Configurations and conformations of glycosyl sulfoxides

Article abstract of DOI:10.1139/V10-091

X-ray crystallographic studies of two axial glycosyl sulfoxides having R_S configurations (derivatives of phenyl 2-azido-2-deoxy-1-thio - d-galactopyranoside S-oxide) show that they adopt anti conformations in the solid state, in contrast to pre

Full text of DOI:10.1139/V10-091

1154
Configurations and conformations of glycosyl
sulfoxides
Hong Liang, Micheline MacKay, T. Bruce Grindley, Katherine N. Robertson, and
T. Stanley Cameron
Abstract: X-ray crystallographic studies of two axial glycosyl sulfoxides having RS configurations (derivatives of phenyl
2-azido-2-deoxy-1-thio-a-D-galactopyranoside S-oxide) show that they adopt anti conformations in the solid state, in con-
trast to previous observations and assumptions. Density functional theory (DFT) calculations at the B3lYP6–311G+(d,p)/
6–31G(d) level confirm that anti conformations of both phenyl and methyl RS glycosyl sulfoxides of 2-azido-2-deoxy-a-D-
pyranosides are more stable than exo-anomeric conformations in the gas phase. 1D NOE measurements indicate that the
more polar exo-anomeric conformers are only populated to a slight extent in solution. The anti conformations are distorted
so that the glycosyl substituents are closer to being eclipsed with H1. This distortion allows S n ? s* overlap if the sulfur
lone pair is a p-type lone pair. Evidence for this overlap comes from short C1–S bond distances, as short as the compara-
ble bond distances in the X-ray crystal structure and in the results from DFT calculations for the SS glycoside, which does
adopt the expected exo-anomeric conformation, both in the solid state and in solution, and has normal n ? s* overlap.
For 2-deoxy derivatives not bearing a 2-azido group, gas-phase DFT calculations at the same level indicate that the anti-
and exo-anomeric conformers have comparable stabilities. Comparison of the results of the two series shows that electro-
negative substituents in equatorial orientations at C2 destabilize conformations with parallel S–O arrangements, the confor-
mation favored by having an endocyclic C–O dipole antiparallel to the S–O dipole, by about 2.5 kcal mol–1 (1 cal =
4.184 J). An equatorial glycosyl sulfoxide, (SS) phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-b-D-glucopyrano-
side S-oxide, also adopts an anti conformation in the solid state as shown by X-ray diffraction. It also adopts this confor-
mation in solution, in contrast to studies of other equatorial glycosyl sulfoxides.
Key words: sulfoxide configurations, glycosyl sulfoxides, conformational analysis, density functional theory (DFT) calcula-
tions, 1D NOE measurements, X-ray crystallography.
´
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Resume : Des etudes de cristallographie par diffraction des rayons-X de deux glycosyles sulfoxydes axiaux de configura-
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tions RS, des derives du S-oxyde de 2-azido-2-desoxy-1-thio-a-galactopyranoside de phenyle, montrent qu’ils adoptent des
`
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´
conformations anti a l’etat solide, contrairement aux observations anterieures et aux hypotheses. Des calculs selon la theo-
´
rie de la fonctionnelle de la densite (TFD) au niveau B31YP6–311G+(d,p)/6–31G(d) confirment que les conformations
´
´
anti que, en phase gazeuse, chacun des RS glycosyles sulfoxydes, 2-azido-2-desoxy-1-thio-a-galactopyranoside tant de me-
´
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thyle que de phenyle sont plus stable dans les conformations anomeres exo. Des mesures d’effet Overhauser nucleaire
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(eOn) 1D indiquent que, en solution, les conformeres anomeres les plus polaires ne forment qu’une faible partie de la po-
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pulation. Les conformations anti sont deformees de fac¸on a ce que les substituants glycolyses soient dans une position pra-
´
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tiquement eclipsee avec le H1. Cette distorsion permet un recouvrement S n ? s* sur la paire libre du soufre est une
paire libre de type p. Un support pour ce recouvrement vient des courtes longueurs de liaison C1–S, pratiquement aussi
´
´
courtes que les longueurs mesurees par diffraction des rayons-X dans la structure cristalline et en accord avec les resultats
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des calculs TFD pour le SS glycoside qui adopte la conformation anomere exo attendue, tant a l’etat solide qu’en solution,
´
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et pour le recouvrement n ? s* normal. Pour les derives 2-desoxy ne portant pas de groupe azido, les calculs de TFD en
ˆ
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phase gazeuse, au meme niveau, indiquent que les conformeres anomeres anti et exo ont des stabilites comparables. Une
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comparaison des resultats des deux series montre que les substituants electronegatifs en orientations equatoriales en
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C2 destabilisent les conformations avec des arrangements S–O paralleles, la conformation favorisee par un dipole C–O en-
–1
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docyclique antiparallele au dipole S–O par environ 2,5 kcal mol (1 cal = 4.184 J). La diffraction des rayons-X montre
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aussi que, a l’etat solide, un glycosyle sulfoxyde equatorial, le S-oxyde du SS 3,4,6-tri-O-acetyl-2-desoxy-2-phtalimido-1-
´
thio-b-D-glucopyranoside de phenyle, adopte aussi une conformation anti. Il adopte aussi cette conformation en solution,
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en opposition a ce qui a ete observe dans les etudes sur glycosyles sulfoxydes equatoriaux.
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Mots-cles : configurations de sulfoxydes, glycosyles sulfoxydes, analyse conformationnelle, calculs selon la theorie de la
´
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fonctionnelle de la densite (TFD), mesures d’effet Overhauser nucleaire (eOn) 1D, cristallographie.
Received 3 January 2010. Accepted 11 June 2010. Published on the NRC Research Press Web site at canjchem.nrc.ca on 5 November
2010.
This article is part of a Special Issue dedicated to Professor R. J. Boyd.
H. Liang, M. MacKay, T.B. Grindley,1 K.N. Robertson, and T.S. Cameron. Department of Chemistry, Dalhousie University, Halifax,
NS B3H 4J3, Canada.
1Corresponding author (e-mail: Bruce.Grindley@Dal.ca).
Can. J. Chem. 88: 1154–1174 (2010)
doi:10.1139/V10-091
Published by NRC Research Press

Liang et al.
1155
phy,16,17,23,28,32–34 augmented by empirical rules developed
from NMR measurements26 and from the use of chiral shift
reagents.33,35 Khiar26 proposed two methods for making as-
signments directly based on NMR results. For ethyl sulfox-
ides, the methylene protons of the ethyl group are
diastereotopic. For equatorial sulfoxides of D-pyranosides,
Introduction
One of the most important techniques for the formation of
glycosides employs glycosyl sulfoxides activated by electro-
philes as leaving groups.1 This method has been used to form
glycosides that have widely varying structures for both the
glycosyl donors and aglycones.2–14 The activated sulfoxide is
sufficiently reactive that reactions in solution can be con-
ducted at –78 8C and it can also be used in solid-phase reac-
tions.15 The configuration of the sulfoxide does not influence
the stereochemistry of glycosylation reactions but does affect
the rate of glycosylation reactions16 and the rates of compet-
ing elimination and hydrolysis reactions.17,18 The stabilities
of the different sulfoxide diastereomers and the physical
properties of the diastereomers are inherently linked to the
conformations that they adopt. The conformations are termed
exo if the aglycone is gauche to both the ring oxygen atom
and H1 and anti if the aglycone is anti to the ring oxygen as
shown in Figs. 1 and 2. The staggered conformations where
the aglycone is gauche to both the ring oxygen and C2 are
much less stable and will not be considered here.
1
the chemical shift differences between the H NMR signals
of these diasterotopic protons are considerably larger for the
RS isomer than the SS isomer.17,26 This observation has been
rationalized in terms of the assumption that the major con-
formations present for the RS sulfoxides are those in which
the ethyl group adopts the exo orientation,26 which agreed
with results from semiempirical (AM1) calculations.33 This
conformation of the RS sulfoxides has the sulfoxide sulfur
lone pair anti to the C1–O5 bond, aligned so that n ? s*
overlap can occur (see Figs. 1 and 2). Crich et al.23 com-
mented in a footnote that they have observed several excep-
tions to the tendency for the methylene protons of ethyl
sulfoxides to have larger chemical shift differences in partic-
ular diastereomers.
The second method proposed for assigning sulfoxide con-
figurations from NMR spectral measurements was based on
the 13C NMR chemical shifts of anomeric carbons; those for
RS sulfoxides of equatorial D-pyranosides are more shielded
by >2 ppm for both aryl and alkyl sulfoxides.17,26 For axial
sulfoxides of D-pyranosides, the minor SS isomer exhibits
the more shielded anomeric carbon and the larger chemical
shift difference between the diastereotopic protons of ethyl
sulfoxides.17 The larger shielding was attributed to the n ?
s* overlap mentioned above.26 If it is assumed that the con-
tribution of conformers with the aglycone gauche to both the
ring oxygen and C2 are negligible, this arrangement only
occurs in the exo conformation of the equatorial RS sulfox-
ide of D-sugars and in the exo conformation of the minor SS
isomer of axial sulfoxides (see Figs. 1 and 2).
Crich et al.23 have suggested that S–O C1–O5 dipole re-
pulsion is very important in determining the conformations
of axial sulfoxides. For a-D-pyranosides, the RS sulfoxide,
which is the major product of oxidation, has the S–O group
anti to the ring C1–O5 bond if the conformation adopted is
that favored by the exo-anomeric effect. This group has in-
terpreted equilibration results on glycosyl allyl sulfoxides in
terms of the importance of dipole–dipole repulsion.23
Most of the conclusions about sulfoxide conformation and
configuration have been based on X-ray crystallogra-
phy,16,17,23,28,32–34 supported by AM1 calculations.33 With
one exception,23 the ten glycosyl sulfoxides previously
studied adopted conformations in the solid state with the
sulfoxide alkyl or aryl group in the exo-anomeric conforma-
tion. This paper was prompted by our studies of three glyco-
syl phenyl sulfoxides, all of which adopt conformations in
the solid state with the phenyl group anti to the ring C–O
bond. We report these crystallographic studies here. In addi-
tion, NMR studies have been performed in which NOE
buildup rates have been used to determine the preferred con-
formations of these apparently anomalous sulfoxides in sol-
ution. Extensive molecular orbital calculations using density
functional theory at the B3LYP6–311+(d,p) level have now
provided improved understanding of the factors that deter-
mine the relative stabilities of the conformations of the two
sulfoxide configurations. These calculations suggest that the
It has been assumed that these conformations are influ-
enced primarily by the tendency of the aglycones to adopt
exo conformations, the exo-anomeric effect,19–22 with contri-
butions from repulsion between C–O and S–O dipoles.23 The
exo-anomeric effect is a result of several factors:24,25 n ?
s* donation,26 dipole dipole repulsion, reduced steric inter-
actions, and electrostatic attraction.27 Glycosyl sulfoxides
provide platforms that allow the examination of the geomet-
rical effects of the contributions of n ? s* donation on
conformer stability because the availability of two diaster-
eomers allows the contributions of the two lone pairs to be
evaluated individually, albeit with the complication of an
additional polar S–O bond. We will show herein that the
exo-anomeric effect is much less dominant in controlling
the conformations of glycosyl sulfoxides than that of glyco-
syl sulfides or of normal glycosides and that C–O S–O di-
pole repulsion is less important than previously thought. We
will also show that the conformer stabilities are consistent
with the sulfoxide lone pair being a p-type lone pair, rather
than an sp3 lone pair.
Crich et al.23,28 observed that oxidation of axial thioglyco-
sides on pyranoside rings gave one stereoisomer predomi-
nantly, the RS isomer for a-D-pyranosides. Stereoselectivity
is particularly high if the pyranoside rings are made rigid
by fusion to 4,6-O-benzylidene acetals.29,30 The stereoselec-
tivity attained is consistent23 with kinetically controlled oxi-
dation of the accessible face of the sulfur atom in the most
stable conformer of the thioglycoside, the conformer favored
by the exo-anomeric effect. This group23 and others31
observed that oxidation of equatorial sulfoxides was unse-
lective. Khiar et al.17,26 also found that oxidation of O2-
protected equatorial thioglycosides was normally unselective
but noted that oxidation of O2-unprotected equatorial thio-
glycosides is highly diastereoselective. A few O2-substituted
equatorial thioglycosides were also found to exhibit highly
selective oxidations; peresters of b-thiophenyl or b-ethyl 2-
tetrachlorophthalimido-2-deoxy-D-glucopyranosides gave di-
asteromeric ratios >9:1.17
The assignment of configuration of the product sulfoxides
has been based on results from X-ray crystallogra-
Published by NRC Research Press

1156
Can. J. Chem. Vol. 88, 2010
4
Fig. 1. Exo conformations of the glycosyl sulfoxides of D-sugars in C1 chair conformations.
4
Fig. 2. Anti conformations of the glycosyl sulfoxides of D-sugars in C1 chair conformation.
Scheme 1. (a) PhCHO or p-MeOPhCHO, p-methoxybenzoic acid in DMF–benzene, reflux; (b) Ac2O/Py; (c) MCPBA, DCM, –78 8C.
configuration of the glycosyl sulfoxide determines which
conformations are populated; a glycosyl sulfoxide, which
can adopt a conformation with the aglycone exo and the sul-
fur lone pair anti, will favor that conformation (the SS con-
figuration for b-D-pyranosides, the RS configuration for a-D-
pyranosides); for the other diastereomer, the conformer with
the aglycone anti is more stable or comparable in stability
with the exo conformer.
X-ray crystal structure determinations were performed on
compounds 6, 8R, 8S, and 9R. The phenyl thioglycoside, 6,
adopted the exo conformation (Fig. 3). A compilation of all
22 structures previously published that contain axial thiogly-
cosides was assembled from the Cambridge Data File and
data from this compilation is listed in the Supplementary
data as Table S1. In all previous 22 structures, as well as in
the one determined here, the conformation adopted was exo.
The X-ray crystal structure determinations of the kineti-
cally favored sulfoxides 8R and 9R show that both adopt
anti conformations, different from the exo conformations
present in the five previous determinations of axial glycosyl
sulfoxides. Two RS ethyl 1-thio-a-D-mannopyranoside S-oxides
adopted exo conformations,28 as did an RS 2-cyanoethyl 1-
thio-a-D-glucopyranoside S-oxide,34 and two 1-thio-b-D-
galactofuranoside S-oxides with the sulfur atom in pseudo-
axial positions also adopt exo-like conformations.16 ORTEP
diagrams for 8R and 9R are shown in Figs. 4 and 5. The
minor diastereomer, 8S, adopts an exo conformation in the
solid state. Its ORTEP diagram is shown in Fig. 6.
Results
Axial glycosyl sulfoxides
As previously reported,36 the treatment of 2-azido-2-de-
oxy-1,3,4,6-tetra-O-acetyl-a-D-galactopyranoside37 with thio-
phenol and boron trifluoride etherate in chloroform gave
close to a 1:1 mixture of the a- and b-isomers. Deacetylation
gave a mixture of compounds 1 and 2 that were separated
by column chromatography. As shown in Scheme 1, the a-
isomer was converted using standard methods into the 4,6-O-
benzylidene acetal (3) and the 4,6-O-p-methoxybenzylidene
acetal (5) that were acetylated to give compounds 6 and 7,
respectively. Compound 3 had been made previously by a
different route but was not fully characterized.38 Oxidation
with m-chloroperbenzoic acid (MCPBA) in dichloromethane
(DCM) at –76 8C yielded two isomeric sulfoxides for the
4,6-benzylidene derivative (8R and 8S) and for the 4,6-O-p-
methoxybenzylidene derivative (9R and 9S). In both cases,
the sulfoxide diastereomers were separated by column chro-
matography. The preferences for the oxidation reactions to
yield the RS isomer were much less than noted for gluco34,39
and manno5,29 analogues, being 3/1 for compound 3 and 7/2
for compound 5.
The geometries about the anomeric centre deviate from
perfect staggering to different extents in the three axial sulf-
oxide X-ray crystal structure determinations. The torsional
angles are shown in Fig. 7. In the crystal of the parent phe-
nyl thioglycoside, 6, the quaternary phenyl carbon atom is
perfectly staggered between the ring O and H1. In the crys-
Published by NRC Research Press

Liang et al.
1157
Fig. 6. ORTEP diagram of 8S.
Fig. 3. ORTEP diagram of 6.
Fig. 4. ORTEP diagram of 8R.
Fig. 7. Newman diagrams from C1 to S indicating torsional angles
about the anomeric centres of 6, 8R, 8S, and 9R calculated for
bond angles using the program PLATON.40 The top two structures
have the azide groups in gauche minus conformations, whereas the
bottom two are in gauche plus conformations (see the following for
further discussion).
Fig. 5. ORTEP diagram of 9R.
tals of the two sulfoxides that adopt anti conformations, 8R
and 9R, the quaternary phenyl carbon atom is much further
away from C2 than expected for a staggered conformation,
having C2–C1–S–C7 torsional angles of 80.6(3)8 and
75(1)8, for 8R and 9R, respectively. In contrast, in the crys-
tal of the sulfoxide that adopts an exo conformation, 8S, the
quaternary phenyl carbon atom is closer to the ring oxygen
(O–C1–S–C7 torsional angle of 48.0(2)8) than expected for
a staggered conformation.
Full geometry optimizations were carried out at the
B3LYP/6–31G(d) level of theory on the parent phenyl thio-
glycoside, 6, its oxides 8R and 8S, and their SMe analogs
(10, 11R, and 11S) in the gas phase. Frequency calculations
confirmed that all structures identified as conformers were
minima on the potential energy surfaces. In these cases,
single-point calculations were performed for all conformers
Published by NRC Research Press

1158
Can. J. Chem. Vol. 88, 2010
at the B3LYP/6–311G+(d,p) level of theory. The conforma-
tional situation is more complicated for these compounds.
Rotamer geometries and energies about two torsional angles
were evaluated, the glycosidic torsional angle, O5–C1–S–C,
and the torsional angle to the azide group, H2–C2–N–N. All
other torsional angles were allowed to rotate freely to mini-
mum energy values.
Fig. 8. Diagrams indicating the conformations calculated to be
adopted by the minima of compound 8R.
Anti conformations about the C1–S bond of the phenyl
thioglycoside, 6, were not minima on this potential energy
surface; initial geometries obtained from a variety of strat-
egies always rotated smoothly back to the exo conformer on
minimization. The anti conformer of the methyl analogue 10
was a minimum, 2.30 kcal mol–1 (1 cal = 4.184 J) less stable
than the exo conformer at the B3LYP/6–31G(d) + ZPVE
and 1.70 kcal mol–1 less at the B3LYP/6–311G+(d,p) +
ZPVE level of theory. Initial geometries for the two addi-
tional rotamers about the C2–N bond were obtained by start-
ing from the minimized geometry for each C1–S rotamer
and rotating about this bond. Several of these C–N rotamers
minimized to previously minimized structures, but two sets
of exo and anti minima were obtained for 8R and 11R, and
one set of two for the exo conformer of 6. Only one azide
rotamer was found for each of the exo and anti conformers
of 8S and 11S.
calculated for the a conformations with respect to the gp
conformations. H2–C2–N–N torsional angles were calcu-
lated to be small, having absolute values of 388–468 in all
gp and gm conformers. In the three C–N anti conformers,
the H2–C2–N–N torsional angles were between 1278 and
1478 with the N close to being eclipsed by C3.
The relative energies calculated for the anomeric con-
formers of these axial glycosyl sulfoxides (Table 1) were
unexpected in view of all previous discussion.17,23,33 The
anti conformers of the kinetically favored RS sulfoxides
were calculated to be more stable than the exo conformers
by 2.0 and 1.4 kcal mol–1 at the B3LYP/6–311G+(d,p) +
ZPVE level of theory for the phenyl and methyl sulfoxides,
respectively. For the minor sulfoxides, the SS diastereomers,
the exo conformer is calculated to be more stable by
1.1 kcal mol–1 for the phenyl glycoside and 2.0 kcal mol–1
for the methyl glycoside.
The interesting variations in geometry from perfect stag-
gering around the C1–S bond observed in the X-ray results
were evident here for all conformers (see Fig. 9). In particu-
lar, the quaternary phenyl carbon atom in the anti conformer
of 8R (gp) is calculated to be about as far away from C2 as
observed in the crystal, having a C2–C1–S–C7 torsional an-
gle of 818. In the methyl sulfoxide (11Ragp), this angle is
calculated to be slightly smaller, 768. The exo conformers
of 8R are calculated to deviate more from perfect staggering
in the unexpected direction than observed in the X-ray struc-
ture of 8S; the O1–C1–S–C7 angle was calculated to be 318
in the most stable gp conformer. In the two previously de-
termined X-ray structures of a-D-mannopyranosyl ethyl sulf-
oxides, the comparable angles observed were larger, 50.78–
56.88.28
The conformers obtained for 8R are illustrated in Fig. 8.
These are named with the compound number, followed by e
or a to indicate the anomeric conformation (exo or anti, re-
spectively), which is then followed by a, gp, or gm, to indi-
cate whether the azide N–N–C2–H2 torsional angle is anti,
gauche plus, or gauche minus, respectively. Conformer
stabilities are listed in Table 1.
For the conformers arising because of rotation about the
C2–N bond, the gauche plus (gp) and gauche minus (gm)
conformers are calculated to be more stable than the anti
(a) conformer. The gp conformer is always a minimum on
the potential energy surface. In the three cases where the a
conformation is a minimum (6, 8R, 11R), it is less stable
than the gp conformer by 1.0 0.2 kcal mol–1. The gauche
minus (gm) conformer was calculated to be a minimum only
for Re sulfoxide conformers, 8Re and 11Re, but in those
two cases, it was calculated to be more stable than the gp
conformer by 0.7 and 0.9 kcal mol–1, respectively. The
azides in the crystal structures of 6 (exo conformer) and 8R
(anti conformer) are present in gm conformations, while
those in 8S (exo conformer) and 9R (anti conformer) are
present in gp conformations, consistent with the small en-
ergy differences between the latter two conformations and
probably small barriers between these two minima. The ab-
sence of anti conformations for azides in these crystal struc-
tures are consistent with the larger energetic destabilizations
In view of the distance determinations obtained from
NOE measurements (vide infra) and the difference between
calculated and X-ray geometries mentioned earlier, the var-
iations in energy as a function of two different torsional an-
gles were evaluated for compound 8R. Rotation about the
Published by NRC Research Press

Table 1. Calculated conformational energies and dipole moments for axial glycosyl sulfoxides.
DE (6–31G(d)) DE (6–31G(d)) DE (6–31G(d)) + ZPVE
DE (6–31G(d)) + ZPVE
DE (6–311+G(d,p)) + ZPVE DE (6–311+G(d,p)) + Dipole moment
Conformer
6egpd
6ea
10egp
10agp
(kcal mol–1)a
0.0
(kcal mol–1)b
0.0
(kcal mol–1)a
0.0
(kcal mol–1)b
0.0
(kcal mol–1)a
0.0
ZPVE (kcal mol–1)b
(D)c
1.84
1.96
2.24
0.57
2.54
3.31
5.55
5.73
2.54
3.17
5.64
5.75
3.49
2.62
3.33
2.99
0.0
1.08
0.0
1.70
0.0
0.83
2.02
2.92
0.0
1.05
1.42
2.54
0.0
1.08
0.0
1.21
0.0
1.21
0.0
1.28
0.0
1.28
0.0
2.33
0.0
1.07
3.12
3.62
0.0
1.16
2.86
3.35
0.0
1.08
0.0
2.30
2.03
3.04
5.36
5.97
2.36
3.47
5.62
6.08
0.0
2.30
0.0
1.01
3.33
3.94
0.0
1.11
3.26
3.72
0.0
2.33
2.00
3.08
5.12
5.63
2.42
3.58
5.29
5.62
0.0
1.70
2.25
3.08
4.27
5.18
2.61
3.67
4.04
5.16
0.0
8Ragp
8Raa
8Regm
8Regp
11Ragp
11Raa
11Regm
11Regp
8Segp
8Sagp
11Segp
11Sagp
1.39
0.0
1.39
0.0
1.41
0.0
1.41
0.0
2.46
1.08
0.0
1.96
2.45
2.45
2.46
1.96
aRelative to the most stable conformer of all diastereomers of this compound.
bRelative to the most stable conformer of this diastereomer.
cCalculated at the 6–311G+(d,p) level of theory.
dNo anti conformation of compound 6 was calculated to be a minimum.

1160
Can. J. Chem. Vol. 88, 2010
Table 2. Comparison of results obtained by different methods.
a
˚
Internuclear distance (A)
Relative energy
Compound
6
Method
NOE
DFT (egp)
DFT (ea)
X-ray (egm)
NOE
r(HSPo,H1)
3.0
2.64
2.64
2.84
3.0
r(HSPo,H3)
NOc
5.09
5.59
4.78
4.7
r(HSPo,H5)
3.4
3.40
3.46
2.67
3.6
(kcal mol–1)b
NAd
0.00
1.08
NAd
8R
NAd
DFT (agp)
DFT (aa)
DFT (egm)
DFT (egp)
X-ray (agm)
X-ray (agp)
NOE
2.55
2.51
2.96
2.93
2.68
2.53
3.4
3.84
4.17
4.12
3.96
3.92
3.86
4.6
5.15
5.11
2.38
2.38
5.18
5.07
3.3
0.00
0.83
2.02
2.92
NAd
9R
8S
NAd
NAd
DFT (egp)
DFT (agp)
X-ray (egp)
2.64
3.02
2.95
4.66
4.76
4.58
2.87
4.45
2.55
0.00
1.08
NAd
aThe distance to the closest ortho H (HSPo).
bFrom 6–311G+(d,p) + ZPVE/6-31G(d) calculations.
cNO = not observed.
dNA = not applicable.
Fig. 9. Newman projections from C1 to S showing torsional angles about the anomeric centre calculated for the various conformers of
compounds 6, 10, 8R, 11R, 8S, and 11S.
Published by NRC Research Press

Liang et al.
1161
Fig. 10. Variation in energy and internuclear distances calculated using B3LYP6–31G(d) as a function of O5–C1–S–C7 torsional angle for
compound 8R. Right: internuclear distances. Left: energies.
axis of the glycosyl phenyl ring was evaluated first. The tor-
sion angle C1–S–C7–C8 was held constant at fixed values in
108 intervals from the value found at the minimum for the
conformer 8Regp. The energy change as a function of tor-
sional angle is fairly symmetrical about the minima indicat-
ing that the measured NOE should represent the minimum
well (Fig. S1 in the Supplementary data). Then the torsion
angle O1–C1–S–C7 was held constant at values ranging
from 58 to 108 increments about the value found at the mini-
mum for the conformer 8Regp. Figure 10 shows how the
energy and the internuclear distances vary as a function of
this angle. For torsional angles >908, the energy decreased
in a nonsymmetric way because the azide conformation
minimized from the gm arrangement was most stable in
8Re and to the gp conformation was most stable for 8Ra.
The variation in energy is not symmetric about this angle,
being much flatter towards values of the torsional angle that
are larger than that of the minimum. Hence, the time-averaged
O1–C1–S–C7 torsional angle will be significantly larger than
that present in the geometry of the minimum and the NOEs
observed for this conformer and will yield longer H1–HSPo
and H5–HSPo distances than calculated for the minimum.
To determine the cause of the method of assignment of
sulfoxide configuration based on 13C NMR chemical
shifts,26 the Gauge invariant atomic orbital (GIAO)
method41,42 was used to calculate 13C shieldings for all car-
bons of the 8R and 8S conformers using the 6–311+G(d,p)
basis set and 6–31G(d) geometries. TMS was used as the
chemical shift reference. The chemical shifts obtained are
listed in Table S5 in the Supplementary data and all calcu-
lated values were slightly larger than the experimental val-
ues. Plots of experimental chemical shifts against the
chemical shifts calculated for all nonaromatic carbons gave
good straight lines with correlation constants of 0.989–
0.996 and slopes ranging from 0.947 to 0.982 (not shown).
The anomeric chemical shifts of the carbons consistently de-
viated from the lines, having calculated values that were
larger than the experimental values by greater amounts than
those of carbons with similar shifts. According to the
method proposed by Khiar,26 to assign glycosyl sulfoxide
stereochemistry from anomeric carbon chemical shifts, C1
of the SS sulfoxide should be more shielded that that of the
RS sulfoxide. This was observed experimentally: the C1
chemical shifts were 92.5, 96.4, 89.9, and 96.5 ppm for 8S,
8R, 9S, and 9R, respectively. The values calculated for the
four 8R conformers were 108.9, 112.6, 114.8, and
114.8 ppm for 8Ragp, 8Raa, 8Regp, and 8Regm, respec-
tively, and those for 8Segp and 8Sagp were 106.1 and
105.7 ppm, respectively. Thus, all values for 8S conformers
were less than those for 8R conformers, which is in agree-
ment with both experiment and prediction. A value for 8R
in between that of 8Ragp and those of the exo conformers
and one for 8S of the exo conformer would give a difference
very similar to those observed in solution for the 8 and 9 di-
astereomers. Khiar26 ascribed the shielding of the SS isomers to
n ? s* overlap. The value calculated for C1 of 8Sagp, which
cannot have n ? s* overlap, is the lowest of all, indicating
that n ? s* overlap does not cause this shielding effect.
The conformation adopted in solution was investigated by
measuring initial NOE buildup rates using both selective 1D
NOE measurements with the double pulsed field gradient
spin echo (DPFGSE) sequence43 and 2D NOESY experi-
ments using a variety of mixing times. The initial rates are
directly proportional to the internuclear distances (rIS) and
were calibrated using a known internuclear distance (rref) as
follows:
Published by NRC Research Press

1162
Can. J. Chem. Vol. 88, 2010
ꢀ
ꢁ
1=6
tance obtained from the NOE. The H1–HSPo distance, ob-
NOEref
NOEIS
rIS ¼ rref
˚
tained from the NOE, was 3.05 A. The average of DFT
˚
calculated values in the two exo conformers is 2.95 A and is
˚
˚
2.53 A in the two anti conformers. These results indicate that
The distance between ortho phenyl protons (HSPo; 2.8 A)
was used as the reference distance (rref).44 The results are
given in Table 2 along with the results obtained by the pre-
vious methods.
For the parent compound 6, the NOE results fit the geom-
etry calculated for the exo conformer well. The distances
a mixture of the exo and anti conformers is present in solution.
A very approximate estimate of the amount of the exo
conformer present can be obtained from the H5–HSPo dis-
tances calculated for exo and anti conformers and the value
obtained from the NOE measurement using r6 averaging.
˚
˚
˚
The use of 3.6 A for the average, 5.15 A for the anti con-
from HSPo obtained to H1 and to H5 are within 0.4 A of
˚
former, and 2.38 A for the exo conformer yields 7% of the
those calculated and no NOE was observed for the interac-
tion with H3, as expected. However, the H5–HSPo distance
obtained from the NOE measurement was much longer than
that measured from the X-ray results. As discussed previ-
ously, the potential surface is fairly flat with respect to
changes in the O1–C1–S–C7 torsional angle from the 808
value calculated for the gas phase. Crystal packing presum-
ably causes this value to be altered from that calculated for
the minimum to the 59.4(5)8 value observed in the solid
state. The average of all 23 O1–C1–S–C7 torsional angles
from the crystal structures in the Cambridge data file (Table
S1 in the Supplementary data) was 61.58.
For the RS sulfoxide, the distances obtained from the NOE
measurements do not match the pattern obtained from the
X-ray results or from the geometries calculated for the two
lowest energy minima, the global minimum, the 8Ragp con-
former, and the other anti conformer (see Table 2). In both
anti conformers, the H5–HSPo distance is calculated by DFT
exo conformer. This amount corresponds to a DG8 value of
1.5 kcal mol–1 for the equilibrium between conformers,
which is on the same order as that calculated.
Evaluation of the effect of the 2-azido group
To examine whether the above results were influenced by
the 2-azido group, calculations were performed on the
2-deoxy analogs shown below at the same level of theory,
except that conformations were also minimized at the
B3LYP/6–311+G(d,p) level. As previously, calculations were
performed on two conformations of each of these, the anti (a)
and exo (e) conformers. In addition, calculations were per-
formed on the endo conformers of the methyl glycosyl sulfox-
ides, 15Sen and 15Ren, to check whether the earlier
assumption that this class of conformer was too energetic to
contribute to the mixture present was valid. The anti conform-
ers of both SS diastereomers, that is, 13Sa and 15Sa, were not
minima on their potential energy surfaces and neither was one
of the endo conformers, 15Ren. The results are given in
Table 3 and Newman projections showing the relationships
among groups at the anomeric centres are shown in Fig. 11.
˚
to be >5 A, too large to give an NOE. However, an H5–HSPo
NOE was observed and the distance calculated from it was
3.62 A. For both exo conformers, the H5–HSPo distances are
calculated by DFT to be 2.38 A, much shorter than the dis-
˚
˚
The exo conformer of the methyl 2-deoxythioglycoside
(14) was calculated to be somewhat more stable with respect
to the anti conformer than its 2-azido-2-deoxy analogue (10)
(3.2 vs 2.3 kcal mol–1). For this series, the anti conformer of
the phenyl thioglycoside was also a minimum, 2.3 kcal
mol–1 less stable than the exo conformer. For the RS sulfox-
ide of the 2-deoxy analogue, 15, the exo conformer (15e)
was more stable than the anti conformer (15a) by 1.5 kcal
mol–1. The two conformers of the RS phenyl 2-deoxy sulfox-
ides (13) were calculated to be almost equally stable at the
B3LYP 6–311+G(d,p) level of theory, the exo conformer
being 0.1 kcal mol–1 more stable. Neither of the anti con-
formers of the SS sulfoxides of the 2-deoxy derivatives
(13Sa and 15Sa) were minima at this level of theory.
expected for perfect staggering, being 708 for R13a and 788
for R15a. In contrast, the exo conformers of R13 and R15
deviate from perfect staggering in the opposite direction
from their 2-azido analogues. In the latter derivatives (see
Fig. 9), the O5–C1–S–C7 torsional angle had values in the
318–388 range, whereas the O–S–C1–C2 angle was in the
848–918 range. For 13Re and 15Re, the values of the O5–
C1–S–C7 torsional angles are 828 and 718, respectively,
whereas those of the O–S–C1–C2 angles are 418 and 528,
respectively. These changes are consistent with relief of di-
pole–dipole repulsion between the potentially parallel C–N
and S–O dipoles of the 2-azido derivatives. When the 2-
azido group was removed, the conformational minima have
O–S–C1–C2 angles <608 and the O5–C1–S–C7 values
are >608, relieving steric strain from the interaction of the
aglycone with the pyranose ring.
As shown in Fig. 11, the C2–C1–S–C7 torsional angles in
the anti conformers of the RS sulfoxides are similar to those
of their 2-azido analogues; the values are greater than those
Published by NRC Research Press

Liang et al.
1163
Table 3. Calculated conformational energies and dipole moments for axial 2-deoxyglycosyl sulfoxides.
DE (6–31G(d)) + ZPVE
DE (6–311+G(d,p)) + ZPVE
Conformer
12e
12a
13Re
13Ra
13Se
14e
(kcal mol–1)a
(kcal mol–1)a
Dipole moment (D)b
0.0
0.0
2.26
0.0
0.08
0.45
0.0
3.16
0.0
0.98
2.55
2.96
3.76
3.29
0.78
2.24
3.18
3.33
3.32
3.75
2.45
0.29
0.0
0.84
0.0
3.22
0.37
1.34
0.0
14a
15Re
15Ra
15Se
15Sen
1.54
0.14
5.25
5.82
aRelative to the most stable conformer of all diastereomers of this compound.
bCalculated at the 6–311G+(d,p) level of theory.
Fig. 11. Newman projections from C1 to S showing torsional angles about the anomeric centre calculated for the conformers of compounds
12R, 12S, 13R, 13S, 14R, 14S, 15R, and 15S.
An equatorial glycosyl sulfoxide
from a solution of 1% ethanol in hexanes. Its crystal struc-
ture (Fig. 12) establishes the SS configuration. Interestingly,
the compound adopts the conformation with the phenyl
group anti to the C1–O5 bond, in contrast to the results
from all previous X-ray determinations of equatorial glyco-
syl sulfoxides except one23 (see Table S1 in the Supplemen-
tary data for data on previous X-ray determinations of
glycosyl sulfoxides). In this conformation, the phenyl and
phthalimido groups lie roughly parallel to each other and
perpendicular to the plane of the tetrahydropyran ring, in an
arrangement typical of p stacking.
Treatment of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-
b-D-glucopyranoside45–47 (16) with thiophenol and boron tri-
fluoride etherate gave phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-
phthalimido-1-thio-b-D-glucopyranoside (17), previously
prepared by another method,48 in an 81% yield. Oxidation
with 1 equiv of m-chloroperbenzoic acid in dichloromethane
at –78 8C yielded 92% of a 2.1:1 mixture (18) of the SS
(18S) and RS (18R) isomers. It had previously been reported
that oxidation under similar conditions gave a 3:1 ratio of
the same isomers.17 The isomers were separated using flash
chromatography on silica gel with 5% acetone in dichloro-
methane as eluent.
This conformation of 18S persists in solution in chloroform-
d. The nearly parallel alignment of the aryl groups is evident
in both the chemical shifts of the phenyl protons and of the
phthalamido protons, which are affected by the anisotropic
chemical shift effects of these aryl groups (for recent sum-
maries of these effects, see papers by Lazzeretti and co-
1
workers49,50). In the H NMR spectrum of the starting mate-
rial (17), the phenyl ortho Hs appear at 7.45 ppm, whereas
the meta and para Hs appear as a complex multiplet from
7.2 to 7.3 ppm. Similar shifts have been reported for cyclo-
The major isomer (18S), the SS isomer, was recrystallized
Published by NRC Research Press

1164
Can. J. Chem. Vol. 88, 2010
Fig. 13. Part of the 400 MHz 1H NMR spectrum of compound 18R.
Fig. 12. ORTEP diagram of 18S.
1
Fig. 14. Part of the 400 MHz H NMR spectrum of compound 18S.
hexyl phenyl sulfide, 7.38 (ortho), 7.25 (meta), and 7.17
(para) ppm.51 Conversion to the sulfoxide results in de-
shielding, e.g., in the spectrum of cyclohexyl phenyl sulfox-
ide, 7.54 (ortho), 7.45 (meta), and 7.45 (para) ppm,51 and
also in that of compound 18R, 7.90 (ortho), 7.58 (meta), and
1
7.70 (para) ppm (see Fig. 13). In contrast, in the H NMR
spectrum of 18S, these signals appear at 7.49 (ortho),
7.21 (meta), and 7.13 (para) ppm (Fig. 14). All signals are
shielded in comparison with those of the RS isomer, Dd 0.41
(ortho), 0.37 (meta), and 0.57 (para) ppm, which are consis-
tent with the effects of a nearly parallel phthalimido group.
The effects on the phthalimido protons are more dramatic.
AA’BB’ patterns typical of disubstituted benzenes with iden-
tical ortho substituents are observed for the parent com-
pound with chemical shifts of 7.76 and 7.87 ppm and for
18R with chemical shifts of 7.77 and 7.90 ppm (Fig. 13). In
contrast, the phthalimido proton signals in the spectrum of
18S are exchange broadened (Fig. 14). A broad singlet at
7.67 ppm is superimposed on a much broader smooth low
band centered at about 7.73 ppm. Rotation of the phthali-
mido group is hindered by the favorable interactions associ-
ated with the near parallel arrangement of the phenyl and
phthalimido groups. If there was a rapid equilibrium be-
tween anti and exo conformations, the phthalimido group
would be able to rotate freely when the phenyl group was
exo. Thus, the observation of a single pattern exhibiting hin-
dered rotation indicates that the anti conformation is essen-
tially the only conformation populated in solution and that
rotation about the C1–S bond to the exo conformation is
slow, as are rotation about both the phenyl C–S bond and
the C2–N bond.
Quantum mechanical calculations were performed with
density functional theory as implemented in Gaussian 0352
with Becke’s three parameter exchange functional and Lee–
Yang–Parr correlational functionals.53,54 The X-ray structure
of compound 18S provided the initial geometry of the glyco-
syl sulfoxide. The initial geometries for the second stag-
gered rotamer were generated by rotating about the C1–S
bond and those for the other sulfoxide diastereomer were
generated by inverting at sulfur. The third staggered ro-
tamer, with the aglycone gauche to both C2 and the ring
oxygen, was not used as a starting point for geometry mini-
mization. Initial geometries for the SMe analog and its sulf-
oxides were obtained from the minimized thiophenyl
conformers. Initial geometries for 17 and its methyl ana-
logue, 17Me, were obtained by removing an oxygen atom
from the minimized sulfoxide conformers. Full geometry op-
timizations were carried out at the B3LYP/6–31G(d) level of
theory on 17, 18S, and 18R, and their SMe analogs (17Me,
18SMe, and 18RMe). However, neither Hartree–Fock mo-
lecular orbital theory nor current implementations of density
functional theory, which use local approximations of the
density, are capable of accurately describing the dispersion
forces, which are the major interaction causing p stacking.55
Theoretical methods that could provide accurate measures of
the dispersion forces are too time-consuming for molecules
of the size of compound 18S. Thus, the stabilities of con-
formers with geometries in which two arene rings are close
to parallel will be underestimated.
All starting conformations, that is, both anti and exo con-
formations, of the parent thioglycosides, 17 and 17Me,
smoothly changed geometry on optimization to that of the
exo conformers. On this potential energy surface, the anti
conformations are not minima. The results for the glycosyl
sulfoxides are shown in Table 4. The most stable conformer
of the SS diastereomer is calculated to be more stable than
that of the RS diastereomer by 1.85 and 1.36 kcal mol–1 for
the phenyl and methyl glycosyl sulfoxides, respectively. For
all compounds, the exo conformers are calculated to be more
stable than the anti conformers. For 18S, which was observed
to adopt the anti conformer both in the solid state and in sol-
ution, the exo conformer was calculated to be the more stable
conformer by 1.57 kcal mol–1, although the anti conformer is
calculated to have the larger dipole moment, 5.63 vs 1.40 D.
For 18R, which is present as the exo conformer in solution,
the calculated difference is 3.03 kcal mol–1.
Published by NRC Research Press

Liang et al.
1165
Table 4. Calculated conformational energies and dipole moments for the equatorial glycosyl sulfoxides.
DE (6–31G(d)) DE (6–31G(d))
Torsional angle
O5–C1–S–C (8)
–157.7
–67.6
–176.1
–54.2
–145.1
–65.5
–168.4
–44.9
Torsional angle
O5–C1–S–O (8)
91.4
–177.1
–66.5
56.7
103.7
–175.3
–59.4
66.4
Dipole moment
(D)c
Conformer
18Santi
18Sexo
18Ranti
18Rexo
18SMeanti
18SMeexo
18RMeanti
18RMeexo
(kcal mol–1)a
1.57
0.0
(kcal mol–1)b
1.57
5.63
1.41
6.60
4.00
4.61
0.86
6.46
3.85
0.0
3.03
0.0
4.88
1.85
2.31
0.0
2.31
0.0
3.48
0.0
4.83
1.36
aRelative to the most stable conformer of all diastereomers of this compound.
bRelative to the most stable conformer of this diastereomer.
cCalculated at the 6–31G(d) level of theory.
oxide of the 2-deoxy analogue, 15, the exo conformer (15e)
was more stable than the anti conformer (15a) by
1.5 kcal mol–1. Therefore, the extent to which the anti con-
former of the methyl thioglycoside was stabilized on oxida-
tion to the RS diastereomer was smaller for the 2-deoxy
derivative, 1.5 kcal mol–1, but was still substantial. For the
phenyl thioglycoside (12), the corresponding stabilization of
the anti conformer of the RS sulfoxide was calculated to be
2.2 kcal mol–1, again at the B3LYP 6–311+G(d,p) level of
theory.
Comparison of the geometries of the RS exo conformers
of the 2-deoxy derivatives with the 2-azido-2-deoxy deriva-
tives shows that the 2-azido substituent has a significant ef-
fect. The O5–C1–S–O torsional angles calculated for 8Regp,
8Regm, 11Regp, 11Regm, 13Re, and 15Re are 139.38,
144.48, 145.08, 146.28, 168.58, and 179.58, respectively. The
latter two values are consistent with minimization of steric
interactions for the R group and dipole–dipole repulsion due
to interaction of the endocyclic C–O bond and the sulfoxide
S–O bond. When the 2-azido group is present, dipole–dipole
repulsion between the parallel C2–N bond and the S–O bond
causes rotation about the C1–S bond resulting in much
smaller O5–C1–S–O torsional angles. This is a significant
effect because it is at the expense of increased R pyranose
ring steric interactions and increased dipole–dipole repulsion
due to interaction of the endocyclic C–O bond and the sulf-
oxide S–O bond. The small effect of the latter type of
dipole–dipole repulsion suggests that it is not as important
as other factors in determining conformational preferences
for glycosyl sulfoxides.
In terms of energies, the most stable azide conformers of
the anti RS 2-azido-2-deoxy derivatives are calculated to be
more stable than the most stable azide conformers of the exo
RS 2-azido-2-deoxy derivatives by 2.0 and 1.4 kcal mol–1 for
the phenyl and methyl sulfoxides, respectively, at the
B3LYP6–311+G(d,p) level of theory. For the 2-deoxy deriv-
atives, without the parallel C–N dipole, the exo conformers
are now more stable by 0.1 and 1.5 kcal mol–1 for the phe-
nyl and methyl sulfoxides, respectively. This represents
changes of 2.1 and 2.9 kcal mol–1 for the phenyl and methyl
sulfoxides, respectively, and represents the costs of having
these dipoles parallel.
Discussion
Axial glycosyl sulfoxides
The gas phase DFT calculations indicate that axial glyco-
syl sulfides favor the exo-anomeric conformers over anti
conformers by substantial amounts, 1.7 kcal mol–1 for the
methyl 2-azido-2-deoxythioglycoside (10) and 3.2 kcal
mol–1 for the methyl 2-deoxythioglycoside (14). For the phe-
nyl 2-azido-2-deoxythioglycosides, the anti conformations
were not minima on the potential energy surfaces. The fact
that in all 23 X-ray structure determinations of axial glyco-
syl sulfides, the conformation observed was the exo confor-
mation (Table S3 in the Supplementary data) confirms these
calculated results.
Of the two diastereomers of the glycosyl sulfoxides, 8 and
11, the most stable conformer of the minor diastereomers,
8S and 11S, are calculated to be more stable than that of
the major diastereomers by 2.3 and 2.6 kcal mol–1, respec-
tively. Because the diastereomers obtained to a greater ex-
tent from the oxidation are calculated to be less stable than
the diastereomers obtained in lesser amounts, this result
strongly supports the conclusion that the stereoselectivity of
oxidation is kinetically controlled and results from the pre-
ferred exo conformation of the sulfide.23,28
The 2-azido-2-deoxy SS sulfoxides (8S and 11S), which
retain the sulfur lone pair anti to the C1–O5 bond in the
exo conformers, were calculated to have about the same
conformational preferences for these exo conformers as the
parent sulfides. One factor favoring this conformer must be
n ? s* donation from the sulfur lone pair into the C1–O5
antibonding orbital. This conformer is calculated to have
the shortest C1–S bonds of all conformers of 8 and 13 (see
Fig. 15), which is consistent with this overlap. Thus, the exo
arrangement of the aglycone plus the n ? s* overlap helps
explain the greater stability of this conformer of the kineti-
cally disfavored diastereomer.
However, for the RS sulfoxide (11Ragp), which does not
have an anti lone pair in the exo conformation, the conforma-
tional preference is calculated to shift from being in favor of
the exo conformer for the parent methyl sulfide (10egp) by
1.7 kcal mol–1 to being in favor of the anti conformer by
1.4 kcal mol–1, a change of 3.1 kcal mol–1 (3.7 kcal mol–1 for
the phenyl glycoside, if it is assumed that the sulfide prefer-
ence is the same as for the methyl glycoside). For the RS sulf-
Published by NRC Research Press

1166
Can. J. Chem. Vol. 88, 2010
Fig. 15. Calculated structural features for axial phenyl sulfide and phenyl sulfoxide conformers.
Crich et al.23 equilibrated the two sulfoxide diastereomers
of allyl 2,3,4-tri-O-benzoyl-1-thio-a-D-xylopyranoside oxide
(19) and allyl 2,3-di-O-benzyl-4,6-O-benzylidene-1-thio-a-D-
mannopyranoside oxide (20) in both benzene-d6 and methanol-
d4 at 60 8C. The former compound is most analogous to
lated to be 2.4 kcal mol–1 more stable than 11Ragp), even
though the C2 substituent is very different. Since the SS dia-
stereomers are calculated to have somewhat larger dipole
moments (3.3 vs 2.5 D for 18, 3.5 vs 2.5 D for 11), the de-
creased preference for this diastereomer in methanol is un-
expected and may be due to specific solvation of the RS
diastereomer as suggested by Crich et al.23
For compound 20, the preferences for the RS diastereomer
are 0.7 and 0.6 mol–1 at 60 8C in benzene and methanol, re-
spectively. Using the value estimated previously, this result
indicates that the RS diastereomer is stabilized
by >2.6 kcal mol–1 when the equatorial 2-O-benzoyl group
is converted to axial. Comparison of the calculated relative
stabilities of the analogous 2-azido-2-deoxy diastereomers
(11) with their 2-deoxy analogs (15) shows a similar
2.5 kcal mol–1 relative stabilization of the RS diastereomer
on removal of the equatorial 2-azido group. From these re-
sults, it is clear that the C2 configuration has a large effect
on diastereomer stability.
4
those studied here because in its C1 conformation it bears
an equatorial substituent at C2. For 19, the SS diastereomer
was favored by 2 to 1 in benzene but the other diastereomer
was favored by 2.5 to 1 in methanol. The results here indi-
cate that 19S will prefer the exo conformation, 19Se, rather
than the anti conformation, 19Sa, because this allows the
allyl group to assume the sterically preferred exo orientation
and because the sulur lone pair is correctly oriented for n ?
s* overlap. Crich et al.’s23 results do not provide a direct
estimate of the preference for the SS diastereomer because
the RS diastereomer ring inverts completely (as determined
3
from JH,H values) to the 1C4 chair. To compare relative
stabilities of particular conformers of the SS and RS diaster-
eomers, the same ring conformations must be employed. If
1
4
the conformational preference for C4 over C1 is estimated
at >9/1, the equilibration results for 19 correspond to DG8
values of >1.9 and >0.8 kcal mol–1 at 60 8C in benzene and
methanol, respectively, in favor of the SS diastereomer in the
4C1 conformation. The value in benzene is in the same range
as that calculated by DFT methods here (11Segp is calcu-
It remains to be considered why the anti conformers of
the RS sulfoxides are more stable relative to the exo con-
formers than expected based on normal23 conformational ar-
guments. It is very well established that glycosides and
thioglycosides prefer exo-anomeric conformations. Several
factors influence this preference: n ? s* overlap, dipole–
Published by NRC Research Press

Liang et al.
1167
dipole repulsion, and reduced steric interactions and electro-
static attraction. Changing from a sulfide in the exo-anomeric
conformation to the RS sulfoxide results in the loss of the n
? s* overlap but adds a dipole in its most favorable ar-
rangement with respect to the endocyclic C1–O5 dipole,
namely, antiparallel. However, in 8Re and 11Re, it also
adds a parallel dipole–dipole repulsive interaction between
the S–O dipole and the C2–N dipole. As noted previously,
the anti conformers have C2–C1–S–C7 torsional angles that
are considerably greater than staggered, both in the presence
and absence of electronegative substituents on C2. This de-
viation from perfect staggering has the effect of minimizing
steric interactions at the expense of increasing dipole–dipole
repulsion between the S–O bond and the endocyclic C–O
bond. Clearly, the latter factor is less important than the for-
mer and any other interactions. It is interesting that the C7–
S–O units in the anti conformers are close to being eclipsed
by the H1–C1–C2 unit (see Fig. 13, 8Ra and 11Ra, and
Fig. 12, 13Ra and 15Ra). If they were eclipsed, the sulfur
lone pair would be syn to the C1–O5 bond. The C1–S bonds
in the most stable Ra conformers, 8Ragp and 13a, are cal-
culated to be almost as short as they are in the conformers
having n ? s* overlap, 8Sepg and 13Se, which is consistent
with an extra stabilizing interaction. This interaction is be-
tween orbitals of correct symmetry if the S lone pair that
overlaps with the C1–O5 s* orbital is a p-type lone pair.
All of the other conformers are calculated to have C1–S
adopts the anti conformation about the glycosidic linkage in
the solid state and the NMR evidence described in the Re-
sults section demonstrated conclusively that this conforma-
tion is the predominant one in solution. The near parallel
alignment of the SPh and phthalimido groups suggests that
p stacking contributes to the stabilization of this conforma-
tion. p Stacking was recently shown to influence the confor-
mation about the glycosidic bond in a disaccharide.57 Such
interactions provide stabilizations on the order of
2.8 kcal mol–1 for the most favorable displaced parallel geo-
metries.55,58–61 This factor is presumably very important in
causing compound 18S to adopt the anti conformation. It is
notable that compound 18R, which could also adopt a p-
stacked conformation, clearly adopts the conformation fa-
vored by the exo-anomeric effect (as shown by its NMR
spectra data) with the phenyl group exo and the lone pair
on sulfur correctly aligned for n ? s* overlap with the C1–
O5 antibonding orbital.
The DFT calculations for the glycosyl sulfoxides indicate
that the exo conformers of both diastereomers are more sta-
ble in the gas phase. For the phenyl glycosyl sulfoxides, the
differences are calculated to be 1.57 and 3.03 kcal mol–1 for
18S and 18R, respectively. The 18R exo conformer is stabi-
lized by having the S lone pair anti to the ring C–O bond,
which is geometry suitable for n ? s* overlap. This con-
former is calculated to have the shortest C1–S bond length,
˚
˚
1.878 vs 1.885 A for the 18S exo conformer and >1.89 A
for the anti confomers, which is in agreement that this over-
lap is significant.
˚
bond lengths that are 0.02–0.05 A longer (see Fig. 15).
Based on a perturbation molecular orbial (MO) approach
21
for dimethoxymethane,56 Tvaroska and Bleha have con-
ˇ
Even though the conformation adopted by the SS diaster-
eomer is not that predicted on the basis of the exo-anomeric
effect, the 13C NMR chemical shift of its carbon atom
(89.1 ppm) was greater than that of the corresponding car-
bon atom of the RS diastereomer (86.1 ppm), which is in
agreement with the method for assignment of sulfoxide con-
figuration proposed by Khiar.26
cluded that both the s and p lone pairs on oxygen can over-
lap with the C–O s* orbital and both overlaps provide
similar stabilization. The overlap advocated here is similar
to the oxygen atom p ? s* overlap of that view.21
Comparison of the Re and Se conformers of the 2-deoxy
derivatives allows an evaluation of the relative strengths of
n ? s* overlap and adoption of antiparallel endocyclic C–
O and S–O dipoles (see Fig. 12 for Newman projections of
the relevant relationships). The Re conformers have antipar-
allel endocyclic C–O and S–O dipoles. The Se conformers
adopt shapes with ideal geometries for n ? s* overlap but
are presumably destabilized by gauche interactions between
endocyclic C–O and S–O dipoles. For both the phenyl and
methyl sulfoxides, the Re conformers are calculated to be
slightly more stable, by 0.45 and 0.14 kcal mol–1, respec-
tively, suggesting that the two interactions are comparable
in magnitude.
Conclusions
The evidence presented here shows that the most stable
configurations of glycosyl sulfoxides are those that can
adopt conformations with the aglycone exo and the lone
pair on sulfur anti to the C1–O5 bond, because of the n ?
s* overlap possible in this orientation. For D-pyranosides,
these are the SS configurations of the a-anomers and the RS
configurations of the b-anomers. Equilibration studies by
Crich et al.23 are in agreement with the conclusions drawn
here for glycosyl sulfoxides with substitutents at C2 equato-
rial but indicate that the configuration at C2 has a major
effect on glycosyl sulfoxide conformer stability. Electroneg-
ative substituents in equatorial orientations at C2 destabilize
the conformation with the sulfoxide oxygen atom anti by
about 2.5 kcal mol–1. The calculations indicate that n ? s*
overlap and the preference for the endocyclic C–O dipole
and the S–O to adopt antiparallel conformations have effects
that are about equal in size in determining glycosyl sulfox-
ide conformations in the gas phase or nonpolar solvents.
For the less stable but kinetically favoured RS diastereomers
of the b-anomers, anti conformers are comparable in stabil-
ity to the exo conformers because of the n ? s* overlap
possible if the sulfur lone pair is a p-type lone pair.
Equatorial glycosyl sulfoxides
Equatorial alkyl and aryl thioglycosides overwhelmingly
adopt exo-anomeric conformations in the solid state (22 out
of 25, see Table S1 in the Supplementary data), indicating
that there is a strong thermodynamic preference for this con-
formation. The results of DFT (6–31G(d) B3LYP) calcula-
tions support this conclusion, since the anti conformations
of both the thiophenyl and thiomethyl glycosides smoothly
change geometry on minimization to the exo conformer,
although this level of theory underestimates55 the stabilizing
effect of p stacking.
In contrast, (SS) phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-
phthalimido-1-thio-b-D-glucopyranoside
S-oxide
(18S)
Published by NRC Research Press

1168
Can. J. Chem. Vol. 88, 2010
The method for assignment of glycosyl sulfoxide configu-
least-squares refinement using the setting angles of a mini-
mum of 24 reflections (with the exception of 12R where
only 10 reflections were obtained). The data were collected
at temperatures of 23 8C (8S and 18S), –100 8C (6 and 9R),
or –130 8C (8R) using the u–2q scan technique. The inten-
sities of three representative reflections were measured after
every 150 reflections; no decay corrections were applied. An
empirical absorption correction62 based on azimuthal scans
of several reflections was applied for every structure except
9R. The data were corrected for Lorentz and polarization ef-
fects. Data reduction was carried out using the TEXSAN
software package.63 The structures were solved by direct
methods using SIR-92.64,65 Full-matrix least-squares refine-
ment was carried out on F2 data using SHELXL-97.66 Sec-
ondary extinction was refined for 18S. In all cases, the non-
hydrogen atoms were refined anisotropically. Hydrogen
atoms were included but not refined. They were placed in
geometrically calculated positions and allowed to ride on
the heavy atom to which they were bonded with isotropic
temperature factors (Uiso) equal to 1.2 times Ueq of the
heavy atom (1.5 times Ueq for methyl hydrogens).
rations by comparing the 13C NMR chemical shifts of C1 for
the two diastereomers proposed by Khiar26 was supported by
the chemical shifts calculated by the Gauge invariant atomic
orbital (GIAO) method. However, the explanation advanced
for the rule that C1 from the SS sulfoxide is more shielded
that that of the RS sulfoxide, because of n ? s* overlap in
the SS sulfoxide, does not appear to be correct.
Experimental section
General methods
Melting points were determined with a Fisher-Johns melt-
1
ing point apparatus and are uncorrected. H and 13C NMR
spectra were recorded at 300 K in 5 mm NMR tubes on
Bruker NMR spectrometers (AC-250, AMX-400, or
Avance-500) operating at 250.13, 400.13, or 500.13 MHz
for proton spectra and 62.9, 100.08, or 125.77 MHz for car-
bon spectra, respectively, on solutions in chloroform-d, un-
less otherwise indicated. Chemical shifts are given in parts
per million (ppm; 0.01 ppm) relative to that of tetramethyl-
1
silane (TMS; 0.00 ppm) in the case of H NMR spectra and
to the central line of chloroform-d (d 77.16) for the 13C
NMR spectra. All assignments were confirmed by COSY,
HETCOR, HMQC, HSQC, or HMBC experiments. Exact
masses measured using electron ionization (EI; 70 eV) were
done on a CEC 21-110B mass spectrometer. Electrospray
mass spectra were recorded on a Fisons Quattro mass spec-
trometer with a Quattro source (cone voltage, 55 V; flow
rate, 5 mL/min; complexing agent, potassium acetate; sol-
vent, 75:25 v/v acetonitrile/water). Optical rotations were de-
termined with a Rudolph Instruments Digipol 781 automatic
polarimeter or with a PerkinElmer model 141 polarimeter.
Thin layer chromatography (TLC) was performed on alumi-
num-backed plates bearing 200 mm silica gel 60 F254 (Merck
or Silicycle). The ratio of the solvents used in TLC and col-
umn chromatography was a volume ratio. Compounds were
visualized by UV where applicable and (or) were located by
spraying with a solution of 2% ceric sulfate in 1 mol/L sul-
furic acid followed by heating on a hot plate until colour de-
veloped. Compounds were purified on silica gel (TLC
standard grade, 230–400 mesh) by flash chromatography us-
ing specified eluents. Elemental analyses were performed by
the Canadian Microanalytical Service, Delta, British Colum-
bia.
NMR experiments
Experiments were performed on 0.04 mol/L solutions in
acetone-d6 unless otherwise specified. NOESY spectra were
recorded on the Bruker Avance 500 MHz NMR spectrome-
ter using different mixing times. Spectra were processed
with Bruker’s XWIN-NMR package. The matrices were
transformed to a final size of 8192 and 2048 points in F2
and F1 dimensions, respectively. The signal was multiplied
by a shifted qsin bell window in both dimensions prior to
Fourier transformation, then phase and baseline corrections
on both dimensions were applied. The numbers of contour
layers were set at 18. For compound 6, spectra were re-
corded with a relaxation delay of 1 s with mixing times of
0.3, 0.5, 0.7, 1, and 1.5 s. For 8R, spectra were recorded
with a relaxation delay of 2.5 s and mixing times of 0.5,
0.7, 0.9, 1.1, and 1.3 s. For compound 9R, spectra were re-
corded with a relaxation delay of 1 s and mixing times of
0.3, 0.5, 0.7, 1, and 1.5 s.
Relaxation times were determined for compounds 6 and
8R by the inversion recovery method to set the relaxation
delays for the 1D NOE experiments. The t1ir pulse program
on the 500 MHz NMR spectrometer was used to acquire
data and the proc_t1 program was used to process data. The
results are shown in Table S4 in the Supplementary data.
Based on these results, the delay time used for 1D gradient
NOE experiments was set at 10 s. The selnogp pulse se-
quence was used for 1D gradient NOE experiments. For
compounds 6, 8R, and 8S, the signals of H–SPo were irradi-
ated and mixing times of of 0.3, 0.5, 0.75, 0.9, 1, 1.1, and
1.25 s; 0.3, 0.9, 1.25, 1.5, 1.75, and 2.25 s; and 0.5, 0.75, 1,
1.25, 1.5, 1.75, 2, 2.25, 2.5, and 3 s, respectively, were used.
Pyridine was dried by refluxing over calcium hydride fol-
lowed by distillation and stored over molecular sieves. Am-
berlite IR-120 (H+) resin was washed with
a 10%
hydrochloric acid solution and distilled water, and then dried
under vacuum at 50 8C overnight. Ammonium cerium (IV)
nitrate and sodium azide were ground to powders and dried
in vacuuo for 2 days. Boron trifluoride diethyl etherate was
distilled before use.
X-ray crystallography
˚
The distance between ortho phenyl protons (r = 2.8 A)
Crystals for X-ray structural determinations were mounted
on glass fibers. All measurements were made on a Rigaku
AFC5R diffractometer equipped with graphite-monochromated
Mo Ka radiation (6, 8R, 8S, and 9R) or Cu Ka radiation
(18S) and a rotating anode generator. Cell constants and an
orientation matrix for data collection were obtained from a
was used as the reference distance to calculate internuclear
distances using the equation
ꢀ
ꢁ
1=6
NOEref
NOEIS
rIS ¼ rref
Published by NRC Research Press

Liang et al.
1169
Computational methods
1H, J1,2 = 10.0 Hz, H-1), 4.53 (d, 1H, J3,OH = 7.3 Hz, OH-
3), 4.05 (d, 1H, J4,OH = 4.1 Hz, OH-4), 3.98 (dd, 1H, J3,4
=
Most geometry optimizations were carried out at the
B3LYP hybrid density functional in conjunction with the
B3LYP/6–31G(d) basis set using the Gaussian 03 suite of
programs.52 The B3LYP functional is a combination of
Becke’s three-parameter hybrid exchange functional and
Lee–Yang–Parr correlational functional.53,54 Harmonic vi-
brational frequencies and zero-point vibrational energies
(ZPVEs) were obtained at the same level of theory. Relative
energies were obtained by performing single-point calcula-
tions at the B3LYP level of theory with the 6–311G+(d,p)
basis set using the above optimized geometries and by in-
cluding the zero-point vibrational energy, i.e., B3LYP/6–
311G+(d,p)//B3LYP/6–31G(d) + ZPVE. Compounds 12–15
were also optimized at the 6–311G+(d,p) level of theory.
The GIAO method was used for 13C shielding calculations
using the 6–311+G(d,p) basis set.
3.2 Hz, J4,5 < 1 Hz, H-4), 3.90 (dd, 1H, J6,OH = 6.8 Hz,
J6’,OH = 6.6 Hz, OH-6), 3.79 (m, 2H, H6 and H6’), 3.68
(ddd, 1H, J2,3 = 10.5 Hz, H –3), 3.65 (dd, 1H, J5,6 = 6.6 Hz,
J5,6’ = 3.9 Hz, H-5), 3.57 (dd, 1H, H-2). 13C NMR (acetone-
d6) d: 132.5, 129.8, 128.3 (Ph), 86.8 (C-1), 80.1 (C-5), 74.9
(C-3), 69.3 (C-4), 64.2 (C-2), 62.2 (C-6). HR-MS (EI, m/z)
calcd. for [C12H15N3O4S]+: 297.0783; found: 297.0794.
Phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-a-D-
galactopyranoside (3)
A solution of compound 1 (2.98 g, 10.0 mmol), p-me-
thoxybenzoic acid (0.10 g), and benzaldehyde (5 mL,
50.0 mmol, 5 equiv) in DMF–benzene (100 mL, 3:2 v/v)
was refluxed in an apparatus for the azeotropic removal of
water for 15 h. After TLC showed complete disappearance
of the starting material, the reaction mixture was cooled to
RT, neutralized with anhydrous potassium carbonate
(1.00 g), filtered, and concentrated to yield an orange syrup,
which was purified by flash column chromatography. Crys-
tallization from ethanol–hexanes gave the title compound (3)
Synthetic procedures
Phenyl 2-azido-2-deoxy-1-thio-a-D-galactopyranoside (1)
and phenyl 2-azido-2-deoxy-1-thio-b-D-galactopyranoside
(2)
Freshly distilled boron trifluoride diethyl etherate (19 mL,
151.3 mmol, 5.6 equiv) was added dropwise to a stirred
clear colorless solution of thiophenol (14 mL, 136.0 mmol,
as colorless needles; yield: 3.50 g (91%); mp 114.5–
23
115.5 8C. ½aꢁ
+157.78 (c 0.8, CHCl3); lit. value38
[a]D +134.98 D (c 0.5, CHCl3). Rf
=
0.35 (ethyl
1
acetate – hexanes 1:3). H NMR d: 7.48–7.28 (m, 10H, Ph),
5.76 (d, 1H, J1,2 = 5.3 Hz, H-1), 5.62 (s, 1H, CHPh), 4.34
(dd, 1H, J3,4 = 3.4 Hz, J4,5 = 0.8 Hz, H-4), 4.27 (bs, 1H, H-
5), 4.26 (dd, 1H, J5,6a = 1.6 Hz, J6a,6e = 12.5 Hz, H-6a), 4.21
(dd, 1H, J2,3 = 10.5 Hz, H-2), 4.16 (dd, 1H, J5,6e = 1.5 Hz,
H-6e), 4.03 (ddd, 1H, J3,OH = 10.4 Hz, H –3), 2.54 (d, 1H,
3-OH). 13C NMR d: 137.2, 137.7, 131.2, 129.5, 129.2,
128.4, 127.5, 126.2 (Ph), 101.4 (CHPh), 87.4 (C-1), 75.2
(C-4), 69.6 (C-3), 69.2 (C-6), 63.7 (C-5), 61.5 (C-2). HR-
MS (EI, m/z) calcd. for [C19H19N3O4S]+: 385.1096; found:
385.1107.
5
equiv) and 2-azido-2-deoxy-1,3,4,6-tetra-O-acetyl-a-D-
galactopyranoside37 (10.07 g, 27.0 mmol) in chloroform
(175 mL) at 0 8C. The reaction mixture was stirred at room
temperature (RT) for 24 h. The clear orange solution was
washed with saturated sodium bicarbonate aqueous solution
(3 ꢀ 30 mL) and distilled water (3 ꢀ 30 mL), dried (anhy-
drous sodium sulphate), filtered, and concentrated to give a
yellow syrup, phenyl 3,4,6-tetra-O-acetyl-2-azido-2-deoxy-1-
thio-O-acetyl-D-galactopyranoside.
The yellow syrup was taken up in methanol (100 mL) and
a solution of sodium methoxide in methanol (100 mL,
1.2 mol/L) was added. The basic solution was stirred for
1 h, neutralized by Amberlite IR-120 (H+), filtered, and con-
centrated to a yellow syrup, phenyl 2-azido-2-deoxy-1-thio-
D-galactopyranoside. The a–b mixture was separated by col-
umn chromatography (ethyl acetate – hexanes, 10:1). The
pure anomers were crystallized from ethanol–hexanes.
Phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-b-D-
galactopyranoside (4)
Following the same procedure as in the preparation of
compound 3, compound 4 (3.21 g, 10.8 mmol) gave the title
compound as colorless needles; yield: 3.70 g (89%); mp
20
79.0–80.0 8C. ½aꢁD –23.08 (c 0.5, CHCl3). Rf = 0.4 (ethyl
1
acetate – hexanes, 1:1). H NMR (500 MHz) d: 7.79–7.33
a-Isomer (1)
(m, 10H, Ph), 5.58 (s, 1H, CHPh), 4.47 (d, 1H, J1,2
=
Colorless needles; yield: 3.21 g (40%); mp 130.0–
25
9.8 Hz, H-1), 4.46 (dd, 1H, J5,6a = 1.2 Hz, H-6a), 4.24 (d,
1H, J3,4 = 3.5 Hz, 1H, H-4), 4.09 (dd, 1H, J5,6e = 1.4 Hz,
1
133.0 8C. ½aꢁD +252.28 (c 1.3, ethanol). Rf = 0.34. H NMR
(acetone-d6) d: 7.58–7.29 (m, 5H, Ph), 5.67 (d, 1H, J1,2
=
J6a,6e = 12.5 Hz, H-6e), 3.70 (ddd, 1H, J2,3 = 9.7 Hz, JOH,3
=
5.4 Hz, H-1), 4.47 (d, 1H, J3,OH = 7.1 Hz, OH-3), 4.31 (t,
1H, H-5), 4.17 (dd, 1H, J2,3 = 10.5 Hz, H-2), 4.15 (d, 1H,
J4,OH = 3.7 Hz, OH-4), 4.09 (ddd, 1H, J3,4 = 3.4 Hz, J4,5
1.3 Hz, H-4), 3.84 (ddd, 1H, H-3), 3.79–3.69 (m, 3H, 2 ꢀ
H-6, OH-6). 13C NMR (acetone-d6) d: 135.4, 133.1, 129.9,
128.2 (Ph), 88.8 (C-1), 73.2 (C-5), 71.1 (C-3), 70.0 (C-4),
62.1 (C-6), 62.0 (C-2). HR-MS (EI, m/z) calcd. for
[C12H15N3O4S]+: 297.0783; found: 297.0793.
9.8 Hz, H-3), 3.58 (dd, 1H, H-2), 3.57 (bs, 1H, H-5), 2.55
1
(d, 1H, 3-OH). H NMR (acetone-d6, 500 MHz) d: 7.74–
=
7.31 (m, 10H, Ph), 5.68 (s, CHPh), 4.68 (d, 1H, J1,2
=
9.9 Hz, H-1), 4.58 (d, 1H, JOH,3 = 8.8 Hz, 3-OH), 4.33 (d,
1H, J3,4 = 2.7 Hz, 1H, H-4), 4.27 (dd, 1H, J5,6a = 1.4 Hz,
J6a,6e = 12.2 Hz, H-6a), 4.18 (dd, 1H, J5,6e = 1.6 Hz, H-6e),
3.81 (ddd, 1H, J2,3 = 9.7 Hz, H-3), 3.79 (bs, 1H, H-5), 3.69
(d, 1H, H-2). 13C NMR d: 137.4, 134.3, 130.4, 129.5, 129.0,
128.5, 128.3, 126.5 (Ph), 101.5 (CHPh), 85.2 (C-1), 74.5 (C-
4), 73.3 (C-3), 69.9 (C-5), 69.3 (C-6), 62.2 (C-2). 13C NMR
(acetone-d6) d: 139.0, 133.1, 132.1, 129.0, 128.8, 128.0,
127.9, 126.7 (Ph), 100.9 (CHPh), 84.9 (C-1), 75.5 (C-4),
b-Isomer (2)
Colorless needles; yield: 3.09 g (39%); mp 149.0–
25
1
149.5 8C. ½aꢁD +24.08 (c 0.3, ethanol). Rf = 0.26. H NMR
(acetone-d6) d: 7.58–7.29 (m, 5H, aromatic protons), 4.60 (d,
Published by NRC Research Press

1170
Can. J. Chem. Vol. 88, 2010
73.0 (C-3), 70.1 (C-5), 69.1 (C-6), 62.5 (C-2). HR-MS (EI,
as colorless needles; yield: 1.26 g (97%); mp 138.5–
m/z) calcd. for [C19H19N3O4S]+: 385.1096; found: 385.1088.
140.0 8C. [a] +206.28 (c 0.6, CHCl3). Rf = 0.33 (ethyl
1
acetate – hexanes, 1:3). H NMR d: 7.50–6.88 (m, 9H, Ph),
Phenyl 2-azido-2-deoxy-4,6-O-(p-methoxybenzylidene)-1-
thio-a-D-galactopyranoside (5)
5.80 (d, 1H, J1,2 = 5.5 Hz, H-1), 5.51 (s, 1H, CHPh), 5.12
(dd, 1H, J2,3 = 11.0 Hz, J3,4 = 3.1 Hz, H –3), 4.57 (dd, 1H,
H-2), 4.50 (d, 1H, H-4), 4.24 (bs, 1H, H-5), 4.20 (dd, 1H,
A solution of compound 1 (0.97 g, 3.26 mmol), p-anisal-
dehyde (3.2 mL), and p-toluenesulfonic acid (80.0 mg) in
DMF–benzene (65 mL, 3:2) was refluxed for 45 h in an ap-
paratus for the azeotropic removal of water. After TLC
showed that the starting material had disappeared, the reac-
tion mixture was cooled to RT, neutralized by anhydrous
potassium carbonate (1.00 g), filtered, and concentrated to a
brown syrup. Purification by column chromatography (ethyl
acetate – hexanes, 1:3) gave a colorless solid that crystallized
from ethanol–hexanes as colorless needles; yield: 1.18 g
J5,6a = 1.4 Hz, J6a,6b = 12.8 Hz, H-6a), 4.07 (dd, 1H, J5,6b
=
1.5 Hz, H-6b), 3.81 (s, 3H, OCH3), 2.16 (s, 3H, COCH3).
13C NMR d: 170.3 (C=O), 160.2, 133.4, 130.0 (tertiary aro-
matic carbons), 131.3, 129.1, 127.5, 113.6 (Ph), 100.9
(CHPh), 87.3 (C-1), 73.1 (C-4), 71.4 (C-3), 69.1 (C-6), 63.4
(C-5), 57.8 (C-2), 55.3 (OCH3), 20.95 (COCH3).
(RS) Phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-thio-a-D-
galactopyranoside S-oxide (8R) and (SS) phenyl 2-azido-
4,6-O-benzylidene-2-deoxy-1-thio-a-D-galactopyranoside S-
oxide (8S)
23
(87%); mp 133.5–134.0 8C. ½aꢁD +89.18 (c 0.5, chloroform).
1
Rf = 0.43 (ethyl acetate – hexanes, 1:2). H NMR d: 7.48–
7.26 (m, 8H, Ph), 6.91 (d, 1H, Ph), 5.76 (d, 1H, J1,2
5.3 Hz, H-1), 5.58 (s, 1H, CHPh), 4.32 (bd, 1H, J3,4
=
=
A solution of m-chloroperbenzoic acid (0.22 g, 77%,
1.02 mmol, 1.1 equiv) in dichloromethane (2 mL) was
added to a mixture of compound 6 (0.40 g, 0.93 mmol) and
sodium bicarbonate (0.10 g, 1.21 mmol, 1.3 equiv) in di-
chloromethane (8 mL) at –76 8C. The reaction mixture was
stirred at –76 8C for 16 h. The reaction mixture was allowed
to warm to RT and then diluted with dichloromethane
(10 mL). The mixture was washed with 20% sodium thiosul-
fate (5 mL), saturated aqueous sodium bicarbonate solution
(5 mL), and distilled water (5 mL), and then dried (sodium
sulphate), filtered, and concentrated to give a colorless solid.
3.5 Hz, H-4), 4.26 (bs, 1H, H-5), 4.24 (bd, 1H, H-6a), 4.20
(dd, 1H, J2,3 = 10.6 Hz, H-2), 4.12 (dd, 1H, J5,6a = 1.5 Hz,
J6a,6b = 12.3 Hz, H-6b), 4.03 (ddd, 1H, J3,OH = 10.4 Hz, H-
3), 2.55 (d, 1H, 3-OH). 13C NMR d: 160.5, 133.7, 129.7 (ter-
tiary aromatic carbons), 131.2, 129.2, 127.7, 127.5, 113.7
(Ph), 101.4 (CHPh), 87.3 (C-1), 75.1 (C-4), 69.6 (C-3), 69.2
(C-6), 63.7 (C-5), 61.5 (C-2), 55.4 (OCH3).
Phenyl 3-O-acetyl-2-azido-4,6-O-benzylidene-2-deoxy-1-
thio-a-D-galactopyranoside (6)
Fractionation
by
column
chromatography
(ethyl
Acetic anhydride (1.5 mL, 97%, 15.0 mmol, 5 equiv) was
added to a solution of compound 3 (1.15 g, 2.98 mmol) in
dry pyridine (10 mL). The reaction mixture was stirred at
RT for 24 h, and then concentrated under vacuum to give a
colorless syrup. The syrup was dissolved in chloroform
(15 mL). The solution was washed with saturated sodium bi-
carbonate aqueous solution (3 mL) and distilled water
(3 mL), dried over sodium sulphate anhydrous, filtered, and
concentrated to yield a colorless syrup. The syrup was crys-
tallized from diethyl ether to give a colorless solid and re-
crystalized from ethanol–chloroform as colorless needles;
yield: 1.20 g (94%); mp 154.5–155.5 8C. [a] +198.98 (c
acetate – hexanes, 1:2) yielded three compounds.
Compound 8R was crystallized from ethanol–chloroform;
22
yield: 247.5 mg (60%); mp 191.5–192.5 8C. ½aꢁD +34.68 (c
1
0.4, CHCl3). Rf = 0.20. H NMR (500 MHz) d: 7.54 (m, 2H,
Ho-SPh), 7.45 (m, 3H, Hp-SPh and Hm-SPh), 7.36 (m, 5H,
Ho-CHPh, Hm-CHPh, and Hp-CHPh), 5.78 (dd, 1H, J2,3
=
10.8 Hz, J3,4 = 3.4 Hz, H-3), 5.53 (s, 1H, CHPh), 4.95 (s,
1H, J1,2 = 5.7 Hz, H-1), 4.65 (dd, 1H, H-2), 4.62 (d, 1H, H-
4), 4.11 (bs, 1H, H-5), 4.14 (dd, 1H, J5,6e = 1.5 Hz, H-6e),
4.02 (dd, 1H, J5,6a = 2.2 Hz, J6a,6e = 12.3 Hz, H-6a), 2.16
1
(s, 3H, COCH3). H NMR (acetone-d6, 500 MHz) d: 7.86
1
0.6, CHCl3). H NMR d: 7.50–7.24 (m, 10H, Ph), 5.81 (d,
(d, 2H, Ho-SPh), 7.65 (t, 2H, Hm-SPh), 7.60 (t, 2H, Hp-
SPh), 7.51 (m, 2H, Ho-CHPh), 7.39 (m, 3H, Hm-CHPh and
Hp-CHPh), 5.85 (dd, 1H, J2,3 = 11.0 Hz, J3,4 = 3.5 Hz, H-3),
5.69 (s, 1H, CHPh), 5.15 (d, 1H, J1,2 = 6.6 Hz, H-1), 4.78
(dd, 1H, H-2), 4.66 (d, 1H, H-4), 4.32 (bs, 1H, H-5), 4.21
(dd, 1H, J5,6a = 1.5 Hz, J6a,6e = 12.7 Hz, H-6a), 4.09 (dd,
1H, J1,2 = 5.3 Hz, H-1), 5.56 (s, 1H, CHPh), 5.13 (dd, 1H,
J2,3 = 11.0 Hz, J3,4 = 3.4 Hz, H-3), 4.57 (dd, 1H, H-2), 4.53
(d, 1H, H-4), 4.26 (bs, 1H, H-5), 4.22 (dd, 1H, J5,6a
1.4 Hz, J6a,6e = 12.6 Hz, H-6a), 4.09 (dd, 1H, J5,6e
=
=
1.7 Hz, H-6e), 2.16 (s, 3H, COCH3). 13C NMR (acetone-d6)
d: 170.6 (C=O), 139.5, 134.5, 132.9, 129.3, 128.9, 128.5,
127.3 (Ph), 101.4 (CHPh), 88.3 (C-1), 74.2 (C-4), 71.5 (C-
3), 69.6 (C-6), 64.7 (C-5), 59.0 (C-2), 20.8 (COCH3). HR-
MS (EI, m/z) calcd. for [C21H21N3O5S]+: 427.1202; found:
427.1202.
1
1H, J5,6e = 1.5 Hz, H-6a), 2.12 (s, 3H, COCH3). H NMR
(CD2Cl2, 500 MHz) d: 7.77 (m, 2H, Ho-SPh), 7.63 (m, 2H,
Hm-SPh), 7.61 (t, 2H, Hp-SPh), 7.50 (m, 2H, Ho-CHPh),
7.43 (m, 3H, Hm-CHPh and Hp-CHPh), 5.86 (dd, 1H, J2,3
=
10.8 Hz, J3,4 = 3.5 Hz, H-3), 5.58 (s, 1H, CHPh), 5.01 (d,
1H, J1,2 = 5.6 Hz, H-1), 4.67 (dd, 1H, H-2), 4.61 (d, 1H, H-
Phenyl 3-O-acetyl-2-azido-2-deoxy-4,6-O-(p-
4), 4.20 (bs, 1H, H-5), 4.15 (dd, 1H, J5,6a = 1.6 Hz, J6a,6e
=
methoxybenzylidene)-1-thio-a-D-galactopyranoside (7)
Acetic anhydride (2 mL, 97%, 20.0 mmol) was added to a
solution of compound 5 (1.18 g, 2.84 mmol) in dry pyridine
(10 mL) and the reaction mixture was stirred at RT for 16 h,
and was then concentrated under vacuum to give a orange
syrup that was azeotroped with toluene (3 ꢀ 4 mL) to give
a yellow solid that on crystallization from ethanol, appeared
12.8 Hz, H-6a), 4.07 (dd, 1H, J5,6e = 1.6 Hz, H-6a), 2.19 (s,
1
3H, COCH3). H NMR (CD3CN, 500 MHz) d: 7.80 (m, 2H,
Ho-SPh), 7.63 (m, 3H, Hm-SPh and Hp-SPh), 7.48 (m, 2H,
Ho-CHPh), 7.42 (m, 3H, Hm-CHPh and Hp-CHPh), 5.78
(dd, 1H, J2,3 = 11.0 Hz, J3,4 = 3.4 Hz, H-3), 5.61 (s, 1H,
CHPh), 5.07 (d, 1H, J1,2 = 5.6 Hz, H-1), 4.70 (dd, 1H, H-2),
Published by NRC Research Press

Liang et al.
1171
(RS) Phenyl 3-O-acetyl-2-azido-2-deoxy-4,6-O-(p-
4.54 (d, 1H, H-4), 4.14 (bs, 1H, H-5), 4.05 (dd, 1H, J5,6a
1.4 Hz, J6a,6e = 12.9 Hz, H-6a), 3.95 (dd, 1H, J5,6e
=
=
methoxybenzylidene)-1-thio-a-D-galactopyranoside S-oxide
(9R) and (SS) phenyl 3-O-acetyl-2-azido-2-deoxy-4,6-O-(p-
methoxybenzylidene)-1-thio-a-D-galactopyranoside S-oxide
(9S)
Following the same procedure as for compound 6, com-
pounds 9R and 9S were obtained from compound 8
(0.30 g), m-chloroperbenzoic acid (0.13 g), and sodium hy-
drogen carbonate (0.07 g), followed by separation by col-
umn chromatography on silica gel using the same solvent
system.
1.4 Hz, H-6a), 2.17 (s, 3H, COCH3). 13C NMR d: 170.1
(C=O), 141.3, 137.2, 131.3, 129.2, 129.2, 128.3, 126.0,
124.8 (Ph), 100.7 (CHPh), 96.3 (C-1), 72.7 (C-4), 70.2 (C-
3), 68.9 (C-6), 67.6 (C-5), 57.9 (C-2), 20.9 (COCH3). HR-
MS (EI, m/z) calcd. for [C21H21N3O6S – N2]+: 415.1089;
found: 415.1096.
Compound 8S was crystallized from ethanol–chloroform;
yield: 82.1 mg (20%); mp 197.5–198.5 8C. [a]D +367.78 (c
1
0.6, CHCl3). Rf = 0.45. H NMR (500 MHz) d: 7.63 (d, 2H,
Compound 9R was crystallized from ethanol–chloroform
to give colorless needles; yield: 0.22 g (70%); mp 161.5–
Ho-SPh), 7.55 (t, 1H, Hp-SPh), 7.52 (t, 2H, Hm-SPh), 7.43
(m, 2H, Ho-CHPh), 7.35 (m, 3H, Hm-CHPh and Hp-
CHPh), 5.94 (dd, 1H, J2,3 = 10.9 Hz, J3,4 = 3.3 Hz, H-3),
5.49 (s, 1H, CHPh), 4.90 (s, 1H, H-5), 4.76 (dd, 1H, J1,2
6.6 Hz, H-2), 4.61 (d, 1H, H-4), 4.56 (d, 1H, H-1), 4.01 (dd,
23
163.0 8C. ½aꢁD +44.48 (c 0.3, chloroform). Rf = 0.17 (ethyl
1
acetate – hexanes, 1:2). H NMR d: 7.71–6.89 (m, 9H, aro-
=
matic protons), 5.76 (dd, 1H, J2,3 = 11.0 Hz, J3,4 = 3.7 Hz,
H-3), 5.48 (s, 1H, CHPh), 4.95 (d, 1H, J1,2 = 5.5 Hz, H-1),
4.64 (dd, 1H, H-2), 4.60 (bd, 1H, J4,5 < 1 Hz, H-4), 4.08 (bs,
1H, J5,6e = 1.4 Hz, J6a,6e = 12.9 Hz, H-6e), 3.90 (dd, 1H,
1
J5,6a = 1.3 Hz, H-6a), 2.12 (s, 3H, COCH3). H NMR (ace-
1H, H-5), 4.10, 3.98 (2H, AB part of ABX pattern, J5,6a
=
tone-d6, 500 MHz) d: 7.78 (d, 2H, Ho-SPh), 7.67 (t, 2H,
Hm-SPh), 7.62 (t, 2H, Hp-SPh), 7.48 (m, 2H, Ho-CHPh),
7.37 (t, 3H, Hm-CHPh and Hp-CHPh), 6.02 (m, 1H, H-3),
5.64 (s, 1H, CHPh), 4.92–4.89 (m, 3H, H-1, H-2, H-5), 4.63
(d, 1H, J3,4 = 2.5 Hz, H-4), 4.07 (dd, 1H, J5,6e = 1.3 Hz,
J6a,6e = 12.8 Hz, H-6e), 3.85 (dd, 1H, J5,6a = 1.4 Hz, H-6a),
2.12 (s, 3H COCH3). 13C NMR d: 170.0 (C=O), 140.5,
137.3, 131.1, 129.2, 129.1, 128.2, 126.0, 124.7 (Ph), 100.7
(CHPh), 92.5 (C-1), 73.0 (C-4), 71.2 (C-3), 68.8 (C-4), 68.7
(C-6), 57.3 (C-2), 21.0 (COCH3). 13C NMR (acetone-d6) d:
169.6 (C=O), 141.4, 138.7, 130.9, 129.8, 128.8, 128.0,
126.4, 125.0 (Ph), 100.4 (CHPh), 92.4 (C-1), 73.2 (C-4),
70.4 (C-3), 69.1 (C-5), 68.4 (C-6), 58.2 (C-2), 20.1
(COCH3). MS (ESI, m/z) calcd. for [C21H21N3O6S + Na]+:
466.0; found: 466.0. HR-MS (EI, m/z) calcd. for
[C21H21N3O6S – C6H5OS]+: 318.1090; found: 318.1098.
The third fraction was phenyl 2-azido-4,6-O-benzylidene-
1.2 Hz, J5,6b = 2.4 Hz, J6a,6b = 12.5 Hz, H-6a, H-6b), 3.80
(s, 3H, OCH3), 2.16 (s, 3H, COCH3). 13C NMR d: 170.2
(C=O), 160.3, 141.4, 131.4, 129.7, 129.2, 127.4, 124.9,
113.7 (Ph), 100.8 (CHPh), 96.3 (C-1), 72.7 (C-4), 70.4 (C-
3), 68.9 (C-6), 67.6 (C-5), 57.9 (C-2), 55.3 (OCH3), 20.9
(COCH3). HR-MS (EI, m/z) calcd. for [C22H23N3O7S –
C6H5OS]+: 348.1195; found: 348.1188.
Compound 9S was crystallized from ethanol–chloroform
to give colorless needles; yield: 56 mg (19%); mp 224.0–
224.5 8C. [a] +153.88 (c 0.3, chloroform). Rf = 0.30 (ethyl
1
acetate – hexanes, 1:2). H NMR d: 7.65–7.54 (m, 5H, PhH),
7.36, 6.87 (2d, 4H, PhH), 5.86 (dd, 1H, J2,3 = 11.0 Hz, J3,4
=
3.4 Hz, H-3), 5.47 (s, 1H, CHPh), 5.14 (d, 1H, J1,2 = 6.3 Hz,
H-1), 4.65 (dd, 1H, H-2), 4.61 (bd, 1H, J4,5 < 1 Hz, H-4),
4.43 (bs, 1H, H-5), 4.02, 3.98 (2H, AB part of ABX pattern,
J5,6a = 1.5 Hz, J5,6b = 1.6 Hz, J6a,6b = 12.8 Hz, H-6a, H-6b),
3.79 (s, 3H, OCH3), 2.16 (s, 3H, COCH3). 13C NMR d:
170.3 (C=O), 160.4, 138.7, 134.4, 129.8, 129.4, 128.9,
127.6, 113.8 (Ph), 100.9 (CHPh), 89.9 (C-1), 72.7 (C-4),
69.9 (C-3), 68.8 (C-6), 67.1 (C-5), 56.2 (C-2), 55.5 (OCH3),
21.1 (COCH3).
2-deoxy-1-thio-a-D-galactopyranoside
46.8 mg (11%); mp 183.0–184.0 8C. ½aꢁD +131.48 (c 0.4,
dioxide;
yield:
23
1
CHCl3). Rf = 0.42. H NMR (acetone-d6, 500 MHz) d: 8.04
(d, 2H, o-SPh), 7.82 (t, 1H, p-SPh), 7.73 (t, 2H, m-SPh),
7.41 (d, 2H, J = 7.1 Hz, o-Ph), 6.92 (d, 2H, m-Ph), 5.85
(dd, 1H, J2,3 = 11.3 Hz, J3,4 = 3.4 Hz, H-3), 5.63 (s, 1H,
CHPh), 5.55 (d, 1H, J1,2 = 6.0 Hz, H-1), 4.83 (dd, 1H, H-
2), 4.64 (bs, 1H, H-4), 4.41 (bs, 1H, H-5), 4.16 (d, 1H,
J6a,6e = 12.4 Hz, H-6a), 3.89 (d, 1H, H-6e), 3.82 (s, 3H,
Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-b-
D-glucopyranoside (17)
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-phthalimido-b-D-gluco-
pyranose45–47 (72.2 g, 0.15 mol) was treated with thiophenol
and boron trifluoride etherate to give the title compound as a
solid that was crystallized from 15% ethyl acetate in hex-
anes; yield: 64.4 g (81%); mp 140–141 8C, lit.value48 mp
1
OCH3), 2.83 (s, 3H, COCH3). H NMR (500 MHz) d: 7.92
(d, 2H, o-SPh), 7.68 (t, 1H, p-SPh), 7.58 (t, 2H, m-SPh),
25
145–146 8C. ½aꢁD 49.48 (c 0.88, chloroform); lit. value48
7.44–7.35 (m, 4H, Ph), 5.87 (dd, 1H, J2,3 = 11.1 Hz, J3,4
=
25
½aꢁD 53.08.
3.4 Hz, H-3), 5.52 (s, 1H, CHPh), 5.13 (d, 1H, J1,2 = 6.3 Hz,
H-1), 4.66 (dd, 1H, H-2), 4.64 (bs, 1H, H-4), 4.35 (bs, 1H,
H-5), 4.06 (d, 1H, J5,6a = 1.3 Hz, J6a,6e = 12.8 Hz, H-6a),
3.99 (d, 1H, J5,6e = 1.2 Hz, H-6e), 3.82 (s, 3H, OCH3), 2.17
(s, 3H, COCH3). 13C NMR d: 170.1 (C=O), 138.8, 137.3,
134.4, 129.4, 128.9, 128.4, 126.1 (Ph), 100.9 (CHPh), 89.9
(C-1), 72.7 (C-4), 69.9 (C-3), 68.9 (C-6), 67.1 (C-5), 56.3
(C-2), 21.1 (COCH3). MS (ESI, m/z) calcd. for
[C21H21N3O7S + Na]+: 482.0; found: 482.0. HR-MS (EI, m/z)
calcd. for [C21H21N3O7S – C6H5O2S]+: 318.1090; found:
318.1092.
(SS) Phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-
thio-b-D-glucopyranoside S-oxide (18S)
A solution of m-chloroperbenzoic acid (0.60 g, 70%,
3.4 mmol, 1.0 equiv) in dry dichloromethane (7 mL) was
added to a precooled solution of compound 17 (1.22 g,
2.31 mmol) in dichloromethane (18 mL) at –78 8C. The re-
action mixture was stirred at –78 8C for 26 h and then al-
lowed to warm to RT over 12 h. The mixture was washed
with saturated sodium bicarbonate solutions (3 ꢀ 25 mL)
and water (25 mL), and then dried (sodium sulphate), fil-
Published by NRC Research Press

1172
Can. J. Chem. Vol. 88, 2010
tered, and concentrated to give a bright yellowish solid.
Separation by flash column chromatography (ethyl
acetate – hexanes, 1:1) gave the starting material (0.22 g)
and colorless crystals of the product (0.95 g, 92% based on
starting material consumed). Further fractionation using
flash column chromatography (5% acetone in chloroform)
gave 18S as fluffy crystals that were recrystallized from 1%
ethanol in hexanes to give clear colorless needles; mp 124–
Supplementary data for this article are available on the
journal Web site (canjchem.nrc.ca).
Acknowledgements
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC) for financial support and the
Atlantic Region Magnetic Resonance Centre (ARMRC) for
NMR time. We thank Dr. B.M. Pinto for discussions and a
referee for a suggestion. Some of the computational facilities
were provided by the Atlantic Computational Excellence net-
work (ACEnet), the regional high-performance computing
consortium for universities in Atlantic Canada. ACEnet is
funded by the Canada Foundation for Innovation (CFI), the
Atlantic Canada Opportunities Agency (ACOA), and the
provinces of Newfoundland and Labrador, Nova Scotia, and
New Brunswick.
25
126 8C. ½aꢁD +1138 (c 0.6, chloroform). Rf = 0.68 (5% ace-
1
tone in chloroform). H NMR (400 MHz) d: 7.68 (bd s, 2H,
Phth-H), 7.84–7.60 (very bd s, 2H, Phth-H), 7.49 (d, 2H, J =
7.5 Hz, o-Ar H), 7.21 (t, 2H, J = 7.5 Hz, m-Ar H), 7.13 (t,
1H, J = 7.3 Hz, p-Ar H), 5.77 (t, 1H, J2,3 = J3,4 = 9.7 Hz, H-
3), 5.40 (d, 1H, J1,2 = 10.1 Hz, H-1), 5.16 (t, 1H, J3,4 = J4,5
=
9.7 Hz, H-4), 4.89 (t, 1H, H-2), 4.20 and 4.28 (AB part of
ABX pattern, 2H, J6a,6b = 12.3 Hz, J5,6a = J5,6b = 4.9 Hz, 2
H-6), 3.91 (m, 1H, H-5), 2.09, 2.05, 1.85 (3s, 9H, 3 Ac). 13C
NMR (100 MHz) d: 170.1, 169.8, 168.9 (3 Ac C=O), 167.6
(2 phth C=O), 138.8, 130.2, 128.4, 123.0 (S-Ph C), 133.9,
130.8, 123.9 (Phth C), 89.1 (C-1), 76.0 (C-5), 71.1 (C-3),
67.6 (C-4), 61.4 (C-6), 47.4 (C-2), 20.4, 20.2, 20.0 (Ac Me).
The second fraction was obtained as colorless fluffy crys-
tals that decomposed on standing or on attempted recrystal-
References
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Phth-H), 7.70 (t, 1H, J = 7.5 Hz, p-Ar H), 7.58 (t, 2H, J =
7.7 Hz, m-Ar H), 5.81 (t, 1H, J2,3 = J3,4 = 9.7 Hz, H-3), 5.51
(d, 1H, J1,2 = 10.6 Hz, H-1), 5.02 (t, 1H, J3,4 = J4,5 = 9.7 Hz,
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phth C=O), 137.9, 130.1, 128.6, 123.4 (S-Ph C), 134.2,
131.3, 124.4 (Phth C), 86.1 (C-1), 76.3 (C-5), 71.2 (C-3),
67.8 (C-4), 61.4 (C-6), 49.4 (C-2), 20.3, 20.2, 20.0 (Ac Me).
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25
deoxy-2-phthalimido-D-glucal; ½aꢁD – 15.78 (c 5.1, chloro-
1
form), lit.67 [a]D – 15.08. H NMR (250.13 MHz) d: 7.96–
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7.74 (AA’BB’ pattern, 4H, Phth-H), 6.78 (s, 1H, H-1), 5.61
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Supplementary data
Supplementary data for this article are available on the
journal Web site (canjchem.nrc.ca). CCDC 782358–782362
contain the X-ray data in CIF format for this manuscript.
These data can be obtained, free of charge, via www.ccdc.
cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax +44 1223 336033; or deposit@ccdc.
cam.ac.uk).
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