Ru/C-catalyzed carbonylation at ortho-C-H bonds in 2-phenylpyridines

Article abstract of DOI:10.1055/s-2006-958451

Ru/C also exhibits catalytic activity for carbonylation at ortho-C-H bonds in 2-phenylpyridines. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-958451

170
LETTER
Ru/C-Catalyzed Carbonylation at ortho-C–H Bonds in 2-Phenylpyridines
R
u/C-Catalyze
h
d Carbonyla
i
tion at
n
ortho-C–H B
y
onds in 2-P
h
a
enylpyridine
s
Imoto,a Takeshi Uemura,a Fumitoshi Kakiuchi,b Naoto Chatani*a
a
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Fax +81(6)68797396; E-mail: chatani@chem.eng.osaka-u.ac.jp
b
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan
Received 21 September 2006
Abstract: Ru/C also exhibits catalytic activity for carbonylation at
ortho-C–H bonds in 2-phenylpyridines.
cat. Ru/C
N
+
+
CO
H2C CH2
7 atm
Key words: acylations, carbonylations, catalysis, heterocycles, ru-
thenium
160 °C, 20 h
20 atm
1a
O
In the course of our studies on the development of catalyt-
ic reactions, involving the cleavage of C–H bonds,1 we
previously reported on a series of direct carbonylations at
C–H bonds catalyzed by rhodium or ruthenium carbonyl
complexes.2–6 A variety of sp2-nitrogen-containing sub-
strates were found to undergo regioselective carbonyla-
tion with CO and olefins to give ketone derivatives.
Although the regioselectivity at the position where the
carbonylation takes place is dependent on the structure of
substrates used, selectivity is exclusive in all cases report-
ed, thus far, no other regioisomers have been detected.
When chelation could not be utilized, no reaction oc-
curred, indicating that coordination of the sp2 nitrogen to
the catalyst is required for the reaction to proceed.
Heterogeneous catalysts, such as Pd/C7 and Ru/C8 have
recently been used as the catalyst because of its many sa-
lient advantages, (1) an inexpensive source, (2) ease of
separation from the reaction mixture by simple filtration,
(3) it can sometimes be recycled, and (4) it can be used
without ligands. This prompted us to examine Ru/C as a
catalyst for direct carbonylation of C–H bonds. We wish
to report here that Ru/C can be used in the carbonylation
at ortho-C–H bonds in 2-phenylpyridine derivatives.
N
N
+
O
O
3a
2a
toluene
DMA
62%
81%
0%
1%
Scheme 1
no reaction took place, indicating that the recovered black
solids did not possess any catalytic activity. We anticipat-
ed that the active ruthenium species do not remain on the
carbon, but leaches into the solvent under the reaction
conditions employed. In fact, the color of the reaction
mixture was orange, the color similar to that of Ru3(CO)12
in DMA. After exposure of Ru/C under the reaction con-
ditions in the absence of 1a, the black solids were re-
moved. The recovered black solids again showed no
catalytic activity. In contrast, the orange-colored filtrate
showed comparable catalytic activity (2a: 90% yield),
clearly indicating that the active ruthenium species leach-
es from the Ru/C into the solvent under the reaction con-
ditions employed. While the structure of the leached
ruthenium complexes could not be identified, the reaction
mechanism of the Ru/C-catalyzed reaction is essentially
the same as that of the Ru3(CO)12-catalyzed reaction.4a
The reaction of 2-phenylpyridine (1a, 2 mmol) with car-
bon monoxide (20 atm at r.t.) and ethylene (7 atm) in the
presence of 5 wt% Ru/C (101 mg, corresponding to 0.05
mmol of Ru atom) in toluene (6 mL) at 160 °C for 20
hours gave 1-[2-(2-pyridinylphenyl)]-1-propanone (2a) in
62% yield (Scheme 1). We recently reported that DMA
(N,N-dimethylacetamide) is the solvent of choice for the
carbonylation of C–H bonds.4e,f The use of DMA signifi-
cantly improved the yield of 2a to 81% yield, along with
1% of the dicarbonylation product 3a. The use of
Ru3(CO)12 (0.017 mmol) as the catalyst gave comparable
yields of 2a (86% yield) and biscarbonylation product 3a
(8% yield). After the reaction, the black solids were re-
moved by filtration and reused as the catalyst; however,
The effects of a methyl group on the pyridine ring were
next examined, as shown in Scheme 2. Similar to the
Ru3(CO)12-catalyzed reaction of 2-phenylpyridines,4a the
presence of a methyl group at the 6-position retarded the
reaction because of steric hindrance to the coordination of
the nitrogen to ruthenium. The presence of a methyl group
at the 4- and 5-positions had no significant effects on the
reactivity of the substrates.
The results for the reactions of some 2-arylpyridines are
shown in Table 1. The reaction of para-substituted 2-
phenylpyridines selectively gave monocarbonylation
products 4–6. In the case of meta-substituted 2-phenyl-
pyridines, carbonylation occurred exclusively at the less
hindered C–H bonds to give the corresponding ketones
SYNLETT 2007, No. 1, pp 0170–0172
0
4.
0
1.
2
0
0
7
Advanced online publication: 20.12.2006
DOI: 10.1055/s-2006-958451; Art ID: U11106ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Ru/C-Catalyzed Carbonylation at ortho-C–H Bonds in 2-Phenylpyridines
171
R
R
R
Table 2 Ru/C-Catalyzed ortho-Carbonylation of C–H Bonds in a
4
cat. Ru/C
O
Benzene Ringa
5
6
3
CO, H2C CH2
Yieldb,c
DMA
N
N
N
Substrate
Product
O
O
12
54% (23%)
1
O
O
N
N
3
2
R = H (1a)
1%
81%
O
3-Me (1b)
4-Me (1c)
5-Me (1d)
6-Me (1e)
0%
29%
78%
81%
19%
13
14
27%
19%
N
N
N
N
6%
0%
O
N
Scheme 2
30% (2%)
N
N
N
Table 1 Ru/C-Catalyzed Reaction of 2-Arylpyridines with CO and
Ethylenea
O
2-Arylpyridine
Product
Yieldb,c
a Reaction conditions: substrate (2 mmol), ethylene (7 atm), CO (20
atm), Ru/C (101 mg) in DMA (6 mL) for 20 h.
b Yields are isolated yields based on substrate.
c The number in parentheses is the yield of biscarbonylation product.
N
N
R
R
O
7–9, irrespective of the nature of the substituent, as similar
to the case of the Ru3(CO)12-catalyzed reaction.4a
R = OMe
R = Me
4
5
6
77%
79% (4%)
34%
Some other nitrogen-containing compounds also under-
went regioselective carbonylation of C–H bonds to give
the corresponding ketones, as shown in Table 2.
R = CF3
In contrast to g-carbonylation, as shown in Table 1 and
Table 2, Ru/C was not effective for the a- and b-carbony-
lation of C–H bonds, although it is likely that the active
ruthenium species leaches from the Ru/C into the DMA
solution. While no reaction took place, even when a 10-
fold excess of catalyst was loaded in the reaction of N-
methylimidazole in DMA, the use of toluene as the sol-
vent gave the corresponding kentone in 39% yield
(Scheme 3). N-Methylbenzimidazole was unreactive in
both solvent systems.
R
R
N
N
O
R = OMe
R = Me
7
8
82%
70%
22%
70%
R = CF3
9
10
In summary, we demonstrate that Ru/C also exhibit cata-
lytic activity for carbonylation at ortho-C–H bonds.9 Be-
cause of the catalyst leaching from the Ru/C into DMA
solution under the reaction conditions employed, Ru/C
cannot be recycled. However, it is an advantage to use Ru/
C as a catalyst, because Ru/C is cheap and easily handled
compared to Ru3(CO)12.
S
S
N
N
1h
O
11
96%
N
N
Ru/C
12 mol%
N
N
1i
O
tBu
tBu
+
+
CO
solvent 3 mL
160 °C, 20 h
N
N
a Reaction conditions: 2-arylpyridine (2 mmol), ethylene (7 atm), CO
(20 atm), Ru/C (101 mg) in DMA (6 mL) for 20 h.
O
b Yields are isolated yields based on 2-arylpyridine.
1 mmol 20 atm
4 mmol
0%
DMA
c The number in parentheses is the yield of biscarbonylation product.
toluene
39%
Scheme 3
Synlett 2007, No. 1, 170–172 © Thieme Stuttgart · New York

172
S. Imoto et al.
LETTER
(5) Chatani, N.; Yorimitsu, S.; Asaumi, T.; Kakiuchi, F.; Murai,
S. J. Org. Chem. 2002, 67, 7557.
Acknowledgment
This work was supported, in part, by grants from Ministry of Edu-
cation, Culture, Sports, Science and Technology, Japan. N.C. wis-
hes to acknowledge The Sumitomo Foundation and The General Oil
Foundation for financial support.
(6) Chatani, N.; Asaumi, T.; Ikeda, T.; Yorimitsu, S.; Ishii, Y.;
Kakiuchi, F.; Murai, S. J. Am. Chem. Soc. 2000, 122, 12882.
(7) Recent reviews on Pd/C, see: (a) Blaser, H.-U.; Indolese,
A.; Schnyder, A.; Steiner, H.; Studer, M. J. Mol. Catal. A:
Chem. 2001, 173, 3. (b) Biffis, A.; Zecca, M.; Basato, M. J.
Mol. Catal. A: Chem. 2001, 173, 249. (c) Felpin, F.-X.;
Ayad, T.; Mitra, S. Eur. J. Org. Chem. 2006, 2679.
(8) For a paper on Ru/C-catalyzed reaction, see: Murahashi, S.;
Naota, T.; Kuwabara, T.; Saito, T.; Kumobayashi, H.;
Akutagawa, S. J. Am. Chem. Soc. 1990, 112, 782.
References and Notes
(1) For a recent review, see: Kakiuchi, F.; Chatani, N. Adv.
Synth. Catal. 2003, 345, 1077.
(2) (a) Chatani, N.; Fukuyama, T.; Kakiuchi, F.; Murai, S. J.
Am. Chem. Soc. 1996, 118, 493. (b) Chatani, N.; Fukuyama,
T.; Tatamidani, H.; Kakiuchi, F.; Murai, S. J. Org. Chem.
2000, 65, 4039.
(9) General Procedure for the Ru/C-Catalyzed Reactions of
2-Arylpyridines with Ethylene and CO.
In a 50-mL stainless-steel autoclave were placed 5 wt%
Ru/C (101 mg, corresponding to 0.05 mmol of Ru atom), 2-
phenylpyridine (1a, 310 mg, 2 mmol), and DMA (6 mL).
After flushing the system with 10 atm of ethylene three
times, it was pressurized with ethylene to 7 atm and then
with CO to an additional 20 atm. The autoclave was then
immersed in an oil bath at 160 °C. After 20 h had elapsed, it
was removed from the oil bath, allowed to cool and the gases
were then released. The contents were transferred to a round-
bottomed flask with EtOAc. After evaporation, the resulting
residue was subjected to column chromatography on silica
gel with hexane–EtOAc as the eluent to give 1-{2-[2-
(pyridinyl)phenyl]}-1-propanone (2a, 346 mg, 81% yield)
and 1-[2-(3-propionyl-2-pyridinyl)phenyl]-1-propanone
(3a, 6 mg, 1% yield).
(3) Fukuyama, T.; Chatani, N.; Tatsumi, J.; Kakiuchi, F.; Murai,
S. J. Am. Chem. Soc. 1998, 120, 11522.
(4) (a) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Org. Chem.
1997, 62, 2604. (b) Fukuyama, T.; Chatani, N.; Kakiuchi,
F.; Murai, S. J. Org. Chem. 1997, 62, 5647. (c) Ie, Y.;
Chatani, N.; Ogo, T.; Marshall, D. R.; Fukuyama, T.;
Kakiuchi, F.; Murai, S. J. Org. Chem. 2000, 65, 1475.
(d) Asaumi, T.; Chatani, N.; Matsuo, T.; Kakiuchi, F.;
Murai, S. J. Org. Chem. 2003, 68, 7538. (e) Asaumi, T.;
Matsuo, T.; Fukuyama, T.; Ie, Y.; Kakiuchi, F.; Chatani, N.
J. Org. Chem. 2004, 69, 4433. (f) Chatani, N.; Uemura, T.;
Asaumi, T.; Ie, Y.; Kakiuchi, F.; Murai, S. Can. J. Chem.
2005, 83, 755.
Synlett 2007, No. 1, 170–172 © Thieme Stuttgart · New York

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