1018
Published on the web September 5, 2011
Ruthenium-catalyzed Acylation of Arylpyridines
with Acyl Chlorides via ortho-Selective C-H Bond Cleavage
Takuya Kochi, Aoi Tazawa, Kazuki Honda, and Fumitoshi Kakiuchi*
Department of Chemistry, Faculty of Science and Technology, Keio University,
3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522
(Received June 29, 2011; CL-110547; E-mail: kakiuchi@chem.keio.ac.jp)
Ruthenium-catalyzed ortho-selective acylation of arylpyr-
Table 1. Ruthenium-catalyzed regioselective acylation of 1a
with 2aa
idines with acyl chlorides via C-H bond cleavage is described.
Aromatic acyl chlorides as well as ¡,¢-unsaturated acyl
chlorides were coupled with arylpyridines to give aromatic
ketones in the presence of [RuCl2(PPh3)3] as a catalyst and
potassium carbonate as a base.
Cl
10 mol % [RuCl2(PPh3)3]
+
N
K2CO3
toluene, 24 h, 120 °C
O
1a
2a
N
N
Direct functionalization of arenes via regioselective C-H
bond cleavage by transition-metal catalysts has been one of the
most extensively studied areas in organometallic catalysis in the
past decade.1 Although selective introduction of carbonyl
functionalities onto aromatic rings would be valuable in organic
synthesis, the scope of such reactions via transition-metal-
catalyzed C-H bond cleavage is still limited. For example, C-H
acylation has been achieved using several strategies. Rhodium-
catalyzed coupling of diphenylketene with benzene was reported
in 1978.2 Three-component coupling of aromatic and hetero-
aromatic compounds with carbon monoxide and olefins have
been studied extensively,3,4 but these methods can only allow for
the introduction of aliphatic acyl groups. In contrast, introduc-
tion of aroyl groups via C-H bond cleavage by transition metals
had not been known until Cheng and co-workers developed
palladium-catalyzed oxidative acylation of arenes with benzal-
dehyde derivatives in 2009.5a Since then, several reports have
been made on catalytic C-H aroylation using aldehydes and
alcohols in the presence of oxidizing agents.5b-5f In early 2009,
our group reported that ruthenium-catalyzed introduction of
amide and ester groups via aromatic C-H bond cleavage
proceeds using chlorocarbonyl compounds such as carbamoyl
chlorides and alkyl chloroformates.6 We envisioned that catalytic
C-H acylation may be achieved when acyl chlorides are used as
coupling partners. The reaction of aromatic compounds with
acyl chlorides in the presence of Lewis acids, Friedel-Crafts
acylation, is widely known as a general method for acylation of
arenes. However, if chelation-assisted C-H bond cleavage can
be employed for the acylation, unlike Friedel-Crafts methods,
the reaction should be ortho-selective and relatively electron-
deficient arenes may also be used as substrates.
+
O
3a
4a
GC yield/%
3a
K2CO3
/equiv
Toluene
/mL
Entry
4a
1
2
3
4
5
2.5
2.5
2.5
1.2
5.0
6
3
2
3
3
58
76
68
71
7
4
3
3
3
97 (95)b
aReaction conditions: 1a (1 mmol), 2a (2.5 mmol), K2CO3,
[RuCl2(PPh3)3] (0.1 mmol), toluene, 120 °C, 24 h. bIsolated
yield (%).
in 7% yield by decarbonylation. Reduction of the amount of
toluene solvent to 3 mL improved the yield of 3a to 76%
(Entry 2), but further decrease to 2 mL resulted in 68% yield
(Entry 3). The amount of potassium carbonate was then
investigated. When the amount of the base was lowered to 1.2
equiv, slight decrease of the product yield was observed
(Entry 4). In contrast, the use of 5.0 equiv of potassium
carbonate led to 97% GC yield of acylation product 3a
(Entry 5).7 Using these conditions, product 3a was isolated by
silica gel column chromatography in 95% yield in a pure form,
which does not contain arylation product 4a. It is worthy to
note that Rh(I)-catalyzed coupling of 1a with 2a was reported by
Yu,8 but phenylation product 4a was obtained exclusively via
decarbonylation. In contrast, decarbonylation is surpressed in
our system to give acylation product 3a as a major product.
The acylation of 1a with various benzoyl chloride deriva-
tives was then examined (Table 2). The reactions with benzoyl
chlorides bearing electron-donating Me and OMe groups at para
position (2b and 2c) provided the corresponding acylation
products 3b and 3c in 81% and 88% yields, respectively (Entries
1 and 2). The structure of 3b was confirmed by X-ray
crystallography, and the result clearly showed that the 10-
position of 1a was selectively acylated. The reaction with
benzoyl chloride with a p-CF3 group (2d) afforded 63% yield of
3d (Entry 3), but the use of 20 mol % of triphenylphosphine as
Herein we report ruthenium-catalyzed acylation of arylpyr-
idines with acyl chlorides via aromatic C-H bond cleavage.
Direct introduction of aroyl and alkenoyl groups without
oxidizing agents was achieved using the corresponding aroyl
and alkenoyl chlorides.
The acylation was first examined with benzo[h]quinoline
(1a) and benzoyl chloride (2a) as substrates. When the reaction
of 1a with 2a using [RuCl2(PPh3)3] was conducted following
our previously reported aminocarboxylation procedure, the
desired acylation product 3a was obtained in 58% GC yield
(Table 1, Entry 1). Phenylation product 4a was also formed
Chem. Lett. 2011, 40, 1018-1020
© 2011 The Chemical Society of Japan