PAPER
Reductive Formylation of Indoles and Quinolines Using Formic Acid
1231
1
3
with EtOAc (2 × 10 mL). The organic layer was dried (Na SO ) and
C NMR (75 MHz, CDCl ): d = 157.5, 130.7, 127.5, 126.2, 124.2,
2
4
3
concentrated under reduced pressure. The crude product was puri-
fied by flash chromatography. NMR data for the major conformers
only are provided below.
116.7, 109.5, 53.1, 35.7, 20.3.
+
MS (C H NO): m/z (%) = 161 (63) [M ], 146 (33), 132 (11), 118
(
1
0
11
100), 91 (25).
Indoline-1-carbaldehyde (Table 2, Entry 1)
Yield: 146 mg; reddish purple solid; mp 60–62 °C.
Ethyl 1-Formylindoline-2-carboxylate (Table 2, Entry 7)
Yield: 110 mg; yellow solid; mp 92–93 °C.
1
H NMR (300 MHz, CDCl ): d = 8.89 (s, 1 H), 7.15 (m, 4 H), 4.02
1
3
H NMR (300 MHz, CDCl ): d = 8.98 (s, 1 H), 7.21 (m, 3 H), 7.06
3
(
t, J = 8.1 Hz, 2 H), 3.11 (t, J = 8.4 Hz, 2 H).
(
m, 1 H), 5.04 (ddd, J = 11.2, 4.2, 0.9 Hz, 1 H), 4.23 (dq, J = 6.9,
1
3
C NMR (75 MHz, CDCl ): d = 157.5, 140.6, 131.7, 127.3, 125.8,
1.2 Hz, 2 H), 3.55 (dd, J = 16.5, 11.1 Hz, 1 H), 3.19 (dd, J = 16.5,
3.9 Hz, 1 H), 1.28 (t, J = 7.2 Hz, 3 H).
3
1
24.1, 109.2, 44.4, 26.8.
+
13
MS (C H NO): m/z (%) = 147 (52) [M ], 118 (100), 91 (12), 77 (2),
C NMR (75 MHz, CDCl ): d = 170.2, 157.4, 140.5, 128.0, 125.8,
9
9
3
6
5 (4).
124.4, 116.5, 109.4, 61.7, 57.6, 32.3, 14.0.
+
MS (C H NO ): m/z (%) = 219 (14) [M ], 191 (5), 146 (22), 118
1
2
13
3
5
-Methylindoline-1-carbaldehyde (Table 2, Entry 2)
(
100), 91 (13).
Yield: 142 mg; brown oil.
1
H NMR (300 MHz, CDCl ): d = 8.87 (s, 1 H), 7.02 (m, 3 H), 4.03
3,4-Dihydroquinoline-1(2H)-carbaldehyde (Table 2, Entry 8)
Yield: 160 mg; light brown solid; mp 122–124 °C.
3
(
t, J = 8.7 Hz, 2 H), 3.10 (t, J = 8.4 Hz, 2 H), 2.31 (s, 3 H).
1
3
1
C NMR (75 MHz, CDCl ): d = 157.4, 133.9, 131.9, 127.9, 126.6,
H NMR (300 MHz, CDCl ): d = 8.75 (s, 1 H), 7.12 (m, 4 H), 3.77
3
3
1
16.2, 108.9, 44.6, 27.0, 20.8.
(t, J = 6.0 Hz, 2 H), 2.78 (t, J = 6.3 Hz, 2 H), 1.92 (quintet, J = 6.3
+
Hz, 2 H).
MS (C H NO): m/z (%) = 161 (58) [M ], 132 (100), 117 (12), 103
1
0
11
1
3
(
4), 77 (7), 65 (3).
C NMR (75 MHz, CDCl ): d = 160.7, 137.4, 129.2, 128.2, 126.7,
3
1
24.1, 116.6, 39.8, 26.7, 21.8.
5
-Methoxyindoline-1-carbaldehyde (Table 2, Entry 3)
+
MS (C H NO): m/z (%) = 161 (57) [M ], 132 (100), 118 (23), 104
1
0
11
Yield: 166 mg; maroon solid; mp 68–70 °C.
(
10), 77 (20).
1
H NMR (300 MHz, CDCl ): d = 8.80 (s, 1 H), 7.05 (d, J = 8.7 Hz,
3
1
H), 6.73 (m, 2 H), 4.03 (t, J = 9.0 Hz, 2 H), 3.77 (s, 3 H), 3.10 (t,
6-Methyl-3,4-dihydroquinoline-1(2H)-carbaldehyde (Table 2,
J = 9.0 Hz, 2 H).
Entry 9)
1
3
Yield: 161 mg; yellow oil.
C NMR (75 MHz, CDCl ): d = 157.0, 133.2, 116.9, 112.5, 111.8,
3
1
1
10.9, 109.6, 55.5, 44.6, 27.2.
H NMR (300 MHz, CDCl ): d = 8.75 (s, 1 H), 7.01 (m, 3 H), 3.79
3
+
(t, J = 6.0 Hz, 2 H), 2.77 (t, J = 6.3 Hz, 2 H), 2.30 (s, 3 H), 1.94
MS (C H NO ): m/z (%) = 177 (81) [M ], 162 (5), 148 (7), 134
(
1
0
11
2
(
quintet, J = 6.3 Hz, 2 H).
100), 117 (4), 104 (5).
1
3
C NMR (75 MHz, CDCl ): d = 161.0, 134.1, 130.1, 128.6, 127.6,
3
5
-Fluoroindoline-1-carbaldehyde (Table 2, Entry 4)
122.1, 116.8, 40.2, 27.0, 22.3, 20.6.
Yield: 142 mg; white solid; mp 100–101 °C.
+
MS (C H NO): m/z (%) = 175 (52) [M ], 146 (100), 132 (30), 118
(12), 91 (10).
1
1
13
1
H NMR (300 MHz, CDCl ): d = 8.83 (s, 1 H), 7.07 (dd, J = 9.0, 4.5
3
Hz, 1 H), 6.89 (m, 2 H), 3.97 (t, J = 9.0 Hz, 2 H), 3.04 (t, J = 8.9 Hz,
2
H).
6-Methoxy-3,4-dihydroquinoline-1(2H)-carbaldehyde (Table 2,
1
3
Entry 10)
Yield: 178 mg; yellow oil.
C NMR (75 MHz, CDCl ): d = 157.2, 133.8, 133.7, 117.2, 117.1,
3
1
2
14.2, 113.9, 113.4, 113.1, 112.2, 111.9, 109.8, 109.6, 44.6, 27.1,
7.1.
1
H NMR (300 MHz, CDCl ): d = 8.67 (s, 1 H), 7.05 (d, J = 8.7 Hz,
3
1
9
1 H), 6.72 (m, 2 H), 3.78 (s, 3 H), 3.77 (t, J = 7.2 Hz, 2 H), 2.78 (t,
F NMR (282 MHz, CDCl ): d = –119.2.
3
J = 6.6 Hz, 2 H), 1.94 (quintet, J = 6.3 Hz, 2 H).
+
MS (C H FNO): m/z (%) = 165 (64) [M ], 136 (100), 109 (29), 83
(
9
8
13
C NMR (75 MHz, CDCl ): d = 160.7, 156.5, 130.2, 123.8, 118.1,
3
8), 57 (4).
1
14.3, 112.3, 55.3, 40.0, 27.0, 22.2.
+
7
-Methylindoline-1-carbaldehyde (Table 2, Entry 5)
MS (C H NO ): m/z (%) = 191 (100) [M ], 176 (11), 162 (29),
11 13 2
Yield: 156 mg; light brown solid; mp 92–93 °C.
148 (90), 130 (11).
1
H NMR (300 MHz, CDCl ): d = 8.99 (s, 1 H), 7.10 (d, J = 7.2 Hz,
3
6
-Hydroxy-3,4-dihydroquinoline-1(2H)-carbaldehyde (Table 2,
1
H), 6.98 (m, 2 H), 4.14 (t, J = 8.4 Hz, 2 H), 3.08 (t, J = 8.7 Hz, 2
Entry 11)
H), 2.43 (s, 3 H).
Yield: 158 mg; white solid; mp 124–126 °C.
1
3
C NMR (75 MHz, CDCl ): d = 160.2, 133.2, 130.6, 123.9, 123.3,
3
1
H NMR (300 MHz, CDCl ): d = 8.65 (s, 1 H), 6.99 (d, J = 9.0 Hz,
3
1
22.4, 117.7, 45.2, 27.6, 20.9.
1
H), 6.72 (m, 2 H), 6.42 (br s, 1 H), 3.79 (t, J = 6.3 Hz, 2 H), 2.76
+
MS (C H NO): m/z (%) = 161 (48) [M ], 132 (100), 117 (33), 105
1
0
11
(t, J = 6.3 Hz, 2 H), 1.94 (quintet, J = 6.3 Hz, 2 H).
(
10), 77 (15), 65 (8).
1
3
C NMR (75 MHz, CDCl ): d = 161.2, 153.4, 130.8, 123.8, 118.5,
3
1
16.0, 114.0, 40.3, 27.0, 22.3.
2
-Methylindoline-1-carbaldehyde (Table 2, Entry 6)
+
Yield: 87 mg; brown oil.
MS (C H NO ): m/z (%) = 177 (100) [M ], 148 (89), 133 (16),
1
0
11
2
1
120 (10), 103 (6).
H NMR (300 MHz, CDCl ): d = 8.81 (s, 1 H), 7.10 (m, 3 H), 6.97
3
(
t, J = 7.2 Hz, 1 H), 4.65 (m, 1 H), 3.29 (dd, J = 17.1, 9.4 Hz, 1 H),
2
.58 (dd, J = 16.2, 2.4 Hz, 1 H), 1.27 (d, J = 6.3 Hz, 3 H).
Synthesis 2011, No. 8, 1227–1232 © Thieme Stuttgart · New York