Ru th en iu m - a n d Rh od iu m -Ca ta lyzed Dir ect Ca r bon yla tion of th e
Or th o C-H Bon d in th e Ben zen e Rin g of N-Ar ylp yr a zoles
Taku Asaumi, Takuya Matsuo, Takahide Fukuyama,† Yutaka Ie,‡ Fumitoshi Kakiuchi, and
Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Suita, Osaka 565-0871, J apan
chatani@chem.eng.osaka-u.ac.jp
Received J anuary 23, 2004
The direct carbonylation of C-H bonds in the benzene ring of N-phenylpyrazoles via catalysis by
ruthenium or rhodium complexes is described. The reaction of N-phenylpyrazoles with carbon
monoxide and ethylene in the presence of Ru3(CO)12 or Rh4(CO)12 resulted in the site-selective
carbonylation of the ortho C-H bonds in the benzene ring to give the corresponding ethyl ketones.
A variety of functional groups on the benzene ring can be tolerated. N-Phenylpyrazoles have higher
reactivities than would be expected, based on the pKa values of the conjugate acid of pyrazole. The
choice of solvent for this reaction is significant, and N, N-dimethylacetamide (DMA) gives the best
result.
In tr od u ction
by irradiation in the presence of RhCl(CO)(PMe)2 as a
catalyst.7 Similar photoirradiated transformations have
been reported by several groups.8 In 1992, Moore reported
on the ruthenium-catalyzed acylation of pyridines, utiliz-
ing carbon monoxide and alkenes, in which a highly
effective and site-selective carbonylation was acheived.9
We also have reported a series on catalytic carbonylation
reactions at C-H bonds utilizing chelation assistance.10,11
The chelation-assisted carbonylation reactions at sp2
C-H bonds thus reported can be classified into four
types, depending on the position where the carbonylation
takes place (Chart 1).9-11
The direct functionalization of C-H bonds represents
one of the most useful synthetic strategies in organic
synthesis, since transforming C-H bonds into C-X bonds
(X ) Br, I, OTf, etc.) prior to the formation of C-C bonds
is not necessary.1 Among the several reported transfor-
mations, the transition-metal-catalyzed carbonylation of
C-H bonds provides an effective and attractive method
for the introduction of a carbonyl moiety into molecules.
Hong and Yamazaki reported that propiophenone is
obtained by the reaction of benzene with CO and ethylene
in the presence of Rh4(CO)12, although it was a minor
product.2 The Pd- and/or Cu-catalyzed carboxylation of
arenes and alkanes in trifluoroacetic acid, leading to the
corresponding carboxylic acids, was reported by Fuji-
wara.3 Eisenberg developed the Ir-,4 Rh-,5 or Ru6-
catalyzed photoirradiated carbonylation of benzene. Tana-
ka achieved a more efficient carbonylation of benzene or
hexane into the benzaldehyde or heptanal, respectively,
In all cases, the presence of an sp2 nitrogen atom as a
directing group is essential for the carbonylation to
proceed. Directing groups, such as a pyridine ring, an
oxazoline ring, and an imino group, were found to
function as a directing group for the carbonylation of the
benzene ring ((iii) in Chart 1). In this paper we wish to
(7) Sakakura, T.; Tanaka, M. Chem. Lett. 1987, 249. Sakakura, T.;
Tanaka, M. J . Chem. Soc., Chem. Commun. 1987, 758. Sakakura, T.;
Tanaka, M. Chem. Lett. 1987, 1113. Sakakura, T.; Sasaki, K.;
Tokunaga, Y.; Wada, K.; Tanaka, M. Chem. Lett. 1988, 155. Sakakura,
T.; Sodeyama, T.; Sasaki, K.; Wada, K.; Tanaka, M. J . Am. Chem. Soc.
1990, 112, 7221.
(8) Bowse, W. T.; Goldman, A. S. J . Am. Chem. Soc. 1992, 114, 350.
Boyd, S. E.; Field, L. D.; Partridge, M. G. J . Am. Chem. Soc. 1994,
116, 9492. Rosini, G. P.; Boese, W. T.; Goldman, A. S. J . Am. Chem.
Soc. 1994, 116, 9498. Bridgewater, J . S.; Lee, B.; Bernhard, S.;
Schoonover, J . R.; Ford, P. C. Organometallics 1997, 16, 5592.
Bitterwolf, T. E.; Kline, D. L.; Linehan, J . C.; Yonker, C. R.; Addleman,
R. S. Angew. Chem., Int. Ed. 2001, 40, 2692. Choi, J .-C.; Kobayashi,
Y.; Sakakura, T. J . Org. Chem. 2001, 66, 5262. Choi, J .-C.; Sakakura,
T. J . Am. Chem. Soc. 2003, 125, 7762.
† Present address: Department of Chemistry, Faculty of Arts and
Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, J apan.
‡ Present address: The Institute of Scientific and Industrial Re-
search, Osaka University, Mihoga-oka, Ibaraki, Osaka 567-0047, J apan
(1) For recent reviews, see: Shilov, A. E.; Shul’pin, G. B. Chem. Rev.
1997, 97, 2879. Kakiuchi, F.; Murai, S. In Activation of Unreactive
Bonds and Organic Synthesis; Murai, S., Ed.; Springer: Berlin,
Germany, 1999; pp 47-79. Guari, Y.; Sabo-Etienne, S.; Chaudret, B.
Eur. J . Inorg. Chem. 1999, 1047. Dyker, G. Angew. Chem., Int. Ed.
1999, 38, 1698. Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002,
102, 1731. Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345,
1077.
(2) Hong, P.; Yamazaki, H. Chem. Lett. 1979, 1335. Hong, P.;
Yamazaki, H. J . Mol. Catal. 1984, 26, 297.
(3) For reviews, see: Fujiwara, Y.; Takaki, K.; Taniguchi, Y. Synlett
1996, 591. J ia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001,
34, 633.
(4) Fisher, B. J .; Eisenberg, R. Organometallics 1983, 2, 764. Kunin,
A. J .; Eisenberg, R. J . Am. Chem. Soc. 1986, 108, 535.
(5) Kunin, A. J .; Eisenberg, R. Organometallics 1988, 7, 2124.
(6) Gordon, E. M.; Eisenberg, R. J . Mol. Catal. 1988, 45, 57.
(9) Moore, E. J .; Pretzer, W. R.; O’Connell, T. J .; Harris, J .;
LaBounty, L.; Chou, L.; Grimmer, S. S. J . Am. Chem. Soc. 1992, 114,
5888.
(10) For our papers on direct carbonylation at C-H bonds in the
benzene ring catalyzed by Ru3(CO)12, see: (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.
10.1021/jo049864j CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/26/2004
J . Org. Chem. 2004, 69, 4433-4440
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