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F. Tjosꢀas et al. / Tetrahedron 63 (2007) 11893–11901
138.0 (Ph-C-1), 134.1 (C-40), 130.4 (Ph-C-4), 129.8 (Ph-C-
3/5), 128.9 (C-80), 127.5 (Ph-C-2/6), 118.1 (C-8), 115.9
(C-4); NMR assignments are based on HSQC and HMBC
experiments; MS: m/z 242/240 (M+, 32/100%), 105 (46),
177 (14), 151 (18), 102 (14); HRMS: calcd for
C14H9N2Cl: 240.0454; obsd 240.0449.
(py-C-5), 134.4 (py-C-3), 147.1 (py-C-6), 147.8 (py-C-2),
148.4 (py-C-4); NMR assignments are based on APT,
HSQC, HMBC and NOESY experiments. The following
NOESY NMR interactions were observed: H-2/H-4, Ha-3/
H-2, Ha-3/H-4, H-4/Ha-5, Hb-3/Hb-5, Hb-3/CH2Br, Hb-5/
CH2Br, CH2OH/H-4, py-H-2/Hb-3, py-H-2/Hb-5. MS: m/z
273/271 (M+, 1%), 252/254 (4), 234/236 (5), 208/210 (2),
178 (10), 174 (13), 160 (44), 156 (31), 143 (100), 132
(95), 117 (98), 106 (44), 91 (25); HRMS: calcd for
C11H14NO279Br: 271.0208; obsd 271.0202. Anal. Calcd
for C11H14NO2Br: C, 48.55; H, 5.19; N, 5.15. Found: C,
48.45; H, 5.04; N, 5.23.
4.1.18. 2-(4-Hydroxymethyl-3-pyridyl)-4-penten-1-ol
(16). A solution of 8 (725 mg, 2.9 mmol) in dry THF
(12 mL) was drop-wise added to a solution of LiAlH4
(165 mg, 4.38 mmol) in dry THF (13 mL) at 0 ꢀC. The reac-
tion was stirred at room temperature for 2 h, cooled to 0 ꢀC
and diethyl ether (25 mL) was added, followed by a NH4Cl
solution (saturated, 40 mL) and water (40 mL). The product
was extracted from basic solution by diethyl ether
(3ꢂ50 mL) and yielded 17 (287 mg, 51%), pure by 1H and
13C NMR; IR (film) nmax: 3682 (w), 3620 (w), 3400 (br),
3019 (s), 2976 (m), 1523 (w), 1421 (m), 1216 (s), 1046
4.1.20. cis-Tetrahydro-2-iodomethyl-4-(4-hydroxy-
methyl-3-pyridyl)-furan (17b). A solution of the diol 16
(80 mg, 0.4 mmol) in dichloromethane (5 mL) was stirred
at room temperature for 24 h after the addition of I2
(50 mg, 0.2 mmol, 0.5 equiv).31 The solvent was decanted
and the solid precipitate was dissolved in dichloromethane
(5 mL) and acetone (10 mL) and Na2S2O3 (5% solution,
25 mL) was added. The crude product was extracted with di-
chloromethane (5ꢂ30 mL)) and flash chromatography (1%
methanol in dichloromethane) yielded the product (32 mg,
24%), pure by 1H and 13C NMR. Rf 0.05 (acetone/n-pentane
1:2); IR (film) nmax: 3682 (w), 3620 (w), 2975 (m), 1520 (w),
1
(m), 928 (m) cmꢁ1; H NMR (600 MHz, CDCl3): dH 8.32
(1H, s, py-H-2), 8.22 (1H, d, J 5.4 Hz, py-H-6), 7.24 (1H,
d, J 5.4, 1.3 Hz, py-H-5), 5.65 (1H, dd, J 17.0, 10.2 Hz,
H-4, –CH]), 5.15 (1H, dd, J 17.0, 1.8 Hz, H-5, terminal
]CHaHb), 4.98 (1H, dd, J 10.2, 1.8 Hz, H-5, terminal
]CHaHb), 4.78 (1H, d, J 13.0 Hz, py-CHaHbOH), 4.47
(1H, d, J 13.0 Hz, py-CHaHbOH), 3.90 (1H, dd, J 10.0,
4.8 Hz, ‘malonate’-CHaHbOH), 3.62 (1H, dd, J 10.0,
9.4 Hz, ‘malonate’-CHaHbOH), 3.46 (2H, s, 2ꢂOH), 3.19
(1H, m, H-2), 2.46 (1H, m, H-3, –CHaHb-C), 2.39 (1H, m,
H-3, –CHaHb-C); 13C NMR (100 MHz, CDCl3): dC 36.0
(C-3), 40.9 (C-2), 61.6 (py-CH2OH), 66.5 (C-1, CH2OH),
117.2 (C-5, ]CH2), 123.0 (py-C-5), 135.2 (C-4, –CH]),
136.5 (py-C-3), 147.2 (py-C-6), 147.7 (py-C-2), 148.8 (py-
C-4); NMR assignments are based on APT, HSQC and
HMBC experiments; MS: m/z 193 (M+, 1%), 180 (6), 170
(4), 164 (13), 157 (14), 145 (66), 134 (39), 130 (49), 117
(66), 106 (100), 91 (68); HRMS: calcd for C11H15NO2:
193.1103; obsd 193.1094. Anal. Calcd for C11H15NO2; C,
68.37; H, 7.82; N, 7.25. Found: C, 68.10; H, 7.68; N, 7.15.
1
1422 (w), 1215 (s), 1046 (m), 929 (m) cmꢁ1; H NMR
(400 MHz, CDCl3): dH 8.56 (1H, s, py-H-2), 8.41 (1H, d, J
4.8 Hz, py-H-6), 7.39 (1H, d, J 4.8 Hz, py-H-5), 4.76 (2H,
s, py-CH2OH), 4.21 (1H, dd, J 8.4, 7.7 Hz, H-5, CHaHb),
4.13 (1H, m, H-2), 3.96 (1H, dd, J 8.4, 8.2 Hz, H-5, CHaHb),
3.72 (1H, m, H-4), 3.35 (1H, dd, J 11.6, 5.8 Hz, side chain
CHaHb I), 3.38 (1H, dd, J 11.6, 5.8 Hz, side chain CHaHb
I), 2.59 (1H, m, H-3, CHaHb), 1.88 (1H, m, H-3, CHaHb);
13C NMR (100 MHz, CDCl3): dC 9.4 (CH2I), 39.3 (C-3),
40.6 (C-4), 61.3 (py-CH2OH), 74.0 (C-5), 79.0 (C-2),
121.7 (py-C-5), 134.4 (py-C-3), 147.3 (py-C-6), 147.9 (py-
C-2), 148.0 (py-C-4); NMR assignments are based on
APT, HSQC, HMBC and NOESY experiments. The follow-
ing NOESY NMR interactions were observed: H-2/H-4,
Ha-3/H-2, Ha-3/H-4, H-4/Ha-5, Hb-3/Hb-5, Hb-3/CH2I,
Hb-5/CH2I, CH2OH/H-4, py-H-2/Hb-3, py-H-2/Hb-5. MS:
m/z 319 (M+, 5%), 271 (3), 192 (12), 178 (22), 178 (22),
160 (30), 143 (100), 91 (13); HRMS: calcd for
C11H14NO2I: 319.0069; obsd 319.0061. Anal. Calcd for
C11H14NO2I: C, 41.40; H, 4.42; N, 4.39. Found: C, 41.49;
H, 4.51; N, 4.29.
4.1.19. cis-Tetrahydro-2-bromomethyl-4-(4-hydroxy-
methyl-3-pyridyl)-furan (17a). A solution of the diol 16
(88 mg, 0.45 mmol) in THF (2 mL) and water (0.15 mL)
was cooled to ꢁ78 ꢀC and NBS (89 mg, 0.50 mmol,
1.1 equiv) was added.37 After 2 h of stirring, the temperature
was raised to room temperature. Water (30 mL) was added
and the crude product was extracted with ethyl acetate
(3ꢂ15 mL). Flash chromatography (10% methanol in di-
chloromethane) yielded the product (50 mg, 40%), pure by
1H and 13C NMR. Rf 0.1 (acetone/n-pentane 1:1); IR (film)
nmax: 3682 (w), 3619 (w), 3018 (s), 2975 (m), 1600 (m),
1521 (w), 1477 (w), 1419 (m), 1215 (s), 1046 (m), 928
References and notes
1. Effenberger, F.; Koch, M.; Streicher, W. Chem. Ber. 1991, 124,
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3. (a) Holt, J.; Tjosas, F.; Bakke, J.; Fiksdahl, A. J. Heterocycl.
1
(m), 877 (w) cmꢁ1; H NMR (600 MHz, CDCl3): dH 8.53
(1H, s, py-H-2), 8.38 (1H, d, J 4.8 Hz, py-H-6), 7.10 (1H,
d, J 4.8 Hz, py-H-5), 4.77 (2H, s, py-CH2OH), 4.32 (1H,
m, H-2), 4.18 (1H, dd, J 8.4, 7.8 Hz, H-5, CHaHb, cis to
H-4, trans to –CH2Br), 3.92 (1H, dd, J 8.4, 8.2 Hz, H-5,
CHaHb, trans to H-4, cis to –CH2Br), 3.71 (1H, m, H-4),
3.57 (1H, dd, J 11.0, 5.5 Hz, side chain CHaHb Br), 3.54
(1H, dd, J 11.0, 5.5 Hz, side chain CHaHb Br), 2.55 (1H,
m, H-3, CHaHb, cis to H-4, trans to –CH2Br), 1.94 (1H, m,
H-3, CHaHb, trans to H-4, cis to –CH2Br); 13C NMR
(100 MHz, CDCl3): dC 36.3 (CH2Br), 38.8 (C-3), 39.0
(C-4), 61.3 (py-CH2OH), 74.0 (C-5), 78.8 (C-2), 122.0
ꢀ
Chem. 2004, 41, 987; (b) Tjosas, F.; Fiksdahl, A. Molecules
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