i: R3 = Cl, 11
10
1e: R3 = Cl
aReaction conditions: 1 (0.25 mmol), 2 (0.5 mmol), [(Ru(p-
cymene)Cl2)2] (0.013 mmol), Cu(OAc)2¢H2O (0.5 mmol) in
DMF (3 mL) at 100 °C for 4 h under N2. Isolated yield based
on the amount of 1 used. [(Ru(p-cymene)Cl2)2] (0.005 mmol)
was used. E/Z = 4:1.
b
c
d
styrene (2e) also underwent alkenylation with 1a to afford 3d
and 3e albeit in lower yields (Entries 5 and 6). Under the present
conditions, the reaction with N,N-dimethylacrylamide was
sluggish.
The reactions of substituted 1-phenylpyrazoles with 2a were
next examined. 3-Methyl-1-phenylpyrazole (1b) underwent the
Chem. Lett. 2011, 40, 1165-1166
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1166
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alkenylation to afford a separable mixture of mono- and
dialkenylated products, 3f and 4f (Entry 7). The reaction of
3,5-dimethyl-1-phenylpyrazole (1c) gave monoalkenylated 3g
exclusively (Entry 8). 1-(4-Methylphenyl)pyrazole (1d) and
1-(4-chlorophenyl)pyrazole (1e) also underwent the reaction to
produce the corresponding 3 and 4 (Entries 9 and 10).
Besides pyrazoles, 2-phenylbenzothiazole also reacted with
2a in the presence of the [Ru(p-cymene)Cl2]2/Cu(OAc)2¢H2O
catalyst system to form the corresponding monoalkenylated
product, albeit in a low yield (ca. 20%). The reactions of
1-methyl-2-phenylimidazole and 2-phenylpyridine were more
sluggish to afford only trace amounts of alkenylated products
under similar conditions.
In addition, benzanilide (5) was found to undergo the
coupling with 2a under Ru catalysis (Scheme 1).11 In this case,
the reaction proceeded smoothly in o-xylene rather than in DMF
to afford lactam 6, an alkenylation/nucleophilic cyclization
product, in 80% yield.
In summary, we have demonstrated that phenylpyrazoles
and benzanilide efficiently undergo regioselective alkenylation
in the presence of a ruthenium catalyst and a copper oxidant.12
The present Ru catalyst system and related ones are expected
to be applicable to other oxidative coupling reactions. Work is
underway toward further development of the catalysis.
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This work was partly supported by Grants-in-Aid from
MEXT and JSPS, Japan.
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Chem. Lett. 2011, 40, 1165-1166
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/