roethyl Ester (8). To a solution of 6 (1.16 g, 1.89 mmol) in
dioxane/H2O (3:1) was added OsO4 (10 mL, 1 mg/mL in dioxane/
H2O 1:1) at room temperature. The reaction mixture was stirred
for 10 min and then NaIO4 (1.21 g, 5.68 mmol) was added in
portions over a period of 15 min. The resulting suspension was
stirred for a further 4 h and then filtered through a Celite pad
and the filter cake was rinsed with CHCl3. The aqueous phase
was extracted with CHCl3 and the combined organic portions
were washed with saturated Na2S2O3, dried over anhydrous Na2-
SO4, filtered, and concentrated under reduced pressure. The
resulting aldehyde 7 was dissolved in 20 mL of EtOH. NaBH4
(140 mg, 3.70 mmol) was added in portions at 0 °C. The mixture
was stirred for 2 h, and then quenched with acetone. Organic
solvent was evaporated under reduced pressure, the resulting
residue was suspended in water (20 mL) and extracted with
CHCl3 (3 × 30 mL), and the combined organic liquors were dried
over anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The crude product was purified by column
chromatography (hexanes/EtOAc 6:1) to give 8 (701 mg, 70%)
as a colorless oil: [R]22D -35.4 (c 0.59, CHCl3); IR (neat) ν 3433,
3030, 2940, 2931, 2858, 1715, 1472, 1456, 1407, 1331, 1254,
1138, 1092, 1064, 837, 777, 701 cm-1; 1H NMR δ (two rotamers
in a ratio of about 6:4) -0.22 (s, 3H × 0.4), -0.20 (3H, 3H ×
0.6), 0.01 (s, 3H), 0.87 (s, 9H × 0.4), 0.88 (s, 9H × 0.6), 1.20-
1.64 (m, 7H), 1.65-1.89 (m, 1H), 1.95-2.10 (m, 1H), 2.15-2.38
(m, 2H), 2.77 (s, 3H × 0.4), 2.78 (s, 3H × 0.6), 3.57 (dd, J )
13.5, 6.6 Hz, 2H), 4.00-4.20 (m, 1H), 4.44 (A of AB, 1H × 0.4),
4.59 (t, J ) 6.6 Hz, 1H × 0.6), 4.62 (t, J ) 6.6 Hz, 1H × 0.4),
4.68-4.84 (A′B′, 2H × 0.6), 5.00 (B of AB, 1H × 0.4), 7.14-7.40
(m, 5H) ppm; 13C NMR δ -4.70, -4.66, -4.3, 18.4, 22.4, 22.8,
26.1, 28.6, 32.0, 32.2, 32.6, 32.8, 44.2, 44.3, 53.1, 62.9, 63.0, 72.7,
72.8, 75.1, 95.8, 96.2, 126.21, 126.24, 127.4, 127.5, 128.2, 128.3,
(A′B′, 2H × 0.6), 5.00 (B of AB, 1H × 0.4), 7.19-7.40 (m, 5H)
ppm; 13C NMR δ -4.7, -4.6, -4.2, 18.4, 24.8, 25.1, 26.1, 28.7,
31.4, 31.5, 32.5, 32.8, 33.7, 33.9, 44.2, 44.3, 53.0, 72.7, 72.8, 75.1,
95.8, 96.2, 126.2, 127.4, 127.6, 128.3, 128.4, 144.5, 144.8, 154.7
ppm; MS (EI) m/z 530/532/534/536 (M+ - tBu), 456/458/460/462
(100), 352/354/356/358, 318, 221, 98; HRMS calcd for C19H28
-
BrCl3NO3Si (M - tBu, A + 2 ion) m/z 532.0058, found 532.0024;
HRMS calcd for C19H28BrCl3NO3Si (M - tBu, A + 4 ion) m/z
534.0034, found 534.0027.
(S)-2-[1-Methylpiperidin-(2S)-2-yl]-1-phenylethanol (10).
A suspension of 9 (440 mg, 0.75 mmol) and Zn dust (0.8 g) in
HOAc/CH2Cl2 (3/1) (12 mL) was stirred vigorously at room
temperature for 4 h. The mixture was filtered, and the filtrate
was concentrated under reduced pressure, basified with a
saturated K2CO3 solution (15 mL), and extracted with CHCl3 (3
× 20 mL). The combined organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by column chroma-
tography (CHCl3/MeOH/NH4OH 30:1:0.2) to give 10 (238 mg,
96%) as a colorless oil: [R]22D -87.6 (c 0.93, CHCl3); IR (neat) ν
3029, 2931, 2857, 2780, 1463, 1254, 1005, 836, 773, 700 cm-1
;
1H NMR δ -0.25 (s, 3H), 0.02 (s, 3H), 0.89 (s, 9H), 1.23-1.78
(m, 6H), 1.90 (m, 1H), 2.10-2.40 (m, 3H), 2.31 (s, 3H), 2.86 (dt,
J ) 12.0, 3.3 Hz, 1H), 4.70 (dd, J ) 9.6, 3.0 Hz, 1H), 7.19-7.39
(m, 5H) ppm; 13C NMR δ -4.7, -4.1, 18.4, 23.6, 25.5, 26.1, 30.5,
42.8, 43.1, 56.5, 60.6, 72.5, 126.0, 127.2, 128.2, 145.6 ppm; MS
(EI) m/z 333 (M+), 318, 276, 98 (100), 73; HRMS calcd for C30H35-
NOSi m/z 333.2482, found 333.2493.
(-)-Sedamine (11). To a solution of 10 (185 mg, 0.55 mmol)
in EtOH (10 mL) was added concentrated HCl (0.1 mL). After 3
h at 55-60 °C, the reaction mixture was basified with saturated
aqueous K2CO3 solution (10 mL). The aqueous layer was
extracted with CHCl3 (3 × 20 mL). The combined organic layers
were dried over anhydrous Na2SO4, filtered, and concentrated
under reduced pressure. The crude product was purified by
column chromatography (CHCl3/MeOH/NH4OH 10:1:0.2) to give
11 (124 mg, quantitative yield) as a white solid: mp 58-59 °C
(lit.5 mp 58-60 °C); [R]22D -89.4 (c 1.0, EtOH) [lit.5 mp -87.1 (c
0.93, EtOH)]; IR (KBr) ν 3362, 3060, 3028, 2935, 2855, 2795,
1450, 1061, 701 cm-1; 1H NMR δ 1.25-1.82 (m, 7H), 2.12 (ddd,
J ) 14.4, 10.5, 9.6 Hz, 1H), 2.49 (s, 3H), 2.55 (m, 1H), 2.85 (m,
1H), 3.06 (m, 1H), 4.89 (dd, J ) 10.8, 2.7 Hz, 1H), 7.20-7.42
(m, 10H) ppm; 13C NMR δ 20.7, 22.6, 26.0, 40.0, 40.2, 51.4, 61.1,
74.9, 125.6, 127.1, 128.3, 145.7 ppm; MS (EI) m/z 219 (M+), 129,
112, 104, 98 (100), 77, 70; HRMS calcd for C14H21NO m/z
219.1618, found 219.1614.
144.5, 144.8, 154.7, 154.8 ppm; MS (EI) m/z 468/470/472 (M+
-
tBu) (100), 454/456/462, 364/366/368, 259, 233, 221, 73; HRMS
calcd for C19H2935Cl3NO4Si (M+ - tBu) m/z 468.0926, found
468.0919; HRMS calcd for C27H3335Cl237ClNO4Si (M+ - tBu) m/z
470.0896, found 470.0889.
{(1S)-1-[(2S)-2-(tert-Butyldimethylsilanoxy)-2-phenyl-
ethyl]-5-bromopentyl}methylcarbamic Acid 2,2,2-Trichlo-
roethyl Ester (9). To a solution of 8 (570 mg, 1.08 mmol) and
CBr4 (464 mg, 1.40 mmol) in CH2Cl2 (10 mL) was added dropwise
at 0 °C a solution of PPh3 (386 mg, 1.47 mmol) in CH2Cl2 (5
mL). The mixture was stirred at 0 °C for 1 h and poured into
hexanes/EtOAc (4:1) (60 mL). The resulting suspension was
filtered through a short silica gel column with hexanes/EtOAc
(4:1). The combined filtrates were concentrated under reduced
pressure. The crude product was purified by column chroma-
tography (hexanes/EtOAc 20:1) to give 9 (595 mg, 93%) as a
colorless oil: [R]22D -28.4 (c 0.89, CHCl3); IR (neat) ν 3031, 2945,
2930, 2886, 2857, 1717, 1457, 1252, 1142, 1092, 837, 777, 701
cm-1; 1H NMR δ (two rotamers in a ratio of about 6:4) -0.22 (s,
3H × 0.4), -0.20 (3H, 3H × 0.6), 0.01 (s, 3H), 0.87 (s, 9H × 0.4),
0.88 (s, 9H × 0.6), 1.25-1.60 (m, 4H), 1.68-1.95 (m, 3H), 1.98-
2.10 (m, 1H), 2.77 (s, 3H × 0.4), 2.78 (s, 3H × 0.6), 3.29-3.38
(m, 2H), 4.06-4.20 (m, 1H), 4.44 (A of AB, 1H × 0.4), 4.59 (t, J
) 6.6 Hz, 1H × 0.6), 4.62 (t, J ) 6.6 Hz, 1H × 0.4), 4.67-4.86
Acknowledgment. This research was supported by
NIH grants DA 00399 and DA 13519.
Supporting Information Available: General experimen-
tal methods and NMR spectra of all new compounds. This
material is available free of charge via the Internet at
JO048848J
J. Org. Chem, Vol. 69, No. 24, 2004 8517