SPECIAL TOPIC
Copper(I)-Catalyzed Coupling of Terminal Acetylenes
1711
The N-acetyl-2-ethynylaniline was prepared from 2-iodoacetanilide
by Sonogashira coupling and was obtained as a light brown solid in
45% yield.
5-Chloro-7-fluoro-2-phenyl-1H-indole
The general procedure was used to convert 4-chloro-2-fluoro-6-
iodo-phenylamine and phenylacetylene to the title product. Purifi-
cation by flash chromatography gave the analytically pure product
as a white solid (92% yield); mp 153–155 °C.
2-Phenyl-1H-indole
The general procedure was used to convert phenylacetylene and 2-
iodoaniline to the title product. Purification by flash chromatogra-
phy gave the analytically pure product as a white solid (92% yield);
mp 183–184 °C.
1H NMR (300 MHz, DMSO-d6): d = 11.54 (s, 1 H), 7.86–7.84 (d,
J = 7.15 Hz, 2 H), 7.53–7.50 (d, J = 7.72 Hz, 1 H), 7.45–7.40 (t, J =
7.72 Hz, 3 H), 7.30–7.25 (t, J = 7.34 Hz, 1 H), 7.01–6.96 (t, J = 6.97
Hz, 1 H), 6.87 (s, 1 H).
1H NMR (300 MHz, DMSO-d6): d = 12.13 (s, 1 H), 7.98–7.95 (d,
J = 7.72 Hz, 2 H), 7.51–7.46 (t, J = 7.53 Hz, 2 H), 7.44 (s, 1 H),
7.40–7.35 (t, J = 7.72 Hz, 1 H), 7.11–7.07 (d, J = 10.92 Hz, 1 H),
6.96 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 150.98, 147.70, 141.53,
133.51, 132.04, 129.73, 129.04, 126.54, 124.59, 124.10, 116.44,
108.27, 100.39.
Anal. Calcd for C14H9ClFN: C, 68.44; H, 3.69; Cl, 14.43; F, 7.73;
N, 5.70. Found: C, 68.26; H, 3.76; Cl, 14.70; F, 7.5; N, 5.72.
13C NMR (75 MHz, DMSO-d6): d = 138.48, 138.01, 133.09,
132.43, 132.30, 129.76, 129.25, 128.24, 125.84, 122.44, 120.93,
120.24, 112.18, 99.55.
5-Bromo-2-phenyl-1H-indole
Anal. Calcd for C14H11N: C, 87.01; H, 5.74; N, 7.25. Found: C,
86.87; H, 5.72; N, 6.99.
The general procedure was used to convert 4-bromo-2-iodobenz-
enamine and phenylacetylene to the title product. Purification by
flash chromatography gave the analytically pure product as a white
solid (60% yield); mp 181–183 °C.
2-p-Tolyl-1H-indole
The general procedure was used to convert 1-ethynyl-4-methyl-
benzene and 2-iodoaniline to the title product. Purification by flash
chromatography gave the analytically pure product as a white solid
(74% yield); mp 213–215 °C.
1H NMR (300 MHz, DMSO-d6): d = 11.47 (s, 1 H), 7.74 (d, J = 7.72
Hz, 2 H), 7.50 (d, J = 7.72 Hz, 2 H), 7.38 (d, J = 7.91 Hz, 1 H), 7.25
(d, J = 7.72 Hz, 2 H), 7.11–7.06 (t, J = 7.91 Hz, 1 H), 7.01–6.96 (t,
J = 7.35 Hz, 1 H), 6.83 (s, 1 H), 2.34 (s, 3 H).
1H NMR (300 MHz, DMSO-d6): d = 11.77 (s, 1 H), 7.88–7.85 (d,
J = 7.4 Hz, 2 H), 7.72 (s, 1 H), 7.50–7.45 (t, J = 7.5 Hz, 2 H), 7.39–
7.35 (m, 2 H), 7.23–7.20 (dd, J = 8.5, 1.8 Hz, 1 H), 6.89 (s, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 139.06, 135.69, 131.54,
130.41, 128.88, 127.78, 125.09, 123.89, 122.04, 113.15, 111.78,
98.16.
Anal. Calcd for C14H10BrN: C, 61.79; H, 3.70; Br, 29.36; N, 5.15.
Found: C, 61.60; H, 3.74; N, 5.02.
13C NMR (75 MHz, DMSO-d6): d = 138.63, 137.85, 137.60,
130.31, 129.55, 125.77, 122.17, 120.72, 120.14, 112.04, 98.89,
21.65.
4-(1-Acetyl-1H-indol-2-yl)benzonitrile
The general procedure was used to convert 4-iodobenzonitrile and
N-(2-ethynylphenyl)acetamide to the title product. Purification by
flash chromatography gave the analytically pure product as a white
solid (36% yield); mp 158–160 °C.
Anal. Calcd for C15H13N: C, 86.92; H, 6.32; N, 6.67. Found: C,
86.69; H, 6.24; N, 6.76.
2-(4-Vinylphenyl)-1H-indole
1H NMR (300 MHz, DMSO-d6): d = 8.16–8.13 (d, J = 8.4 Hz, 1 H),
7.95–7.92 (d, J = 8.6 Hz, 2 H), 7.76–7.73 (d, J = 8.4 Hz, 2 H), 7.67–
7.65 (d, J = 7.7 Hz, 1 H), 7.42–7.36 (dt, J = 7.3, 1.5 Hz, 1 H), 7.33–
7.28 (dt, J = 7.7, 1.1 Hz, 1 H), 6.94 (s, 1 H), 2.28 (s, 3 H).
13C NMR (75 MHz, DMSO-d6): d = 171.42, 139.15, 139.09,
137.98, 133.23, 130.31, 129.57, 126.25, 124.40, 121.99, 119.54,
116.08, 113.63, 111.49, 28.56.
The general procedure was used to convert 1-ethynyl-4-vinylben-
zene and 2-iodoaniline to the title product. Purification by flash
chromatography gave the analytically pure product as a white solid
(72% yield); mp 135.5–137.5 °C.
1H NMR (300 MHz, CDCl3): d = 8.31 (br s, 1 H), 7.64–7.61 (d, J =
8.29 Hz, 3 H), 7.49–7.46 (d, J = 8.29 Hz, 2 H), 7.40–7.38 (d, J =
8.10 Hz, 1 H), 7.22–7.16 (dt, J = 6.97 Hz, 1 H), 7.14–7.09 (dt, J =
7.91 Hz, 1 H), 6.84 (s, 1 H), 6.78–6.69 (dd, J = 10.73 Hz, 1 H),
5.82–5.76 (dd, J = 17.70 Hz, 1 H), 5.30–5.26 (dd, J = 10.73 Hz, 1
H).
Anal. Calcd for C17H12N2O: C, 78.44; H, 4.65; N, 10.76. Found: C,
78.19; H, 4.63; N, 10.68.
1-[2-(4-Methoxyphenyl)-1H-indol-1-yl]ethanone
The general procedure was used to convert 1-iodo-4-methoxyben-
zene and N-(2-ethynylphenyl)acetamide to the title product. Purifi-
cation by flash chromatography gave the analytically pure product
as a slightly yellow solid (60% yield); mp 68–71 °C.
1H NMR (300 MHz, DMSO-d6): d = 8.23–8.21 (d, J = 8.1 Hz, 1 H),
7.56–7.54 (d, J = 7.5 Hz, 1 H), 7.43–7.40 (d, J = 8.8 Hz, 2 H), 7.31–
7.21 (m, 2 H), 7.02–7.00 (d, J = 8.8 Hz, 2 H), 6.64 (s, 1 H), 3.78 (s,
3 H), 2.03 (s, 3 H).
5,7-Dichloro-2-phenyl-1H-indole
The general procedure was used to convert 2,4-dichloro-6-iodo-
phenylamine and phenylacetylene to the title product. Purification
by flash chromatography gave the analytically pure product as a
white solid (85% yield); mp 143–144 °C.
1H NMR (300 MHz, DMSO-d6): d = 11.82 (s, 1 H), 8.01–7.98 (d,
J = 8.2 Hz, 2 H), 7.57 (s, 1 H), 7.51–7.46 (t, J = 7.15 Hz, 2 H), 7.40–
7.36 (t, J = 7.15 Hz, 1 H), 7.26 (d, J = 1.88 Hz, 1 H), 6.95 (d, J =
2.07 Hz, 1 H).
13C NMR (75 MHz, DMSO-d6): d = 171.96, 160.37, 140.53,
137.75, 131.13, 129.71, 126.58, 125.29, 124.24, 121.18, 116.30,
114.97, 111.10, 56.06, 28.33.
13C NMR (75 MHz, DMSO-d6): d = 141.99, 133.71, 131.98,
131.86, 129.60, 129.10, 126.98, 124.85, 121.56, 119.11, 117.40,
100.90.
Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C,
76.90; H, 5.74; N, 5.08.
Anal. Calcd for C14H9Cl2N: C, 64.15; H, 3.46; Cl, 27.05; N, 5.34.
Found: C, 64.09; H, 3.37; Cl, 27.05; N, 5.28.
1-(2-p-Tolyl-1H-indol-1-yl)ethanone
The general procedure was used to convert 1-iodo-4-methylbenzene
and N-(2-ethynylphenyl)acetamide to the title product. Purification
Synthesis 2005, No. 10, 1706–1712 © Thieme Stuttgart · New York