Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5243
acetone (50 mL) and water (5 mL) was added sodium azide (3.94
g, 60.6 mmol) as a solid. The mixture was heated to 50 °C for
4 h until 2 was consumed. The mixture was concentrated under
reduced pressure. Ethyl ether (300 mL) and water (10 mL) were
added, and the solution was chilled to 0 °C followed by addition
of 20% H2SO4 aqueous solution (30 mL) dropwise. The solution
was stirred vigorously at 20 °C for 48 h. The organic layer was
collected and concentrated. The pure product (5.27 g, 87%) was
isolated as a colorless oil by silica gel chromatography with
and dissolved in a mixture of water (30 mL), CH3CN (20 mL),
and CCl4 (20 mL). NaIO4 (3.98 g, 18.6 mmol) and RuCl3 hydrate
(23 mg, 0.11 mmol) were added, and the solution was vigorously
stirred for 3 h at ca. 40 °C until the cyclic sulfite was totally
consumed. Ethyl ether (250 mL) was added to the cooled
mixture, and the organic layer was removed. It was necessary
to add a small amount of activated carbon (10 mg) to the organic
layer in order to remove the brown color. The organic layer was
then dried (MgSO4) and concentrated under reduced pressure.
The pure cyclic sulfate (2.77 g, 91%) was isolated as a colorless
oil by silica gel chromatography with hexanes-ethyl acetate (85:
hexanes-ethyl acetate (75:25 v/v). [R]20 ) -78 (c 2.8, CHCl3);
D
IR (neat) 3436 (OH), 3037, 2979, 2113 (N3), 1738 (CdO) cm-1
;
1H NMR δ 1.18 (d, J ) 6.3 Hz, 3H), 1.60 (s, 3H), 4.00 (q, J ) 6.3
15 v/v): [R]20 ) -9.1 (c 2.64, CHCl3); IR (neat) 2695, 1742 (Cd
D
Hz, 1H), 5.26 (s, 2H), 7.40 (s, 5H); 13C NMR 17.6, 18.1, 67.6,
O), 1380 (sulfate) cm-1; 1H NMR (200 MHz, CDCl3) δ 0.97 (d, J
) 6.4 Hz, 6H), 1.49 (d, J ) 6.4 Hz, 3H), 1.77 (s, 3H), 2.01 (m,
1H), 4.03 (m, 2H), 4.87 (d, J ) 6.4 Hz, 1H); 13C NMR 14.5, 18.8,
21.3, 27.6, 73.0, 84.5, 90.7, 167.0 ppm; FAB-MS MH+ 253, MNa+
275. Anal. Calcd for C9H16O6S: C, 42.86; H, 6.35. Found: C,
42.46; H, 6.11.
+
70.3, 71.2, 128.0 (m), 134.8, 171.5 ppm; FAB-MS MNH4 267;
HRMS MNH4+ calcd for C12H19O3N4 267.1457, found 267.1442.
Anal. Calcd for C12H15O3N3: C, 57.82; H, 6.07; N, 16.85.
Found: C, 57.97; H, 6.11; N, 16.77.
(2S,3S) 2-Meth ylth r eon in e (4). A solution of 3 (3.10 g,
12.45 mmol) and a small amount of Pd-carbon in methanol (100
mL) was pressurized with 45 psi H2 for 12 h. The Pd-carbon
solid was removed through filtration, and the product was
concentrated under reduced pressure. The crude product was
dissolved in H2O (30 mL) and purified by Amberlite IR-120 (plus)
ion-exchange resin with water and then 1 N aqueous NH3 to
Isob u t yl (2S,3R)-2-Azid o-3-h yd r oxy-2-m et h ylb u t yr a t e
(10). To a stirred solution of 9 (0.80 g, 3.17 mmol) in DMF (15
mL) was added sodium azide (260 mg, 4 mmol) as a solid. The
mixture was stirred at room temperature for 4 h and then heated
at 50 °C for ca. 3 h until 9 was consumed. The mixture was
concentrated under reduced pressure. Ethyl ether (100 mL) and
water (3 mL) were added, and the solution was chilled to 0 °C
followed by addition of 20% H2SO4 aqueous solution (5 mL)
dropwise. The solution was stirred vigorously at 20 °C for 48
h. The organic layer was collected and concentrated. The pure
product (545 mg, 80%) was isolated as a colorless oil by silica
gel chromatography with hexanes-ethyl acetate (75:25 v/v):
give 4 as a white solid (1.59 g, 96%): mp 265-267 °C (dec); [R]20
D
) +11.7 (c 1.35, H2O); 1H NMR (360 MHz, DMSO-d6) δ 1.01 (d,
J ) 6.1 Hz, 3H), 1.21 (s, 3H), 3.74 (q, J ) 6.1 Hz, 1H); FAB-MS
+
MNH4 151. Anal. Calcd for C5H11O3N: C, 45.11; H, 8.27; N,
10.5. Found: C, 45.27; H, 8.33, N, 10.2.
N-(ter t-Bu tyloxycar bon yl)-(2S,3S)-2-m eth ylth r eon in e (5).
Compound 4 (2.0 g, 1.5 mmol) was dissolved in n-butanol (20
mL) followed by addition of (Boc)2O (3.33 g, 15.3 mmol). The
solution was stirred vigorously for 24 h. After removal of the
solvent under reduced pressure, the pure product (2.20 g, 63%)
was crystallized by adding hexane (20 mL) in ethyl acetate (2
mL) at 0 °C. The single crystal of 5 was obtained from ethyl
[R]20 ) -43.6 (c 3.40, CHCl3); IR (neat) 3502 (OH), 2113 (N3),
D
1731 (CdO) cm-1; 1H NMR (200 MHz, CDCl3) δ 0.97 (d, J ) 6.4
Hz, 3H), 1.23 (d, J ) 6.4 Hz, 3H), 1.45 (s, 3H), 2.01 (m, 1H),
2.19 (d, J ) 7.6 Hz, 3H), 4.00 (m, 3H); FAB-MS MH+ 215, MNa+
238. Anal. Calcd for C9H17O3N3: C, 50.23; H, 7.96; N, 19.53.
Found: C, 50.20; H, 7.77; N, 19.76.
acetate solution at 20 °C: mp 138-141 °C; [R]20 ) +10.0 (c
Isobu tyl (2S,3R)-2-Meth ylth r eon in a te (11). Compound 11
D
1.22, CHCl3); 1H NMR (360 MHz, CDCl3) δ 1.18 (d, J ) 6.1 Hz,
3H), 1.45 (s, 9H), 1.59 (s, 3H), 4.23 (q, J ) 6.5 Hz, 1H); FAB-MS
MH+ 234. Anal. Calcd for C10H19O5N: C, 51.50; H, 8.15; N,
6.01. Found: C, 51.65; H, 8.23; N, 6.05.
was obtained from 10 by the same procedure as described for 4:
1
yield 98%; [R]20 ) -8.1 (c 1.11, CH3OH); H NMR (200 MHz,
D
CHCl3) δ 0.95 (d, J ) 6.8 Hz, 3H), 1.16 (d, J ) 6.4 Hz, 3H), 1.26
(s, 3H), 1.98 (m, 4H), 3.92 (m, 3H); FAB-MS MH+ 190, MNa+
212. Anal. Calcd for C9H19O3N: C, 56.14; H, 10.05; N, 7.40.
Found: C, 56.48; H, 810.00; N,7.11.
Ben zyl (2S,3S)-2-Br om o-3-h ydr oxy-2-m eth ylbu tyr ate (6).
To a stirred solution of cyclic sulfate 2 (4.0 g, 13.9 mmol) in DMF
(60 mL) was added solid lithium bromide (1.33 g, 15.3 mmol).
The mixture was heated at 50 °C for 3 h until 2 was consumed.
The mixture was concentrated under reduced pressure. Ethyl
ether (400 mL) and water (10 mL) were added, and the solution
was chilled to 0 °C followed by addition of 20% H2SO4 aqueous
solution (30 mL) dropwise. The solution was stirred vigorously
at 20 °C for 48 h. The organic layer was collected and
concentrated. The pure product (3.71 g, 93%) as a colorless oil
was isolated by silica gel chromatography with hexanes-ethyl
acetate (70:30 v/v): [R]20D ) +12.5 (c 1.27, CHCl3); IR (neat) 3450
(OH), 3091, 3065, 3034, 2983, 2935, 1734 (CdO) cm-1; 1H NMR
(300 MHz) δ 1.35 (d, J ) 6.6 Hz, 3H), 1.89 (s, 3H), 4.36 (q, J )
6.3 Hz, 1H), 5.25 (m, 2H), 7.38 (s, 5H); FAB-MS MH+ 287; HRMS
MH+ calcd for C12H16O3Br 287.0283, found 287.0283. Anal.
Calcd for C12H15O3Br: C, 50.35; H, 5.24. Found: C, 50.53; H,
5.30.
(2S,3R)-2-Meth ylth r eon in e (12). A solution of 11 (116.3
mg, 0.88 mmol) was dissolved in methanol (2 mL) and cooled to
0 °C. Sodium hydroxide (1 N, 1.76 mL, 1.76 mmol) was added
dropwise. The solution was brought to room temperature and
stirred for 3 h. The solvent was removed, and the resulting solid
was purified via ion-exchange chromatography to give the
product (104.6 mg, 89.4%) as a white solid: [R]20 ) +10.5 (c
D
2.09, H2O); 1H NMR (360 MHz, D2O) δ 1.20 (d, J ) 6.1 Hz, 3H),
1.35 (s, 3H), 4.13 (d, J ) 6.1 Hz, 1H); FAB-MS MH+ 134.
Ben zyl (2S,3R)-2,3-Dim eth ylazir idin e-2-car boxylate (13).
To a stirred solution of azido alcohol 3 (2.40 g, 9.64 mmol) in
acetonitrile (45 mL) was added PPh3 (5.05 g, 19.3 mmol) as a
solid. The mixture was stirred at 20 °C for 1 h and then refluxed
for 4 h until 3 was consumed. After removal of the solvent, the
pure product (1.88 g, 91%) was isolated by silica gel chroma-
tography with hexanes-ethyl acetate (70:30 v/v): [R]20 ) +57
D
Isobu tyl (2R,3R)-2,3-Dih yd r oxy-2-m eth ylbu tyr a te (8).
Compound 8 was obtained using the same procedure as de-
scribed for 1 with AD-mix â. The pure product (4.8 g, 85%) was
obtained as a colorless oil by silica gel chromatography with
hexanes-ethyl acetate (70:30 v/v): [R]20D ) -6.6 (c 1.42, CHCl3);
IR (neat) 3449 (OH), 2964, 1725 (CdO) cm-1; 1H NMR (200 MHz,
CDCl3) δ 0.96 (d, J ) 6.8 Hz, 6H), 1.17 (d, J ) 6.6 Hz, 3H), 1.45
(c 1.4, CHCl3); IR (neat) 3291 (NH), 3092, 3071, 3035, 3005, 2963,
2937, 1723 (CdO) cm-1 1H NMR δ 1.11 (d, J ) 5.7 Hz, 3H),
;
1.33 (s, 3H), 2.28 (q, J ) 5.7 Hz, 1H), 5.09 (m, 2H), 7.28 (s, 5H);
13C NMR 13.1, 13.3, 37.7, 38.3, 66.8, 127.0 (m), 135.1, 174.2 ppm;
FAB-MS MH+ 206; HRMS MH+ calcd for C12H16O2N 206.1181,
found 206.1189. Anal. Calcd for C12H15O2N: C, 70.22; H, 7.36;
N, 6.82. Found: C, 70.18; H, 7.34; N, 6.56.
(s, 3H), 1.99 (m, 1H), 3.83 (q, J ) 6.4 Hz, 1H), 3.99 (m, 2H); 13
C
Ben zyl (2S,3R)-N-(Ben zyloxyca r bon yl)-2,3-d im eth yla zir -
id in e-2-ca r boxyla te (14). To a stirred solution of aziridine 13
(1.00 g, 4.88 mmol) in pyridine (20 mL) were added solid
N-[(benzyloxycarbonyl)oxy]succinimide (Cbz-OSu) (2.43 g, 9.76
mmol) and 4-(dimethylamino)pyridine (DMAP) (89 mg, 0.73
mmol). The mixture was stirred at 4 °C for 24 h. After removal
of the solvent, the pure product (1.44 g, 86%) was isolated by
silica gel chromatography with hexanes-ethyl acetate (90:10
NMR 17.5, 18.8, 22.3, 27.5, 72.0, 72.1, 77.2, 175.6 ppm; FAB-
MS MH+ 191, MNa+ 213. Anal. Calcd for C9H18O4: C, 56.84;
H, 9.47. Found: C, 56.57; H, 9.40.
Cyclic Su lfa te 9. To a stirred solution of 8 (2.30 g, 12.1
mmol) in methylene chloride (20 mL) at 0 °C was added thionyl
chloride (1.88 mL, 24.0 mmol) dropwise. The solution was
warmed to 40 °C and stirred while the HCl evolved was swept
away by a stream of nitrogen. After 2.5 h, the solution was
concentrated under reduced pressure to remove excess SOCl2
and solvent. The crude cyclic sulfite was dried in vacuo for 2 h
v/v): [R]20 ) +19.4 (c 1.22, CHCl3); IR (neat) 3291 (NH), 3092,
D
3071, 3035, 3005, 2963, 2937, 1723 (CdO) cm-1; 1H NMR δ 1.33
(d, J ) 5.7 Hz, 3H), 1.54 (s, 3H), 3.13 (q, J ) 5.7 Hz, 1H), 5.14