Hypervalent iodine in synthesis. 77. An efficient method for the synthesis of N-arylindoles by the copper-catalyzed N-arylation of indole with diaryliodonium salts

Article abstract of DOI:10.1081/SCC-120002702

N-arylindoles were prepared in good yields by copper-catalyzed N-arylation of indole with diaryliodonium salts.

Full text of DOI:10.1081/SCC-120002702

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HYPERVALENT IODINE IN SYNTHESIS. 77. AN EFFICIENT
METHOD FOR THE SYNTHESIS OF N-ARYLINDOLES BY
THE COPPER-CATALYZED N-ARYLATION OF INDOLE WITH
DIARYLIODONIUM SALTS
Tao Zhou a & Zhen-Chu Chen a
a Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou, 310028, P.R. China
Published online: 16 Aug 2006.
To cite this article: Tao Zhou & Zhen-Chu Chen (2002): HYPERVALENT IODINE IN SYNTHESIS. 77. AN EFFICIENT METHOD
FOR THE SYNTHESIS OF N-ARYLINDOLES BY THE COPPER-CATALYZED N-ARYLATION OF INDOLE WITH DIARYLIODONIUM SALTS,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:6, 903-907
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SYNTHETIC COMMUNICATIONS, 32(6), 903–907 (2002)
HYPERVALENT IODINE IN
SYNTHESIS. 77. AN EFFICIENT
METHOD FOR THE SYNTHESIS
OF N-ARYLINDOLES BY
THE COPPER-CATALYZED
N-ARYLATION OF INDOLE
WITH DIARYLIODONIUM SALTS
*
Tao Zhou and Zhen-Chu Chen
Department of Chemistry, Zhejiang University
(Xixi Campus), Hangzhou, 310028, P.R. China
ABSTRACT
N-arylindoles were prepared in good yields by copper-
catalyzed N-arylation of indole with diaryliodonium salts.
In continuation of our interest in exploring the utility of transition
metal-catalyzed arylation reaction,1 we examined N-arylation of indole with
diaryliodonium salts in the presence of copper catalyst (Scheme 1). The
results are summarized in Table 1.
We found that copper-catalyzed N-arylation of indole with diaryl-
iodonium salts could proceed smoothly at 140–150ꢀC and gave N-arylin-
doles in good yields. Compared with the traditional Ullmann reaction2
*Corresponding author.
903
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

904
ZHOU AND CHEN
Scheme 1.
Table 1. Copper-Catalyzed N-Arylation of Indole
Copper
Catalyst
Yielda
(%)
Entry
Ar2IþBFÀ4
Ph2IþBFÀ4 1a
1a
Product
1
2
3
4
5
6
7
8
9
Cu(OAc)2
Cu(acac)2
CuI
3a
3a
3a
3b
3c
3d
3e
3f
52
83
83
87
92
80
81
76
72
1a
ð p-TolÞ2IþBFÀ4 1b
ð p-ClC6H4Þ2IþBF4À 1c
ð p-CH3OC6H4Þ2IþBF4À 1d
ð p-BrC6H4Þ2IþBF4À 1e
ð m-NO2C6H4Þ2IþBF4À 1f
ð p-CH3CONH C6H4Þ2IþBF4À 1g
CuI
CuI
CuI
CuI
CuI
CuI
3g
aYield of isolated pure product.
(190–210ꢀC), the reaction temperature was lower greatly. Furthermore,
stoichiometric copper powder was not needed. Among the tested copper
catalysts including CuI, Cu(OAc)2 and Cu(acac)2, though each of them
can catalyze this reaction, CuI is the most effective and practical. Several
diaryliodonium salts with various substituents such as methyl, chloro, meth-
oxy, bromo, nitro and acetamido groups were tested. It was found that the
reaction is general for these substrates.
In conclusion, we provide an effective synthesis for N-arylindoles by
copper-catalyzed N-arylation of indole with diaryliodonium salts. It has
some advantages over others3–10 such as mild reaction conditions, simplicity
of procedure, using nonpoisonous, accessible reagents and good yields.
EXPERIMENTAL
Melting points were uncorrected. 1H NMR data were recorded
on Avance 400 spectrometer using CDCl3 as the solvent with TMS as an

HYPERVALENT IODINE IN SYNTHESIS. 77
905
internal standard. IR spectra were determined on Vector 22 infrared
spectrometer with KBr pallet. MS spectra were recorded on HP5859B
mass spectrometer. Elemental analyses were performed on EA1110.
General procedure for preparation of N-arylindoles. A mixture of
diaryliodonium salt 1 (1 mmol), indole 2 (1 mmol), K2CO3 (3 mmol), CuI
(10mol%) and DMF (5 ml) was stirred under a nitrogen atmosphere
at 140–150ꢀC for 6–7 h. After cooling, the reaction mixture was diluted
with saturated NH4Cl aqueous (20ml), and extracted with diethyl ether
(3 ꢁ 15 ml). The combined organic layer was washed with brine, dried
over anhydrous sodium sulfate. After removal of the solvent under
vacuum, the residue was chromatographed on silica gel plate using petro-
leum ether for 3a–3e, c-hexane/ethyl acetate (20: 1) for 3f and c-hexa-
ne/ethyl acetate (1 : 1) for 3g as a developer to give pure product.
Physical and Spectroscopic Data
N-Phenylindole 3a. Oil (lit2(c) oil). 1H NMR d H 6.67 (m, 1H), 7.20(m,
2H), 7.33 (m, 2H), 7.49 (m, 4H), 7.55 (m, 1H), 7.68 (m, 1H). IR nmax/cmÀ1
1597, 1515, 1498, 1457, 1332, 1234, 1213, 1136, 774, 742, 696.
1
N-(4-Methylphenyl)indole 3b: Oil (lit2(c) oil). H NMR dH 2.42 (s, 3H),
6.65 (m, 1H), 7.15 (m, 1H), 7.20(m, 1H), 7.29 (m, 3H), 7.37 (m, 2H), 7.52
(m, 1H), 7.68 (m, 1H). IR nmax/cmÀ1 1519, 1458, 1334, 1234, 1213, 1135,
822, 762, 741.
N-(4-Chlorophenyl)indole 3c. M.p. 66–67ꢀC (lit2(c) m.p. 64–66ꢀC).
1H NMR dH 6.69 (m, 1H), 7.20(m, 2H), 7.29 (m, 1H), 7.43–7.52 (m, 5H),
7.68 (m, 1H). IR nmax/cmÀ1 1592, 1516, 1492, 1331, 1233, 1211, 1132, 1088,
1011, 831, 762, 737.
N-(4-Methoxyphenyl)indole 3d. M.p. 56–58ꢀC (lit2(c) m.p. 57–58ꢀC).
1H NMR dH 3.88 (s, 3H), 6.65 (m, 1H), 7.03 (m, 2H), 7.15–7.20 (m, 2H),
7.27 (m, 1H), 7.39 (m, 2H), 7.44 (m, 1H), 7.68 (m, 1H). IR nmax/cmÀ1 1611,
1517, 1457, 1333, 1301, 1248, 1213, 1179, 1134, 1105, 835, 762, 747.
N-(4-Bromophenyl)indole 3e. M.p. 64–65ꢀC (lit9 m.p. was not
1
reported). H NMR dH 6.69 (m, 1H), 7.17 (m, 1H), 7.24 (m, 1H), 7.29 (m,
1H), 7.39 (m, 2H), 7.51 (m, 1H), 7.63 (m, 2H), 7.68 (m, 1H). IR nmax/cmÀ1
1588, 1516, 1491, 1455, 1334, 1310, 1233, 1211, 1133, 1101, 1072, 1009, 828,
762, 738, 722. MS m/z 271 (Mþ, 100), 273 (Mþ þ 2, 98.14). Anal. Calcd for
C14H10BrN: C, 61.79; H, 3.70; N, 5.14. Found: C, 61.56; H, 3.74; N, 5.28.
N-(3-Nitrophenyl)indole 3f. M.p. 65–67ꢀC (lit2(b) m.p. 67–68ꢀC).
1H NMR dH 6.76 (m, 1H), 7.24 (m, 1H), 7.29 (m, 1H), 7.38 (m, 1H), 7.59
(m, 1H), 7.71 (m, 2H), 7.87 (m, 1H), 8.19 (m, 1H), 8.40(m, 1H). IR
n
max/cmÀ1 1607, 1534, 1487, 1455, 1349, 1236, 1211, 1137, 742.

906
ZHOU AND CHEN
N-(4-Acetamidophenyl)indole 3g. M.p. 161–162ꢀC. H NMR dH 2.23
1
(s, 3H), 6.67 (m, 1H), 7.16–7.21 (m, 2H), 7.29 (m, 1H), 7.38 (s, 1H, N-H),
7.45 (m, 2H), 7.51 (m, 1H), 7.64–7.69 (m, 3H). IR nmax/cmÀ1 3243, 3052,
1659, 1612, 1519, 1461, 1415, 1371, 1316, 1266, 1236, 1215, 1139, 1014, 969,
840, 764, 744. MS m/z 250(M þ, 100). Anal. Calcd for C16H14N2O: C, 76.78;
H, 5.64; N, 11.19. Found: C, 76.62; H, 5.68; N, 11.27.
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Received in the Netherlands April 23, 2001