Chlorodifluoromethyl-substituted monosaccharide derivatives-radical activation of the carbon-chlorine-bond

Article abstract of DOI:10.1016/j.carres.2006.08.023

The dithionite-mediated addition of BrCF₂Cl to 3,4-di-O-pivaloyl-d-xylal (1) generated preferably 1-CF₂Cl-substituted products, that is, (2-bromo-2-deoxy-3,4-di-O-pivaloyl-β-d-xylopyranosyl)-chlorodifluoromethane and (2-deoxy-3,4-di-

Full text of DOI:10.1016/j.carres.2006.08.023

Carbohydrate Research 341 (2006) 2641–2652
Chlorodifluoromethyl-substituted monosaccharide
derivatives—radical activation of the carbon–chlorine-bondI
Anita Wegert,a Martin Hein,a Helmut Reinke,a Norbert Hoffmannb and Ralf Miethchena,*
aInstitut fu¨r Chemie, Organische Chemie, Universita¨t Rostock, Albert-Einstein-Strasse 3a, D-18059 Rostock, Germany
bLaboratoire des Re´actions Se´lectives et Applications, UMR 6519 CNRS et Universite´ de Reims Champagne-Ardenne,
UFR Sciences, B.P. 1039, F-51687 Reims Cedex 02, France
Received 4 July 2006; received in revised form 22 August 2006; accepted 26 August 2006
Available online 20 September 2006
Dedicated to Professor Dr. Dieter Naumann on the occasion of his 65th birthday
Abstract—The dithionite-mediated addition of BrCF2Cl to 3,4-di-O-pivaloyl-D-xylal (1) generated preferably 1-CF2Cl-substituted
products, that is, (2-bromo-2-deoxy-3,4-di-O-pivaloyl-b-D-xylopyranosyl)-chlorodifluoromethane and (2-deoxy-3,4-di-O-pivaloyl-
b-D-threo-pentopyranosyl)-chlorodifluoromethane. Selected chlorodifluoromethyl-substituted monosaccharide derivatives were
hydrodechlorinated or alkylated at the CF2Cl-group using tin reagents under radical reaction conditions. Thus,
hydrodechlorinations of (2,3,4-tri-O-acetyl-6-deoxy-a-L-galactopyranosyl)-chlorodifluoromethane and of methyl 3,4-di-O-acetyl-
2-C-chlorodifluoromethyl-2,6-dideoxy-a/b-L-glucopyranoside are reported using tri-n-butyltin hydride initiated by AIBN. UV-
initiated allylations are reported for reactions of (2-deoxy-3,4-di-O-pivaloyl-b-D-threo-pentopyranosyl)-chlorodifluoromethane,
(2,3,4-tri-O-acetyl-6-deoxy-a-L-galactopyranosyl)-chlorodifluoromethane, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-
a-D-glucopyranose, 1,3,4,6-tetra-O-acetyl-2-C-chlorodifluoromethyl-2-deoxy-a-D-mannopyranose and methyl 3,4-di-O-acetyl-2-C-
chlorodifluoromethyl-2-deoxy-a/b-D-rabinopyranoside with allyltri-n-butyltin.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Glycals; Chlorodifluoromethylation; Fluorinated sugars; C–Cl-bond activation; Radical hydrodechlorination; Radical allylation
1. Introduction
more that 18% at present.10 In view of potential biolog-
ical properties, new gem-difluorinated compounds
attract special attention.11,12 Moreover, a difluoro-
methylene group introduced instead of an oxygen atom
in compounds with a sensitive C–O-bond (e.g., a glyco-
sidic bond) can be used to stabilize such compounds
without significantly changing the electronic properties
of the parent substance. However, selective methods of
fluoroalkylation are fairly rare, especially, in carbo-
hydrate chemistry.13
The interest in fluorinated analogues of natural sub-
stances is increasing continuously because introduction
of fluorine or fluoroalkyl groups may significantly mod-
ify the chemical, physical and biological properties of
the natural substances.2–9 ‘Organic fluorine’ has proven
to be valuable and auspicious in bioorganic and medical
chemistry, because fluorine can, when strategically posi-
tioned, suppress adventitious metabolism, relative to the
hydrocarbon analogue. The occurrence of a fluorine
substituent in commercial pharmaceutical compounds
continues to increase from 2% in 1970 to estimates of
2. Results and discussion
2.1. Chlorodifluoromethylation of glycals
q Organofluorine Compounds and Fluorinating Agents, Part 34; for
Part 33 see Ref. 1.
In previous papers,1,14,15 we reported the introduction of
a chlorodifluoromethyl group into 1,2-unsaturated
*
Corresponding author. Fax: +49 381 498 6412; e-mail: ralf.
miethchen@uni-rostock.de
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.08.023

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A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
carbohydrates by dithionite-mediated addition of BrC-
F2Cl to the double bond. The starting materials were
the peracetylated D-glucal,14,15 L-rhamnal,1,14 D-ribal
(D-arabinal)14 and D-xylal.14 In all cases, the chlorodiflu-
oromethyl group was predominantly added to the
more electron-rich 2-position of the glycals. As radical
intermediates are involved in the sodium dithionite-
mediated fluoroalkylations of unsaturated substrates,16,17
transformations of unsaturated carbohydrates lead to
different by-products. Thus, 3,4-di-O-acetyl-D-xylal
reacted with BrCF2Cl to give 3,4-di-O-acetyl-2-C-chloro-
difluoromethyl-2-deoxy-D-xylopyranose in an isolated
yield of 54%, in addition to some unidentified by-prod-
ucts.14 It could be shown by complete elucidation of the
by-products from L-rhamnal and BrCF2Cl that some of
the by-products were compounds with a chlorodifluoro-
methyl group at the 1-position.1
1-Chlorodifluoromethyl derivatives are interesting
C-glycosides, which could be suitable precursors for
CF2-bridged glycoside mimetics. Therefore, we focussed
our efforts on finding a method that allows regioselective
1-chlorodifluoromethylations. The aim was achieved by
modification of the 1,2-unsaturated sugar derivatives.
Thus, peracylated 2-hydroxy-glycals, that is, 1,5-an-
hydro-2,3,4-tri-O-pivaloyl-D-threo-pent-1-enitol, 2,3,4-
tri-O-acetyl-1,5-anhydro-6-deoxy-L-lyxo-hex-1-enitol and
2,3,4,6-tetra-O-acetyl-1,5-anhydro-D-arabino-hex-1-enitol
were used as starting materials. The dithionite-mediated
additions of BrCF2Cl to these compounds produced
the desired C-glycosides 1,5-anhydro-1-(S)-chlorodifluo-
romethyl-2,3,4-tri-O-pivaloyl-D-ribitol, 2,3,4-tri-O-acet-
yl-1,5-anhydro-1-(R)-chlorodifluoromethyl-6-deoxy-L-
galactitol and 2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-
(S)-chlorodifluoromethyl-D-glucitol, respectively, in
moderate to good yields.1
acetyl protecting groups) the more bulky pivaloyl
groups could direct a ClCF2-group into the 1-position
of peracylated glycals. Thus, 3,4-di-O-pivaloyl-D-arabi-
nal, 3,4,6-tri-O-pivaloyl-D-glucal, and 3,4-di-O-piva-
loyl-D-xylal (1) were reacted with BrCF2Cl in the
presence of sodium dithionite.19 The result was that
the D-arabinal and D-glucal derivatives only produced
product mixtures similar to those obtained from the cor-
responding acetylated analogues19 (for further reference
data see also Refs. 14 and 15). However surprisingly, the
pivaloylated D-xylal derivative 1 formed predominantly
two 1-fluoroalkylated products (overall yield 46%) as
shown in Scheme 1. Although the mixed fraction of
these two compounds 4 and 5 could not be separated
by flash chromatography, crystals of the pure com-
pounds were obtained from the crystalline mixture of
this fraction. Thus, the most important analytical data,
including X-ray measurements, could be determined
for each of the two compounds. Because the two prod-
ucts show the same configuration at C-1, the mixture
was treated with sodium dithionite in DMF/methanol
to reduce bromo derivative 4 into the product 5. By
analogy with the procedure described by Constantino
et al.20 for hydrodeiodinations of 2-iodo-2-deoxy-sug-
ars, the dithionite reagent allowed the desired hydro-
dehalogenation yielding methylene derivative 5 in pure
form.
The structure of the 2-bromo-derivative 4 (Fig. 1)
shows the equatorial arrangement of the substituents
at the 1- and 2-positions. This indicates a trans-addition
of the BrCF2Cl reagent to the D-xylal derivative 1; the
bromine atom was likewise introduced trans to the pro-
tective group at the 3-position. The structure of 5 was
likewise confirmed by X-ray-analysis.19 When the radi-
cal addition of BrCF2Cl to 3,4-di-O-pivaloyl-D-xylal
(1) was carried out in dry methanol, the overall yield
of the products was only low and the introduction of
the CF2Cl-group was not exclusively introduced at the
1-position. Under these reaction conditions, we ob-
tained the anomeric methyl glycosides 6 in 22% yield
Although an earlier experiment showed that 3,4,6-tri-
O-pivaloyl-D-galactal and CF2Br2 give the correspond-
ing 2-C-bromodifluoromethyl-substituted D-galactose
derivative in a dithionite-mediated reaction,18 we tested
three additional models to determine if (compared with
O
O
O
ii
PivO
PivO
PivO
CF2Cl
PivO
OCH3
+
1
CF2Cl
6 (22%)
PivO
PivO
5 (7%)
i
O
O
PivO
+
CF2Cl
PivO
PivO
PivO
OH
O
O
PivO
+
CF2Cl
CF2Cl
2 (19%)
PivO
4
Br
+
O
C
F
PivO
3 (9%)
5
PivO
46%
Scheme 1. Reagents and conditions: (i) BrCF2Cl, Na2S2O4, NaHCO3, CH3CN, H2O, ꢀ10 ꢁC ! rt, 9 h; (ii) BrCF2Cl, Na2S2O4, NaHCO3, MeOH,
ꢀ10 ꢁC ! rt, 9 h.

A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
2643
Figure 1. Molecular structure of (2-bromo-2-deoxy-3,4-di-O-pivaloyl-b-D-xylopyranosyl)-chlorodifluoromethane (4) with 30% probability of the
thermal ellipsoids.
and product 5 in 7% yield (Scheme 1); bromo-derivative
4 was not found.
but instead deprotonation of the likewise acidified pro-
ton at C-1 occurred. The unsaturated product, formed
in very poor yields under HF-elimination, has an exo-
cyclic fluoromethylene group at C-1.
2.2. Transformation of the chlorodifluoromethyl group
Subsequently, radical activation of the CF2X-group
was investigated. First, a chloro-pyridino-cobaloxime(I)-
complex21 was used to activate the CF2Br-group of
compound 1118 and simultaneously reacted with 1-
octene. The column chromatographic separation of the
product mixture gave a pure fraction of methyl 3,4,
6-tri-O-acetyl-2-deoxy-2-C-difluoromethyl-b-D-glucopy-
ranoside18 in 14% isolated yield and a mixed fraction of a
saturated and at least two unsaturated products, proba-
bly compound 12 and E/Z-mixtures of products contain-
ing a double bond in the side chain. The latter was
reduced with Pd/C and H2 yielding exclusively product
12 in 68% overall yield (Scheme 3).
The application of this procedure on the reaction of
chlorodifluoromethyl derivative 7 with 1-octene resulted
in a complex product mixture containing only small
amounts of the desired product of C–C-coupling. The
major component was the CF2H-derivative 8.
Similarly, the reaction of the anomeric chlorodifluo-
romethyl derivatives 14 with the more reactive ethyl
vinyl ether yielded only products of hydrodechlorination
(Scheme 4). In this case the reaction was carried out in
the presence of n-Bu3SnH/AIBN for the radical genera-
tion. Following the procedure described in Section 4.10,
the a-anomer 15 was isolated in 32% yield. When the
Chlorodifluoromethylated sugars open new possibilities
for consecutive reactions by activation of the C–Cl-
bond. Previously, the transformation of a chlorodi-
fluoromethyl group into a trifluoromethyl group was
reported.15 However, because of the lower reactivity of
the CF2–Cl bond compared to a CF2–Br bond of
bromodifluoromethylated sugars,18 the transformation
required a more active fluorination reagent (TBAF/
CsF).15
gem-Difluorinated compounds are of particular inter-
est in view of their potential biological properties.11,12
Therefore, we studied some possibilities to activate the
carbon–chlorine bond of the chlorodifluoromethyl
group. At first, compound 71 was hydrodechlorinated
by treatment with tri-n-butyltin hydride and AIBN in
toluene. The isolated yield of product 8 was 88%
(Scheme 2). In a second experiment, the possibility of
a selective deprotonation of the CF2H moiety was inves-
tigated as a prerequisite for the following C–C-bond for-
mations with selected electrophiles. Initially, compound
8 was transformed into a benzyl derivative 10 as shown
in Scheme 2 (overall yield of 10 via two steps: 80%). Sub-
sequent treatment of 10 with lithium diisopropylamide
did not result in deprotonation of the CF2H-group,
O
O
i
AcO
CF2Cl
OAc
AcO
CF2H
OAc
8 (88%)
AcO
ii
AcO
7
O
O
iii
BnO
BnO
CF2H
8
HO
CF2H
OBn
10 (80%)
OH
HO
9
Scheme 2. Reagents and conditions: (i) n-Bu3SnH, AIBN, toluene, argon, reflux, 3 h; (ii) cat. t-BuOK, CH3OH, rt, 12 h; (iii) BnBr, NaH, DMF, rt,
6 h.

2644
A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
AcO
AcO
AcO
AcO
O
O
i
ii
AcO
OCH3
CF2Br
OCH3
AcO
CF2C8H17
11
12 (68%)
AcO
AcO
O
N
H
O
N
OCH3
O
N
H3C
H3C
CH3
CH3
Co
N
O
N
O
AcO
CF2H
H
Cl
13 (14%)
Chloro-pyridino-
cobaloxime(III)-complex
Scheme 3. Reagents and conditions: (i) 1-octene, Al, I2, chloro-
pyridino-cobaloxime(III)-complex, CH3OH, 0 ꢁC–rt, 4–5 h; (ii) H2
(1 atm), Pd/C, EtOAc, rt, 3 d.
Figure 2. Molecular structure of methyl 3,4-di-O-acetyl-2-C-difluoro-
methyl-2,6-dideoxy-a-L-glucopyranoside (15) with 50% probability of
the thermal ellipsoids.
procedure was modified in such a way, that solutions of
n-Bu3SnH and AIBN were simultaneously added drop
by drop, no significant change of the product spectrum
was observed. b-Configurated products could not be
identified in the product mixtures, however, decomposi-
tion was observed. Consequently, only some small frac-
tions of fluorine-free (not identified) compounds could
be separated beside product 15. The 19F NMR spectra
of these fractions did not show any signals related to a
CF2H-group or to the expected CF2–C-group.
a hydrodechlorinated CF2H-derivative, compound 19,
with intact allyl group at C-1 (Scheme 5).
The 19F NMR spectrum of compound 18 shows two
doublets at ꢀ93.8 and ꢀ106.5 ppm with a fluorine–fluo-
rine coupling of 242 Hz. These chemical shifts and cou-
pling indicate the replacement of the chlorine atom by a
carbon atom. The corresponding 1H and 13C NMR
spectra contain appropriate signals for three new CH2-
groups, whereas a new signal for a CH3-group, required
for product (I), was not found. The fact that C-2 of com-
pound 18 is quaternary and C-3 is tertiary proves that
the product is 2,3-unsaturated. The 13C NMR signal
for C-3 has a chemical shift of 119.3 ppm, which is
typical for carbon atoms in double bonds.
Compound 15 crystallized from n-heptane and EtOAc
in single crystals. Its molecular structure shows that the
1
a-L-gluco-configured ring adopts a C4-chair-conforma-
tion. All substituents with the exception of the methoxy
group are equatorially arranged (Fig. 2).
The radical activations with AIBN/tri-n-butyltin
hydride have shown that this reagent system induces
predominantly the reduction of a F2C–X-bond to a
F2C–H-bond. Therefore, we tested finally the allyltri-n-
butyltin reagent,25,26 which was already used for radical
allylations of a CF2Br-group27,28 and of chlorodifluoro-
acetic acid,29 respectively. The reactions of the CF2Cl-
substituted sugars 5, 7, 22,14,15 2415 and 26a,b with
allyltri-n-butyltin in EtOAc, carried out in a quartz tube,
were initiated by UV-irradiation (k = 254 nm). Scheme
6 shows the results of these CF2-allylations. The
products 20, 21, 23, 25 and 27a,b were isolated with
yields between 48% and 73%.
The following experiment is based on a strategy of
Arnone et al.22 Under radical reaction conditions, the
authors cyclized different allyl ethers of 1-chloro-1,1-
difluoro-3-(p-tolylsulfonyl)propan-2-ols leading to five-
membered carbocyclic rings. We started with allyl
derivative 17, prepared from 1614 analogous to Refs.
23 and 24 (Scheme 5). However, because the CF2Cl-
group of 17 is linked to a sp2-hybridized carbon, a rad-
ical cyclization would lead to a sp2-hybridized bridging
carbon in a system of condensed rings, that is, the
formation of the bicyclic compound (I) (5-exo-trig
reaction) is not expected. Nevertheless, the bicyclic
byproduct 18 with a fused six-membered ring (6-endo-
trig reaction) was formed in 11% yield. However, the
major product (isolated yield 80%) was also in this case,
The reactions were uniformly stopped after 2–3 h,
although the conversion of the starting materials was
not completed in each case. However, an extension of
O
O
i
OCH3
+
several side products
(not identified)
OCH3
CF2Cl
AcO
AcO
AcO
CF2H
AcO
14
15 (32%)
Scheme 4. Reagents and condition: n-Bu3SnH, AIBN, ethyl vinyl ether, benzene, reflux, 12 h.

A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
2645
AcO
AcO
AcO
AcO
AcO
AcO
O
O
O
i
ii
CH3
CF2Cl
CF2Cl
AcO
F
(I)
17 (42%)
16
F
ii
AcO
AcO
AcO
AcO
O
O
+
F
CF2H
18 (11%)
19 (80%)
F
Scheme 5. Reagents and conditions: (i) AllSiMe3, BF3ÆEt2O, CH2Cl2, 0 ꢁC ! rt, 24 h; (ii) AIBN, n-Bu3SnH, benzene, reflux, 4 h.
O
O
O
i
i
CF2Cl
CF2CH2CH=CH2
PivO
AcO
PivO
PivO
PivO
5
20 (62%)
O
CF2Cl
CF2CH2CH=CH2
AcO
AcO
OAc
AcO
AcO
OAc
7
21 (73%)
AcO
AcO
O
O
O
i
i
OAc
OAc
AcO
AcO
CF2CH2CH=CH2
AcO
CF2Cl
22
23 (73%)
AcO
AcO
AcO
AcO
O
OAc
OAc
AcO
CF2CH2CH=CH2
AcO
CF2Cl
25 (48%)
24
O
O
O
i
OCH3
OCH3
AcO
AcO
OCH3
AcO
+
27α + 27β
(64%)
AcO
CF2Cl
AcO
CF2CH2CH=CH2
AcO
CF2CH2CH=CH2
27α
27β
26α:26β (1:1)
Scheme 6. Reagents and conditions: allyltri-n-butyltin, EtOAc, k = 254 nm, 2–3 h.
the reaction time by 15–30 min led to larger amounts of
by-products but not to higher yields of the desired prod-
ucts. Ethyl acetate was selected as the solvent for the
photoreaction, after the evaluation of solvents of a
range of polarities as it yielded the best results at rela-
tively short reaction times.
monosaccharide derivative without an acyloxy group
in 2-position (see Ref. 1). However, this dithionite-med-
iated addition of BrCF2Cl to the starting material
3,4-di-O-pivaloyl-D-xylal (1) requires the use of aceto-
nitrile/water as the solvent system to produce
the major products (2-bromo-2-deoxy-3,4-di-O-piva-
loyl-b-D-xylopyranosyl)-chlorodifluoromethane (4) and
(2-deoxy-3,4-di-O-pivaloyl-b-D-threo-pentopyranosyl)-
chlorodifluoromethane (5).
3. Conclusion
Activation of CF2Cl-groups may be achieved by rad-
ical reaction conditions. Tri-n-butyltin hydride/AIBN
leads to satisfying results with reference to a reduction
For the first time, a CF2Cl-group was preferentially
introduced into the 1-position of an 1,2-unsaturated

2646
A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
of this group to a CF2H-moiety. Under UV irradiation
(k = 254 nm), reaction with allyltri-n-butyltin leads to
allylation of the CF2Cl-group yielding a CF2-allyl unit.
The allylations with allyltri-n-butyltin are the first exam-
ples of radical substitution at CF2Cl-groups of carbo-
hydrates. The C-glycosides, available in this way, are
very interesting unsaturated building blocks for novel
potentially bioactive substances.
8 h, the cold trap is removed and stirring is continued
for further 12 h at ꢁ25 ꢁC. Finally, Et2O (50 mL) and
H2O (30 mL) were added. The organic phase was sepa-
rated, washed with H2O (2 · 30 mL), dried (Na2SO4)
and concentrated under reduced pressure. The residue
was purified by column chromatography.
4.3. Photochemical allylation of carbohydrates with a
CF2Cl-group
4. Experimental
The CF2Cl containing derivative (0.3 mmol) was
dissolved in 4 mL of dry EtOAc in a quartz tube
(d = 1 cm, l = 25 cm) under argon. Allyltri-n-butyltin
(5 equiv) was added and the solution degassed with
argon for 30 min. The quartz tube was closed with a
septum and the reaction mixture was irradiated for
2–3 h at k = 254 nm in a Rayonet apparatus. After-
wards, the solvent was removed under reduced pressure
and the syrupy residue was purified by column
chromatography.
4.1. General methods
Column chromatography: Particle size for silica gel 63–
200 lm; thin layer chromatography (TLC): E. Merck
Silica Gel 60 F254 foils; NMR: Bruker instruments AC
250 and ARX 300; internal standard (CH3)4Si. Melting
points were measured using a polarising microscope
Leitz (Laborlux 12 Pol) equipped with a hot stage
(Mettler FP 90). Chemicals: Na2S2O4 (85%, Fluka),
tri-n-butyltin hydride (96%, Fluka), allyltri-n-butyltin
(ABCR), AIBN (98%, Fluka), allyltrimethylsilane
(97%, Fluka), BF3ÆEt2O (Fluka).
4.4. 2-C-Chlorodifluoromethyl-2-deoxy-3,4-di-O-pivaloyl-
D-xylopyranose (2), 1,5-anhydro-2-C-fluoroformyl-1,2-
dideoxy-3,4-di-O-pivaloyl-D-threo-pent-1-enitol (3),
(2-bromo-2-deoxy-3,4-di-O-pivaloyl-b-D-xylopyranosyl)-
chlorodifluoromethane (4) and (2-deoxy-3,4-di-O-piva-
loyl-b-D-threo-pentopyranosyl)-chlorodifluoromethane (5)
For the X-ray structure determination of 4, 519 and
15, an X8 Apex with CCD area detector with Mo-
˚
Ka-radiation (k = 0.71073 A) and graphite monochro-
mator was used. The structures were solved by direct
methods (Bruker SHELXTL, 1990, SHELXS-9730). The
refinement was done in all cases by the full matrix
least-squares method of Bruker SHELXTL, Vers.5.10,
Copyright 1997, Bruker Analytical X-ray Systems. All
nonhydrogen atoms were refined anisotropically. The
hydrogen atoms were put into theoretical positions
and refined using the riding model. Crystallographic
data (excluding structure factors) for the structures in
this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publica-
tion nos. CCDC 612996 (4), 612997 (5),19 612998 (15).
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK, (fax: +44 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk).
3,4-Di-O-pivaloyl-D-xylal (1)31 (0.57 g, 2.0 mmol) was
reacted as described in Section 4.2. The syrupy residue
(0.7 g) was separated by column chromatography (hep-
tane/EtOAc, 10:1 v/v) yielding successively 0.15 g
(19%) of 2, 0.34 g of 4 and 5 together (46%) and
0.06 g (9%) of 3.
Compound 2: Rf = 0.40 (heptane/EtOAc, 2:1 v/v),
1
colourless syrup; H NMR (250 MHz, CDCl3): d 5.85
3
3
(dd, 1H, J2,3 = 11.0, J3,4 = 9.4 Hz, H-3), 5.60 (d, 1H,
3J1,2 = 3.2 Hz, H-1), 4.94 (ddd, 1H, J3,4 = 9.4,
3
3J4,5a = 10.5, J4,5b = 6.3 Hz, H-4), 3.88 (t, 1H,
3
2J5a,5b = 10.9 Hz, H-5a), 3.79 (dd, 1H, J4,5b = 6.3,
3
2J5a,5b = 10.9 Hz, H-5b), 3.04 (br s, 1H, OH, HO-1),
3
3
2.95–2.81 (m, 1H, J1,2 = 3.2, J2,3 = 11.0 Hz, H-2),
1.15, 1.15 (2s, 18H, 2 · C(CH3)3); 13C NMR (75
MHz, CDCl3): d 177.9, 176.6 (2 · C@O), 127.7 (t,
4.2. Dithionite-initiated radical addition of BrCF2Cl to
glycals
1JC,F = 297 Hz, CF2Cl), 90.9 (t, JC,F = 5 Hz, C-1),
4
70.1 (C-4), 66.7 (C-3), 58.6 (C-5), 53.9 (t, 2JC,F = 22 Hz,
A solution of protected glycal (10 mmol) in CH3CN and
H2O (2:1, 30 mL) (or 30 mL dry CH3OH) was stirred for
1 h at rt under an argon atmosphere. After cooling to
ꢀ10 ꢁC, NaHCO3 (1.5 equiv) was suspended with vigor-
ous stirring and then BrCF2Cl (about 5 mL) was intro-
duced (install an dry ice/acetone-cooled trap for
condensation of Freon vapor). Subsequently, Na2S2O4
(1.5 equiv) was added and the mixture was warmed to
ꢁ25 ꢁC. At about 4 ꢁC, Freon 12a reaches reflux. After
C-2), 38.9, 38.8 (2 · C(CH3)3), 27.2, 27.2 (2 · C(CH3)3);
2
19F NMR (235 MHz, CDCl3): d ꢀ47.6 (d, JFa,Fb
=
2
172 Hz, Fa), ꢀ48.8 (d, JFa,Fb = 172 Hz, Fb); Anal.
Calcd for C16H25ClF2O6 (386.82): C, 49.68; H, 6.51.
Found: C, 50.30; H, 6.49.
Compound 3: Rf = 0.56 (heptane/EtOAc, 2:1 v/v),
22
colourless syrup, ½aꢂD ꢀ111.5 (c 1.0, CHCl3); 1H
NMR (250 MHz, CDCl3): d 7.90 (s, 1H, H-1), 5.48
3
(t, 1H, J2,3 = 3J3,4 = 2.3 Hz, H-3), 4.95–4.91 (m, 1H,

A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
2647
2
3
3
H-4), 4.48 (dt, 1H, J5a,5b = 12.7, J = 2.1, J = 4.1 Hz,
1H NMR (250 MHz, CDCl3): d 5.75 (dd, 1H,
2
3
H-5a), 4.07–4.00 (m, 1H, J5a,5b = 12.7 Hz, H-5b), 1.19,
3J2,3 = 11.1, J3,4 = 9.3 Hz, H-3), 4.90 (ddd, 1H,
1.17 (2s, 18H, 2 · C(CH3)3); 13C NMR (75 MHz,
3J3,4 = 9.3, J4,5a = 6.1, J4,5b = 10.8 Hz, H-4), 5.00 (d,
3
3
3
3
3
CDCl3): d 177.0, 176.7 (2 · C@O), 163.1 (d, JC,F
=
1H, J1,2 = 3.3 Hz, H-1), 3.75 (dd, 1H, J4,5a = 6.1,
2J5a,5b = 10.8 Hz, H-5a), 3.58 (t, 1H, 3J4,5b
2J5a,5b = 10.8 Hz, H-5b), 3.39 (s, 3H, OCH3), 2.92–2.78
1
6 Hz, C-1), 156.6 (d, JC,F = 335 Hz, COF), 100.0 (d,
2JC,F = 60 Hz, C-2), 65.3 (C-5), 64.9 (C-4), 60.9 (C-3),
39.0, 38.8 (2 · C(CH3)3), 27.2, 27.0 (2 · C(CH3)3);
19F NMR (235 MHz, CDCl3): d +13.4 (s, COF);
HRMS-ESI: Calcd [M+Na]+: 353.1382. Found:
353.1376.
=
3
3
(m, 1H, J1,2 = 3.3, J2,3 = 11.1 Hz, H-2), 1.13, 1.12
(2s, 18H, 2 · C(CH3)3); 13C NMR (63 MHz, CDCl3): d
1
177.7, 177.4 (2 · C@O), 128.6 (t, JC,F = 296 Hz,
CF2Cl), 97.6 (C-1), 69.9, 66.9, (C-3, C-4), 63.8 (C-5),
2
Compound 4: Rf = 0.62 (heptane/EtOAc, 2:1 v/v),
Mp 143–144 ꢁC (i-PrOH); 1H NMR (250 MHz, CDCl3):
55.7 (OCH3), 53.8 (t, JC,F = 22 Hz, C-2), 38.9, 38.8
(2 · C(CH3)3), 27.2, 27.1 (2 · C(CH3)3); 19F NMR
d 5.39 (t, 1H, J2,3 = 3J3,4 = 9.6 Hz, H-3), 4.93 (dd, 1H,
(235 MHz, CDCl3): d ꢀ46.9 (d, JFa,Fb = 168 Hz, Fa),
3
2
3J3,4 = 9.6, J4,5a = 5.6 Hz, H-4), 4.25 (dd, 1H,
ꢀ49.0 (d, JFa,Fb = 168 Hz, Fb); HRMS-ESI: Calcd
3
2
3J4,5a = 5.6, J5a,5b = 11.8 Hz, H-5a), 4.01–3.94 (m, 2H,
[M+Na]+: 423.1362. Found: 423.1356.
2
H-1, H-2), 3.43 (t, 1H, J = 11.0 Hz, H-5b), 1.15, 1.14
Compound 6b: Rf = 0.60 (heptane/EtOAc, 2:1 v/v),
1
(2s, 18H, 2 · C(CH3)3); 13C NMR (75 MHz, CDCl3): d
colourless syrup; H NMR (250 MHz, CDCl3): d 5.50
1
3
177.2, 176.8 (2 · C@O), 127.0 (t, JC,F = 296 Hz,
(t, 1H, J2,3 = 3J3,4 = 8.3 Hz, H-3), 4.92–4.85 (m, 1H,
3
3
CF2Cl), 81.5 (t, JC,F = 27 Hz, C-1), 73.9 (C-3), 68.9
H-4), 4.76 (d, 1H, J1,2 = 4.5 Hz, H-1), 4.23–4.13 (m,
(C-4), 67.0 (C-5), 43.3 (C-2), 38.9, 38.8 (2 · C(CH3)3),
2H, H-5a, H-5b), 3.41 (s, 3H, OCH3), 2.75–2.62 (m,
3
3
27.3, 27.2 (2 · C(CH3)3); 19F NMR (235 MHz, CDCl3):
1H, J1,2 = 4.5, J2,3 = 8.3 Hz, H-2), 1.14, 1.13 (2s,
2
2
d = ꢀ54.3 (d, JFa,Fb = 176 Hz, Fa), ꢀ57.5 (d, JFa,Fb
=
18H, 2 · C(CH3)3); 13C NMR (63 MHz, CDCl3): d
176 Hz, Fb); HRMS-ESI: Calcd [M+Na]+: 471.0356.
Found: 471.0349.
177.9, 177.6 (2 · C@O), 128.5 (t, JC,F = 296 Hz,
1
CF2Cl), 98.8 (C-1), 70.0, 70.0, (C-3, C-4), 63.6 (C-5),
2
Compound 5: Rf = 0.62 (heptane/EtOAc, 2:1 v/v),
56.2 (OCH3), 53.8 (t, JC,F = 22 Hz, C-2), 38.9, 38.7
23
Mp 122.0–122.6 ꢁC (Et2O), ½aꢂD ꢀ34.3 (c 1.0, CHCl3);
(2 · C(CH3)3), 27.2, 27.1 (2 · C(CH3)3); 19F NMR
3
2
1H NMR (250 MHz, CDCl3): d 5.09 (dd, 1H, J2a,3
=
(235 MHz, CDCl3): d ꢀ49.9 (d, JFa,Fb = 170 Hz, Fa),
3
3
2
5.0, J3,4 = 10.0 Hz, H-3), 5.02 (dd, 1H, J3,4 = 10.0,
ꢀ50.8 (d, JFa,Fb = 170 Hz, Fb); HRMS-ESI: Calcd
3J4,5a = 5.4 Hz, H-4), 4.24 (dd, 1H, J4,5a = 5.4,
[M+Na]+: 423.1362. Found: 423.1356.
3
2J5a,5b = 11.2 Hz, H-5a), 3.94–3.87 (m, 1H, J1,2a = 2.1,
3
3J1,2b = 11.8 Hz, H-1), 3.33 (dd, 1H, J4,5b = 10.0,
4.6. (2,3,4-Tri-O-acetyl-6-deoxy-a-L-galactopyranosyl)-
difluoromethane (8)
3
2J5a,5b = 11.2 Hz, H-5b), 2.39 (m, 1H, J1,2a = 2.1,
3
3J2a,3 = 5.0, H-2a), 1.77 (m, 1H, J1,2b = 11.8 Hz,
3
H-2b), 1.20, 1.18 (2s, 18H, 2 · C(CH3)3); 13C NMR
(75 MHz, CDCl3): d 177.7, 177.5 (2 · C@O), 127.2 (t,
Compound 71 (0.75 g, 2.09 mmol) was dissolved in dry
toluene (20 mL). Under argon, 0.76 g of n-Bu3SnH
(2.61 mmol) and 0.01 g of AIBN (0.06 mmol) were
added. The reaction mixture was heated under reflux
for 3 h. Then, the reaction was quenched by the addition
of an aq KF solution (10% in H2O, 10 mL) and stirred
for one hour at rt. The heterogenic solution was filtered
over Kieselguhr and the filter cake washed with toluene.
The toluene phase was washed with H2O (2 · 20 mL)
and brine (20 mL), dried over Na2SO4 and concentrated
under reduced pressure. The syrupy residue (1.60 g) was
separated by column chromatography (heptane/EtOAc,
4:1v/v) yielding 0.58 g (88%) of 8.
1JC,F = 294 Hz, CF2Cl), 78.2 (t, JC,F = 29 Hz, C-1),
3
70.0 (C-3), 68.7 (C-4), 67.2 (C-5), 38.9, 38.9
(2 · C(CH3)3), 30.2 (C-2), 27.2, 27.0 (2 · C(CH3)3); 19F
NMR (235 MHz, CDCl3): d ꢀ62.7 (d, 2JFa,Fb = 169 Hz,
2
Fa), ꢀ64.7 (d, JFa,Fb = 169 Hz, Fb); Anal. Calcd for
C16H25ClF2O5: C, 51.82; H, 6.80. Found: C, 51.80;
H, 7.11.
4.5. Methyl 2-C-chlorodifluoromethyl-2-deoxy-3,4-di-O-
pivaloyl-a-D-xylopyranoside (6a) and methyl 2-C-chloro-
difluoromethyl-2-deoxy-3,4-di-O-pivaloyl-b-D-xylo-
pyranoside (6b)
Compound 8: Rf = 0.55 (heptane/EtOAc, 1:2 v/v),
1
colourless syrup; H NMR (250 MHz, CDCl3): d 5.94
3,4-Di-O-pivaloyl-D-xylal (1)31 (0.32 g, 1.13 mmol) was
dissolved in dry CH3OH (10 mL) and converted as de-
scribed in Section 4.2. The syrupy residue (0.5 g) was
separated by column chromatography (heptane/EtOAc,
20:1 v/v) yielding 0.17 g (22%) of an anomeric mixture
of 6a/b (a:b = 1:0.65).
(ddd, 1H, JH,Fa,b = 54.1, JH,Fa,b = 56.7, JH,1 =
2
2
3
2.6 Hz, CF2H), 5.38–5.33 (m, 2H, H-2, H-3), 5.29 (t,
3
1H, J3,4 = 3J4,5 = 2.6 Hz, H-4), 4.41–4.24 (m, 1H, H-
3
1), 4.24–4.14 (m, 1H, J5,6 = 6.7 Hz, H-5), 2.13, 2.06,
3
1.99 (3s, 9H, 3 · CH3), 1.17 (d, 3H, J5,6 = 6.7 Hz,
CH3-6); 13C NMR (63 MHz, CDCl3): d 170.4, 170.1,
1
1
Compound 6a: Rf = 0.60 (heptane/EtOAc, 2:1 v/v),
colourless syrup.
169.9 (3 · C@O), 115.8 (dd, JC,Fa = 246, JC,Fb =
2
248 Hz, CF2H), 70.4 (t, JC,F = 22 Hz, C-1), 69.8

2648
A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
3
(C-4), 69.7 (C-5), 68.6 (t, JC,F = 2 Hz, C-2), 66.3 (C-3),
20.8, 20.7, 20.7 (3 · CH3), 16.1 (C-6); 19F NMR
added under argon. The reaction mixture was irradiated
with ultrasound for 2–3 min (until the brownish colour
disappeared) and afterwards again 10–20 mg of iodine
was added and activated by ultrasound. The mixture
was cooled to 0 ꢁC under argon. With vigorous stirring,
chloro-pyridino-cobaloxime(III)-complex21 (50 mg, 0.12
mmol), 1-octene (1 mL, 6.42 mmol) and compound 1118
(340 mg, 0.78 mmol) were added. The reaction mixture
was warmed to rt within 2 h and was stirred for another
2–3 h at rt. The mixture was diluted with EtOAc (20–
30 mL), filtered over Kieselguhr and concentrated
under reduced pressure. The syrupy residue was sepa-
rated by column chromatography (heptane/EtOAc,
3:1 ! 2:1 v/v) yielding 260 mg of a major fraction;
Rf = 0.30 (heptane/EtOAc, 3:1 v/v), which consisted of
at least three compounds and, as well 40 mg (14%) of
methyl 3,4,6-tri-O-acetyl-2-deoxy-2-C-difluoromethyl-
b-D-glucopyranoside (13);18 Rf = 0.15 (heptane/EtOAc,
3:1 v/v).
2
(235 MHz, CDCl3): d ꢀ121.6 (d, JFa,Fb = 297 Hz, Fa),
2
ꢀ125.4 (d, JFa,Fb = 297 Hz, Fb); HRMS-ESI: Calcd
[M+Na]+: 347.0918. Found: 347.0926.
4.7. (2,3,4-Tri-O-benzyl-6-deoxy-a-L-galactopyranosyl)-
difluoromethane (10)
To a solution of compound 8 (0.47 g, 1.45 mmol) in dry
CH3OH (10 mL), t-BuOK (0.01 g, 0.087 mmol) was
added, and the solution was stirred for 12 h at rt. Moni-
toring of the reaction by TLC indicated the complete con-
version of 8. The reaction mixture was filtered through
Kieselguhr and the CH3OH was evaporated under
reduced pressure. The syrupy residue 9 (0.35 g) was at
once dissolved in dry DMF (15 mL). At 0 ꢁC, 0.19 g of
NaH (60% in paraffin wax, 4.8 mmol) was added. With
a syringe, benzyl bromide (0.53 mL, 4.45 mmol) was
quickly added to the reaction mixture. The solution was
stirred for about 6 h at rt until complete conversion of
the starting material 9 (TLC). Five millilitres of CH3OH
and 5 mL of H2O were added and the aqueous phase was
extracted with toluene (3 · 20 mL). The organic phase
was washed with satd aq NaHCO3-soln, brine and H2O
(each 3 · 50 mL), dried over Na2SO4 and concentrated
under reduced pressure. The syrupy residue (0.90 g) was
separated by column chromatography (heptane/EtOAc,
4:1 v/v) yielding successively 0.54 g of 10. This corre-
sponds to a yield of 80% after two steps from 8.
The syrupy residue of the major fraction (260 mg) was
dissolved in dry EtOAc (20 mL) and hydrogenated with
H2 (1 atm) and 20 mg of Pd/C (10%) for 48–72 h. After
filtration of the reaction mixture over Kieselguhr and
concentration of the solution under reduced pressure,
250 mg (68%) of almost pure product 12 could be
obtained.
Compound 12: Colourless syrup; 1H NMR
3
(250 MHz, CDCl3):
d
5.45 (dd, 1H, J3,4 = 8.9,
3J2,3 = 9.8 Hz, H-3), 5.03 (dd, 1H, J4,5 = 10.1 Hz, H-
3
3
4), 4.46 (d, 1H, J1,2 = 7.6 Hz, H-1), 4.26 (dd, 1H,
2
Compound 10: Rf = 0.59 (heptane/EtOAc, 1:2 v/v),
3J5,6a = 4.9 Hz, H-6a), 4.07 (dd, 1H, J6a,6b = 12.3 Hz,
22
1
3
colourless syrup, ½aꢂD ꢀ15.18 (c 1.0, CHCl3); H NMR
H-6b), 3.66 (ddd, 1H, J5,6b = 2.6 Hz, H-5), 3.47 (s,
3H, OCH3), 2.44 (dddd, 1H, J2,Fa,b = 19.1, 6.1 Hz, H-
3
(250 MHz, CDCl3): d 7.42–7.22 (m, 15H, 3 · Ph), 5.91
2
2
3
(ddd, 1H, JH,Fa,b = 55.7, JH,Fa,b = 61.3, JH,1
=
2), 2.04, 1.98, 1.96 (all s, 9H, 3 acetyl CH3), 1.72–2.09
5.4 Hz, CF2H), 4.79–4.57 (m, 4H, 2 · CH2Ph), 4.56–
(m, 2H, a-CH2), 1.13–1.54 (m, 12H, 6CH2), 0.84 (t
3
3
4.52 (m, 2H, CH2Ph), 4.33–4.20 (m, 1H, J5,6
=
(br), 3H, JH,H = 6.6 Hz, CH3); 13C NMR (63 MHz,
6.8 Hz, H-5), 4.16–4.03 (m, 1H, H-1), 3.91–3.84 (m,
CDCl3): d 170.6, 169.8, 169.7 (all s, 3CO), 123.8 (dd,
3
3
3H, H-2, H-3, H-4), 1.43 (d, 3H, J5,6 = 6.8, CH3-6);
1JC,Fa,b = 247.5, 245.6 Hz, CF2), 100.5 (t, JC-1,Fa,b
=
13C NMR (63 MHz, CDCl3): d 138.5, 138.4, 137.7
(3 · qC–Ph), 128.6, 128.6, 128.2, 127.9, 127.9, 127.9,
6.7, 6.7 Hz, C-1), 71.1 (s, C-5), 69.4 (s, C-4), 68.7 (dd,
3JC-3,Fa,b = 4.0, 2.6 Hz, C-3), 62.3 (s, C-6), 56.7 (s,
1
2
127.8, 127.8, 127.7 (3 · Ph), 115.7 (dd, JC,Fa = 240,
OCH3), 50.4 (dd, JC-2,Fa,b = 21.9, 20.5 Hz, C-2), 36.7
1JC,Fb = 244 Hz, CF2H), 75.3 (C-3), 75.2 (C-2), 74.5
(C-4), 73.4, 73,4, 72.4 (3 · CH2Ph), 71.3 (C-5), 68.8
(t, JC,Fa,b = 23.8, 23.8 Hz, a-CH2), 31.7, 29.2, 29.2,
2
3
29.0, 22.6 (all s, 5CH2), 21.7 (dd, JC,Fa,b = 5.7,
2
(dd, JC,F = 23, 27 Hz, C-1), 14.2 (C-6); 19F NMR
3.8 Hz, b-CH2), 20.7, 20.7, 20.6 (all s, 3 acetyl-CH3),
14.0 (s, CH3); 19F NMR (235 MHz, CDCl3): d ꢀ99.8
2
(235 MHz, CDCl3): d ꢀ126.1 (d, JFa,Fb = 295 Hz, Fa),
2
2
ꢀ127.8 (d, JFa,Fb = 295 Hz, Fb). Anal. Calcd for
(d, JFa,Fb = 256 Hz, Fa), ꢀ101.7 (d, Fb); Anal. Calcd
C28H30F2O4 (468.54): C, 71.78; H, 6.45. Found: C,
72.27; H, 6.61.
for C22H36F2O8 (466.52): C, 56.64; H, 7.78. Found: C,
56.77; H, 7.78.
4.8. Methyl 3,4,6-tri-O-acetyl-2-deoxy-2-C-(1,1-difluoro-
nonyl)-b-D-glucopyranoside (12) and methyl 3,4,6-tri-O-
acetyl-2-deoxy-2-C-difluoromethyl-b-D-glucopyranoside
(13)
4.9. Methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-
2,6-dideoxy-a-L-glucopyranoside (14a) and methyl 3,4-di-
O-acetyl-2-C-chlorodifluoromethyl-2,6-dideoxy-b-L-
glucopyranoside (14b)
Aluminium powder (0.2 g, 7.41 mmol) was suspended in
dry CH3OH (15–20 mL) and iodine (10–20 mg) was
3,4-Di-O-acetyl-L-rhamnal32,33 (2.14 g, 10 mmol) was
dissolved in dry CH3OH (30 mL) and converted like

A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
2649
described in Section 4.2. After purification by column
chromatography (toluene/EtOAc, 10:1), the two
anomers 14a and 14b were separated (14a: 49%, 14b:
24%).
under reduced pressure. The syrupy residue (0.7 g) was
separated by column chromatography (heptane/EtOAc,
5:1 v/v) yielding 85 mg (32%) of 15. There was another
fraction (230 mg, Rf = 0.53) containing traces of com-
pound 15 and various other products, but none of them
contained a new CF2–C-bond.
Compound 14a: Rf = 0.48 (toluene/EtOAc, 5:1), Mp
19
1
85.8 ꢁC (Et2O), ½aꢂD ꢀ139.9 (c 1.1, CHCl3); H NMR
3
(250 MHz, CDCl3):
d
5.65 (dd, 1H, J3,4 = 9.2,
Compound 15: Rf = 0.56 (heptane/EtOAc, 1:2 v/v),
22
3J2,3 = 11.2 Hz, H-3), 4.99 (d, 1H, J1,2 = 3.4 Hz, H-1)
4.80–4.70 (m, 1H, H-4), 3.98–3.85 (m, 1H,
3J5,6 = 6.3 Hz, H-5), 3.39 (s, 3H, OCH3), 2.97–2.82
Mp 105.0–106.5 ꢁC (heptane/EtOAc), ½aꢂD ꢀ162.5 (c
3
1
1.1, CHCl3); H NMR (250 MHz, CDCl3): d 5.82 (dt,
3
2
1H, JH,2 = 7.3, JH,Fa,b = 55.5 Hz, CF2H), 5.44 (dd,
3
3
3
3
(m, 1H, J1,2 = 3.4, J2,3 = 11.2 Hz, H-2), 2.04, 2.00
1H, J3,4 = 9.5, J2,3 = 11.2 Hz, H-3), 4.79 (d, 1H,
3J1,2 = 3.6 Hz, H-1), 4.77 (t, 1H, 3J = 9.7 Hz, H-4),
3
(2s, 6H, 2 · CH3), 1.19 (d, 3H, J5,6 = 6.3 Hz, CH3-6);
13C NMR (63 MHz, CDCl3):
d
170.1, 169.6
3.86 (ddd, 1H, J5,6 = 6.3, J4,5 = 9.9 Hz, H-5), 2.46–
3
3
1
3
3
3
(2 · C@O), 127.0 (t, JC,F = 281, CF2Cl), 97.1 (dd,
2.28 (m, 1H, J1,2 = 3.6, JH,2 = 7.3, J2,3 = 11.2 Hz,
H-2), 2.03, 1.99 (2s, 6H, 2 · CH3), 1.18 (d, 3H,
3J5,6 = 6.3 Hz, CH3-6); 13C NMR (63 MHz, CDCl3): d
170.6, 170.0 (2 · C@O), 116.3 (t, JC,Fa,b = 243 Hz,
CF2H), 97.1 (t, JC,F = 8 Hz, C-1), 73.8 (C-4), 67.8 (t,
3JC,Fa = 3.9, JC,Fb = 5.8 Hz, C-1), 74.5 (C-3), 67.8
3
2
(C-4), 65.2 (C-5), 55.4 (OCH3), 53.9 (t, JC,F = 22 Hz,
C-2), 20.8, 20.7 (2 · CH3), 17.3 (C-6); 19F NMR
1
2
3
(235 MHz, CDCl3): d ꢀ48.3 (d, JFa,Fb = 168 Hz, Fa),
2
ꢀ50.6 (d, JFa,Fb = 168 Hz, Fb); Anal. Calcd for
3JC,F = 4 Hz, C-3), 65.6 (C-5), 55.3 (OCH3), 49.0 (t,
2JC,F = 19 Hz, C-2), 20.8, 20.7, (2 · CH3), 17.7 (C-6);
19F NMR (235 MHz, CDCl3): d ꢀ119.8 (s, CF2H);
Anal. Calcd for C12H18F2O6 (296.27): C, 48.65; H,
6.12. Found: C, 48.07; H, 6.14.
C12H17ClF2O6 (330.71): C, 43.58; H, 5.18. Found: C,
43.31; H, 5.23.
Compound 14b: Rf = 0.41 (toluene/EtOAc, 5:1), col-
19
ourless syrup, ½aꢂD ꢀ28.3 (c 1.1, CHCl3); 1H NMR
3
(250 MHz, CDCl3): d 5.49–5.40 (m, 1H, J3,4 = 9.8 Hz,
3
3
H-3), 4.83 (dd, 1H, J3,4 = 9.8, J4,5 = 9.9 Hz, H-4),
4.11. 3-(4,6-Di-O-acetyl-2-C-chlorodifluoromethyl-2,3-
dideoxy-a-D-erythro-hex-2-enopyranosyl)-propene (17)
3
4.59 (d, 1H, J1,2 = 7.4 Hz, H-1), 3.60 (ddd, 1H,
3J5,6 = 6.2, J4,5 = 9.9 Hz, H-5), 2.81–2.72 (m, 1H,
3
3J1,2 = 7.4 Hz, H-2), 2.04, 2.01 (2s, 6H, 2 · CH3), 1.25
To a solution of compound 1614 (2.0 g, 5.61 mmol) in
dry CH2Cl2, allyltrimethylsilane (2.6 mL, about 3 equiv)
and BF3ÆEt2O (3.5 mL, about 5 equiv) were added at
0 ꢁC with stirring. The reaction mixture was then
allowed to warm to rt. After 24 h, allyltrimethylsilane
(1.3 mL) and BF3ÆEt2O (1.75 mL) were added. After
further 5 h stirring at rt, the reaction mixture was
worked up. The CH2Cl2 phase was washed with a satd
aq NaHCO3 (3 · 20 mL) and brine (3 · 20 mL), dried
over Na2SO4 and concentrated under reduced pressure.
The syrupy residue was separated by column chroma-
tography (heptane/EtOAc, 2:1 v/v) yielding successively
0.76 g (42%) of 17.
(d, 3H, J5,6 = 6.2 Hz, CH3-6); 13C NMR (63 MHz,
3
CDCl3):
d
169.8, 169.6 (2 · C@O), 128.1 (t,
3
1JC,F = 283 Hz, CF2Cl), 100.7 (d, JC,F = 5 Hz, C-1),
3
74.0 (t, JC,F = 34 Hz, C-3), 69.7 (C-4), 68.9 (C-5),
2
2
57.1 (OCH3), 55.1 (dd, JC,Fa = 22, JC,Fb = 18 Hz, C-
2), 20.9, 20.8 (2 · CH3), 17.7 (C-6); 19F NMR
2
(235 MHz, CDCl3): d ꢀ45.9 (d, JFa,Fb = 174 Hz, Fa),
2
ꢀ49.5 (d, JFa,Fb = 174 Hz, Fb); Anal. Calcd for
C12H17ClF2O6 (330.71): C, 43.58; H, 5.18. Found: C,
43.77; H, 5.38.
4.10. Methyl 3,4-di-O-acetyl-2-C-difluoromethyl-2,6-
dideoxy-a-L-glucopyranoside (15)
Compound 17: Rf = 0.56 (heptane/EtOAc, 1:3 v/v),
22
1
colourless syrup, ½aꢂD +93.6 (c 1.2, CHCl3). H NMR
(250 MHz, CDCl3): d 6.36–6.30 (m, 1H, H-3), 5.97–
5.79 (m, 1H, H-2-allyl), 5.35–5.27 (m, 1H, H-4), 5.21–
5.10 (m, 2H, CH2-allyl), 4.61–4.52 (m, 1H, H-1),
4.20–4.15 (m, 2H, H-6a, H-6b), 3.99–3.91 (m, 1H, H-
5), 3.62–2.53 (m, 2H, CH2-allyl), 2.11, 2.08 (2s, 6H,
2 · CH3); 13C NMR (63 MHz, CDCl3): d 170.1, 170.0
(2 · C@O), 139.2 (t, 2JC,F = 25 Hz, C-2), 133.7 (C-allyl),
A mixture of 14a/14b (0.3 g, 0.91 mmol) was dissolved
in dry benzene (5 mL) in a Schlenk flask under argon.
After ethylvinyl ether (0.4 mL, 5 equiv) and a catalytic
amount of AIBN (ca. 3–5 mg) were added, the reaction
mixture was heated to 75 ꢁC. At this temperature, a
solution of 0.26 mL (0.91 mmol) n-Bu3SnH in dry ben-
zene (5 mL) was slowly added within 3 h. After complete
conversion of the starting material (TLC), the solution
was concentrated under reduced pressure. The syrupy
residue was treated with an aq KF-soln (10% in H2O,
10 mL) and stirred for 30 min. The aq phase was
extracted with EtOAc (3 · 50 mL) and afterwards the
organic phase was washed with H2O (2 · 50 mL) and
brine (1 · 50 mL), dried over Na2SO4 and concentrated
1
3
131.3 (t, JC,F = 290 Hz, CF2Cl), 127.7 (dd, JC,Fa = 6,
3JC,Fb = 8 Hz, C-3), 117.9 (CH2-allyl), 71.3 (C-1), 67.6
(C-5), 64.5 (C-4), 63.1 (C-6), 36.3 (CH2-allyl), 21.0,
20.9 (2 · CH3); 19F NMR (235 MHz, CDCl3): d ꢀ45.8
2
2
(d, JFa,Fb = 170.2 Hz, Fa), ꢀ52.8 (d, JFa,Fb = 170 Hz,
Fb). Anal. Calcd for C14H17ClF2O5 (338.74): C, 49.64;
H, 5.06. Found: C, 49.51; H, 5.06.

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A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
2
4.12. (2R,3S,8aR)-2-Acetoxymethyl-3-acetoxy-5,5-di-
fluoro-3,5,6,7,8,8a-hexahydro-2H-benzopyrane (18) and
3-(4,6-di-O-acetyl-2,3-dideoxy-2-C-difluoromethyl-a-D-
erythro-hex-2-enopyranosyl)-propene (19)
(235 MHz, CDCl3): d ꢀ111.3 (d, JFa,Fb = 304 Hz, Fa),
2
ꢀ119.9 (d, JFa,Fb = 304 Hz, Fb); HRMS-ESI: Calcd
[M+Na]+: 327.1020. Found: 327.1015.
4.13. 4,4-Difluoro-4-(2-deoxy-3,4-di-O-pivaloyl-b-D-
threo-pentopyranosyl)-butene (20)
To a solution of compound 17 (0.21 g, 0.62 mmol) in
2 mL of dry benzene, AIBN (3 mg, 0.018 mmol) was
added under argon at rt (Schlenk flask). After the reac-
tion mixture was heated to 75 ꢁC, a solution of n-
Bu3SnH (0.18 mL, 0.62 mmol) in dry benzene (10 mL)
was slowly added within 3 h. When the conversion of
the starting material was completed (TLC control), the
solution was concentrated under reduced pressure.
The syrupy residue was treated with and aq KF-soln
(10% in H2O, 10 mL) and stirred for 30 min. The aq
phase was extracted with EtOAc (3 · 50 mL) and after-
wards the combined organic phases were washed with
H2O (2 · 50 mL) and brine (1 · 50 mL), dried over
Na2SO4 and concentrated under reduced pressure.
The syrupy residue was separated by column chroma-
tography (heptane/EtOAc, 4:1 v/v) yielding succes-
sively 0.15 g (80%) of 19 (Rf = 0.36) and 0.02 g of 18
(11%).
Compound 5 (0.11 g, 0.29 mmol) dissolved in dry
EtOAc (3 mL) was converted as described in Section
4.3. The syrupy residue (0.6 g) was separated by column
chromatography (heptane/EtOAc, 20:1 v/v) yielding
0.07 g (62%) of 20; Rf = 0.63 (heptane/EtOAc, 5:1
1
v/v), colourless syrup; H NMR (250 MHz, CDCl3): d
5.88–5.65 (m, 1H, CH-allyl), 5.28–5.14 (m, 2H, CH2-
allyl), 5.08–4.86 (m, 2H, H-3, H-4), 4.15 (dd, 1H,
2
3J4,5a = 5.4, J5a,5b = 11.2 Hz, H-5a), 3.68–3.52 (m, 1H,
3
3J1,2a = 2.1, J1,2b = 11.8 Hz, H-1), 3.20 (dd, 1H,
2
3J4,5b = 10.0, J5a,5b = 11.2 Hz, H-5b), 2.85–2.57 (m,
3
3
2H, CH2-allyl), 2.28 (ddd, 1H, J1,2a = 2.1, J2a,3 = 5.0,
3
J = 12.7 Hz, H-2a), 1.69 (dd, 1H, J1,2b = 11.8,
J = 23.9 Hz, H-2b) 1.16, 1.14 (2s, 18H, 2 · C(CH3)3);
13C NMR (75 MHz, CDCl3):
d
177.7, 177.5
3
3
(2 · C@O), 128.7 (dd, JC,F = 3, JC,F = 8 Hz, CH-
Compound 18: Rf = 0.32 (heptane/EtOAc, 1:2 v/v),
1
allyl), 127.1 (t, JC,F = 245 Hz, CF2), 121.0 (CH2-allyl),
22
1
colourless syrup, ½aꢂD +76.7 (c 1.2, CHCl3); H NMR
(250 MHz, CDCl3): d 6.13–6.06 (m, 1H, H-4), 5.24–
5.16 (m, 1H, H-3), 4.37–4.27 (m, 1H, H-8a), 4.27 (dd,
2
2
75.6 (dd, JC,F = 27, JC,F = 34 Hz, C-1), 70.7 (C-3),
69.2 (C-4), 67.4 (C-5), 38.9, 38.8 (2 · C(CH3)3), 37.9
2
2
(dd, JC,F = 24, JC,F = 26 Hz, CH2-allyl), 28.8 (t,
3
2
1H, J2,9a = 6.0, J9a,9b = 12.0 Hz, H-9a), 4.17 (dd, 1H,
3JC,F = 4 Hz, C-2), 27.2, 27.1 (2 · C(CH3)3); 19F NMR
3J2,9b = 3.8, J9a,9b = 12.0 Hz, H-9b), 3.90 (ddd, 1H,
2
2
(235 MHz, CDCl3): d ꢀ107.9 (d, JFa,Fb = 255 Hz, Fa),
3J2,3 = 9.6, J2,9a = 6.0, J2,9b = 3.8 Hz, H-2), 2.32–2.18
(m, 1H, H-6a), 2.16–2.11 (m, 1H, H-8a), 1.92–1.82 (m,
1H, H-7a), 1.79–1.69 (m, 1H, H-6b), 1.43–1.31 (m, 1H,
H-7b), 1.31–1.23 (m, 1H, H-8b), 2.10, 2.09 (2s, 6H,
2 · CH3); 13C NMR (63 MHz, CDCl3): d 170.4, 170.3,
3
3
2
ꢀ111.6 (d, JFa,Fb = 255 Hz, Fb); HRMS-ESI: Calcd
[M+Na]+: 399.1959. Found: 399.1962.
4.14. 4,4-Difluoro-4-(2,3,4-tri-O-acetyl-6-deoxy-a-L-
galactopyranosyl)-butene (21)
2
2
(2 · C@O), 138.7 (dd, JC,Fa = 21, JC,Fb = 24 Hz, C-
4a), 119.9 (dd, JC,Fa = 235, JC,Fb = 250 Hz, CF2),
119.3 (dd, JC,Fa = 7, JC,Fb = 9 Hz, C-4), 71.1 (C-8a),
1
1
3
3
Compound 7 (0.15 g, 0.42 mmol) dissolved in dry
EtOAc (3 mL) was converted as described in Section
4.3. The syrupy residue (0.9 g) was separated by column
chromatography (heptane/EtOAc, 10:1 v/v) yielding
0.11 g (73%) of product 21; Rf = 0.27 (heptane/EtOAc,
1:1 v/v); colourless syrup; 1H NMR (250 MHz, CDCl3):
2
70.5 (C-2), 64.7 (C-3), 62.6 (C-9), 35.3 (dd, JC,Fa = 22,
2JC,F = 27 Hz, C-6), 31.4 (C-8), 21.1, 20.9 (2 · CH3),
18.3 (C-7); 19F NMR (235 MHz, CDCl3): d ꢀ93.8 (d,
2JFa,Fb = 242 Hz, Fa), ꢀ106.5 (d, JFa,Fb = 242 Hz,
2
Fb); HRMS-ESI: Calcd [M+Na]+: 327.1020. Found:
327.1015.
3
d 5.87–5.68 (m, 1H, CH-allyl), 5.48 (dd, 1H, J2,3 = 9.8,
3J3,4 = 3.3 Hz, H-3), 5.32 (dd, 1H, 3J2,3 = 9.8,
3J1,2 = 6.2 Hz, H-2), 5.30 (dd, 1H, 3J4,5 = 1.8,
3J3,4 = 3.3 Hz, H-4), 5.27–5.18 (m, 2H, CH2-allyl),
Compound 19: Rf = 0.34 (heptane/EtOAc, 1:2 v/v),
22
1
colourless syrup, ½aꢂD +94.3 (c 1.6, CHCl3); H NMR
(250 MHz, CDCl3): d 6.09 (br s, 1H, H-3), 6.06 (t, 1H,
CF2H), 5.98–5.79 (m, 1H, CH-allyl), 5.29–5.20 (m, 1H,
H-4), 5.21–5.07 (m, 2H, CH2-allyl), 4.53–4.40 (m, 1H,
H-1), 4.19–4.15 (m, 2H, H-6a, H-6b), 4.01–3.95 (m,
1H, H-5), 2.56–2.49 (m, 2H, CH2-allyl), 2.09, 2.08 (2s,
6H, 2 · CH3); 13C NMR (75 MHz, CDCl3): d 170.8,
3
4.46–4.29 (m, 1H, J1,2 = 6.2 Hz, H-1), 4.14–4.01 (m,
3
1H, J5,6 = 6.4 Hz, H-5), 2.77–2.57 (m, 2H, CH2-allyl),
2.12, 2.04, 1.99, (3s, 9H, 3 · CH3), 1.16 (d, 3H,
3J5,6 = 6.4 Hz, CH3); 13C NMR (63 MHz, CDCl3): d
3
170.6, 170.4, 169.8 (3 · C@O), 128.3 (t, JC,F = 5 Hz,
CH-allyl), 124.4 (t, 1JC,F = 250 Hz, CF2), 121.3 (CH2-al-
2
2
170.3 (2 · C@O), 137.9 (dd, JC,F = 21, JC,F = 22 Hz,
2
2
3
C-2), 133.9 (C-allyl), 127.7 (t, JC,Fa = 3JC,Fb = 10 Hz,
lyl), 70.9 (dd, JC,F = 25, JC,F = 28 Hz, C-1), 69.9 (C-
4), 68.8 (C-5), 68.5 (C-2), 66.4 (C-3), 39.7 (t,
2JC,F = 25 Hz, CH2-allyl), 20.8, 20.7, 20.6 (3 · CH3),
16.2 (C-6); 19F NMR (235 MHz, CDCl3): d ꢀ98.7 (d,
1
C-3), 117.8 (CH2-allyl), 114.4 (t, JC,F = 239 Hz,
CF2H), 70.6 (C-1), 68.1 (C-5), 64.6 (C-4), 63.1 (C-6),
36.5 (CH2-allyl), 20.9, 20.8 (2 · CH3); 19F NMR

A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
2651
2
2JFa,Fb = 258 Hz, Fa), ꢀ100.0 (d, JFa,Fb = 258 Hz, Fb);
HRMS-ESI: Calcd [M+H]+: 365.1412. Found:
365.1415.
4.17. Methyl 3,4-di-O-acetyl-2-C-chlorodifluoromethyl-2-
deoxy-a-D-arabinopyranoside (26a) and methyl 3,4-di-O-
acetyl-2-C-chlorodifluoromethyl-2-deoxy-b-D-arabinopyr-
anoside (26b)
4.15. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-C-(4,4-difluoro-
butene-4-yl)-a-D-glucopyranose (23)
3,4-Di-O-acetyl-D-arabinal34 (2.5 g, 12.5 mmol) dis-
solved in dry CH3OH (30 mL) was converted as de-
scribed in Section 4.2. The syrupy residue (3.30 g) was
separated by column chromatography (heptane/EtOAc,
6:1 v/v) yielding 2.88 g (72%) of an anomeric mixture of
26a/26b (a:b = 1:1).
1-O-Acetyl derivative 2214,15 (0.27 g, 0.65 mmol) dis-
solved in dry EtOAc (5 mL) was converted as described
in procedure 2. The syrupy residue (1.3 g) was separated
by column chromatography (heptane/EtOAc, 8:1 v/v)
yielding 0.20 g (73%) of 23; Rf = 0.34 (heptane/EtOAc,
1:1 v/v); colourless syrup; 1H NMR (250 MHz, CDCl3):
Compound 26a: Rf = 0.20 (heptane/EtOAc, 3:1 v/v),
1
colourless syrup; H NMR (250 MHz, CDCl3): d 5.40
3
3
(dd, 1H, J2,3 = 8.8, J3,4 = 3.8 Hz, H-3), 5.26–5.19 (m,
3
d 6.35 (d, 1H, J1,2 = 3.2 Hz, H-1), 5.82–5.74 (m, 1H,
3
1H, H-4), 4.67 (d, 1H, J1,2 = 5.2 Hz, H-1), 3.97 (dd,
3
3
CH-allyl), 5.65 (dd, 1H, J2,3 = 11.5, J3,4 = 9.3 Hz,
H-3), 5.28–5.13 (m, 2H, CH2-allyl), 5.02 (t, 1H,
3J3,4 = 3J4,5 = 9.3 Hz, H-4), 4.35–4.20 (m, 2H, H-6a,
H-6b), 4.07–3.94 (m, 1H, H-5), 2.80–2.46 (m, 3H, H-2,
CH2-allyl), 2.11, 2.02, 1.99, 1.98 (4s, 12H, 4 · CH3);
13C NMR (63 MHz, CDCl3): d 170.6, 169.7, 169.6,
3
2
1H, J4,5a = 4.6, J5a,5b = 12.3 Hz, H-5a), 3.74 (dd, 1H,
3J4,5b = 3.4, J5a,5b = 12.3 Hz, H-5b), 3.47 (s, 3H,
2
3
3
OCH3), 2.98–2.84 (m, 1H, J1,2 = 5.2, J2,3 = 8.8 Hz,
H-2), 2.10, 2.04 (2s, 6H, 2 · CH3); 13C NMR
(75 MHz, CDCl3): d 170.3, 169.8 (2 · C@O), 128.6 (t,
1JC,F = 297 Hz, CF2Cl), 99.5 (C-1), 66.7 (C-3), 66.1
3
168.4 (4 · C@O), 128.1 (t, JC,F = 5 Hz, CH-allyl),
2
(C-4), 61.8 (C-5), 56.7 (OCH3), 51.7 (t, JC,F = 22 Hz,
1
121.7 (CH2-allyl), 121.1 (t, JC,F = 248 Hz, CF2), 88.7
C-2), 21.0, 20.8 (2 · CH3); 19F NMR (235 MHz,
3
(t, JC,F = 6 Hz, C-1), 79.5 (C-5), 67.7 (3JC,F = 4 Hz,
2
CDCl3): d ꢀ47.5 (d, JFa,Fb = 170 Hz, Fa), ꢀ48.7 (d,
2
C-3), 66.5 (C-4), 61.7 (C-6), 47.6 (t, JC,F = 22 Hz, C-
2JFa,Fb = 170 Hz, Fb); Anal. Calcd for C11H15ClF2O6
(316.69): C, 41.72; H, 4.77. Found: C, 41.59; H, 4.51.
Compound 26b: Rf = 0.26 (heptane/EtOAc, 3:1 v/v),
colourless syrup (anomeric mixture).
2
2), 41.3 (t, JC,F = 25 Hz, CH2-allyl), 21.1, 20.8, 20.7,
20.6 (4 · CH3); 19F NMR (235 MHz, CDCl3): d ꢀ98.2
2
2
(d, JFa,Fb = 248 Hz, Fa), ꢀ99.2 (d, JFa,Fb = 248 Hz,
Fb) HRMS-ESI: Calcd [M+Na]+: 445.1286. Found:
445.1294.
1H NMR (250 MHz, CDCl3): d 5.55 (dd, 1H,
3J2,3 = 11.5, J3,4 = 3.2 Hz, H-3), 5.24–5.17 (m, 1H, H-
3
3
4), 5.06 (d, 1H, J1,2 = 3.2 Hz, H-1), 3.95 (dd, 1H,
3J4,5a = 1.4, J5a,5b = 13.0 Hz, H-5a), 3.69 (dd, 1H,
2
4.16. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-C-(4,4-difluoro-
butene-4-yl)-a-D-mannopyranose (25)
3J4,5b = 2.1, J5a,5b = 13.0 Hz, H-5b), 3.39 (s, 3H,
2
3
3
OCH3), 3.19–3.03 (m, 1H, J1,2 = 3.2, J2,3 = 11.5 Hz,
H-2), 2.13, 1.99 (2s, 6H, 2 · CH3); 13C NMR
(75 MHz, CDCl3): d = 170.4, 169.7 (2 · C@O), 128.7
1-O-acetyl derivative 2415 (0.29 g, 0.69 mmol) dissolved
in dry EtOAc (5 mL) was converted as described in Sec-
tion 4.3. The syrupy residue (1.4 g) was separated by col-
umn chromatography (heptane/EtOAc, 8:1 v/v) yielding
0.17 g of a mixture of 25 and starting material (ratio
1:0.2) corresponding to a yield of 48% for compound
25; Rf = 0.32 (heptane/EtOAc, 1:1 v/v), colourless syrup;
1
(t, JC,F = 298 Hz, CF2Cl), 97.9 (C-1), 66.6 (C-3), 66.1
2
(C-4), 60.8 (C-5), 55.8 (OCH3), 49.4 (t, JC,F = 22 Hz,
C-2), 21.1, 20.8 (2 · CH3); 19F NMR (235 MHz,
2
CDCl3): d ꢀ48.2 (d, JFa,Fb = 170 Hz, Fa), ꢀ49.7
2
(d, JFa,Fb = 170 Hz, Fb); Anal. Calcd for C11H15ClF2-
1H NMR (250 MHz, CDCl3):
d
6.43 (d, 1H,
O6 (316.69): C, 41.72; H, 4.77. Found: C, 41.59; H,
4.51.
3J1,2 = 3.3 Hz, H-1), 5.82–5.63 (m, 1H, CH-allyl), 5.43–
5.33 (m, 1H, H-3), 5.27–5.13 (m, 3H, H-4, CH2-allyl),
3
4.12 (d, 2H, J5,6 = 3.2 Hz, H-6a, H-6b), 4.02–3.92 (m,
4.18. Methyl 3,4-di-O-acetyl-2-C-(4,4-difluorobutene-4-
yl)-2-deoxy-a-D-arabinopyranoside (27a) and methyl 3,4-
di-O-acetyl-2-C-(4,4-difluorobutene-4-yl)-2-deoxy-b-D-
arabinopyranoside (27b)
1H, H-5), 2.86–2.62 (m, 3H, H-2, CH2-allyl), 2.09, 2.02,
2.02, 2.01 (4s, 12H, 4 · CH3); 13C NMR (63 MHz,
CDCl3): d 170.5, 169.8, 169.3, 168.6 (4 · C@O), 128.3
3
1
(t, JC,F = 6 Hz, CH-allyl), 122.3 (t, JC,F = 248 Hz,
CF2), 121.3 (CH2-allyl), 89.6 (t, 3JC,F = 5 Hz, C-1), 70.3
(C-5), 67.9 (C-3), 66.9 (C-4), 62.6 (C-6), 45.2 (t,
The 1:1 anomeric mixture of 26a/26b (1.6 g, 5.05 mmol)
dissolved in dry EtOAc (10 mL) was converted as de-
scribed in Section 4.3. The syrupy residue (9.2 g) was
separated by column chromatography (heptane/EtOAc,
6:1 v/v) yielding 0.97 g (64%) of the anomeric mixture
27a/27b (a:b = 1:1); HRMS-ESI of the a/b mixture:
Calcd [M+Na]+: 345.1126. Found: 345.1118.
2JC,F = 23 Hz, C-2), 40.9 (t, JC,F = 26 Hz, CH2-allyl),
2
20.9, 20.8, 20.6, 20.5 (4 · CH3); 19F NMR (235 MHz,
2
CDCl3): d ꢀ94.7 (d, JFa,Fb = 258 Hz, Fa), ꢀ96.2 (d,
2JFa,Fb = 258 Hz, Fb). HRMS-ESI: Calcd [M+Na]+:
445.1286. Found: 445.1295.

2652
A. Wegert et al. / Carbohydrate Research 341 (2006) 2641–2652
5. Fluoroorganic Chemistry: Synthetic Challenges and Bio-
medical Rewards; Resnati, G., Soloshonok, V. A., Eds.;
Pergamon Press: Oxford, 1996.
6. Yamamoto, H. Organofluorine Compounds—Chemistry
and Applications; Springer: Berlin, 2000.
7. Carbohydr. Res., Special Issue, Fluoro Sugars; Miethchen,
R., Defaye, J., Eds.; Elsevier: Amsterdam, 2000; Vol. 327,
pp 1–218.
8. Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis,
Reactivity, Applications; Wiley-VCH: Weinheim, 2004.
9. Ja¨ckel, C.; Koksch, B. Eur. J. Org. Chem. 2005, 4483–
4503.
Compound 27a: Rf = 0.43 (heptane/EtOAc, 1:1 v/v),
1
colourless syrup; H NMR (250 MHz, CDCl3): d 5.89–
3
5.69 (m, 1H, CH-allyl), 5.37 (dd, 1H, J2,3 = 8.4,
3J3,4 = 3.7 Hz, H-3), 5.28–5.16 (m, 3H, CH2-allyl, H-
3
4), 4.55 (d, 1H, J1,2 = 5.8 Hz, H-1), 3.96 (dd, 1H,
2
3J4,5a = 5.0, J5a,5b = 12.3 Hz, H-5a), 3.60 (dd, 1H,
2
3J4,5b = 3.0, J5a,5b = 12.3 Hz, H-5b), 3.45 (s, 3H,
3
3
OCH3), 2.93–2.62 (m, 1H, J1,2 = 5.8, J2,3 = 8.4 Hz,
H-2), 2.62–2.44 (m, 2H, CH2-allyl), 2.07, 2.00 (2s, 6H,
2 · CH3); 13C NMR (75 MHz, CDCl3): d 170.3, 169.8
3
10. Isanbor, C.; O’Hagan, D. J. Fluorine Chem. 2006, 127,
303–319, and references cited therein.
11. Tozer, M. J.; Herpin, T. Tetrahedron 1996, 52, 8619–8683,
and references cited therein.
(2 · C@O), 128.9 (t, JC,F = 5 Hz, CH-allyl), 122.9 (t,
1JC,F = 248 Hz, CF2), 121.1 (CH2-allyl), 99.2 (t,
3
3JC,F = 6 Hz, C-1), 66.4 (C-4), 66.1 (t, JC,F = 4 Hz, C-
2
3), 61.2 (C-5), 56.4 (OCH3), 47.1 (t, JC,F = 22 Hz, C-
12. Burkholder, C. R.; Dolbier, W. R.; Medebielle, M. J.
Fluorine Chem. 2001, 109, 39–48, and references cited
therein.
13. Hein, M.; Miethchen, R. In Advances in Organic Synthesis,
Modern Organofluorine Chemistry—Synthetic Aspect;
Laali, K. K., Ed.; Bentham Science Publ. Ltd, 2006; Vol.
2, pp 381–430, and references cited therein.
14. Tews, S.; Miethchen, R.; Reinke, H. Synthesis 2003, 707–
716 (Erratum: Synthesis 2003, 1136) and references cited
therein.
15. Wegert, A.; Reinke, H.; Miethchen, R. Carbohydr. Res.
2004, 339, 1833–1837.
16. Huang, W.-Y. J. Fluorine Chem. 1992, 58, 1–8.
17. Plenkiewicz, H.; Dmowski, W.; Lipinski, M. J. Fluorine
Chem. 2001, 111, 227–232.
3
2), 41.7 (t, JC,F = 25 Hz, CH2-allyl), 20.9, 20.9
(2 · CH3); 19F NMR (235 MHz, CDCl3): d ꢀ97.6 (d,
2
2JFa,Fb = 258 Hz, Fa), ꢀ98.3 (d, JFa,Fb = 258 Hz, Fb).
Compound 27b: Rf = 0.45 (heptane/EtOAc, 3:1 v/v),
colourless syrup.
1H NMR (250 MHz, CDCl3): d 5.89–5.69 (m, 1H,
3
3
CH-allyl), 5.43 (dd, 1H, J2,3 = 12.0, J3,4 = 3.4 Hz,
H-3), 5.27–5.16 (m, 3H, CH2-allyl, H-4), 4.93 (d, 1H,
3
3J1,2 = 3.2 Hz, H-1), 3.91 (dd, 1H, J4,5a = 1.3,
3
2J5a,5b = 13.0 Hz, H-5a), 3.65 (dd, 1H, J4,5b = 2.0,
2J5a,5b = 13.0 Hz, H-5b), 3.36 (s, 3H, OCH3), 2.93–2.73
3
3
(m, 1H, J1,2 = 3.2, J2,3 = 12.0 Hz, H-2), 2.75–2.35
(m, 2H, CH2-allyl), 2.11, 1.98 (2s, 6H, 2 · CH3); 13C
NMR (75 MHz, CDCl3): d 170.4, 169.7 (2 · C@O),
18. Miethchen, R.; Hein, M.; Reinke, H. Eur. J. Org. Chem.
1998, 919–923.
19. Wegert, A. Dissertation, University of Rostock, 2006.
20. Constantino, V.; Fattorusso, E.; Imperatore, C.; Mang-
oni, A. Tetrahedron Lett. 2002, 43, 9047–9050.
21. Schrauzer, G. N. Inorg. Synth. 1968, 11, 61–70.
22. Arnone, A.; Bernardi, R.; Bravo, P.; Cardillo, R.; Ghir-
inghelli, D.; Cavicchio, G. J. Chem. Soc., Perkin Trans. 1
1991, 1887–1891.
23. Danishefsky, S. J.; DeNinno, S.; Lartey, P. J. Am. Chem.
Soc. 1987, 109, 2082–2089.
24. Toshima, K.; Ishizuka, T.; Matsuo, G.; Nakata, M.
Tetrahedron Lett. 1994, 35, 5673–5676.
3
1
129.1 (t, JC,F = 5 Hz, CH-allyl), 122.4 (t, JC,F
=
3
248 Hz, CF2), 120.5 (CH2-allyl), 97.8 (t, JC,F = 7 Hz,
C-1), 67.6 (C-4), 65.7 (t, JC,F = 4 Hz, C-3), 60.7 (C-5),
3
2
55.3 (OCH3), 45.0 (t, JC,F = 25 Hz, C-2), 40.0 (t,
3JC,F = 25 Hz, CH2-allyl), 20.9, 20.8 (2 · CH3); 19F
NMR (235 MHz, CDCl3): d ꢀ93.9 (d, 2JFa,Fb = 258 Hz,
2
Fa), ꢀ98.3 (d, JFa,Fb = 258 Hz, Fb).
Acknowledgements
25. Keck, G. E.; Yates, J. B. J. Am. Chem. Soc. 1982, 104,
5829–5831.
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The authors are grateful to Professor Dr. Manfred
Michalik (Leibniz-Institut fur Organische Katalyse
¨
Rostock) for recording the NMR spectra and, to
Claudia Vinke (Universita¨t Rostock) and Dominique
´
Harakat (Universite de Reims Champagne-Ardenne,
France) for technical assistance.
29. Yoshida, M.; Morinaga, Y.; Iyoda, M. J. Fluorine Chem.
1994, 68, 33–38.
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