Facial selectivities in the nucleophilic additions of 2,3-unsaturated 3-arylsulfinyl pyranosides

Article abstract of DOI:10.1016/j.carres.2013.07.002

2,3-Unsaturated 3-arylsulfinyl pyranosides undergo nucleophilic additions at C-2, with facial selectivities depending on the nucleophile and the substituent on sulfinyl sulfur. The reactions of such sugar vinyl sulfoxides lead to the addition of nucleophi

Full text of DOI:10.1016/j.carres.2013.07.002

Carbohydrate Research 380 (2013) 51–58
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Facial selectivities in the nucleophilic additions of 2,3-unsaturated
3-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 10 May 2013
Received in revised form 27 June 2013
Accepted 2 July 2013
Available online 16 July 2013
2,3-Unsaturated 3-arylsulfinyl pyranosides undergo nucleophilic additions at C-2, with facial selectivities
depending on the nucleophile and the substituent on sulfinyl sulfur. The reactions of such sugar vinyl
sulfoxides lead to the addition of nucleophile preferring an axial orientation at C-2, with concomitant
formation of an allylic bond at C-3 to C-4. This trend in the addition pattern is observed for primary
amine, carbon and sulfur nucleophiles, whereas secondary amines prefer an equatorial addition at C-2.
The effect of p-tolylthio- versus (p-isopropylphenyl)thio vinyl sulfoxide is that the equatorial nucleophilic
addition is preferred even more with the latter vinyl sulfoxide.
Keywords:
Conjugate additions
Nucleophiles
Ó 2013 Published by Elsevier Ltd.
Stereoselective addition
Unsaturated sugars
Vinyl sulfoxides
1. Introduction
and electronic influences generally affect the rate of conjugate
addition reactions, as well as, stereochemistry of the products.14–
1,2-Unsaturated sugars, namely, glycals are excellent examples
of a double bond present endocyclic to the sugar ring and its reac-
tivity in varied types of reactions.1–3 Sugars with exocyclic double
bond also find applications in synthesis.4–7 For example, the utility
of exo-glycals to incorporate hetero-atoms8 and synthesis of ano-
meric azido esters,9 a useful intermediate for the preparation of
anomeric amino acids, were demonstrated. Among unsaturated su-
gar derivatives, the particular class of 2,3-unsaturated sugars serve
as important derivatives for modification of monosaccharides.10,11
In our efforts to study the reactions of 2,3-unsaturated sugars, hav-
ing a sulfoxide functionality at C-3, we demonstrated the prepara-
tion of such vinyl sulfoxides from 2,3-unsaturated thioglycosides
(I), in the presence of trifluoromethanesulfonic acid (TfOH) or tri-
methylsilyl trifluoromethanesulfonate (TMSOTf) (Scheme 1).12
The reaction led to the regioselective intramolecular transposition
of C-1 alkyl/arylthio-moiety to C-3 to afford alkyl 2,3-dideoxy-3-al-
kyl/arylthio-arabino-hexopyranosides (II), through formation of 3-
alkyl/arylthio-glycal intermediate, followed by glycosylation with
an acceptor alcohol. The Pummerer rearrangement reaction on II
was identified, in order to form 2,3-unsaturated vinyl sulfide (IV)
from saturated sugar sulfide II. Thus, formation of sulfoxide III, fol-
lowed by the Pummerer rearrangement reaction afforded vinyl sul-
fide IV.13 The resulting vinyl sulfide was elaborated further to vinyl
sulfoxides (V), suitable for conjugate addition reactions. The steric
17 Conjugate addition of V with alkoxide nucleophiles was verified
and the addition afforded derivative VI, with axial orientation of
the substituent at C-2, as a single diastereomer at sulfinyl sulfur
moiety. Realizing the reactivity of new 2,3-unsaturated sulfoxides,
namely, vinyl sulfoxides, as acceptors for conjugate addition reac-
tions with alcohols, further studies were undertaken to verify their
reactivities with nitrogen, carbon, and sulfur derived nucleophiles.
A detailed study of stereoselectivities of conjugate addition reac-
tions of 2,3-unsaturated sulfoxides is presented herein. The nature
of nucleophile and the substituent at sulfinyl sulfur plays an
important role in these reactions. Whereas conjugate addition
reactions of vinyl sulfoxides of organic synthons are known,18,19
we report herein such reactions on newer vinyl sulfoxides.
2. Results and discussion
Conjugate addition reaction of amines with vinyl sulfoxide 113
was undertaken first with primary amines, namely, n-butylamine
and cyclohexylamine. The reaction of 1 with amines was con-
ducted in MeOH, under reflux for 8–10 h (Scheme 2). Upon re-
moval of solvents, 1H NMR spectrum of the product was
analyzed to establish addition pattern of the nucleophile.
The H-1 nucleus was observed at 5.24 ppm (d, J = 2.6 Hz) for the
product of reaction with n-butylamine and at 5.42 ppm (app.
singlet) for the reaction with cyclohexylamine. A new vinylic
proton at 6.50 and 6.39 ppm was also observed in both the
reactions. The product of the reaction of 1 with n-butylamine
⇑
Corresponding author. Tel.: +91 80 2293 2578; fax: +91 80 2360 0529.
E-mail address: jayaraman@orgchem.iisc.ernet.in (N. Jayaraman).
0008-6215/$ - see front matter Ó 2013 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.carres.2013.07.002

52
A. Mukherjee, N. Jayaraman / Carbohydrate Research 380 (2013) 51–58
AcO
AcO
AcO
AcO
O
O
M
CPBA, CH2Cl2
O
BnOH, TMSOTf,
CH2Cl2
AcO
R(O)S
AcO
RS
40 min., -78 - 0°C
SR
OBn
OBn
I
II
III
R = alkyl, aryl
0°C, 30 min.
TFAA, Py
0°C - rt, 16 h
AcO
AcO
AcO
HO
HO
OR'
O
MCPBA, CH2Cl2
10 min, -78°C
R'OH, R'ONa
reflux, 12 - 18 h
O
O
O
AcO
HO
HO
R(O)S
R(O)S
RS
R(O)S
OBn
V (1:1 epimer)
OBn
OBn
OBn
IV
VI
VII
R' = Me, Et, CHMe2
(single diastereomer)
Scheme 1.
NH(CH2)3CH3
HO
O
n-Butylamine
2
(94%)
AcO
O
MeOH, reflux
8 - 10 h
p-Tol-(O)S
AcO
OBn
p-Tol-(O)S
NH
OBn
HO
1
O
Cyclohexylamine
3 (95%)
p-Tol-(O)S
OBn
Scheme 2.
and cyclohexylamine was a single diastereomer and that a double
bond evolved during the addition reaction. The doublet with the
coupling constant JH-1–H-2 = 2.6 Hz and the apparent singlet nature
of the anomeric proton of the product of each reaction suggested
trans-diequatorial nature of H-1–H-2 protons. The products were
characterized further by 1D and 2D NMR techniques. The H-4 at
6.50 ppm (d, J = 1.2 Hz) was identified from cross peak of COSY
spectrum to H-5 (3.76–3.72 ppm) for the reaction with n-butyl-
amine. Similarly, H-4 at 6.39 ppm was identified from the cross
peak of COSY spectrum with H-5 (3.96–3.94 ppm) for the reaction
with cyclohexylamine. Cross peaks due to through-bond coupling
of remaining protons were also observed in the COSY spectrum.
Mass spectral analysis showed m/z 452.1872 for the product of
the reaction with n-butylamine and m/z 478.2026 for the reaction
with cyclohexylamine, which suggested loss of an acetate moiety,
in addition to loss of an acetyl moiety. Combining results of NMR
and mass spectral analyses, the constitution of the product was
established as 2, resulting from reaction of 1 with n-butylamine,
and 3, resulting from reaction with cyclohexylamine.
In comparison to conjugate addition with alkoxide nucleophiles
which also led to the axial nucleophilic addition, important obser-
vation of the reaction of 1 with primary amines is that the addi-
tions of nucleophiles lead to a concomitant elimination of acetate
at C-4, even when the addition occurred at axial orientation at C-
2.20 No other product formed during the course of the reaction,
thereby ruling-out formation of an intermediate, which would
then subject itself to an elimination, leading to the reaction being
considered as SN20 reaction. It is pertinent to note that the isolated
yields of reactions are excellent and the products were stereo-
chemically pure. The 1:1 epimeric mixture at sulfinyl sulfur of 1
led to only one diastereomerically pure 2 and 3.
nances at 5.10 ppm (d, J1,2 = 3.8 Hz, H-1) and at 3.00 ppm (d,
J1,2 = 3.8 Hz, H-2). On the other hand, product with axial orienta-
tion of substituent at C-2 showed resonances at 5.25 ppm (app. s,
H-1) and 3.97 ppm (app. s, H-2).
In the case of reaction with pyrrolidine and morpholine, a major
product was isolated in each case. 1H NMR analysis of the products
revealed that the conjugate addition to amines occurred at the
equatorial face of C-2 (ꢀ5.12 ppm, J = 4 Hz, H-1). With the inability
to isolate the minor product with pyrrolidine and morpholine, the
reaction mixture prior to purification was analyzed. The spectrum
of the reaction mixture exhibited the presence of a set of peaks in
the 1H NMR spectrum, indicating the presence of an epimeric
mixture. A comparison of the resonances corresponding to the
anomeric proton at 5.25 (app. s) and at 5.13 (d, J = 4 Hz) showed
a ratio of 1:3. The resonance at 5.25 ppm as an apparent singlet
corresponded to 1,2-trans-diequatorial relation of H-1–H-2 pro-
tons in 5, whereas the resonance at 5.13 ppm with J = 4 Hz related
to 1,2-equatorial-axial relation of H-1–H-2 protons in 6. The major
products having the equatorial-orientation at C-2, namely, erythro-
epimer of 4–6 was characterized further through 2D NMR
techniques of COSY, HSQC, and NOESY. The NOESY spectrum
showed absence of cross peak between H-2–H-5 protons, in line
with the equatorial substituent at C-2.
From the above experiments, we observe that whereas conju-
gate addition to sugar vinyl sulfoxide with primary amines afford
the products with axial orientation of the substituent at C-2 diaste-
reoselectively, the reaction with secondary amines lead to an epi-
meric mixture at C-2, the major product being the epimer with
substituent in the equatorial orientation.
Carbon and sulfur nucleophiles were examined next, in order to
assess the conjugate addition pattern with the vinyl sulfoxide. For
this purpose, dimethyl malonate and potassium thioacetate (KSC-
OCH3) were chosen as carbon and sulfur nucleophiles, respectively.
The reaction of 1 with dimethyl malonate and KSCOCH3 was con-
ducted under reflux overnight (Scheme 4). The malonate and thio-
acetate derivative 7 and 8 were isolated in good yields after
purification.
Reactivities of sugar vinyl sulfoxide were assessed with second-
ary amines, namely, piperidine, pyrrolidine, and morpholine. The
reactions were conducted with 1, in MeOH under reflux condition
for 10–12 h (Scheme 3). 1H NMR spectral analysis of products iso-
lated from reaction of 1 with piperidine indicated that the addition
occurred to afford products with both equatorial and axial orienta-
tions of the substituent at C-2, in a ratio of 3:1. The product with
equatorial orientation of the substituents at C-2 showed reso-
The H-1 and H-2 nuclei of 7 resonated at 5.01 and 2.74 ppm as a
doublet (J = 2 Hz) and doublet of doublet (J = 2, 7.2 Hz), respec-

A. Mukherjee, N. Jayaraman / Carbohydrate Research 380 (2013) 51–58
53
HO
O
piperidine
pyrrolidine
4 (91%)
equatorial: axial = 3:1
p-Tol-(O)S
OBn
N
AcO
AcO
p-Tol-(O)S
HO
O
MeOH, reflux
10 - 12 h
O
5 (69%, equatorial product)
equatorial: axial = 3:1
OBn
p-Tol-(O)S
OBn
OBn
N
1
HO
morpholine
6
O
(67%, equatorial product)
equatorial: axial = 3:1
p-Tol-(O)S
N
O
Scheme 3.
CH(COOMe)2
O
HO
CH2(COOMe)2
KOtBu
7
(94%)
AcO
p-Tol-(O)S
O
THF, reflux
10-12 h
OBn
AcO
p-Tol-(O)S
AcO
SCOCH3
O
KSCOCH3
OBn
1
8
(96%)
p-Tol-(O)S
OBn
Scheme 4.
tively. The threo-configuration of 7 was confirmed further by
NOESY experiments, wherein, cross-peaks between H-2–H-5 and
H-1–CH(COOMe)2 were observed. In the absence of an external
base in the reaction of 1 with thioacetate, the conjugate addition
product was found to retain the acetate protecting group at C-6.
As observed in the case of reactions with primary amines, the dia-
stereoselectivity of the reaction with carbon and sulfur nucleo-
philes was retained fully in favor of the axial orientation of the
substituent at C-2.
preferred an axial face for primary amines, carbon and sulfur de-
rived nucleophiles. In contrary, secondary amines afforded C-2
addition products with equatorial orientation of the substituent
as the major product. Approach of the nucleophile through either
axial (re) or equatorial (si) face of the electron-deficient double
bond might encounter a steric influence of the substituent at the
sulfinyl functionality. In the light of the observed addition pattern,
the following scenario was envisaged (Fig. 1).
Steric influence, arising from the nature of a-substituent to the
The above set of experiments illustrated that the conjugate
addition to nitrogen, carbon, and sulfur derived nucleophiles with
vinyl sulfoxide 1 underwent conjugate addition at C-2 with con-
comitant elimination of acetic acid to form 3,4-unsaturated sugar
sufinyl functionality, may play a dominant role in relation to the
addition pattern. It is noted that the above model envisaging the
role of steric influence of
a-substituent is considered un-affected
even when the lone pair of electrons on the sulfoxide moiety is
co-planer with the endocyclic double bond. With this presumption,
reactions involving a more bulky (p-isopropylphenyl)thio-moiety,
installed in place of p-tolyl-moiety as in 1, were undertaken.
Vinyl sulfoxide 13 was synthesized following a similar reaction
sequence as in 1. An 1,3-shift of 924 was initiated by TMSOTf, in the
presence of benzyl alcohol to afford glycoside 10 (Scheme 5).12
Treatment of 10 with MCPBA afforded sulfoxide 11, as a single dia-
stereomer at sulfinyl sulfur moiety. The Pummerer rearrangement
of 11, in the presence of TFAA and pyridine afforded vinyl sulfide
12, which upon a controlled oxidation produced vinyl sulfoxide
13, in ꢀ1:1 epimeric ratio at the sulfinyl sulfur moiety (Scheme 5).
Conjugate addition reactions of vinyl sulfoxide 13 were
performed with a primary and a secondary amine. The reactions
were performed similar to those in the case of reaction of amines
with 1 (Scheme 6). As the reactions were conducted to identify
2–8. We presume that
a-sulfinyl carbanion, formed during the
nucleophilic addition, is stabilized further through planar sulfinate
anion formation. Subsequent elimination of the acetate accounts
the product formation.
It was observed that the conjugate addition to 1 did not proceed
when sugar vinyl sulfoxide was having either free hydroxyl groups
or the hydroxyl groups protected as benzyl ethers. It is thus likely
that the electron withdrawing nature and good leaving group abil-
ity of the acetate group may play an important role in the reaction.
Such an addition-elimination reaction sequence is known earlier in
the conjugate addition to 3-nitro hex-2-enopyranoside with car-
bon nucleophiles.21,22 Addition, followed by elimination was sug-
gested occurring through a SN20 reaction mechanism, although
without a chiral induction originating from the vinyl nitrate func-
tionality. Further, we come across the recent report of Pathak and
co-workers on 4,6-benzylidene protected vinyl sulfoxide modified
hex-2-enopyranosides and their Michael addition reactions.23 An
Nu-
axial entry of the nucleophile at C-2 of
a
-anomer and ꢀ2:1 axial
R
R
and equatorial entry of nucleophile at C-2 of the b-anomer were re-
ported. Only the conjugate addition products were obtained in
these instances. The authors presumed a directing influence of
sulfoxide when ꢀ2:1 axial and equatorial entry of the nucleophile
at C-2 was observed.
O
O
AcO
AcO
AcO
AcO
OBn
R = H (or) alkyl
S
OBn
Nu-
S
O
O
Whereas addition and subsequent elimination occurred, leading
to the formation of products with an allylic bond, the addition itself
Figure 1. Facial approaches of the nucleophile in the conjugate addition on to vinyl
sulfoxide.

54
A. Mukherjee, N. Jayaraman / Carbohydrate Research 380 (2013) 51–58
AcO
S
O
AcO
AcO
AcO
AcO
O
MCPBA, CH2Cl2
40 min. -78 - 0°C
BnOH, TMSOTf
O
AcO
O
S
OBn
11 (90%)
CH2Cl2, 0°C - rt, 1 h
S
OBn
9
10 (80%)
TFAA, pyridine,
0
oC - rt, 16 h
AcO
AcO
AcO
AcO
MCPBA, CH2Cl2
10 min. -78°C
O
O
S
S
OBn
OBn
O
13
12
(93%)
(80%)
Scheme 5.
the addition pattern in the product with either axial or equatorial
orientation at C-2, 1H NMR analysis of the reaction product prior to
purification was conducted. A set of anomeric protons at 5.25 ppm
(app. s) and at 5.11 ppm (d, J = 4 Hz) was observed in the 1H NMR
spectrum of 14 for the reaction of 13 with n-butylamine. The cou-
pling constants with J1,2 of 4 Hz indicated the equatorial-axial rela-
tionship of H-1 and H-2, whereas, the apparent singlet at 5.25 ppm
suggested the trans-diequatorial relationship of H-1 and H-2. From
the integration of peaks at 5.11 and 5.25 ppm, an epimeric ratio of
1.5:1 was adjudged. Mass spectrometric analysis showed that the
product formed as a result of addition-elimination reaction se-
quence. In comparison to the conjugate addition to primary amines
with vinyl sulfoxide 1, which afforded 2 and 3 exclusively, reaction
of 13 with primary amine led to the formation of an epimeric mix-
ture of 14, in 1.5:1 ratio in favor of product with equatorial orien-
tation of the substituent at C-2.
ary amines and (iii) with (p-isopropylphenyl)vinyl sulfoxide 13,
formation of C-2 equatorial epimer was observed in higher ratio,
when compared to the p-tolyl vinyl sulfoxide 1, with both primary
and secondary amines.
Conjugate addition across vinyl sulfoxide occurs in a conformer
in which sulfoxide oxygen is co-planar with respect to the double
bond. In the absence of severe steric crowding, the nucleophiles
would preferably approach anti- to the lone pair of electrons on
sulfur, or to bulky substituent on aryl sulfinyl sulfur.18,25 Thus,
the preference of an axial attack was observed with alkoxide nucle-
ophiles, as well as, primary amine, carbon and sulfur nucleophiles
to vinyl sulfoxide 1. With secondary amines, the equatorial ap-
proach would originate to avoid the steric crowding between the
incoming nucleophiles and the aryl substituent on the sulfoxide,
in a preferred conformation of vinyl sulfoxide, as shown in Figure
1. The steric hindrance was even more pronounced, when the p-to-
lyl group was replaced by p-isopropylphenyl group.
Another important observation of the study was that whereas
conjugate additions were feasible with alkoxide nucleophiles even
when sugar hydroxyl groups remained in the anionic form, the
reaction did not proceed with amine, carbon and sulfur derived
nucleophiles when free-hydroxyl group containing sugar vinyl
sulfoxide (VII) was used. Rather, the acetate group underwent facile
elimination, so as to afford product with C-3 to C-4 unsaturation.
The vinyl sulfoxide starting materials were 1:1 diastereomeric ra-
tio at the sulfoxide functionality. In the earlier work with alkoxide
nucleophiles, it was found that one of the sulfoxide epimers was
more reactive than the other. The electrostatic repulsion between
sugar alkoxide anion and sulfur lone pair of electrons was probably
accountable for the slow inversion at sulfoxide moiety in the case
of alkoxide nucleophiles. Such a situation is absent in the conjugate
addition-elimination reaction involving nitrogen, carbon and sul-
fur nucleophiles, studied herein. On the other hand, an influence
An 1H NMR analysis of the product formed in the reaction with
pyrrolidine showed an H-1 resonance at 5.17 ppm (J = 3.8 Hz) and
5.28 ppm (app. s). From the observed coupling constants and com-
parison of the integration, the addition product was adjudged to af-
ford equatorial versus axial in 7:1 ratio. The major 15, with
equatorial orientation of the substituent at C-2, was separated
through column chromatography and characterized.
The following observations were made when comparing the
conjugate addition reaction with alkoxide nucleophiles13 and con-
jugate addition-elimination reactions observed with nitrogen, car-
bon and sulfur nucleophiles in the present work: (i) O-deacetylated
vinyl sulfoxide starting material VII (Scheme 1) was also recovered
in the conjugate addition with alkoxides, whereas vinyl sulfoxide
starting material was fully consumed in the addition-elimination
reactions; (ii) conjugate addition with alkoxide afforded products
with the axial orientation of the substituent at C-2, whereas
addition-elimination reaction sequence was found to afford
axial-orientation at C-2 with primary amines, carbon and sulfur
nucleophiles, whereas an epimeric mixtures formed with second-
by the nature of the
a-substituent of sulfoxide moiety was
observed in the stereochemical preference of the nucleophile
HO
O
14
(92%)
n-Butylamine
MeOH, reflux
equatorial:axial = 1.5:1
S
OBn
O
NH(CH2)3CH3
13
10 - 12 h
HO
Pyrrolidine
O
15
(78%, equatorial product)
equatorial:axial = 7:1
S
OBn
N
O
Scheme 6.

A. Mukherjee, N. Jayaraman / Carbohydrate Research 380 (2013) 51–58
55
addition. Whereas SN20 reactions are known in vinyl nitrates of
4.3. Benzyl 2,3,4-trideoxy-2-N-cyclohexylamino-3-(p-
tolylsulfinyl)- -threo-hex-3-enopyranoside (3)
sugars,21,22 the present study establishes stereochemical prefer-
ences for such SN20 reactions on chiral vinyl sulfoxides of sugars.
a-D
A solution of 1 (0.05 g, 0.1 mmol) in MeOH (8 mL) was treated
with cyclohexylamine (0.08 mL, 0.65 mmol), refluxed for 10 h, sol-
vents were removed in vacuo, and the residue was purified (SiO2)
(72% EtOAc/pet. ether) to afford 3 (0.046 g, 95%), as a gum.
3. Conclusion
The present study establishes the diastereoselective addition
pattern of nitrogen, carbon, and sulfur derived nucleophiles react-
ing with newer sugar vinyl sulfoxides, where the nature of the
Rf = 0.4 (80% EtOAc/pet. ether). [a]
+33 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.48–7.30 (band, 9H, Aromatic), 6.39 (app. s,
1H, H-4), 5.42 (app. s, 1H, H-1), 4.65–4.51 (band, 2H, PhCH2),
3.94 (dd, 1H, J = 3, 12 Hz, H-6a), 3.96–3.94 (m, 1H, H-5), 3.92–
3.88 (band, 2H, H-2, H-6b), 2.43 (s, 3H, –C6H4CH3), 1.72–1.44 (band,
11H, –NHC6H11); 13C NMR (100 MHz, CDCl3): d 149.2, 137.4, 137.0,
136.8, 130.2, 128.5, 128.4, 128.2, 128.0, 127.9 (Aromatic, C-3, C-4),
93.2 (C-1), 72.1 (PhCH2), 70.9 (C-5), 70.5 (C-6), 70.1 (C-2), 69.6
(–NHC6H11), 53.6, 51.3 (–NHC6H11), 34.7, 31.7 (–NHC6H11), 24.7
(–NHC6H11), 21.4 (–C6H4CH3). HRMS: m/z calcd for C26H33NO4S:
478.2028 [M+Na]+; found 478.2026.
nucleophile and the substituent
a- to the sulfinyl sulfur moiety
play a role in the facial preference of the addition reaction.
Whereas, primary amine, carbon and sulfur nucleophiles afford
product with axial orientation of the substituent at C-2, secondary
amines provide conjugate addition product with equatorial orien-
tation of the substituent at C-2, with concomitant formation of
an allylic bond at C-3 to C-4. Secondary amines undergo pro-
nounced steric interactions with the bulkier (p-isopropylphe-
nyl)vinyl sulfoxide when compared to p-tolylvinyl sulfoxide,
leading to the conjugate addition product with higher levels of fa-
cial differentiation. The present study demonstrates the reaction of
varied nucleophiles with sugar vinyl sulfoxides in conjunction with
that reported by us previously, involving alkoxide nucleophiles.
The method of vinyl sulfoxide conjugate addition opens-up further
possibilities of enriching functionalization of monosaccharides.
4.4. Benzyl 2,3,4-trideoxy-2-N-piperidino-3-(p-tolylsulfinyl)-
a-
D-erythro/threo-hex-3-enopyranoside (4)
A solution of 1 (0.04 g, 0.08 mmol) in MeOH (6 mL) was treated
with piperidine (0.06 mL, 0.52 mmol), refluxed for 10 h, solvents
were removed in vacuo, and the residue was purified (SiO2) (76%
EtOAc/pet. ether) to afford 4, as a gum.erythro-isomer: Yield:
4. Experimental
0.026 g, 68%. Rf = 0.2 (85% EtOAc/pet. ether). [a] +63 (c 1, CHCl3).
D
1H NMR (400 MHz, CDCl3): d 7.50–7.22 (band, 9H, Aromatic),
6.68 (app. s, 1H, H-4), 5.10 (d, 1H, J = 3.8 Hz, H-1), 4.78 (d, 1H,
J = 12 Hz, PhCH2a), 4.58 (d, 1H, J = 12 Hz, PhCH2b), 4.48 (br, 1H, H-
5), 3.74–3.71 (band, 2H, H-6a, H-6b), 3.00 (d, 1H, J = 3.8 Hz, H-2),
2.76–2.73 (band, 2H, –NCH2), 2.51–2.48 (band, 2H, –NCH2), 2.38
(s, 3H, –C6H4CH3), 1.64 (br, 2H, –NCH2CH2), 1.47 (br, 4H, –NCH2-
CH2CH2); 13C NMR (100 MHz, CDCl3): d 150.1, 143.4, 141.7, 137.4,
130.1, 128.4, 127.9, 127.8, 126.4, 126.3, (Aromatic, C-3, C-4), 94.1
(C-1), 71.7 (PhCH2), 70.5 (C-5), 69.2 (C-6), 64.5 (C-2), 60.7
(–NCH2), 50.6 (–NCH2CH2), 24.6 (–NCH2CH2CH2), 21.4 (–C6H4CH3).
4.1. General methods
Chemicals were purchased from commercial sources and were
used without further purification. Solvents were dried and distilled
according literature procedures. Analytical TLC was performed on
commercial plates coated with silica gel GF254 (0.25 mm). Silica
gel (230–400 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 nu-
cleus, with residual solvent signal acting as the internal standard.
COSY and HMQC analyses were performed on a 400 MHz NMR
spectrometer. 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.
HRMS: m/z calcd for
464.1873.threoepimer: Yield: 9 mg, 23%. Rf = 0.26 (85% EtOAc/pet.
ether). [
+48 (c 1, CHCl3). 1H NMR (400 MHz, CDCl3): d 7.38–
C
25H31NO4S: 464.1872 [M+Na]+; found
a]
D
7.22 (band, 9H, Aromatic), 6.52 (app. s, 1H, H-4), 5.25 (app. s, 1H,
H-1), 4.78 (band, 2H, PhCH2), 4.65–4.60 (band, 1H, H-5), 3.97
(app. s, 1H, H-2), 3.95–3.83 (band, 2H, H-6a, H-6b), 2.76–2.73 (m,
4H, –NHCH2CH2), 2.51–2.38 (m, 4H, –NHCH2CH2), 2.39 (s, 3H, –
C6H4CH3), 2.04–2.00 (m, 2H, –NHCH2CH2CH2); 13C NMR
(100 MHz, CDCl3): d 150.2, 142.1, 141.6, 137.4, 130.2, 130.1,
128.4, 128.0,126.2, 125.6, (Aromatic, C-4, C-3), 95.7 (C-1), 71.7
(PhCH2), 70.5 (C-5), 69.3 (C-6), 64.6 (C-2), 60.8 (–NHCH2), 50.6
(–NHCH2CH2), 26.4 (–NHCH2CH2CH2), 21.6 (–C6H4CH3). HRMS:
m/z calcd for C25H31NO4S: 464.1872 [M+Na]+; found 464.1873.
4.2. Benzyl 2,3,4-trideoxy-2-N-butylamino-3-(p-tolylsulfinyl)-
-threo-hex-3-eno-pyranoside (2)
a-
D
A solution of 1 (0.05 g, 0.1 mmol) in MeOH (8 mL) was treated
with n-butylamine (0.06 mL, 0.65 mmol), refluxed for 8 h, solvents
were removed in vacuo, and the residue was purified (SiO2) (76%
EtOAc/pet. ether) to afford 2 (0.043 g, 94%), as a gum.
4.5. Benzyl 2,3,4-trideoxy-2-N-pyrrolidino-3-(p-tolylsulfinyl)-
a-
D-erythro-hex-3-enopyranoside (5)
Rf = 0.5 (85% EtOAc/pet. ether). [a]
+46 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.38–7.26 (band, 9H, Aromatic), 6.50 (d, 1H,
J = 1.2 Hz, H-4), 5.24 (d, 1H, J = 2.6 Hz, H-1), 4.76 (d, 1H, J = 12 Hz,
PhCH2a), 4.62 (d, 1H, J = 12 Hz, PhCH2b), 3.88–3.86 (band, 1H, H-
6b), 3.82 (dd, 1H, J = 3.6, 12 Hz, H-6a), 3.76–3.72 (band, 2H, H-5,
H-2), 2.38 (s, 3H, –C6H4CH3), 2.32–2.30 (band, 2H, –NH(CH2)3CH3),
1.23 (br, 4H, –NH(CH2)3CH3), 0.84–0.80 (band, 3H, –NH(CH2)3CH3);
13C NMR (100 MHz, CDCl3): d 150.6, 141.9. 138.8, 137.5, 137.1,
129.9, 128.3, 127.9, 126.5, 125.7, 124.1 (Aromatic, C-3, C-4), 94.1
(C-1), 71.8, (PhCH2), 70.8, (C-5), 69.5 (C-6), 63.4 (C-2), 61.6 (–
NH(CH2)3CH3), 54.3 (–NH(CH2)3CH3), 46.4 (–NH(CH2)3CH3), 21.3
(–C6H4CH3), 20.1 (–NH(CH2)3CH3). HRMS: m/z calcd for C24H31NO4-
S: 452.1872 [M+Na]+; found 452.1872.
A solution of 1 (0.04 g, 0.08 mmol) in MeOH (8 mL) was treated
with pyrrolidine (0.04 mL, 0.52 mmol), refluxed for 12 h, solvents
were removed in vacuo, and the residue was purified (SiO2) (78%
EtOAc/pet. ether) to afford 5 (0.021 g, 69%), as a gum.
Rf = 0.3 (82% EtOAc/pet. ether). [a]
+53 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.48 (d, 2H, J = 8 Hz, Aromatic), 7.44–7.25
(band, 7H, Aromatic), 6.60 (app. s, 1H, H-4), 5.13 (d, 1H, J = 4 Hz,
H-1), 4.76 (d, 1H, J = 12 Hz, PhCH2a), 4.52 (d, 1H, J = 12 Hz, PhCH2b),
4.50 (br, 1H, H-5), 3.72 (dd, 1H, J = 3.2, 11.6 Hz H-6a), 3.66 (dd, 1H,
J = 6, 11.6 Hz, H-6b), 3.22 (d, 1H, J = 4 Hz, H-2), 2.71 (br, 4H, –NCH2),
2.34 (s, 3H, –C6H4CH3), 1.63 (br, 4H, –NCH2CH2); 13C NMR
(100 MHz, CDCl3): d 141.5, 137.2, 129.8, 129.6, 128.5, 128.4,

56
A. Mukherjee, N. Jayaraman / Carbohydrate Research 380 (2013) 51–58
127.8, 125.6, 125.3 (Aromatic, C-3, C-4), 95.6 (C-1), 70.5 (C-5), 69.4
(PhCH2), 64.6 (C-6), 54.7 (C-2), 48.1 (–NCH2), 24.1 (–NCH2CH2),
21.4 (–C6H4CH3). HRMS: m/z calcd for C24H29NO4S: 450.1715
[M+Na]+; found 450.1718.
(PhCH2), 70.1 (C-5), 69.8 (C-6), 67.7 (C-2), 30.0 (SCOCH3), 21.5 (–
C6H4CH3), 20.7 (OCOCH3). HRMS: m/z calcd for C24H26O6S2:
497.1060 [M+Na]+; found 497.1067.
4.9. p-Isopropylphenyl 4,6-di-O-acetyl-2,3-dideoxy-1-thio-
erythro-hex-2-enopyrano-side (9)
a-D-
4.6. Benzyl 2,3,4-trideoxy-2-N-morpholino-3-(p-tolylsulfinyl)-
a
-
D
-erythro-hex-3-enopyranoside (6)
A mixture of tri-O-acetyl glucal26 (2 g, 73 mmol) and CAN (0.4 g,
73 mmol) in MeCN (10 mL) was stirred at 0 °C for 15 min. A solu-
tion of p-isopropylthiophenol (9 mL, 59 mmol) was added drop-
wise to the reaction mixture, stirring was continued for 16 h at
room temperature, and the reaction mixture concentrated in va-
cuo. The resulting crude product was purified (SiO2) (12% EtOAc/
pet. ether) to afford 9 (2.1 g, 79%), as a foamy solid.
A solution of 1 (0.035 g, 0.08 mmol) in MeOH (6 mL) was trea-
ted with morpholine (0.05 mL, 0.53 mmol), refluxed for 10 h, sol-
vents were removed in vacuo, and the residue was purified
(SiO2) (70% EtOAc/pet. ether) to afford 6 (0.023 g, 67%), as a gum.
Rf = 0.4 (78% EtOAc/pet. ether). [a]
+87 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.40–7.22 (band, 9H, Aromatic), 6.46 (app. s,
1H, H-4), 5.12 (d, 1H, J = 4 Hz, H-1), 4.84 (d, 1H, J = 12 Hz, PhCH2a),
4.58 (d, 1H, J = 12 Hz, PhCH2b), 4.54–4.47 (br-m, 1H, H-5), 3.70–
3.68 (band, 2H, H-6a, H-6b), 3.60 (d, 1H, J = 4 Hz, H-2), 3.40–3.35
(band, 2H, –NCH2), 3.24–3.21 (band, 2H, –NCH2), 2.82–2.71 (m,
4H, –NCH2CH2), 2.41 (s, 3H, –C6H4CH3); 13C NMR (100 MHz,
CDCl3): d 143.3, 141.9, 139.3, 137.0, 132.0, 12.8, 129.6, 128.4,
128.3, 128.1, 127.9, 126.7 (Aromatic, C-3, C-4), 94.2 (C-1), 72.6
(C-5), 70.1 (PhCH2), 67.1(C-6), 64.5 (C-2), 60.3 (–NCH2CH2), 50.4
(–NCH2CH2), 21.4 (–C6H4CH3). HRMS: m/z calcd for C24H29NO5S:
466.1664 [M+Na]+; found 466.1664.
Rf = 0.4 (15% EtOAc/pet. ether). [
a]
ꢁ78 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.47 (d, 2H, J 8 Hz, Aromatic), 7.17 (d, 2H,
J = 8 Hz, Aromatic), 6.06 (dd, 1H, J = 1.6, 10 Hz, H-3), 5.84 (app. d,
1H, J = 10 Hz, H-2), 5.70 (app. s, 1H, H-1), 5.38 (dd, 1H, J = 1.6,
9.6 Hz, H-4), 4.51–4.47 (band, 1H, H-5), 4.31–4.21 (band, 2H, H-
6a, H-6b), 2.92–2.81 (m, 1H, CHMe2), 2.11 (s, 3H, COCH3), 2.09 (s,
3H, COCH3), 1.25 (d, 3H, J = 6.8 Hz CHMe2), 1.23 (d, 3H, J = 6.8 Hz,
CHMe2); 13C NMR (100 MHz, CDCl3): d 170.7, 170.2 (CO), 148.7,
133.1, 132.3, 131.2, 128.6, 127.3, 127.0, 126.8 (C-2, C-3, Aromatic),
83.9 (C-1), 67.1 (C-4), 65.1 (C-5), 63.0 (C-6), 33.7, (CHMe2), 23.8
(CHMe2), 20.9, 20.7 (COCH3). HRMS: m/z calcd for C19H24O5S:
387.1242 [M+Na]+; found 387.1240.
4.7. Benzyl 2,3,4-trideoxy-2-C-bis(methoxycarbonyl)methyl-3-
(p-tolylsulfinyl)-a-D-threo-hex-3-enopyranoside (7)
4.10. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-isopropylphenyl)
A solution of 1 (0.04 g, 0.098 mmol) in THF (4 mL) was added
drop-wise to the stirred solution of dimethyl malonate (0.02 mL,
0.19 mmol) and tBuOK (0.011 g, 0.098 mmol) in THF (4 mL), re-
fluxed under N2 atmosphere for 11 h, solvents were removed in va-
cuo, and the residue was purified (SiO2) (60% EtOAc/pet. ether) to
afford 7 (0.039 g, 94%) as a gum.
thio-a-D-arabino-hexopyranoside (10)
TMSOTf (70 mol % in CH2Cl2) was added to a stirred solution of
9 (0.2 g, 0.54 mmol) and BnOH (0.4 mL, 0.44 mmol) in CH2Cl2
(6 mL) and stirred at 0 °C for 1 h. The reaction mixture was concen-
trated in vacuo and purified (SiO2) (10% EtOAc/pet. ether) to afford
10 (0.2 g, 80%), as a gum.
Rf = 0.4 (65% EtOAc/pet. ether). [a]
+56 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.42–7.29 (band, 5H, Aromatic), 7.18 (d, 2H,
J = 8 Hz, Aromatic), 7.12–7.07 (band, 2H, Aromatic), 6.81 (d, 1H,
J = 2 Hz, H-4), 5.01 (d, 1H, J = 2 Hz, H-1), 4.65 (d, 1H, J = 12 Hz,
PhCH2a), 4.47–4.42 (br-m, 1H, H-5), 4.40 (d, 1H, J = 12 Hz, PhCH2b),
3.88 (dd, 1H, J = 3.6, 11.6 Hz, H-6a), 3.79 (s, 3H, CH(COOMe)2), 3.78–
3.73 (band, 2H, H-6b, CH(COOMe)2), 3.68 (s, 3H, CH(COOMe)2), 2.74
(dd, 1H, J = 2, 7.2 Hz, H-2), 2.37 (s, 3H, –C6H4CH3); 13C NMR
(100 MHz, CDCl3): d 168.1, 167.6 (CO), 142.6, 140.8, 137.9, 137.2,
130.2, 129.9, 128.2, 127.9, 127.5, 127.2, 127.0, 126.6 (Aromatic,
C-3, C-4), 97.0 (C-1), 71.6 (PhCH2), 70.2 (C-5), 69.6 (C-6), 64.1 (C-
2), 53.9 (CH(COOMe)2), 53.1 (CH(COOMe)2), 38.0 (CH(COOMe)2),
21.5 (–C6H4CH3). HRMS: m/z calcd for C25H28O8S: 511.1403
[M+Na]+; found 511.1401.
Rf = 0.5 (15% EtOAc/pet. ether). [
a]
ꢁ57 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.39–7.30 (band, 9H, Aromatic), 4.98 (app. d,
1H, J = 1.6 Hz, H-1), 4.82 (dd, 1H, J = 3, 11.6 Hz, H-4), 4.60 (d, 1H,
J = 12 Hz, PhCH2a), 4.55 (d, 1H, J = 12 Hz, PhCH2b), 4.35–4.11 (band,
3H, H-5, H-6a, H-6b), 4.05–3.97 (m, 1H, H-3), 2.91–2.83 (m, 1H,
CHMe2), 2.45–2.31 (band, 1H, H-2), 2.11 (s, 2H, COCH3), 2.09 (s,
2H, COCH3), 2.07 (s, 2H, COCH3), 2.03–1.97 (band, 1H, H-2), 1.23
(d, 3H, J = 6.8 Hz, CHMe2), 1.21 (d, 3H, J = 6.8 Hz, CHMe2); 13C
NMR (100 MHz, CDCl3): d 170.7, 170.2 (CO), 147.8, 137.5, 131.8,
128.4, 128.3, 127.9, 127.5, 126.9 (Aromatic), 93.6 (C-1), 69.4 (C-
4), 69.1 (C-5), 67.0 (PhCH2), 65.2 (C-6), 44.7 (C-3), 35.2 (C-2),
33.6 (CHMe2), 23.8 (CHMe2), 20.9, 20.7 (COCH3). HRMS: m/z calcd
for C26H32O6S: 495.1817 [M+Na]+; found 495.1814.
4.8. Benzyl 6-O-acetyl-2,3,4-trideoxy-2-thioacetyl-3-(p-
4.11. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-
tolylsulfinyl)-
a-
D-threo-hex-3-eno-pyranoside (8)
isopropylphenyl)sulfinyl-a-D-arabino-hexopyranoside (11)
A solution of 1 (11 mg, 0.1 mmol) in THF (5 mL) was added
drop-wise to a solution of CH3COSK (0.04 g, 0.1 mmol) in THF
(5 mL) at rt, refluxed under N2 atmosphere for 12 h, solvents were
removed in vacuo, and the residue was purified (SiO2) (20% EtOAc/
pet. ether) to afford 8 (0.039 g, 96%), as a gum.
A mixture of 10 (0.15 g, 0.31 mmol) and MCPBA (0.054 g,
0.31 mmol) in CH2Cl2 (8 mL) was stirred at ꢁ78 °C under N2 atmo-
sphere for 40 min. The reaction mixture was diluted with CH2Cl2
(10 mL), washed with satd aq NaHCO3 solution (2 ꢂ 5 mL), dried
(Na2SO4), concentrated in vacuo, and purified (SiO2) (35% EtOAc/
pet. ether) to afford 11 (0.14 g, 90%), as a foamy solid.
Rf = 0.3 (30% EtOAc/pet. ether). [a]
+32 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.35–7.31 (m, 9H, Aromatic), 6.77 (d, 1H,
J = 2.4 Hz, H-4), 5.32 (d, 1H, J = 2.4 Hz, H-1), 4.80 (d, 1H, J = 12 Hz,
PhCH2a), 4.61 (d, 1H, J = 12 Hz, PhCH2b), 4.16–4.11 (band, 1H, H-
5), 4.26–4.23 (band, 1H, H-6a), 4.02 (dd, 1H, J = 4.8, 11.2 Hz, H-6b)
3.89 (d, 1H, J = 2.4 Hz, H-2), 2.62 (s, 3H, SCOCH3), 2.42 (s, 3H, –
C6H4CH3), 1.99 (s, 3H, –OCOCH3); 13C NMR (100 MHz, CDCl3): d
193.5 (SCO), 169.3 (OCO), 143.5, 142.2, 139.7, 137.0, 136.9, 129.7,
128.1, 128.0, 127.9, 126.9 (Aromatic, C-3, C-4), 95.6 (C-1), 70.2
Rf = 0.4 (40% EtOAc/pet. ether). [
a]
ꢁ26 (c 1 CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.61 (d, 2H, J = 8 Hz), 7.42 (d, 2H, J = 8 Hz),
7.39–7.31 (band, 4H, Aromatic), 7.29–7.27 (band, 1H, Aromatic),
5.94–5.01 (band, 2H, H-1, H-4), 4.80 (d, 1H, J = 12 Hz, PhCH2a),
4.63 (d, 1H, J = 12 Hz, PhCH2b), 4.30–4.26 (band, 1H, H-5), 4.22
(dd, 1H, J = 6, 12 Hz, H-6b), 4.01 (dd, 1H, J = 3, 12 Hz, H-6a), 3.50–
3.46 (m, 1H, H-3), 2.99–2.92 (m, 1H, CHMe2), 2.71–2.65 (band,
1H, H-2), 2.30–2.23 (band, 1H, H-2), 2.01 (s, 3H, COCH3), 1.60 (s,

A. Mukherjee, N. Jayaraman / Carbohydrate Research 380 (2013) 51–58
57
3H, COCH3), 1.26 (d, 3H, J = 6.8 Hz, CHMe2), 1.24 (d, 3H, J = 6.8 Hz,
CHMe2); 13C NMR (100 MHz, CDCl3): d 170.5, 169.5, 153.2, 141.5,
137.3, 128.3, 127.6, 127.5, 126.0 (Aromatic), 95.8 (C-1), 69.4
(PhCH2) 67.8 (C-5), 67.4 (C-4), 62.6 (C-6), 59.8 (C-3), 34.1 (CHMe2),
26.9 (C-2), 23.7, 23.6 (CHMe2), 20.6, 20.1 (COCH3). HRMS: m/z calcd
for C26H32O7S: 511.1756. Found 511.1766.
PhCH2b, H-5), 3.87–3.83 (dd, 2H, J 3.6, 11.6 Hz H-6a, H-6b), 3.26–
3.21 (band, 2H, H-2, CHMe2), 2.31–2.26 (band, 2H, –NCH2), 1.25
(d, 3H, J = 6.8 Hz, CHMe2), 1.23 (d, 3H, J = 6.8 Hz, CHMe2), 0.94–
0.86 (band, 7H, –N(CH2)3CH3); 13C NMR (100 MHz, CDCl3): d
152.2, 137.5, 137.0, 128.4, 128.3, 128.0, 127.7, 127.4 (Aromatic,
C-3, C-4), 93.0 (C-1), 71.1 (PhCH2), 70.8 (C-5), 69.7 (C-6), 69.5 (C-
2), 64.5 (–NCH2), 54.3 (–N(CH2)3CH3), 46.4 (–N(CH2)3CH3), 34.0
(CHMe2), 23.7, 23.2 (CHMe2), 19.8 (–N(CH2)3CH3). HRMS: m/z calcd
for C26H35NO4S: 458.2365 [M+Na]+; found 458.2368.
4.12. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-
isopropylphenyl)thio-a-D-erythro-hex-2-enopyranoside (12)
threo-isomer: Yield: (0.015 g, 37%). Rf = 0.67 (85% EtOAc/pet.
TFAA (0.2 mL, 1.43 mmol) was added drop-wise to a solution of
11 (0.14 g, 0.28 mmol) and pyridine (0.23 mL, 2.86 mmol) in CH2-
Cl2 (5 mL), under N2 atmosphere and at 0 °C. The reaction mixture
was stirred for 16 h at rt, concentrated in vacuo and purified (SiO2)
(10% EtOAc/pet. ether) to afford 12 (0.107 g, 80%), as a gum.
ether). [a]
+76 (c 1, CHCl3). 1H NMR (400 MHz, CDCl3): d 7.36–
D
7.27 (band, 9H, Aromatic), 6.52 (app. s, 1H, H-4), 5.25 (app. s, 1H,
H-1), 4.79 (d, 1H, J = 12 Hz, PhCH2a), 4.55 (d, 1H, J = 12 Hz, PhCH2b),
4.52 (br, 1H, H-5), 3.75–3.71 (m, 2H, H-6a, H-6b), 3.95–3.90 (band,
2H, H-2, CHMe2), 2.30–2.26 (band, 2H, –NCH2), 1.96–1.89 (band,
2H, –N(CH2)3CH3), 1.26 (d, 3H, J 6.8 Hz, CHMe2), 1.24 (d, 3H,
J = 6.8 Hz, CHMe2), 0.94–0.82 (band, 5H, –N(CH2)3CH3); 13C NMR
(100 MHz, CDCl3): d 152.5, 137.1, 128.4, 128.1, 127.8, 126.8 (Aro-
matic, C-3, C-4), 94.1 (C-1), 71.6 (PhCH2), 70.8 (C-5), 70.4 (C-6),
69.7 (C-2), 64.4 (–N(CH2)3CH3), 54.3 (–N(CH2)3CH3), 46.4 (–
N(CH2)3CH3), 34.3 (CHMe2), 23.7, 23.6 (CHMe2), 20.2 (–N(CH2)3-
CH3). HRMS: m/z calcd for C26H35NO4S: 458.2365 [M+Na]+; found
458.2368.
Rf = 0.4 (12% EtOAc/pet. ether). [a]
+34 (c 1, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.42–7.31 (band, 6H, Aromatic), 7.23–7.21
(band, 3H, Aromatic), 5.69 (d, 1H, J = 9 Hz, H-4), 5.33 (d, 1H,
J = 2 Hz, H-2), 5.10 (d, 1H, J = 2 Hz, H-1), 4.74 (d, 1H, J = 12 Hz,
PhCH2a), 4.54 (d, 1H, J = 12 Hz, PhCH2b), 4.27–4.23 (band, 2H, H-
5, H-6a), 4.05 (app. d, 1H, J = 10.8 Hz, H-6b), 2.94–2.87 (m, 1H,
CHMe2), 2.10 (s, 3H, COCH3), 2.07 (s, 3H, COCH3), 1.26 (d, 3H,
J = 6.8 Hz, CHMe2), 1.24 (d, 3H, J = 6.8 Hz, CHMe2); 13C NMR
(100 MHz, CDCl3): d 170.6, 170.0, (CO), 149.9, 140.2, 137.4, 134.6,
128.4, 128.0, 127.6, 121.8 (C-2, C-3, Aromatic), 94.5 (C-1), 70.0
(C-4), 68.0 (C-5), 66.2 (PhCH2), 62.6 (C-6), 33.8 (CHMe2), 23.7
(CHMe2), 20.7, 20.5 (COCH3). HRMS: m/z calcd for C26H30O6S:
493.1661 [M+Na]+; found 493.1657.
4.15. Benzyl 2,3,4-trideoxy-2-N-pyrrolidino-3-(p-
isopropylphenyl)sulfinyl-a-D-erythro-hex-3-enopyranoside (15)
A solution of 13 (0.04 g, 0.08 mmol) in MeOH (6 mL) was trea-
ted with pyrrolidine (0.04 mL, 0.49 mmol), refluxed for 12 h, sol-
vents were removed in vacuo, and the residue was purified
(SiO2) (68% EtOAc/pet. ether) to afford 15 (0.029 g, 78%), as a gum.
4.13. Benzyl 4,6-di-O-acetyl-2,3-dideoxy-3-(p-
isopropylphenyl)sulfinyl-a-D-erythro-hex-2-enopyranoside (13)
Rf = 0.5 (72% EtOAc/pet. ether). [a]
+22 (c 1, CHCl3). 1H NMR
D
A mixture of vinyl sulfide 12 (0.107 g, 0.22 mmol) and MCPBA
(0.04 g, 0.22 mmol) in CH2Cl2 (8 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 (2 ꢂ 10 mL), dried
(Na2SO4), concentrated in vacuo, and purified (SiO2) (40% EtOAc/
pet. ether) to afford 13 (0.103 g, 93%), as an epimer (1:1) and as
a foamy solid.
(CDCl3): d 7.35–7.27 (9H, band, Aromatic), 6.64 (app. s, 1H, H-4),
5.17 (d, 1H, J = 3.6 Hz, H-1), 4.80 (d, 1H, J = 12 Hz, PhCH2a), 4.56
(d, 1H, J = 12 Hz, PhCH2b), 4.51 (br, 1H, H-5), 3.82 (dd, 1H, J = 3.2,
12 Hz, H-6a), 3.76–3.72 (band, 1H, H-6b), 3.27 (d, 1H, J = 3.6 Hz,
H-2), 2.95–2.89 (m, 1H, CHMe2), 2.75 (br, 4H, –NCH2), 1.67 (br,
4H, –NCH2CH2), 1.26 (d, 3H, J = 6.8 Hz, CHMe2), 1.24 (d, 3H,
J = 6.8 Hz, CHMe2); 13C NMR (100 MHz, CDCl3): d 140.5, 137.1,
128.4, 128.3, 127.9, 127.8, 127.6, 127.5 (Aromatic, C-3, C-4), 94.1
(C-1), 70.5 (PhCH2), 69.4 (C-5), 64.6 (C-6), 54.6 (C-2), 48.0 (–
NCH2), 34.0 (CHMe2), 24.1 (–NCH2CH2), 23.7 (CHMe2). HRMS: m/z
calcd for C26H33NO4S: 456.2209 [M+Na]+; found 456.2209.
Rf = 0.3 (45% EtOAc/pet. ether). 1H NMR (400 MHz, CDCl3): d
7.39–7.32 (band, 18H, Aromatic), 6.83 (br, 2H, H-2), 5.75 (d, 1H,
J = 9.8 Hz, H-4), 5.38 (br, 2H, H-1), 5.15 (d, 1H, J 9.8 Hz, H-4), 4.82
(d, 2H, J = 12 Hz, PhCH2), 4.69–4.64 (band, 2H, PhCH2), 4.20–4.16
(band, 3H, H-5, H-6a, H-6b), 4.12–4.04 (band, 3H, H-5, H-6a, H-
6b), 2.98–2.93 (band, 2H, CHMe2), 2.08 (s, 6H, COCH3), 2.07 (s,
6H, COCH3), 1.28 (br, 12H, CHMe2); 13C NMR (100 MHz, CDCl3): d
170.5, 170.4, 169.9, 169.7 (CO), 153.7, 146.9, 145.6, 139.3, 138.4,
137.0, 136.9, 130.6, 128.5, 128.0, 127.9, 127.7, 127.5, 127.1,
125.9, 125.5 (Aromatic, C-2, C-3), 93.7 (C-1), 93.5 (C-1), 72.9
(PhCH2), 72.7 (PhCH2), 70.5 (C-5), 70.0 (C-5), 68.1 (C-4), 63.6 (C-
4), 63.5 (C-6), 60.5 (C-6), 34.1 (CHMe2), 23.6 (CHMe2), 20.6, 20.5,
20.0 (COCH3). HRMS: m/z calcd for C26H30O7S: 509.1610
[M+Na]+; found 509.1607.
Acknowledgments
We thank the Department of Science and Technology, New Del-
hi, and the Department of Biotechnology, New Delhi, for a financial
support. A.M. thanks the Council of Scientific and Industrial Re-
search, New Delhi, for a research fellowship.
Supplementary data
Supplementary data (spectral data for all new compounds,
COSY, HMQC spectra of 2, 5 and 11 and NOESY spectra of 5 and
7) associated with this article can be found, in the online version,
at http://dx.doi.org/10.1016/j.carres.2013.07.002.
4.14. Benzyl 2,3,4-trideoxy-2-N-butylamino-3-(p-
isopropylphenyl)sulfinyl-a-D-erythro/threo-hex-3-
enopyranoside (14)
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(76% EtOAc/pet. ether) to afford 14, as a gum.
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