8914
Y. Chen et al. / Tetrahedron 65 (2009) 8908–8915
134.4, 135.2, 137.3, 158.5; HRMS (EI) calcd for C22H18ClNO 347.1077,
found 347.1079.
115.4, 118.8, 122.2, 123.3, 127.7, 128.3, 129.2, 133.4, 135.4, 147.7,
149.0; HRMS (EI) calcd for C20H23NO3 325.1678, found 325.1685.
4.5.10. 5-Bromo-2-(3,5-dimethoxyphenyl)-1-methyl-3-(thiophen-2-
4.5.17. Methyl 2-(3-methoxyphenyl)-1-methyl-3-(thiophen-3-yl)-
yl)indole (3j). This ꢀproduct was obtained as a yellow solid in a 74%
indole-5-carboxylate (3q). This product was obtained as a yellow
yield: mp 181–183 C; 1H NMR (400 MHz, CDCl3)
d
3.63 (s, 3H), 3.77
oil in a 70% yield: 1H NMR (400 MHz, CDCl3)
d 3.67 (s, 3H), 3.75
(s, 6H), 6.53–6.55 (m, 3H), 6.95–6.96 (m,1H), 6.99–7.01 (m, 1H), 7.17
(s, 3H), 3.94 (s, 3H), 6.87 (s, 1H), 6.86 (m, 3H), 7.18–7.27 (m, 1H),
(d, J¼5.0 Hz, 1H), 7.23–7.26 (m, 1H), 7.37–7.39 (m, 1H), 8.03 (s, 1H);
7.30–7.42 (m, 3H), 8.00 (d, J¼8.6 Hz, 1H), 8.57 (s, 1H); 13C NMR
13C NMR (100 MHz, CDCl3)
d
31.1, 55.5, 101.0, 108.0, 109.2, 111.2,
(100 MHz, CDCl3) d 31.3, 52.0, 55.4, 109.4, 111.8, 114.5, 116.5, 121.8,
113.8, 122.3, 123.9, 125.2, 127.0, 128.4, 132.8, 135.6, 136.2, 139.2,
160.8; HRMS (EI) calcd for C21H18BrNO2S 427.0242, found 427.0251.
122.3, 122.8, 123.4, 123.8, 124.9, 126.6, 128.8, 129.8, 132.8, 134.5,
138.9, 139.7, 159.7, 168.2; HRMS (EI) calcd for C22H19NO3S
377.1086, found 377.1095.
4.5.11. 5-Bromo-2-(3,5-dimethoxyphenyl)-1-methyl-3-(thiophen-3-
yl)indole (3k). This product was obtained as a yellow solid in a 76%
4.6. General procedure for the microwave-assisted, one-pot
synthesis of 1H-indoles
yield: mp 172–174 ꢀC; 1H NMR (400 MHz, CDCl3)
d
3.66 (s, 3H), 3.75
(s, 6H), 6.48–6.52 (m, 3H), 6.94 (d, J¼4.0 Hz, 1H), 7.15–7.16 (m, 1H),
7.23–7.26 (m, 2H), 7.36–7.38 (m, 1H), 7.93 (s, 1H); 13C NMR
In an oven-dried 20 mL microwave vial, N-trifluoroacetyl-2-
iodoaniline (0.6 mmol) was dissolved in Et3N (4 mL), then
PdCl2(PPh3)2 (12.6 mg, 0.018 mmol, 3 mol %), CuI (2.3 mg,
0.012 mmol, 2 mol %), and the alkyne (0.63 mmol) were added. The
vial was flushed with Ar, sealed, and stirred at 60 ꢀC under micro-
wave irradiation for 20–30 min. The resulting mixture was dis-
solved in CH3CN (4 mL), ArI (0.66 mmol) and Cs2CO3 (586 mg,
1.8 mmol) were added, and the vial was flushed with Ar, sealed, and
stirred at 100 ꢀC under microwave irradiation for 30 min. To the
reaction mixture were added ethyl acetate (10 mL) and brine
(10 mL) and the aqueous layer was extracted with ethyl acetate
(2ꢁ10 mL). The combined organic layers were dried over anhy-
drous MgSO4 and concentrated under vacuum to afford the crude
product, which was purified by flash chromatography on silica gel
using ethyl acetate/hexanes as eluent.
(100 MHz, CDCl3)
d 31.3, 55.6, 100.8, 109.1, 110.0, 111.2, 113.7, 121.5,
122.4, 124.9, 125.1, 128.6, 128.7, 133.4, 134.7, 136.0, 138.8, 160.8;
HRMS (EI) calcd for C21H18BrNO2S 427.0242, found 427.0251.
4.5.12. 5-Bromo-1-methyl-3-(thiophen-2-yl)-2-(thiophen-3-yl)in-
dole (3l). This product ꢀwas obtained as a light yellow solid in an
85% yield: mp 151–153 C; 1H NMR (400 MHz, CDCl3)
d 3.65 (s, 3H),
6.96–6.97 (m, 1H), 7.01–7.03 (m, 1H), 7.10 (d, J¼5.0 Hz, 1H), 7.20 (d,
J¼5.0 Hz, 1H), 7.23–7.26 (m, 1H), 7.36–7.38 (m, 2H), 7.42–7.44 (m,
1H), 8.01 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 31.2, 108.7, 111.2,
113.9, 122.4, 124.1, 125.2, 125.3, 126.2, 127.16, 127.20, 128.4, 129.5,
131.0, 134.5, 135.8, 136.3; HRMS (EI) calcd for C17H12BrNS2
372.9595, found 372.9604.
4.5.13. 5-Bromo-1-methyl-2-phenyl-3-(thiophen-2-yl)indole
(3m). This product was obtained as a yellow solid in a 79% yield:
4.6.1. Ethyl 3-(2-phenylindol-3-yl)benzoate (3r). This product was
mp 190–192 ꢀC; 1H NMR (400 MHz, CDCl3)
d
3.61 (s, 3H), 6.90 (d,
obtained as a yellow solid in a 93% yield: mp 145–147 ꢀC; 1H NMR
J¼2.8 Hz, 1H), 6.98 (t, J¼4.4 Hz, 1H), 7.15 (d, J¼4.6 Hz, 1H), 7.25–7.27
(400 MHz, CDCl3)
d
1.34 (t, J¼7.1 Hz, 3H), 4.34 (q, J¼7.1 Hz, 2H), 7.16
(m, 1H), 7.38–7.40 (m, 3H), 7.45–7.46 (m, 3H), 8.03 (s, 1H); 13C NMR
(t, J¼7.5 Hz, 1H), 7.22–7.29 (m, 4H), 7.37–7.43 (m, 4H), 7.54 (d,
J¼7.7 Hz, 1H), 7.66 (d, J¼7.9 Hz, 1H), 7.97 (d, J¼7.8 Hz, 1H), 8.21 (s,
(100 MHz, CDCl3)
d 31.2, 108.3, 111.2, 114.0, 122.5, 123.9, 125.28,
125.32, 127.1, 128.6, 128.7, 129.0, 131.23, 131.26, 135.9, 136.4, 139.5;
HRMS (EI) calcd for C19H14BrNS 367.0030, found 367.0040.
1H), 8.41 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 14.5, 61.1, 111.2, 114.1,
119.6, 120.8, 123.0, 127.6, 128.0, 128.4, 128.7, 128.8, 128.9, 131.0,
131.3, 132.5, 134.8, 134.9, 135.7, 136.1, 167.0; HRMS (EI) calcd for
C23H19NO2 341.1416, found 341.1426.
4.5.14. Ethyl 3-(1,5-dimethyl-2-phenylindol-3-yl)benzoate (3n). This
product was obtained as a yellow oil in a 68% yield: 1H NMR
(400 MHz, CDCl3)
d
1.33 (t, J¼7.1 Hz, 3H), 2.48 (s, 3H), 3.63 (s, 3H),
4.6.2. 2-(3-Methoxyphenyl)-3-(4-methoxyphenyl)indole (3s). This
4.31 (q, J¼7.1 Hz, 2H), 7.13 (dd, J¼8.3, 1.1 Hz, 1H), 7.29 (d, J¼8.3 Hz,
4H), 7.36 (m, 3H), 7.40 (dt, J¼7.7, 1.3 Hz, 1H), 7.56 (s, 1H), 7.84 (dt,
J¼7.8, 1.3 Hz, 1H), 8.07 (t, J¼1.3 Hz, 1H); 13C NMR (100 MHz, CDCl3)
product was obtained as a yellow oil in an 82% yield: 1H NMR
(400 MHz, CDCl3)
d
3.62 (s, 3H), 3.79 (s, 3H), 6.79 (ddd, J¼8.3, 2.6,
0.9 Hz, 1H), 6.89–6.99 (m, 4H), 7.09–7.22 (m, 3H), 7.32–7.37 (m, 3H),
d
14.5, 21.8, 31.1, 60.9, 109.5, 113.8, 119.0, 124.1, 126.7, 127.1, 128.30,
7.62 (d, J¼7.9 Hz, 1H), 8.19 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 55.3,
128.33, 128.6, 129.9, 130.6, 131.0, 131.2, 131.9, 134.3, 135.9, 138.4,
166.9; HRMS (EI) calcd for C25H23NO2 369.1729, found 369.1732.
55.4, 111.1, 113.5, 113.6, 114.2, 115.0, 119.8, 120.5, 122.8, 127.5, 129.1,
129.9, 131.4, 133.7, 134.2, 135.9, 158.3, 159.7; HRMS (EI) calcd for
C22H19NO2 329.1416, found 329.1425.
4.5.15. 3-(4-Chlorophenyl)-2-(4-methoxyphenyl)-1,5-dimethylindole
(3o). This product was obtained as a colorless solid in a 94% yield:
4.6.3. 2-(4-Methoxyphenyl)-5-methyl-3-(3-nitrophenyl)indole
mp 165–167 ꢀC; 1H NMR (400 MHz, CDCl3)
d
2.46 (s, 3H), 3.61 (s,
(3t). This product was obtained as an orange oil in an 88% yield: 1H
3H), 3.82 (s, 3H), 6.90 (d, J¼8.3 Hz, 2H), 7.11 (d, J¼8.2 Hz, 1H), 7.19–
NMR (400 MHz, CDCl3)
d
2.43 (s, 3H), 3.77 (s, 3H), 6.83 (d, J¼8.7 Hz,
7.22 (m, 6H), 7.27 (d, J¼8.3 Hz, 1H), 7.51 (s, 1H); 13C NMR (100 MHz,
2H), 7.06 (d, J¼7.8 Hz, 1H), 7.20–7.28 (m, 3H), 7.40–7.46 (m, 2H),
7.65 (d, J¼7.7 Hz, 1H), 8.06 (d, J¼8.2 Hz, 1H), 8.23 (s, 1H), 8.30 (s,
CDCl3)
d 21.8, 31.1, 55.5, 109.5, 113.3, 114.2, 118.9, 123.9, 124.0, 127.1,
128.5, 129.8, 131.0, 131.1, 132.4, 134.3, 135.9, 138.1, 159.7; HRMS (EI)
calcd for C23H20ClNO 361.1233, found 361.1241.
1H); 13C NMR (100 MHz, CDCl3)
d 21.8, 55.4, 110.9, 111.3, 114.6, 118.3,
120.9, 124.5, 124.6, 124.7 128.4, 129.4, 129.7, 130.4, 134.2, 135.6,
136.4, 137.7, 148.7, 159.7; HRMS (EI) calcd for C22H18N2O3 358.1317,
found 358.1325.
4.5.16. 2-([3-(3,4-Dimethoxyphenyl)]-1,5-dimethylindol-2-yl)etha-
nol (3p). This product was obtained as a light brown oil in a 33%
yield: 1H NMR (400 MHz, CDCl3)
d
1.66 (br s, 1H), 2.42 (s, 3H), 3.11
4.6.4. 4-(5-Methyl-3-phenylindol-2-yl)benzonitrile (3u). This ꢀprod-
(t, J¼6.8 Hz, 2H), 3.74 (s, 3H), 3.81 (t, J¼6.8 Hz, 2H), 3.88 (s, 3H), 3.92
(s, 3H), 6.96 (d, J¼8.2 Hz, 1H), 7.01 (dd, J¼8.1, 1.8 Hz, 1H), 7.05 (d,
J¼8.2 Hz, 2H), 7.22 (d, J¼8.3 Hz, 1H), 7.36 (s, 1H); 13C NMR
uct was obtained as a yellow solid in a 66% yield: mp 219–221 C; 1H
NMR (400 MHz, acetone-d6)
7.29–7.39 (m, 7H), 7.59 (s, 4H), 10.53 (s, 1H); 13C NMR (100 MHz,
acetone-d6) 21.6, 110.7, 111.8, 116.7, 117.9, 119.0, 119.5, 125.5, 127.1,
d
2.37 (s, 3H), 7.02 (d, J¼8.2 Hz, 1H),
(100 MHz, CDCl3)
d
21.6, 28.5, 30.2, 56.1, 62.4, 108.9, 111.6, 113.6,
d