Copper(I)-2-(2′-pyridyl)benzimidazole catalyzed N-arylation of indoles

Article abstract of DOI:10.1016/j.tet.2009.10.014

CuI-2-(2′-pyridyl)benzimidazole catalyst system can serve efficiently to promote N-arylation of various indoles to afford the N-arylated indoles. The bidentate ligand, 2-(2′-pyridyl)benzimidazole was proved superior to monodentate nitrogen-based ligands and well-known bidentate ligands such as 2,2′-bipyridyl and 1,10-phenanthroline.

Full text of DOI:10.1016/j.tet.2009.10.014

Tetrahedron 65 (2009) 10459–10462
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Copper(I)-2-(20-pyridyl)benzimidazole catalyzed N-arylation of indoles
*
Satoshi Haneda, Yusuke Adachi, Masahiko Hayashi
Department of Chemistry, Graduate School of Science, Kobe University, Kobe 657-8501, Japan
a r t i c l e i n f o
a b s t r a c t
CuI-2-(20-pyridyl)benzimidazole catalyst system can serve efficiently to promote N-arylation of various
indoles to afford the N-arylated indoles. The bidentate ligand, 2-(20-pyridyl)benzimidazole was proved
superior to monodentate nitrogen-based ligands and well-known bidentate ligands such as 2,20-bipyr-
idyl and 1,10-phenanthroline.
Article history:
Received 17 September 2009
Received in revised form 5 October 2009
Accepted 5 October 2009
Available online 8 October 2009
Ó 2009 Published by Elsevier Ltd.
Keywords:
N-arylation
Nitrogen ligand
Bidentate ligand
Benzimidazole
1. Introduction
been used in copper-catalyzed coupling reactions.17,18 We have
interest in the ability of ligand acceleration of 2-(20-pyr-
In 1983, Kosugi and Migita first reported the coupling reaction of
aryl bromides with tin amide in the presence of PdCl2-(P(o-tol)3)2.1
The disadvantage of this reaction is to use stoichiometric amounts
of tributyltin amides. After their pioneering works, Buchwald2 and
Hartwig3 reported the amination of aryl halides using free amine by
the use of palladium and phosphine ligands such as P(o-tol)3 and
BINAP in 1995. After that, Yamamoto and Koike in Tosoh group
idyl)benzimidazole in copper-catalyzed coupling reaction. Herein,
we report copper(I)-2-(20-pyridyl)benzimidazole catalyzed N-ary-
lation of indoles.19
2. Results and discussion
2.1. Screening of ligands
4
introduced t-Bu3P as a phosphine ligand in 1998. In this system,
that is, Pd(OAc)2, t-Bu3P and NaOt-Bu, aryl chloride can be used as
a substrate. The characteristic features of t-Bu3P, that have, steric
hindrance and electron rich substituent gave the guidelines for
development of the design of phosphine ligands. In most cases of
these reactions, strong bases such as NaOt-Bu or LiHMDS are often
used.5 On the other hand, we have interested in coupling reaction
using metal–nitrogen ligand system. For example, we reported
monodentate imidazole or imidazoline derivatives as ligands for
the palladium-catalyzed Mizoroki–Heck reaction and Suzuki–
Miyaura coupling reaction.6,7 We also reported bidentate 2-(20-
pyridyl)benzimidazole–PdCl2 complex efficiently catalyzed
Mizoroki–Heck reaction.8,9,10 On the other hand, copper-catalyzed
coupling reactions have much attention these days. There are some
advantages in the use of copper as coupling catalyst; abundant
reserve, low toxicity and low cost. As the ligands, diamines,11 di-
ols,12 amino acids and amino alcohols,13 oxime phosphines,14 sali-
We first examined the effect of the nitrogen-based ligands in the
reaction of N-arylation of indoles with 4-iodotoluene using CuI–
nitrogen-based ligand system. 4-Bromotoluene and 4-chlor-
otoluene were inert for N-arylation of indoles in our system. We
examined the effect of solvents such as toluene, dioxane, CH3CN,
DMF, DMSO and NMP (N-methylpyrrolidone) and bases such as
t-BuOK, CsCO3, K2CO3, CsF and K3PO4. Among those, the
combination of DMF and K3PO4 gave the best results. As for the
reaction temperature, 110 ꢀC wad proved to be necessary for this
reaction. As shown entries 2 and 3 in Table 1, imidazoline and
imidazole derived monodentate ligands 1 and 2 did not accelerate
the reaction (44% and 15% yield, respectively) compared with none
catalyst system (37%). Therefore, we turned our attention to
bidentate ligands such as 2-(20-pyridyl)imidazoline 3 and 2-(20-
pyridyl)benzimidazole 4. It should be mentioned that well-known
bidentate nitrogen ligands, such as 2,20-bipyridyl 5 and 1,10-phe-
nanthroline 6 did not give the product in high yield (47% and 40%,
respectively). 2-(20-Pyridyl)benzimidazole 4 was easily prepared by
the reaction of 2-pyridyncarbaldehyde with 1,2-phenylenediamine
in the presence of activated carbon under oxygen atmosphere
(Scheme 1).20
cylaldoximes,15
b-diketones and b
-keto esters,16 and so on have
* Corresponding author. Tel.: þ81 78 803 5687; fax: þ81 78 803 5688.
E-mail address: mhayashi@kobe-u.ac.jp (M. Hayashi).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.10.014

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S. Haneda et al. / Tetrahedron 65 (2009) 10459–10462
Table 1
Table 2
Ligand effect in the Cu-catalyzed N-arylation of indole with 4-iodotoluenea
Reaction of substituted indoles with 4-iodotoluenea
R2
5 mol% CuI
I
R1
5 mol% ligand
N
R2
5 mol% CuI
+
R3
5 mol% ligand 4
I
N
N
1.1 eq. K3PO4
1.1 eq. K3PO4
H
R3
R1
Me
+
DMF, 110 °C, 24 h
Me
DMF, 110 °C, 24 h
N
H
Me
Me
Entry
Ligand
Yieldb/%
Entry
R1
R2
R3
Yieldb/%
1
None
37
44
15
81
83
47
40
2c
3c
4
1
2
3
4
5
6
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
83
92
83
82
88
76
83
97
23
38
Me
OMe
Cl
CN
NH2
H
H
H
H
5
6
7
Me
CO2Me
H
H
H
N
H
N
H
N
Me
Ph
10
N
N
N
N
a
All reactions were carried out using 4-iodotoluene (2 mmol) and indole
(3 mmol) in DMF (4 mL) at 110 ꢀC.
2
3
1
b
Isolated yields after silica-gel column chromatography.
H
N
N
N
N
N
N
N
Table 3
Reaction of indole with substituted aryl iodidesa
4
5
6
5 mol% CuI
.
5 mol% ligand 4
a
All reactions were carried out using 4-iodotoluene (2 mmol) and indole
N
I
1.1 eq. K3PO4
(3 mmol) in DMF (4 mL) at 110 ꢀC.
+
b
DMF, 110 °C, 24 h
Isolated yields after silica-gel column chromatography.
10 mol % of ligand was used.
N
H
R1
R3
R1
R3
c
R2
R2
activated carbon
NH2
O2
N
Entry
R1
R2
R3
Yieldb/%
+
1
2
3
4
5
H
H
H
H
H
H
H
Cl
H
Me
OMe
Cl
H
H
83
78
86
89
73
OHC
N
N
H
N
NH2
Scheme 1.
Me
a
All reactions were carried out using 4-iodotoluene (2 mmol) and indole
(3 mmol) in DMF (4 mL) at 110 ꢀC.
2.2. CuI-2-(20-pyridyl)benzimidazole catalyzed N-arylation
of indoles
b
Isolated yields after silica-gel column chromatography.
Then, we examined the reaction of substituted indoles with
4-iodotoluene. The reactions were carried out using 5 mol % of CuI,
5 mol % of ligand 4 in the presence of 1.1 equiv of K3PO4 in DMF at
110 ꢀC for 24 h. The obtained results are summarized in Table 2. All
substituted indoles except for having substituents at R1 gave the
products in high yield. Low yield in the case of entries 9 and 10
(R1¼Me and Ph) may be due to the steric hindrance.
with 5-hydroxyindole, the mixture of N-(4-methylphenoxy)-1H-
indole (8) and N-(4-methylphenyl)-5-(4-methylphenoxy)indole (9)
was obtained (Table 4). N-(40-Methylphenyl)-5-hydroxyindole (7)
was not obtained. These results indicate the formation of C–O bond
takes place faster than C–N bond formation.
Next, we examined the reaction of indole with substituted aryl
iodides (Table 3). All the substituted aryl iodides reacted with in-
dole to afford the coupling products in good to high yield. We did
not observe any limitation as for aryl iodide derivative.
Table 4
Reaction of 5-hydroxyindole with 4-iodotoluenea
5 mol% CuI
5 mol% ligand 4
HO
I
5 mol% metal precursor
1.1 eq. K3PO4
N
+
5 mol% ligand 4
HO
DMF, 110 °C, 24 h
N
H
I
N
Me
1.1 eq. K3PO4
Me
+
7
N
H
DMF, 110 °C, 24 h
Me
Me
Me
Me
NH
N
+
metal precursor = CuI; 83%
PdCl2; no reaction
O
O
Me
8
9
Entry
Ratio
Yieldb/%
It should be mentioned that the combination of PdCl2 and ligand
4 did not give the product.
5-Hydroxyindole
4-Iodotoluene
7
8
9
1
2
3
1
1
2
2
1
1
0
0
0
82
55
69
16
19
10
2.3. C–N vs C–O
The present CuI-2-(20-pyridyl)benzimidazole also catalyzes C–O
bond formation.21–24 Actually, when 4-iodotoluene was treated
a
All reactions were carried out in DMF (4 mL) at 110 ꢀC.
Isolated yields after silica-gel column chromatography.
b

S. Haneda et al. / Tetrahedron 65 (2009) 10459–10462
10461
3. Conclusions
124.8, 124.4, 111.2, 124.1, 103.7, 103.1, 20.9. Anal. Calcd for C16H12N2:
C, 82.73; H, 5.21. Found: C, 82.91; H, 5.26.
We found the CuI-2-(20-pyridyl)benzimidazole catalyst system
works efficiently to promote N-arylation of various indoles to
afford the N-arylated indoles. The bidentated ligand, 2-(20-pyr-
idyl)benzimidazole was proved superior to monodentate nitro-
gen-based ligands and well-known bidentate ligands such as
2,20-bipyridyl and 1,10-phenanthroline.
4.1.6. N-(4-Methylphenyl)-5-aminoindole. Yield: 67%; Rf¼0.58
(hexane:ethyl acetate¼1:1); mp 92–93 ꢀC; IR (KBr): vmax (cmꢁ1);
3752, 3744, 3741, 2336, 1734, 1653, 1218, 1162, 823, 795; 1H NMR
(400 MHz, CDCl3):
6.67 (d, J¼12.0 Hz, 1H), 6.50 (d, J¼3.2 Hz, 1H), 3.50 (br, 2H), 2.41 (s,
3H), 13C NMR (100.6 MHz, CDCl3):
139.9, 137.5, 135.8, 130.8, 130.2,
d 7.4–7.3 (m, 3H), 7.3–7.2 (m, 3H), 6.96 (s, 1H),
d
4. Experimental section
130.0, 128.3, 123.8, 115.8, 112.9, 111.1, 105.7, 102.1, 20.9. Anal. Calcd
for C15H14N2: C, 81.05; H, 6.33. Found: C, 80.96; H, 6.44.
4.1. General procedure for N-arylation of indole
4.1.7. N-(4-Methylphenyl)-3-methylindole26. Yield: 83%; Rf¼0.70
(hexane:ethyl acetate¼10:1); mp 43–44 ꢀC (lit.25 43–44 ꢀC); IR
(KBr): vmax (cmꢁ1) 3042, 2943, 1653, 1608, 1507, 1457, 1517, 1221,
K3PO4 (467.0 mg, 2.2 mmol) was added to a Schlenk tube
equipped with a stirring bar and the tube was dried under vacuum
and then filled with an argon. CuI (19.0 mg, 0.1 mmol) and ligand
(0.1 mmol) and DMF (4.0 mL) were added and the mixture was
stirred at 50 ꢀC for 1 h, aryl iodide (2.0 mmol) and indole
(3.0 mmol) were added, and then the mixture was stirred at 110 ꢀC
for 24 h. After the completion of the reaction, the mixture was
cooled, then the precipitate was removed by filtration and the
product was extracted with diethyl ether. The combined organic
layer was dried over anhydrous Na2SO4 and filtered. After evapo-
ration, the obtained residue was purified by silica-gel column
chromatography to give the N-arylated product.
786, 731; 1H NMR (400 MHz, CDCl3):
d
7.62 (d, J¼7.2 Hz,1H), 7.51 (d,
J¼7.0 Hz, 1H), 7.36 (d, J¼7.2 Hz, 2H), 7.21 (t, J¼7.2 Hz, 1H), 7.16 (t,
J¼7.1 Hz, 1H), 7.11 (s, 1H), 2.42 (s, 3H), 2.38 (s, 3H); 13C NMR
(100.6 MHz, CDCl3):
d 137.4, 136.0, 135.7, 130.0, 129.6, 125.5, 123.9,
122.2, 119.5, 119.1, 112.4, 110.3, 21.0, 9.5.
4.1.8. N-(4-Methylphenyl)methyl indole-3-carboxylate26. Yield: 97%;
Rf¼0.30 (hexane); IR (KBr): vmax (cmꢁ1) 3037, 2947, 1694, 1538,
1455, 1211, 1108, 1050, 823, 776; 1H NMR (400 MHz, CDCl3):
d 8.24
(d, J¼8.4 Hz, 1H), 7.99 (s, 1H), 7.48 (d, J¼8.4 Hz, 1H), 7.5–7.3 (m, 6H),
3.98 (s, 3H), 2.45(s, 3H); 13C NMR (100.6 MHz, CDCl3):
d
165.4, 137.7,
4.1.1. N-(4-Methylphenyl)indole25. Yield: 83%; Rf¼0.78 (hex-
ane:ethyl acetate¼5:1); IR (KBr): vmax (cmꢁ1) 3042, 1529, 1526,
1495, 1480, 1330, 1221, 1153, 822, 694; 1H NMR (400 MHz, CDCl3):
136.7, 135.9, 134.2, 130.3, 126.8, 124.6, 123.2, 122.3, 121.7, 110.9,
108.7, 60.3, 51.0, 21.0, 14.1.
d
7.67 (d, J¼7.7 Hz, 1H), 7.57 (d, J¼8.4 Hz, 1H), 7.37 (d, J¼7.7 Hz, 2H),
7.30–7.2 (m, 3H); 7.2–7.1 (m, 2H), 6.65 (d, J¼2.8 Hz,1H), 2.42 (s, 3H);
13C NMR (100.6 MHz, CDCl3):
137.3,136.3,136.0,130.1,129.1,128.0,
4.1.9. N-(4-Methylphenyl)-2-methylindole28. Yield: 23%; Rf¼0.70
(hexane:ethyl acetate¼10:1); IR (KBr): vmax (cmꢁ1) 3042, 2943,
1653, 1608, 1507, 1457, 1517, 1221, 786, 731; 1H NMR (400 MHz,
d
124.3, 122.1, 121.1, 120.1, 110.4, 103.2, 21.0.
CDCl3):
J¼8.0 Hz, 2H), 7.1–7.0 (m, 3H), 6.38 (s, 1H), 2.46 (s, 3H), 2.29
(s, 3H); 13C NMR (100.6 MHz, CDCl3):
138.2, 137.5, 137.0, 135.2,
130.1, 129.9, 128.1, 127.7, 126.3, 120.9, 119.8, 119.4, 109.9, 100.9,
21.1, 13.3.
d
7.56 (d, J¼8.0 Hz, 1H), 7.32 (d, J¼7.9 Hz, 2H), 7.22 (d,
4.1.2. N-(4-Methylphenyl)-5-methylindole26. Yield: 92%; Rf¼0.24
(hexane); IR (KBr): vmax (cmꢁ1) 3033, 2918, 1529, 1526, 1480, 1333,
d
1221, 1158, 822, 793; 1H NMR (400 MHz, CDCl3):
d
7.5–7.4 (m, 4H),
7.3–7.2 (m, 3H), 7.02 (d, J¼10.0 Hz, 1H), 6.57 (d, J¼2.8 Hz, 1H); 2.46
(s, 3H), 2.42 (s, 3H); 13C NMR (100.6 MHz, CDCl3):
137.4, 135.9,
d
4.1.10. N-(4-Methoxyphenyl)indole27,29. Yield: 78%; Rf¼0.63 (hex-
ane:ethyl acetate¼5:1); mp 57–58 ꢀC (lit.26,28 57–58 ꢀC); IR (KBr):
vmax (cmꢁ1) 3048, 1517, 1457, 1247, 1229, 1214, 1027, 762, 746; 1H
134.3, 130.0, 129.5, 129.4, 127.9, 124.0, 123.8, 120.7, 110.2, 102.7,
21.3, 21.0.
NMR (400 MHz, CDCl3):
d
7.45 (d, J¼7.6 Hz, 1H), 7.40 (d, J¼7.6 Hz,
4.1.3. N-(4-Methylphenyl)-5-methoxyindole27. Yield: 83%; Rf¼0.63
(hexane:ethyl acetate¼5:1); mp 59–60 ꢀC (lit.27 57–58 ꢀC); IR
(KBr): vmax (cmꢁ1) 3106, 2954, 1480, 1447, 1262, 1221, 1160, 1028,
2H), 7.28 (d, J¼7.0 Hz, 2H), 7.20 (t, J¼7.6 Hz, 1H), 7.17 (t, J¼1.6 Hz,
1H), 7.03 (d, J¼7.6 Hz, 2H), 6.65 (d, J¼0.8 Hz, 1H), 3.88 (s, 3H); 13C
NMR (100.6 MHz, CDCl3)
d 158.2, 136.3, 132.8, 128.9, 128.2, 126.9,
799, 765; 1H NMR (400 MHz, CDCl3):
d
7.61 (d, J¼8.0 Hz,1H), 7.4–7.3
122.1, 120.9, 120.0, 114.7, 110.3, 102.8, 55.5.
(m, 2H), 7.3–7.2 (m, 2H), 7.25 (s, 1H), 7.13 (d, J¼2.0 Hz, 1H), 6.86 (dd,
J¼7.1, 4.8 Hz, 1H), 6.58 (d, J¼2.0 Hz, 1H), 3.87 (s, 3H), 2.43 (s, 3H);
4.1.11. N-(4-Chlorophenyl)indole30. Yield: 86%; Rf¼0.26 (hexane); IR
(KBr): vmax (cmꢁ1) 1595, 1497, 1495, 1456, 1332, 1234, 1211, 1089,
13C NMR (100.6 MHz, CDCl3):
d 154.4, 137.4, 136.1, 131.2, 130.1, 129.7,
128.4, 123.9, 112.4, 111.3, 102.8, 102.6, 55.8, 21.0.
831, 761, 742; 1H NMR (400 MHz, CDCl3):
d
7.67 (d, J¼8.4 Hz, 1H),
7.5–7.4 (m, 5H), 7.28 (d, J¼8.4 Hz, 1H), 7.2–7.1 (m, 2H), 6.68 (d,
4.1.4. N-(4-Methylphenyl)-5-chloroindole. Yield:
82%;
Rf¼0.26
J¼0.8 Hz, 1H); 13C NMR (100.6 MHz, CDCl3)
d 138.3, 135.7, 131.9,
(hexane); mp 42–43 ꢀC; IR (KBr): vmax (cmꢁ1) 3107, 1519, 1457,
129.7, 129.3, 127.6, 125.4, 122.6, 121.2, 120.6, 110.2, 104.0.
1329, 1224, 1204, 1063, 799.5, 712.2; 1H NMR (400 MHz, CDCl3):
d
7.63 (s, 1H), 7.41 (d, J¼8.8 Hz, 2H), 7.4–7.3 (m, 4H), 7.14 (d,
4.1.12. N-(3-Chlorophenyl)indole31. Yield: 89%; Rf¼0.26 (hexane); IR
(KBr): vmax (cmꢁ1) 1594, 1517, 1487, 1455, 1333, 1234, 1135, 760, 740,
J¼8.8 Hz, 1H), 6.60 (d, J¼0.8 Hz, 1H), 2.43 (s, 3H); 13C NMR
(100.6 MHz, CDCl3):
d
136.8, 136.7, 134.4, 130.2, 130.1, 129.3, 125.8,
688; 1H NMR (400 MHz, CDCl3):
d
7.68 (d, J¼7.6 Hz, 1H), 7.55 (d,
124.9, 124.2, 122.4, 120.3, 111.9, 111.5, 102.7, 21.0. Anal. Calcd for
C15H12ClN: C, 74.53; H, 5.00. Found: C, 74.87; H, 5.01.
J¼7.6 Hz, 1H), 7.51 (d, J¼7.6 Hz, 1H), 7.42–7.40 (m, 2H), 7.3–7.2 (m,
2H), 7.24 (t, J¼6.8 Hz, 1H), 6.69 (d, J¼0.8 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3):
d 140.9, 135.6, 135.1, 130.6, 129.4, 127.5, 126.4,
4.1.5. N-(4-Methylphenyl)-5-cyanoindole. Yield:
88%;
Rf¼0.50
124.3, 122.7, 122.2, 121.3, 120.7, 110.3, 104.3.
(hexane:ethyl acetate¼5:1); mp 88–89 ꢀC; IR (KBr): vmax (cmꢁ1
)
2955, 2255, 1519, 1480, 1447, 1262, 1160, 1028, 799, 765; 1H NMR
4.1.13. N-(2-Methylphenyl)indole25. Yield: 73%; Rf¼0.24 (hexane);
IR (KBr): vmax (cmꢁ1) 3053, 1603, 1581, 1512, 1510, 1496, 1457, 1306,
(400 MHz, CDCl3):
d
8.02 (s, 1H), 7.51 (d, J¼8.4 Hz, 1H), 7.4–7.3 (m,
5H), 6.73 (d, J¼3.6 Hz, 1H), 2.45 (s, 3H), 2.43 (s, 3H); 13C NMR
764, 740; 1H NMR (400 MHz, CDCl3):
d
7.70 (d, J¼6.4 Hz,1H), 7.4–7.3
(100.6 MHz, CDCl3):
d
137.4, 137.3, 135.9, 130.4, 130.2, 128.6, 126.4,
(m, 4H), 7.2–7.1 (m, 4H), 6.67 (d, J¼2.8 Hz,1H), 2.06 (s, 3H); 13C NMR

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S. Haneda et al. / Tetrahedron 65 (2009) 10459–10462
Kempe, R.; Wurst, K. J. Organomet. Chem. 2001, 634, 39–46; (g) Kawano, T.;
d 138.3, 136.9, 135.8, 131.2, 128.6, 128.3, 128.2,
(100.6 MHz, CDCl3):
128.1, 126.7, 122.0, 120.8, 119.8, 110.5, 102.5, 17.6.
Shinomaru, T.; Ueda, I. Org. Lett. 2002, 4, 2545–2547; (h) Grasa, G. A.; Singh, R.;
Stevens, E. D.; Nolan, S. P. J. Organomet. Chem. 2003, 687, 269–279; (i) Na´jera, C.;
´
¨
Gil-Molto, J.; Karlstrom, S.; Falvello, L. R. Org. Lett. 2003, 5, 1451–1454; (j) Iyer,
S.; Kulkarni, G. M.; Ramesh, C. Tetrahedron 2004, 60, 2163–2172; (k) Gupta, A.
K.; Song, C. H.; Oh, C. H. Tetrahedron Lett. 2004, 45, 4113–4116; (l) Reddy, K. R.;
Krishna, G. G. Tetrahedron Lett. 2005, 46, 661–663; (m) Cui, X.; Zhou, Y.; Wang,
N.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2007, 48, 163–167.
4.1.14. N-(4-Methylphenyl)-2-phenylindole32. Yield: 38%; Rf¼0.30
(hexane); IR (KBr): vmax (cmꢁ1) 3029, 1500, 1459, 1449, 1324, 1257,
1212, 1134, 793, 742, 710, 692; 1H NMR (400 MHz, CDCl3):
d 7.67 (d,
J¼6.0 Hz, 1H), 7.3–7.1 (m, 12H), 6.78 (s, 1H), 2.38 (s, 3H); 13C NMR
10. Nitrogen monodentate–palladium catalyzed Mizoroki–Heck reactions: (a)
Gossage, R. A.; Jenkins, H. A.; Yadav, P. N. Tetrahedron Lett. 2004, 45, 7689–7691;
(b) Eisnor, C. R.; Gossage, R. A.; Yadav, P. N. Tetrahedron 2006, 62, 3395–3401
and references cited therein.
(100.6 MHz, CDCl3):
d 140.7, 139.1, 137.0, 135.8, 132.6, 129.8, 128.8,
128.2, 128.1, 127.7, 127.2, 122.2, 120.5, 120.4, 110.6, 103.4, 21.1.
11. (a) Klapars, A.; Antila, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123,
7727–7729; (b) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002,
124, 7421–7428; (c) Antila, J. C.; Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc.
2002, 124, 11684–11688; (d) Antila, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S.
L. J. Org. Chem. 2004, 69, 5578–5587.
12. (a) Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4, 581–584; (b) Job,
G. E.; Buchwald, S. L. Org. Lett. 2002, 4, 3703–3706.
13. (a) Ma, D.; Zhang, Y.; Yao, J.; Wu, S.; Tao, F. J. Am. Chem. Soc. 1998, 120, 12459–
12467; (b) Ma, D.; Xia, C. Org. Lett. 2001, 3, 2583–2586; (c) Ma, D.; Cai, Q.;
Zhang, H. Org. Lett. 2003, 5, 2453–2455; (d) Zhang, H.; Cai, Q.; Ma, D. J. Org.
Chem. 2005, 70, 5164–5173.
14. (a) Zhu, D.; Xu, L.; Wu, F.; Mao, J.; Wan, B. Tetrahedron Lett. 2006, 47, 5781–
5784; (b) Xu, L.; Mao, J.; Zhu, D.; Wu, F.; Wang, R.; Wan, B. Tetrahedron 2006, 61,
6553–6560.
15. (a) Cristeau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M. Chem.dEur. J. 2004, 10,
5607–5622; (b) Cristeau, H.-J.; Cellier, P. P.; Spindler, J.-F.; Taillefer, M. Eur. J. Org.
Chem. 2004, 695–700; (c) Jiang, Q.; Jiang, D.; Jiang, H.; Fu, H.; Zhao, Y. Synlett
2007, 1836–1842.
16. (a) Shafir, A.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 8742–8743; (b) de
Lange, B.; Lambers-Verstappen, M. H.; de Schmieder-van Vondovoroort, L.;
Sereinig, N.; Rijk, R.; de Vries, A. H. M.; de Vries, J. G. Synlett 2006, 3105–3109;
(c) Shafir, A.; Lichtor, P. A.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3490–
3491; (d) Xia, N.; Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 337–339.
17. Other ligands, see: (a) Lu, Z.; Twieg, R. J. Tetrahedron Lett. 2005, 46, 2997–3001;
(b) Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2005, 70, 8107–8109; (c) Zhu,
X.; Ma, Y.; Su, L.; Song, H.; Chen, G.; Liang, D.; Wan, Y. Synthesis 2006, 3955–
3962; (d) Altman, R. A.; Koval, E. D.; Buchwald, S. L. J. Org. Chem. 2007, 72, 6190–
6199; (e) Rout, L.; Jammi, S.; Punniyamurthy, T. Org. Lett. 2007, 9, 3397–3399; (f)
Xu, H.; Wolf, C. Chem. Commun. 2009, 1715–1717.
18. For reviews, see: (a) Hassan, J.; Sevignon, M.; Cozzi, C.; Schulz, E.; Lamaire, M.
Chem. Rev. 2002, 102, 1359–1470; (b) Ley, S. V.; Thomas, A. W. Angew. Chem.,
Int. Ed. 2003, 42, 5400–5449; (c) Kunz, K.; Scholz, U.; Ganzer, D. Synlett
2003, 2428–2439; (d) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev.
2004, 248, 2337–2364; (e) Monnier, F.; Tailefer, M. Angew. Chem., Int. Ed.
2008, 47, 3096–3099; (f) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev.
2008, 108, 3054–3131.
4.1.15. 5-(4-Methylphenoxy)-1H-indole (entry 1 in Table 4). Yield:
82%; Rf¼0.68 (hexane:ethyl acetate¼1:1); IR (KBr): vmax (cmꢁ1
)
3019, 1516, 1474, 1454, 1324, 1217, 1212, 1153, 1115, 1070, 788, 753;
1H NMR (400 MHz, CDCl3):
(s, 1H), 6.77 (d, J¼8.0 Hz, 1H), 6.63 (s, 1H), 4.54 (s, 1H), 2.42 (s, 3H);
13C NMR (100.6 MHz, CDCl3):
149.8,137.3,136.2,131.4,130.1,130.0,
d 7.6–7.4 (m, 3H), 7.3–7.2 (m, 3H), 7.07
d
128.8, 124.0, 111.8, 111.3, 105.3, 102.4, 21.0. Anal. Calcd for C15H13NO:
C, 80.69; H, 5.87. Found: C, 80.30; H, 5.92.
4.1.16. N-(4-Methylphenyl)-5-(4-methylphenoxy)indole27 (entry 2 in
Table 4). Yield: 19%; Rf¼0.85 (hexane:ethyl acetate¼1:1); IR (KBr):
vmax (cmꢁ1) 3058, 3032, 1609, 1518, 1470, 1250, 1219, 1167, 756,
736; 1H NMR (400 MHz, CDCl3):
d
7.46 (d, J¼9.2 Hz, 2H), 7.36 (d,
J¼6.0 Hz, 3H), 7.3–7.2 (m, 4H), 7.08 (d, J¼8.8 Hz, 2H), 6.9–6.8 (m,
3H), 7.08 (d, J¼8.8 Hz, 2H), 6.57 (s, 1H), 2.41 (s, 3H), 2.30 (s, 3H);
13C NMR (100.6 MHz, CDCl3):
d 156.7, 150.1, 137.2, 136.4, 132.7,
131.5, 130.1, 130.0, 129.7, 129.0, 124.1, 117.7, 115.5, 1113.3, 110.7,
103.0, 21.0, 20.6.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Re-
search on Priority Areas ‘Advanced Molecular Transformations of
Carbon Resources’ and No. B17340020 from the Ministry of Edu-
cation, Culture, Sports, Science and Technology, Japan. S.H. is
grateful to Grant-in-Aid for JSPS Fellows.
Supplementary data
19. Forcopper-catalyzed N-arylation of indoles: (a) 11(c); (b) 13(d); (c) Kantam, M. L.;
Yadav, J.; Laha, S.; Sreedhar, B.; Jha, S. Adv. Synth. Catal. 2007, 349, 1938–1942; (d)
Periasamy, M.; Vairaprakash, P.; Dalai, M. Organometallics 2008, 27, 1963–1966;
(e) Tang, B.-X.; Guo, S.-M.; Zhang, M.-B.; Li, J.-H. Synthesis 2008, 1707–1716.
20. (a) Kawashita, Y.; Nakamichi, N.; Kawabata, H.; Hayashi, M. Org. Lett. 2003, 5,
3713–3716; (b) Hayashi, M. Chem. Rec. 2008, 8, 252–267.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2009.10.014.
References and notes
21. Naidu, A. B.; Raghunath, O, R.; Prasad, D. J. C.; Sekar, G. Tetrahedron Lett. 2008,
49, 1057–1061.
22. Chang, J. W. W.; Chee, S.; Mak, S.; Buranaprasertsuk, P.; Chevasiri, W.; Chan, P.
W. H. Tetrahedron Lett. 2008, 49, 2018–2022.
23. Jammi, S.; Sakthivel, S.; Rout, L.; Mukherjee, T.; Mandal, S.; Mitra, R.; Saha, P.;
Punniyamurthy, T. J. Org. Chem. 2009, 74, 1971–1976.
1. Kosugi, M.; Kameyama, M.; Migita, T. Chem. Lett. 1983, 12, 927–928.
2. Guram, A. S.; Rennel, R. A.; Buchwald, S. L. Angew. Chem., Int. Ed. Engl. 1995, 34,
1348–1350.
3. Louie, J.; Hartwig, J. F. Tetrahedron Lett. 1995, 36, 3609–3612.
24. The yields of the reactions of 4-iodotoluene with phenol to give 4-phenoxy-
toluene are as follows (in DMF, 110 ꢀC, 24 h), 60% yield (5 mol % CuI, 5 mol %
ligand 4, 1.1 equiv K3PO4); 39% (5 mol % CuI, without ligand 1.1 equiv K3PO4); 0%
(without CuI, without ligand 1.1 equiv K3PO4).
25. Mino, T.; Harada, Y.; Shindo, H.; Sakamoto, M.; Fujita, T. Synlett 2008, 614–620.
26. Nishio, T. J. Org. Chem. 1988, 53, 1323–1326.
27. Qi, T.; Qiu, W.; Liu, Y.; Zhang, H.; Gao, X.; Liu, Y.; Lu, K.; Du, C.; Yu, G.; Zhu, D.
J. Org. Chem. 2008, 73, 4638–4643.
28. Old, D. W.; Harris, M. C.; Buchwald, S. L. Org. Lett. 2000, 10, 1403–1406.
29. Smith, C. J.; Tsang, M. W. S.; Holmes, A. B.; Danheiser, R. L.; Tester, J. W. Org.
Biomol. Chem. 2005, 3, 3767–3781.
4. Nishiyama, M.; Yamamoto, T.; Koike, Y. Tetrahedron Lett. 1998, 39, 617–620.
5. Review on the Pd-catalyzed amination Hartwig, J. F. Synlett 2006, 1283–1294.
6. Haneda, S.; Ueba, C.; Eda, K.; Hayashi, M. Adv. Synth. Catal. 2007, 349, 833–835.
7. Kawamura, K.; Haneda, S.; Gan, Z.; Eda, K.; Hayashi, M. Organometallics 2008,
27, 3748–3752.
8. Haneda, S.; Gan, Z.; Eda, K.; Hayashi, M. Organometallics 2007, 26, 6551–6555.
9. Other examples of nitrogen ligand–palladium catalyzed coupling reactions: (a)
Cabri, W.; Candiani, I.; Bedeschi, A.; Santi, R. J. Org. Chem. 1993, 58, 7421–7426;
(b) Asselt, R.; Elsevier, C. J. Tetrahedron 1994, 50, 323–334; (c) Done, M. C.;
Ru¨ther, T.; Cavell, K. J.; Kilner, M.; Peacock, E. J.; Braussaud, N.; Skelton, B. W.;
White, A. H. J. Organomet. Chem. 2000, 607, 78–92; (d) Ru¨ther, T.; Done, M. C.;
Cavell, K. J.; Peacock, E. J.; Skelton, B. W.; White, A. H. Organometallics 2001, 20,
5522–5531; (e) Silberg, J.; Schareina, T.; Kempe, R.; Wurst, K.; Buchmeiser, M. R.
J. Organomet. Chem. 2001, 622, 6–18; (f) Buchmeiser, M. R.; Schareina, T.;
30. Mao, J.; Guo, J.; Song, H.; Ji, S. Tetrahedron 2008, 64, 1383–1387.
31. Zbiral, E.; Drescher, M. Synthesis 1998, 735–738.
32. Kasper, L. T.; Ackermann, L. Tetrahedron 2005, 11311–11316.