Catalytic ceric ammonium nitrate mediated synthesis of 2-deoxy-1- thioglycosides

Article abstract of DOI:10.1016/j.carres.2004.07.010

Synthesis of 2-deoxy-1-thioglycosides from glycals, mediated by catalytic amounts of ceric ammonium nitrate is reported. Glycosylation reactions of the thioglycosides with both aglycosyl and glycosyl acceptors afford α-anomeric glycosides exclusively. Synthesis of 2-deoxy-1-thioglycosides from glycals, mediated by catalytic amounts of ceric ammonium nitrate is reported. Apart from the 2-deoxy-1-thioglycosides, formation of the 2,3-unsaturated enose, corresponding to the Ferrier product, is also observed, especially for the glucal substrates. A radical oxocarbenium ion and a thiolate intermediates are most likely to mediate the reaction. Upon synthesis of 2-deoxy-1-thioglycosides, few representative glycosylation reactions with both aglycosyl and glycosyl acceptors were performed and α-anomeric 2-deoxy glycosides were obtained exclusively.

Full text of DOI:10.1016/j.carres.2004.07.010

Carbohydrate
RESEARCH
Carbohydrate Research 339(2004) 21 97 –2204
Catalytic ceric ammonium nitrate mediated synthesis of
-deoxy-1-thioglycosides
2
Somak Paul and Narayanaswamy Jayaraman*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 29April 2004; received in revised form 17 July 2004; accepted 18 July 2004
Available online 14 August 2004
Abstract—Synthesis of 2-deoxy-1-thioglycosides from glycals, mediated by catalytic amounts of ceric ammonium nitrate is reported.
Apart from the 2-deoxy-1-thioglycosides, formation of the 2,3-unsaturated enose, corresponding to the Ferrier product, is also ob-
served, especially for the glucal substrates. A radical oxocarbenium ion and a thiolate intermediates are most likely to mediate the
reaction. Upon synthesis of 2-deoxy-1-thioglycosides, few representative glycosylation reactions with both aglycosyl and glycosyl
acceptors were performed and a-anomeric 2-deoxy glycosides were obtained exclusively.
Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: Carbohydrates; Deoxysugars; Enoses; Thioglycosides
1
. Introduction
deoxy glycoside. In these efforts to derive a thioglycoside
of 2-azido-2-deoxy-sugar derivative, a clean and facile
formation of 2-deoxy-1-thioglycoside was encountered
upon subjecting the glycal to CAN-mediated reaction
1,2-Unsaturated glycopyranosides, namely, glycals, are
versatile synthetic intermediates for the elaboration to
a number of functionalized glycosyl derivatives.
1
A
in the presence of NaN and a thiol source. Details of
3
major utility of glycals is their conversion to 2-deoxy glyc-
osyl derivatives, mediated primarily by the lanthanum
the synthesis of 2-deoxy-1-thioglycosides with this new
method are reported herein. Being excellent activated
glycosyl donors, few representative glycosylation reac-
tions were performed with the newly formed 2-deoxy-
1-thioglycosides.
IV
salt, namely, Ce . The azidonitration reaction, reported
2
by Lemiuex and Ratcliffe, is an excellent example to
illustrate the facile reactivity of glycals in the presence
of metal salts. The azidonitration reaction mediated by
ceric ammonium nitrate (CAN) provides a general
3
method to prepare 2-azido-2-deoxy glycosides. The
2. Results and discussion
mechanism of CAN-mediated azidonitration is pre-
sumed to proceed through either by the attack of the
vinyl ether double bond by the azide radical or the
transfer of azide via a ceric–azide complex. We were
interested to extend this reaction with other radicals or
nucleophiles, so as to derive the corresponding 2-
Early attempts were focused primarily on the conversion
of the glycals to the corresponding 2-azido-2-deoxy-1-
thioglycosides. Thus, 3,4,6-tri-O-acetyl galactal (1) was
reacted with NaN and EtSH in the presence of CAN
3
in MeCN, in a procedure similar to an azidonitration
reaction. This reaction led neatly to the formation of an
anomeric mixture of ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-
thio-D-lyxo-hexopyranoside (5, 6) (Scheme 1), without
incorporation of the azide moiety. Ethyl 4,6-di-O-
acetyl-2,3-dideoxy-1-thio-D-threo-hex-2-enopyranoside
azido-2-deoxy glycopyranoses or pyranosides.
A
reaction of interest in this respect was to incorporate al-
kylthio moiety at the anomeric center of a 2-azido-2-
4
*
Corresponding author. Tel.: +91-80-2293-2406/2403; fax: +91-80-
360-0529; e-mail: jayaraman@orgchem.iisc.ernet.in
(12, 13), corresponding to the Ferrier reaction product,
was also isolated.
2
0
008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.07.010

2198
S. Paul, N. Jayaraman / Carbohydrate Research 339 (2004) 2197–2204
R3 OR1
R3 OR1
R3 OR1
(
NH4)2Ce(NO3)6 (10 mol %), EtSH
o
2
O
2
O
O
R
R
R5
R4
R2
1
1
+
R5
R4
R O
R O
MeCN, 0 C
rt, 15 h
1
2
3
1
2
3
1
2
3
1
2
3
4
: R = Ac,R = H,R = OAc
5: R = Ac,R = H, R = OAc
12: R = Ac,R = H, R = OAc
4
5
4
5
R = SEt, R = H
R = SEt, R = H
1
2
3
: R = Ac,R = OAc,R = H
1
2
3
1
2
3
6
: R = Ac,R = H, R = OAc
13: R = Ac,R = H, R = OAc
1
2
3
4
5
4
5
: R = Bn,R = H,R = OBn
R = H,R = SEt
R = H,R = SEt
1
2
3
1
2
3
1
2
3
: R = Bn,R = OBn,R = H
7: R = Ac,R = OAc,R = H
14: R = Ac,R = OAc, R = H
4
5
4
5
R = H,R = SEt
R = SEt, R = H
1
2
3
1
2
3
8
9
: R = Bn,R = H, R = OBn
15: R = Ac,R = OAc, R = H
4
5
4
5
R = SEt,R = H
R = H,R = SEt
1
2
3
1
2
3
: R = Bn,R = H, R = OBn
16: R = Bn,R = OBn, R = H
4
5
4
5
R = H,R = SEt
R = SEt, R = H
1
2
3
1
2
3
1
0: R = Bn,R = OBn,R = H
17: R = Bn,R = OBn, R = H
4
5
4
5
R = SEt,R = H
R = H,R = SEt
1
2
3
1
1: R = Bn,R = OBn,R = H
4
5
R = H,R = SEt
Scheme 1. CAN-mediated synthesis of thioglycosides 5–11 and 1-thio-2,3-unsaturated enoses 12–17.
An examination of the literature shows that a method
to prepare such 2-deoxy-1-thioglycosides was to treat
the glycal with a specially treated sulfonic acid resin,
are presented in Scheme 1 and Table 1. Apart from
the thioglycoside, the Ferrier product is also formed
under the reaction conditions and the Ferrier product
resulted significantly with glucals than galactals. In all
the cases, a catalytic amount of CAN is found to be suf-
ficient to mediate the reaction and experiments per-
formed without CAN did not lead to any conversion.
Also, excess CAN afforded the products similar to that
of the reaction mediated by catalytic amounts. In an at-
tempt to minimize the Ferrier product, the reaction was
conducted in varied conditions such as low temperatures
5
in the presence of a soluble halide ion. A reagent system
comprising of (diacetoxyiodo)benzene, NaN3 and di-
phenylselenide was also known previously to prepare
6
an analogous 2-azido-2-deoxy-1-seleno-glycosides.
Reaction of glycals with CAN and EtSH in MeCN
afforded the 2-deoxy-1-thioglycosides as a mixture of
a- and b-anomers. The results of the reaction with
O-acetylated and O-benzylated galactals and glucals
Table 1. Yield, a:b ratio of 2-deoxythioglycosides (5–11) and 2,3-unsaturated-1-thio enoses (12–17)
Substrate identity
Substrate
Products
Yield (a:b) (%)
Yield (a:b) (%)
AcO OAc
a
b
1
2
O
5, 6
70 (14:11)
12,13
9( 95 :5)
AcO
OAc
a
b
O
7
35 (b only)
14, 15
55 (31:19)
AcO
AcO
BnO OBn
O
a
3
8, 9
85 (3:2)
––
––
BnO
BnO OBn
b
b
4
O
10, 11
68 (1.2:1)
16, 17
15 (4:1)
BnO
a
Isolated yields.
Estimated from the H NMR spectrum.
b
1

S. Paul, N. Jayaraman / Carbohydrate Research 339 (2004) 2197–2204
2199
Table 2. NIS/TMSOTf-mediated glycosylation of 2-deoxy-1-thioglycoside with acceptor alcohols
AcO OAc
AcO OAc
ROH, NIS, TMSOTf, CH2Cl2
O
O
AcO
AcO
o
4
Å MS, 0 C, 15 min
OR
SEt
5
18- 20
Entry
1
Glycosyl donor
Acceptor alcohol
Product
AcO OAc
Yield (%)
O
9
0
AcO
5
HO
O
1
8
AcO OAc
O
AcO
2
3
5
5
83
75
HO
HO
O
1
9
AcO OAc
O
AcO
O
BzO
BzO
BzO
O
O
BzO
OMe
BzO
BzO
OMe
2
0
(
À20 and À35°C) and solvent such as CH Cl , however,
coupling constant J2a,3 ꢀ 12.0Hz in the 2-deoxy deriva-
2
2
none of these conditions altered the ratio of the product
formed significantly.
tives indicates a diaxial orientation of H-2 and H-3 pro-
a
tons. Lack of the coupling between H-4 and H-5 for
compounds 5, 6, 8, 9, and 18–20 as well as a J4,5 of
ꢀ7.5–9.5Hz for the compounds 10 and 11 confirm lyxo-
and arabino-configurations, respectively. The pattern of
the H-1 resonance (Figs. 1 and 3) with a coupling con-
stant of J1,2a ꢀ 5.7Hz (for compounds 5, 8, 10) and of
J1,2a ꢀ 3Hz (for compounds 18–20) indicates the a-con-
figuration at the anomeric center. In comparison, all b-
isomers exhibited H-1 resonance as double doublets
The catalytic amount of CAN required to mediate the
above reaction points to the possibility that the reaction
involves a radical mechanism. An electron transfer from
the glycal to form the radical oxocarbenium ion would
be more preferable in the formation of 1-thioglycosides
and the Ferrier products.
The formation of 1-thioglycosides 5–11 and the 2,3-
unsaturated enose products 12–17 largely depends on
the gluco-or galacto-configurations of the glycal. It is
likely that 3-O-acetyl group in the gluco-configuration
is able to release the acetyl radical more freely than that
in the galacto-configuration. Also, the formation of the
radical oxocarbenium ion and the thiolate anion should
(Fig. 2) with J1,2a ꢀ 11.7Hz and J
ꢀ 2–3Hz. Absence
1,2e
of a coupling between H-1 and H-2 for compounds 5,
e
8, 10, and 18–20 and a coupling between H-4 and H-5
for compounds 5, 6, 8, 9, and 18–20 is associated with
an anti-periplanar orientation of the ring oxygen to
7
,8
be relatively faster, since the addition of NaN did not
3
one of the protons involved in vicinal coupling.
1
13
affect the course of the reaction, indicating the absence
of the formation of ceric-azide intermediate, as sug-
gested for the reactions involving CAN–NaN in the
Assignments of the resonances of H NMR and
NMR (Fig. 4) for all compounds were confirmed further
C
1
with the aid of H– H COSY, H– H TOCSY and
1
1
1
3
2
1
13
H– C HMQC experiments.
typical azidonitration reactions.
Upon synthesis of 2-deoxy-1-thioglycosides, few thio-
glycosides-mediated glycosylation reactions were per-
formed. The results of NIS-TMSOTf-promoted
glycosylation with aglycosyl as well as a glycosyl accep-
tors are presented in Table 2. The glycosylation pro-
ceeded smoothly to afford the a-anomer of the
glycosides exclusively and in good yields.
A number of methods are known to prepare 2-deoxy-
glycosides, few of which are: (i) radical-mediated dehalo-
genation,
9
,10
11
desulfurization, and deselenelation of
12
halo-, thio- or phenylseleno-group at the C-2 of the gly-
coside, respectively; (ii) deiodination at the C-2 of a pyr-
1
anose by Na S O ; (iii) treatment of the glycals with
3
2
2
4
acceptor alcohol in the presence (a) triphenylphosphine
14
1
15
16
A detailed H NMR characterizations of 5–11 and
8–20 (Tables 3–5) were conducted to confirm the
hydrobromide,
and (d) specially treated sulfonic acid resin-soluble halide
ion reagent.
(b) CAN,
(c) CeCl Æ7H O–NaI
3 2
1
configurations of all newly formed compounds. The
5

1
3
Table 3. H NMR chemical shift and multiplicities in CDCl of compounds 5–11 and 18–20
a
a
6
b
7
b
8
b
9
a
10
a
11
a
18
a
19
a
5
20
H-1
H-2
5.54 (d)
2.44 (ddd)
4.68 (dd)
4.58 (app. dd) 5.43 (d)
1.77 (ddd)
4.43 (dd)
2.13 (ddd)
5.45 (d)
2.05 (ddd)
4.52 (dd)
1.78 (ddd)
4.93 (d)
5.09 (d)
4.97 (d)
2.03–1.91 (band)
d
c
c
c
c
a
2.59–2.35
2.01–1.97 (band) 2.06–1.91
band)
(
c
2
.07–2.00
(
band) (H-2a,e
)
c
1.82–1.76 (band)
H-2
H-3
e
1.88 (dd)
2.30 (app. dd) 1.89(dd)
1. 98 (app. dd)
2.26 (dd)
2.36 (ddd)
1.86 (dd)
1.81–1.66
band)
5.24 (ddd)
(
5.20 (ddd)
5.02 (ddd)
3.57–3.54 (m) 3.55–3.41 (broad) 3.87 (ddd)
3.70–3.65 (m) 5.22 (ddd)
4
.97–4.92 (m)
H-3,H-4)
5.24–5.16 (m)
(H-3,H-4)
(
H-4
H-5
5.33 (app. s)
4.55 (app. t)
5.29(app. d)
3.85 (app. t)
3.81–3.75
broad)
3.58–3.54 (m) 4.18 (app. t)
3.77 (app. s)
3.61 (app. t)
4.14 (ddd)
3.50 (app. t)
5.25 (app. s)
5.26 (app. s)
4.17 (app. t)
(
3.70–3.65 (m) 4.08 (app. t)
4.07 (app. t)
3
.55–3.41
broad)
(
(
H-5, H-6a,b)
H-6
a
4.17
(
4.20
(dd)
3.81
(dd)
4.02
(d)
dd)
4
.11 (app. d)
3.81–3.75
(broad)
(H-6a,b)
3.46–3.42
(m)
(H-6a,b)
4.02
(app. d)
(H-6a,b)
3.90
(app. t)
(H-6a,b)
(H-6a,b)
H-6b
SCH
CH
COCH
4.11 (dd)
2.68–2.52 (m) 2.79–2.67(m)
4.03 (dd)
2.72–2.59 (m) 2.59–2.35 (m) 2.72–2.51(m)
3.76 (dd)
2.78–2.48 (m) 2.78–2.48 (m) ––
–– ––
4.01 (d)
––
2
––
3
1.30
2.14 (s),
1.291.23
2.14,
1.16
2.00 (s),
1.18
––
1. 12 .92 3
––
2.01–1.97
(band),
1.91 (s)
––
3
––
––
––
2.06–1.91
(band)
2.03–1.91 (band),
1.82–1.76 (band)
2
1
.04 (s),
.98 (s)
2.07–2.00 (band) 1.97 (s),
1.96 (s)
PhCH
2
––
––
––
4.84 (d),
.49–4.30 (m) 4.60–4.49(m),
.37–4.30 (m)
7.26–7.13 (m) 7.24–7.14 (m)
4.85 (d),
4.89(d),
4.69–4.59 (m), 4.64–4.56 (m),
4.55 (d) 4.49–4.46 (m)
7.34–7.16 (m) 7.34–7.16 (m) ––
4.88 (d),
––
––
4
4
Ph-H
––
––
––
––
––
––
––
8.01–7.88 (m),
7.45–7.19(m)
6.08 (t), 5.56 (t),
Others
signal
––
––
––
––
3.56 (m),
3.32 (m),
3.48 (m),
1.81–1.66 (m), 5.24–5.16 (band),
1.28–1.14 (m) 4.17 (m), 3.79(dd),
3.55 (dd), 3.41 (s)
1
0
.66–1.25 (m),
.83 (t)
a 1
b 1
c
H NMR recorded in 400MHz NMR instrument.
H NMR recorded in 300MHz NMR instrument.
Signal overlapped with COCH
3
signal.
d
Signal overlapped with SCH
2
signal.

S. Paul, N. Jayaraman / Carbohydrate Research 339 (2004) 2197–2204
Table 4. The H– H coupling constants (Hz) for compounds 5–11 and 18–20
2201
1
1
Compound
J
1,2a
J
1,2e
J
2a,2e
J
2a,3
J
2e,3
J
3,4
J
4,5
J
5,6a
J
5,6b
J
6a,6b
a
c
5
5.8
ꢀ0
12.912.7
d
4.93.1
ꢀ0
6.4
6.6
5.1
6.4
6.6
2.5
a
6
10.8
11.7
5.4
3.0
d
11.0
11.7
5.92.7
3.3
4.2
ꢀ0
11.3
12.3
b
d
d
d
d
7
11.8
12.9
11.7
13.2
11.8
b
8
d
d
d
ꢀ0
3.0
ꢀ0
1.6
ꢀ0
ꢀ0
ꢀ0
6.3
d
6.3
d
b
d
d
9
11.4
5.7
11.7
11.7
11.8
12.3
ꢀ0
7.7
9.6
ꢀ0
a
10
11
18
19
20
3.0
5.0
4.7
7.7
9.6
3.0
4.2
d
1.8
d
10.6
d
a
11.7
3.0
a
c
d
c
12.3
d
6.4
6.6
6.5
6.4
6.6
6.5
a
3.1
2.5
12.2
d
4.8
d
3.0
d
ꢀ0
a,e
d
d
a 1
b 1
c
H NMR recorded in 400MHz instrument.
H NMR recorded in 300MHz instrument.
Respective protons are both chemically and magnetically equivalent.
Not determined.
Coupling constant of the 2-deoxy sugar of disaccharide is presented.
d
e
13
Table 5. C NMR chemical shift assignment of compound 5–11 and 18–20
Compound
C-1
C-2
C-3
C-4
C-5
C-6
S-CH
2
Others signals
a
5
79.93
80.29
79.85
80.12
80.14
80.10
80.66
97.37
30.27
31.63
29.66
31.30
32.50
35.78
36.95
29.67
66.72
69.33
71.77
73.32
74.06
78.01
79.27
66.54
66.72
65.40
68.94
73.21
73.45
77.97
78.41
66.30
66.80
74.48
75.89
70.38
70.04
71.75
71.76
66.74
62.38
62.03
66.66
69.37
69.29
69.48
68.79
62.56
24.77
25.09
25.07
24.64
24.53
24.79
24.83
––
170.44–169.87, 20.80–20.69, 14.74
170.42–169.97, 20.77–20.66, 15.01
170.75–169.74, 20.87–20.69, 14.95
138.74–127.99, 75.40-69.90, 14.75
138.85–127.21, 78.32–71.74, 14.97
138.47–127.45, 77.21–71.43, 14.84
138.39–127.50, 76.99–70.83, 15.01
170.55–170.11, 67.89, 31.57, 29.67,
a
6
b
7
b
8
b
9
a
1
1
1
0
1
8
a
a
2
9.38, 25.87, 22.56, 20.87–20.73, 14.10
170.47–170.35, 75.39, 33.29, 31.53,
9.65, 25.23, 23.92, 20.85–20.71
170.45–165.21, 133.40–128.25, 96.96, 72.05,
0.40, 69.44, 68.21, 66.69, 55.59, 20.69–20.54
a
1
2
9
0
95.47
97.48
30.71
29.80
66.60
66.09
66.39
65.90
66.83
66.74
62.56
62.62
––
––
2
a
7
a 13
b 13
C NMR recorded in 100MHz instrument.
C NMR recorded in 75MHz instrument.
1
13
3
Figure 1. H (400MHz) and C (100MHz) NMR spectra of 5 in CDCl .
1
7
A desire for the development of methods for prepar-
ing 2-deoxyglycosides is based on the importance
of such units present in many biologically important
natural products, such as, olivomycin, chromomycin,
campactin, calicheamycin, and many other antitumor
antibiotics.
The method described herein should
be useful, since an activated glycosyl donor, namely,
2-deoxy-1-thioglycoside, is derived. Such activated glyc-
osyl donor should find utility in the glycosylation of a
variety of glycosyl acceptors.

2202
S. Paul, N. Jayaraman / Carbohydrate Research 339 (2004) 2197–2204
1
13
3
Figure 2. H (400MHz) and C (100MHz) NMR spectra of 6 in CDCl .
1
Figure 3. H NMR (400MHz) spectrum of 20 in CDCl
3
.
13
3
Figure 4. C NMR (100MHz) spectrum of 20 in CDCl .
1
13
3
. Experimental
zation (ESI) technique. H and C NMR spectral anal-
yses were performed on a spectrometer operating at 300/
400 and 75/100MHz, respectively, with residual solvent
signal acting as the internal standard. The following
abbreviations were used to explain the multiplicities: s,
singlet; d, doublet; t, triplet; m, multiplet; band, several
overlapping signals and br., broad.
3
.1. General methods
Chemicals were purchased from commercial sources and
were used without further purification. CAN (AR grade)
was dried at 60–70°C for 48h at high vacuum before
being used. Solvents were dried and distilled according
to the literature procedures. Analytical TLC was per-
formed on commercial Merck plates coated with silica
gel GF254 (0.25mm). Silica gel (100–200 mesh) was used
for column chromatography. Optical rotations were re-
corded on a Jasco Model DIP-370 polarimeter at the so-
dium D line at 25°C. High-resolution mass spectra were
obtained from Q-TOF instrument by electrospray ioni-
3.2. General procedure for the synthesis of 2-deoxy-1-
thioglycosides
A mixture of tri-O-acetyl/tri-O-benzyl glycal (1mmol),
CAN (10mol%) in MeCN was stirred at 0°C for
15min. A solution of EtSH (5mmol) in MeCN was
added dropwise to the reaction mixture and stirring

S. Paul, N. Jayaraman / Carbohydrate Research 339 (2004) 2197–2204
2203
1
3
was continued for 15h at room temperature, the reac-
2.07 (s, 3H, COCH ), 1.33 (t, 3H, J = 7.5Hz, CH );
3
C
3
tion mixture extracted with ether, dried, concentrated
in vacuo. The resulting crude product was subjected to
column chromatography to afford 2-deoxy-1-thioglyco-
sides.
NMR (CDCl , 75MHz) d : 170.57, 170.29, 131.99 (C-2),
3
123.67 (C-3), 79.68 (C-1), 66.61(C-4), 63.43 (C-5), 62.65
(C-6), 25.59(SCH ), 20.79, 20.71, 15.21. b-anomer (13):
2
1
H NMR (CDCl , 300MHz) d : 5.87–5.77 (m, 2H, H-3,
3
H-2), 5.29(app. s, 1H, H-1), 5.07–5.04 (m, 1H, H-4),
4.20–4.24 (m, 2H, H-6a, H-6b), 3.98–3.90 (m, 1H, H-
3.3. Ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-a-D-lyxo-
hexopyranoside (5)
5), 2.53–2.65 (m, 2H, SCH ), 2.09(s, 3H, COCH 3),
2
2.07 (s, 3H, COCH ), 1.32 (t, 3H, J = 7.5Hz, CH ).
3 3
3
CHCl3). HR-MS: m/z calcd for C H O SNa =
9%; R = 0.45 (35% EtOAc/pet.ether); [a] +263 (c 1.2,
HR-MS: m/z calcd for C H O SNa = 297.0773.
12 18 5
f
D
Found: 297.0763.
14
22
7
3
57.0984. Found: 357.0970.
3.10. Ethyl 4,6-di-O-acetyl-2,3-dideoxy-1-thio-D-erythro-
hex-2-enopyranoside
1
8
3.4. Ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-b-D-lyxo-
hexopyranoside (6)
5
5%; R = 0.32 (15% EtOAc/pet.ether). a-anomer (14):
f
1
3
CHCl3). HR-MS: m/z calcd for C H O SNa =
1%; R = 0.38 (35% EtOAc/pet.ether); [a] +29( c 1.00,
H NMR (CDCl , 300MHz) d: 5.94 (dd, 1 H, J = 2.1,
f
D
3
10.5Hz, H-3), 5.78 (d, 1H, J = 10.5Hz, H-2), 5.58 (br.
s, 1H, H-1), 5.37 (dd, 1H, J = 1.5, 9.3Hz, H-4), 4.35–
14
22
7
3
57.0984. Found: 357.0981.
4.15 (m, 3H, H-5, H-6a, H-6b), 2.79–2.59 (m, 2H,
SCH ), 2.09(br. s, 6H, COCH 3), 1.26 (t, 3H,
3.5. Ethyl 2-deoxy-3,4,6-tri-O-acetyl-1-thio-b-D-arabino-
hexopyranoside (7)
2
1
3
J = 7.5Hz, CH3);
C NMR (CDCl , 75MHz) d:
3
170.69, 170. 21, 129.04 (C-2), 126.71 (C-3), 80.02 (C-
1), 66.67 (C-4), 65.03 (C-5), 62.91 (C-6), 25.99 (SCH ),
3
CHCl ). HR-MS: m/z calcd for C H O SNa =
5%; R = 0.41 (35% EtOAc/pet.ether); [a]D À45 (c 1.2,
f
2
1
20.92, 20.69, 15.22. b-anomer (15): H NMR (CDCl ,
3
14 22
7
3
3
57.0984. Found: 357.1000.
300MHz) d: 5.94–5.85 (m, 2H, H-3, H-2), 5.40 (app. s,
1H, H-1), 5.29(app. d, 1H, J = 8.1Hz, H-4), 4.25–4.22
3.6. Ethyl 2-deoxy-3,4,6-tri-O-benzyl-1-thio-a-D-lyxo-
hexopyranoside (8)
(m, 2H, H-6a, H-6b), 3.88–3.82 (m, 1H, H-5), 2.75–
2.57 (m, 2H, SCH ), 2.09(br. s, 6H, COCH ), 1.29(t,
2
3
1
3
3
H, J = 7.5Hz, CH3); C NMR (CDCl , 75MHz) d:
3
5
0
5
1%; R = 0.44 (15% EtOAc/pet.ether); [a]D +133 (c
170.74, 170.15, 130.44 (C-2), 127.01 (C-3), 78.80 (C-1),
74.75 (C-4), 64.70 (C-5), 63.26 (C-6), 23.24 (SCH2),
20.92, 20.76, 15.04. HR-MS: m/z calcd for C H O S-
f
.98, CHCl ). HR-MS: m/z calcd for C H O SNa =
01.2076. Found: 501.2095.
3
29 34
4
1
2
18
5
Na = 297.0773. Found: 297.0777.
3.7. Ethyl 2-deoxy-3,4,6-tri-O-benzyl-1-thio-b-D-lyxo-
hexopyranoside (9)
3.11. Ethyl 4,6-di-O-benzyl-2,3-dideoxy-1-thio-D-erythro-
hex-2-enopyranoside
3
CHCl ). HR-MS: m/z calcd for C H O SK =
4%; R = 0.37 (15% EtOAc/pet.ether); [a] À29( c 0.94,
f
D
15%; R = 0.47 (15% EtOAc/pet.ether). a-anomer (16):
3
29 34
4
f
1
5
17.1815. Found: 517.1841.
H NMR (CDCl , 400MHz) d: 7.33–7.23 (m, 10H, aro-
3
matic-H), 5.95 (d, 1H, J = 10.2Hz, H-2), 5.85 (dd, 1H,
J = 1.8, 10.1Hz, H-3), 5.57 (br s, 1H, H-1), 4.66–4.45
3.8. Ethyl 2-deoxy-3,4,6-tri-O-benzyl-1-thio-D-arabino-
hexopyranoside (10, 11)
(m, 4H, PhCH ), 4.25 (dd, 1H, J = 1.7, 9.2Hz, H-4),
2
3.79–3.74 (m, 2H, H-5, H-6a), 3.69 (dd, 1H, J = 1.8,
10.6Hz, H-6b), 2.77–2.62 (m, 2H, SCH ), 1.28 (t, 3H,
68%; R = 0.33 (15% EtOAc/pet.ether). HR-MS: m/z
calcd for C H O SK = 517.1815. Found: 517.1837.
f
2
1
3
J = 7.4Hz, CH3); C NMR (CDCl , 100MHz) d:
3
2
9
34
4
138.18, 138.10, 128.39(C-2), 128.34, 127.8 ,9 127.88,
127.85, 127.77 (C-3), 80.29(C-1), 73.32 (C-4), 71.0,9
3.9. Ethyl 4,6-di-O-acetyl-2,3-dideoxy-1-thio-D-threo-
hex-2-enopyranoside
70.23, 68.99 (C-5), 68.87(C-6), 25.98 (SCH ), 15.32. b-
2
1
anomer (17): H NMR (CDCl , 400MHz) d: 7.31–7.24
3
9
%; R = 0.31 (15% EtOAc/pet.ether). a-anomer (12):
(m, 10H, aromatic-H), 6.01 (dd, 1H, J = 1.9, 10.2, H-
3), 5.81 (dd, 1H, J = 1.8, 10.2Hz, H-2), 5.37 (d, 1H,
f
1
H NMR (CDCl , 300MHz) d : 6.11 (dd, 1 H, J = 2.8,
3
1
0.2Hz, H-3), 6.02 (d, 1H, J = 10Hz, H-2), 5.66 (app.
s, 1H, H-1), 5.08 (dd, 1H, J = 2.4, 4.8Hz, H-4), 4.55
J = 1.8Hz, H-1), 4.58–4.41 (m, 4H, PhCH ), 4.18–4.15
2
(m, 3H, H-4, H-6a, H-6b), 4.07–4.09(m, 1H, H-5),
2.73–2.58 (m, 2H, SCH ), 1.26 (t, 3H, J = 7.4Hz,
(app. t, 1H, J = 4.9Hz, H-5), 4.27–4.22 (m, 2H, H-6a,
H-6b), 2.79–2.60 (m, 2H, SCH ), 2.09(s, 3H, COCH ),
2
1
3
CH3); C NMR (CDCl , 100MHz) d: 138.39, 137.91,
2
3
3

2204
S. Paul, N. Jayaraman / Carbohydrate Research 339 (2004) 2197–2204
1
(
7
29.11 (C-2), 128.57, 128.44, 127.94, 127.73, 127.63
C-3), 127.55, 79.10 (C-1), 77.89, 73.39 (C-4), 71.30,
0.02 (C-5), 69.77 (C-6), 23.65 (SCH ), 15.23. HR-MS:
References
1
. For illustrative review articles, see: (a) Danishefsky, S. J.;
Bilodeau, M. T. Angew. Chem., Int. Ed. 1996, 35,
2
m/z calcd for C H O SNa = 393.1500. Found:
3
2
2
26
1
380–1419; (b) Ramesh, N. G.; Balasubramanian, K. K.
3
93.1508.
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. Lemiuex, R. U.; Ratcliffe, R. M. Can. J. Chem. 1979, 57,
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2
3
3.12. General procedure for the synthesis of 2-deoxy
glycosides
. For example: (a) Pozsgay, V. J. Org. Chem. 1999, 64,
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277–7280; (b) Seeberger, P. H.; Roehrig, S.; Schell, P.;
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To a stirred solution of 2-deoxy-1-thioglycoside
(1mmol), alcohol (1.2mmol), NIS (1.2mmol) and
(
2
˚
molecular sieves (4A) (0.4g) in CH Cl (6mL) at 0°C,
TMSOTf (10mol% in CH Cl ) was added. After
1
tracted with CH Cl , washed with aq Na S O (5%)
2
2
4
2
2
5
5min stirring at 0°C, the reaction mixture was ex-
2
2
2
2
3
5
6
solution, brine, and concentrated in vacuo. The desired
-deoxy glycoside was purified by column chromato-
graphy.
2
7
8
9
3
pyranoside (18)
.13. Hexyl 2-deoxy-3,4,6-tri-O-acetyl-a-D-lyxo-hexo-
1
30, 125–134.
0. Roush, W. R.; Bennett, C. E. J. Am. Chem. Soc. 1999, 121,
541–3542.
1. (a) Roush, W. R.; Sebesta, D. P.; Bennett, C. E.
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Sebesta, D. P.; James, R. A. Tetrahedron 1997, 53,
8837–8852; (c) Nicolaou, K. C.; Ladduwahetty, T.;
Randall, J. L.; Chucholowski, A. J. Am. Chem. Soc.
1
1
9
CHCl3). HR-MS: m/z calcd for C H O Na =
0%; R = 0.59(35% EtOAc/pet.ether); [ a]D +93 (c 1.5,
f
3
18
30
8
3
97.1838. Found: 397.1835.
3.14. Cyclohexyl 2-deoxy-3,4,6-tri-O-acetyl-a-D-lyxo-
hexopyranoside (19)
1
986, 108, 2466–2467; (d) Ito, Y.; Ogawa, T. Tetrahedron
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8
1
3
3%; R = 0.51 (35% EtOAc/pet.ether); [a]D +108 (c
f
.00, CHCl ). HR-MS: m/z calcd for C H O Na =
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3
18 28
8
1
1
2. Perez, M.; Beau, J.-M. Tetrahedron Lett. 1989, 30, 75–78.
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3
.15. Methyl 2,3,4-tri-O-benzoyl-6-O-(2-deoxy-3,4,6-tri-
O-acetyl-a-D-lyxo-hexopyranosyl)-a-D-glucopyranoside
20)
1
1
1
1
4. Bolitt, V.; Mioskowski, C. J. Org. Chem. 1990, 55,
(
5
812–5813.
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7
75%; R = 0.69(60% EtOAc/pet.ether); [ a] +83 (c 1.07,
D
CHCl3). HR-MS: m/z calcd for C H O Na =
f
6. Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.; Satyanaray-
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40
42 16
8
01.2371. Found: 801.2401.
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Acknowledgements
We thank Department of Science and Technology,
India, for the financial support. S.P. thanks Council of
Scientific and Industrial Research, New Delhi, for a
research fellowship.
1
8. (a) Babu, B. S.; Balasubramanian, K. K. Tetrahedron Lett.
1999, 40, 5777–5778; (b) Yadav, J. S.; Reddy, B. V. S.;
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