J. Zhou et al. / Tetrahedron xxx (2018) 1e7
5
(s, 1H), 6.65 (s, 1H), 6.85e6.90 (m, 3H), 7.24e7.28 (s, 1H); 13C NMR
(100 MHz, CDCl3) 28.3, 55.2, 55.9, 63.5, 79.0, 109.7, 111.2, 113.7,
114.4, 121.3, 126.0, 128.8, 129.4, 143.7, 147.3, 147.9, 159.7; IR (KBr)
3069, 3008, 2956, 2837, 1605, 1505, 1247, 1095 cm¡1; HRMS (ESI)
m/z calc. for C18H20O4 [MþNa]þ: 323.1259; found: 323.1245.
(100 MHz, CDCl3)
d
28.2, 55.9, 56.0, 63.8, 78.1, 109.3, 111.5, 123.7,
d
126.1, 127.4, 129.7, 147.6, 147.7, 148.3, 149.4; IR (KBr) 3065, 3002,
2940, 2854, 1608, 1522, 1460, 1343, 1265, 1210, 1101 cm¡1; HRMS
(ESI) m/z calc. for C17H17NO5 [MþNa]þ: 338.1004; found: 338.0991.
4.2.12. 1-(2,4-Dichlorophenyl)-6,7-dimethoxyisochroman (3k)
4.2.6. 1-(3,4-Dimethoxyphenyl)-6,7-dimethoxyisochroman (3e)
[7b]
White solid, 335 mg,99% yield;1H NMR (400 MHz, CDCl3)
d2.73e2.78 (m, 1H), 3.00e3.06 (m, 1H), 3.68 (s, 3H), 3.86e3.89 (s,
White solid, 317 mg, 96% yield; 1H NMR (400 MHz, CDCl3)
1H), 3.88 (s, 3H),4.09e4.14 (m, 1H), 6.14 (s, 1H), 6.20 (s, 1H), 6.65 (s,
1H), 7.10 (d, J ¼ 8.4 Hz, 1H), 7.17 (dd, J ¼ 2.0, 8.4 Hz, 1H), 7.46 (s, 1H);
d
2.70e2.75 (m, 1H), 3.00e3.07 (m, 1H), 3.67 (s, 3H), 3.83 (s, 3H),
3.86e3.89 (m, 1H), 3.88 (s, 6H), 4.11e4.15 (m, 1H), 5.62 (s, 1H), 6.25
(s, 1H), 6.65 (s, 1H), 6.83 (m, 3H); 13C NMR (100 MHz, CDCl3)
28.3,
13C NMR (100 MHz, CDCl3)
d28.0, 55.7, 55.8, 63.5, 74.3, 108.9, 111.2,
d
126.1, 127.1, 127.5, 129.1, 131.5, 134.2, 134.7, 138.4, 147.4, 148.0; IR
(KBr) 3058, 2982, 2913, 2842, 1615, 1502, 1467, 1255, 1216,
55.9, 55.9, 63.6, 79.1, 109.8, 110.6, 111.1111.7, 121.6, 126.1, 129.1, 134.7,
147.2, 147.9, 148.9, 149.0; IR (KBr) 3075, 2996, 2949, 2843, 1605,
1505, 1460, 1261, 1155, 1082 cm¡1; HRMS (ESI) m/z calc. for
1088 cm¡1
361.0374; found: 361.0360.
;
HRMS (ESI) m/z calc. for C17H16Cl2O3 [MþNa]þ:
C
19H22O5 [MþNa]þ: 353.1365; found: 353.1360.
4.2.13. 1-(2-Chloro-4-fluorophenyl)-6,7-dimethoxyisochroman (3l)
4.2.7. 6,7-Dimethoxy-1-(naphthalen-2-yl)isochromane (3f) [13]
White solid, 319 mg,99% yield;1H NMR (400 MHz, CDCl3)
White solid, 321 mg, 98% yield; 1H NMR (400 MHz, CDCl3)
d2.73e2.77 (m, 1H), 3.00e3.07 (m, 1H), 3.68 (s, 3H), 3.88 (s, 3H),
d
2.76e2.80 (m, 1H), 3.06e3.13 (m, 1H), 3.60 (s, 3H), 3.90 (s, 3H),
3.87e3.3.98 (m,1H), 4.11e4.14 (m,1H), 6.15 (s, 1H), 6.20 (s, 1H), 6.65
3.90e3.94 (m, 1H), 4.17e4.19 (m, 1H), 5.85 (s, 1H), 6.26 (s, 1H), 6.70
(s, 1H), 7.41 (d, J ¼ 8.4 Hz, 1H), 7.49 (t, J ¼ 6.4 Hz, 2H), 7.77 (s, 1H),
(s, 1H), 6.90e6.94 (m, 1H), 7.17e7.18 (m, 2H); 13C NMR (100 MHz,
2
CDCl3)
d
27.9, 55.5, 63.3, 74.1, 108.9, 111.1, 113.8 (d, JC-F ¼ 20.8 Hz),
7.82 (d, J ¼ 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d28.3, 55.8, 63.5,
116.3 (d, 3JC-F ¼ 24.6 Hz), 126.0, 127.7, 131.7 (d, 4JC-F ¼ 10.2 Hz), 134.6
79.2, 109.7, 111.2, 125.9, 126.0, 126.1, 126.5, 127.6, 128.0, 128.1, 128.3,
128.7, 133.0, 133.2, 139.5, 147.3, 147.9; IR (KBr) 3069, 2956, 2916,
2837, 1612,1505,1460, 1353,1261, 1207, 1088 cm¡1; HRMS (ESI) m/z
calc. for C21H20O3 [MþNa]þ: 343.1310; found: 343.1296.
(d, 5JC-F ¼ 10.2 Hz), 135.7 (d, 5JC-F ¼ 3.5 Hz), 147.3, 147.8, 161.6 (d, 1JC-
¼ 248.9 Hz); IR (KBr) 3080, 2956, 2925, 2847, 1615, 1514, 1460,
F
1257, 1218, 1093 cm¡1; HRMS (ESI) m/z calc. for C17H16ClFO3
[MþNa]þ: 345.0670; found: 345.0648.
4.2.8. 1-(4-Fluorophenyl)-6,7-dimethoxyisochroman (3g) [7b]
4.2.14. 1-Hexyl-6,7-dimethoxyisochroman (3m) [11]
White solid, 290 mg,98% yield;1H NMR (400 MHz, CDCl3)
White solid, 275 mg, 99% yield; 1H NMR (400 MHz, CDCl3)
d
2.70e2.74 (m, 1H), 3.03 (m, 1H), 3.66 (s, 3H), 3.86e3.88 (m, 1H),
d
0.87e0.90 (m, 3H), 1.27e1.38 (m, 6H), 1.44 (d, J ¼ 8.1 Hz, 2H),
3.88 (s, 3H), 4.11e4.14 (m, 1H), 5.66 (s, 1H), 6.18 (s, 1H), 6.65 (s, 1H),
1.75e1.84 (m, 2H), 2.58e2.62 (m, 1H), 2.86e2.94 (m, 1H), 3.72e3.74
(m, 1H), 3.86 (s, 3H), 4.09e4.14 (m, 1H), 4.67e4.69 (m, 1H), 6.55 (s,
7.03 (t, J ¼ 8.0 Hz, 2H), 7.28 (t, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz,
2
CDCl3)
d
28.4, 56.0, 63.7, 78.5, 109.7, 111.3, 115.3 (d, JC-F ¼ 21.3 Hz),
1H), 6.59 (s, 1H); 13C NMR (100 MHz, CDCl3)
d14.1, 22.7, 25.3, 28.7,
3
4
126.2, 128.8, 130.7 (d, JC-F ¼ 8.2 Hz), 138.2 (d, JC-F ¼ 3.0 Hz), 147.4,
29.5, 31.9, 36.2, 55.9, 56.1, 63.2, 75.6, 108.0, 111.5, 126.0, 130.5, 147.5;
IR (KBr) 2925, 2854, 1686, 1506, 1452, 1249, 1101 cm¡1; HRMS (ESI)
m/z calc. for C17H26O3 [MþNa]þ: 301.1780; found: 301.1770.
1
148.0, 162.6 (d, JC-F ¼ 245.0 Hz); IR (KBr) 3073, 2971, 2917, 2847,
1600, 1514, 1467, 1257, 1218, 1086 cm¡1; HRMS (ESI) m/z calc. for
C
17H17FO3 [MþNa]þ: 311.1059; found: 311.1050.
4.2.15. 1-Butyl-6,7-dimethoxyisochroman (3n) [11].
4.2.9. 1-(4-Chlorophenyl)-6,7-dimethoxyisochroman (3h) [7b]
White solid, 243 mg, 97% yield; 1H NMR (400 MHz, CDCl3)
White solid, 301 mg,99% yield;1H NMR (400 MHz, CDCl3)
d0.92e0.94 (m, 3H), 1.36e1.47 (m, 4H), 1.74e1.88 (m, 2H),
d
2.71e2.75 (m, 1H), 3.01e3.05 (m, 1H), 3.67 (s, 3H), 3.86e3.89 (m,
2.58e2.62 (m, 1H), 2.8e2.92 (m, 1H), 3.71e3.76 (m, 1H), 3.85 (s,
6H), 4.11e4.12 (m, 1H), 4.67 (d, J ¼ 8.0 Hz, 1H), 6.56 (s, 1H), 6.59 (s,
1H), 3.88 (s, 3H), 4.11e4.13 (m, 1H), 5.66 (s, 1H), 6.18 (s, 1H), 6.65 (s,
1H), 7.24 (d, J ¼ 8.0 Hz, 2H), 7.32 (d, J ¼ 8.0 Hz, 2H); 13C NMR
1H); 13C NMR (100 MHz, CDCl3)
d13.9, 22.6, 27.2, 28.5, 35.6, 55.6,
(100 MHz, CDCl3)
d28.3, 55.9, 63.6, 78.4, 109.6, 111.3, 126.1, 128.4,
55.8, 62.9, 75.3, 107.7, 111.3, 125.8, 130.3, 147.2; IR (KBr) 2948, 2847,
128.6, 130.3, 133.9, 140.8, 147.4, 148.0; IR (KBr) 3065, 2963, 2932,
2831, 1608, 1514, 1467, 1249, 1218, 1086 cm¡1; HRMS (ESI) m/z calc.
for C17H17ClO3 [MþNa]þ: 327.0764; found: 327.0749.
1608, 1514, 1467, 1335, 1249, 1109 cm¡1; HRMS (ESI) m/z calc. for
C
15H22O3 [MþNa]þ: 273.1467; found: 273.1461.
4.2.16. (E)-6,7-Dimethoxy-1-(1-phenylprop-1-en-2-yl)isochroman
4.2.10. 4-(6,7-Dimethoxyisochroman-1-yl)benzonitrile (3i) [11]
(3o)
White solid, 292 mg,99% yield;1H NMR (400 MHz, CDCl3)
White solid, 285 mg, 92% yield; 1H NMR (400 MHz, CDCl3)
d1.76
d
2.73e2.77 (m, 1H), 3.00e3.07 (m, 1H), 3.66 (s, 3H), 3.87e3.89 (m,
(s, 3H), 2.59e2.63 (m, 1H), 3.05 (m, 1H), 3.80 (s, 3H), 3.85e3.90 (m,
1H), 3.89 (s, 3H), 4.20e4.30 (m,1H), 5.21 (s,1H), 6.60 (s,1H), 6.65 (d,
J ¼ 3.2 Hz, 2H), 7.26 (s, 1H), 7.36 (s, 4H); 13C NMR (100 MHz, CDCl3)
1H), 3.88 (s, 3H), 4.10e4.12 (m, 1H), 5.71 (s, 1H), 6.15 (s, 1H), 6.67 (s,
1H), 7.43 (d, J ¼ 7.6 Hz, 2H), 7.64 (d, J ¼ 7.6 Hz, 2H); 13C NMR
(100 MHz, CDCl3)
d28.2, 56.0, 56.1, 63.8, 78.4, 109.5, 111.6, 112.1,
d13.7, 28.4, 55.9, 56.0, 64.1, 83.7, 108.6, 111.4, 126.6, 126.8, 127.9,
118.8, 126.2, 127.5, 129.6, 132.3, 147.5, 147.6, 148.4; IR (KBr) 3080,
2956, 2932, 2831, 2356, 2215, 1615, 1506, 1467, 1296, 1241,
1093 cm¡1; HRMS (ESI) m/z calc. for C18H17NO3 [MþNa]þ: 318.1106;
found: 318.1086.
128.2, 129.1, 130.3, 137.4, 138.6, 147.6, 147.9; IR (KBr) 3065, 2963,
2925, 2847, 1608, 1506, 1467, 1350, 1249, 1218, 1086 cm¡1; HRMS
(ESI) m/z calc. for C20H22O3 [MþNa]þ: 333.1467; found: 333.1461.
4.2.17. 6-Methoxy-1-(4-methoxyphenyl)isochroman (3p) [11]
4.2.11. 6,7-Dimethoxy-1-(4-nitrophenyl)isochroman (3j) [11]
White solid, 254 mg, 94% yield; 1H NMR (400 MHz, CDCl3)
d2.77e2.81 (m, 1H), 3.10e3.17 (m, 1H), 3.80 (s, 3H), 3.89e3.95 (m,
White solid, 315 mg,99% yield;1H NMR (400 MHz, CDCl3)
d
2.73e2.77 (m, 1H), 3.01e3.09 (m, 1H), 3.65 (s, 3H), 3.87e3.89 (s,
1H), 4.18e4.20 (m, 1H), 5.68 (s, 1H), 6.66 (d, J ¼ 8.4 Hz, 1H), 6.71 (d,
1H), 3.88 (s, 3H), 4.10e4.14 (m, 1H), 5.75 (s, 1H), 6.15 (s, 1H), 6.67 (s,
J ¼ 8.6 Hz, 2H), 6.89 (d, J ¼ 8.6 Hz, 2H), 6.93 (d, J ¼ 7.6 Hz,1H), 7.28 (t,
1H), 7.49 (d, J ¼ 8.0 Hz, 2H), 8.19 (d, J ¼ 8.0 Hz, 2H); 13C NMR
J ¼ 7.7 Hz, 1H);13C NMR (100 MHz, CDCl3)
d29.1, 55.2, 63.8, 79.3,
Please cite this article in press as: J. Zhou, et al., Synthesis of isochromans via Fe(OTf)2-catalyzed Oxa-PicteteSpengler cyclization, Tetrahedron