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I. Andreu et al. / Tetrahedron 61 (2005) 8282–8287
133.5, 129.6, 129.4, 128.8, 128.4, 127.9, 127.6, 127.5,
126.6, 46.6, 43.5, 29.2, 21.4. EIMS m/z (%) 363 [M]C(17),
208 (100), 165 (32), 133 (25), 91 (56). HRMS (EI) (MC)
calcd for C22H21NO2S 363.1293, found 363.1273. Anal.
Calcd for C22H21NO2S: C, 72.70; H, 5.82; N, 3.85. Found:
C, 72.83; H, 5.77; N, 3.87.
3.3.5. 8-(Pyridin-3-yl)-2-[(4-methylphenyl)sulfonyl]-1,2,
3,4-tetrahydroisoquinoline (14). Column chromatography
(cyclohexane/EtOAc, 80:20) yielded a beige solid (95 mg,
0.26 mmol, 27%). Mp: 104–106 8C. IR: 3457, 2924, 2850,
2360, 1597, 1457, 1338, 1163, 1019, 950, 815, 785, 751,
1
661 cmK1. H NMR (CDCl3, 400 MHz) d 8.68 (br s, 1H),
8.50 (br s, 1H), 7.57 (d, 2H, JZ8.0 Hz), 7.30–7.23 (m, 5H),
7.14 (d, 1H, JZ7.6 Hz), 7.03 (d, 1H, JZ7.6 Hz), 4.07 (s,
2H), 3.37 (t, 2H, JZ5.9 Hz), 3.03 (t, 2H, JZ5.9 Hz), 2.41
(s, 3H). 13C NMR (CDCl3, 100 MHz) d 149.5, 149.0, 143.7,
136.7, 136.3, 134.0, 133.3, 129.7, 128.9, 128.2, 127.6,
126.9, 46.6, 43.5, 29.2, 21.5. EIMS m/z (%) 364.[M]C(36),
209 (100), 180 (49), 155 (23), 91 (73). HRMS (EI) (MC)
calcd for C21H20N2O2S 364.1245, found 364.1221. Anal.
Calcd for C21H20N2O2S: C, 69.21; H, 5.53; N, 7.69. Found:
C, 69.44; H, 5.58; N, 7.73.
3.3.2. 8-(4-Methylphenyl)-2-[(4-methylphenyl)sulfonyl]-
1,2,3,4-tetrahydroisoquinoline (11). Column chromato-
graphy (petroleum ether/EtOAc, 96:4) yielded a white solid
(180 mg, 0.48 mmol, 50%). Mp: 178–180 8C. IR: 3424,
2919, 2855, 2360, 1592, 1515, 1458, 1358, 1338, 1168, 952,
940, 789, 750 cmK1. 1H NMR (CDCl3, 400 MHz) d 7.57 (d,
2H, JZ8.3 Hz), 7.27 (d, 2H, JZ8.0 Hz), 7.23–7.16 (m, 3H),
7.08 (d, 2H, JZ8.0 Hz), 7.06–7.02 (m, 2H), 4.12 (s, 2H),
3.35 (t, 2H, JZ6.0 Hz), 2.97 (t, 2H, JZ6.0 Hz), 2.42 (s,
3H), 2.40 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 143.5,
140.6, 137.1, 137.0, 133.6, 133.5, 129.6, 129.5, 129.1,
128.6, 128.0, 127.7, 127.6, 126.5, 46.7, 43.6, 29.2, 21.5,
21.2. EIMS m/z (%) 377 [M]C(10), 221 (74), 178 (37), 132
(66), 104 (51), 91 (100), 77 (37). HRMS (EI) (MC) calcd for
C23H23NO2S 377.1449, found 377.1391. Anal. Calcd for
C23H23NO2S: C, 73.18; H, 6.14; N, 3.71. Found: C, 73.09;
H, 6.22; N, 3.84.
3.3.6. 8-Phenyl-2-[(4-methylphenyl)sulfonyl]-1,2,3,4-
tetrahydroisoquinolin-4-ol (15). Column chromatography
(petroleum ether/CH2Cl2/EtOAc, 90:4:6) yielded a white
solid (188 mg, 0.50 mmol, 54%). Mp: 122–124 8C. IR:
3517, 3065, 3029, 2920, 2855, 1595, 1497, 1458, 1340,
1252, 1219, 1161, 1089, 952, 811, 762, 703 cmK1. 1H NMR
(CDCl3, 400 MHz) d 7.57 (d, 2H, JZ8.3 Hz), 7.43–7.36 (m,
4H), 7.29–7.26 (m, 3H), 7.18–7.16 (m, 2H), 7.12–7.10 (m,
1H), 4.80 (br s, 1H), 4.26 (d, 1H, JZ15.5 Hz), 3.83 (d, 1H,
JZ15.5 Hz), 3.58 (dd, 1H, JZ12.0, 3.8 Hz), 3.16 (dd, 1H,
JZ12.0, 3.8 Hz), 3.10 (br s, 1H), 2.38 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d 144.0, 140.3, 139.7, 135.8, 133.0,
133.5, 129.9, 129.8, 129.3, 128.7, 128.6, 128.5, 127.7,
127.3, 66.4, 50.8, 47.1, 21.5. EIMS m/z (%) 379 [M]C(8),
224 (48), 206 (34), 196 (100), 167 (57), 155 (24), 91 (38).
HRMS (EI) (MC) calcd for C22H21NO3S 379.1242, found
379.1266. Anal. Calcd for C22H21NO3S: C, 69.63; H, 5.58;
N, 3.69. Found: C, 69.57; H, 5.52; N, 3.81.
3.3.3. 8-(2-Acetylphenyl)-2-[(4-methylphenyl)sulfonyl]-
1,2,3,4-tetrahydroisoquinoline (12). Column chromato-
graphy (cyclohexane/EtOAc, 80:20) yielded a beige syrup
(225 mg, 0.56 mmol, 58%). Mp: !50 8C. IR: 3430, 2920,
2840, 2360, 2342, 1684, 1596, 1457, 1337, 1164, 1090, 953,
815, 668 cmK1. 1H NMR (CDCl3, 400 MHz) d 7.63 (d, 1H,
JZ7.3 Hz), 7.46–7.37 (m, 4H), 7.16 (d, 2H, JZ7.8 Hz),
7.05 (dd, 2H, JZ7.3, 1.2 Hz), 6.99 (d, 1H, JZ7.6 Hz), 6.79
(d, 1H, JZ7.3 Hz), 3.96 (d, 1H, JZ15.6 Hz), 3.72 (d, 1H,
JZ15.6 Hz), 3.30 (m, 1H), 3.17 (m, 1H), 2.86 (m, 2H), 2.28
(s, 3H), 1.97 (s, 3H). 13C NMR (CDCl3, 100 MHz) d 201.4,
143.5, 139.3, 139.2, 138.5, 133.5, 131.3, 130.4, 129.5,
129.4, 128.6, 128.3 127.9, 127.4, 127.3, 126.4, 46.3, 43.3,
29.3, 28.9, 21.3. LC–MS (ES positive mode) m/z 405 [MC
1]C. EIMS m/z (%) 250 (100), 91 (26). HRMS (EI) (MC)
calcd for C24H23NO3S 405.1398, found 405.1352. Anal.
Calcd for C24H23NO3S: C, 71.09; H, 5.72; N, 3.45. Found:
C, 70.88; H, 5.64; N, 3.39.
3.3.7. 8-(4-Methylphenyl)-2-[(4-methylphenyl)sulfonyl]-
1,2,3,4-tetrahydroisoquinolin-4-ol (16). Column chroma-
tography (petroleum ether/EtOAc/CH2Cl2, 90:4:6) yielded
a yellow solid (240 mg, 0.61 mmol, 66%). Mp: 190–192 8C.
IR: 3550, 3025, 2894, 2361, 2319, 1594, 1514, 1448, 1352,
1
1336, 1168, 955, 815, 730, 698 cmK1. H NMR (CDCl3,
400 MHz) d 7.61 (d, 2H, JZ8.2 Hz), 7.43 (d, 1H, JZ
7.6 Hz), 7.33–7.30 (m, 3H), 7.23 (d, 2H, JZ7.8 Hz), 7.15
(d, 1H, JZ7.6 Hz), 7.08 (d, 2H, JZ7.8 Hz), 4.80 (br s, 1H),
4.36 (d, 1H, JZ15.4 Hz), 3.75 (m, 2H), 3.06 (dd, 1H, JZ
12.0, 2.9 Hz), 2.70 (br s, 1H), 2.43 (s, 6H). 13C NMR
(CDCl3, 100 MHz) d 143.9, 140.3, 137.4, 136.6, 135.7,
132.9, 129.0, 129.7, 129.3, 129.2, 128.5, 128.3, 127.7,
127.3, 66.4, 50.8, 47.1, 21.5, 21.2. EIMS m/z (%) 393
[M]C(9), 238 (31), 210 (77), 165 (41), 91 (100). HRMS (EI)
(MC) calcd for C23H23NO3S 393.1398, found 393.1386.
Anal. Calcd for C23H23NO3S: C, 70.20; H, 5.89; N, 3.56.
Found: C, 70.01; H, 5.97; N, 3.44.
3.3.4. 8-(3,4-Dimethoxyphenyl)-2-[(4methylphenyl)-sul-
fonyl]-1,2,3,4-tetrahydroisoquinoline (13). Column
chromatography (cyclohexane/EtOAc, 80:20) yielded a
brown syrup (200 mg, 0.47 mmol, 49%). Mp: !50 8C. IR:
3433, 2923, 2832, 2357, 2255, 1598, 1516, 1464, 1337,
1
1164, 1025, 952, 814, 749, 660 cmK1. H NMR (CDCl3,
400 MHz) d 7.44 (d, 2H, JZ8.2 Hz), 7.12 (d, 2H, JZ
8.2 Hz), 7.03 (t, 1H, JZ7.4 Hz), 6.92 (m, 2H), 6.78 (d, 1H,
JZ8.1 Hz), 6.62 (dd, 1H, JZ8.1, 1.9 Hz), 6.57 (d, 1H, JZ
1.9 Hz), 3.97 (s, 2H), 3.80 (s, 3H), 3.72 (s, 3H), 3.21 (t, 2H,
JZ6.1 Hz), 2.84 (t, 2H, JZ6.1 Hz), 2.25 (s, 3H). 13C NMR
(CDCl3, 100 MHz) d 148.4, 148.1, 140.0, 134.0, 133.1,
132.4, 129.3, 127.7, 127.5, 127.3, 126.3, 120.8, 111.8,
111.0, 55.6, 55.5, 46.4, 43.3, 28.9, 21.1. EIMS m/z (%) 423
[M]C(12), 274 (100), 268 (44), 149 (28), 137 (18), 106 (59),
98 (11). HRMS (EI) (MC) calcd for C24H25NO4S 423.1504,
found 423.1504. Anal. Calcd for C24H25NO4S: C, 68.06; H,
5.95; N, 3.31. Found: C, 68.04; H, 5.91; N, 3.28.
3.3.8. Synthesis of 8-phenylisoquinolin-4-ol (17). The
synthesis was done using the same procedure as for
compounds 10–14, using the corresponding starting
material, 8-BrIQ-4-ol (7, 250 mg, 1.12 mmol). After usual
workup the crude material was purified through silica gel
column chromatography (cyclohexane/EtOAc, 70:30)
yielded a brown solid (127 mg, 0.57 mmol, 51%). Mp:
174–176 8C. IR: 3438, 2360, 2326, 1613, 1577, 1409, 1297,