Okamoto et al.
dispersion) at 0 °C, and the mixture was stirred at room
temperature for 10 min. The reaction mixture was cooled to 0
°C, and iodomethane (0.12 mL, 1.81 mmol) was added to the
mixture. The mixture was stirred for 10 h with gradual
warming to room temperature. The reaction mixture was
diluted with ether (30 mL) and saturated aqueous sodium
bicarbonate (15 mL). The aqueous layer was separated and
extracted with ether (3 × 30 mL). The combined organic
extracts were washed with brine (50 mL), dried over sodium
sulfate, filtered, and concentrated in vacuo. The residue was
purified by chromatography on silica gel (30 g, 7:1 n-hexane/
ethyl acetate) to give (2S,3R)-10 (500 mg, 97%) as a colorless
70.0, 79.5, 85.7, 114.9, 127.5, 127.8, 128.0, 128.6, 130.3, 136.9,
155.8, 158.5. Anal. Calcd for C22H29NO5: C, 68.20; H, 7.54; N,
3.61. Found: C, 68.22; H, 7.65; N, 3.38.
(2S,3S)-3-(4-Ben zyloxyp h en yl)-2-ter t-bu toxyca r bon yl-
a m in o-3-m eth oxy-1-p r op a n ol [(2S,3S)-11]. Prepared as
described for (2S,3R)-11 with (2S,3S)-10: mp 62-65 °C; [R]28
D
+43.2 (c 0.72, CHCl3); IR (KBr) 3498, 3326, 2932, 1670, 1510,
1176 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.37 (9H, s), 3.23 (3H,
s), 3.66-3.76 (3H, m), 4.36 (1H, d, J ) 4.3 Hz), 5.06 (2H, s),
6.97 (2H, d, J ) 8.5 Hz), 7.22 (2H, d, J ) 8.6 Hz), 7.33-7.44
(5H, m); 13C NMR (100 MHz, CDCl3) δ 28.3, 56.9, 57.2, 63.8,
70.0, 79.6, 82.8, 114.8, 127.4, 128.0, 128.2, 128.6, 130.5, 136.9,
158.7. Anal. Calcd for C22H29NO5‚1/3H2O: C, 67.15; H, 7.60;
N, 3.56. Found: C, 67.05; H, 7.61 N, 3.47.
oil: [R]27 -10.7 (c 0.31, CHCl3); IR (KBr) 2931, 1695, 1611,
D
1510, 1385, 1245, 1172, 1092 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.26-1.71 (15H, m), 3.30 (3H, m), 3.72-3.80 (1H, m), 3.90-
4.14 (2H, m), 4.11-4.59 (1H, m), 5.03 (2H, m), 6.96 (2H, m),
7.21-7.42 (7H, m); 13C NMR (100 MHz, CDCl3) δ 24.3, 25.9,
28.4, 63.5, 64.4, 70.0, 74.6, 94.6, 114.6 and 114.9 (rotamers),
127.1, 127.4, 127.9, 128.6, 133.4, 137.0, 158.2; HRFABMS
(NBA) calcd for C25H34NO5 (M + H) 428.2437, found 428.2420.
(2R,3S)-3-(4-Ben zyloxyp h en yl)-2-ter t-bu toxyca r bon yl-
a m in o-3-m eth oxy-1-p r op a n ol [(2R,3S)-11]. Prepared as
described for (2S,3R)-11 with (2R,3S)-10: mp 70-72 °C; [R]29
D
+19.7 (c 0.5, CHCl3); IR (KBr) 3360, 2821, 1688, 1611, 1536,
1
1243, 1064 cm-1; H NMR (400 MHz, CDCl3) δ 1.44 (9H, m),
2.81 (1H, d, J ) 7.4 Hz), 3.30 (3H, s), 3.48-3.54 (1H, m), 3.66
(1H, brs), 3.84 (1H, dt, J ) 2.9, 11.5 Hz), 4.52 (1H, s), 5.06
(2H, s), 5.38 (1H, d, J ) 7.5 Hz), 6.99 (2H, d, J ) 8.8 Hz), 7.25
(2H, d, J ) 8.4 Hz), 7.31-7.45 (5H, m); 13C NMR (100 MHz,
CDCl3) δ 28.3, 56.2, 57.9, 60.3, 61.5, 70.0, 79.5, 85.7, 114.9,
127.4, 127.8, 128.0, 128.6, 130.3, 136.9, 158.5; Anal. Calcd for
(4S)-4-[(1S)-1-(4-Ben zyloxyp h en yl)m eth oxym eth yl]-3-
ter t-b u t oxyca r b on yl-2,2-d im et h yloxa zolid in e [(2S,3S)-
10]. Prepared as described for (2S,3R)-10 with (2S,3S)-7b:
[R]29 -41.7 (c 0.59, CHCl3); 1H NMR (400 MHz, CDCl3) δ
D
0.78-1.52 (15H, m), 3.27 (3H, s), 3.89-4.74 (4H, m), 5.07 (2H,
s), 6.95 (2H, d, J ) 8.4 Hz), 7.21 (2H, d, J ) 8.2 Hz), 7.26-
7.43 (5H, m); 13C NMR (100 MHz, CDCl3) δ 24.5, 25.5, 28.5,
57.2, 60.5, 69.9, 114.4, 127.4, 127.9, 128.5, 128.9, 130.3, 137.0,
158.6; HRFABMS (NBA) calcd for C25H34NO5 (M + H) 428.2437,
found 428.2420.
C
22H29NO5: C, 68.20; H, 7.54; N, 3.61. Found: C, 68.33; H,
7.62; N, 3.64.
(2R,3R)-3-(4-Ben zyloxyp h en yl)-2-ter t-bu toxyca r bon yl-
a m in o-3-m eth oxy-1-p r op a n ol [(2R,3R)-11]. Prepared as
described for (2S,3R)-11 with (2R,3R)-10: mp 60-63 °C; [R]28
D
(4R)-4-[(1S)-1-(4-Ben zyloxyp h en yl)m eth oxym eth yl]-3-
ter t-bu toxyca r bon yl-2,2-d im eth yloxa zolid in e [(2R,3S)-
-40.9 (c 0.72, CHCl3); IR (KBr) 3490, 3324, 2932, 1691, 1510,
1176 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.37 (9H, s), 3.24 (3H,
s), 3.65-3.76 (3H, m), 4.36 (1H, d, J ) 4.2 Hz), 5.06 (2H, s),
6.97 (2H, d, J ) 8.6 Hz), 7.21 (2H, d, J ) 8.6 Hz), 7.31-7.45
(5H, m); 13C NMR (100 MHz, CDCl3) δ 28.3, 56.9, 60.4, 63.9,
70.0, 79.6, 82.9, 114.8, 127.5, 128.0, 128.2, 128.6, 130.4, 136.9,
158.7. Anal. Calcd for C22H29NO5‚1/3H2O: C, 67.15; H, 7.60;
N, 3.56. Found: C, 67.45; H, 7.44; N, 3.64.
10]. Prepared as described for (2S,3R)-10 with ent-7a : [R]27
D
+9.68 (c 0.37, CHCl3); IR (neat) 2979, 1699, 1509, 1365, 1233
1
cm-1; H NMR (400 MHz, CDCl3) δ 1.32 and 1.34 (rotamer,
9H, s), 1.52-1.78 (6H, m), 3.31 (3H, s), 3.73-3.82 (1H, m),
3.91-4.05 (1H, m), 4.10-4.15 (1H, m), 4.36-4.59 (1H, m), 5.05
(2H, s), 6.97-6.98 (2H, m), 7.22-7.45 (7H, m); 13C NMR (100
MHz, CDCl3) δ 23.3 and 24.9 (rotamers), 26.6 and 26.8
(rotamers), 28.2 and 28.3 (rotamers), 62.3 and 62.5 (rotamers),
63.6 and 64.4 (rotamers), 70.0, 94.1 and 94.7 (rotamers), 114.6
and 114.8 (rotamers), 127.4, 128.0 and 128.1 (rotamers), 128.6,
131.3, 137.0, 158.4; HRFABMS (NBA) calcd for C25H34NO5 (M
+ H) 428.2437, found 428.2408.
(2R,3R)-3-(4-Ben zyloxyp h en yl)-2-ter t-bu toxyca r bon yl-
a m in o-3-m eth oxyp r op ion ic Acid [(2R,3R)-4]. To a stirred
solution of (2S,3R)-11 (1.00 g, 2.58 mmol) in dichloromethane
(7.7 mL) was added triethylamine (1.80 mL, 12.9 mmol) at -15
°C. A solution of pyridine-sulfur trioxide complex (2.04 g, 12.9
mmol) in DMSO (7.7 mL) was added to the above solution in
one portion. The mixture was stirred at the same temperature
for 10 min. The mixture was poured into ice-saturated sodium
chloride (225 mL) and extracted with cold ether (3 × 100 mL).
The combined organic extracts were washed with 10% citric
acid (50 mL) and brine (50 mL), dried over sodium sulfate,
filtered, and concentrated in vacuo to give an aldehyde, which
was used in the following reaction without further purification.
(4R)-4-[(1R)-1-(4-Ben zyloxyp h en yl)m eth oxym eth yl]-3-
ter t-bu toxyca r bon yl-2,2-d im eth yloxa zolid in e [(2R,3R)-
10]. Prepared as described for (2S,3R)-10 with ent-7b: [R]29
D
+40.7 (c 0.61, CHCl3); IR (neat) 2931, 1737, 1698, 1509, 1365,
1230 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.77-1.71 (15H, m),
3.27 (3H, s), 3.88-4.74 (4H, m), 5.06 (2H, s), 6,95 (2H, d, J )
8.5 Hz), 7.20 (2H, d, J ) 8.5 Hz), 7.30-7.43 (5H, m); 13C NMR
(100 MHz, CDCl3) δ 24.5, 25.5, 28.5, 57.3, 60.4, 70.0, 80.3,
114.4, 127.5, 127.9, 128.6, 128.9, 130.3, 137.0, 158.6; HR-
FABMS (NBA) calcd for C25H34NO5 (M + H) 428.2437, found
428.2420.
The crude aldehyde, 2-methyl-2-butene (1.37 mL, 12.9
mmol), and potassium dihydrogenphosphate (351 mg, 2.58
t
mmol) was dissolved in BuOH (74.5 mL)-water (19.9 mL).
Sodium chlorite (875 mg, 7.74 mmol) was added portionwise
at 0 °C. After stirring at room temperature for 1 h, the reaction
mixture was cooled to 0 °C, acidified with 10% citric acid, and
extracted with ethyl acetate (3 × 70 mL). The combined
extracts were washed with brine (30 mL), dried over sodium
sulfate, filtered, and concentrated in vacuo. The residue was
purified by chromatography on silica gel (25 g, 1:4 n-hexane/
ethyl acetate) to give (2R,3R)-4 (978 mg, 90%) as colorless
solids: mp 106-109 °C; [R]22D -46.6 (c 0.96, MeOH); IR (KBr)
3359, 2981, 1722, 1512, 1242 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.39 (9H, s), 3.32 (3H, s), 4.36 (1H, m), 4.58 (1H, m), 5.06
(2H, s), 6.98 (2H, d, J ) 7.6 Hz), 7.25 (2H, d, J ) 7.6 Hz),
7.40-7.47 (5H, m); 13C NMR (100 MHz, CDCl3) δ 28.2, 57.3,
58.2, 70.0, 80.3, 82.9, 114.8, 127.5, 128.0, 128.4, 128.6, 128.8,
136.8, 155.3, 159.0, 174.2. Anal. Calcd for C22H27NO6‚2/3H2O:
C, 63.91; H, 6.91; N, 3.39. Found: C, 63.77; H, 6.82; N,
3.39.
(2S,3R)-3-(4-Ben zyloxyp h en yl)-2-ter t-bu toxyca r bon yl-
a m in o-3-m eth oxy-1-p r op a n ol [(2S,3R)-11]. To a stirred
solution of (2S,3R)-10 (1.9 g, 4.44 mmol) in methanol (44.6 mL)
was added p-TsOH‚H2O (169 mg, 0.9 mmol). After stirring at
room temperature for 4 h, the reaction mixture was concen-
trated in vacuo. The residue was redissolved in ethyl acetate
(30 mL). The solution was washed with saturated aqueous
sodium bicarbonate (15 mL) and brine (15 mL), dried over
sodium sulfate, filtered, and concentrated in vacuo. The
residue was purified by chromatography on silica gel (30 g,
1:1 n-hexane/ethyl acetate) to give (2S,3R)-11 (1.36 g, 79%)
as colorless solids: mp 76-77 °C; [R]26D -19.7 (c 0.53, CHCl3);
IR (KBr) 3360, 2982, 1685, 1532, 1244, 1173, 1064 cm-1; H
NMR (400 MHz, CDCl3) δ 1.44 (9H, s), 2.73 (1H, brs), 3.31
(3H, m), 3.48-3.54 (1H, m), 3.66 (1H, brs), 3.84 (1H, d, J )
11.5 Hz), 4.52 (1H, brs), 6.99 (2H, d, J ) 8.8 Hz), 7.21-7.45
(7H, m); 13C NMR (100 MHz, CDCl3) δ 28.3, 56.2, 57.9, 61.5,
9214 J . Org. Chem., Vol. 67, No. 26, 2002