Cyclic sulfates in the regioselective synthesis of 5- and 6-amino and 5- and 6-fluorohexofuranoses

Article abstract of DOI:10.1016/S0008-6215(99)00124-X

Cyclic sulfates of 5,6- and 3,5-D-glucofuranose were used to prepare 6- and 5-azido (amino) and 6- and 5-fluoro derivatives of 1,2-O-isopropylidenehexofuranoses (D-gluco and L-ido configurations). The reactions were completely regioselective and, in the c

Full text of DOI:10.1016/S0008-6215(99)00124-X

www.elsevier.nl/locate/carres
Carbohydrate Research 319 (1999) 192–198
Note
Cyclic sulfates in the regioselective synthesis of 5- and
6-amino and 5- and 6-fluorohexofuranoses
Jose´ Fuentes *, Manuel Angulo, M. Angeles Pradera
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, Uni6ersidad de Se6illa, Apartado de Correos No 553,
E-41071 Se6ille, Spain
Received 18 March 1999; revised 11 May 1999; accepted 20 May 1999
Abstract
Cyclic sulfates of 5,6- and 3,5-
derivatives of 1,2-O-isopropylidenehexofuranoses (
D
-glucofuranose were used to prepare 6- and 5-azido (amino) and 6- and 5-fluoro
-gluco and -ido configurations). The reactions were completely
D
L
regioselective and, in the case of stereogenic centers (substitution at C-5), completely stereoselective. © 1999 Elsevier
Science Ltd. All rights reserved.
Keywords: Cyclic sulfates; Amino sugars; Azido sugars; Fluoro sugars
pared from the corresponding diols [13,14]
The cyclic sulfates of 6ic-diols are synthetic
equivalents of epoxides and cyclic sulfites
which have been widely used in organic syn-
thesis [1,2]. However, their applications in car-
bohydrate chemistry are limited [1,3–11].
In a recent letter [12], we have communi-
cated the preliminary results on the use of
glucofuranose cyclic sulfates in the prepara-
tion of 6- and 5-azido(fluoro) aldofuranose
derivatives. In this paper, we go further into
the preparation of 5,6- and 3,5-glucofuranose
cyclic sulfates and the nucleophilic opening of
the ester rings with sodium azide and different
fluoronucleophiles.
through the cyclic sulfites, which were ob-
tained as mixtures of diastereomers that were
directly oxidized [2] with the reagent sodium
periodate–ruthenium trichloride hydrate.
The nucleophilic opening of the sulfate ring
of compounds 1–4 with sodium azide pro-
duced the 6-azido-6-deoxy- -glucofuranose
D
derivatives 6–9 in high yields in a completely
regioselective manner. In the case of the 3-O-
mesyl derivative 8, no displacement of the
mesyloxy group at C-3 was observed under
the conditions used for the ring opening of the
cyclic sulfate 3; this mesyloxy group was sta-
ble even on treatment of 3 or 8 with sodium
azide at 105 °C in DMF for 6 h. The nucle-
The previously described [3]
nose (1, 2) and -allofuranose (4) 5,6-cyclic
sulfates and the new -glucofuranose 5,6- (3)
D-glucofura-
D
D
and 3,5- (5) cyclic sulfates were used as start-
ing materials. Compounds 3 and 5 were pre-
* Corresponding author. Fax: +34-95-462-4960.
E-mail address: jfuentes@cica.es (J. Fuentes)
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00124-X

J. Fuentes et al. / Carbohydrate Research 319 (1999) 192–198
193
The reaction of the cyclic sulfate 5 with
tetraethylammonium fluoride dihydrate led to
complex mixtures of decomposition products.
In the case of anhydrous tetrabutylammonium
fluoride, the reaction was strongly dependent
on the nucleophile/starting material ratio, on
ophilic sulfate ring opening of the non-vicinal
cyclic sulfate 5, using the same work-up as for
the preparation of 6–9, produced exclusively
the 5-azido-5-deoxy- -idofuranose derivative
L
11, as seen from the downfield shift of the H-5
and C-5 resonances.
1
temperature, and on reaction time. Both H
and 13C NMR spectra showed the formation
of 21 as a minor product, and a major elimi-
1
nation compound for which the H NMR
spectrum [6.04 (d, 1 H, J1,2 3.4 Hz, H-1), 5.42
(s, 1 H, H-3), 5.17 (dd, 1 H, J5,6a 9.7, J5,6b 6.5,
H-5), 5.05 (d, 1 H, H-2), 4.81 (dd, 1 H, J6a,6b
12.5, H-6a), 4.70 (dd, 1 H, H-6b)] and re-
ported data on related eliminations [10] sug-
gest structure 23. The best ratio (23:21, 5:3) of
substitution product was obtained when the
reaction was conducted in DMF at 0 °C for
40 h. When tris(dimethylamino)sulfur(trime-
thylsilyl)difluoride (TAS-F) was used as a nu-
cleophile, practically only the 5-fluoroderiva-
tive 21 was formed (23:21 ratio, measured by
Conventional Zemple´n deacetylation of 6
and 11 afforded the known azido sugar
derivatives 10 and 12, respectively [15].
1
digital integration of the H NMR signals,
:1:100). Treatment of 21 with sulfuric acid in
THF produced quantitatively the 5-fluoro- -
L
Catalytic (10% PdꢀC) hydrogenation of the
idofuranose derivative 22.
azidoglycofuranose derivatives 8, 9, and 12
The NMR spectra of the 6-fluoroglycofura-
nose derivatives 16–20 had the signals for
H-6a and H-6b at 4.51–4.71 ppm (2JH,F :47
Hz) and for C-6 at 83.2–85.0 ppm (1JC,F:169
Hz) in agreement with the presence of a
yielded quantitatively the 6-amino-
-allofuranose
-idofuranose (15)
D-gluco-
furanose (13), the 3,6-diamino-
D
(14), and the 5-amino-
L
derivatives, respectively.
This method to introduce an azido or
amino function into a sugar molecule through
a cyclic sulfate is a valuable option for the
synthesis of 6-amino sugars. It is particularly
interesting in the case of 5-amino-5-deoxyfuran-
oses because there are no problems of mix-
tures of epimers, as in the reduction of oxime
derivatives [16], or of competition between
elimination and substitution, as in methods
based on inversion of the C-5 configuration
[15], and the number of steps from the diol
derivative is only three, with high overall
yields.
fluorine atom. In the case of the 5-fluoro- -id-
L
ofuranoses 21 and 22, the resonances for H-5
and C-5 appeared at low field (4.90 and 90.3
2
ppm, respectively) and the values for JH5,F
1
and JC5,F were :90.4 and :175 Hz, respec-
tively, also supporting the introduction of the
fluorine atom.
In conclusion, we describe a new, short and
inexpensive method for the regio- and
stereoselective preparation of 6- and 5-azido,
6- and 5-amino, and 6- and 5-fluoro glyco-
furanoses. The method is especially useful in
the case of the 5-substituted- -ido derivatives.
L
The 6 - fluoro - 6 - deoxy-
(16–18) and -allo-furanose (19) were pre-
D
- gluco - furanose
D
pared analogously by sulfate ring opening of
1–4 using tetraethylammonium fluoride dihy-
drate as a nucleophile. Subsequent reduction
1. Experimental
of the 3-azido-6-fluoro- -allofuranoside 19
D
General methods.—Melting points are un-
corrected. Optical rotations were measured at
2494 °C in 1 cm cells. FTIR spectra were
gave the amino-fluoro derivative 20 in a high
yield.

194
J. Fuentes et al. / Carbohydrate Research 319 (1999) 192–198
recorded for KBr discs. H and 13C NMR
spectra were obtained for solutions in CDCl3
or MeOH-d4. Assignments were confirmed by
homonuclear 2D COSY and heteronuclear 2D
correlated experiments. FAB mass spectra
were recorded with a Kratos MS-80RFA in-
strument with a resolution of 1000 (10% valley
definition). HREIMS (70 eV), HRCIMS (150
eV) experiments were performed with a
Micromass AutoSpecQ instrument with a res-
olution of 10,000 (5% valley definition). Ions
were produced by a beam of xenon atoms
(6–7 keV) using a matrix consisting of thio-
glycerol or 3-nitrobenzyl alcohol and NaI as
salt. TLC was performed on Silica Gel HF254,
with detection by UV light or charring with
H2SO4. Silica Gel 60 (E. Merck, 230–400
mesh) was used for preparative chro-
matography.
1
Hz, H-6a), 4.78 (dd, 1 H, J5,6b 5.5 Hz, H-6b),
4.58 (dd, 1 H, J4,5 8.4 Hz, H-4), 3.12 (s, 3 H,
Ms), 1.53, 1.34 (2 s, each 3 H, CMe2) ppm;
13C NMR (125.7 MHz, CDCl3): l 113.5
(CMe2), 105.3 (C-1), 83.4 (C-2), 80.8 (C-3),
77.1 (C-4), 76.2 (C-5), 70.3 (C-6), 38.2 (OMs),
26.6, 26.0 (CMe2) ppm; FABMS m/z 383
([M+Na]+). Anal. Calcd for C10H16O10S2: C,
33.33; H, 4.47. Found: C, 33.22; H, 4.39.
6-O-Acetyl-1,2-O-isopropylidene-h- -gluco-
D
furanose 3,5-cyclic sulfate (5). Column chro-
matography (3:1 Et2O–light petroleum ether)
of the residue gave 5 as a solid (292 mg, 90%),
which crystallized from Et2O–light petroleum
ether: mp 116–118 °C (dec); [h]2D4= +38° (c
1.0, CH2Cl2); IR wmax 1753, 1398, 1254, 1204,
1
1094, 1042 and 866 cm−1; H NMR (500
MHz, CDCl3): l 6.06 (d, 1 H, J1,2 3.7 Hz,
H-1), 5.19 (d, 1 H, J3,4 2.5 Hz, H-3), 5.00 (t d,
1 H, J4,5 2.5, J5,6a =J5,6b 6.4 Hz, H-5), 4.79 (d,
1 H, H-2), 4.57 (m, 1 H, H-6a), 4.54 (m, 1 H,
H-6b), 4.35 (t, 1 H, H-4), 2.13 (s, 3 H,
COCH3), 1.53, 1.36 (2 s, each 3 H, CMe2)
Preparation of cyclic sulfates 3 and 5.—To
an ice-cooled and magnetically stirred solution
of the corresponding diol [11,12] (1 mmol) and
pyridine (4.08 mmol) in dry CH2Cl2 (5 mL), a
solution of thionyl chloride (2 mmol) in
CH2Cl2 (0.4 mL) was added dropwise over a
period of 10 min. Stirring was continued at
0 °C until TLC analysis showed complete con-
version of the starting material into cyclic
sulfite. The mixture was diluted with CH2Cl2
(15 mL), washed three times with water, dried
(MgSO4), and concentrated. To a solution (7
mL) of the residue in (2:2:3) CH2Cl2 –MeCN–
water, NaIO4 (2 equiv) and RuCl3·H2O (2 mg)
were added. The resulting mixture was stirred
for 20–60 min at rt. After dilution with
CH2Cl2 (15 mL), the organic layer was sepa-
rated and washed with water, dried (MgSO4),
and concentrated. The corresponding cyclic
13
ppm; C NMR (125.7 MHz, CDCl3): l 169.9
(CO), 113.2 (CMe2), 104.8 (C-1), 85.1 (C-3),
82.9 (C-5), 82.5 (C-2), 71.7 (C-4), 61.5 (C-6),
26.5, 26.0, (CMe2), 20.4 (COCH3) ppm;
FABMS: m/z 347 ([M+Na]+). Anal. Calcd
for C11H16O9S: C, 40.74; H, 4.97. Found: C,
40.78; H, 5.09.
General procedure for the preparation of
azido deri6ati6es 6–12.—A solution of the
corresponding cyclic sulfate 1–5 (1 mmol) and
sodium azide (2 mmol) in DMF (5 mL) at
50 °C was stirred for 10–60 min until total
consumption of the starting material, moni-
toring by TLC, then the mixture was concen-
trated and dissolved in THF (5 mL). Concd
H2SO4 (50 mL) and water (18 mL) were added
and the mixture was stirred for 20–60 min at
rt. The reaction mixture was diluted with
EtOAc (15 mL) and washed with sat aq
NaHCO3. The organic layer was separated,
washed three times with water, dried
(MgSO4), and concentrated to dryness. The
residue was purified by column chromatogra-
phy (1:2 Et2O–light petroleum ether) to give
6–9 or 11 (1:1 to 3:1 Et2O–light petroleum
ether), respectively. Zemple´n deacetylation of
9 and 11 yielded 10 and 12.
sulfates
chromatography.
1,2-O-Isopropylidene-3-O-mesyl-h-
were
purified
by
column
D
-gluco-
furanose-5,6-cyclic sulfate (3). Column chro-
matography (1:1 Et2O–light petroleum ether)
of the residue gave 3 as a solid (252 mg, 70%)
which crystallized from Et2O–light petroleum
ether: mp 154–157 °C; [h]2D1= −40° (c 1.0,
CH2Cl2); IR wmax 1385, 1215, 1175, 1094, 1026
and 980 cm−1; H NMR (500 MHz, CDCl3):
1
l 5.99 (d, 1 H, J1,2 3.4 Hz, H-1), 5.09 (d, 1 H,
J3,4 3.1 Hz, H-3), 5.06 (m, 1 H, H-5), 4.78 (d,
1 H, H-2), 4.85 (dd, 1 H, J5,6a 6.3, J6a,6b 9.3

J. Fuentes et al. / Carbohydrate Research 319 (1999) 192–198
195
346 ([M+Na]+). HREIMS: m/z obsd
308.0548, calcd for C9H14N3O7S 308.0552
([M−CH3]+). Anal. Calcd for C10H17O7N3S:
C, 37.14; H, 5.30; N, 13.00; S, 9.92. Found: C,
37.32; H, 5.23; N, 12.66; S, 10.14.
3-O-Acetyl-6-azido-6-deoxy-1,2-O-isopropy-
lidene-h- -glucofuranose (6).—Syrup (238 mg,
D
83%); [h]2D3 +9° (c 0.8, CH2Cl2); IR wmax 3472,
2104, 1742, 1375, 1228, 1084, 1024 and 864
cm−1; 1H NMR (500 MHz, CDCl3): l 5.89 (d,
1 H, J1,2 3.6 Hz, H-1), 5.27 (d, 1 H, J3,4 2.6
Hz, H-3), 4.58 (d, 1 H, H-2), 4.17 (dd, 1 H,
J4,5 9.2 Hz, H-4), 3.72 (ddd, 1 H, J5,6a 2.7, J5,6b
6.4 Hz, H-5), 3.58 (dd, 1 H, J6a,6b 12.7 Hz,
H-6a), 3.47 (dd, 1 H, H-6b), 2.16 (s, 3 H,
COCH3), 1.53, 1.32 (2 s, each 3 H, CMe2)
3,6-Diazido-3,6-dideoxy-1,2-O-isopropyli-
dene-h- -allofuranose (9).—Amorphous solid
D
(216 mg, 80%); [h]2D6+128° (c 1.0, CH2Cl2);
IR wmax 2108, 1379, 1262, 1107, 1026, and 872
cm−1; 1H NMR (500 MHz, CDCl3): l 5.80 (d,
1 H, J1,2 3.6 Hz, H-1), 4.77 (dd, 1 H, J2,3 4.7
Hz, H-2), 4.08-4.05 (m, 1 H, H-4), 4.07–4.03
(m, 1 H, H-5), 3.58 (dd, 1 H, J3,4 8.9 Hz, H-3),
3.54 (dd, 1 H, J5,6a 7.6, J6a,6b 12.7 Hz, H-6a),
3.45 (dd, 1 H, J5,6b 3.7 Hz, H-6b), 2.37 (d, 1
H, J5,OH 3.5 Hz, OH), 1.59, 1.38 (2 s, each 3
H, CMe2) ppm; 13C NMR (125.7 MHz,
CDCl3): l 113.4 (CMe2), 104.1 (C-1), 80.6
(C-2), 77.7 (C-4), 70.3 (C-5), 60.2 (C-3), 52.7
(C-6), 26.4 (2C, CMe2) ppm; FABMS: m/z
293 ([M+Na]+). Anal. Calcd for C9H14N6O4:
C, 40.00; H, 5.22; N, 31.10. Found: C, 40.18;
H, 4.93; N, 30.75.
13
ppm; C NMR (125.7 MHz, CDCl3): l 171.2
(CO), 112.4 (CMe2), 104.7 (C-1), 83.0 (C-2),
79.3 (C-4), 76.4 (C-3), 67.5 (C-5), 53.9 (C-6),
26.5, 26.1 (CMe2), 20.6 (COCH3) ppm;
FABMS: m/z 310 ([M+Na]+). Anal. Calcd
for C11H17N3O6: C, 45.99; H, 5.96; N, 14.63.
Found: C, 46.24; H, 5.58; N, 14.28.
6-Azido-3-O-benzyl-6-deoxy-1,2-O-isopropy-
lidene-h- -glucofuranose (7).—Syrup (265 mg,
D
79%); [h]2D8−54° (c 1.1, CH2Cl2); IR wmax
3493, 2104, 1080 and 1022 cm−1; lit. [17]
1
3500(OH) and 2100(N3); H NMR (500 MHz,
CDCl3): l 7.39–7.33 (m, 5 H, Ar), 5.93 (d, 1
H, J1,2 3.7 Hz, H-1), 4.75 (d, 1 H, JH,H 11.8
Hz, CHHPh), 4.64 (d, 1 H, H-2), 4.53 (d, 1 H,
CHHPh), 4.09 (m, 3 H, H-3, H-4, and H-5),
3.54 (m, 1 H, H-6a), 3.42 (dd, 1 H, J5,6b 5.4,
J6a,6b 12.5 Hz, H-6b), 2.28 (d, 1 H, J5,OH 4.2
Hz, OH), 1.49, 1.33 (2 s, each 3 H, CMe2)
ppm; 13C NMR (125.7 MHz, CDCl3): l
136.8–127.9 (6 C, Ar), 111.9 (CMe2), 105.1
(C-1), 81.9 (C-2), 81.4 (C-3*), 79.8 (C-4*),
71.9 (CH2Ph) 68.3 (C-5), 54.3 (C-6), 26.7, 26.2
(CMe2) ppm; HREIMS m/z obsd 320.1243,
calcd for C15H18N3O5 320.1246 ([M−CH3]+).
6-Azido-6-deoxy-1,2-O-isopropylidene-3-O-
6-Azido-6-deoxy-1,2-O-isopropylidene-h- -
D
glucofuranose (10).—[h]2D7+1° (c 0.6, Me2CO);
lit. [15] [h]2D7+2.48° (Me2CO).
6-O-Acetyl-5-azido-5-deoxy-1,2-O-isopropy-
lidene-i- -idofuranose (11).—Solid (201 mg,
L
70%); mp 72–74 °C (Et2O–light petroleum
ether); [h]2D6= −57° (c 1.0, CH2Cl2); IR wmax
3443, 2104, 1740, 1373, 1260, 1082 and 1020
cm−1; 1H NMR (500 MHz, CDCl3): l 5.98 (d,
1 H, J1,2 3.7 Hz, H-1), 4.53 (d, 1 H, H-2), 4.32
(dd, 1 H, J6a,6b 11.7 Hz, H-6a), 4.22 (m, 1 H,
H-3), 4.14 (dd, 1 H, H-6b), 4.13 (dd, 1 H, J3,4
2.5 Hz, H-4), 3.94 (t d, 1 H, J4,5 7.6, J5,6a 3.4,
J5,6b 7.6, Hz H-5), 2.66 (d, 1 H, OH), 2.13 (s,
3 H, COCH3), 1.50, 1.32 (2 s, each 3 H,
CMe2); 13C NMR (125.7 MHz, CDCl3): l
170.9 (CO), 112.0 (CMe2), 104.5 (C-1), 85.2
(C-2), 79.6 (C-4), 75.2 (C-3), 63.8 (C-6), 59.8
(C-5), 26.7, 26.1 (CMe2), 20.6 (COCH3);
FABMS: m/z 310 ([M+Na]+). Anal. Calcd
for C11H17N3O6: C, 45.99; H, 5.96; N, 14.63.
Found: C, 46.04; H, 5.94; N, 14.77.
methanesulfonyl-h-D-glucofuranose
(8).—
Syrup (284 mg, 88%); [h]2D1−27° (c 1.1,
CH2Cl2) IR wmax 3528, 2106, 1360, 1171, 1088,
1020, 943 and 851 cm−1; 1H NMR (300 MHz,
CDCl3): l 5.93 (d, 1 H, J1,2 3.6 Hz, H-1), 5.14
(d, 1 H, J3,4 2.7 Hz, H-3), 4.75 (d, 1 H, H-2),
4.22 (dd, 1 H, J4,5 9.3 Hz, H-4), 3.97 (ddd, 1
H, J5,6a 2.8, J5,6b 6.0 Hz, H-5), 3.64 (dd, 1 H,
J6a,6b 12.7 Hz, H-6a), 3.52 (dd, 1 H, H-6b),
3.15 (s, 3 H, Ms), 1.52, 1.33 (2 s, each 3 H,
5-Azido-5-deoxy-1,2-O-isopropylidene-i- -
L
idofuranose (12).—[h]2D1−77° (c 1.2, MeOH);
13
CMe2) ppm; C NMR (75.4 MHz, CDCl3): l
lit. [15] [h]2D0−77.0 (c 2.6, MeOH).
112.8 (CMe2), 104.9 (C-1), 83.1 (C-2), 81.1
(C-3), 78.7 (C-4), 67.3 (C-5), 54.0 (C-6), 38.0
(OMs), 26.5, 26.1 (CMe2) ppm; FABMS: m/z
General procedure for the preparation of
amino deri6ati6es 13–15.—A mixture of the

196
J. Fuentes et al. / Carbohydrate Research 319 (1999) 192–198
corresponding azidoderivative 8, 9 or 12 (1
mmol) and 10% Pd–C (20% for 9) in MeOH
(26 mL) was hydrogenated at rt for 45–90
min followed by filtration and evaporation to
dryness to give 13–15, respectively.
(d, 1 H, H-2), 4.12 (d, 1 H, J3,4 2.9 Hz, H-3),
4.05 (dd, 1 H, J4,5 6.2 Hz, H-4), 3.62 (dd, 1 H,
J5,6a 5.3, J6a,6b 10.9 Hz, H-6a), 3.52 (dd, 1 H,
J5,6b 6.0 Hz, H-6b), 3.14 (m, 1 H, H-5), 1.43,
1.28 (2 s, each 3 H, CMe2) ppm; 13C NMR
(125.7 MHz, MeOD): l 115.1 (CMe2), 108.4
(C-1), 89.6 (C-2), 83.8 (C-4), 79.2 (C-3), 67.0
(C-6), 55.8 (C-5), 29.5, 28.9 (CMe2) ppm;
FABMS: m/z 220 ([M+H]+).
General procedure for the preparation of
fluoro deri6ati6es 16–19.—To a solution of the
corresponding cyclic sulfate 1–4 (1 mmol) in
Me2CO (5 mL), tetraethylammonium fluoride
dihydrate (1.5 mmol) was added, and the mix-
ture was stirred at rt until the TLC analysis
(3:1 Et2O–light petroleum ether) showed com-
plete conversion of the cyclic sulfate into base-
line material. The mixture was concentrated,
and dissolved in THF (5 mL). Concd H2SO4
(50 mL) and water (18 mL) were added and the
mixture was stirred for 15–45 min at rt. The
reaction mixture was diluted with EtOAc (15
mL) and washed with sat aq NaHCO3. The
organic layer was separated, washed three
times with water, dried (MgSO4), and concen-
trated to dryness. The residue was purified by
column chromatography.
6-Amino-6-deoxy-1,2-O-isopropylidene-3-O-
methanesulfonyl-h- -glucofuranose (13). Iso-
D
lated as an amorphous solid (297 mg, 100%)
after column chromatography (4:1 CH2Cl2–
MeOH); [h]2D4−44° (c 1.0, CH2Cl2); IR wmax
3368, 3304, 1348, 1171, 1086, 1018, and 959
cm−1; 1H NMR (500 MHz, CDCl3): l 5.87 (d,
1 H, J1,2 3.7, Hz, H-1), 5.02 (d, 1 H, J3,4 2.8
Hz, H-3), 4.70 (d, 1 H, H-2), 4.02 (dd, 1 H,
J4,5 9.3 Hz, H-4), 3.72 (m, 1 H, H-5), 3.15 (s,
3 H, Ms), 3.05 (bd, 1 H, J6a,6b 12.7 Hz, H-6a),
2.84 (dd, 1 H, J5,6b 6.0 Hz, H-6b), 1.50, 1.32 (2
s, each 3 H, CMe2) ppm; 13C NMR (125.7
MHz, CDCl3): l 112.5 (CMe2), 105.0 (C-1),
83.5 (C-2), 82.3 (C-3), 79.6 (C-4), 67.4 (C-5),
43.8 (C-6), 38.0 (1C, OMs), 26.5, 26.1 (CMe2)
ppm; FABMS: m/z 298 ([M+H]+);
HRCIMS: m/z obsd 298.095089; calcd for
C10H20NO7S 298.096049 ([M+H]+).
3,6-Diamino-3,6-dideoxy-1,2-O-isopropyli-
dene-h- -allofuranose (14). Isolated as an
D
amorphous solid (218 mg, 100%). [h]2D4+50°
(c 1.0, MeOH); IR wmax 3372, 3304, 1589,
3-O-Acetyl-6-deoxy-6-fluoro-1,2-O-isopropy-
1
1377, 1217, 1098, 1017 and 874 cm−1; H
lidene-h- -glucofuranose (16). Isolated as a
D
NMR (500 MHz, MeOD): l 5.75 (d, 1 H, J1,2
3.7 Hz, H-1), 4.56 (dd, 1 H, J2,3 4.8 Hz, H-2),
3.65–3.62 (m, 1 H, H-5), 3.59 (dd, 1 H, J3,4
9.0, J4,5 6.1 Hz, H-4), 3.10 (dd, 1 H, H-3), 2.84
(dd, 1 H, J5,6a 3.7, J6a,6b 13.3 Hz, H-6a), 2.69
(dd, 1 H, J5,6b 6.8 Hz, H-6b), 1.51, 1.32 (2 s,
each 3 H, CMe2) ppm; 13C NMR (125.7 MHz,
MeOD): l 113.2 (CMe2), 105.7 (C-1), 82.2
(C-2), 83.2 (C-4), 74.7 (C-5), 58.2 (C-3), 45.6
(C-6), 26.9, 26.6 (CMe2) ppm; FABMS: m/z
219 ([M+H]+); HREIMS: m/z obsd
203.1030, calcd for C8H15N2O4 203.1032
([M−CH3]+); HRCIMS: m/z obsd 219.1345;
calcd for C9H19N2O4 219.1345 ([M+H]+).
syrup (227 mg, 86%) after column chromatog-
raphy (1:1 Et2O–light petroleum ether);
[h]2D3+11° (c 1.1, CH2Cl2); IR wmax 3489, 1742,
1
1460, 1425, 1379, 1088 and 1022 cm−1; H
NMR (500 MHz, CDCl3): l 5.90 (d, 1 H, J1,2
3.6 Hz, H-1), 5.31 (d, 1 H, J3,4 2.6 Hz, H-3),
4.67 (ddd, 1 H, J5,6a 2.2, J6a,6b 9.6, J6a,F 47.4
Hz, H-6a), 4.57 (ddd, 1 H, J5,6b 5.3, J6b,F 47.3
Hz, H-6b), 4.56 (d, 1 H, H-2), 4.22 (dd, 1 H,
J4,5 9.3 Hz, H-4), 3.85 (m, 1 H, H-5), 2.15 (s,
3 H, COCH3), 1.52, 1.32 (2 s, each 3 H,
CMe2) ppm; 13C NMR (125.7 MHz, CDCl3):
l 170.6 (CO), 112.4 (CMe2), 104.8 (C-1), 84.5
(d, JC,F 169.7 Hz, C-6), 83.0 (C-2), 77.8 (d,
JC,F 7.5 Hz, C-4), 76.3 (C-3), 67.5 (d, JC,F 18.8
Hz, C-5), 26.5, 26.1 (CMe2), 20.6 (COCH3)
ppm; FABMS: m/z 287 ([M+Na]+).
HREIMS: m/z obsd 249.0780, calcd for
C10H14FO6 249.0774 ([M−CH3]+). Anal.
Calcd for C11H17FO6: C, 50.00; H, 6.48.
Found: C, 49.62; H, 6.38.
5-Amino-5-deoxy-1,2-O-isopropylidene-i- -
L
idofuranose (15). Crystallized from EtOH: mp
179–183 °C, [h]2D4−6° (c 0.6, MeOH); lit. [17]
mp 184–185 °C, [h]2D0= −3.7° (c 1.1, MeOH);
lit. [18] mp 178 °C, [h]2D5= −3.0° (c 0.9,
MeOH); lit. [19] mp 176–179 °C, [h]2D0=
−3.4° (c 1.0, MeOH);.1H NMR (500 MHz,
MeOD): l 5.89 (d, 1 H, J1,2 3.7 Hz, H-1), 4.46

J. Fuentes et al. / Carbohydrate Research 319 (1999) 192–198
197
3-O-Benzyl-6-deoxy-6-fluoro-1,2-O-iso-
propylidene-h- -glucofuranose (17). Isolated as
J1,2 3.6 Hz, H-1), 4.77 (dd, 1 H, J2,3 4.8 Hz,
H-2), 4.58 (ddd, 1 H, J5,6a 4.0, J6a,6b 9.7, J6a,F
46.6 Hz, H-6a), 4.54 (ddd, 1 H, J5,6b 6.3, J6b,F
47.4 Hz, H-6b), 4.17 (m, 1 H, H-5), 4.12 (dd,
1 H, J4,5 4.6 Hz, H-4), 3.63 (dd, 1 H, J3,4 9.2
Hz, H-3), 2.38 (d, 1 H, J5,OH 4.3 Hz, OH),
1.58, 1.37 (2 s, each 3 H, CMe2) ppm; 13C
NMR (125.7 MHz, CDCl3): l 113.4 (CMe2),
104.1 (C-1), 83.2 (d, JC,F 169.7 Hz, C-6), 80.5
(C-2), 76.8 (d, JC,F 7.3 Hz, C-4), 70.1 (d, JC,F
20.1 Hz, C-5), 60.6 (C-3), 26.4 (2C, CMe2)
ppm; FABMS: m/z 270 ([M+Na]+). Anal.
Calcd for C9H14FN3O4: C, 43.72; H, 5.71; N,
17.00. Found: C, 44.10; H, 5.44; N, 16.81.
3 - Amino - 3,6 - dideoxy - 6 - fluoro - 1,2-O-iso-
D
a syrup (218 mg, 70%) after column chro-
matography (1:2 Et2O–light petroleum ether);
[h]2D0−38° (c 0.9, CH2Cl2); IR wmax 3474, 1456,
1
1379, 1217, 1082 and 1020 cm−1; H NMR
(500 MHz, CDCl3): l 7.38–7.34 (m, 5 H, Ar),
5.95 (d, 1 H, J1,2 3.7 Hz, H-1), 4.73 (d, 1 H,
JH,H 11.6 Hz, CHHPh), 4.71–4.57 (m, 1 H,
H-6a), 4.64 (d, 1 H, H-2), 4.58 (d, 1 H,
CHHPh), 4.60–4.48 (m, 1 H, H-6b), 4.19 (m,
1 H, H-5), 4.17 (m, 1 H, H-4), 4.14 (m, 1 H,
H-3), 1.50, 1.33 (2 s, each 3 H, CMe2) ppm;
13C NMR (125.7 MHz, CDCl3): l 137.0–
127.8 (6C, Ar), 111.9 (CMe2), 105.1 (C-1),
85.0 (d, JC,F 168.4 Hz, C-6), 82.0, 81.9 (C-2,3),
78.6 (d, JC,F 6.3 Hz, C-4), 72.2 (CH2Ph), 68.3
(d, JC,F 17.6 Hz, C-5), 26.7, 26.2 (CMe2) ppm;
FABMS: m/z 335 ([M+Na]+). HREIMS:
m/z obsd 312.1362, calcd for C16H21FO5
312.1373. Anal. Calcd for C16H21FO5: C,
61.53; H, 6.78. Found: C, 61.26; H, 6.79.
6-Fluoro-6-deoxy-1,2-O-isopropylidene-3-O-
propylidene-h- -allofuranose (20).—Prepared
D
following the general procedure described
above for 13–15. Column chromatography
(20:1 CH2Cl2–MeOH) of the residue gave 20
as a syrup (221 mg, 83%); [h]2D5 +53° (c 1.3,
CH2Cl2); IR wmax 3381, 3312, 1377, 1219, 1099,
1
1013 and 874 cm−1; H NMR (300 MHz,
CDCl3): l 5.78 (d, 1 H, J1,2 3.7 Hz, H-1), 4.59
(ddd, 1 H, J5,6a 2.6, J6a,6b 9.9, J6a,F 47.4 Hz,
H-6a), 4.51 (ddd, 1 H, J5,6b 4.9, J6b,F 47.6 Hz,
H-6b), 4.46 (dd, 1 H, J2,3 4.6 Hz, H-2), 3.95
(dddd, 1 H, J5,F 23.2 Hz, H-5), 3.65 (dd, 1 H,
J4,5 7.9 Hz, H-4), 3.20 (dd, 1 H, J3,4 9.5 Hz,
H-3), 2.35 (bs, 1 H, OH), 1.55, 1.35 (2 s, each
3 H, CMe2) ppm; 13C NMR (75.4 MHz,
CDCl3): l 112.3 (CMe2), 104.5 (C-1), 84.1 (d,
JC,F 170.4 Hz, C-6), 80.1 (C-2), 76.1 (d, JC,F
7.5 Hz, C-4), 73.2 (d, JC,F 18.1, C-5), 58.6
(C-3), 26.4, 26.3 (CMe2) ppm; FABMS: m/z
mesyl-h- -glucofuranose (18). Isolated as a
D
syrup (258 mg, 86%) after column chromatog-
raphy (2:1 Et2O–light petroleum ether);
[h]2D1−28° (c 1.0, CH2Cl2); IR wmax 3528, 1362,
1
1173, 1090, 1026 and 955 cm−1; H NMR
(500 MHz, CDCl3): l 5.95 (d, 1 H, J1,2 3.6 Hz,
H-1), 5.13 (d, 1 H, J3,4 2.7 Hz, H-3), 4.78 (d,
1 H, H-2), 4.67 (ddd, 1 H, J5,6a 2.1, J6a,6b 9.8,
J6a,F 47.5 Hz, H-6a), 4.59 (ddd, 1 H, J5,6b 4.7,
J6b,F 47.2 Hz, H-6b), 4.28 (dd, 1 H, J4,5 9.5 Hz,
H-4), 4.01 (dddd, 1 H, J5,F 21 Hz, H-5), 3.15
(s, 3 H, Ms), 1.51, 1.33 (2 s, each 3 H, CMe2)
222
([M+Na]+).
Anal.
Calcd
for
13
ppm; C NMR (125.7 MHz, CDCl3): l 112.8
C9H16FNO4: C, 48.86; H, 7.29; N, 6.33.
Found: C, 49.16; H, 7.14; N, 6.18.
(CMe2), 105.0 (C-1), 84.4 (d, JC,F 168.4 Hz,
C-6), 83.2 (C-2), 81.7 (C-3), 77.3 (d, JC,F 7.0
Hz, C-4), 67.4 (d, JC,F 18.8 Hz, C-5), 38.0 (1C,
OMs), 26.5, 26.1 (CMe2) ppm; FABMS: m/z
323 ([M+Na]+). HREIMS: m/z obsd
285.0438, calcd for C9H14FO7S 285.0444
([M−CH3]+). Anal. Calcd for C10H17FO7S:
C, 40.00; H, 5.71; S, 10.68. Found: C, 39.99;
H, 6.11; S, 11.01.
6-O-Acetyl-5-fluoro-5-deoxy-1,2-O-isopro-
pylidene-i- -idofuranose (22).—A solution of
L
TAS-F (100 mg) in CH2Cl2 (1.5 mL) was
added dropwise, at −10 °C, to a stirred solu-
tion of the cyclic sulfate 5 (35 mg). After 24 h,
the reaction mixture was warmed to 35 °C,
and kept at this temperature for a further 72
h. The solvent was evaporated under dimin-
ished pressure, and the crude was purified by
column chromatography using 2:1 CH2Cl2–
Me2CO as eluent to give tris(dimethyl-
amino)sulfonium 6-O-acetyl-5-fluoro-5-de-
3 - Azido - 3,6 - dideoxy - 6 - fluoro - 1,2 - O-iso-
propylidene-h- -allofuranose (19). Isolated as
D
a syrup (198 mg, 80%) after column chro-
matography (2:1 Et2O–light petroleum ether);
[h]2D5+107° (c 1.1, CH2Cl2); IR wmax 3472,
oxy-1,2-O-isopropylidene-b- -idofuranose-3-
L
2112, 1379, 1258, 1111, 1026 and 874 cm−1
;
sulfate (21) (29 mg, 53%) as a syrup. 1H NMR
(500 MHz, CDCl3): l 5.98 (d, 1 H, J1,2 3.6,
1H NMR (500 MHz, CDCl3): l 5.82 (d, 1 H,

198
J. Fuentes et al. / Carbohydrate Research 319 (1999) 192–198
H-1), 5.01 (m, 1 H, H-2), 5.02-4.89 (m, 1 H,
H-5), 4.80 (d, 1 H, J3,4 2.8 Hz, H-3), 4.58 (m,
1 H, H-6a), 4.48–4.43 (m, 1 H, H-4), 4.48–
4.39 (m, 1 H, H-6b), 2.97 (s, 18 H, NMe2), 2.10
(s, 3 H, COCH3), 1.49, 1.30 (2 s, each 3 H,
CMe2); 13C NMR (125.7 MHz, CDCl3): l
171.4 (CO), 112.0 (CMe2), 105.0 (C-1), 90.3 (d,
JC,F 174.7 Hz, C-5), 83.5 (C-2), 79.3 (d, JC,F 7.5
Hz, C-3), 78.2 (d, JC,F 20.1 Hz, C-4), 63.2 (d,
JC,F 20.1 Hz, C-6), 38.6 (NMe2), 26.8, 26.3
(CMe2), 20.7 (COCH3). Compound 21 (29 mg)
was dissolved in THF (0.4 mL) and a catalytic
amount of H2SO4 was added. The mixture was
stirred for 30 min at rt and then diluted with
EtOAc (5 mL) and washed with sat aq
NaCO3H. The organic layer was separated,
washed three times with water, dried (MgSO4),
and concentrated to dryness to yield 22 (15
mg, 100%) as a syrup. [h]2D4−28° (c 0.8,
CH2Cl2); IR wmax 3455, 1742, 1377, 1260, 1084,
financial support (grant numbers PB94/1440-
C02-01 and PB97/0730) and for the award of
a grant to M.A.
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1020 and 799 cm−1; H NMR (500 MHz,
CDCl3): l 5.94 (d, 1 H, J1,2 3.7 Hz, H-1), 4.90
(dtd, 1 H, J5,6a 2.6, J5,6b 6.3, J5,F 49.4 Hz, H-5),
4.46 (m, 1 H, H-2), 4.37 (ddd, 1 H, J6a,6b 12.7,
J6a,F 27.0 Hz, H-6a), 4.21 (m, 1 H, H-3), 4.22
(ddd, J3,4 2.9, J4,5 6.3, J4,F 17.1 Hz, 1 H, H-4),
4.29 (ddd, 1 H, J6b,F 23.6 Hz, H-6b), 2.06 (s, 3
H, COCH3), 1.43, 1.26 (2 s, each 3 H, CMe2);
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112.1 (CMe2), 104.8 (C-1), 90.5 (d, JC,F 176.0
Hz, C-5), 85.3 (C-2), 78.6 (d, JC,F 17.6 Hz,
C-4), 75.5 (d, JC,F 5.7 Hz, C-3), 63.6 (d, JC,F
22.6 Hz, C-6), 26.7, 26.2 (CMe2), 20.6
(COCH3); FABMS: m/z 287 ([M+Na]+).
HRCIMS: m/z obsd 265.1073, calcd for
C11H18FO6 265.1087 ([M+H]+).
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Acknowledgements
We thank the Direccio´n General de Inves-
tigacio´n Cient´ıfica y Te´cnica of Spain for
.