Modular access to heterocycles
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1-Deoxy-1-azido-2,3:4,6-di-O-isopropylidene-
a-L-sorbofuranose (9, C12H19N3O5)
methanol); H NMR (250 MHz, CDCl3): d = 1.20, 1.26,
1.32, 1.38 (4 s, 12H, CH3), 3.57–3.65 (m, 1H, H-1b), 3.78
Sodium azide (1.51 g, 23.23 mmol) was added to a
solution of 8 (1.72 g, 4.65 mmol) in 8 cm3 DMSO, and
the mixture was stirred at 100 ꢁC for 24 h. After cooling to
room temperature, the mixture was diluted with EA, and
the organic layer was washed with water, then dried over
MgSO4. After filtration the solvent was removed by
evaporation in vacuo. The obtained residue was purified
by flash chromatography (eluent: PE/EA:9/1, m/m;
Rf = 0.24) to afford 9 (1.16 g, 88%) as a colorless syrup,
which crystallized on standing [40]; mp 55–56 ꢁC;
(d, 1H, J6a,6b = 13.3 Hz, H-6a), 3.94 (d, 1H, J6b,6a =
13.3 Hz, H-6b), 3.97 (s, 1H, H-5), 4.21 (s, 1H, H-4), 4.29
(dd, 1H, J1a,1b = 14.4 Hz, J1a,NH = 7.2 Hz, H-1a), 4.35 (s,
1H, H-3), 4.60–4.80 (m 2H, CH2-Ph), 6.54 (bs, 1H, NH),
6.77 (bs, 1H, NH), 7.16–7.26 (m, 5H, CHAr) ppm; 13C
NMR (62.5 MHz, CDCl3): d = 18.6, 26.3, 27.2, 29.0
(CH3), 48.9 (C-1), 49.3 (CH2), 60.2 (C-6), 72.5 (C-4), 73.3
(C-5), 84.9 (C-3), 97.7 (C-2), 113.6 (29C), 127.6, 128.1
(29CH), 128.6 (29CH), 137.6, 183.4 (C=S) ppm; IR
(KBr): m = 3334 (NH), 2990, 2933 (CHAr) cm-1; MS (IS):
ꢀ
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[a]D = -56ꢁ g-1 cm3 dm-1 (c = 1, methanol); 1H
m/z = 409.5 [M ? 1]?.
NMR (250 MHz, CDCl3): d = 1.36, 1.42, 1.46, 1.52
(4 s, 12H, CH3), 3.40 (d, 1H, J1a,1b = 13.1 Hz, H-1a),
3.71 (d, 1H, J1b,1a = 13.1 Hz, H-1b), 3.97-4.04 (m, 2H, H-
6a, H-6b), 4.12–4.16 (m, 1H, H-5), 4.33 (d, 1H,
J4,5 = 2.1 Hz, H-4), 4.41 (s, 1H, H-3) ppm; 13C NMR
(62.5 MHz, CDCl3): d = 18.7, 26.2, 27.6, 28.9 (CH3), 53.4
(C-1), 60.4 (C-6), 72.8 (C-4), 73.1 (C-5), 84.6 (C-3), 97.4
N-(1-deoxy-2,3:4,6-di-O-isopropylidene-a-L-
sorbofuranosyl)-N0-phenylthiourea (11b, C19H26N2O5S)
To a solution of 10 (0.058 g, 0.2 mmol) in 0.8 cm3 dry
toluene containing pyridine (0.033 cm3, 0.4 mmol) was
added 0.036 cm3 aniline (0.4 mmol). After stirring the
mixture at 50 ꢁC for 24 h, the solvent was removed by
evaporation in vacuo. The obtained residue was purified by
flash chromatography (eluent: PE/AE:7/3, m/m; Rf = 0.2) to
afford 11b (0.054 g, 81%) as white solid; mp 78–80 ꢁC
ꢀ
(C-2), 112.9, 114.1 (C(CH3)2) ppm; IR (KBr): m = 2098
(N3) cm-1; MS (IS): m/z = 286 [M ? 1]?.
(diethyl ether); [a]D = -58ꢁ g-1 cm3 dm-1 (c = 1,
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1-Deoxy-1-isothiocyanato-2,3:4,6-di-O-isopropylidene-
a-L-sorbofuranose (10, C13H19NO5S)
methanol); 1H NMR (250 MHz, DMSO-d6): d = 1.24,
1.35, 1.38, 1.42 (4 s, 12H, CH3), 3.82–3.91 (m, 2H, H-1),
3.99 (s, 1H, H-5), 4.04–4.20 (m, 2H, H-6), 4.26 (s, 1H, H-
4), 4.59 (s, 1H, H-3), 7.09 (t, 1H, J = 7.7 Hz, CHAr), 7.30
(t, 2H, J = 7.7 Hz, CHAr), 7.49 (d, 2H, J = 7.7 Hz, CHAr),
7.53 (bs, 1H, NH), 9.69 (bs, 1H, N’H) ppm; 13C NMR
(62.5 MHz, DMSO-d6): d = 18.8, 26.5, 27.0, 28.8 (CH3),
47.8 (C-1), 59.3 (C-6), 71.5 (C-4), 73.0 (C-5), 84.6 (C-3),
96.9 (C-2), 110.8, 113.3 (29C), 122.9, 124.1, 128.4
To a solution of 9 (0.2 g, 0.7 mmol) in 12 cm3 dry 1,4-
dioxane was added carbon disulfide (0.81 cm3, 13.32 mmol),
then triphenylphosphine (0.194 g, 0.74 mmol). The mixture
was stirred for 5 h at room temperature, then 27 h at 50 ꢁC.
After removal of the solvent by evaporation in vacuo, the
obtained residue was purified by flash chromatography
(eluent: PE/EA:9/1, m/m; Rf = 0.24) to afford 10 (0.188 g,
89%) as a colorless oil; [a]D = -6ꢁ g-1 cm3 dm-1
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(c = 1, methanol); 1H NMR (250 MHz, DMSO-d6):
d = 1.28, 1.35, 1.39, 1.44 (4 s, 12H, CH3), 3.81 (d, 1H,
J6b,6a = 13.1 Hz, H-6b), 3.96 (d, 1H, J1b,1a = 14.9 Hz,
H-1b), 4.01-4.07 (m, 1H, H-6a), 4.07 (s, 1H, H-5), 4.16 (d,
1H, J1a,1b = 14.9 Hz, H-1a), 4.38 (s, 2H, H-4, H-3) ppm;
13C NMR (62.5 MHz, DMSO-d6): d = 18.6, 26.5, 27.2,
28.9 (CH3), 48.5 (C-1), 59.3 (C-6), 72.3 (C-4), 72.7 (C-5),
84.4 (C-3), 96.9 (C-2), 111.6, 112.4 (C(CH3)2), 128.9
(29CH), 139.5, 181.0 (C=S) ppm; IR (KBr): m = 3302
ꢀ
(NH), 2990, 2934 (CHAr) cm-1; MS (IS): m/z = 395.5
[M ? 1]?.
N-(1-deoxy-2,3:4,6-di-O-isopropylidene-a-L-
sorbofuranosyl)-N0-(2-methoxycarbonylphenyl)thiourea
(11c, C21H28N2O7S)
To a solution of 10 (0.060 g, 0.2 mmol) in 0.8 cm3 dry
toluene containing pyridine (0.033 cm3, 0.4 mmol) was
added methyl anthranilate (0.052 cm3, 0.4 mmol). After
stirring the mixture at 50 ꢁC for 24 h, the solvent was
removed by evaporation in vacuo. The obtained residue
was purified by flash chromatography (eluent: PE/EA:7/3,
m/m; Rf = 0.26) to afford 11c (0.066 g, 73%) as a white
(C=S) ppm; IR (NaCl): m = 2178 (NCS) cm-1; MS (IS):
ꢀ
m/z = 302 [M ? 1]?.
N-(1-deoxy-2,3:4,6-di-O-isopropylidene-a-L-
sorbofuranosyl)-N0-benzylthiourea (11a, C20H28N2O5S)
To a solution of 10 (0.08 g, 0.26 mmol) in 1 cm3 dry
toluene containing pyridine (0.045 cm3, 0.53 mmol) was
added 0.058 cm3 benzylamine (0.53 mmol). After stirring
the mixture at 50 ꢁC for 18 h, the solvent was removed by
evaporation in vacuo. The obtained residue was purified by
flash chromatography (eluent: PE/EA:7/3, m/m; Rf = 0.26)
to afford 11a (0.078 g, 90%) as a white solid; mp 76–78 ꢁC
1
solid; mp 77–79 ꢁC (diethyl ether); H NMR (250 MHz,
DMSO-d6): d = 1.28, 1.35, 1.38, 1.42 (4 s, 12H, CH3),
3.75 (s, 3H, OCH3), 3.82–3.91 (m, 2H, H-1a, H-1b), 3.99
(s, 1H, H-5), 4.04–4.20 (m, 2H, H-6a, H-6b), 4.29 (s, 1H,
H-4), 4.64 (s, 1H, H-3), 7.19 (t, 1H, J = 7.6 Hz, CHAr),
7.30 (t, 1H, J = 7.6 Hz, CHAr), 7.82 (t, 1H, J = 7.6 Hz,
CHAr), 7.98 (d, 1H, J = 7.6 Hz, CHAr), 8.61 (bs, 1H, NH),
(diethyl ether); [a]D = -36ꢁ g-1 cm3 dm-1 (c = 1,
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