S. A. Testero, R. A. Spanevello / Carbohydrate Research 341 (2006) 1057–1060
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1.2. Preparation of methyl 2,3:4,6-di-O-benzylidene-a-D-
mannopyranoside (5)
(225 mg, 0.65 mmol, 65%) as long white needles: [a]D
123.07 (c 1.51, CHCl3); mp 100–101 °C [lit.8 mp
92 °C]; IR (NaCl) mmax 2943, 1747, 1727, 1273, 1130,
1
Methyl-a-D-mannopyranoside (4) (0.4 g, 2.06 mmol)
was dissolved in CHCl3 (20 mL), and camphorsulfonic
acid (18 mg, 0.072 mmol) and a,a-dimethoxytoluene
(0.71 mL, 4.74 mmol) were added successively. The
resulting mixture was stirred and refluxed in a flask fit-
ted with a Dean–Stark trap for solvents heavier than
1111, 1044, 931, 702 cmÀ1; H NMR (CDCl3): d 8.10–
8.05 (m, 2H, aromatics); 7.65–7.57 (m, 1H, aromatics);
7.50–7.42 (m, 2H, aromatics); 5.44 (d, 1H, J 10.1 Hz,
H-4); 5.22 (d, 1H, J 3.97 Hz, H-1); 4.42–4.34 (m, 1H,
H-5); 3.75–3.58 (m, 2H, H-6); 3.45 (s, 3H, C–OCH3);
2.92 (ddd, 1H, J 14.2 Hz, J 4.0 Hz, J 0.84 Hz, H-2a);
2.72 (dd, 1H, J 14.3 Hz, J 1.09 Hz, H-2b); 13C NMR
(CDCl3): d 32.5 (C-6); 46.0 (C-2); 55.3 (C-14); 70.4 (C-
5); 75.7 (C-4); 99.5 (C-1); 128.4 (2C, C-meta); 128.7
(C-ipso); 129.9 (2C, C-ortho); 133.5 (C-para); 164.7 (C-
7); 196.8 (C-3). Anal. Calcd for C14H15BrO5: C, 49.00;
H, 4.41; Br, 23.28. Found: C, 49.09; H, 4.46; Br, 23.28.
˚
water and loaded with 4 A molecular sieves (1.5 g, acti-
vated at 350 °C for 3 h) for 3 h. K2CO3 (85 mg,
0.6 mmol) was then added, and the reaction mixture
was refluxed for an additional 30 min. The hot reaction
mixture was filtered through a filter funnel with a poro-
sity E sintered glass fritted disc with suction, and the
filtrate was concentrated under reduced pressure. The
resulting crude product was purified by flash chroma-
tography to furnish a mixture of isomers 5 (655 mg,
1.77 mmol, 86%) and used without further purification
in the next synthetic transformation. Spectroscopic data
were in complete agreement with those previously
reported.6,8
1.5. Methyl 4-O-benzoyl-2,6-dideoxy-6-iodo-a-D-erythro-
hexopyranosid-3-ulose (8)
A mixture of the bromodeoxy derivative 7 (97 mg,
0.283 mmol) and KI (280 mg) in N,N-dimethylform-
amide (1 mL) was stirred for 15 h at 50 °C. The mixture
was poured onto ice and then dissolved in EtOAc. The
solution was washed successively with 5% aq NaHSO3
and water, and the dried (Na2SO4) organic layer was
evaporated. The resulting crude product was purified
by flash chromatography to furnish the deoxyiodo
derivative 8 (100 mg, 0.257 mmol, 91%); mp 127–
128 °C; [a]D 99.70 (c 0.515, CHCl3); IR (NaCl) mmax
2940, 1751, 1727, 1272, 1234, 1126, 1109, 1045, 921,
1.3. Preparation of methyl 4,6-O-benzylidene-2-deoxy-
a-D-erythro-hexopyranosid-3-ulose (6)
A solution of the diastereoisomeric mixture of acetals 5
(819 mg, 2.2 mmol) in THF (16 mL) under nitrogen was
cooled to À40 °C. Butyllithium in hexane (1.36 M,
3.5 mL, 4.8 mmol) was added, and the temperature
was kept for 30 min below À30 °C. When all the starting
material disappeared, the solution, still at À30 °C was
poured into ice water containing NH4Cl (2.2 g). With-
out separation of the layer, the THF was removed on
a rotatory evaporator. The aqueous slurry remaining
was cooled to 0 °C, and the crystalline deoxy ketone 6
was filtered and dried. The resulting crude product
was purified by flash chromatography to furnish the
ketone 6 (352 mg, 1.33 mmol, 60%). Spectroscopic data
were in complete agreement with those previously
reported.6,8
1
703 cmÀ1; H NMR (CDCl3): d 8.10–8.05 (m, 2H, aro-
matics); 7.65–7.57 (m, 1H, aromatics); 7.50–7.42 (m,
2H, aromatics); 5.30 (d, 1H, J 9.92 Hz, H-4); 5.21 (d,
1H, J 3.93 Hz, H-1); 4.13–4.03 (m, 1H, H-5); 3.57(dd,
1H, J 11.0 Hz, J 2.43 Hz, H-6a); 3.47 (s, 3H, C–
OCH3); 3.40 (dd, 1H, J 11.0 Hz, J 7.11 Hz, H-6b);
2.93 (ddd, 1H, J 14.2 Hz, J 4.1 Hz, J 0.75 Hz, H-2a);
2.71 (dd, 1H, J 14.2 Hz, J 1.12 Hz, H-2b); 13C NMR
(CDCl3): d 5.7 (C-6); 45.8 (C-2); 55.4 (C-14); 70.3 (C-
5); 77.6 (C-4); 99.4 (C-1); 128.4 (2C, C-meta); 128.6
(C-ipso); 129.9 (2C, C-ortho); 133.5 (C-para); 164.7 (C-
7); 196.9 (C-3); HRCIMS: Calcd for C14H15IO5:
(M+H+) 391.0042. Found: (M+H+) 391.0052.
1.4. Preparation of methyl 4-O-benzoyl-6-bromo-2,6-
dideoxy-a-D-erythro-hexopyranosid-3-ulose (7)8
1.6. Preparation of methyl 4-O-benzoyl-2,6-dideoxy-4,5-
C-methylene-a-D-erythro-hexopyranosid-3-ulose (9)
Ba2CO3 (1.6 g) and N-bromosuccinimide (216 mg,
1.2 mmol) were added to a solution of compound 6
(267 mg, 1.01 mmol) in dry CCl4 (30 mL). The mixture
was boiled under reflux for 1 h under normal room
illumination. The mixture, originally colourless, became
orange and finally yellow. The suspension was filtered, and
the filtrate was evaporated. The residue was extracted
with EtOAc, washed with water, dried with Na2SO4
and evaporated. The resulting residue was purified by
flash chromatography, followed by crystallization from
CHCl3–hexanes to give the bromodeoxy derivative 7
1.6.1. From methyl 4-O-benzoyl-6-bromo-2,6-dideoxy-a-
D-erythro-hexopyranosid-3-ulose (7). The bromodeoxy
derivative 7 (55 mg, 0.16 mmol) was dissolved in dry
pyridine (2 mL), and AgF (63 mg, 0.49 mmol) was
added. The mixture was stirred for 1 h at room temper-
ature, protected from light. After complete reaction, the
mixture was filtered through a filter funnel with a poro-
sity E sintered glass fritted disc with Celite and suction.