M. Lafrance, N. Blaquiere, K. Fagnou
FULL PAPER
tert-Butyl 1-[(5-Bromobenzo[d][1,3]dioxol-6-yl)methyl]-3,4-dihydro-
6,7-dimethoxyisoquinoline-2(1H)-carboxylate (9d): The carbamate
was prepared following the general procedure (71%), m.p. 145–
127.8, 130.0, 131.3, 137.7, 145.8, 146.1, 154.1 ppm. HRMS calcd.
for C18H15BrNO3 (M+ – C4H9O) 372.0235; found: 372.0224.
tert-Butyl 1-(2-Bromobenzyl)-3,4-dihydro-6-methoxyisoquinoline-
2(1H)-carboxylate (9g): The carbamate was prepared following the
146 °C (CHCl ). ν
= 2985, 1688, 1518, 13.64, 1165, 1099, 1038.
˜
3
max
1H NMR analysis revealed the presence of two amide rotamers
general procedure (86%), m.p. 112–113 °C (CHCl ). ν
= 2999,
˜
3
max
1
present in a 4:1 ratio. H NMR (300 MHz, CDCl3, 293 K, TMS,
1679, 1502, 1461, 1422, 1365, 1239, 1170. NMR analysis revealed
the presence of two amide rotamers present in a 5:1 ratio. 1H NMR
(300 MHz, CDCl3, 293 K, TMS, major rotamer): δ = 1.08 (s, 9 H),
2.68–2.75 (m, 1 H), 2.79–3.10 (m, 2 H), 3.23–3.33 (m, 2 H), 3.80
(s, 3 H), 4.39 (dd, J = 13.2, 4.7 Hz, 1 H), 5.42 (dd, J = 10.9, 2.8 Hz,
1 H), 6.68 (d, J = 2.5 Hz, 1 H), 6.81 (dd, J = 8.5, 2.6 Hz, 1 H),
7.01–7.24 (m, 3 H), 7.31 (d, J = 8.5 Hz, 1 H), 7.56 (dd, J = 7.8,
1.0 Hz, 1 H); minor rotamer: 1.32 (s, 9 H), 2.68–2.75 (m, 1 H),
2.79–3.10 (m, 2 H), 3.23–3.33 (m, 1 H), 3.84–3.48 (m, 1 H), 3.78
(s, 3 H), 3.96 (dt, J = 12.9, 5.1 Hz, 1 H), 5.47 (dd, J = 9.6, 5.0 Hz,
1 H), 6.64 (m, 1 H), 6.71 (dd, J = 8.5, 2.4 Hz, 1 H), 7.01–7.24 (m,
4 H), 7.50 (d, J = 7.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3,
293 K, TMS, major rotamer): δ = 27.9, 27.9, 35.9, 42.9, 55.3, 53.5,
79.4, 112.8, 113.3, 125.3, 127.5, 128.1, 128.2, 129.5, 131.8, 132.5,
135.8, 138.2, 154.3, 158.1; (peaks corresponding to the minor rot-
amer were also detected): 28.3, 29.1, 37.5, 42.5, 53.6, 55.2, 79.4,
112.2, 113.2, 127.0, 127.9, 129.3, 129.5, 130.2, 131.4 ppm. HRMS
calcd. for C18H17BrNO2 (M+ – C4H9O) 358.0443; found: 358.0393.
major rotamer): δ = 1.20 (s, 9 H), 2.61–2.66 (m, 1 H), 2.84–2.92
(m, 2 H), 3.14–3.26 (m, 2 H), 3.85 (s, 6 H), 4.36 (d, J = 12.0 Hz, 1
H), 5.28–5.31 (m, 1 H), 5.90 (d, J = 11.7 Hz, 1 H), 6.57 (s, 1 H),
6.62 (s, 1 H), 6.78 (s, 1 H), 7.02 (s, 1 H); minor rotamer: 1.38 (s, 9
H), 2.61–2.66 (m, 1 H), 2.84–2.92 (m, 2 H), 3.14–3.26 (m, 1 H),
3.33–3.41 (m, 1 H), 3.77 (s, 6 H), 4.00–4.09 (m, 1 H), 5.28–5.31 (m,
1 H), 5.90 (d, J = 11.7 Hz, 1 H), 6.57 (s, 1 H), 6.62 (s, 1 H), 6.96
(s, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 293 K, TMS, major
rotamer): δ = 27.7, 27.9, 35.9, 42.1, 53.6, 55.5, 55.6, 79.0, 101.3,
109.4, 111.0, 111.1, 112.0, 114.9, 126.1, 128.4, 130.9, 146.9, 146.9,
147.0, 147.5, 153.8; (peaks corresponding to the minor rotamer
were also detected): 27.8, 28.0, 38.2, 41.6, 53.4, 79.0, 101.1, 109.8,
110.5, 110.8, 115.1, 125.9, 130.8, 146.5, 146.7, 147.3 ppm. HRMS
calcd. for C20H19BrNO6 (M+ – C4H9O) 432.0450; found: 432.0418.
tert-Butyl 1-[(1-Bromonaphth-2-yl)methyl]-3,4-dihydro-6,7-dimeth-
oxyisoquinoline-2(1H)-carboxylate (9e): The carbamate was pre-
pared following the general procedure (87 %), m.p. 144–145 °C
(CHCl ). ν
= 2933, 1687, 1519, 1391, 1364, 1241, 1165, 1165.
˜
3
max
tert-Butyl 1-(2-Bromobenzyl)-3,4-dihydro-7-methoxyisoquinoline-
2(1H)-carboxylate (9h): The carbamate was prepared following the
NMR analysis revealed the presence of two amide rotamers present
in a 5:1 ratio. 1H NMR (300 MHz, CDCl3, 293 K, TMS, major
rotamer): δ = 0.84 (s, 9 H), 2.66–2.71 (m, 1 H), 2.87–2.98 (m, 1 H),
3.17–3.27 (m, 1 H), 3.31–3.41 (m, 1 H), 3.53–3.59 (m, 1 H), 3.82
(s, 3 H), 3.87 (s, 3 H), 4.41 (dd, J = 13.2, 4.5 Hz, 1 H), 5.49 (dd, J
= 10.6, 4.0 Hz, 1 H), 6.63 (s, 1 H), 6.82 (s, 1 H), 7.20 (d, J = 8.3 Hz,
1 H), 7.48 (dd, J = 7.0, 7.0 Hz, 1 H), 7.59 (dd, J = 7.0, 7.0 Hz, 1
H), 7.72 (d, J = 8.3 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 1 H), 8.34 (d, J
= 8.5 Hz, 1 H); minor rotamer: 1.32 (s, 9 H), 2.66–2.71 (m, 1 H),
2.77–2.82 (m, 1 H), 3.17–3.27 (m, 1 H), 3.31–3.41 (m, 1 H), 3.53–
3.59 (m, 1 H), 3.82 (s, 3 H), 3.83 (s, 3 H), 3.95 (dt, J = 13.2, 4.8 Hz,
1 H), 5.49 (m, 1 H), 6.28 (s, 1 H), 6.59 (s, 1 H), 7.37 (d, J = 8.3 Hz,
1 H), 7.42–7.81 (m, 4 H), 8.27 (d, J = 8.5 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3, 293 K, TMS, major rotamer): δ = 27.5, 28.1,
31.5, 36.3, 43.6, 53.9, 55.8, 79.1, 109.7, 111.3, 124.6, 126.0, 126.4,
126.8, 127.3, 127.3, 127.9, 128.8, 128.9, 132.2, 133.4, 136.3, 147.3,
147.8, 154.1; (peaks corresponding to the minor rotamer were also
detected): 28.8, 35.1, 43.5, 54.7, 56.0, 79.9, 110.7, 111.5, 125.6,
126.4, 126.9, 127.6, 128.0, 128.3, 129.0, 133.8, 136.7, 147.4, 148.1,
154.9 ppm. HRMS calcd. for C23H21BrNO3 (M+ – C4H9O)
438.0700; found: 438.0656.
general procedure (57%), m.p. 113–115 °C (CHCl ). ν
= 2999,
˜
3
max
1679, 1502, 1461, 1422, 1365, 1239, 1170. NMR analysis revealed
the presence of two amide rotamers present in a 5:1 ratio. 1H NMR
(300 MHz, CDCl3, 293 K, TMS, major rotamer): δ = 1.08 (s, 9 H),
2.66–2.73 (m, 1 H), 2.76–3.15 (m, 2 H), 3.24–3.34 (m, 2 H), 3.82
(s, 3 H), 4.38 (dd, J = 13.3, 4.8 Hz, 1 H), 5.44 (dd, J = 11.2, 2.9 Hz,
1 H), 6.78 (dd, J = 8.4, 2.5 Hz, 1 H), 6.93 (d, J = 2.5 Hz, 1 H),
7.00–7.23 (m, 4 H), 7.58 (d, J = 7.9 Hz, 1 H); minor rotamer: 1.32
(s, 9 H), 2.66–2.73 (m, 1 H), 2.76–3.15 (m, 2 H), 3.24–3.34 (m, 1
H), 3.39–3.48 (m, 1 H), 3.71 (s, 3 H), 3.97 (dt, J = 12.6, 5.3 Hz, 1
H), 5.49 (dd, J = 9.7, 5.0 Hz, 1 H),, J = 2.1, 1 H Hz 6.63 (d), 6.74
(dd, J = 8.7, 2.7 Hz, 1 H), 7.00–7.23 (m, 4 H), 7.51 (d, J = 7.9 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3, 293 K, TMS, major rot-
amer): δ = 27.7, 27.8, 36.3, 42.7, 54.0, 55.3, 79.4, 112.0, 112.8,
125.3, 126.5, 127.4, 128.2, 130.0, 131.8, 132.5, 138.0, 138.2, 154.2,
157.8; (peaks corresponding to the minor rotamer were also de-
tected): 27.7, 28.3, 38.9, 42.0, 54.2, 55.2, 111.8, 113.0, 127.0, 129.4,
131.4, 137.9, 154.3 ppm. HRMS calcd. for C18H17BrNO2 (M+
C4H9O) 358.0443; found: 358.0417.
–
tert-Butyl 3,4-Dihydro-1-(2-iodobenzyl)isoquinoline-2(1H)-carboxyl-
tert-Butyl 5-(2-Bromobenzyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquin- ate (9j): The carbamate was prepared following the general pro-
oline-6(5H)-carboxylate (9f): The carbamate was prepared follow- cedure (82%), m.p. 105–107 °C (CHCl ). ν = 2976, 1690, 1419,
ing the general procedure (70%), m.p. 131–132 °C (CHCl ). ν
˜
3
max
=
max
1364, 1245, 1164, 1121. 1H NMR analysis revealed the presence of
two amide rotamers present in a 4:1 ratio. 1H NMR (300 MHz,
CDCl3, 293 K, TMS, major rotamer): δ = 1.07 (s, 9 H), 2.75–2.80
(m, 1 H), 2.95–3.35 (m, 4 H), 4.42 (dd, J = 13.9, 5.2 Hz, 1 H), 5.44
(dd, J = 10.9, 2.7 Hz, 1 H), 6.96 (t, J = 7.8 Hz, 1 H), 7.07–7.29 (m,
5 H), 7.53 (d, J = 7.4 Hz, 1 H), 7.86 (d, J = 7.8 Hz, 1 H); minor
rotamer: 1.33 (s, 9 H), 2.75–2.80 (m, 1 H), 2.95–3.35 (m, 4 H), 3.98
(dt, J = 13.1, 4.8 Hz, 1 H), 5.49 (dd, J = 9.3, 5.4 Hz, 1 H), 6.88 (t,
J = 7.6 Hz, 1 H), 7.07–7.29 (m, 5 H), 7.53 (d, J = 7.4 Hz, 1 H),
7.78 (d, J = 7.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 293 K,
TMS, major rotamer): δ = 28.0, 28.6, 36.2, 46.9, 79.5, 101.7, 126.1,
˜
3
2979, 1693, 1481, 1416, 1249, 1166, 1040. 1H NMR analysis re-
vealed the presence of two amide rotamers present in a 4:1 ratio.
1H NMR (300 MHz, CDCl3, 293 K, TMS, major rotamer): δ =
1.07 (s, 9 H), 2.60–2.65 (m, 1 H), 2.72–3.07 (m, 2 H), 3.22–3.30 (m,
2 H), 4.36 (dd, J = 13.0, 3.9 Hz, 1 H), 5.36 (dd, J = 11.1, 1.7 Hz,
1 H), 5.91 (s, 2 H), 6.59 (s, 1 H), 6.88 (s, 1 H), 7.06–7.26 (m, 3 H),
7.56 (d, J = 7.7 Hz, 1 H); minor rotamer: 1.31 (s, 9 H), 2.60–2.65
(m, 1 H), 2.72–3.07 (m, 2 H), 3.22–3.30 (m, 2 H), 3.35–3.44 (m, 1
H), 3.94 (dt, J = 13.2, 4.1 Hz, 1 H), 5.42 (d, J = 4.6 Hz, 1 H), 5.92
(s, 2 H), 6.56 (s, 1 H), 6.62 (s, 1 H), 7.06–7.26 (m, 3 H), 7.51 (d, J
= 7.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 293 K, TMS, 126.8, 127.1, 128.4, 128.4, 129.2, 131.0, 134.5, 137.2, 139.2, 141.2,
major rotamer): δ = 27.7, 28.5, 35.9, 42.6, 53.8, 79.3, 100.8, 106.7,
108.5, 125.2, 127.4, 127.4, 130.1, 131.7, 132.4, 137.9, 146.0, 146.3,
154.0 (peaks corresponding to the minor rotamer were also de-
tected): 28.2, 28.7, 38.5, 42.0, 53.8, 79.2, 100.7, 107.1, 108.2, 126.9,
154.3; (peaks corresponding to the minor rotamer were also de-
tected): 28.4, 28.8, 38.9, 46.5, 79.3, 101.7, 126.1, 126.7, 127.4, 128.1,
128.3, 129.7, 130.6, 136.9, 154.3 ppm. HRMS calcd. for
C17H15INO (M+ – C4H9O) 376.0198; found: 376.0231.
820
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Eur. J. Org. Chem. 2007, 811–825