1304 J . Org. Chem., Vol. 65, No. 5, 2000
Seki et al.
2.50-3.00 (m, 3H), 3.92-4.05 (m, 1H), 4.70-4.74 (m, 1H),
Hz, 2H), 6.95-7.33 (m, 7H); SIMS m/z 511 (M+); [R]25D +32.5°
(c, 0.34, MeOH). Anal. Calcd for C27H29NO7S: C, 63.37; H, 5.71;
N, 2.74. Found: C, 63.58; H, 5.46; N, 3.01.
5.10-5.30 (m, 1H), 7.14-7.36 (m, 10H); SIMS m/z 396 (M+
+
1); [R]25 +55.7° (c, 0.68, MeOH). Anal. Calcd for C24H29NO4:
D
C, 72.89; H, 7.39; N, 3.54. Found; C, 72.76; H, 7.52; N, 3.77.
A Typ ica l P r oced u r e for th e Hyd r ogen a tion of th e
Alk yla ted 4-Bu ta n olid es 7. (2S,3R)-3-ter t-Bu toxyca r bo-
n yla m in o-2-m eth yl-4-p h en ylbu ta n oic Acid 2a . A mixture
of 7a (200 mg, 0.686 mmol) and 10% palladium on charcoal
(20 mg) in methanol (5 mL) was hydrogenated at 25 °C in Parr
apparatus (H2: 3.5 kg/cm2) for 2 h. The mixture was filtered,
and the filtrate was evaporated. The residue was crystallized
by adding ether to afford 2a (170 mg, 84%) in colorless
crystals: mp 156-157 °C; IR (KBr) 3360, 1690 cm-1; 1H NMR
(CDCl3) δ 1.25 (d, 3H, J ) 6.8 Hz), 1.32 (s, 9H), 2.68-2.90 (m,
2H), 3.95-4.30 (m, 1H), 4.65-4.90 (m, 1H), 7.18-7.35 (m, 5H),
8.50-9.50 (br, 1H); 13C NMR (CDCl3) δ 13.1, 28.2 (2q), 38.2
(t), 43.5, 53.5, 126.5, 128.4, 129.3 (5d), 138.0, 150.0, 155.7 (3s);
(4S,5R)-4,5-Diben zyl-1-ter t-bu toxyca r bon ylim id a zoli-
d in -2-on e (22). After a mixture of 1c (112 mg, 0.35 mmol),
concentrated hydrochloric acid (1.5 mL), and water (1.5 mL)
was refluxed for 4 h, the mixture was evaporated. The
crystalline residue was dissolved in a mixed solvent of tet-
rahydrofuran and water (2:1, 3 mL). Into the mixture were
added di-tert-butyl dicarbonate (143 mg, 0.654 mmol) and 2
N aq NaOH (0.49 mL, 0.98 mmol) at 10 °C, and the mixture
was stirred for 2 h. Tetrahydrofuran was evaporated, and the
aqueous residue was washed with ether and acidified to pH 2
with aq citric acid. The mixture was extracted with ethyl
acetate, washed with water, dried over anhydrous magnesium
sulfate, and evaporated. The residue was purified by silica gel
column chromatography (CHCl3 to CHCl3:MeOH ) 10:1), and
the carboxylic acid obtained was dissolved in acetonitrile. To
the solution were added diphenylphosphoryl azide (96.3 mg,
0.35 mmol) and triethylamine (35.4 mg, 0.35 mmol). The
mixture was stirred at 70 °C for 5 h and evaporated. The
residue was purified by silica gel column chromatography (n-
hexane:AcOEt ) 2:1) to afford 22 (78.2 mg, 61%) in colorless
SIMS m/z 294 (M+ + 1); [R]25 +4.9° (c, 0.20, MeOH). Anal.
D
Calcd for C16H23NO4: C, 65.50; H, 7.90; N, 4.77. Found: C,
65.73; H, 7.74; N, 4.59.
(2S ,3R )-3-t er t -B u t o x y c a r b o n y la m in o -2-b e n z y l-4-
p h en ylbu ta n oic Acid 2b: mp 175-176 °C; IR (KBr) 2978,
1
1703, 1654 cm-1; H NMR (CDCl3) δ 1.31 (s, 9H), 2.67-3.00
(m, 4H), 4.00-4.27 (m, 1H), 4.60-4.82 (m, 1H), 6.00-6.20 (m,
1H), 6.90-7.40 (m, 10H), 7.90-8.80 (br, 1H); 13C NMR (CDCl3)
δ 28.2 (q), 34.6, 38.3 (2t), 51.6, 53.3 (2d), 79.9 (s), 126.5, 128.4,
128.6, 128.9, 129.4 (6d), 137.9, 138.9, 156.0, 178.3 (4s); SIMS
oil: IR (Nujol) 3240, 1764 cm-1 1H NMR (CDCl3) δ 1.57 (s,
;
9H), 2.41-2.75 (m, 3H), 3.20-3.28 (m, 1H), 3.44-3.50 (m, 1H),
4.09-4.14 (m, 1H), 5.30 (s, 1H), 6.89-6.94 (m, 2H), 7.09-7.31
(m, 8H); SIMS m/z 367 (M+ + 1).
m/z 370 (M+ + 1); [R]25 -11.4° (c, 0.21, MeOH). Anal. Calcd
(4S,5R)-4, 5-Diben zyl-1-ter t-bu toxyca r bon ylim id a zo-
lid in -2-on e (23). A mixture of 2b (50 mg, 0.135 mmol),
diphenylphosphoryl azide (44.7 mg, 0.162 mmol), and triethy-
lamine (16.4 mg, 0.162 mmol) in acetonitrile (1 mL) was stirred
at 70 °C for 5 h and evaporated. The residue was purified by
silica gel column chromatography (n-hexane:AcOEt ) 2:1) to
afford 23 (50 mg, quant) in colorless oil: IR (Nujol) 3297, 1782
cm-1; 1H NMR (CDCl3) δ 1.42 (s, 9H), 2.69-2.81 (m, 2H), 3.01-
3.22 (m, 2H), 3.97-43.08 (m, 1H), 4.59-4.70 (m, 2H), 7.09-
7.13 (m, 2H), 7.13-7.33 (m, 8H); SIMS m/z 367 (M+ + 1).
A Typ ica l P r oced u r e for th e Syn th esis of Dia ster eo-
m er ic Ur ea s. (2S,3S,4R,1′R)-2-Ben zyl-3-(1′-m eth ylben zyl-
a m in o)-4-p h en yl-4-bu ta n olid e (25a ). A mixture of 7b (100
mg, 0.272 mmol) and 4 N hydrogen chloride in 1,4-dioxane (1
mL) was stirred at 25 °C for 17 h, and the mixture was
evaporated. Into the residue were added dichloromethane (1
mL), triethylamine (0.11 mL, 0.82 mmol), and (R)-1-methyl-
benzyl isocyanate (60 mg, 0.41 mmol) at 10 °C, and the mixture
was stirred at 25 °C for 17 h. The mixture was evaporated,
and the residue was purified by silica gel plate (n-hexane:
AcOEt ) 2:1) to afford 25a (82.6 mg, 73%) in colorless oil: IR
D
for C22H27NO4: C, 71.52; H, 7.37; N, 3.79. Found: C, 71.36;
H, 7.57; N, 4.02.
(2S,3R)-3-ter t-Bu toxyca r bon yla m in o-2-(3,4,5-tr im eth -
oxyben zyl)-4-p h en ylbu ta n oic Acid 2c: mp 182-185 °C; IR
(KBr) 3360, 1688 cm-1 1H NMR (DMSO-d6) δ 1.27 (s, 9H),
;
2.50-2.86 (m, 4H), 3.61 (s, 3H), 3.73 (s, 6H), 3.67-3.90 (m,
2H), 6.46 (s, 2H), 6.83 (d, 1H, J ) 9.4 Hz), 7.15-7.29 (m, 5H);
13C NMR (DMSO-d6) δ 41.6 (q), 48.3, 52.6 (2t), 65.7, 66.6 (2d),
69.2, 73.4 (2q), 90.9 (s), 119.6, 139.3, 141.4, 142.6 (3d), 149.0,
152.4, 166.0, 168.6, 188.6 (5s); SIMS m/z 460 (M+ + 1); [R]25
D
-0.22° (c, 0.45, MeOH). Anal. Calcd for C25H33NO7: C, 65.34;
H, 7.24; N, 3.05. Found: C, 65.56; H, 7.51; N, 3.11.
(2S,3R)-3-ter t-Bu toxyca r bon yla m in o-2-p h en ylp r op yl-
4-p h en ylbu ta n oic Acid 2d: mp 138-140 °C; IR (KBr) 2932,
1695 cm-1; 1H NMR (CDCl3) δ 1.31 (s, 9H), 1.50-1.90 (m, 4H),
2.59-2.91 (m, 5H), 3.80-4.20 (m, 1H), 4.50-4.70 (m, 1H),
7.14-7.30 (m, 10H); 13C NMR (CDCl3) δ 28.1, 29.2, 35.7 (4t),
28.2 (q), 38.4, 49.4 (2d), 125.9, 126.5, 128.3, 128.4, 129.4 (6d),
137.8, 141.9, 155.7, 178.8 (4s); SIMS m/z 398 (M+ + 1); [R]25
D
-8.6° (c, 0.57, MeOH). Anal. Calcd for C24H31NO4: C, 72.52;
1
H, 7.86; N, 3.52. Found: C, 72.78; H, 7.57; N, 3.44.
(Nujol) 1795, 1652 cm-1; H NMR (CDCl3) δ 1.29 (d, 3H, J )
(2S,3S,4R,)-2-Meth yl-4-ph en yl-3-(p-tolu en esu lfon ylam i-
n o)-4-bu ta n olid e (20). A mixture of 7a (300 mg, 1.03 mmol)
and 4 N hydrogen chloride in 1,4-dioxane (5 mL) was stirred
at 25 °C for 1 h. The mixture was evaporated, and the residue
was crystallized by adding ether to afford an amine hydro-
chloride. It was dissolved in a mixture of water and ethyl
acetate (1:1, 10 mL), and p-toluenesulfonyl chloride (296 mg,
1.55 mmol) and potassium carbonate (847 mg, 6.13 mmol) were
added. The mixture was stirred at 25 °C for 17 h. The organic
layer was separated and washed with water, dried over
anhydrous magnesium sulfate, and evaporated. The residue
was purified by silica gel column chromatography (n-hexane:
AcOEt ) 4:1) to afford 20 (292 mg, 82%) in colorless crystals:
6.4 Hz), 2.78-2.89 (m, 1H), 3.09-3.30 (m, 2H), 3.80 (q, 1H, J
) 7.8 Hz), 4.46-4.75 (m, 3H), 5.29 (d, 1H, J ) 7.8 Hz), 7.08-
7.37 (m, 15H); SIMS m/z 415 (M+ + 1).
(2R,3R,1′R)-Meth yl 3-(1′-Meth ylben zyla m in oca r bon yl-
a m in o)-2-ben zyl-4-p h en ylbu ta n oa te (24a ). IR (Nujol) 1728,
1627 cm-1; 1H NMR (CDCl3) δ 1.39 (d, 3H, J ) 6.6 Hz), 2.51-
2.76 (m, 3H), 2.85-2.95 (m, 1H), 3.52 (s, 3H), 4.02-4.19 (m,
1H), 4.68-4.84 (m, 3H), 5.58 (d, 1H, J ) 9 Hz), 6.89-7.36 (m,
15H); SIMS m/z 431 (M+ + 1).
(2R, 3R, 1′S)-Meth yl 3-(1′-Meth ylben zyla m in oca r bo-
n yla m in o)-2-ben zyl-4-p h en ylbu ta n oa te (24b). IR (Nujol)
1722, 1632 cm-1; 1H NMR (CDCl3) δ 1.45 (d, 3H, J ) 6.6 Hz),
2.45-2.55 (m, 1H), 2.70-2.94 (m,4H), 3.54 (s, 3H), 4.13-4.26
(m, 1H), 4.62-4.79 (m, 2H), 5.37 (d, 1H, J ) 9.4 Hz), 6.98-
7.41 (m, 15H); SIMS m/z 431 (M+ + 1).
1
mp 129-132 °C; IR (KBr) 3170, 1768 cm-1; H NMR (CDCl3)
δ 1.26 (d, 3H, J ) 7.2 Hz), 2.36 (s, 3H), 2.59-2.90 (m, 1H),
3.61-3.75 (m, 1H), 4.94 (d, 1H, J ) 8.6 Hz), 5.67 (d, 1H, J )
(2S,3S,4R,1′S)-2-Ben zyl-3-(1′-m et h ylb en zyla m in o)-4-
1
8.8 Hz), 7.02-7.45 (m, 9H); SIMS m/z 346 (M+ + 1); [R]25
p h en yl-4-bu ta n olid e (25b). IR (Nujol) 1780, 1632 cm-1; H
D
+31.3° (c, 0.43, MeOH). Anal. Calcd for C18H19NO4S: C, 62.59;
NMR (CDCl3) δ 1.34 (d, 3H, J ) 6.7 Hz), 2.97-3.28 (m, 3H),
3.86 (q, 1H, J ) 8 Hz), 4.50-4.76 (m, 3H), 5.13 (d, 1H, J ) 7.9
Hz), 7.06-7.39 (m, 10H); SIMS m/z 415 (M+ + 1).
H, 5.54; N, 4.06. Found: C, 62.44; H, 5.81; N, 4.22.
(2S,3S,4R)-4-P h en yl-3-(p-tolu en esu lfon ylam in o)-2-(3,4,5-
tr im eth oxyben zyl)-4-bu ta n olid e (21). According to the
procedure for the synthesis of 20, the compound 21 was
obtained in 91% yield from 7c: mp 149-151 °C; IR (KBr) 3250,
1794 cm-1; 1H NMR (CDCl3) δ 2.33 (s, 3H), 2.95-3.16 (m, 3H),
3.81 (s, 6H), 3.87 (s, 3H), 3.97-4.22 (m, 1H), 4.93 (d, 1H, J )
7.2 Hz), 5.68 (d, 1H, J ) 8 Hz), 6.51 (s, 2H), 6.68 (d, J ) 7.2
Ack n ow led gm en t. The authors are indebted to Mr.
Hajime Hiramatsu in this company for the X-ray
analyses.
J O991241W