6632 J . Org. Chem., Vol. 63, No. 19, 1998
Kita et al.
1.64 and 1.63 (6H, s); IR (KBr) 1700, 1670, 1499, 1244, 1146
cm-1; LRMS (EI) m/z 393 (M+), 378 (M+ - Me); HRMS (EI)
calcd for C20H18NO4F3 393.1188, found 393.1186.
(1H, d, J ) 15.0 Hz); IR (KBr) 1690, 1685, 1509, 1439, 1283
cm-1; LRMS (EI) m/z 285 (M+); HRMS (EI) calcd for C17H19
-
NO3 285.1365, found 285.1332.
14f: 1H NMR (270 MHz, CDCl3) δ (ppm) 7.30-7.39 (10H,
m), 7.01 (1H, s), 6.91 (2H, d, J ) 9.9 Hz), 6.41 (2H, d, J ) 9.9
Hz), 4.93 (2H, s), 3.91 (2H, t, J ) 5.9 Hz), 2.39 (2H, t, J ) 5.9
Hz), 0.42 (9H, s); 13C NMR (75.0 MHz, CDCl3) δ (ppm) 185.6,
156.5 (m), 150.6, 147.3, 146.2, 140.2, 134.8, 134.4, 129.2, 128.3,
126.1, 125.6, 117.9, 116.0 (m), 113.5, 48.1, 46.3, 45.0, 35.7, 0.8;
IR (KBr) 1700, 1665, 1453, 1240, 1144, 1021 cm-1; LRMS (EI)
m/z 589 (M+), 574 (M+ - Me), 512 (M+ - Ph); HRMS (EI) calcd
for C33H30NO4F3Si 589.1896, found 589.1898. Anal. Calcd for
Ga la n th a m in e (1). To a stirring solution of 2 (3.0 mg,
0.011 mmol) in tetrahydrofuran (0.50 mL) was added 1 M
solution of L-Selectride (Aldrich) in tetrahydrofuran (0.040 mL,
0.040 mmol) at -78 °C and the mixture stirred at the same
temperature for 2 h. The mixture was then stirred at ice-bath
temperature for 30 min, H2O was added, and the resulting
mixture was extracted with ethyl acetate and dried. Prepara-
tive thin-layer chromatography (SiO2, CHCl3/MeOH ) 10:1)
yielded 1 (3.2 mg, 0.011 mmol, quant) as white crystals: mp
119-120 °C (from Et2O (lit.24 mp 127-129 °C)); 1H NMR (500
MHz, CDCl3) δ (ppm) 6.66 (1H, d, J ) 8.0 Hz), 6.62 (1H, d, J
) 8.0 Hz), 6.07 (1H, d, J ) 10.5 Hz), 6.02 (1H, dd, J ) 10.5
Hz, 5.0 Hz), 4.61 (1H, brs), 4.13 (1H, t, J ) 5.0 Hz), 4.09 (1H,
d, J ) 15.0 Hz), 3.83 (3H, s, OMe), 3.68 (1H, d, J ) 15.0 Hz),
3.27 (1H, t, J ) 14.0 Hz), 3.05 (1H, d, J ) 14.0 Hz), 2.68 (1H,
d, J ) 15.0 Hz), 2.40 (3H, s, NMe), 2.06-2.11 (1H, m), 1.99-
2.04 (1H, m), 1.58 (1H, m); IR (KBr) 1507, 1439, 1283, 1266,
1048 cm-1; LRMS (EI) m/z 287 (M+); HRMS (EI) calcd for
C
33H30NO4F3Si: C, 67.22; H, 5.13; N, 2.38. Found: C, 67.50;
H, 5.05; N, 2.26.
15f: 1H NMR (200 MHz, CDCl3) δ (ppm) 7.51-7.52 (4H,
m), 7.35-7.37 (6H, m), 7.00 and 6.89 (2H, d, J ) 10.0 Hz),
6.86 and 6.69 (1H, s), 6.61 and 6.60 (1H, s), 6.29 and 6.28 (2H,
d, J ) 10.0 Hz), 4.75 and 4.92 (2H, s), 3.92 and 3.89 (2H, t, J
) 6 Hz), 2.37 and 2.33 (2H, t, J ) 6.0 Hz); IR (KBr) 1669,
1626, 1497, 1451, 1242, 1199, 1167, 1146, 1046, 1021 cm-1
;
LRMS (EI) m/z 517 (M+), 440 (M+ - Ph); HRMS (EI) calcd for
C
30H22NO4F3 517.1501, found 517.1510.
C
17H21NO3 287.1521, found 287.1517.
14j: 1H NMR (300 MHz, CDCl3) δ (ppm) 7.27-7.42 (10H,
Lycor a m in e (3). To a stirring solution of 1 (1.8 mg, 0.0060
m), 6.96 (1H, s), 6.92 (2H, d, J ) 10.0 Hz), 6.42 (2H, d, J )
10.0 Hz), 4.91 (2H, s), 3.89 (2H, t, J ) 6.0 Hz), 2.37 (2H, t, J
) 6.0 Hz), 0.95-0.97 (9H, m); 13C NMR (75.0 MHz, CDCl3) δ
(ppm) 185.7, 156.4 (q, J ) 36.0 Hz), 150.8, 147.1, 146.1, 140.3,
135.2, 131.4, 128.9, 128.2, 128.1, 125.5, 117.9, 117.2 (m), 114.2,
47.8, 46.3, 44.9, 35.7, 7.6, 4.5; IR (KBr) 1700, 1667, 1453, 1262,
1238, 1206, 1181, 1144, 1049, 1021 cm-1; LRMS (FAB) m/z
632 (M+H); HRMS (EI) calcd for C36H37NO4F3Si 632.2444,
found 632.2427.
mmol) in ethyl acetate (3.00 mL) was added Pd-C (3.0 mg)
and the mixture stirred at room temperature for 4 h under
hydrogen atmosphere (4.0 atm). Pd-C was removed by Celite
filtration, and 3 (2.00 mg, 0.006 mmol, quant) was isolated as
white crystals: mp 101-102 °C (from Et2O (lit.17c mp 98-102
°C)); 1H NMR (500 MHz, CDCl3) δ (ppm) 6.67 (1H, d, J ) 8.3
Hz), 6.60 (1H, d, J ) 8.0 Hz), 4.38 (1H, t, J ) 2.8 Hz), 4.08-
4.14 (1H, m), 4.61 (1H, brs), 4.04 (1H, d, J ) 14.8 Hz), 3.86
(3H, s, OMe), 3.64 (1H, d, J ) 14.8 Hz), 3.24 (1H, t, J ) 14.0
Hz), 3.06 (1H, d, J ) 14.0 Hz), 2.51 (1H, t, J ) 15.8 Hz), 2.37
(3H, s, NMe), 1.58-2.04 (10H, m); IR (KBr) 3607, 2900, 1622,
1507, 1437, 1280, 1032 cm-1; LRMS (EI) m/z 289 (M+), 288
(M+ - H); HRMS (EI) calcd for C17H23NO3 289.1678, found
289.1674.
Nor ga la n th a m in e (4). To a stirring solution of 17 (6.4 mg,
0.017 mmol) in H2O (1.00 mL) and MeOH (1.00 mL) was added
potassium carbonate (24.0 mg, 0.17 mmol) and the mixture
stirred at room temperature for 2 h. Ethyl acetate was added
to the reaction mixture. The solvent in the organic layer was
removed using an evaporator. To a stirring solution of the
resulting residue in tetrahydrofuran (2.00 mL) was added a 1
M solution of L-Selectride in tetrahydrofuran (0.070 mL, 0.070
mmol) at -78 °C and the mixture stirred at the same
temperature for 2 h. The mixture was warmed to 0 °C and
stirred for 30 min, H2O was added, and the resulting mixture
was extracted with ethyl acetate and dried. Preparative thin-
layer chromatography (SiO2, CHCl3/MeOH ) 5:1) yielded 4 (3.8
mg, 0.014 mmol, 82%) as white crystals: mp 158-159 °C (from
Et2O (lit.21a mp 156-158 °C, lit.18 mp 149-152 °C, lit.21b mp
152.5-153 °C, lit.21c mp 171-173 °C, lit.21d mp 156-158 °C));
1H NMR (500 MHz, CDCl3) δ (ppm) 6.65 (1H, d, J ) 8.0 Hz),
6.62 (1H, d, J ) 8.0 Hz), 6.06 (1H, d, J ) 10.0 Hz), 6.01 (1H,
dd, J ) 10.5, 5.0 Hz), 4.61 (1H, brs), 4.14 (1H, t, J ) 5.0 Hz),
4.03 (1H, d, J ) 15.0 Hz), 3.96 (1H, d, J ) 15.0 Hz), 3.84 (3H,
s, OMe), 3.37 (1H, d, J ) 14.0 Hz), 3.23 (1H, t, J ) 14.0 Hz),
2.70 (1H, d, J ) 15.0 Hz), 1.73-2.04 (3H, m); IR (KBr) 1506,
1437, 1280, 1265 cm-1; LRMS (EI) m/z 273 (M+); HRMS (EI)
calcd for C16H19NO3 273.1365, found 273.1390.
N-Dem eth yl-N-(tr iflu or oa cetyl)n a r w ed in e (17). To a
20-mL flask were added 14f (11.8 mg, 0.020 mmol), a magnetic
stirring bar, and trifluoroacetic acid (4.00 mL) and the mixture
stirred at room temperature for 45 min. 14f was quantita-
tively converted to 16. The solvent was removed under
vacuum, and acetone (5 mL), potassium carbonate (5.5 mg,
0.040 mmol), and dimethyl sulfate (0.0080 mL, 0.080 mmol)
were added. The mixture was refluxed for 1.5 h, saturated
NaHCO3 was added, and the resulting mixture was extracted
with ethyl acetate and dried. Column chromatography (n-
hexane/AcOEt ) 1:1) yielded 17 (7.5 mg, 0.020 mmol, quant)
as a white amorphous solid: 1H NMR (200 MHz, CDCl3) δ
(ppm) 6.93-6.92 (3H, m), 6.11 and 6.09 (1H, d, J ) 10.4 Hz),
5.32 and 4.92 (1H, d, J ) 15.8 Hz), 4.75 and 4.74 (2H, s), 4.55
and 4.14 (1H, d, J ) 15.8 Hz), 4.63 and 4.36 (1H, d, J ) 15.8
Hz), 3.86 (3H, s), 3.36-3.80 (1H, m), 3.26 and 3.17 (1H, d, J )
2.6 Hz), 2.80 and 2.71 (1H, t, J ) 2.6 Hz), 2.13-2.21 (1H, m);
13C NMR (75.0 MHz, CDCl3) δ (ppm) 193.6, 156.4 (m), 147.7
and 147.6, 144.9, 142.6 and 142.1, 129.5, 128.1 and 127.9, 126.6
and 126.1, 122.4 and 121.2, 116.3 (m), 112.1, 87.8 and 87.7,
56.0, 52.9 and 52.0, 48.8 and 48.8, 46.9 and 46.7, 37.8 and 34.8,
37.1 and 37.1; IR (KBr) 1693, 1512, 1439, 1281, 1252, 1208,
1169, 1143 cm-1; LRMS (EI) m/z 367 (M+); HRMS (EI) calcd
for C18H16NO4F3 367.1031, found 367.1024.
Na r w ed in e (2). To a stirring solution of 17 (2.6 mg, 0.0074
mmol) in H2O (1.00 mL) and MeOH (1.00 mL) was added
potassium carbonate (10.2 mg, 0.074 mmol) and the mixture
stirred at room temperature for 2 h. The reaction mixture was
extracted with ethyl acetate. The organic layer was removed
using an evaporator. To the stirring solution of the resultant
residue in H2O (2.00 mL) were added HCOOH (0.0020 mL,
0.0041 mmol) and 35% HCHO (0.0010 mL, 0.0089 mmol) and
the mixture refluxed for 10 h. To the reaction mixture was
added saturated NaHCO3, and the resulting mixture was
extracted with ethyl acetate, washed with brine, and dried.
Column chromatography (Al2O3, AcOEt only) yielded 2 (2.5
mg, 0.0088 mmol, quant) as white crystals: mp 185-188 °C
(from Et2O, lit.16h mp 187-188 °C); 1H NMR (500 MHz, CDCl3)
δ (ppm) 6.95 (1H, d, J ) 10.0 Hz), 6.70 (1H, d, J ) 8.0 Hz),
6.65 (1H, d, J ) 8.0 Hz), 6.04 (1H, d, J ) 10.0 Hz), 4.73 (1H,
brs), 4.09 (1H, d, J ) 15.0 Hz), 3.84 (3H, s, OMe), 3.75 (1H, d,
J ) 15.0 Hz), 3.19 (3H, m), 2.75 (1H, dd, J ) 15.0 Hz, 4.0 Hz),
2.44 (3H, s, NMe), 2.28 (1H, dt, J ) 15.0 Hz, 4.0 Hz), 1.85
Sa n gu in e (5). To a 20-mL flask were added 14f (95.0 mg,
0.161 mmol), a magnetic stirring bar, and trifluoroacetic acid
(4.00 mL), and the mixture was stirred at room temperature
for 45 min. The solvent was removed under vacuum, and DMF
(1.50 mL), imidazole (27.0 mg, 0.403 mmol), and tert-butyldi-
methylsilyl chloride (29.0 mg, 0.192 mmol) were added. The
mixture was stirred at room temperature for 2 h, saturated
NaHCO3 was added, and the resulting mixture was extracted
with ethyl acetate and dried. Column chromatography (n-
hexane/AcOEt ) 1:1) yielded N-demethyl-O-demethyl- O-(tert-
butyldimethylsilyl)-N-(trifluoroacetyl)narwedine (54.0 mg, 0.115
(24) Biot, H. G. Chem. Ber. 1954, 87, 681-683.