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S. Kobayashi et al. / Tetrahedron 60 (2004) 6923–6930
dd, J¼8.1, 2.0 Hz), 4.10–4.07 (1H, m), 1.55 (3H, s), 1.45
(3H, s), 1.34 (6H, s). 13C NMR d¼24.39 (1C, s), 24.88 (1C,
s), 25.90 (1C, s), 26.00 (1C, s), 66.60 (1C, d, J¼22.3 Hz),
70.39 (1C, s), 70.47 (1C, s), 70.55 (1C, s), 82.04 (1C, d,
J¼167.9 Hz), 96.15 (1C, s), 108.78 (1C, s), 109.63 (1C, s).
19F NMR d¼2231.73 (1F, dt, J¼47.6, 14.0 Hz).
HRMS (EI) Calcd for C12H19O5F (Mþ) 262.1216. Found
262.1215.
3.4. Glycosyl fluorides synthesis using DFMBA
3.4.1. Preparation of 2,3;5,6-di-O-isopropylidene-D-
mannofuranosyl fluoride (9a).31 DFMBA (205 mg,
1.2 mmol), 8a (187 mg, 1.0 mmol), and CH2Cl2 (2 ml)
were introduced into a reaction vessel made of Teflone
PFA with a tight screw cap and the mixture was stirred at
room temperature for 1 h. After the reaction, the mixture
was poured into aq NaHCO3 and extracted with ether three
times. The combined ethereal layers were dried over MgSO4,
concentrated under reduced pressure. Purification by column
chromatography (silica gel/hexane–Et2O) gave 9a in 90%
yield as a mixture of a and b isomers in a ratio of 43:57.
3.3.2. Preparation of methyl 5-fluoro-2,3-O-isopropyl-
(6b).28
idene-5-deoxy-b-D-ribofuranoside
DFMBA
(533 mg, 2.5 mmol), KF (232 mg, 4.0 mmol), 5b (204 mg,
1.0 mmol), and 1,4-dioxane (1 ml) were introduced into a
reaction vessel made of Teflone PFA with a tight screw cap
and kept at 100 8C for 16 h in an oil bath. After the reaction,
the mixture was poured into aq NaHCO3 and extracted with
ether three times. The combined ethereal layers were dried
over MgSO4, concentrated under reduced pressure. Purifi-
cation by column chromatography (silica gel/hexane–Et2O)
gave 6b in 67% yield; IR (neat) 2941, 2837, 1458, 1383,
1212, 1090, 871 cm21. 1H NMR d¼4.99 (1H, d, J¼2.4 Hz),
4.71 (1H, d, J¼6.1 Hz), 4.60 (1H, d, J¼5.9 Hz), 4.39 (3H,
dm, J¼37.8 Hz), 3.33 (3H, s), 1.50 (3H, s), 1.33 (3H, s). 13C
NMR d¼24.87 (1C, s), 26.37 (1C, s), 54.85 (1C, s), 81.00
(1C, d, J¼4.1 Hz), 82.91 (1C, d, J¼172.9 Hz), 84.36 (1C,
s), 84.59 (1C, s), 85.05 (1C, s), 109.21 (1C, s). 19F NMR
d¼2225.39 to 2225.68 (1F, m). HRMS (EI) Calcd for
C9H14O4F (Mþ2H) 205.0876. Found 205.0869.
(9a-a), IR (neat) 2989, 1374, 1212, 1130, 1070, 972,
849 cm21. 1H NMR d¼5.69 (1H, d, J¼59.5 Hz), 4.77–4.43
(2H, m), 4.43–4.38 (1H, m), 4.18–4.05 (3H, m), 1.46 (6H,
s), 1.39 (3H, s), 1.35 (3H, s). 13C NMR d¼24.49 (1C, s),
25.14 (1C, s), 25.80 (1C, s), 26.86 (1C, s), 66.64 (1C, s),
72.68 (1C, s), 78.56 (1C, s), 82.60 (1C, s), 84.72 (1C, d,
J¼42.2 Hz), 109.39 (1C, s), 113.20 (1C, s), 113.64 (1C, d,
J¼221.6 Hz). 19F NMR d¼2129.25 (1F, dd, J¼59.5,
6.7 Hz). HRMS (EI) Calcd for C12H19O5F (MþþH)
263.1295. Found 263.1317.
(9a-b), mp 113–114 8C (lit.31 114–115 8C). IR (neat) 2985,
1377, 1263, 1216, 1125, 1089, 1062, 1001, 846, 527 cm21
.
1H NMR d¼5.51 (1H, dd, J¼3.7, 66.5 Hz), 4.87–4.84 (1H,
m), 4.75–4.69 (1H, m), 4.50–4.46 (1H, m), 4.22–4.17 (1H,
m), 4.11 (2H, d, J¼3.7 Hz), 1.57 (3H, s), 1.46 (3H, s), 1.41
(3H, s), 1.39 (3H, s). 13C NMR d¼25.24 (2C, s), 25.67 (1C,
s), 26.94 (1C, s), 66.45 (1C, s), 73.52 (1C, s), 77.55 (1C, s),
81.00 (1C, d, J¼1.7 Hz), 81.23 (1C, d, J¼19.8 Hz), 107.42
(1C, d, J¼234.9 Hz), 109.39 (1C, s), 115.74 (1C, s). 19F
NMR d¼2125.13 (1F, ddd, J¼66.5, 15.3, 5.5 Hz). HRMS
(EI) C12H20O5F (MþþH) 263.1295. Found 263.1288
3.3.3. Methyl 5-fluoro-2,3-O-isopropylidene-5-deoxy-a-
D-ribofuranoside (6c).28 IR (neat) 2939, 1371, 1215,
1
1098 cm21. H NMR d¼4.96 (1H, s), 4.67–4.62 (2H, m),
4.58 (2H, dm, J¼47.8 Hz), 4.25 (1H, dm, J¼30.7 Hz), 3.51
(3H, s), 1.58 (3H, s), 1.37 (3H, s). 13C NMR d¼25.56 (1C,
s), 25.89 (1C, s), 56.14 (1C, s), 79.71 (1C, d, J¼26.5 Hz),
79.66 (1C, s), 80.46 (1C, s), 83.18 (1C, d, J¼172.0 Hz),
103.17 (1C, s), 115.26 (1C, s). 19F NMR d¼2232.72 (1F,
dt, J¼47.8, 30.7 Hz).
3.4.2. 2,3,5-Tri-O-benzyl-a-D-arabinofuranosyl fluoride
(9b-a).13 IR (neat) 2895, 1725, 1496, 1453, 1376, 1110,
872, 752, 699 cm21. 1H NMR d¼7.30–7.17 (15H, m), 5.55
(1H, d, J¼67.1 Hz), 4.63–4.47 (6H, m), 4.18–4.01 (3H, m),
3.56–3.47 (2H, m). 13C NMR d¼69.32 (1C, s), 72.04 (1C,
s), 72.09 (1C, s), 73.36 (1C, s), 82.45 (1C, s), 84.07 (1C, s),
86.82 (1C, d, J¼33.9 Hz), 113.50 (1C, d, J¼225.0 Hz),
127.66–128.50 (15C, s), 136.89 (1C, s), 137.41 (1C, s),
137.83 (1C, s). 19F NMR d¼2127.30 (1F, ddd, J¼65.3,
20.8, 5.5 Hz). HRMS (EI) Calcd for C26H27O4F (Mþ)
422.1893. Found 422.1896.
3.3.4. 1,2,3,4-Tetra-O-acetyl-6-deoxy-6-fluoro-a-D-
glucopyranose (6d).29 Mp 122–125 8C (lit.26 128–
129 8C). IR (KBr) 2959, 1757, 1370, 1217, 1079,
1
1038 cm21. H NMR d¼5.74 (1H, d, J¼8.1 Hz), 5.32–
5.11 (3H, m), 4.60–4.37 (2H, m), 3.89–3.79 (1H, m), 2.12
(3H, s), 2.06 (3H, s), 2.04 (3H, s), 2.03 (3H, s). 13C NMR
d¼25.55 (1C, s), 20.76 (1C, s), 67.46 (1C, d, J¼6.6 Hz),
70.11 (1C, s), 72.70 (1C, s), 73.20 (1C, s), 80.61 (1C, s),
91.55 (1C, s), 168.95 (1C, s), 169.15 (1C, s), 169.28 (1C, s),
170.12 (1C, s). 19F NMR d¼2232.73 (1F, dt, J¼47.0,
22.6 Hz).
(9b-b), mp 78–79 8C (lit.13 77–78 8C). IR (neat) 3062,
3030, 2865, 1454, 1115, 1028, 738, 698 cm21. H NMR
1
3.3.5. 50-Fluoro-20,30-O-isopropylidene-50-deoxyuridine
(6e).30 IR (neat) 2990, 1687, 1437, 1382, 1274,
d¼7.30–7.17 (15H, m), 5.79 (5H, d, J¼61.5 Hz), 4.73–
4.45 (7H, m), 4.17 (1H, dd, J¼9.3, 2.2 Hz), 3.96 (1H, dd,
J¼5.1, 2.0 Hz), 3.64–3.57 (2H, m). 13C NMR d¼71.52 (1C,
s), 72.48 (1C, s), 72.63 (1C, s), 73.45 (1C, s), 81.53 (1C, s),
82.35 (1C, s), 84.52 (1C, d, J¼21.5 Hz), 108.32 (1C, d,
J¼229.9 Hz), 127.66–128.51 (15C, s), 137.18 (1C, s),
137.73 (1C, s), 137.87 (1C, s). 19F NMR d¼2121.23 (1F,
dd, J¼61.6, 9.2 Hz). HRMS (EI) Calcd for C26H27O4F (Mþ)
422.1893. Found 422.1882.
1
1082 cm21. H NMR d¼9.18 (1H, brs), 7.33 (1H, d, J¼
8.1 Hz), 5.84 (1H, s), 5.76 (1H, d, J¼8.1 Hz), 4.94–4.88
(2H, m), 4.74–4.71 (1H, m), 4.62–4.59 (1H, m), 4.43–4.35
(1H, m), 1.60 (3H, s), 1.36 (3H, s). 13C NMR d¼25.15 (1C,
s), 27.02 (1C, s), 79.90 (1C, d, J¼7.4 Hz), 82.84 (1C, d,
J¼172.4 Hz), 84.50 (1C, s), 85.62 (1C, d, J¼18.2 Hz),
93.73 (1C, s), 102.66 (1C, s), 114.57 (1C, s), 141.49 (1C, s),
150.19 (1C, s), 163.61 (1C, s). 19F NMR d¼2229.973 to
2230.292 (1F, m). HRMS Calcd for C12H15N2O5F (Mþ)
286.0965. Found 286.0967.
3.4.3. 2,3,4,5-Tetra-O-acetyl-a-D-glucopyranosyl fluor-
ide (9c).32 Mp 77–78 8C. IR (neat) 2942, 1761, 1439, 1378,