1150
Z. Wang et al. / Journal of Fluorine Chemistry 128 (2007) 1143–1152
(
brine, dried over Mg SO , concentrated by rotary evaporator.
15 mL, 3ꢁ). The combined organic layer was washed with
ꢀ116.7 (m, 1F, Ar–F); IR (neat) 3463 (NH), 2929, 1567, 1323,
ꢀ
9 5 4
1
+
1258, 1174, 835 cm ; HRMS: m/z calcd for C H F N [M ]:
2
4
The residue was then purified by column chromatography (20:1
hexane–EtOAc) on neutral Al O to offer the products 5.
203.0358, Found: 203.0361.
2
3
4
.6.5. 6-Chloro-2-trifluoromethylindole (5e)
5e was obtained as a yellow viscous liquid in 45% yield,
4
.6.1. 2-Trifluoromethylindole (5a)
a was obtained as a light yellow solid in 78% yield from 2a,
1
5
using 1.5 equiv. of magnesium ribbon: mp 145 8C (dec.); H
NMR (500 MHz) d 8.41 (br, 1H, NH), 7.59 (d, J = 8.5 Hz, 1H,
Ar–H), 7.43–7.16 (m, 2H, Ar–H), 6.91 (s, 1H, CH C–CF );
1
and 61% yield from 4a: mp 107–108 8C; H NMR (500 MHz) d
.30 (br, 1H, NH), 7.68 (d, J = 8.0 Hz, 1H, Ar–H), 7.40 (d,
J = 8.0 Hz, 1H, Ar–H), 7.32 (t, J = 7.5 Hz, 1H, Ar–H), 7.20 (t,
8
3
1
3
2
C NMR (125 MHz) d 136.4, 130.7, 126.4 (q, J
1
C–CF ), 125.1, 123.0, 122.1, 120.9 (q, J
= 38.8 Hz,
= 266.3 Hz, CF ),
C–F 3
C–F
1
3
J = 7.5 Hz, 1H, Ar–H), 6.92 (s, 1H, CH C–CF ); C NMR
3
3
2
125 MHz) d 136.1, 126.6, 125.7 (q, J
3
19
(
= 38.8 Hz, C–CF3),
= 266.2 Hz, CF ), 121.1, 111.7,
111.6, 104.3 (q, JC–F = 3.5 Hz, CH C–CF3); F NMR
(470 MHz) d ꢀ60.71 (s, 3F); IR (neat) 3425 (NH), 1554,
C–F
1
24.8, 122.1, 121.2 (q, J
1
1
C–F 3
19
= 3.3 Hz, CH C–CF3); F NMR (470 MHz) d
3
04.3 (q, J
ꢀ1
1417, 1356, 1313, 1125, 922, 826 cm ; HRMS: m/z calcd for
C–F
+
C H ClF N [M ]: 219.0063, Found: 219.0059.
ꢀ
60.50 (s, 3F); IR (neat) 3389 (NH), 2921, 1375, 1306, 1168,
9
5
3
ꢀ
103, 940, 818, 754 cm ; Anal. Calcd for C H F N: C, 58.38;
9 6 3
1
1
H, 3.27; N, 7.57. Found: C, 58.39; H, 3.32; N, 7.55. HRMS: m/z
+
calcd for C H F N [M ]: 185.0452, Found: 185.0452.
4.6.6. 2-Difluoromethylindole (5g)
5g was obtained as a yellow solid in 77% yield from 2g, and
9
6 3
1
58% yield from 4g: mp 56–58 8C; H NMR (500 MHz) d 8.33
4
.6.2. 3-Methyl-2-trifluoromethylindole (5b)
b was obtained as a yellow solid in 82% yield using
(br, 1H, NH), 7.65 (d, J = 8.0 Hz, 1H, Ar–H), 7.36 (d,
J = 8.0 Hz, 1H, Ar–H), 7.28 (t, J = 7.5 Hz, 1H, Ar–H), 7.16 (t,
5
1
1
.5 equiv. of magnesium ribbon: mp 73–74 8C; H NMR
500 MHz) d 8.16 (br, 1H, NH) 7.64 (d, J = 8.0 Hz, 1H, Ar–H),
J = 7.5 Hz, 1H, Ar–H), 6.79 (t, JH–F = 54.5 Hz, 1H, CF H),
2
1
3
(
6.73 (d, JH–F = 2.0 Hz, 1H, CH C–CF H);
2
C NMR
(125 MHz) d 136.2, 130.0 (t, JC–F = 24.2 Hz, C–CF H),
2
7
7
.38 (d, J = 8.5 Hz, 1H, Ar–H), 7.32 (t, J = 7.7 Hz, 1H, Ar–H),
.19 (t, J = 7.5 Hz, 1H, Ar–H), 2.44 (q, J = 1.7 Hz, 3H, CH –
2
1
126.9, 124.1, 121.6, 120.6, 111.6, 110.5 (t, J
= 233.4 Hz,
C–F
3
1
3
3 19
CF H), 103.9 (t, JC–F = 6.9 Hz, CH C–CF H); F NMR
C C–CF ); C NMR (125 MHz) d 135.2, 128.1, 124.8, 122.1
3
2
2
1
q, J
2
= 266.3 Hz, CF ), 121.6 (q, J
(
= 36.7 Hz, C–CF3),
= 2.9 Hz, CH –C C–CF ), 111.6,
(470 MHz) d ꢀ109.83 (d, J
= 54.9 Hz, 2F); IR (neat) 3395
ꢀ1
C–F
3
C–F
F–H
3
20.4, 120.1, 114.1 (q, J
1
8
(NH), 2924, 1621, 1371, 1069, 1015, 810, 750 cm ; HRMS:
C–F
3
3
19
+
m/z calcd for C H F N [M ]: 167.0547, Found: 167.0547.
.3 (CH –C C–CF ); F NMR (470 MHz) d ꢀ58.61 (s, 3F);
3
3
9 7 2
IR (neat) 3393 (NH), 2925, 1454, 1321, 1263, 1166, 1116,
ꢀ
1
+
56 cm ; HRMS: m/z calcd for C H F N [M ]: 199.0609,
7
Found: 199.0610.
4.6.7. 2-Difluoromethyl-5-methoxyindole (5h)
5h was obtained as a yellow solid in 78% yield, using
1
0 8 3
1
1
.5 equiv. of magnesium ribbon: mp 76–78 8C; H NMR
4
.6.3. 5-Methoxy-2-trifluoromethyl indole (5c)
c was obtained as a light yellow solid in 75% yield: mp 50–
1 8C; H NMR (500 MHz) d 8.30 (br, 1H, NH), 7.32 (d,
(500 MHz) d 8.33 (br, 1H, NH), 7.24 (d, J = 9.0 Hz, 1H, Ar–H),
7.08 (d, J = 2.5 Hz, 1H, Ar–H), 6.95 (dd, J = 9.0, 2.5 Hz, 1H,
5
1
5
J = 8.5 Hz, 1H, Ar–H), 7.10 (d, J = 2.5 Hz, 1H, Ar–H), 7.00
Ar–H), 6.77 (t, JH–F = 55.0 Hz, 1H, CF H), 6.66 (d, J = 2.0 Hz,
2
1
3
1H, CH C–CF H), 3.84 (s, 3H, Ar–OCH ); C NMR
2 3
2
(125 MHz) d 154.6, 131.5, 130.6 (t, JC–F = 24.2 Hz, C–
(
dd, J = 9.0, 2.5 Hz, 1H, Ar–H), 6.85 (s, 1H, CH C–CF ), 3.86
3
1
3
s, 3H, Ar–OCH ); C NMR (125 MHz) d 154.8, 131.3, 127.1,
1
CF H), 127.4, 114.8, 112.4, 110.4 (t, J
(
= 233.8 Hz, CF H),
C–F 2
3
2
2
26.2 (q, J
1
= 38.4 Hz, C–CF ), 121.2 (q, J
3
1
CF ), 115.7, 112.6, 103.8 (q, J
= 265.9 Hz,
= 3.3 Hz, CH C–CF3),
103.6 (t, JC–F = 6.8 Hz, CH C–CF H), 102.7, 55.7 (Ar–
2
C–F
3
3
C–F
19
OCH3); F NMR (470 MHz) d ꢀ109.8 (d, J
= 55.0 Hz, 2F);
F–H
3
C–F
1
9
102.8, 55.7 (Ar–OCH3); F NMR (470 MHz) d ꢀ60.45 (s, 3F);
IR (neat) 3402 (NH), 2949, 1559, 1461, 1224, 1174, 1117,
IR (neat) 3459 (NH), 2959, 1561, 1456, 1206, 1173, 1070, 983,
ꢀ
1
+
809 cm ; HRMS: m/z calcd for C H F NO [M ]: 197.0652,
1
0 9 2
ꢀ
1
01 cm ; HRMS: m/z calcd for C H F NO [M ]: 215.0558,
+
8
Found: 215.0557.
Found: 197.0654.
1
0 8 3
4
.6.8. 3-Methyl-2-perfluoropropylindole (5i)
5i was obtained as a light yellow solid in 79% yield, using
4
.6.4. 6-Fluoro-2-trifluoromethylindole (5d)
d was obtained as a yellow viscous liquid in 62% yield: mp
1
5
1.5 equiv. of magnesium ribbon: mp 73–75 8C; H NMR
(500 MHz) d 8.18 (br, 1H, NH), 7.67 (d, J = 8.0 Hz, 1H, Ar–H),
7.41 (d, J = 8.0 Hz, 1H, Ar–H), 7.35 (m, 1H, Ar–H), 7.22 (m, 1H,
1
1
26 8C (dec.); H NMR (500 MHz) d 8.40 (br, 1H, NH), 7.58
dd, J = 8.8, 5.2 Hz, 1H, Ar–H), 7.06 (dd, J = 9.0, 1.8 Hz, 1H,
(
Ar–H), 6.96 (td, J = 9.0, 2.2 Hz, 1H, Ar–H), 6.88 (s, 1H,
1
3
Ar–H), 2.45 (t, J = 2.2 Hz, 3H, CH –C C–C F ); C NMR
3
3 7
1
3
1
C NMR (125 MHz) d 161.2 (d, JC–
2
CH C–CF3);
(125 MHz) d 136.0, 128.3, 124.9, 120.4, 120.1, 119.3 (t, J
C–
3
240.0 Hz), 136.2 (d, JC–F = 12.5 Hz), 126.2 (q, JC–
2
1
= 28.1 Hz. C–C F ), 118.0 (qt, JC–F = 286.2 Hz, JC–F
2
=
=
=
= 3.8 Hz, CH –C C–
F
F
3 7
3
39.2 Hz, C–CF ), 123.2 (d, JC–F = 10.0 Hz), 123.1,
3
33.8 Hz, CF CF CF ), 116.6 (t, J
F
3
2
2
3
C–F
3
1
2
= 265.8 Hz, CF ), 110.4 (d, J
1
2
1
21.0 (q, J
04.4 (q,
= 25.0 Hz),
C F ), 114.1 (tt,
3 7
JC–F = 253.1 Hz,
JC–F = 31.9 Hz,
C–F
3
3
C–F
2
= 3.3 Hz, CH C–CF3), 97.9 (d, JC–
1
J
CF CF CF ), 111.5, 109.2 (m, CF CF CF ), 8.5 (q, J =
2 2 3 2 2 3
C–F
9
1
19
=
26.2 Hz); F NMR (470 MHz) d ꢀ60.66 (s, 3F, CF3),
2.1 Hz, CH –C C–C F ); F NMR (470 MHz) d ꢀ80.26 (t,
F
3
3 7