Stereoselective total synthesis of both (6R,9R,10S,7E)- and (6S,9R,10S,7E)-epimers of oxylipin (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid

Article abstract of DOI:10.1016/j.tet.2012.12.076

An asymmetric synthesis of both the stereoisomers (2a & 2b) of the structure 2 proposed for (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid, an immunostimulant oxylipin from the n-butanol extract of the corms of Dracontium loretense, has been accomplished. The key steps involved are using Jacobsen's hydrolytic kinetic resolution (HKR), Julia-Kocienski olefination, regioselective epoxide ring opening and Wittig olefination. The configuration (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid was established as 2a from comparison of NMR data, HPLC analysis and [α]_D values of naturally derived (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid, and comparison with the synthetic diastereomers 2a and 2b.

Full text of DOI:10.1016/j.tet.2012.12.076

Tetrahedron 69 (2013) 2157e2166
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective total synthesis of both (6R,9R,10S,7E)- and
(6S,9R,10S,7E)-epimers of oxylipin (9R,10S,7E)-6,9,10-
trihydroxyoctadec-7-enoic acid
*
Bishwajit Saikia, Thongam Joymati Devi, Nabin C. Barua
Natural Products Chemistry Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An asymmetric synthesis of both the stereoisomers (2a & 2b) of the structure 2 proposed for (9R,10S,7E)-
6,9,10-trihydroxyoctadec-7-enoic acid, an immunostimulant oxylipin from the n-butanol extract of the
corms of Dracontium loretense, has been accomplished. The key steps involved are using Jacobsen’s hy-
drolytic kinetic resolution (HKR), JuliaeKocienski olefination, regioselective epoxide ring opening and
Wittig olefination. The configuration (9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid was established
Received 11 November 2012
Received in revised form 28 December 2012
Accepted 31 December 2012
Available online 11 January 2013
as 2a from comparison of NMR data, HPLC analysis and [a] values of naturally derived (9R,10S,7E)-
D
6,9,10-trihydroxyoctadec-7-enoic acid, and comparison with the synthetic diastereomers 2a and 2b.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
PBMC
Dracontium loretense
Oxylipin
Immunostimulant
Asymmetric synthesis
Epimer
1. Introduction
Amazon has been used as folk medicine to enhance immune
function. Despite existence of effective chemotherapy millions of
Oxylipins1 constitute a family of oxygenated natural products,
which are biologically active lipids generated from fatty acids by
pathways involving at least one step of dioxygen-dependent oxi-
dation. These are widely distributed in aerobic organisms including
plants, animals and fungi and are an important class of signalling
molecule in plants, especially related to plant stress responses and
innate immunity.2 The major precursors of oxylipins in plant and
animal kingdoms are C18 and C20 polyenoic fatty acids. Many of the
oxylipins have physiological and pathological significance. One of
the most biologically important groups of oxylipins in mammals is
the eicosanoid, which include prostaglandins and leukotrienes. In
general, eicosanoids are not stored within cells, but are synthesized
from the esterified fatty acids as required. Eicosanoids are potent
regulators of host immune responses and often opposing effects on
smooth muscle and blood platelets.3
people die from AIDS due to the emergence of human immune-
deficiency virus (HIV) poses an even greater challenge to the
health systems. These challenges have prompted the urgent search
for novel anti-HIV chemotherapy drugs. Medicinal properties of D.
loretense have been exploited for long time in crude form, e.g.,
combination of the extracts or infusion of D. loretense and Uncaria
tomentosa are used by AIDS patients to reinforce the immune sys-
tem, and as a results it has been a frontline drug in therapy of AIDS.
ꢀ
D. loretense Engl. is known as ‘jergon sacha’ in the Peruvian Ama-
zon, which has been used as a well known herbal medicine in
Peruvian and can be found as dried powder, tincture, alcoholic and
aqueous-alcoholic mixture. Recently, Pizza et al.4 isolated four
novel oxylipins 1e4 from the n-butanol extract of the corms of
D. loretense (Fig. 1). Among all four novel oxylipins, only
(9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid (oxylipin 2)
exhibited potential immunostimulatory effects as revealed by a 3H-
thymidine incorporation assay with OKT3-activated human pe-
The Araceae family is one of the most dominant tropical families
among the 3300 species and 105 genera of herbs and vines, and
many of the species are used as traditional remedies or food.4
Traditionally the infusion obtained from the corms of the plant
Dracontium loretense, of Araceae family, available in Peruvian
ripheral blood mononuclear cells (PBMCs) at 10 mM, which makes it
either potential drug or therapeutic lead candidate against various
diseases. Structure-modification studies on oxylipin 2 and similar
molecule like oxylipin 3 indicated that the 10S-configuration of the
hydroxyl group is the important factor for tight interaction with the
enzyme. Hence, one can imagine that if the configuration of the C-
10 hydroxyl group is altered, this substrate will not dock in the
* Corresponding author. Tel.: þ91 376 2371283; fax: þ91 376 2370011; e-mail
addresses: ncbarua2000@yahoo.co.in, ncbarua12@rediffmail.com (N.C. Barua).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.076

2158
B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
OH OH
OH
O
COOH
( )
OH
7
OH
OH
OH
2
1
OH OH
OH
O
( )
OH
OH
7
OH
OH
OH
3
O
4
Scheme 1. Retrosynthetic approach towards the synthesis of the two epimers of
(9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid 2.
Fig. 1. Oxylipin 2 and its structurally related compounds.
carbon long chain substituent at C-11 in 2 could be introduced
through regioselective epoxide ring opening with Grignard reagent 7
derived from commercially available 1-bromoheptane.
binding site in a proper way and hence reacts much slower. This
reveals that the configuration at C-10, play a vital role in the po-
tential biological activity of the molecule containing it.
The synthesis began with the monoprotection of hexanediol as
its silyl ether, followed by oxidation to yield intermediate aldehyde.
Exposure of 1,6-hexanediol 10 with tert-butyldimethylsilyl chloride
(TBDMSCl) and imidazole in dry dichloromethane (DCM) at room
temperature afforded the monoprotected alcohol 11 as a colourless
liquid in 91% yield.11 Pyridinium chlorochromate (PCC) oxidation12
of the alcohol 11 followed by one carbon Wittig olefination with
methylene triphenylphosphorane, prepared in situ by treating
methyltriphenylphosphonium iodide with n-BuLi at low tempera-
ture afforded 12 in 87% yield over two steps. The resulting olefin,
when treated with mCPBA in methylene chloride, yielded the ep-
oxide 13.13 Then the racemic epoxide 13 was subjected to Jacobsen’s
HKR using (R,R)-(salen)CoIIIOAc complex to give (R)-9 (44% yield;
98% ee) as the optically enriched isomer with diol 14 as a side
product (Scheme 2). Selective tosylation of 14 was achieved by the
action of p-TsCl and triethylamine in the presence of Bu2SnO giving
monotosylated alcohol 16.14 Upon treatment with potassium car-
bonate in methanol, 16 gave epoxide (S)-9 in 97% yield with 98% ee.
The enantiomeric epoxides (R)-9 and (S)-9 were thus converted to
the sulfides (R)-15 and (S)-15 via regioselective ring opening of the
epoxides with 1-phenyl-1H-tetrazole-5-thiol (PT-SH). This reaction
was carried out in less than 2 h in DCM in the presence of mont-
morillonite K-10 clay.15 Oxidation of the sulfide was carried out
with meta-chloroperoxybenzoic acid (mCPBA) to generate the
In view of the potential biological activity displayed by this
molecule coupled with unique stereogenic variations within these
four oxylipins (1e4), we have put our efforts towards the synthesis
of oxylipin 2 involving novel strategies from cheap naturally oc-
curring organic compounds. Oxylipin 2, one of nature’s most in-
triguing molecules, was found to have a trihydroxy terminal acid
with a trans double bond. To the best of our knowledge recently,
Sharma’s group5 achieved the synthesis of (6S,9R,10S,7E)-isomer of
the proposed structure 2, none for (6R,9R,10S,7E)-isomer of 2 has
yet appeared in the literature. In our view the reported synthetic
route has several limitations, such as, the use of costly reagents, low
yield and time taking olefin cross metathesis step in the synthetic
sequence. Although synthesis of natural compounds require
a highly enantioselective access to these substrates and that can be
efficiently derived from readily available naturally occurring and
inexpensive starting material. In this regard poly-functionalized
chiral molecule, such as L-ascorbic acid is an important and versa-
tile unit extensively used in the preparation of complex target
natural products. Similarly, the hydrolytic kinetic resolution (HKR)
catalyzed by (salen)Co(III) complex has emerged as an effective
route for the preparation of highly enantioenriched terminal ep-
oxides, having found widespread use in the synthesis of complex
natural products.6 In continuation of our long-term interest on
asymmetric synthesis of pharmacologically important natural and
synthetic compounds employing novel and efficient synthetic
routes,7 herein we report a convergent synthesis of both stereo-
isomers (6R,9R,10S,7E-2 and 6S,9R,10S,7E-2: C-6 epimers) of
immunostimulant oxylipin (9R,10S,7E)-6,9,10-trihydroxyoctadec-
7-enoic acid 2 by an approach that features the use of highly ef-
fective asymmetric catalytic reactions to set all stereo centre in-
dependently. In this paper, we report our synthesis of both C-6
epimers of oxylipin 2 using Jacobsen’s hydrolytic kinetic resolution8
(HKR), JuliaeKocienski olefination,9 regioselective epoxide ring
opening and Wittig olefination10 as the key steps.
a
HO
b, c
HO
OTBS
OH
OTBS
11
12
10
(R)
e
+
d
HO
OTBS
OTBS
OTBS
O
O
f
OH
13
(R)-9
14
O
S
O
N
N
N
N
N
N
N
d
S
(R)-9
OTBS
OTBS
N
OH
(R)-15
OH
(R)-6
Ph
Ph
f
h
g
OTBS
2. Results and discussion
TsO
OTBS
14
O
OH
(S)-9
16
Our retrosynthetic analysis for both the isomers of (9R,10S,7E)-
6,9,10-trihydroxyoctadec-7-enoic acid is depicted in Scheme 1. We
envisioned that the C7eC8 trans double bond of the target compound
2 would be constructed through JuliaeKocienski olefination be-
tween aldehyde 5 and enantiomeric sulfones (R)-6 and (S)-6. We
anticipated that sulfones (R)-6 and (S)-6 would be obtained from the
hexane-1,6-diol 10 in two main steps involving (salen)Co complex
catalyzed efficient hydrolytic kinetic resolution and regioselective
epoxide opening. The aldehyde 5 would be synthesized from com-
N
O
S
O
N
N
N
d
N
N
S
OTBS
N
Ph
OTBS
N
Ph
OH
OH
(S)-15
(S)-6
Scheme 2. Synthesis of chiral sulfones (R)-6 & (S)-6. Reagents and conditions: (a) TBSCl,
imidazole, DCM, rt, 6 h, 91%; (b) PCC, DCM, 3 A MS, 0 ꢀC to rt; (c) CH3PPh3þIꢁ, n-BuLi, dry
ꢁ
THF, ꢁ78 ꢀC to rt, 4 h, 87%, over two steps; (d) mCPBA, CH2Cl2, 0 ꢀC, 6 h (93% for 13, 90% for
R-6 and 82% for S-6); (e) (R,R)-(salen) CoIIIOAc (0.5 mol %), distilled H2O (0.55 equiv), 0 ꢀC,
14 h, (44% for R-9, 46% for 14); (f) PTSH, dry DCM, Mont K-10, rt, 6 h (94% for R-15 and 85%
for S-15); (g) Bu2SnO, TsCl, Et3N, DCM, rt, 2 h, 98%; (h) K2CO3, MeOH, rt, 2.5 h, 97%.
mercially available inexpensive -ascorbic acid 8. Finally the seven
L

B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
2159
enantiomeric sulfones (R)-6 and (S)-6 in 90% (99% ee, as de-
termined by chiral column HPLC)16 and 82% (98% ee, as determined
by chiral column HPLC)16 yield, respectively (Scheme 2).
The key intermediate 19 was more conveniently obtained by a
known efficient route17 starting with
L-ascorbic acid
8
(Scheme 3). Acetonide protection of
L-Ascorbic acid with 2,2-
dimethoxypropane using hydrochloric acid at room temperature
afforded the compound 17 (88% yield), which on further oxidation
with hydrogen peroxide furnished the threonic acid derivative 18
(89% yield). Esterification of 18 with dimethylsulfate and sodium
bicarbonate in water yielded the methyl ester 19 in 95% yield. To
this end, the secondary hydroxyl group in 19 was protected as
benzyl ether with BnBr and weak base Ag2O in dry dimethyl
formamide (DMF) at low temperature to afforded compound 20 in
98% yield with 99% ee (as determined by chiral column HPLC).
DIBAL-H reduction18 of 20 under carefully controlled conditions in
ether at ꢁ90 ꢀC afforded aldehyde 5 (Scheme 3), which was used
without purification for the next reaction.
HO
O
H
H
(S)
H
HO
O
O
O
O
(R)
O
O
b
O
(R)
(R)
a
(S)
O
HOH2C
OR
HO
OH
HO
17
OH
18 R = H
19 R = CH3
c
8
Scheme 4. Synthesis of C-6 epimers of oxylipin 2. Reagents and conditions: (a)
KHMDS, dry THF, ꢁ78 ꢀC, 16 h, 66% for 21a & 60% for 21b; (b) TBHP, t-BuOH/eH2O
(1:1), reflux, 1 h, 95% for 22a & 91% for 22b; (c) Bu2SnO, TsCl, Et3N, DCM, rt, 8 h, 98% for
23a & 94% for 23b; (d) K2CO3, MeOH, rt, 2.5 h, 98% for 24a & 91% for 24b; (e) Active Mg
metal, heptyl bromide, C2H4Br2, dry THF, rt, 2.5 h; (f) CuI, heptylmagnesium bromide,
dry THF, ꢁ20 ꢀC, 4 h, 89% for 25a & 78% for 25b, over two steps; (g) TBSCl, imidazole,
DCM, rt, 4 h, 95% for 26a & 93% for 26b; (h) pTSA, MeOH, 0 ꢀC, 30 min, 96% for 27a &
87% for 27b; (i) DesseMartin periodinate, NaHCO3, DCM, rt, 8 h; (j) NaClO2, NaHPO4,
Me2CCHMe, tBuOH, H2O, rt, 1 h, 84% for 28a & 80% for 28b, over two steps; (k) DDQ,
DCM:H2O (10:1), rt, 12 h; (l) HCl (cat), methanol, 0 ꢀC, 1 h, 94% for both 2a & 2b, over
two steps.
BnO
BnO
(S)
(S)
O
O
O
e
d
(R)
(R)
O
O
O
H
OMe
5
20
Scheme 3. Synthesis of key intermediate aldehyde 5 from L-ascorbic acid. Reagents
and conditions: (a) 2,2-dimethoxypropane, acetone, HCl gas, rt, 88%; (b) CaCO3, 30% aq
H2O2, charcoal, 10% Pd/C, H2O, 20 ꢀCe40 ꢀC, 89%; (c) NaHCO3, (CH3O)2SO2, H2O, 40 ꢀC,
6 h, 95%; (d) BnBr, Ag2O, dry DMF, 0 ꢀC to rt, 3 h, 98%; (e) DIBAL, Et2O, ꢁ90 ꢀC, 2 h.
After achieving both the fragments, we turned to the strategy
that would involve the use of the JuliaeKocienski olefination re-
action to construct the C7eC8 bridge (trans double bond). Utilizing
the robust and reliable procedure reported by Kocienski,9 the sul-
fones (R)-6 and (S)-6 were deprotonated with potassium bis-(tri-
methylsilyl)amide (KHMDS) and treated with crude aldehyde 5 to
afford the isomeric olefins 21a and 21b, respectively, with excellent
E/Z selectivity (E/Z¼>99:1) (Scheme 4). Acetonide deprotection was
two steps. Finally deprotection of the benzyl group24 by DDQ in DCM/
H2O solvent system followed by acid catalyzed (HCl in MeOH)
deprotection of the silyl25 (TBS) groups of the acid 28a and 28b fur-
nished the desired products 2a (94% yield, 99% ee)16 & 2b (94% yield,
98% ee),16 respectively over two steps (Scheme 4).
Synthetic compound 2a exhibited almost identical physical
properties (1H NMR, 13C NMR, TLC, HPLC, IR, ½a D
ꢂ
25) to those of
natural 2,4 thus marking the end of the campaign. The assigned (R)-
stereochemistry at C-6 stereogenic centre is rested on the
observed coupling constant (J6,7¼15.3, 6.5 Hz), which was further
supported by the sign of rotation with the reported natural product
t
performed by using aqueous BuOH as solvent under reflux condi-
tions furnishes the triols 22a and 22b in 95% (98% ee) and 91% (97%
ee) yield, respectively.19 Again selective monotosylation of primary
hydroxyl group of triols 22a and 22b was achieved by the action of p-
TsCl and triethylamine in the presence of Bu2SnO to afford mono-
tosylated alcohols 23a and 23b, respectively. Both the chiral diols
23a and 23b was then subjected to K2CO3 in methanol at room
temperature afforded two chiral epoxides 24a (98% yield; 99% ee)
and 24b (91% yield; 97% ee).14 The next step was the regioselective
epoxide ring opening of 24a and 24b by the Grignard reagent de-
rived from heptyl bromide (C7H15Br) in the presence of activator CuI
in dry THF at ꢁ20 ꢀC provided long chain diols 25a & 25b in excellent
yield20 followed by TBS protection of the free hydroxyl groups to give
the compounds 26a and 26b, respectively. It is well known that
primary silyloxy groups are cleaved under acidic conditions more
easily than secondary ones. In this approach, regioselective depro-
tection of the primary alcoholic group of 26a and 26b was accom-
plished by its treatment with p-toluene sulfonic acid in methanol21
at low temperature affording the primary alcohol 27a and 27b in
96% (98% ee) and 87% (98% ee) yield, respectively.
{½a 2D5
ꢂ
ꢁ10.4 (c 0.11, MeOH); lit.4
½
a 2D5
ꢂ
ꢁ10.7 (c 0.15, MeOH)}. Al-
though we observed a somewhat lower negative rotation, than that
of reported one, we are confident of our value since synthetic 2a
was determined to be pure by 300 MHz 1H NMR, 75 MHz 13C NMR
and HPLC analysis and since the enantiomeric purity (HPLC, Chir-
acel OD packed in a SS column) was >99%.
3. Conclusion
In conclusion, we have completed the synthesis of (6R,9R,
10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid and its C-6 epimer
[(6S,9R,10S,7E)-6,9,10-trihydroxyoctadec-7-enoic acid] in 7.7% and
3.6% overall yield, respectively. Total synthesis of oxylipin 2 to
possess the 6R,9R,10S,7E-configuration were accomplished by
comparison of the spectral data and optical rotation of the synthetic
sample with those of the natural products. We present herein
a highly convergent total synthesis of 2 that would potentially be
amenable to large-scale production of this important oxylipin.
These results will contribute towards the synthesis of more com-
plicated congeners carrying the same carbon framework and the
creation of biologically more potent substances.
Treatment of 27a and 27b with DesseMartin periodinate22 in
methylene chloride furnished the intermediate aldehydes, which
were further oxidized without purification using NaClO2, NaH2PO4,
tBuOH and 2-methyl-2-butene23 tothe corresponding carboxylic acid
28a and 28b in 84% (99% ee) and 80% (99% ee) yield, respectively, over

2160
B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
4. Experimental section
4.5. tert-Butyl-hept-6-enyloxy-dimethyl-silane (12)
4.1. General
To a stirred solution of Wittig salt (1.7 g, 4.3 mmol) in dry THF
(10 mL) was added dropwise a 1.6 M solution of n-BuLi (0.275 g,
4.3 mmol) at ꢁ40 ꢀC and immediately the colour becomes orange.
After 30 min crude aldehyde (0.860 g) in THF (2 mL) was added
dropwise at ꢁ40 ꢀC to the above solution and stirred it for some
time at the same temperature, the orange colour becomes dis-
appeared. Slowly we increased the temperature and finally
allowed to stir at room temperature for 4 h. After completion of
the reaction, saturated solution of NH4Cl (15 mL) was added and
extracted with ether (3ꢃ15 mL). The extract was washed with
water (3ꢃ10 mL) and saturated solution of brine (3ꢃ10 mL). The
organic part was dried with anhydrous Na2SO4 and evaporated
under reduced pressure. The crude material was purified by col-
umn chromatography on silica gel (1% EtOAc/Hexane) to afford
the tert-butyl-hept-6-enyloxy-dimethyl-silane 12 (0.854 g,
3.74 mmol, 87%) as a colourless liquid; Elemental analysis calcd.
Found: C, 68.30; H, 12.31; O, 6.93. C13H28OSi requires C, 68.35; H,
12.35; O, 7.00%; Rf (10% EtOAc/Hexane) 0.75; IR nmax (film) 2947,
1H NMR and 13C NMR spectra were recorded using a Bruker
DPX-300 NMR machine. IR spectra were recorded on a Per-
kineElmer 1640 FT-IR spectrometer. Elemental analysis data were
measured on a PerkineElmer (Model no. AE 2400) CHN analyzer.
Optical rotations were measured using a PerkineElmer 343 polar-
imeter. Mass spectra were recorded on WATERS Micro-mass ZQ
4000 (ESI Probe) spectrometer. Flash chromatography (Combi-
Flash) was performed with Merck silica gel (230e400 mesh), col-
umn chromatography was performed with Merck silica gel
(100e200 mesh) and preparative TLC was carried out on plates
prepared with Merck Silica gel G. Moisture sensitive reactions were
conducted under a dry nitrogen atmosphere. THF was distilled from
benzophenone ketyl prior to use. All solvents were distilled at their
boiling point and other commercially available reagents were used
as received, unless otherwise stated. Glassware was oven dried at
120 ꢀC overnight. All the reagents were used as purchased from
commercial suppliers without further purification. All analytical
data were recorded at Analytical Chemistry Division (CSIR-NEIST,
Jorhat-6, Assam, India).
2842, 1628, 1459, 1343, 1133 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
5.80e5.71 (1H, m, 6CH), 4.97e4.86 (2H, m, 7CH2), 3.57 (2H, t,
J¼6.51 Hz, 1CH2), 2.03 (2H, t, J¼6.6 Hz, 5CH2), 1.57e1.28 (6H, m,
2CH23CH24CH2), 0.84 {9H, s, (CH3)3(CH3)2Si}, 0.009 {6H, s,
(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 140.6, 114.4, 65.8,
4.2. 6-(tert-Butyl-dimethyl-silanyloxy)-hexan-1-ol (11)
34.3, 33.5, 30.0, 26.4, 20.7, 14.7, ꢁ6.5; MS (ESI, positive ion): m/z
(%)¼228.4 (100) [Mþ].
Hexan-1,6-diol (2 g, 16.92 mmol) was dissolved in dry DCM.
Imidazole (1.15 g, 16.92 mmol) and tert-butyldimethylsilyl chloride
(2.55 g, 16.92 mmol) were added, and the mixture was stirred at
room temperature for overnight. After dilution with Et2O (20 mL),
the solution was washed with water (3ꢃ20 mL), dried over anhy-
drous Na2SO4 and filtered and evaporated under reduced pressure
and purified by silica gel column chromatography (10% EtOAc/
Hexane) to furnished the product 11 (3.57 g, 15.39 mmol, 91%) as
a colourless liquid; Elemental analysis calcd. Found: C, 62.00; H,
12.10; O, 13.72. C12H28O2Si requires C, 62.01; H, 12.14; O, 13.77%; Rf
(10% EtOAc/Hexane) 0.75; IR nmax (film) 3428 (br), 2947, 2831, 1459,
4.6. tert-Butyl-dimethyl-(5-oxiranyl-pentyloxy)-silane (13)
To a stirred solution of alkene 12 (0.500 g, 2.18 mmol) in dry
DCM (5 mL) was added mCPBA (0.412 g, 2.39 mmol) at 0 ꢀC. The
mixture was stirred at room temperature for 6 h. After comple-
tion of the reaction, it was diluted with ethyl acetate (15 mL), an
aqueous solution of KI (5 mL) was added and the liberated I2 was
reduced by adding a solution of Na2S2O3 (6 mL) washed with
a saturated solution of NaHCO3 (3ꢃ10 mL) and brine (3ꢃ10 mL).
The organic fraction was dried over anhydrous Na2SO4 and the
solvent was removed under reduced pressure. The crude material
was purified by column chromatography on silica gel (1% EtOAc/
Hexane) to afford the epoxide 13 (0.493 g, 2.02 mmol, 93%) as
a colourless liquid; Elemental analysis calcd. Found: C, 63.80; H,
11.50; O, 13.00. C13H28O2Si requires C, 63.87; H, 11.55; O, 13.09%;
Rf 0.85 (10% EtOAc/Hexane); IR nmax (film) 2943, 2843, 1450,
1365 cmꢁ1; 1H NMR (300 MHz, CDCl3)
3.57 (2H, t, J¼3.9 Hz, 1CH2), 2.0 (1H, br s, OH), 1.55e1.45 (4H, m,
2CH2, 5CH2), 1.33e1.28 (4H, m, 3CH2, 4CH2), 0.85e0.83 {9H, m,
(CH3)3(CH3)2Si}, 0.009 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
d
3.61 (2H, t, J¼6.5 Hz, 6CH2),
CDCl3)
d
65.8, 63.0, 34.2, 33.2, 26.3, 20.7,14.7, ꢁ6.5; MS (ESI, positive
ion): m/z (%)¼255.4 (100) [MþNa]þ.
1276 cmꢁ1
; d 3.58 (2H, t,
1H NMR (300 MHz, CDCl3)
4.3. Preparation of Wittig salt (CH3PPh3D L
I )
J¼6.3 Hz, 1CH2), 2.87e2.85 (1H, m, OCH), 2.71e2.68 (1H, m,
OCHH), 2.43e2.40 (1H, m, OCHH), 1.50e1.30 (8H, m,
2CH23CH24CH25CH2), 0.84 {9H, s, (CH3)3(CH3)2Si}, 0.00 {6H, s,
Dissolve 6 g of triphenylphosphine in 10 mL of toluene in
a round bottom flask. Add a stir bar and attach a reflux condenser.
Prepare a solution of 4 g of methyl iodide in 8 mL of toluene and
add it dropwise to the triphenylphosphine solution through the
top of the condenser. The mixture will warm up and a solid will
precipitate. Stir the mixture for 45 min and then filter the solid
(8.54 g, 21.12 mmol, 97%). Wash the white solid with hexane
(3ꢃ15 mL).
(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 65.8, 49.8, 46.7, 34.2,
33.5, 26.0, 25.9, 20.7, 14.7, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼
267.4 (100) [MþNa]þ.
4.7. tert-Butyl-dimethyl-(5-oxiranyl-pentyloxy)-silane {(R)-9}
& 7-(tert-butyl-dimethyl-silanyloxy)-heptane-1,2-diol (14)
A mixture of (R,R)-N,N/-bis (3,5-di-tert-butyl-salicyclidene)-1,2-
cyclohexane diamino cobalt (0.012 g, 0.02 mmol), toluene
(0.400 mL) and AcOH (0.002 mL, 0.04 mmol) was stirred while
open to air for 1 h at room temperature. The solvent was removed
by rotary evaporator under reduced pressure and the brown resi-
due was dried under vacuum. The epoxide 13 (1 g, 4.09 mmol) was
added in one portion, and the mixture was cooled in an ice bath,
H2O (0.609 mL, 33.9 mmol) was slowly added over 5 min, whilst
keeping the temperature below 20 ꢀC. The ice bath was removed
and the reaction mixture was stirred for 12 h and the crude material
was purified by column chromatography on silica gel (eluent: 1%
4.4. Preparation of intermediate aldehyde 6-(tert-butyl-di-
methyl-silanyloxy)-hexanal
Alcohol 11 (1.0 g, 4.3 mmol) was added dropwise at 0 ꢀC in
10 min to a suspension of PCC (1.2 g, 5.71 mmol) in dry DCM
(12 mL). After 2 h the dark suspension was filtered twice through
a pad of silica gel and washed with Et2O (3ꢃ20 mL). The solvent
was evaporated in vacuo to afford the crude aldehyde, which was
used without further purification.

B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
2161
ethyl acetate in petroleum ether) to get the chiral epoxide (R)-9
(0.437 g, 1.79 mmol, 44%) and diol 14 (0.493 g, 1.88 mmol, 46%) both
are colourless liquid.
(CH3)3(CH3)2Si}, 0.009 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
CDCl3)
d
63.0, 54.1, 47.1, 34.1, 32.7, 26.3, 26.1, 19.8, 14.0, ꢁ6.5; MS
(ESI, positive ion): m/z (%)¼267.4 (100) [MþNa]þ.
Compound (R)-9: Elemental analysis calcd. Found: C, 63.82; H,
11.51; O, 13.04. C13H28O2Si requires C, 63.87; H, 11.55; O, 13.09%; Rf
4.10. 7-(tert-Butyl-dimethyl-silanyloxy)-1-(1-phenyl-1H-tet-
razol-5-ylsulfanyl)-heptan-2-ol {(R)-15}
0.85 (10% EtOAc/Hexane) 0.85; ½a D25
ꢂ
þ3.82 (c 4.4, CHCl3); IR nmax
(film) 2943, 2843, 1450, 1272 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
3.58 (2H, t, J¼6.36 Hz, 1CH2), 2.86 (1H, br s, OCH), 2.72e2.69 (1H,
A mixture of epoxide (R)-9 (0.500 g, 2.04 mmol), PTSH (0.363 g,
2.04 mmol) and montmorillonite K-10 clay (0.020 g, catalytic
amount) in DCM (4 mL) was placed in a round bottom flask and
the mixture was stirred at room temperature for 6 h. The course of
the reaction was monitored by TLC until complete disappearance
of the starting material was observed. After that it was filtered and
concentrated under reduced pressure. The resulting residue was
purified by column chromatography on silica gel (10% EtOAc/
Hexane) to afford the sulfide (R)-15 (0.810 g, 1.91 mmol, 94%) as
gum; Elemental analysis calcd. Found: C, 56.76; H, 8.03; N, 13.19.
C20H34N4O2SSi requires C, 56.83; H, 8.11; N, 13.26%; Rf (40% EtOAc/
m, OCHH), 2.43e2.41 (1H, m, OCHH), 1.50e1.34 (8H, m,
2CH23CH24CH25CH2), 0.84 {9H, s, (CH3)3(CH3)2Si}, 0.009 {6H, s,
(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 63.0, 52.2, 47.0, 34.1,
32.7, 26.3, 26.1, 19.8, 14.0, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼
244.4 (100) [Mþ].
Compound 14: Elemental analysis calcd. Found: C, 59.41; H,
11.50; O, 18.24 C13H30O3Si requires C, 59.49; H, 11.52; O, 18.29%; Rf
(50% EtOAc/Hexane) 0.35; ½a D25
ꢁ1.89 (c 2.1, CHCl3); IR nmax (film)
ꢂ
3458 (br), 2947, 2822, 1365, 1142 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
3.64e3.59 (2H, m, 1CH2), 3.58 (2H, t, J¼6.4 Hz, 7CH2), 3.41e3.35
(1H, m, 2CH), 2.02e2.00 (1H, br s, OH),1.87 (1H, br s, OH/),1.54e1.30
(8H, m, aliphatic chain), 0.84 {9H, s, (CH3)3(CH3)2Si}, 0.00 {6H, s,
Hexane) 0.48; ½a D25
ꢂ
ꢁ7.1 (c 1.05, CHCl3); IR nmax (film) 3436 (br),
2932, 2828, 1431, 1216 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d
74.8, 70.6, 65.8, 34.2,
d 7.55e7.50 (5H, m, Aromatic), 4.06e3.99 (1H, m, 2CH), 3.63e3.54
33.9, 26.6, 24.1, 20.7, 14.7, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼
(3H, m, 1CHH, 7CH2), 3.31e3.27 (1H, m, 1CHH), 2.00 (1H, br s, OH),
1.58e1.21 (8H, m, 3CH24CH25CH26CH2), 0.86e0.83 {9H, m,
(CH3)3(CH3)2Si}, 0.05e(ꢁ)0.04 {6H, m, (CH3)3(CH3)2Si}; 13C NMR
262.4 (100) [Mþ].
4.8. Toluene-4-sulfonic acid 7-(tert-butyl-dimethyl-silany-
(75 MHz, CDCl3) d 154.2, 129.1, 76.5, 69.2, 51.8, 36.8, 34.6, 26.2,
loxy)-2-hydroxy-heptyl ester (16)
23.1, 20.7, 14.7, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼422.6
(100) [Mþ].
To a stirred solution of alcohol 14 (0.500 g, 1.90 mmol) in dry
CH2Cl2 (6 mL) were added Bu2SnO (0.009 g, 0.038 mmol), p-TsCl
(0.208 g, 1.90 mmol) and Et3N (0.166 mL). The reaction mixture
was stirred until TLC indicated complete consumption of the
starting material. The mixture was filtered and concentrated under
reduced pressure. The crude material was purified by column
chromatography on silica gel (8% EtOAc/Hexane) to afford the
monotosylated product 16 (0.774 g, 1.86 mmol, 98%) as a colour-
less liquid; Elemental analysis calcd. Found: C, 57.60; H, 8.68; O,
19.19. C20H36O5SSi requires C, 57.65; H, 8.71; O, 19.20%; Rf (40%
4.11. 7-(tert-Butyl-dimethyl-silanyloxy)-1-(1-phenyl-1H-tet-
razol-5-ylsulfanyl)-heptan-2-ol {(S)-15}
Epoxide (S)-9 was converted into sulfide (S)-15 following the
same synthetic procedure that was applied in the synthesis of (R)-
15 from (R)-9 (0.646 g, 1.53 mmol, 85%). It was a colourless gum;
Elemental analysis calcd. Found: C, 56.75; H, 8.09; N, 13.17.
C20H34N4O2SSi requires C, 56.83; H, 8.11; N, 13.26%; Rf (40% EtOAc/
Hexane) 0.45; ½a D25
ꢂ
þ2.8 (c 1.05, CHCl3); IR nmax (film) 3423 (br),
EtOAc/Hexane) 0.65; ½a D25
ꢂ
ꢁ2.17 (c 1.8, CHCl3); IR nmax (film) 3422
2939, 2827, 1427,1223 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 7.54e7.44
(br), 2940, 2828, 1370, 1119 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.78
(5H, m, Aromatic), 4.09e4.01 (1H, m, 2CH), 3.62e3.54 (3H, m,
1CHH, 7CH2), 3.35e3.28 (1H, m, 1CHH), 2.01 (1H, br s, OH),
1.60e1.31 (8H, m, 3CH24CH25CH26CH2), 0.83e0.82 {9H, m,
(CH3)3(CH3)2Si}, 0.009e(ꢁ)0.015 {6H, m, (CH3)3(CH3)2Si}; 13C NMR
(2H, d, J¼8.1 Hz, Aromatic), 7.33 (2H, d, J¼8.04 Hz, Aromatic),
4.01e3.99 (1H, m, 2CH), 3.87e3.81 (2H, m, 1CH2), 3.56 (2H, t,
J¼6.3 Hz, 7CH2), 2.42 (3H, s, CH3), 2.00 (1H, d, J¼4.26 Hz, OH),
1.50e1.28 (8H, m, 3CH24CH25CH26CH2), 0.84 {9H, s,
(CH3)3(CH3)2Si}, 0.00 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
(75 MHz, CDCl3) d 154.2, 129.1, 76.6, 69.2, 51.8, 36.8, 34.2, 26.2, 23.1,
20.7, 14.9, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼445 (100) [MþNa]þ.
CDCl3)
d 143.6, 131.9, 130.7, 127.8, 127.0, 72.3, 69.5, 66.2, 35.2, 34.2,
26.6, 24.2, 21.9, 20.7, 14.7, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼
4.12. 7-(tert-Butyl-dimethyl-silanyloxy)-1-(1-phenyl-1H-tet-
razole-5-sulfonyl)-heptan-2-ol {(R)-6}
416.6 (100) [Mþ].
4.9. tert-Butyl-dimethyl-(5-oxiranyl-pentyloxy)-silane {(S)-9}
Sulfide (R)-15 (0.800 g, 1.89 mmol) in dry DCM (8 mL) at 0 ꢀC,
mCPBA (0.326 g, 1.89 mmol) was added, and stirred for 6 h. After
completion, the reaction mixture was diluted with EtOAc (10 mL)
and a saturated solution of KI (6 mL) in water was added, the lib-
erated I2 was reduced by a saturated solution Na2S2O3 (6 mL),
washed with a saturated solution of NaHCO3 (3ꢃ15 mL) and brine
(3ꢃ15 mL). The organic fraction was dried over anhydrous Na2SO4
and the solvent was removed under reduced pressure. The crude
material was purified by column chromatography on silica gel (15%
EtOAc/Hexane) to afford the sulfone (R)-6 (0.772 g, 1.70 mmol, 90%)
as a colourless liquid; Elemental analysis calcd. Found: C, 52.79; H,
7.51; N, 12.29. C20H34N4O4SSi requires C, 52.83; H, 7.54; N, 12.32%;
To a stirred solution of alcohol 16 (0.774 g, 1.86 mmol) in
methanol (5 mL) was added potassium carbonate (0.282 g,
2.04 mmol) at room temperature and the mixture was stirred for
2.5 h. After completion of the reaction, it was diluted with ice-
cooled water (15 mL), the resulting mixture was extracted with
ether (3ꢃ10 mL). The extract was washed with water (3ꢃ15 mL),
brine (3ꢃ15 mL), dried over anhydrous Na2SO4 and concentrated
under vacuum. Purification was done by column chromatography
on silica gel (8% EtOAc/Hexane) to afford the chiral epoxide (S)-9
(0.440 g, 1.80 mmol, 97%) as a colourless liquid; Elemental analysis
calcd. Found: C, 63.83; H, 11.53; O, 13.01. C13H28O2Si requires C,
Rf (40% EtOAc/Hexane) 0.50; ½a D25
ꢁ11.1 (c 1.0, CHCl3); IR nmax (film)
ꢂ
63.87; H, 11.55; O, 13.09%; Rf (10% EtOAc/Hexane) 0.85; ½a D25
ꢂ
ꢁ2.36
3421 (br), 2945, 2830, 1441, 1221 cmꢁ1; 1H NMR (300 MHz, CDCl3)
(c 0.95, CHCl3); IR nmax (film) 2945, 2823, 1441, 1276 cmꢁ1; 1H NMR
d 7.60e7.55 (5H, m, Aromatic), 4.06e4.01 (1H, m, 2CH), 3.67 (2H, t,
(300 MHz, CDCl3)
OCH), 2.71e2.69 (1H, m, OCHH), 2.43e2.40 (1H, m, OCHH),
1.55e1.34 (8H, m, 2CH23CH24CH25CH2), 0.85e0.83 {9H, s,
d
3.58 (2H, t, J¼6.36 Hz, 1CH2), 2.86 (1H, br s,
J¼6.4 Hz, 7CH2), 3.63e3.59 (1H, m, 1CHH), 3.37e3.29 (1H, m,
1CHH), 1.82e1.25 (8H, m, 3CH24CH25CH26CH2), 0.12e0.00 {9H, m,
(CH3)3(CH3)2Si}, ꢁ0.42 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,

2162
B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
CDCl3)
d
154.7, 133.5, 130.2, 129.8, 123.8, 70.2, 66.6, 62.6, 36.2, 32.4,
aqueous NH4Cl (8 mL). The layers were separated and the
aqueous phase was extracted with Et2O (3ꢃ10 mL). The com-
bined organic phases were washed with brine (3ꢃ10 mL), dried
with anhydrous Na2SO4, filtered and concentrated under reduced
pressure. The resulting residue was purified by column chro-
matography on silica gel (3% EtOAc/Hexane) to give the com-
pound 21a (0.344 g, 0.719 mmol, 66%) as colourless liquid;
Elemental analysis calcd. Found: C, 67.68; H, 9.63; O, 16.68.
C27H46O5Si requires C, 67.74; H, 9.68; O, 16.71%; Rf (20% EtOAc/
25.5, 25.2, 21.0, 14.9, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼477.6
(100) [MþNa]þ.
4.13. 7-(tert-Butyl-dimethyl-silanyloxy)-1-(1-phenyl-1H-tet-
razole-5-sulfonyl)-heptan-2-ol {(S)-6}
This compound was prepared from (S)-15 following the same
procedure as in case of (R)-6. Compound (S)-6 (0.568 g, 1.25 mmol,
82%) was a colourless liquid; Elemental analysis calcd. Found: C,
52.75; H, 7.49; N, 12.27. C20H34N4O4SSi requires C, 52.83; H, 7.54; N,
Hexane) 0.85; ½a D25
ꢂ
ꢁ23.2 (c 0.28, CHCl3); IR nmax (film) 3418,
2947, 2837, 1341, 1149, 1032 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
12.32%; Rf (40% EtOAc/Hexane) 0.48; ½a D25
ꢂ
þ9.1 (c 0.91, CHCl3); IR
d
7.33e7.27 (5H, m, Aromatic), 5.88 (1H, dd, J¼15.6, 6.9 Hz, 3CH),
nmax (film) 3450 (br), 2947, 2837, 1432, 1220 cmꢁ1
;
1H NMR
5.80 (1H, dd, J¼15.6, 6.9 Hz, 2CH), 4.63 (2H, s, OCH2Ph),
4.25e4.20 (1H, m, CHO), 4.07 (1H, q, J¼6.7 Hz, 4CH), 3.95 (1H, dd,
J¼6.7, 4.5 Hz, 1CH), 3.86 (2H, dd, J¼6.9, 3.8 Hz, CH2O), 3.57 (2H, t,
J¼6.8 Hz, 9CH2), 2.01 (1H, br s, OH), 1.49 (4H, s, 5CH2, 8CH2), 1.45
(6H, s, 2CH3), 1.28e1.25 (4H, m, 6CH27CH2), 0.85 (9H, s,
(CH3)3(CH3)2Si), 0.01 (6H, s, (CH3)3(CH3)2Si); 13C NMR (75 MHz,
(300 MHz, CDCl3)
d 7.55e7.48 (5H, m, Aromatic), 3.99 (1H, br s,
2CH), 3.62e3.58 (1H, m, 1CHH), 3.57 (2H, t, J¼4.2 Hz, 7CH2),
3.32e3.25 (1H, m, 1CHH), 2.10 (1H, br s, OH), 1.71e1.20 (8H, m,
3CH24CH25CH26CH2), 0.84 {9H, m, (CH3)3(CH3)2Si}, 0.00 {6H, m,
(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 154.7, 133.5, 130.2,
129.8, 123.8, 70.1, 66.6, 62.6, 36.2, 32.4, 25.5, 25.2, 21.0, 14.9, ꢁ6.5;
CDCl3) d 138.3, 131.7, 130.9, 128.6, 127.6, 127.4, 127.1, 109.4, 85.4,
MS (ESI, positive ion): m/z (%)¼454.6 (100) [Mþ].
80.1, 77.9, 75.4, 72.2, 69.7, 38.9, 35.2, 29.2, 26.8, 24.8, 20.7,
15.2, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼478.7 (100) [Mþ].
4.14. Benzyloxy-(2,2-dimethyl-[1,3]dioxolan-4-yl)-acetic acid
methyl ester (20)
4.17. 1-Benzyloxy-9-(tert-butyl-dimethyl-silanyloxy)-1-
(2,2-dimethyl-[1,3]dioxolan-4-yl)-non-2-en-4-ol (21b)
A solution of methyl ester 19 (1.60 g, 8.43 mmol) in DMF (10 mL)
was treated with benzyl bromide (1.58 g, 1.09 mL, 9.2 mmol) and
argentous oxide (2.73 g, 11.8 mmol), the resulting mixture was
stirred under inert atmosphere for 3 h and then chromatographed
using 3% EtOAc/Hexane as eluent to afford the benzyl ether 20
(2.31 g, 8.26 mmol, 98%) as an oil; Elemental analysis calcd. Found:
C, 64.21; H, 7.09; O, 28.50. C15H20O5 requires C, 64.27; H, 7.19; O,
Compound 21b was synthesized by the reaction of 5 with (S)-6
following the same procedure that was used for the synthesis of
21a. Compound 21b (0.313 g, 0.654 mmol, 60%) was a colourless
liquid; Elemental analysis calcd. Found: C, 67.62; H, 9.58; O, 16.61.
C27H46O5Si requires C, 67.74; H, 9.68; O, 16.71%; Rf (20% EtOAc/
Hexane) 0.82; ½a D25
ꢂ
þ17.56 (c 0.28, CHCl3); IR nmax (film) 3422 (br),
28.54%; Rf (20% EtOAc/Hexane) 0.65; ½a D25
ꢂ
þ10.2 (c 1.0, CHCl3); IR
2942, 2840, 1328, 1150, 1022 cmꢁ1 1H NMR (300 MHz, CDCl3)
;
nmax (film) 2737, 1323, 1249, 1089 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.33e7.28 (5H, m, Aromatic), 5.87 (1H, dd, J¼15.6, 6.9 Hz, 3CH),
d
7.54e7.50 (5H, m, Aromatic), 4.92e4.90 (1H, m, CHO), 4.63 (2H, s,
5.79 (1H, dd, J¼15.6, 6.9 Hz, 2CH), 4.63 (2H, s, OCH2Ph), 4.25e4.21
(1H, m, CHO), 4.08 (1H, q, J¼6.5 Hz, 4CH), 3.95 (1H, dd, J¼6.7, 4.5 Hz,
1CH), 3.86 (2H, dd, J¼6.7, 3.5 Hz, CH2O), 3.57 (2H, t, J¼6.7 Hz, 9CH2),
2.01 (1H, br s, OH), 1.49 (4H, s, 5CH2, 8CH2), 1.45 (6H, s, 2CH3),
1.28e1.25 (4H, m, 6CH27CH2), 0.85 {9H, s, (CH3)3(CH3)2Si}, 0.01 {6H,
CH2Ph), 4.02 (1H, dd, J¼7.9, 1.1 Hz, CHOCH2), 3.86 (2H, dd, J¼8.0,
2.7 Hz, CH2O), 3.69 (3H, s, OCH3), 1.57 (6H, s, 2CH3); 13C NMR
(75 MHz, CDCl3) d 179.4, 140.3, 128.3, 128.1, 127.4, 127.2, 126.4, 104.1,
80.4, 78.6, 73.8, 68.9, 50.3, 28.9, 28.4; MS (ESI, positive ion): m/z
(%)¼280.3 (100) [Mþ].
s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 138.2, 131.8, 130.9,
128.6, 127.6, 127.4, 127.1, 109.4, 85.4, 80.2, 77.9, 75.4, 72.1, 69.7, 38.9,
35.2, 29.7, 26.8, 24.9, 20.7, 15.2, ꢁ6.5; MS (ESI, positive ion): m/z
(%)¼478.2 (100) [Mþ].
4.15. Benzyloxy-(2,2-dimethyl-[1,3]dioxolan-4-yl)-acetalde-
hyde (5)
Ester 20 (0.305 g, 1.09 mmol) in diethylether (5 mL) was cooled
to ꢁ90 ꢀC and treated dropwise with a 1.2 M solution of DIBAL-H in
toluene (0.154 g, 0.194 mL, 1.09 mmol) at a temperature of below
ꢁ85 ꢀC. The mixture was stirred for 2 h at ꢁ90 ꢀC. A saturated
aqueous solution of tartaric acid (10 mL) was added and the organic
layer was separated, washed with brine, dried over magnesium
sulfate and concentrated under reduced pressure. The aldehyde 5
was prepared by reduction of 20 using DIBAL-H was used without
further purification.
4.18. 3-Benzyloxy-11-(tert-butyl-dimethyl-silanyloxy)-undec-
4-ene-1,2,6-triol (22a)
To a suspension of acetonide protected alcohol 21a (0.500 g,
1.04 mmol) in t-BuOH/H2O (1:1) (6 mL) was added TBHP (70% so-
lution in H2O, 0.187 g, 2.08 mmol). The mixture was reflux until the
completion of the reaction (1 h, monitored by TLC). The solvent was
evaporated under reduced pressure. The residue was purified by
column chromatography on silica gel (25% EtOAc/Hexane) to fur-
nished the corresponding product 22a (0.433 g, 0.988 mmol, 95%)
as a white solid; Elemental analysis calcd. Found: C, 65.68; H, 9.60;
O, 18.21. C24H42O5Si requires C, 65.71; H, 9.65; O, 18.24%; Rf (100%
4.16. 1-Benzyloxy-9-(tert-butyl-dimethyl-silanyloxy)-1-(2,2-
dimethyl-[1,3]dioxolan-4-yl)-non-2-en-4-ol (21a)
EtOAc) 0.45; ½a 2D5
ꢂ
ꢁ6.8 (c 0.15, CHCl3); IR nmax (KBr) 3448 (br), 2940,
KHMDS (0.217 g, 0.247 mL, 0.199 mmol) was added to a stir-
red solution of sulfone (R)-6 (0.500 g, 1.09 mmol) in dry THF
(5 mL) under inert atmosphere at 0 ꢀC. The reaction mixture was
then warmed to room temperature and allowed to undergo
stirring at that temperature for 20 min. The solution was cooled
to ꢁ78 ꢀC and the crude aldehyde 5 (0.290 g, 1.09 mmol) in THF
(1 mL) was added and the reaction was continued at that tem-
perature for 3 h and then the temperature was slowly raised to
room temperature and the reaction was allowed to continue for
12 h. It was then quenched by adding equal volumes of saturated
2833, 1440, 1140 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 7.25e7.15 (5H,
m, Aromatic), 5.89 (1H, dd, J¼15.6, 6.9 Hz, 5CH), 5.78 (1H, dd,
J¼15.6, 6.9 Hz, 4CH), 4.63 (2H, s, OCH2Ph), 3.95 (1H, dd, J¼6.7,
4.5 Hz, 3CH), 3.90e3.89 (1H, m, 6CH), 3.60 (1H, m, 2CH), 3.58 (2H, t,
J¼7.39 Hz, 11CH2), 3.56 (2H, dd, J¼10.5, 3.9 Hz, 1CH2), 2.01 (3H, br s,
3OH), 1.58 (4H, s, 7CH2, 10CH2), 1.29 (4H, s, 8CH29CH2), 0.99 {9H, s,
(CH3)3(CH3)2Si}, 0.009 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
CDCl3) d 138.2, 132.1, 131.7, 128.6, 128.4, 127.4, 127.3, 127.1, 79.6, 77.4,
75.9, 74.2, 68.2, 65.9, 37.9, 35.1, 27.2, 24.9, 20.8, 14.9, ꢁ6.5; MS (ESI,
positive ion): m/z (%)¼438.6 (100) [Mþ].

B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
2163
4.19. 3-Benzyloxy-11-(tert-butyl-dimethyl-silanyloxy)-undec-
4.22. 1-Benzyloxy-9-(tert-butyl-dimethyl-silanyloxy)-1-
4-ene-1,2,6-triol (22b)
oxiranyl-non-2-en-4-ol (24a)
The synthetic procedure of compound 22b was same as that was
used for the synthesis of 22a. Compound 22b (0.249 g, 0.569 mmol,
91%) was a white solid; Elemental analysis calcd. Found: C, 65.62; H,
9.59; O, 18.20. C24H42O5Si requires C, 65.71; H, 9.65; O, 18.24%; Rf
To a stirred solution of alcohol 23a (0.500 g, 0.843 mmol) in
methanol (5 mL) was added K2CO3 (0.116 g, 0.843 mmol) at room
temperature, and the mixture was stirred for 2.5 h. After addition of
ice-cooled water, the resulting mixture was extracted with ether
(3ꢃ15 mL). The extract was washed with H2O (3ꢃ10 mL), brine
(3ꢃ10 mL), dried over anhydrous Na2SO4 and concentrated under
reduced pressure. Purificationwas done bycolumn chromatography
on silica gel (4% EtOAc/Hexane) to furnished the corresponding
product 24a (0.347 g, 0.826 mmol, 98%) as a colourless liquid; Ele-
mental analysis calcd. Found: C, 68.50; H, 9.50; O, 15.20. C24H40O4Si
requires C, 68.53; H, 9.58; O, 15.21%; Rf (10% EtOAc/Hexane) 0.45;
(100% EtOAc) 0.44; ½a D25
ꢂ
þ5.4 (c 0.11, CHCl3); IR nmax (KBr) 3434 (br),
2942, 2836, 1456, 1143 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.26e7.15
(5H, m, Aromatic), 5.89 (1H, dd, J¼15.6, 6.9 Hz, 5CH), 5.78 (1H, dd,
J¼15.6, 6.9 Hz, 4CH), 4.61 (2H, s, OCH2Ph), 3.95 (1H, dd, J¼6.7,
4.4 Hz, 3CH), 3.92e3.90 (1H, m, 6CH), 3.60 (1H, m, 2CH), 3.57 (2H, t,
J¼7.4 Hz, 11CH2), 3.56 (2H, dd, J¼10.0, 3.9 Hz, 1CH2), 2.1 (3H, br s,
3OH), 1.58 (4H, s, 7CH2, 10CH2), 1.29 (4H, s, 8CH29CH2), 0.98 {9H, s,
(CH3)3(CH3)2Si}, 0.009 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
½
a 2D5
1334, 1141 cmꢁ1
ꢂ
ꢁ7.11 (c 0.35, CHCl3); IR nmax (film) 3428 (br), 2937, 2841, 1421,
CDCl3)
d
138.3, 132.5, 131.1, 128.5, 128.0, 127.8, 127.3, 127.2, 79.8,
;
1H NMR (300 MHz, CDCl3)
d
7.32e7.30 (5H, m,
77.5, 76.0, 74.3, 68.3, 65.3, 37.2, 35.3, 27.2, 24.9, 20.8, 14.9, ꢁ6.5; MS
Aromatic), 5.89 (1H, dd, J¼16.4, 6.1 Hz, 3CH), 5.76 (1H, dd, J¼16.4,
6.1 Hz, 2CH), 4.63 (2H, s, OCH2Ph), 4.07 (1H, q, J¼6.5 Hz, 4CH), 3.95
(1H, dd, J¼6.7, 4.5 Hz, 1CH), 3.58 (2H, t, J¼1.9 Hz, 9CH2), 2.88e2.84
(1H, m, CHO), 2.53 (2H, dd, J¼12.8, 5.8 Hz, CH2O), 2.01 (1H, br s, OH),
1.56e1.51 (4H, m, 5CH2, 8CH2), 1.41e1.37 (4H, m, 6CH27CH2), 1.12
{9H, s, (CH3)3(CH3)2Si}, 0.02 {6H, s, (CH3)3(CH3)2Si}; 13C NMR
(ESI, positive ion): m/z (%)¼438.6 (100) [Mþ].
4.20. Toluene-4-sulfonic acid 3-benzyloxy-11-(tert-butyl-di-
methyl-silanyloxy)-2,6-dihydroxy-undec-4-enyl ester (23a)
To a stirred solution of triol 22a (0.400 g, 0.911 mmol) were
added Bu2SnO (0.004 g, 0.018 mmol), p-TsCl (0.099 g, 0.911 mmol)
and Et3N (0.132 mL). The reaction mixture was stirred until TLC
indicated complete consumption of the starting material (8 h). The
mixture was filtered and concentrated under vacuum to get the
crude product. The residue was purified by column chromatogra-
phy on silica gel (15% EtOAc/Hexane) to furnished the corre-
sponding product 23a (0.529 g, 0.892 mmol, 98%) as a white
amorphous solid; Elemental analysis calcd. Found: C, 62.78; H, 8.10;
O, 18.82. C31H48O7SSi requires C, 62.80; H, 8.16; O, 18.89%; Rf (30%
(75 MHz, CDCl3) d 137.2, 131.8, 129.6, 128.4, 127.6, 127.5, 80.0, 76.1,
74.4, 65.8, 57.2, 40.9, 37.9, 34.2, 26.7, 24.2, 20.7, 14.7, ꢁ6.5; MS (ESI,
positive ion): m/z (%)¼420.6 (100) [Mþ].
4.23. 1-Benzyloxy-9-(tert-butyl-dimethyl-silanyloxy)-1-
oxiranyl-non-2-en-4-ol (24b)
Compound 24b was prepared from 23b according to the same
procedure that was followed for the synthesis of 24a. Compound 24b
(0.193 g, 0.460mmol, 91%) was a colourless liquid; Elemental analysis
calcd. Found: C, 68.46; H, 9.49; O,15.17. C24H40O4Si requires C, 68.53;
EtOAc/Hexane) 0.35; ½a D25
ꢁ17.02 (c 0.25, CHCl3); IR nmax (KBr) 3540
ꢂ
(br), 2940, 2822, 1375, 1345, 1147 cmꢁ1; 1H NMR (300 MHz, CDCl3)
H, 9.58; O, 15.21%; Rf (10% EtOAc/Hexane) 0.42; ½a D25
þ4.81 (c 0.22,
ꢂ
d
7.82e7.40 (4H, m, Aromatic), 7.28e7.12 (5H, m, Aromatic), 5.88
CHCl3); IR nmax (film) 3436 (br), 2940, 2843,1412,1311,1143 cmꢁ1; 1H
NMR (300 MHz, CDCl3) 7.55e7.48 (5H, m, Aromatic), 5.89 (1H, dd,
J¼16.4, 6.1 Hz, 3CH), 5.76 (1H, dd, J¼16.4, 6.1 Hz, 2CH), 4.68 (2H, s,
OCH2Ph), 4.09 (1H, q, J¼6.5 Hz, 4CH), 3.95 (1H, dd, J¼6.7, 4.5 Hz,1CH),
3.58 (2H, t, J¼1.9 Hz, 9CH2), 2.88e2.84 (1H, m, CHO), 2.53 (2H, dd,
J¼12.8, 5.8 Hz, CH2O), 2.01 (1H, br s, OH), 1.56e1.51 (4H, m, 5CH2,
8CH2),1.41e1.37 (4H, m, 6CH27CH2),1.12 {9H, s, (CH3)3(CH3)2Si}, 0.02
(1H, dd, J¼15.4, 6.8 Hz, 5CH), 5.78 (1H, dd, J¼15.4, 6.8 Hz, 4CH), 4.63
(2H, s, OCH2Ph), 4.07 (1H, q, J¼6.5 Hz, 6CH), 3.95 (1H, dd, J¼6.7,
4.5 Hz, 3CH), 3.59 (1H, m, 2CH), 3.57 (2H, t, J¼7.3 Hz, 11CH2), 3.56
(2H, dd, J¼9.8, 3.9 Hz, 1CH2), 2.35 (3H, s, CH3), 2.01 (2H, br s, 2OH),
1.58 (4H, s, 7CH2, 10CH2), 1.29 (4H, s, 8CH29CH2), 0.98 {9H, s,
(CH3)3(CH3)2Si}, 0.009 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
CDCl3)
d
142.7, 137.6, 135.6, 131.7, 131.6, 130.4, 128.4, 128.3, 127.6,
{6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 137.2,131.7,129.6,
127.5, 126.2, 85.6, 74.9, 74.2, 73.9, 68.2, 49.2, 38.2, 34.5, 26.9, 24.2,
20.7, 14.1, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼615.8 (100)
[MþNa]þ.
128.4,127.6,127.5, 80.1, 76.1, 74.4, 65.8, 57.2, 40.9, 37.9, 34.2, 26.7, 24.2,
20.7,14.7, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼443.3 (100) [MþNa]þ.
4.24. 9-Benzyloxy-1-(tert-butyl-dimethyl-silanyloxy)-octa-
4.21. Toluene-4-sulfonic acid 3-benzyloxy-11-(tert-butyl-di-
dec-7-ene-6,10-diol (25a)
methyl-silanyloxy)-2,6-dihydroxy-undec-4-enyl ester (23b)
Active magnesium metal (0.50 g, 2.08 mmol) was taken in dry
THF (2 mL) in a two necked round bottom flask under inert at-
mosphere. A drop of 1,2-dibromoethane was used as an initiator for
the reaction. The flask is fitted with a reflux condenser, and the
mixture is warmed over a water bath for 20e30 min. After initia-
tion of the reaction added 1-bromoheptane (0.372 g, 2.08 mmol) in
dry THF (2 mL) dropwise using dropping funnel. To a stirred solu-
tion of epoxide 24a (0.300 g, 0.713 mmol) at ꢁ20 ꢀC was added
anhydrous CuI (0.027 g, 0.142 mmol) and stirred for 30 min. Crude
heptylmagnesium bromide (0.145 g, 0.713 mmol) in dry THF (4 mL)
was added dropwise over 10 min. The reaction mixture was stirred
at ꢁ25 ꢀC for 2 h and warmed to room temperature. After com-
pletion of the reaction (1 h), it was quenched by saturated solution
of NH4Cl (20 mL) and washed with ether (3ꢃ15 mL) and brine
(3ꢃ15 mL) and dried over anhydrous Na2SO4 and purified by silica
gel flash chromatography (7% EtOAc/Hexane) to give 25a (0.330 g,
0.634 mmol, 89%) as a white solid; Elemental analysis calcd. Found:
C, 71.41; H, 10.77; O, 12.22. C31H56O4Si requires C, 71.48; H, 10.84; O,
Compound 23b was prepared from 22b according to the same
procedure that was followed for the synthesis of 23a. Compound
23b (0.304 g, 0.514 mmol, 94%) was a white amorphous solid; El-
emental analysis calcd. Found: C, 62.72; H, 8.09; O, 18.81.
C31H48O7SSi requires C, 62.80; H, 8.16; O, 18.89%; Rf (30% EtOAc/
Hexane) 0.37; ½a D25
ꢂ
þ9.81 (c 0.20, CHCl3); IR nmax (KBr) 3524 (br),
2941, 2826, 1371, 1335, 1140 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
7.82e7.43 (4H, m, Aromatic), 7.28e7.11 (5H, m, Aromatic), 5.88
(1H, dd, J¼15.4, 6.8 Hz, 5CH), 5.78 (1H, dd, J¼15.4, 6.8 Hz, 4CH), 4.61
(2H, s, OCH2Ph), 4.04 (1H, q, J¼6.8 Hz, 6CH), 3.95 (1H, dd, J¼6.7,
4.5 Hz, 3CH), 3.59 (1H, m, 2CH), 3.57 (2H, t, J¼7.0 Hz, 11CH2), 3.56
(2H, dd, J¼10.0, 3.9 Hz, 1CH2), 2.36 (3H, s, CH3), 2.0 (2H, br s, 2OH),
1.58 (4H, s, 7CH2, 10CH2), 1.30 (4H, s, 8CH29CH2), 0.98 {9H, s,
(CH3)3(CH3)2Si}, 0.009 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz,
CDCl3)
d 142.5, 137.2, 135.1, 131.4, 131.5, 130.4, 128.4, 128.1, 127.6,
127.5, 126.1, 85.5, 75.0, 74.3, 73.7, 68.3, 49.1, 38.2, 34.5, 27.0, 24.1,
20.6, 14.1, ꢁ6.5; MS (ESI, positive ion): m/z (%)¼592.8 (100) [Mþ].

2164
B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
12.29%; Rf (30% EtOAc/Hexane) 0.55; ½a D25
ꢂ
ꢁ8.56 (c 0.82, CHCl3); IR
1H NMR
26b (0.186 g, 0.249 mmol, 93%) was a colourless gum; Elemental
nmax (KBr) 3423 (br), 2951, 2841, 1312, 1134 cmꢁ1
;
analysis calcd. Found: C, 68.89; H, 11.27; O, 8.50. C48H84O4Si3 re-
(300 MHz, CDCl3)
d
7.32e7.30 (5H, m, Aromatic), 5.75 (1H, dd,
quires C, 68.92; H, 11.30; O, 8.54%; Rf (10% EtOAc/Hexane) 0.84; ½a D25
ꢂ
J¼15.3, 6.5 Hz, 7CH), 5.70 (1H, dd, J¼15.3, 6.5 Hz, 8CH), 4.63 (2H, s,
OCH2Ph), 4.07 (1H, q, J¼6.5 Hz, 6H), 3.95 (1H, dd, J¼6.7, 4.4 Hz,
9CH), 3.60e3.58 (1H, m, 10CH), 3.53 (2H, t, J¼4.2 Hz, 1CH2), 2.01
(2H, br s, 2OH), 1.56e1.51 (8H, m, aliphatic chain), 1.40e1.25 (14H,
m, aliphatic chain),1.10 {9H, s, (CH3)3(CH3)2Si}, 0.94 (3H, t, J¼6.7 Hz,
18CH3), 0.09 {6H, s, (CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
þ17.5 (c 0.25, CHCl3); IR nmax (film) 2947, 2851, 1430, 1145,
1038 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 7.33e7.29 (5H, m, Aromatic),
5.89 (1H, dd, J¼15.6, 6.9 Hz, 7CH), 5.78 (1H, dd, J¼15.6, 6.9 Hz, 8CH),
4.63 (2H, s, OCH2Ph), 4.09 (1H, q, J¼6.5 Hz, 6CH), 3.95 (1H, dd, J¼6.7,
4.5 Hz, 9CH), 3.60e3.58 (1H, m, 10CH), 3.57 (2H, t, J¼7.3 Hz, 1CH2),
1.55e1.49 (8H, m, aliphatic chain), 1.32e1.26 (14H, m, aliphatic
chain), 1.0 {27H, s, 3(CH3)3(CH3)2Si}, 0.96 (3H, t, J¼6.7 Hz, 18CH3),
d
137.9, 132.1, 131.9, 128.4, 127.6, 127.4, 127.1, 84.1, 75.3, 75.2, 73.9,
66.3, 38.1, 34.9, 32.8, 32.4, 30.8, 30.6, 30.1, 27.1, 24.8, 24.2, 23.3, 20.7,
0.08 {18H, s, 3(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 137.9,
15.1, 14.2, ꢁ6.2; MS (ESI, positive ion): m/z (%)¼520.8 (100) [Mþ].
131.9, 131.8, 128.6, 128.3, 128.1, 127.3, 127.1, 91.1, 74.5, 74.3, 74.1, 69.1,
40.2, 38.6, 35.2, 32.9, 30.8, 30.3, 30.1, 26.8, 24.4, 23.9, 20.7, 15.6,14.3,
ꢁ6.3; MS (ESI, positive ion): m/z (%)¼772.1 (100) [MþNa]þ.
4.25. 9-Benzyloxy-1-(tert-butyl-dimethyl-silanyloxy)-octa-
dec-7-ene-6,10-diol (25b)
4.28. 9-Benzyloxy-6,10-bis-(tert-butyl-dimethyl-silanyloxy)-
The synthetic procedure of compound 25b was same as that was
used for the synthesis of 25a. Compound 25b (0.144 g, 0.277 mmol,
78%) was a white solid; Elemental analysis calcd. Found: C, 71.38; H,
10.73; O, 12.20. C31H56O4Si requires C, 71.48; H, 10.84; O, 12.29%; Rf
octadec-7-en-1-ol (27a)
An ice-bath cooled solution of the tris-TBS ether 26a (0.400 g,
0.533 mmol) in MeOH (5 mL) was treated with p-TsOH (0.009 g,
0.052 mmol) as a solid. The reaction mixture was stirred at the
same temperature for 30 min. The reaction mixture was quenched
with solid NaHCO3 (3 g) and filtered. The filtrate was concentrated
under reduced pressure. The residue was purified by flash column
chromatography (7% EtOAc/Hexane) to afford 27a (0.324 g,
0.511 mmol, 96%) as a colourless gummy liquid; Elemental analysis
calcd. Found: C, 69.92; H, 11.10; O, 10.05. C37H70O4Si2 requires C,
(30% EtOAc/Hexane) 0.54; ½a D25
ꢂ
þ12.01 (c 0.54, CHCl3); IR nmax (KBr)
3434 (br), 2941, 2831, 1312, 1130 cmꢁ1
;
1H NMR (300 MHz, CDCl3)
d
7.33e7.25 (5H, m, Aromatic), 5.82 (1H, dd, J¼15.6, 7.0 Hz, 7CH),
5.76 (1H, dd, J¼15.6, 6.9 Hz, 8CH), 4.63 (2H, s, OCH2Ph), 4.08 (1H, q,
J¼6.7 Hz, 6H), 3.95 (1H, dd, J¼6.7, 4.2 Hz, 9CH), 3.61e3.58 (1H, m,
10CH), 3.53 (2H, t, J¼4.3 Hz, 1CH2), 2.01 (2H, br s, 2OH), 1.58e1.53
(8H, m, aliphatic chain), 1.41e1.34 (14H, m, aliphatic chain), 1.11
{9H, s, (CH3)3(CH3)2Si}, 0.94 (3H, t, J¼6.7 Hz, 18CH3), 0.09 {6H, s,
69.97; H, 11.11; O, 10.08%; Rf (40% EtOAc/Hexane) 0.45; ½a D25
ꢁ33.56
ꢂ
(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d
137.9, 132.2, 131.6,
(c 0.25, CHCl3); IR nmax (film) 3422 (br), 2941, 2833, 1642, 1440,
128.4, 127.7, 127.3, 127.0, 84.3, 75.3, 75.1, 73.9, 66.5, 37.9, 34.9, 32.8,
32.3, 30.6, 30.5, 30.1, 27.1, 24.8, 24.2, 23.4, 20.7, 15.1, 14.3, ꢁ6.2; MS
(ESI, positive ion): m/z (%)¼520.6 (100) [Mþ].
1142 cmꢁ1 1H NMR (300 MHz, CDCl3)
; d 7.31e7.27 (5H, m, Aro-
matic), 5.89 (1H, dd, J¼15.5, 6.5 Hz, 7CH), 5.79 (1H, dd, J¼15.5,
6.5 Hz, 8CH), 4.64 (2H, s, OCH2Ph), 4.07 (1H, q, J¼6.5 Hz, 6CH), 3.95
(1H, dd, J¼6.7, 4.4 Hz, 9CH), 3.60e3.58 (1H, m, 10CH), 3.53 (2H, t,
J¼7.3 Hz, 1CH2), 2.01 (1H, br s, OH), 1.55e1.50 (8H, m, aliphatic
chain), 1.39e1.25 (14H, m, aliphatic chain), 1.0 {18H,
s, 2(CH3)3(CH3)2Si}, 0.94 (3H, t, J¼6.7 Hz, 18CH3), 0.09 {12H,
4.26. [1-[3,8-Bis-(tert-butyl-dimethyl-silanyloxy)-oct-1-enyl]-
2-(tert-butyl-dimethyl-silanyloxy)-decyloxymethyl]-benzene
(26a)
s, 2(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 137.8, 132.1, 131.9,
Diol 25a (0.330 g, 0.634 mmol) was dissolved in dry DCM (4 mL).
Imidazole (0.043 g, 0.634 mmol) and TBSCl (0.095 g, 0.634 mmol)
were added, and the mixture was stirred at room temperature for
4 h. After completion of the reaction the mixture was diluted with
Et2O (8 mL), the solution was washed with H2O (3ꢃ10 mL), dried
over anhydrous Na2SO4 and concentrated under reduced pressure.
The resulting residue was purified by column chromatography on
silica gel (2% EtOAc/Hexane) to give the compound 26a (0.451 g,
0.602 mmol, 95%) as colourless gum; Elemental analysis calcd.
Found: C, 68.90; H, 11.28; O, 8.51. C48H84O4Si3 requires C, 68.92; H,
128.9, 128.7, 127.6, 127.5, 127.2, 84.7, 74.3, 74.1, 73.6, 63.8, 40.1, 33.5,
33.2, 32.5, 30.3, 30.1, 26.7, 24.5, 24.2, 23.1, 20.7, 15.1, 14.7, ꢁ6.2; MS
(ESI, positive ion): m/z (%)¼635.1 (100) [Mþ].
4.29. 9-Benzyloxy-6,10-bis-(tert-butyl-dimethyl-silanyloxy)-
octadec-7-en-1-ol (27b)
The synthetic procedure of compound 27b was same as that was
used for the synthesis of 27a. Compound 27b (0.110 g, 0.174 mmol,
87%) was a colourless gum; Elemental analysis calcd. Found: C,
69.90; H, 11.0; O, 10.01. C37H70O4Si2 requires C, 69.97; H, 11.11; O,
11.30; O, 8.54%; Rf (10% EtOAc/Hexane) 0.85; ½a D25
ꢂ
ꢁ15.2 (c 0.12,
CHCl3); IR nmax (film) 2940, 2841, 1429, 1142, 1055 cmꢁ1
;
1H NMR
10.08%; Rf (40% EtOAc/Hexane) 0.45; ½a D25
ꢂ
þ23.71 (c 0.25, CHCl3); IR
(300 MHz, CDCl3)
d
7.31e7.29 (5H, m, Aromatic), 5.86 (1H, dd,
nmax (film) 3419 (br), 2947, 2812, 1638, 1441, 1143 cmꢁ1 1H NMR
;
J¼15.3, 6.5 Hz, 7CH), 5.76 (1H, dd, J¼15.3, 6.5 Hz, 8CH), 4.63 (2H, s,
OCH2Ph), 4.07 (1H, q, J¼6.5 Hz, 6CH), 3.95 (1H, dd, J¼6.7, 4.4 Hz,
9CH), 3.60e3.58 (1H, m, 10CH), 3.57 (2H, t, J¼7.3 Hz, 1CH2),
1.54e1.49 (8H, m, aliphatic chain), 1.32e1.25 (14H, m, aliphatic
chain), 1.0 {27H, s, 3(CH3)3(CH3)2Si}, 0.96 (3H, t, J¼6.7 Hz, 18CH3),
(300 MHz, CDCl3) d 7.33e7.29 (5H, m, Aromatic), 5.89 (1H, dd,
J¼15.5, 6.6 Hz, 7CH), 5.79 (1H, dd, J¼15.6, 6.6 Hz, 8CH), 4.64 (2H, s,
OCH2Ph), 4.08 (1H, q, J¼6.5 Hz, 6CH), 3.96 (1H, dd, J¼6.7, 4.4 Hz,
9CH), 3.60e3.59 (1H, m, 10CH), 3.54 (2H, t, J¼7.3 Hz, 1CH2), 2.0 (1H,
br s, OH), 1.55e1.49 (8H, m, aliphatic chain), 1.39e1.26 (14H, m, al-
iphatic chain), 1.0 {18H, s, 2(CH3)3(CH3)2Si}, 0.94 (3H, t, J¼6.7 Hz,
18CH3), 0.09 {12H, s, 2(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
0.08 {18H, s, 3(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 137.9,
131.9, 131.8, 128.9, 128.7, 128.6, 127.5, 127.2, 127.0, 91.0, 74.5, 74.3,
74.1, 69.1, 40.2, 38.6, 35.2, 32.9, 30.9, 30.3, 30.1, 26.8, 24.5, 23.7, 20.7,
15.6, 14.2, ꢁ6.3; MS (ESI, positive ion): m/z (%)¼749.3 (100) [Mþ].
d
137.8, 132.3, 131.2, 128.8, 128.5, 127.7, 127.5, 127.2, 84.5, 74.8, 74.7,
73.6, 64.0, 40.2, 33.3, 33.2, 32.4, 30.2, 30.1, 26.9, 24.4, 23.8, 23.1, 20.5,
15.2, 14.7, ꢁ6.2; MS (ESI, positive ion): m/z (%)¼635 (100) [Mþ].
4.27. [1-[3,8-Bis-(tert-butyl-dimethyl-silanyloxy)-oct-1-enyl]-
2-(tert-butyl-dimethyl-silanyloxy)-decyloxymethyl]-benzene
(26b)
4.30. 9-Benzyloxy-6,10-bis-(tert-butyl-dimethyl-silanyloxy)-
octadec-7-enoic acid (28a)
Compound 26b was prepared from 25b according to the same
procedure that was followed for the synthesis of 26a. Compound
Alcohol 27a (0.300 g, 0.472 mmol) was dissolved in CH2Cl2
(3 mL) and treated with the DMP (0.240 g, 0.566 mmol, 1.2 equiv).

B. Saikia et al. / Tetrahedron 69 (2013) 2157e2166
2165
The mixture was stirred for 8 h, then treated with CH2Cl2 (7 mL),
10% aqueous Na2S2O3 (3 mL) and saturated aqueous NaHCO3
(3 mL). After stirring for 10 min, the mixture was transferred to
a separatory funnel, and the layers were shaken and separated. The
aqueous layer was extracted with CH2Cl2 (5 mL) and the combined
organics were washed with 10% aqueous Na2S2O3 (3ꢃ10 mL), sat-
urated aqueous NaHCO3 (3ꢃ10 mL). The organic layer was dried
over anhydrous Na2SO4 and concentrated to afford the crude al-
dehyde, which was used in the subsequent Pinnick oxidation
without purification. The crude aldehyde (0.320 g) was dissolved in
a mixture of t-BuOH (5 mL) and 2-methyl-2-butene (0.264 g,
0.55 mL, 3.77 mmol) at room temperature. A solution of NaClO2
(0.256 g, 2.83 mmol) and NaH2PO4 (0.368 g, 3.06 mmol) in water
(7 mL) was added dropwise to this mixture over 5 min at room
temperature. The mixture was stirred at room temperature for 1 h,
quenched with salt NH4Cl (2 g), extracted with ethyl acetate
(20 mL), washed with brine (3ꢃ10 mL), dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The resulting
residue was purified by column chromatography on silica gel (50%
EtOAc/Hexane) to give the compound 28a (0.257 g, 0.396 mmol,
84%) as colourless viscous gum; Elemental analysis calcd. Found: C,
68.42; H, 10.53; O, 12.31. C37H68O5Si2 requires C, 68.46; H, 10.56; O,
under reduced pressure to give the crude product. The resulting
residue was purified by column chromatography on silica gel (50%
EtOAc/Hexane) to give the compound 2a (0.047 g, 0.144 mmol, 94%)
as white amorphous powder; Elemental analysis calcd. Found: C,
65.40; H, 10.32; O, 24.19. C18H34O5 requires C, 65.42; H, 10.37; O,
24.21%; Rf (100% EtOAc) 0.15; ½a D25
ꢂ
ꢁ10.4 (c 0.11, CH3OH); IR nmax
(KBr) 3412 (br), 2947, 2835, 1727, 1459, 1142 cmꢁ1
;
1H NMR
(300 MHz, CDCl3)
d
5.75 (1H, dd, J¼15.3, 6.5 Hz, 7CH), 5.70 (1H, dd,
J¼15.3, 6.5 Hz, 8CH), 4.07 (1H, q, J¼6.5 Hz, 6CH), 3.95 (1H, dd, J¼6.5,
4.4 Hz, 9CH), 3.52e3.50 (1H, m, 10CH), 2.27 (2H, t, J¼7.3 Hz, 2CH2),
1.63e1.61 (2H, m, 3CH2), 1.56e1.50 (6H, m, 5CH2, 11CH2, 17CH2),
1.39e1.35 (12H, m, aliphatic chain), 0.94 (3H, t, J¼6.7 Hz, 18CH3);
13C NMR (75 MHz, CDCl3)
d 179.4, 136.9, 130.8, 76.5, 75.5, 73.1, 38.0,
36.3, 33.4, 33.3, 30.5, 30.3, 30.2, 30.1, 26.6, 26.4, 23.8, 14.6; MS (ESI,
positive ion): m/z (%)¼330.4 (100) [Mþ].
4.33. Compound 2b
Compound 2b was prepared from 28b and same procedure was
followed as in the case of 2a. White amorphous powder (0.031 g,
0.094 mmol, 94%); Elemental analysis calcd. Found: C, 65.39; H,
10.31; O, 24.16. C18H34O5 requires C, 65.42; H, 10.37; O, 24.21%; Rf
12.32%; Rf (100% EtOAc) 0.42; ½a D25
ꢁ15.26 (c 0.15, CH3OH); IR nmax
ꢂ
(100% EtOAc) 0.15; ½a D25
þ6.52 (c 0.1, CH3OH); IR nmax (KBr) 3512,
ꢂ
(film) 2940, 2819, 1729, 1449, 1141 cmꢁ1; 1H NMR (300 MHz, CDCl3)
2947, 2831, 1720, 1451, 1365, 1142 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.30e7.27 (5H, m, Aromatic), 5.80 (1H, dd, J¼15.3, 6.5 Hz, 7CH),
d
5.77 (1H, dd, J¼15.3, 6.2 Hz, 7CH), 5.71 (1H, dd, J¼15.2, 6.2 Hz,
5.75 (1H, dd, J¼15.3, 6.5 Hz, 8CH), 4.65 (2H, s, OCH2Ph), 4.07 (1H, q,
J¼6.5 Hz, 6CH), 3.95 (1H, dd, J¼6.7, 4.4 Hz, 9CH), 3.60e3.58 (1H, m,
10CH), 2.27 (2H, t, J¼7.3 Hz, 2CH2), 1.63e1.61 (2H, m, 3CH2),
1.55e1.50 (8H, m, aliphatic chain), 1.39e1.25 (10H, m, aliphatic
chain), 1.0 {18H, s, 2(CH3)3(CH3)2Si}, 0.94 (3H, t, J¼6.7 Hz, 18CH3),
8CH), 4.09 (1H, q, J¼6.4 Hz, 6CH), 3.95 (1H, dd, J¼6.5, 4.4 Hz, 9CH),
3.52e3.49 (1H, m,10CH), 2.27 (2H, t, J¼7.3 Hz, 2CH2),1.63e1.60 (2H,
m, 3CH2), 1.54e1.49 (6H, m, 5CH2, 11CH2, 17CH2), 1.40e1.35 (12H, m,
aliphatic chain), 0.94 (3H, t, J¼6.7 Hz, 18CH3); 13C NMR (75 MHz,
CDCl3)
d 179.4, 136.9, 130.8, 76.6, 75.5, 73.9, 38.1, 36.3, 33.4, 33.3,
0.009 {12H, s, 2(CH3)3(CH3)2Si}; 13C NMR (75 MHz, CDCl3)
d 179.0,
30.5, 30.3, 30.2, 30.1, 26.6, 26.4, 23.8, 14.5; MS (ESI, positive ion): m/
z (%)¼330 (100) [Mþ].
137.6, 132.5, 132.1, 128.9, 128.7, 127.6, 127.5, 127.3, 85.6, 74.5, 74.1,
38.6, 35.8, 32.9, 31.7, 30.6, 30.3, 30.0, 25.5, 24.5, 23.9, 20.9, 15.1, 14.0,
ꢁ6.2; MS (ESI, positive ion): m/z (%)¼649 (100) [Mþ].
Acknowledgements
4.31. 9-Benzyloxy-6,10-bis-(tert-butyl-dimethyl-silanyloxy)-
octadec-7-enoic acid (28b)
We would like to thank Director, CSIR-NEIST, Jorhate785006 for
providing necessary facilities to carry out this work. B.S. and T.J.D.
thankful CSIR-New Delhi for the award of fellowship.
Compound 28b was prepared from 27b and same procedure
was followed as in the case of 28a. Compound 28b (0.081 g,
0.125 mmol, 80%) is a colourless viscous gum; Elemental analysis
calcd. Found: C, 68.40; H, 10.51; O, 12.29. C37H68O5Si2 requires C,
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.12.076.
68.46; H, 10.56; O, 12.32%; Rf (100% EtOAc) 0.42; ½a D25
ꢂ
þ9.33 (c 0.10,
CH3OH); IR nmax (film) 2949, 2825, 1727, 1451, 1139 cmꢁ1
;
1H NMR
(300 MHz, CDCl3)
d 7.31e7.27 (5H, m, Aromatic), 5.81 (1H, dd,
References and notes
J¼15.3, 6.5 Hz, 7CH), 5.74 (1H, dd, J¼15.3, 6.5 Hz, 8CH), 4.65 (2H, s,
OCH2Ph), 4.09 (1H, q, J¼6.5 Hz, 6CH), 3.95 (1H, dd, J¼6.7, 4.4 Hz,
9CH), 3.60e3.58 (1H, m, 10CH), 2.29 (2H, t, J¼7.3 Hz, 2CH2),
1.64e1.62 (2H, m, 3CH2), 1.55e1.51 (8H, m, aliphatic chain),
1.39e1.25 (10H, m, aliphatic chain), 1.0 {18H, s, 2(CH3)3(CH3)2Si},
0.94 (3H, t, J¼6.7 Hz, 18CH3), 0.009 {12H, s, 2(CH3)3(CH3)2Si}; 13C
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