Gold(I)-catalyzed direct C-H arylation of pyrazine and pyridine with aryl bromides

Article abstract of DOI:10.1016/j.tetlet.2009.01.059

An efficient procedure for the direct C-H arylation of electron-poor aromatics such as pyrazine and pyridine with aryl bomides is described. In the presence of catalytic amount of Cy₃PAuCl and with the use of t-BuOK as base, pyrazine undergoes the direct C-H arylation with aryl bromides at 100 °C, and the yields of the arylated products depend on the nature of aryl bromides. In the cases of electron-rich aryl bromides used, the arylated pyrazines can be obtained in good to high yields. For electron-poor aryl bromides, the addition of AgBF₄ is the crucial point to accelerate the coupling reaction to give the arylated products in moderate yields. Pyridine also reacts with electron-rich aryl bromides catalyzed by Cy₃PAuCl to give a mixture of arylated regioisomers in moderate yield. However, in order to realize the direct C-H arylation of pyridine with electron-poor aryl bromides, the addition of silver salt as additive and a milder reaction temperature (60 °C) are required.

Full text of DOI:10.1016/j.tetlet.2009.01.059

Tetrahedron Letters 50 (2009) 1478–1481
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Gold(I)-catalyzed direct C–H arylation of pyrazine and pyridine with
aryl bromides
*
Ming Li, Ruimao Hua
Department of Chemistry, Tsinghua University, Innovative Catalysis Program, Key Laboratory of Organic Optoelectronics and Molecular Engineering of Ministry of
Education, Beijing 100084, China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient procedure for the direct C–H arylation of electron-poor aromatics such as pyrazine and pyr-
idine with aryl bomides is described. In the presence of catalytic amount of Cy3PAuCl and with the use of
t-BuOK as base, pyrazine undergoes the direct C–H arylation with aryl bromides at 100 °C, and the yields
of the arylated products depend on the nature of aryl bromides. In the cases of electron-rich aryl bro-
mides used, the arylated pyrazines can be obtained in good to high yields. For electron-poor aryl bro-
mides, the addition of AgBF4 is the crucial point to accelerate the coupling reaction to give the
arylated products in moderate yields. Pyridine also reacts with electron-rich aryl bromides catalyzed
by Cy3PAuCl to give a mixture of arylated regioisomers in moderate yield. However, in order to realize
the direct C–H arylation of pyridine with electron-poor aryl bromides, the addition of silver salt as addi-
tive and a milder reaction temperature (60 °C) are required.
Received 22 November 2008
Revised 12 January 2009
Accepted 13 January 2009
Available online 19 January 2009
Keywords:
Arylation
Aryl bromide
Gold(I)
Pyrazine
Pyridine
Ó 2009 Elsevier Ltd. All rights reserved.
Transition-metal-catalyzed direct arylation of aromatic com-
pounds by C–H activation with aryl halides has recently become
one of the most important and attractive research topic in syn-
thetic chemistry.1 Because such C(sp2)–C(sp2) bond formation pro-
cedure gives hydrogen halides (HX) as the by-product having the
higher atom-efficiency than other often employed procedures such
as Suzuki–Miyaura,2 Stille3 cross-coupling reactions, in which not
only is the reaction partner of organometallic derivatives aryl-M
(M = B(OH)2, SnR3) required to be pre-prepared, but also the reac-
tion gives organometallic salt (MX), which has a higher molecular
weight than HX as the by-product. Therefore, the direct C–H aryla-
tion of aromatics with aryl halides is an economical procedure and
a powerful tool for synthesis of biaryl molecules,4 particularly for
the synthesis of aryl-heteroaryl compounds by employing different
heteroaromatics. For example, the direct C–H arylation of furans,5
thiophenes,5a,6 pyrrole,5b indolizines,7 thiazoles,6b,8 and oxazoles9
with aryl halides has been developed for the synthesis of their cor-
responding arylated derivatives. However, until recently, the re-
ported procedures are limited to electron-rich aromatics and
heteroaromatics having active C–H bond, the examples for the di-
rect C–H arylation of electron-poor heteroaromatics such as pyra-
zine and pyridine with aryl halides are rare.10
with aryl halides. In the continuation of our study of C–C bond for-
mation of aromatics via activation of C–H bond12 and of the pur-
pose of developing the efficient catalytic system for the direct C–
H arylation of electron-poor heteroaromatics, we now report our
new findings of Cy3PAuCl-catalyzed direct C–H arylation of pyra-
zine and pyridine with aryl bromides promoted by use of t-BuOK
as base (Eq. (1)).
R
R
N
N
E
Au(I)
t-BuOK
+
Br
ð1Þ
E
E = N, C
Initially, the reaction of bromobenzene (1a) with an excess
amount of pyrazine (as solvent) under different reaction conditions
was studied and the results were summarized in Table 1. Entries
1–6 demonstrated that Ph3PAuCl showed no catalytic activity at
all under nitrogen at 100 °C without base or even with the pres-
i
ence of bases such as Bu3N, Pr2NEt, K2CO3, Na3PO4, and Cs2CO3,
which are usually employed as promoter in cross-coupling reac-
tion of aryl halides. In these cases, the starting materials were
recovered completely. However, when t-BuOK was used, Ph3PAuCl
showed an obvious catalytic activity to catalyze the formation of 2-
phenylpyrazine (2a) in 51% GC yield, indicating the occurrence of
direct C–H phenylation of pyrazine with 1a (entry 7). GC–MS and
GC analyses of the reaction mixture revealed that 1a was converted
in almost quantitative yield, and the formation of t-butoxybenzene
(9%, based on 1a), benzene (34%, based on 1a) and diphenyl (3%,
Recently, gold(I) and gold(III) compounds have been proven to
be the versatile catalysts in diverse organic syntheses,11 but there
is no report on the gold-catalyzed direct C–H arylation of aromatics
* Corresponding author. Tel./fax: +86 10 62792596.
E-mail address: ruimao@mail.tsinghua.edu.cn (R. Hua).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.059

M. Li, R. Hua / Tetrahedron Letters 50 (2009) 1478–1481
1479
Table 1
Table 2
Gold(I)-catalyzed reaction of pyrazine with bromobenzene (1a)a
Cy3PAuCl-catalyzed reaction of pyrazine with aryl bromidea
Au(I) (2.0 mol%,
N
R
R
N
N
relative to 1a)
N
Cy3PAuCl (2.0 mol%)
t-BuOK, 100 oC
+
Br
+
Br
base, 100 oC, 12 h
N
N
N
N
1a (0.5 mmol)
5.0 mmol
2a
1 (0.5 mmol)
5.0 mmol
2
Entry
1
Ar-Br
Time (h)
Product
Yieldb (%)
58
Entry
Catalyst
Base (mmol)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
(o-Toly)3PAuCl
Cy3PAuCl
—
—
0
0
0
0
0
0
51
55
N
Bu3N (1)
Br
iPr2NEt (1)
K2CO3 (1)
Na3PO4 (1)
Cs2CO3 (1)
t-BuOK (1)
t-BuOK (1)
t-BuOK (1)
t-BuOK (1)
t-BuOK (0.5)
Bu3 N (1)
Cs2CO3 (1)
12
N
N
Me
Me
2
3
24
24
82
86
3-Me, 1c
3-Me, 2c
90 (81)
4
24
44
35
46
0
Br
Cy3PAuCl
Cy3PAuCl
Cy3PAuCl
N
0
N
a
Reactions were carried out using 0.5 mmol of bromobenzene (1a), 5 mmol of
Br
5
6
7
8
9
12
12
12
12
12
64
60
56
40
<5
pyrazine, 0.01 mmol of catalyst, and 1.0 mmol or 0.5 mmol of base.
b
N
N
GC yield based on the amount of 1a charged. Number in parenthesis is isolated
OMe
OMe
yield.
4-OMe, 1f
4-OMe, 2f
based on 1a), as by-products was also observed. The formation of t-
butoxybenzene is due most likely to the nucleophilic substitution
of 1a with t-BuOK under the reaction conditions, and benzene
comes from the hydrodebromination of 1a with t-BuOK as reduc-
tant.4e The formation of diphenyl is considered to be from the Ull-
mann-type coupling reaction of 1a.
Br
N
2-Br, 1 h
2 h
N
As shown in entry 8, (o-tolyl)3PAuCl, which is ligated by more
basic phosphine displayed a slightly higher catalytic activity than
Ph3PAuCl to afford 2a in 55% GC yield. Fortunately, when Cy3PAuCl
was used, 2a was formed in 90% GC yield, along with the formation
of t-butoxybenzene (4%) and trace amount of benzene (entry 9).
During the preparation of this Letter, Itami and co-workers re-
ported that t-BuOK was the efficient base to promote the direct
C–H arylation of pyrazine with 1a under microwave irradiation
to afford 2a in 54% yield, thus we examined the reaction without
Cy3PAuCl at 100 °C for 12 h. Indeed, a low yield of 2a was obtained
(entry 10). In addition, decreasing the amount of t-BuOK to
1.0 equiv of 1a resulted in the decrease in the yield of 2a to 46%
(entry 11 vs entry 9). Moreover, the use of Bu3N and Cs2CO3 to re-
place t-BuOK as bases led to no formation of 2a at all (entries 12
and 13).
Br
N
Cl
Cl
10c
11c
4-Cl, 1i
2-Cl, 1j
12
12
4-Cl, 2i
2-Cl, 2j
36
25
CF3
CF3
N
N
12c
24
24
31
Br
N
N
N
13c
24
Br
N
a
Reactions were carried out using 0.5 mmol of aryl bromide, 5 mmol of pyrazine,
These obtained results indicate that the present direct arylation
of pyrazine with aryl bromides is highly base dependent, pointing
to the uniqueness of t-BuOK.
0.01 mmol of Cy3PAuCl, and 1.0 mmol of t-BuOK.
b
Isolated yield based on the amount of 1 charged.
AgBF4 (2 mol %) was added.
c
In addition, when the reaction was carried out using an excess
amount of 1a (5 equiv, as solvent) under the reaction conditions
indicated in entry 9, only trace amount of 2a was determined in
the reaction mixture by GC–MS analysis, and the major product
was t-butoxybenzene.
The results of Cy3PAuCl-catalyzed direct C–H arylation of pyra-
zine with a variety of aryl bromides were summarized in Table 2.
The coupling reaction of pyrazine with 2-bromotoluene (1b),
which is a sterically hindered aryl bromide, also occurred under
the reaction conditions indicated in entry 9 of Table 1, albeit
slowly, resulting in the formation of 2b in 58% isolated yield (Table
2, entry 1). A satisfactory yield of 2b could be achieved by prolong-
ing the reaction time to 24 h (Table 2, entry 2).13 The correspond-
ing arylated product 2c was isolated in 82% yield from the reaction
of pyrazine with 3-bromotoluene for 24 h (1c) (Table 2, entry 3). In
the cases of 1-bromo-2,4-dimethylbenzene (1d), 1-bromo-2-
methoxybenzene (1e), and 1-bromo-4-methoxybenzene (1f) used,
the coupling reactions afforded the desired products in moderate
yields after 12 or 24 h (Table 2, entries 4–6). In addition, the mod-
erate yields of 2-(1-naphthyl)pyrazine (2g) and 2-(2-naphthyl)pyr-
azine (2h) could be obtained from the reactions of pyrazine with 1-
bromonaphthalene (1g) and 2-bromonaphthalene (1h) for 12 h
(Table 2, entries 7 and 8).
In contrast to electron-rich aryl bromides, electron-poor aryl
bromides are apparently easier to undergo the hydrodebromina-
tion, since the reaction of pyrazine with 1-bromo-4-chlorobenzene
(1i) gave only small amount of the corresponding arylated product
2i under a similar reaction conditions. In this case, chlorobenzene

1480
M. Li, R. Hua / Tetrahedron Letters 50 (2009) 1478–1481
was the major product formed after 12 h with complete conversion
of 1i (Table 2, entry 9). Because there were some reports on the sig-
nificant difference in the catalytic activity between R3PAuCl and
R3PAuCl/AgBF4,14 the reaction of pyrazine with 1i was repeated
by addition of catalytic amount of AgBF4 to the reaction mixture,
and the arylated product 2i was obtained in 36% isolated yield,
along with the formation of chlorobenzene (Table 2, entry 10).
These results indicated that Cy3PAuCl/AgBF4 could accelerate the
direct C–H arylation of pyrazine with electron-poor aryl bromide.
Indeed, other electron-poor aryl bromides such as 1-bromo-2-
chlorobenzene (1j), 1-bromo-2-trifluromethylbenzene (1k), and
2-bromopyridine (1l) reacted with pyrazine to give the corre-
sponding coupled products in fair yields (Table 2, entries 11–13).
Encouraged by the successful direct C–H arylation of pyrazine
with aryl bromides, we next examined the reaction of pyridine
with aryl bromides, and the results are summarized in Table 3.
As is apparent from these results, the reactivity of pyridine is much
more sluggish than that of pyrazine, and most of the reactions gave
three arylated regioisomers in the order of o-arylpyridine (3) > m-
arylpyridine (30) > p-arylpyridine (300). In the presence of 5.0 mol %
of Cy3PAuCl, the reaction of pyridine (as solvent) with 1a at 100 °C
for 24 h produced a mixture of regioisomers in 57% of total GC
yield with o-(3a), m-(3a0), and p-phenylpyridine (3a00) in a ratio
of 44:35:21 (Table 3, entry 1). The formation of t-butoxybenzene
as the major by-product was also observed (31% GC yield). The
reactions with 1b, 1c, and 4-bromotoluene (1m) afforded arylated
pyridines in the total isolated yield of 26%, 32%, and 48%, respec-
tively (Table 3, entries 2–4). Reactions with electron-poor aryl bro-
mides at 100 °C produced small amount of desired arylated
pyridine only, and the formation of t-butoxyarenes was found in
almost quantitative yield. For example, heating a mixture of pyri-
dine, 1i, and t-BuOK in the presence of Cy3PAuCl at 100 °C afforded
1-chloro-4-t-butoxybenzene as major product (>90%), only small
amount of arylated pyridines (3e) was detectable by GC and GC–
MS (Table 3, entry 5). The addition of AgBF4 (5 mol %) was ineffec-
tive at this reaction temperature, but decreasing the reaction tem-
perature to 60 °C resulted in the formation of desired arylated
pyridines in 38% total isolated yield (Table 3, entries 6 and 7). In
addition, it was found that AgClO4 and AgNO3 displayed the similar
role as AgBF4 did (Table 3, entries 8 and 9). Finally, the reaction of
pyridine with 2-bromo-6-chlorotoluene (1n) to afford selectively
2-chloro-6-(2-pyridinyl)toluene (3f) in 32% isolated yield (Table
3, entry 10).
Since the free radical mechanism was proposed in other reac-
tion systems for the direct C–H arylation of pyrazine and pyri-
dine,10 the present Cy3PAuCl-catalyzed reactions of pyrazine and
pyridine with 1a in the presence of 1,2-dihydroxybenzene
(10 mol %, as radical inhibitor) were examined again. It was found
that 2a was formed in 65% GC yield, while 3a could not be detected
at all by GC and GC–MS. On the basis of these results, the pathway
involving the formation of radical aryl by the electron transfer from
Au(I)15 to aryl halides, and the reaction of radical aryl with pyridine
to give arylated product 3 is highly probable. However, the mech-
anism for the Au(I)-catalyzed direct C–H arylation of pyrazine with
aryl bromides remains to be elucidated.
In conclusion, in this Letter, we have developed the direct C–H
arylation of pyrazine and pyridine with a wide range of aryl bro-
mides catalyzed by Cy3PAuCl in the presence of t-BuOK as base.
For the reactions of pyrazine with electron-rich aryl bromides, Cy3-
PAuCl served as an efficient catalyst to produce the arylated pyra-
zines in good to high yields. For the reaction of pyrazine with
electron-poor aryl bromides, the nucleophilic substitution of aryl
bromides with t-BuOK became the main reaction, but by the addi-
tion of AgBF4, the direct C–H arylation could be improved. In addi-
tion, in the case of pyridine employed, Cy3PAuCl could also
catalyze the reaction with electron-rich aryl bromides such as bro-
mobenzene, bromotoluene at 100 °C to afford a mixture of the ary-
lated regioisomers in moderate yield, but in the case of electron-
poor aryl bromides used, the addition of AgBF4 and a milder reac-
tion temperature (60 °C) are required to realize the coupling
reaction.
Table 3
Cy3PAuCl-catalyzed reaction of pyridine with aryl bromidea
R
R
N
N
Cy3PAuCl (5.0 mol%)
+
Br
(1) A typical experimental procedure for arylation of pyrazine with
bromobenzene (1a) to afford phenylpyrazine (2a) (Table 1, entry 9):
A mixture of pyrazine (400.0 mg, 5.0 mmol), bromobenzene (1a)
(78.5 mg, 0.5 mmol), Cy3PAuCl (6.0 mg, 0.01 mmol), and t-BuOK
(112.0 mg, 1.0 mmol) under nitrogen in a screw-capped thick-
walled Pyrex tube was heated at 100 °C (oil bath temperature)
with stirring; the mixture became homogeneous within a few min-
utes and turned to deep-red. After heating for 12 h, the reaction
mixture was cooled and diluted with CH2Cl2 (4.0 mL), and then
both n-hexadecane (22.6 mg, 0.1 mmol), and n-octadecane
(25.5 mg, 0.1 mmol) were added as internal standards for GC anal-
ysis. After GC and GC–MS analyses, the mixture solution was
passed through a short silica pad. The filtrate was then concen-
trated and pyrazine was recovered (ca. 80%), the residue was then
subjected to preparative TLC isolation (silica gel, eluted with a mix-
ture solvent of ethyl acetate and petroleum ether (1:4) to give 2a as
a white solid (63.2 mg, 0.41 mmol, 81%). GC analysis of the reaction
mixture revealed that 2a was formed in 90% GC yield. Compound
2a: 1H NMR (300 MHz, CDCl3) d 9.05 (s, 1H), 8.64 (s, 1H), 8.52 (s,
1H), 8.01–8.04 (m, 2H), 7.48–7.53 (m, 3H). 13C NMR (75 MHz,
CDCl3) d 153.0, 144.3, 143.1, 142.4, 136.5, 130.1, 129.2, 127.1.
GCMS m/z (% relative intensity): 156 (M+, 36), 129 (11), 103 (81),
91 (11), 80 (25), 77 (18).
t-BuOK (4.0 mmol), 24 h
1 (2.0 mmol)
4.0 mL
3
(49.0 mmol)
Entry
Ar-Br
Temp (°C)
Yieldb(%)
o-(3)
m-(30)
p-(300)
1
2
3
1a
1b
1c
100
100
100
3a
3b
3c
24 (25)
14
15
14 (20)
8
10
11 (12)
4
7
Br
1m
4
100
3d
22
17
9
5
1i
1i
1i
1i
1i
100
100
60
60
60
3e
3e
3e
3e
3e
(<5)
(<5)
20 (24)
(19)
(19)
—
—
—
—
5 (8)
(5)
(4)
6c
7
13 (17)
(14)
(13)
8d
9e
Br
1n
10c
60
3f
32
—
—
Cl
a
Reactions were carried out using 2.0 mmol of aryl bromide, 0.1 mmol of
Cy3PAuCl, and 4.0 mmol of t-BuOK in 4.0 mL of pyridine for 24 h.
b
Isolated yield based on the amount of 1 charged. Numbers in parentheses are
(2) A typical experimental procedure for arylation of pyridine with
bromobenzene (1a) to afford o-, m-, p-phenylpyrazine (3a) (Table 3,
entry 1). A mixture of pyridine (4.0 mL), bromobenzene (1a)
(314.0 mg, 2.0 mmol), Cy3PAuCl (52.0 mg, 0.1 mmol) and t-BuOK
GC yields.
c
AgBF4 (5 mol %) was added.
AgClO4 (5 mol %) was added.
AgNO3 (5 mol %) was added.
d
e

M. Li, R. Hua / Tetrahedron Letters 50 (2009) 1478–1481
1481
4. (a) Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M. Angew. Chem., Int. Ed. 1997,
36, 1740–1742; (b) Dyker, G.; Borowski, S.; Heiermann, J.; Körning, J.; Opwis,
K.; Henkel, G.; Köckerling, M. J. Organomet. Chem. 2000, 606, 108–111; (c)
Bedford, R. B.; Limmert, M. E. J. Org. Chem. 2003, 68, 8669–8682; (d) Oi, S.;
Watanabe, S.-i.; Fukita, S.; Inoue, Y. Tetrahedron Lett. 2003, 44, 8665–8668; (e)
Fujita, K-i.; Nonogawa, M.; Yamaguchi, R. Chem. Commun. 2004, 1926–1927; (f)
Campean, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am. Chem. Soc. 2006, 128,
581–590; (g) Özdemir, I.; Demir, S.; Cetinkaya, B.; Gourlaouen, C.; Maseras, F.;
Bruneau, C.; Dixneuf, P. H. J. Am. Chem. Soc. 2008, 130, 1156–1157; (h) Bedford,
R. B.; Betham, M.; Caffyn, A. J. M.; Charmant, J. P. H.; Lewis-Alleyne, L. C.; Long,
P. D.; Polo-Cerón, D.; Prashar, S. Chem. Commun. 2008, 990–992.
5. (a) Glover, B.; Harvey, K. A.; Liu, B.; Sharp, M. J.; Tymoschenko, M. F. Org. Lett.
2003, 5, 301–304; (b) Yanagisawa, S.; Sudo, T.; Noyori, R.; Itami, K. J. Am. Chem.
Soc. 2006, 128, 11748–11749; (c) Battace, A.; Lemhadri, M.; Zair, T.; Doucet, H.;
Santelli, M. Organometallics 2007, 26, 472–474.
6. (a) Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem. Soc. 2002, 124,
5286–5287; (b) Masui, K.; Mori, A.; Okano, K.; Takamura, K.; Kinoshita, M.;
Ikeda, T. Org. Lett. 2004, 6, 2011–2014; (c) Yokooji, A.; Satoh, T.; Miura, M.;
Nomura, M. Tetrahedron 2004, 60, 6757–6763; (d) Borghese, A.; Geldhof, G.;
Antoine, L. Tetrahedron Lett 2006, 47, 9249–9252.
(448.0 mg, 4.0 mmol) under nitrogen in a screw-capped thick-
walled Pyrex tube was heated at 100 °C (oil bath temperature)
with stirring for 24 h. After work-up as described above, three phe-
nylpyridines 3a (as yellow oil, 74.5 mg, 0.48 mmol, 24%), 3a0 (as
yellow oil, 43.4 mg, 0.28 mmol, 14%), and 3a00 (as white solid,
34.2 mg, 0.22 mmol, 11%) were isolated. GC analysis of the reaction
mixture revealed that a mixture of three phenylpyridines in 57% of
total GC yield with o- (3a), m- (3a0), and p-phenylpyridine (3a00) in a
ratio of 44:35:21 was obtained. Compound 3a: 1H NMR (300 MHz,
CDCl3) d 8.68 (dt, 1H, J = 4.8, 1.3 Hz), 7.94–8.00 (m, 2H), 7.73–7.65
(m, 2H), 7.48–7.36 (m, 3H), 7.21–7.14 (m, 1H). 13C NMR (75 MHz,
CDCl3) d 157.5, 149.7, 139.4, 136.8, 129.0, 128.8, 127.0, 122.1,
120.6. GCMS m/z (% relative intensity): 155 (M+, 100), 127 (16),
102 (12), 77 (10); 3a0: 1H NMR (300 MHz, CDCl3) d 8.86 (s, 1H),
8.60 (m, 1H), 7.90–7.86 (m, 1H), 7.60–7.57 (m, 2H), 7.51–7.35
(m, 4H). 13C NMR (75 MHz, CDCl3) d 148.5, 148.4, 137.9, 136.8,
134.6, 129.2, 128.3, 127.3, 123.7. GC–MS m/z (% relative intensity):
155 (M+, 100), 127 (17), 102 (5), 77 (20). Compound 3a00: 1H NMR
(300 MHz, CDCl3) d 8.66 (d, 2H, J = 6.2 Hz), 7.68–7.61 (m, 2H),
7.52–7.43 (m, 5H). 13C NMR (75 MHz, CDCl3) d 150.3, 148.5,
138.2, 129.3, 129.2, 127.1, 121.8. GCMS m/z (% relative intensity):
155 (M+, 100), 140 (5), 127 (16), 115 (12), 77 (2).
7. Park, C. H.; Ryabova, V.; Seregin, I. V.; Sromek, A. W.; Gevorgyan, V. Org. Lett.
2004, 6, 1159–1162.
8. (a) Yokooji, A.; Okazawa, T.; Satoh, T.; Miura, M.; Nomura, M. Tetrahedron
2003, 59, 5685–5689; (b) Mori, A.; Sekiguchi, A.; Masui, K.; Shimada, T.;
Horie, M.; Osakada, K.; Kawamoto, M.; Ikeda, T. J. Am. Chem. Soc. 2003, 125,
1700–1701; (c) Gottumukkala, A. L.; Doucet, H. Eur. J. Inorg. Chem. 2007,
3626–3632.
9. Flegeau, E. F.; Popkin, M. E.; Greaney, M. Org. Lett. 2008, 10, 2717–2720.
10. During the preparation of this manuscript, Itami et al. reported that t-BuOK
could efficiently promote the direct C–H arylation of pyrazine and pyridine
with aryl iodides under microwave irradiation, and in the case of the reaction
of bromobenzene with pyrazine (only one example of aryl bromide used),
phenylpyrazine was obtained in 54% yield. See: Yanagisawa, S.; Ueda, K.;
Taniguchi, T.; Itami, K. Org. Lett. 2008, 10, 4673–4676; In addition, there is only
one report on the direct C–H phenylation of pyridine with halobenzene in the
presence of Pd/C promoted by Zn/H2O. See: Mukhopadhyay, S.; Rothenberg, G.;
Gitis, D.; Baidossi, M.; Ponde, D. E.; Sasson, Y. J. Chem. Soc., Perkin Trans. 2 2000,
1809–1812.
Acknowledgment
This project (20590360) was supported by National Natural Sci-
ence Foundation of China.
Supplementary data
11. Au-catalyzed: For recent reviews, see: (a) Dyker, G. Angew. Chem., Int. Ed. 2000,
39, 4237–4239; (b) Arcadi, A.; Giuseppe, S. D. Curr. Org. Chem. 2004, 8, 795–
812; (c) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–403; (d) Hashmi, A. S. K.
Chem. Rev. 2007, 107, 3180–3211; (e) Skouta, R.; Li, C-J. Tetrahedron 2008, 64,
4917–4938; (f) Arcadi, A. Chem. Rev. 2008, 108, 3266–3325.
General method, characterization data, and charts of 1H, 13C
NMR for all products are concluded. Supplementary data associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2009.01.059.
12. (a) Sun, H.-B.; Hua, R.; Li, B.; Yin, Y. Eur. J. Org. Chem. 2006, 4231–4236; (b)
Jiang, J.-L.; Ju, J.; Hua, R. Org. Biomol. Chem. 2007, 5, 1854–1857.
13. Except for entry 1 of Table 2, under the chosen reaction conditions, aryl
bromides were converted in almost quantitative yields. The competitive
reactions are the hydrodebromination of aryl bromides and the nucleophilic
substitution of aryl bromides with t-BuOK. The former reaction was the main
side reaction in the cases of electron-rich aryl bromides used, and the latter
was observed as major reaction in the cases of electron-poor aryl bromides
employed.
14. (a) Luzung, M. R.; Markham, J. P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,
10858–10859; (b) Horino, Y.; Luzung, M. R.; Toste, F. D. J. Am. Chem. Soc. 2006,
128, 11364–11365; In addition, silver salts can efficiently accelerate the
conversion of organometallic halides, see: (c) Wang, C.; Xi, Z. Chem. Soc. Rev.
2007, 36, 1395–1406.
References and notes
1. For selected reviews, see: (a) Campeau, L-C.; Fagnou, K. Chem. Commun. 2006,
1253–1264; (b) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107,
174–238; (c) Satoh, T.; Miura, M. Chem. Lett. 2007, 36, 200–205; (d) Seregin, I.
V.; Gevorgyan, V. Chem. Soc. Rev. 2007, 36, 1173–1193.
2. For selected reviews, see: (a) Suzuki, A. Pure Appl. Chem. 1991, 63, 419–422; (b)
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (c) Suzuki, A. J.
Organomet. Chem. 1999, 576, 147–168; (d) Miyaura, N. Top. Curr. Chem. 2002, 219,
11–59; (e) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633–9695.
3. For selected reviews, see: (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25,
508–524; (b) Mitchell, T. N. Synthesis 1992, 803–815.
15. In the present catalytic procedure, t-BuOK is considered to be the efficient
reductant to reduce Au(II) to Au(I) and promote the catalytic cycle. Ref. 4e.