11746 J. Am. Chem. Soc., Vol. 119, No. 49, 1997
Burkart et al.
with a R/â ratio of 2:1. 1H NMR (CDCl
, 400 MHz): δ 5.54 (d, J )
°C for 12 h, diluted with EtOAc (50 mL), and washed with water. The
3
5
.0 Hz, 1 H), 5.25 (t, J ) 2.6 Hz, 1 H), 5.09 (ddd, J ) 3.6, 9.3, 13.0
organic layer is dried over MgSO
by column chromatography (MeOH/CHCL
4
, filtered, evaporated, and purified
) 1/18) to yield 3S (32.2
3
mg, 60%) and 3R (10.8 mg, 20%). 3S: H NMR (400 MHz, CDCl )
Hz, 1 H), 4.63 (m, 2 H), 4.51 (ddd, J ) 7.7, 9.8, 58.8 Hz, 1 H), 4.34
3
1
(
2
3
dd, J ) 1.7, 8.0 Hz, 1 H), 4.32 (dd, J ) 2.3, 5.0 Hz, 1 H), 4.01 (m,
H), 3.83 (m, 2 H), 2.16 (s, 3H), 2.05 (s, 3H), 1.54 (s, 3H), 1.45 (s,
δ 6.05-6.03 (m, 1 H), 5.41-5.32 (m, 2 H), 5.28 (dt, J ) 8.5, 2.7 Hz,
1 H), 4.94 (dd, J ) 49.6, 2.3 Hz, 1 H), 4.91 (dt, J ) 12.2, 2.4 Hz, 1
H), 4.45-4.32 (m, 2 H), 4.09 (dd, J ) 12.4, 8.5 Hz, 1 H), 3.85 (s, 3
H), 2.17 (s, 3 H), 2.10 (s, 3 H), 2.09 (s, 3 H), 2.04 (s, 3 H), 1.91 (s, 3
H), 1.35 (s, 3H), 1.33 (s, 3H), 1.21 (d, J ) 6.4 Hz, 3H); 13C NMR
3
(CDCl , 125 MHz): 170.5, 170.1, 108.8 (d, J ) 75.5), 101.3 (d, J )
2
7
2
6
6
4
7.5), 96.2, 87.8 (d, J ) 232.5), 71.5 (d, J ) 22.5), 70.8 (d, J ) 11.3),
0.6, 70.5, 70.5, 69.1, 68.7, 66.2, 29.7, 26.1, 26.0, 24.9, 24.4, 20.7,
H); 13C NMR (125 MHz, CDCl
3
) δ 172.07, 171.43, 170.69, 170.50,
+
0.6, 15.9; HRMS (M + Cs ) calcd for C22
H33FO11 625.1061, found
170.36, 167.37, 94.34 (d, J ) 25.6 Hz), 86.76 (d, J ) 185.4 Hz), 72.65,
71.22, 69.28 (d, J ) 17.2 Hz), 68.39, 62.76, 58.65, 53.32, 45.00, 23.09,
25.1084. 3,4-Di-O-acetyl-2-deoxy-2-fluoro-r-L-fucopyranosyl-(1-
1
)-1,2:3,4-di-O-isopropylidine-r-D-galactopyranose: H NMR (CDCl
3
,
21.10, 20.97, 20.87, 20.78, 20.69; HRMS (M + Cs) calcd for C20H -
28
1
00 MHz): δ 5.18 (d, J ) 5.0 Hz, 1 H), 5.39 (ddd, J ) 3.5, 10.6, 14.0
3
FNO13Cs, 642.0599; found 642.0578. 3R: H NMR (400 MHz, CDCl )
Hz, 1 H), 5.32 (ddd, J ) 1.1, 3.4, 5.5 Hz, 1 H), 5.16 (d, J ) 3.8 Hz,
H), 4.75 (ddd, J ) 3.9, 10.2, 50.0 Hz, 1 H), 4.64 (dd, J ) 2.4, 7.9
δ 5.90-5.72 (m, 1 H), 5.37-5.18 (m, 3 H), 4.89 (dd, J ) 49.5, 9.4
Hz, 1 H), 4.46-4.15 (m, 3 H), 3.97 (dd, J ) 12.5, 7.1 Hz, 1 H), 3.93
(s, 3 H), 2.13 (s, 3 H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.01 (s, 3 H), 1.88
(s, 3 H).
Condition G. 2,3,4,6-Tetra-O-benzyl-D-glucopyranosyl Fluoride.
2,3,4,6-Tetra-O-benzyl-D-glucopyranoside (37 mg, 0.07 mmol) was
1
Hz, 1 H), 4.31 (m, 3 H), 4.12 (dd, J ) 7.2, 11.4 Hz, 1 H), 4.05 (ddd,
J ) 2.0, 6.1, 7.7 Hz, 1 H), 3.92 (dd, J ) 7.6, 9.7 Hz, 1 H), 3.66 (dd,
J ) 6.0, 9.7 Hz, 1 H), 2.16 (s, 3H), 2.04 (s, 3H), 1.55 (s, 3H), 1.44 (s,
3
H), 1.35 (s, 3H), 1.33 (s, 3H), 1.13 (d, J ) 6.4 Hz, 3H); 13C NMR
(CDCl
3
, 125 MHz): 170.5, 170.1, 109.0 (d, J ) 58.8), 96.2, 96.1 (d,
dissolved in anhydrous DMF/SMe (1:1, 3 mL), and to this solution
2
J ) 25.0), 85.3 (d, J ) 237.5), 71.8 (d, J ) 9.4), 70.8, 70.5, 68.7 (d,
was added F-TEDA-BF (72.6 mg, 0.21 mmol). After 5 min, the
4
J ) 2.3), 66.3, 65.7, 64.5, 29.7, 26.0, 26.0, 24.9, 24.6, 20.7, 20.6, 15.6;
solution was diluted with 50 mL EtOAc, washed with water and brine,
+
HRMS (M + Cs ) calcd for C22
H33FO11 625.1061, found 625.1085.
and dried over MgSO . Silica gel chromatography yielded product (26
4
Condition D. Benzyl 3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-r-D-
mannopyranoside. To 3,4,5-tri-O-acetyl glucal (200 mg, 0.73 mmol)
in dry acetonitrile (3 mL) with 4 Å powdered M.S. (100 mg) was
added anhydrous benzyl alcohol (1 mL), 2,6-di-tert-butyl-4-methylpy-
mg, 70%) and unreacted starting material. The spectral data are
consistent with published results.22
Condition H. 2,3,4,6-Tetra-O-benzoyl-r-D-galactopyranosyl Fluo-
ride. To a mixture of thiocresyl 2,3,4,6-tetra-O-benzoyl-â-D-galacto-
pyranoside (100 mg, 0.142 mmol) and 4 Å powdered M.S. (300 mg)
ridine (226 mg, 1.1 mmol), F-TEDA-BF
solution was stirred for 12 h. The reaction was then diluted with
EtOAc/Et O (9:1, 100 mL) to precipitate salts. The solution was filtered
4
(390 mg, 1.1 mmol), and the
in dry CH
added F-TEDA-BF
°C for 20 min, then solid NaHCO
mixture was stirred for 5 min, diluted with CH
diluted with Et O (20 mL), and then filtered through Celite. The solid
cake was washed with CH Cl /Et O (1:1, 40 mL). The residue was
concentrated and chromatographyed (SiO , hexanes-AcOEt 4:1f 2:1)
to give title compound (69.5 mg, 82%): 1H NMR (CDCl
, 400 MHz):
δ 5.82, 5.68 (dd, 1H, J ) 2.6 and 53.2 Hz), 5.48 (d, 1H, J ) 2.0 Hz),
.30 (dd, 1H, J ) 3.2 and 10.9 Hz), 5.16, 5.10 (ddd, 1H, J ) 2.7, 10.9
3
CN (3 mL), stirred at 0 °C for 15 min under argon, was
(78 mg, 0.220 mmol). The mixture was stirred at
(200 mg) was added, and the
Cl (20 mL), further
2
4
and evaporated to a clear oil. Repeated coevaporation with water
removes excess benzyl alcohol. Silica gel chromatography (4:1 hexane/
0
3
2
2
EtOAc) yielded products (171 mg, 60%), 67% mannose form. Proton
2
1
NMR shows R/â ratio 2.5:1: (R
f
0.49, hexane/EtOAc 3:1) H NMR
2
2
2
(
3
CDCl , 400 MHz) δ 7.35 (m, 5H), 5.33 (dd, J ) 1.5, 2.9 Hz, 1H),
2
5
4
1
.06 (dd, J ) 1.9, 7.4 Hz, 1H), 4.75 (dt, J ) 2.1, 2.1, 49.9Hz, 1H),
.58 (ABq, J ) 11.8, 62.8 Hz, 2H), 4.28 (m, 2H), 4.06 (dd, J ) 2.3,
2.3 Hz, 1H), 3.99 (ddd, J ) 2.2, 4.6, 9.3 Hz, 1H), 2.10 (s, 3H), 2.08
3
5
1
3
(
s, 3H), 2.03 (s, 3H); C NMR (CDCl
69.5, 136.1, 128.6,128.4, 128.3, 127.9, 96.2 (d, J ) 36.3 Hz), 87.0
d, J ) 223.2 Hz), 69.9 (d, J ) 21.8 Hz), 69.8, 68.7, 65.8, 62.0; HRMS
M + Na) calcd for C19 23FNaO 421.1275, found 421.1288. Benzyl
,4,6-tri-O-acetyl-2-deoxy-2-fluoro-â-D-glucopyranoside: H NMR
CDCl , 400 MHz) δ 7.35 (m, 5H), 5.29 (dt, J ) 9.4, 14.5 Hz, 1H),
.04 (t, J ) 9.4 Hz, 1H), 4.82 (ABq, J ) 12.0, 95.9 Hz), 4.62 (dd, J
3
, 125 MHz) δ 170.8, 170.1,
and 23.8 Hz), 4.36 (t, 1H, J ) 6.3 Hz), 4.09 (m, 2H), 2.11, 2.07, 2.01,
1
(
(
3
(
1
.96 (s, 3H each).
Condition I. 2,3,4,6-Tetra-O-benzoyl-â-D-galactopyranosyl-(1-
)-1,2:3,4-di-O-isopropylidene-r-D-galactopyranose. A mixture of
H
8
6
1
a thio-cresyl 2,3,4,6-tetra-O-benzoyl-â-D-galactopyranoside (67 mg,
.096 mmol), 1,2:3,4-di-O-isopropylidene-R-D-galactopyranoside (30
mg, 0.115 mmol), and M.S. 4 Å (powder, 300 mg) in dry CH CN (4
mL), under Ar protection, was stirred at 0 °C for 15 min. BF -Et
12 µL, 0.096 mmol) and F-TEDA-BF (38.8 mg, 0.110 mmol) were
added successively. The reaction was stirred at 0 ˚C for 15 min, solid
NaHCO (200 mg) was added and stirred for 5 min, diluted with CH
Cl (20 mL), and further diluted with Et O (20 mL). The mixture was
stirred for 5 min then filtered through Celite. The solid cake was
washed with CH Cl /Et O (1:1, 40 mL). The residue was concentrated
and chromatographyed (SiO , hexanes-AcOEt 4:1f 2:1) to give the
title compound (68.4 mg, 85%): 1H NMR (CDCl
, 500 MHz): δ 5.99
d, 1H, J ) 3.0 Hz), 5.81 (dd, 1H, J ) 8.0 and 10.5 Hz), 5.61 (dd, 1H,
3
0
5
3
)
)
2
2.6, 7.7 Hz, 1H), 4.36 (dd, J ) 7.7, 9.4, 50.6 Hz, 1H), 4.28 (dd, J
4.8, 12.3 Hz, 1H), 4.14 (dd, J ) 2.4, 12.3 Hz, 1H), 3.67 (ddd, J )
3
2
O
(
4
.4, 4.8, 10.0 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.01 (s, 3H); 13
C
NMR (C
6
6
D , 125 MHz) δ 170.1, 169.7, 169.1, 137.4, 128.7, 128.3,
3
2
-
1
27.8, 96.7 (d, J ) 36.3 Hz), 87.5 (d, J ) 223.0 Hz), 70.4 (d, J ) 20.9
2
2
Hz), 69.7, 69.4, 66.1, 61.9.
Condition E. 2-Deoxy-2-fluoro-D-mannopyranose. To a 4 mL
aqueous solution of glucal (200 mg, 1.4 mmol) cooled in an ice bath
was added F-TEDA-BF (744 mg, 2.1 mmol). The solution was
4
allowed to reach room temperature, stirred for 1 h, and evaporated to
dryness. Quantitative acetylation with pyridine and acetic anhydride
2
2
2
2
3
(
J ) 3.0 and 10.5 Hz), 5.42 (d, 1H, J ) 5.0 Hz), 5.02 (d, 1H, J ) 8.0
Hz), 4.67 (dd, 1H, J ) 6.5 and 11.0 Hz), 4.35 (t, 11H, J ) 6.5 Hz),
(2:1, 50 mL) followed by evaporation and coevaporation twice with
toluene gives a yellow oil. Silica gel chromatography (4:1 CH Cl /
2
2
4
.21 (dd, 1H, J ) 2.5 and 5.0 Hz), 1.40, 1.24, 1.22, and 1.20 (S, 3H
MeOH) yielded products (174 mg, 85%) 2-deoxy-2-fluoro-D-glucopy-
ranose and 2-deoxy-2-fluoro-D-mannopyranose (1:2). The spectral
13
each); C NMR (CDCl
3
, 125 MHz): δ 166.0, 165.5, 165.5, 165.3,
09.2, 108.4, 101.7, 96.1, 71.8, 71.2, 70.9, 70.5, 70.3, 69.6, 68.4, 68.1,
7.4, 62.0, 26.0, 25.9, 25.0, 24.2; HRMS (M + Cs) calcd for C46
1
6
2
7
data are consistent with published results.
46 15
H O -
Condition F. Methyl 5-Acetetamido-4,7,8,9-tetra-O-acetyl-3,5-
dideoxy-3-S-fluoro-D-erythro-L-gluco-2-nonulopyranosonate and
Methyl 5-Acetetamido-4,7,8,9-tetra-O-acetyl-3,5-di-deoxy-3-R-fluoro-
D-erythro-L-gluco-2-nonulopyranosonate. To methyl 5-acetetamido-
Cs 971.1891, found 971.1920.
Acknowledgment. We thank Dr. A. Yudin in Professor
Sharpless’ group for helpful discussions concerning fluorination
reagents. This paper is dedicated to Professor Samuel Dan-
ishefsky on the occasion of his 60th birthday, for his inspiration,
mentorship, and great contribution in science.
4
,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-galactonon-2-enon-
ate (50 mg, 0.11 mmol) in DMF (0.75 mL) is added H O (0.25 mL)
and F-TEDA-BF (150 mg, 0.42 mmol). The solution is stirred at 50
2
4
(27) Adamson, J.; Foster, A. B.; Hall, L. D.; Johnson, R. N.; Hesse, R.
H. Carbohydr. Res. 1970, 15, 351.
JA9723904