Versatile syntheses of mono- or bis-allylhalothiol-carbonates of some alditol or sugar derivatives via cyclic thionocarbonates as intermediates

Article abstract of DOI:10.1016/j.carres.2009.11.018

We describe herein an extension of the halogenation of 1,2 or 1,3-diols via a cyclic thionocarbonate functionality by reaction with an allyl halide instead of methyl iodide, which is usually used. This investigation was successfully carried out under both conventional heating and microwave solvent-free conditions with some alditol, thioanhydroalditol, and aldose derivatives.

Full text of DOI:10.1016/j.carres.2009.11.018

Carbohydrate Research 345 (2010) 346–351
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Versatile syntheses of mono- or bis-allylhalothiol-carbonates of some alditol
or sugar derivatives via cyclic thionocarbonates as intermediates
*
Mohammed Benazza , Rami Kanso, Gilles Demailly
Laboratoire des Glucide UMR 6219-CNRS, Université de Picardie Jules Verne, 33 Rue Saint-Leu, 80039 Amiens Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
We describe herein an extension of the halogenation of 1,2 or 1,3-diols via a cyclic thionocarbonate func-
tionality by reaction with an allyl halide instead of methyl iodide, which is usually used. This investiga-
tion was successfully carried out under both conventional heating and microwave solvent-free conditions
with some alditol, thioanhydroalditol, and aldose derivatives.
Received 3 September 2009
Received in revised form 8 November 2009
Accepted 17 November 2009
Available online 20 November 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Halogenation
Cyclic thionocarbonate
Alditols
Sugars
Thiolane
Allylthiolcarbonate
1. Introduction
leading to the iodomethyl thionocarbonate derivative F (Path
3).15 On the other hand, when bis-cyclic thionocarbonates in linear
Halosugars and haloalditols are helpful intermediates in organic
synthesis.1,2 Some of them are also enzyme inhibitors3 or alkylat-
ing agents.4 As intermediates, we have shown in previous work
that some bis-halogenated alditols, for instance, efficiently gave
systems (alditols and linear aldoses) were used as a starting mate-
rial, we showed that reaction with S2ꢀ or Se2ꢀ ions led efficiently to
heterocyclization reactions (Scheme 1b).2b,13
More recently, we have been interested in investigating the
behavior of the cyclic thionocarbonate function when it reacts with
alkyl halides different from methyl iodide. The aim is to widen the
scope of these compounds with potential easy access to new hal-
othionocarbonate compounds for further development in organic
synthesis or biological fields. To the best of our knowledge, only
Vedejs and Wu, in 1974,16 have reported the reaction of isopropyl
iodide instead of methyl iodide with some vic-diol cyclic thiono-
both
a,x a,x
-diazido5 and -di-S-alkylalditols in good yields.6 On
the other hand, sulfur- or selenium-induced heterocyclizations oc-
curred spontaneously in all cases by reaction with sulfide or sele-
nide as binucleophilic ions, respectively.7 This methodology has
allowed us8 and others9 to readily accumulate thioheterocycles
as the starting materials in the synthesis of sulfonium-ion salacin-
ol10 analogues (glycosidase inhibitors).
The ring opening of vicinal cyclic thionocarbonate B (Scheme
1a) is widely used in the literature. When this occurs by nucleo-
philic attack without initial activation (Path 1), the substituted
compound C, with a free adjacent hydroxyl group, is obtained. Azi-
do, thiolate11, and more recently the cyanide ions12 have been
introduced efficiently. With halide ions as nucleophiles, a Schön-
berg rearrangement to a cyclic thiocarbonate takes place (E) (Path
2).14 This is due to the intramolecular ring closure of the thiolate
intermediate D. This well-known and interesting isomerization is
prevented when the sulfide atom undergoes simultaneous protec-
tion during the ring-opening process. The latter mechanism is usu-
ally encountered when methyl iodide is used as the alkyl halide,
carbonate. We showed in recent preliminary work that D-glucofu-
ranose derivative 1 (Scheme 2), gave, upon reaction with alkyl
halides RX, where R = allyl, propargyl, n-butyl or acetamido groups,
the corresponding alkylthiolcarbonates 2–5 in good yields. This
investigation was successfully carried out under both conventional
heating and microwave solvent-free conditions.17
Although, the haloalkylation of diols via cyclic thionocarbonate
intermediate is well known, its generalization to the use of a range
of alkyl halides different from methyl iodide, such as allyl bromide,
is of great interest, not the least because this would allow the sub-
sequent synthesis of a novel macrocyclic thionocarbonate (Scheme
3). In fact, compound 2, obtained in excellent yield (90%), was sub-
sequently thioetherified with allylthiol to lead to
a,x-diene 6 in
65% yield. The latter compound, when submitted to ring-closing
metathesis reaction with Grubbs second generation catalyst, gave
* Corresponding author. Tel.: +33 322827527; fax: +33 322827560.
E-mail address: mohammed.benazza@u-picardie.fr (M. Benazza).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.11.018

M. Benazza et al. / Carbohydrate Research 345 (2010) 346–351
347
a.
Substitution and isomerisation reactions
O
O
O
S
S-
X
R
I-
O
O C
MeS
O
O
Path 2
X = Br- or I-
C S+Me
I
-
R
R
R
O
D
F
E (Cyclic
: Iodomethanethiol
carbonate
thiolcarbonate)
Path 3 MeI
S
OH
R
(1)
OH
O
C
Path 1
- COS
(2)
OH
Nu
O
R
R
Nu -
A
B
C
(vic-diol)
(Cyclic
thionocarbonate)
b. Heterocyclization reaction
OH
R
O
O
S
O
O
S
S=
R
+
S
R
S
n' = 1, 2 or 3
n = 0, 1 or 2
OH
OH
HO
HO
OH
R = CH(SBn)2 or H
Scheme 1. Cyclic thionocarbonate ring-opening process and isomerization to cyclic thiolcarbonate.
free conditions. The bidirectional haloalkylthiolcarbonation takes
place successfully, and the bis-haloallylthiol derivatives 10 and
12 were obtained in acceptable yields (60% and 62%, respectively).
The erythro derivative 9 seems to be halogenated more quickly
than the ribo derivative 11 as only 10 min at 90 °C was needed
for completion (compared to 110 °C and 1 h with 11) under con-
ventional conditions. This is probably due to the bent conformation
of ribo configuration. However, when the reaction is done under
microwave conditions, only 10 min was needed to provide 12 in
60% yield.
O
O
S
X
O
RX
OAc
O
OAc
O
RS
O
O
O
O
O
1
2 :
(90%)
R = Allyle;
X = Br
3 : R = Propargyle; X = Br (72%)
4 :
(77%)
R = nBu; X = I
5 : R = Acetamide; X =I (88%)
Both compounds were characterized by signals in the 13C NMR
spectrum at 169.8 ppm and 169.1 ppm for carbonyl groups, and
2.2 ppm and 1.5 ppm for C-1,4 (in 10) and C-1,5 (in 12), and the
iodinated carbon atoms, respectively. It should be noted that when
the reaction occurred with 11 and allyl bromide instead of allyl
iodide, bromoalkylation led to a similar yield in bromo derivative
13 under close conditions (entry 3).
Scheme 2.
stereoselective access to a single 10-membered thionocarbonate 7
with the Z-configuration in good yield (75%). This initial interesting
result constitutes a new way for the stereoselective synthesis of
unsaturated glycoconjugate thiols (e.g., 8).
In an extension of this investigation, we showed that this halo-
alkylation also occurred with secondary–secondary vic-diol cyclic
thionocarbonates. The study was first undertaken with the known
2. Results and discussion
3,4-O-thionocarbonyl-D
-mannitol derivative 1420 (entry 4). With al-
In continuation of these studies, we report herein an extension
of the crucial haloalkylation step to other vicinal or 1,3-cyclic thi-
onocarbonate substrates including 9 and 11, alditol derivatives
that could be functionalized in a bidirectional manner (Table 1, en-
lyl iodide as the reagent, the haloallylation quickly gave the 3-iodo-
4-allylthiolcarbonate derivative 15 under microwave and solvent
conditions (65% yield at 250 W and only 10 min). Secondly, we stud-
ied the erythro thiolane 19 (entry 5) obtained from 18, which was in
turn accessed by deacetylation of the previously described thioan-
hydro sugar 172b (Scheme 4). A problem that could compromise this
haloallylation is the possible reaction of the endocyclic sulfur atom
with the allyl halide to give a sulfonium salt 21 (Scheme 5). Surpris-
ingly, the corresponding bromoallyl thiocarbonate derivative 20
(D,L-threo) was obtained in good yield (82%), without any by-prod-
ucts, regardless of the experimental conditions.
Although it was easy to identify 15 by NMR spectroscopy,
doubts persisted concerning the structure of 20, which could also
tries 1–3), the
thioanhydroalditol 19 (entries 5 and 6), and one example of 1,3 pri-
mary-secondary cyclic thionocarbonate 24 with the -xylo config-
D-manno compound 14 (entry 4), the meso-erythro
D
uration as the sugar derivative (entry 7). We submitted those
starting materials to the haloalkylation reaction with allyl halides
a (allyl iodide), b (allyl bromide), or c (allyl chloride).
The previously reported bis-cyclic thionocarbonates18,19 9, with
the erythro configuration (entry 1), and 11, with the ribo stereo-
chemistry (entry 2), were allowed to react with a large excess
(20 equiv) of allyl iodide under conventional heating and solvent-
S
S
S
Br
O
O
OAc
O
OAc
O
OH
O
OAc
S
O
O
S
O
S
O
SH HO
AllylBr
(i)
(ii)
1
O
O
O
O
O
75%
65%
O
O
O
O
2
7 (Z)
8
6
Scheme 3. Reagents: (i) allyl SH, NaH, DMSO/THF; (ii) Grubbs second generation.

348
M. Benazza et al. / Carbohydrate Research 345 (2010) 346–351
Table 1
Haloalkylation of alditol and sugar derivatives via 1,2 and 1,3-cyclic thionocarbonate or 1,2:3,4 and 1,2:4,5-bis-cyclic thionocarbonate
Entry
Substrate
RX (20 equiv)
t (°C)
Heat or
lW
Time
Product (yield)
O
S
O
S
O
I
I
O
1
O
S
O
S
O
O
10 (60%)
a
90
D
10 min
9 (Erythro)
O
O
S
I
S
S
S
O
O
O
O
I
O
2
O
OAc
OAc
a
D
120
120
1 h
12 : (62%)
11 (Ribo)
(60%)
W
10 min
O
O
S
Br
S
Br
O
O
3
OAc
3 h
120
120
D
13 : (65%)
11 (Ribo)
b
W
30 min
(60%)
S
I
O
O
O
O
S
O
O
O
O
O
O
O
4
Altro
O
a
a
14 (Manno)
150
150
D
5 h
15 (50%)
(65%)
W
10 min
O
S
O
S
S
O
S
S
Br
5
6
O
120
120
D
3 h
19 (Erythro)
20 (80%)
W
20 min
(82%)
O
S
O
Cl
19 (Erythro)
c
120
W
W
20 min
23 (40%)
O
S
O
O
S
O
Br
O
O
7
O
O
O
O
25
b
120
30 min
26 (80%)
W = 250 W microwave;
D = thermal heating; a = allyl; b = allyl Br; c = allyl Cl.
O
O
OR
AcO
Br
iii
i
S
S
S
OR
Br
OAc
16 (Erythro)
17 (R = Ac)
18 (R = H)
19
ii
Scheme 4. Synthesis of 2,3-thiocarbonylthioanhydroerythritol 19. Reagents and conditions: (i) 16 and 17 were previously described;2a (i) Na2S, 9H2O, DMSO, rt, 5 min; (ii)
MeONa, MeOH, rt; (iii) Im2CS, THF, 70 °C, 1 h.
correspond to thietane from possible ring contraction from sulfo-
nium salt intermediate S1 (Scheme 6, Path 1). The reason is that
the C-1,2 of 20 could have the same chemical shift as for C-1,2 of
thietane 22. In contrast, the chloro derivative analogue 23 obtained
in 40% yield with allyl chloride c had a thiolane form (entry 6). This
was proven in 13C NMR spectra by the signal with C-2 at 61.44 ppm
and two S-linked methylene signals at 36.92 for C-4 and 33.01 ppm
for C-1 carbon atoms. Consequently, compound 20 with C-4 at
37.03 and C-1 at 32.84 similar to 23, probably also had a thiolane
ring. It is interesting to note that no sulfonium-ion formation (e.g.,
S2) was detected by electrospray mass spectrometry in spite of the
use of a large excess of allyl halide reagents (Path 2). However, sul-

M. Benazza et al. / Carbohydrate Research 345 (2010) 346–351
349
O
Br
O
S
O
S
S
S+
S
+
S
O
O
Br-
O
Br
Br
19 (Meso)
20
21
Scheme 5.
4
1
O
S
3
2
O
4
3
S
O
S
path 1
d
+S
Br-
S
O
O
O
Br
Br
S
2
1
20
S1
22
path 2
O
d
O
O
O
S
S
path 3
S+
S2
S
S
S
O
O
Cl
23
Br
Br-
19 (Meso)
Scheme 6. Possible ring contraction of thiolane 20.
fonium formation could not be excluded, because the allyl groups
were likely removed by nucleophilic attack by bromide ion under
the drastic conditions used. Finally, we note that the two structures
of 20 and 23 were elucidated by high resolution mass spectrometry
as their sulfoxide forms, 20a and 23a, respectively (Fig. 1), after
unavoidable oxidation during the ionization process.
S
OH
O
O
O
HO
O
i
O
O
O
O
After the above-mentioned cases, we studied as a last example
24(D-Xylo)
25 (45%)
compound 25 (
D-xylo) with 1,3-cyclic thionocarbonate function,
which was synthesized from 1,2-O-isopropylidene-
D
-xylose 23 in
Scheme 7. Synthesis of 3,5-thiocarbonyl-1,2-O-isopropylidene-
Reagents and conditions: (i) Im2CS, THF, 70 °C, 1H.
D-xylose 24 and 25.
45% yield (Scheme 7). Subsequent bromoalkylation with allyl bro-
mide is also efficient because the corresponding allyl thiolcarbonte
26 is obtained in good yield (82%) (entry 7).
(2450 MHz) in conditions reported in Table 1. All chemical reagents
were purchased from Aldrich or Acros (France). Melting points were
determined with a Buchi 535 apparatus and are uncorrected. 1H and
13C NMR spectra were recorded in CDCl3 on a Bruker 300 WB spec-
trometer; chemical shifts are reported in d (ppm). All 13C NMR sig-
nals were assigned through C–H correlated HSQC spectra. TLC was
performed on Silica Gel 60 F254 230 mesh (E. Merck) with cyclohex-
ane–EtOAc as an eluent, and spots were detected by vanillin–H2SO4
reagent. Preparative column chromatography was performed using
230–400 mesh Merck silica gel (purchased from Aldrich). Optical
rotations were determined with Perkin–Elmer instruments, model
343 polarimeter (1 mL cell). Low resolution electrospray mass
spectra (ESI-MS) in the positive ion mode were obtained on a
Waters-Micromass ZQ quadripole instrument equipped with an
electrospray (Z-spray) ion source (Waters-Micromass, Manchester,
UK). High resolution electrospray experiments (ESI-HRMS) were
performed on a Waters-Micromass Q-TOF Ultima Global hybrid
quadrupole time-of-flight instrument, equipped with an electro-
spray (Z-spray) ion source (Waters-Micromass, Manchester, UK).
Finally, we found that in most cases, halogenation under micro-
wave conditions is unnecessary as the mono or dihalogenation reac-
tions occurred under conventional thermal conditions in quite
acceptable reaction times and yields. However, it was interesting to
show that the association of microwave with solvent-free conditions
was feasible even in a complicated case like a thiaheterocycle 19.
In conclusion, we have reported a new development of cyclic
thionocarbonate ring opening with an alkyl halide different from
the usually employed methyl iodide. This occurred under both con-
ventional thermal heating and lW, in solvent or under solvent-free
conditions. This offers an efficient and versatile method of intro-
ducing the three widely used halogen atoms chloride, bromide
and iodide, and allylthiolcarbonate function at 2 or 3-position. Fur-
ther developments of this reaction are highlighted in our ongoing
research program.
3. Experimental
3.1. General methods
3.2. General procedure for the preparation of halogenoalkyl-
thiolcarbonate
Syntheses under microwave irradiation were performed under
pressure conditions with a single-mode CEM Discover apparatus
Method A. Microwave conditions: A mixture of substrate and
alkyl halide was reacted under pressure and stirring in a pressur-
ized vial purchased from CEM Corporation, under solvent-free con-
ditions unless otherwise mentioned. Time and temperature are
reported in Table 1. In all microwave experiments, TLC was per-
formed every 10 min and the reaction was stopped after complete
disappearance of the starting material. The power and maximum
O
S
O
S
O
S
O
S
O
O
Cl
23a
Br
20a
Figure 1. Oxidized forms of 22 and 23 detected in ESI-HRMS determination.

350
M. Benazza et al. / Carbohydrate Research 345 (2010) 346–351
temperature were fixed under a pressure control system. Volatiles
were removed under pressure and the crude product was purified
by chromatography on silica gel with cyclohexane–EtOAc mixtures
as the eluent.
Method B. Thermal heating conditions: The substrate and alkyl
halide were reacted under pressure and stirred in a closed reactor
at the temperature indicated in Table 1. The crude product ob-
tained after concentration was purified by chromatography on sil-
ica gel with cyclohexane–EtOAc mixtures as the eluent.
3.6. 4-Allylthiocarbonyl-3-deoxy-3-iodo-1,2-5,6-di-O-isopropy-
lidene- -altritol (15)
D
Method A: Allyliodide(0.42 mL, 4.6 mmol)and1,2-5,6-O-disopro-
pylidene-3,4-thiocarbonyl-
-mannitol (14)20 (70 mg, 0.23 mmol)
D
were reacted under 250 W microwave irradiation, at 120 °C for
20 min. After concentration and flash chromatography (95:5 cyclo-
hexane–EtOAc), 15 was isolated as a yellow syrup (70 mg, 65%).
½
a 2D0 +25 (c 0.1; MeOH); Rf = 0.3 (95:5 cyclohexane–EtOAc); 13C
ꢁ
NMR (CDCl3, 75 MHz): d 169.9 (C@O), 132.7 (C-20), 118.7 (C-30),
110.1, 109.6 (each C (iPr)) 76.5 (C-4), 76.3 (C-5), 75.5 (C-2), 69.0 (C-
6), 65.8 (C-1), 34.8 (C-3), 34.1 (C-10), 26.6, 26.5, 25.6, 25.4 (CH3(iPr)).
1H NMR (CDCl3, 300 MHz): d 5.95–5.80 (m, 1H; H-20), 5.20 (2d,
J = 16.2, 10.0 Hz, 2H; H-30), 4.90 (t, J = 5.6 Hz, 1H; H-4), 4.55 (q,
J = 6.2 Hz, 1H; H-5), 4.25– 4.20 (m, 1H; H-3), 4.15– 4.00 (m, 3H; H-
1a, H-6a, H-2), 3.90– 3.70 (m, 2H; H-1b, H-6b), 3.50 (d; J = 6.9 Hz,
2H; H-10), 1.50 (s, 3H; CH3(iPr)), 1.40 (s, 3H; CH3(iPr)), 1.30 (s, 6H;
CH3(iPr)). HRMS calcd for C16H25INaO6S [(M+Na)+] 495.0314; found
495.0325.
3.3. 2,3-Di-O-allylthiocarbonyl-1,4-diiodo-1,4-di-deoxyerythritol
(10)
Method A: Allyl iodide (1 mL, 10.9 mmol) and 1,2,3,4-dithiono-
carbonyl-erythritol (9) (100 mg, 0.49 mmol) were reacted at
90 °C for 10 min. After concentration and flash chromatography
(95:5, cyclohexane–EtOAc), 10 was isolated as a yellow solid
(38 mg, 60%). Rf = 0.3 (95:5 cyclohexane–EtOAc); mp 68–71 °C;
13C NMR (CDCl3, 75 MHz): d 169.8 (C@O), 132.4 (C-20), 118.8 (C-
30), 74.9 (C-2, C-3), 34.1 (C-10), 2.2 (C-1, C-4). 1H NMR (CDCl3,
300 MHz): d 6.00–5.75 (m, 2H; H-20), 5.25 (2d, J = 15.7, 9.1 Hz,
4H; H-30), 5.10 (t, J = 2.9, 2H; H-2, H-3), 3.55 (d, J = 6.9 Hz, 4H; H-
10), 3.50 (dd, J = 3.2, 11.4 Hz, 2H; H-1b, H-4b), 3.25 (dd, J = 5.6,
11.4 Hz, 2H; H-1a, H-4a). HRMS calcd for C12H16I2NaO4S2
[(M+Na)+] 564.8477; found 564.8480.
3.7. 1,4-Thioanhydroerythritol (18)
1,4-Thioanhydroerythritol (18) was obtained by methanolysis
of 2,3-O-acetyl-1,4-thioanhydroerythritol (17) with MeONa in
MeOH at rt overnight. After concentration and flash chromatogra-
phy (2:3 cyclohexane–EtOAc), 18 was isolated as a white solid in
62% yield (115 mg). Rf = 0.3 (2:3 cyclohexane–EtOAc); mp 135–
137 °C; 13C NMR (D2O, 75 MHz): d 74.9 (C-2, C-3), 32.3 (C-1, C-4).
1H NMR (D2O, 300 MHz): d 4.70 (s, 2H; OH), 4.20–4.10 (m, 2H;
H-2, H-3), 2.90 (dd, J = 5.7, 11.0 Hz, 2H; H-1b, H-4b), 2.60 (dd,
J = 5.5, 11.1 Hz, 2H; H-1a, H-4a). HRMS calcd for C4H8NaO2S
[(M+Na)+] 143.0143; found 143.0140.
3.4. 3-O-Acetyl-2,4-di-O-allylthiocarbonyl-1,5-diiodo-1,5-di-
deoxyribitol (12)
Method A: Allyl iodide (0.66 mL, 7.2 mmol) and 11 (100 mg,
0.36 mmol) were reacted under 250 W microwave irradiation, at
120 °C for 20 min. After concentration and flash chromatography
(95:5 cyclohexane–EtOAc), 12 was isolated as a yellow syrup
(137 mg, 62%).
Method B: Allyl iodide (1.98 mL, 21.6 mmol) and 11 (300 mg,
1.08 mmol) were reacted at 120 °C in a closed reactor for 1 h to
give the desired product 12 in a 60% yield. Rf = 0.3 (95:5 cyclohex-
ane–EtOAc); 13C NMR (CDCl3, 75 MHz): d 170.1, 169.1 (C@O), 132.4
(C-70), 118.8 (C-80), 74.0 (C-2, C-4), 73.0 (C-3); 34.1 (C-60), 20.8
(CH3), 1.5 (C-1, C-5). 1H NMR (CDCl3, 300 MHz): d 5.90–5.75 (m,
2H; H-7, H-70), 5.30 (d, J = 1.3 Hz, 1H; H-3), 5.25–5.10 (m, 6H; H-
2, H-4, H-80), 3.54 (d, J = 6.9 Hz, 4H; H-60), 3.45 (dd, J = 3.9,
11.3 Hz, 2H; H-1b, H-5b), 3.25 (dd, J = 7.6, 11.3 Hz, 2H; H-1a, H-
5a), 2.1 (s, 3H; C(O)CH3). HRMS calcd for C15H20I2NaO6S2
[(M+Na)+] 636.8688; found 636.8687.
3.8. 1,4-Thioanhydro-2,3-thionocarbonylerythritol (19)
Compound 18 (400 mg, 3.34 mmol) and Im2CS (712 mg,
4 mmol) were reacted in THF (10 mL) for 1 h at 50 °C. The desired
product 19, produced as a white solid after purification by flash
chromatography (3:2 cyclohexane–EtOAc). Rf = 0.3 (2:3 cyclohex-
ane–EtOAc); mp 155 °C; 13C NMR (DMSO-d6, 75 MHz): d 191.1
(C@S), 88.7 (C-2, C-3), 38.4 (C-1, C-4). 1H NMR (DMSO-d6,
300 MHz): d 5.70 (m, 2H; H-2, H-3), 3.20–3.10 (m, 2H; H-1b, H-
4b), 2.90–2.10 (m, 2H; H-1a, H-4a). HRMS calcd for C5H6NaO2S2
[(M+Na)+] 184.9707; found 184.9713.
3.5. 3-O-Acetyl-2,4-di-O-allylthiocarbonyl-1,5-dibromo-1,5-di-
3.9. 2-Bromo-2-deoxy-3-O-allylthiocarbonyl-1,4-thioanhydro-
deoxyribitol (13)
D,L
-threitol (20)
Method A: Allyl bromide (1.26 mL, 14.4 mmol) and 3-O-acetyl-
1,2:4,5-dithionocarbonylribitol (11)3 (200 mg, 0.72 mmol) were
reacted under 250 W microwave irradiation at 120 °C for 30 min.
After concentration and flash chromatography (6:1 cyclohexane–
EtOAc), 13 was isolated as a yellow syrup (243 mg, 65%).
Method B: Allyl bromide (0.63 mL, 7.2 mmol) and 11 (100 mg,
0.36 mmol) were reacted at 120 °C in a closed reactor for 3 h to
give the desired product 13 in a 60% yield. Rf = 0.3 (6:1 cyclohex-
ane–EtOAc); 13C NMR (CDCl3, 75 MHz): d 170.1, 169.0 (C@O),
132.4 (C-70), 118.8 (C-80), 73.1 (C-2, C-4), 71.4 (C-3), 34.0 (C-60),
29.7 (C-1, C-5), 20.7 (CH3). 1H NMR (CDCl3, 300 MHz): d 5.90–
5.75 (m, 2H; H-70), 5.40–5.10 (m, 7H; H-2, H-3, H-4, H-80), 3.60
(dd, J = 3.5, 11.5 Hz, 2H; H-1b, H-5b), 3.50 (d, J = 6.9 Hz, 4H; H-
60), 3.48 (dd, J = 7.2, 11.5 Hz, 2H; H-1a, H-5a), 2.10 (s, 3H;
C(O)CH3). HRMS calcd for C15H20Br2NaO6S2 [(M+Na)+] 542.8945;
found 542.8895.
Method A: Allyl bromide (1.82 mL, 24.7 mmol) and 19 (200 mg,
1.23 mmol) were reacted under 250 W microwave irradiation, at
120 °C for 30 min. After concentration and flash chromatography
(98:2, cyclohexane–EtOAc), 20 was isolated as a yellow syrup in
82% yield (286 mg).
Method B: Allyl bromide (1.82 mL, 24.7 mmol) and 19 (200 mg,
1.23 mmol) were reacted at 120 °C in a closed reactor for 3 h to
give the desired product 20 in 80% yield. Rf = 0.3 (98:2 cyclohex-
ane–EtOAc); 13C NMR (CDCl3, 75 MHz): d 169.7 (C@O), 132.4 (C-
20), 118.5 (C-30), 83.2 (C-3), 50.8 (C-2), 37.0 (C-4), 33.8 (C-10),
1
32.8 (C-1). H NMR (CDCl3, 300 MHz): d 5.90–5.75 (m, 1H; H-20),
5.50–5.45 (m, 1H; H-3), 5.10 (2d, J = 11.0, 15.6 Hz, 2H; H-30), 4.50
(q, J = 3.8 Hz, 1H; H-2), 3.50–3.30 (m, 3H; H-1b, H-4b, H-10), 3.10
(dd, J = 3.8, 12.4 Hz, 1H; H-1a), 2.90 (dd, J = 2.9, 12.0 Hz, 1H; H-
4a). HRMS calcd for C8H1179BrNaO3S2 [(M+O+Na)+] 320.9231;
found 320.9234.

M. Benazza et al. / Carbohydrate Research 345 (2010) 346–351
351
3.10. 2-Chloro-2-deoxy-3-O-allylthiocarbonyl-1,4-thioanhydro-
Acknowledgments
D
,L-threitol (22)
We thank the Conseil Régional de Picardie and le Fonds Social
Européen for their financial support.
Method A: Allyl chloride (1.0 mL, 12.3 mmol) and 19 (100 mg,
0.62 mmol) were reacted under 250 W microwave irradiation, at
120 °C for 40 min. After concentration and flash chromatography
(98:2 cyclohexane–EtOAc), 23 was isolated as a colorless syrup
(58 mg, 40%). Rf = 0.3 (98:2 cyclohexane–EtOAc); 13C NMR (CDCl3,
75 MHz): d 170.0 (C@O), 132.6 (C-20), 118.8 (C-30), 83.0 (C-3), 61.4
(C-2), 36.9 (C-4), 34.1 (C-10), 33.0 (C-1). 1H NMR (CDCl3, 300 MHz):
d 5.90–5.80 (m, 1H; H-20), 5.50–5.45 (m, 1H; H-3), 5.20 (2d,
J = 10.1, 16.2 Hz, 2H; H-30), 4.50 (q, J = 3.5 Hz, 1H; H-2), 3.50 (d,
J = 6.2 Hz, 1H; H-10), 3.45–3.50 (m, 2H; H-1b, H-4b), 3.05 (dd,
J = 3.3, 12.2 Hz, 1H; H-1a), 2.95 (dd, J = 2.7, 12.3 Hz, 1H; H-4a). HRMS
calcd for C8H1135ClNaO3S2 [(M+O+Na)+] 276.9736; found 276.9740.
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Method A: A mixture of 25 (200 mg, 0.86 mmol) and allyl bromide
(1.5 mL, 17.24 mmol) were reacted under 250 W microwave irradi-
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ꢀ36 (c 0.1; CHCl3); Rf = 0.32 (95:5 cyclo-
ꢁ
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