A formal synthesis of valiolamine from myo-inositol

Article abstract of DOI:10.1016/j.tet.2011.08.027

An efficient formal synthesis of racemic valiolamine starting from readily available myo-inositol is reported. In all the synthetic steps only one regioisomer is formed, which circumvents laborious purification of products. Regioselective benzylation of myo-inositol orthoformate, super-hydride mediated deoxygenation of a cyclitol derivative and stereoselective addition of dichloromethyllithium to an inosose are the key reactions in the synthesis.

Full text of DOI:10.1016/j.tet.2011.08.027

Tetrahedron 67 (2011) 7963e7970
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A formal synthesis of valiolamine from myo-inositol
*
Rajendra C. Jagdhane, Mysore S. Shashidhar
Division of Organic Chemistry, National Chemical Laboratory, 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:
Received 23 May 2011
Received in revised form 8 August 2011
Accepted 9 August 2011
Available online 16 August 2011
An efficient formal synthesis of racemic valiolamine starting from readily available myo-inositol is re-
ported. In all the synthetic steps only one regioisomer is formed, which circumvents laborious purifi-
cation of products. Regioselective benzylation of myo-inositol orthoformate, super-hydride mediated
deoxygenation of a cyclitol derivative and stereoselective addition of dichloromethyllithium to an in-
osose are the key reactions in the synthesis.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Amino sugar
Carbohydrate
Cyclitol
Natural product
Inositol
Valiolamine
1. Introduction
trisphosphate (PIP3), racemic tetrodotoxin, polyoxin J, and
nojirimycin.
myo-Inositol (1), the most abundant cyclitol occurring in nature,
plays an important role as structural basis for a number of sec-
ondary messengers in eukaryotic cells.1 The cyclic polyol core as
well as the well investigated regioselective reactions of myo-ino-
sitol and its derivatives2 would be useful for the synthesis of
compounds with potential biological, medicinal and material
properties. myo-Inositol has been used as a starting material for the
synthesis of natural products,3 such as phosphatidyl inositol 3,4,5-
The attempts to synthesize useful products from myo-inositol
and its derivatives, have been hampered by the formation of
regioisomeric products due to the subtle differences in the re-
activity of their hydroxyl groups as well as the meso configuration
of myo-inositol, which requires either desymmetrization or reso-
lution at some stage in the synthesis for accessing optically active
products. We have addressed the former issue in our work, which
resulted in the development of efficient methods for the synthesis
Fig. 1. Structure of myo-inositol and few aminocyclitols.
of a diverse group of diastereomeric cyclitol derivatives and analogs
from myo-inositol.4 The regioselectivity in the O-alkylation of ino-
sitol derivatives was attributed to the chelation of the counter ion
(lithium or sodium) used in the base, with the inositol derivatives
* Corresponding author. E-mail address: ms.shashidhar@ncl.res.in (M.S.
Shashidhar).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.027

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R.C. Jagdhane, M.S. Shashidhar / Tetrahedron 67 (2011) 7963e7970
undergoing reactions. The aim of the current work is to demon-
strate the flexibility, adaptability and utility of the reactions and
synthetic methods developed earlier,4 for the targeted synthesis.
Accordingly we herein present results on the formal synthesis of
valiolamine from myo-inositol.
replaced by a hydroxyl group. Key reactions in our synthetic ap-
proach to achieve these changes in myo-inositol were (i) lithium
hydride mediated selective benzylation of the C4- and C6-hydroxyl
groups of myo-inositol orthoformate 7; (ii) a novel deoxygenation
reaction of the tosylate 11,7 and (iii) stereospecific nucleophilic
addition of dichloromethyllithium to the inosose 15 (Scheme 1).3e
myo-Inositol orthoformate 7 was obtained from myo-inositol
using a known procedure;8 the C4- and C6-hydroxyl groups were
selectively benzylated using lithium hydride and benzyl bromide.10
The dibenzyl ether 8 was converted to the tribenzyl ether 9 by
transient protection of the C2-hydroxyl group to enable selective
cleavage, of the orthoformate moiety2e,f (with DIBAL-H) to the
corresponding formaldehyde acetal. Good yield could be obtained
consistently for both the O-alkylation reactions (preparation of 8
and its PMB ether) on 10 g scale. The tribenzyl ether 9 was obtained
in a yield of 90% over four steps from 8. The free hydroxyl group in 9
was converted to the corresponding tosylate 10, by heating with
tosyl chloride in pyridine. Although tosylates of secondary alcohols
are known to quaternize tertiary amines, such as pyridine, the
tosylate 10 was stable at elevated temperatures in the presence of
pyridine (Scheme 1, step ‘d’), perhaps because of the rigidity
imparted by the 1,3-acetal bridge on the molecule. Subjecting 10 to
acetolysis using trifluoroacetic anhydride and acetic acid11 resulted
2. Results and discussion
Valiolamine5 (2, Fig. 1) is a pseudo-amino sugar first isolated
from the fermentation broth of Streptomyces hygroscopicus subsp.
Limoneus and was found to be more potent against a-glucosidase,
maltase, iso-maltase and sucrase compared to valienamine, vali-
damine, and hydroxyvalidamine. This subsequently resulted in
extensive chemical modification of valiolamine and led to the
preparation of voglibose 5 (coded as AO-128),6 an orally active anti-
diabetic agent. A comparison of the structure of valiolamine and
myo-inositol reveals that the relative orientation of the C4-, C5-,
and C6-hydroxyl groups is same in both the molecules. To convert
myo-inositol to racemic valiolamine, (a) the C2-hydroxyl group has
to be replaced by a hydrogen; (b) C3(1)-hydroxyl group must be
converted to an amino group with inversion of configuration at the
C3(1)ecarbon; (c) the C1(3)-hydroxyl group must be replaced by
a hydroxymethyl group; and (d) the C1(3)-hydrogen must be
Scheme 1. Reagents and conditions: (a) as in Ref. 8; (b) DMF, LiH, BnBr, rt, 25 h 30 min, 65%; (c) i. DMF, NaH, PMBCl, 0 ꢀC to rt, 3 h; ii. DCM, DIBAL-H, 0 ꢀC to rt, 4 h; iii. DMF, NaH,
BnBr, 0 ꢀC to rt, 1 h; iv DCM/H2O, DDQ, 0 ꢀC to rt, 5 h; 90% (over four steps); (d) Pyridine TsCl, DMAP, 80 ꢀC, 9 h, 93%; (e) i. DCM, TFAA, AcOH, 0 ꢀC to rt, 12 h; ii. K2CO3, MeOH, rt, 8 h,
90%; (f) THF, LiEt3BH, 0 ꢀC to rt; 4 h, 85%; (g) DCM, 2,6-lutidine, TBSOTf, 0 ꢀC to rt, 90 min, 95%; (h) CSA, MeOH, 0 ꢀC to rt; 35 min, 95%; (i) AcOEt, IBX, reflux, 8 h, 95%; (j) THF, LDA
(2.0 equiv), CH2Cl2, ꢁ78 ꢀC to 0 ꢀC, 4 h, 82%; (k) i. DMSO, aq (nBu)4NOH, rt, 8 min, then MeOH, NaBH4, 0 to 5 ꢀC, 20 min; ii. Bu2SnO, MeOH, toluene, reflux, 24 h then BnBr, n-Bu4NBr,
toluene, reflux, 5 h, 43%; (l) AcOEt, IBX, reflux, 7 h, 65%; (m) as in Ref. 9.

R.C. Jagdhane, M.S. Shashidhar / Tetrahedron 67 (2011) 7963e7970
7965
in cleavage of the methylidene acetal (with concomitant flipping of
the carbocyclic ring2e,f) to furnish the diol 11 in good yield. Acid
catalyzed solvolysis or hydrolysis of the acetal 10 (with HCl or TsOH
in MeOH or THF) was very sluggish (50% conversion to 11 after
boiling for 4e5 days). This indicated that protic acids are not strong
enough to bring about cleavage of the acetal. Hence we had to use
a stronger (Lewis) acid, acylium ion, to cleave the methylidene
acetal in 10. Reaction of the tosylate 11 with excess lithium trie-
thylborohydride (super-hydride)7 in THF resulted in the reduction
of the tosylate and inversion of one of the hydroxyl groups through
the in situ stereoselective reduction of the intermediate ketone 20
(Scheme 2), to give the protected racemic vibo-quercitol 12.12,13
The dichloromethyl group in 16 was hydrolyzed with aqueous
tetrabutylammonium hydroxide3e,15 to get the corresponding al-
dehyde, which was reduced with sodium borohydride to obtain the
hydroxymethyl derivative with concomitant cleavage of the TBS
group. However, it is not clear whether the TBS ether was cleaved
during the hydrolysis of the dichloromethyl derivative to the cor-
responding aldehyde or during the borohydride reduction of the
aldehyde to the corresponding alcohol (Scheme 3). This hydrox-
ymethyl derivative was converted to benzyloxymethyl derivative
1716 by its reaction with dibutyltin oxide (MeOH/toulene) followed
by benzyl bromide. The secondary hydroxyl group in 17 was oxi-
dized with IBX to obtain the racemic ketone 18.16 Synthesis of
(þ)-valiolamine as well as voglibose (AO-128) from (þ)-18 is
reported in the literature.9
Scheme 3. Intermediates involved in the conversion of 16 to 17. (a) DMSO, aq (nBu)
NOH, rt, 8 min; (b) MeOH, NaBH4, 0e5 ꢀC, 20 min; (c) Bu2SnO, MeOH, toluene, reflux,
24 h then BnBr, n-Bu4NBr, toluene, reflux, 5 h.
Scheme 2. Mechanism for the formation of the diol 12.
Initially, we carried out addition of dichloromethyllithium to the
ketone 15 using 3 equiv of dichloromethyllithium. However results
of these experiments were not consistent and in some trials we
observed the formation of the alkyne 21 (29%), while major amount
of 15 remained unreacted (Scheme 4). Formation of the chloro-
alkyne 21 (from 15 and dichloromethyllithium) is quite surprising
and to the best of our knowledge this seems unprecedented in the
literature. A plausible mechanism is depicted in Scheme 4. To cir-
cumvent this problem, amount of dichloromethyllithium was
lowered to 2 M equiv, which produced the dichloromethyl de-
rivative 16 consistently in good yield.
We also carried out silylation of 12 with 1 equiv of TBSOTf and
its benzylation with sodium hydride and benzyl bromide (Scheme
5). The former reaction resulted in the formation of the equatorial
TBS ether 25 exclusively, and benzylation gave the axial benzyl
ether 29 as the major product. Similar instances of reversal of se-
lectivity during the O-substitution reactions of cyclitol derivatives
have been observed earlier.4,10,17 Extensive investigation of the O-
alkylation reaction of inositol derived diols and triols in our labo-
ratory4,10,17 had revealed that predominant O-alkylation occurs at
a hydroxyl group situated adjacent to a cis-oxygen atom. Pre-
dominant formation of 29 from 12 is in agreement with our prior
observations.4,10,17
In order to gain access to the axial TBS protected ketone 15, the
diol 12 was converted into the bis-silyl derivative 13 in quantitative
yield using excess of TBSOTf and 2,6-lutidine in dichloromethane.
The bis-silyl ether 13 was then subjected to regioselective depro-
tection of the equatorial TBS ether using an equimolar amount of
camphorsulphonic acid in methanol, leaving the axial TBS ether
unaffected. The free hydroxyl group in 14 was oxidized using IBX
(2-iodoxy benzoic acid)14 in refluxing ethyl acetate to give the de-
sired ketone 15 in excellent yield. For the introduction of the
equatorial hydroxymethyl group, the ketone 15 was reacted with
dichloromethyllithium (generated by reacting lithium di-
isopropylamide with dichloromethane in THF at ꢁ78 ꢀC)3e,15 to
get exclusively the dichloromethyl derivative 16. The selectivity
observed for the addition of dichloromethyllithium to the ketone
15, is perhaps due to the presence of the bulky axial silyl ether,
which restricts the approach of the nucleophile to one face of the
ketone. It is also possible that the lithium ion chelates between the
axial oxygen (of the TBS ether) and the carbonyl oxygen to aid in the
formation of the product carrying an equatorial dichloromethyl
group. This line of thought is supported by the fact that addition of
dichloromethyllithium to the epimer of 15 (26, see below), which
has an equatorial TBS ether resulted in the formation of a mixture of
isomeric chlorooxiranes.
Reaction of the ketone 26 with dichloromethyllithium (Scheme
5) resulted in the formation of two isomeric chlorooxiranes 27 and
Scheme 4. Unexpected formation of the alkyne 21 from the ketone 15.

7966
R.C. Jagdhane, M.S. Shashidhar / Tetrahedron 67 (2011) 7963e7970
Scheme 5. Reagents and conditions: (a) DCM, 2,6-lutidine, TBSOTf, 0 ꢀC to rt, 3 h, 83%; (b) AcOEt, IBX, reflux, 8 h, 85%; (c) NaH, BnBr, DMF, 0 ꢀC to rt, 17 h, 60%; (d) i. AcOEt, IBX,
reflux, 8 h; ii. silica gel, Et3N, 79%; (e) THF, LDA, CH2Cl2, ꢁ78 ꢀC to rt, 3 h 30 min.
28 (in the ratio 4.7:1), which were separable by column chroma-
tography. The minor product, chlorooxirane 28, could be crystal-
lized from acetonitrile at room temperature. Single crystal X-ray
diffraction analysis of these crystals revealed the axial disposition
of the oxirane oxygen in 28 (see ESD). The ketone 26 was obtained
by the oxidation of 25 with IBX and was purified by passing it
through a small column of silica gel (in less than 2 h). Initially, we
used silica gel pre-treated with triethylamine for the column
chromatographic purification of the ketone 26, since we were
concerned that the acidity of the silica gel used, could cleave the
TBS ether in 26. However, this procedure resulted in the formation
carried out in an atmosphere of argon. Sodium hydride used in
experiments was 60% suspension in mineral oil. In thin layer
chromatography (TLC) spots were rendered visible either by shin-
ing UV light or by charring the plates with chromic acid solution.
Column chromatographic separations (silica gel, 100e200 mesh)
and flash column chromatographic separations (silica gel,
230e400 mesh) were carried out with light petroleum/ethyl ace-
tate mixtures as eluent. For column chromatographic separation of
compounds containing the PMB/TBS group (except for ketones 15
and 26), the silica gel used was pre-eluted with a triethylamine/
light petroleum (1:49, 3e5 mL/g) mixture. Work-up ‘as usual’ im-
plies washing of the organic layer with water followed by brine,
drying the organic extract over anhydrous sodium sulfate, and re-
moval of the solvent under reduced pressure using a rotary evap-
orator. All the melting points reported are uncorrected. All the
asymmetrically substituted myo-inositol derivatives reported are
racemic; however only one of the enantiomers is shown in all the
schemes.
of the a,b-unsaturated ketone 30 probably through its enol form.
Although there are several reports9,18 on the synthesis of
valiolamine, only one report used myo-inositol as the starting
material.19 This synthesis involved the bio-deoxygenation of myo-
inositol employing bacterial strains to produce mainly (ꢁ)-vibo-
quercitol,20 together with (ꢁ)-epi- and (ꢁ)-proto-quercitol. These
quercitols (deoxyinositols) were then separated and purified by
a combination of chromatography on ion-exchange-resin columns
and subsequent recrystallization. (ꢁ)-vibo-Quercitol was then
biochemically oxidized under the influence of Gluconobacter sp.
AB10277. Apart from these laborious procedures, the synthesis also
relies on the protection of myo-inositol hydroxyl groups as acetal/
ketal, which leads to the formation of unwanted regioisomeric
products during the synthesis.
4.2. Experimental procedure and characterization data for
compounds
4.2.1. 4,6-Di-O-benzyl-myo-inositol-1,3,5-orthoformate (8). To a so-
lution of the orthoformate 7 (10.0 g, 52.63 mmol) in DMF (500 mL)
was added lithium hydride (1.68 g, 210.52 mmol) at ambient
temperature and stirred for 90 min. To the above thick slurry,
benzyl bromide (13.77 mL, 115.78 mmol) was added and stirred for
24 h. Ice was added to reaction mixture and stirred for 5 h, solvents
were removed under reduced pressure and the residue worked up
with ethyl acetate ‘as usual’. The crude product was crystallized
from ethyl acetate to afford the dibenzyl ether 8 (12.7 g, 65%). Mp
122e124 ꢀC (lit.8c Mp 124e125 ꢀC).
3. Conclusion
A formal synthesis of racemic valiolamine from myo-inositol
presented here demonstrates the utility and potential of the syn-
thetic methods developed in our laboratory4,10,17b,c (for the selec-
tive reactions of inositol hydroxyl groups), for the targeted
synthesis of cyclitol derivatives. Although we have used one type of
protecting group (benzyl) for C4-, C5-, C6-hydroxyl groups (see 9,
Scheme 1), one can use orthogonal protection at these positions
based on the chemistry developed earlier in our laboratory.4 Use of
orthogonal protection could in principle give access to a variety of
derivatives or analogs of natural product, which has implications
from structureeactivity relationship point of view. Development of
efficient methods for the desymmetrization of inositol derivatives
is currently being investigated in our laboratory.
4.2.2. 4,5,6-Tri-O-benzyl-1,3-methylidene-myo-inositol (9). To an ice
cooled solution of the dibenzyl ether 8 (10.1 g, 27.27 mmol) in DMF
(100 mL) was added sodium hydride (2.18 g, 54.53 mmol) followed
by 4-methoxybenzyl chloride (5.55 mL, 40.9 mmol) and the re-
action mixture was stirred for 3 h at ambient temperature. Ice was
added to reaction mixture and solvents were removed under re-
duced pressure and the residue worked up ‘as usual’ with ethyl
acetate to obtain crude PMB ether (16 g).
This crude PMB ether (16 g) was taken in dichloromethane
(70 mL), cooled using ice bath and DIBAL-H (68.2 mL, 1.0 M soln in
toluene) was added and the resulting mixture was stirred at am-
bient temperature for 4 h. The reaction mixture was poured onto
a rapidly stirred, cooled solution of saturated aq ammonium chlo-
ride (200 mL) and sodium potassium tartarate (150 g in 250 mL of
water). Ethyl acetate (400 mL) was added to it and stirred for 12 h at
4. Experimental section
4.1. General methods
All the solvents were purified according to literature pro-
cedures21 before use. All air or moisture sensitive reactions were

R.C. Jagdhane, M.S. Shashidhar / Tetrahedron 67 (2011) 7963e7970
7967
ambient temperature. The two layers were separated and the
aqueous layer was extracted with ethyl acetate (3ꢂ300 mL); the
combined organic layers were washed with brine, dried over an-
hydrous sodium sulfate, solvent was evaporated under reduced
pressure to afford the crude benzylidene acetal (17 g).
The crude acetal (17 g) was taken in DMF (100 mL) cooled using
an ice bath and sodium hydride (2.18 g, 54.53 mmol) was added
followed by benzyl bromide (4.86 mL, 40.9 mmol), and the mixture
was stirred for 1 h at ambient temperature. Ice was added to the
reaction mixture, solvents were removed under reduced pressure;
the residue obtained was taken in ethyl acetate and worked up ‘as
usual’ to afford the crude tribenzyl ether (18 g).
(200 MHz, CDCl3):
d
7.85e7.75 (m, 2H), 7.40e7.27 (m, 17H), 5.08 (t,
J¼2.0 Hz, 1H), 4.86 (s, 2H), 4.87 (d, J¼11.1 Hz, 2H), 4.72 (d, J¼11.1 Hz,
2H), 3.75e3.60 (m, 4H), 3.55e3.43 (m,1H), 2.45 (s, CH3, 3H), 2.40 (d,
J¼2.0 Hz, OH, 2H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 144.5, 138.1,
133.6, 129.4, 128.4, 128.3, 128.1, 127.9, 127.8, 127.7, 127.6, 82.8, 82.1,
81.4, 75.5, 75.4, 69.9, 21.6 ppm. Elemental Anal. C34H36O8S (604.71):
calcd C, 67.53; H, 6.00 found C, 67.28; H, 6.04%.
4.2.5. Racemic 1,5,6-tri-O-benzyl-3-deoxy-myo-inositol (2,3,4-tri-O-
benzyl-vibo-quercitol, 12). To an ice cooled solution of the tosylate
11 (3.0 g, 4.96 mmol), in THF (20 mL) was added lithium trie-
thylborohydride (super-hydride) (19.8 mL, 1.0 M soln in THF,
19.8 mmol) and stirred at ambient temperature for 4 h. Ice was
added to the reaction mixture and the solvent evaporated under
reduced pressure; the residue obtained was worked up with ethyl
acetate ‘as usual’. The crude product was purified by flash column
chromatography (eluent: ethyl acetate/light petroleum, 2:3) to af-
ford the racemic diol 1212 (1.83 g, 85%) as a colorless solid. Mp
To an ice cooled solution of the crude tribenzyl ether (9 g) in
DCM/H2O (300:3 mL), DDQ (4.64 g, 20.45 mmol) was added and
stirred at ambient temperature for 5 h. The reaction mixture was
diluted with DCM (200 mL) and washed with 40% aq sodium hy-
drogen carbonate solution (2ꢂ400 mL), followed by brine and dried
over anhydrous sodium sulfate. The solvent was removed under
reduced pressure and the residue was purified by flash column
chromatography (gradient elution: ethyl acetate/light petroleum
2:8e3:7) to afford 9 (5.68 g, 90%) as a solid. Mp 76e78 ꢀC; IR
n
100.5e102.5 ꢀC; IR (Neat):
CDCl3):
n
3600e3200 cmꢁ1; 1H NMR (200 MHz,
d
7.45e7.27 (m, 15H), 5.01 (d, J¼11.4 Hz, 1H), 4.92 (d,
J¼10.7 Hz,1H), 4.82 (d, J¼10.7 Hz,1H), 4.78e4.63 (m, 3H), 4.17e4.08
(m, 1H), 4.05e3.90 (m, 1H), 3.84 (t, J¼9.3 Hz, 1H), 3.50 (dd, J¼9.3
and 3.1 Hz, 1H), 3.27 (t, J¼9.3 Hz, 1H), 2.48 (br s, OH, 1H), 2.40e2.17
(m, 1OH, 2H), 1.48e1.28 (m, 1H) ppm; 13C NMR (50.3 MHz, CDCl3):
(CHCl3): 3250e3550 (OH) cmꢁ1 1H NMR (200 MHz, CDCl3):
;
d
7.40e7.26 (m, 15H), 4.92 (d, J¼7.0 Hz, 1H), 4.84 (d, J¼7.0 Hz, 1H),
4.77 (s, 2H), 4.71 (d, J¼11.6 Hz, 2H), 4.57 (d, J¼11.6 Hz, 2H), 4.09 (d,
J¼2.5 Hz, 2H), 3.97 (d, J¼7.6 Hz, 2H), 3.83 (m, which becomes t,
J¼2.3 Hz on D2O exchange, 1H), 3.68 (t, J¼7.7 Hz, 1H), 3.21 (d,
d
138.5, 137.8, 128.4, 128.3, 127.8, 127.7, 127.5, 86.1, 83.1, 81.4, 75.6,
75.3, 72.6, 67.8, 65.8, 33.7 ppm. Elemental Anal. C27H30O5 (434.52):
calcd C, 74.63; H, 6.96 found C, 74.29; H, 6.71%.
J¼10.7 Hz, OH, 1H) ppm; 13C NMR (50.3 MHz, CDCl3)
d: 138.2, 137.2,
128.4, 128.2, 127.89, 127.86, 127.8, 127.6, 127.5, 85.2, 81.3, 75.2, 74.5,
71.5, 62.9 ppm. Elemental Anal. C28H30O6 (462.53) calcd C, 72.71; H,
6.54 found C, 72.74; H, 6.65%.
4.2.6. Preparation of diTBS ether 13. To an ice cooled solution of the
diol 12 (3.0 g, 6.90 mmol) in dichloromethane (10 mL), 2,6-lutidine
(2.0 mL, 17.26 mmol) was added followed by TBSOTf (3.65 mL,
15.88 mmol). Resulting reaction mixture was stirred at room tem-
perature for 90 min. Ice was added to the reaction mixture, and
worked up ‘as usual’ with dichloromethane. The crude product was
purified by column chromatography (eluent: ethyl acetate/light
petroleum, 1:9) to afford racemic 13 (4.34 g, 95%) as a gum. 1H NMR
4.2.3. 4,5,6-Tri-O-benzyl-1,3-methylidene-2-O-tosyl-myo-inositol
(10). The myo-alcohol 9 (9.5 g, 20.54 mmol), pyridine (25 mL), tosyl
chloride (9.79 g, 51.35 mmol), and DMAP (0.1 g) were heated at
80 ꢀC for 9 h. The reaction mixture was cooled to ambient tem-
perature, ice was added and the solvent was removed under re-
duced pressure, the residue was taken in ethyl acetate and worked
up as usual. The crude product was purified by flash column
chromatography (eluent: ethyl acetate/light petroleum 1:4) to af-
ford the tosylate 10 (11.8 g, 93%) as a gum. In a few trials on a lower
scale (3 g of 9) the tosylate 10 was obtained as a solid, Mp 76e77 ꢀC
(crystals from ethyl acetate/light petroleum); 1H NMR (200 MHz,
(200 MHz, CDCl3): d 7.40e7.20 (m, 15H), 4.92e4.72 (m, 4H), 4.68 (s,
2H), 4.20e4.00 (m, 2H), 3.86 (t, J¼9.5 Hz, 1H), 3.38e3.24 (m, 2H),
2.05e1.87 (m, 1H), 1.50e1.30 (m, 1H), 0.89 (s, 18H), 0.08 (s, 3H), 0.06
(s, 6H), 0.04 (s, 3H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 139.1, 139.0,
138.6, 128.2, 128.1, 127.9, 127.7, 127.5, 127.3, 127.2, 87.0, 83.3, 81.4,
75.8, 75.7, 72.9, 70.4, 67.6, 38.4, 25.9, 25.8, 18.1, 18.0, ꢁ4.4, ꢁ4.5,
ꢁ4.6, ꢁ5.2 ppm. Elemental Anal. calcd C39H58O5Si2 (663.05) C,
70.65; H, 8.82 found C, 70.58; H, 8.66%.
CDCl3):
d
7.87e7.73 (m, 2H), 7.40e7.15 (m, 17H), 5.03 (d, J¼6.0 Hz,
1H), 4.92e4.83 (m, 2H), 4.58 (s, 2H), 4.50 (d, J¼11.7 Hz, 2H), 4.41 (d,
J¼11.7 Hz, 2H), 4.15 (br s, 2H), 3.90 (br d, J¼4.4 Hz, 2H), 3.63 (t,
J¼4.5 Hz, 1H) 2.36 (s, 3H) ppm; 13C NMR (50.3 MHz, CDCl3):
d
145.0,
4.2.7. Preparation of the racemic TBS ether 14. To an ice cooled
solution of the diTBS ether 13 (1.54 g, 2.32 mmol) in methanol
(16 mL) was added camphorsulphonic acid (0.54 g, 2.32 mmol) and
stirred at ambient temperature for 35 min. The acid was neutralized
by the addition of triethylamine (0.5 mL), the reaction mixture was
concentrated under reduced pressure and the residue was worked
up with ethyl acetate ‘as usual’. The crude product was purified by
column chromatography (eluent: ethyl acetate/light petroleum,
1:6) to afford the racemic TBS ether 14 (1.21 g, 95%) as a gum. IR
137.8, 137.2, 133.4, 129.8, 128.3, 127.9, 127.8, 127.72, 127.67, 85.3,
80.8, 78.7, 73.0, 72.6, 71.7, 71.4, 21.5 ppm. Elemental Anal.
C35H36O8S (616.72): calcd C, 68.16; H, 5.88 found C, 67.80; H, 5.86%.
4.2.4. 4,5,6-Tri-O-benzyl-2-O-tosyl-myo-inositol (11). To an ice
cooled solution of the tosylate 10 (7.0 g, 11.35 mmol) in dichloro-
methane (15 mL), trifluoroacetic anhydride (6.31 mL, 45.40 mmol)
was added followed by glacial acetic acid (2.6 mL, 45.40 mmol) and
stirred at ambient temperature for 12 h. The reaction mixture was
cooled (ice bath), andpotassium carbonatewasadded and stirredfor
4 h (till the pH was neutral, as indicated by pH paper). The resulting
mixture was passed through a bed of Celite and the filtrate was
concentrated. The residue obtained (10 g) was taken in THF/MeOH
(1:1, 20 mL) and potassium carbonate (6.3 g, 45.40 mmol) was
added, stirred for 8 h. Ice was added to the reaction mixture, solvents
were removed under reduced pressure and the residue was worked
up with ethyl acetate ‘as usual’. The crude product was flash column
chromatoghraphed (eluent: ethyl acetate/light petroleum, 2:3) to
affordthe diol 11 (6.17 g, 90%)as a colorless solid. Mp133.5e135.5 ꢀC;
(CHCl3):
7.41e7.23 (m, 15H), 5.08e4.90 (m, 2H), 4.85e4.57 (m, 4H),
n
3300e3600 (OH) cmꢁ1 1H NMR (200 MHz, CDCl3):
;
d
4.25e4.15 (m, 1H), 4.05e3.85 (m, 2H), 3.43e3.20 (m, 2H), 2.26 (br s,
OH, 1H), 2.15e1.95 (m, 1H), 1.45e1.22 (m, 1H), 0.88 (s, 9H), 0.07 (s,
3H), 0.05 (s, 3H) ppm; 13C NMR (100.6 MHz, CDCl3):
d 138.71,
138.67, 138.5, 128.6, 128.3, 128.2, 128.1, 128.0, 127.9, 127.5, 127.4,
86.6, 83.6, 81.4, 75.5, 72.6, 68.4, 67.2, 35.9, 25.8, 18.1, ꢁ4.6,
ꢁ5.0 ppm. Elemental Anal. calcd for C33H44O5Si (548.78) C, 72.22;
H, 8.08 found C, 71.93; H, 7.79%.
4.2.8. Preparation of the ketone 15. A mixture of the TBS ether 14
(1.1 g, 2.00 mmol), ethyl acetate (15 mL), and IBX (1.68 g,
IR (CHCl3):
n
3550e3500, 3500e3400 (OH) cmꢁ1
;
1H NMR

7968
R.C. Jagdhane, M.S. Shashidhar / Tetrahedron 67 (2011) 7963e7970
6.00 mmol) was refluxed for 8 h. The reaction mixture was cooled
to room temperature and passed through a bed of Celite. The bed of
Celite was washed with ethyl acetate (2ꢂ50 mL), and the combined
filtrate was evaporated under reduced pressure. The residue was
purified by passing through a short column of silica gel (eluent:
ethyl acetate/light petroleum, 1:9) to afford the racemic ketone 15
eluent: ethyl acetate/light petroleum, 3:7) to afford the racemic
tetrabenzyl ether 1716 (0.075 g, 43%) as a low melting solid. IR
(CHCl3): d 7.45e7.15
n
3650e3150 cmꢁ1; 1H NMR (200 MHz, CDCl3):
(m, 20H), 4.99 (d, J¼10.6 Hz, 1H), 4.92 (d, J¼11 Hz, 1H), 4.84 (d,
J¼10.6 Hz, 1H), 4.75 (s, 2H), 4.55 (d, J¼11 Hz, 1H), 4.45 (d, J¼11.9 Hz,
1H), 4.38 (d, J¼11.9 Hz, 1H), 4.25e4.05 (m, 2H), 3.67 (d, J¼9.6 Hz,
1H), 3.57e3.37 (m, 2ꢂOH, 4H), 3.19 (d, J¼8.6 Hz,1H), 2.05 (dd, J¼3.2
and 15.4 Hz, 1H), 1.85 (dd, J¼2.8 and 15.4 Hz, 1H) ppm.
(1.05 g, 95%) as a gum. IR (CHCl3):
(200 MHz, CDCl3): 7.45e7.20 (m, 15H), 5.00e4.78 (m, 3H), 4.74 (s,
n
1737 (C]O) cmꢁ1 1H NMR
;
d
2H), 4.57 (d, J¼11.7 Hz, 1H), 4.32e4.25 (m, 1H), 4.15e3.95 (m, 2H),
3.68 (dd, J¼2.0 and 8.3 Hz,1H), 2.55e2. 35 (m, 2H), 0.86 (s, 9H), 0.05
4.2.11. Preparation of the racemic ketone 18. A mixture of the diol 17
(0.016 g, 0.029 mmol), IBX (0.024 g, 0.087 mmol) and ethyl acetate
(3 mL) was refluxed for 7 h. The reaction mixture was cooled to
ambient temperature and passed through a bed of Celite and
washed with ethyl acetate (2ꢂ15 mL), concentrated under reduced
pressure. The crude residue was purified by column chromatogra-
phy (100e200 silica gel, eluent: ethyl acetate/light petroleum, 1:3)
to afford the racemic ketone 1816 (0.01 g, 65%) as a solid. Mp
91e92 ꢀC (crystals from Et2O/light petroleum (1:2) at rt); IR
(s, 6H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 203.7, 138.4, 138.1, 137.8,
128.3, 128.2, 128.05, 128.03, 127.64, 127.59, 127.5, 85.6, 82.1, 81.7,
75.7, 73.3, 72.9, 67.7, 45.0, 25.6, 18.0, ꢁ4.62, ꢁ5.16 ppm. Elemental
Anal. C33H42O5Si (546.77): calcd C, 72.49; H, 7.74 found C, 72.15; H,
8.12%.
4.2.9. Preparation of the racemic dichloromethyl derivative 16. To
a cooled (dry ice-acetone, ꢁ78 ꢀC) solution of LDA (1.17 mL, 2.0 M
soln in THF/heptanes/ethyl benzene, 2.34 mmol) in THF (4.0 mL)
was added dichloromethane (0.75 mL, 11.7 mmol) followed by
(after 5 min) a solution of the ketone 15 (0.64 g, 1.17 mmol) in THF
(4.0 mL). The reaction mixture was stirred at ꢁ78 ꢀC for 2 h and
then at 0 ꢀC for 2 h. To the reaction mixture, a saturated solution of
aq ammonium chloride (3.0 mL) was added, and concentrated
under reduced pressure; the residue was worked up with ethyl
acetate ‘as usual’. The crude product was purified by flash column
chromatography (eluent: ethyl acetate/light petroleum, 1:33) to
afford racemic 16 (0.60 g, 82%) as a gum, which converted to a solid
on storing in a refrigerator. Mp 59e60 ꢀC (crystallized from pentane
(CHCl3):
CDCl3):
n
3600e3250 (OH), 1738 (C]O) cmꢁ1; 1H NMR (400 MHz,
7.50e7.27 (m, 18H), 7.23e7.13 (m, 2H), 5.05e4.90 (m, 3H),
d
4.74 (d, J¼10.8 Hz, 1H), 4.61e4.52 (m, 2H), 4.47 (d, J¼11.8 Hz, 1H),
4.41 (d, J¼11.8 Hz, 1H), 4.19e4.10 (m, 1H), 4.09e3.97 (m, 2H), 3.53
(d, J¼8.8 Hz, 1H), 3.15 (d, J¼8.8 Hz, 1H), 2.84 (d, J¼14.5 Hz, 1H), 2.47
(d, J¼14.5 Hz, 1H), 2.40 (br s, D2O exchangeable, OH, 1H) ppm.
4.2.12. Preparation of the alkyne 21. To a cooled (dry ice-acetone,
ꢁ78 ꢀC) solution of LDA (2.88 mL, 2.0 M soln in THF/heptanes/
ethyl benzene, 5.76 mmol) in THF (6.0 mL) was added dichloro-
methane (1.23 mL, 19.2 mmol) followed by (after 5 min) a solution
of the ketone 15 (1.05 g, 1.92 mmol) in THF (6.0 mL). The reaction
mixture was stirred at ꢁ78 ꢀC for 4 h. To the reaction mixture
a saturated solution of aq ammonium chloride (8.0 mL) was added
and concentrated under reduced pressure, the residue was worked
up with ethyl acetate ‘as usual’. The crude product was purified by
flash column chromatography (eluent: ethyl acetate/light petro-
leum, 1:33) to afford starting ketone 15 (0.63 g, 60%) and the ra-
cemic 21 (0.37 g, 29%) as a solid. Mp 93e95 ꢀC (crystals from light
at rt); IR (CHCl3):
CDCl3): 7.45e7.15 (m, 15H), 5.94 (s, 1H), 5.08 (s, OH, 1H), 5.04 (d,
n
3500e3200 (OH) cmꢁ1 1H NMR (200 MHz,
;
d
J¼11Hz, 1H), 4.97 (d, J¼10.7 Hz, 1H), 4.86 (d, J¼10.7 Hz, 1H),
4.83e4.62 (m, 3H), 4.44e4.36 (m, 1H), 4.21 (t, J¼9.6 Hz,1H), 3.84 (d,
J¼9.5 Hz, 1H), 3.42 (dd, J¼9.6 and 2.8 Hz, 1H), 2.27 (dd, J¼14.9 and
3.7 Hz, 1H), 1.79 (dd, J¼14.9 and 2.4 Hz, 1H), 0.90 (s, 9H), 0.11 (s, 6H)
ppm; 13C NMR (50.3 MHz, CDCl3):
d 138.3, 138.1, 138.0, 128.32,
128.27, 127.89, 127.86, 127.7, 127.63, 127.59, 127.56, 82.6, 81.9, 81.1,
79.5, 75.9, 75.7, 73.5, 70.1, 30.2, 25.7, 18.1, ꢁ4.5, ꢁ5.5 ppm. Mass
calcd M (þNa) 653.23 found 653.26. Elemental Anal. calcd for
C34H44Cl2O5Si (630.23) C, 64.65; H, 7.02 found C, 64.59; H, 6.74%.
petroleum at rt); IR (Nujol):
n
3500e3250 (OH), 2229 (C^C) cmꢁ1
7.50e7.27 (m, 15H), 4.92 (s, 2H), 4.89
;
1H NMR (200 MHz, CDCl3):
d
(s, 2H), 4.84 (s, D2O exchangeable, OH, 1H), 4.79 (d, J¼11.6 Hz, 1H),
4.69 (d, J¼11.6 Hz, 1H), 4.30e4.20 (m, 1H), 4.07 (t, J¼9.6 Hz, 1H),
3.50 (d, J¼9.5 Hz, 1H), 3.36 (dd, J¼9.7 and 2.7 Hz, 1H), 2.32 (dd,
J¼15.0 and 3.6 Hz, 1H), 1.75 (dd, J¼15.0 and 2.2 Hz, 1H), 0.88 (s, 9H),
4.2.10. Preparation of the racemic diol 17. To a solution of the
dichloromethyl derivative 16 (0.23 g, 0.36 mmol) in DMSO (3 mL)
was added n-tetrabutylammonium hydroxide (1.3 mL, 35% solution
in H2O, 1.82 mmol), at ambient temperature and stirred for 8 min.
The reaction mixture was poured into a saturated solution of aq
ammonium chloride (20 mL), diluted with ethyl acetate, and
worked up with ethyl acetate ‘as usual’. The residue obtained was
taken in methanol (60 mL), cooled using ice bath and a solution of
sodium borohydride (0.016 g, 0.44 mmol) in H2O (12 mL) was
added and stirred at 0e5 ꢀC for 20 min. Acetone (2.0 mL) was added
to the reaction mixture, stirred for 10 min and concentrated under
reduced pressure. The residue was worked up with ethyl acetate ‘as
usual’. The crude product was purified by column chromatography
(eluent: ethyl acetate/light petroleum, 4:1) to afford the racemic
triol (0.09 g) as a thick gum.
A mixture of the triol (0.075 g, 0.16 mmol), dibutyltin oxide
(0.046 g, 0.19 mmol), toluene (1 mL), methanol (1 mL) was refluxed
for 24 h. The reaction mixture was cooled to ambient temperature,
concentrated under reduced pressure and the residue co-
evaporated with toluene (2ꢂ3 mL). To the residue, toluene
(2.0 mL), benzyl bromide (0.038 mL, 0.32 mmol), and n-tetrabu-
tylammonium bromide (0.01 g, 0.032 mmol) were added and
refluxed for 5 h. The reaction mixture was cooled to ambient
temperature, concentrated under reduced pressure and the residue
was purified by column chromatography (100e200 mesh silica gel,
0.08 (s, 6H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 138.6, 138.1, 138.0,
128.5, 128.3, 128.2,127.9, 127.7, 127.6, 127.53,127.49, 86.2, 82.2, 79.6,
76.2, 75.9, 73.6, 71.6, 70.9, 70.6, 62.3, 39.7, 25.6, 18.0, ꢁ4.5,
ꢁ5.5 ppm. Mass calcd M (þNa) 629.26; observed 629.25. Elemental
Anal. C35H43ClO5Si (606.26): calcd C, 69.23; H, 7.14 found C, 69.15;
H, 6.90%.
4.2.13. Preparation of the racemic TBS ether 25. To a cooled (ice and
salt mixture) mixture of the diol 12 (1.02 g, 2.35 mmol), dichloro-
methane (5 mL), and 2,6-lutidine (0.68 mL, 5.86 mmol) was added
TBSOTf (0.8 mL, 3.52 mmol) and the reaction mixture was allowed
to warm upto 10 ꢀC over 1 h and then stirred at ambient temper-
ature for 2 h. Ice was added to the reaction mixture, diluted with
dichloromethane and worked up as usual. The crude product was
purified by flash column chromatography (eluent: ethyl acetate/
light petroleum, 1:4) to obtain the racemic TBS ether 25 (1.07 g,
83%) as a gum. IR (Neat):
(200 MHz, CDCl3):
n
3300e3600 (OH) cmꢁ1 1H NMR
;
d
7.40e7.20 (m, 15H), 4.90 (d, J¼11.1 Hz, 1H), 4.81
(d, J¼11.1 Hz, 1H), 4.82 (s, 2H), 4.73 (d, J¼11.5 Hz, 1H), 4.65 (d,
J¼11.5 Hz, 1H), 4.16e4.00 (m, 2H), 3.79 (t, J¼9.5 Hz, 1H), 3.46 (dd,
J¼9.5 and 3.1 Hz, 1H), 3.30 (t, J¼9.2 Hz, 1H), 2.42 (br s, OH, 1H),
2.22e2.07 (m, 1H), 1.50e1.30 (m, 1H), 0.89 (s, 9H), 0.10 (s, 3H), 0.06
(s, 3H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 139.1, 138.8, 138.0, 128.4,

R.C. Jagdhane, M.S. Shashidhar / Tetrahedron 67 (2011) 7963e7970
7969
128.2, 128.1, 127.89, 127.86, 127.7, 127.4, 127.1, 86.5, 82.9, 81.4, 75.9,
recovered]. Mp 133e135 ꢀC; IR (Nujol):
NMR (200 MHz, CDCl3): d 7.45e7.26 (m, 20H), 5.10e4.95 (m, 2H),
n
3400e3100 (OH) cmꢁ1; 1H
75.5, 72.8, 69.7, 66.1, 36.0, 25.8, 17.9, ꢁ4.5, ꢁ4.64 ppm. Elemental
Anal. C33H44O5Si (548.78): calcd C, 72.22; H, 8.08 found C, 72.29; H,
7.92%.
4.81 (d, J¼10.7 Hz, 1H), 4.73e4.60 (m, 5H), 4.02 (t, J¼9.5 Hz, 1H),
4.00e3.80 (m, 2H), 3.46 (dd, J¼9.6 and 2.9 Hz, 1H), 3.29 (t, J¼9.2 Hz,
1H), 2.40e2.18 (br s and dt, J¼13.9 and 4.3 Hz, OH, 2H), 1.33e1.15
4.2.14. Preparation of the racemic ketone 26. The TBS ether 25
(1.0 g, 1.82 mmol), ethyl acetate (13 mL), and IBX (1.53 g,
5.46 mmol) were refluxed for 8 h. The reaction mixture was cooled
to room temperature and passed through a bed of Celite. The bed of
Celite was washed with ethyl acetate (2ꢂ40 mL), and the combined
filtrate was evaporated under reduced pressure. The residue was
purified by passing through a small column of silica gel (eluent:
ethyl acetate/light petroleum, 1:6) to afford the racemic ketone 26
(m, 1H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 138.8, 138.7, 138.4,
128.6, 128.29, 128.2, 128.0, 127.8, 127.6, 127.56, 127.52, 86.4, 83.4,
81.8, 75.6, 75.3, 72.5, 72.1, 71.5, 68.1, 31.9 ppm. Elemental Analysis
calcd for C34H36O5 (524.65); C, 77.84; H, 6.92; found C, 78.09; H,
7.16%.
4.2.17. Preparation of 30. The TBS ether 25 (1.22 g, 2.22 mmol),
ethyl acetate (15 mL), and IBX (1.87 g, 6.67 mmol) were refluxed for
8 h. The reaction mixture was cooled to room temperature and
passed through a bed of Celite; the latter was washed with ethyl
acetate, and the combined washings were evaporated under re-
duced pressure. Crude product obtained was purified by flash col-
umn chromatography (eluent: ethyl acetate/light petroleum,1:9) to
(0.85 g, 85%) as a colorless solid. Mp 53e55 ꢀC; IR (CHCl3):
(C]O) cmꢁ1 1H NMR (200 MHz, CDCl3):
7.45e7.20 (m, 15H),
n
1732
;
d
5.00e4.67 (m, 5H), 4.56 (d, J¼11.5 Hz, 1H), 4.25 (d, J¼9.5 Hz, 1H),
3.90e3.55 (m, 3H), 2.70e2.45 (m, 2H), 0.86 (s, 9H), 0.06 (s, 3H), 0.04
(s, 3H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 204.2,138.3,138.2, 137.5,
128.3, 128.2, 128.1, 127.9, 127.8, 127.6, 127.5, 85.06, 85.04, 81.8, 75.4,
74.9, 73.5, 69.5, 45.9, 25.7, 17.8, ꢁ4.7, ꢁ4.9 ppm. Elemental Anal.
C33H42O5Si (546.77): calcd C, 72.49; H, 7.74 found C, 72.28; H, 7.82%.
afford the
solid. The silica gel used was pre-eluted with triethylamine/light
petroleum (1:49, 3e5 mL/g) mixture. Mp 72e74 ꢀC; IR (CHCl3):
1697 (C]O) cmꢁ1; 1H NMR (200 MHz, CDCl3):
7.40e7.27 (m,10H),
a,b-unsaturated ketone 30 (0.85 g, 79%) as a colorless
n
d
4.2.15. Preparation of chlorooxiranes 27 and 28. To a cooled (dry ice-
acetone, ꢁ78 ꢀC) solution of LDA (0.82 mL, 2.0 M soln in THF/hep-
tanes/ethyl benzene, 1.64 mmol) in THF (1.0 mL), was added
dichloromethane (0.35 mL, 5.49 mmol) followed by (after 5 min) the
ketone 26 (0.30 g, 0.55 mmol). Resulting reaction mixture was stirred
at ꢁ78 ꢀC for 90 min, at 0 ꢀC for 1 h and then at ambient temperature
for 2 h. To the reaction mixture, a saturated solution of aq ammonium
chloride (1.0 mL) was added and the volatiles were evaporated under
reduced pressure, the residue was worked up with ethyl acetate ‘as
usual’. The crude product was purified by flash column chromatog-
raphy (eluent: ethyl acetate/light petroleum 1:32) to afford racemic
27 (0.24 g, 70%) as a gum and racemic 28 (0.05 g, 15%) as a colorless
5.68 (d, J¼3.3 Hz, 1H), 4.83 (q, J¼12.4 Hz, 2H), 4.67 (q, J¼11.9 Hz,
2H), 4.20e4.05 (m, 2H), 2.96e2.81 (m, 1H), 2.60e2.43 (m, 1H), 0.87
(s, 9H), 0.07 (s, 6H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 191.8, 150.3,
137.9, 135.7, 128.5, 128.4, 128.0, 127.8, 127.7, 127.3, 115.0, 78.3, 72.6,
71.3, 69.7, 44.7, 25.6, 17.9, ꢁ4.8, ꢁ4.9 ppm. Elemental Anal.
C26H34O4Si (438.63): calcd C, 71.19; H, 7.81, found C, 71.17; H, 7.98%.
Acknowledgements
R.J. thanks Council of Scientific and Industrial Research, New
Delhi for a Senior Research Fellowship. Help from Ms. Shobhana
Krishnaswamy in solving the crystal structure of 28 is gratefully
acknowledged. Technical help of Ms. Richa Sardessai is much
appreciated. Financial assistance for this work was provided by the
Department of Science and Technology, New Delhi.
solid. Data for 27: 1H NMR (400 MHz, CDCl3):
d 7.35e7.17 (m, 15 H),
5.39 (s, 1H), 4.92 (d, J¼11 Hz, 1H), 4.85 (d, J¼11 Hz, 1H), 4.79 (s, 2H),
4.64 (d, J¼10.5 Hz, 1H), 4.58 (d, J¼10.5 Hz, 1H), 3.83e3.73 (m, 2H),
3.51e3.42 (m, 2H), 2.09 (dd, J¼13.3 and 5.0 Hz,1H),1.99 (t, J¼12.8 Hz,
1H), 0.9 (s, 9H), 0.11 (s, 3H), 0.07 (s, 3H) ppm; 13C NMR (100.6 MHz,
Supplementary data
CDCl3):
d 138.6, 138.3, 137.7, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8,
X-ray data table and ORTEP diagram for 28 and copies of 1H and
13C NMR spectra for all the compounds appearing in schemes.
Crystallographic data (excluding structure factors) for the com-
pound 28 have been deposited with the Cambridge Crystallo-
graphic Data Centre as CCDC no. 823204. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: þ44 (0) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.Uk). Supplementary data associated with this
article can be found in online version at doi:10.1016/
j.tet.2011.08.027.
127.6,127.5,127.4, 85.9, 83.1, 79.2, 76.1, 75.8, 75.4, 70.5, 70.0, 62.0, 34.1,
25.8, 17.9, ꢁ4.64, ꢁ4.74 ppm. Mass calcd M (þNa), 617.25; observed
617.30. Elemental anal. C34H43ClO5Si (594.26): calcd C, 68.60; H, 7.28
found C, 68.95; H, 7.38%.
Data for 28: Mp 106e108 ꢀC (Crystals obtained from acetonitrile
at room temperature); 1H NMR (200 MHz, CDCl3):
d 7.40e7.15 (m,
15H), 5.17 (s, 1H), 5.00e4.70 (m, 5H), 4.54 (d, J¼11.5 Hz, 1H),
4.01e3.86 (m, 1H), 3.77e3.61 (m, 2H), 3.54e3.42 (m, 1H), 2.01 (dd,
J¼14.1, 5.3 Hz, 1H), 1.81 (dd, J¼14.0, 11.2 Hz, 1H), 0.89 (s, 9H), 0.08 (s,
3H), 0.06 (s, 3H) ppm; 13C NMR (50.3 MHz, CDCl3):
d 138.7, 138.3,
137.2, 128.6, 128.3, 128.2, 128.1, 127.9, 127.6, 127.4, 127.3, 86.3, 83.1,
77.3, 76.0, 75.6, 75.1, 71.2, 70.5, 62.3, 33.8, 25.8, 17.9, ꢁ4.6,
ꢁ4.7 ppm. Mass: calcd M (þNa), 617.25; observed 617.32. Elemental
Anal. C34H43ClO5Si (594.26): calcd C, 68.60; H, 7.28 found C, 68.62;
H, 7.65%.
References and notes
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Commun. 2009, 1204e1206 and references cited therein.
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4477e4503; (b) Yamauchi, S.; Hayashi, M.; Watanabe, Y. Synlett 2009,
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Gammon, D. W.; Oscarson, S.; Karlsson, E. Tetrahedron 2011, 67, 618e623; (d)
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0.58 mmol) in DMF (0.7 mL) and stirred at ambient temperature for
17 h. Ice was added to the reaction mixture, solvents were evapo-
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