An unexpected rearrangement giving a new thiosubstituted carbohydrate

Article abstract of DOI:10.1016/j.carres.2010.03.024

A new thiosubstituted 'd-arabino'-type derivative was obtained from an open carbohydrate via a cascade of four consecutive transformations in a single reaction process. Molecular orbital computations were also performed to explain the stereochemical outcome of the reaction.

Full text of DOI:10.1016/j.carres.2010.03.024

Carbohydrate Research 345 (2010) 1088–1093
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
An unexpected rearrangement giving a new thiosubstituted carbohydrate
Agathe Martinez, Eric Hénon, Claire Coiffier, Aline Banchet, Dominique Harakat, Jean-Marc Nuzillard,
*
Arnaud Haudrechy
Institut de Chimie Moléculaire de Reims, UMR CNRS, Université de Reims, BP 1039, F-51687 REIMS Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
A new thiosubstituted ‘D-arabino’-type derivative was obtained from an open carbohydrate via a cascade
Received 24 November 2009
Received in revised form 16 March 2010
Accepted 18 March 2010
of four consecutive transformations in a single reaction process. Molecular orbital computations were
also performed to explain the stereochemical outcome of the reaction.
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 21 March 2010
Keywords:
Thiosugars
Theoretical
Conformational bias
DFT
Transition state
1. Introduction
2. Results and discussion
During our studies toward the efficient synthesis of
a
-C-(alky-
The alcohol derivative 11 was easily obtained after several
straightforward reactions of the known
-arabinose derivative 8.9
nyl)-galactosides,1,2 we identified an interesting side-product, the
thiosugar 3 (Scheme 1).3 This unexpected rearrangement, which
occurred during the multigram scale-up synthesis of the epoxydi-
thio compound 2, was solely dependent on reaction conditions and
can be explained by the cascade of reactions depicted in Scheme 1.
Intrigued by this unusual transformation, we anticipated that
the same kind of reaction could be applied to a formal synthesis
D
The unstable compound 7 (not shown) was then formed by mesy-
lation of 11 in quantitative yield and was used in the next step
without further purification. Although the reaction was slow, di-
rect treatment with TBAF at 0 °C cleanly gave a product in 65%
yield. It was first speculated that compound 6 had been formed
as expected (Scheme 3).
of salacinol 4, a highly potent
a
-glucosidase inhibitor.4,5
However, comparison of the 1H NMR data (Table 1, see Scheme
3 for numbering) clearly showed that the isolated product was dif-
ferent from the known compound 6.8,10
As described by Ghavami et al.,6 the four-carbon sulfated side
chain could be easily introduced starting from the known sulfur
derivative 5. Furthermore, anomeric reduction of the thiobenzyl
moiety can be performed in two steps (Hg(OAc)2/AcOH followed
by Et3SiH/TMSOTf),7 giving the well-known sulfur derivative 6 as
an interesting target.8 The followed strategy for the synthesis of
compound 6 was directly inspired from our serendipitously discov-
ered rearrangement.3 Compared to our earlier work, two changes
were made to precursor 1. A TBS group was used in position 5
and the terminal aldehyde was protected as a dithiobenzyl acetal
(compound 7). It was expected that the thiobenzyl group in the fi-
nal anomeric position would be easier to deprotect (Scheme 2).
Moreover, supplementary COSY and HSQC experiments unam-
biguously showed that the signal for C-1 in our compound ap-
peared at 80.8 ppm. This characteristic deshielding indicated that
the anomeric position possessed one oxygen and one sulfur atom.
An HMBC experiment confirmed the thioether function with a cor-
relation between H-4 and a SCH2Ph, and consequently a pyranose
form for this compound. Finally, NOESY experiments showed that
spatially, H-4 was closest to H-3 (and H-1 to H-2). This implied that
the configuration at C-4 is R, and that the anomeric configuration is
b. Consequently, the structure of the isolated compound was pos-
tulated to be that of 12.
According to the cascade mechanism which had first been envi-
sioned, it was thought that the formation of compound 12 followed
an intra-SN1 mechanism. Indeed, the direct attack of the interme-
diate alkoxide on the anomeric center via an intra-SN2 mechanism
is impossible because it is governed in this case by a 5-endo-Tet
* Corresponding author. Tel.: +33 (0)3 2691 3236; fax: +33 (0)3 2691 3166.
E-mail address: arnaud.haudrechy@univ-reims.fr (A. Haudrechy).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.03.024

A. Martinez et al. / Carbohydrate Research 345 (2010) 1088–1093
1089
EtS
BnO
EtS
BnO
SEt
SEt
KOH
1-2% H2O
MeOH
PivO
OBn
OBn
O
OMs OBn
OBn
1
2 (90%)
Et
EtS
SEt
BnO
S
+
SEt
S
SEt
anh. KOH
MeOH
K+ -
O
EtO
BnO
1
OBn
O
BnO
OBn
OBn
OBn
K+
OBn
OBn
2
3 (85%)
Scheme 1. Synthesis of thiosugar 3.
HO
OH
OSO3
BnS
MsO
SBn
OBn
-
S
S
+
S
Reference 7
TBAF
Reference 6
BnO
SBn
OBn
BnO
BnO
HO
TBSO
OH
OBn
HO
BnO
OBn
6
4
5
7
Scheme 2. Salacinol 4 and target compound 6.
BnS
R2O
SBn
OBn
1) MsCl
CH2Cl2 / Et3N
BnS
O
O
SBn
OH
5
1
S
4
3
SBn
NaH / BnBr
R1O
BnO
2
2) TBAF
OBn
OBn
BnO
OH
8
0°C
THF
6
9 R1, R2 = CMe2
10 R1, R2 = H
AcOH / H2O
TBSCl / Imidazole
11 R1 = TBS, R2 = H
Scheme 3. Synthesis of the alcohol derivative 11 and approach to salacinol.
process, forbidden by Baldwin’s rules (Scheme 4).11 The observa-
tion of an anomerically pure b-product could only result from
the final ring-closure occurring on the Re face.
As can be seen in Table 2, comparison of PCM values with the
gas-phase results indicates that there is no significant solvent ef-
fect on the relative energies (entries 1 and 2). This is not surprising
owing to the small THF dielectric constant (7.58). The different the-
ory levels used produced consistent results, except the MP2/AUG-
cc-pVDZ method (entry 5) which indicated that the 12beq
conformer was less stable than the 12bax one. CCSD(T) studies
could not be achieved due to expensive computational calcula-
tions. It was clear however that the experimental b-stereochemis-
try of the anomeric carbon could not be explained from the relative
stability of the final product 12. Actually, the 12aax isomer was
predicted to be one of the more stable isomers but it was not ob-
served experimentally.
Molecular orbital computations were performed to better
understand the stereochemical outcome of the reaction. Due to a
prohibitive computational cost, the calculations in the present
work were performed on a model system obtained by replacing
all benzyl groups with methyl groups. According to the proposed
mechanism for the formation of 12, the final ring closing reaction
involving the sulfonium cation B (Scheme 4) should lead to the
two possible isomers of 12, both adopting 1C4 and 4C1 chair confor-
mations, respectively (Fig. 1).
We decided to first look at the energy levels of the different con-
formations. When considering destabilizing effects, a maximum
Therefore, in order to explain the reaction selectivity, we exam-
ined the final ring-closure mechanism leading to 12. Only the final
formation of the O–C bond was studied. For the sake of simplicity, a
number of equatorial groups should favor the 12
but the stabilizing anomeric effect is a good argument in favor of
both the 12 ax and 12bax conformations. We thus decided to calcu-
aeq conformation,
*
a
B3LYP/6-31G stretching energy profile was performed for all the
late the energies of these final structures by carefully estimating
possible final structures 12 to characterize the dissociative reaction
the influence of several theoretical levels on the results (Table 2).
pathway instead of the bonding one.
Table 1
Comparison of 1H and 13C NMR data of known 6 and the isolated compound 12
d in ppm (J in hertz)
6
12
6
12
H-1
H-2
H-3
H-4
H-5a
H-5b
SCH2Ph
4.36 (4.6)
4.20 (4.6)
4.20 (5.0)
3.47 (5.0, 7.2, 7.3)
3.55 (7.2, 9.3)
3.85 (7.3, 9.3)
3.87
4.77 (1.9)
3.42 (1.9, 3.5)
3.55 (3.5, 3.1)
3.17 (3.1, 4.7, 10.4)
3.63 (10.4, 11.0)
3.85 (4.7, 11.0)
3.80 (C-1)–3.71 (C-4)
C-1
C-2
C-3
C-4
C-5
SCH2Ph
52.0
86.6
84.9
47.4
73.6
35.7
80.8
76.0
76.6
42.7
66.5
34.7 (C-1)–36.5 (C-4)

1090
A. Martinez et al. / Carbohydrate Research 345 (2010) 1088–1093
+
BnS
O-
Bn
OBn SBn
SBn
-O
O
SBn
OBn
+
S
SBn
OBn
H
O
OBn
OBn
BnS
K+
BnS
BnO
OBn
OBn
12
B
A
Scheme 4. Proposed mechanism for the formation of 12.
1C4
4C1
1C4
4C1
SMe
H
H
MeO
MeO
O
O
O
H
SMe
O
SMe MeS
OMe
MeS
OMe
H
SMe
OMe
MeS
OMe
12βeq
OMe
12αax
OMe
12αeq
MeS
12βax
Figure 1. 1C4 and 4C1 chair conformations for isomers 12
a and 12b.
Table 2
ters. The corresponding optimized structure is a seven-membered
‘tetravalent sulfur’ heterocycle intermediate (Fig. 2) having an en-
ergy about 1–3 kcal/mol above the sulfonium five-membered ring
A (Scheme 4).
Isomer ZPE corrected relative energies (given in kcal molꢀ1
)
Entry
12aeq
12aax
12bax
12beq
1
2
3
4
5
B3LYP/6-31G*
6.4
6.4
6.8
6.3
4.9
0.1
0.3
0.1
0.0
0.0
4.6
4.9
4.4
4.8
2.1
0.0
0.0
0.0
0.1
3.3
B3LYP/6-31G*/PCMa
MP2/6-31G*
The B3LYP/6-311++G** barrier height, computed for the transi-
tion state connecting this seven-membered heterocycle to the
most stable final products 12aeq and 12beq, was predicted to be
13.0 and 11.9 kcal molꢀ1, respectively. By contrast, the final closure
of precursors 12aax and 12bax exhibited a barrier-free energy pro-
file. Indeed, due to the above-mentioned O–S covalent interaction,
the early O–S ring closure prevents the O–C ring closure when oxy-
gen and sulfur atoms are in a face-to-face orientation (aeq or beq
approach) in the open structure B (Scheme 4) preceding cycliza-
tion. These theoretical results strongly suggest that only the aax
and bax preformed geometries can favor a six-membered ring cycli-
zation. Why then is the aax isomer not obtained experimentally?
**
B3LYP/6-311++G
MP2/AUG-cc-pVDZb
a
Fully optimized in the field of THF within the Polarized Continuum Model
(PCM).
b
Dual level: MP2/AUG-cc-pVDZ energy, Zero Point Energy (ZPE) correction
obtained at the MP2/6-31G* theory level.
First, we focused on the 12aax and 12bax isomeric forms. As ex-
pected for a dissociation reaction yielding a zwitterionic species,
the energy increased when the O–C distance was scanned from
its value in 12 to more than 4.0 Å. No minimum was found on
the potential energy surface corresponding to the open structure
preceding the cyclic system. Obviously, the reaction coordinates
are not simply governed by the ultimate rupture of the C–O bond.
In reality, some rotational rearrangement in the last stage of the
dissociation process should be included to reach a minimum en-
ergy structure. The first steps in the reverse direction from com-
pound 12 are very informative however, particularly for the
12aeq and 12beq isomers. Interestingly, due to the proximity of
the oxygen and sulfur atoms during the potential energy scan of
the C–O bond cleavage for these two species, an O–S covalent
interaction is formed between these two atoms (from C–O approx-
imately 3.2 Å), resulting in a local minimum as shown in Figure 2
within the 12beq approach.
During the simulation of the C–O breaking in 12aax and 12bax, a
specific relative spatial orientation of the forming –[C@S+-Me] group
with respect to the neighboring methoxy group as depicted in Figure
3 was computationally observed and seems to be a key element.
Surprisingly, while a free rotation is possible around the C-1/C-2
bond, the open geometry of 12bax seems to adopt an unfavorable
syn conformation in the early stage of the dissociation process.
To complete our study, the open structures were thus examined
(syn or anti) and a series of four models of increasing complexity
were used as shown in Figure 4.
In the more realistic model (F), the anion was saturated with a
hydrogen atom to form an alcohol and thus avoid ring closure dur-
ing geometry optimizations. The syn and anti conformations were
examined for each model structure by considering the 4C1 or 1C4
chair arrangement (except for the smallest model C). Results are
summarized in Table 3.
*
p ) of the
This result is not surprising since the LUMO orbital (
open structure is found to be delocalized over both the C and S cen-
Irrespective of the considered model or chair arrangement, the
syn conformation is 2.6–5.0 kcal molꢀ1 more stable than the anti
one. TheOCCS torsiondihedralangle is closeto 0° in all the synmodel
structures. Relative energy
DE analysis with a series of analogue
compounds of model C allowed us to understand this syn conforma-
tional preference. Our calculations emphasize a clear interaction of
*
r (S-Me) orbital with the oxygen lone pairs.
the antibonding
αax
βax
SMe
OMe
MeO
OMe
O
H
O
H
MeS
SMe
OMe
MeO
**
Figure 2. B3LYP/6-311++G optimized structure of the seven-membered ‘tetrava-
lent sulfur’ heterocycle.
Figure 3. Specific anti and syn arrangements before closure giving 12.

A. Martinez et al. / Carbohydrate Research 345 (2010) 1088–1093
1091
SMe
SMe
SMe
SMe
OH
1
2
1
2
1
2
1
2
5
H
4
4
H
H
H
H
H
3
3
3
OMe
OMe
H
OMe
MeS
OMe
H
H
H
OMe
OMe
OMe
E
F
D
C
Figure 4. Internal rotation examined in open model structures.
Table 3
Relative B3LYP/6-311++G** ZPE corrected energies (kcal molꢀ1) of syn and anti conformers for two approaches (B3LYP/6-31G* values are in brackets)
Arrangement
Conformation
Model
Ca
D
E
F
1C4
4C1
syn
anti
0.0 (0.0)
4.9 (5.5)
4.0 (2.2)
8.7 (7.3)
5.8 (4.7)
10.8 (10.2)
0.0 (0.0)
b(4.8)
syn
anti
0.0 (0.0)
4.9 (5.5)
0.0 (0.0)
4.8 (3.2)
0.0 (0.0)
4.3 (3.4)
0.2 (0.8)
2.8 (3.3)
a
1C4 and 4C1 arrangements can not be distinguished for this model.
The molecular system goes back to the sulfonium five-membered ring during optimization.
b
The transition state connecting the syn and anti conformations
hyde system. Flash column chromatography separations (silica
gel, 40–63 m) were carried out with light petroleum ether–ethyl
of model C has been calculated. The calculated interconversional
rotational barrier is 8.5 or 3.7 kcal molꢀ1 above the syn or anti
structures, respectively. Thus, the equilibrium process is likely to
occur under our experimental conditions (273 K). According to
the energy values in Table 3, the resulting Boltzmann distribution
shows that only the syn structure is expected to have a population
l
acetate mixtures as eluent. NMR spectra were recorded on a DRX
500 Bruker spectrometer (500 MHz for 1H and 125 MHz for 13C),
using standard pulse programs, except for NOESY spectrum in
which zero-quantum effects where suppressed.13 Chemical shifts
(d) reported are referred to internal tetramethylsilane.
for a given chair arrangement. This rules out
a
isomer formation
FT IR spectra were recorded on Nicolet Avatar 320 FT-IR as
films. Optical rotations were measured on a Perkin–Elmer 341
polarimeter. Elemental analyses were performed with a Thermo
Flash EA 1112 Series. Electrospray ionization mass spectrometry
experiments (MS and HRMS) were obtained on a hybrid tandem
quadrupole/time-of-flight (Q-TOF) instrument, equipped with a
pneumatically assisted electrospray (Z-spray) ion source (Micro-
mass, Manshester, UK) operated in positive mode (EV = 30 V,
(from both the 1C4 and 4C1 chair closure). Finally, the 4C1/syn ap-
proach (beq) being prevented by the C–S closure as previously ex-
plained, only the bax conformer is therefore expected. The
subsequent ring flipping between the two alternative chair forms
could lead to both 12bax and 12beq anomers. These theoretical re-
sults correlate with experimental findings. According to the AUG-
MP2/cc-pVDZ level of theory used (Table 2), the 12bax conformer
should be the major product, but higher levels of theory are needed
to ascertain their relative energy.
80 °C, injection flow 5 ll/min).
5. Computational details
3. Conclusion
Full electron calculations were performed using the GAUSSIAN 03
package.14 The structures were fully optimized at several theoret-
ical levels. The HF-DFT (B3LYP)15–18 level of theory was first ap-
plied using analytical gradients and the 6-31G* basis set (thus
adding one set of d polarization functions on the carbon, oxygen,
and sulfur atoms). The Polarized Continuum Model (PCM)19–21
within the Self Consistent Reaction Field (SCRF) method was used
in combination with method B3LYP/6-31G* to evaluate the implicit
solvent effect on the energy of the modeled compounds. The min-
imum energy structures were fully optimized in the THF field.
Additionally, the ab initio MP2 method was employed to compare
with the DFT results. Finally, higher-level basis sets were used to
account for more reliable relative energies. The Pople basis set
6-311++G** (a triple-zeta basis set supplemented with polarization
and diffuse functions) was used in conjunction with B3LYP while
the Dunning correlation consistent basis set AUG-cc-pVDZ was
employed within the MP2 treatment. The restricted approach
was used for all species. Vibrational frequencies were determined
within the harmonic approximation, at the same theory level (vac-
uum and PCM), except for the MP2/AUG-cc-pVDZ level for which
We have discovered a reaction giving access to a new thiosub-
stituted carbohydrate, via an interesting rearrangement mecha-
nism. Molecular orbital computations were performed in parallel
with the experimental work to better explain the formation of
the observed product. Based upon an electronic stabilization factor,
the conformational bias for the syn conformation of C-1 and C-2
substituents in the open structure preceding the final cyclization
promotes the b stereochemistry. As several diastereoisomers in
the
D
D-xylo series have already shown enzymatic activity for fungal
-xylanases,12 an evaluation of the biological activity of derivatives
of compound 12 would be of interest.
4. Experimental
4.1. General methods
All reactions were carried out under argon. Dry solvents were
used in all experiments. Thin layer chromatography was per-
formed on E. Merck pre-coated 60 F254 plates and compounds were
observed by UV or by charring the plates with an acidic anisalde-
*
MP2/6-31G frequencies were used for computational efficiency.

1092
A. Martinez et al. / Carbohydrate Research 345 (2010) 1088–1093
All transition states were characterized by one imaginary fre-
quency (first order saddle points on the potential energy surface
(PES) associated with the desired reaction pathway). In order to
keep the computational CPU time to reasonable limits the B3LYP/
4), 3.65 (dd, 1H, J5a,4 3.5 Hz, J5a,5b 9.9 Hz, H-5a), 3.55 (large dd,
1H, J5b,4 4.9 Hz, H-5b); 13C NMR (CDCl3): d 138.4–138.6 (Cq Bn),
127.1–129.5 (CHBn), 82.1 (C-2), 78.7 (C-3), 74.8 and 74.1 (2CH2Ph),
71.4 (C-4), 64.0 (C-5), 51.6 (C-1), 36.7 (CH2Ph from SBn), 35.4
(CH2Ph from SBn); LRMS/HRMS (m/z, ESI): (M+Na) = 687.282
(calcd), 687.281 (found).
*
6-31G gas phase formalism was applied for all potential energy
scans. The B3LYP/6-311++G** level of theory was found to be a
suitable choice from test calculations (effective in giving satisfac-
tory energies at a relatively small computational cost). Reported
values refer to this level of theory if not otherwise noted. Thermo-
chemical data were computed by using the KISTHEP software
suite.22
5.4. 2,3-Di-O-benzyl-4-S-benzyl-thio b-D-arabinopyranoside
(12)
To a solution of 11 (186 mg, 275
were slowly added at 0 °C triethylamine (384
methane sulfonyl chloride (100 L, 1.29 mmol). After stirring for
l
mol) in dry CH2Cl2 (8 mL)
lL, 2.75 mmol) and
5.1. 2,3-Di-O-benzyl-4,5-O-isopropylidene-
D
-arabinose dibenzy
l
ldithioacetal (9)
15 min, the reaction mixture was diluted with diethylether
(100 mL), washed with saturated NH4Cl (5 mL), and then with
brine (5 mL). The organic phase was dried with MgSO4, and after
filtration and evaporation to dryness, the residue was used for
the next step without further purification. The crude mixture
was dissolved in dry THF (9 mL), to this solution at 0 °C was added
To a solution of diol 8 (12.9 g, 30.8 mmol) in dry DMF (76 mL) at
0 °C, were added sodium hydride (3.7 g, 60% in mineral oil), nBu4N+
Iꢀ (10 mg, 27
lmol) and imidazole (10 mg, 147 lmol). After stir-
ring for 15 min, benzyl bromide (12.2 mL, 102.6 mmol) was added
dropwise and the mixture was stirred for 16 h. The reaction was
quenched by the addition of methanol at 0 °C and after evaporation
to dryness, the residue was purified by column chromatography to
a solution of TBAF 1 M in THF (500 lL, 500 lmol). After stirring at
0 °C for 15 h, calcium carbonate (50 mg, 0.5 mmol)), Dowex 50WX
8-400 (1.68 g) and methanol (2 mL) were added.23 After stirring for
2 h at room temperature, the reaction mixture was filtered on Cel-
ite and washed with methanol. After evaporation to dryness, the
residue was purified by column chromatography to give 12
(94 mg, 63%) as a colorless oil.
give 9 (17.51 g, 94%) as a slightly yellow oil. ½a D20
ꢀ29.7 (c 0.94,
ꢁ
CHCl3); 1H NMR (CDCl3): d 7.04–7.37 (m, 20H, 4Ph), 4.83 (d, 1H, J
12.3 Hz, CH2Ph), 4.57 (d, 1H, J 12.3 Hz, CH2Ph), 4.48 (d, 1H, J
11.4 Hz, CH2Ph), 4.42 (d, 1H, J 11.4 Hz, CH2Ph), 3.87–4.05 (m, 2H,
H-3, H-4), 3.65–3.93 (m, 7H, H-1, H-2, 2 H-5, 2CH2Ph), 1.33 (s,
3H, CH3), 1.27 (s, 3H, CH3); 13C NMR (CDCl3): d 138.2–138.6 (Cq
Bn), 127.1–129.4 (CH Bn), 108.7 (Cq isopropylidene), 82.8 (C-2),
79.8 (C-3), 76.4 (C-4), 74.8 and 74.7 (2CH2Ph), 66.5 (C-5), 51.2
(C-1), 36.6 (CH2Ph from SBn), 35.5 (CH2Ph from SBn), 26.7 (CH3 iso-
propylidene), 25.4 (CH3 isopropylidene); LRMS/HRMS (m/z, ESI):
(M+Na) = 623.236 (calcd), 623.200 (found).
1H NMR (CDCl3): See main text; LRMS/HRMS (m/z, ESI):
(M+Na) = 565.185 (calcd), 555.184 (found).
Acknowledgments
WewouldliketothankDr. K. Pléforhelpfuldiscussions. Thecom-
putational center of the University of Reims Champagne-Ardenne
(ROMEO, http://www.romeo2.fr) and the C.R.I.H.A.N computing
centre are acknowledged for the CPU time donated. C. Coiffier thanks
the ‘Region Champagne-Ardenne’ and Professor P. Goekjian for
financial support.
5.2. 2,3-Di-O-benzyl-D-arabinose dibenzyldithioacetal (10)
A solution of compound 9 (17.31 g, 28.8 mmol) in acetic acid
(200 mL) and water (70 mL) was heated to reflux for 3 h. After
evaporating to dryness, the residue was purified by column chro-
matography to give the diol 10 (14.71 g, 91%) as a slightly yellow
Supplementary data
oil. ½a 2D0
ꢁ
+20.0 (c 1.65, CHCl3); 1H NMR (CDCl3): d 7.08–7.31 (m,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.03.024.
20H, 4Ph), 4.80 (d, 1H, J 12.1 Hz, CH2Ph), 4.59 (d, 1H, J 12.1 Hz,
CH2Ph), 4.44 (2d, 2H, J 11.5 Hz, CH2Ph), 3.90–3.62 (m, 7H, H-1, H-
2, H-3, 2CH2Ph), 3.55–3.45 (m, 3H, H-4, 2 H-5); 13C NMR (CDCl3):
d 137.7–138.1 (Cq Bn), 126.9–129.2 (CHBn), 81.8 (C-2), 78.5 (C-
3), 74.2 and 73.9 (2CH2Ph), 70.9 (C-4), 63.2 (C-5), 50.6 (C-1), 35.9
(CH2Ph from SBn), 35.7 (CH2Ph from SBn); LRMS/HRMS (m/z,
ESI): (M+Na) = 583.205 (calcd), 583.200 (found).
References
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ꢁ
ꢀ85.7 (c 0.14, CHCl3); 1H
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13.0 Hz, SCH2Ph), 3.75 (d, 1H, J 13.3 Hz, SCH2Ph), 3.66 (m, 1H, H-

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