E. Jestin et al. / Tetrahedron Letters 47 (2006) 6869–6873
6873
Synthesis of 9: Paraformaldehyde (54 mg, 1.8 mmol) was
dissolved in 10 ml of anhydrous CHCl3 and was heated at
30 ꢁC for 5 min for depolymerisation. O-(3-Iodobenzyl)-
hydroxylamine 6 (0.3 g, 1.2 mmol) was added. The reac-
tion mixture was heated at reflux for 1 h and then cooled.
The solvent was evaporated. Product was obtained after
purification by column chromatography in 95% yield
(0.3 g, 1.14 mmol). Eluent: CHCl3/MeOH (90/10); Rf: 0.3;
Synthesis of 11: L-fucose (12.5 mg, 0.076 mmol);
3-iodophenylhydrazide 3 (40 mg, 0.15 mmol). Eluent of
chromatography: CHCl3/MeOH (80/20). Rf = 0.4. Yield:
96% (29.9 mg, 0.073 mmol). [MꢀH+] = 407. 1H NMR
(DMSO-d6): 1.12 (d, CH3 a form, 3J = 6.4 Hz); 1.14 (d,
3
0
0
0
0
CH3 b form, J = 6.4 Hz); 3.4 (m; 8H, H2 =H3 =H4 =H5
b
0
form + H2/H3/H4/H5
a
form); 3.81 (d, 1H, H1 b,
J = 8.4 Hz); 4.39 (d, 1H, H1 a, 3J = 5.2 Hz); 5 (s, 3H,
OH); 5.9 (s, 1H, NH); 7.28 (t, 1H, H5, 3J = 8 Hz); 7.87 (d,
3
0
1
[M+H+]: 262; H NMR (CDCl3): 5.06 (s, 2H, CH2); 6.49
(d, 1H, CH2@N, 3J = 8.2 Hz); 7.1 (d, 1H, CH2@N,
3J = 7.9 Hz); 7.1 (t, 1H, H5, 3J = 7.6 Hz); 7.33 (d, 1H,
1H, H4, J = 7.6 Hz); 7.91 (d, 1H, H6, J = 8 Hz); 8.2 (s,
3
3
1H, H2); 10.2 (s, 1H, NH). 13C NMR (DMSO-d6): 18.6
3
3
0
0
0
H4, J = 7.6 Hz), 7.65 (d, 1H, H6, J = 7.6 Hz ); 7.73 (s,
1H, H2). 13C NMR (CDCl3): 75.6 (CH2); 93 (C3); 128.4
(C6); 130 (C5); 135.4 (C2); 135.9 (C4); 136.4 (CH2@N); 141
(C1). Oxime 7 (0.3 g, 1.14 mmol) was dissolved in 5 ml of
absolute ethanol. Sodium cyanoborohydride (0.2 g,
3.4 mmol) was added. The pH was adjusted to 3 with
HCl 12 N. The reaction was stirred for 30 min at room
temperature under nitrogen atmosphere. The solvent was
evaporated. A NaOH aqueous solution was used to obtain
a pH 8. The aqueous layer was extracted with CH2Cl2.
The organic layer was dried over Na2SO4, filtered and
evaporated. Product 9 was obtained quantitatively (0.3 g,
1.14 mmol). [M+H+]: 264; 1H NMR (CDCl3): 2.73 (s, 3H,
CH3); 4.64 (s, 2H, CH2); 5.12 (s, 1H, NH); 7.08 (t, 1H, H5,
3J = 7.6 Hz); 7.32 (d, 1H, H4, 3J = 7.3 Hz), 7.63 (d, 1H,
(CH3); 55.9 ð C5 ðaÞÞ; 71.2 ðC2 Þ;71.9 ðC3 ðaÞÞ; 72.2
0
0
0
0
ðC5 ðbÞ þ C3 ðbÞÞ; 73.6 ðCH2 þ C4 Þ; 87 ðC1 ðaÞÞ; 91
0
ð C1 ðbÞÞ; 95.2 (C3); 126.7 (C6); 130.5 (C5); 134.9 (C2);
135.5 (C4); 139.7 (C1); 163.9 (C@O).
Synthesis of 12: L-Fucose (9.8 mg, 0.06 mmol); O-(3-
iodobenzyl)-hydroxylamine 6 (30 mg, 0.12 mmol). Eluent
of chromatography: CHCl3/MeOH(90/10). Rf = 0.2.
Yield: 90% (21.4 mg, 0.054 mmol). [MꢀH+] = 394. 1H
NMR (DMSO-d6): 1.05 (d, 3H, CH3); 3.1–3.6 (m,
0
0
0
0
0
8H, H2 =H3 cyclics þ H3 =H4 =H5 acyclics þ 3OH); 3.83
3
0
0
(quint, 1H, H5 cyclic, J = 6.4 Hz); 4.1 (d, 1H, H4 cyclic,
3
3
0
J = 6.4 Hz); 4.3 (d, 1H, H1 b, J = 7.63 Hz); 4.55 (d, 1H,
H1 a, 3J = 5.17 Hz); 4.6 (d, 1H, H2 acyclic, 3J = 7 Hz);
0
0
4.96 (s, 2H, CH2); 7.17 (t, 1H, H5, 3J = 7.6 Hz); 7.35
(d, 1H, H4, 3J = 7.6 Hz); 7.49 (d, 1H, H1 acyclic,
0
3
H6, J = 8 Hz); 7.73 (s, 1H, H2). 13C NMR (CDCl3): 33.9
3J = 7.3 Hz); 7.65 (d, 1H, H6, 3J = 7.6 Hz); 7.69 (s, 1H,
H2). 13C NMR (DMSO-d6): 20 (CH3); 64.9 ðC5 Þ; 68 ðC2 Þ;
0
0
(CH3); 73.3 (CH2); 94.5 (C3); 127.2 (C6); 130.3 (C5); 135.9
(C2); 136.3 (C4); 141.5 (C1).
0
0
0
72.2/72.7 ðC3 =CH2Þ; 73.6 ðC1 cyclic=C4 Þ; 94.7 (C3); 127.3
Synthesis of 10: O-(3-Iodobenzyl)-hydroxylamine 6 (0.1 g,
0.4 mmol) was dissolved in acetone. The mixture was
heated at reflux for 1 h and was then cooled. The solvent
was evaporated. The product was purified by column
chromatography in 90% yield (104 mg, 0.36 mmol). Elu-
ent: CHCl3/MeOH (90/10); Rf: 0.3; [M+H+]: 290; 1H
NMR (CDCl3): 1.88 (s, 3H, CH3); 1.9 (s, 3H, CH3); 5 (s,
(C6); 130.5 (C5); 136.3 (C2/C4); 140.6 (C1); 153.4
0
ðC1 acyclicÞ.
Synthesis of 13: L-Fucose (9.9 mg, 0.06 mmol); N-methyl-
O-(3-iodobenzyl)-hydroxylamine 9 (32 mg, 0.12 mmol).
Eluent of chromatography: CHCl3/MeOH(90/10).
Rf = 0.3. Yield: 98% (24.4 mg, 0.059 mmol). [MꢀH+] =
408. 1H NMR ((CD3)2CO): 1.17 (d, CH3 a form,
3J = 6.4 Hz); 1.18 (d, CH3 b form, 3J = 6.4 Hz); 2.6 (s,
3
2H, CH2); 7.08 (t, 1H, Hc, J = 8 Hz); 7.32 (d, 1H, Hb,
3J = 7.6 Hz), 7.62 (d, 1H, Hd, 3J = 7.3 Hz); 7.7 (s, 1H,
Ha). 13C NMR (CDCl3): 15.8 (CH3); 21.9 (CH3); 74.19
(CH2); 94.3 (C3); 126.9 (C6); 130 (C5); 136.7 (C2/C4); 140.8
(C1); 155.7 (N@CH2).
3H, CH3–N); 3.6 (m, 8H, H2 =H3 =H4 = H5 b formþ
0
0
0
0
H2 = H30=H4 =H5 a form); 3.97 (d, 1H, H1 ðbÞ, 3J =
0
0
0
0
3
0
8.9 Hz); 4.38 (d, H1 ðaÞ, J = 5.2 Hz); 4.68 (s, 2H, CH2);
7.13 (t, 1H, H5, 3J = 7.9 Hz); 7.41 (d, 1H, H4,
3J = 7.6 Hz); 7.63 (d, 1H, H6,3J = 7.9 Hz); 7.74 (s, 1H,
H2). 13C NMR ((CD3)2CO): 16.9 (CH3); 39 (CH3–N); 68.9
Oxime 8 (104 mg, 0.36 mmol) was dissolved in 5 ml of
absolute ethanol. Sodium cyanoborohydride (67.8 mg,
1.08 mmol) was added. The pH was adjusted to 3 with
12 N HCl. The reaction was stirred for 30 min at room
temperature under nitrogen atmosphere. The solvent was
evaporated. A 6 N NaOH aqueous solution was used to
obtain a pH 8. The aqueous layer was extracted with
CH2Cl2. The organic layer was dried over Na2SO4, filtered
and evaporated. Product 10 was obtained quantitatively
0
0
0
0
ðC5 ðaÞÞ; 72.5 ðC2 Þ; 72.9 ðC5 ðbÞÞ; 74.7 ðC3 ðaÞÞ; 74.9
0
0
0
0
ðC3 ðbÞÞ; 76 (CH2); 88.2 ðC4 Þ; 94.4 ð C1 ðaÞÞ; 94.5 ðC1 ðbÞÞ;
101.3 (C3); 129 (C6); 131.1 (C5); 137.5 (C2); 138.5 (C4);
141.7 (C1).
Synthesis of 14: L-Fucose (8.5 mg, 0.052 mmol);
N-isopropyl-O-(3-iodobenzyl)-hydroxylamine 10 (30 mg,
0.1 mmol). Eluent of chromatography: CHCl3/MeOH (90/
10). Rf = 0.4. Yield: 85% (19.2 mg, 0.044 mmol).
[MꢀH+] = 436. 1H NMR (CD3OD): 1.05 (d, 6H, CH3–
1
(104.7 mg, 0.36 mmol). [M+H+]: 292; H NMR (CDCl3):
1.07 (d, 6H, 2 · CH3, 3J = 6.1 Hz); 3.17 (m, 1H, CH,
3J = 6.4 Hz); 4.65 (s, 2H, CH2); 5.37 (s, 1H, NH); 7.08 (t,
CH, J = 6.1 Hz); 1.18 (d, CH3 a form, 3J = 6.4 Hz); 1.21
3
3
3
3
1H, H5, J = 7.6 Hz); 7.32 (d, 1H, H4, J = 7.6 Hz), 7.63
(d, 1H, H6, 3J = 7.9 Hz); 7.72 (s, 1H, H2). 13C NMR
(CDCl3): 21.7 (2 · CH3); 53.3 (CH); 76.9 (CH2); 95.9 (C3);
128.9 (C6); 131.6 (C5); 138.3 (C2); 138.7 (C4); 142.1 (C1).
33. Mitsunobu, O. Synthesis 1981, 1–28.
(d, CH3 b form, J = 6.4 Hz); 2.97 (m, 1H, CH); 3.5 (m,
0
0
0
0
0
0
0
0
8H, H2 =H3 =H4 =H5 b form þ H2 =H3 =H4 =H5 a form);
4.3 (d, 1H, H1 (b), J = 8.9 Hz); 4.5 (d, H1 ðaÞ, 3J =
4.8 Hz); 4.7 (s, 2H, CH2); 6.96 (t, 1H, H5, 3J = 7.6 Hz);
7.18 (d, 1H, H4, 3J = 7.7 Hz); 7.7 (d, 1H, H6, 3J = 7.8 Hz);
7.8 (s, 1H, H2). 13C NMR (CD3OD): 17.6 (CH3); 19
3
0
0
34. Baalam, B.; Hamon, A.; Maudet, M. Tetrahedron Lett.
1998, 39, 7865–7868.
0
0
0
(2 · CH3); 47 (CH); 64.1 ðC5 ðaÞÞ; 66.4 ðC2 Þ; 67.1 ðC5 ðbÞÞ;
0
0
0
35. General method for the coupling to L-fucose: L-Fucose
(1 equiv) and 2 equiv of aryliodide precursors were
dissolved in a mixture of solvent MeOH/CH3COOH
glacial (85/15). The reaction mixture was stirred for 20 h
at room temperature. The solvent was evaporated. The
product was purified by chromatography.
71.1 ðC3 ðaÞÞ; 74.1 ðC3 ðbÞÞ; 75 ðC4 Þ; 75.1 (CH2); 82.1
0
ðC1 Þ; 97.5 (C3); 126.2 (C6); 130.3 (C5); 135.9 (C2); 136
(C4); 143 (C1).
36. Kett, W. C.; Batley, M.; Redmond, J. W. Carbohydr. Res.
1997, 299, 129–141.
37. IUPAC-IUBMB Carbohydr. Res. 1997, 297, 1–92.