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Z. Kałuz_a et al. / Tetrahedron 64 (2008) 2321e2328
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4.4.4. (1R) (1-Isopropyl-6,7-dimethoxy-1,2,3,4-tetrahydro-
isoquinolin-1-yl)-methanol (4e)
111.3, 112.4, 148.2, 149.4, 161.6, 190.8. Minor rotamer. H
NMR: 2.82 (m, 1H), 2.95 (m, 1H), 3.65 (s, 3H), 3.75 (m,
2H, overlap with proton major rotamer), 3.90 (s, 3H), 6.35
(s, 1H), 6.73 (s, 1H), 8.01 (s, 1H), 9.88 (s, 1H). 13C NMR:
28.2, 36.8, 55.9, 56.1, 73.8, 111.7, 112.1, 148.2, 149.3,
163.2, 194.4.
Yield: 0.584 g, 55%; foam; [a]2D3 þ25.6 (c 1.68, CH2Cl2);
IR (CH2Cl2): 3362, 2961, 1609 cmꢁ1. MS (ES, HR) m/z:
(MþHþ) calcd for C15H23NO3: 266.1750. Found: 266.1754.
1H NMR: 0.81 (d, 3H, J¼6.9 Hz), 0.99 (d, 3H, J¼6.9 Hz),
2.15 (h, 1H, J¼6.9 Hz), 2.61 (m, 1H), 2.69 (m, 1H), 2.74
(br s, exchangeable with D2O), 2.94 (m, 1H), 3.19 (m, 1H),
3.61 (d, 1H, J¼10.6 Hz), 3.74 (d, 1H, J¼10.6 Hz), 3.84 and
3.85 (two s, 6H), 6.57 and 6.62 (two s, 2H). 13C NMR:
17.1, 18.4, 30.2, 36.6, 39.9, 55.7, 56.1, 61.3, 67.1, 108.6,
111.7, 128.8, 130.9, 147.3, 147.6.
4.6.2. (1S) 6,7-Dimethoxy-1-methyl-3,4-dihydro-1H-
isoquinoline-1,2-dicarbaldehyde (5b)
Yield: 1.99 g, 84%; colourless crystals; mp 180e181 ꢀC
(ethyl acetate); [a]D23 ꢁ96.2 (c 0.9, CH2Cl2); IR (CH2Cl2):
2940, 2838, 1729, 1666 cmꢁ1. MS (EI, HR) m/z: (Mþ) calcd
for C14H17NO4: 263.1157. Found: 263.1153. Anal. Calcd for
C14H17NO4: C, 63.87; H, 6.51; N, 5.32. Found: C, 63.87; H,
4.5. 2,3,9,10-Tetramethoxy-7a,14a-diphenyl-
5,6,7,7a,12,13,14,14a-octahydro-6a,13a-diaza-
dibenzo[a,h]anthracene-7,14-diol (8)
1
6.52; N, 5.25. H Selected spectral data taken from w1:17
mixture of rotamers. Major rotamer. NMR: 1.77 (s, 3H),
2.87 (m, 1H), 3.08 (m, 1H), 3.45 (m, 1H), 3.85 (s, 3H), 3.89
(s, 3H), 3.92 (m, 1H), 6.61 (s, 1H), 8.23 (s, 1H), 9.16 (s,
1H). 13C NMR: 19.9, 29.8, 41.1, 55.9, 56.0, 66.4, 110.1,
111.6, 122.6, 127.2, 148.5, 148.9, 161.9, 193.7. Minor ro-
tamer. NMR: 1.81(s, 3H), 2.92 (m, 1H), 3.24 (m, 1H), 4.54
(m, 1H), 6.51(s, 1H), 6.70 (s, 1H), 8.18 (s, 1H), 9.31 (s, 1H).
Into a solution of 2a (0.7 mmol, 0.260 g) in acetonitrile
(8 mL) sodium carbonate (3.2 mmol, 8 mL of 0.4 M
Na2CO3eH2O) was added in one portion. The reaction mix-
ture was initially stirred for 1 h at room temperature then stir-
ring was switched off, and left for 2 weeks at this temperature.
Precipitated crystals were filtrated, washed with acetonitrilee
H2O¼1:1 mixture and dried. Yield 0.099 g, 47%; colourless
crystals; mp 263e266 ꢀC (ethyl acetate); [a]2D3 þ193.9
(c 1.2, CH2Cl2); IR (CH2Cl2): 2938, 1610 cmꢁ1. MS (ES,
HR) m/z: (MꢁOH)þ calcd for C36H37N2O5: 577.2697. Found:
577.2719. 1H NMR: 2.46 (m, 2H), 2.88 (m, 2H), 3.36 (m, 4H),
3.78 (s, 6H), 3.79 (s, 6H), 5.39 (s, 2H), 6.51(s, 2H), 6.93 (s,
2H), 7.03 (m, 10H). 13C NMR: 27.5, 49.0, 55.8, 56.2, 74.0,
104.2, 110.0, 111.5, 125.1, 126.7, 127.9, 130.1, 131.1,
144.7, 147.3, 147.4.
4.6.3. (1S) 6,7-Dimethoxy-1-phenylethynyl-3,4-dihydro-1H-
isoquinoline-1,2-dicarbaldehyde (5c)
Yield: 0.943 g, 30%; white solid; [a]2D3 ꢁ24.9 (c 1.0,
CH2Cl2); IR (CH2Cl2): 3054, 2940, 2837, 2233, 1739,
.
1673 cmꢁ1
C21H19NO4Na: 372.1206. Found: 372.1203. Selected data
MS (ES, HR) m/z: (MþNaþ) calcd for
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taken from w1:1.6 mixture of rotamers. Major rotamer. H
NMR: 2.86 (m, 1H, overlap with protons minor rotamer),
3.10 (m, 1H), 3.59 (m, 1H), 3.86 (s, 3H), 3.88 (s, 3H), 3.99
(m, 1H, overlap with protons of minor rotamer), 6.65 (s,
1H), 6.99 (s, 1H), 8.29 (s, 1H), 9.09 (s, 1H). 13C NMR:
29.5, 41.4, 56.0, 56.2, 64.3, 85.3, 86.1, 111.0, 111.5, 120.4,
4.6. General procedure for the preparation of N-formyl
aldehydes (5aee)
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122.1, 148.8, 149.6, 162.0, 188.4. Minor rotamer. H NMR:
Into a solution of 2 (9 mmoL) in DMSO (30 mL), 2-iodoxy
benzoic acid (18 mmol, 5.04 g) was added in one portion. Re-
action was heated to 45 ꢀC and stirred for 2e3 h until all sub-
strate was consumed (TLC control). Then, the solution was
poured into water (200 mL) and extracted with ethyl acetate
(3ꢂ100 mL). Collected extracts were washed with water
(2ꢂ100 mL), dried (MgSO4) and evaporated in vacuo. Crude
5 was purified on silica gel.
2.71 (m, 1H), 2.86 (m, 1H, overlap with protons of major ro-
tamer), 3.69 (m, 1H), 3.90 (s, 1H), 3.91 (s, 1H), 3.99 (m, 1H,
overlap with protons of major rotamer), 6.70 (s, 1H), 7.19 (s,
1H), 8.84 (s, 1H), 9.35 (s, 1H). 13C NMR: 27.6, 37.0, 56.0,
56.3, 66.3, 82.1, 93.5, 110.8, 111.8, 120.2, 120.7, 148.5,
149.8, 162.9, 188.6.
4.6.4. (1R) 1-Cyclohexyl-6,7-dimethoxy-3,4-dihydro-1H-
isoquinoline-1,2-dicarbaldehyde (5d)
4.6.1. (1S) 6,7-Dimethoxy-1-phenyl-3,4-dihydro-1H-
isoquinoline-1,2-dicarbaldehyde (5a)
Yield: 2.028 g, 68%; colourless crystals; mp 182e183 ꢀC
(acetone); [a]2D3 þ93.5 (c 1.1, CH2Cl2); IR (CH2Cl2): 2934,
2855, 1724, 1669 cmꢁ1. MS (EI, HR) m/z: (Mþ) calcd for
C19H25NO4: 331.1783. Found: 331.1789. Anal. Calcd for
C19H25NO4: C, 68.86; H, 7.60; N, 4.23. Found: C, 68.79; H,
7.67; N, 4.29. Selected data taken from w1:3.2 mixture of
Yield: 2.196 g, 75%; colourless crystals; mp 148e150 ꢀC
(diethyl ether); [a]D23 þ100.4 (c 1.0, CH2Cl2); IR (CH2Cl2):
2939, 2855, 1727, 1666 cmꢁ1. MS (EI, HR) m/z: (Mþ) calcd
for C19H19NO4: 325.1314. Found: 325.1308 Anal. Calcd for
C19H19NO4: C, 70.14; H, 5.89; N, 4.31. Found: C, 70.13; H,
5.81; N, 4.08. Selected data taken from w1:5.5 mixture of ro-
tamers. Major rotamer. 1H NMR: 2.88 (m, 1H), 3.15 (m, 1H),
3.38 (m, 1H), 3.66 (s, 3H), 3.75 (m, 1H, overlap with protons
of minor rotamer), 3.91 (s, 3H), 6.38 (s, 1H), 6.71 (s, 1H), 8.09
(s, 1H), 9.45 (s, 1H). 13C NMR: 29.6, 40.5, 55.9, 56.0, 71.9,
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rotamers. Major rotamer. H NMR: 3.53 (m, 1H), 3.82 (s,
3H), 3.86 (s, 1H), 3.93 (m, 1H, overlap with proton minor
rotamer), 6.59 (s, 1H), 6.60 (s, 1H), 8.28 (s, 1H), 9.11 (s,
1H). 13C NMR: 26.56 (overlap with carbon), 27.5, 29.4,
29.8, 30.3, 43.4, 45.7, 55.8, 56.1, 72.8, 110.2, 111.6, 120.8,
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128.4, 148.6, 148.8, 162.5, 191.2. Minor rotamer. H NMR: