Assembly of Conjugated Enynes and Substituted Indoles
argon. After the reaction completed monitored by TLC, the cooled
mixture was partitioned between ethyl acetate and water. The
organic layer was separated, and the aqueous layer was extracted
with ethyl acetate twice. The combined organic layers were washed
7.06 (d, J ) 8.4 Hz, 1H), 6.79 (s, 1H), 3.55 (s, 2H), 2.28 (s, 6H);
13
C NMR (CDCl
3
, 75 MHz) δ 138.3, 137.1, 132.5, 129.7, 128.9
(2C), 128.6, 127.6, 125.2 (2C), 121.9, 120.2, 111.7, 99.6, 44.9, 36.4
+
(2C); MS m/z 250 (M ); MALDI-HRMS calcd for C17
H N
19 2
(M
+
with brine, dried over Na
2
SO
4
, and concentrated in vacuo. The
+ H) 251.1535, found 251.1543.
N-Benzyl-N-methyl(2-phenylindol-6-ylmethyl)amine (8k): H
1
residual oil was loaded on a silica gel column and eluted with 1/10
1
to 1/8 ethyl acetate/petroleum ether to afford 8a. H NMR (CDCl
3
,
NMR (CDCl
3
, 300 MHz) δ 8.28 (s, 1H), 7.60 (d, J ) 8.7 Hz, 2H),
3
7
00 MHz) δ 8.30 (s, 1H), 7.58-7.54 (m, 3H), 7.37-7.21 (m, 4H),
7.55 (d, J ) 8.4 Hz, 1H), 7.41-7.23 (m, 9H), 7.12 (d, J ) 8.7 Hz,
1H), 6.77 (s, 1H), 3.61 (s, 2H), 3.53 (s, 2H), 2.19 (s, 3H);
+
13
.18-7.04 (m, 2H), 6.74 (s, 1H); MS m/z 193 (M ).
C
General Procedure for the Coupling Reaction of 2-Bromot-
NMR (CDCl , 75 MHz) δ 139.3, 137.9, 137.1, 133.5, 132.4, 129.0
3
rifluoroacetanilides with 1-Alkynes Catalyzed by CuI and
L-Proline. A mixture of bromide (1.1 mmol), alkyne (1.0 mmol),
(2C), 128.9 (2C), 128.4, 128.2 (2C), 127.5, 126.7, 125.1 (2C), 121.8,
+
120.2, 111.2, 99.8, 62.3, 61.7, 42.1; MS m/z 326 (M ); MALDI-
+
CuI (0.02 mmol), L-proline (0.06 mmol), and K
2
CO
3
(2 mmol) in
HRMS calcd for C23
H
23
N
2
(M + H) 327.1840, found 327.1856.
1
2
mL of DMF was heated in a sealed tube to 80 °C under argon.
2-Phenylindole-5-carboxylic acid methyl ester (8l): H NMR
(CDCl
After the reaction completed monitored by TLC, the cooled mixture
was partitioned between ethyl acetate and water. The organic layer
was separated, and the aqueous layer was extracted with ethyl
acetate twice. The combined organic layers were washed with brine,
3
, 300 MHz) δ 8.59 (s, 1H), 8.40 (s, 1H), 7.92 (d, J ) 9.0
Hz, 1H), 7.68 (d, J ) 8.1 Hz, 2H), 7.49-7.36 (m, 4H), 6.91 (s,
+
1H), 3.95 (s, 3H); MS m/z 251 (M ).
1
5,7-Dichloro-2-phenylindole (8m): H NMR (CDCl , 300 MHz)
3
dried over Na
2
SO
4
, and concentrated in vacuo. The residual oil
δ 8.49 (s, 1H), 8.57 (s, 1H), 7.69 (d, J ) 7.5 Hz, 1H), 7.51-7.48
was loaded on a silica gel column and eluted with 10/1 to 5/1
petroleum ether/ethyl acetate to afford the corresponding indole.
(m, 3H), 7.39 (d, J ) 7.5 Hz, 1H), 7.19 (s, 1H), 6.78 (s, 1H); MS
+
m/z 262 (M ).
1
1
2-(4-Chlorophenyl)indole (8b): H NMR (CDCl
3
, 300 MHz)
4-Methoxy-2-phenylindole (8n): H NMR (CDCl , 300 MHz)
3
δ 8.27 (s, 1H), 7.62 (d, J ) 7.5 Hz, 1H), 7.55 (d, J ) 6.9 Hz, 2H),
δ 8.38 (s, 1H), 7.63 (d, J ) 8.7 Hz, 2H), 7.41 (t, J ) 7.5 Hz, 2H),
7
.41-7.36 (m, 3H), 7.24-7.10 (m, 2H), 6.80 (s, 1H); MS m/z 227
7.29 (t, J ) 7.2 Hz, 1H), 7.12 (d, J ) 7.8 Hz, 1H), 7.02 (d, J ) 8.1
+
13
(
M ).
Hz, 1H), 6.94 (s, 1H), 6.54 (d, J ) 7.5 Hz, 1H), 3.95 (s, 3H);
C
1
4
-(Indol-2-yl)benzoic acid methyl ester (8c): H NMR (CDCl
3
,
3
NMR (CDCl , 75 MHz) δ 153.4, 138.2, 136.4, 132.4, 129.0 (2C),
127.4, 124.9 (2C), 123.1, 104.3, 100.0, 97.2, 97.2, 55.4; ESI-MS
3
8
7
3
00 MHz) δ 8.43 (s, 1H), 8.11 (d, J ) 8.1 Hz, 2H), 7.74 (d, J )
.1 Hz, 2H), 7.65 (d, J ) 8.1 Hz, 1H), 7.42 (d, J ) 8.1 Hz, 1H),
.24 (t, J ) 7.8 Hz, 1H), 7.14 (t, J ) 7.5 Hz, 1H), 6.96 (s, 1H),
+
+
m/z 224 (M + H) ; ESI-HRMS calcd for C15
H
14NO (M + H)
224.1069, found 224.1070.
+
1
.95 (s, 3H); MS m/z 251 (M ).
5-Methoxy-2-phenyl-1H-pyrrolo[3,2-b]pyridine (8o): H NMR
1
2
-(4-Methoxyphenyl)indole (8d): H NMR (CD
3
COCD
3
, 300
(CDCl
3
, 300 MHz) δ 8.75 (s, 1H), 7.65 (d, J ) 7.8 Hz, 2H), 7.57
MHz) δ 10.56 (s, 1H), 7.79 (d, J ) 6.9 Hz, 1H), 7.53 (d, J ) 8.1
(d, J ) 8.7 Hz, 1H), 7.44 (d, J ) 7.2 Hz, 2H), 7.34 (d, J ) 7.5 Hz,
13
Hz, 2H), 7.38 (d, J ) 7.8 Hz, 1H), 7.10-6.98 (m, 4H), 6.77
1H), 6.88 (s, 1H), 6.60 (d, J ) 8.4 Hz, 1H), 4.01 (s, 3H); C NMR
(CDCl , 75 MHz) δ 160.5, 143.9, 140.0, 132.0, 129.1 (2C), 128.1,
125.7, 125.1 (2C), 121.6, 105.9, 99.9, 53.4; MS m/z 224 (M );
+
(
s, 1H), 3.84 (s, 3H); MS m/z 223 (M ).
3
1
+
3
Acetic acid 3-(indol-2-yl)phenyl ester (8e): H NMR (CDCl ,
+
3
7
8
00 MHz) δ 8.40 (s, 1H), 7.62 (d, J ) 7.5 Hz, 1H), 7.46 (d, J )
MALDI-HRMS calcd for C14
225.1022.
2-n-Pentylindole (12a): H NMR (CD
H
13
N
2
O (M + H) 225.1033, found
.5 Hz, 1H), 7.37-7.34 (m, 3H), 7.19-7.11 (m, 2H), 7.01 (d, J )
13
1
.1 Hz, 1H), 6.78 (s, 1H), 2.34 (s, 3H); C NMR (CDCl
3
, 75 MHz)
3
COCD , 300 MHz) δ
3
δ 169.9, 151.6, 137.3, 137.2, 134.4, 130.4, 129.5, 128.8, 123.0,
7.81 (s, 1H), 7.27 (d, J ) 7.8 Hz, 1H), 7.52(d, J ) 7.2 Hz, 1H),
7.13-7.04 (m, 2H), 6.23 (s, 1H), 2.72 (t, J ) 7.5 Hz, 2H), 1.73-
1.68 (m, 2H), 1.39-1.34 (m, 4H), 0.92-0.88 (m, 3H); MS m/z
+
1
21.2, 121.0, 120.7, 118.7, 111.4, 101.0, 21.6; MS m/z 251 (M ).
+
MALDI-HRMS calcd for C16
2
H14NO
2
(M + H) 252.1028, found
+
52.1019.
187 (M ).
1
1
5-Methoxy-2-phenylindole (8f): H NMR (CDCl
3
, 300 MHz)
2-(Benzyloxymethyl)indole (12b): H NMR (CDCl
3
, 300 MHz)
δ 8.24 (s, 1H), 7.64 (d, J ) 7.5 Hz, 2H), 7.43 (t, J ) 8.1 Hz, 2H),
δ 8.44 (s, 1H), 7.58 (d, J ) 8.1 Hz, 1H), 7.35-7.29 (m, 6H), 7.17-
13
7
6
.34-7.29 (m, 2H), 7.09 (s, 1H), 6.85 (dq, J ) 8.7, 1.2 Hz, 1H),
7.09 (m, 2H), 6.43 (s, 1H), 4.69 (s, 2H), 4.52 (s, 2H); C NMR
(CDCl , 75 MHz) δ 137.7, 136.4, 135.0, 128.5 (2C), 128.1, 127.9
+
.76 (s, 1H), 3.87 (s, 3H); MS m/z 223 (M ).
3
1
5
-Ethyl-2-phenylindole (8g): H NMR (CDCl
3
, 300 MHz) δ
(2C), 127.8, 122.0, 120.5, 119.8, 110.9, 101.9, 71.8, 65.1; MS m/z
+
+
8
(
(
7
.26 (s, 1H), 7.65 (d, J ) 7.5 Hz, 2H), 7.46-7.44 (m, 3H), 7.31
237 (M ); MALDI-HRMS calcd for C16
H
16NO (M + H)
d, J ) 7.8 Hz, 2H), 7.05 (d, J ) 7.8 Hz, 1H), 6.77 (s, 1H), 2.75
238.1236, found 238.1226.
q, J ) 7.2 Hz, 2H), 1.29 (t, J ) 7.5 Hz, 3H); 13C NMR (CDCl
2-(Tetrahydropyran-2-yloxymethyl)indole (12c): 1H NMR
3
,
5 MHz) δ137.9, 136.3, 135.3, 132.6, 129.5, 128.9 (2C), 127.5,
3
(CDCl , 300 MHz) δ 8.52 (s, 1H), 7.58 (d, J ) 7.5 Hz, 1H), 7.36
(d, J ) 7.2 Hz, 1H), 7.20-7.06 (m, 2H), 6.44 (s, 1H), 4.89-4.70
(m, 3H), 3.98-3.92 (m, 1H), 3.60-3.56 (m, 1H), 1.88-1.72 (m,
+
1
25.1 (2C), 122.9, 119.0, 110.6, 99.7, 28.9, 16.4; MS m/z 221 (M );
+
MALDI-HRMS calcd for C16
22.1277.
5
H
16N (M + H) 222.1284, found
2H), 1.62-1.52 (m, 4H); 13C NMR (CDCl
, 75 MHz) δ 136.5,
2
3
1
-Nitro-2-phenylindole (8h): H NMR (CD
3
COCD
3
, 300 MHz)
135.2, 128.2, 122.0, 120.6, 119.8, 110.9, 101.8, 98.4, 62.9, 62.8,
+
δ 11.39 (s, 1H), 8.57 (s, 1H), 8.05 (d, J ) 8.4 Hz, 1H), 7.91 (d, J
30.7, 25.4, 19.8; MS m/z 231 (M ); MALDI-HRMS calcd for
+
)
7.5 Hz, 2H), 7.58 (d, J ) 9.0 Hz, 1H), 7.54-7.49 (m, 2H), 7.42
C
14
H
17NNaO
2
(M + Na) 254.1142, found 254.1152.
+
(
d, J ) 7.5 Hz, 1H), 7.18 (s, 1H); MS m/z 238 (M ).
5-Methoxy-2-((tetrahydro-2H-pyran-2-yloxy)methyl)indole
1
1
2
-Phenylindole-6-carboxylic acid methyl ester (8i): H NMR
3
(12d): H NMR (CDCl , 300 MHz) δ 8.45 (s, 1H), 7.22 (d, J )
(
CDCl
3
, 300 MHz) δ 8.68 (s, 1H), 8.19 (s, 1H), 7.82 (d, J ) 8.7
8.7 Hz, 1H), 7.03 (d, J ) 2.4 Hz, 1H), 6.83 (dd, J ) 8.7, 2.4 Hz,
1H), 6.36 (s, 1H), 4.86-4.68 (m, 1H), 3.96-3.92 (m, 1H), 3.83
Hz, 1H), 7.72 (d, J ) 8.1 Hz, 2H), 7.64 (d, J ) 8.7 Hz, 1H), 7.51-
7
.46 (m, 2H), 7.39 (d, J ) 9.0 Hz, 1H), 6.87 (s, 1H), 3.96 (s, 3H);
C NMR (CD
32.0, 129.0 (2C), 128.2, 125.5 (2C), 123.5, 120.6, 119.8, 113.3,
9.4, 51.1; MS m/z 251 (M ); MALDI-HRMS calcd for C16
(s, 3H), 3.59-3.55 (m, 1H), 1.83-1.72 (m, 2H), 1.63-1.50 (m,
13
13
3
COCD
3
, 75 MHz) δ 167.3, 141.6, 136.7, 132.9,
4H); C NMR (CDCl
3
, 75 MHz) δ 154.1, 135.9, 131.6, 128.6,
1
9
112.1, 111.5, 102.3, 101.5, 98.3, 62.8, 62.7, 55.8, 30.6, 25.3, 19.7;
+
+
+
H
14
-
MS m/z 261 (M ); MALDI-HRMS calcd for C15
H20NO
3
(M + H)
+
NO
N,N-Dimethyl(2-phenylindol-6-ylmethyl)amine (8j): H NMR
CDCl , 300 MHz) δ 8.72 (s, 1H), 7.66 (d, J ) 7.8 Hz, 2H), 7.55
d, J ) 7.8 Hz, 1H), 7.44-7.39 (m, 2H), 7.31 (d, J ) 7.5 Hz, 2H),
2
(M + H) 252.1026, found 252.1019.
262.1448, found 262.1438.
1
5-Ethyl-2-((tetrahydro-2H-pyran-2-yloxy)methyl)indole (12e):
H NMR (CDCl , 300 MHz) δ 8.44 (s, 1H), 7.38 (s, 1H), 7.23 (d,
3
1
(
(
3
J ) 8.1 Hz, 1H), 7.02 (d, J ) 8.4 Hz, 1H), 6.37 (s, 1H), 4.85-
J. Org. Chem, Vol. 72, No. 13, 2007 4849