Ruthenium-catalyzed cross-metathesis with electron-rich phenyl vinyl sulfide enables access to 2,3-dideoxy-d-ribopyranose ring system donors

Article abstract of DOI:10.1039/c4ra01668h

2,3-Dideoxy-d-ribopyranose units are important ring systems found in nature. Herein, we develop a metal-mediated strategy to form this important scaffold featuring a cross-metathesis reaction of the corresponding sugar-derived hydroxyalkene with electron-

Full text of DOI:10.1039/c4ra01668h

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Ruthenium-catalyzed cross-metathesis with
electron-rich phenyl vinyl sulfide enables access to
2,3-dideoxy-D-ribopyranose ring system donors†
Cite this: RSC Adv., 2014, 4, 19794
Received 25th February 2014
Accepted 15th April 2014
*
Omar Boutureira, M. Isabel Matheu, Yolanda Dıaz and Sergio Castillon
´
´
DOI: 10.1039/c4ra01668h
www.rsc.org/advances
2,3-Dideoxy-D-ribopyranose units are important ring systems found in functional groups that were originally detrimental for a
nature. Herein, we develop a metal-mediated strategy to form this productive reaction.10 For example, by using allyl chalcogens11
important scaffold featuring a cross-metathesis reaction of the cor- as “forbidden”-atom-containing reactive handles, new and
responding sugar-derived hydroxyalkene with electron-rich phenyl exciting applications such as chemical protein modications
vinyl sulfide using commercially available ruthenium-catalysts under are now accessible,12 hence representing the renaissance of
microwave irradiation as a key step. The final 2,3-dideoxyhexopyr- such groups in catalysis. However, despite all this progress, CM
anose ring is generated in a single step upon 6-endo electrophilic reactions with electron-rich vinyl olens13 remains an under-
cyclization.
represented area of olen metathesis when compared to other
twin systems such as ring-opening cross-metathesis (ROCM),14
ring-closing metathesis (RCM)15 and enyne cross-metathesis
(EYCM).16 To the best of our knowledge, only a few examples of
Ru-CM reactions involving electron-rich vinyl suldes with
model vinyl chlorides17 and silanes18 have been described to
date, yet the use of such procedures for the preparation of more
advanced, synthetically challenging systems remains largely
unexplored. This reduced and sometimes non-existent reac-
tivity has been attributed to the formation of relatively unreac-
tive Fischer carbenes, which either rapidly decompose or fail to
react further.19 These ndings encouraged us to demonstrate
that this particularly challenging transformation can be applied
to the construction of an important 2,3-dideoxyhexopyranosyl
ring system. Thus, a exible strategy was envisaged starting
from 2-deoxy-D-ribofuranose and featuring a CM reaction of the
corresponding sugar-derived hydroxyalkene with electron-rich
Introduction
2,3-Dideoxy- and 2,3,6-trideoxyhexoses are carbohydrate ring
systems found in a variety of natural products.1 These structures
are primary constituents of the oligosaccharide side chains of
various antibiotics such as kigamicins,2 landomycins,3 urda-
mycins3,4 and amicetin,5 among others. Moreover, synthetic 2,3-
dideoxy-D-ribopyranosyl nucleoside antibiotics have shown
promising antitumor and antiviral activities and also constitute
the repeating unit of unnatural hexopyranosyl-(60 / 40)-oligo-
nucleotide systems6 (Fig. 1).
Previous strategies for the preparation of such structures are
mainly limited to classical carbohydrate methods (from D-glu-
cal), which typically suffer from long linear and operationally
tedious sequences.1,7 Metal-mediated protocols have recently
emerged as attractive alternatives because they enable
straightforward access to key sugar intermediates and rare
building blocks using a reduced number of steps.8 As such,
olen cross-metathesis (CM) represents a versatile, powerful
metal-mediated C–C bond forming process for the construction
of complex carbohydrate-based products.9 A number of novel
applications have become possible due to major advances in
catalyst design that led to high yielding transformations, under
mild conditions and remarkably, in the presence of a variety of
´
´
´
`
Departament de Quımica Analıtica i Quımica Organica, Universitat Rovira i Virgili,
´
C/Marcel$lı Domingo s/n, 43007 Tarragona, Spain. E-mail: omar.boutureira@urv.
cat; Fax: +34 977558446; Tel: +34 977558288
† Electronic supplementary information (ESI) available: Copies of 1H and 13C
Fig.
1 Representative examples of compounds containing 2,3-
NMR spectra for compounds 3, 6, 9c and 11. See DOI: 10.1039/c4ra01668h
dideoxy- and 2,3,6-trideoxyhexose ring systems.
19794 | RSC Adv., 2014, 4, 19794–19799
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Table
1
Optimization of the microwave-assisted CM reaction
phenyl vinyl sulde using commercially available Ru-catalysts
under microwave (MW) irradiation as a key step (Scheme 1).
Indeed, this transformation will enable the concise synthesis
of key 3-deoxysulfanyl alkene intermediate 3 from readily
available starting materials that will be further elaborated to
the expected 2,3-dideoxy ring system donors 11 (a ready-to-use
1-thioglycosyl donor) and 12 in very few steps.
conditions of 2 with electron-rich phenyl vinyl sulfidea
Results and discussion
The rst step of the proposed route involves a ve-to-six carbon
homologation of 2-deoxy-D-ribofuranose 1 to afford 2 using a
reported Wittig olenation.20 We next focused on the synthesis
of 3-deoxysulfanyl alkene intermediate 3 using the aforemen-
tioned CM of 2-deoxysugar hydroxyalkene 2 and phenyl vinyl
sulde as a key step (Table 1).
Distributionb (%)
Catalyst
T
t
Z/E
Entry (mol%) Solvent (ꢀC) (h)
2
3
ratiob of 3
1c
2c
3c
4d
5
6
7
8
9
4 (20)
5 (20)
4 (20)
4 (20)
4 (20)
4 (20)
4 (10)
4 (20)f
7 (20)
7 (20)
7 (20)
CH2Cl2
40 20 100
PhCH3 110 17 100
—
—
37
—
—
1 : 1
PhCH3 110 20
63
To select the most suitable catalyst and reaction conditions,
initial investigations were carried out under thermal heating
using catalysts 4 and 5 (entries 1–3). Reactions in reuxing
CH2Cl2 with 4 or toluene with 5 failed to generate any CM
product (entries 1 and 2). Fortunately, even though the reaction
did not reach complete conversion aer 20 h in reuxing
toluene, the coupled product was obtained in 37% yield and
1 : 1 Z/E ratio (entry 3) using 4. With the above results in hand,
we carried out additional experiments under MW irradiation to
shorten the prolonged reaction time and elevated temperature
necessary for these CM reactions, which usually leads to
thermal degradation of the ruthenium catalysts.21 Despite its
widespread application in catalytic reactions, microwave-assis-
ted metathesis reactions have only recently gained increasing
popularity.22 In particular, recent reports of dramatic improve-
ments in reaction rates and yields in challenging CM reactions
provided by MW irradiation23 prompted us to explore this
avenue (entries 4–11). MW irradiation with readily available Ru-
catalyst 4 improved the yield (up to 50%) while impressively
reducing the reaction time from 20 to 1 h. Since prolonged
reaction times did not increased the conversion, we found that
the crude can be puried and subjected to another round of
metathesis to nally increase the isolated yield up to 80% (entry
4). Indeed, results from entries 4–6 suggest that the reaction
PhCH3 150
PhCH3 110
PhCH3 120
PhCH3 120
PhCH3 175
PhCH3 150
1
4
2
1
2
1
1
2
50
50(80)e 1 : 1
93
7
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 2
80
90
20
10
37
18
30
5
53g
54g
60g
20
10
DCB
DCB
200
200
11h
a
General conditions: a solution of phenyl vinyl sulde (5 equiv.), catalyst
(20 mol%) and 2 (1 equiv.) in dry and degassed solvent (0.5 M) was
microwave irradiated in a sealed tube using a CEM-Discover™ single-
mode synthesizer (temperature control using an external surface
sensor, xed hold time off, normal absorption mode) unless otherwise
indicated. Determined by 1H NMR. Thermal heating under open
b
c
d
vessel reux conditions. Prolonged reaction times did not increased
e
the conversion. Isolated yield aer two consecutive reaction cycles
f
(see Experimental section for details). Added in two portions.
g
Variable amounts of isomerization byproduct 6 (10–28% and 1 : 5
Z/E ratio) were also detected. 2,6-Dichloro-1,4-benzoquinone (10 mol
%) was added as an additive. DCB ¼ 1,2-dichlorobenzene.
h
more determinant factor in microwave-assisted CM reactions
between 2 and phenyl vinyl sulde.24 Because no decomposition
of starting material was observed in any case, the formation of 3
seems to be only dependent on the catalytically active ruthe-
nium species, which is also reected in the correlation of yield
with the relative amount of the employed ruthenium complex 4
(entries 6 and 7). However, it is worth noting that a reaction
temperature higher than 150 ꢀC did not always lead to a higher
conversion. Thus, raising the temperature to 175 ꢀC resulted in
a decreased yield (37%), most likely due to catalyst decompo-
sition as well as to the formation of 10% of isomerized
byproduct 6. In addition, no signicant improvement in the
conversion was observed when catalyst 4 was added in two
portions separated by a 1 h period (entry 8). We next investi-
gated the reactivity of Hoveyda–Grubbs catalyst 7. The reaction
in toluene afforded 18% conversion to CM product 3 and 10% to
isomerized 6 (entry 9). Interestingly, by changing the solvent
from toluene to 1,2-dichlorobenzene (DCB) and increasing the
temperature from 150 to 200 ꢀC, the conversion increased from
18 to 30%. Furthermore, this change in the solvent properties
ꢀ
temperature (110–150 C) reached in the reaction vessel is the
Scheme 1 Proposed strategy for the preparation of 2,3-dideoxy-D-
ribopyranose ring system donors 11 and 12 using a CM reaction with
electron-rich phenyl vinyl sulfide as a key step.
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resulted in a reduction of 6 from 28 to 10% (entry 10). Repeating
the reaction using 2,6-dichloro-1,4-benzoquinone (10 mol%) as
an additive to prevent olen isomerization25,26 led only to the
CM product in 5% conversion and 1 : 2 Z/E ratio, although this
may be a reection of incompatibility of either 2 or phenyl vinyl
sulde with the additive (entry 11).
Collectively, the above observations suggest that the forma-
tion of Fischer-type carbenes during the Ru-catalyzed CM
reactions between electron-rich phenyl vinyl sulde and
terminal 2-deoxysugar hydroxyalkene 2 decreases productive
CM drastically, although good conversions (up to 80%) are still
achieved using a 40 mol% of catalyst loading. The higher
Scheme 3 Electrophilic cyclizations of 3 and synthesis of represen-
tative glycosyl donors 11 and 12.
Conclusions
concentration of reactive phenyl vinyl sulde olen causes less In summary, we have demonstrated that the particularly chal-
interaction between the catalyst and the hydroxyalkene, lenging CM of a 2-deoxysugar hydroxyl alkene with electron-rich
reducing the formation of active vinylalkylidene species and phenyl vinyl sulde using readily available Ru-catalysts as a key
necessitating higher temperatures in order to achieve signi- step can be applied to the construction of 2,3-dideoxy-D-ribo-
cant conversion. Importantly, this elevated concentrations are pyranose ring system donors and analogs. MW irradiation
otherwise required since the stepwise addition of increasing allows the required high reaction temperature to be reached
amounts of phenyl vinyl sulde showed the incipient detection quickly and homogeneously, thereby providing enough energy
of small amounts of undesired dimerization byproducts.
The substrate scope was expanded next using alkenols 8a–c
with phenyl vinyl sulde as electron-rich olen partner under
optimized reaction conditions (Scheme 2). Despite the expected
for a successful metathesis reaction.
Experimental section
negative outcome observed with allyl alcohol, due to the known Proton (1H NMR) and carbon (13C NMR) nuclear magnetic
isomerization process previously shown in this type of resonance spectra were recorded on a (400 MHz for 1H) and
compounds and their ether counterparts with both rst and (100.6 MHz for 13C) spectrometer. Spectra were fully assigned
second Grubbs catalysts,27 cross-metathesis products 9b,c using COSY, HSQC, HMBC and NOESY. All chemical shis are
where pleasingly obtained in good yields (up to 66% aer three quoted on the d scale in ppm using residual solvent as the
reaction cycles) and 1 : 1 Z/E ratio.
internal standard (1H NMR: CDCl3 ¼ 7.26, CD3OD ¼ 4.87; and
Additional experiments with phenyl vinyl selenide as elec- 13C NMR: CDCl3 ¼ 77.23; CD3OD ¼ 49.0). Coupling constants (J)
tron-rich olen partner to afford selanyl alkenes28 with the are reported in Hz with the following splitting abbreviations: s
ultimate goal of developing the corresponding selenoglycosyl ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, quin ¼ quintet
donors proved unsuccessful.
and app ¼ apparent. Infrared (IR) spectra were recorded on a
Having established a exible method for accessing workable Jasco FT/IR-600 Plus ATR Specac Golden Gate spectrophotom-
amounts of acyclic hexosulfanyl alkene 3, we next demonstrated eter. Absorption maxima (nmax) are reported in wavenumbers
that this intermediate is able to generate a hexopyranose ring (cmꢁ1). Elemental analyses (C, H, N, and S) were performed with
system, in a single step, upon 6-endo electrophilic cyclization29 a Carlo Erba EA 1108 Analyzer in the Servei de Recursos
´
(Scheme 3). Thus, NIS- or NBS-induced 6-endo cyclization Cientıcs (URV). Optical rotations were recorded on a Perkin-
ꢀ
afforded intermediates 10a,b in moderate yields (up to 56%) Elmer 241 MC polarimeter in a 1 dm cell at 20 C. Concentra-
and 1 : 1 epimeric mixtures at both C-1 and C-2 (for 10a) that tions (c) are given in g per 100 mL. Gas chromatography-mass
were subsequently transformed into 1-thioglycosyl donor 11 spectrometry (GC-MS) was measured on an Agilent 9575C MSD
(88% from 10b) and 3-deoxyglycal 12 (71% from 10a) aer C– apparatus with electronic impact ionization (EI, 70 eV). High
halogen reduction.30 These results reinforce the strategic char- resolution mass spectra (HRMS) were recorded on a Waters LCT
acter of 3 since these privileged D-hexopyranose building blocks Premier liquid chromatograph coupled time-of-ight mass
are obtained from a single precursor and, for example, they can spectrometer (HPLC-MS-TOF) with either electrospray ioniza-
be used for the stereoselective synthesis of naturally occurring tion (ESI) or atmospheric pressure chemical ionization (APCI)
2,3,6-trideoxy (D-amicetose)-containing oligosaccharides1,7 and by the ICIQ MS unit. Nominal and exact m/z values are reported
other challenging structures such as marine ladder toxins.31
in Daltons. Thin layer chromatography (TLC) was carried out
using commercial aluminium backed sheets coated with 60F254
silica gel. Visualization of the silica plates was achieved using a
UV lamp (lmax ¼ 254 nm) and/or 6% H2SO4 in EtOH and/or 2%
PdCl2 and 15% H2SO4 in water. Flash column chromatography
was carried out using silica gel 60 (40–63 mm). Radial chroma-
tography was performed on 1, 2, or 4 mm plates of Kieselgel 60
PF254 silica gel, depending on the amount of product. Mobile
phases are reported in relative composition (e.g. 1 : 1 EtOAc–
hexane v/v). All other reagents and anhydrous solvents
a
b
Scheme 2 Reaction scope. The starting material decomposed.
Isolated yield after three consecutive reaction cycles (60 mol% of
catalyst loading in total) and 1 : 1 Z/E ratio.
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(Analytical or HPLC grade) were used as received from 1H); 13C NMR (100.6 MHz, CDCl3) d 136.1–126.7, 125.0, 62.0,
1
commercial suppliers. All reactions using anhydrous conditions 32.9. Data for 9bZ: H NMR (400 MHz, CDCl3) d 7.38–7.17 (m,
were performed using ame-dried apparatus under an atmo- 5H), 6.37 (dd, J ¼ 9.3 and 1.6 Hz, 1H), 5.86 (dt, J ¼ 9.3 and 7.4,
sphere of argon.
1H), 3.77 (bt, J ¼ 6.2 Hz, 2H), 2.55 (ddd, J ¼ 14.0, 6.2 and 1.6 Hz,
2H), 1.46 (bs, 1H); 13C NMR (100.6 MHz, CDCl3) d 136.1–126.7,
126.3, 62.1, 36.6. Spectroscopic data are consistent with those
reported.32
(Z/E)-4,6-Di-O-benzyl-1,2,3-trideoxy-1-phenylsulfanyl-D-
erythro-hex-1-enitol (3)
A solution of 2 (ref. 20) (40 mg, 0.13 mmol), phenyl vinyl sulde
(86 mL, 0.64 mmol) and catalyst 4 (22 mg, 20 mol%) in dry and
(Z/E)-10-Phenylsulfanyl-9-decen-1-ol (9c)
degassed toluene (256 mL) was microwave irradiated in a sealed A solution of 9-decen-1-ol 9c (37.2 mg, 0.23 mmol), phenyl vinyl
ꢀ
tube at 150 C for 1 h (temperature control using an external sulde (156 mL, 1.15 mmol) and catalyst 4 (39 mg, 20 mol%) in
surface sensor, xed hold time off, normal absorption mode) dry and degassed toluene (462 mL) was microwave irradiated in
ꢀ
using a CEM-Discover™ single-mode synthesizer. The residue a sealed tube at 150 C for 1 h (temperature control using an
was ltered through a short path of silica (1 : 1 EtOAc–petrol) external surface sensor, xed hold time off, normal absorption
and the solvent evaporated. The crude was subsequently sub- mode) using a CEM-Discover™ single-mode synthesizer. The
jected to a second round of the initial reaction conditions (two residue was ltered through a short path of silica (1 : 1 EtOAc–
reaction cycles in total). The solvent was then evaporated and petrol) and the solvent evaporated. The crude was subsequently
the crude product was puried by radial chromatography (from subjected to a second round of the initial reaction conditions
hexane to 1 : 3 EtOAc–hexane) to afford 3 (32 mg, 80%) as an (this protocol was repeated up to three reaction cycles in total).
inseparable 1 : 1 Z/E mixture as a colourless syrup. Rf (1 : 4 The solvent was then evaporated and the crude product was
EtOAc–hexane): 0.28. Data for 3E: 1H NMR (400 MHz, CDCl3) d puried by column chromatography (1 : 3 EtOAc–hexane) to
7.36–7.25 (m, 15H), 6.24 (d, J ¼ 15.0 Hz, 1H), 6.00 (ddd, J ¼ 15.0, afford 9c (40.2 mg, 66%) as an inseparable 1 : 1 Z/E mixture as a
7.5 and 7.5 Hz, 1H), 4.67–4.49 (m, 4H), 3.87–3.84 (m, 1H), 3.70– brownish syrup. Rf (1 : 3 EtOAc–hexane): 0.28; IR (ATR) nmax
/
3.53 (m, 3H), 2.66–2.64 (m, 1H), 2.54–2.43 (m, 1H), 2.44 (d, J ¼ cmꢁ1 3364, 3074, 2925, 2853, 1709, 1584, 1479, 1439, 1361,
5.2 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) d 138.4–124.5, 128.6, 1220, 1054, 949, 909, 737; HRMS (ESI) m/z calcd for C16H24NaOS
125.4, 79.0, 73.6, 72.3, 71.5, 71.2, 34.1. Data for 3Z: 1H NMR (400 [M + Na]+ 287.1414, found 287.1435. Data for 9cE: 1H NMR (400
MHz, CDCl3) d 7.36–7.25 (m, 15H), 6.31 (d, J ¼ 11.0 Hz, 1H), 5.94 MHz, CDCl3) d 7.36–7.17 (m, 5H), 6.14 (dd, J ¼ 14.8 and 1.2 Hz,
(ddd, J ¼ 11.0, 7.2 and 7.2 Hz, 1H), 4.67–4.49 (m, 4H), 3.89–3.86 1H), 6.01 (dt, J ¼ 14.8 and 7.0 Hz, 1H), 3.69–3.62 (m, 2H), 2.17
(m, 1H), 3.70–3.53 (m, 3H), 2.66–2.64 (m, 1H), 2.54–2.43 (m, (ddd, J ¼ 14.4, 7.0 and 1.2 Hz, 2H), 1.60–1.23 (m, 12H); 13C NMR
1H), 2.49 (d, J ¼ 4.8 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) d (100.6 MHz, CDCl3) d 137.9–126.2, 120.9, 63.3, 33.3–25.9. Data
138.3–124.2, 128.5, 125.4, 78.8, 73.6, 72.5, 71.7, 71.1, 30.0. for 9cZ: 1H NMR (400 MHz, CDCl3) d 7.36–7.17 (m, 5H), 6.20 (dd,
Spectroscopic data are consistent with those reported.29
J ¼ 9.3 and 1.6 Hz, 1H), 5.83 (dt, J ¼ 9.3 and 7.4, 1H), 3.69–3.62
(m, 2H), 2.26 (ddd, J ¼ 14.4, 7.4 and 1.6 Hz, 2H), 1.60–1.23 (m,
12H); 13C NMR (100.6 MHz, CDCl3) d 136.8–126.2, 122.8, 63.3,
33.3–25.9.
(Z/E)-4-Phenylsulfanyl-3-buten-1-ol (9b)
A solution of 3-buten-1-ol 8b (17 mg, 0.23 mmol), phenyl vinyl
sulde (156 mL, 1.15 mmol) and catalyst 4 (39 mg, 20 mol%) in
dry and degassed toluene (462 mL) was microwave irradiated in
Phenyl 4,6-di-O-benzyl-2,3-dideoxy-2-iodo-1-thio-a/b-D-
arabino/ribo-hexopyranoside (10a)
ꢀ
a sealed tube at 150 C for 1 h (temperature control using an
external surface sensor, xed hold time off, normal absorption NIS (164.1 mg, 0.67 mmol) was added to a solution of 3 (1 : 1 Z/
ꢀ
mode) using a CEM-Discover™ single-mode synthesizer. The E) (180 mg, 0.43 mmol) in dry CH3CN (3.5 mL) at ꢁ30 C and
residue was ltered through a short path of silica (1 : 1 EtOAc– stirred for 0.5 h. The mixture was diluted with CH2Cl2 and
petrol) and the solvent evaporated. The crude was subsequently washed with saturated aqueous Na2S2O3. The combined organic
subjected to a second round of the initial reaction conditions layers were dried over MgSO4, ltered and concentrated. The
(this protocol was repeated up to three reaction cycles in total). residue was puried by radial chromatography (from hexane to
The solvent was then evaporated and the crude product was 1 : 3 EtOAc–hexane) to afford 10a (130 mg, 56%) as a 1 : 1 a/b
puried by column chromatography (1 : 3 EtOAc–hexane) to mixture and 1 : 1 ax/eq. mixture at C-2 (arabino/ribo) as a
1
afford 9b (25 mg, 60%) as an inseparable 1 : 1 Z/E mixture as a yellowish syrup. Selected data for ribo-10a: H NMR (400 MHz,
brownish syrup. Rf (1 : 3 EtOAc–hexane): 0.17; IR (ATR) nmax
/
CDCl3) d 7.36–7.19 (m, 15H), 4.83 (dd, J ¼ 9.9 and 5.1 Hz, 1H),
cmꢁ1 3345, 3259, 3056, 2923, 2853, 1749, 1583, 1479, 1439, 4.82 (dd, J ¼ 10.0 and 4.4 Hz, 1H), 4.22 (m, 1H), 3.86 (ddd, J ¼
1240, 1047, 741; MS (EI, 70 eV) m/z (%) 180.1 (52) [M]+, 149.1 13.0, 9.5 and 4.4 Hz, 1H), 3.69 (m, 2H), 3.66 (m, 2H), 3.49 (dt, J ¼
(100), 134.1 (35), 116.1 (61), 109.1 (13), 103.1 (3), 91.1 (4), 85.0 10.8 and 4.8 Hz, 1H), 3.45 (ddd, J ¼ 10.4, 9.5 and 4.4 Hz, 1H),
(4), 77.1 (12), 71.0 (6), 65.1 (9), 51.0 (10); HRMS (APCI) m/z calcd 2.85 (dt, J ¼ 12.8 and 4.4 Hz, 1H), 2.60 (dt, J ¼ 12.2 and 4.7 Hz,
for C10H13OS [M + H]+ 181.0682, found 181.0683. Data for 9bE: 1H), 2.45 (dt, J ¼ 13.2 and 9.8 Hz, 1H), 2.10 (ddd, J ¼ 13.0, 12.8
1H NMR (400 MHz, CDCl3) d 7.38–7.17 (m, 5H), 6.29 (dd, J ¼ 15.2 and 10 Hz, 1H); 13C NMR (100.6 MHz, CDCl3) d 138.4–124.2,
and 1.6 Hz, 1H), 5.92 (dt, J ¼ 15.2 and 7.4 Hz, 1H), 3.72 (bt, J ¼ 99.2, 92.1, 79.0–53.6, 41.7, 35.9, 25.7, 22.6. Selected data for
1
6.2 Hz, 2H), 2.44 (ddd, J ¼ 13.6, 6.2 and 1.6 Hz, 2H), 1.46 (bs, arabino-10a: H NMR (400 MHz, CDCl3) d 7.36–7.18 (m, 15H),
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4.43 (s, 1H), 4.27 (s, 1H), 4.16 (m, 1H), 3.90 (m, 1H), 3.80 (m,
2H), 3.73 (m, 2H), 3.67 (m, 2H), 2.60 (ddd, J ¼ 14.5, 4.2 and 3.7
Hz, 1H), 2.30–2.17 (m, 2H), 2.05 (ddd, J ¼ 14.5, 10.2 and 3.6 Hz,
1H); 13C NMR (100.6 MHz, CDCl3) d 138.3–127.7, 93.4, 84.6,
79.2–69.5, 37.0, 33.1, 29.6, 26.8.
Acknowledgements
´
We thank the Ministerio de Economıa y Competitividad, Spain
(CTQ2011-22872BQU) for generous nancial support. We also
´
´
thank Dr I. Marın for preliminary results and Ms. M. Salvado,
´
Ms. E. Breso, Dr A. Lishchynskyi and the ICIQ MS unit for
technical assistance. O.B. thanks the Ministerio de Ciencia e
Phenyl 4,6-di-O-benzyl-2,3-dideoxy-1-thio-a/b-D-erythro-
hexopyranoside (11)
´
Innovacion, Spain (Juan de la Cierva Fellowship) and the
European Commission (Marie Curie Career Integration Grant).
NBS (63.5 mg, 0.36 mmol) was added to a solution of 3 (1 : 1
ꢀ
Z/E) (100 mg, 0.23 mmol) in dry CH3CN (3.4 mL) at ꢁ30 C
Notes and references
and stirred for 2.5 h. The mixture was diluted with CH2Cl2
and washed with saturated aqueous Na2S2O3. The combined
organic layers were dried over MgSO4, ltered and concen-
trated. The residue was ltered through a short silica plug
(from hexane to 1 : 3 EtOAc–hexane) and the solvent evapo-
rated to afford phenyl 4,6-di-O-benzyl-2,3-dideoxy-2-bromo-1-
thio-a/b-D-arabino/ribo-hexopyranoside 10b (53 mg, 45%) as a
brownish syrup. The isolated product decomposed on
standing and was therefore quickly subjected to the next
reaction. A mixture of 10b (40 mg, 0.08 mmol) and NaOAc (9.6
mg, 0.12 mmol) were dissolved in THF (0.5 mL) and acetic
acid (7 mL) at 0 ꢀC. Zn/Cu couple (53 mg) was then added and
the reaction was le to stir at the same temperature for 1.5 h.
The mixture was then diluted with CH2Cl2 and washed with
saturated aqueous NaHCO3. The combined organic layers
were dried over MgSO4, ltered and concentrated. The
residue was puried by radial chromatography (from hexane
to 1 : 5 EtOAc–hexane) to afford 11 (31 mg, 88%) as a col-
ourless syrup. 1H NMR (400 MHz, CDCl3) d 7.61–7.22 (m,
15H), 4.71 (d, J ¼ 10.4 Hz, 1H), 4.61–4.40 (m, 4H), 3.80–3.68
(m, 4H), 3.58 (ddd, J ¼ 9.6, 4.8 and 2.0 Hz, 1H), 3.47 (ddd, J ¼
9.6, 10.4 and 4.4 Hz, 1H), 2.88 (ddd, J ¼ 12.4, 4.8 and 4.4 Hz,
1H), 2.03 (ddd, J ¼ 12.4, 11.2 and 10.4 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3) d 133.4–127.8, 89.5, 82.0, 73.6, 72.7, 71.7,
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19798 | RSC Adv., 2014, 4, 19794–19799
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