7 Experimental Section
7.3 Analytical Data
7.3.6 Analytical Data for the Products of Ruthenium(II)-Catalyzed Isoquinoline Synthesis- 151 -
Synthesis of 9-Methyl-2,3-diphenyl-8,9-dihydro-7H-benzo[de]quinoline (176ba)
The representative procedure F was followed using substrate 194b (88 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 40/1) yielded 176ba (157 mg, 94%) as a yellow solid.
- 152 -
13C NMR (75 MHz, C2D2Cl4, 100 °C): δ = 162.0 (Cq), 148.7 (Cq), 141.3 (Cq), 138.0 (Cq), 138.0 (Cq), 136.2 (Cq), 131.2 (CH), 130.3 (CH), 129.3 (CH), 128.4 (Cq), 127.9 (CH), 127.0 (CH), 126.7 (CH), 126.4 (CH), 124.3 (CH), 123.3 (CH), 123.0 (Cq), 37.4 (CH), 30.8 (CH2), 27.8 (CH2), 19.6 (CH3).
IR (ATR): ṽ = 2929, 1604, 1577, 1442, 1377, 1306, 1178, 1071, 1023, 767, 699 cm–1. MS (EI) m/z (relative intensity) 335 (91) [M]+, 334 (100), 320 (50), 241 (8), 43 (13).
HR-MS (EI): m/z calcd for C25H20N+ [M–H]+ 334.1590, found 334.1608.
The spectral data were in accordance with those reported in the literature.255
Synthesis of 3,4-Diphenyl-1-n-propylisoquinoline (176ca)
The representative procedure F was followed using substrate 194c (82 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 50/1) yielded 176ca (144 mg, 89%) as a yellow solid.
M. p.: 118–120 °C.
1H NMR (300 MHz, CDCl3): δ = 8.23–8.14 (m, 1H), 7.64–7.56 (m, 1H), 7.54–7.45 (m, 2H), 7.37–7.22 (m, 5H), 7.20–7.05 (m, 5H), 3.32 (t, J = 7.7 Hz, 2H), 1.95 (dt, J = 7.7, 7.3 Hz 2H), 1.08 (t, J = 7.3 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ = 161.3 (Cq), 149.3 (Cq), 141.1 (Cq), 137.8 (Cq), 136.3 (Cq), 131.4 (CH), 130.3 (CH), 129.6 (CH), 128.9 (Cq), 128.2 (CH), 127.5 (CH), 127.5 (CH), 127.1 (CH), 126.9 (CH), 126.3 (CH), 125.6 (Cq), 125.2 (CH), 37.7 (CH2), 23.2 (CH2), 14.5 (CH3).
IR (ATR): ṽ = 3063, 2962, 1612, 1568, 1550, 1444, 1385, 1087, 1031, 757, 697 cm–1. MS (EI) m/z (relative intensity) 323 (22) [M]+, 295 (100), 308 (16), 252 (7).
HR-MS (EI): m/z calcd for C24H20N+ [M–H]+ 322.1590, found 322.1607.
Synthesis of 1-n-Butyl-3,4-diphenylisoquinoline (176da)
The representative procedure F was followed using substrate 194d (89 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 40/1) yielded 176da (151 mg, 89%) as a yellow solid.
The representative procedure G was followed using substrate 194d (89 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 40/1) yielded 176da (144 mg, 85%) as a yellow solid.
M. p.: 78–80 °C.
1H NMR (300 MHz, CDCl3): δ = 8.27–8.21 (m, 1H), 7.69–7.64 (m, 1H), 7.60–7.54 (m, 2H), 7.40–7.31 (m, 5H), 7.26–7.15 (m, 5H), 3.42 (t, J = 8.0 Hz, 2H), 2.02–1.90 (m, 2H), 1.58 (dt, J = 7.7, 7.3 Hz, 2H), 1.04 (t, J = 7.3 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ = 161.5 (Cq), 149.3 (Cq), 141.1 (Cq), 137.7 (Cq), 136.3 (Cq), 131.4 (CH), 130.3 (CH), 129.6 (CH), 128.8 (Cq), 128.2 (CH), 127.5 (CH), 127.5 (CH), 127.0 (CH), 126.8 (CH), 126.3 (CH), 125.4 (Cq), 125.2 (CH), 35.5 (CH2), 32.1 (CH2), 23.1 (CH2), 14.1 (CH3).
IR (ATR): ṽ = 3061, 2958, 2876, 1611, 1504, 1442, 1382, 1337, 1172, 1073, 763, 697 cm–1. MS (EI) m/z (relative intensity) 337 (6) [M]+, 308 (10), 295 (100), 252 (6).
HR-MS (EI): m/z calcd for C25H22N+ [M–H]+ 336.1747, found 336.1747.
Synthesis of 1-Isopropyl-3,4-diphenylisoquinoline (176ea)
The representative procedure F was followed using substrate 194e (82 mg, 0.50 N
Ph Ph n-Pr
N Ph Ph n-Bu
N Ph Ph i-Pr
- 153 -
mmol), diphenylacetylene (155a) (178 mg, 1.00 mmol) and molecular sieves 4 Å (100 mg).
Purification by column chromatography (n-hexane/EtOAc: 400/1) yielded 176ea (70 mg, 43%) as a yellow solid.
M.p.: 140–142 °C.
1H NMR (300 MHz, CDCl3): δ = 8.32–8.24 (m, 1H), 7.68–7.62 (m, 1H), 7.58–7.51 (m, 2H), 7.47–7.39 (m, 2H), 7.39–7.31 (m, 3H), 7.28–7.20 (m, 2H), 7.20–7.13 (m, 3H), 4.02 (dt, J = 6.7, 6.7 Hz, 1H), 1.52 (d, J = 6.7 Hz, 6H).
13C NMR (75 MHz, CDCl3): δ = 164.8 (Cq), 148.4 (Cq), 141.2 (Cq), 138.0 (Cq), 136.4 (Cq), 131.3 (CH), 130.5 (CH), 129.3 (CH), 128.3 (Cq), 128.2 (CH), 127.3 (CH), 127.0 (CH), 126.8 (CH), 126.4 (CH), 126.2 (CH), 124.69 (Cq), 124.43 (CH), 31.4 (CH), 22.34 (CH3).
IR (ATR): ṽ = 3073, 2969, 1551, 1446, 1381, 1258, 1104, 1007, 866 cm–1. MS (EI) m/z (relative intensity) 322 (100) [M]+, 295 (86), 252 (13), 176 (8).
HR-MS (EI): m/z calcd for C24H20N+ [M–H]+ 322.1590, found 322.1596.
Synthesis of 1-Cyclopropyl-3,4-diphenylisoquinoline (176fa)
The representative procedure F was followed using substrate 194f (81 mg, 0.50 mmol), diphenylacetylene (155a) (178 mg, 1.00 mmol) and molecular sieves 4 Å (100 mg). Purification by column chromatography (n-hexane/EtOAc: 200/1) yielded 176fa (135 mg, 84%) as a yellow solid.
M. p.: 148–150 °C.
1H NMR (300 MHz, CDCl3): δ = 8.50 (dd, J = 7.2, 2.0 Hz, 1H), 7.69–7.62 (m, 1H), 7.62–7.51 (m, 2H), 7.42–7.27 (m, 5H), 7.27–7.21 (m, 2H), 7.20–7.08 (m, 3H), 2.89–2.74 (m, 1H), 1.44–1.32 (m, 2H), 1.18–1.05 (m, 2H).
13C NMR (75 MHz, CDCl3): δ = 160.6 (Cq), 148.7 (Cq), 141.2 (Cq), 138.0 (Cq), 136.1 (Cq), 131.4 (CH), 130.4 (CH), 129.6 (CH), 128.2 (CH), 128.0 (Cq), 127.3 (CH), 127.0 (CH), 126.8 (CH), 126.3 (CH), 126.3 (Cq), 126.2 (CH), 124.8 (CH), 13.6 (CH), 9.4 (CH2).
IR (ATR): ṽ = 3055, 1611, 1568, 1547, 1444, 1410, 1318, 1261, 1075, 1014, 767, 694 cm–1. MS (EI) m/z (relative intensity) 321 (68) [M]+, 320 (100), 278 (5), 243 (8), 152 (5), 43 (13).
HR-MS (EI): m/z calcd for C24H18N+ [M–H]+ 320.1434, found 320.1438.
The spectral data were in accordance with those reported in the literature.256
Synthesis of 1-Cyclohexyl-3,4-diphenylisoquinoline (176ga)
The representative procedure F was followed using substrate 194g (102 mg, 0.50 mmol), diphenylacetylene (155a) (178 mg, 1.00 mmol) and molecular sieves 4 Å (100 mg). Purification by column chromatography (n-hexane/EtOAc: 200/1) yielded 176ga (147 mg, 81%) as a yellow solid.
M. p.: 158–160 °C.
1H NMR (300 MHz, CDCl3): δ = 8.31–8.25 (m, 1H), 7.68–7.62 (m, 1H), 7.58–7.49 (m, 2H), 7.46–7.40 (m, 2H), 7.38–7.32 (m, 3H), 7.26–7.20 (m, 2H), 7.20–7.14 (m, 2H), 3.68–3.57 (m, 1H), 2.12–1.75 (m, 7H), 1.64–1.31 (m, 3H).
13C NMR (75 MHz, CDCl3): δ = 164.4 (Cq), 148.6 (Cq), 141.3 (Cq), 138.1 (Cq), 136.5 (Cq), 131.4 (CH), 130.6 (CH), 129.3 (CH), 128.25 (CH), 128.23 (Cq), 127.4 (CH), 127.0 (CH), 126.8 (CH), 126.5 (CH), 126.2 (CH), 124.7 (Cq), 124.5 (CH), 41.8 (CH), 32.5 (CH2), 26.9 (CH2), 26.3 (CH2).
IR (ATR): ṽ = 2924, 2850, 1670, 1612, 1551, 1504, 1446, 1373, 1334, 1260, 1029, 758, 696 cm–1. N
Ph Ph
N Ph Ph
- 154 -
MS (EI) m/z (relative intensity) 362 (50) [M]+, 334 (13), 308 (100), 295 (50), 280 (8), 43 (6).
HR-MS (EI+): m/z calcd for C27H24N+ [M–H]+ 362.1903, found 362.1903.
The spectral data were in accordance with those reported in the literature.256
Synthesis of 1-Benzyl-3,4-diphenylisoquinoline (176ha)
The representative procedure F was followed using substrate 194h (106 mg, 0.50 mmol), diphenylacetylene (155a) (178 mg, 1.00 mmol) and molecular sieves 4 Å (100 mg). Purification by column chromatography (n-hexane/EtOAc: 100/1) yielded 176ha (100 mg, 54%) as a yellow solid.
M. p.: 118–120 °C.
1H NMR (300 MHz, CDCl3): δ = 8.26–8,19 (m, 1H), 7.69–7.62 (m, 1H), 7.56–7.46 (m, 2H), 7.46–7.39 (m, 4H), 7.39–7.14 (m, 11H), 4.79 (s, 2H).
13C NMR (75 MHz, CDCl3): δ = 159.1 (Cq), 149.4 (Cq), 140.9 (Cq), 139.7 (Cq), 137.5 (Cq), 136.7 (Cq), 131.3 (CH), 130.4 (CH), 129.7 (CH), 129.6 (Cq), 129.0 (Cq), 128.7 (CH), 128.4 (CH), 128.2 (CH), 127.6 (CH), 127.2 (CH), 127.0 (CH), 126.6 (CH), 126.4 (CH), 126.2 (CH), 125.7 (CH), 42.4 (CH2).
IR (ATR): ṽ = 3024, 1616, 1576, 1554, 1521, 1493, 1490, 1473, 1440, 1376, 1072, 754, 697 cm–1. MS (EI) m/z (relative intensity) 370 (100) [M]+, 293 (7), 265 (6), 91 (5), 43 (13).
HR-MS (EI+): m/z calcd for C28H20N+ [M–H]+ 370.1590, found 370.1584.
Synthesis of 6-Bromo-1-methyl-3,4-diphenylisoquinoline (176ia)
The representative procedure F was followed using substrate 194i (107 mg, 0.50 mmol), diphenylacetylene (155a) (178 mg, 1.00 mmol) and molecular sieves 4 Å (100 mg). Purification by column chromatography (n-hexane/EtOAc: 20/1) yielded 176ia (102 mg, 55%) as a yellow solid.
M. p.: 193–195 °C.
1H NMR (300 MHz, CDCl3): δ = 8.06 (d, J = 8.9 Hz, 1H), 7.80 (d, J = 2.0 Hz, 1H), 7.67 (dd, J = 8.9, 2.0 Hz, 1H), 7.39–7.30 (m, 5H), 7.23–7.14 (m, 5H), 3.06 (s, 3H).
13C NMR (75 MHz, CDCl3): δ = 157.6 (Cq), 150.5 (Cq), 140.5 (Cq), 137.3 (Cq), 136.7 (Cq), 131.2 (CH), 130.0 (CH), 129.9 (CH), 128.3 (CH), 128.3 (CH), 128.2 (Cq), 127.6 (CH), 127.4 (CH), 127.2 (CH), 127.1 (CH), 125.0 (Cq), 124.5 (Cq), 22.8 (CH3).
IR (ATR): ṽ = 3064, 1597, 1561, 1481, 1445, 1386, 1329, 1259, 1071, 1029, 751, 697 cm–1. MS (EI) m/z (relative intensity) 375/373 (100/100) [M]+, 293 (26), 252 (28), 189 (15), 43 (56).
HR-MS (ESI): m/z calcd for C22H1779BrN+ [M+H]+ 374.0539, found 374.0538.
The spectral data were in accordance with those reported in the literature.257
Synthesis of 1-Methyl-3,4-diphenyl-5H-pyrido[4,3-b]indole (176ja)
The representative procedure F was followed using substrate 194j (87 mg, 0.50 mmol) diphenylacetylene (155a) (178 mg, 1.00 mmol) and molecular sieves 4 Å (100 mg). Purification by column chromatography (n-hexane/EtOAc: 20/1) yielded 176ja (62 mg, 37%) as a yellow solid.
M. p.: 182–184 °C.
1H NMR (300 MHz, CDCl3): δ = 8.47 (s, 1H), 8.18 (dd, J = 7.8, 1.0 Hz, 1H), 7.50–7.26 (m, 10H), 7.22–7.13 (m, 3H), 3.13 (s, 3H).
N Ph Ph
N Ph Ph Me
Br
N H
N Me Ph Ph
- 155 -
13C NMR (75 MHz, CDCl3): δ = 151.9 (Cq), 151.5 (Cq), 143.8 (Cq), 140.4 (Cq), 139.5 (Cq), 136.1 (Cq), 130.3 (CH), 130.2 (CH), 129.0 (CH), 127.6 (CH), 127.4 (CH), 127.1 (CH), 126.0 (CH), 122.6 (Cq), 122.3 (CH), 120.8 (CH), 116.9 (Cq), 116.82 (Cq), 110.81 (CH), 23.8 (CH3).
IR (ATR): ṽ = 3640, 3050, 1594, 1492, 1405, 1234, 1118, 1020, 793 cm–1. MS (EI) m/z (relative intensity) 334 (30) [M]+, 291 (5), 167 (8), 77 (2).
HR-MS (EI): m/z calcd for C24H19N2+ [M+H]+ 335.1543, found 335.1541.
Synthesis of 1-Methyl-3,4-diphenylisoquinoline (176aa)
The representative procedure G was followed using substrate 194a (68 mg, 0.50 mmol) diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 20/1) yielded 176aa (96 mg, 65%) as a yellow solid.
M. p.: 152–155 °C.
1H NMR (300 MHz, CDCl3): δ = 8.23–8.20 (m, 1H), 7.71–7.67 (m, 1H), 7.63–7.57 (m, 2H), 7.44–7.32 (m, 5H), 7.29–7.17 (m, 5H), 3.11 (s, 3H).
13C NMR (75 MHz, CDCl3): δ = 157.7 (Cq), 149.4 (Cq), 141.0 (Cq), 137.6 (Cq), 136.0 (Cq), 131.4 (CH), 130.2 (CH), 129.9 (CH), 129.1 (Cq), 128.1 (CH), 127.6 (CH), 127.1 (CH), 126.9 (CH), 126.5 (CH), 126.2 (CH), 126.1 (Cq), 125.5 (CH), 22.7 (CH3).
IR (ATR): ṽ = 3025, 1567, 1389, 1334, 1072, 1026, 765, 695, 612, 563, 496 cm–1.
MS (EI) m/z (relative intensity) 295 (50) [M]+, 294 (100), 278 (5), 252 (17), 177 (15), 43 (14).
HR-MS (EI): m/z calcd for C22H17N+ [M]+ 295.1356, found 295.1348.
The spectral data were in accordance with those reported in the literature.255
Synthesis of 1,6-Dimethyl-3,4-diphenylisoquinoline (176ka)
The representative procedure G was followed using substrate 194k (75 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 10/1) yielded 176ka (124 mg, 80%) as a white solid.
M. p.: 160–163 °C.
1H NMR (300 MHz, CDCl3): δ = 8.09 (d, J = 9.2 Hz, 1H), 7.44–7.39 (m, 2H), 7.39–7.30 (m, 5H), 7.25–7.14 (m, 5H), 3.05 (s, 3H), 2.43 (s, 3H).
13C NMR (75 MHz, CDCl3): δ = 157.3 (Cq), 149.5 (Cq), 141.1 (Cq), 140.1 (Cq), 137.7 (Cq), 136.2 (Cq), 131.4 (CH), 130.2 (CH), 128.7 (Cq), 128.6 (CH), 128.1 (CH), 127.5 (CH), 127.0 (CH), 126.8 (CH), 125.4 (CH), 125.0 (CH), 124.5 (Cq), 22.6 (CH3), 22.1 (CH3).
IR (ATR): ṽ = 3062, 1495, 1444, 1385, 1336, 1071, 1029, 813, 767, 755, 696, 614 cm–1. MS (EI) m/z (relative intensity) 309 (40) [M]+, 308 (100), 293 (5), 265 (5), 252 (12), 43 (4).
HR-MS (ESI): m/z calcd for C23H20N+ [M+H]+ 310.1590, found 310.1592.
The spectral data were in accordance with those reported in the literature.255
Synthesis of 1-Ethyl-6-fluoro-3,4-diphenylisoquinoline (176la)
The representative procedure G was followed using substrate 194l (83 mg, 0.50 mmol) and diphenyl acetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 15/1→12/1) yielded 176la (98 mg, 60%) as a white solid.
N Me Ph
Ph
N Me Ph
Ph
Me
N Et Ph
Ph
F
- 156 - M. p.: 141–142 °C.
1H NMR (300 MHz, CDCl3): δ = 8.27 (dd, J = 9.2, 5.7 Hz, 1H), 7.45– 7.10 (m, 12H), 3.42 (q, J = 7.5 Hz, 2H), 1.53 (t, J = 7.5 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ = 163.0 (d, 1JC–F = 245 Hz, Cq), 162.0 (Cq), 150.7 (Cq), 140.8 (Cq), 138.4 (d,
3JC–F = 10 Hz, Cq), 137.3 (Cq), 131.2 (CH), 130.3 (CH), 128.7 (d, 4JC–F = 5 Hz, Cq), 128.4 (CH), 128.2 (d,
3JC–F = 10 Hz, CH), 127.6 (CH), 127.3 (CH), 127.1 (CH), 122.5 (d, 4JC–F = 1 Hz, Cq), 116.6 (d, 2JC–F = 25 Hz, CH), 110.0 (d, 2JC–F = 22 Hz, CH), 28.9 (CH2), 13.9 (CH3).
19F NMR (282 MHz, CDCl3): δ = –107.9 (s).
IR (ATR): ṽ = 2973, 1619, 1573, 1447, 1386, 1182, 1072, 876, 788, 753, 697 cm–1.
MS (EI) m/z (relative intensity) 327 (53) [M]+, 326 (100), 311 (12), 298 (10), 98 (10), 57 (10).
HR-MS (ESI): m/z calcd for C23H19FN+ [M+H]+ 328.1496, found 328.1498.
Synthesis of 6-(Trifluoromethyl)-1-methyl-3,4-diphenylisoquinoline (176ma)
The representative procedure G was followed using substrate 194m (102 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 12/1) yielded 176ma (86 mg, 47%) as an orange solid.
M. p.: 109–114 °C.
1H NMR (300 MHz, CDCl3): δ = 8.31 (d, J = 8.8 Hz, 1H), 7.96 (d, J = 1.8 Hz, 1H), 7.75 (dd, J = 8.8, 1.8 Hz, 1H), 7.40–7.33 (m, 5H), 7.23–7.16 (m, 5H), 3.10 (s, 3H).
13C NMR (75 MHz, CDCl3): δ = 157.8 (Cq), 150.9 (Cq), 140.4 (Cq), 136.5 (Cq), 135.4 (Cq), 131.5 (q, 2JC–F
= 32 Hz, Cq), 131.2 (CH), 130.2 (CH), 129.7 (Cq), 128.5 (CH), 127.7 (CH), 127.6 (CH), 127.3 (CH), 127.0 (Cq), 126.8 (CH), 123.9 (q, 3JC–F = 5 Hz, CH), 123.8 (d, 1JC–F = 272 Hz, Cq), 122.2 (q, 3JC–F = 3 Hz, CH), 22.8 (CH3).
19F NMR (282 MHz, CDCl3): δ = –62.9 (s).
IR (ATR): ṽ = 2958, 1555, 1336, 1305, 1257, 1176, 1155, 1134, 1082, 909, 769, 696, 618 cm–1. MS (EI) m/z (relative intensity) 363 (50) [M]+, 362 (100), 252 (8), 146 (5), 43 (5).
HR-MS (EI): m/z calcd for C23H16F3N+ [M]+ 363.1229, found 363.1219.
The spectral data were in accordance with those reported in the literature.257
Synthesis of 5,6-(Methylenedioxy)-1-methyl-3,4-diphenylisoquinoline (176na)
The representative procedure G was followed using substrate 194n (90 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 10/1) yielded 176na (146 mg, 86%) as a white solid.
M. p.: 251–254 °C.
1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 8.8 Hz, 1H), 7.37–7.06 (m, 11H), 5.83 (s, 2H), 2.99 (s, 3H).
13C NMR (75 MHz, CDCl3): δ = 157.7 (Cq), 150.2 (Cq), 147.6 (Cq), 141.7 (Cq), 140.8 (Cq), 138.4 (Cq), 131.1 (CH), 130.2 (CH), 127.5 (CH), 127.0 (CH), 126.8 (CH), 126.7 (CH), 124.8 (Cq), 123.2 (Cq), 122.5 (Cq), 120.9 (CH), 110.8 (CH), 101.4 (CH2), 23.4 (CH3).
IR (ATR): ṽ = 2899, 1626, 1549, 1512, 1432, 1383, 1353, 1279, 1209, 1119, 1049, 794 cm–1. MS (EI) m/z (relative intensity) 339 (100) [M]+, 338 (98), 310 (18), 292 (14), 176 (5).
HR-MS (EI): m/z calcd for C23H17NO2+ [M]+ 339.1254, found 339.1252.
Me N
F3C Ph
Ph
N O
O
Me Ph
Ph
- 157 - Synthesis of 1,7-Dimethyl-3,4-diphenylisoquinoline (176oa)
The representative procedure G was followed using substrate 194o (75 mg, 0.50 mmol) and diphenylacetylene (155a) (178 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 12/1) yielded 176oa (119 mg, 77%) as a pale orange solid.
M. p.: 134–139 °C.
1H NMR (300 MHz, CDCl3): δ = 7.96 (dq, J = 1.8, 0.9 Hz, 1H), 7.57 (d, J = 8.6 Hz, 1H), 7.45–7.30 (m, 6H), 7.26–7.14 (m, 5H), 3.06 (s, 3H), 2.57 (s, 3H).
13C NMR (75 MHz, CDCl3): δ = 156.9 (Cq), 148.6 (Cq), 141.0 (Cq), 137.7 (Cq), 136.3 (Cq), 134.1 (Cq), 132.0 (CH), 131.3 (CH), 130.2 (CH), 129.0 (Cq), 128.1 (CH), 127.5 (CH), 127.0 (CH), 126.7 (CH), 126.2 (Cq), 126.0 (CH), 124.4 (CH), 22.7 (CH3), 21.8 (CH3).
IR (ATR): ṽ = 3023, 2914, 1551, 1504, 1442, 1386, 1321, 1073, 1027, 831 cm–1.
MS (EI) m/z (relative intensity) 309 (65) [M]+, 293 (8), 265 (5), 252 (15), 146 (5), 100 (100).
HR-MS (ESI): m/z calcd for C23H20N+ [M+H]+ 310.1590, found 310.1592.
The spectral data were in accordance with those reported in the literature.258
Synthesis of 1-Methyl-3,4-di-n-propylisoquinoline (176ad)
The representative procedure G was followed using substrate 194a (68 mg, 0.50 mmol) and oct-4-yne (155d) (110 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 12/1) yielded 176ad (87 mg, 77%) as a yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.06 (dd, J = 8.5, 0.8 Hz, 1H), 7.94 (dd, J = 8.5, 0.8 Hz, 1H), 7.3 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.47 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 3.01–2.92 (m, 2H), 2.92–2.84 (m, 2H), 2.89 (s, 3H), 1.84–1.72 (m, 2H), 1.71–1.58 (m, 2H), 1.07 (t, J = 6.7 Hz, 3H), 1.03 (t, J
= 7.1 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ = 155.6 (Cq), 151.7 (Cq), 135.4 (Cq), 129.3 (CH), 126.1 (Cq), 126.1 (CH), 126.0 (Cq), 125.2 (CH), 123.5 (CH), 37.4 (CH2), 29.8 (CH2), 24.2 (CH2), 23.8 (CH2), 22.4 (CH3), 14.6 (CH3), 14.4 (CH3).
IR (neat): ṽ = 2957, 2870, 1617, 1568, 1454, 1391, 1333, 1027, 754, 614 cm–1.
MS (EI) m/z (relative intensity) 227 (40) [M]+, 212 (80), 198 (100), 184 (50), 171 (55), 128 (23), 115 (16).
HR-MS (EI): m/z calcd for C16H21N+ [M]+ 227.1669, found 227.1674.
The spectral data were in accordance with those reported in the literature.255
Synthesis of 4-n-Butyl-3-(4-methoxyphenyl)-1-methylisoquinoline (176ae)
The representative procedure G was followed using substrate 194a (68 mg, 0.50 mmol) and 1-(p-tolyl)-1-hexyne (155e) (172 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 12/1) yielded 176ae (70 mg, 46%) as an orange oil.
1H NMR (300 MHz, CDCl3): δ = 8.14 (dd, J = 8.6, 0.9 Hz, 1H), 8.04 (dt, J = 8.6, 0.9 N
Me Ph
Ph
Me
N Me n-Pr
n-Pr
N Me n-Bu
OMe
- 158 -
Hz, 1H), 7.70 (ddd, J = 8.3, 6.8, 1.3 Hz, 1H), 7.56 (ddd, J = 8.3, 6.8, 1.2 Hz, 1H), 7.39 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 3.03–2.91 (m, 2H), 2.95 (s, 3H), 2.41 (s, 3H), 1.70–1.56 (m, 2H), 1.34 (dt, J = 7.3, 7.3 Hz, 2H), 0.86 (t, J = 7.3 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ = 155.6 (Cq), 150.9 (Cq), 139.0 (Cq), 136.9 (Cq), 135.4 (Cq), 129.6 (CH), 129.1 (CH), 128.7 (CH), 127.2 (Cq), 126.5 (Cq), 126.2 (CH), 126.0 (CH), 124.2 (CH), 33.4 (CH2), 28.3 (CH2), 23.0 (CH2), 22.5 (CH3), 21.2 (CH3), 13.8 (CH3).
IR (neat): ṽ = 2955, 2923, 2869, 1614, 1563, 1513, 1438, 1391, 1333, 1026, 825, 755 cm–1. MS (EI) m/z (relative intensity) 289 (50) [M]+, 260 (70), 246 (100), 231 (30), 216 (8).
HR-MS (EI): m/z calcd for C21H23NO+ [M]+ 305.1774, found 305.1771.
Synthesis of 4-(4-Chloro-n-butyl)-1-methyl-3-phenylisoquinoline (176af)
The representative procedure G was followed using substrate 194a (68 mg, 0.50 mmol) and 6-chloro-1-phenylhexyne (155f) (193 mg, 1.00 mmol). Purification by column chromatography (n-hexane/EtOAc: 12/1) yielded 176af (112 mg, 72%) as a yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.16 (ddd, J = 8.4, 1.3, 0.8 Hz, 1H), 8.04 (dd, J = 8.4, 0.8 Hz, 1H), 7.73 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.59 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.53–7.34 (m, 5H), 3.42 (t, J = 6.2 Hz, 2H), 3.03–2.95 (m, 2H), 2.97 (s, 3H), 1.86–1.68 (m, 4H).
13C NMR (75 MHz, CDCl3): δ = 156.1 (Cq), 151.1 (Cq), 141.6 (Cq), 135.2 (Cq), 129.9 (CH), 129.2 (CH), 128.2 (CH), 127.5 (CH), 126.6 (Cq), 126.4 (Cq), 126.3 (CH), 126.2 (CH), 124.0 (CH), 44.4 (CH2), 32.3 (CH2), 28.1 (CH2), 27.5 (CH2), 22.5 (CH3).
IR (neat): ṽ = 2953, 1614, 1561, 1504, 1437, 1391, 1331, 1027, 756 cm–1.
MS (EI) m/z (relative intensity) 311/309 (14/41) [M]+, 246 (95), 232 (100), 217 (16), 202 (6), 189 (6).
HR-MS (EI): m/z calcd for C20H2035ClN+ [M]+ 309.1279, found 309.1297.
7.3.7 Selected NMR Spectra
nOe 187ba
-1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5
0.0 f1 (ppm)
N Me Ph Cl
NN
OOMMee MMee MMee
MMee HH
- 159 - nOe 187bb
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0
f1 (ppm)
nOe 187bj
NN
OOMMeeMMee HH
- 160 -
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0
f1 (ppm)
nOe 187aa
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5
f1 (ppm)
NN
OOMMee MMee MMee HH
PPhh
NN
MMee MMee
MMee HH
HH
- 161 - nOe 187da
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5
f1 (ppm)
nOe 187ea
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5
f1 (ppm)
HMBC 187ja NN
MMee MMee
MMee HH
OO MMee
NN
MMee MMee
MMee OO OOMMee
HH
- 162 -
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0
f2 (ppm)
30 40 50 60 70 80 90 100 110 120 130 140 150 160
f1 (ppm)
1H NMR
13C APT
nOe 187qb
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5
f1 (ppm)
N
MeMe Me MeO
H H
NN OOMMee
MMee
- 163 - nOe 187rb
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.5 5.0
6.0 6.5 7.5 7.0
8.0 8.5 9.0 9.5
f1 (ppm)
nOe 187ta
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0
f1 (ppm)
HMBC 187ta
Me Me Me N
S H
NN
MMee MMeeOO
HH
HH
- 164 -
- 165 - nOe 196ca
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5
f1 (ppm)
nOe 196eb
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5
8.0 f1 (ppm)
Me OMe N N
NN
MMee MMee MMee NN
HH
HH
- 166 - nOe 198aa
1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0
f1 (ppm)
nOe 198ba
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5
f1 (ppm)
N N
Me MeMe OMe H
H H
MeMe Me N N
- 167 - NOESY 189ca
6.6 6.7 6.8 6.9 7.1 7.0
7.3 7.2 7.5 7.4
7.7 7.6 7.8 7.9 8.0 8.1
8.2 f2 (ppm)
1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 2.6 2.8 3.0 3.2
f1 (ppm)
1H NMR
1H NMR
NOESY 189da
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5
9.0 f1 (ppm)
nOe 206ee
Et O
Me MeMe H
H
Me OMe Me O
H
- 168 -
-1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 .5
f1 (ppm)
NOESY 206ce
7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8
f2 (ppm)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
f1 (ppm)
1H NMR
1H NMR
MeO
O Me
H
H
O Me
H H
- 169 -
- 170 -
- 171 - NOESY 209
4.2 4.4 4.6 4.8 5.0 5.2 5.4 5.6 5.8 6.0 6.2 6.4 6.6 6.8 7.0 7.2 7.4 7.6 7.8 8.0 8.2 8.4
f2 (ppm)
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5
f1 (ppm)
1H NMR
1H NMR
NOESY 215ea
Me O
F
H H
H
- 172 -
- 173 -
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5
f1 (ppm)
15N,1H-HMBC 215ba
HN N N
OMe Me MeMe
- 174 -