HSAB-driven regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-substituted glycals with sulfur and oxygen nucleophiles: Direct versus allylic substitution

Article abstract of DOI:10.1016/j.tet.2011.09.122

A remarkable regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-acteoxymethyl glycals with thiophenols and phenols has been observed. The reaction with thiophenols led to preferential formation of a new class of compounds viz. 2-C-ar

Full text of DOI:10.1016/j.tet.2011.09.122

Tetrahedron 67 (2011) 9322e9328
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HSAB-driven regioselectivity difference in the Lewis-acid catalyzed reactions of
2-C-substituted glycals with sulfur and oxygen nucleophiles: direct versus allylic
substitution
*
Paramathevar Nagaraj, Namakkal G. Ramesh
Department of Chemistry, Indian Institute of TechnologyeDelhi, Hauz Khas, New Delhi 110016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2011
Received in revised form 14 September 2011
Accepted 27 September 2011
Available online 5 October 2011
A remarkable regioselectivity difference in the Lewis-acid catalyzed reactions of 2-C-acteoxymethyl
glycals with thiophenols and phenols has been observed. The reaction with thiophenols led to prefer-
ential formation of a new class of compounds viz. 2-C-arylthiomethyl glycals via direct attack at the C-2
side chain primary carbon bearing the leaving group. In contrast, phenols were reported to afford pre-
dominantly 2-C-methylene-O-aryl glycosides via allylic attack at the anomeric carbon. The observed
results correlate well with the HSAB principle proposed earlier for similar type of reactions with simple
glycals. In addition, formation of an unusual bis-thioarylated product in presence of an excess of thio-
phenol is also reported.
Dedicated to the memory of Dr. Vipin
Kumar
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Glycals
HSAB concept
Regioselective
Thioglycosides
Carbohydrates
1. Introduction
under mild conditions make them the preferred choice of glycosyl
donors in oligosaccharide synthesis. Conventional synthesis of
Carbohydrates are ubiquitous in nature and play vital roles in
various physiological functions and biological processes, such as
cell proliferation, cell adhesion, cellecell interactions etc.1 In order
to understand the precise roles of carbohydrates in biological sys-
tems, it is essential to isolate complex oligosaccharides in pure and
homogeneous forms. However, this has become a formidable task
due to the existence of oligosaccharides in micro-heterogeneity
forms and hence it has been realized that chemical synthesis is the
viable alternative to obtain homogeneous oligosaccharides in large
quantities.2 Oligosaccharides are generally synthesized through
glycosylation reaction of a protected glycosyl donor and an aglycon
in presence of a promoter or an activator.2,3 In this context, thio-
glycosides have received immense attention of chemists due to
their unique and dual reactivity of acting both as glycosyl donors as
well as acceptors.2e4 Furthermore, their high stability, long shelf-
life, remarkable tolerance towards various chemical manipula-
tions coupled with their facile activation with thiophilic reagents
thioglycosides involves a Lewis-acid catalyzed nucleophilic dis-
placement of a suitable leaving group by thiols at the anomeric
carbon of sugars.4 Among the various thioglycosides that have been
investigated, 2,3-unsaturated thioglycosides enjoyed immense
applications in carbohydrate chemistry, as the unsaturation
allowed the introduction of a variety of functionalities through
chemical transformations.5
The most common method to access 2,3-unsaturated thio-
glycosides is through the acid catalyzed Ferrier rearrangement of
glycals with thiols (Scheme 1).6 This rearrangement was reported to
be condition dependant resulting in the formation of two regioi-
someric products, namely, 2,3-dideoxy-hex-2-enothiopyranosides
2 and 3-deoxy-3-alkylthio-hex-2-enitols 3, the former being the
kinetic product and the latter the thermodynamic one (Scheme 1).
The product distribution, however, could be tuned towards either
one of them by properly defining the reaction conditions.6 Complete
equilibration of the kinetic to the thermodynamic product could be
effected in presence of a Lewis acid,6,7 longer reaction time or even
during chromatographic purification of 2 over silica gel.8 On the
other hand, literature reports on the exclusive formation of 2,3-
* Corresponding author. Tel.: þ91 11 26596584; fax: þ91 11 26581102; e-mail
address: ramesh@chemistry.iitd.ac.in (N.G. Ramesh).
dideoxy-hex-2-enothiopyranoside 2 are also quite abundant.9
A
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.122

P. Nagaraj, N.G. Ramesh / Tetrahedron 67 (2011) 9322e9328
9323
plausible explanation based on Pearson’s HSAB (Hard Soft Acid Base)
concept was proposed by Priebe and Zamojski for the formation of
the regioisomers under different reaction conditions.6
compound 4b was treated with 1.0 equiv of thiophenol in the
presence of 20 mol % of BF3$Et2O at 0 ꢀC in acetonitrile as the sol-
vent and the progress of the reaction was monitored by TLC. The
reaction was found to be complete in 15 min as indicated by the
disappearance of the spot due to the starting material and ap-
pearance of a new spot in TLC. The product was purified by column
chromatography over silica gel. Analysis of the 1H NMR spectrum of
the product revealed the presence of only one olefinic proton in the
R2
OAc
O
OAc
O
OAc
O
R2
R2
R1
AcO
Lewis acid
R1
C-3
R1
1a R1= OAc, R2 = H
1b R1= H, R2 = OAc
C-1
C-3
C-1
I
II
molecule (that resonated at
d 6.14 as a singlet) indicating the for-
mation of 2-C-phenylthiomethyl galactal 10. This was further
RSH
OAc
supported by its 13C NMR spectrum, which displayed a signal at
RSH
R2
d
108.7 (resonating as a singlet in its off-resonance spectrum) and
another signal at 141.6 (resonating as a doublet in its off-
resonance spectrum) due to the -olefinic and -olefinic carbons
R2
OAc
O
d
R1
R1
O
b
a
RS
of the enoleether moiety of 10, respectively. On the other hand, the
Ferrier rearranged product 9 should display two signals in the
olefinic region in its 1H NMR spectrum for the two terminal exo-
methylene protons and two signals in the 13C NMR spectrum (a
singlet and a triplet in the off-resonance spectrum) for the olefinic
carbons as well. The possibility of an intramolecular equilibration/
isomerization of an initially formed 9 to 10 during purification by
column chromatography over silica gel8 was ruled out as the 1H
NMR spectrum of the crude reaction mixture itself showed the
presence of 10 as the major product (ꢁ90%), along with a very small
amount (ꢂ10%) of Ferrier rearranged product 9. Similar results
were obtained irrespective of the nature of the Lewis acid (Table 1),
although InCl3 was found to be the best among them in terms of
mildness of the reaction and yield (Table 1, entry 3). Hence, all
subsequent reactions were performed with InCl3. Change in the
reaction conditions, such as temperature, solvent, amount of the
catalyst etc. did not bring about any significant change in the
product formation.
SR
R1= OAc, R2 = H 2a
R1= H, R2 = OAc 2b
3a
3b
Scheme 1. Lewis-acid catalyzed reactions of thiols with glycals.
As a part of our research on the use of unsaturated carbohy-
drates for the synthesis of small natural and unnatural biologically
active compounds, we became interested in exploring the Lewis-
acid catalyzed reaction of 2-C-acetoxymethyl glycals 4 with thio-
phenols. Surprisingly, a thorough literature search revealed that
this reaction remained uninvestigated so far, although similar re-
action with phenols has been explored in detail by several groups.10
Interest in this research arose not only from the synthetic point of
view, but from its mechanistic aspect as well, as this reaction is also
expected to yield two regioisomeric products. If the reaction pro-
ceeds in a similar fashion as phenols react, one would expect the
formation of the 2-C-methylene arylthioglycosides 5. On the other
hand, sulfur being a soft nucleophile, an HSAB-driven reaction
would give rise to 2-C-arylthiomethyl glycals 6 as the major
products. Formation of either or both of them is advantageous as
these are versatile substrates for further synthetic exploitations.
Experimental results of the Lewis-acid catalyzed reaction of 2-C-
substituted glycals with thiophenols are quite suggestive of the
influence of HSAB principle. The reaction afforded predominantly
hitherto unreported 2-C-arylthiomethyl glycals 6a via direct attack
at the C-2 side chain primary carbon bearing the leaving group with
only a trace amount (not isolable in pure forms) of products 5
arising out of Ferrier rearrangement. In contrast, phenols were re-
ported to afford predominantly 2-C-methylene-O-aryl glycosides 7
via allylic attack at the anomeric carbon (Scheme 2) under acidic
conditions. Further, unusual formation of a dithioarylated de-
rivative 28 in presence of an excess of thiophenol that further
supports the HSAB concept is also reported in this article.
Table 1
Reaction of 2-C-acetoxymethyl galactal 4b with thiophenol in presence of 20 mol %
of catalyst
Lewis acid
PhSH
OBn
O
OBn
O
OBn
O
BnO
BnO
BnO
BnO
BnO
BnO
+
CH3CN
SPh
15 min. 0 0C
SPh
OAc
4b
9
10
minor
major
Entry
Catalyst
Isolated yield of
10 (%)
1
2
3
4
5
BF3$Et2O
BiCl3
InCl3
ZnCl2
CAN
62
68
87
70
72
R2
R2
R2
OBn
O
OBn
O
OBn
O
Lewis acid
ArXH
R1
BnO
R1
BnO
R1
BnO
+
XAr
In order to study the effect of leaving group on the regiochem-
ical outcome, the reaction was performed with substrates (11, 12
and 13) possessing relatively poor leaving groups, such as methoxy,
benzyloxy and a free hydroxyl group etc. at the C-2 side chain
carbon. Hardly any difference was noticed in the reactivity as
compared to the acetyl case (Table 2, entries 1e4). Even the re-
action of 2-C-hydroxymethyl galactal 13 with thiophenol under
Mitsunobu condition followed a similar trend (Table 2, entry 5)
affording only the 2-C-thiophenylmethyl galactal 10 in 66% yield.
The generality of InCl3 catalyzed reaction was tested with a few
substituted thiophenols. In all the cases, 2-C-arylthiomethyl gal-
actals, 14e17, were obtained as the major products and in high
yields (Table 2, entries 6e9). Change in the nucleophilicity of sulfur
derivatives have often been shown to alter the regioselectivity of
OAc
XAr
4a R1 = OBn, R2 = H
4b R1 = H, R2 = OBn
4a R1 = OBn, R2 = H
4b R1 = H, R2 = OBn
5a X = S
6a X = S
5b X = S
7a X = O
6b X = S
8a X = O
8b X = O
7b X = O
Scheme 2. Lewis-acid catalyzed reactions of thiophenols and phenols with 2-C-ace-
toxymethyl glycals 4a and 4b.
2. Results and discussion
The required starting materials, namely, 3,4,6-tri-O-benzyl-2-C-
acetoxymethyl glycals 4a and 4b, were prepared according to the
literature reported procedure.11 In a preliminary experiment,

9324
P. Nagaraj, N.G. Ramesh / Tetrahedron 67 (2011) 9322e9328
Table 2
Reaction of 2-C-substituted glycals with sulfur nucleophiles under different conditions
R2
R2
R2
OBn
OBn
O
OBn
O
sulfur nucleophile
R1
R1
BnO
R1
BnO
O
+
BnO
XAr
OR
4a,4b,11-13
XAr
10, 14-21
9
Entry
Substrate
R
R1
R2
Nucleophile
Reaction
X
Ar
Productb
Yieldc
%
conditionsa
1
2
3
4
5
6
7
8
4b
11
12
13
13
4b
4b
4b
4b
4b
4a
4a
4a
Ac
Me
Bn
H
H
H
H
H
H
H
H
H
H
H
OBn
OBn
OBn
OBn
OBn
OBn
OBn
OBn
OBn
OBn
C6H5SH
C6H5SH
C6H5SH
C6H5SH
A
A
A
A
B
A
A
A
A
C
A
A
A
S
S
S
S
S
S
S
S
S
SO2
S
S
S
C6H5
C6H5
C6H5
C6H5
10
10
10
10
10
14
15
16
17
18
19
20
21
87
62
70
56
66
84
84
85
80
84
78
80
82
H
C6H5SH
C6H5
Ac
Ac
Ac
Ac
Ac
Ac
Ac
Ac
p-CH3eC6H4eSH
p-OCH3eC6H4eSH
p-CleC6H4eSH
p-BreC6H4eSH
PhSO2Na
C6H5SH
p-CH3eC6H4eSH
p-OCH3eC6H4eSH
p-CH3eC6H4
p-OCH3eC6H4
p-CleC6H4
p-BreC6H4
C6H5
C6H5
p-CH3eC6H4
p-OCH3eC6H4
9
10
11
12
13
OBn
OBn
OBn
H
H
H
a
A: InCl3 (20 mol %), (substituted) thiophenols (1 equiv), CH3CN, 0 ꢀC, 15 min; B: Ph3P (1.5 equiv), DEAD (1.5 equiv), thiophenol (1 equiv). dry benzene, 0 ꢀC, 30 min; C: InCl3
(20 mol %), PhSO2Na (1.1 equiv), CH3CN, room temperature, 1 h.
b
In all these cases, the 2-C-methylene-thioglycosides, such as 9, were obtained only in very small quantities that were not isolated.
Isolated yields after column chromatography.
c
organic reactions. In view of this, it was of interest to study the
reaction with another sulfur based nucleophile and hence readily
available sodium benzensulfinate was chosen for this purpose.
InCl3 catalyzed reaction of compound 4b with sodium benzene-
sulfinate was also found to adopt the same pathway as thiophenols.
The reaction afforded the 2-C-phenylsulfonylmethyl galactal 18 in
84% yield (Table 2, entry 10). Extension of this acid-catalyzed sub-
stitution reaction to 2-C-acetoxymethyl glucal 4a with various
substituted thiophenols also delivered the same type of products
19e21, respectively, in high yields (Table 2, entries 11e13).
thermodynamic products, namely, 2-C-arylthiomethylglycals, such
as 6 (Scheme 3).
R
R2
R2
OBn
O
OBn
O
Lewis acid
R1
BnO
R1
BnO
7
4
OH
(hard acid) (hard base)
III
The acid-catalyzed reaction of compounds 4a and 4b or similar
systems with phenols has been the subject of research interest of
several groups, including us, for almost the past two decades.10
Ferrier rearrangement was the main reaction in all the examples
reported, affording the 2-C-methylene-O-aryl-glycosides 7, through
the attack of the phenols at the anomeric carbon.10b,feh In some
cases, the reaction proceeded further, under the reaction conditions,
resulting in the formation of pyrano[2,3-b]benzopyrans.10a,cee,i In
contrast to the behaviour of phenols, our present research reveals
that thiophenols prefer to attack at the C-2 side chain primary car-
bon bearing the leaving group rather than at the anomeric carbon.
These intriguing results can be best rationalized based on the con-
cept of HSAB.12e15 It has been known in literature that, in many or-
ganic reactions, the reactivities of sulfur compounds do not parallel
with their oxygen analogues, persumably because of the difference
in their hard/soft character.15e,16 Priebe and Zamojski had pioneered
in proposing the HSAB concept to rationalize the behaviour of thiols
towards glycals 1 in the presence of an acid (Scheme 1),6 which was
subsequently substantiated by other groups as well.7,8
In a similar way, one can rationalize the regiochemical outcome
in the present case based on HSAB concept. The formation of res-
onating allylic carbocations III and IV in the acid-catalyzed re-
actions of 4a and 4b has been well established by us as well as by
other groups.10,17b As per the HSAB concept, carbocation III with
a positive charge on C-1 is a ‘hard acid’ while IV with a positive
charge on the side chain primary carbon is soft in nature. Phenols
being ‘hard bases’ prefer to react with the ‘hard acid’ (carbocation
III) resulting in the formation of kinetically favoured 2-C-methye-
lene glycosides 7. Thiophenols, which are classified as ‘soft bases’
react with ‘soft acid’ (carbocation IV) to afford directly the
R
R2
OBn
O
6
R1
BnO
SH
(soft acid)
IV
(soft base)
Scheme 3. HSAB based rationalization for the regioselective formation of compounds
7 and 6, respectively, with phenols and thiophenols.
An interesting example is the InCl3 catalyzed reaction of sodium
benzenesulfinate with compound 4b (Scheme 4). Sodium benze-
nesulfinate is an ambident nucleophile having both sulfur and ox-
ygen atoms as nucleophilic sites.18 Based on the HSAB concept and
literature precedence, this reaction was expected to result either in
the formation of sulfone 18 (softesoft combination) or sulfinate
ester 22 (hardehard pair). It is likely that exclusive formation of 18
(Table 2, entry 10) under the given reaction condition is probably
due to the synergistic effect of both HSAB concept and thermody-
namic parameter. The formation of sulfone 18 was inferred from two
strong bands that appeared in its IR spectrum at 1308 and 1149 cmꢃ1
due to asymmetric and symmetric stretching frequencies of the S]
O bond of sulfonyl group. Further, the appearance of a signal at d 55.9
(t) in its 13C NMR spectrum is in accordance with the expected value
for the side chain methylene carbon at C-2 position of 18.
With a variety of 2-C-thioarylmethyl glycals in hand, it appeared
worthwhile to explore their chemistry and hence, compound 10
was exposed further to InCl3 catalyst. Our curiosity for such an
investigation arose from the fact that this simple reaction could

P. Nagaraj, N.G. Ramesh / Tetrahedron 67 (2011) 9322e9328
9325
OBn
O
compound 4b was treated with an excess of thiophenol in presence
of InCl3 as a catalyst. It was expected that this reaction should result
in the formation of a dithioarylated compound, such as 28. Indeed,
as anticipated, reaction of glycal 4b with 2.5 equiv of thiophenol in
presence of 20 mol % of InCl3 afforded the dithioarylated compound
28 in 87% yield, as a single diastereomer in 30 min (Scheme 7)
thereby providing further support for the HSAB concept.
OBn
O
BnO
BnO
BnO
BnO
a
a
4b
OSOPh
SO2Ph
18
22
4b
Scheme 4. InCl3 catalyzed reaction of compound 4b with sodium benzensulfinate.
InCl3 (20 mol%)
OBn
O
BnO
PhS
PhSH (2.5 equiv.)
possibly lead to five different products through various mechanistic
pathways as outlined in Scheme 5. Path ‘a’ involves an InCl3 cata-
lyzed thio-Claisen rearrangement resulting in the formation of 2-C-
methylene-C-aryl glycoside 23. Alternatively, InCl3 catalyzed
1,3-alkoxy migration,17a (through the intermediate allylic carboca-
tion V) would lead to 2,3-unsaturated glycoside 24 (path ‘b’). On the
other hand, intramolecular FriedeleCrafts type alkylation of the
4b
CH3CN
30 min. 30 0C, 87%
SPh
28
Scheme 7. Synthesis of dithioarylated compounds 28.
3. Conclusions
carbocation
V
might give rise to regioisomeric tetrahy-
drothiochromeno pyrans 25 (path ‘c’) and/or 26 (path ‘d’). Path ‘e’
represents an InCl3 catalyzed 1,3-transposition of thiophenyl group
to give 2-C-methylene-thioglycoside 27.
In conclusion, a new class of thioarylated glycals has been pre-
pared through a Lewis-acid catalyzed reaction of 2-C-substituted
glycals with thiophenols. A rationale fortheobservedregioselectivity
based on HSAB concept has been provided. InCl3 catalyzed facile 1,3-
benzyloxy migration and formation of a novel dithioarylated com-
pound provide further support for HSAB principle. 2-C-Thioar-
ylmethyl glycals reported here are ideal substrates to be exploited for
thermal [3,3]-sigmatropic (thio-Claisen) rearrangement as well as
novel glycosyl donors for the synthesis of unsaturated oligosaccha-
rides. Research in these directions is currently underway in our lab.
OBn
O
BnO
BnO
OBn
O
BnO
HS
OBn
S
23
path 'b'
InCl3
24
catalyzed
[3,3]-shift
BnO
path 'a'
InCl3
OBn
O
OBn
O
BnO
BnO
path 'c'
4. Experimental section
10
InCl3
catalyzed
[1,3]-shift
S
25
S
4.1. General considerations
path 'e'
V
All solvents were purified by standard procedures. Thin-layer
chromatography (TLC) was performed on Merck silica gel pre-
coated on aluminium plates. Flash column chromatography was
performed on 230e400 mesh silica gel. Melting points are un-
corrected. Optical rotations were recorded on an Autopol V
(Rudolph Research Flanders, New Jersey) instrument. All the rota-
tions were measured at 589 nm (sodium D0 line). IR spectra were
taken over the 4000e400 cmꢃ1 range as KBr pellets on a Nicolet
path 'd'
OBn
OBn
BnO
BnO
BnO
O
O
S
S
26
27
Scheme 5. Possible mechanistic pathways for the reaction of compound 10 with InCl3.
ꢀ ꢀ
(Madison, USA) FTIR spectrophotometer (Model Protege 460). All
Experimental results clearly revealed that among the various
possibilities, 1,3-alkoxy migration (path ‘b’) was the only reaction of
choice and compound 24 was formed, under the experimental
condition, as a single product in 1 h in 79% yield as an anomeric
mixture in a ratio of 10:1 (Scheme 6). The preferential 1,3-
benzyloxy migration (path ‘b’) over intramolecular FriedeleCrafts
type alkylations (path ‘c’ or ‘d’) is note worthy. A similar type of 1,3-
alkoxy migration reaction from C-3/C-1 in simple glycals have
been reported earlier by us and others, and is in accordance with
the HSAB principle.17
the 1H and 13C NMR spectra were recorded on a 300 MHz Bruker
Spectrospin DPX FT-NMR spectrometer. Chemical shifts are re-
d values (ppm) relative to Me4Si as internal standard.
Mass spectra were recorded with an Applied Biosystems Q-Star and
Bruker Microtof-Q-II instruments.
ported as
4.2. General procedure for the InCl3 catalyzed reaction of
glycals 4a and 4b with substituted thiophenols
Glycal 4a or 4b (1 equiv) was taken in a flame-dried three-necked
round bottomed flask and dissolved with 10 mL of dry acetonitrile.
Thiophenol or substituted thiophenol (1 equiv) was added to it and
stirred for 5 min under argon atmosphere. Anhydrous InCl3
(20 mol %) was then added to the reaction mixture. The progress of
the reaction was monitored by TLC. After 15 min, when TLC in-
dicated the disappearance of the starting material, the reaction
mixture was quenched with saturated sodium bicarbonate solution
and extracted with chloroform (3ꢄ50 mL). The combined organic
layer was washed with water, dried over anhydrous sodium sulfate,
filtered and concentrated. The product was purified by column
chromatography over silica gel using hexane/ethyl acetate mixture
as an eluent to obtain 2-C-arylthiomethyl glycals 10, 14e17, 19e21.
InCl3 (10 mol%)
CH2Cl2, 30 0C
1 h, 79%
10
24
Scheme 6. InCl3 catalyzed 1,3-alkoxy migration of compound 10 to 24.
Based on the above observation, it was expected that addition of
an external ‘soft’ nucleophile in the above reaction (path ‘b’) should
result in the attack of the soft nucleophile at C-3 position rather
than at C-1 position of the carbocation V. In order to verify our
hypothesis, thiophenol itself was chosen as a ‘soft’ base and

9326
P. Nagaraj, N.G. Ramesh / Tetrahedron 67 (2011) 9322e9328
4.2.1. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-thiophenyl
methyl- -lyxo-hex-1-enitol (10). Obtained in 87% yield (3.6 g) as
a colourless solid from the reaction of 4b (3.76 g, 7.7 mmol) with
(0.470 g) as a colourless solid from the reaction of 4b (0.460 g,
0.942 mmol) with p-bromothiophenol (0.178 g, 0.942 mmol) in
presence of InCl3 (20 mol %, 0.041 g, 0.18 mmol). Mp 60 ꢀC; Rf (10%
D
thiophenol (0.874 mL, 7.7 mmol) in presence of InCl3 (20 mol %,
EtOAc/hexane) 0.44; ½a D28
þ141.4 (c0.21, CHCl3); nmax (KBr)3061,3030,
ꢅ
0.34 g,1.54 mmol). Mp 64 ꢀC; Rf (10% EtOAc/hexane) 0.65; ½a D28
ꢅ
þ130
2907, 2865,1661,1461,1414,1373,1345,1217,1184,1089, 901, 811, 744,
(c 0.18, CHCl3); nmax (KBr) 3062, 3025, 2916, 2873, 1654, 1595, 1486,
693 cmꢃ1
; dH (300 MHz CDC13) 7.38e7.21 (17H, m, aromatic),
1451,1409,1345,1306,1214,1147,1089,1025, 901, 868, 804, 733, 695,
7.13e7.10 (2H, m, aromatic), 6.16 (1H, s), 4.84e4.77 (2H, m), 4.62e4.55
(2H, m), 4.48 (1H, d, J¼12.0 Hz), 4.40e4.34 (2H, m), 4.10 (1H, m), 3.96
(1H, m), 3.74e3.61 (3H, m), 3.44 (1H, d, J¼13.2 Hz); dC (75 MHz, CDCl3)
141. 8, 138.17, 138.10, 137.7, 132.1, 131.7, 128.3, 127.9, 127.8, 127.76,
127.70, 120.3, 108.4, 75.6, 73.4, 73.3, 73.2, 71.8 (2ꢄ CH), 68.1, 34.7;
HRMS (ESI): [M]þ, found 639.1176. C34H33O4SBrNa requires 639.1175.
603 cmꢃ1
; dH (300 MHz CDC13) 7.35e7.17 (20H, m, aromatic), 6.14
(1H, s), 4.84e4.78 (2H, m), 4.63e4.58 (2H, m), 4.48 (1H, d, J¼11.7 Hz),
4.40e4.36 (2H, m), 4.11 (1H, m), 3.96 (1H, m), 3.75e3.60 (3H, m),
3.47 (1H, d, J¼13.2 Hz); dC (75 MHz, CDCl3) 141.6, 138.2, 138.1, 137.8,
135.9, 130.8, 128.7, 128.2, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 126.4,
108.7, 75.6, 73.36 (2ꢄ CH2), 73.31, 71.7, 71.5, 68.1, 34.7; HRMS (ESI):
[MþNa]þ, found 561.2092. C34H34O4SNa requires 561.2076.
4.2.6. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-thiophenylmethyl-
D-arabino-hex-1-enitol (19). Obtained in 78% yield (0.184 g) as
4.2.2. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-(p-methyl-
a colourless viscous liquid from the reaction of 4a (0.215 g,
0.440 mmol) with thiophenol (0.045 mL, 0.44 mmol) in presence of
InCl3 (20 mol %, 0.019 g, 0.088 mmol). Rf (10% EtOAc/hexane) 0.55;
thiophenyl)methyl- -lyxo-hex-1-enitol (14). Obtained in 84% yield
D
(0.415 g) as a colourless solid from the reaction of 4b (0.44 g,
0.90 mmol) with p-methylthiophenol (0.111 g, 0.90 mmol) in
presence of InCl3 (20 mol %, 0.039 g, 0.18 mmol). Mp 70 ꢀC; Rf (10%
½
a 2D8
ꢅ
þ56.8 (c 0.70, CHCl3); nmax (KBr) 3061, 3030, 2916, 2864, 1659,
1582, 1483, 1450, 1361, 1288, 1242, 1091, 918, 740, 695, 614 cmꢃ1
;
dH
EtOAc/hexane) 0.51; ½a D28
ꢅ
þ156 (c 0.20, CHCl3); nmax (KBr) 3058,
(300 MHz CDC13) 7.36e7.17 (20H, m, aromatic), 6.19 (1H, s),
4.77e4.53 (6H, m), 4.40 (1H, d, J¼4.8 Hz), 4.13e4.05 (1H, m), 3.95
(1H, m), 3.79e3.61 (3H, m), 3.47 (1H, d, J¼13.5 Hz); dC (75 MHz,
CDCl3) 142.3, 138.2, 137.8, 135.7, 131.1, 129.1, 128.7, 128.4, 128.36,
128.31, 127.8, 127.67, 127.61, 126.5, 108.6, 76.5, 74.4, 74.3, 73.3, 73.0,
72.7, 67.9, 34.6; HRMS (ESI): [MþNa]þ, found 561.2055.
C34H34O4SNa requires 561.2070.
3027, 2867, 1657, 1449, 1373, 1347, 1314, 1224, 1185, 1149, 1101, 1027,
953, 906, 858, 738, 691, 608 cmꢃ1
; dH (300 MHz CDC13) 7.33e7.01
(19H, m, aromatic), 6.07 (1H, s), 4.83e4.77 (2H, m), 4.62e4.58 (2H,
m), 4.47 (1H, d, J¼11.7 Hz), 4.39e4.35 (2H, m), 4.11 (1H, m),
3.95e3.93 (1H, m), 3.75e3.61 (3H, m), 3.40 (1H, d, J¼13.5 Hz), 2.28
(3H, s); dC (75 MHz, CDCl3) 141.4, 138.3, 138.1, 137.8, 136.6, 132.0,
131.6, 129.5, 128.2, 127.9, 127.8, 127.7, 127.6, 127.5, 109.0, 75.6, 73.4
(2ꢄ CH2), 73.3, 71.7 (2ꢄ CH), 68.1, 35.4, 21.0; HRMS (ESI): [MþNa]þ,
found 575.2256. C35H36O4SNa requires 575.2232.
4.2.7. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-(p-methyl-
thiophenyl)methyl- -arabino-hex-1-enitol (20). Obtained in 80%
D
yield (0.345 g) as a colourless viscous liquid from the reaction of 4a
(0.382 g, 0.782 mmol) with p-methylthiophenol (0.097 g,
0.782 mmol) in presence of InCl3 (20 mol %, 0.034 g, 0.15 mmol). Rf
4.2.3. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-(p-methox-
ythiophenyl)methyl- -lyxo-hex-1-enitol (15). Obtained in 84% yield
D
(0.415 g) as a colourless solid from the reaction of 4b (0.43 g,
0.88 mmol) with p-methoxythiophenol (0.108 mL, 0.88 mmol) in
presence of InCl3 (20 mol %, 0.038 g, 0.17 mmol). Mp 76 ꢀC; Rf (10%
(10% EtOAc/hexane) 0.44; ½a D28
þ8.16 (c 0.60, CHCl3); nmax (KBr)
ꢅ
3029, 2917, 2861, 1658, 1599, 1494, 1454, 1371, 1302, 1241, 1208,
1096, 1031, 906, 806, 740, 699 cmꢃ1
; dH (300 MHz CDC13) 7.37e7.23
EtOAc/hexane) 0.32; ½a D28
ꢅ
þ177.6 (c 0.21, CHCl3); nmax (KBr) 3032,
(17H, m, aromatic), 7.10e7.08 (2H, m), 6.13 (1H, s), 4.89e4.83 (2H,
m), 4.68e4.64 (2H, m), 4.55e4.40 (3H, m), 4.16 (1H, br s), 4.00 (1H,
m), 3.77e3.65 (3H, m), 3.44 (1H, d, J¼13.2 Hz), 2.34 (3H, s); dC
(75 MHz, CDCl3) 141.4, 138.3, 138.1, 137.8, 136.6, 131.9, 131.7, 129.54,
128.3, 127.9, 127.85, 127.80, 127.68, 127.60, 109.0, 75.6, 73.3 (3ꢄ
CH2), 71.7 (2ꢄ CH), 68.1, 35.5, 21.0; HRMS (ESI): [MþK]þ, found
591.2000. C35H36O4SK requires 591.1966.
2911, 2878,1656,1585,1488,1452,1346,1288,1242,1145,1090,1026,
901, 867, 815, 733, 695, 609 cmꢃ1
; dH (300 MHz CDC13) 7.53e7.23
(17H, m, aromatic), 6.75 (2H, d, J¼8.4 Hz, aromatic), 5.98 (1H, s),
4.83e4.79 (2H, m), 4.63e4.59 (2H, m), 4.49e4.35 (3H, m), 4.10 (1H,
m), 3.95 (1H, m), 3.74e3.58 (6H, m, with the signal of OCH3 proton
merged), 3.31 (1H, d, J¼13.2 Hz); dC (75 MHz, CDCl3) 159.1, 141.3,
138.3, 138.1, 137.8, 134.5, 128.3, 127.9, 127.8, 127.7, 127.6, 127.5, 125.7,
114.3,109.0, 75.6, 73.3 (3ꢄ CH2), 71.8 (2ꢄ CH), 68.1, 55.1, 36.6; HRMS
(ESI): [MþNa]þ, found 591.2200. C35H36O5SNa requires 591.2176.
4.2.8. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-(p-methox-
ythiophenyl)methyl- -arabino-hex-1-enitol (21). Obtained in 82%
D
yield (0.308 g) as a colourless viscous liquid from the reaction of 4a
(0.322 g, 0.659 mmol) with p-methoxythiophenol (0.081 mL,
0.659 mmol) in presence of InCl3 (20 mol %, 0.029 g, 0.13 mmol). Rf
4.2.4. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-(p-chlor-
othiophenyl)methyl- -lyxo-hex-1-enitol (16). Obtained in 85% yield
D
(0.430 g) as a colourless solid from the reaction of 4b (0.435 g,
0.89 mmol) with p-chlorothiophenol (0.128 g, 0.89 mmol) in pres-
ence of InCl3 (20 mol %, 0.039 g, 0.17 mmol). Mp 60 ꢀC; Rf (10%
(10% EtOAc/hexane) 0.28; ½a D28
þ117.5 (c 0.90, CHCl3); nmax (KBr)
ꢅ
3061, 3030, 2920, 2861, 1659, 1593, 1493, 1456, 1361, 1286, 1243,
1172, 1095, 1032, 825, 740, 698 cmꢃ1
; dH (300 MHz CDC13)
EtOAc/hexane) 0.36; ½a D28
ꢅ
þ151.2 (c 0.16, CHCl3); nmax (KBr) 3062,
7.34e7.27 (17H, m, aromatic), 6.81e6.79 (2H, m), 6.05 (1H, s),
4.81e4.70 (4H, m), 4.62 (2H, m), 4.47 (1H, d, J¼4.8 Hz), 4.12 (1H, m),
3.99 (1H, m), 3.79e3.71 (5H, m with the signal of OCH3 merged),
3.57 (1H, d, J¼13.2 Hz), 3.34 (1H, d, J¼13.2 Hz); dC (75 MHz, CDCl3)
159.2, 142.1, 138.3, 137.92, 137.90, 134.9, 128.45, 128.42, 128.3, 127.9,
127.8, 127.7, 127.6, 125.6, 114.3, 108.9, 76.5, 74.3, 74.2, 73.4, 73.1, 72.7,
68.0, 55.2, 36.5; HRMS (ESI): [M]þ, found 591.2196. C35H36O5SNa
requires 568.2176.
3029, 2915, 2875, 1653, 1570, 1459, 1410, 1374, 1345, 1308, 1217,
1146, 1088, 1017, 900, 867, 812, 734, 693, 604 cmꢃ1
; dH (300 MHz
CDC13) 7.42e7.15 (19H, m, aromatic), 6.16 (1H, s), 4.84 (1H, d,
J¼12.0 Hz), 4.82 (1H, d, J¼12.0 Hz), 4.63 (1H, d, J¼9.9 Hz), 4.60 (1H,
d, J¼9.9 Hz), 4.52e4.38 (3H, m), 4.12 (1H, br s), 4.0e3.98 (1H, m),
3.75e3.55 (3H, m), 3.45 (1H, d, J¼13.2 Hz); dC (75 MHz, CDCl3) 141.
7, 138.1, 138.0, 137.7, 134.4, 132.3, 132.0, 128.8, 128.3, 128.1, 127.9,
127.8, 127.7, 127.69, 127.66, 108.4, 75.6, 73.4 (2ꢄ CH2), 73.2, 71.7,
71.2, 68.0, 34.9; HRMS (ESI): [MþNa]þ, found 595.1689.
C34H33O4SCl Na requires 595.1680.
4.3. Synthesis of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-
benzenesulfonyl-D-lyxo-hex-1-enitol (18)
4.2.5. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-C-(p-bromothio-
Glycal 4b (0.45 g. 0.922 mmol) was taken in a flame-dried three-
necked round bottomed flask and dissolved with 10 mL of dry
phenyl)methyl- -lyxo-hex-1-enitol (17). Obtained in 80% yield
D

P. Nagaraj, N.G. Ramesh / Tetrahedron 67 (2011) 9322e9328
9327
acetonitrile. Sodium benzenesulfinate (0.166 g, 1.01 mmol) was
added to it and stirred for 5 min under argon atmosphere. Anhy-
drous InCl3 (0.040 g, 0.18 mmol) was then added to the reaction
mixture. The progress of the reaction was monitored by TLC. After
1 h, when TLC indicated the disappearance of the starting material,
the reaction mixture was quenched with saturated sodium bi-
carbonate solution and extracted with chloroform (3ꢄ50 mL). The
combined organic layer was washed with water, dried over anhy-
drous sodium sulfate, filtered and concentrated. The product was
purified by column chromatography over silica gel using hexane/
ethyl acetate mixture (5:1) as an eluent to obtain 18 as a colourless
low melting solid in 84% yield (0.440 g). Rf (30% EtOAc/hexane)
low melting solid in 87% yield (0.152 g). Rf (10% EtOAc/hexane) 0.68;
a 2D8
ꢃ123 (c 0.60, CHCl3); nmax (KBr) 3054, 2908, 2862, 1655, 1443,
1422, 1409, 1373, 1251, 1194, 1145, 1099, 1057, 1024, 925, 785,
697 cmꢃ1
dH (300 MHz CDC13) 7.41e6.91 (20H, m, aromatic), 6.39
(1H, s), 4.57e4.37 (4H, m), 4.16 (1H, br s), 4.04 (1H, dd, J¼12.0,
1.8 Hz), 3.89 (1H, d, J¼14.1 Hz), 3.74e3.59 (3H, m), 3.52e3.47 (1H,
m); dC (75 MHz, CDCl3) 143.8, 137.8, 135.9, 134.4, 132.7, 131.0, 129.2,
128.8,128.2,127.6,126.6,105.7, 73.2, 72.7, 71.8, 70.8, 69.2, 43.9, 36.5;
HRMS (ESI): [MþNa]þ, found 563.1694C33H32O3S2Na requires
563.1691.
½
ꢅ
;
Acknowledgements
0.33; ½a 2D8
ꢃ71.4 (c 0.56, CHCl3); nmax (KBr) 3063, 3032, 2924, 2862,
ꢅ
1648, 1587, 1450, 1399, 1366, 1308, 1246, 1209, 1149, 742, 691 cmꢃ1
;
Authors are grateful to the Department of Science and Tech-
nology, New Delhi, India for financial assistance. P.N. thanks IIT
Delhi for a senior research fellowship. We thank the DST-FIST for
funding of the ESI HRMS facility at IITD.
dH (300 MHz CDC13) 7.80e7.24 (20H, m, aromatic), 6.13 (1H, s),
4.83e4.71 (2H, m), 4.57e4.35 (5H, m), 4.17e4.13 (2H, m), 3.98 (1H,
m), 3.68e3.56 (2H, m), 3.46 (1H, d, J¼12.0 Hz); dC (75 MHz, CDCl3)
146.7, 138.4, 137.9, 137.6, 133.5, 129.0, 128.2, 127.7, 101.4, 75.9, 73.8,
73.3, 73.1, 72.8, 69.9, 68.0, 55.9; HRMS (ESI): [MþNa]þ, found
593.1981. C34H34O6SNa requires 593.1974.
Supplementary data
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.09.122.
4.4. Synthesis of benzyl-4,6-di-O-benzyl-2,3-dideoxy-2-C-
thiophenylmethyl-D-threo-hex-2-enopyranoside (24)
References and notes
Compound 10 (0.250 g, 0.464 mmol) was taken in a flame-dried
three-necked round bottomed flask and dissolved with 10 mL of
dry dichloromethane. After 5 min, anhydrous InCl3 (0.010 g,
0.046 mmol) was added to the reaction mixture and it was stirred
under argon atmosphere. The progress of the reaction was moni-
tored by TLC. After 1 h, when TLC indicated the disappearance of
the starting material, the reaction mixture was quenched with
saturated sodium bicarbonate solution and extracted with chloro-
form (3ꢄ50 mL). The combined organic layer was washed with
water, dried over anhydrous sodium sulfate, filtered and concen-
trated. The product was purified by column chromatography over
silica gel using hexane/ethyl acetate mixture (15:1) as an eluent to
obtain 24 as an anomeric mixture in a ratio of 10:1. Yield 79%
(0.198 g). Colourless viscous liquid. Rf (10% EtOAc/hexane) 0.32;
1. (a) Galan, M. C.; Benito-Alifonso, D.; Watt, G. M. Org. Biomol. Chem. 2011, 9,
3598e3610; Varki, A.; Lowe, J. B. In Essentials of Glycobiology; Varki, A., Ed.; Cold
Spring Harbor Laboratory: 2009; Part 1, Chapter 6, pp 80e81; Lowe, J. B. Cell
2001, 104, 804e812; (b) Rudd, P. M.; Elliot, T.; Cresswell, P.; Wilson, I. A.; Dwek,
R. A. Science 2001, 291, 2370e2376; (c) Varki, A. Glycobiology 1993, 3, 97e130
and references cited in these articles.
2. Zhu, X.; Schmidt, R. R. Angew. Chem., Int. Ed. 2009, 48, 1900e1934 and refer-
ences cited therein.
3. For some very recent reviews on the chemical syntheses of glycosides and
oligosaccharides: (a) Weishaupt, M.; Eller, S.; Seeberger, P. H. Methods Enzymol.
2010, 478, 463e484; (b) Guo, J.; Ye, X.-S. Molecules 2010, 15, 7235e7265; (c)
Seibel, J.; Buchholz, K. Adv. Carbohydr. Chem. Biochem. 2010, 63, 101e138; (d)
Muthana, S.; Cao, H.; Chen, X. Curr. Opin. Chem. Biol. 2009, 13, 573e581; (e) Hou,
D.; Lowary, T. L. Carbohydr. Res. 2009, 344, 1911e1940.
4. For reviews on the synthesis and applications of thioglycosides in carbohydrate
chemistry: (a) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P. Tetrahedron 2008, 64,
7659e7683; (b) El Ashrey, E. S. H.; Awad, L. F.; Atta, A. I. Tetrahedron 2006, 62,
Specific rotation reported here is for the anomeric mixture. ½a D28
ꢅ
ꢀ
2943e2998; (c) Codee, J. D. C.; Litjens, R. E. J. N.; van den Bos, L. J.; Overkleeft,
ꢃ59.4 (c 0.70, CHCl3); nmax (KBr) 3031, 2916, 2864, 1585, 1486, 1452,
H. S.; van der Marel, G. A. Chem. Soc. Rev. 2005, 34, 769e782.
1379, 1101, 1030, 951, 740, 697 cmꢃ1
;
1H and 13C NMR values re-
5. (a) Yousuf, S. K.; Mukherjee, D.; Mallikharjunrao, L.; Taneja, S. C. Org. Lett. 2011,
13, 576e579; (b) Ellis, D.; Norman, S. E.; Osborn, H. M. I. Tetrahedron 2008, 64,
2832e2854; (c) Donohoe, T. J.; Blades, K.; Moore, P. R.; Waring, M. J.; Winter, J.
J. G.; Helliwell, M.; Newcombe, N. J.; Stemp, G. J. Org. Chem. 2002, 67,
7946e7956; (d) Jakel, C.; Dotz, K. H. J. Organomet. Chem. 2001, 624, 172e185; (e)
Engstrom, K. M.; Mendoza, M. R.; Navarro-Villalobos, M.; Din, D. Y. Angew.
Chem., Int. Ed. 2001, 40, 1128e1130; (f) Kan, C.; Long, C. M.; Paul, M.; Ring, C. M.;
Tullu, S. E.; Rojas, C. M. Org. Lett. 2001, 3, 381e384; (g) Sugimura, H. Nucleosides,
Nucleotides Nucleic Acids 2000, 19, 629e635; (h) Takeda, K.; Kaji, E.; Nakamura,
H.; Akiyama, A.; Konda, Y.; Mizuno, Y.; Takayanagi, H.; Harigaya, Y. Synthesis
1996, 341e348; (i) Lopez, J. C.; Gomez, A. M.; Valverde, S.; Frser-Reid, B. J. Org.
Chem. 1995, 60, 3851e3858; (j) Takeda, K.; Nakamura, H.; Ayabe, A.; Harigaya,
Y.; Mizuno, Y. Tetrahedron Lett. 1994, 35, 125e128; (k) Griffith, D. A.; Dani-
shefsky, S. J. Am. Chem. Soc. 1991, 113, 5863e5864; (l) Valverde, F.; Garcia-
Ochoa, S.; Martín-Lomas, M. J. Chem. Soc., Chem. Commun. 1987, 383e384.
6. Priebe, W.; Zamojski, A. Tetrahedron 1980, 36, 287e297.
ported here are due -anomer only from a mixture of anomers
a
(10:1). dH (300 MHz CDC13) 7.35e7.10 (20H, m, aromatic), 5.86 (1H,
d, J¼5.1 Hz), 5.36 (1H, s), 4.83 (1H, d, J¼11.4 Hz), 4.66e4.53 (3H, m),
4.39 (1H, d, J¼11.7 Hz), 4.25e4.18 (2H, m), 3.85e3.69 (3H, m), 3.59
(2H, br s); dC (75 MHz, CDCl3) 138.4, 138.3, 137.8, 137.3, 135.3, 130.5,
128.8, 128.37, 128.30, 128.2, 127.7, 127.58, 127.52, 126.9, 126.6, 124.1,
94.2, 73.3, 70.0, 69.8, 69.6, 69.4, 67.4, 36.7; HRMS (ESI): [MþNa]þ
found 561.2075. C34H34O6SNa requires 561.2112.
4.5. Synthesis of 1,5-anhydro-4,6,-di-O-benzyl-2,3-didoexy-3-
thiophenyl-2-thiophenylmethyl-D-lyxo-hex-1-enitol (28)
7. Mukherjee, A.; Jayaraman, N. Carbohydr. Res. 2011, 346, 1569e1575.
8. Dunkerton, L. V.; Adair, N. K.; Euske, J. M.; Brady, K. T.; Robinson, P. D. J. Org.
Chem. 1988, 53, 845e850.
Glycal 4b (0.160 g, 0.327 mmol) was taken in a flame-dried three-
necked round bottomed flask and dissolved with 10 mL of dry ace-
tonitrile. Thiophenol (0.084 mL, 0.82 mmol) was added to it and
stirred for 5 min under argon atmosphere. Anhydrous InCl3 (0.014 g,
0.065 mmol) was then added to the reaction mixture. The progress
of the reaction was monitored by TLC. After 30 min, when TLC in-
dicated the disappearance of the starting material, the reaction
mixture was quenched with saturated sodium bicarbonate solution
and extracted with chloroform (3ꢄ50 mL). The combined organic
layer was washed with water, dried over anhydrous sodium sulfate,
filtered and concentrated. The product was purified by column
chromatography over silica gel using hexane/ethyl acetate mixture
as an eluent to obtain dithioarylated compounds 28 as a colourless
9. For some very recent reports on the synthesis of 2,3-unsaturated thioglyco-
sides: (a) Reddy, B. V. S.; Divyavani, C.; Yadav, J. S. Synthesis 2010, 1617e1620;
(b) Levecque, P.; Gammon, D. W.; Jacobs, P.; De Vos, D.; Sels, B. Green Chem.
2010, 12, 828e835; (c) Balamurugan, R.; Koppolu, S. R. Tetrahedron 2009, 65,
8139e8142; (d) Gorityala, B. K.; Lorpitthaya, R.; Bai, Y.; Liu, X.-W. Tetrahedron
2009, 65, 5844e5848; (e) Gorityala, B. K.; Cai, S.; Ma, J.; Liu, X.-W. Bioorg. Med.
Chem. Lett. 2009, 19, 3093e3095 and reference cited in these articles.
10. (a) Roy, S.; Chakraborty, A.; Chattopadhyay, B.; Bhattacharya, A.; Mukherjee, A.
K.; Ghosh, R. Tetrahedron 2010, 66, 8512e8521; (b) Nagaraj, P.; Ramesh, N. G.
Tetrahedron 2010, 66, 599e644; (c) Santhi, M.; Balasubramanian, K. K.; Bha-
gavathy, S. Carbohydr. Res. 2009, 344, 521e525; (d) Ghosh, R.; Chakraborty, A.;
Maiti, D. K.; Puranik, V. G. Tetrahedron Lett. 2005, 46, 8047e8051; (e) Ghosh, R.;
Chakraborty, A.; Maiti, D. K.; Puranik, V. G. Org. Lett. 2005, 6, 1061e1064; (f)
Gupta, A.; Vankar, Y. D. Tetrahedron 2000, 56, 8525e8531; (g) Bouoit, S.; Goux,
C.; Sinou, D. Carbohydr. Lett. 1997, 2, 267e272; (h) Ramesh, N. G.;

9328
P. Nagaraj, N.G. Ramesh / Tetrahedron 67 (2011) 9322e9328
Balasubramanian, K. K. Tetrahedron 1995, 51, 255e272; (i) Booma, C.; Balasu-
bramanian, K. K. Tetrahedron Lett. 1993, 34, 6757e6760.
6848e6854; (d) Molteni, G.; Ponti, A. ARKIVOC 2006, 16, 49e56; (e) Jacquot-
Rousseau, S.; Schmitt, G.; Khatyr, A.; Knorr, M.; Kubicki, M. M.; Vigier, E.;
Blacque, O. Eur. J. Org. Chem. 2006, 1555e1562; (f) Tundo, P.; Bressanello, S.;
Loris, A.; Sathicq, G. Pure Appl. Chem. 2005, 77, 1719e1725; (g) Breysee, E.; Fa-
jula, F.; Finiels, A.; Fremy, G.; Tichit, D.; Moreau, C. J. Catal. 2005, 233, 288e296.
16. (a) Rawal, G. K.; Rani, S.; Kumari, N.; Vankar, Y. D. J. Org. Chem. 2009, 74,
5349e5355; (b) Tundo, P.; Rossi, L.; Loris, A. J. Org. Chem. 2005, 70, 2219e2224;
(c) Castro, E. A.; Pavez, P.; Santos, J. G. J. Org. Chem. 2003, 68, 9034e9039.
17. (a) Kumaran, E.; Santhi, M.; Balasubramainain, K. K.; Bhagavathy, S. Carbohydr.
Res. 2011, 346, 1654e1661; (b) Nagaraj, P.; Ramesh, N. G. Eur. J. Org. Chem. 2008,
4607e4614; (c) Descotes, G.; Martin, J.-C. Carbohydr. Res. 1977, 56, 168e172.
18. (a) Grossert, J. S.; Dubay, P. K.; Elwood, T. Can. J. Chem. 1985, 63, 1263e1267; (b)
Meek, J. S.; Fowler, J. S. J. Org. Chem. 1968, 33, 3422e3424.
11. (a) Ramesh, N. G.; Balasubramanian, K. K. Eur. J. Org. Chem. 2003, 4477e4487; (b)
Booma, C.; Balasubramanian, K. K. J. Chem. Soc., Chem. Commun.1993,1394e1395.
12. Pearson, R. G. J. Am. Chem. Soc. 1963, 85, 3533e3539.
13. Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1828e1836.
14. For reviews on HSAB: (a) Woodward, S. Tetrahedron 2002, 58, 1017e1050; (b)
Pearson, R. G. Inorg. Chim. Acta 1995, 240, 93e98; (c) Ho, T.-L. Tetrahedron 1985,
41, 3e86; (d) Ho, T.-L. Chem. Rev. 1975, 75, 1e20.
15. For some recent reports on HSAB-driven selectivity in organic reactions: (a)
Zhu, Y.; Zhai, C.; Yang, L.; Hu, W. Eur. J. Org. Chem. 2011, 1113e1124; (b) Rosa-
milia, A. E.; Arico, F.; Tundo, P. J. Org. Chem. 2008, 73, 1559e1562; (c) Gamba-
corta, A.; Tofani, D.; Loreta, M. A.; Gasperi, T.; Bernini, R. Tetrahedron 2006, 62,