15
Preparation of
the Thiohydroximate 19
NCS (0.88 g, 6.6 mmol) was
added to a solution of aldoxime 18 (1.75
g, 6 mmol) in DMF (5 mL), and the mixture was left at r.t. for 4
h. After cooling to -78 °C, ethanethiol (1.33
mL, 18 mmol) then Et3N (2.5 mL, 18 mmol) were added dropwise.
The reaction mixture was slowly allowed to reach r.t. and stirred
for a further 12 h. After hydrolysis (H2O, 100 mL) and
extraction with CH2Cl2 (3 ¥ 100
mL), the combined organic phases were washed with brine (3 ¥ 50
mL), dried over MgSO4, filtered, and then evaporated.
Purification of the residue over silica gel (PE-EtOAc,
7:3) afforded the 4-O-silylated derivative of 24 as
an oil. This intermediate was dissolved in THF (20 mL) and reacted
with TBAT (1.2 equiv) at r.t. for 14 h. H2O (20 mL) was
then added and the mixture was extracted with CH2Cl2 (3 ¥ 30
mL). The combined organic phases were washed with brine, dried over MgSO4,
then evaporated under reduced pressure. S-Ethyl 2,3-O-isopropylidene-l-erythronimidothioate
(19) was isolated as a colorless solid
(1.2 g, 84% yield) by silica gel flash chromatography (PE-EtOAc,
1:1). Mp 40-41 °C; R
f
= 0.18
(PE-EtOAc, 1:1); [a]D
²0 -54
(c 1.0, CHCl3). IR (KBr):
3356, 2992, 1688, 1451, 1375, 1269, 1223, 1208, 1056, 998, 895,
859, 806, 740 cm-¹. ¹H
NMR (400 MHz, CDCl3): d = 1.33 (t, 3 H, J = 7.6 Hz,
CH3CH2), 1.40 and 1.53 [2 s, 6 H,
C(CH3)2], 3.11 (m, 2 H, CH3CH2),
3.68 (m, 1 H, H-4b), 3.79 (m, 1 H, H-4a), 4.40 (dd, 1 H, J
2,3 = 6.0
Hz, J
3,4 = 4.4
Hz, H-3), 4.89 (d, 1 H, J
2,3 = 6.0
Hz, H-2), 9.40 (s, 1 H, NOH). ¹³C NMR
(100 MHz, CDCl3) : d = 15.1 (CH3CH2),
25.6 (CH3CH2), 25.4, 27.3 [C(CH3)2],
61.7 (C-4), 76.9 (C-2), 78.6 (C-3), 109.5 (C(CH3)2),
150.8 (C=N). MS (IS): m/z = 236.0 [M + H]+.
ESI-HRMS: m/z [M + H]+ calcd for
C9H18NO4S: 236.0957; found: 236.0968.
16
Preparation of
the Thioimidate N
-Oxide
21
Ph3P (55 mg, 0.21 mmol) was added to
a solution of DEAD (40% in toluene, 95 mL, 0.21 mmol) in
THF (10 mL). After 10 min of stirring, the thiohydroximate 19 (50 mg, 0.21 mmol) was added, and the
reaction mixture was kept at reflux overnight. After hydrolysis
(H2O, 20 mL) and extraction with CH2Cl2 (3 ¥ 30
mL), the combined organic phases were dried over MgSO4,
filtered, and then evaporated. (3S,4S)-2-Ethylsulfanyl-3,4-isopropylidene-dioxy-3,4-dihydro-5H-pyrrole-1-oxide (21)
was isolated as a colorless solid (45 mg, 98% yield) after
silica gel flash chromatography (EtOAc). Mp 145-150 °C; R
f
= 0.5 (EtOAc); [a]D
²0 -136.5
(c 1.0, MeOH). IR (neat): 1570, 1422,
1383, 1261, 1234, 1204, 1154, 1076, 1021, 864, 836, 706, 663 cm-¹. ¹H
NMR (400 MHz, CDCl3): d = 1.37
(t, 3 H, J = 7.6
Hz, CH3CH2), 1.39 and 1.44 [2 s,
6 H, C(CH3)2], 3.13 (q, 2 H, J = 7.6 Hz,
CH3CH2), 4.06 (dt, 1 H, ²
J
5b,5a = 14.7
Hz, J
5b,4 = 5
J
5b,3 = 1.2
Hz, H-5b), 4.13 (dd, 1 H, ²
J
5b,5a = 14.7
Hz, J
5a,4 = 5.3
Hz, H-5a), 4.90 (ddd, 1 H, J
4,3 = 6.5
Hz, J
4,5a = 5.3 Hz, J
4,5b = 1.4
Hz, H-4), 5.34 (d, 1 H, J
4,3 = 6.5
Hz, H-3).
¹³C NMR (100 MHz,
CDCl3): d = 15.6 (CH3CH2),
23.4 (CH3CH2), 26.0, 27.2 [C(CH3)2],
66.4 (C-5), 73,1 (C-4), 81.7 (C-3); 112.8 [C(CH3)2],
144.0 (C-2). MS (IS): m/z = 218.0 [M + H]+.
ESI-HRMS: m/z [M + H]+ calcd
for C9H16NO3S: 218.0851; found:
218.0841.