776
G.T. Giuffredi et al. / Journal of Fluorine Chemistry 132 (2011) 772–778
mixture was stirred for 1 h at room temperature. Evaporation in
vacuo and purification by column chromatography on silica gel
(gradient hexane/EtOAc 85:15 ! 75:25) afforded triflate 5 [16]
(0.90 g, 51%) and enol triflate 6 (0.20 g, 15%).
(376 MHz, DMSO-d6)
d
ꢁ195.0 (ddd, J = 50, 31, 21 Hz); ESI HR-
MS (positive mode) m/z 503.1829 ([M+Na]+, calculated for
C28H29FNaO6+: 503.1840).
4.5. Methyl 4-deoxy-4-fluoro-6-O-trityl-a-D-idopyranoside 2
4.3.1. Data for methyl 4-deoxy-4-fluoro-3-O-
trifluoromethanesulfonyl-6-O-trityl-
White solid. mp 84 8C; [
25 = +29.3 (c = 0.45, CHCl3); IR
(CHCl3) (
, cmꢁ1): 3444 (O-H), 2941 (C-H); 1H NMR (400 MHz,
DMSO-d6) 7.43–7.39 (6 H, m, 6 arom. H), 7.38–7.33 (6 H, m, 6
arom. H), 7.30–7.25 (3 H, m, 3 arom. H), 5.68 (1 H, br. s, HO-2), 5.15
(1 H, dt, 3J(H,F) = 28.2, J = 3.2 Hz, H-3), 4.96 (1 H, br. d,
2J(H,F) = 51.2 Hz, H-4), 4.75 (1 H, br. s, H-1), 4.05 (1 H, ddd,
3J(H,F) = 30.1, J = 7.1, 5.3 Hz, H-5), 3.88 (1 H, t, J ꢂ 1.7 Hz, H-2), 3.36
(3 H, s, OMe), 3.25 (1 H, dd, J = 9.5, 6.8 Hz, HA-6), 3.16 (1 H, dd,
a
-
D
-mannopyranoside 5
A solution of acetate 7 (50 mg, 0.10 mmol) in MeOH (2 mL) was
treated with NaOMe (5.4 mg, 0.10 mmol), stirred at room
temperature for 3 h, treated with Dowex gel 50W-X8 (H+ form),
and filtered. Evaporation in vacuo and purification by column
chromatography on silica gel (hexane/EtOAc 50:50) afforded diol 2
a]
D
n
d
(32 mg, 73%). [
3429 (O–H), 3059, 3033, 2937 (C–H); 1H NMR (400 MHz, DMSO-
d6) 7.43–7.40 (6 H, m, 6 arom. H), 7.38–7.33 (6 H, m, 6 arom. H),
a] n
25 = +5.6 (c = 0.18, CHCl3); IR (CH2Cl2) ( , cmꢁ1):
D
d
7.30–7.28 (3 H, m, 3 arom. H), 5.29 (2 H, d, J = 5.0 Hz, 2 OH), 4.48 (1
H, d, J = 4.2 Hz, H-1), 4.44 (1 H, ddd, 2J(H,F) = 50.0, J = 4.5, 3.0 Hz, H-
4), 4.11 (1 H, ddt, 3J(H,F) = 31.0, J ꢂ 7.2, 3.6 Hz, H-5), 3.57 (1 H, ddt,
3J(H,F) = 22.1, J = 9.1, 4.7 Hz, H-3), 3.40 (3 H, s, OMe), 3.32–3.29 (1
H, m, H-2), 3.20 (1 H, br. dd, J = 9.3, 7.1, 4J(H,F) < 1.5 Hz, HA-6), 3.06
J = 9.5, 5.1 Hz, HB-6); 13C NMR (101 MHz, C6D6)
d 144.1 (3 C of Tr),
128.2, 128.0, 127.7 (15 CH of Tr), 119.9 (q, 1J(C,F) = 320 Hz, CF3),
101.7 (C-1), 88.6 (d, 1J(C,F) = 187 Hz, C-4), 87.4 (CPh3), 81.2 (d,
2J(C,F) = 15 Hz, C-3), 69.0 (C-2), 68.7 (d, 2J(C,F) = 18 Hz, C-5), 62.5
(d, 3J(C,F) = 5 Hz, C-6), 54.8 (OMe); 19F NMR (376 MHz, DMSO-d6)
d
(1 H, dd, J = 9.6, 4.4 Hz, HB-6); 13C NMR (101 MHz, CDCl3)
d 143.7 (3
ꢁ74.6 (3F, s, CF3), ꢁ214.1 (1F, dt, J = 51, 29 Hz, F-4); ESI HR-MS
C of Tr), 128.6, 127.9, 127.2 (15 CH of Tr), 101.7 (C-1), 89.1 (d,
1J(C,F) = 180 Hz, C-4), 87.0 (CPh3), 67.4 (d, 2J(C,F) = 23 Hz, C-3), 67.3
(C-2), 64.9 (d, 2J(C,F) = 18 Hz, C-5), 62.2 (d, 3J(C,F) = 6 Hz, C-6), 55.7
(positive mode) m/z 593.1225 ([M+Na]+, calculated for
C
27H26F4NaO7S+: 593.1228).
(OMe); 19F NMR (376 MHz, CDCl3)
d
ꢁ193.8 (ddd, J = 53, 31, 22 Hz);
ESI HR-MS (positive mode) m/z 461.1727 ([M+Na]+, calculated for
C
26H27FNaO5+: 461.1735).
4.3.2. Data for methyl 2,4-dideoxy-4-fluoro-3-O-
trifluoromethanesulfonyl-6-O-trityl-
a
-D
-threo-hex-2-enopyranoside
6
White solid. mp decomp. 110 8C; IR (CH2Cl2) (
n
, cmꢁ1): 3060,
7.49–7.43 (6
4.6. Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-
trifluoromethanesulfonyl- -glucopyranoside 9 [16]
2939 (C-H), 1688 (C55C); 1H NMR (400 MHz, CDCl3)
d
a-D
H, m, 6 arom. H), 7.35–7.30 (6 H, m, 6 arom. H), 7.29–7.24 (3 H, m, 3
arom. H), 6.15 (1 H, t, J = 4J(H,F) = 3.1 Hz, H-2), 5.20 (1 H, t,
J = 5J(H,F) = 3.2 Hz, H-1), 4.76 (1 H, dd, 2J(H,F) = 49.9, J = 1.9 Hz, H-
4), 4.18 (1 H, br. ddd, 3J(H,F) = 29.2, J = 6.6, 6.3 Hz, H-5), 3.55 (1 H,
ddd, J = 9.9, 6.6, 4J(H,F) = 1.4 Hz, HA-6), 3.49 (3 H, s, OMe), 3.40 (1 H,
A solution of
a-D-glucopyranoside 8 [16] (2.5 g, 6.7 mmol) in
CH2Cl2 (37 mL) and pyridine (10 mL) was cooled to ꢁ15 8C, treated
with Tf2O (3.8 g, 13 mmol), stirred for 15 min at ꢁ15 8C and for 1 h
at room temperature, and evaporated in vacuo. A solution of the
residue in CHCl3 (15 mL) was washed with water (10 mL), dried
over MgSO4, and filtered. Evaporation in vacuo and purification by
column chromatography on silica gel (hexane/EtOAc 67:33)
dd, J = 9.9, 6.0 Hz, HB-6); 13C NMR (126 MHz, CDCl3)
d 145.8 (d,
2J(C,F) = 19 Hz, C-3), 143.6 (3 C of Tr), 128.6, 127.9, 127.2 (15 CH of
Tr), 118.4 (q, 1J(C,F) = 320 Hz, CF3), 121.3 (d, 3J(C,F) = 7 Hz, C-2),
94.8 (d, 4J(C,F) = 1 Hz, C-1), 87.1 (CPh3), 81.7 (d, 1J(C,F) = 186 Hz, C-
4), 69.7 (d, 2J(C,F) = 19 Hz, C-5), 61.6 (d, 3J(C,F) = 7 Hz, C-6), 56.2
delivered triflate 9 (3.3 g, 97%) as
(400 MHz, CDCl3) 7.52–7.28 (10 H, m, 10 arom. H), 5.58 (1 H,
a
white solid. 1H NMR
d
(OMe); 19F NMR (376 MHz, CDCl3)
d
ꢁ73.4 (3 F, d, 1FJ(F,F) = 4 Hz,
s, CHPh), 4.98 (1 H, d, J = 3.4 Hz, H-1), 4.86 and 4.78 (2 H, 2 d,
J = 10.9 Hz, CH2Ph), 4.76 (1 H, dd, J = 9.5, 3.8 Hz, H-2), 4.33 (1 H, dd,
J = 10.2, 4.6 Hz, Heq-6), 4.14 (1 H, t, J = 9.4 Hz, H-3), 3.90 (1 H, td,
J = 9.9, 4.6 Hz, H-5), 3.77 (1 H, t, J = 10.3 Hz, Hax-6), 3.71 (1 H, t,
CF3), ꢁ199.3 (1 F, ddq, J = 50, 29, 1FJ(F,F) = 4 Hz, 4-F); ESI HR-MS
(positive mode) m/z 725.0723 ([M+Na]+, calculated for
C
27H24F4NaO6S: 725.07209).
J = 9.4 Hz, H-4), 3.49 (3 H, s, OMe); 13C NMR (101 MHz, CDCl3)
d
4.4. Methyl 3-O-acetyl-4-deoxy-4-fluoro-6-O-trityl-
a
-
D
-
137.3, 136.9 (2 C of Ph), 129.2, 128.3, 128.3, 128.3, 127.9, 126.0 (10
CH of Ph), 120.0 (q, 1J(C,F) = 321 Hz, CF3), 101.5 (CHPh), 97.6 (C-1),
83.6 (C-2), 82.0 (C-4), 75.3 (CH2Ph), 75.0 (C-3), 68.7 (C-6), 62.2 (C-
idopyranoside 7
A solution of triflate 5 (0.46 g, 0.8 mmol) in DMF (2 mL) was
treated with NaOAc (0.33 g, 4.0 mmol) and stirred at 40 8C for
6 h. Evaporation in vacuo and purification by column chroma-
tography on silica gel (gradient hexane/EtOAc 80:20 ! 50:50)
5), 55.8 (OMe); 19F NMR (376 MHz, CDCl3)
527.1 (100%, [M+Na]+).
d
ꢁ74.8 (s); ESI MS
4.7. Methyl 3-O-benzyl-4-6-O-benzylidene-2-deoxy-2-fluoro-a-D-
mannopyranoside 10 [16]
afforded acetate
(c = 0.425, CHCl3); IR (CH2Cl2) (
2938 (C–H), 1745 (C55O); 1H NMR (400 MHz, DMSO-d6)
7
(0.26 g, 68%). mp 84 8C;
, cmꢁ1): 3469 (O–H), 3058,
7.43–
[
a
]
25 = +24.4
D
n
d
A solution of triflate 9 (0.26 g, 0.50 mmol) in tBuOH (5 mL) was
treated TBAFꢀ3H2O (1.6 g, 5.0 mmol), stirred at 60 8C for 72 h,
cooled to room temperature, diluted with Et2O (25 mL), washed
with 1 M aqueous HCl (2 ꢅ 15 mL). The combined organic layers
were washed with saturated NaHCO3 solution (15 mL), dried over
MgSO4, and filtered. Evaporation in vacuo and purification by
column chromatography on silica gel (gradient hexane/EtOAc
88:12 ! 67:33) afforded fluoride 10 (0.14 g, 77%) as a colourless
7.39 (6 H, m, 6 arom. H), 7.37–7.32 (6 H, m, 6 arom. H), 7.30–
7.25 (3 H, m, 3 arom. H), 5.62 (1 H, d, J = 5.6 Hz, OH), 4.95 (1 H,
ddd, 3J(H,F) = 20.8, J = 8.3, 4.7 Hz, H-3), 4.65 (1 H, ddd,
2J(H,F) = 49.9, J = 4.7, 3.1 Hz, H-4), 4.57 (1 H, d, J = 4.3 Hz, H-
1), 4.12 (1 H, ddt, 2J(H,F) = 30.9, J = 7.2, 3.5 Hz, H-5), 3.48 (1 H, dt,
J ꢂ 8.3, 4.9 Hz, H-2), 3.41 (3 H, s, OMe), 3.24 (1 H, br. dd, J = 9.7,
7.3, 4J(H,F) < 1.5 Hz, HA-6), 3.07 (1 H, dd, J = 9.9, 3.8 Hz, HB-6),
2.04 (3 H, s, OAc); 13C NMR (101 MHz, CDCl3)
d
169.7 (C55O),
oil. 1H NMR (400 MHz, CDCl3)
d 7.55–7.25 (10 H, m, 10 arom. H),
143.7 (3 C of Tr), 128.6, 127.9, 127.1 (15 CH of Tr), 101.5 (C-1),
87.5 (d, 1J(C,F) = 179 Hz, C-4), 87.1 (CPh3), 69.0 (d,
2J(C,F) = 27 Hz, C-3), 67.0 (C-2), 66.0 (d, 2J(C,F) = 18 Hz, C-5),
62.1 (d, 3J(C,F) = 6 Hz, C-6), 55.6 (OMe), 20.9 (MeC55O); 19F NMR
5.65 (1 H, s, CHPh), 4.91–4.84 (2 H, m, CHAPh, H-1), 4.76 (1 H, dt,
2J(H,F) = 48.8, J = 2.0 Hz, H-2), 4.76 (1 H, d, J = 12.2 Hz, CHBPh), 4.30
(1 H, dd, J = 9.2, 3.5 Hz, Heq-6), 4.13 (1 H, t, J = 9.0 Hz, H-4), 3.94 (1
H, ddd, 3J(H,F) = 27.6, J = 9.9, 2.3 Hz, H-3), 3.90–3.79 (2 H, m, H-5,