A. B. J. Bracca, T. S. Kaufman
FULL PAPER
was chromatographed, providing 16 (550 mg, 100%), as an oil. IR
3.37 (s, 3 H, CHOCH3), 3.57 (dd, J = 6.3, 15.7 Hz, 1 H, CH2CH),
(film): ν = 2933, 2857, 1733, 1601, 1493, 1372, 1239, 1083, 961, 801 3.80 (s, 3 H, OCH3-1), 3.82 (s, 3 H, OCH3-2), 4.39 (dd, J = 3.5,
˜
1
cm–1. H NMR (200.13 MHz): δ = 0.70–0.98 (m, 2 H), 1.00–1.40
6.3 Hz, 1 H, CHOCH3), 5.75 (dd, J = 4.7, 12.4 Hz, 1 H, 5-H), 6.68
(d, J = 8.7 Hz, 1 H, 4-H), 7.14 (d, J = 8.7 Hz, 1 H, 3-H), 7.74 (d,
(m, 2 H), 1.45–1.70 (m, 4 H), 1.85–2.17 (m, 4 H), 1.97 (s, 3 H,
CH3CO2), 2.95 (dt, J = 7.2, 14.2 Hz, 1 H, 12-H), 3.00 (dt, J = 5.1, J = 8.9 Hz, 2 H, Har-2, Har-6), 8.16 (d, J = 8.9 Hz, 2 H, 3-Har, 5-
14.2 Hz, 1 H, 12-H), 3.82 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3),
Har) ppm. 13C NMR (50.33 MHz): δ = 20.39 (C-9), 20.54 (C-8),
6.43 (dd, J = 5.9, 11.0 Hz, 1 H, 5-H), 6.85 (d, J = 8.6 Hz, 1 H, 3-
23.39 (C-7), 25.24 (C-12), 26.86 (C-10), 27.71 (C-11), 34.51 (C-6),
H), 7.09 (d, J = 8.6 Hz, 1 H, 4-H) ppm. 13C NMR (50.33 MHz): δ 46.92 (CH2CH), 54.87 (CHOCH3), 55.40 (CHOCH3),* 55.48 (2-
= 20.50, 20.90, 21.29 (CH3CO2), 23.35, 24.60, 26.17, 27.95, 35.63 OCH3),* 56.71 (C-5), 60.44 (1-OCH3), 105.11 (CHOCH3), 109.83
(C-6), 55.41 (2-OCH3), 60.24 (1-OCH3), 71.61 (C-5), 110.41 (C-3), (C-3), 122.90 (C-4), 123.49 (Car-3, Car-5), 128.14 (Car-2, Car-6),
122.16 (C-4), 131.96 (C-4a), 134.84 (C-12a), 146.95 (C-1), 152.02
(C-2), 170.24 (CH3CO2) ppm.
129.80 (C-12a), 135.53 (C-4a), 146.87 (C-1), 147.47 (Car-1), 149.38
(Car-4), 152.27 (C-2) ppm.
Without further purification, 16 (234 mg, 0.80 mmol) was dissolved
in THF/MeOH (10:1, 16.5 mL), treated with a solution of NaOH
(2.75 N, 1.75 mL), and the resulting biphasic system was stirred 6 h
at 50 °C. The mixture was submitted to the conventional work-up
Without further purification, EtOH (0.22 mL) and 6 HCl
(0.23 mL) were successively added to a cold solution of tosyl acetal
19 (121 mg, 0.23 mmol) in dioxane (1 mL) and the resulting solu-
tion submitted to reflux until complete dissapearence of the start-
ing material (30 min). The reaction was then diluted with EtOAc
(25 mL) and successively washed with brine (5 mL) containing 10%
Na2CO3 (0.5 mL) and brine (5 mL). The organic phase was dried
with Na2SO4, concentrated under reduced pressure and chromato-
graphed, furnishing 20 (73 mg, 68%), as a solid. M.p. 137–139 °C
procedure, furnishing 17 (220 mg, 91%), as an oil. IR (film): ν =
˜
3477, 2921, 2857, 1600, 1487, 1271, 1082, 974, 824 cm–1. 1H NMR
(200.13 MHz): δ = 0.85 (dt, J = 2.2, 10.3 Hz, 1 H, 8u-H), 1.00–
1.20 (m, 2 H, 8d-H, 7u-H), 1.30–1.52 (m, 5 H, 7d-H, 9-H, 10-H),
1.52–1.78 (m, 2 H, OH, 11u-H), 1.90 (ddd, J = 2.5, 5.9, 11.4 Hz, 1
H, 11d-H), 1.93–2.07 (m, 2 H, 6-H), 2.78 (ddd, J = 5.1, 12.1,
13.6 Hz, 1 H, 12u-H), 2.95 (ddd, J = 3.1, 6.0, 13.7 Hz, 1 H, 12d-
H), 3.83 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 5.37 (t, J = 8.1 Hz,
1 H, 5-H), 6.88 (d, J = 8.8 Hz, 1 H, 3-H), 7.15 (d, J = 8.8 Hz, 1
H, 4-H) ppm. 13C NMR (50.33 MHz): δ = 21.56 (C-7), 21.82 (C-
(hexane/EtOAc). IR (KBr): ν = 2956, 2861, 1605, 1589, 1479, 1349,
˜
1231, 1174, 1099, 998, 852, 739, 619 cm–1. 1H NMR (200.13 MHz):
δ = 0.80–1.10 (m, 1 H, 10d-H), 1.20–1.35 (m, 2 H, 9d-H, 10u-H),
1.35–1.48 (m, 2 H, 11-H), 1.48–1.72 (m, 4 H, 8d-H, 9u-H, 12-H),
1.75–2.15 (m, 3 H, 8u-H, 13-H), 2.63 (ddd, J = 7.4, 14.4, 14.5 Hz,
8), 23.97 (C-12), 25.61 (C-9),* 27.15 (C-11), 28.59 (C-10),* 39.47 1 H, 7d-H), 2.67 (ddd, J = 7.4, 14.0, 14.4 Hz, 1 H, 7u-H), 3.70 (s,
(C-6), 56.12 (2-OCH3), 60.92 (1-OCH3), 63.32 (C-5), 111.50 (C-3), 3 H, 6-OCH3), 3.75 (s, 3 H, 5-OCH3), 5.50 (dd, J = 5.1, 10.1 Hz,
121.93 (C-4), 134.30 (C-12a), 136.71 (C-4a), 147.57 (C-1), 152.28
(C-2) ppm. HRMS calcd. C16H24O3: 264.17255; found 264.17283.
1 H, 13a-H), 6.15 (d, J = 7.1 Hz, 1 H, 3-H), 6.37 (s, 1 H, 4-H),
6.54 (d, J = 7.1 Hz, 1 H, 2-H), 7.77 (d, J = 8.8 Hz, 2 H, HAr-2,
H
Ar-6), 8.07 (d, J = 8.8 Hz, 2 H, HAr-3, HAr-5) ppm. 13C NMR
N-(2,2-Dimethoxyethyl)-4-nitrobenzenesulfonamide (18): Et3N
(1.6 mL, 11.4 mmol) and 4-nitrobenzenesulfonyl chloride (929 mg,
4.2 mmol) were successively added to a solution of aminoacetalde-
hyde dimethyl acetal (400 mg, 3.89 mmol) in CH2Cl2 (25 mL) co-
oled to –20 °C. The reaction mixture was stirred 6 h at room tem-
perature, when it was diluted with brine (10 mL) and extracted with
EtOAc (4ϫ25 mL). The organic extracts were dried (Na2SO4),
concentrated under reduced pressure and chromatographed, yield-
(50.33 MHz): δ = 21.20 (C-10), 24.14 (C-11), 25.99 (C-12), 26.62
(C-7), 27.33 (C-13), 27.90 (C-9), 31.81 (C-8), 53.10 (C-13a), 54.43
(5-OCH3), 59.96 (6-OCH3), 107.61 (C-3), 117.57 (C-4), 121.92 (C-
2), 122.06 (C-6a), 123.44 (CAr-3, CAr-5), 124.73 (C-13b), 127.43
(CAr-2, CAr-6), 132.88 (C-3a), 144.67 (C-6), 148.11 (CAr-1), 148.60
(CAr-4), 151.38 (C-5) ppm.
Sulfonamide 20 (13 mg, 0.027 mmol) was dissolved in EtOH
ing 18 (1001 mg, 91%), as an oil. IR (film): ν = 3700–3300, 3209, (1 mL), 10% Pd/C (2 mg) was added and the resultant mixture was
˜
2958, 2899, 1609, 1538, 1464, 1346, 1167, 1095, 970, 858, 735, 612
submitted to room temperature hydrogenation at 1 atm. After 4 h,
the catalyst was removed by filtration and washed with EtOAc
(2 mL). The combined organic fractions were concentrated under
1
cm–1. H NMR (200.13 MHz): δ = 3.12 (dd, J = 5.3, 5.8 Hz, 2 H,
NCH2), 3.34 (s, 6 H, 2ϫOCH3), 4.36 (t, J = 5.3 Hz, 1 H, CH2CH),
5.07 (t, J = 5.8 Hz, 1 H, NH), 8.06 (d, J = 8.8 Hz, 2 H, 2-Har, reduced pressure and the residue was purified through a short pad
6-Har), 8.37 (d, J = 8.8 Hz, 2 H, 3-Har, 5-Har) ppm. 13C NMR
of silica, furnishing sulfanilamine 21 (12.1 mg, 100%), as a solid.
(50.33 MHz): δ = 44.49 (NCH2), 54.64 (2 C, OCH3), 102.34 M.p. 65–67 °C (EtOAc). IR (KBr): ν = 3472, 3378, 2921, 2850,
˜
[CH(OCH3)2], 124.22 (Car-3, Car-5), 128.17 (Car-2, Car-6), 145.77 1627, 1596, 1479, 1310, 1231, 1153, 1092, 830, 726 cm–1. 1H NMR
(Car-1), 149.96 (Car-4) ppm. HRMS calcd. C10H14N2O6S:
290.05726; found 290.05758.
(200.13 MHz): δ = 0.93 (dt, J = 6.2, 12.0, 12.5 Hz, 1 H), 1.10–1.30
(m, 4 H), 1.33–1.46 (m, 3 H), 1.45–1.75 (m, 3 H), 1.80–2.05 (m, 3
H), 2.61 (ddd, J = 2.6, 10.0, 20.0 Hz, 1 H, 7-H), 2.68 (ddd, J =
10.0, 12.8, 20.0 Hz, 1 H, 7-H), 3.74 (s, 3 H, OCH3), 3.79 (s, 3 H,
OCH3), 5.46 (dd, J = 4.4, 9.8 Hz, 1 H, 13a-H), 6.42 (s, 1 H, 4-H),
6.43 (d, J = 8.6 Hz, 2 H, Har-3, Har-5), 6.56 (d, J = 7.3 Hz, 1 H,
3-H), 6.78 (d, J = 8.6 Hz, 1 H, 2-H), 7.41 (d, J = 8.6 Hz, 2 H, Har-
2, Har-6) ppm. 13C NMR (50.33 MHz): δ = 21.19, 24.30, 26.10,
26.44, 27.40, 27.90, 31.44 (C-13), 52.38 (C-13a), 55.43 (5-OCH3),
60.27 (6-OCH3), 107.19 (C-3), 113.45 (2 C, Car-3, Car-5), 114.01
(C-4), 122.42 (C-2),* 122.99 (C-13b),* 123.20 (C-6a), 125.66 (Car-
1), 127.77 (C-3a), 128.46 (2 C, Car-2, Car-6), 132.93 (C-2), 147.57
(C-6), 150.17 (Ca r-4), 151.22 (C-5) ppm. HRMS calcd.
C24H30N2O4S: 475.19028 [MH+]; found 475.19075.
{4-[(5,6-Dimethoxy-7,8,9,10,11,12,13,13a-octahydro-1H-cyclodeca-
[ij]isoquinolin-1-yl)sulfonyl]phenyl}amine (21): Triphenylphosphane
(273 mg, 1.04 mmol), N-nosylaminoacetal (18, 302 mg, 1.04 mmol)
and DIAD (0.20 mL, 1.01 mmol) were sequentially added to a
solution of alcohol 17 (87 mg, 0.35 mmol) in dry THF (4 mL) and
the solution was stirred 4 h at 60 °C. Then, the solvent was removed
under reduced pressure, leaving an oily residue, which was chro-
matographed furnishing 19 (115 mg, 65%), as an oil. IR (film): ν
˜
= 2938, 2844, 1604, 1531, 1490, 1385, 1275, 1157, 1055, 958, 855,
1
736, 686 cm–1. H NMR (200.13 MHz): δ = 0.80–0.93 (m, 1 H, 7-
H), 1.00–1.20 (m, 2 H), 1.30–1.68 (m, 7 H), 1.84 (ddd, J = 4.4,
12.5, 13.5 Hz, 1 H, 6-H), 2.31 (dt, J = 6.0, 12.5 Hz, 1 H, 6-H), 2.71
(ddd, J = 4.9, 14.0, 20.4 Hz, 1 H, 12-H), 2.70–2.80 (m, 1 H, 12-H), N-{4-[(5,6-Dimethoxy-2,3,7,8,9,10,11,12,13,13a-decahydro-1H-cyclo-
3.30 (dd, J = 3.5, 15.7 Hz, 1 H, CH2CH), 3.33 (s, 3 H, CHOCH3), deca[ij]isoquinolin-1-yl)sulfonyl]phenyl}acetamide (23): 10% Pd/C
5290
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Eur. J. Org. Chem. 2007, 5284–5293