S.R. Banini et al. / Tetrahedron 67 (2011) 3603e3611
3609
J¼7.2 Hz, 1H), 7.15 (d, J¼9.0 Hz, 1H), 7.11 (d, J¼2.4 Hz, 1H), 6.86 (dd,
J¼9.0, 2.4 Hz, 1H), 4.59 (q, J¼7.2 Hz, 1H), 3.85 (s, 3H), 1.84 (d,
(88 mg, 0.78 mmol), and CO (6 atm) in DMF (5 mL), as described for
6, gave after chromatography (hexanes/EtOAc, 9:1) 27 (112 mg,
0.55 mmol, 79%) as a pale yellow solid. Mp 61 ꢀC (lit.26 61e62 ꢀC).
J¼7.2 Hz, 3H); 13C NMR
d 155.9, 151.5, 141.3, 129.2, 128.9, 128.7,
127.6, 127.4, 116.3, 114.1, 112.3, 100.7, 55.8, 38.4, 20.0;23 IR (ATR)
3243, 2212 cmꢁ1
277.1341; found, 277.1335.
;
HRMS (ESI) calcd for C18H17N2O (MþHþ)
4.3.8. 2-Methylindole (21). Reaction of 14 (158 mg, 0.97 mmol), Pd
(OAc)2 (16 mg, 0.06 mmol), PPh3 (61 mg, 0.23 mmol), t-BuOK
(86 mg, 0.77 mmol), and CO (6 atm) in DMF (5 mL), as described for
6, gave after chromatography (hexanes/EtOAc, 9:1) 21 (113 mg,
0.86 mmol, 89%) as a pale yellow solid.
4.3. Method B
4.3.1. 4-Cyano-2-methyl-6-methoxyquinoline (6). Reaction of
4
(101 mg, 0.43 mmol), Pd(OAc)2 (15 mg, 0.05 mmol), PPh3 (63 mg,
0.23 mmol), DBU (72 L, 0.48 mmol), and CO (6 atm) in DMF (5 mL),
4.3.9. 3-Cyano-2-(1-phenyl-1-ethenyl)-5-methoxyindole (30), 3-cy-
ano-2-(1-methyl-1-hydroxybenzyl)-6-methoxyindole (31), and 3-cy-
ano-6-methoxyindole (32)27. Reaction of 28 (86 mg, 0.28 mmol),
Pd(OAc)2 (10 mg, 0.04 mmol), PPh3 (44 mg, 0.17 mmol), DBU
m
as described for 5 gave after chromatography (hexanes/EtOAc, 8:2)
6 (76 mg, 0.38 mmol, 88%) as a pale yellow solid. Mp 156 ꢀC;
1H NMR
d
7.98 (d, J¼9.6 Hz, 1H), 7.57 (s, 1H), 7.44 (dd, J¼9.6, 3.0 Hz,
(50 mL, 0.33 mmol), and CO (6 atm) in DMF (4 mL), as described
1H), 7.33 (d, J¼2.4 Hz, 1H), 3.99 (s, 3H), 2.75 (s, 3H); 13C NMR
for 6, gave after chromatography (hexanes/EtOAc, 95:5) in order
of elution 30 (29 mg, 0.08 mmol, 38%) and a 7:1 mixture of 31 and
32 (44 mg, 47% and 8%) as pale yellow solids. Spectral data for 30:
d
159.4, 155.6, 144.3, 131.2, 125.9, 125.7, 124.3, 117.4, 116.2, 102.3,
56.0, 24.9; IR (ATR) 3009, 2230, 1475 cmꢁ1; HRMS (ESI) calcd for
C12H11N2O (MþHþ) 199.0871; found, 199.0866.
mp 160 ꢀC; 1H NMR
d
8.16 (s, 1H), 7.44 (m, 3H), 7.39 (m, 2H), 7.27
(d, J¼9.0 Hz, 1H), 7.17 (d, J¼3.0 Hz, 1H), 6.93 (dd, J¼9.0, 3.0 Hz,
1H), 6.19 (s, 1H), 5.78 (s, 1H), 3.89 (s, 3H); 13C NMR
156.7, 144.3,
4.3.2. 4-Cyano-6-methoxyquinoline (22). Reaction of
0.40 mmol), Pd(OAc)2 (14 mg, 0.05 mmol), PPh3 (60 mg, 0.23 mmol),
DBU (65 L, 0.43 mmol), and CO (6 atm) in DMF (5 mL), as described
8
(87 mg,
d
138.7, 138.2, 129.4, 129.2, 129.1, 129.0, 128.2, 120.0, 116.4, 115.5,
112.6, 100.5, 85.5, 55.8; IR (ATR) 3287, 2217 cmꢁ1; HRMS (ESI)
calcd for C18H15N2O (MþHþ) 275.1184; found, 275.1179. Spectral
m
for 6, gave after chromatography (hexanes/EtOAc, 8:2) 22 (65 mg,
0.35 mmol, 88%) to afford a pale yellow solid. Mp 145 ꢀC (lit.24 157 ꢀC).
data for 31 from the mixture: 1H NMR
d 9.03 (s, 1H), 7.52 (dt,
J¼7.2, 1.2 Hz, 2H), 7.36 (t, J¼7.2 Hz, 2H), 7.31 (t, J¼7.2 Hz, 1H), 7.26
4.3.3. 2-Butyl-4-cyano-6-methoxyquinoline (3)2. Reaction of
(105 mg, 0.38 mmol), Pd(OAc)2 (11 mg, 0.04 mmol), PPh3 (45 mg,
0.16 mmol), DBU (60 L, 0.41 mmol), and CO (6 atm) in DMF (5 mL)
as described for 6 gave after chromatography (hexanes/EtOAc, 8:2)
3 (72 mg, 0.30 mmol, 79%) as a pale yellow solid.
1
(t, J¼9.0 Hz, 1H), 7.08 (d, J¼2.4 Hz, 1H), 6.90 (dd, J¼9.0, 2.4 Hz,
1H), 3.87 (s, 3H), 2.75 (br s, 1H), 2.22 (s, 3H); 13C NMR
d 155.9,
m
152.0, 144.1, 129.6, 128.8, 128.4, 127.9, 125.3, 116.2, 114.6, 112.7,
100.5, 82.35, 73.81, 55.8, 29.1. HRMS (ESI) calcd for C18H17N2O2
(MþHþ) 293.1291; found, 293.1285. Spectral data for 32 from the
mixture: 1H NMR
d
8.74 (s, 1H), 7.65 (d, J¼9.0 Hz, 1H), 7.33 (d,
4.3.4. 4-Cyanoquinoline (23). Reaction of 9 (156 mg, 0.83 mmol), Pd
J¼9.0 Hz, 1H), 7.17 (d, J¼2.4 Hz, 1H), 6.96 (dd, J¼9.0, 2.4 Hz, 1H),
(OAc)2 (16 mg, 0.07 mmol), PPh3 (55 mg, 0.21 mmol), DBU (170
mL,
3.84 (s, 3H); 13C NMR
d 156.1, 131.8, 129.7, 128.9, 116.0, 115.2, 112.9,
1.14 mmol), and CO (6 atm) in DMF (5 mL) as described for 6 gave
after chromatography (hexanes/EtOAc, 9:1) 23 (106 mg, 0.69 mmol,
83%) as a pale yellow solid. Mp 106e107 ꢀC (lit.25 103e104 ꢀC).
100.6, 87.2, 55.8. HRMS (ESI) calcd for C10H9N2O (MþHþ)
173.0715; found, 173.0710.
4.3.10. 3-Cyclohexyl-2-iodo-2-propenenitrile (33). To a solution of
cyanomethyltriphenylarsonium bromide28 (1.66 g, 3.90 mmol) in
MeCN (15 mL) at 10 ꢀC was added potassium carbonate (536 mg,
3.88 mmol) and iodine (997 mg, 3.93 mmol). The solution was
stirred under a nitrogen atmosphere (ambient temperature, 30 h)
where after potassium carbonate (564 mg, 4.08 mmol), cyclo-
hexylcarboxaldehyde (556 mg, 5.00 mmol) and H2O (0.5 mL) were
added.
4.3.5. 5-Aza-2-butyl-4-cyano-6-methoxyquinoline (24). Reaction of
10 (159 mg, 0.58 mmol), Pd(OAc)2 (12.1 mg, 0.06 mmol), PPh3
(61 mg, 23 mmol), DBU (90 mL, 0.61 mmol), and CO (6 atm) in DMF
(5 mL) as described for 6 gave after chromatography (hexanes/
EtOAc, 98:2) 24 (99 mg, 0.40 mmol, 69%) as a pale yellow solid. Mp
68 ꢀC; 1H NMR
d
8.18 (d, J¼9.0 Hz, 1H), 7.70 (s, 1H), 7.20 (d, J¼9.6 Hz,
1H), 4.16 (s, 3H), 2.98 (t, J¼7.8 Hz, 2H), 1.80 (p, J¼7.8 Hz, 2H), 1.43
(sextet, J¼7.8 Hz, 2H), 0.97 (t, J¼7.8 Hz, 3H); 13C NMR
d
163.3, 160.2,
After additional 48 h, the solvents were removed under reduced
pressure and the resulting crude product was purified by chro-
matography (hexanes/EtOAc, 95:5) to give 33 (171 mg, 0.65 mmol,
141.9, 139.7, 139.0, 127.4, 118.6, 118.2, 115.4, 54.4, 38.1, 31.9, 22.4,
13.9; IR (ATR) 2233 cmꢁ1; HRMS (ESI) calcd for C14H16N3O (MþHþ)
242.1293; found, 242.1288.
17%)29 as a brown oil. 1H NMR
d
6.89 (d, J¼10.2 Hz, 1H), 2.54 (qt,
J¼10.8, 3.6 Hz, 1H), 1.77e1.73 (m, 6H), 1.25e1.14 (m, 4H); 13C NMR
4.3.6. 1,1-Dimethylethyl 4-aza-5-methoxyindole-3-carboxylate (25)6
and 1,1-dimethylethyl 5-aza-6-methoxyquinoline-4-carboxylate
(26). Reaction of 12 (234 mg, 0.79 mmol), Pd(OAc)2 (16 mg,
0.06 mmol), PPh3 (56 mg, 0.30 mmol), t-BuOK (92 mg, 0.82 mmol),
and CO (6 atm) in DMF (5 mL), as described for 6, gave after chro-
matography (hexanes/EtOAc, 9:1) in order of elution 26 (130 mg,
0.50 mmol, 63%) and 25 (48 mg, 0.19 mmol, 24%) both as pale yel-
d 167.3, 116.1, 49.7, 45.7, 45.0, 31.4, 25.3, 25.0; IR (ATR) 2935, 2851,
2211, 1447, 1148 cmꢁ1; HRMS (ESI) calcd for C9H12NaNI (MþNaþ)
283.9912; found, 283.9906.
4.3.11. 3-Cyclohexyl-2-(2-nitrophenyl)-2-propenenitrile (34). Reaction
of tributyl(2-nitrophenyl) stannane30 (273 mg, 0.66 mmol), 33
(171 mg, 0.65 mmol), PdCl2(PhCN)2 (16 mg, 0.04 mmol), AsPh3
(22 mg, 0.07 mmol), and CuI (22 mg, 0.12 mmol) in NMP (3 mL), as
described for 13 (80 ꢀC, 76 h), gave after chromatography (hexanes/
EtOAc, 9:1) 34 (82 mg, 0.32 mmol, 48%, as a 14:1 mixture of isomers)
low solids. Analytical data for 26: mp 126e127 ꢀC; 1H NMR
d 8.80
(d, J¼4.8 Hz, 1H), 8.20 (d, J¼9.0 Hz, 1H), 7.60 (d, J¼4.2 Hz, 1H), 7.15
(d, J¼9.0 Hz, 1H), 4.08 (s, 3H), 1.68 (s, 9H); 13C NMR
d 166.3, 162.4,
147.4,142.6, 139.9, 139.2, 138.3, 121.8, 117.2, 82.8, 54.0, 28.3; IR (ATR)
1694, 1592, 1508, 1346, 1204 cmꢁ1; HRMS calcd for C14H16N2O3
(MþHþ) 261.1239; found, 261.1233.
as a pale brown oil.31 1H NMR
d
8.03 (d, J¼9.6 Hz, 1H), 7.65
(t, J¼7.2 Hz, 1H), 7.55 (t, J¼7.2 Hz, 1H), 7.41 (d, J¼7.8 Hz, 1H), 6.31
(d, J¼10.2 Hz, 1H), 2.78 (tq, J¼4.2, 0.8 Hz, 1H), 1.87 (d, J¼2.6 Hz, 2H),
1.79 (dt, J¼13.8 Hz, 3.0 Hz, 2H), 1.72 (dt, J¼13.2, 3.6 Hz, 1H), 1.40 (tq,
4.3.7. 4-Phenylquinoline (27). Reaction of 13 (167 mg, 0.70 mmol),
Pd(OAc)2 (16 mg, 0.07 mmol), PPh3 (60 mg, 0.23 mmol), t-BuOK
J¼12.6, 3.6 Hz, 2H), 1.23 (m, 3H); 13C NMR
d 156.7, 147.8, 133.5, 131.7,
129.9, 129.7, 124.9, 115.2, 110.6, 41.2, 31.6, 25.5, 25.1; IR (ATR) 2928,