Ru/Ag-catalyzed oxidative alkenylation of benzamides and phenylazoles through regioselective C-H bond cleavage

Article abstract of DOI:10.1246/cl.2012.151

Oxidative alkenylation of N,N-disubstituted benzamides with alkenes accompanied by regioselective C-H bond cleavage proceeds efficiently in the presence of a Ru/Ag catalyst system together with a copper oxidant. The procedure is also applicable to phenyla

Full text of DOI:10.1246/cl.2012.151

doi:10.1246/cl.2012.151
Published on the web January 28, 2012
151
Ru/Ag-Catalyzed Oxidative Alkenylation of Benzamides and Phenylazoles
through Regioselective C-H Bond Cleavage
Yuto Hashimoto,1 Timon Ortloff,2 Koji Hirano,1 Tetsuya Satoh,*1 Carsten Bolm,2 and Masahiro Miura*1
1Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871
2Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52056 Aachen, Germany
(Received November 17, 2011; CL-111115; E-mail: satoh@chem.eng.osaka-u.ac.jp, miura@chem.eng.osaka-u.ac.jp)
Table 1. Reaction of benzamides 1 with alkenes 2a
Oxidative alkenylation of N,N-disubstituted benzamides
with alkenes accompanied by regioselective C-H bond cleavage
[Ru(p-cymene)Cl2]2
O
NR1
O
NR1
2
2
AgSbF6
proceeds efficiently in the presence of a Ru/Ag catalyst system
together with a copper oxidant. The procedure is also applicable
to phenylazoles.
R2
+
R2
Cu(OAc)2•H2O
t-AmOH
2
1
3
Entry
1
2
Product, Yield/%
Direct C-C coupling reactions through regioselective C-H
bond cleavage have attracted much attention as atom- and step-
economic tools for precise synthesis, and various catalytic
processes involving different modes to activate the ubiquitously
available bond have been developed.1 Among the most promis-
ing strategies is the chelate-assisted version with the aid of
directing groups. Particularly, the transition-metal-catalyzed
ortho-alkenylation of aromatic substrates through oxidative
coupling with readily available alkenes2 is a useful method to
selectively construct ³-conjugated alkenylarene frameworks,
which can be widely seen in organic materials.3 As early
examples, we demonstrated that 2-phenylphenols,4 N-(arylsul-
fonyl)-2-phenylanilines,5 and benzoic acids5,6 undergo directed
alkenylation under Pd- or Rh-catalysis. Since then, a number
of related oxidative alkenylation reactions have been disclosed
by us7 and others.8 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 acids9 and phenylazoles10 undergo directed
alkenylation under Ru-catalysis. Although the Ru-catalyzed
alkenylation11,12 seems to be attractive due to relatively lower
catalyst cost compared to Pd and Rh, the effective substrates
have so far been limited. Consequently, we have investigated
retuning our Ru-catalyst system to improve the activity and to
expand its applicability and found that addition of AgSbF6 as a
cocatalyst together with [Ru(p-cymene)Cl2]2 enables N,N-di-
substituted benzamides13 to undergo the regioselective alkenyl-
ation smoothly. Actually, the reaction did not proceed at all
without the cocatalyst. The catalyst system [Ru(p-cymene)Cl2]2/
AgSbF6 was also found to be effective for the alkenylation of
phenylazoles. These new findings are described herein.
O
NMe2
O
NMe2
R2
R2
1b
2
3
4
5
2a: R2 = CO2(n-Bu)
2a: R2 = CO2(n-Bu)
2b:R2 = CO2Et
2c: R2 = CO2Cy
2d:R2 = Ph
3a: R2 = CO2(n-Bu), 0
1a
3a: R2 = CO2(n-Bu), 98
3b:R2 = CO2Et, 92
3c: R2 = CO2Cy, 82
3d:R2 = Ph, 62
O
O
N
N
O
N
CO2(n-Bu)
6
7
1b
1c
2a
2a
3e, 82
O
N
CO2(n-Bu)
3f, 75
aReaction conditions: 1 (0.25 mmol), 2 (0.5 mmol), [Ru(p-
cymene)Cl2]2 (0.013 mmol), AgSbF6 (0.05 mmol), Cu(OAc)2¢
H2O (0.5 mmol), in t-AmOH (3 mL) at 100 °C for 4 h under N2.
bWithout AgSbF6.
(2c) acrylates proceeded similarly to give the corresponding
alkenylated products 3b and 3c in good yields (Entries 3 and 4).
Styrene (2d) also underwent the reaction with 1a smoothly to
give a stilbene derivative 3d (Entry 5). Besides 1a, N-benzoyl-
piperidine (1b) and -pyrrolidine (1c) also reacted with 2a to
afford alkenylated products, 3e and 3f, respectively (Entries 6
and 7). Note that ortho-alkenylbenzamide derivatives are of
interest due to their photochemical reactivity as well as
applicabilities as photosensitizers and chiral auxiliaries.15
In the presence of the [Ru(p-cymene)Cl2]2/AgSbF6 catalyst
system, the alkenylation of phenylazoles was also found to be
promoted. Previously, we reported that the reaction of 2-
phenylbenzothiazole (4) with 2a using [Ru(p-cymene)Cl2]2 gave
the corresponding alkenylated product 5 in a low yield (ca.
20%).10a The reaction efficiency was considerably improved by
the addition of AgSbF6 cocatalyst to produce 5 in 61% yield
(Scheme 1).
In an initial attempt, N,N-dimethylbenzamide (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 t-
AmOH(tert-pentyl alcohol) at 100 °C for 4 h under N2. Under
such conditions similar to those previously employed for the
reactions of 1-phenylpyrazoles,10a the starting materials were
recovered almost completely (Entry 1 in Table 1). Addition of
AgSbF6 (0.05 mmol) promoted the reaction dramatically to
quantitatively afford the corresponding alkenylated product,
N,N-dimethyl-2-[(E)-(n-butoxycarbonyl)ethenyl]benzamide (3a)
(Entry 2).14 The reactions of 1a with ethyl (2b) and cyclohexyl
Chem. Lett. 2012, 41, 151-153
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

152
References and Notes
[Ru(p-cymene)Cl2]2 (0.013 mmol)
AgSbF6 (0.05 mmol)
1
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+
S
N
S
N
CO2Bu
CO2Bu
Cu(OAc)2•H2O (0.5 mmol)
t-AmOH, N2, 100 °C, 4 h
2a (0.5 mmol)
4 (0.25 mmol)
5, 61%
Scheme 1.
Table 2. Reaction of phenylazoles 6 with alkenes 2a
[Ru(p-cymene)Cl2]2
N
N
N
Me
N
Me
AgSbF6
+
R
R
Cu(OAc)2•H2O
t-AmOH
2
6
7
Entry
6
2
Product, Yield/%
N
N
N
N
Me
Me
R
R
6a
1
2a: R = CO2(n-Bu)
2a: R = CO2(n-Bu)
2b: R = CO2Et
2c: R = CO2Cy
2d: R = Ph
7a: R = CO2(n-Bu), 57
7a: R = CO2(n-Bu), 8c
7b: R = CO2Et, 70
7c: R = CO2Cy, 61
7d: R = Ph, 71d
2b
3
4
5
N
N
N
Me
N
Me
2
CO2(n-Bu)
6
6b
2a
7e, 82
aReaction conditions: 6 (0.25 mmol), 2 (0.5 mmol), [Ru(p-
cymene)Cl2]2 (0.013 mmol), AgSbF6 (0.05 mmol), Cu(OAc)2¢
H2O (0.5 mmol), in t-AmOH (3 mL) at 100 °C for 4 h under N2.
c
d
bWithout AgSbF6. GC yield. E/Z = 9:l.
With the result in hand, we reexamined the alkenylation of
phenylazoles using [Ru(p-cymene)Cl2]2/AgSbF6. As a result,
1-methyl-2-phenylimidazole (6a) was found to undergo the
alkenylation with 2a to produce 7a selectively (Entry 1 in
Table 2). In the absence of AgSbF6, only a small amount of 7a
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(Entries 3-5).16 The reaction of 1-methyl-2-phenylbenzimida-
zole (6b) with 2a also proceeded efficiently to give 7e in 82%
yield (Entry 6).
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expected to be applicable to other oxidative coupling reactions.19
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This work was partly supported by Grants-in-Aid from
MEXT and JSPS, Japan, Deutsche Forschungsgemeinschaft
(IRTG 1628), and the Fonds der Chemischen Industrie,
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16 In the case using 2d, a minor amount of (Z)-7d was also
formed. However, the reason why the Z-isomer formation
was observed only in this case is obscure.
17 Through the present study, dialkenylation products could not
be detected.
9
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19 A report of ortho-alkenylation of aromatic ketones using a
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Chem. Lett. 2012, 41, 151-153
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/