2,3-Unsaturated enoses. A Pummerer rearrangement route to sugar vinyl sulfides and synthesis of 3-deoxy-3-alkyl/arylsulfinyl pyranosides

Article abstract of DOI:10.1016/j.tet.2012.08.011

A Pummerer rearrangement of 2,3-dideoxy-3-alkyl/arylsulfinyl-arabino- hexopyranosides is reported. Treatment of sulfinyl-arabino-hexopyranoside derivatives, obtained through oxidation of the corresponding thio-derivatives, with trifluoroacetic anhydride (TFAA)/pyridine led to a facile formation of 2,3-dideoxy-3-alkyl/arylthio-hex-2-enopyranosides. Upon conversion of sugar vinyl sulfides to vinyl sulfoxides, conjugate addition reactions were conducted with alkoxides, to afford 3-deoxy-3-alkyl/arylsulfinyl pyranosides, in the manno-configuration exclusively. Whereas the conjugate addition reaction did not proceed with ether protecting groups, ester protecting groups and free hydroxyl groups in the sugar vinyl sulfoxide permitted the reaction.

Full text of DOI:10.1016/j.tet.2012.08.011

Tetrahedron 68 (2012) 8746e8752
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2,3-Unsaturated enoses. A Pummerer rearrangement route to sugar vinyl sulfides
and synthesis of 3-deoxy-3-alkyl/arylsulfinyl pyranosides
*
Arunima Mukherjee, Narayanaswamy Jayaraman
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 May 2012
Received in revised form 1 August 2012
Accepted 6 August 2012
Available online 11 August 2012
A Pummerer rearrangement of 2,3-dideoxy-3-alkyl/arylsulfinyl-arabino-hexopyranosides is reported.
Treatment of sulfinyl-arabino-hexopyranoside derivatives, obtained through oxidation of the corre-
sponding thio-derivatives, with trifluoroacetic anhydride (TFAA)/pyridine led to a facile formation of 2,3-
dideoxy-3-alkyl/arylthio-hex-2-enopyranosides. Upon conversion of sugar vinyl sulfides to vinyl sulf-
oxides, conjugate addition reactions were conducted with alkoxides, to afford 3-deoxy-3-alkyl/ar-
ylsulfinyl pyranosides, in the manno-configuration exclusively. Whereas the conjugate addition reaction
did not proceed with ether protecting groups, ester protecting groups and free hydroxyl groups in the
sugar vinyl sulfoxide permitted the reaction.
Keywords:
Conjugate addition
Pummerer rearrangement
Unsaturated sugars
Vinyl sulfides
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
rearrangement products were elaborated further towards conju-
gate addition reactions. This report describes the utility of 3-alkyl/
Thioglycosides and sulfoxides are reactive intermediates in
sugar chemistry. Elegant examples are their high reactivities in
glycosylation reactions.1e3 On the other hand, the labile nature of
thioglycosides under acidic conditions was verified in few in-
stances, for example, in the case of 2,3-unsaturated thio-
glycosides.4e11 We disclosed previously that 2,3-unsaturated
thioglycosides, resulting from the reaction of 1,2-unsaturated
sugars with alkyl/arylthiols, underwent a facile 1,3-migration in
the presence of trifluoromethanesulfonic acid (TfOH) and afforded
2,3-dideoxy-3-alkyl/arylthio hexopyranosides.12 Realizing a poten-
tial for such 3-alkyl/arylthio 2-deoxy sugar derivatives, we un-
dertook efforts to implement the well-known Pummerer
rearrangement13,14 upon suitable modification of such derivatives.
Implementation of Pummerer rearrangement would permit the
formation of vinyl sulfides from satd sulfides. Carbohydrate-
derived vinyl sulfides can, in principle, form as reactive synthetic
equivalents for further synthetic manipulations. An interesting
elaboration of vinyl sulfides is their conversion to vinyl sulfoxides,
through an oxidation. Reactivities of vinyl sulfoxides are known
elegantly, for example, in conjugate addition reactions.15e17 Vinyl
sulfoxides of a sugar would also encounter stereochemical re-
strictions imposed by varying configurations of oxymethine car-
bons of the sugar. Attracted by these possibilities, the Pummerer
arylthio 2-deoxy glycosides in Pummerer rearrangement reaction
to afford vinyl sulfides, and their subsequent elaboration in con-
jugate addition reactions with few alkoxides.
2. Results and discussion
In a previous study, the susceptibility of 2,3-unsaturated thio-
glycosides towards 1,3-migration in the presence of TfOH was
demonstrated, an example is shown in Fig. 1.12 In this reaction,
protected alkyl/arylthio-hex-2,3-enopyranosides underwent a 1,3-
shift initiated by TfOH, in the presence of alcohols, and afforded
alkyl 2,3-dideoxy-3-alkyl/arylthio-arabino-hexopyranosides, with
equatorial configuration of the substituent at C-3. A nearly exclu-
sive a-anomeric configuration of the glycosides was obtained when
trimethylsilyl trifluoromethanesulfonate (TMSOTf) was used. For-
mation of such alkyl 2,3-dideoxy-3-alkyl/arylthio glycopyranosides
provided an access to install unsaturation on the pyranosides, for
which, the Pummerer rearrangement became the reaction of
AcO
AcO
AcO
EtS
BnOH, TfOH, CH2Cl2
0 oC, 30 min.
O
O
AcO
SEt
α > β
OBn
* Corresponding author. Tel.: þ91 80 2293 2578; fax: þ91 80 2360 0529; e-mail
Fig. 1. 1,3-Migration, followed by glycosylation of a 2,3-unsaturated sugar in the
address: jayaraman@orgchem.iisc.ernet.in (N. Jayaraman).
presence of TfOH and an alcohol.12
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.011

A. Mukherjee, N. Jayaraman / Tetrahedron 68 (2012) 8746e8752
8747
choice. The conversion of the sulfide to a sulfoxide was conducted
first for this purpose. Thus, oxidation of 3-deoxy-3-p-tolylthio-
arabino-hexopyranoside 112 using m-chloroperbenzoic acid
(MCPBA)18 at ꢀ78 ꢁC for 40 min afforded the corresponding sulf-
oxide 2, in a good yield (Scheme 1). Protecting groups at C-4 and C-
6 were either acetyl (2) or benzyl (3) groups, the later was prepared
through O-deacetylation of 2, followed by O-benzylation. Sulfox-
ides 2 and 3 were obtained as w1:1 diastereomeric mixture at the
sulfoxide functionality and configurations at the carbon centres
were ascertained through NMR spectroscopy. Sulfoxides 2 and 3
were subjected to Pummerer rearrangement subsequently. Re-
action of 2 and 3 with TFAA in the presence of pyridine for 16 h led
to the formation of vinyl sulfides 4 and 5, in good yields.
O-deacylation product 11. Formation of 8 was ascertained through
J1,2 of 1.4 Hz, whereas equatorial configuration at C-3 showed J2,3 of
3.6 Hz and J3,4 of 9.8 Hz. The constitution of 8 was confirmed by
correlated (COSY), heteronuclear single quantum coherence (HSQC)
spectroscopies. Further, ethoxide and isopropoxide were also
reacted with 6, to afford products 9 and 10 with manno-configu-
ration, in moderate yields. In these instances too, unreacted starting
material 6 was recovered as the O-deacylated product 11. Nuclear
Overhauser effect (NOESY) experiments were performed on 8 and
10, from which dipolar coupling of H-3eH-5, H-1eOCH3 and H-
4eOCH3 were observed. One of the two epimers of 11 crystallized
upon storing and the structure was solved by single crystal X-ray
crystallography (Fig. 2). The structure showed the co-planarity of
l
l
l
l
Scheme 1. Reaction conditions: (i) MCPBA, CH2Cl2, 40 min, ꢀ78 to 0 ꢁC; (ii) NaOMe, MeOH, 2 h; (iii) NaH, BnBr, DMF, rt, 6 h; (iv) TFAA, pyridine, 0 ꢁC to rt, 16 h; (v) MCPBA, CH2Cl2,
10 min, ꢀ78 ꢁC.
The rearrangement to vinyl sulfides 4 and 5 possibly occurred
through formation of an -trifluoroacetoxy sulfide initially, fol-
sulfoxide oxygen with C-2eC-3 double bond, in addition to features
of half-chair conformation and the orientation of substituents
around the pyranoside.
a
lowed by an elimination. Alternatively, a deprotonation at the stage
of ylidine-p-tolyl-sulfonium ion might have also led to the elimi-
nation.19 Structures of 4 and 5 were ascertained from 1H NMR
spectra, wherein the appearance of a doublet at 5.30 ppm (4) and
5.09 ppm (5) corresponded to the H-2 nucleus, with concomitant
disappearance of resonances H-2 and H-3 nucleus of 2 (w3.6, 3.0
and 1.9 ppm) and of 3 (w3.1, 2.2 and 2.1 ppm), respectively. Dis-
appearance of resonances of C-2 and C-3 in 2 (w60.4, 26.3,
23.6 ppm) and 3 (w62.6, 28.3, 24.2 ppm) was also observed in the
13C NMR spectra of 4 and 5. Formation of vinyl sulfides 4 and 5 was
thus achieved through Pummerer rearrangement on sulfoxides 2
and 3. Whereas a Pummerer rearrangement is demonstrated here
on a pyranose structure, such a rearrangement is known in nucle-
osides synthesis previously.20
Fig. 2. ORTEP diagram of an epimer of 11.
Towards further synthetic manipulations, vinyl sulfides 4 and 5
were subjected first to a controlled oxidation at ꢀ78 ꢁC for a shorter
duration, to afford vinyl sulfoxides 6 and 7, in good yields. Products
6 and 7 formed as a diastereomeric mixture at the sulfoxide func-
tionality, in w1:1 ratio.
Upon formation of the endocyclic sugar vinyl sulfoxides, conju-
gate addition reactions were undertaken with alkoxide nucleo-
philes, with the anticipation that the addition would lead to either
an axial or equatorial substitution of C-2 and C-3 in the resulting
pyranoside. Conjugate addition reactions on 2,3-unsaturated
nitroolefins21e24 and sulfones,25e27 originating from constitution-
ally varying pyranoside sugars, were reported previously.
When the reaction was attempted with O-benzyl protected vinyl
sulfoxide 7, it was observed that no reaction occurred and only the
starting material was recovered even after prolonged reaction du-
ration. In the light of the above reactivity patterns in the presence of
ether and ester protecting groups, conjugate addition with vinyl
sulfoxide 11, having free hydroxyl groups, was conducted. The re-
action of 11 with NaOMe/MeOH led to the formation of 8, in a good
yield, thereby illustrating that the conjugate addition was de-
pendant on the nature of the protecting group. Lack of reactivity in
the conjugate addition with benzyl protecting group might result
from its electron-donating nature.
It was found further that sulfoxide 8 could be subjected to yet
another Pummerer rearrangement to generate the corresponding
vinyl sulfide. Thus, 8 was O-acetylated initially (Ac2O/pyridine) and
then subjected to Pummerer rearrangement (TFAA/pyridine). The
reaction led to the formation of vinyl sulfide 12, in a moderate yield
(Scheme 2).
The reactions of 6 and 7 with alkoxides were performed using
the corresponding alcohol as the solvent under reflux for several
hours (Scheme 2). Reaction of 6 with NaOMe in MeOH afforded the
C-2 addition product. An analysis of the product revealed that
the addition occurred from an axial face, to afford sulfoxide 8
with manno-configuration, in
a
moderate yield, along with
l
l
l
Scheme 2. Reaction conditions: (i) RONa, ROH, reflux, 12e18 h; (ii) Ac2O, pyridine, rt, 16 h; (iii) TFAA, pyridine, 0 ꢁC to rt, 24 h; (iv) NaOMe, MeOH, reflux, 24e30 h.

8748
A. Mukherjee, N. Jayaraman / Tetrahedron 68 (2012) 8746e8752
In order to assess whether the substituent on sulfoxide moiety
slow-reacting epimer also, yet leading to the recovery of unreacted
starting material as a deprotected vinyl sulfoxide 11. Two important
observations were made in these reactions: (i) addition products
8e10, 18 and 19 were obtained as single diastereomers and (ii) O-
deacetylated product 11 was obtained as an epimeric mixture,
whereas 17, was a single epimer, the difference being p-tolylthio-
moiety in 11 and ethylthio-moiety in 17. In the light of these ob-
servations, we assume that there is only one reactive epimer of 6,
the R-epimer, and of 16, the S-epimer, which undergoes conjugate
addition reaction to afford 8e10, 18 and 19, respectively, as single
diastereomers. The other slow-reacting epimer of 6 (S) and 16 (R)
possibly exhibits a propensity for inversion of configuration at the
sulfinyl centre at higher reaction temperature, by which the yields
of the conjugate addition products are increased more than 50%,
with respect to the vinyl sulfoxide starting materials 6 and 16 (1:1
epimeric mixture). We further presume that the rate of addition
reaction versus inversion may be different for 6 and 16, leading to
differing amounts of the addition products (as single di-
astereomers) and the O-deacetylated products 11 and 17, with
varying proportions of epimers at the sufinyl sulfur functionality.
would influence the addition of the nucleophile, a study was con-
ducted in which an ethylthio-moiety was installed in place of p-
tolylthio-moiety as in 1. The sequence of reactions to install
ethylthio-moiety was similar as described previously (Scheme 3).
Thus, benzyl-2,3-dideoxy-3-ethylthio-arabino-hexopyranoside 13,
which was prepared through a 1,3-migration reaction protocol,12
was subjected (i) MCPBA mediated oxidation of 13 to sulfoxide
14; (ii) Pummerer rearrangement using TFAA/pyridine to vinyl
sulfide 15 and (iii) oxidation of 15 to vinyl sulfoxide 16. The re-
actions were high yielding in general. Conjugate addition of sodium
methoxide and isopropoxide with 16 was conducted, under re-
action conditions similar to that in the case of reaction of nucleo-
philes with 6. Analysis of the reaction showed that the addition of
methoxide and isopropoxide remained similar, leading to the for-
mation 3-deoxy-3-alkylsulfinyl pyranosides 18 and 19, wherein the
addition occurred from an axial face to afford the manno-configu-
ration of the substituent. However, lower yields of conjugate ad-
dition products were observed with vinyl sulfoxide 16, than that
with 6. Remaining product of the reaction was found to be the free
hydroxyl group containing vinyl sulfoxide 17. Thus, among alkyl-
and arylsulfoxides, conjugate addition occurred better with aryl-
sulfoxides than with former, thereby indicating a role, possibly an
electronic effect, by the aryl group in stabilizing the conjugate an-
ion, which would form in situ during the reaction of nucleophile
with vinyl sulfoxides. In the course of reactions, we also observed
that the hydrolysis product 17, formed during the conjugate addi-
tion reaction, was obtained as a single epimer at the sulfoxide
functionality. On the other hand, similar hydrolysis product 11,
having the arylsulfoxide moiety, was found to be a 1:1 epimeric
mixture, even when the conjugate addition reaction was initiated
with 1:1 epimeric ratio in both aryl and alkyl vinyl sulfoxides.
3. Conclusion
The present study demonstrates implementation of the Pum-
merer rearrangement on 2,3-dideoxy-3-aryl/alkylsulfinyl hex-
opyranosides in order to prepare 2,3-unsaturated enoses, namely,
vinyl sulfides, in good yields. It is pertinent to note that vinyl sul-
fides and vinyl sulfonium ions derived from thereof are known to
be excellent synthetic equivalents for vinyl sulfide-oxonium ion
cyclizations30 and as electrophiles,31 respectively. In exploring the
reactivities of endocyclic sugar vinyl sulfides of pyranosides, an
oxidation to the corresponding vinyl sulfoxides was performed. The
AcO
AcO
AcO
AcO
EtS
AcO
AcO
Et(O)S
16
O
O
(i)
O
(ii)
(iii)
O
AcO
Et(O)S
AcO
(92 %)
(83 %)
(82 %)
EtS
OBn
OBn
OBn
OBn
(iv)
13
14
15
OR
O
HO
HO
O
HO
HO
+
Et(O)S
Et(O)S
OBn
OBn
17
18: R = Me (56 %)
19: R = CHMe2 (53 %)
Scheme 3. (i) MCPBA, CH2Cl2, ꢀ78 to 0 ꢁC, 40 min; (ii) TFAA, pyridine, 0 ꢁC to rt, 4 h; (iii) MCPBA, CH2Cl2, ꢀ78 ꢁC, 10 min; (iv) RONa, ROH, reflux, 12e18 h.
It is agreed generally that a vinyl sulfoxide would present the
sulfoxide oxygen co-planar with the double bond and the lone pair
of electrons on the sulfur would prefer to orient away from the path
of the nucleophile entry.28,29 This could be extended to sugar vinyl
sulfoxides of the present study, in which case, the preference for an
axial attack would originate from a face anti to the lone pair of
electrons on the sulfur of sulfoxide functionality, leading to the
formation of the product with manno-configuration.
In the conjugate addition reactions, O-deacetylated vinyl sulf-
oxide 17 (44e47%) was obtained along with 18 (56%) and 19 (53%),
with NaOMe and NaOiPr, respectively. Thus, one of the sulfoxide
epimers appeared to be more reactive when compared to the other.
The remaining amount was unreactive sulfoxide 16, which un-
derwent O-deacetylation under the basic condition to afford 17.
Assuming the co-planarity of the double bond and the sulfoxide
oxygen (S-configuration of 16) conducive for the addition reaction
to afford 18 and 19, the O-deacetylated vinyl sulfoxide 17 was an-
ticipated to have the R-configuration at the sulfoxide.
Aryl-substituted vinyl sulfoxide 6 showed improved yields of con-
jugate addition products 8e10 (w66%), indicating a reactivity of the
efficiency of such vinyl sulfoxides in conjugate addition reactions
was studied with alkoxides. The reactions showed that the newly
entered alkoxide moiety at C-2 was retained in the manno-config-
uration. In an example, the resulting conjugate addition product,
namely, 3-deoxy 3-arylsulfinyl pyranoside was subjected to a sec-
ond Pummerer rearrangement, leading to the formation of 2,3-
unsaturated sugar vinyl sulfide, with an alkoxide substituent at
C-2. A change in the substituent on the sulfoxide showed that the
conjugate addition was relatively more efficient with arylsulfinyl
moiety than with alkylsulfinyl moiety. The present study illustrates
Pummerer rearrangementeconjugate addition reaction sequence
on a sugar structure, towards functionalization of C-2 and C-3
carbons of pyranosides.
4. Experimental section
4.1. General methods
Chemicals were purchased from commercial sources and were
used without further purification. Solvents were dried and distilled

A. Mukherjee, N. Jayaraman / Tetrahedron 68 (2012) 8746e8752
8749
according literature procedures.32 Analytical TLC was performed on
commercial plates coated with silica gel GF254 (0.25 mm). Silica gel
(230e400 mesh) was used for column chromatography. Optical
rotations were recorded on a polarimeter at the sodium D line at
24 ꢁC. High-resolution mass spectra were obtained from Q-TOF
instrument by electron spray ionization (ESI) technique. NMR
spectral analyses were performed on a spectrometer operating at
400 MHz for 1H nucleus and 100 MHz spectrometer for 13C nucleus,
with residual solvent signal acting as the internal standard. COSY
and HSQC analyses were performed on a 400 MHz NMR spec-
trometer. Standard abbreviations s, d, t, dd, br, app., m and band
refer to singlet, doublet, triplet, doublet of doublet, broad, apparent,
multiplet and set of resonances, respectively. Configuration at sul-
finyl sulfur is given on the assumption that only the R-epimer of 6
and the S-epimer of 16 undergo the conjugate addition reaction.
(C-3), 28.3 (C-2), 24.2 (C-2), 21.3 (eC6H4CH3); HRMS (ES-MS):
MNaþ, found 579.2186. C34H36O5SNa requires 579.2181.
4.4. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-tolylthio)-
erythro-hex-2-enopyranoside (4)
a-D-
TFAA (0.31 mL, 2.17 mmol) was added drop-wise to a solution of
2 (200 mg, 0.434 mmol) and pyridine (0.35 mL, 4.34 mmol) in
CH2Cl2 (6 mL), under N2 atmosphere and at 0 ꢁC. The reaction
mixture was stirred for 16 h at rt, concentrated in vacuo and puri-
fied (SiO2) (15% EtOAc/hexane) to afford 4 (144 mg, 75%), as a gum;
Rf (11% EtOAc/hexane) 0.4; [
(400 MHz, CDCl3):
a
]
þ21.3 (c 0.4, CHCl3); 1H NMR
D
d
7.53e7.35 (9H, m, Aromatic), 5.65 (1H, d, J4,5
8.8 Hz, H-4), 5.30 (1H, d, J1,2 1.8 Hz, H-2), 5.08 (1H, d, J1,2 1.8 Hz, H-
1), 4.70 (1H, d, J 12 Hz, PhCH2a), 4.52 (1H, d, J 12 Hz, PhCH2b),
4.31e4.20 (2H, band, H-5, H-6a), 4.05 (1H, app. d, J 10.4 Hz, H-6b),
2.34 (3H, s, eC6H4CH3), 2.09 (3H, s, COCH3), 2.07 (3H, s, COCH3); 13
C
4.2. (RS/SS)-Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-tolylsulfinyl)-
a
-
D
-arabino-hexopyranoside (2)
NMR (100 MHz, CDCl3): d 170.6, 170.0 (CO), 140.4 137.4, 135.6, 134.5,
130.2, 128.4, 127.9, 126.3, 124.8, 121.8 (Aromatic, C-2, C-3), 94.4 (C-
1), 70.0 (C-4), 68.5 (C-5), 67.0 (PhCH2), 62.6 (C-6), 21.1 (eC6H4CH3),
20.7, 20.6 (COCH3); HRMS (ES-MS): MNaþ, found 465.1348.
C24H26O6SNa requires 465.1348.
A mixture of 112 (300 mg, 6.75 mmol) and MCPBA (116 mg,
6.75 mmol) in CH2Cl2 (8 mL) was stirred under a nitrogen atmo-
sphere at ꢀ78 ꢁC for 40 min. The reaction mixture was diluted with
CH2Cl2 (10 mL), washed with satd aq NaHCO3 solution (2ꢂ5 mL),
dried (Na2SO4), concentrated in vacuo and purified (SiO2) (40%
EtOAc/hexane) to afford 2 (280 mg, 90%), as an inseparable epi-
meric mixture (1:1) and as a foamy solid; Rf (43% EtOAc/hexane)
4.5. Benzyl 4,6-di-O-benzyl-2,3-dideoxy-3-(p-tolylthio)-
a-D-
erythro-hex-2-enopyranoside (5)
0.3; 1H NMR (400 MHz, CDCl3):
d 7.64e7.54 (2H, m, Aromatic),
TFAA (0.2 mL, 1.35 mmol) was added to a solution of 3 (150 mg,
0.269 mmol) and pyridine (0.21 mL, 2.69 mmol) in CH2Cl2 (5 mL)
under N2 atmosphere and stirred at 0 ꢁC. The reaction mixture was
stirred for 16 h at rt, concentrated in vacuo and purified (SiO2) (8%
EtOAc/hexane) to afford 5 (110 mg, 75%), as a gum; Rf (6% EtOAc/
7.41e7.23 (16H, m, Aromatic), 5.34 (1H, app. t, J 10.2 Hz, H-4),
5.01e4.97 (3H, band, H-1ꢂ2, H-4), 4.70e4.56 (4H, band, PhCH2ꢂ2),
4.40e4.27 (3H, band, H-5, H-6a, H-6b), 4.17e3.95 (3H, band, H-5, H-
6a, H-6b), 3.64e3.59 (1H, m, H-3), 3.04e3.02 (1H, m, H-3), 2.32 (6H,
s, eC6H4CH3), 2.29e2.21 (2H, m, H-2), 2.09 (3H, s, COCH3), 2.08 (3H,
s, COCH3), 2.03 (3H, s, COCH3), 1.97 (3H, s, COCH3),1.90e1.85 (2H, m,
hexane) 0.4; [
a
]
D þ37.6 (c 0.58, CHCl3); 1H NMR (400 MHz, CDCl3):
H-2); 13C NMR (100 MHz, CDCl3):
d 170.6 (CO), 169.3 (CO), 141.9,
d
7.30e7.15 (19H, m, Aromatic), 5.09 (1H, app. s, H-2), 5.05 (1H, d,
J1,2 2.8 Hz, H-1), 4.75 (1H, d, J 12 Hz, PhCH2), 4.69e4.43 (6H, band,
PhCH2, H-4), 4.12 (1H, m, H-5), 3.75 (1H, dd, J5,6a, 6a,6b 3.8, 10.4 Hz,
141.3, 137.2, 136.9, 130.0, 129.8, 128.4, 128.3, 127.9, 127.8, 127.7,
125.2, 124.4, 124.2 (Aromatic), 95.2 (C-1), 71.8 (C-4), 69.1 (C-4), 68.3
(C-5), 67.5 (C-5), 65.2 (PhCH2), 64.8 (PhCH2), 63.0 (C-6), 62.4, (C-6),
60.4 (C-3), 59.6 (C-3), 26.3 (C-2), 23.6 (C-2), 21.3 (eC6H4CH3), 20.8,
20.7, 20.6 (COCH3); HRMS (ES-MS): MNaþ, found 483.1450.
C24H28O7SNa requires 483.1453.
H-6a), 3.59 (1H, app. d, J 10.4 Hz, H-6b), 2.34 (3H, s, eC6H4CH3); 13
C
NMR (100 MHz, CDCl3):
d 145.3, 135.0, 134.4, 131.2, 130.2, 130.1,
129.7, 128.5, 128.3, 128.2, 128.1, 127.8, 127.7, 128.5, 128.2, 128.1,
128.0, 127.7, 127.5, 127.0, 126.9, 119.3 (Aromatic, C-2, C-3), 94.8 (C-
1), 73.7 (C-4,), 73.4 (C-5), 69.8 (PhCH2), 68.5 (PhCH2), 68.3 (C-6),
21.2 (eC6H4CH3); HRMS (ES-MS): MNaþ, found 561.2076.
C34H34O4SNa requires 561.2076.
4.3. (RS/SS)-Benzyl 4,6-di-O-benzyl-2,3-dideoxy-3-(p-tolylsulfinyl)-
a
-
D
-arabino-hexopyranoside (3)
Sulfoxide 2 (250 mg, 0.543 mmol) in MeOH (9 mL) was admixed
4.6. (RS/SS)-Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-tolylsulfinyl)-
with NaOMe in MeOH (0.4 mL), stirred for 2 h at rt and concen-
trated in vacuo. The resulting residue (200 mg, 0.531 mmol) in DMF
(4 mL) was added to a solution of NaH (60% dispersion in oil)
(420 mg, 1.06 mmol) in DMF (4 mL) at 0 ꢁC and stirred for 45 min,
followed by addition of BnBr (0.2 mL, 1.59 mmol) and stirred fur-
ther for 6 h. The reaction mixture was neutralized with AcOH/
MeOH (1:10, v/v), diluted with EtOAc (20 mL), washed with H2O
(2ꢂ10 mL), dried (Na2SO4), concentrated in vacuo and purified
(SiO2) (20% EtOAc/hexane) to afford 3 (267 mg, 88%, after two
steps), as an epimeric mixture (1:1) and as a gum; Rf (16% EtOAc/
a
-
D
-erythro-hex-2-enopyranoside (6)
A mixture of vinyl sulfide 4 (166 mg, 0.375 mmol) and MCPBA
(64.5 mg, 0.375 mmol) in CH2Cl2 (6 mL) was stirred at ꢀ78 ꢁC for
10 min. The reaction mixture was then diluted with CH2Cl2 (15 mL),
washed with satd aq NaHCO3 solution (2ꢂ10 mL), dried (Na2SO4),
concentrated in vacuo and purified (SiO2) (40% EtOAc/hexane) to
afford 6 (160 mg, 92%), as an epimeric mixture (1:1) and as a gum;
Rf (33% EtOAc/hexane) 0.2; 1H NMR (400 MHz, CDCl3):
d 7.54 (2H, d,
J 8 Hz, Aromatic), 7.44 (2H, d, J 8 Hz, Aromatic), 7.38e7.34 (9H, m,
Aromatic), 7.30e7.26 (5H, m, Aromatic), 6.82 (1H, d, J1,2 1.6 Hz, H-2),
6.79 (1H, d, J1,2 1.6 Hz, H-2), 5.75 (1H, d, J4,5 9 Hz, H-4), 5.35e5.32
(2H, band, H-1ꢂ2), 5.12 (1H, d, J4,5 9 Hz, H-4), 4.82 (2H, d, J 12 Hz,
PhCH2), 4.68 (1H, d, J 12 Hz, PhCH2a), 4.65 (1H, d, J 12 Hz, PhCH2b),
4.19e4.13 (3H, band, H-5, H-6a, H-6b), 4.09e3.98 (3H, band, H-5, H-
6a, H-6b), 2.40 (6H, s, eC6H4CH3), 2.08 (6H, s, COCH3), 2.06 (6H, s,
hexane) 0.35; 1H NMR (400 MHz, CDCl3):
d 7.41e7.38 (7H, m, Aro-
matic), 7.36e7.26 (28H, m, Aromatic), 7.22e7.07 (3H, m, Aromatic),
5.00 (2H, app. d, J 2.6 Hz, H-1), 4.97 (1H, d, J 12 Hz, PhCH2a),
4.93e4.37 (11H, band, PhCH2), 4.06 (1H, app. t, J 9.8 Hz, H-4),
3.92e3.82 (3H, band, H-5, H-6a, H-6b), 3.74e3.60 (4H, band, H-4, H-
5, H-6a, H-6b), 3.07e3.00 (2H, m, H-3), 2.39 (6H, s, eC6H4CH3),
2.29e2.25 (2H, m, H-2), 2.11 (2H, ddd, J1,2a, 1,2e, 2,3 3.8, 13.2, 13.6 Hz,
COCH3); 13C NMR (100 MHz, CDCl3):
d 169.7, 169.4, 169.3 (CO),
H-2); 13C NMR (100 MHz, CDCl3):
d
142.2, 140.8, 137.7, 137.5, 137.3,
146.9, 145.3, 143.0, 142.8, 139.1, 138.2, 137.0, 133.2, 130.6, 130.3,
130.1, 129.6, 128.5, 128.1, 128.0, 127.7, 126.8, 126.2, 126.0, 125.9
(Aromatic, C-2, C-3), 93.7 (C-1), 93.5 (C-1), 70.6 (PhCH2), 70.5
(PhCH2), 68.3 (C-5), 68.2 (C-5), 63.7 (C-4), 62.5 (C-4), 62.1 (C-6), 21.5
137.2, 129.8, 128.4, 128.3, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5,
125.0, 124.1 (Aromatic), 95.7 (C-1), 95.5 (C-1), 75.4 (C-4), 73.5 (C-5),
72.2 (C-5), 71.5 (PhCH2), 68.9 (PhCH2), 68.5 (C-6), 62.6 (C-3), 61.2

8750
A. Mukherjee, N. Jayaraman / Tetrahedron 68 (2012) 8746e8752
(eC6H4CH3), 21.4 (eC6H4CH3), 20.6, 20.5, 20.2 (COCH3); HRMS (ES-
130.1, 128.5, 128.0, 127.9, 125.7 (Aromatic), 94.1 (C-1), 74.6 (C-2),
71.9 (C-5), 70.6 (PhCH2), 69.2 (eOCH2CH3), 67.8 (C-4), 66.0 (C-6),
62.7 (C-3), 21.5 (eC6H4CH3), 18.4 (OCH2CH3); HRMS (ES-MS):
MNaþ, found 443.1503. C22H28O6SNa requires 443.1504.
MS): MNaþ, found 481.1297. C24H26O7SNa requires 481.1297.
4.7. (RS/SS)-Benzyl 4,6-di-O-benzyl-2,3-dideoxy-3-(p-tolylsulfinyl)-
a
-
D
-erythro-hex-2-enopyranoside (7)
4.10. (RS)-Benzyl 2-O-isopropyl-3-deoxy-3-(p-tolylsulfinyl)-
A mixture of vinyl sulfide 5 (180 mg, 0.334 mmol) and MCPBA
a-D-manno-pyranoside (10) and (RS/SS)-benzyl-2,3-dideoxy-3-
(57.4 mg, 0.334 mmol) in CH2Cl2 (6 mL) was stirred at ꢀ78 ꢁC for
10 min. The reaction mixture was then diluted with CH2Cl2 (15 mL),
washed with satd aq NaHCO3 solution (2ꢂ10 mL), dried (Na2SO4),
concentrated in vacuo and purified (SiO2) (4% EtOAc/hexane) to
afford 7 (160 mg, 90%), as an epimeric mixture (1:1) and as a gum;
(p-tolylsulfinyl)-
a
-
D
-erythro-hex-2-enopyranoside (11)
i
A solution of 6 (52.2 mg, 0.114 mmol) in PrOH (10 mL) was
treated with NaOiPr (71.3 mg, 0.871 mmol) in iPrOH (6 mL),
refluxed for 18 h, solvents removed in vacuo and purified (SiO2)
(65% EtOAc/hexane) to afford 10 (30.7 mg, 66%), as a gum; Rf (80%
EtOAc/pet. ether) 0.3; [
CDCl3þDMSO-d6):
Rf (14% EtOAc/hexane) 0.4; 1H NMR (400 MHz, CDCl3):
d 7.58e7.56
(4H, m, Aromatic), 7.45e7.28 (30H, m, Aromatic), 7.16e7.14 (4H, m,
Aromatic), 6.73 (2H, app. s, H-2), 5.35 (2H, d, J1,2 2 Hz, H-1), 4.82
(2H, d, J 12 Hz, PhCH2), 4.67 (3H, d, J 12 Hz, PhCH2, H-4), 4.60e4.56
(3H, m, PhCH2, H-4), 4.48 (2H, d, J 12 Hz, PhCH2), 4.32 (2H, d, J 12 Hz,
PhCH2), 4.05 (2H, app. d, J 12 Hz, PhCH2), 4.02e3.96 (3H, band, H-5,
H-6a, H-6b), 3.59e3.55 (3H, band, H-5, H-6a, H-6b), 2.40 (6H, s,
a
]
D þ61.9 (c 0.7, CHCl3); 1H NMR (400 MHz,
d
7.68e7.66 (2H, m, Aromatic), 7.35e7.29 (7H, m,
Aromatic), 5.27 (1H, d, J1,2 3 Hz, H-1), 4.84 (1H, d, J 12 Hz, PhCH2a),
4.64 (1H, d, J 12 Hz, PhCH2b), 4.31 (1H, br, H-4), 4.11e4.04 (2H, m, H-
5, H-6a), 3.77e3.73 (1H, app. d, J 11 Hz, H-6b), 3.49 (1H, app. d, J
11 Hz, H-3), 3.37 (1H, app. s, H-2), 2.88e2.83 (1H, m, eOCHMe2),
2.42 (3H, s, eC6H4CH3), 2.13e2.04 (6H, m, eOCHMe2); 13C NMR
(CDCl3þDMSO-d6): 150.7, 142.6, 138.0, 137.5, 136.5, 130.0, 128.5,
128.3, 125.8 (Aromatic), 97.3 (C-1), 71.9 (C-2), 70.1 (C-5), 67.6
(PhCH2), 65.3 (eOCHMe2), 64.5 (C-4), 64.4 (C-6), 61.5 (C-3), 21.4
(eC6H4CH3), 20.3 (eOCHMe2); HRMS (ES-MS): MNaþ, found
457.1661. C23H30O6SNa requires 457.1661.
eC6H4CH3); 13C NMR (CDCl3):
d 150.0, 149.1, 142.6, 138.5, 137.5,
137.3, 137.1, 130.1, 129.8, 128.4, 128.3, 128.1, 128.0, 127.9, 127.8, 127.7,
127.0, 126.6, 126.5 (Aromatic, C-2, C-3), 94.2 (C-1), 74.7, 73.4, 71.3
(PhCH2), 71.1 (C-5), 70.4 (C-5), 70.2 (C-4), 69.4 (C-4), 68.1 (C-6), 68.0
(C-6), 21.5 (eC6H4CH3), 21.4 (eC6H4CH3); HRMS: MNaþ, found
577.2021. C34H34O5SNa requires 577.2025.
Compound 11: yield: 24.3 mg. (epimer 1:1). Epimer a (R-epi-
4.8. (RS)-Benzyl 2-O-methyl-3-deoxy-3-(p-tolylsulfinyl)-
pyranoside (8)
a
-
D
-manno-
mer): Rf (67% EtOAc/hexane) 0.24; [
NMR (400 MHz, CDCl3þDMSO-d6):
a
]
þ59.7 (c 0.42, CHCl3); 1H
D
d
7.58e7.56 (2H, m, Aromatic),
7.40e7.35 (7H, m, Aromatic), 6.50 (1H, app. s, H-2), 5.24 (1H, app. s,
H-1), 4.76 (1H, d, J 12 Hz, PhCH2a), 4.58 (1H, d, J 12 Hz, PhCH2b),
3.83e3.76 (2H, band, H-4, H-5), 3.74e3.69 (2H, band, H-6a, H-6b),
2.35 (3H, s, eC6H4CH3); 13C NMR (100 MHz, CDCl3þDMSO-d6):
A solution of 6 (75.0 mg, 0.164 mmol) in MeOH (8 mL) was
treated with NaOMe (70.2 mg, 1.30 mmol) in MeOH (5 mL),
refluxed for 12 h, solvents were removed in vacuo and purified
(SiO2) (87% EtOAc/hexane) to afford 8 (45.3 mg, 68%), as a gum; Rf
d
150.7, 141.8, 138.8, 137.5, 129.8, 128.3, 127.7, 125.7, 124.0 (Aromatic,
(90% EtOAc/hexane) 0.4; [
CDCl3):
a
]
D ꢀ39.3 (c 1, CHCl3); 1H NMR (400 MHz,
C-2, C-3), 94.1 (C-1), 71.9 (PhCH2), 70.2 (C-4), 63.2 (C-5), 61.4 (C-6),
21.3 (eC6H4CH3); HRMS (ES-MS): MNaþ, found 397.1085.
C20H22O5SNa requires 397.1086. Epimer b (S-epimer): Rf¼0.26 (71%
d
7.62 (2H, d, J 8 Hz, Aromatic), 7.37 (2H, d, J 8 Hz, Aromatic),
7.32 (2H, d, J 8 Hz, Aromatic), 7.24e7.22 (3H, m, Aromatic), 4.89 (1H,
d, J1,2 1.4 Hz, H-1), 4.69 (1H, d, J 12 Hz, PhCH2a), 4.61 (1H, app. t, J
9.8 Hz, H-4), 4.43 (1H, d, J 12 Hz, PhCH2b), 3.94 (1H, dd, J5,6a, 6a,6b 3.8,
EtOAc/hexane); [
CDCl3þDMSO-d6):
a
d
]
þ32.8 (c 0.7, CHCl3); 1H NMR (400 MHz,
7.58e7.56 (2H, m, Aromatic), 7.40e7.32 (7H, m,
D
12 Hz, H-6a), 3.83 (1H, dd, J5,6b,
4.8, 12 Hz, H-6b), 3.73e3.68
Aromatic), 6.52 (1H, app. s, H-2), 5.25 (1H, app. s, H-1), 4.77 (1H, d, J
12 Hz, PhCH2a), 4.64 (1H, d, J 12 Hz, PhCH2b), 3.98e3.96 (1H, m, H-
4), 3.88e3.85 (1H, m, H-5), 3.75e3.60 (2H, band, H-6a, H-6b), 2.39
6a,6b
(1H, m, H-5), 3.27 (3H, s, OCH3), 3.24 (1H, dd, J2,3, 3,4 3.6, 9.8 Hz, H-
3), 2.93 (1H, dd, J1,2, 2,3 1.4, 3.7 Hz, H-2), 2.45 (3H, s, eC6H4CH3); 13
NMR (CDCl3): 142.9, 139.0, 136.6, 130.3, 128.5, 128.1, 128.0, 125.4
C
d
(3H, s, eC6H4CH3); 13C NMR (100 MHz, CDCl3þDMSO-d6):
d 150.7,
(Aromatic), 93.8 (C-1), 76.0 (C-2), 71.9 (C-5), 69.3 (PhCH2), 67.9
(OCH3), 66.6 (C-4), 62.7 (C-6), 57.8 (C-3), 21.5 (eC6H4CH3); HRMS
(ES-MS): MNaþ, found 429.1348. C21H26O6SNa requires 429.1348.
Alternatively, 8 was synthesized from 11 as follows: a solution of
11 (60.0 mg, 0.160 mmol) in MeOH (8 mL) was treated with NaOMe
(65.3 mg, 1.21 mmol) in MeOH (5 mL), refluxed for 24e30 h, sol-
vents removed in vacuo and the residue purified (SiO2) (87% EtOAc/
hexane) to afford 8 (49.2 mg, 75%), as a gum.
142.6,138.0,137.5,136.5,130.0,129.9, 128.5, 128.3 (Aromatic, C-2, C-
3), 94.1 (C-1), 70.1 (PhCH2), 67.6 (C-4), 65.3 (C-5), 64.5 (C-6), 21.3
(eC6H4CH3); HRMS (ES-MS): MNaþ, found 397.1085. C20H22O5SNa
requires 397.1086.
4.11. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-2-O-methyl-3-(p-tol-
ylthio)-a-D-erythro-hex-2-enopyranoside (12)
Acetic anhydride (0.06 mL, 0.741 mmol) was added to a solution
of 8 (100 mg, 0.246 mmol) and pyridine (0.09 mL, 1.23 mmol) in
CH2Cl2 (3 mL) at 0 ꢁC and stirred for 16 h at rt. The reaction mixture
was diluted with CH2Cl2 (20 mL), washed with dil HCl (10%)
(2ꢂ5 mL), dried (Na2SO4) and concentrated in vacuo. TFAA
(0.17 mL, 1.23 mmol) was added to a solution of the crude reaction
mixture and pyridine (0.18 mL, 1.22 mmol) in CH2Cl2 (5 mL), stirred
at rt for 24 h, after which the reaction mixture was concentrated in
vacuo and purified (SiO2) (11% EtOAc/hexane) to afford 12 (57.1 mg,
4.9. (RS)-Benzyl 2-O-ethyl-3-deoxy-3-(p-tolylsulfinyl)-
pyranoside (9)
a-D-manno-
A solution of 6 (52.2 mg, 0.114 mmol) in EtOH (10 mL) was
treated with NaOEt (59.2 mg, 0.871 mmol) in EtOH (6 mL), refluxed
for 18 h, solvents were removed in vacuo and purified (SiO2) (67%
EtOAc/hexane) to afford 9 (31.1 mg, 66%), as a gum; Rf (85% EtOAc/
hexane) 0.3; [
a
]
ꢀ31.8 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3):
D
d
7.63 (1H, d, J 8 Hz, Aromatic), 7.38e7.35 (2H, m, Aromatic),
49%, after two steps), as a gum; Rf (16% EtOAc/hexane) 0.4; [a]
D
7.31e7.28 (3H, m, Aromatic), 7.26e7.23 (3H, m, Aromatic), 4.94 (1H,
app. s, H-1), 4.70e4.64 (2H, band, PhCH2a, H-4), 4.42 (1H, d, J 12 Hz,
PhCH2b), 3.94e3.90 (2H, m, H-5, H-6a), 3.88e3.86 (1H, m, H-6b),
3.78e3.66 (1H, m, H-3), 3.59e3.52 (2H, m, eOCH2CH3), 2.93 (1H,
app. d, J 2.4 Hz, H-2), 2.44 (3H, s, eC6H4CH3), 1.23 (3H, app. s,
þ22.1 (c 1, CHCl3); 1H NMR (CDCl3):
d 7.36e7.31 (9H, m, Aromatic),
5.64 (1H, d, J4,5 9.2 Hz, H-4), 5.03 (1H, s, H-1), 4.84 (1H, d, J 12 Hz,
PhCH2a), 4.58 (1H, d, J 12 Hz, PhCH2b), 4.31e4.16 (3H, band, H-5, H-
6a, H-6b), 3.30 (3H, s, OCH3), 2.30 (3H, s, eC6H4CH3), 2.19e2.08 (6H,
br-s, COCH3); 13C NMR (100 MHz, CDCl3): 170.6, 170.0 (CO), 140.4,
137.4, 137.1, 135.6, 134.6, 134.5, 130.2, 128.4, 127.9 (Aromatic, C-2, C-
eOCH2CH3); 13C NMR (CDCl3):
d 149.8, 137.3, 136.6, 133.4, 130.3,

A. Mukherjee, N. Jayaraman / Tetrahedron 68 (2012) 8746e8752
8751
3), 93.8 (C-1), 70.0 (C-4), 69.1 (C-5), 68.0 (PhCH2), 66.2 (OCH3), 59.6
(C-6), 21.1 (eC6H4CH3), 20.7, 20.6 (COCH3); HRMS (ES-MS): MNaþ,
found 495.1458. C25H28O7SNa requires 495.1453.
2.79e2.69 (1H, m, SCH2aCH3), 2.63e2.54 (1H, m, SCH2bCH3), 2.11
(12H, br, COCH3), 1.32e1.30 (3H, m, SCH2CH3), 1.26e1.24 (3H, m,
SCH2CH3); 13C NMR (100 MHz, CDCl3):
d 170.5, 170.4, 169.2 (CO),
144.7, 144.4, 137.0, 128.9, 128.0, 127.9, 127.8 (Aromatic, C-2, C-3),
93.8 (C-1), 93.4 (C-1), 70.5 (PhCH2), 68.0 (C-5), 67.6 (C-5), 64.4 (C-4),
63.5 (C-4), 62.1 (C-6), 62.0 (C-6), 48.1 (SCH2CH3), 45.1 (SCH2CH3),
20.7, 20.6, 20.4 (COCH3), 5.9 (SCH2CH3), 5.2 (SCH2CH3); HRMS (ES-
MS): MNaþ, found 419.1140. C19H24O7SNa requires 419.1140.
4.12. (RS/SS)-Benzyl 4,6-di-O-acetyl-2,3-dideoxy-(3-ethylsulfinyl)-
a
-
D
-arabino-hexopyranoside (14)
A mixture of 1312 (140 mg, 0.366 mmol) and MCPBA (63.0 mg,
0.366 mmol) in CH2Cl2 (5 mL) was stirred at ꢀ78 ꢁC under N2 at-
mosphere for 40 min. The reaction mixture was diluted with CH2Cl2
(10 mL), washed with satd aq NaHCO3 solution (2ꢂ5 mL), dried
(Na2SO4), concentrated in vacuo and purified (SiO2) (40% EtOAc/
hexane) to afford 14 (120 mg, 83%), as an inseparable epimeric
mixture (1:1) and as a gum; Rf (75% EtOAc/pet. ether) 0.2; 1H NMR
4.15. (SS)-Benzyl 2-O-methyl-3-deoxy-(3-ethylsulfinyl)-
a-D-
manno-pyranoside (18)
A solution of 16 (45.0 mg, 0.113 mmol) in MeOH (8 mL) was
treated with NaOMe (45.3 mg, 0.84 mmol) in MeOH (5 mL),
refluxed for 12 h, solvents were removed in vacuo and purified
(SiO2) (3% MeOH/EtOAc) to afford 18 (22.4 g, 56%), as a gum; Rf (90%
(400 MHz, CDCl3): d 7.42e7.26 (10H, m, Aromatic), 5.25 (1H, app. t, J
10.0 Hz, H-4), 5.20e5.17 (2H, band, H-1, H-4), 5.11 (1H, app. d, J
2.4 Hz, H-1), 4.69 (2H, d, J 12 Hz, PhCH2), 4.53 (2H, d, J 12 Hz,
PhCH2), 4.31e4.23 (3H, band, H-5, H-6a, H-6b), 4.06e4.02 (3H,
band, H-5, H-6a, H-6b), 3.60e3.53 (1H, m, H-3), 3.08e3.01 (1H, m,
H-3), 2.79e2.75 (2H, m, CH3CH2S), 2.66e2.42 (2H, m, CH3CH2S),
2.32e2.22 (2H, m, H-2), 2.15e1.98 (13H, band, COCH3, H-2), 1.90
(1H, ddd, J1,2a, 1,2e, 2,3 3.62, 13.24, 16.41 Hz, H-2), 1.36e1.30 (6H, m,
EtOAc/pet. ether) 0.4; [
a
]
þ42.5 (c 1, CHCl3); 1H NMR (400 MHz,
D
CDCl3):
d
7.35e7.27 (5H, m, Aromatic), 4.99 (1H, app. s, H-1), 4.63
(1H, d, J 12 Hz, PhCH2a), 4.56 (1H, d, J 12 Hz, PhCH2b), 3.92e3.78
(6H, band, H-2, H-3, H-4, H-5, H-6a, H-6b), 3.40 (3H, s, eOCH3),
2.93e2.87 (2H, m, SCH2CH3), 1.30e1.26 (3H, m, SCH2CH3); 13C NMR
(100 MHz, CDCl3):
d 147.0, 137.2, 136.8, 128.4, 127.9, 127.8 (Aro-
CH3CH2S); 13C NMR (100 MHz, CDCl3):
d
170.6, 170.1, 170.0, 169.2
matic), 93.0 (C-1), 75.3 (C-2), 72.6 (C-5), 71.5 (PhCH2), 70.5
(eOCH3), 69.4 (C-4), 64.1 (C-6), 58.3 (C-3), 46.2 (SCH2CH3), 7.4
(SCH2CH3); HRMS (ES-MS): MNaþ, found 367.1193. C16H24O6SNa
requires 367.1191.
(CO), 137.0, 136.9, 128.5, 128.1, 127.9 (Aromatic), 95.5 (C-1), 95.2 (C-
1), 72.5 (C-4), 69.4 (C-4), 69.3 (C-5), 68.6 (C-5), 65.9 (PhCH2), 65.2
(PhCH2), 62.4 (C-6), 62.2 (C-6), 56.0 (C-3), 54.9 (C-3), 42.9
(CH3CH2S), 41.2 (CH3CH2S), 27.5 (C-2), 24.7 (C-2), 20.8, 20.7, 20.6
(COCH3), 7.7 (CH3CH2S), 7.4 (CH3CH2S); HRMS (ES-MS): MNaþ,
found 421.1296. C19H26O7SNa requires 421.1297.
4.16. (SS)-Benzyl 2-O-isopropyl-3-deoxy-(3-ethylsulfinyl)-
glucopyranoside (19) and (RS)-benzyl-2,3-dideoxy-(3-
a-D-
ethylsulfinyl)-
a-
D-erythro-hex-2-enopyranoside (17)
4.13. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-(3-ethylthio)-
erythro-hex-2-enopyranoside (15)
a-D-
i
A solution of 16 (50.0 mg, 0.126 mmol) in PrOH (10 mL) was
treated with NaOiPr (75.7 mg, 0.911 mmol) in iPrOH (6 mL),
refluxed for 18 h, solvents removed in vacuo and purified (1%
MeOH/CHCl3) to afford 19 (21.2 mg, 53%), as a gum; Rf (10% MeOH/
TFAA (0.17 mL, 1.25 mmol) was added drop-wise to a solution of
14 (100 mg, 0.251 mmol) and pyridine (0.2 mL, 2.51 mmol) in
CH2Cl2 (5 mL), under N2 atmosphere and at 0 ꢁC. The reaction
mixture was stirred for 4 h at rt, concentrated in vacuo and purified
(SiO2) (9% EtOAc/hexane) to afford 15 (78.0 mg, 82%), as a gum; Rf
CHCl3) 0.6; [
a]
þ53.9 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3):
D
d
7.50e7.34 (5H, m, Aromatic), 5.24 (1H, app. s, H-1), 4.82e4.75 (2H,
band, PhCH2a, H-4), 4.62 (1H, d, J 12 Hz, PhCH2b), 3.95e3.78 (5H,
band, H-2, H-3, H-5, H-6a, H-6b), 3.12e2.99 (2H, m, SCH2CH3),
2.93e2.87 (1H, m, eOCHMe2), 1.25 (6H, s, eOCHMe2), 0.88e0.83
(6% EtOAc/hexane) 0.4; [
a
]
þ76.2 (c 1, CHCl3); 1H NMR (CDCl3):
D
d
7.40e7.35 (5H, m, Aromatic), 5.58 (1H, d, J4,5 9.2 Hz, H-4), 5.49
(1H, app. s, H-2), 5.21 (1H, d, J1,2 2.4 Hz, H-1), 4.78 (1H, d, J 12 Hz,
PhCH2a), 4.60 (1H, d, J 12 Hz, PhCH2b), 4.28e4.20 (2H, band, H-5, H-
6a), 4.04 (1H, app. d, J 11.6 Hz, H-6b), 2.74e2.68 (2H, m, SCH2CH3),
2.12 (3H, s, COCH3), 2.09 (3H, s, COCH3), 1.28e1.25 (3H, band,
(3H, m, SCH2CH3); 13C NMR (100 MHz, CDCl3):
d 140.9, 137.2, 128.4,
127.9 (Aromatic), 93.4 (C-1), 71.5 (C-2), 71.4 (C-5), 70.5 (PhCH2),
64.8 (eOCHMe2), 64.2 (C-4), 61.8 (C-6), 61.6 (C-3), 44.9 (SCH2CH3),
14.0 (eOCHMe2), 6.4 (SCH2CH3); HRMS (ES-MS): MNaþ, found
395.1503. C18H28O6SNa requires 395.1504.
SCH2CH3); 13C NMR (100 MHz, CDCl3):
d 170.6, 170.1 (CO), 139.2,
137.5, 124.4, 128.0, 118.5 (Aromatic, C-2, C-3), 94.4 (C-1), 70.0 (C-4),
67.8 (C-5), 66.0 (PhCH2), 62.5 (C-6), 25.0 (SCH2CH3), 20.7, 20.6
(COCH3), 12.9 (SCH2CH3); HRMS (ES-MS): MNaþ, found 403.1190.
C19H24O6SNa requires 403.1191.
Compound 17: yield: 16.5 mg (41%), foamy solid; Rf 0.67 (10%
MeOH/CHCl3); [
a
]
þ63.1 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3):
D
d
7.37e7.32 (5H, m, Aromatic), 6.21 (1H, app. s, H-2), 5.25 (1H, app.
s, H-1), 4.78 (1H, d, J 12.0 Hz, PhCH2a), 4.74 (1H, d, J 12.0 Hz,
PhCH2b), 4.52e4.48 (1H, br, H-6a), 4.38 (1H, app. t, J 9.6 Hz, H-6b),
4.09e3.98 (2H, band, H-4, H-5), 3.20e3.13 (1H, m, SCH2aCH3),
3.10e3.02 (1H, m, SCH2bCH3), 1.42e1.38 (3H, m, SCH2CH3); 13C NMR
4.14. (RS/SS)-Benzyl 4,6-di-O-acetyl-2,3-dideoxy-(3-ethylsulfinyl)-
a
-
D
-erythro-hex-2-enopyranoside (16)
(CDCl3): d 147.0, 137.2, 136.8, 128.4, 127.9, 127.8 (Aromatic, C-2, C-3),
A mixture of vinyl sulfide 15 (80.0 mg, 0.211 mmol) and MCPBA
95.0 (C-1), 72.6 (PhCH2), 71.5 (C-4), 70.5 (C-5), 62.1 (C-6), 44.7
(SCH2CH3), 5.8 (SCH2CH3); HRMS (ES-MS): MNaþ, found 335.0938.
C15H20O5SNa requires 335.0929.
(31.5 mg, 0.183 mmol) in CH2Cl2 (6 mL) was stirred at ꢀ78 ꢁC for
10 min. The reaction mixture was then diluted with CH2Cl2 (15 mL),
washed with satd aq NaHCO3 solution (2ꢂ10 mL), dried (Na2SO4),
concentrated in vacuo and purified (SiO2) (7% MeOH/EtOAc) to af-
ford 16 (76.2 mg, 92%), as an epimeric mixture (1:1) and as a gum;
Rf (75% EtOAc/pet. ether) 0.3; 1H NMR (400 MHz, CDCl3):
Acknowledgements
We thank the Department of Science and Technology, New
Delhi, and the Department of Biotechnology, New Delhi, for fi-
nancial support. We thank Professor T.N. Guru Row and Mr. Amol G.
Dikundwar, Solid State and Structural Chemistry Unit, Indian In-
stitute of Science, Bangalore, for their kind help to determine the
crystal structure. A.M. thanks the Council of Scientific and In-
dustrial Research, New Delhi, for a research fellowship.
d
7.37e7.32 (10H, m, Aromatic), 6.65 (1H, d, J1,2 1.6 Hz, H-2), 6.59
(1H, d, J1,2 1.6 Hz, H-2), 5.91 (1H, d, J4,5 9.2 Hz, H-4), 5.48 (1H, d, J4,5
9.2 Hz, H-4), 5.33 (2H, app. s, 2ꢂH-1), 4.84 (1H, d, J 11.6 Hz, PhCH2a),
4.81 (1H, d, J 11.6 Hz, PhCH2b), 4.68 (1H, d, J 11.6 Hz, PhCH2a), 4.65
(1H, d, J 11.6 Hz, PhCH2b), 4.29e4.19 (4H, band, 2ꢂH-5, H-6a, H-6b),
4.17e4.08 (2H, band, H-6a, H-6b), 3.07e2.97 (2H, m, SCH2CH3),

8752
A. Mukherjee, N. Jayaraman / Tetrahedron 68 (2012) 8746e8752
11. Whittman, M. D.; Halcomb, R. L.; Danishefsky, S. J.; Golik, J.; Vyas, D. J. Org.
Supplementary data
Chem. 1990, 55, 1979e1981.
12. Mukherjee, A.; Jayaraman, N. Carbohydr. Res. 2011, 346, 1569e1575.
13. Pummerer, R. Ber. Dtsch. Chem. Ges. 1909, 42, 2275e2282.
14. (a) Feldman, K. S. Tetrahedron 2006, 62, 5003e5034; (b) Smith, L. H. S.; Coote, S.
C.; Sneddon, H. F.; Procter, D. J. Angew. Chem., Int. Ed. 2010, 49, 5832e5844.
The complete crystallographic data of 11 have been deposited
with the Cambridge Crystallographic Data Centre. Copies of this
information may be obtained free of charge from the Director,
Cambridge Crystallographic Data Centre,12 Union Road, Cambridge
CB2 1EZ, UK (fax: þ44 1223 336033, e-mail: depos-
it@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk) on quoting CCDC
888212. Spectral data for all new compounds. Supplementary data
associated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2012.08.011
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