H2SO4-silica: An eco-friendly heterogeneous catalyst for the differential protection of myo-inositol hydroxyl groups

Article abstract of DOI:10.1039/c3ra40506k

There is enormous interest in myo-inositol derivatives as they serve as precursors for the synthesis of several biologically important phosphoinositols, natural products, catalyst, supramolecular architectures etc. However the presence of six secondary hy

Full text of DOI:10.1039/c3ra40506k

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H2SO4-silica: an eco-friendly heterogeneous catalyst for
the differential protection of myo-inositol hydroxyl
groups3
Cite this: RSC Advances, 2013, 3,
7321
Amol M. Vibhute and Kana M. Sureshan*
There is enormous interest in myo-inositol derivatives as they serve as precursors for the synthesis of several
biologically important phosphoinositols, natural products, catalyst, supramolecular architectures etc.
However the presence of six secondary hydroxyl groups of similar reactivity warrants protection of inositol
hydroxyl groups for effective synthesis. Acid catalyzed protection of inositol hydroxyl groups as orthoesters
or ketals are the most commonly used protecting strategy in inositol chemistry. Traditionally,
homogeneous acid catalysts such as para-toluene sulfonic acid (p-TSA) or camphorsulfonic acid (CSA)
are used for these transformations. While the reversible nature of these reactions necessitates the catalyst
removal, aqueous work up cannot be employed for their removal as the products are water soluble. We
have circumvented this problem by using H2SO4-silica as the solid supported catalyst, which can be
removed by filtration, for these transformations. Treatment of myo-inositol with trialkylorthoesters in
presence of H2SO4-silica under normal conditions resulted in esterification at the least reactive hydroxyl
group (C2-OH) giving exclusively the corresponding 2-O-acyl-myo-inositol. By doing the reaction in a rotary
evaporator under reduced pressure resulted in the formation of the corresponding orthoesters, wherein
three hydroxyl groups of inositol are protected simultaneously. We could synthesize different myo-inositol
orthoesters 6–10 in excellent yields by this method. Monoketaliziation of myo-inositol with one equivalent
of 1,1-dimethoxycyclohexane or 2,2-dimethoxypropane in presence of H2SO4-silica under similar
conditions resulted in the simultaneous protection of 1-OH and 2-OH giving the 1,2-O-cyclohexylidene-
myo-inositol (11) or 1,2-O-isopropylidene-myo-inositol (12) in excellent yields. Also, diketalization of myo-
inositol with 2,2-dimethoxypropane gave three diketals namely (¡)-1,2:4,5-di-O-isopropylidene-myo-
inositol (17), (¡)-1,2:5,6-di-O-isopropylidene-myo-inositol (18) and (¡)-1,2:3,4-di-O-isopropylidene-myo-
inositol (19) in considerable yields. Similarly when dimethoxycyclohexane was used, the dicyclohexylidene
derivatives (¡)-1,2:4,5-di-O-cyclohexylidene-myo-inositol (20), (¡)-1,2:5,6-di-O-cyclohexylidene-myo-inosi-
tol (21) and (¡)-1,2:3,4-di-O-cyclohexylidene-myo-inositol (22), were obtained in good yield. While the
yields of 1,2:3,4-di-O-alkylidene-myo-inositols are negligibly small by other known methods, interestingly,
our method give these diketals in good yields and hence can be exploited synthetically. Thus by using a
cheap, eco-friendly, easy-to-make and easy-to-handle H2SO4-silica as the catalyst, we could tune the
conditions to make mono-protected, di-protected, tri-protected or tetra-protected inositol derivatives.
These strategies can be applied for the economic synthesis of various key intermediates of inositol for
various purposes.
Received 29th January 2013,
Accepted 5th March 2013
DOI: 10.1039/c3ra40506k
www.rsc.org/advances
After the Ca2+ release, through the activation of its receptor
located on endoplasmic reticulum, IP3 get recycled through
Introduction
The hydrolysis of membrane bound phosphatidylinositol-4,5-
bisphosphate [PI(4,5)P2], by the action of phospholipase C
produces D-myo-inositol-1,4,5-trisphosphate (IP3), which is a
second messenger involved in intracellular calcium release.1
the action of several kinases and phosphatases with the
intermediacy of several lower and higher inositol phosphates
[(IPns), Table 1].2 Recently, the pyrophosphorylated inositols
(PPmIPn) are shown to exist in cells and have been implicated
in several biological processes.3 Also, several phosphatidylino-
sitol phosphate lipids [(PIPns), Table 1] are involved in various
cellular events. For instance, phosphatidylinsitol-3,4,5-trispho-
sphate [PI(3,4,5)P3] is involved in Akt signalling and signal
transduction,4 non-capacitative calcium influx5 and cell
School of Chemistry, Indian Institute of Science Education and Research
Thiruvananthapuram, Kerala, 695016, India. E-mail: kms@iisertvm.ac.in;
Fax: +914712597427
Electronic supplementary information (ESI) available: The spectral data of
3
compound 8 and 15. See DOI: 10.1039/c3ra40506k
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Table 1 Examples of naturally occurring inositol phosphates and phosphatidy-
linositol phosphates
IPs/PIPs
R1
R2
R3
R4
R5
R6
22
22
I(1)P
I(3)P
I(4)P
I(1,3)P2
PO3
H
H
PO322
PO322
PO322
PO322
PO3
H
H
H
H
H
H
H
H
H
H
H
PO3
H
PO3
H
H
H
H
PO3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
22
22
22
22
Scheme 1 The acid catalyzed ketalization of myo-inositol.
I(1,4)P2
PO322
22
22
I(1,4,5)P3
I(1,3,4)P3
I(1,3,4,5)P4
I(3,4,5,6)P4
I(1,3,4,5,6)P5
I(1,2,3,4,5,6)P6 PO3
1-IP7
5-IP7
1,5-IP8
PI
PI(4)P
PI(3)P
PO322 PO3
22
PO322 PO322
H
the 1,2-O-alkylidene-myo-inositol (2) as the sole product in very
good yields.20 Diketalization of myo-inositol gives a mixture of
three diketals 3–5 along with the monoketal 2 in moderate
yields.21 Several elegant strategies to separate these isomers or
improve their relative yields have been reported.21b,22
Ketalization strategy has been successfully used in phosphoi-
nositol synthesis,23 natural product synthesis13a–c and in the
synthesis of myo-inositol based supramolecular entities.12a
Another commonly used strategy is orthoesterification of
myo-inositol. Acid mediated transorthoesterification of myo-
inositol (Scheme 2) with trialkylorthoester lead to the
simultaneous protection of three hydroxyl groups giving myo-
inositol 1,3,5-orthoester in very good yields.24 In addition to
the simultaneous protection of three hydroxyl group in a
single operation, orthoesterification leads to a conformational
inversion (ring flip) rendering the otherwise least reactive
axial-2-OH to a more reactive equatorial-OH. So the relative
reactivity of hydroxyl groups can be inverted by orthoester-
ification. Several methods for selective functionalization of
one or two of the remaining three hydroxyl groups of myo-
inositol orthoesters have been reported.24d,25 Myo-inositol
orthoesters have served as the precursors for the synthesis of
phosphoinositols,26 metal complexing agents27 and other
synthetic derivatives.12b,13e,28
PO322 PO322 PO322
22
H
PO322 PO322 PO322 PO322
22
PO322
PO322 PO322 PO322 PO322
22
PO322 PO322 PO322 PO322 PO322
32
P2O5
PO322 PO322 PO322 PO3
PO322
22
32
PO3
PO322 PO322 PO322 P2O532 PO322
32
P2O5
PO3
H
H
H
H
H
H
H
H
PO3
H
H
PO3
H
PO322
PO3
H
PO3
H
PO3
H
H
H
P2O5
H
H
PO3
H
H
H
H
H
H
H
H
PO22DAG
PO22DAG
PO22DAG
PO22DAG
PO22DAG
PO22DAG
PO22DAG
PO22DAG
22
22
22
H
22
PI(5)P
PO322
PI(3,5)P2
PI(3,4)P2
PI(4,5)P2
PI(3,4,5)P3
PO3
22
PO322
H
22
PO322 PO322
22
PO3
PO3
PO3
regulation.6 However, a clear picture about the cellular role
played by many phosphoinositols is lacking.7,8 Two major
hurdles in studying the function of these various phosphoi-
nositols are the scarcity of these natural products and their
tedious isolation from the natural sources. There is a huge
demand for the supply of these materials and their analogues
in sufficient quantities for biological exploration. Thus, the
chemical synthesis of various phosphoinositols and their
unnatural analogues constitute an important area of
research.9,10 Additionally, the realization of synthetic inositol
derivatives as catalysts,11 supramolecular scaffolds,12 inter-
mediates for natural product synthesis13 etc. gave further
momentum to inositol chemistry.
As myo-inositol (1) has six secondary hydroxyl groups,
selective functionalization of a particular hydroxyl group or a
select group of hydroxyl groups is a major challenge.14 In order
to synthesize the required phosphoinositol or natural product,
protection and deprotection15 of inositol hydroxyl groups are
unavoidable. Unlike in sugars, where there is reactivity
difference between the anomeric, primary and secondary
hydroxyl groups and hence can be protected selectively,16
achieving selectivity between different secondary hydroxyl
groups of myo-inositol is rather difficult.
Results and discussion
The commonly used acid catalysts for orthoesterification and
ketalization are p-toluene sulfonic acid (p-TSA),21b and
camphorsulfonic acid (CSA). These homogeneous catalysts
need to be neutralized and removed from the reaction mixture
Two important strategies14,17 for the initial protection of
myo-inositol are the acid catalyzed ketalization18 and orthoes-
terification.19 Acid mediated ketalization of myo-inositol
(Scheme 1) with one equivalent of ketalizing reagent gives
Scheme 2 The acid catalyzed orthoesterification of myo-inositol.
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Fig. 1 Adsorption of water molecules on the H2SO4-silica.
Scheme 3 Proposed mechanism for the orthoester cleavage in presence of acid
and water.
inert atmosphere, the presence of water adsorbed on silica,
due to its high affinity for water cannot be avoided.33 The
initially formed orthoester I undergoes acid catalysed cleavage
to form dioxenium cation II. Since this dioxenium cation II has
three hydroxyl groups at less favorable axial orientation, it
undergoes ring flipping to form boat conformation for both
heterocyclic and inositol rings. The boat form then undergoes
structural rearrangement and gives a relatively stable dioxole-
nium cation III. The trace amount of water adsorbed on the
H2SO4-silica (Fig. 1) might attack the dioxolenium cation III to
form unstable orthoacid IV, which undergoes cleavage to give
axial 2-O-ester V.34
From the mechanisms explained previously and the similar
studies on orthoester hydrolysis35 it is clear that, presence of
orthoester in contact with acid and water (adsorbed on silica,
Fig. 1) gives 2-O-ester product. To overcome this problem, it is
necessary to remove the water and alcohol (methanol/ethanol
generated during the reaction, Scheme 4) from the reaction
mixture.
Thus we carried out the orthoesterification reaction by
heating the flask (at 60 uC), containing a suspension of myo-
inositol, freshly made and dried H2SO4-silica (4 h in oven at
130 uC) and trialkyl orthoester in appropriate solvent (DMSO/
DMF) in a rotary evaporator under reduced pressure (400
mbar) for about 1 h. By this method, trace amount of water on
silica gel and the alcohol generated during the reaction will be
removed as soon as generated. Satisfyingly, we could isolate
the expected orthoester product in good yield after purification
(Table 2).
as these hygroscopic catalysts or their salt absorb water and
facilitate the hydrolysis of the ketal or orthoester to inositol
(backward reaction). However, aqueous work-up cannot be
used, as the products (orthoesters or ketals) with several
hydroxyl groups are water soluble. Also, the reaction by using
p-toluene sulfonic acid usually requires higher temperature,
longer reaction time and tedious work-up.29 Noting the
importance of the protected inositol derivatives and also
limitations of the commonly used catalysts, there is need of a
simple and eco-friendly catalyst for the protection of inositol
hydroxyl groups to provide building blocks for the synthesis of
phosphoinositols and other natural products. We herein
report the use of very cheap, eco-friendly and easily available
H2SO4-silica as the catalyst for the high-yielding ketalization
and orthoesterification of inositol hydroxyl groups.
Though H2SO4-silica has been used as a heterogeneous
acidic catalyst for various transformations,30 it has not been
used for the protection of inositol hydroxyl groups. Initially
our goal was to protect the myo-inositol hydroxyl groups by
transorthoesterification using H2SO4-silica as the catalyst.
Thus myo-inostiol was treated with trimethylorthobenzoate
in presence of H2SO4-silica in DMSO, expecting the orthoes-
terified product, myo-inositol 1,3,5-orthobenzoate (6).
Surprisingly, instead of 6, we got 2-O-benzoyl-myo-inositol as
the exclusive product in good yield. Also, similar results were
obtained with other orthoesters; in every case we got the
corresponding 2-O-acyl-myo-inositol. Careful monitoring of the
reaction revealed that the initially formed orthoester under-
goes acid catalysed orthoester cleavage to form 2-O-acyl-myo-
inositol. These facts were illustrated in our recent commu-
nication.31 Prior to our report, Potter et al. reported a TFA
mediated hydrolysis of myo-inositol orthobenzoate to 2-
O-benzoyl-myo-inositol and this has been exploited in the
efficient synthesis of myo-inositol pentaphosphate.32
Adopting this method, the reaction of myo-inositol with
trimethylorthobenzoate in presence of H2SO4-silica in DMSO,
We have proposed a mechanism (Scheme 3) similar to that
was proposed by Potter et al. and the mechanism involves the
addition of a water molecule to dioxolenium cation III.
Though the reaction was carried out in a dry solvent under
Scheme 4 Acid catalyzed cleavage of orthoester in presence of alcohol.
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Table 2 Synthesis of myo-inositol 1,3,5-orthoesters
Scheme 5 Reagents and conditions: (a) 1,1-dimethoxycyclohexane (1 equiv),
H2SO4-silica, DMF, 60 uC on a rotavapor (400 mbar), 30 min, 81%; (b) 2,2-
dimethoxypropane (1 equiv), H2SO4-silica, DMF, 60 uC on a rotavapor (400
mbar), 30 min, 83%.
Entry Reagent
Solvent
Time (h) Product
Yield (%)
83
1
2
3
4
PhC(OMe)3
DMSO
n-C4H9C(OEt)3 DMSO
n-C3H7C(OEt)3 DMF
0.5
0.5
1.0
1.5
6, R = Ph
7, R = n-C4H9 75
8, R = n-C3H7 80
CH3C(OMe)3
DMF
9, R = Me
79
1,2:3,4-di-O-cyclohexylidene-myo-inositol (22, 22%, Scheme 7).
These diketals were separated and purified according to the
reported method.21,22
1) HC(OMe)3 1) DMF
2) Ac2O 2) Pyridine
5
3.0
10
75
While the yields of ketal derivatives 17, 18, 20 and 21, by
our method, were comparable to the yields reported in the
literature, interestingly, the yields of (¡)-1,2:3,4-di-
satisfyingly gave the myo-inositol 1,3,5-orthobenzoate (6) in
good yield. The orthopentanoate 7 and orthobutanoate 8 were
also obtained in good yields by the same method (Table 2). In
all these cases, the reaction mixture was quenched by adding a
NaHCO3 solution, diluted with water and extracted with ethyl
acetate and passed through a filtration column and evaporated
to obtain the pure orthoester. In the case of orthoacetate, the
reaction solvent had to be evaporated as the water soluble
orthoacetate could not be extracted to ethyl acetate layer. Thus
the reaction was carried out in dry DMF as the solvent. The
orthoacetate 9 was isolated in good yield by evaporating the
reaction solvent and passing the crude through a small bed of
silica gel. As the orthoformate is more hydrophilic and more
labile (under the post-reaction treatment), it was isolated as its
triacetate derivative 10 after acetylation. Thus we could show
that H2SO4-silica can be used as a general catalyst for
orthoesterification of myo-inositol. While the yields of ortho-
benzoate 6 and orthopentanoate 7 are comparable with
previously reported yields, the yield of orthoacetate 9 was
better than the reported yield.
O-isopropylidene-myo-inositol
(19)
and
(¡)-1,2:3,4-di-
O-cyclohexylidene-myo-inositol (22) were higher. Since the
1,2:3,4-diketals are formed in very lower yields by existing
methods, they have not been exploited for phosphoinositol
synthesis. The fact that our method offers easy access to these
conveniently protected derivatives in moderate yields, opens
avenues for possible exploitation of these diketals for the
synthesis of various phosphoinositols and other derivatives.
Conclusions
In conclusion, we have reported, for the first time, the use of
H2SO4-silica as a cheap heterogeneous catalyst for the efficient
protection of myo-inositol hydroxyl groups under mild reaction
conditions. The number of hydroxyl groups being protected
and the regioselectivity can be tuned by changing the reaction
The success with orthoesterification prompted us to explore
the H2SO4-silica mediated ketalization of myo-inositol.
Treatment of myo-inositol (1) with one equivalent of 1,1-
dimethoxycyclohexane gave (¡)-1,2-O-cyclohexylidene-myo-
inositol 11 in good yield (Scheme 5). Similarly, the reaction
of 1 with 2,2-dimethoxypropane in DMF in presence of H2SO4-
silica on a rotavapor selectively gave (¡)-1,2-O-isopropylidene-
myo-inositol (12) in excellent yield (Scheme 5). Our method
using H2SO4-silica is operationally simpler than the previously
reported methods using homogeneous catalysts.20a,b
Treatment of myo-inositol with
5 equivalent of 2,2-
dimethoxypropane in DMF in presence of H2SO4-silica on a
rotary evaporator gave a mixture of diketals; (¡)-1,2:4,5-di-
O-isopropylidene-myo-inositol
O-isopropylidene-myo-inositol
(17),
(18) and
(¡)-1,2:5,6-di-
(¡)-1,2:3,4-di-
O-isopropylidene-myo-inositol (19, Scheme 6). Similarly, dike-
talization with 5 equivalent of 1,1-dimethoxycyclohexane gave
(¡)-1,2:4,5-di-O-cyclohexylidene-myo-inositol (20, 25%), (¡)-
1,2:5,6-di-O-cyclohexylidene-myo-inositol (21, 40%) and (¡)-
Scheme 6 Reagents and conditions: (a) 2,2-dimethoxypropane (5 equiv),
H2SO4-silica, DMF, 60 uC, on rotavapor (400 mbar), 30 min; (b) Benzoyl chloride,
pyridine, 0–rt, 2 h; (c) NaOMe, MeOH, reflux, 30 min.
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multiplet (m)], coupling constants [Hz], integration and peak
identification). All NMR signals were assigned on the basis of
1H NMR, 13C NMR, COSY, HMBC and HMQC experiments. 13
C
spectra were recorded with complete proton decoupling.
Carbon chemical shifts are reported in ppm (d) relative to
TMS with the respective solvent resonance as the internal
standard. All NMR data were collected at 25 uC. Melting points
were determined using Stuart SMP30 melting point apparatus
and are uncorrected. Flash column chromatography was
performed using silica gel (200–400 mesh, FINAR make). All
reactions were carried out under argon or nitrogen atmo-
sphere employing oven dried glassware.
Scheme 7 Reagents and conditions: (a) 1,1-dimethoxycyclohexane (5 equiv),
H2SO4-silica, DMF, 60 uC, on rotavapor (400 mbar) 45 min, (20, 25%; 21, 40%;
22, 22%).
Preparation of H2SO4-silica
conditions and the reagent. Reaction of myo-inositol with
trialkylorthoesters in presence of H2SO4-silica under normal
reaction set-up gives the 2-O-acyl-myo-inositol (mono pro-
tected) exclusively in very good yields. But the same reaction
under reduced pressure in a rotary evaporator leads to the
simultaneous protection of three hydroxyl groups giving the
corresponding myo-inositol 1,3,5-orthoester in excellent yields.
Such control on the number of hydroxyl groups being
protected and regioselectivity just by changing the reaction
conditions is not reported so far. Ketalization of myo-inositol
with one equivalent of ketalization reagent (2,2-dimethoxypro-
pane or 1,1-dimethoxycyclohexane) leads to the protection of
two hydroxyl groups providing the 1,2-O-alkylidene-myo-inosi-
tol 11 and 12 in excellent yields. Use of excess reagent leads to
simultaneous protection of four hydroxyl groups leading to a
mixture of three separable diketals namely; (¡)-1,2:4,5-di-
O-alkylidene myo-inositol (13 or 20), (¡)-1,2:5,6-di-
O-alkylidene myo-inositol (18 or 21) and (¡)-1,2:3,4-di-
O-alkylidene myo-inositol (19 or 22). All these reactions could
be scaled-up to 10 g scale. In general, ketalization with 1,1-
dimethoxycyclohexane gave better yields. The use of H2SO4-
silica requires shorter reaction time, simple work-up and gives
the products in good yields. It is clear that use of H2SO4-silica
affords diverse kinds of protected inositols, which are
important for phosphoinositol synthesis, natural product
synthesis etc.
A slurry of 20 g of silica gel (200–400 mesh) with 150 mL of
diethyl ether was made in a 250 mL RB flask. To this slurry, 1
mL of conc. H2SO4 was added very slowly with vigorous
shaking over a period of 30 min. The ether was evaporated
under reduced pressure and the free flowing silica was heated
at 130 uC in an oven for 4 h. The resulting solid was kept under
high vacuum at room temperature for 2 h and was stored in a
desiccator for further use.
Preparation of orthoesters
Myo-inositol 1,3,5-orthobenzoate (6)
A mixture of myo-inositol (1) (0.36 g, 2 mmol), trimethylortho-
benzoate (0.41 mL, 2.4 mmol) and H2SO4-silica (50 mg) in dry
DMSO (5 mL) was heated on a rotary evaporator at 60 uC under
reduced pressure (400 mbar). When the TLC showed complete
disappearance of the starting material, the reaction was cooled
to room temperature under nitrogen atmosphere. Solid
NaHCO3 (0.1 g) was added to the reaction mixture. The
reaction mixture was filtered through a Wattman filter paper
and washed with ethyl acetate (2 6 10 mL). The filtrate and
the washings were diluted with ethyl acetate (30 mL) and
washed with water (2 6 50 mL) and finally with brine. The
organic layer was dried over anhyd. sodium sulfate and
concentrated on a rotary evaporator. The thick syrup thus
obtained was chromatographed using ethyl acetate as eluent
to get 6 as a white solid (0.44 g, 83%). The NMR data was
indistinguishable from the reported data.24a
Myo-inositol 1,3,5-orthopentanoate (7)
Experimental section
A mixture of myo-inositol (1) (0.36 g, 2 mmol), triethylortho-
pentanoate (0.55 mL, 2.4 mmol) and H2SO4-silica (50 mg) in
dry DMSO (5 mL) was heated on rotary evaporator at 60 uC
under reduced pressure (400 mbar). When the TLC showed
complete disappearance of the starting material, the reaction
was cooled to room temperature under nitrogen atmosphere.
Solid NaHCO3 (0.1 g) was added to the reaction mixture. The
reaction mixture was filtered through a Wattman filter paper
and washed with ethyl acetate (2 6 10 mL). The filtrate and
washings were diluted with ethyl acetate (40 mL) and washed
with water (2 6 50 mL) and finally with brine. The organic
layer was dried over sodium sulfate and evaporated under
reduced pressure. The thick syrup thus obtained was
chromatographed using ethyl acetate as eluent, to get 7 as a
Materials and general methods
All the chemicals were purchased from TCI, Aldrich or AVRA
Chemicals. The solvents were purchased from Merck and were
used after distillation. Chromatograms were visualized under
UV light and by dipping plates into either phosphomolybdic
acid in MeOH or anisaldehyde in ethanol, followed by heating.
The 1H NMR, COSY, HMBC and HMQC spectra were recorded
on a Bruker (500 MHz) NMR spectrometer. Proton chemical
shifts are reported in ppm (d) relative to internal tetramethyl-
silane (TMS, d 0.0 ppm) or with the solvent reference relative to
TMS employed as the internal standard (CDCl3, d 7.26 ppm;
D2O, d 4.79 ppm). Data are reported as follows: chemical shift
(multiplicity [singlet (s), doublet (d), triplet (t), quartet (q), and
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white solid (0.37 g, 75%). The NMR data was indistinguishable
from the reported data.24c
anhydride (0.75 mL, 8 mmol). The reaction was allowed to stir
at room temperature for 2 h. When TLC showed complete
disappearance of the orthoformate, the reaction was quenched
by adding a few drops of water. The reaction mixture was
concentrated and the residue was dissolved in ethyl acetate (50
mL) and washed with water (2 6 50 mL) and finally with brine.
The organic layer was dried over sodium sulfate and
concentrated under reduced pressure. The thick syrup thus
obtained was chromatographed using 30% ethyl acetate in
petroleum ether as the eluent, to get 10 as a white solid (0.47 g,
75%). The 1H NMR data was indistinguishable from the
reported data.19
Myo-inositol 1,3,5-orthobutanoate (8)
A mixture of myo-inositol (1) (0.36 g, 2 mmol), triethylortho-
butanoate (0.52 mL, 2.4 mmol) and H2SO4-silica (50 mg) in dry
DMF (5 mL) was heated on a rotary evaporator at 60 uC under
reduced pressure (400 mbar). When the TLC showed complete
disappearance of the starting material, the reaction was cooled
to room temperature under nitrogen atmosphere. Solid
NaHCO3 (0.1 g) was added to the reaction mixture. The
reaction mixture was filtered through a Wattman filter paper
and washed with ethyl acetate (2 6 10 mL). The combined
filtrate and washings were diluted with ethyl acetate (50 mL)
and washed with water (2 6 50 mL) and finally with brine. The
organic layer was dried over sodium sulfate and evaporated
under reduced pressure. The thick syrup thus obtained was
chromatographed using ethyl acetate as eluent, to get 8 as a
white solid (0.59 g, 80%). MP 131–133 uC; elemental analysis
(found: C, 51.41; H, 7.17 for C10H16O6 calculated C, 51.72; H,
6.94%) 1H NMR (500 MHz, DMSO-d6) d 5.40 (d, J = 6.0 Hz, 2H,
H-1, H-3), 5.12 (d, J = 6.0 Hz, 1H, H-2), 4.22 (bs, 2H, H-4, H-6),
4.03 (bs, 1H, H-5), 3.97-3.96 (m, 3H, C2, C4 & C6-OHs), 1.53-
1.50 (m, 2H, CH2), 1.40-1.36 (m, 2H, CH2), 0.84 (t, J = 7.4 Hz,
3H, CH3). 13C NMR (125 MHz, DMSO-d6) d 113.42, 80.04,
74.33, 72.56, 63.05, 44.18, 20.99, 19.12.
( )-1,2-O-cyclohexylidene-myo-inositol (11)
To a mixture of myo-inositol (1) (0.36 g, 2 mmol), and 1,1-
dimethoxycyclohexane (0.31 mL, 2 mmol), in dry DMF (10 mL),
H2SO4-silica (50 mg) was added and the mixture was heated on
a rotary evaporator at 60 uC under reduced pressure (400
mbar). After 30 min, triethylamine (1 mL) was added to
quench the reaction. The unreacted myo-inositol and the
catalyst were filtered off. The filtrate was evaporated to get the
known 11 (0.42 g, 81%) as a white solid.20b
( )-1,2-O-isopropylidene-myo-inositol (12)
To a mixture of myo-inositol (1) (0.36 g, 2 mmol), and 2,2-
dimethoxypropane (0.25 mL, 2 mmol), in dry DMF (10 mL) was
added 50 mg H2SO4-silica. The mixture was then heated on a
rotary evaporator at 60 uC under reduced pressure (400 mbar).
After 30 min when reaction mixture became light yellow in
color, triethylamine (1 mL) was added to quench the reaction.
The unreacted myo-inositol and catalyst were filtered and
washed with methanol. The filtrate was evaporated to get 12
(0.365 g, 83%) as a white solid. The NMR data was identical to
the reported data.20a
Myo-inositol 1,3,5-orthoacetate (9)
A mixture of myo-inositol (1) (0.36 g, 2 mmol), trimethy-
lorthoacetate (0.3 mL, 2.4 mmol) and H2SO4-silica (50 mg) in
dry DMF (10 mL) was heated on a rotary evaporator at 60 uC
under reduced pressure (400 mbar). When TLC showed
complete disappearance of the starting material, the reaction
was cooled to room temperature under nitrogen atmosphere
and was quenched by adding solid NaHCO3 (0.1 g). The
reaction mixture was filtered through a Wattman filter paper
and washed with ethyl acetate (2 6 10 mL). The combined
filtrate and washings were evaporated on a rotary evaporator to
get a thick residue. The residue was then chromatographed on
a silica gel column using ethyl acetate as the eluent, to get 9 as
a white solid (0.32 g, 79%). The NMR data was indistinguish-
able from the data reported in the literature.24d
( )-3,6-Di-O-benzoyl-1,2:4,5-di-O-isopropylidene-myo-inositol
(13), ( )-3,4-di-O-benzoyl-1,2:5,6-di-O-isopropylidene-myo-
inositol (14), ( )-5,6-di-O-benzoyl-1,2:3,4-di-O-isopropylidene-
myo-inositol (15)
A
mixture of myo-inositol (1) (10 g, 55.5 mmol), 2,2-
dimethoxypropane (34 mL, 277.7 mmol), and H2SO4-silica
(0.2 g) in DMF (100 mL) was heated to 60 uC for 30 min on a
rotary evaporator (400 mbar). When the reaction was complete,
the reaction mixture was neutralized using triethylamine (2
mL). The catalyst was filtered off and the low boiling solvents
were evaporated under reduced pressure. The resulting thick
mass was dissolved in pyridine (100 mL) and then benzoyl
chloride (50 mL) was added drop-wise using an addition
funnel with stirring at 0 uC during 15-20 min. The reaction
mixture was stirred for an additional 2 h. The precipitated
solid was filtered and washed successively with pyridine,
water, and acetone. The white solid was then washed with
diethyl ether to get 13 (6.4 g, 25%) as a white solid. The NMR
data was indistinguishable from the reported data.36 The
combined filtrate and all the washings were neutralized with 1
N HCl solution (100 mL) and extracted with DCM. The organic
layer was concentrated to get a thick gummy residue. The thick
residue was purified by column chromatography using 15%
acetone–hexane as the eluent to get 3,4-dibenzoate 14 and 5,6-
2,4,6-Tri-O-acetyl-myo-inositol 1,3,5-orthoformate (10)
A mixture of myo-inositol (1) (0.36 g, 2 mmol), trimethylortho-
formate (0.26 mL, 2.4 mmol) and H2SO4-silica (50 mg) in dry
DMF (10 mL) was heated on a rotary evaporator at 60 uC under
reduced pressure (400 mbar). When TLC showed complete
disappearance of the starting material, the reaction was cooled
to room temperature under inert atmosphere. The reaction
was quenched by the addition of solid NaHCO3 (0.1 g). The
reaction mixture was filtered through a Wattman filter paper
and washed with ethyl acetate (2 6 10 mL). The combined
filtrate and washings were evaporated on a rotary evaporator to
get thick residue. This residue was co-evaporated with toluene
(2 6 20 mL) and pyridine (20 mL) then dried under vacuum
for 1 h. The residue was then dissolved in dry pyridine (20 mL)
and cooled to 0 uC. To this solution, a catalytic amount (5 mg)
of DMAP was added followed by slow addition of acetic
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dibenzoate 15 as
a mixture and further elution gave
( )-1,2:3,4-Di-O-isopropylidene-myo-inositol (19)
tetrabenzoate 16. The mixture of 14 and 15 was dissolved in
minimum amount of ethyl acetate (10 mL) and a little amount
of petroleum ether (15 mL) was added. After 12 h, the pellet-
like crystals of 15 were seen at the bottom of the flask. The
supernatant solution was decanted and the crystals of 15 (3.8
g, 15%) were collected. The decanted solution was concen-
trated to get a thick mass. This thick mass was again
recrystallized form ethyl acetate and petroleum ether to get
pure known dibenzoate 14 (5.1 g, 20%).21b
A mixture of 15 (1 g, 2.1 mmol) and sodium methoxide (0.14 g,
2.5 mmol) in MeOH (20 mL) was refluxed for 1.5 h. When the
TLC showed complete disappearance of the starting material,
the reaction was allowed to cool to room temperature and then
quenched by the addition of Dowex 50-ion exchange resin. The
reaction mixture was filtered through a Wattman filter paper
and washed with methanol (2 times). The combined filtrate
was concentrated on a rotary evaporator to get thick gummy
mass. The thick mass was dissolved in dichloromethane (5–6
mL) and precipitated with petroleum ether (15 mL). The
supernatant solution was decanted and the precipitate was
then washed with 20% ethyl acetate in petroleum ether to
remove residual methyl benzoate. The precipitate was then
dried to get the known 19 (0.52 g, 94%) as white solid.37
Data of 15
1
MP 95–97 uC. H NMR (500 MHz, DMSO-d6) d 7.96 (d, J = 7.5
Hz, 2H, Ar-H), 7.91 (d, J = 7.5 Hz, 2H, Ar-H), 7.67 (t, J = 7.3 Hz,
2H, Ar-H), 7.53 (dd, J = 7.7 & 7.6 Hz, 4H, Ar-H), 5.53 (dd, J = 9.2
& 5.5 Hz, 1H, Ins-H), 5.43 (dd, J = 5.2 & 5.0 Hz, 1H, Ins-H), 4.77
(dd, J = 5.7 & 3.1 Hz, 1H, Ins-H), 4.62 (dd, J = 5.5 & 5.1 Hz, 1H,
Ins-H), 4.30 (dd, J = 9.8 & 9.5 Hz, 1H, Ins-H), 4.19 (dd, J = 10.0 &
2.9 Hz, 1H, Ins-H), 1.58 (s, 3H, CH3), 1.44 (s, 3H, CH3), 1.39 (s,
3H, CH3), 1.35 (s, 3H, CH3). 13C NMR (125 MHz, DMSO-d6) d
165.73, 164.49, 133.75, 129.38, 129.25, 129.09, 128.82, 128.77,
111.55, 110.84, 77.57, 75.44, 74.45, 74.25, 72.65, 71.17, 26.81,
26.65, 26.62, 24.85. Elemental analysis (found: C, 66.87; H,
6.10 for C26H28O8, calculated C, 66.66; H, 6.02%)
( )-1,2:4,5-Di-O-cyclohexylidene-myo-inositol (20), ( )-1,2:5,6-
di-O-cyclohexylidene-myo-inositol (21), and ( )-1,2:3,4-di-
O-cyclohexylidene-myo-inositol (22)
A mixture of myo-inositol (1, 5 g, 27.7 mmol), 1,1-dimethox-
ycyclohexane (21.3 mL, 138 mmol) and catalytic amount of
H2SO4-silica (0.2 g) in DMF (100 mL) was heated to 60 uC under
reduced pressure (400 mbar). After 45 min, the reaction
mixture was quenched by addition of triethylamine. The
catalyst and the unreacted myo-inositol was filtered off. The
filtrate was concentrated under reduced pressure to get a thick
gummy mass, which was dissolved in dichloromethane (100
mL) and washed with water, sodium bicarbonate and finally
with brine. The organic layer was dried over sodium sulfate
and concentrated to get a thick syrup. This syrup was dissolved
in minimum amount of acetone (15 mL) and then 30 mL of
petroleum ether was added. After 2–3 h, the crystals of the
known 20 (2.4 g, 25%) were collected.38 The remaining
acetone–petroleum ether solution was concentrated and syrup
thus obtained was purified by flash column chromatography
(200–400 mesh silica gel, 2 : 1 chloroform–acetone as eluent)
to get the known (¡)-1,2:3,4-di-O-cyclohexylidene-myo-inositol
(22) (2.1 g, 22%) and (¡)-1,2:5,6-di-O-cyclohexylidene-myo-
inositol (21) (3.8 g, 40%).21a
( )-1,2:4,5-Di-O-isopropylidene-myo-inositol (17)
A mixture of 13 (5 g, 10.5 mmol) and sodium methoxide (0.69
g, 12.8 mmol) in MeOH (100 mL) was refluxed for 1.5 h. When
the TLC showed complete disappearance of the starting
material, the reaction was allowed to cool to room temperature
and then quenched by adding Dowex 50-ion exchange resin.
The reaction mixture was filtered through a Wattman filter
paper and washed with methanol (2 times). The combined
filtrate was concentrated on a rotary evaporator to get a thick
gummy mass. The thick mass was then dissolved in
dichloromethane (20 mL) and precipitated by the addition of
petroleum ether (40 mL). The supernatant solution was
decanted. The precipitate was then washed with 20% ethyl
acetate in petroleum ether to remove residual methyl
benzoate. The precipitate was then dried to get the known
17 (2.6 g, 93%) as a white solid.21b
Acknowledgements
( )-1,2:5,6-Di-O-isopropylidene-myo-inositol (18)
KMS thanks the Department of Science and Technology (DST),
India, for financial support and Ramanujan Fellowship. AMV
thanks University Grants Commission (UGC), India for Junior
Research Fellowship (JRF) during this work.
A mixture of 14 (5 g, 10.5 mmol) and sodium methoxide (0.69
g, 12.8 mmol) in MeOH (100 mL) was refluxed for 1.5 h. When
the TLC showed complete disappearance of the starting
material, the reaction was allowed to cool to room temperature
and then quenched by the addition of Dowex 50-ion exchange
resin. The reaction mixture was filtered through a Wattman
filter paper and washed with methanol (2 times). The
combined filtrate was concentrated on a rotary evaporator to
get thick oily mass. The thick mass was dissolved in
dichloromethane (20 mL) and precipitated with petroleum
ether (40 mL). The supernatant solution was decanted and the
precipitate was then washed with 20% ethyl acetate in
petroleum ether to remove residual methyl benzoate. The
precipitate was then dried to get the known 18 (2.65 g, 95%) as
a white solid.21b
Notes and references
1 B. V. L. Potter and D. Lampe, Angew. Chem., Int. Ed. Engl.,
1995, 34, 1933.
2 (a) A. J. Hatch and J. D. York, Cell, 2010, 143, 1030; (b) G. Di
Paolo and P. De Camilli, Nature, 2006, 443, 651.
3 (a) T. Wundenberg and G. W. Mayr, Biol. Chem., 2012, 393,
979; (b) A. M. Riley, H. Wang, J. D. Weaver, S. B. Shears and
B. V. L. Potter, Chem. Commun., 2012, 48, 11292; (c)
A. Saiardi, R. Bhandari, A. C. Resnick, A. M. Snowman and
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 7321–7329 | 7327

View Article Online
Paper
S. H. Snyder, Science, 2004, 306, 2101; (d) R. F. Irvine and
M. J. Schell, Nat. Rev. Mol. Cell Biol., 2001, 2, 327.
4 (a) B. Vanhaesebroek, S. J. Leevers, G. Panayotou and M.
D. Waterfield, Trends Biochem. Sci., 1997, 22, 267; (b) L.
E. Rameh and L. C. Cantley, J. Biol. Chem., 1999, 274, 8347.
5 P. H. Tseng, H. P. Lin, H. Hu, C. Wang, M. X. Zhu and C.
S. Chen, Biochemistry, 2004, 43, 11701.
RSC Advances
17 Though there are other elegant methods to protect inositol
hydroxyl groups, either the generality of these methods
have not been established or the yields are poor; (a)
Y. Watanabe, T. Fujimoto, T. Shinohara and S. Ozaki, J.
Chem. Soc., Chem. Commun., 1991, 428; (b) S. Yamauchi,
M. Hayashi and Y. Watanabe, Synlett, 2009, 14, 2287.
18 (a) S. J. Angyal, M. E. Tate and S. D. Gero, J. Chem. Soc.,
1961, 4116; (b) J. Gigg, R. Gigg, S. Payne and R. Conant,
Carbohydr. Res., 1985, 142, 132.
19 H. W. Lee and Y. Kishi, J. Org. Chem., 1985, 50, 4402.
20 (a) F. Fabrizio, R. Enrico, A. Paulon and O. D. Lucchi,
Tetrahedron Lett., 2007, 47, 4835; (b) P. J. Garegg and
B. Lindberg, Carbohydr. Res., 1988, 173, 205; (c) C.
M. Nkambule, N. W. Kwezi, H. H. M. G. Kinfe Nokwequ,
D. W. Gammon, S. Oscarson and E. Karlsson, Tetrahedron,
2011, 67, 618.
6 B. A. Hemmings, Science, 1997, 277, 534.
7 (a) M. Wu, B. E. Dul, A. J. Trevisan and D. Fiedler, Chem.
Sci., 2013, 4, 405; (b) A. Chakraborty, M. A. Koldobskiy, N.
T. Bello, M. Maxwell, J. J. Potter, K. R. Juluri, D. Maag,
S. Kim, A. S. Huang, M. J. Dailey, M. Saleh, A. M. Snowman,
T. H. Moran, E. Mezey and S. H. Snyder, Cell, 2010, 143,
897.
8 Y.-S. Lee, S. Mulugu, J. D. York and E. K. O’Shea, Science,
2007, 316, 109.
21 (a) P. J. Garegg, T. Iversen, R. Johansson and B. Lindberg,
Carbohydr. Res., 1984, 130, 322; (b) S. M. Khersonsky and Y.
T. Chang, Carbohydr. Res., 2002, 337, 75.
22 S. K. Chung, Y. Ryu, Y. T. Chang, D. Whang and K. Kim,
Carbohydr. Res., 1994, 253, 13.
23 (a) J. P. Vacca, S. J. deSolms, J. R. Huff, D. C. Billington,
R. Saker, J. J. Kulagowaski and I. M. Mawer, Tetrahedron,
1989, 45, 5679; (b) S. Ozaki, Y. Watanabe, T. Ogasawara,
Y. Kondo, N. Shiotani, H. Nishii and T. Matsuki,
Tetrahedron Lett., 1986, 27, 3157; (c) S. K. Chung, Y.
T. Chang and K. H. Sohn, Chem. Commun., 1996, 163; (d) S.
K. Chung, Y. U. Kwon, J. H. Shin, Y. T. Chang, C. Lee, B.
G. Shin, K. C. Kim and M. J. Kim, J. Org. Chem., 2002, 67,
5626.
9 B. M. Swarts and Z. Guo, J. Am. Chem. Soc., 2010, 132, 6648.
10 (a) K. M. Sureshan, A. M. Riley and B. V. L. Potter,
Tetrahedron Lett., 2007, 48, 1923; (b) K. M. Sureshan,
T. Yamasaki, M. Hayashi and Y. Watanabe, Tetrahedron:
Asymmetry, 2003, 14, 1771; (c) K. M. Sureshan and
Y. Watanabe, Tetrahedron: Asymmetry, 2004, 15, 1193.
11 (a) A. Falshaw, G. J. Gainsford, C. Lensink, A. T. Slade and
L. J. Wright, Polyhedron, 2007, 26, 329; (b) T. Akiyama,
M. Hara, K. Fuchibe, S. Sakamoto and K. Yamaguchi,
Chem. Commun., 2003, 1734; (c) G. Cousins, A. Falshaw and
J. O. Hoberg, Org. Biomol. Chem., 2004, 2, 2272; (d) A.
M. Ramadan, J. M. C. Sala and T. N. Parac-Vogt, Dalton
Trans., 2011, 40, 1230.
12 (a) D. Blunk, N. Bongartz, C. Stubenrauch and V. Gartner,
Langmuir, 2009, 25, 7872; (b) T. H. Kim, M. Giles and A.
B. Holmes, Chem. Commun., 2000, 2421; (c) Y. Watanabe,
T. Miyasou and M. Hayashi, Org. Lett., 2004, 6, 1547; (d) K.
M. Sureshan, K. Yamaguchi, Y. Sei and Y. Watanabe, Eur. J.
Org. Chem., 2004, 4703; (e) A. Hosoda, Y. Miyake,
E. Nomura and H. Taniguchi, Chem. Lett., 2003, 32, 1042.
13 (a) T. Suzuki, T. S. Suzuki, I. Yamada, Y. Koashi, K. Yamada
and N. Chida, J. Org. Chem., 2002, 67, 2874; (b) K. Okada,
K. Hashizume, H. Tanino, H. Kakoi and S. Inoue, Chem.
Pharm. Bull., 1989, 37, 791; (c) S. Inoue, K. Okada,
A. Tanino, K. Hashizume and I. Kakoi, Tetrahedron, 1994,
50, 2129; (d) N. Chida and J. Synth, J. Synth. Org. Chem. Jpn.,
2000, 58, 642; (e) K. Sato, S. Akai, N. Sugita, T. Ohsawa,
T. Kogure, H. Shoji and J. Yoshimura, J. Org. Chem., 2005,
70, 7496; (f) A. Krief, W. Dumont, D. Billen, J.-J. Letesson,
P. Lestrate, P. J. Murphy and D. Lacroix, Tetrahedron Lett.,
2004, 45, 1461; (g) Y.-K. Kwon, C. Lee and S.-K. Chung, J.
Org. Chem., 2002, 67, 3327.
24 (a) G. Bhosekar, C. Murali, R. G. Gonnade, M.
S. Shashidhar and M. M. Bhadbhade, Cryst. Growth Des.,
2005, 5, 1977; (b) A. M. Riley, H. Y. Godage, M. F. Mahon
and B. V. L. Potter, Tetrahedron: Asymmetry, 2006, 17, 171;
(c) M. A. Biamonte and A. Vasella, Helv. Chim. Acta, 1998,
81, 688; (d) S. W. Garrett, C. Liu, A. M. Riley and B. V.
L. Potter, J. Chem. Soc., Perkin Trans. 1, 1998, 1367.
25 (a) K. M. Sureshan and M. S. Shashidhar, Tetrahedron Lett.,
2001, 42, 3037; (b) D. C. Billington, R. Baker, J.
J. Kulagowski, I. M. Mawer, J. P. Vacca, S. J. Desolms and
J. R. Huff, J. Chem. Soc., Perkin Trans. 1, 1989, 1423; (c) K.
M. Sureshan and M. S. Shashidhar, Tetrahedron Lett., 2000,
41, 4185; (d) P. Andersch and M. P. Schneider, Tetrahedron:
Asymmetry, 1993, 4, 2135; (e) T. Banerjee and M.
S. Shashidhar, Tetrahedron Lett., 1994, 35, 8053; (f) K.
M. Sureshan, S. Devaraj and M. S. Shashidhar, Tetrahedron,
2009, 65, 2703.
26 (a) J. M. Swarbrick, S. Cooper, G. Bultynckb and P. R.
J. Gaffney, Org. Biomol. Chem., 2009, 7, 1709; (b) S. J. Mills,
K. Backers, C. Erneux and B. V. L. Potter, Org. Biomol.
Chem., 2003, 1, 3546; (c) Y. Watanabe, T. Ogasawara,
H. Nakahira, T. Matsuki and S. Ozaki, Tetrahedron Lett.,
1988, 29, 5259; (d) S. Ballereau, S. N. Poirier,
G. Guillemette, B. Spiess and G. Schlewer, J. Chem. Soc.,
Perkin Trans. 1, 1998, 1859; (e) S. J. Conway and G. J. Miller,
Nat. Prod. Rep., 2007, 24, 687; (f) M. D. Best, H. Zhang and
G. D. Prestwich, Nat. Prod. Rep., 2010, 27, 1403; (g) M.
S. Shashidhar, ARKIVOC, 2002, 7, 63; (h) F. Song, J. Zhang,
Y. Zhao, W. Chen, L. Li and Z. Xi, Org. Biomol. Chem., 2012,
10, 3642.
14 (a) K. M. Sureshan, M. S. Shashidhar, T. Praveen and
T. Das, Chem. Rev., 2003, 103, 4477; (b) B. K|lbas and
M. Balci, Tetrahedron, 2011, 67, 2355.
15 T. W. Greene and P. G. M. Wuts, Protective Groups in
Organic Synthesis, 3rd edn, Wiley, New York, 1999.
16 (a) Y. Demizu, Y. Kubo, H. Miyoshi, T. Maki, Y. Matsumura,
N. Moriyama and O. Onomura, Org. Lett., 2008, 10, 5075;
(b) T. Kawabata, W. Muramatsu, T. Nishio, T. Shibata and
H. Schedel, J. Am. Chem. Soc., 2007, 129, 12890; (c) C.-
C. Wang, J.-C. Lee, S.-Y. Luo, S. S. Kulkarni, Y.-W. Huang,
C.-C. Lee, K.-L. Chang and S.-C. Hung, Nature, 2007, 446,
896.
7328 | RSC Adv., 2013, 3, 7321–7329
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
27 (a) K. M. Sureshan, M. S. Shashidhar and A. J. Varma, J.
Chem. Soc., Perkin Trans., 2001, 2, 2298; (b) K. M. Sureshan,
M. S. Shashidhar and A. J. Varma, J. Org. Chem., 2002, 67,
6884; (c) P.-M. Leo, C. Morin and C. Philouze, Beilstein J.
Org. Chem., 2010, 6, 1022.
28 B. P. Gurale, M. S. Shashidhar and R. G. Gonnade, J. Org.
Chem., 2012, 77, 5801.
29 T. Desai, J. Gigg, R. Gigg, E. Mart|n-Zamora and N. Schnetz,
Carbohydr. Res., 1994, 258, 135.
30 (a) M. A. Zolfigol, Tetrahedron, 2001, 57, 9509; (b)
B. Mukhopadhyay, Tetrahedron Lett., 2006, 47, 4337; (c) V.
K. Rajput and B. Mukhopadhyay, Tetrahedron Lett., 2006,
47, 5939; (d) S. Mandal, H. M. Gauniyal, K. Pramanik and
B. Mukhopadhyay, J. Org. Chem., 2007, 72, 9753.
31 A. M. Vibhute, A. Vidyasagar, S. Sarala and K. M. Sureshan,
Chem. Commun., 2012, 48, 2448.
32 H. Y. Godage, A. M. Riley, T. J. Woodman and B. V.
L. Potter, Chem. Commun., 2006, 2989.
33 W. Hertl and M. L. Hair, Nature, 1969, 223, 1150.
34 It has been known that orthoacids of cis diols undergoe
rearrangement to give axial ester and equatorial hydroxyl
group. (a) J. F. King and A. D. Allbutt, Can. J. Chem., 1970,
48, 1754; (b) R. U. Lemieux and H. Driguez, J. Am. Chem.
Soc., 1975, 97, 4069.
35 P. W. K. Lam and R. A. McClellamd, J. Chem. Soc., Chem.
Commun., 1980, 883.
36 S. K. Chung and Y. Ryu, Carbohydr. Res., 1994, 258, 145.
37 K. M. Sureshan, T. Murakami, T. Miyasou and
Y. Watanabe, J. Am. Chem. Soc., 2004, 126, 9174.
38 I. D. Spiers, C. H. Schwalbe, A. J. Blake, K. R. H. Solomons
and S. Freeman, Carbohydr. Res., 1997, 302, 43.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 7321–7329 | 7329