Synthesis of 2,3-O-benzyl-ribose and xylose and their equilibration

Article abstract of DOI:10.1016/j.tetasy.2014.09.004

The preparation and NMR analysis of 2,3-di-O-benzyl d-ribose and 2,3-di-O-d-xylose are described. In DMSO-d₆ the sugars adopt a conformation in which the hydroxyl groups are in an equatorial position. In CDCl₃ and CD₂Cl₂ the sugars adopts a conformation in which intramolecular hydrogen bonding plays an important role in determining the equilibrium composition. These findings were also confirmed by DFT studies and, in the solid phase, by X-ray single crystal diffraction.

Full text of DOI:10.1016/j.tetasy.2014.09.004

Tetrahedron: Asymmetry 25 (2014) 1424–1429
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of 2,3-O-benzyl-ribose and xylose and their equilibration
a
a
b
Reignier Jeffrey a, Gurdial Singh a, , Patrice G. J. Plaza-Alexander , Nadia Singh , Jonathan M. Goodman ,
⇑
Alessia Bacchi c, Francesco Punzo d
a Department of Chemistry, University of the West Indies, St. Augustine, Trinidad and Tobago
b Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
c Dipartimento di Chimica, Università degli Studi di Parma, Parco Area delle Scienze 17/A, Parma 43124, Italy
d Dipartimento di Scienze del Farmaco, Sezione Chimica, Università di Catania, Viale Andrea Doria, 6, 95125 Catania, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 September 2014
Accepted 12 September 2014
The preparation and NMR analysis of 2,3-di-O-benzyl D-ribose and 2,3-di-O-D-xylose are described. In
DMSO-d6 the sugars adopt a conformation in which the hydroxyl groups are in an equatorial position.
In CDCl3 and CD2Cl2 the sugars adopts a conformation in which intramolecular hydrogen bonding plays
an important role in determining the equilibrium composition. These findings were also confirmed by
DFT studies and, in the solid phase, by X-ray single crystal diffraction.
Ó 2014 Elsevier Ltd. All rights reserved.
O
OH
1. Introduction
HO
HO
1C4 chair
4C1 chair
O
HO
OH
OH
OH
Carbohydrates are essential biochemicalbuilding blocks for com-
plex life forms to develop. Major strides have been made in the syn-
thesis of complex structures encompassing carbohydrates over the
last decade. However a universal strategy for glycosylation that
readily results in the synthesis of oligosaccharideshas remained elu-
sive.1 Understanding the biological activity of saccharides and of
their oligomers by its very nature necessitates that we know the
structure and stability of the different conformations that these
molecules can adopt. A major obstacle in obtaining a basic structure
is due to that fact that these can form strong hydrogen bonds in
water and other polar solvents, whichin turn can result in conforma-
tional changes taking place that may lead to a different biological
effect being observed. As a result of these observations, a number
OH
OH
α-anomer
O
HO
HO
OH
Scheme 1.
We have recently reported NMR equilibration studies leading to
the synthesis of arabinofuranosides using an iterative protocol.5
Herein we report on our findings relating to 2,3-O-dibenzylribo-
and xylo-furanosides and the former use for the synthesis of
oligosaccharides.
Following on from these studies, we reasoned that ribosides and
their xylo analogues should be capable of providing access to oligo-
saccharides using similar procedures. In addition these studies
should provide insight into the conformation of these pentoses
and the stereochemical effects as a result of the change in the sub-
stitution patterns at C-2 and C-3. Furthermore, we wished to con-
trol the mutarotation of these partially protected sugars with the
specific goal of being able to selectively prepare furanosides from
a mixture of isomers. The success of the proposed strategy depends
upon the selectivity of the attack of the primary hydroxyl group on
the glycosyl intermediate species that results.5 At the outset we
wished to study the equilibrium composition of these two sugars
and compare the experimental findings with theoretical predic-
tions arising from the use of the density functional theory with
respect to the possible conformations arising in solution and the
effect the solvents have on these.
of investigations into the conformations of 2-deoxy-D-ribose have
been reported2 using Fourier-transform microwave spectroscopy
in conjunctionwith UV spectroscopyusing a laser source. In aqueous
solution
whilst in RNA it is present as a furanose. In aqueous solution
exists as a mixture of - and b-pyranoses that are present in their
D
-ribose exists primarily as
a
- and b-pyranose3 forms
-ribose
D
a
low energy chair conformations, 4C1 and 1C4. These configurations
proceed through ring inversion leading to an axial or equatorial
OH group for each conformer. Additionally, extra stabilisation pro-
vided by the anomeric effect results in the preference for an axial
OH group at the C1 carbon over the empirically expected equatorial
orientation4 (Scheme 1).
⇑
Corresponding author.
E-mail address: Gurdial.Singh@sta.uwi.edu (G. Singh).
http://dx.doi.org/10.1016/j.tetasy.2014.09.004
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.

R. Jeffrey et al. / Tetrahedron: Asymmetry 25 (2014) 1424–1429
1425
O
OH
OH
HO
TrO
MeOH, cat. H+
rt, 20h
O
O
TrCl, py
rt, 18h
OMe
NaH, BnBr, DMF
0oC to rt, 4h
OMe
HO
OH
ribo
HO
OH
OH
HO
2a
3a
3b
1a D-ribose
1b
2b xylo
D-xylose
HO
TrO
O
O
O
OH
OMe
OBn
MeCN:H2O:TFA (4:3:1)
95oC, 12h
HO
OH
OBn
5a
5b
OBn
5a
OBn
75%, overall
5b 69%, overall
BnO
BnO
4a
Scheme 2. Preparation of 2,3-di-O-benzyl ribose 5a and 2,3-di-O-benzyl xylose 5b.
The ratios of the four anomers were obtained by integration of
the anomeric resonance in its 1H spectrum (Table 2).
2. Results and discussion
2,3-Di-O-benzylated
mercially available
was protected selectively at the primary hydroxyl group using tri-
tyl chloride7 followed by benzylation to give the fully protected
sugars. Removal of the trityl group and the anomeric methyl group
was accomplished in one step to yield the desired compounds.
D
-ribose was synthesized from the com-
D
-ribose (Scheme 2). The methyl furanoside6
Table 2
*
Percent pyranose and furanose forms of 5a in CDCl3, DMSO-d6 and CD2Cl2
CDCl3
DMSO-d6
CD2Cl2
a
-Furanose
b-Furanose
-Pyranose
b-Pyranose
18
13
24
45
—
—
—
100
15
17
21
47
2,3-Di-O-benzyl-D-xylose was also synthesized from commercially
a
available -xylose using the same procedures.
D
The pure 2,3-di-O-benzyl derivatives 5a and 5b obtained after
column chromatography were analysed using one dimensional
and two-dimensional NMR in three solvents: CDCl3, CD2Cl2 and
DMSO-d6. The equilibrium proportions of the various isomers in
solution were determined by integration of the anomeric proton
NMR signals.
*
Ratios calculated using spectra obtained immediately after dissolution in the
respective solvents.
Benzylation of the 2,3-hydroxy groups of ribose results in a
thermodynamic equilibrium which results in the b-pyranose being
the sole isomer that is observed in DMSO and the solid state, in
contrast to the unprotected sugar which gives a mixture of all four
isomers in water (Table 3).
The 1H NMR spectrum of 5a in deuterated chloroform showed
the presence of four major anomers; the
a- and b-pyranoses and
the - and b-furanoses. Neither the acyclic aldehyde nor hydrate
a
was detected by natural abundance of NMR. The anomeric protons
of the furanoses resonated at lower fields than those of the pyra-
Table 3
% pyranose and furanose forms of D-ribose 1a and D-xylose 1b in D2O3b
noses, with chemical shifts of 5.30 and 5.31 ppm for the
a- and
1a
6.5
13.5
21.5
58.5
1b
b-anomers, respectively, (Table 1).
a
-Furanose
b-Furanose
-Pyranose
b-Pyranose
<1
<1
36.5
63.0
Table 1
a
a
Chemical shift data for compounds 5a and 5b in CDCl3
5a
5b
a-Furanose
H-1, C-1
5.30
96.3 5.47
95.5
OH
For 5a in CDCl3 and CD2Cl2, the composition of the four isomers
were similar with the two pyranose forms occurring in 69% and
68%, respectively, indicative of similar solvent effects. In the more
polar DMSO-d6 only the b-pyranose isomer was detected upon
immediate dissolution and subsequent acquisition of the NMR
data. The resonances observed, excluding the benzyl signals are
detailed in Table 4 for the sake of clarity. This indicated that in
solid 5a, the b-pyranose isomer was the sole observed component
upon dissolution and immediate accumulation of the spectroscopic
data. The anomeric resonance occurred at d 4.88 and in its 13C
spectrum the resonance was observed at d 93.34.
H-2, C-2
H-3, C-3
H-4, C-4
3.61
3.69
3.82
76.9 4.00
62.4 4.18
80.6 4.35
82.4
82.9
81.2
62.2
O
OH
H-5a, 5b, C-5* 3.83, 3.86 62.2 3.73,3.89
BnO
OBn
b-Furanose
OH
O
H-1, C-1
5.31
99.8 5.30
101.2
H-2, C-2
H-3, C-3
H-4, C-4
4.22
4.25
3.69
82.0 4.02
82.0 4.16
72.8 4.29
87.4
82.0
77.7
OH
H-5a, 5b, C-5* 3.92, 3.88 64.6 3.72, 3.83 61.9
BnO
OBn
-Pyranose
HO
a
H-1, C-1
5.21
93.5 5.01
91.8
H-2, C-2
H-3, C-3
3.75
3.88
66.0 3.52
77.8 3.83
77.2
76.8
O
H-4, C-4
3.77
65.9 3.63
67.6
BnO
OH
H-5a, 5b, C-5* 3.89, 3.93 67.6 3.83, 3.85 64.9
Table 4
Chemical shift data for 5a in DMSO-d6
OBn
b-Pyranose
H-1, C-1
4.91
92.4 4.96
94.1
b-Pyranose in DMSO-d6
HO
H-2, C-2
H-3, C-3
3.96
3.87
77.3 3.48
78.0 3.72
76.0
76.6
OH-1
6.62 J = 6.00 Hz
O
H-4, C-4
3.54
61.7 3.69
67.0
H-1, C-1
H-2, C-2
H-3, C-3
4.88
3.32
3.93
93.34
79.02
76.5
BnO
OH
H-5a, 5b, C-5* 4.18, 4.20 76.8 3.83, 3.85 61.7
OBn
OH-4, H-4, C-4
H-5, H-50, C-5
4.62, 3.70
3.53, 3.60
67.4
63.7
a
All values are given as chemical shifts in ppm.
H-5a and H-5b unassigned.
*

1426
R. Jeffrey et al. / Tetrahedron: Asymmetry 25 (2014) 1424–1429
We were able to crystallise the pure b-anomer of 5a from ethyl
acetate by allowing the slow evaporation of the solvent to obtain
thin white needles with a mp of 82–83 °C, [ D = ꢀ19.6 (c 1.0,
2,3-di-O-methyl ribosides along with the xylose analogues, using
B3LYP/6-31G⁄⁄ and Schrodinger’s Jaguar software, version 7.6, on
geometries generated by conformation searches using MacroMod-
el (BatchMin v9.7) and the OPLS_2005 force field. These calcula-
tions indicated that the major isomer in DMSO, (Table 7), would
have a b-pyranose structure. This is in agreement with our exper-
imental findings in both the solution and solid states. When dis-
solved in CD2Cl2 and CDCl3 the crystalline b-ribopyranoside
afforded a mixture of furanosides and pyranosides.
In DMSO-d6 the anomer with the least steric interactions was
the most abundant.10 The hydrogen bond interaction between
the solvent and the hydroxyl groups increases the effective size
of the substituents. In CDCl3, which does not interact with the
solute via hydrogen bonding, other effects come into play
including the anomeric effect and ring strain or torsional strain.
Intramolecular hydrogen bonding also influences the equilibrium
because conformations containing these interactions are preferen-
tially stabilized.11
a]
CHCl3). With this isomer in hand we undertook single X-ray crys-
tallographic analysis. This confirmed that crystalline 5a existed in
a pyranose structure, which was in agreement with the solution
structure observed in DMSO. The crystal structure belongs to the
monoclinic P21 space group with a = 10.558(3), b = 6.878(2),
c = 12.275(4) and b = 97.543(4)° with Z = 2 thus showing two inde-
pendent molecules in the unit cell. The ring puckering analysis per-
formed on the crystalline structure8 evidenced the presence of a
chair conformation as reported in Table 5. More interestingly, the
structure presents no solvent accessible voids, being available only
two small volumes of less than 15 Å3 which are not suitable for any
small solvent molecule to fit, and a resulting high packing index9
(64.2%). The solid state hydrogen bond network is reported in
Table 6. There are both inter- and intra-molecular hydrogen bonds
as well as weak
p stacking interactions between the aromatic rings
of the structure, particularly along the 1 ꢀ x, ꢀ1/2 + y, 1 ꢀ z direc-
In order to account for possible stereoelectronic effects we
undertook DFT calculations with D-arabinose. These suggested that
tion (Fig. 1).
Prior to the commencement of these studies we had undertaken
density functional theory (DFT) calculations of 2,3-di-O-benzyl and
in a polar solvent the pyranose structure should predominate. This
was at variance with our experimental findings5 wherein it was
established that the furanose and pyranose ring systems occurred
in equal percentages. These findings suggest that the stereochem-
istry of the C-2 hydroxy group plays a predominant role in
determining the ring size of pentoses. This is not too surprising
since the C-2 hydroxy function in both ribose and xylose is in the
Table 5
Ring puckering coordinates and their e.s.d. for the Cremer and Pople analysis
performed on the anomeric ring and its resulting conformation
Q (Å)
q2 (Å)
/
(°)
q3 (Å)
h (°)
Conformation
Chair
2
preferred equatorial orientation whilst in the case of
it has a higher energy axial geometry.
D
-arabinose
0.570 (5)
0.016 (5)
353 (20)
ꢀ0.570 (5)
177.9 (5)
Table 6
Potential hydrogen bonds analysis. Bond lengths, together with their standard uncertainties (s.u.) are given in Å; bond angles (D–Hꢁ ꢁ ꢁA) in (°)
Bond type
Donor
–H
Acceptor
D–H
Hꢁ ꢁ ꢁA
Dꢁ ꢁ ꢁA
D–Hꢁ ꢁ ꢁA
Inter-i
Inter-ii
Intra-
Intra-
O3
C19
O2
–H30
–H19
–H20
–H19
..O2
..O3
..O5
..O3
0.79 (7)
0.93
0.83 (7)
0.93
1.96 (7)
2.59
2.00 (8)
2.59
2.738 (5)
3.503 (7)
2.696 (6)
3.503 (7)
166 (7)
166
141 (7)
166
C19
Symmetry codes: (i) x, ꢀ1 + y, z; (ii) x, 1 + y, z.
0
Figure 1. Packing diagram viewed down the b axis. Hydrogens are shown as fixed-size spheres of an arbitrary radius of 0.15 ÅA and the ellipsoids probability level set to 30%
for the sake of clarity.

R. Jeffrey et al. / Tetrahedron: Asymmetry 25 (2014) 1424–1429
1427
Table 7
2,3,Di-O-Bn ribose
2,3-Di-O-Me ribose
ab initio B3LYP
2,3-Di-O-Bn xylose
Model %
Exp DMSO %
Exp CDCl3
%
Model DMSO
Exp DMSO
Exp CDCl3
a
-Furanose
0.0
0.0
4.8
0.0
00
0.0
100.0
18.0
13.0
24.0
45.0
0.0
0.0
2.0
0.6
0.0
44.2
55.2
0.0
0.0
13.0
87.0
0.0
0.0
44.4
55.6
6.9
5.6
31.2
56.3
b-Furanose
a-Pyranose
b-Pyranose
95.2
98.0
Arabinose
2,3-Di-O-Me arabinose
2,3-Di-O-Bn arabinose
Model dry
Model H2O
Literature3b
Model DMSO
Model DMSO
Exp DMSO
Exp CDCl3
a
-Furanose
b-Furanose
-Pyranose
b-Pyranose
0.0
0.0
2.0
0.0
0.0
10.0
90.0
2.5
2.0
60.0
35.5
6.7
48.1
0.0
8.7
11.9
0.0
35.0
16.0
24.0
25.0
26.0
21.0
26.0
27.0
a
98.0
45.2
79.4
Differences in the chemical shifts and the coupling constants of
the anomeric protons when the solvent was changed from CDCl3 to
DMSO-d6 were related to a change in conformation, particularly in
conformation was assigned based on the well-known fact that an
equatorial proton resonates at a lower field than a chemically sim-
ilar but axial proton. Thus 2,3-di-O-benzyl-
exists primarily as the 1C4 conformer in CDCl3.12 while 2,3-di-O-
benzyl- -ribopyranose 5a exists as a mixture of both conformers
a,D-xylopyranose 5b,
the pyranose forms. Both 2,3-di-O-benzyl-b-D-ribopyranose 5a and
2,3-di-O-benzyl-b- -xylopyranose 5b experienced conformational
D
a,D
changes due to the change in solvent as indicated by the values
of the J1,2 coupling constants (Table 8).
in either solvent. These observations suggest that intramolecular
hydrogen bonding is present in the absence of a hydrogen bonding
solvent.13 This intramolecular hydrogen bonding occurs even in
the presence of bulky benzyl substituents and stabilizes the con-
former in which these groups are axial, in spite of unfavourable
1,3-diaxial interactions14 (Fig. 2).
Having this information in hand, we will begin to investigate
the application of these findings to the synthesis of furano-oligo-
saccharides. In particular we wish to undertake an iterative syn-
thesis of 1-O-linked ribosides. We reason that we should be able
to selectively react the equilibrium mixture in order to obtain
the desired furano linked ribosides.
In CDCl3, 2,3-di-O-benzyl-b-D-ribopyranose 5a exists primarily
as the 1C4 conformer as indicated by the J1,2 value of 1.99 Hz
(Table 8). In DMSO-d6, however, a J1,2 value of 5.6 Hz suggests that
this anomer exists as a mixture of the 1C4 and 4C1 conformers, with
the equilibrium favouring the latter.3e Similarly, 2,3-di-O-benzyl-
b-D
-xylopyranose 5b exists primarily in the 4C1 conformation, in
which all substituents are in an equatorial position, in DMSO-d6
but as a mixture of the two chair conformations in the less polar,
non-hydrogen bonding CDCl3 with the equilibrium in favour of
the 1C4 conformer. In 2,3-di-O-benzyl-
a,D-xylopyranose 5b the
Table 8
Comparison of chemical shifts in ppm and coupling constants (in Hz) of anomeric protons of compounds 5a and 5b
5a
5b
CDCl3
CD2Cl2
DMSO-d6
CDCl3
CD2Cl2
DMSO-d6
a
-Furanose
b-Furanose
-Pyranose
b-Pyranose
5.30 (6.1)
5.31 (3.8)
4.91 (10.0)
5.21 (1.99)
5.27 (4.0)
5.35 (4.7)
4.88 (10.0)
5.23
5.47 (4.2)
5.30
5.01 (2.2)
4.96 (2.6)
5.44 (3.85)
5.23
5.01 (2.28)
4.92 (3.5)
a
5.20 (5.4)
4.47 (6.6)
4.88 (5.6)
DMSO- d6
DMSO- d6
CDCl3
CDCl3
2,3-di-O-benzyl-β-D-ribopyranose
2,3-di-O-benzyl-α-D-ribopyranose
OH
OH
HO
O
O
O
O
HO
OH
OBn
BnO
OH
OBn
BnO
OH
OH
OBn
OBn
OBn
4C1
1C4
OH
1C4
4C1
2,3-di-O-benzyl-β-D-xylopyranose
2,3-di-O-benzyl-α-D-ribopyranose
OH
OBn
OBn
HO
BnO
O
O
OH
O
O
HO
BnO
OH
OBn
OH
OBn
OBn
OBn
OH
1C4
4C1
1C4
4C1
OH
Figure 2. Major chair conformations of 5a and 5b.

1428
R. Jeffrey et al. / Tetrahedron: Asymmetry 25 (2014) 1424–1429
mixture was stirred at 40 °C for 20 h. The solvent was removed
3. Conclusion
in vacuo and the crude product dissolved in pyridine (50 mL). Trityl
chloride7 (9.3 g, 33.3 mmol) was added and the mixture was stir-
red at rt overnight. The reaction mixture was then poured into
an ice-water mixture and allowed to warm up to room tempera-
ture. The mixture was then extracted with chloroform
(3 ꢂ 50 mL). The organic layers were then combined and washed
using saturated aqueous ammonium chloride (2 ꢂ 50 mL) and
water (2 ꢂ 50 mL). The organic layer was then dried (Na2SO4)
and the solvents removed in vacuo. The solvent was removed
under reduced pressure and the residue obtained purified via col-
umn chromatography (CHCl3 followed by CHCl3/MeOH; 9:1). The
tritylated methyl glycoside was then benzylated under standard
benzylation conditions. Deprotection of the trityl and methyl
groups was carried out by refluxing in a solution of CH3CN/H2O/
TFA (4:3:1; 1:20 w/v) at 95 °C for 12 h. The solvent was then
removed in vacuo and the residue neutralized using saturated
aqueous NaHCO3 (20 mL) and solid NaHCO3. The mixture was then
extracted using EtOAc (2 ꢂ 20 mL). The organic layers were com-
bined and dried (Na2SO4) and the solvent removed under reduced
pressure. The residue obtained was purified via column chroma-
tography using CHCl3/MeOH (95:5).
In conclusion, we have investigated the equilibria present in
2,3-di-O-benzylated pentose sugars and established that in polar
solvents, the b-pyranose form is the major isomer, whilst in less
polar solvents a mixture of both furanose and pyranose isomers
can be found.
4. Experimental
4.1. General
All chemicals used were reagent or HPLC grade and used as sup-
plied without prior purification unless otherwise stated. Solvents:
DCM and diethyl ether were dried over calcium hydride for 24 h,
distilled and stored over 4 Å molecular sieves. Flash column chro-
matography was carried out using forced flow of the indicated sol-
vent on Merck (230–400 mesh) silica gel. TLC was performed using
pre-coated silica gel 60 F254 plates; compounds were visualized
using acidic ammonium molybdate solution [ammonium molyb-
date(VI) tetrahydrate (25 g) in 1 M H2SO4 (500 mL)]. Anhydrous
reactions were performed under argon in oven dried apparatus;
anhydrous transfers were carried out with standard syringe
techniques.
4.4. 2,3-Di-O-benzyl-D-ribose 5a
1H, 13C and 31P NMR spectra were recorded on Bruker 600,
400 MHz spectrometers in the deuterated solvent stated. For ease
of interpretation, protons are expressed as multiples of 1. Refer
to the main text for equilibrium ratios. IR spectra were recorded
on a Perkin Elmer Spectrum RXI FT-IR spectrometer. High resolu-
tion mass data was obtained using a Bruker Daltonics micrOTof-
Q instrument in the electron spray ionization mode. Melting points
were measured in open capillaries and are uncorrected.
The resultant light yellow oil solidified on standing, 75% yield
overall. A portion of this was recrystallized from EtOAc mp of
82–83 °C, [
a
]
D
23 = ꢀ19.6 (c 1.0, CHCl3). NMR (600 MHz) CDCl3 dH
(ppm): shared resonances: 7.2–7.4 (40H, m, aromatic protons),
4.5–4.8 (4H, benzylic protons + 1 hydroxyl proton), 4.25 (1H, 1
hydroxyl proton), 3.5–4.0 (3H, 3 hydroxyl protons) 1.55–2.85
(3H, 3 hydroxyl protons);
a-furanose: 5.30 (1H, d, J = 6.1 Hz, H-
1), 3.61 (1H, H-2), 3.69 (1H, H-3), 3.82 (1H, H-4), 3.83 (1H, H-5a),
3.86 (1H, H-5b); b-furanose: 5.31 (1H, d, J = 3.8 Hz, H-1), 4.22
(1H, H-2), 4.25 (1H, H-3), 3.69 (1H, H-4), 3.92 (1H, H-5b), 3.88
(1H, H-5a); b-pyranose: 4.91 (1H, d, J = 1.99 Hz, H-1), 3.96 (1H,
H-2), 3.87 (1H, H-3), 3.54 (1H, H-4), 4.18 (1H, H-5a), 4.20 (1H, H-
4.2. Crystallographic structure determination
The single crystals used for structure determination were
mounted on a glass capillary; the small dimensions and some
twinning did not allow collection of high quality data and resolu-
tion, but were nevertheless perfectly suitable for satisfactory struc-
tural determination. Single crystal X-ray diffraction data were
5b);
a-pyranose: 5.21 (1H, d, J = 10 Hz, H-1), 3.75 (1H, H-2), 3.88
(1H, H-3), 3.77 (1H, H-4), 3.89 (1H, H-5b), 3.93 (1H, H-5a); 13C
(150 MHz) CDCl3 dC (ppm): shared resonances: 138.1, 137.7,
137.7, 137.6, 137.4, 137.3, 137.3, 128.7, 128.7, 128.7, 128.7,
128.7128.6, 128.5, 128.5, 128.4, 128.4,128.4, 128.3, 128.3, 128.2,
128.1, 128.0, 128.0, 128.0, 128.0, 127.9, 127.9, 127.9, 127.9,
127.7, 127.7, 127.7, 127.7 (aromatic-C), 76.1, 73.8, 73.6, 73.0,
collected at T = 293 K using the MoKa radiation (k = 0.71073 Å)
on a SMART APEX2 diffractometer. Lorentz, polarization and
absorption corrections were applied.15 The structure was solved
by direct methods using SIR200416 and refined by full-matrix
least-squares on all F2 using SHELXL-201317 implemented in the
Olex2 package.18 Hydrogen atoms were introduced in calculated
positions riding on their carrier atoms with the exception of
hydroxylic hydrogens that were located on the difference map
and refined isotropically. Anisotropic displacement parameters
were refined for all non-hydrogen atoms. Due to slight twinning
the Flack parameter does not converge to zero, although the abso-
lute structure is assessed by chemical argumentation. Hydrogen
bonds have been analysed with SHELXL201317 and PARST9719
and extensive use was made of the Cambridge Crystallographic
Data Centre packages20 for the analysis of crystal packing. CCDC
1022046 contains the Supplementary crystallographic data for this
paper. Copies of the data can be obtained free of charge on applica-
tion to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax: (+44)
1223 336 033; e-mail: deposit@ccdc.cam.ac.uk).
73.0, 72.8, 72.3, 70.6 (benzylic-C);
(C-2), 62.4 (C-3), 80.6 (C-4), 62.2 (C-5); b-furanose: 99.8 (C-1),
82.0 (C-2), 82.0 (C-3),72.8 (C-4), 64.6 (C-5); -pyranose: 92.4 (C-
a-furanose: 96.3 (C-1), 76.9
a
1), 77.3 (C-2), 78.0 (C-3), 61.7 (C-4), 76.8 (C-5); b-pyranose: 93.5
(C-1), 66.0 (C-2), 77.8 (C-3), 65.9 (C-4), 67.6 (C-5).
1H NMR (600 MHz) CD2Cl2 dH (ppm): shared resonances: 7.2–
7.4 (40H, m, aromatic protons), 4.4–4.8 (4H, benzylic protons + 1
hydroxyl proton), 3.5–4.0 (3H, 3 hydroxyl protons) 3.09 (1H, br s;
hydroxyl proton), 1.24–2.73 (3H; hydroxyl protons);
a-furanose:
5.29 (1H, d, J = 4.0 Hz, H-1), 3.72 (1H, H-2), 3.90 (1H, H-3), 3.60
(1H, H-4), 3.77 (1H, H-5a), 3.73 (1H, H-5b); b-furanose: 5.32 (1H,
d, J = 4.7 Hz, H-1), 3.92 (1H, H-2), 4.21 (1H, H-3), 3.63 (1H, H-4),
4.83 (1H, H-5b), 4.84 (1H, H-5a); b-pyranose: 5.35 (1H, H-1), 3.98
(1H, H-2), 4.21 (1H, H-3), 3.88 (1H, H-4), 4.19 (1H, H-5a), 4.22
(1H, H-5b);
a-pyranose: 4.88 (1H, d, J = 10 Hz, H-1), 3.64 (1H,
H-2), 3.52 (1H, H-3), 3.77 (1H, H-4), 3.44 (1H, H-5b), 3.46 (1H,
H-5a); 13C (150 MHz) CD2Cl2 dC (ppm): shared resonances: 138.8,
138.4, 138.3, 138.2, 138.1, 138.1, 129.0, 128.9, 128.8, 128.8,
128.8, 128.5, 128.4, 128.4, 128.4, 128.3, 128.3, 128.3, 128.3,
128.2, 128.2, 128.1, 128.0 (aromatic-C), 73.5, 73.4, 73.1, 73.0,
4.3. General procedure for preparation of 2,3-di-O-benzyl sugars
The starting sugar (5.0 g, 33.3 mmol) was suspended in metha-
nol,6 after which p-TSA (290 mg, 1.5 mmol) was added and the
72.8, 71.0 (benzylic-C, overlapping resonances);
a-furanose: 97.8

R. Jeffrey et al. / Tetrahedron: Asymmetry 25 (2014) 1424–1429
1429
(C-1), 77.9 (C-2), 67.8 (C-3), 62.2 (C-4), 65.2 (C-5); b-furanose:
100.3 (C-1), 78.6 (C-2), 77.4 (C-3),78.6 (C-4), 74.2 (C-5); -pyra-
1H NMR (600 MHz) DMSO-d6 dH (ppm): shared resonances: 7.2–
7.4 (20H, m, aromatic protons), 4.6–4.9 (8H, benzylic protons + 2H;
a
nose: 92.8 (C-1), 76.9 (C-2), 63.0 (C-3), 66.5 (C-4), 67.8 (C-5);
b-pyranose: 94.0 (C-1), 78.0 (C-2), 82.4 (C-3), 81.6 (C-4), 85.6 (C-5).
1H NMR (600 MHz) DMSO-d6 dH (ppm): 7.2–7.4 (10H, m, aro-
matic protons), 4.71–4.77 (4H, benzylic protons) 4.62 (1H, br s,
hydroxyl proton, OH-4); b-pyranose: 6.62 (1H, d, J = 6.0 Hz; OH-
1), 4.88 (1H, overlapping dd, J = 6.8 Hz, H-1), 3.32 (1H, H-2), 3.93
(1H, H-3), 3.70 (1H, H-4), 3.60 (1H, dd, J = 10.8 Hz, 3.6 Hz, H-5a),
3.53 (1H, dd, J = 7.8 Hz, 3.6 Hz, H-5b); 13C (150 MHz) DMSO-d6 dC
(ppm): 139.3, 138.8, 128.1, 128.0, 127.3, 127.3, 127.2, 127.0
(aromatic-C), 72.3, 71.7 (benzylic-C); b pyranose: 93.3 (C-1), 79.0
(C-2), 76.5 (C-3), 67.4 (C-4), 63.7 (C-5); m/z found (M+) 330.1453;
C19H22O5 requires 330.1467.
hydroxyl protons); a-pyranose: 6.89 (1H, d, J = 6.5 Hz; OH-1), 5.14
(1H, m, H1) 3.31 (1H, H-2), 3.57 (1H, H-3), 3.45 (1H, H-4), 3.38 (1H,
H-5a), 3.53 (1H, H-5b); b-pyranose: 5.20 (1H, d, J = 5.4 Hz; OH-1),
4.47 (1H, overlapping dd, J = 6.6 Hz, H-1), 3.09 (1H, H-2), 3.30
(1H, H-3), 3.51 (1H, H-4), 3.09 (1H, H-5a), 3.66 (1H, H-5b); 13C
(150 MHz) DMSO-d6 dC (ppm): shared resonances: 139.4, 139.1,
138.9, 138.7, 128.2, 128.1, 128.1, 128.0, 127.9, 127.9, 127.9,
127.5, 127.4, 127.3, 127.3, 127.2, 127.1, 127.0, 126.7 (aromatic-
C), 74.0 (2C), 73.7, 71.5 (benzylic-C); a-pyranose: 89.9 (C-1), 79.6
(C-2), 81.2 (C-3), 70.0 (C-4), 61.1 (C-5); b-pyranose: 97.5 (C-1),
82.5 (C-2), 84.3 (C-3), 69.9 (C-4), 65.4 (C-5). m/z found (M+)
330.1530; C19H22O5 requires 330.1467.
4.5. 2,3-Di-O-benzyl-
D
-xylose 5b
Acknowledgments
Colourless oil which solidified after storage under vacuum to
We thank the University of the West Indies for scholarships
(PGJP-A, R.J.).
give an off-white solid. 69% yield overall; mp 80–82 °C,
[
a]
26 = ꢀ4.4 (c 1.1 CHCl3);
m
max(film)/cmꢀ1 3406, 2928, 1721,
D
1453, 1357, 1274, 1215 and 1094. 1H NMR (600 MHz) CDCl3 dH
(ppm): shared resonances: 7.2–7.4 40H/m (aromatic protons),
4.4–4.7 (16H; benzylic protons), 3.40–4.20 (4H; hydroxyl protons);
References
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580–589.
2.55–3.30 (4H; hydroxyl protons);
a-furanose: 5.47 (1H, d,
J = 4.2 Hz, H-1), 4.00 (1H, H-2), 4.18 (1H, H-3), 4.35 (1H, H-4),
3.73 (H-5a) 3.89 (H-5b); b-furanose: 5.30 (1H, s, H-1), 4.02 (1H,
H-2), 4.16 (1H, H-3), 4.29 (1H, H-4), 3.72 (1H, H-5a), 3.83 (1H, H-
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a-pyranose: 5.01 (1H, d, J = 2.2 Hz, H-1), 3.52 (1H, H-2), 3.83
(1H, H-3), 3.63 (1H, H-4), 3.83 (1H, H-5a), 3.85 (1H, H-5b); b-pyra-
nose: 4.96 (1H, d, J = 2.6 Hz, H-1), 3.48 (1H, H-2), 3.72 (1H, H-3),
3.69 (1H, H-4), 3.55 (1H, H-5a), 4.13 (1H, H-5b) 13C (150 MHz)
CDCl3 dC (ppm): shared resonances: 137.9, 137.3, 137.2, 137.1,
137.0, 136.9, 128.7, 128.7, 128.7, 128.6, 128.6, 128.6, 128.6,
128.4, 128.4, 128.4, 128.3, 128.3, 128.2, 128.1, 128.1, 128.1,
128.00, 128.0, 127.9, 127.9, 127.8, 127.7 (aromatic-C) 73.7,
73.7.6, 73.3, 73.1, 73.1, 72.8, 72.5, 72.0 (benzylic-C);
95.5 (C-1), 82.4 (C-2), 82.9 (C-3), 81.2 (C-4), 62.2 (C-5); b-furanose:
101.2 (C-1), 87.4 (C-2), 82.0 (C-3), 77.7 (C-4), 61.9 (C-5); -pyra-
a-furanose:
7. Saeki, H.; Iwashige, T. Chem. Pharm. Bull. 1968, 16, 1129–1132.
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a
nose: 91.8 (C-1), 77.2 (C-2), 76.8 (C-3), 67.6 (C-4), 64.9 (C-5);
b-pyranose: 94.1 (C-1), 76.0 (C-2), 76.6 (C-3), 67.0 (C-4), 61.7 (C-5);
1H NMR (600 MHz) CD2Cl2 dH (ppm): shared resonances: 7.2–
7.4 40H/m (aromatic protons), 4.4–4.7 (16H; benzylic protons),
3.40–4.20 (4H; hydroxyl protons); 2.55–3.30 (4H; hydroxyl pro-
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tons);
a-furanose: 5.44 (1H, d, J = 3.85 Hz, H-1), 4.02 (1H, H-2),
4.18 (1H, H-3), 4.33 (1H, H-4), 3.74 (H-5a) 3.90 (H-5b); b-furanose:
5.23 (1H, s), 4.01 (1H, H-2), 4.12 (1H, H-3), 4.24 (1H, H-4), 3.69 (1H,
H-5a), 3.78 (1H, H-5b);
a-pyranose: 5.01 (1H, d, J = 2.28 Hz, H-1),
3.52 (1H, H-2), 3.83 (1H, H-3), 3.63 (1H, H-4), 3.83 (1H, H-5a),
3.85 (1H, H-5b); b-pyranose: 4.92 (1H, d, J = 3.5 Hz, H-1), 3.47
(1H, H-2), 3.71 (1H, H-3), 3.69 (1H, H-4), 3.49 (1H, H-5a), 4.10
(1H, H-5b) 13C (150 MHz) CDCl3 dC (ppm): shared resonances:
138.7, 137.9, 137.9, 137.7, 129.0, 129.0, 129.0, 129.0, 129.0,
128.6, 128.6, 128.6, 128.5, 128.4, 128.4, 128.4, 128.3, 128.3,
128.3, 128.2, 128.1 (aromatic-C) 74. 73.9, 73.5, 73.5, 73.4, 73.2,
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72.8, 72.3 (benzylic-C);
(C-3), 81.7 (C-4), 62.6 (C-5); b-furanose: 101.7 (C-1), 88.0 (C-2),
82.8 (C-3), 78.2 (C-4), 62.2 (C-5); -pyranose: 92.1 (C-1), 78.2
a-furanose: 96.0 (C-1), 82.4 (C-2), 82.8
a
(C-2), 77.3 (C-3), 68.1 (C-4), 65.2 (C-5); b-pyranose: 94.7 (C-1),
76.9 (C-2), 77.3 (C-3), 67.5 (C-4), 62.2 (C-5);