6860 J . Org. Chem., Vol. 62, No. 20, 1997
Schultz and Pettus
quenched with saturated NH4Cl. The aqueous layer was
extracted with CH2Cl2, and the combined organic layers were
dried and concentrated. Flash chromatography of the residue
gave 15 (1.67 g, 84%) as a white foam. IR (CHCl3) 3479, 3017,
(2 H, m), 1.61 (1 H, m), 0.92 (3 H, t, J ) 7.5 Hz). 13C NMR
(CDCl3) δ 170.5, 141.4, 135.2, 132.3, 128.2, 126.5, 122.1, 119.6,
118.1, 116.9, 112.4, 110.9, 110.1, 62.8, 43.2, 43.0, 23.4, 20.6,
7.2. CI-MS, m/z (relative intensity) 295 (M+ + 1, 100%). CI-
HRMS Calcd for C19H22N2O: (M+ + 1) 295.1810, Found:
295.1805.
2969, 1653, 1520 cm-1
.
Rf ) 0.13 (1:2 hexane:EtOAc). 1H
NMR (CDCl3) δ 8.08 (1 H, br), 7.60 (1 H, d, J ) 7.2 Hz), 7.40-
7.05 (3 H, m), 5.60 (3 H, br), 3.84 (2 H, m), 3.61 (2 H, m), 3.46
(1 H, d, J ) 12.2 Hz), 3.36 (1 H, d, J ) 12.0 Hz), 2.98 (2 H, t,
J ) 6.9 Hz), 2.09 (2 H, t, J ) 7.3 Hz), 1.95 (1 H, m), 1.43 (1 H,
m), 1.33 (2 H, m), 1.13 (1 H, m), 0.77 (3 H, m), 0.13 (9 H, s).
13C NMR (CDCl3) δ 173.8, 136.3, 127.2, 122.1, 122.0, 119.4,
118.5, 112.7, 111.2, 67.3, 60.5, 42.8, 39.7, 37.3, 29.6, 26.3, 25.1,
14.1, 7.6, 1.3. CI-MS, m/z (relative intensity) 405 (M+ +1, 7%).
CI-HRMS Calcd for C22H36N2O3Si: (M+ + 1) 405.2573,
Found: 405.2558.
Am in o Alcoh ol 18. To a solution of 17 (60 mg, 0.20 mmol)
in THF (3 mL) at 0 °C was added BH3‚THF (0.92 mL of 1 M
solution, 0.92 mmol). After stirring at room temperature for
2 h, the mixture was cooled to 0 °C, and then EtOH (0.36 mL),
H2O (0.14 mL), 6 N NaOH (0.36 mL), and H2O2 (0.84 mL of
30% wt) were added. The mixture was heated at an oil bath
temperature of 55 °C for 1.5 h and then cooled to room
temperature and extracted with CH2Cl2 (2 × 10 mL). The
combined organic layers were dried, concentrated, and chro-
matographed to afford 18 (52 mg, 86% yield) as a white solid
Alk en e 16a . A solution of 15 (92 mg, 2.3 mmol) in THF (5
mL) was added to a mixture of KH (2.61 g, 35%, 22.8 mmol)
suspended in THF (5 mL) at 0 °C. After the resulting mixture
was stirred at room temperature for 3 h, it was poured into
saturated NH4Cl (20 mL) cooled with ice. The solution was
extracted with CH2Cl2 (3 × 30 mL), and the organic layers
were combined, dried, and concentrated. Flash chromatogra-
phy of the residue provided 16a (60 mg, 84%) as a colorless
(mp 167.0-168.0 °C) (lit.7 mp 166-168 °C). [R]23 -98.0° (c
D
1.0, CHCl3). IR (CHCl3) 3496, 3017, 2966 cm-1. Rf ) 0.38 (1:1
hexane/EtOAc). 1H NMR (CDCl3) δ 7.83 (1 H, br), 7.47 (1 H,
d, J ) 7.8 Hz), 7.30 (1 H, dd, J ) 8.0, 0.7 Hz), 7.13 (1 H, dt, J
) 7.1, 1.3 Hz), 7.09 (1 H, dt, J ) 7.7, 1.2 Hz), 6.58 (1 H, br),
3.75 (1 H, dt, J ) 11.7, 3 Hz), 3.42 (1 H, m), 3.35 (1 H, s), 3.17
(2 H, m), 3.03 (1 H, m), 2.66 (2 H, m), 2.43 (1 H, m), 2.12 (1 H,
m), 1.78 (1 H, m), 1.71-1.61 (5 H, m), 1.33 (1 H, m), 1.12 (3
H, t, J ) 7.5 Hz). 13C NMR (CDCl3) δ 135.9, 132.2, 126.6,
121.6, 119.3, 118.1, 111.8, 110.5, 67.0, 58.6, 56.2, 53.9, 40.7,
38.7, 35.5, 32.2, 22.9, 21.2, 8.4. CI-MS, m/z (relative intensity)
oil. [R]23 -4.0° (c 1.0, CHCl3). IR (CHCl3) 3480, 3019, 1657,
D
1520 cm-1. Rf ) 0.26 (5% CH2Cl2 in MeOH). 1H NMR (CDCl3)
δ 8.09 (1 H, br), 7.60 (1 H, d, J ) 8.0 Hz), 7.37 (1 H, d, J ) 8.1
Hz), 7.21 (1 H, m), 7.13 (1 H, m), 7.04 (1 H, s), 5.53 (1 H, m),
5.51 (2 H, br), 5.14 (1 H, d, J ) 10.9 Hz), 4.91 (1 H, d, J )
17.8 Hz), 3.60 (2 H, m), 3.35 (2 H, m), 2.96 (2 H, m), 2.75 (1 H,
t, J ) 6.4 Hz), 2.08 (2 H, t, J ) 7.1 Hz), 1.77 (1 H, m), 1.60 (1
H, m), 1.41 (1 H, m), 1.35 (1 H, m), 0.79 (3 H, t, J ) 6.8 Hz).
13C NMR (CDCl3) δ 174.2, 142.7, 136.3, 127.1, 122.1, 121.8,
119.1, 118.4, 114.5, 112.3, 111.3, 64.4, 44.3, 39.8, 30.5, 28.0,
26.9, 25.0, 7.6. CI-MS, m/z (relative intensity) 315 (M+ + 1,
39%). HRMS (CI) Calcd for C19H26N2O2: (M+ + 1) 315.2072,
Found: 315.2066.
299 (M+ + 1, 100%). HRMS (CI) calcd for C19H26N2O: (M+
H) 299.2123, Found: 299.2115.
+
(-)-Ebu r n a m on in e (4). To a solution of 18 (51 mg, 0.17
mmol) and a small amount of ground molecular sieves in
CH2Cl2 (5 mL) was added N-methylmorpholine N-oxide (41
mg, 0.34 mmol) followed by tetrapropylammonium perruth-
enate (7 mg, 0.02 mmol) 10 min later. After the resulting
mixture was stirred for 1 h, it was filtered through a small
pad of Celite. The Celite was washed with a large amount of
CH2Cl2, and the filtrate was washed with saturated Na2SO3
(8 mL), brine (5 mL), and saturated CuSO4 (5 mL). The
organic layer was separated, dried, and concentrated. The
residue was chromatographed to afford (-)-eburnamonine (4)
La cta m 17. To a mixture of 16a (130 mg, 0.41 mmol) and
small amount of ground molecular sieves in CH2Cl2 (10 mL)
at 0 °C was added N-methylmorpholine N-oxide (54 mg, 0.45
mmol) followed by tetrapropylammonium perruthenate (7 mg,
0.02 mmol) 10 min later. The mixture was stirred at room
temperature for 2 h, diluted with CH2Cl2 (30 mL), and filtered
through a small pad of Celite. The filtrate was washed with
saturated Na2SO3 (5 mL), brine (5 mL) and saturated CuSO4
(5 mL). The organic layer was dried, concentrated, and
chromatographed to afford 16b (90 mg, 70%) as a colorless
oil. IR (CHCl3) 3479, 3015, 1723, 1662, 1519 cm-1; Rf ) 0.36
(1:1 hexane/EtOAc). 1H NMR (CDCl3) δ 9.37 (1 H, s), 8.04 (1
H, br), 7.60 (1 H, d, J ) 8.1 Hz), 7.38 (1 H, d, J ) 7.3 Hz), 7.21
(1 H, d, J ) 7.1 Hz), 7.13 (1 H, m), 7.05 (1 H, s), 5.71 (1 H, m),
5.49 (1 H, br), 5.33 (1 H, dd, J ) 11.0, 0.7 Hz), 5.11 (1 H, dd,
J ) 17.8, 0.7 Hz), 3.59 (2 H, m), 2.97 (2 H, t, J ) 6.6 Hz), 2.04
(2 H, m), 1.98 (2 H, m), 1.64 (2 H, m), 0.82 (3 H, t, J ) 7.7 Hz).
13C NMR (CDCl3) δ 172.2, 171.1, 136.7, 136.3, 127.2, 122.1,
122.0, 119.4, 118.6, 117.9, 112.8, 111.2, 55.6, 39.6, 31.0, 27.4,
25.8, 25.1, 7.9. CI-MS, m/z (relative intensity) 313 (M+ + 1,
100%). HRMS (CI) Calcd for C19H26N2O2: (M+ + 1) 313.1916,
Found: 313.1919. Aldehyde 11 readily decomposed at room
temperature and, therefore, was used immediately in the next
step.
(49 mg, 97% yield) as a white solid. Mp 173-175 °C. [R]23
D
) -93.0° (c 0.5, CHCl3). 1H NMR, 13C NMR, and IR spectra
and TLC behavior were identical to those of the authentic
sample {mp 174-176 °C. [R]23 -94.0° (c ) 0.5, CHCl3)}
D
purchased from Aldrich Chemical Co. Mixed mp of synthetic
and authentic samples: 173-176 °C.
Am id e 20. A solution of 12 (1.93 g, 6.82 mmol) and
p-toluenesulfonic monohydrate (1.97 g, 10.2 mmol) in benzene
(50 mL) and water (5.5 mL) was refluxed for 48 h. The
aqueous layer was separated and extracted with CH2Cl2. The
combined organic layers were dried and concentrated to give
13 as a pale yellow oil which was not purified. To a solution
of 13 in THF (50 mL) at 0 °C were added tryptamine (1.45 g,
8.87 mmol) and Et3N (1.91 mL, 13.6 mmol). After the mixture
was stirred at 0 °C for 10 min, diphenylphosphoryl azide (1.97
mL, 8.87 mmol) was added. The reaction mixture was warmed
to room tempererature and stirred overnight. After volatile
material was removed under reduced pressure, the residue was
dissolved in CH2Cl2 (200 mL). The resulting solution was
washed with 15% NaOH, brine, 2 N HCl, and saturated
NaHCO3. The organic layer was separated, dried, and evapo-
rated. Chromatography afforded 20 as a pale yellow amor-
A solution of 16b (90 mg, 0.29 mmol) in CH2Cl2 (5 mL) at
-55 °C was treated with CF3CO2H (0.11 mL, 1.4 mmol) and
then stirred for 10 h and quenched with saturated NaHCO3.
The aqueous layer was separated and extracted with CH2Cl2
(30 mL). The organic layers were combined, dried, and
concentrated. An NMR spectrum of the reaction mixture
showed an approximately 18/1 mixture of R/â epimers. The
residue was chromatographed to give the major diastereomer
17 (75 mg, 88% yield) as a colorless solid (mp 265.0-267.0
°C). [R]23D -98.0° (c 1.0, CHCl3). IR (CHCl3) 3453, 3018, 2969,
phous solid (1.88 g, 84%). [R]23 -13.0° (c 1.0, CHCl3). IR
D
(CHCl3) 3479, 3027, 1760, 1663, 1519 cm-1
. Rf ) 0.10 (1:3
hexane:EtOAc). 1H NMR (CDCl3) δ 8.50 (1 H, br s), 7.58 (1
H, d, J ) 7.8 Hz), 7.35 (1 H, t, J ) 1.0 Hz), 7.17 (1 H, td, J )
7.7, 1.2 Hz), 7.10 (1 H, td, J ) 7.8, 1.0 Hz), 6.98 (1 H, d, J )
2.2 Hz), 5.81 (1 H, br s), 4.21 (2 H, t, J ) 7.6 Hz), 3.58 (2 H,
q, J ) 6.6 Hz), 2.97 (2 H, t, J ) 6.9 Hz), 2.38 (1 H, m), 2.15-
2.04 (3 H, m), 1.82 (2 H, m), 1.58 (2 H, m), 0.92 (3 H, t, J ) 7.5
Hz). 13C NMR (CDCl3) δ 180.9, 172.0, 136.3, 127.1, 122.0,
121.9, 119.2, 118.5, 112.5, 111.2, 65.1, 45.7, 39.6, 31.6, 31.1,
30.3, 28.0, 25.0, 8.4. CI-MS, m/z (relative intensity) 329 (M+
+ 1, 100%). Anal. Calcd for C19H24N2O3: C, 69.49; H, 7.37,
Found: C, 69.67; H 7.41.
1632, 1426 cm-1
.
Rf ) 0.34 (1:1 hexane/EtOAc). 1H NMR
(CDCl3) δ 8.36 (1 H, br), 7.48 (1 H, d, J ) 7.8 Hz), 7.30 (1 H,
dd, J ) 8.1, 1.0 Hz), 7.17 (1 H, dt, J ) 7.5, 1.0 Hz), 7.10 (1 H,
dt, J ) 7.5, 1.0 Hz), 6.03 (1 H, dd, J ) 17.8, 10.95 Hz), 5.49 (1
H, dd, J ) 10.85, 0.80 Hz), 5.26 (1 H, dd, J ) 17.95, 0.8 Hz),
4.97 (1 H, m), 4.68 (1 H, s), 3.05 (1 H, m), 2.84 (1 H, dt, J )
12.5, 4.4 Hz), 2.69 (1 H, m), 2.42 (2 H, m), 2.03 (1 H, m), 1.84
La ctol 21. To a solution of 20 (90 mg, 0.27 mmol) in CH2Cl2
(5 mL) at -78 °C was added diisobutylaluminum hydride (1.32