The orientation of the β-hydroxyl group controls the diastereoselectivity during the hydride reduction and Grignard reaction of inososes

Article abstract of DOI:10.1016/j.tet.2013.04.081

A comparison of the results of the Grignard reaction and the hydride reduction of the carbonyl group of epi- and scyllo-inososes reveals that the extent of diastereoselectivity of these reactions is decided by the orientation of the β-hydroxyl group (or i

Full text of DOI:10.1016/j.tet.2013.04.081

Tetrahedron 69 (2013) 5144e5151
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The orientation of the b-hydroxyl group controls the
diastereoselectivity during the hydride reduction and Grignard
reaction of inososes
,
Rajendra C. Jagdhane a y, Madhuri T. Patil a, Shobhana Krishnaswamy b,
,
Mysore S. Shashidhar a
*
a The Division of Organic Chemistry, National Chemical LaboratorydCouncil of Scientific and Industrial Research (CSIR), Pashan Road,
Pune 411 008, India
b The Center for Materials Characterization, National Chemical LaboratorydCouncil of Scientific and Industrial Research (CSIR), Pashan Road,
Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A comparison of the results of the Grignard reaction and the hydride reduction of the carbonyl group of
Received 27 October 2012
Received in revised form 15 April 2013
Accepted 17 April 2013
epi- and scyllo-inososes reveals that the extent of diastereoselectivity of these reactions is decided by the
orientation of the b-hydroxyl group (or its derivative). Presence of an axial b-hydroxyl group generally
results in the formation of relatively larger amount of the axial alcohol as a result of the reduction of the
carbonyl group. The possible reasons for the observed differences in diastereoselectivity between the
reactions of these isomeric epi- and scyllo-inososes have been discussed. The sequence of reactions re-
ported here provides convenient access to C-alkylated inositols, such as iso-laminitol and iso-mytilitol as
well as 2-O-methyl epi-inositol, an epimer of the naturally occurring ononitol.
Available online 23 April 2013
Keywords:
Cyclitol
Diastereoselectivity
Grignard
Ó 2013 Elsevier Ltd. All rights reserved.
Inositol
Nucleophile
Reduction
1. Introduction
diastereo- and enantio-selectivities based on molecular proper-
ties, such as electronic and steric effects as well as the ability of
Extensive research to understand the role of phosphoinositols1
in cellular functions of eukaryotic systems over the past three
decades resulted in the synthesis of a wide variety of cyclitols,
their derivatives and analogs.2 Naturally abundant, myo-inositol
is often used as a starting material for the synthesis of phos-
phoinositols, diastereomeric cyclitols as well as natural products
and their analogs.3 Regiospecific oxidation of inositol hydroxyl
groups to the corresponding inosose is of significance since the
latter provides access to isomeric inositol derivatives (by hydride
reduction), inosamines (by reductive amination) and C-alkyl
inositols (e.g., by Grignard reaction). Nucleophilic addition to
carbonyl groups is a ubiquitous reaction in organic synthetic
protocols. This reaction has been well investigated and
attempts have been made to rationalize or predict the observed
the substrate molecules to chelate with metal ions present in
reagents or catalysts.4 Crystal structure correlation has also been
utilized to understand the geometry of the approach of the nu-
cleophiles to the carbonyl group, during the addition reaction.5
We recently reported an instance of protecting group directed
diastereoselective reduction of an inosose.6 The present work
shows the crucial role played by the orientation of a neighboring
hydroxyl group (OH) or its protected derivative (OPG) in con-
trolling the diastereoselectivity during the hydride reduction and
Grignard reaction of inososes. We explored these reactions in our
endeavor to obtain C-alkylated inositols, which are being tested
as agents to intervene in cellular processes to facilitate the de-
velopment of drugs for various diseases.7 Reactivity and product
selectivity during the reactions of small molecules containing
several other functional groups (as in inositols and their de-
rivatives), are expected to be influenced by each other. Knowledge
of such effects would be of immense utility in planning synthetic
sequences involving heavily functionalized small molecules,
since such an understanding often allows the prediction of the
structure of the product.
* Corresponding author. E-mail address: ms.shashidhar@ncl.res.in (M.S.
Shashidhar).
y
Present address: The Department of Chemistry, University of Saskatchewan, 110
Science Place, Saskatoon S7N 5C9, Canada.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.081

R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
5145
2. Results and discussion
selective,6 while the reduction of the scyllo-inosose 5 gives a mix-
ture of diastereomeric inositol derivatives. The ratio of the di-
astereomeric products estimated by 1H NMR spectroscopy on
reduction of the inososes 1 and 5 were, respectively, 98/2 (14/16)
and 80/20 (18/20). The isolated yield of the products 17 and 19 were
79% and 16%, respectively. This is similar to the outcome of their
Grignard reaction (Scheme 1) in that, the C-methylation of the
Results of the reaction of epi- and scyllo-inosose derivatives with
methyl magnesium iodide are shown in Scheme 1. Addition of
methyl magnesium iodide to the epi-inosose 16 was completely
selective (to yield 2) while the addition to scyllo-inosose 5 gave
a mixture of 6 and 7. The C-methyl inositol derivatives 6 and 7 could
be separated by column chromatography. Global deprotection of 2
and 6 gave iso-laminitol (3) and iso-mytilitol (8), respectively. Both
3 and 8 were characterized as their acetates 4 and 9, respectively,
and their structure established by single-crystal X-ray diffraction
analysis.
inosose 1 having a b-axial benzyloxy group is more selective than
the corresponding inosose 5 having a
b-equatorial benzyloxy
group.
OR1
OH
R1O
BnO
BnO
OR1
R1
O
OBn
OBn
b, c
Me
Me
OBn
a
R1O
OR1
OBn
BnO
BnO
OR1
OBn
OBn
2
1
3 H
Ac
4
OH
OBn
Me
O
OBn
OBn
Me
OBn
a
OH
OBn
BnO
BnO
BnO
BnO
BnO
OBn
BnO
OBn
OBn
7
OBn
6
5
b, d
Scheme 3. Reagents and conditions: (a) NaBH4, DCM/MeOH, 0 ꢀC-ambient temp,
30 min; (b) pyridine, Ac2O, DMAP, reflux, 20 h.
OH
R2
H
R2O
R2O
R2O
8
Me
The epi-inosose 1 was prepared as reported earlier6 and the
synthesis of scyllo-inosose 5 from the known diol 218 is shown in
Scheme 4. The myo- and scyllo-inositol derivatives 17 and 19 were
converted to their acetates 18 and 20, respectively. These acetates
were useful for the estimation (by 1H NMR spectroscopy) of the
ratio of the diastereomeric inositols formed on reduction of the
scyllo-inosose 5, as the two diastereomeric acetates 18 and 20 ex-
OR2
9 Ac
OR2
Scheme 1. Reagents and conditions: (a) MeMgI, THF, 0 ꢀC-ambient temp, 93% (for 2),
76% (for 6), 18% (for 7); (b) THF/EtOH/H2O/TFA, 20% Pd(OH)2/C, H2 (60 psi); (c) pyridine,
DMAP, Ac2O, reflux, 18 h, 88%; (d) as in (c) at ambient temp, 88%.
Sodium borohydride reduction of the epi-inosose 1 gave the epi-
inositol derivative 10;6 O-methylation and global deprotection of 10
gave racemic iso-ononitol 12, which was characterized as its penta
acetate 13 (Scheme 2). Structure of 13 was confirmed by single-
crystal X-ray diffraction analysis. The synthesis described herein
provided racemic 2-O-methyl epi-inositol (12) in an overall yield of
41% in nine steps starting from myo-inositol. This represents the
first synthesis of 2-O-methyl epi-inositol (12, iso-ononitol), which is
an epimer of the naturally occurring ononitol.
hibit characteristic peaks at
NMR spectra.
d
2.17 and 1.83, respectively, in their 1H
BnO
OR1
BnO
O
OBn
α
OBn
a
β
OBn
OBn
BnO
BnO
BnO
1
BnO
R1
H
10
11
Scheme 4. Reagents and conditions: (a) benzene, NaH, BnBr, reflux, 1.5 h, 78%; (b)
pyridine, DMAP, Ac2O, reflux, 18 h, 94% (for 18) and 95% (for 20); (c) IBX, ethyl acetate,
reflux, 6 h, 95%; (d) benzene, TPP, imidazole, 4-NO2BzOH, 89%; (e) 1% NaOH, THF/
MeOH, 98%; (f) DMF, NaH, BnBr, 90%.
b
Me
c, d
A comparison of the structure of the two inososes 1 and 5 shows
that they differ only in the orientation of the benzyloxy group at the
-position with respect to the keto group (axial in 1 and equatorial
in 5). We wondered whether the effect of the orientation of the b-
OR group on the diastereoselectivity in the reactions shown in
Schemes 1 and 3 was real or incidental. Hence we compared the
outcome of the reactions of a carbonyl group in molecular systems
similar to 1 and 5, encountered previously in our laboratory as well
as elsewhere.
R2O
OMe
OR2
R2
H
OR2
b
12
R2O
OR2
13 Ac
Scheme 2. Reagents and conditions: (a) NaBH4, DCM/MeOH, 0 ꢀC-ambient temp,
30 min, 94%;6 (b) DMF, NaH, MeI, 96%; (c) THF/EtOH/H2O/TFA, Pd(OH)2/C, H2 (60 psi),
20 h; (d) pyridine, Ac2O, DMAP, reflux, 18 h, 83%.
a and b refer to the position of the
inositol ring carbon atoms with reference to the carbonyl carbon atom, in these
inososes.
A comparison of the result of the hydride reduction of inososes
containing a
left-half of the scheme have a b-OH or OR group in the axial ori-
b
-OR group is shown in Scheme 5.9 The inososes in the
Sodium borohydride reduction of the scyllo-inosose 5 gave
a mixture of the myo- and scyllo-inositol derivatives 17 and 19. A
comparison of the reduction of the epi- and scyllo-inososes
(Scheme 3) reveals that reduction of the epi-inosose 1 is highly
entation while the inososes in the right-half have the same sub-
stituent in the equatorial orientation. Results of the hydride
reduction of these pairs of inososes clearly show that the

5146
R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
Scheme 5. Result of sodium borohydride reduction of inososes, which differ only in the orientation of the b-OR group. For the reduction of 27 and 36, yield of the major product is
shown. See Ref. 9 for details.
diastereoselectivity for the formation of the axial alcohol is much
better when the -OR group is in the axial orientation.
Scheme 6 shows the result of the reduction of ketones having
-axial-OR group, for which exact comparison of the corre-
sponding ketone with -equatorial-OR group is not
available.9bed,10 However the last three ketones (56e58), which
have a -equatorial-OR group exhibit relatively less selectivity
during their reduction, reiterating the effect of the orientation of
the -OR group on the diastereoselectivity of addition to carbonyl
ketones having b-axial substituent does not correlate with the bulk
b
of the hydroxyl protecting group. For instance, perusal of the lit-
erature available12 on the reduction of silyl ether containing cy-
clohexanones reveals that the effect of the TBS group is similar to
a hydroxyl or a benzyl group (see 54, 55 in Scheme 6). If the se-
lectivity of reduction was completely dependent on the steric bulk
a
b
a
b
b
of the b-OR group, the reduction of silyl ether containing ketones
(such as 55) should have resulted in the formation of relatively
greater proportion of the axial alcohol, as compared to the inososes
carrying smaller groups (such as 54). This result suggests that al-
b
groups of inososes.
Scheme 7 shows the result of reductive amination of inososes.
All the inososes give the corresponding axial amine as the major
product.11 From the results shown in Schemes 5e7, it is clear that
though steric bulk of the b-OR group does play a role in deciding the
diastereoselectivity, it may not be the sole reason for the observed
diastereoselectivity during the reduction of these ketones.
the orientation of the
reochemical outcome of the addition of nucleophiles to the car-
bonyl group of inososes.
b
-OR group plays a decisive role in the ste-
The preferential equatorial approach of the nucleophile (facile
formation of the axial alcohol) can also be explained based on the
chelation of the metal ions present in the reaction medium leading to
the enhanced formation of the 1,3-diaxial diols. Experimental and
theoretical investigations13 on the complexation of metal ions with
inositols had revealed that cyclitols, which have a sequence of three
consecutive hydroxyl groups in the axialeequatorialeaxial ar-
rangement form complexes readily with metal ions. The suggestion
that the chelation of cations of the reducing agent (hydride or
Higher selectivity during the nucleophilic addition to the car-
bonyl group in inososes having a
b
-axial-OR group as compared to
-equatorial-OR group could arise due to the
-axial substituent, which could force the nu-
inososes having a
steric bulk of the
b
b
cleophile to approach the carbonyl group equatorially. However,
the degree of selectivity for the formation of the axial alcohol from
H
Ph
BnO
HO
OBn
PBBO
O
O
O
O
OPCB
O
O
O
O
O
OBn
O
OBn
O
OBn
AcO
OBn
OBn
BnO
BnO
BnO
TsO
O
O
AllO
OPMB
O
PMBO
OAll
OBn
OBn
OTs
44 (98%)
42 (100%)
45 (96%)
43 (100%)
47 (93%)
46 (95%)
HO
HO
HO
O
OH
HO
OH
OH
OBn
OH
OBn
O
OBn
PBBO
O
OPCB
O
OBn
OBn
OBn
BnO
O
OH
OH
OBn
OH
BnO
O
OH
OBn
BnO
OBn
OAc
OBn
53 (78%)
OH
51 (90%)
OBn
50 (90%)
48 (91%)
52 (87%)
49 (91%)
TBSO
OH
O
BnO
O
O
O
OBn
OPCB
Ph
MeO2C
TBSO
OBn
OBn
OBn
OAll
O
O
OH
O
O
OBn
OBn
58 (50%)
O
BDA
AllO
57 (50%)
56 (25%)
55 (71%)
54 (axial major)
Scheme 6. Ketones, which give axial alcohol as the major product on reduction with sodium borohydride. The extent of the axial alcohol obtained is shown in parenthesis. The last
three ketones (56e58), which lack
-OR group in the axial orientation are shown for comparison. See Refs. 9bed,10 for details. PMB¼CH2Ph(4-OMe), PBB¼CH2Ph(4-Br),
BDA¼butanediacetal, PCB¼CH2Ph(4-Cl).
b

R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
5147
HO
HO
OBn
X
OBn
NaBH4
OBn
OBn
OBn
O
Y
AcO
AcO
OBn
Na
71
72 X=OH; Y=H
73 X=H; Y=OH
(72:73=1:99)
X
BnO
NaBH4
OBn
OBn
HO
OBn
HO
O
Y
AcO
OBn
AcO
OBn
Na
74
75 X=OH; Y=H
76 X=H; Y=OH
(75:76=1:99)
Scheme 9. Diastereoselectivity of the reduction of ketones (with sodium borohydride),
which have alternate sites for metal ion chelation, do not depend on the orientation of
the b-hydroxyl group (marked in bold). The ratio of axial:equatorial alcohols formed
are shown in parenthesis. See Ref. 9d for details.
the involvement of a transition state with product-like geometry.14
However, further investigations are required to completely rule out
or rule in the involvement of chelation of metal ions during hydride
reduction of these inososes.
3. Conclusions
A comparative study of the hydride reduction and the Grignard
reaction of inososes reveals the role played by the orientation of
Scheme 7. Reductive amination (amine, NaBH3CN) and Grignard reaction (of 65 with
MeMgI) of inososes having a -OR group in the axial position. Isolated yields are shown
in parenthesis. See Ref. 11 for details.
b
the
b-OR group on the outcome of the diastereoselectivity of these
reactions. An axial orientation of the
b
-OR group results in better
diastereoselectivity during the addition of a nucleophile to the
carbonyl group. This comparative study also suggests the possi-
bility of a subtle role of the metal ions on the outcome of the
nucleophilic addition to a carbonyl group. We had earlier shown
that metal ions play a decisive role in the outcome of O-sub-
stitution reactions in partially protected inositol derivatives.15
Knowledge of such effects is valuable while planning a synthetic
scheme and could help to avoid or minimize the formation of
undesired isomeric products.
Grignard reagents) could be playing a significant role in the observed
stereoselectivity of these reactions is supported by the following
observations. (a) The reversal of the observed stereoselectivity of
inososes on reduction with sodium borohydride and tetramethy-
lammonium triacetoxyborohydride. The latter reagent gives the
equatorial alcohol as the major product since involvement of an in-
termediate, such as 68 precludes the chelation of the cation between
the carbonyl oxygen atom and the
b
-OR group (Scheme 8).9c,d,10a
4. Experimental section
AcO
O
OAc
H
B
HO
O
4.1. General experimental methods
OAc
OAc
b
O
General experimental methods are as reported earlier.15 All the
asymmetrically substituted myo-inositol derivatives reported are
racemic; however only one of the enantiomers is shown in schemes
for convenience and clarity.
OBn
OBn
OBn
BnO
67
OBn
68
BnO
a
4.2. Experimental procedure and characterization data for
compounds
HO
HO
OH
OAc
OAc
OH
OBn
OBn
4.2.1. Racemic 1,3,4,5,6-penta-O-benzyl-2-C-methyl epi-inositol
(2). To a stirred solution of penta-O-benzyl epi-inosose 16 (0.63 g,
1.00 mmol) inTHF (7 mL), methyl magnesium iodide (3 M solution in
ether, 0.5 mL, 1.5 mmol) was added at 0 ꢀC and the reaction mixture
stirred at 0 ꢀC for 15 min then at ambient temperature for 2 h. The
reaction mixture was cooled to 0 ꢀC and quenched by adding ethyl
acetate (0.5 mL) followed by aqueous ammonium chloride solution
(1 mL). The resulting mixture was concentrated under reduced
pressure and the residue obtained was worked up with ethyl ace-
tate. The crude product was purified by column chromatography
(silica gel 100e200 mesh; eluent, ethyl acetate/light petroleum,
3/22, v/v) to get 2 as a colorless solid (0.60 g, 93%); mp 147e150 ꢀC;
OBn
+
OBn
BnO
BnO
70
69
Scheme 8. Contrast in the reduction of inososes with borohydrides. (a) NaBH4d69/
70¼49/1; (b) Me4NBH(OAc)3d69/70¼1/99. See Refs. 9c,d,10a for details.
(b) Stereoselectivity of the reduction of inososes (such as 71 and
74, Scheme 9), in which alternate sites for metal ion chelation are
available, do not depend on the orientation of the b-OR group. As
mentioned earlier, metal ions tend to chelate better with 1,3-diaxial
hydroxyl groups.13
Furthermore, investigations on the mechanism and diaster-
eoselectivity on sodium borohydride reduction of ketones strongly
suggest the possibility of chelation of sodium ion to the ketone and
IR (Nujol): d 1.21 (s,
n
3500e3700 cmꢁ1; 1H NMR (200 MHz; CDCl3):
3H, CH3), 2.93 (d, J¼2.4 Hz, 1H, Ins H), 3.06 (d, J¼9.6 Hz, 1H, Ins H),
3.34e3.45 (dd, J1¼2.5 Hz, J2¼9.8 Hz, 1H, Ins H), 4.12 (t, J¼2.5 Hz, 1H,

5148
R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
Ins H), 4.20 (t, J¼9.8 Hz,1H, Ins H), 4.36e4.48 (m, 2H), 4.58e5.03 (m,
9H), 7.19e7.44 (m, 25H, Ar H) ppm; 13C NMR (50 MHz; CDCl3):
22.3
3/22, v/v) to get racemic 7 (0.023 g, 18%) and racemic 6 (0.098 g,
76%) as colorless solids. Data for 6: mp 103e106 ꢀC; IR (Nujol):
3557 cmꢁ1; 1H NMR (200 MHz; CDCl3):
1.23 (s, 3H, CH3), 2.12 (br s,
d
n
(CH3) 72.0 (CH2), 73.0 (CH2), 75.2 (CH2), 75.8 (CH2), 76.09 (CH2),
76.14 (Ins C), 76.8 (Ins C), 77.3 (Ins C), 80.7 (Ins C), 84.2 (Ins C), 127.4
(Ar C),127.5 (Ar C),127.6 (Ar C),127.7 (Ar C),127.8 (Ar C),128.0 (Ar C),
128.08 (Ar C), 128.15 (Ar C), 128.2 (Ar C), 128.3 (Ar C), 128.4 (Ar C),
137.3 (Ar C), 137.5 (Ar C), 138.2 (Ar C), 138.3 (Ar C), 138.7 (Ar C); el-
emental analysis calcd for C42H44O6: C 78.23, H 6.88; found C 78.43;
H 6.96%.
d
1H, D2O exchangeable, OH), 3.21 (d, J¼9.6 Hz, 2H, Ins H), 3.54 (t,
J¼9.6 Hz, 1H, Ins H), 3.99 (t, J¼9.5 Hz, 2H, Ins H), 4.64 (d, J¼10.9 Hz,
2H, CH2Ph), 4.80e5.03 (m, 8H, CH2Ph), 7.21e7.40 (m, 25H, Ar
H) ppm; 13C NMR (100 MHz; CDCl3):
d 23.0 (CH3), 75.1 (Ins C-2),
75.78 (CH2), 75.84 (CH2), 76.1 (CH2), 82.88 (Ins C), 82.93 (Ins C), 83.3
(Ins C), 127.52 (Ar C), 127.57 (Ar C), 127.7 (Ar C), 127.8 (Ar C), 128.3
(Ar C), 128.4 (Ar C), 137.9 (Ar C), 138.6 (Ar C) ppm; elemental
analysis calcd for C42H44O6: C 78.23, H 6.88; found C 77.81; H 6.97%.
4.2.2. Racemic1,2,3,4,5,6-hexa-O-acetyl-2-C-methyl-epi-inositol(4). The
racemic pentabenzyl ether 2 (0.10 g, 0.16 mmol), THF (2 mL), water
(0.50 mL), EtOH (2 mL), and trifluoroacetic acid (TFA, 0.50 mL) were
taken in a hydrogenation bottle and 20% Pd(OH)2/C (0.050 g) was
added in one portion. The reaction mixture was stirred in an
atmosphere of hydrogen (60 psi) at ambient temperature for 20 h.
The reaction mixture was then diluted with aqueous ethanol
(1/1,10 mL) and filtered through a small bed of Celite. The Celite bed
was washed with hot water and ethanol (2ꢂ5 mL) alternately. The
combined filtrate was evaporated under reduced pressure and the
residue was co-evaporated with absolute ethanol (2ꢂ5 mL) to get
crude racemic 2-C-methyl epi-inositol 3 (0.032 g), which was used
in the next step.
Data for 7: mp 160e163 ꢀC; IR (Nujol):
NMR (400 MHz; CDCl3):
n
3500e3600 cmꢁ1
;
1H
d
1.30 (s, 3H, CH3), 2.18 (br s, 1H, D2O ex-
changeable, OH), 3.46 (d, J¼9.8 Hz, 2H, Ins H), 3.53 (t, J¼9.2 Hz, 2H,
Ins H), 3.62 (t, J¼9.1 Hz, 1H, Ins H), 4.79e4.94 (m, 10H, CH2Ph),
7.23e7.38 (m, 25H, Ar H) ppm; 13C NMR (100 MHz; CDCl3):
d 17.6
(CH3), 75.78 (CH2), 75.84 (CH2), 76.0 (Ins C), 76.1 (CH2), 82.8 (Ins C),
83.5 (Ins C), 84.8 (Ins C), 127.65 (Ar C), 127.69 (Ar C), 127.9 (Ar C),
128.40 (Ar C),128.43 (Ar C),138.4 (Ar C),138.8 (Ar C) ppm; elemental
analysis calcd for C42H44O6: C 78.23, H 6.88; found C 77.94; H 6.93%.
4.2.5. 1,3,4,5,6-Penta-O-acetyl-2-C-methyl-myo-inositol (9). The 2-
C-methyl-myo-inositol 6 (0.92 g, 1.43 mmol), THF (6 mL), ethanol
(3 mL), water (1.5 mL), and TFA (1.50 mL) were taken in a hydro-
genation bottle and 20% Pd(OH)2/C (0.75 g) was added in one
portion. The hydrogenolysis reaction was carried out as in the
preparation of 4; the crude 2-C-methyl-myo-inositol (8, 0.27 g)
obtained was used in the next step.
A mixture of the crude 3 (0.032 g), pyridine (2 mL), DMAP
(0.01 g), and acetic anhydride (0.27 mL, 2.88 mmol) was refluxed
for 18 h. The reaction mixture was cooled to ambient temperature
and quenched by adding few pieces of ice. The solvent was evap-
orated under reduced pressure and the residue obtained was
worked up with ethyl acetate. The crude product obtained was
purified by column chromatography (silica gel 100e200 mesh;
eluent, ethyl acetate/light petroleum, 1/2, v/v) to get 4 as a color-
less solid (0.061 g, 88%); mp 133e137 ꢀC (crystals by slow evapo-
Crude 8 (0.27 g) was acetylated (at ambient temperature) using
pyridine (5 mL), DMAP (0.01 g), and acetic anhydride (2.43 mL,
25.74 mmol) as in the preparation of
4 and purified by
column chromatography (silica gel 100e200 mesh; eluent, ethyl
acetate/light petroleum, 3/7, v/v) to get 9 as a colorless solid
(0.51 g, 88%); mp 133e137 ꢀC (crystals by slow evaporation of
ration of a warm methanol solution); IR (Nujol):
NMR (200 MHz; CDCl3): 1.25 (s, 3H, CH3), 1.99 (s, 3H, CH3), 2.02
n
1748 cmꢁ1 1H
;
d
(s, 3H, CH3), 2.09 (s, 3H, CH3), 2.11 (s, 3H, CH3), 2.14 (s, 3H, CH3),
2.16 (s, 3H, CH3), 4.95e5.07 (m, 2H, Ins H), 5.08e5.18 (dd, J¼3.8 Hz,
J2¼10.5 Hz, 1H, Ins H), 5.57 (t, J¼3.5 Hz, 1H, Ins H), 5.70 (t,
a warm methanol solution); IR (Nujol):
n
1746, 3200e3600 cmꢁ1
;
1.14 (s, 3H, CH3), 1.99 (s, 6H, CH3),
1H NMR (400 MHz; CDCl3):
d
2.01 (s, 3H, CH3), 2.13 (s, 6H, CH3), 2.15 (br s, 1H, OH, D2O ex-
changeable), 5.05 (d, J¼10.0 Hz, 2H, Ins H), 5.22 (t, J¼9.8 Hz, 1H, Ins
H), 5.53 (t, J¼9.9 Hz, 2H, Ins H) ppm; 13C NMR (100 MHz; CDCl3):
J¼10.2 Hz, 1H, Ins H) ppm; 13C NMR (50 MHz; CDCl3):
d 19.8 (CH3),
20.4 (CH3), 20.5 (CH3), 20.7 (CH3), 22.5 (CH3), 67.9 (Ins C), 68.4 (Ins
C), 70.1 (Ins C), 73.7 (Ins C), 82.8 (Ins C-4), 168.8 (CO), 169.4 (CO),
169.6 (CO), 169.7 (CO), 169.8 (CO), 170.0 (CO) ppm; elemental
analysis calcd for C19H26O12: C 51.12, H 5.87; found C 51.26; H
5.80%.
d
20.49 (CH3), 20.52 (CH3), 22.1 (CH3), 70.6 (Ins C), 70.7 (Ins C), 73.1
(Ins C), 73.4 (Ins C-2), 169.6 (CO), 169.73 (CO), 169.75 (CO) ppm;
elemental analysis calcd for C17H24O11: C 50.49, H 5.98; found C
50.26; H 5.66%.
4.2.3. 1,2,3,4,5-Penta-O-benzyl-scyllo-inosose (5). To a solution of 17
(2.70 g, 4.28 mmol) in ethyl acetate (30 mL), IBX (3.60 g, 12.8 mmol)
was added and the resulting mixture was refluxed for 6 h. The re-
action mixture was cooled to ambient temperature and filtered
through a bed of Celite. The filtrate was concentrated under reduced
pressure and the residue was purified by flash column chromatog-
raphy (silica gel 230e400 mesh; eluent, ethyl acetate/light petro-
leum, 3/22, v/v) to get the scyllo-inosose 5 (2.56 g, 95%) as a colorless
solid; mp 159e162 ꢀC (lit.16 mp 163e164 ꢀC).
4.2.6. Racemic 1,3,4,5,6-penta-O-benzyl-2-O-methyl-epi-inositol (11).
To a solution of the alcohol 106 (0.063 g, 0.10 mmol) in DMF (2 mL),
sodium hydride (0.005 g, 0.12 mmol) was added at 0 ꢀC. The re-
action mixture was stirred at 0 ꢀC for 10 min and then at ambient
temperature for 30 min. The reaction mixture was cooled again to
0
ꢀC and methyl iodide (9
mL, 0.15 mmol) was added to it. The re-
action mixture was allowed to come to ambient temperature and
stirred for 2 h. Few pieces of ice were added and the reaction
mixture was concentrated under reduced pressure. The residue
obtained was worked up with ethyl acetate. The crude product
obtained was purified by column chromatography (silica gel,
100e200 mesh; eluent, ethyl acetate/light petroleum, 3/22, v/v) to
get the racemic methyl ether 11 (0.062 g, 96%) as a gum. 1H NMR
4.2.4. 1,3,4,5,6-Penta-O-benzyl-2-C-methyl-myo-inositol (6) and 1-
C-methyl-2,3,4,5,6-penta-O-benzyl-scyllo-inositol (7). To a stirred
solution of scyllo-inosose 5 (0.13 g, 0.20 mmol) in THF (3 mL),
methyl magnesium iodide (3 M solution in ether, 0.10 mL,
0.30 mmol) was added at 0 ꢀC and the reaction mixture stirred at
(200 MHz; CDCl3):
Ins H), 3.69 (s, 3H, OCH3), 3.89 (br s, 1H, Ins H), 4.10 (br s, 1H, Ins H),
d
3.13 (t, J¼2.3 Hz, 1H, Ins H), 3.20e3.35 (m, 2H,
0
ꢀC for 15 min then at ambient temperature for 2 h. The reaction
4.31 (t, J¼9.7 Hz, 1H, Ins H), 4.43e4.99 (m, 10H, CH2Ph), 7.13e7.53
mixture was cooled to 0 ꢀC and quenched by adding ethyl acetate
(1 mL) followed by aqueous ammonium chloride solution. The
resulting mixture was concentrated under reduced pressure and
the residue obtained was worked up with ethyl acetate. The
products obtained were separated by column chromatography
(silica gel 100e200 mesh; eluent, ethyl acetate/light petroleum,
(m, 25H, Ar H) ppm; 13C NMR (50 MHz; CDCl3):
d 61.3 (CH3), 71.1
(CH2), 72.6 (CH2), 73.6 (CH2), 74.8 (Ins C), 75.8 (CH2), 78.1 (Ins C),
78.4 (Ins C), 79.2 (Ins C), 80.3 (Ins C), 80.7 (Ins C), 126.8 (Ar C), 127.1
(Ar C), 127.32 (Ar C), 127.35 (Ar C), 127.47 (Ar C), 127.54 (Ar C), 127.6
(Ar C), 127.7 (Ar C), 127.9 (Ar C), 128.1 (Ar C), 128.20 (Ar C), 128.24
(Ar C), 128.3 (Ar C), 137.9 (Ar C), 138.57 (Ar C), 138.63 (Ar C),

R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
5149
139.1(Ar C), 139.5 (Ar C) ppm; elemental analysis calcd for
C42H44O6: C 78.23, H 6.88; found C 78.36; H 7.21%.
a solution of benzyl bromide (0.7 mL, 5.86 mmol) in benzene (2 mL)
was added and the reaction mixture refluxed for 1.5 h. The reaction
mixture was then allowed to come to ambient temperature, a few
pieces of ice were added and the solvent was removed under re-
duced pressure. The residue obtained was worked up with ethyl
acetate. The filtrate was concentrated under reduced pressure and
the crude product obtained was purified by flash column chroma-
tography (silica gel 230e400 mesh; eluent, ethyl acetate/light pe-
troleum, 3/17, v/v) to get 17 (2.75 g, 78%) as a colorless solid;
mp 125e128 ꢀC (lit.16 mp 125e127 ꢀC).
4.2.7. Racemic 1,3,4,5,6-penta-O-acetyl-2-O-methyl epi-inositol (13).
The racemic pentabenzyl ether 11 (0.134 g, 0.21 mmol) was sub-
jected to hydrogenolysis in a mixture of THF (2 mL), ethanol (2 mL),
water (0.50 mL), and TFA (0.50 m L) in the presence of 20% Pd(OH)2/C
(0.050 g) as in the preparation of 4. The product obtained was co-
evaporated with absolute ethanol (2ꢂ5 mL) to get racemic 2-O-
methyl epi-inositol 12 (0.039 g).
The crude 12 (0.039 g) was acetylated using pyridine (2 mL),
DMAP (0.01 g), and acetic anhydride (0.30 mL, 3.15 mmol) as in the
preparation of 4. The product was purified by column chromatog-
raphy (silica gel 100e200 mesh; eluent, ethyl acetate/light petro-
leum, 1/2, v/v) to get 13 as a colorless solid (0.071 g, 83%);
mp 131e133 ꢀC (crystals by slow evaporation of a warm methanol
4.2.11. 1,3,4,5,6-Penta-O-benzyl-2-O-acetyl-myo-inositol (18). The
pentabenzyl ether 17 (0.063 g, 0.10 mmol) was acetylated using dry
pyridine (2 mL), DMAP (0.01 g), and acetic anhydride (20
mL,
0.20 mmol) as in the preparation of 4. The product obtained was
purified by column chromatography (silica gel 100e200 mesh; el-
uent, ethyl acetate/light petroleum, 3/22, v/v) to get 18 as a color-
less solid (0.063 g, 94%); mp 107e110 ꢀC (lit.17 mp 110e111 ꢀC).
solution); IR (Nujol):
2.00 (s, 3H, CH3), 2.03 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.10 (s, 3H,
n
1747 cmꢁ1 1H NMR (400 MHz; CDCl3):
;
d
CH3), 2.15 (s, 3H, CH3), 3.50 (s, 3H, OCH3), 3.92 (br s, 1H, Ins H),
4.89e4.95 (dd, J1¼3.3 Hz, J2¼10.3 Hz, 1H, Ins H), 4.98e5.05 (m, 2H,
Ins H), 5.54e5.58 (m, 1H, Ins H), 5.72 (t, J¼10.3 Hz, 1H, Ins H) ppm;
4.2.12. 1,2,3,4,5-Penta-O-benzyl scyllo-inositol (19). To a stirred so-
lution of the diol 23 (2.90 g, 5.36 mmol) in dry DMF (30 mL) was
added sodium hydride (0.215 g, 5.37 mmol) at 0 ꢀC. The reaction
mixture was stirred at 0 ꢀC for 10 min then at ambient temperature
for 30 min. The reaction mixture was again cooled to 0 ꢀC and
a solution of benzyl bromide (0.65 mL, 5.42 mmol) in DMF (2 mL)
was added and the reaction mixture was allowed to come to am-
bient temperature and stirred for 1 h. The reaction was quenched
by adding few pieces of ice and the solvent was removed under
reduced pressure. The residue obtained was worked up with
ethyl acetate. The crude product obtained was purified by flash
column chromatography (silica gel 230e400 mesh; eluent, ethyl
acetate/light petroleum, 3/17, v/v) to get 19 (3.03 g, 90%) as a col-
orless solid; mp 103e106 ꢀC (lit.16 mp 108e109 ꢀC).
13C NMR (100 MHz; CDCl3):
d 20.5 (CH3), 20.6 (CH3), 20.7 (CH3),
20.8 (CH3), 61.3 (OCH3), 67.4 (Ins C), 68.4 (Ins C), 68.5 (Ins C), 68.8
(Ins C), 71.3 (Ins C), 77.9 (Ins C), 169.5 (CO), 169.6 (CO), 169.7 (CO),
169.9 (CO), 170.6 (CO) ppm; elemental analysis calcd for C17H24O11
C 50.49, H 5.98; found C 50.36; H 5.81%.
:
4.2.8. Reduction of 1,2,3,4,5-penta-O-benzyl-scyllo-inosose 5. The
scyllo-inosose 5 (0.063 g, 0.10 mmol) was dissolved in DCM (4 mL)/
methanol (1 mL) mixture. To this solution sodium borohydride
(0.008 g, 0.20 mmol) was added in one portion at 0 ꢀC and the
reaction mixture was stirred at 0 ꢀC for 5 min then at ambient
temperature for 30 min. The reaction was quenched by adding
saturated solution of ammonium chloride (1 mL). The resulting
mixture was concentrated under reduced pressure and the residue
was worked up with ethyl acetate and the products were separated
by column chromatography (silica gel 230e400 mesh; eluent, ethyl
acetate/light petroleum, 3/22, v/v) to get the penta-O-benzyl-myo-
alcohol 1716 (0.050 g, 79%) and penta-O-benzyl-scyllo-alcohol 1916
(0.010 g, 16%).
4.2.13. 1-O-Acetyl-2,3,4,5,6-penta-O-benzyl-scyllo-inositol (20). The
pentabenzyl ether 19 (0.063 g, 0.10 mmol) was acetylated using dry
pyridine (2 mL), DMAP (0.01 g), and acetic anhydride (20
mL,
0.20 mmol) as in the preparation of 4. The crude product obtained
was purified by column chromatography (silica gel 100e200 mesh;
eluent, ethyl acetate/light petroleum, 3/22, v/v) to get 20 as a col-
orless solid (0.064 g, 95%); mp 118e122 ꢀC; IR (Nujol): 1741 cmꢁ1
n
;
4.2.9. Procedure for the reduction of inosose and estimation of the
products. The inosose (0.10 mmol) was dissolved in DCM (4 mL)/
methanol (1 mL) mixture. To this solution sodium borohydride
(0.20 mmol) was added in one portion at 0 ꢀC and the reaction
mixture stirred at 0 ꢀC for 5 min and then at ambient temperature
for 30 min. The reaction was quenched by adding aqueous am-
monium chloride solution. The resulting mixture was concentrated
under reduced pressure and the residue obtained was worked up
with ethyl acetate. The crude product obtained was acetylated as
below.
A mixture of the product obtained above, dry pyridine (2 mL),
DMAP (0.01 g), and acetic anhydride (0.20 mmol) was refluxed for
18 h. The reaction mixture was cooled to ambient temperature and
quenched by adding few pieces of ice. The solvent was evaporated
under reduced pressure and the residue obtained was worked up
with ethyl acetate and the diastereomeric acetates were estimated
by 1H NMR spectroscopy. Reduction of 1 (at 0 ꢀC) as above gave 14
and 16 in the ratio 98/2. Reduction of 5 (at 0 ꢀC) as above gave 18
and 20 in the ratio 80/20. Reduction of 5 (at ꢁ55 ꢀC) as above gave
18 and 20 in the ratio 92/8.
1H NMR (200 MHz; CDCl3):
d 1.83 (s, 3H, CH3), 3.42e3.67 (m, 5H, Ins
H), 4.63 (d, J¼11.4 Hz, 2H, CH2Ph), 4.75e4.95 (m, 8H, CH2Ph), 5.16 (t,
J¼9.5 Hz, 1H, Ins H), 7.13e7.38 (m, 25H, Ar H) ppm; 13C NMR
(50 MHz; CDCl3):
d 20.9 (CH3), 73.5 (Ins C), 75.5 (CH2), 76.0 (CH2),
80.6 (Ins C), 82.7 (Ins C), 82.8 (Ins C), 127.7 (Ar C), 127.8 (Ar C), 128.0
(Ar C), 128.4 (Ar C), 138.2 (Ar C), 138.3 (Ar C), 170.0 (CO) ppm; el-
emental analysis calcd for C43H44O7: C 76.76, H 6.59; found C 76.69;
H 6.56%.
4.2.14. Racemic 1,2,3,4-tetra-O-benzyl-scyllo-inositol (23). To a stir-
red solution of 2218 (2.14 g, 3.10 mmol) in THF (3 mL) were added
methanol (9 mL) and 1% aqueous sodium hydroxide solution
(1.5 mL). The reaction mixture was refluxed for 4 h and then
allowed to attain ambient temperature. The solvent was removed
under reduced pressure. The residue was worked up with ethyl
acetate. The crude product was purified by column chromatogra-
phy (silica gel 60e120 mesh; eluent, ethyl acetate/light petroleum,
1/2, v/v) to get 23 (1.65 g, 98%) as a colorless solid; mp 164e168 ꢀC;
IR (Nujol):
n
3200e3350 cmꢁ1 1H NMR (400 MHz; CDCl3):
; d 2.77
(br s, 2H, OH, D2O exchangeable), 3.38e3.44 (m, 2H, Ins H),
3.47e3.52 (m, 2H, Ins H), 3.56e3.61 (m, 2H, Ins H), 4.80 (d, J¼6 Hz,
2H, CH2Ph), 4.84e4.94 (m, 6H, CH2Ph), 7.19e7.40 (m, 20H, Ar
4.2.10. 1,3,4,5,6-Penta-O-benzyl-myo-inositol (17). To a stirred so-
lution of the diol 218 (3.01 g, 5.57 mmol) in dry benzene (30 mL)
was added sodium hydride (1.81 g, 45.20 mmol) and the mixture
was stirred at ambient temperature for 30 min. To this mixture,
H) ppm; 13C NMR (100 MHz; CDCl3):
d 73.8 (Ins C), 75.5 (CH2), 75.8
(CH2), 82.3 (Ins C), 83.0 (Ins C), 127.7 (Ar C), 127.8 (Ar C), 127.9 (Ar
C), 128.4 (Ar C), 128.5 (Ar C), 138.3 (Ar C), 138.4 (Ar C); elemental

5150
R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
Table 1
Single-crystal X-ray diffraction data for crystals of 4, 9, 13, and 22
Compound no.
4
9
13
22
Chemical formula
Mr
Temperature (K)
Morphology
Crystal size
C19H26O12
446.40
297(2)
C17H24
O
11$0.25(H2O)
C17H24O11
404.36
297(2)
C41H39O9N
689.73
297(2)
408.36
297(2)
Prism
0.46ꢂ0.41ꢂ0.27
Triclinic
Pꢁ1
Plate
Plate
Plate
0.37ꢂ0.27ꢂ0.19
Monoclinic
P21/c
10.983(7)
32.95(2)
14.886(7)
90
112.22(4)
90
4987(5)
8
0.33ꢂ0.26ꢂ0.19
Triclinic
Pꢁ1
0.32ꢂ0.06ꢂ0.05
Monoclinic
P21/c
18.144(4)
7.9967(19)
25.775(6)
90
100.167(4)
90
3681.0(15)
4
Crystal system
Space group
ꢀ
a (A)
8.5062(7)
9.5170(8)
26.338(2)
98.029(4)
93.690(4)
100.574(4)
2066.6(3)
4
10.4171(14)
13.5098(18)
15.498(2)
77.756(2)
79.661(2)
88.350(2)
2096.8(5)
4
ꢀ
b (A)
ꢀ
c (A)
a
b
g
(ꢀ)
(ꢀ)
(ꢀ)
3
ꢀ
V (A )
Z
Dcalcd (g cmꢁ3
)
1.189
0.100
1.313
0.112
1.281
0.108
1.245
0.088
m
(mmꢁ1
)
F(000)
1888
864
856
1456
Absorption correction Tmin/Tmax
h, k, l (min, max)
Multi-scan 0.964/0.981
(ꢁ13, 13),
(ꢁ39, 39),
(ꢁ17, 17)
28,956
8744
4605
0.0955
Multi-scan 0.951/0.971
(ꢁ10, 10),
(ꢁ11, 11),
(ꢁ31, 31)
46,382
7276
6277
0.045
Multi-scan 0.965/0.980
(ꢁ12, 12),
(ꢁ16, 16),
(ꢁ18, 18)
20,199
7361
5391
0.0328
Multi-scan 0.973/0.996
(ꢁ21, 21),
(ꢁ9, 9),
(ꢁ30, 30)
34,551
6496
4908
0.0590
Reflns collected
Unique reflns
Observed reflns
Rint
No. of parameters
GoF
621
1.061
529
1.106
526
1.070
464
1.271
R1[I>2
wR2[I>2
s
(I)]
(I)]
0.1032
0.2679
0.0491
0.1281
0.1018
0.2599
0.1028
0.2064
s
R1_all data
0.1732
0.0568
0.1195
0.1347
wR2_all data
Drmax, Drmin(e A
CCDC No.
0.3127
0.1327
0.2805
0.2208
ꢀꢁ3
)
0.20, ꢁ0.24
0.59, ꢁ0.12
0.96, ꢁ0.28
0.22, ꢁ0.18
902249
898796
902247
902248
analysis calcd for C34H36O6: C 75.53, H 6.71; found C 75.36; H
6.81%.
Research Fellowships of the Council of Scientific and Industrial
Research, New Delhi. Dr. Rajesh Gonnade’s generous help in solving
the crystal structure of 9 is much appreciated.
4.2.15. Crystallographic details. Single-crystal X-ray intensity mea-
surements for crystals of 4, 9, 13, and 22 were recorded at ambient
Supplementary data
temperature on a Bruker SMART APEX single-crystal X-ray CCD dif-
ꢀ
fractometer with graphite-monochromatized (Mo K
a
¼0.71073 A)
NMR spectroscopic data for compounds 2, 4, 6, 7, 9, 11, 13, 20, 23
and mixture of 18 and 20; ORTEP diagrams of 4, 9, 13, and 22.
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2013.04.081.
radiation. The X-ray generator was operated at 50 kV and 30 mA.
Diffraction datawere collected with a
scanwidthof 0.3ꢀ at different
settings of 4 (0, 90, 180, and 270ꢀ) keeping the sample-to-detector
distance fixed at 6.145 cm and the detector position (2 ) fixed
u
q
at ꢁ28ꢀ. The X-ray data acquisition was monitored by SMART pro-
gram (Bruker, 2003).19 All the data were corrected for Lorentz-
polarization effects using SAINT programs.19 A semi-empirical ab-
sorption correction (multi-scan) based on symmetry equivalent
reflections was applied using the SADABS program.19 Lattice
parameters were determined from least-squares analysis of all re-
flections. The structures were solved by direct methods and refined
by full matrix least squares, based on F2, using SHELX-97 software
package.20 Molecular diagrams were generated using ORTEP-32.21
Geometrical calculations were performed using SHELXTL19 and
PLATON.22 The crystallographic data are summarized in Table 1.
ORTEP diagrams are included in the Supplementary data. Crystallo-
graphic data (excluding structure factors) for the structures in this
paper have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication nos. CCDC 898796,
902247, 902248, and 902249. Copies of the data can be obtained, free
ofcharge, onapplication to CCDC,12 Union Road, Cambridge CB21EZ,
UK (fax: þ44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
References and notes
1. (a) Potter, B. V. L.; Lampe, D. Angew. Chem., Int. Ed. Engl. 1995, 34, 1933e1972; (b)
In Phosphoinositides: Chemistry, Biochemistry and Biomedical Applications; Bru-
zik, K. S., Ed.; ACS Symposium Series; American Chemical Society: Washington
DC, USA, 1999; Vol. 718; (c) Hancock, J. T. Cell Signalling; Oxford University: New
Delhi, India, 2005; (d) Mentel, M.; Laketa, V.; Subramanian, D.; Gillandt, H.;
Schultz, C. Angew. Chem., Int. Ed. 2011, 50, 3811e3814.
2. (a) Sureshan, K. M.; Shashidhar, M. S.; Praveen, T.; Das, T. Chem. Rev. 2003, 103,
4477e4503; (b) Kilbas, B.; Balci, M. Tetrahedron 2011, 67, 2355e2389 and ref-
erences cited therein.
3. (a) Chida, N.; Ogawa, S. Chem. Commun. 1997, 807e813; (b) Gurale, B. P.; Sha-
shidhar, M. S.; Gonnade, R. G. J. Org. Chem. 2012, 77, 5801e5807 and references
cited therein.
4. (a) Eliel, E. L.; Wilen, S. H.; Mandeer, L. N. Stereochemistry of Carbon Compounds;
John Wiley & sons: New York, NY, 1994; (b) Rosenberg, R. E.; Abel, R. L.; Drake,
M. D.; Fox, D. J.; Ignatz, A. K.; Kwiat, D. M.; Schaal, K. M.; Virkler, P. R. J. Org.
Chem. 2001, 66, 1694e1700.
€
5. (a) Burgi, H. B.; Dunitz, J. D.; Lehn, J. M.; Wipff, G. J. Tetrahedron 1974, 30,
€
1563e1572; (b) Burgi, H. B.; Dunitz, J. D. Acc. Chem. Res. 1983, 16, 153e161; (c)
Praveen, T.; Samanta, U.; Das, T.; Shashidhar, M. S.; Chakrabarti, P. J. Am. Chem.
Soc. 1998, 120, 3842e3845; (d) Krishnaswamy, S.; Shashidhar, M. S.; Bhadb-
hade, M. M. CrystEngComm 2011, 13, 3258e3264 and references cited therein.
6. Patil, M. T.; Krishnaswamy, S.; Sarmah, M. P.; Shashidhar, M. S. Tetrahedron Lett.
2011, 52, 3756e3758.
Acknowledgements
7. (a) Ley, S. V.; Parra, M.; Redgrave, A. J.; Sternfeld, F. Tetrahedron 1990, 46,
4995e5026; (b) Kozikowski, A. P.; Fauq, A. H.; Wilcox, R. A.; Challiss, R. A. J.;
Nahorski, S. R. J. Med. Chem. 1994, 37, 868e872; (c) Fauq, A. H.; Kozikowski, A. P.;
The Department of Science and Technology, New Delhi, sup-
ported this work. R.C.J., M.T.P., and S.K. are recipients of Senior

R.C. Jagdhane et al. / Tetrahedron 69 (2013) 5144e5151
5151
Oqnyanov, V. I.; Wilcox, R. A.; Nahorski, S. R. J. Chem. Soc., Chem. Commun. 1994,
1301e1302; (d) Conway, S. J.; Miller, G. J. Nat. Prod. Rep. 2007, 24, 687e707; (e)
Swarbrick, J. M.; Cooper, S.; Bultynck, G.; Gaffney, P. R. J. Org. Biomol. Chem.
2009, 7, 1709e1715; (f) Swarbrick, J. M.; Gaffney, P. R. J. J. Org. Chem. 2010, 75,
4376e4386.
12. (a) Reddy, K. K.; Saady, M.; Falck, J. R. J. Org. Chem. 1995, 60, 3385e3390; (b)
~
~
Acena, J. L.; Arjona, O.; Manas, R.; Plumet, J. J. Org. Chem. 2000, 65, 2580e2582;
(c) Izuhara, T.; Katoh, T. Tetrahedron Lett. 2000, 41, 7651e7655; (d) Gravier-
Pelletier, C.; Maton, W.; Dintinger, T.; Tellier, C.; Le Merrer, Y. Tetrahedron 2003,
ꢂ
59, 8705e8720; (e) Prazeres, V. F. V.; Castedo, L.; Gonzalez-Bello, C. Eur. J. Org.
8. Gigg, R.; Warren, C. D. J. Chem. Soc. C 1969, 2367e2371.
Chem. 2008, 3991e4003; (f) Tashiro, T.; Nakagawa, R.; Hirokawa, T.; Inoue, S.;
Watarai, H.; Taniguchi, M.; Mori, M. Bioorg. Med. Chem. 2009, 17, 6360e6373.
13. (a) Angyal, S. J.; Davis, K. P. J. Chem. Soc., Chem. Commun. 1971, 500e501; (b)
Angyal, S. J. Pure Appl. Chem. 1973, 35, 131e146; (c) Angyal, S. J. Aust. J. Chem.
1972, 25, 1957e1966; (d) Hancock, R. D.; Hegetschweiler, K. J. Chem. Soc., Dalton
Trans. 1 1993, 2137e2140.
14. (a) Glass, R. S.; Deardorff, D. R.; Henegar, K. Tetrahedron Lett.1980, 21, 2467e2470;
(b) Yadav, V. K.; Jeyaraj, D. A.; Balamurugan, R. Tetrahedron 2000, 56, 7581e7589;
(c) Suzuki, Y.; Kaneno, D.; Tomoda, S. J. Phys. Chem. A 2009, 113, 2578e2583.
15. Devaraj, S.; Jagdhane, R. C.; Shashidhar, M. S. Carbohydr. Res. 2009, 344,
1159e1166.
16. Lowe, G.; McPhee, F. J. Chem. Soc., Perkin Trans. 1 1996, 1249e1253.
17. Angyal, S. J.; Tate, M. E. J. Chem. Soc. 1965, 6949e6955.
18. Guidot, J. P.; Gall, T. L. Tetrahedron Lett. 1993, 34, 4647e4650.
19. Bruker. SADABS Version 2.05, SMART Version 5.631 and SAINT Version 6.45;
Bruker AXS: Madison, Wisconsin, USA, 2003.
9. (a) Reymond, D. Helv. Chim. Acta 1957, 40, 492e494; (b) Gigg, J.; Gigg, R. Car-
bohydr. Res. 1997, 299, 77e83; (c) Takahashi, H.; Kittaka, H.; Ikegami, S. Tetra-
hedron Lett. 1998, 39, 9707e9710; (d) Takahashi, H.; Kittaka, H.; Ikegami, S. J.
Org. Chem. 2001, 66, 2705e2716.
10. (a) Turnbull, M. D.; Halter, G.; Ledgerwood, D. E. Tetrahedron Lett. 1984, 25,
5449e5452; (b) Fukasa, H.; Horii, S. J. Org. Chem. 1992, 57, 3642e3650; (c)
ꢁ
Catelani, G.; Corsaro, A.; D’Andrea, F.; Mariania, M.; Pistara, V. Bioorg. Med.
Chem. Lett. 2002, 12, 3313e3315; (d) Gravier-Pelletier, C.; Maton, W.; Le Merrer,
Y. Tetrahedron Lett. 2002, 43, 8285e8288; (e) Sarmah, M. P.; Shashidhar, M. S.
Carbohydr. Res. 2003, 338, 999e1001; (f) Begum, L.; Box, J. M.; Drew, M. G. B.;
Harwood, L. M.; Humphreys, J. L.; Lowes, D. J.; Morris, G. A.; Redon, P. M.;
Walker, F. M.; Whitehead, R. C. Tetrahedron 2003, 59, 4827e4841; (g) Jagdhane,
R. C.; Shashidhar, M. S. Eur. J. Org. Chem. 2010, 2945e2953.
11. (a) Fukase, H.; Horii, S. J. Org. Chem. 1992, 57, 3651e3658; (b) Frontier, A. J.;
Raghavan, S.; Danishefsky, S. J. Am. Chem. Soc. 2000, 122, 6151e6159; (c) Sar-
mah, M. P.; Shashidhar, M. S.; Sureshan, K. M.; Gonnade, R. G.; Bhadbhade, M.
M. Tetrahedron 2005, 61, 4437e4446; (d) Sarmah, M. P. Ph.D. Thesis; University
of Pune: India, 2005.
20. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112e122.
21. Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
22. Spek, A. L. J. Appl. Crystallogr. 2009, 65, 148e155.