The Journal of Organic Chemistry
Article
chromatography over silica-gel (n-hexane/EtOAc or CH2Cl2) to give
corresponding isoquinolines.
7.17−7.26 (m, 5H), 7.32−7.44 (m, 5H), 7.54 (d, J = 9.1 Hz, 1H), 7.61−
7.66 (m, 1H), 7.69−7.73 (m, 1H), 7.90 (dd, J = 1.4, 7.7 Hz, 1H), 8.89 (d,
J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 30.7, 124.1, 124.4, 126.8,
127.0, 127.3, 127.4, 127.5, 127.8, 128.4, 128.9, 129.8, 130.4 (over-
lapped), 131.3, 131.8, 133.1, 137.4, 138.2, 140.8, 151.1, 155.6.
2,3-Diphenylindeno[1,2,3-ij]isoquinoline (5k). Pale yellow solid
(Yield: 67 mg, 75%): mp 174−176 °C; 1H NMR (300 MHz, CDCl3) δ
7.21−7.28 (m, 5H), 7.31−7.35 (m, 3H), 7.41−7.47 (m, 4H), 7.55 (dd,
J = 8.4, 0.4 Hz, 1H), 7.64 (dd, J =8.4, 6.4Hz, 1H), 7.79−7.85 (m, 2H), 8.16−
8.19 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 120.6, 122.1, 122.7, 125.6,
125.7, 127.3, 127.4, 127.9, 128.2, 128.8, 130.0, 130.1, 130.8, 131.6, 132.7,
133.1, 137.2, 137.5, 139.3, 140.8, 141.5, 154.3, 160.2; IR (NaCl) ν cm−1 3057,
3027, 1950, 1882, 1811, 1619, 1583, 1568, 1497, 1476, 1427, 1367; HRMS
(EI) m/z calcd for C27H17N [M] 355.1361, found 355.1362.
1-Methyl-3,4-diphenylisoquinoline (5a).10 White solid (Yield:
1
66 mg, 89%): H NMR (300 MHz, CDCl3) δ 3.07 (s, 3H), 7.13−
7.25 (m, 5H), 7.29−7.39 (m, 5H), 7.57−7.61 (m, 2H), 7.63−7.68 (m,
1H), 8.16−8.19 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 22.9, 125.7,
126.3, 126.4, 126.6, 127.1, 127.2, 127.7, 128.3, 129.3, 130.0, 130.4, 131.5,
136.1, 137.7, 141.2, 149.6, 157.9.
6-Methoxy-1-methyl-3,4-diphenylisoquinoline (5b).10 White solid
(Yield: 63 mg, 77%): 1H NMR (300 MHz, CDCl3) δ 3.01 (s, 3H), 3.72
(s, 3H), 6.91 (d, J = 2.4 Hz, 1H), 7.14−7.25 (m, 6H), 7.29−7.36 (m,
5H), 8.10 (d, J = 9.2 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 22.8, 55.4,
104.6, 118.8, 122.0, 127.0, 127.2, 127.6, 127.7, 128.4, 128.7, 130.4, 131.5,
138.0, 138.2, 141.4, 150.3, 157.2, 160.7.
3,4-Diphenylisoquinoline (5l).30 White solid (Yield: 30 mg, 42%):
1H NMR (300 MHz, CDCl3) δ 7.17−7.25 (m, 5H), 7.33−7.39 (m, 5H),
7.60−7.69 (m, 3H), 8.03−8.06 (m, 1H), 9.37 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 125.8, 127.0, 127.2, 127.54, 127.59, 127.7, 127.8, 128.5,
130.4, 130.7, 130.8, 131.4, 136.1, 137.4, 140.9, 150.8, 151.9.
6-Bromo-1-methyl-3,4-diphenylisoquinoline (5c).10 White solid
(Yield: 83 mg, 89%): 1H NMR (300 MHz, CDCl3) δ 3.04 (s, 3H), 7.17−
7.21 (m, 5H), 7.31−7.38 (m, 5H), 7.66 (dd, J = 1.8, 8.9 Hz, 1H), 7.80 (d,
J = 1.8 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
22.9, 124.8, 125.2, 127.3, 127.5, 127.6, 127.8, 128.5, 128.6, 130.2, 130.4,
131.5, 137.0, 137.6, 140.8, 150.8, 157.9.
1,3,4-Triphenylisoquinoline (5m).3c White solid (Yield: 87 mg,
97%): 1H NMR (300 MHz, CDCl3) δ 7.15−7.21 (m, 3H), 7.28−7.31
(m, 2H), 7.34−7.44 (m, 5H), 7.47−7.60 (m, 5H), 7.71 (d, J = 8.2 Hz,
1H), 7.82 (dd, J = 8.3, 1.6 Hz, 2H), 8.18 (d, J = 8.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 125.6, 126.2, 126.7, 127.1, 127.4, 127.7 (over-
lapped), 128.5 (overlapped), 128.7, 129.9, 130.1, 130.4, 130.6, 131.5,
137.1, 137.7, 140.0, 141.1, 149.8, 160.0.
1-Methyl-3,4-dipropylisoquinoline (5d).10 White solid (Yield: 52
mg, 91%): 1H NMR (300 MHz, CDCl3) δ 1.06 (t, J = 7.3 Hz, 3H), 1.11
(t, J = 7.3 Hz, 3H), 1.63−1.74 (m, 2H), 1.75−1.87 (m, 2H), 2.90−3.02
(m, 7H), 7.51 (ddd, J = 8.8, 6.7, 1.1 Hz, 1H), 7.66 (ddd, J = 8.7, 6.8, 1.2
Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 8.09 (dd, J = 8.4, 0.6 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 14.5, 14.8, 22.5, 24.0, 30.0, 37.6, 123.7, 125.4,
126.20, 126.29, 126.3, 129.5, 135.6, 151.8, 155.8.
(E)-3,4-Diphenyl-1-styrylisoquinoline (5n).9b White solid (Yield:
73 mg, 76%): 1H NMR (300 MHz, CDCl3) δ 7.19−7.27 (m, 5H), 7.32−
7.48 (m, 8H), 7.56−7.62 (m, 2H), 7.67−7.73 (m, 3H), 8.08 (d, J = 15.5
Hz, 1H), 8.15 (d, J = 15.6 Hz, 1H), 8.42−8.45 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 123.1, 124.5, 125.6, 125.5, 126.8, 127.2, 127.4, 127.71,
127.74, 128.5, 128.7, 128.9, 130.01, 130.07, 130.7, 131.6, 136.3, 137.0,
137.3, 137.9, 141.3, 150.0, 153.6.
4-Ethyl-1-methyl-3-phenylisoquinoline (5e).3c White solid (Yield:
57 mg, 92%): 1H NMR (300 MHz, CDCl3) δ 1.26 (t, J = 7.4 Hz, 3H),
2.97 (s, 3H), 2.99 (q, J = 7.5 Hz, 2H), 7.38−7.54 (m, 5H), 7.58 (ddd, J =
8.1, 6.8, 1.2 Hz, 1H), 7.72 (ddd, J = 8.4, 6.8, 1.3 Hz, 1H), 8.07 (d, J = 8.5
Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 15.9,
21.8, 22.7, 124.3, 126.3, 126.5, 126.9, 127.6, 128.3, 128.7, 129.4, 130.0,
135.3, 142.1, 150.9, 156.0.
1-(Benzyloxymethyl)-3,4-diphenylisoquinoline (5o). White solid
Methyl 1-methyl-3-phenylisoquinoline-4-carboxylate (5f).10
1
(Yield: 72 mg, 72%): mp 91−93 °C; H NMR (300 MHz, CDCl3) δ
1
White solid (Yield: 48 mg, 70%): H NMR (300 MHz, CDCl3) δ
4.72 (s, 2H), 5.26 (s, 2H), 7.17−7.23 (m, 5H), 7.29−7.40 (m, 10H),
7.56−7.61 (m, 2H), 7.63−7.67 (m, 1H), 8.42−8.47 (m, 1H); 13C NMR
(75 MHz, CDCl3) δ 73.1, 73.8, 126.0, 126.2, 126.3, 127.0, 127.2, 127.4,
127.8, 127.9, 128.2, 128.4, 128.5, 130.2, 130.5, 131.2, 131.4, 136.8, 137.5,
138.2, 140.9, 149.3, 156.3; IR (NaCl) ν cm−1 1029, 1073, 1099, 1156,
1179, 1265, 1347, 1373, 1448, 1504, 1554, 1571, 1614, 1735, 1952,
2856, 2924, 3030, 3060; HRMS (FAB) m/z calcd for C29H24NO
[M + H]+ 402.1858, found 402.1859.
3.04(s, 3H), 3.73 (s, 3H), 7.37−7.49 (m, 3H), 7.60−7.65 (m, 1H),
7.70−7.77 (m, 3H), 8.00 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 23.1, 52.6, 121.9, 124.9, 125.8, 126.0,
127.5, 128.6, 128.8, 131.3, 133.5, 140.5, 149.9, 160.4, 169.7.
4-(4-Chlorobutyl)-1-methyl-3-phenylisoquinoline (5g).3c Yellow
1
liquid (Yield: 58 mg, 72%): H NMR (300 MHz, CDCl3) δ (Major
isomer) 1.69−1.81 (m, 4H), 2.96−3.01 (m, 5H), 3.41 (t, J = 6.2 Hz, 2H),
7.39−7.51 (m, 5H), 7.55−7.61 (m, 1H), 7.70−7.75 (m, 1H), 8.04 (d, J =
8.4 Hz, 1H), 8.15 (dd, J = 8.4, 0.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
(Major isomer) 22.6, 27.6, 28.2, 32.4, 44.5, 124.1, 126.43, 126.46, 126.5,
126.7, 127.6, 128.3, 129.3, 130.1, 135.3, 141.8, 151.2, 156.2; 1H NMR (300
MHz, CDCl3) δ (Minor isomer) 1.69−1.81 (m, 4H), 2.96−3.01 (m, 5H),
3.39 (t, J = 6.2 Hz, 2H), 7.39−7.51 (m, 5H), 7.55−7.61 (m, 1H), 7.70−7.75
(m, 1H), 8.08−8.12 (m, 2H); 13C NMR (75 MHz, CDCl3) δ (Minor
isomer) 22.6, 27.5, 29.8, 34.7, 44.9, 125.4, 125.6, 126.0, 126.5, 126.7, 127.6,
128.6, 129.8, 130.4, 136.1, 137.7, 150.7, 157.6. [Note: major and minor
isomers were obtained as inseparable mixture in 92:8 ratio.]
Methyl-3,4-diphenylisoquinoline-1-carboxylate (5p).9b White
1
solid (Yield: 72 mg, 85%): H NMR (300 MHz, CDCl3) δ 4.11 (s,
3H), 7.17−7.25 (m, 5H), 7.36−7.39 (m, 5H), 7.62−7.73 (m, 3H),
8.71−8.74 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 52.2, 125.3, 126.2,
126.3, 127.6, 127.90, 127.93, 128.1, 128.5, 130.6, 130.7, 131.2, 134.0,
137.0, 137.2, 140.1, 148.6, 149.8, 166.9.
(S)-1-(1-(Methoxymethoxy)ethyl)-3,4-diphenylisoquinoline (8).
20
White solid (Yield: 77 mg, 83%, >95% ee): mp 84−86 °C; [α]D
−83.7 (c 0.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.84 (d, J = 6.9
Hz, 3H), 3.40 (s, 3H), 4.80 (d, J = 6.7 Hz, 1H), 4.76 (d, J = 6.7 Hz, 1H),
6.15−7.23 (m, 5H), 7.33−7.39 (m, 5H), 7.54−7.59 (m, 2H), 7.65−7.69
(m, 1H), 8.66−8.69 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 21.4, 76.3,
95.4, 124.9, 125.6, 126.5, 126.6, 127.1, 127.4, 127.7, 128.42, 128.49, 129.9,
130.4, 130.6, 131.4, 131.5, 137.2, 137.7, 140.9, 149.1, 159.8; IR (NaCl)
ν cm−1 979, 993, 1033, 1099, 1119, 1155, 1213, 1265, 1343, 1375, 1445,
1505, 1553, 1602, 1614, 1951, 2776, 2822, 2887, 2931, 2980, 3027, 3057;
HRMS (EI) m/z calcd for C25H23NO2 [M] 369.1729, found 369.1730.
Determination of the Optical Purity of 8. The optical purity of 8
was determined by 1H NMR spectroscopy after converting to the
corresponding (R)-methoxyphenylacetic acid (MPA) ester derivative of
1-(3,4-diphenylisoquinoline-1yl)ethanol. Deprotection of methoxy-
methyl ether (MOM) moiety from 8 gave (S)-1-(3,4-diphenylisoquino-
line-1yl)ethanol. The deprotection was carried out by the following
procedure:31 BF3·Et2O (0.14 mL, 0.55 mmol) was added dropwise to a
solution of 8 (67 mg, 0.18 mmol) in dimethyl sulfide (3.5 mL) at 0 °C
and the mixture was stirred for 6 h at room temperature. The reaction
mixture was quenched by the saturated aqueous solution of NaHCO3.
(1-Methyl-3-phenylisoquinoline-4-yl)methanol (5h).9b Yellow
1
solid (Yield: 39 mg, 63%): H NMR (300 MHz, CDCl3) δ 2.10 (t,
J = 4.8 Hz, 1H), 2.99 (s, 3H), 4.99 (d, J = 4.7 Hz, 2H), 7.40−7.49 (m,
3H), 7.60−7.66 (m, 3H), 7.75−7.80 (m, 1H), 8.18 (d, J = 8.4 Hz, 1H),
8.27 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 22.8, 59.6, 124.3,
124.6, 126.3, 126.9, 128.1, 128.4, 129.8 (overlapped), 130.7, 135.9,
140.6, 151.9, 158.8.
4-((tert-Butyldimethylsilyloxy)methyl)-1-methyl-3-phenylisoqui-
noline (5i).9b Pale yellow solid (Yield: 69 mg, 76%): H NMR (300
1
MHz, CDCl3) δ (Major isomer) 0.09 (s, 6H), 0.92 (s, 9H), 3.01 (s, 3H),
5.00 (s, 2H), 7.42−7.50 (m, 3H), 7.58−7.63 (m, 1H), 7.70−7.78 (m, 3H),
8.17 (d, J = 8.5 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz,
CDCl3) δ (Major isomer) −5.11, 18.5, 22.9, 26.0, 60.3, 124.6, 125.1, 126.0,
126.6, 126.8, 128.0, 128.2, 130.1, 136.4, 140.8, 151.6, 158.4. [Note: major
and minor isomers were obtained as inseparable mixture in 95:5 ratio.]
1-Methyl-3,4-diphenylbenzo[h]isoquinoline (5j).10 White solid
1
(Yield: 50 mg, 81%): H NMR (300 MHz, CDCl3) δ 3.43 (s, 3H),
G
dx.doi.org/10.1021/jo501465q | J. Org. Chem. XXXX, XXX, XXX−XXX