Notes
J . Org. Chem., Vol. 64, No. 12, 1999 4531
Thex]. Because of its instability, the aldehyde 8 was not further
characterized.
(FAB) m/z (rel intensity) 338 (87) [M]+, 320 (100), 218 (21). To
this salt (1.509 g, 3.56 mmol) in distilled t-BuOH (40 mL) was
added freshly sublimated t-BuOK. The reaction mixture was
refluxed for 2 h and then cooled to room temperature. This
solution was poured into a saturated NH4Cl solution and
extracted with CH2Cl2, and the extract was dried over MgSO4
and filtered. The procedure was repeated three times under the
same conditions. After evaporation of the solvent under reduced
pressure, the crude product was chromatographed over alumina
(70 g) with CH2Cl2/MeOH (100:0 to 94:6) as eluent. Dehy-
drosedamine 13a (1.618 g, 70% yield) was isolated as a yellow-
(1S,2S)-(-)-2-(1-{2-[Dim eth yl-(1,1,2-tr im eth ylp r op yl)-si-
la n yloxy]-1-p h en yleth yl}-1,2,3,6-tetr a h yd r op yr id in -2-yl)-
1-p h en yleth a n ol (9a ). A solution of crude aldehyde 8 (9.44 g,
24.39 mmol) in dry Et2O (80 mL) was added dropwise to an ice-
cooled solution of phenylmagnesium chloride in Et2O (61 mL,
36.59 mmol) under an argon atmosphere. After the addition was
complete, the reaction mixture was warmed to room temperature
and stirred overnight. The resulting solution was poured into a
saturated solution of NH4Cl at 0 °C. This solution was then
extracted with Et2O followed by CH2Cl2. The combined extracts
were dried over MgSO4 and filtered, and the solvents were
evaporated under reduced pressure to give a mixture of alcohols
9a and 10a in a 3:2 ratio (determined by integration of the 1H
NMR spectrum). The diastereoisomers were separated over
alumina (360 g) with heptane/EtOAc (100:0 to 80:20) as eluent.
Major diastereoisomer 9a (4.56 g, 40% yield from 8) was isolated
as a gum: [R]20D -18 (c 0.22, CHCl3); 1H NMR (300 MHz, CDCl3)
δ 0.05 (s, 6 H), 0.75-0.85 (m, 12 H), 1.30 (ddd, J ) 14.7, 2.6, 2.6
Hz, 1 H), 1.40 (m, 1 H), 1.55 (heptuplet, J ) 6.9 Hz, 1 H), 2.12
(m, 1 H), 2.38 (m, 1 H), 3.15 (m, 1 H), 3.75 (m, 2 H), 3.80-4.00
(m, 3 H), 4.70 (dd, J ) 10.9, 2.1 Hz, 1 H), 5.60-5.80 (m, 2 H),
7.15-7.45 (m, 10 H); 13C NMR (75.47 MHz, CDCl3) δ 3.6, 18.5,
20.2, 24.8, 34.1, 40.2, 41.8, 53.3, 66.9, 67.4, 75.2, 123.7, 125.5,
126.2, 128.6, 141.4, 145.2; MS (CI) m/z (rel intensity) 466 (100)
[MH]+, 344 (42), 292 (15); HRMS (CI) calcd for C29H44NO2Si m/z
466.3141, found 466.3152. Minor diastereoisomer 10a (3.63 g,
orange oil: [R]21 -100 (c 0.9, CHCl3), -71 (c 2.0, MeOH); 1H
D
NMR (300 MHz, CDCl3) δ 1.50 (ddd, J ) 14.6, 2.7, 2.7 Hz, 1 H),
1.80-2.00 (m, 2 H), 2.15 (m, 1 H), 2.45 (s, 3 H), 3.20-3.40 (m,
3 H), 4.95 (dd, J ) 10.9, 2.7 Hz, 1 H), 5.55-5.80 (m, 2 H), 7.18-
7.40 (m, 5 H); 13C NMR (75.47 MHz, CDCl3) δ 25.0, 37.1, 40.0,
51.0, 58.2, 75.8, 123.9, 124.5, 125.7, 127.1, 128.3, 145.3; MS (EI)
m/z (rel intensity) 217 (7) [M]•+, 96 (100); HRMS (EI) calcd for
C
14H19NO m/z 217.1467, found 217.1464.
(1S,2S)-(-)-2-(1-Meth ylp ip er id in -2-yl)-1-p h en yleth a n ol
[(-)-Sed a m in e (13b)]. Dehydrosedamine 13a (53 mg, 0.244
mmol) was dissolved in EtOAc (5 mL), and a catalytic amount
of 5% palladium on carbon was added to this solution, which
was stirred overnight under a hydrogen atmosphere. After
filtration on Celite and washing with EtOAc and MeOH, the
solvents were evaporated at reduced pressure. The residue was
then filtered over a short column of alumina with heptane/EtOAc
(100:0 to 50:50). (-)-Sedamine 13b (45 mg, 85% yield) was
obtained as white crystals, from which an analytical sample was
32% yield from 8): [R]20 +24 (c 0.14, CHCl3); 1H NMR (300
D
MHz, CDCl3) δ 0.05 (s, 6 H), 0.75-0.85 (m, 12 H), 1.40 (m, 1 H),
1.42-1.55 (m, 2 H), 2.30 (m, 1 H), 2.32-2.45 (ddd, J ) 14.8,
10.3, 5.2 Hz, 1 H), 2.90 (m, 1 H), 3.55 (m, 2 H), 3.70 (m, 2 H),
3.85 (dd, J ) 11.8, 6.5 Hz, 1 H), 4.93 (dd, J ) 5.1, 5.1 Hz, 1 H),
5.60-5.80 (m, 2 H), 7.10-7.42 (m, 10 H); 13C NMR (75.47 MHz,
CDCl3) δ 3.6, 18.5, 20.3, 25.7, 34.1, 37.3, 42.8, 48.7, 66.5, 67.0,
72.2, 123.9, 124.7, 125.7, 128.5, 141.4, 145.3; HRMS (CI) calcd
for C29H44NO2Si m/z 466.3141, found 466.3123.
recrystallized in Et2O/pentane: [R]21 -95 (c 0.9, EtOH), lit.10
D
[R]D -93 (EtOH); 1H NMR (250 MHz, CDCl3) δ 1.26-2.81 (m, 7
H), 2.12 (ddd, J ) 14.4, 10.6, 9.7 Hz, 1 H), 2.50 (s, 3 H), 2.55 (m,
1 H), 2.87 (m, 1 H), 3.10 (m, 1 H), 4.88 (dd, J ) 10.6, 2.8 Hz, 1
H), 7.20-7.40 (m, 5 H); 13C NMR (75.47 MHz, CDCl3) δ 20.55,
22.50, 25.83, 39.88, 40.06, 51.31, 61.06, 74.98, 125.68, 127.133,
128.39, 145.76; MS (EI) m/z (rel intensity) 219 (57) [M]•+, 98
•
(100) [M]•+ - CH2CH(OH)Ph]; HRMS (EI) calcd for C14H21NO
(1S,1S,2S)-(-)-2-[1-(2-Hyd r oxy-1-p h en yleth yl)-1,2,3,6-tet-
r a h yd r op yr id in -2-yl]-1-p h en yleth a n ol (9b). Adduct 9a (4.56
g, 9.81 mmol) was diluted in a mixture of an aqueous solution
of 10 N HCl and THF (3:1) at room temperature, and the
resulting solution was stirred overnight. The reaction mixture
was extracted in the presence of K2CO3 with Et2O followed by
CH2Cl2, and the extracts were dried over MgSO4, filtered, and
evaporated under reduced pressure to give the crude product,
which was chromatographed over alumina (95 g) with heptane/
EtOAc (100:0 to 0:100) followed by CH2Cl2/MeOH (100:0 to 95:
5) as eluent. Diol 9b (2.38 g, 75% yield) was isolated as a yellow
oil: [R]21D -49 (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.42
(ddd, J ) 14.5, 5.1, 2.4 Hz, 1 H, H), 1.62 (m, 1 H), 2.07 (ddd, J
) 14.5, 10.9, 9.1 Hz, 1 H), 2.40 (m, 1 H), 3.35 (m, 2 H), 3.56 (m,
1 H), 3.80 to 4.00 (m, 3 H), 4.70 (dd, J ) 10.9, 2.4 Hz, 1 H),
5.58-5.80 (m, 2 H), 7.20-7.45 (m, 10 H); 13C NMR (75.47 MHz,
CDCl3) δ 26.5, 38.9, 42.8, 52.6, 65.4, 67.2, 74.7, 124.0, 125.6,
127.2, 128.9, 140.4, 145.1; HRMS (CI) calcd for C21H26NO2 m/z
324.1964, found 324.1965.
m/z 219.1623, found 219.1614. Anal. Calcd for C14H21NO: C,
76.67; H, 9.65; N, 6.39. Found: C, 76.64; H, 9.60; N, 6.25.
(1R,2S)-(+)-2-(1-Meth yl-1,2,3,6-tetr a h yd r op yr id in -2-yl)-
1-p h en yleth a n ol (15a ). Treatment of the dialcohol 10b (1.631
g, 5.05 mmol) using the procedure described above for the
preparation of derivative 12 gave salt 14 (1.506 g, 70% yield) as
a pale beige froth. To this salt (1.506 g, 3.54 mmol) in distilled
t-BuOH (40 mL) was added t-BuOK under the conditions
described previously for the preparation of derivative 13a . The
desired dehydroderivative 15a (235 mg, 31% yield) was isolated
as a yellow-orange oil: [R]21 +29.5 (c 1.86, CHCl3), -5.5 (c 1.8,
D
1
MeOH), -5 (c 1.24, EtOH); H NMR (250 MHz, CDCl3) δ 1.60
(ddd, J ) 14.5, 4.6, 3.5 Hz, 1 H), 1.92 (m, 2 H), 2.25 (ddd, J )
14.8, 10.1, 4.8 Hz, 1 H), 2.40 (s, 3 H), 2.89 (m, 1 H), 3.23 (m, 2
H), 5.05 (dd, J ) 4.7, 4.7 Hz, 1 H), 5.50-5.75 (m, 2 H), 7.20-
7.40 (m, 5 H); 13C NMR (75.47 MHz, CDCl3) δ 25.6, 37.7, 37.9,
51.5, 53.9, 73.0, 123.9, 124.6, 125.7, 126.8, 128.3, 145.6; MS (EI)
m/z (rel intensity) 217 (3) [M]•+, 96 (100); HRMS (EI) calcd for
C14H19NO m/z 217.1467, found 217.1466.
(1R,1S,2S)-(+)-2-[1-(2-Hyd r oxy-1-p h en yleth yl)-1,2,3,6-tet-
r a h yd r op yr id in -2-yl]-1-p h en yleth a n ol (10b). Deprotection of
derivative 10a (3.63 g, 7.80 mmol) under the conditions used
(1R ,2S )-(-)-2-(1-Me t h ylp ip e r id in -2-yl)-1-p h e n yle t h a -
n ol [(-)-Allosed a m in e (15b)]. Dehydroallosedamine (15a ) (68
mg, 0.313 mmol) was hydrogenated under the conditions used
for preparation of (-)-sedamine. (-)-Allosedamine (61 mg, 90%
yield) was obtained as white crystals, from which an analytical
for the deprotection of 9a gave diol 10b (1.79 g, 71% yield): [R]21
D
+52 (c 2.4, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.60-1.70 (m,
2 H), 2.08 (ddd, J ) 13.9, 7.4, 5.7 Hz, 1 H), 2.30 (m, 1 H), 3.02
(dd, J ) 13.1, 6.5 Hz, 1 H), 3.20 (bd, 1 H) 3.28 (bd, 1 H), 3.60
(dd, J ) 9.4, 4.5 Hz, 1 H), 3.68-3.78 (m, 2 H), 4.84 (dd, J ) 6.0,
6.0 Hz, 1 H), 5.57-5.72 (m, 2 H), 7.20-7.35 (m, 10 H); 13C NMR
(75.47 MHz, CDCl3) δ 27.9, 37.7, 43.0, 50.1, 63.5, 67.5, 72.5,
124.1, 124.7, 125.8, 128.7, 139.9, 145.0; HRMS (CI) calcd for
C21H26NO2 m/z 324.1963, found 324.1941.
sample was recrystallized in Et2O/pentane: [R]21 -25 (c 1.95,
D
MeOH)), lit.11 [R]D -30 (EtOH); 1H NMR (250 MHz, CDCl3) δ
1.30 (m, 1 H), 1.55-1.75 (m, 4 H), 1.78-1.90 (m, 2 H), 2.05 (m,
1 H), 2.17 (m, 1 H), 2.28 (m, 1 H), 2.43 (s, 3 H), 2.97 (m, 1 H),
5.12 (dd, J ) 10.7, 3.6 Hz, 1 H), 7.20-7.40 (m, 5 H); 13C NMR
(75.47 MHz, CDCl3) δ 24.4, 25.5, 29.3, 39.5, 43.9, 57.0, 62.7, 72.0,
125.7, 127.0, 128.3, 145.6; MS (EI) m/z (rel intensity) 219 (6)
[M]•+, 98 (100). Anal. Calcd for C14H21NO: C, 76.67; H, 9.65; N,
6.39. Found: C, 76.54; H, 9.69; N, 6.52.
(1S,2S)-(-)-2-(1-Meth yl-1,2,3,6-tetr a h yd r op yr id in -2-yl)-
1-p h en yleth a n ol (13a ). To a solution of diol 9b (4.96 g, 15.3
mmol) in distilled CH3CN (160 mL) was added diphenylmethyl
sulfonium tetrafluoroborate 11 (6.67 g, 21.09 mmol), and the
resulting mixture was refluxed for 48 h. After removal of the
solvent under reduced pressure, the crude product was chro-
matographed over alumina (195 g) with CH2Cl2/MeOH (100:0
to 50:50) as eluent. Salt 12 (4.53 g, 70% yield) was isolated as a
pale beige froth: 1H NMR (300 MHz, CDCl3) δ 3.15 (s, 3 H); MS
(2S,6S)-2-[6-(2-Hyd r oxy-2-p h en yleth yl)-1-m eth yl-1,2,5,6-
tetr a h yd r op yr id in -2-yl]-a cetic Acid Eth yl Ester (18). To an
ice-cooled solution of dehydrosedamine 13a (218 mg, 1.00 mmol)
in CH2Cl2 (10 mL) was added m-CPBA (371 mg, 1.5 mmol). After
15 min, the reaction mixture was briefly filtered over a short
column of alumina with a gradient of CH2Cl2/MeOH (100:0 to
95:5) as eluent. Evaporation of solvents afforded N-oxide 16,