M. Ariza, A. Díaz, R. Suau, M. Valpuesta
FULL PAPER
OMe), 52.0 (COOMe), 50.6, 50.5 (C-4, CH
2
Ph), 46.6 (N-Me), 37.4
7,8-Dimethoxy-2-(methoxycarbonyl)-N-methyl-1-(2-thienyl)-2,3,4,5-
tetrahydro-1H-3-benzazepine (5h): A mixture of isomers of 5h
(77 mg, 93%) were obtained in a cis/trans ratio 1:4 from the salts
4h (cis/trans 1:4, 100 mg, 0.23 mmol). Both isomers of 5h were iso-
(
1
C-5) ppm. IR (neat): ν˜ = 3050, 2930, 1732, 1605, 1514, 1494, 1452,
382 cm . t = 9.40 min. EI-MS: m/z (%) = 369 (7), 311 (21), 310
R
–1
+
(100), 219 (76). HRMS: calcd. for C22
4
H28NO [M + H] 370.2018;
found 370.2012.
2
lated by colunm chromatography (SiO ; cyclohexane/EtOAc, 6:4)
to yield 5h-trans (62 mg, 75%) and 5h-cis (15 mg, 18%).
(
1S,2S)-1-(3Ј,4Ј-Dimethoxybenzyl)-7,8-methylenedioxy-2-(meth-
5
h-trans: Pale yellow solid; m.p. 83–85 °C. 1H NMR (400 MHz,
CDCl , 25 °C): δ = 7.16 (d, J = 4.9 Hz, 1 H, 5Ј-H Ar), 6.89 (dd, J
4.9, 3.5 Hz, 1 H, 4Ј-H Ar), 6.69 (d, J = 3.5 Hz, 1 H, 3Ј-H Ar),
.63, 6.59 (2ϫ s, 1 H each, 6-H, 9-H), 4.76 (d, J = 5.9 Hz, 1 H, 1-
oxycarbonyl)-N-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (5e-
trans): Benzazepine 5e-trans (70 mg, 85%) was obtained from the
salt 4e-trans (100 mg, 0.20 mmol) after heating to reflux for 3 h as a
3
=
6
1
pale yellow oil. [α]
CDCl , 25 °C): δ = 6.78–6.68 (m, 3 H, CH
.47 (br. s, 1 H, 9-H), 5.88 (s, 2 H, OCH O), 3.84, 3.83 (2ϫ s, 3 H
each, 2ϫ OMe), 3.46 (s, 3 H, COOMe), 3.40–3.31 (m, 4 H, 1-H,
-H, 4Ј-H, 5-H), 3.33 (d, J = 9.9 Hz, 1 H, 2-H), 2.92–2.75 (m, 2
H, CH Ar, 5Ј-H), 2.62–2.58 (m, 1 H, CH Ar), 2.52 (s, 3 H, N-Me)
ppm. 13C NMR (100 MHz, CDCl
, 25 °C): δ = 172.3 (CO), 148.6,
47.4, 146.0, 145.6 (C-7, C-8, C-3Ј, C-4Ј), 134.1, 133.5, 133.1 (C-
Ј, C-5a, C-9a), 121.1 (C-6Ј), 112.6, 111.2, 110.8, 110.5 (C-2Ј, C-
Ј, C-6, C-9), 100.7 (OCH O), 65.9 (C-2), 59.8 (C-1), 55.8, 55.7
Ar), 46.5 (N-Me),
6.7 (C-5) ppm. IR (neat): ν˜ = 3033, 2932, 1733, 1613, 1513, 1485,
D
= +48, (c = 1.3, CH
2
Cl
2
). H NMR (400 MHz,
H), 4.09 (d, J = 5.9 Hz, 1 H, 2-H), 3.83, 3.79 (2ϫ s, 3 H each, 2ϫ
OMe), 3.56 (s, 3 H, COOMe), 3.27 (ddd, J = 12.9, 10.4, 2.7 Hz, 1
H, 4-H), 2.94 (ddd, J = 14.2, 10.4, 3.5 Hz, 1 H, 5-H), 2.71 (ddd, J
3
2
Ar), 6.54 (s, 1 H, 6-H),
6
2
=
1
12.9, 6.2, 3.5 Hz, 1 H, 4Ј-H), 2.57 (s, 3 H, N-Me), 2.57–2.51 (m,
H, 5Ј-H) ppm. C NMR (100 MHz, CDCl , 25 °C): δ = 171.5
3
4
1
3
2
2
(
CO), 147.6, 146.7, 144.8 (C-7, C-8, C-2Ј), 133.5, 130.8 (C-5a, C-
3
9
6
a), 126.2, 125.1, 123.9 (C-3Ј, C-4Ј, C-5Ј), 113.8, 113.2 (C-6, C-9),
8.0 (C-2), 55.9, 55.6 (2ϫ OMe), 50.8 (COOMe), 50.1 (C-1), 48.8
1
1
5
(
3
1
(
C-4), 45.9 (N-Me), 34.7 (C-5) ppm. IR (neat): ν˜ = 3006, 2934,
2
–
1
1
736, 1607, 1513, 1448, 1381 cm . t
R
= 9.18 min. EI-MS: m/z (%)
361 (9) [M] , 303 (19), 302 (100). HRMS: calcd. for C19
M + H]+ 362.1420; found 362.1410.
2ϫ OMe), 52.1, 50.7, 50.4 (C-4, COOMe, CH
2
+
=
[
4
H24NO S
–1
R
450, 1368 cm . t = 13.71 min. EI-MS: m/z (%) = 414 (3), 413
5h-cis: Pale yellow oil. 1H NMR (400 MHz, CDCl , 25 °C): δ =
+
(
14) [M] , 355 (22), 354 (100), 262 (7), 203 (25), 151 (65). HRMS:
3
+
7.21 (d, J = 4.9 Hz, 1 H, 5Ј-H Ar), 7.10 (d, J = 3.5 Hz, 1 H, 3Ј-H
Ar), 6.97 (dd, J = 4.9, 3.5 Hz, 1 H, 4Ј-H Ar), 6.62, 6.48 (2ϫ s, 1
H each, 6-H, 9-H), 5.03 (br. s, 1 H, 1-H), 4.00 (br. s, 1 H, 2-H),
3.83, 3.65 (2ϫ s, 3 H each, 2ϫ OMe), 3.54 (s, 3 H, COOMe), 3.25–
3.17 (m, 2 H, 4-H, 5-H), 2.84–2.73 (m, 2 H, 4Ј-H, 5Ј-H), 2.51 (s, 3
calcd. for C23
6
H28NO [M + H] 414.1917; found 414.1909.
(
1R*,2R*)-7,8-Dimethoxy-2-(methoxycarbonyl)-N-methyl-1-naphth-
yl-2,3,4,5-tetrahydro-1H-3-benzazepine (5f-trans): Benzazepine 5f-
trans (74 mg, 91%) was obtained from the salt 4f-trans (100 mg,
0
1
H, N-Me) ppm. 13C NMR (100 MHz, CDCl , 25 °C): δ = 171.0
.27 mmol) as a white solid; m.p. 70–72 °C. H NMR (200 MHz,
3
CDCl
3
, 25 °C): δ = 7.87–7.78 (m, 3 H, 2Ј-H, 4Ј-H, 8Ј-H Ar), 7.58–
(CO), 147.2, 146.8, 144.4 (C-7, C-8, C-2Ј), 132.6, 132.5 (C-5a, C-
7
.33 (m, 4 H, 3Ј-H, 5Ј-H, 6Ј-H, 7Ј-H Ar), 6.75 (s, 1 H, 6-H), 6.11 9a), 126.5, 126.4, 124.5 (C-3Ј, C-4Ј, C-5Ј), 112.5, 112.3 (C-6, C-9),
s, 1 H, 9-H), 5.40 (d, J = 8.8 Hz, 1 H, 1-H), 4.12 (d, J = 8.8 Hz, 69.2 (C-2), 55.9, 55.8 (2ϫ OMe), 51.4 (C-1), 51.0 (COOMe), 47.6
H, 2-H), 3.85, 3.54 (2ϫ s, 3 H each, 2ϫ OMe), 3.32 (s, 3 H,
(C-4), 44.6 (N-Me), 34.6 (C-5) ppm. IR (neat): ν˜ = 3068, 2932,
COOMe), 3.46–3.09 (m, 2 H, 4-H, 5-H), 2.96–2.74 (m, 2 H, 4Ј-H, 1735, 1607, 1461, 1449, 1377 cm . t
(
1
–
1
R
= 9.43 min. EI-MS: m/z (%)
, 303 (19), 302 (100). HRMS: calcd. for C H NO S
Ј-H), 2.44 (s, 3 H, N-Me) ppm. 13C NMR (50 MHz, CDCl
,
= 361 (9) [M]
+
19 24
4
5
2
1
3
[M + H]+ 362.1420; found 362.1432.
5 °C): δ = 172.5 (CO), 147.3, 146.9 (C-7, C-8), 134.2, 131.6, 131.1,
28.8, 127.9, 126.5, 125.8, 125.4, 125.1, 125.0, 124.8, 124.7 (C-5a,
7
,8-Dimethoxy-1-(2-furyl)-2-(methoxycarbonyl)-N-methyl-2,3,4,5-
tetrahydro-1H-3-benzazepine (5i): A mixture of isomers of 5i
74 mg, 92%) were obtained in a cis/trans ratio 1:1 from the salt
i-cis (100 mg, 0.23 mmol). Both isomers of 5i were isolated by
colunm chromatography (SiO ; cyclohexane/EtOAc, 6:4) to yield
i-trans (37 mg, 46%) and 5i-cis (37 mg, 46%).
C-9a, Cquat, CH Ar), 112.3, 112.0 (C-6, C-9), 68.3 (C-2), 55.7, 55.5
2ϫ OMe), 51.9 (C-1), 51.0 (COOMe), 49.7 (C-4), 45.1 (N-Me),
(
(
4
32.9 (C-5) ppm. IR (neat): ν˜ = 3052, 2934, 1725, 1598, 1508, 1449,
–1
+
1398 cm . t
R
= 14.20 min. EI-MS: m/z (%) = 405 (9) [M] , 347
2
(23), 346 (100), 289 (19). HRMS: calcd. for C25
H28NO
4
[M + H]+
5
5
406.2013; found 406.2003.
1
3
i-trans: Yellow oil. H NMR (200 MHz, CDCl , 25 °C): δ = 7.34
(
d, J = 1.8 Hz, 1 H, 5Ј-H Ar), 6.60, 6.50 (2ϫ s, 1 H each, 6-H, 9-
H), 6.26 (dd, J = 3.0, 1.8 Hz, 1 H, 4Ј-H Ar), 5.94 (d, J = 3.0 Hz,
H, 3Ј-H Ar), 4.60 (d, J = 6.7 Hz, 1 H, 1-H), 4.13 (d, J = 6.7 Hz,
1 H, 2-H), 3.82, 3.75, 3.56 (3ϫ s, 3 H each, 3ϫ OMe), 3.27–2.95
m, 2 H, 4-H, 5-H), 2.73–2.56 (m, 2 H, 4Ј-H, 5Ј-H), 2.47 (s, 3 H,
(
1R*,2R*)-7,8-Dimethoxy-2-(methoxycarbonyl)-N-methyl-1-(1-
methyl-1H-2-pyrrolyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (5g-
trans): Benzazepine 5g-trans (74 mg, 90%) was obtained from the
salt 4g-trans (100 mg, 0.23 mmol) as a yellow oil. H NMR
1
1
(
(200 MHz, CDCl
3
, 25 °C): δ = 6.68 (s, 1 H, 6-H), 6.57 (dd, J = 2.4,
.5 Hz, 1 H, 5Ј-H Ar), 6.19 (dd, J = 3.7, 2.4 Hz, 1 H, 3Ј-H Ar),
.10 (t, J = 3.7 Hz, 1 H, 4Ј-H Ar), 6.06 (s, 1 H, 9-H), 4.64 (d, J =
0.1 Hz, 1 H, 1-H), 3.84, 3.63, 3.60 (3ϫ s, 3 H each, 3ϫ OMe),
.75 (d, J = 10.1 Hz, 1 H, 2-H), 3.30–3.20 (m, 1 H, 4-H), 3.25 (s,
1
3
N-Me) ppm. C NMR (50 MHz, CDCl
1
5
(
4
1607, 1512, 1461, 1450, 1381 cm . t = 8.25 min. EI-MS: m/z (%)
R
=
C
3
, 25 °C): δ = 171.6 (CO),
53.9 (C-2Ј), 147.6, 146.8 (C-7, C-8), 141.3 (C-5Ј), 133.3, 128.9 (C-
a, C-9a), 113.6, 113.0, 110.1, 107.4 (C-6, C-9, C-3Ј, C-4Ј), 66.3
1
6
1
3
3
5
2
C-2), 55.8, 55.7 (2ϫ OMe), 50.9 (COOMe), 50.0 (C-1), 47.2 (C-
), 45.5 (N-Me), 34.3 (C-5) ppm. IR (neat): ν˜ = 3080, 2933, 1734,
H, N-Me Ar), 3.09–2.99 (m, 1 H, 5-H), 2.86–2.60 (m, 2 H, 4Ј-H,
–
1
Ј-H), 2.36 (s, 3 H, N-Me) ppm. 1 C NMR (50 MHz, CDCl
3
3
,
+
346 (7), 345 (30) [M] , 287 (32), 286 (100). HRMS: calcd. for
5 °C): δ = 172.0 (CO), 147.3, 147.2 (C-7, C-8), 130.7, 130.6, 130.2
C-2Ј, C-5a, C-9a), 122.2 (C-5Ј), 111.8, 110.6, 107.4, 106.5 (C-6, C-
H24NO
5
[M + H]+ 346.1649; found 346.1649.
19
(
9
1
, C-3Ј, C-4Ј), 67.3 (C-2), 55.7, 55.6 (2ϫ OMe), 51.0 (COOMe), 5i-cis: Yellow oil. H NMR (200 MHz, CDCl
3
, 25 °C): δ = 7.33 (br.
4
8.8 (C-1), 44.9 (C-4), 41.0 (N-Me), 33.5 (N-Me Ar), 32.2 (C-5) s, 1 H, 5Ј-H Ar), 6.61 (br. s, 1 H, 4Ј-H Ar), 6.33, 6.32 (2ϫ s, 1 H
–
1
ppm. IR (neat): ν˜ = 3031, 1722, 1607, 1508, 1462, 1376 cm . t
R
=
each, 6-H, 9-H), 6.24 (br. s, 1 H, 3Ј-H Ar), 4.80 (br. s, 1 H, 1-H),
.79 min. EI-MS: m/z (%) = 359 (9), 358 (38) [M] , 300 (23), 299 3.98 (br. s, 1 H, 2-H), 3.81, 3.64, 3.52 (3ϫ s, 3 H each, 3ϫ OMe),
100), 257 (36), 256 (81), 242 (48). HRMS: calcd. for C20 3.27–3.05 (m, 2 H, 4-H, 5-H), 2.87–2.72 (m, 2 H, 4Ј-H, 5Ј-H), 2.45
M + H]+ 359.1965; found 359.1964.
+
8
(
[
27 2 4
H N O
13
3
(s, 3 H, N-Me) ppm. C NMR (50 MHz, CDCl , 25 °C): δ = 170.8
6516
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Eur. J. Org. Chem. 2011, 6507–6518