994
Chemistry Letters Vol.37, No.9 (2008)
Ortho-selective Arylation of Arylazoles with Aryl Bromides
Catalyzed by Ruthenium Complexes
Shuichi Oi,Ã Hiromi Sasamoto, Raito Funayama, and Yoshio InoueÃ
Department of Biomolecular Engineering, Graduate School of Engineering,
Tohoku University, Sendai 980-8579
(Received June 27, 2008; CL-080646; E-mail: oishu@aporg.che.tohoku.ac.jp)
Ortho-selective direct arylation of arylazoles with aryl
bromides has been accomplished in the presence of a catalytic
amount of ruthenium complexes.
Table 1. Ortho-selective arylation of arylazoles 1 with bromo-
benzene (2a)a
Entry
Equiv of 2a
Product
Yield/%
97
1
Ph
N
N
N
N
1
1b
2.5
4ba
Transition-metal-catalyzed coupling reactions of aromatic
compounds are powerful synthetic methods for the construction
of biaryl structures.1 Recently, C–C bond formation between
aromatic rings including C–H bond cleavage have gained signif-
icant attention.2 In these reactions, regioselectivity of the C–C
bond formation is very important because lack of regioselectiv-
ity causes the formation of a mixture of regioisomers which are
difficult to separate. Steric and electronic properties of the sub-
stituent on the aromatic rings are often effective for regioselec-
tivity. On the other hand, functional-group-directed metalation
provides only ortho selectivity. Although several functional
groups, such as pyridyl,3 imino,4 oxazolinyl,5 acylamino,6 car-
bonyl,7 carbamoyl,8 carboxyl,9 and hydroxy10 groups have been
utilized as directing groups of ortho-selective arylation reac-
tions, expansion of the scope of the directing groups is still de-
sired. Herein, we report on ortho arylation of arylazoles with aryl
bromides catalyzed by ruthenium complexes, in which azole
rings are utilized as new directing groups.11
As shown in Scheme 1, 2-phenylthiazole (1a) smoothly
reacted with 1.2 equiv of bromobenzene (2a) in the presence
of [RuCl2(ꢀ6-C6H6)]2 (2.5 mol %), PPh3 (10 mol %), and K2CO3
(200 mol %) in NMP at 120 ꢀC for 20 h, affording 15% yield of
1:1 ortho-coupling product 3aa and 50% yield of 1:2 coupling
product 4aa. The result indicated that the 1:2 coupling product
was formed preferentially, the tendency being similar to that
observed in the direct arylation of 2-aryloxazolines and -imida-
zolines reported before.5a Thus, the reaction using 2.5 equiv of
bromobenzene gave 4aa as a sole product in 97% yield. Then,
scope of the directing group was examined.12 As shown in
Table 1, the reactions of 1-phenylpyrazole (1b) and 2-phenyl-
benzoxazole (1c) with 2.5 equiv of 2a gave the 1:2 coupling
products 4ba and 4ca, respectively, in good yield (Entries 1
Ph
Ph
O
N
O
2
3
1c
2.5
1.2
4ca 55
N
Ph
N
N
1d
1e
N
3da
3ea
84
70
N
Ph
4
1.2
N
N
N
N
N
N
N
N
Ph
S
S
N
5
6
7
8
9
1f
1g
1h
1i
1.2
1.2
1.2
1.2
2.5
3fa
3ga
3ha
3ia
96
66
92
82
10
Ph
O
O
N
Ph
N
N
N
Ph
N
N
N
N
N
Ph
N
N
N
N
N
1j
3ja
N
Ph
N
N
N
N
N
N
N
10b
1k
1.2
3ka
43
N
Ph
aReactions were carried out using 0.5 mmol of 1, 0.6 or 1.25 mmol of
2a, 0.0125 mmol of [RuCl2(ꢀ6-C6H6)]2, 0.05 mmol of PPh3, and 1.0
or 2.0 mmol of K2CO3 in 1 mL of NMP at 120 ꢀC for 20 h under N2.
bReaction at 140 ꢀC for 48 h.
S
[RuCl2(η6-C6H6)]2, PPh3
N
+
Ph–Br
K2CO3, NMP
1a
2a
120 °C, 20 h
S
Ph
S
N
+
N
and 2). In contrast, 1-methyl-2-phenylimidazole (1d) and 1-
phenylindazole (1e) gave the 1:1 coupling products 3da and 3ea,
respectively (Entries 3 and 4). In these cases, the methyl group of
1d or fused benzene ring of 1e would prevent the second
coupling reaction at the alternate ortho position. Various phenyl-
azoles bearing a methyl group at their ortho position (1f–1i)
successfully underwent the ortho phenylation, affording the
Ph
3aa
Ph
4aa
1.2 equiv of 2a 13%
23%
52%
2.5 equiv of 2a
0%
Scheme 1.
Copyright Ó 2008 The Chemical Society of Japan
Oi, Shuichi
