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G.E. Magoulas et al. / European Journal of Medicinal Chemistry 46 (2011) 721e737
solid; Rf (F): 0.18; IR (KBr, cmꢁ1): 3390, 1603; MS (ESI, 30 eV): m/z
following the procedure described above. Reaction time: 1 h; Yield:
0.5 g (73%), yellow solid; mp 152e154 ꢀC; Rf (E): 0.14; IR (KBr,
cmꢁ1): 3256, 1654; MS (ESI, 30 eV): m/z 231.32 [MH ꢁ H2O]; 1H
511.06 [2M þ H ꢁ H2O], 246.77 [M ꢁ H2O]; 1H NMR (CDCl3,
d): 7.18
(d, 1H, J ¼ 16.0 Hz), 6.84 (d, 1H, J ¼ 16.0 Hz), 6.16 (s, 2H), 5.75 (t, 1H,
J ¼ 6.8 Hz), 4.34 (d, 2H, J ¼ 6.8 Hz), 3.86 (2 s, 6H), 3.84 (s, 3H), 1.94
NMR (CDCl3, d): 8.41 (s, 1H), 8.38 (s, 1H), 8.00e7.94 (m, 4H), 7.63
(s, 3H); 13C NMR (CDCl3,
d): 160.0, 159.2 (2C), 138.3, 134.4, 128.8,
(dd, 1H, J ¼ 1.6 and 8.8 Hz), 7.45 (dt, 2H, J ¼ 3.2 and 9.6 Hz), 6.23
119.2, 108.1, 90.8 (2C), 59.6, 55.7 (2C), 55.3, 12.2.
(t, 1H, J ¼ 6.8 Hz), 4.47 (d, 2H, J ¼ 6.8 Hz), 2.24 (s, 3H); 13C NMR
(CDCl3, d): 139.2, 137.6, 132.2, 132.0, 131.8, 131.2, 131.1, 128.3, 128.2,
4.1.4.3. 5-(3,4-Dimethoxyphenyl)-3-methylpenta-2,4-dien-1-ol
(29). Reaction time: 1 h; Isolated as a mixture of two geometric
isomers in the ratio 2E,4E/2Z,4E ¼ 80:20. Yield: 0.59 g (84%), yellow
solid; Rf (G): 0.16; IR (KBr, cmꢁ1): 3259, 1626, 1596, 1580; MS (ESI,
30 eV): m/z 490.98 [2M þ Na], 216.55 [M ꢁ H2O]; 1H NMR (CDCl3,
127.4, 126.6, 126.0, 125.5, 125.4, 124.5, 124.2, 60.2, 15.9; Anal. Calcd
for C18H16O: C, 87.06; H, 6.49. Found: C, 87.24; H, 6.26.
4.1.5. General procedure for the MnO2-mediated oxidations of
allylic alcohols
d
): 6.99 (s, 1H), 6.98 (d, 1H, J ¼ 8.6 Hz), 6.84 (d, 1H, J ¼ 8.6 Hz), 6.70
To a vigorously stirred solution of alcohols 27e31 (2.2 mmol) in
CH2Cl2 (45 mL), Na2CO3 (4.77 g, 45 mmol) and activated MnO2
powder (3.91 g, 45 mmol) were added. The resulting suspension
was stirred at ambient temperature to complete the reaction
(monitored by TLC) and then passed through a celite pad. The
filtrate was evaporated to dryness to leave a residue. Allylic alde-
hydes 32e36 (only the 2E,4E-isomer is drawn) were obtained from
this residue through FCC purification.
(d, 1H, J ¼ 16.0 Hz), 6.53 (d, 1H, J ¼ 16.0 Hz), 5.80 (t, 1H, J ¼ 6.8 Hz),
4.35 (d, 2H, J ¼ 6.8 Hz), 3.93 and 3.90 (2 s, 6H), 1.92 (s, 3H); 13C NMR
(CDCl3, d): 149.0, 148.7, 136.4, 131.1, 130.5, 130.1, 127.9, 119.6, 111.2,
108.8, 59.4, 55.9, 55.8, 12.6.
4.1.4.4. 5-(4-(Dimethylamino)phenyl)-3-methylpenta-2,4-dien-1-ol
(30). Reaction time: 1 h; Isolated as a mixture of two geometric
isomers in the ratio 2E,4E/2Z,4E ¼ 65:35. Yield: 0.57 g (87%), yellow
solid; Rf (E): 0.16; IR (KBr, cmꢁ1): 3309, 1605; MS (ESI, 30 eV): m/z
4.1.5.1. 5-(4-Methoxy-2,3,6-trimethylphenyl)-3-methylpenta-2,4-
dienal (32). Reaction time: 1 h; Isolated as a mixture of two
geometric isomers in the ratio 2E,4E/2Z,4E ¼ 85:15. Yield: 0.48 g
(90%), yellow solid; Rf (C): 0.28; IR (KBr, cmꢁ1): 2855, 2770, 1684,
1610; MS (ESI, 30 eV): m/z 267.61 [M þ Na], 245.12 [MH]; 1H NMR
218.57 [MH], 217.56 [M], 199.65 [M ꢁ H2O]; 1H NMR (CDCl3,
d): 7.32
(d, 2H, J ¼ 8.8 Hz), 6.70(d, 2H, J ¼ 8.8 Hz), 6.66 (d,1H, J ¼ 16.0 Hz), 6.52
(d,1H, J ¼ 16.0 Hz), 5.73 (t,1H, J ¼ 6.8 Hz), 4.32 (d, 2H, J ¼ 6.8 Hz), 2.97
(s, 6H), 1.91 (s, 3H); 13C NMR (CDCl3,
d): 150.0, 137.3, 133.4, 130.7,
128.5, 127.7 (2C), 122.8, 112.8 (2C), 59.7, 40.7 (2C), 12.8.
(CDCl3,
d
): 10.17 (d,1H, J ¼ 8.0 Hz), 7.16 (d,1H, J ¼ 16.0 Hz), 6.60(s,1H),
6.32 (d,1H, J ¼ 16.0 Hz), 5.99 (d,1H, J ¼ 8.0 Hz), 3.82 (s, 3H), 2.42, 2.30,
4.1.4.5. 3-Methyl-5-(naphthalen-2-yl)penta-2,4-dien-1-ol
2.23 and 2.14 (4 s,12H); 13C NMR (CDCl3,
d
): 191.4,156.9,154.6,136.6,
(31). Reaction time: 1 h; isolated as a mixture of two geometric
isomers in the ratio 2E,4E/2Z,4E ¼ 90:10. Yield: 0.55 g (82%), pale
yellow solid; Rf (E): 0.15; IR (KBr, cmꢁ1): 3306, 2213, 1624, 1590; MS
(ESI, 30 eV): m/z 448.21 [2M], 206.59 [M ꢁ H2O]; 1H NMR (CDCl3,
136.1, 135.3, 134.2, 129.3, 128.7, 128.4, 110.1, 55.5, 21.4, 17.5, 13.3, 11.7.
4.1.5.2. 5-(2,4,6-Trimethoxyphenyl)-3-methylpenta-2,4-dienal
(33). Reaction time: 1 h; Isolated as a mixture of two geometric
isomers in the ratio 2E,4E/2Z,4E ¼ 70:30. Yield: 0.50 g (86%), yellow
solid; Rf (E): 0.24; IR (KBr, cmꢁ1): 2860, 2778, 1653, 1598; MS (ESI,
d
): 7.82e7.77 (m, 4H), 7.64 (dd, 1H, J ¼ 1.2 and 9.6 Hz), 7.46 and 7.42
(two dt, 2H, J ¼ 1.2 and 6.8 Hz), 6.94 (d, 1H, J ¼ 16.0 Hz), 6.74 (d, 1H,
J ¼ 16.0 Hz), 5.86 (t, 1H, J ¼ 6.8 Hz), 4.37 (d, 2H, J ¼ 6.8 Hz), 1.96
30 eV): m/z 285.14 [M þ Na], 263.10 [MH]; 1H NMR (CDCl3,
d): 10.12
(s, 3H); 13C NMR (CDCl3,
d): 136.4, 134.9, 133.7, 133.2, 131.1, 128.3,
(d, 1H, J ¼ 8.4 Hz), 7.45 (d, 1H, J ¼ 16.0 Hz), 7.30 (d, 1H, J ¼ 16.0 Hz),
128.2, 127.9, 127.7 (2C), 126.4, 126.3, 125.8, 123.5, 59.5, 12.7.
6.13 (s, 2H), 6.04 (d, 1H, J ¼ 8.4 Hz), 3.80 (s, 6H), 3.77 (s, 3H), 2.30
(s, 3H); 13C NMR (CDCl3,
d): 191.2, 161.8, 160.4 (2C), 157.4, 132.0,
4.1.4.6. (E)-3-(Pyren-1-yl)but-2-en-1-ol (64). Reaction time: 1 h;
Yield: 0.66 g (80%), pale green solid; mp 115e117 ꢀC; Rf (F): 0.26; IR
(KBr, cmꢁ1): 3234, 1654; MS (ESI, 30 eV): m/z 567.43 [2M þ Na],
295.14 [M þ Na], 273.13 [MH], 255.06 [MH ꢁ H2O]; 1H NMR (CDCl3,
128.3, 127.3, 107.2, 90.7 (2C), 55.7 (2C), 55.3, 12.7.
4.1.5.3. 5-(3,4-Dimethoxyphenyl)-3-methylpenta-2,4-dienal
(34). Reaction time: 1 h; isolated as a mixture of two geometric
isomers in the ratio 2E,4E/2Z,4E ¼ 80:20. Yield: 0.43 g (85%), yellow
solid; Rf (E): 0.21; IR (KBr, cmꢁ1): 2841, 2754, 1685, 1604; MS (ESI,
d
): 8.14 (d, 1H, J ¼ 9.0 Hz), 8.09 (d, 1H, J ¼ 7.4 Hz), 8.08 (d, 1H,
J ¼ 7.4 Hz), 8.06 (d, 1H, J ¼ 8.0 Hz), 7.98 (d, 1H, J ¼ 9.0 Hz), 7.97 (br.s,
2H), 7.92 (t,1H, J ¼ 7.4 Hz), 7.74 (d,1H, J ¼ 8.0 Hz), 5.79 (tq,1H, J ¼ 1.2
and 6.8 Hz), 4.47 (d, 2H, J ¼ 6.8 Hz), 2.21 (d, 3H, J ¼ 1.2 Hz); 13C NMR
30 eV): m/z 233.80 [MH]; 1H NMR (CDCl3,
d): 10.14 (d, 1H,
J ¼ 8.0 Hz), 7.07 (d, 1H, J ¼ 8.2 Hz), 7.03 (s, 1H), 7.02 (d, 1H,
J ¼ 16.0 Hz), 6.87 (d, 1H, J ¼ 8.2 Hz), 6.77 (d, 1H, J ¼ 16.0 Hz), 6.07
(d, 1H, J ¼ 8.0 Hz), 3.95 (s, 3H), 3.93 (s, 3H), 2.39 (s, 3H); 13C NMR
(CDCl3, d): 140.6, 138.9, 131.6, 131.2, 130.5, 130.4, 128.0, 127.5, 127.4,
127.3,126.1,125.8,125.2,125.1 (three C),125.0,124.7, 60.0,19.8; Anal.
Calcd for C20H16O2: C, 88.20; H, 5.92. Found: C, 88.02; H, 6.11.
(CDCl3, d): 191.2, 154.6, 150.3, 149.2, 135.6, 129.4, 129.3, 128.9, 124.5,
111.2, 109.2, 55.9 (2C), 13.1.
4.1.4.7. (E)-3-(6-methoxynaphthalen-2-yl)but-2-en-1-ol
(65). Reaction time: 1 h; Yield: 0.45 g (65%), white solid; mp
118e120 ꢀC; Rf (F): 0.21; IR (KBr, cmꢁ1): 3260, 1626, 1600; MS (ESI,
30 eV): m/z 211.29 [MH ꢁ H2O], 158.15 [211.29-C4H5]; 1H NMR
4.1.5.4. 5-(4-(Dimethylamino)phenyl)-3-methylpenta-2,4-dienal
(35). Reaction time: 1 h; Isolated as a mixture of two geometric
isomers in the ratio 2E,4E/2Z,4E ¼ 70:30. Yield: 0.38 g (81%), yellow
solid; Rf (D): 0.24; IR (KBr, cmꢁ1): 2836, 2777, 1650, 1595; MS
(CDCl3,
d
): 7.76 (br.s, 1H), 7.72 (d, 1H, J ¼ 8.8 Hz), 7.68 (d, 1H,
J ¼ 8.6 Hz), 7.57 (dd, 1H, J ¼ 1.6 and 8.6 Hz), 7.14 (dd, 1H, J ¼ 2.4 and
8.8 Hz), 7.12 (br.s, 1H), 6.11 (t, 1H, J ¼ 6.8 Hz), 4.42 (d, 2H, J ¼ 6.8 Hz),
(ESI, 30 eV): m/z 216.68 [MH]; 1H NMR (CDCl3,
d): 10.17 (d,
1H, J ¼ 8.0 Hz), 7.41 (d, 2H, J ¼ 8.8 Hz), 7.03 (d, 1H, J ¼ 16.0 Hz),
3.92 (s, 3H), 2.17 (s, 3H); 13C NMR (CDCl3,
d): 157.8,137.9,137.7,133.9,
6.72 (d,1H, J16.0 Hz), 6.70 (d, 2H, J¼ 8.8Hz), 6.03(d,1H,J¼8.0 Hz), 3.03
129.6, 128.8, 126.6, 126.3, 124.6, 124.3, 118.9, 105.7, 60.00, 55.3, 15.9;
Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found: C, 79.12; H, 6.88.
(s, 6H), 2.38 (s, 3H); 13C NMR (CDCl3,
d): 191.1, 155.7, 151.1, 136.4, 128.9
(2C), 128.2, 126.5, 123.8, 112.1 (2C), 40.2 (2C), 13.0.
4.1.4.8. (E)-3-(Anthracen-2-yl)but-2-en-1-ol (66). The unsaturated
ester 63 (2.5 mmol) was reduced by using LiAlH4 (0.29 g, 7.5 mmol)
in THF (11 mL) and AlCl3 (0.36 g, 2.7 mmol), to obtain alcohol 66
4.1.5.5. 3-Methyl-5-(naphthalen-3-yl)penta-2,4-dienal
(36). Reaction time: 1 h; Isolated as a mixture of two geometric
isomers in the 2E,4E/2Z,4E ¼ 90:10. Yield: 0.39 g (80%), yellow