Synthesis and structure elucidation of benzoylated deoxyfluoropyranosides

Article abstract of DOI:10.1080/07328303.2010.540055

Benzoylated deoxyfluoropyranosides have been synthesized, starting with protected, unprotected, or fluorinated precursors. Fluorination of eight derivatives was compared using DAST and Deoxo-Fluor as reagents. Deoxo-Fluor was found to be especially useful

Full text of DOI:10.1080/07328303.2010.540055

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Synthesis and Structure Elucidation of
Benzoylated Deoxyfluoropyranosides
Aslan M. Esmurziev a b , Nebojsa Simic a , Bård Helge Hoff a & Eirik
Sundby b
a Norwegian University of Science and Technology , Høgskoleringen
5, NO-7491, Trondheim , Norway
b Sør-Trøndelag University College , E.C. Dahls gate 2, 7004 ,
Trondheim , Norway
Published online: 13 Dec 2010.
To cite this article: Aslan M. Esmurziev , Nebojsa Simic , Bård Helge Hoff & Eirik Sundby (2010)
Synthesis and Structure Elucidation of Benzoylated Deoxyfluoropyranosides, Journal of Carbohydrate
Chemistry, 29:7, 348-367, DOI: 10.1080/07328303.2010.540055
To link to this article: http://dx.doi.org/10.1080/07328303.2010.540055
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Journal of Carbohydrate Chemistry, 29:348–367, 2010
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ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2010.540055
Synthesis and Structure
Elucidation of Benzoylated
Deoxyfluoropyranosides
Aslan M. Esmurziev,1 Nebojsa Simic,2 Ba˚ rd Helge Hoff,2
and Eirik Sundby3
1Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491
Trondheim, Norway; and Sør-Trøndelag University College, E.C. Dahls gate 2, 7004
Trondheim, Norway
2Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491
Trondheim, Norway
3Sør-Trøndelag University College, E.C. Dahls gate 2, 7004 Trondheim, Norway
Benzoylated deoxyfluoropyranosides have been synthesized, starting with protected,
unprotected, or fluorinated precursors. Fluorination of eight derivatives was compared
using DAST and Deoxo-Fluor as reagents. Deoxo-Fluor was found to be especially
useful in the fluorination of methyl 2,3,4-O-tribenzoyl α-D-mannopyranoside and β-
D-glucopyranoside, resulting in better yields and avoiding the 1,6-methoxy migration
experienced with DAST for one derivative. The two reagents gave comparable yields
in the fluorination of other methyl pyranosides, confirming Deoxo-Fluor as a safer al-
ternative to DAST. Methyl α-D-mannopyranoside underwent fluorination to yield the
4,6-difluorotalopyranoside and the corresponding cyclic sulfite. The NMR spectroscopic
properties of 11 benzoyl deoxy-fluoropyranosides are reported.
Keywords Deoxyfluorosugars; Diethylaminosulfur trifluoride; Bis-(2-methoxyethyl)
aminosulfur trifluoride; DAST; Deoxo-Fluor; Benzoyl pyranosides; 19F NMR
INTRODUCTION
Fluorinated molecules have found widespread applications in the field of
medicinal chemistry.[1,2] Also, fluorinated carbohydrates have found their
use among others as biocompatible surfactants,[3,4] mechanistic probes,[5–7]
positron-emitting radiopharmaceuticals,[8,9] potential anticancer agents,[10–13]
and building blocks for other bioactive compounds.[14–16] As compared to their
natural derivatives, fluorinated carbohydrates have altered hydrogen bonding
Received February 25, 2010; accepted November 10, 2010.
Address correspondence to Ba˚rd H. Hoff, Department of Chemistry, Norwegian Univer-
sity of Science and Technology (NTNU) NO-7491, Norway. E-mail: bhoff@chem.ntnu.no
348

Benzoylated Deoxyfluoropyranosides
349
abilities and metabolic stability. 19F NMR opens new possibilities for tracking
distribution, transport, and metabolism of drug derivatives.
Although some unprotected carbohydrates can be fluorinated in decent
yield, most often protection and deprotection schemes are utilized. Having the
options of employing different protecting groups is of importance depending on
the following chemical steps. Esters are often employed, and in terms of molec-
ular mass and cost, the acetate ester is preferred. On the other hand, using
aromatic esters allows for a higher stability, the avoidance/reduction of acyl
migration, and the ability to analyze compounds by UV spectroscopic meth-
ods. Diethylaminosulfur trifluoride (DAST) is a commonly used reagent for the
conversion of hydroxyl groups into fluorinated derivatives.[17,18] Also, partly
benzoylated carbohydrates have been fluorinated with this reagent.[6,19–23]
However, there are hazards connected to the use of DAST, and a safer alterna-
tive, bis-(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor), has been de-
veloped.[24–26] As part of our effort to prepare building blocks for bioactive com-
pounds, a series of benzoylated deoxy-fluoropyranosides have been synthesized
and characterized. The use of DAST and Deoxo-Fluor has also been compared
in fluorination of various hexapyranosides.
RESULTS AND DISCUSSION
Synthesis of Methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-
fluoro-pyranosides
As monofluorination of unprotected carbohydrates can be problem-
atic, the 6-deoxy-6-fluorohexapyranosides were targeted by fluorination of
the methyl 2,3,4-tri-O-benzoylpyranosides (4a–e). These were obtained by
two different routes: compounds 4a–c were synthesized by Candida ru-
gosa lipase (CRL)-catalyzed hydrolysis of the corresponding tetrabenzoates,
2a–c, as previously reported,[27] while 4d–e were obtained by a trityla-
tion/benzoylation/detritylation protocol (Sch. 1).
The methyl 2,3,4-tri-O-benzoylhexapyranosides 4a–e were then subjected
to fluorination using DAST in dichloromethane, THF and diglyme, and Deoxo-
Fluor in THF. The degree of conversion obtained under the various conditions
is shown in Table 1. The galacto derivatives 4a–b were fluorinated very slowly,
giving a maximum of 14% conversion using DAST in dichloromethane. No im-
provement was observed using Deoxo-Fluor. In fluorination of structurally re-
lated methyl 2,3,4-tribenyl D-galactopyranoside, Tashiro et al.[28] also obtained
a cyclic 3,6-ether byproduct. This was not seen in reaction of 4a–b. The low de-
gree of conversion for 4a–b is most likely due to steric hindrance imposed by
the benzoyl groups.

A.M. Esmurziev et al.
350
OMe
O
O
F
F
N
F
F
N
S
F
S
F
O
BzO
F
Deoxo-Fluor
DAST
OBz
BzO
OBz
6d
O
BzO
OMe
BzCl/
pyridine
CRL
BzO
OBz
OH
OH
F
2a-c
DAST or
Deoxo-Fluor
O
O
O
HO
HO
OMe
BzO
BzO
OMe
BzO
BzO
OMe
OH
1a-e
OBz
4a-e
OBz
5a-e
OTr
O
1. TrCl /
pyridine
2. BzCl
FeCl3
BzO
OMe
BzO
OBz
3d-e
Scheme 1: Route to 5a–e, α-D-galactopyranoside (a), β-D-galactopyranoside (b),
α-D-glucopyranoside (c), β-D-glucopyranoside (d), α-D-mannopyranoside (e).
Higher reactivity was observed in fluorination of 4c. The use of DAST in
dichloromethane gave a 54% conversion. This could be increased to 91% by
applying a 1-h refluxing period at the end of the reaction. The use of Deoxo-
Fluor led to a comparable 88% conversion. In fluorination of 4a–c, the 6-deoxy-
6-fluoroderivatives, 5a–c, were the only products in each case. However, in
line with that reported by Lin et al.,[19] DAST fluorination of methyl 2,3,4-tri-
O-benzoyl-β-D-glucopyranoside (4d) gave rise to both 5d and the migration
Table 1: Degree of conversion (%)a in fluorination of 4a–e in various solvents using
DAST (4 eq) and Deoxo-Fluor (4 eq)
DAST
Deoxo-Fluor
b
Substrate CH2Cl2 CH2Cl2
THF Di-glyme Product THF THFb Product
4a
4b
4c
4d
4e
14
12
14
10
91
<1
<1
<1
<1
5a
5b
13
7
88
85
77
13
9
5a
5b
5c
5d
5e
54
41
<1
5c
88
74c
60
>99d
5d + 6d
>99
78
e)
e)
e)
e)
62
5e
aConv. by HPLC.
bRefluxed for 1 h after standard reaction.
cProducts: 5d, 41%; 6d, 33%.
dProducts: 5d, 38%; 6d, 62%.
eNot performed.

Benzoylated Deoxyfluoropyranosides
351
product 6d. A refluxing period at the end of the reaction increased the amount
of the rearrangement product further to 62%. A mechanistic rationale for this
migration has been proposed,[19,29,30] where the glycosidic oxygen acts as a nu-
cleophile on the RO-SF2NEt2 intermediate, possibly assisted by the carbonyl
oxygen situated at C-2 (Sch. 2).
Et2NF2SO
MeO
MeO
OMe
OBz
F
BzO
O
BzO
O
F-
O
O
+
O
Ph
O
OBz
O
OBz
OBz
OBz
Ph
Scheme 2: Possible mechanism for the C-1 to C-6 methoxy migration.
In contrast, the use of Deoxo-Fluor gave 5d as the only product. Full con-
version to 5d was obtained when applying a refluxing period at the end of
the reaction. The reason why Deoxo-Fluor does not cause this migration is
not understood. However, DFT calculations have indicated that the increased
stability of Deoxo-Fluor as compared to DAST is due to coordination of the
ether oxygen with the sulphur atom of the reagent.[24] Possibly, such a coor-
dination could also be present in the RO-SF2N(CH2CH2OCH3)2 intermediate,
both shielding C-6 toward nucleophilic attack from oxygen at C-1 and increas-
ing the strength of the susceptible C-O bond. Deoxo-Fluor also proved to be the
best fluorinating agent for the synthesis of 5e from 4e (77% conv.). Fluorina-
tion of 4e with DAST in dichloromethane gave 60% conversion.
Synthesis of Other Benzoylated Deoxy-fluoropyranosides
We continued to compare the performance of DAST and Deoxo-Fluor
in fluorination of other methyl pyranosides. Methyl 2,3,6-tri-O-benzoyl-α-
D–galactopyranoside (7a), obtained by abrupt benzoylation of 1a, was fluori-
nated using DAST and Deoxo-Fluor (Sch. 3). The product 8c has been prepared
previously using DAST.[20,21]
F
OBz
OBz
OH
O
O
O
O
DAST
or
CRL
DAST
or
F
OMe
F
OMe
HO
OMe
HO
BzO
OMe
Deoxo-Fluor
BzO
OBz
BzO
OBz
BzO
OBz
Deoxo-Fluor
OBz
10c
8c
7a
9a
Scheme 3: Synthesis of methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-fluoro-α-D-glucopyranoside (8c)
and methyl 2,3-di-O-benzoyl-4,6-dideoxy-4,6-difluoro-α-D-glucopyranoside (10c) using DAST
or Deoxo-Fluor.

A.M. Esmurziev et al.
352
Fluorination of 7a with DAST and Deoxo-Fluor using 2.5 equivalents of
fluorinating agent gave a 67% and 65% conversion, respectively. The degree
of conversion for both systems could be improved to 90% by addition of a sec-
ond portion of reagent after 6 h reaction time. The reaction of 7a with DAST
was run in a 23.3 mmol scale, giving 72% isolated yield of 8c. Further, from
7a, Candida rugosa lipase-catalyzed hydrolysis gave 9a, which was submit-
ted to DAST and Deoxo-Fluor fluorination (Sch. 3). The difluorinated α-D-
glucopyranoside 10c was obtained in 74% and 72% isolated yield, respectively,
indicating very similar reactivity for the two reagents. No other fluorinated
byproducts were observed.
DAST fluorination of methyl α-D-mannopyranoside (1e) to yield methyl
4,6-dideoxy-4,6-difluoro-α-D-talopyranoiside (11f) has been reported.[21,31]
The preparation of methyl 4,6-dideoxy-4,6-difluoro-2,3-di-O-benzoyl-α-
D–talopyranoside (10f) was attempted using both DAST and Deoxo-Fluor
followed by benzoylation without isolation of 11f (Sch. 4). In both cases 9
equivalents of fluorinating agent was used and a similar low 26% isolated
yield of 10f was obtained.
OH
F
F
F
O
O
O
O
DAST
BzCl
HO
HO
OMe
F
OMe
F
OMe
F
OMe
or
Pyridine
Deoxo-Fluor
OH
HO
OH
BzO
OBz
O
O
S
1e
11f
10f
12f
O
Scheme 4: Synthesis of methyl 2,3-di-O-benzoyl-4,6-dideoxy-4,6-difluoro-α-D–talopyranoside
(10f) and the structure of the byproduct 12f.
The reasons for the loss in yield were investigated by isolation of
11f. However, in addition to 11f,[31] another difluorinated carbohydrate was
isolated. NMR spectroscopy confirmed this to be a methyl 4,6-dideoxy-
difluorotallopyranoside, but with higher shift values for H-1, H-2, and H-3 as
compared to 11f. Whereas compound 11f underwent benzoylation to afford 10f
(77% isolated yield), the unknown compound failed to react under similar con-
ditions. Based on previous reports on fluorination of inositol derivatives using
and a characteristic IR band at 1215 cm−1 a cyclic sulfite was the
[32,33]
SF4
,
most likely candidate structure. The presence of sulphur was confirmed by
ICP-MS, and a reaction of 11f with thionyl chloride gave a compound with the
same chemical and spectroscopic properties, thus confirming the structure 12f.
The mechanism of formation is expected to follow that outlined for SF4.[33]
We were also interested in obtaining the benzoylated 2-deoxy-2-fluoro-
and 3-deoxy-3-fluoro-D-gluco derivatives as building blocks for bioactive com-
pounds. Methylation and benzoylation of commercially available 3-deoxy-3-
fluoro-D-glucose was attempted as shown in Scheme 5. To avoid the isolation

Benzoylated Deoxyfluoropyranosides
353
OH
OBz
OBz
OH
OBz
1. MeOH/H+
O
O
O
O
O
BzCl
+
HO
OH
BzO
OMe
BzO
OBz
HO
HO
OH
BzO
BzO
OBz
Pyridine
2, BzCl/pyridine
F
OH
F
OBz
F
OBz
F
F
13d
14d
15d
BzCl/pyridine
Scheme 5: Synthesis of benzoylated 3-deoxy-3-fluoro- and 2-deoxy-2-fluoro-
D-glucopyranoside.
of the intermediate methyl glucoside, benzoylation was performed on the crude
reaction product. This, however, gave a mixture of the β-anomer 13d (12% iso-
lated yield) and the tetrabenzoate 14d (3%). Both the low yield and formation
of the β-anomer 13d correspond with results for synthesis of the corresponding
acetates.[34]
Attempts to prepare methyl 3,4,6-tri-O-benzoyl-2-deoxy-2-fluoro-
D–glucopyranoside were also made by the two-step route shown in Scheme
5, but were unsuccessful. Due to the low efficiency in forming the methyl
glycosides, it was considered more useful to prepare the corresponding tetra-
benzoates 14 and 15 by benzoylation (Sch. 5). Crystallization gave 48% and
51% isolated yield of the β-anomers 14d and 15d, respectively. We were not
able to purify the α-anomers present in the mother liquor.
NMR Spectroscopy
The NMR assignments of the compounds 5a–e, 8c, 10c, 10f, 13d, 14d, and
15d were based on the data obtained from 1D 1H, 13C, and 19F and various 2D
experiments. Spin systems and connectivity in the pyranose ring and in the
aromatic systems were identified by DQF-COSY, HMQC, and HSQC-TOCSY
experiments. The connectivity between the pyranose ring and benzoyl groups
was identified in HMBC spectra from long-range correlations between protons
H-2, H-3, H-4, and H-6, the corresponding carbonyl-, and its directly attached
aromatic carbon (Fig. 1).
F
OBz
6
O
5
H
H
2
4
H
OR
O
O
OBz
1
HMBC
H
3
H
H
Figure 1: HMBC correlations revealing connectivity between the pyranoside and benzoyl
groups.

A.M. Esmurziev et al.
354
The 1H and 13C chemical shifts are given in the Experimental section; the
1
resolved H-1H and 19F-1H coupling constants and the 19F chemical shifts are
given Table 2.
1H NMR data of the pyranose part of 5c corresponded with that published
previously.[35] 1H NMR of 5d has been reported, but not assigned,[19] while in
the case of 8c, previously reported shifts for protons at C-6, C-1, and C-2 have
1
to be revised.[20,21] The H chemical shift of H-1 depended on the anomeric
configuration and the configuration at C-2. For the α-anomers 5a, 5c, 8c, and
10c, the H-1 signal resided at higher ppm values than for their β-anomers.
The coupling constants between H-1 and H-2 are also of diagnostic value. In
the case of 13d, both the H-1 shift value and the coupling between H-1 and
H-2 enabled assignment of stereochemistry as β-configured.
The 2JHF couplings for 6-deoxy-6-fluoroderivatives 5a–e, 10c, and 10f were
in the range of 45.6 to 47.5 Hz, while when the fluorine was situated at C-2,
C-3, and C-4, slightly higher coupling values were observed (50.3–52.0 Hz).
The 13C NMR data for 5c corresponded with that reported[35]; data for 8c
has not been found, while in the case of 5d,[19] assignment has not been pro-
vided. The C-1 and the methoxy carbon shifts are strong indicators of anomeric
configuration, and the α-anomers had lower shift values than the β-anomers
for both signals. The chemical shifts of C-6 in the 6-deoxy-6-fluoropyranosides
were only slightly affected by structural variation and appeared from 80.7 to
1
81.7 ppm. The JCF coupling constants varied from 169.6 to 193.2 Hz depend-
ing on the position of the fluorine and pyranose structure. Among others, the
1JCF coupling constants at C-6 depended on the stereochemistry at C-4 and
were higher for 5c–e and 10c than for 5a–b and 10f.
The 19F NMR data of 8c corresponded well with those reported,[20,21] while
reference data for the other compounds have not been published. The shifts for
the fluorine at C-6 varied from −230.50 to −236.15 ppm, while the fluorines at
C-2, C-3, and C-4 resided from −195.53 to −200.19. The 19F-1H coupling con-
stants were in good agreement with those observed from the 1H 1D spectrum.
CONCLUSION
Eleven deoxy-fluoro benzoyl pyranosides, eight of which are new chemical
entities, have been synthesized and characterized by high-field NMR spec-
troscopy. The use of DAST and Deoxy-Fluor was compared in the fluorina-
tion of eight different carbohydrate derivatives and in most cases the reagents
gave similar yields. Surprisingly, in reaction of methyl α-D-mannopyranoside,
a cyclic sulfite was discovered as the major byproduct using both reagents.
The use of Deoxy-Fluor was found to be superior for the fluorination of methyl
2,3,4,-tribenzoyl-β-D-glucopyranoside, avoiding a 1,6-migration experienced
with DAST. Moreover, with Deoxy-Fluor, as compared to DAST, fluorination

355

A.M. Esmurziev et al.
356
of carbohydrates can be performed with good conversion in nonchlorinated sol-
vents (THF) with a less hazardous reagent.
EXPERIMENTAL
General
Methyl α-D-mannopyranoside (1e) was prepared by a known method,[36]
while 1a–d, DAST, and Deoxo-Fluor were purchased from Sigma-Aldrich. Ben-
zoyl chloride and pyridine were from Fluka. 2-Deoxy-2-fluoro-D-glucose and
3-deoxy-3-fluoro-D-glucose were from Toronto Research Chemicals Inc. The
compounds 2a–c, 4a–c, and 9a were prepared as described previously.[27,37]
Solvents were from VWR and were used as received, except for CH2Cl2, which
was dried over CaCl2. Column chromatography was performed using silica gel
60A from Fluka (pore size 40–63 µm). Candida rugosa lipase (type VII, ≥700
units/mg solid) was from Sigma-Aldrich.
Analysis
The HPLC system consisted of an Agilent 1100 series quaternary pump,
Agilent 1100 series variable wavelength UV detector (200–315 nm), and ther-
mostated column compartment. Conversion was analyzed on a Supelcosil C18
column (5-µm particle size, 25 cm) at 254 nm, eluting with a mixture of deion-
ized water containing TFA (0.01%) and MeOH (30:70, vol.-%). Melting points
were determined by a Mettler FP 5 melting point apparatus and are uncor-
rected. Optical rotations were measured using the sodium D line at 589 nm on
a Perkin-Elmer 243 B polarimeter.
NMR Spectroscopic Methods
1
Unless otherwise stated, H and 13C NMR data were recorded using a
Bruker Avance 600 spectrometer operating at a proton frequency of 600.18
MHz with a 5-mm triple-resonance cryo probe equipped with a z-gradient. The
samples containing a solution of 20 mg of substances in CDCl3 were measured
at 298 K with TMS as reference standard. The 19F NMR data were recorded
with a Bruker Avance 500 spectrometer using hexafluorobenzene as reference
standard. Pulse sequences from the Bruker user library were used. The ac-
1
quisition details for the 1D H and 13C NMR, HMQC, HSQC-TOCSY, HMBC,
1
and H,1H DQF-COSY were as described previously.[37] 470 MHz 19F 1D: π/2
pulse for 19F 15.0 µs, spectral width 100 kHz, acquisition time 0.35 s, relax-
ation delay 1.0 s. 470 MHz 19F 1D with proton BB decoupling: π/2 pulse for
19F 15.0 µs, spectral width 94.3 kHz, acquisition time 0.66 s, WALTZ proton
decoupling during acquisition, relaxation delay 1.0 s. In order to distinguish

Benzoylated Deoxyfluoropyranosides
357
close resonances for some of the compounds, additional experiments were run
to obtain higher resolution.
Synthesis
Methyl 2,3,4-tri-O-benzoyl-β-D-glucopyranoside (4d)[38]
Methyl β-D-glucopyranoside (1d) (1.00 g, 5.15 mmol) was first converted
to methyl 2,3,4-tri-O-benzoyl-6-trityl-β-D-glucopyranoside (3d) by tritylation
and benzoylation according to the procedure of Ding et al.[39] This resulted in
an oil that crystallized from EtOH giving 1.25 g (1.67 mmol, 32%) of 3d as a
white solid, mp. 115–116◦C, [α]D22 = −12.2◦ (c 1.0, CHCl3). H NMR (CDCl3,
1
400 MHz) δ: 7.97 (m, 2 H, Ar), 7.82 (m, 2 H, Ar), 7.70 (m, 2 H, Ar), 7.51–7.29
(m, 9 H, Ar), 7.16 (m, 8 H, Ar), 7.09 (m, 7 H, Ar), 5.79 (t, J = 9.6, 1 H, H-3),
5.63 (t, J = 9.6, 1 H, H-4), 5.54 (dd, J2,3 = 9.6, J2,1 = 8.0, 1 H, H-2), 4.72 (d,
J1,2 = 8.0, 1 H, H-1), 3.85 (m, 1 H, H-5), 3.62 (s, 3 H, OCH3), 3.35 (dd, J5,6a
= 2.5, J6a,6b = 10.7, 1 H, H-6a), 3.26 (dd, J5,6b = 5.1, J6b,6a = 10.7, 1H, H-6b).
13C NMR (CDCl3, 100 MHz) δ: 166.1, 165.4, 164.9, 143.9 (3 C), 133.3, 133.25,
133.2, 130.0 (2 C), 129.92 (2 C), 129.8 (2 C), 129.7, 129.5, 129.3, 129.1 (2 C),
128.7 (6 C), 128.4 (2 C), 128.3 (2 C), 127.9 (6 C), 127.0 (3 C), 102.1 (C-1), 86.8
(O-CPh3), 74.0 (C-5), 73.4 (C-3), 72.2 (C-2), 69.6 (C-4), 62.6 (C-6), 56.9 (O-CH3).
Compound 3d (1.00 g, 1.34 mmol) was detritylated using FeCl3·6H2O in
CH2Cl2 according to the procedure described by Ding et al.[40] This gave a white
foam, which was purified by silica gel column chromatography (toluene/EtOAc,
1/1) and then crystallized from pentane/CHCl3 to give 450 mg (0.89 mmol, 66%)
of 4d as white solid, mp. 79–80◦C, [α]D22 = −8.4◦ (c 1.1, CHCl3), lit.[38] −6.6◦ (c
1
1.1, CHCl3). H NMR (CDCl3) and 13C NMR (CDCl3) corresponded with data
reported previously.[27,38]
Methyl 2,3,4-tri-O-benzoyl-α-D-mannopyranoside (4e)[41,42]
Methyl α-D-mannopyranoside (2.00, 10.30 mmol) was converted to methyl
2,3,4-tri-O-benzoyl-6-trityl-α-D-mannopyranoside (3e)[40,43] as described for
4d. This gave 2.70 g (3.61 mmol, 35%) of 3e as a white solid, mp. 113–114◦C,
lit.[43] 110–120◦C, [α]2D2 = −90.5◦ (c 1.0, CHCl3), lit.[40] −45◦(c 2.0, CHCl3). H
1
NMR (CDCl3, 400 MHz) δ: 8.15 (m, 2 H, Ar), 7.83 (m, 2 H, Ar), 7.73 (m, 2 H,
Ar), 7.61 (m, 1 H, Ar), 7.51–7.38 (m, 10 H, Ar), 7.30 (m, 3 H, Ar), 7.18–7.06 (m,
10 H, Ar), 6.02 (t, J = 10.2, 1H, H-4), 5.77 (dd, J3,2 = 3.3, J3,4 = 10.2, 1 H, H-3)
5.68 (m, 1 H, H-2), 5.03 (d, J = 1.5, 1 H, H-1), 4.17 (m, 1 H, H-5), 3.55 (s, 3
H, OCH3), 3.40 (dd, J5,6a = 2.5, J6a,6b = 10.5, 1 H, H-6a), 3.29 (dd, J5,6b = 4.9,
J6b,6a = 10.5, 1 H, H-6b). 13C NMR (CDCl3, 100 MHz) δ: 165.8, 165.7, 165.2,
143.9 (3C), 133.6, 133.2, 133.1, 130.1 (2 C), 129.9 (2 C), 129.8 (2 C), 129.7,
129.5, 128.8 (2 C), 128.77 (6 C), 128.4 (2 C), 128.3 (2 C), 127.8 (6 C), 127.0 (3

A.M. Esmurziev et al.
358
C), 98.7 (C-1), 86.8 (O-CPh3), 70.9 (C-2), 70.7 (C-3), 70.4 (C-5), 67.2 (C-4), 62.5
(C-6), 55.4 (O-CH3).
Detritylation of 3e (2.50 g, 3.34 mmol) was performed as described for 3d to
give 4e, 1.31 g (2.59 mmol, 77%) as a white solid, mp. 69–70◦C, [α]D22 = −127.5◦
(c 0.5, CHCl3), lit.[27] −126.0◦ (c 0.5, CHCl3), lit.[38] −154◦ (c 1.1, CHCl3). NMR
corresponded with that reported previously.[27]
Methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-α-D-galactopyranoside (5a)
DAST (106 µL, ∼129 mg, ∼0.80 mmol) was added drop-wise to a solution
of 4a (100 mg, 0.20 mmol) and DMAP (50 mg, 0.40 mmol) in dry CH2Cl2 (2
mL) at −25◦C under argon. After 12 h the reaction mixture was allowed to
slowly warm to rt and stirred overnight. The reaction mixture was then cooled
to 0◦C and methanol (0.3 mL) was added to quench the reaction. The resulting
solution was further diluted with CH2Cl2 (5 mL) and washed with saturated
NaHCO3 (3 × 5 mL) and water (5 mL), and the combined aqueous phase was
back-extracted once with CH2Cl2 (5 mL). The organic phases were washed once
more with water (10 mL), dried over MgSO4, and concentrated under vacuum.
The residue was purified by silica gel column chromatography (toluene/EtOAc,
9/1) to give 10 mg (0.02 mmol, 10%) of compound 5a as a colorless foam; [α]D22
1
= +78.1◦ (c 0.7, CHCl3). H NMR (CDCl3, 600 MHz) δ: 8.07 (m, 2 H, Ar), 7.98
(m, 2 H, Ar), 7.79 (m, 2 H, Ar), 7.62 (m, 1 H, Ar), 7.52 (m, 1 H, Ar), 7.48 (m, 2 H,
Ar), 7.43 (m, 1 H, Ar), 7.38 (m, 2 H, Ar), 7.24 (m, 2 H, Ar), 5.96 (m, 1 H, H-3),
5.94 (m, 1 H, H-4), 5.67 (dd, 1 H, H-2), 5.32 (d, 1 H, H-1), 4.57 (m, 2 H, H-6ab),
4.52 (m, 1 H, H-5) 3.50 (s, 3 H, OCH3). 13C NMR (CDCl3, 150 MHz) δ: 166.08,
165.58, 165.50, 133.63, 133.41, 133.18, 129.92 (2 C), 129.86 (2 C), 129.69 (2
C), 129.14, 129.10, 129.03, 128.66 (2 C), 128.44 (2 C), 128.27 (2 C), 97.57 (C-
1), 81.72 (d, J = 171.2, C-6), 69.26 (C-2), 69.02 (d, J = 6.6, C-4), 68.23 (C-3),
67.65 (d, J = 23.0, C-5), 55.79 (OCH3). HRMS (ESI): 509.1619 (calcd 509.1606,
M+H+).
Methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-β-D-galactopyranoside (5b)
Compound 5b was synthesized as described for 5a, starting with 4b
(100 mg, 0.20 mmol) giving 9 mg (0.02 mmol, 9%) of a colorless oil; [α]D22
=
+146.0◦ (c 0.5, CHCl3). H NMR (CDCl3, 600 MHz) δ: 8.06 (m, 2 H, Ar), 7.97
(m, 2 H, Ar), 7.78 (m, 2 H, Ar), 7.62 (m, 1 H, Ar), 7.52 (m, 1 H, Ar), 7.48 (m,
2 H, Ar), 7.43 (m, 1 H, Ar), 7.39 (m, 2 H, Ar), 7.24 (m, 2 H, Ar), 5.91 (dd, 1
H, H-4), 5.78 (dd, 1 H, H-2), 5.58 (dd, 1 H, H-3), 4.75 (m, 1 H, H-1), 4.62 (m,
2 H, H-6ab), 4.26 (m, 1 H, H-5), 3.62 (s, 3 H, OCH3). 13C NMR (CDCl3, 150
MHz) δ: 165.58, 165.53, 165.32, 133.69, 133.32, 133.29, 130.01 (2 C), 129.80 (2
C), 129.77 (2 C), 129.30, 128.82, 128.68, 128.64 (2 C), 128.39 (2 C), 128.31 (2
C), 102.42 (C-1), 81.17 (d, J = 172.4, C-6), 72.27 (d, J = 23.0, C-5), 71.65 (C-3),
1

Benzoylated Deoxyfluoropyranosides
359
69.61 (C-2), 67.93 (d, J = 6.6, C-4), 57.38 (OCH3). HRMS (ESI): 509.1612 (calcd
509.1606, M+H+).
Methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-α-D-glucopyranoside (5c)[35]
DAST (190 µL, ∼232 mg, ∼1.44 mmol) was added drop-wise to a solution
of 4c[27] (180 mg, 0.36 mmol) and DMAP (100 mg, 0.80 mmol) in dry CH2Cl2
(3 mL) at −25◦C. After stirring under argon for 12 h, the reaction mixture was
allowed to warm to ambient temperature, stirred overnight, and refluxed for
1 h. The mixture was then cooled to 0◦C and methanol (0.5 mL) was added
to quench the reaction. The reaction mixture was then diluted with CH2Cl2
(10 mL) and washed with saturated NaHCO3 (3 × 10 mL) and water (10 mL),
and the aqueous phase was back-extracted once with CH2Cl2 (10 mL). The
combined organic phases were washed once with water (15 mL), dried over
MgSO4, and concentrated under vacuum. The residue was crystallized twice
from MeOH to give 135 mg (26.55 mmol, 75%) as a white solid, mp. 143–144◦C,
(lit.[35] 145–146◦C), [α]2D2 = +46.8◦ (c 1.5, CHCl3), lit.[35] +52.7◦ (c 1, CHCl3).
1H NMR (CDCl3, 600 MHz) δ: 7.97 (m, 4 H, Ar), 7.87 (m, 2 H, Ar), 7.54 (m, 1
H, Ar), 7.52 (m, 1 H, Ar), 7.43 (m, 1 H, Ar), 7.38 (m, 4 H, Ar), 7.29 (m, 2 H, Ar),
6.19 (t, 1 H, H-3), 5.56 (t, 1H, H-4), 5.28 (m, 1 H, H-2), 5.27 (m, 1 H, H-1), 4.59
(dd, 2 H, H-6ab), 4.27 (ddt, 1 H, H-5), 3.49 (s, 3H, (OCH3). 13C NMR (CDCl3, 150
MHz) δ: 165.80, 165.77, 165.29, 133.56, 133.41, 133.16, 129.94 (2 C), 129.88 (2
C), 129.67 (2 C), 129.12, 128.99, 128.74, 128.49 (2 C), 128.44 (2 C), 128.31 (2
C), 97.04 (C-1), 81.50 (d, J = 175.6, C-6), 71.92 (C-2), 70.25 (C-3), 68.55 (d, J =
6.6, C-4), 68.55 (d, J = 19.8, C-5), 55.74 (OCH3).
Methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-β-D-glucopyranoside (5d)[19]
Deoxo-Fluor in THF (50%, 350 µL, 0.81 mmol) was added drop-wise to a so-
lution of 4d (100 mg, 0.20 mmol) in THF (1 mL) at −25◦C. After stirring under
argon for 12 h, the reaction mixture was allowed to warm to ambient tem-
perature, stirred overnight, and refluxed for 1 hour. The reaction mixture was
cooled to 0◦C and methanol (0.5 mL) was added to quench excess of the reagent.
The reaction mixture was then diluted with CH2Cl2 (5 mL) and washed with
saturated NaHCO3 (3 × 5 mL) and water (5 mL), and the aqueous phases
were back-extracted once with CH2Cl2 (5 mL). The combined organic phases
were washed once with water (10 mL), dried over MgSO4, and concentrated
under vacuum. The residue was purified by silica gel column chromatography
(toluene/EtOAc, 9/1) to give an oil, which was crystallized twice from MeOH to
give 74 mg (0.15 mmol, 74%) of a white solid, mp. 64–65◦C, [α]D22 = −1.6◦ (c 1.0,
CHCl3). 1H NMR (CDCl3, 600 MHz) δ: 7.96 (m, 2 H, Ar), 7.94 (m, 2 H, Ar),7.82
(m, 2 H, Ar), 7.52 (m, 2 H, Ar), 7.42 (m, 1 H, Ar), 7.38 (m, 4 H, Ar), 7.28 (m, 2
H, Ar), 5.91 (t, 1 H, H-3), 5.51 (m, 1 H, H-4), 5.50 (m, 1 H, H-2), 4.76 (d, 1 H,
H-1), 4.62 (dd, 2 H, H-6ab), 4.05 (qt, 1 H, H-5), 3.58 (s, 3H, OCH3). 13C NMR
(CDCl3, 150 MHz) δ: 165.79, 165.24, 165.10, 133.62, 133.28, 133.25, 129.85 (4

A.M. Esmurziev et al.
360
C), 129.75 (2 C), 129.23, 128.72, 128.63, 128.50 (2 C), 128.36 (2 C), 128.31 (2
C), 101.94 (C-1), 81.56 (d, J = 175.6, C-6), 73.22 (d, J = 19.8, C-5), 72.76 (C-3),
71.66 (C-2), 68.83 (d, J = 7.7, C-4), 57.20 (OCH3).
Methyl 2,3,4-tri-O-benzoyl-6-deoxy-6-fluoro-α-D-mannopyranoside (5e)
Compound 5e was prepared as described for 5d, starting with 4e (100 mg,
0.20 mmol). Purification by silica gel column chromatography (toluene/EtOAc,
9/1), followed by crystallization from MeOH gave 64 mg (0.13 mmol, 64%) of
a white solid, mp. 67–68◦C, [α]D22 = −154.3◦ (c 1.0, CHCl3). H NMR (CDCl3,
1
600 MHz) δ: 8.10 (m, 2 H, Ar), 7.97 (m, 2 H, Ar), 7.83 (m, 2 H, Ar), 7.61 (m, 1
H, Ar), 7.53 (m, 1 H, Ar), 7.49 (m, 2 H, Ar), 7.43 (m, 1 H, Ar), 7.39 (m, 2 H, Ar),
7.26 (m, 2 H, Ar), 5.91 (m, 1 H, H-3), 5.89 (m, 1 H, H-4), 5.68 (m, 1 H, H-2), 5.01
(bs, 1 H, H-1), 4.63 (m, 2 H, H-6ab), 4.27 (m, 1 H, H-5), 3.54 (s, 3 H, OCH3). 13
C
NMR (CDCl3, 150 MHz) δ: 165.53, 165.49, 165.42, 133.56 (2 C), 133.19, 129.93
(2 C), 129.80 (2 C), 129.73 (2 C), 129.24, 129.03, 128.84, 128.63 (2 C), 128.50 (2
C), 128.30 (2 C), 98.66 (C-1), 81.70 (d, J = 174.5, C-6), 70.34 (C-2), 69.82 (C-3),
69.58 (d, J = 19.8, C-5), 66.24 (d, J = 6.6, C-4), 55.62 (OCH3). HRMS (ESI):
509.1611 (calcd 509.1606, M+H+).
2,3,4-Tri-O-benzoyl-1-deoxy-1-fluoro-6-methyl-β-D-glucopyranoside (6d)[19]
Compound 6d was obtained according to the procedure described for 5c,
starting with 4d (50 mg, 0.10 mmol) and DAST (52 µL, ∼64 mg, ∼0.40
mmol) in dry CH2Cl2 (1 mL). Purification by silica gel column chromatogra-
phy (toluene/EtOAc, 9.5/0.5) gave 19 mg (0.04 mmol, 38%) of 6d. The structure
1
of compound 6d was verified by comparing H NMR to that reported previ-
ously.[19]
Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-fluoro-α-D-glucopyranoside (8c)[20,21]
using DAST
Compound 8c was synthesized as described for 5a starting with 7a
(11.80 g, 23.30 mmol) and DAST (7.5 mL, ∼9.2 g, ∼56 mmol). After 6 h re-
action time a second portion of DAST (7.5 mL, ∼9.2 g, ∼56 mmol) was added.
This resulted in a syrup, which, upon crystallization from EtOH, gave 8.50 g
(16.72 mmol, 72%) of a white solid, mp. 140–141◦C (lit.[21] 139–141◦C), [α]2D2
=
+101◦ (c 1.5, CHCl3). 1H NMR (CDCl3, 600 MHz) δ: 8.10 (m, 2 H, Ar), 8.02 (m,
2 H, Ar), 7.98 (m, 2 H, Ar), 7.60 (m, 1 H, Ar), 7.52 (m, 2 H, Ar), 7.49 (m, 2 H,
Ar), 7.39 (m, 2 H, Ar), 7.38 (m, 2 H, Ar), 6.13 (m, 1 H, H-3), 5.20 (dd, 1 H, H-2),
5.17 (m, 1 H, H-1), 4.77 (m, 1 H, H-4), 4.62 (ddd, 1 H, H-6a), 4.72 (m, 1 H, H-6b),
4.32 (m, 1 H, H-5), 3.47 (s, 3H, OCH3). 13C NMR (CDCl3, 150 MHz) δ: 166.16,
165.85, 165.58,133.51, 133.32, 133.30, 129.96 (2 C), 129.80 (2 C), 129.73 (2 C),
129.65, 129.27, 128.83, 128.52 (2 C), 128.47 (2 C), 128.39 (2 C), 96.88 (C-1),

Benzoylated Deoxyfluoropyranosides
361
87.36 (d, J = 187.7, C-4), 71.36 (d, J = 7.7, C-2), 70.45 (d, J = 19.8, C-3), 67.10
(d, J = 23.0, C-5), 62.57, 55.69 (OCH3).
Methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-fluoro-α-D-glucopyranoside (8c)[20,21]
using Deoxo-Fluor
Compound 8c was synthesized using Deoxo-Fluor (50% in THF, 415 µL,
∼215 mg, ∼0.97 mmol) and 7a (200 mg, 0.39 mmol) at −25◦C for 12 h followed
by stirring overnight in ambient temperature. Workup was performed as for 5d
and crystallization from EtOH gave 90 mg (0.18 mmol, 45%) of a white solid.
Physical and spectroscopic properties were identical to that obtained using
DAST.
Methyl 2,3-di-O-benzoyl-4,6-dideoxy-4,6-difluoro-α-D-glucopyranoside (10c)
using DAST
Compound 10c was synthesized as described for 5a, starting with 9a[27]
(100 mg, 0.25 mmol) and DAST (300 µL, ∼366 mg ∼2.3 mmol) to give 75 mg
(0.18 mmol, 74%) of the product as a colorless oil, [α]2D2 = +29.4◦ (c 2.0, CHCl3).
1H NMR (CDCl3, 600 MHz) δ: 8.01 (m, 2 H, Ar), 7.97 (m, 2 H, Ar), 7.52 (m, 2
H, Ar), 7.38 (m, 4 H, Ar), 6.10 (m, 1 H, H-3), 5.18 (d, 1 H, H-1), 5.16 (m, 1 H,
H-2), 4.76 (dt, 1 H, H-4), 4.73 (m, 2 H, H-6ab), 4.11 (m, 1 H, H-5), 3.46 (s, 3 H,
OCH3). 13C NMR (CDCl3, 150 MHz) δ: 165.78, 165.58, 133.48, 133.32, 129.95
(2 C), 129.80 (2 C), 129.26, 128.84, 128.45 (2 C), 128.39 (2 C), 97.04 (C-1), 86.01
(dd, J = 187.7, 7.7, C-4), 80.75 (d, J = 174.5, C-6), 71.31 (d, J = 7.7, C-2), 70.39
(d, J = 19.8, C-3), 68.02 (dd, J = 23.0, 17.6, C-5), 55.81 (OCH3). HRMS (ESI):
429.1136 (calcd 429.1126, M+Na+).
Methyl 2,3-di-O-benzoyl-4,6-dideoxy-4,6-difluoro-α-D-glucopyranoside (10c)
using Deoxo-Fluor
Compound 10c was synthesized using Deoxo-Fluor as described for 5d
starting with 9c (100 mg, 0.25 mmol) and Deoxo-Fluor (50% in THF, 960
µL, ∼498 mg ∼2.25 mmol). Purification by silica gel column chromatography
(toluene/EtOAc, 9/1) gave 73 mg (0.18 mmol, 72%) of 10c as colorless oil.
Methyl 2,3-O-dibenzoyl-4,6-dideoxy-4,6-difluoro-α-D-talopyranoside (10f)
using DAST
The fluorination was performed as described for 5a starting with methyl
α-D-mannopyranoside (100 mg, 0.51 mmol) and DAST (610 µL, ∼740 mg
∼4.6 mmol). The reaction mixture was freeze dried to give 108 mg of methyl
4,6-dideoxy-4,6-difluoro-α-D-talopyranoside (11f) as yellowish oil. Crude 11f
was dissolved in dry pyridine (2 mL) and cooled to −10◦C. Benzoyl chloride
(1.46 g, 10.39 mmol) was added drop-wise and the mixture was allowed to reach
rt. After 3 d the reaction mixture was cooled to 0◦C, and saturated NaHCO3
(2 mL) was added. The mixture was then extracted with CHCl3 (2 × 10 mL)

A.M. Esmurziev et al.
362
and the organic phase was washed with saturated NaHCO3 (3 × 15 mL) and
water (15 mL), dried over MgSO4, and concentrated under vacuum to give yel-
low oil. Purification by silica gel column chromatography (toluene/EtOAc, 9/1),
followed by two crystallizations from EtOH, gave 57 mg (0.14 mmol, 27%) of
a yellow amorphous solid, which melted when handled, [α]2D2 = −16.4◦ (c 1.0,
1
CHCl3). H NMR (CDCl3, 600 MHz) δ: 8.15 (m, 2 H, Ar), 7.93 (m, 2 H, Ar),
7.60 (m, 1 H, Ar), 7.51 (m, 1 H, Ar), 7.48 (m, 2 H, Ar), 7.34 (m, 2 H, Ar), 5.53
(m, 1 H, H-3), 5.52 (m, 1 H, H-2), 5.03 (dd, 1 H, H-4), 5.01(bs, 1 H, H-1), 4.73
(m, 2 H, H-6ab), 4.31 (m, 1 H, H-5), 3.50 (s, 3H, OCH3). 13C NMR (CDCl3,
150 MHz) δ: 165.91, 165.33, 133.48, 133.41, 130.09 (2 C), 129.90 (2 C), 129.54,
129.04, 128.51 (2 C), 128.43 (2 C), 99.19 (C-1), 84.95 (dd, J = 190.7, 6.3, C-
4), 81.26 (dd, J = 169.9, 7.1, C-6), 67.99 (C-2), 67.90 (dd, J = 23.6, 18.5, C-5),
66.69 (d, J = 15.9, C-3), 55.63 (OCH3). HRMS (ESI): 429.1132 (calcd 429.1126,
M+Na+).
Methyl 2,3-O-dibenzoyl-4,6-dideoxy-4,6-difluoro-α-D-talopyranoside (10f)
using Deoxo-Fluor
Compound 10f was synthesized as described for 5d starting with methyl
α-D-mannopyranoside (100 mg, 0.51 mmol) and Deoxo-Fluor (50% in THF,
1.95 mL, ∼1.02 g ∼4.6 mmol). Benzoylation and purification as described above
gave 55 mg (0.14 mmol, 26%) of 10f.
Methyl 2,3-O-dibenzoyl-4,6-dideoxy-4,6-difluoro-α-D-talopyranoside (10f) from
11f
To a stirred solution of 11f (50 mg, 0.26 mmol) in pyridine (2 mL)
at −10◦C was added benzoyl chloride (0.70 g, 4.99 mmol). After addi-
tion the mixture was reacted for 3 d at rt. Then the mixture was cooled
to 0◦C, and saturated NaHCO3 (2 mL) was added. The mixture was ex-
tracted with CHCl3 (2 × 10 mL), washed with saturated NaHCO3 (3 ×
10 mL) and water (10 mL), dried over MgSO4, and concentrated under vac-
uum to give yellow oil. Purification by silica gel column chromatography
(toluene/EtOAc, 9/1), followed by two crystallizations from EtOH, gave 78 mg
(0.19 mmol, 74%) of a yellow amorphous solid 10f. The spectroscopic properties
corresponded with that described above.
Isolation of methyl 4,6-dideoxy-4,6-difluoro-α-D-talopyranoside 2,3-cylic sulfite
(12f) and methyl 4,6-dideoxy-4,6-difluoro-α-D-talopyranoside (11f)[21,31]
using DAST
Compound 12f: To a stirred solution of methyl α-D-mannopyranoside (800
mg, 4.12 mmol) in anhydrous CH2Cl2 (25 mL) at −20◦C was added DAST (2.5
mL, 20 mmol). After adding of DAST the mixture was stirred for 2 h at rt.
Then the mixture was cooled and quenched with MeOH (10 mL). The resulting
mixture was concentrated under reduced pressure. Upon addition of MeOH

Benzoylated Deoxyfluoropyranosides
363
(5 mL) and water (20 mL) a white solid precipitated, which was separated
by filtration. This procedure was repeated twice and the combined solid was
recrystallized from MeOH/water to give 270 mg (1.11 mmol, 27%) of 12f as a
white solid, mp. 122.5–123.0◦C, [α]D22 = +3.8◦ (c 1.0, CHCl3). 1H NMR (CDCl3,
600 MHz) δ: 5.21 (bs, 1 H, H-1), 5.01 (dt, J = 23.8, 4.5, 1 H, H-3,), 4.76 (bd, J =
4.9, 1-H, H-2), 4.66 (dd, J = 49.5, 4.5, 1 H, H-4), 4.63 (m, 2 H, H-6ab), 4.07 (m,
J = 28.9, 13.7, 6.1, 1 H, H-5), 3.48 (s, 3 H, OCH3). 13C NMR (CDCl3, 150 MHz)
δ: 96.50 (C-1), 81.48 (dd, J = 170.8, 6.1, C-4), 80.84 (dd, J = 188.5, 6.1, C-6),
76.10 (d, J = 17.1, C-3), 73.67 (C-2), 65.25 (dd, 24.3, 18.2, C-5), 55.83 (O-CH3).
19F NMR (CDCl3, 470 MHz) δ: −231.87 (dt, J = 46.0, 13.8), −210.38 (m) HRMS
(ESI): 245.0289 (calcd 245.0290, M+H+). Compound 11f: Concentration of the
mother liquor followed by silica gel column chromatography (CHCl3/MeOH,
9/1) yielded 390 mg (1.97 mmol, 48%) of 11f as colorless crystals, mp. 88–89◦C,
lit.[21] 90–92◦C. [α]2D2 = +96.2◦ (c 1.0, CHCl3), lit.[31] 101.9 (c 1.02 MeOH). H
1
NMR (CDCl3, 600 MHz) δ: 4.88 (bs, 1 H, H-1), 4.80 (m, J = 50.5, 1.4, 1 H, H-4),
4.63 (m, J = 46.8, 2 H, H-6a,b), 4.08 (m, 1 H- H-5, J = 31.9, 19.3, 6.1), 3.83 (m,
J = 31.6, 3.0, 1 H, H-3), 3.79 (m, 1 H, H-2), 3.43 (s, O-CH3). 13C NMR (CDCl3,
150) δ: 101.53 (C-1), 90.05 (dd, J = 178.0, 6.1, C-4), 81.27 (dd, J = 169.7, 7.2,
C-6), 69.86 (C-2), 67.40 (dd, 23.8, 18.2, C-5), 65.27 (d, J = 16.6, C-3), 55.55
(O-CH3). 19F NMR (CDCl3, 470 MHz) δ: −231.71 (dt, J = 46.0, 13.8), −216.73
(m).
Methyl 4,6-dideoxy-4,6-difluoro-α-D-talopyranoside 2,3-cylic sulfite (12f) from
11f
The synthesis was done essentially as described by Lohray et al.[44] To a
solution of 11f (20 mg, 0.1 mmol) in dry CCl4 (1 mL) was added SOCl2 (20 µL,
0.25 mmol) and triethylamine (35 µL, 0.25 mmol). The mixture was refluxed
for 45 min, then cooled to rt, diluted with CHCl3 (3 mL), and washed with
NaHCO3 (3 × 5 mL) and water (5 mL). Drying over MgSO4 and concentration
in vacuum gave 21 mg of yellow oil. Crystallization from MeOH (0.2 mL) and
water (0.5 mL) gave 11 mg (0.04 mmol, 44%) of a white solid with identical
NMR spectroscopic properties as for 12f described above.
Methyl 2,4,6-tri-O-benzoyl-3-deoxy-3-fluoro-β-D–glucopyranoside (13d)
3-Deoxy-3-fluoro-D-glucose (200 mg, 1.10 mmol) was dissolved in
HCl·MeOH (1 mL, 0.5 N) and refluxed for 3 d. Then, the reaction mixture was
concentrated and submitted to the same treatment once more to give 237 mg
of colorless oil. The crude mixture was then dissolved in dry pyridine (2 mL)
and cooled to 0◦C, followed by drop-wise addition of benzoyl chloride (1.46 g,
10.4 mmol). The reaction mixture was warmed to rt and stirred for 3 d. The
reaction mixture was then cooled to 0◦C, treated with saturated NaHCO3 (5
mL), and extracted with CHCl3 (4 × 10 mL). The organic phases were washed

A.M. Esmurziev et al.
364
with water (20 mL) and concentrated under vacuum. TLC indicated two prod-
ucts that were separated by silica gel column chromatography (toluene/EtOAc,
9.5/0.5). This gave 22 mg (0.04 mmol, 3%) of 14d, and after two crystalliza-
tions from EtOH 70 mg (0.14 mmol, 13%) of 13d, white solid, mp. 146–147◦C,
[α]2D2 = −17.4◦ (c 0.5, CHCl3). 1H NMR (CDCl3, 600 MHz) δ: 8.08 (m, 2 H, Ar),
8.03 (m, 2 H, Ar), 8.01 (m, 2 H, Ar), 7.59 (m, 1 H, Ar), 7.58 (m, 1 H, Ar), 7.54
(m, 1 H, Ar), 7.45 (m, 2 H, Ar), 7.42 (m, 2 H, Ar), 7.39 (m, 2 H, Ar), 5.66 (m, 1
H, H-4), 5.48 (m, 1 H, H-2), 4.96 (dt, 1 H, H-3), 4.66 (m, 1 H, H-6b), 4.64 (d, 1
H, H-1), 4.47 (dd, 1 H, H-6a), 4.02 (m, 1 H, H-5), 3.52 (s, 3 H, OCH3). 13C NMR
(CDCl3, 150 MHz) δ: 166.17, 164.95, 164.92, 133.62, 133.40, 133.20, 129.93 (2
C), 129.92 (2 C), 129.73 (2 C), 129.50, 129.38, 128.91, 128.51 (2 C), 128.44 (2C),
128.39 (2 C), 101.37 (d, J = 10.7, C-1), 91.79 (d, J = 191.3, C-3), 71.99 (d, J =
18.7, C-2), 71.10 (d, J = 7.7, C-5), 69.73 (d, J = 18.7, C-4), 62.96 (d, J = 1.6,
C-6), 57.12 (OCH3). HRMS (ESI): 509.1611 (calcd 509.1612, M+H+).
1,3,4,6-Tetra-O-benzoyl-3-deoxy-3-fluoro-β-D–glucopyranoside (14d)
3-Deoxy-3-fluoro-D-glucose (70 mg, 0.38 mmol) was dissolved in dry pyri-
dine (1 mL) and cooled to −10◦C. Benzoyl chloride (220 mg, 1.57 mmol) was
added drop-wise and the mixture was stirred at rt. After 3 d the reaction mix-
ture was cooled, diluted with saturated NaHCO3 (0.5 mL), and extracted with
CHCl3 (4 × 10 mL). The organic phases were then washed with saturated
NaHCO3 (3 × 10 mL) and water (10 mL), dried over MgSO4, and concentrated
under vacuum. The resulting oil was crystallized twice from MeOH to give 111
mg (0.19 mmol, 49%) of compound 14d as a white solid, mp. 231–232◦C, [α]D22
1
= +9.6◦ (c 1.0, CHCl3). H NMR (CDCl3, 600 MHz) δ: 8.04 (m, 2 H, Ar), 8.02
(m, 6 H, Ar), 7.58 (m, 1 H, Ar), 7.54 (m, 2 H, Ar), 7.53 (m, 1 H, Ar), 7.43 (m,
2 H, Ar), 7.40 (m, 4 H, Ar), 7.39 (m, 2 H, Ar), 6.18 (d, 1 H, H-1), 5.84 (m, 1 H,
H-2), 5.81 (m, 1 H, H-4), 5.11 (dt, 1 H, H-3), 4.66 (dd, 1 H, H-6b), 4.46 (dd, 1 H,
H-6a), 4.26 (m, 1 H, H-5). 13C NMR (CDCl3, 150 MHz) δ: 166.09, 164.89, 164.84,
164.61, 133.94, 133.72, 133.62, 133.16, 130.21 (2 C), 129.96 (2 C), 129.89 (2 C),
129.82 (2 C), 129.43, 128.82, 128.76, 128.56 (4 C), 128.50 (2 C), 128.36 (2 C),
128.27, 91.95 (d, J = 11.0, C-1), 91.64 (d, J = 193.2, C-3), 72.12 (d, J = 6.6, C-
5), 70.87 (d, J = 19.8, C-2), 69.02 (d, J = 19.8, C-4), 62.47 (C-6). HRMS (ESI):
621.1542 (calcd 621.1531, M+Na+).
1,3,4,6-Tetra-O-benzoyl-2-deoxy-2-fluoro-β-D–glucopyranoside (15d)
Compound 15d was synthesized as described for 14d, starting with 2-
deoxy-2-fluoro-D-glucose (70 mg, 0.38 mmol). This gave after crystallization
from MeOH 118 mg (0.20 mmol, 52%) of compound 15d as a white solid, mp.
169–170◦C, [α]D22 = +23.7◦ (c 1.0, CHCl3). H NMR (CDCl3, 600 MHz) δ: 8.12
1
(m, 2 H, Ar), 8.00 (m, 2 H, Ar), 7.99 (m, 2 H, Ar), 7.92 (m, 2 H, Ar), 7.61 (m,
1 H, Ar), 7.53 (m, 1 H, Ar), 7.52 (m, 1 H, Ar), 7.51 (m, 1 H, Ar), 7.46 (m, 2 H,
Ar), 7.38 (m, 2 H, Ar), 7.37 (m, 2 H, Ar), 7.35 (m, 2 H, Ar), 6.28 (dd, 1 H, H-1),

Benzoylated Deoxyfluoropyranosides
365
5.97 (m, 1 H, H-3), 5.71 (t, 1 H, H-4), 4.91 (ddd, 1 H, H-2), 4.62 (dd, 1 H, H-6b),
4.46 (dd, 1 H, H-6a), 4.34 (m, 1 H, H-5). 13C NMR (CDCl3, 150 MHz) δ: 166.03,
165.47, 165.15, 164.44, 133.97, 133.63, 133.51, 133.11, 130.22 (2 C), 129.88 (4
C), 129.78 (2 C), 129.47, 128.82, 128.56 (2 C), 128.53, 128.50 (2 C), 128.45 (2 C),
128.36, 128.34 (2 C), 91.98 (d, J = 24.2, C-1), 88.64 (d, J = 192.1, C-2), 73.03
(d, J = 19.8, C-3), 72.98 (C-5), 68.62 (d, J = 6.6, C-4), 62.58 (C-6). HRMS (ESI):
621.1549 (calcd 621.1531, M+Na+).
ACKNOWLEDGMENTS
NTNU is acknowledged for use of NMR facilities, Anders Jahres Foundation
for financial support, and Anders Brunsvik for HRMS.
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