C O M M U N I C A T I O N S
Supporting Information Available: Data and copies of 1H and 13
C
NMR spectra of new compounds and one CIF file. This material is
References
matics such as pyridine still remains as a challenge to work with.
This consideration made us to search for optimal conditions for
the arylation of pyridine N-oxides with simple arenes since this
approach was envisioned to serve as an efficient alternative way
for the direct arylation of pyridines.
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Among various conditions screened using 1a and benzene,9 we
optimized the oxidative arylation of N-oxides as follows: arenes
(40 equiv), Pd(OAc)2 (10 mol %), and Ag2CO3 (2.2 equiv) at 130
°C.15 The reaction scope was next explored, revealing that it
proceeds with moderate to excellent selectivity for the formation
of monoarylated adducts and the extent of which varies on the
substrates employed (Table 3). For instance, reaction of 1a or its
para derivative with benzene afforded the corresponding ortho
phenylated products with a 3:1 ratio (4/5) in high yields (entries 1
and 2). The ratio was increased up to 20:1 when 3-substitued
pyridine N-oxide was employed (entry 3), indicating the importance
of steric effects on the selectivity. Interestingly, phenylation of
isoquinoline N-oxide with benzene provided 1-phenylisoquinoline
2-oxide as the major product (entry 4).
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Interestingly, N-oxides of quinoline and benzo[h]quinoline were
arylated selectively at the ortho-position in good yields (entries
5-6). It is noteworthy that since previous examples of the Pd-
catalyzed direct coupling of benzo[h]quinoline are shown to proceed
selectively at the C(10) position,16 our present system offers a useful
complementary route for the selective aryl introduction at the ortho
position. Therefore, this may serVe as a notable example of
controlling site-selectiVity by the employment of different directing
groups within the same molecular skeletons. N-Oxides of pyrazine
and quinoxaline were also readily cross coupled with benzene at
the ortho position (entries 7 and 8).
It should be noted that homocoupling between employed arenes
during the course of the direct arylation can be significantly reduced
down to 5% based on the equivalent of pyridine N-oxide used, when
the reaction was carried out in the presence of pyridine or its
derivatives, without deteriorating the reaction efficiency and se-
lectivity.9
(8) (a) Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 8, 1119. (b) Boele,
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(9) See the Supporting Information for details.
(10) Pyridine itself was completely inert under the reaction conditions.
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1338.
Preliminary survey on the scope of arenes revealed that the
arylations indeed take place with a range of unactivated arenes.
Cross-coupling of 1a with selected entries of 1,2-disubstituted arenes
provides monoarylated products as major, and the reacting site on
arenes was at the meta position relative to the 1,2-disubstituents of
the arenes (entries 9-11). Likewise, when 1,3-xylene was em-
ployed, the reaction occurred at the meta position relative to the
dimethyl substituents (entry 12).17
In summary, relying on the Pd-mediated C-H bond activation
strategy, we have developed two highly promising oxidative
protocols for the selective alkenylation and direct arylation of
pyridine N-oxides using olefins and unactivated arenes, respectively.
Mechanistic studies toward the detailed understanding of the
activation pathways and synthetic applications based on the present
approaches are under way.
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(13) Recently, an elegant example of the Pd-catalyzed C-H arylation of
N-iminopyridinium ylides with aryl halides was reported: Larive´e, A.;
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(15) Some catalysts such as PdCl2(PPh3)2 or PdCl2(dppe) showed comparable
or slightly higher activity than Pd(OAc)2, which, however, was selected as
a general catalyst for practical reasons (see the Supporting Information).
(16) (a) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am. Chem.
Soc. 2005, 127, 7330. (b) Yu, W.-Y.; Sit, W. N.; Lai, K.-M.; Zhou, Z.;
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Acknowledgment. Dedicated to Professor Kwan Soo Kim on
the occasion of his 60th birthday. This research was supported by
the Korea Research Foundation Grant (KRF-2006-312-C00587).
We also thank Dr. Junseung Lee for the crystal structure analysis.
(17) When substituted arenes were employed, no regioisomeric products other
than those presented in Table 3 were observed by 1H NMR of the crude
reaction mixture.
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