Studies directed towards the total synthesis of polyether antibiotic ionomycin: Asymmetric synthesis of fragments C(24)-C(32) and C(1)-C(23)

Article abstract of DOI:10.1016/j.tet.2015.08.011

A convergent and stereoselective approach for the synthesis of C1-C23 and C24-C32 segments of polyether antibiotic, ionomycin has been achieved. The key steps involved in this approach are the elaboration of two advanced fragments from a common precursor

Full text of DOI:10.1016/j.tet.2015.08.011

Tetrahedron 71 (2015) 7539e7549
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Tetrahedron
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Studies directed towards the total synthesis of polyether antibiotic
ionomycin: asymmetric synthesis of fragments C(24)eC(32) and
C(1)eC(23)
*
J.S. Yadav , Nagendra Nath Yadav, B.V.Subba Reddy
Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 June 2015
Received in revised form 1 August 2015
Accepted 3 August 2015
Available online 7 August 2015
A convergent and stereoselective approach for the synthesis of C1eC23 and C24eC32 segments of
polyether antibiotic, ionomycin has been achieved. The key steps involved in this approach are the
elaboration of two advanced fragments from a common precursor using enzymatic desymmetrization to
create two methyl chiral centers, desymmetrization of the bicyclic olefin to introduce two methyl and
two hydroxyl chiral centers, the use of Evans auxiliary to introduce another methyl group and the cre-
ation of four chiral centers in bis-tetrahydrofuran ring by Sharpless asymmetric epoxidation and the
regioselective opening of epoxide with methyl sulphone. The coupling of C11eC16 with C17eC23 was
achieved through a Julia-Kocienski olefination and directed Aldol reaction. Oxidation of C9 alcohol fa-
cilitates the coupling of C10eC23 with C1eC9.
Keywords:
Polyether antibiotic
Ionomycin
Desymmetrization
Sharpless asymmetric epoxidation and
regeoselective opening of epoxide
Julia-Kocienski olefination
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
The X-ray structure and absolute stereochemistry of calcium
and cadmium complexes of ionomycin were established by Gou-
Ionomycin (1, Fig. 1) is one of the important polyether antibi-
otics, which was isolated by Meyers and co-workers from fer-
mentation broths of Streptomyces congoblatus in 1978.1 It has the
ability to chelate various inorganic cations so as to transport them
across lipid membranes. Ionomycin has a unique feature that dis-
tinguishes it from all other ionophores. In particular, it chelates
slectively with calcium (and other divalent) ions as a dibasic acid in
an octahedral coordination array,2 while other ionophores exhibit
their chelating property as monobasic acids.
goutas and co-workers in 1979.3 The main structural feature of this
ionophore includes the presence of substituted bis-tetrahydrofuran
ring, 14 stereogenic centers and a
b-dicarbonyl moiety, which is
rare in these natural products. The presence of
b-dicarbonyl moiety
is responsible for ionomycin’s intense ultraviolet absorption at
280 nm and also provides two of the six metal ligation points.
Because of its broad range of therapeutic potentials and unique
structural features, ionomycin has attracted the attention of many
synthetic organic chemists.
A few total syntheses4e7 and many formal synthetic ap-
proaches8 have been reported in the literature. The retrosynthesis
of all the previously published total syntheses of ionomycin em-
ploys similar strategies. Hanessian et al.4 and Evans5 et al. reported
the identical disconnections for the construction of ionomycin
backbone but used different strategies for the synthesis of poly-
propionate and deoxypolypropionate fragments. Hanessian et al.
used the chiron approach using L-glutamic acid and Evans et al.
reported convergent asymmetric synthesis of ionomycin using
chiral enolate chemistry. Lautens6 applied ring opening strategy for
the synthesis of polypropionate and deoxypolypropionate sub-
units, while Trans-tetrahydrofuran motif was prepared via Sharp-
less asymmetric epoxidation and VO(acac)2 catalyzed epoxidation
protocol. Recently, Kocienski et al.7 reported the total synthesis of
Fig. 1. Chemical structure of ionomycin (1).
* Corresponding author. Fax: þ91 40 27160512; e-mail address: yadavpub@iict.
res.in (J.S. Yadav).
http://dx.doi.org/10.1016/j.tet.2015.08.011
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

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J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
ionomycin using gold(III)-catalyzed cycloisomerization of
hydroxyallene and rhodium-catalyzed rearrangement reaction to
generate the -diketone moiety.
a
-
The analytical data of 9 was found to be identical with the data
reported in literature.13 The free hydroxy group of 9 was protected
as its benzyl ether (15). Stereoselective ring opening of the epoxide
(15) with acetone in the presence of BF3$OEt2 at 0 ꢀC afforded the
pure acetonide 16 in 92% yield.9e,14 Debenzylation of 16 under the
Birch conditions15 using liquid ammonia and lithium metal affor-
ded the primary alcohol 8 in 90% yield as a colorless liquid. Swern
oxidation of the primary alcohol 8 followed by C2-Wittig reaction
b
Following our interest in the total synthesis of biologically active
natural products by desymmetrization strategy9,10 and inspiring
biological activity combined with fascinating structural features of
ionomycin (1), we herein report a convergent stereoselective
method for the synthesis of C24eC32 (2) and C1eC23 (3) fragments
of ionomycin. This method involves Sharpless asymmetric epoxi-
dation to generate tetrahydrofuran ring, desymmetrization strat-
egy, Evans alkylation, Julia-Kocienski olefination and directed Aldol
reaction.
Retrosynthetically, ionomycin 1 (Scheme 1) can be synthesized
from four key fragments, 6 (C1eC9), 5 (C11eC16), 4 (C17eC23) and
2 (C24eC32), which is similar to Lautens approach.6 Trans-Tetra-
hydrofuran 2 was proposed to be synthesized via the Sharpless
epoxidation of a suitable allylic alcohol followed by regioselective
ring opening of the epoxide.
afforded the a,b-unsaturated ester 17 in 96% yield over two steps.
Reduction of double bond of the ester 17 with NaBH4 and
NiCl2.6H2O in MeOH16 afforded the saturated ester, which was
further reduced with LiAlH4 in THF to give the saturated alcohol 18
in 96% yield in two steps. Swern oxidation of 18 followed by a two
carbon Wittig reaction resulted in the formation of a,b-unsaturated
ester 19 (exclusively E-isomer) in 91% yield over two steps. Cleavage
of the isopropylidene acetal 19 with 80% aqueous acetic acid
afforded the diol 20 in 96% yield. Selective silyl protection of the
secondary alcohol of 20 with TBSOTf and 2,6-lutidine in CH2Cl2 at
0 ꢀC afforded the silyl ester 21 in 93% yield. Reduction of the ester
21 with DIBAL-H furnished the primary allylic alcohol 22 in 90%
yield (Scheme 2).
Scheme 2. Synthesis of precursor 22 for key intermediate 7a.
Scheme 1. Retrosynthetic analysis of C24eC32 (2) and C1eC23 (3) segments of ion-
omycin (1).
The tetrahydrofuran moiety 7 was achieved by Sharpless
asymmetric epoxidation protocol17,18 using 1 equiv of
L-DET, 1 equiv
of Ti(OiPr)4 and 2.2 equiv of TBHP in CH2Cl2 at ꢁ20 ꢀC to room
temperature. The corresponding product was obtained as a mixture
of syn-diol (major 7a, 83% yield) along with a minor anti-diol (7b,
13% yield, Scheme 3). The formation of 7a and 7b could be
explained by intramolecular stereoselective ring opening of the
epoxide with hydroxyl function catalyzed by Ti(OiPr)4. Both prod-
ucts were easily separated by column chromatography and well
characterized by NMR spectrum.
Polypropionate fragment (4) can be obtained through desym-
metrization of bicyclic olefin developed previously by us.9 Deoxy-
polypropionate segment can be achieved through a common
precursor 12, which in turn can be synthesized by desymmetriza-
tion of meso-diol9k,10 and Evan’s asymmetric alkylation. The three
fragments could be connected through a modified Julia olefination
followed by base catalyzed directed Aldol reaction, while fragment
(2) can be coupled with fragment 4 via sulphone addition to al-
dehyde corresponding to alcohol fragment (4) to finish the total
synthesis.
2. Results and discussion
2.1. Stereoselective synthesis of C24eC32 furanoid fragment
of ionomycin (2)
Accordingly, the synthesis of C24eC32 fragment (2) began from
the readily available starting material tiglic acid. The requisite al-
lylic alcohol 14 was prepared from tiglic acid by esterification11
followed by reduction of the ethyl tiglate.12 Sharpless asymmetric
Scheme 3. Synthesis of key intermediate 7a.
Selective sulfonylation of 1,2-diol19 followed by treatment with
NaH afforded the terminal epoxide 23 in 96% yield over two steps
(Scheme 4). Regioselective opening of terminal epoxide 23 with
epoxidation of allylic alcohol 14 using
D-DIPT, Ti(OiPr)4 and TBHP in
dry CH2Cl2 afforded the epoxy alcohol 9 in 86% yield with 92% ee.

J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
7541
phenylmethyl sulphone anion in the presence of BF3$OEt2 afforded
2.4. Synthesis of C17eC23 fragment (4)
the alcohol 24 in 97% yield.18,20
Synthesis of C17eC23 fragment 4 began with the reductive
cleavage of the bicyclic lactone 10. The key intermediate 10 was
synthesized by desymmetrization of the bicyclic olefin 11.9 Thus
treatment of 10 with LiAlH4 in dry THF afforded the triol 32 in 90%
yield. Selective protection of the primary alcohols with TBDPSCl
and imidazole in CH2Cl2 afforded the di-TBDPS 33 in 92% yield
(Scheme 7).
Scheme 4. Synthesis of C24eC32 furanoid fragment of ionomycin (2).
TMS protection of tert-alcohol with TMSOTf afforded the fur-
anoid fragment (2, 98% yield) of ionomycin in 18 steps from tiglic
alcohol in 33% yield. Analytical data of fragment 2 was found to be
identical with the data reported by Lautens et al.6
2.2. Facile stereoselective synthesis of C1eC9 fragment (6)
Synthesis of C1eC9 fragment 6 started from compound 25. The
synthesis of 25 was reported earlier by enzymatic desymmetriza-
tion of meso-diol.10d Alcohol 25 was subjected to oxidation followed
Scheme 7. Synthesis of C17eC23 fragment (4).
by C2-Wittig reaction to afford the a,b-unsaturated ester 26 in 91%
for two steps. Further reduction of double bond with NaBH4 and
NiCl2.6H2O in MeOH afforded the saturated ester 27 in 98% yield.
Deprotection of TBS group with TBAF in THF afforded the alcohol 6
in 97% yield (Scheme 5).
Conversion of 33 into 4 requires the inversion of configuration of
the hydroxyl group at C5. As reported earlier by our group, the
inversion of configuration of the hydroxyl group at C-5 of the in-
termediate 33 was failed employing the Mitsunobu protocol to give
the required stereochemistry at C-21 of ionomycn. Therefore, we
explored an alternative strategy, i.e., oxidation-reduction strat-
egy.9b Accordingly, oxidation of the secondary alcohol 33 with
Dess-Martin periodinane in CH2Cl2 afforded the corresponding
ketone 34 in 92% yield. Substrate controlled reduction of the keto
group of 34 with NaBH4 in MeOH:THF (4:1) gave the required b-
isomer 35 as a major product in 96% yield (35:33¼9:1). Both iso-
mers were separated by column chromatography and the un-
desired isomer 33 was again converted back to ketone 34. The
structure of major isomer 35 was confirmed by 1H NMR spectrum
Scheme 5. Synthesis of C1eC9 fragment (6).
in which the C5eH of 35 appeared in upfield (
d 3.94) relative to
2.3. Synthesis of C11eC16 fragment (5)
C5eH of 33 ( 4.23) indicating an anti relationship between the
d
methyl group at C-4 and OH group at C-5. Deprotection of TBDPS
ether with TBAF in THF afforded the triol 36 in 93% yield. Finally, the
required fragment 4 was prepared in 90% yield by treatment of triol
36 with 2,2-dimethoxypropane in the presence of a catalytic
amount of camphor sulphonic acid in CH2Cl2 (Scheme 7).
Synthesis of C11eC16 fragment began with alcohol 28, which
was synthesized from mono acetate 12.10 Alcohol (28) was sub-
jected to IBX oxidation followed by one-carbon homologation
through Wittig reaction afforded the terminal olefin 29 in 86% yield
over two steps. Compound 29 was then subjected to hydroboration
using BH3$SMe2 in THF followed by oxidation with alkaline H2O2 to
furnish the primary alcohol 30 in 94% yield.21 Alcohol 30 was
converted into the sulfide 31 in 96% yield6 under Mitsunobu con-
2.5. Coupling of C1eC9 (6), C11eC16 (5) and C17eC23 (4)
fragments: stereoselective synthesis of C1eC23 unit of ion-
omycin (3)
ditions
with
thiol,
(1-phenyl-1H-1,2,3,4-tetraazol-5-
ylhydrosulfide) and a subsequent oxidation of the resulting thio-
ester 31 with m-CPBA afforded the sulfone fragment 5 in 93% yield
(Scheme 6).
After successful completion of the synthesis of polypropionate
fragments 6 (C1eC9), 5 (C11eC16) and 4 (C17eC23), we focused on
the synthesis of C1eC23 unit of ionomycin by the coupling of
fragment 5 with fragment 4 employing Julia-Kocienski olefina-
tion22 followed by the coupling of fragment 6 by base catalyzed
directed Aldol reaction.23
Oxidation of alcohol 4 with IBX in DMSO afforded the corre-
sponding aldehyde, which was then subjected to Julia-Kocienski
olefination with sulphone 5 using KHMDS in dry THF to give the
trans-olefin 37 in 87% yield. The trans-stereochemistry of the olefin
37 was determined by its coupling constant (J¼15.8 Hz). TBDPS
group of 37 was selectively deprotected with TBAF to yield the al-
cohol 38 in 97% yield. Oxidation of the alcohol 38 to the corre-
sponding aldehyde followed by treatment with CH3MgI in ether at
Scheme 6. Synthesis of C11eC16 fragment (5).

7542
J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
ꢁ78 ꢀC afforded the secondary alcohol, which was again trans-
formed into the ketone 39 using Dess-Martin periodinane in 91%
yield over three steps (Scheme 8).
achieved either by exposure to iodine vapor or UV light or by
dipping the plates to ethanolic anisaldehyde-sulphuric acid-acetic
acid or to phosphomolybdic acid-sulphuric acid solution and
heating the plates at 120 ꢀC. Mass spectra were obtained on a Fin-
nigan MAT1020B or micromass VG 70e70H spectrometer operat-
ing at 70 eV using a direct inlet system. Optical rotations were
recorded on PerkinElmer 241 polarimeter in 1.0 dm, 1.0 mL cells.
3.2. (E)-2-Methyl-2-buten-1-ol (14)
To a stirred suspension of LAH (8.5 g, 0.225 mol) in dry ether
(500 mL) at 0 ꢀC was added AlCl3 (9.9 g, 0.075 mol) portion wise in
the time interval of 30 min, After complete addition, the suspension
was allowed to stir for another 30 min at 0 ꢀC during, which the
alane was formed. To this grey suspension at 0 ꢀC was added a so-
lution of ethyl tiglate (24 g, 0.187 mol) in ether (100 mL) dropwise.
The mixture was allowed to stir for 1 h and then quenched with
Na2SO4 at 0 ꢀC and the mixture was stirred overnight. The solid was
filtered through a pad of Celite and washed with ether (5ꢂ100 mL).
The filtrate was then subjected to distillation using short path
condenser to furnish the pure allylic alcohol 14 (13.0 g, 81%) at
140 ꢀC at atmospheric pressure; 1H NMR (300 MHz, CDCl3):
d 5.45
(q, J¼6.6, 13.2 Hz, 1H, olefinic), 3.95 (s, 2H, CH2OH), 1.66 (s, 3H,
CCH3), 1.62 (d, J¼6.7 Hz, 3H, CHCH3), 1.32e1.43 (br s, 1H, OH); 13C
NMR (CDCl3, 75 MHz):
d 135.2, 120.2, 68.5, 13.1, 12.9.
Scheme 8. Synthesis of C1eC23 unit of ionomycin (3).
3.3. [(2R,3R)-2,3-Dimethyloxiran-2-yl]methanol (9)
Next we attempted the coupling of ketone 39 with aldehyde de-
rived fromthealcohol 6. Accordingly, directed Aldol reactionbetween
ketone 39 and the aldehyde (derived from alcohol 6) using KHMDS in
To a 500 mL two neck round bottom flask equipped with
a magnetic bar and a septum with N2 inlet was weighed 8.5 g of 4 A
ꢀ
molecular sieves (dry powder). To this dry CH2Cl2 (200 mL) was
THFat ꢁ78 ꢀC gave the mixture of isomeric
b-hydroxyl ketone in good
added and the solution was then cooled to ꢁ20 ꢀC. To this sus-
yield, which was then converted into 1,3-diketone 3 (C1eC23 unit of
ionomycin) using PDC on Celite24 in 70% yield over two steps.
In summary, a concise, stereoselective and highly convergent
synthetic approach has been developed for the synthesis of fur-
anoid fragment (C24eC32) and C1eC23 unit of ionomycin. The
strategy involves mainly the Sharpless asymmetric epoxidation and
diastereoselective ring opening of the epoxide to construct the
C24eC32 furanoid fragment, desymmetrization strategy to con-
struct the polypropionate subunit, enzymatic desymmetrization of
meso-diol for the deoxypolypropionate subunit, Julia-Kocienski
olefination and directed Aldol reaction as key steps.
pension was added Ti(OiPr)4 (2.9 mL, 9.8 mmol) followed by D-
diisopropyl tartrate (2.41 mL, 11.3 mmol) and the mixture was
stirred vigorously at ꢁ20 ꢀC for 30 min. A solution of allyl alcohol 14
(6.5 g, 75.5 mmol) in 50 mL CH2Cl2 was added to the above mixture
and stirred for another 30 min and then TBHP (30.2 mL, 0.15 mol,
5M solution in toluene) was added at ꢁ20 ꢀC. The mixture was then
set for stirring at the same temperature for another 7 h. The mix-
ture was filtered and the residue was washed with CH2Cl2. The
filtrate and the washings were quenched with water (50 mL) and
then subjected to stirring for 30 min at ꢁ20 ꢀC. Then a solution of
22 mL of 20% NaOH prepared from a saturated NaCl solution was
added to the above reaction mixture and the stirring was continued
at rt for 12 h. The organic layers were separated, dried over anhy-
drous Na2SO4 and concentrated by distillation at atmospheric
temperature to afford the crude epoxy alcohol, which was later
purified on 60e120 silica column using 20% EtOAc/hexane to yield
3. Experimental section
3.1. General
All reactions were carried out under inert atmosphere of argon
or nitrogen using standard syringe, septa, and cannula techniques
unless otherwise mentioned. Commercial reagents were used
without further purification. All solvents were purified by standard
techniques. Infrared (IR) spectra were recorded on a PerkineElmer
683 spectrometer using NaCl optics. Spectra were calibrated
against the polystyrene absorption at 1610 cme1. Samples were
scanned neat, in KBr wafers or in chloroform as a thin film. 1H NMR
spectra were recorded in CDCl3 on Bruker 300, Varian Unity 500
NMR spectrometer. 13C NMR spectra were recorded at 75 MHz in
CDCl3 using tetramethylsilane as a reference standard. Chemical
shifts are in parts per million downfield from tetramethylsilane and
coupling constants (J) are reported in hertz (Hertz). The following
abbreviations are used to designate signal multiplicity: s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet, br¼broad. Column
chromatography was performed using silica gel (60e120 mesh) and
the column was usually eluted with a mixture of ethyl aceta-
teepetroleum ether. Visualization of the spots on TLC plates was
the pure product 9 (6.6 g, 86% yield). Rf¼0.35 (20% EtOAc/hexane);
25
[a
]
þ17.8 (c 1.0, CHCl3); IR (neat):
n 3405, 2976, 2930, 1380,
D
1039 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
3.62 (d, J¼11.4 Hz, 1H,
OCHAHB), 3.50 (d, J¼11.4 Hz, 1H, OCHAHB), 3.11 (q, J¼5.2 Hz, 1H,
CHCH3), 1.85e1.93 (br s, 1H, OH), 1.31 (d, J¼5.2 Hz, 3H, CHCH3), 1.26
(s, 3H, CCH3); 13C NMR (CDCl3, 75 MHz):
d 65.3, 61.0, 55.8, 13.7, 13.3.
3.4. (2R,3R)-2-[(Benzyloxy)methyl]-2,3-dimethyloxirane (15)
To a stirred suspension of NaH (3.85 g, 95.5 mmol) in dry THF
(200 mL) at 0 ꢀC was added the solution of epoxy alcohol 9 (6.5 g,
63.5 mmol) in dry THF (40 mL) dropwise. After complete addition,
the suspension was allowed to stir for 30 min at room temperature
and again cooled to 0 ꢀC and then benzyl bromide (8.55 mL,
70.0 mmol), followed by a catalytic amount of TBAI were added. The
mixture was allowed to stir for 8 h at room temperature. After
completion of reaction as indicated by TLC, the reaction was
quenched with saturated solution of NH4Cl and the organic layer was

J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
7543
extracted with EtOAc (3ꢂ200 mL). The combined organic layers were
dried over Na2SO4, concentrated under reduced pressure and puri-
fied by chromatography on silica gel (EtOAc/hexane,10%) to yield the
was allowed to warm to room temperature and stirred for 30 min. To
the above aldehyde was added (ethoxycarbonylmethylene)triphe-
nylphosphorane (26.1 g, 75 mmol) and the resulting mixture was
stirred for 12 h at room temperature and then quenched with water
and extracted with CH2Cl2 (3ꢂ100 mL). The combined organic layers
were washed with water, brine, dried over Na2SO4 and concentrated
in vacuo. The residue was purified by silica gel column chromatog-
corresponding benzyl ether 15 (11.1 g, 91% yield) as a colorless liquid.
25
Rf¼0.50 (10% EtOAc/hexane); [
a
]
þ1.2 (c 1.0, CHCl3); IR (Neat):
n
D
3030, 2929, 1453, 1097, 741 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
7.20e7.34 (m, 5H, ArH), 4.52 (ABq, J¼12.0 Hz, 2H, OCH2Ph), 3.41 (s,
2H, CH2O), 2.91 (q, J¼5.2Hz, 1H, CHCH3), 1.30 (s, 3H, CCH3), 1.29 (d,
raphy using 10% EtOAc/hexane to furnish the pure 17 (10.9 g, 96%
25
J¼5.2 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d
137.9,128.2,127.4,
yield). Rf¼0.15 (10% EtOAc/hexane); [
(neat):
(300 MHz, CDCl3):
a
]
þ1.5 (c 1.2, CHCl3); IR
D
74.5, 72.9, 59.5, 56.3, 14.0, 13.5; MS (ESI): m/z 215 [MþNa]þ; HRMS:
calcd for C12H16O2Na [MþNa]þ 215.1047, found: 215.1043.
n ;
2984, 2936, 1720, 1374, 1293, 1165, 993 cmꢁ1 1H NMR
d
6.79 (d, J¼15.4 Hz, 1H, olefinic), 6.01 (d,
J¼15.4 Hz, 1H, olefinic), 4.18 (q, J¼7.1 Hz, 2H, CH2CH3), 4.01 (q,
J¼6.4Hz,1H, CHCH3),1.48 (s, 3H, CCH3),1.38 (s, 3H, CCH3),1.35 (s, 3H,
CCH3), 1.30 (t, J¼7.1 Hz, 3H, CH2CH3), 1.21 (d, J¼6.4 Hz, 3H, CHCH3);
3.5. (4S,5R)-4-[(Benzyloxy)methyl]-2,2,4,5-tetramethyl-1,3-
dioxolane (16)
13C NMR (75 MHz, CDCl3):
d 166.2,148.8,121.0,107.9, 82.0, 79.9, 60.3,
To a stirred solution of 15 (12.0 g, 62.5 mmol) in dry acetone
(300 mL) at 0 ꢀC was added BF3$Et2O (17.1 mL, 62.5 mmol) dropwise
and the reaction mixture was stirred at 0 ꢀC for 1 h. After completion
of the reaction, mixture was quenched with solid NaHCO3 at 0 ꢀC
and the solvent was evaporated under reduced pressure and the
residue was diluted with water and extracted with EtOAc
(3ꢂ100 mL). The combined organic layers were washed with brine,
dried over anhydrous Na2SO4, and concentrated under reduced
pressure. Purification on silica gel column chromatography using 8%
27.9, 26.3, 23.8, 14.9, 14.1; MS (ESI): m/z 251 [MþNa]þ; HRMS: calcd
for C12H20O4Na [MþNa]þ 251.1259, found: 251.1266.
3.8. 3-[(4S,5R)-2,2,4,5-Tetramethyl-1,3-dioxolan-4-yl]-1-
propanol (18)
To a cooled (0 ꢀC) solution of 17 (10.5 g, 46.4 mmol) and
NiCl2.6H2O (2.19 g, 9.2 mmol) in MeOH (200 mL), was added NaBH4
(4.15 g, 110.5 mmol) in small portions. During the addition of
NaBH4, the reaction temperature was maintained at 0 ꢀC. After
complete addition of NaBH4, the mixture was stirred for 1 h at room
temperature and the resulting black precipitate was filtered and
then washed with MeOH. The solvent was removed under reduced
pressure and then diluted with water (100 mL) and extracted with
EtOAc (3ꢂ200 mL). The combined organic layers were washed with
water, brine, dried over anhydrous Na2SO4 and concentrated under
reduced pressure to afford the ester.
EtOAc/hexane afforded the compound 16 (14.3 g, 92% yield) as a pale
25
yellow oil. Rf¼0.15 (8% EtOAc/hexane); [
a
]
ꢁ5.7 (c 1.2, CHCl3); IR
D
(neat):
CDCl3):
n
2984, 2867, 1453, 1375, 1100 cmꢁ1
7.19e7.34 (m, 5H, ArH), 4.49 (s, 2H, OCH2Ph), 3.89 (q,
;
1H NMR (300 MHz,
d
J¼5.8 Hz, 1H, CHCH3), 3.40 (d, J¼9.7 Hz, 1H, OCHAHB), 3.18 (d,
J¼9.7 Hz, 1H, OCHAHB), 1.35 (s, 3H, CCH3), 1.35 (s, 3H, CCH3), 1.29 (s,
3H, CCH3), 1.23 (d, J¼6.8 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d
138.1, 128.1, 127.3, 106.6, 81.1, 78.7, 73.1, 72.4, 28.2, 26.4, 21.4, 13.5.
To a stirred suspension of LAH (3.49 g, 92 mmol) in dry THF
(200 mL) at 0 ꢀC was added the above solution of ester in THF
(50 mL) drop wise and the reaction mixture was allowed to stir for
30 min at 0 ꢀC. After completion as indicated by TLC, the reaction
was quenched with Na2SO4 at 0 ꢀC and the mixture was stirred
overnight. The solid was filtered through pad of Celite and washed
with EtOAc (3ꢂ200 mL). The combined organic layers were dried
over Na2SO4 and concentrated and purified by chromatography on
silica gel (EtOAc/hexane, 30%) to yield the corresponding alcohol 18
3.6. [(4S,5R)-2,2,4,5-Tetramethyl-1,3-dioxolan-4-yl]methanol
(8)
To a solution of compound 16 (14.0 g, 56.0 mmol) in THF (20 mL)
in 250 mL 2-necked flask fitted with a septum and ammonia con-
denser and about 100 mL of ammonia was collected in the flask. To
this clear solution at ꢁ33 ꢀC was added lithium metal (0.784 g,
112 mmol) portion wise. After appearance of deep blue color, the
reaction mixture was stirred at the same temperature for 30 min.
After completion of the reaction as confirmed by TLC, the mixture
was quenched with solid NH4Cl till the blue color disappeared and
the ammonia was allowed to evaporate at room temperature. The
mixture was then extracted with ether (5ꢂ100 mL) and the com-
bined organic layers were dried, concentrated under reduced
pressure and then purified by chromatography on silica gel using
(8.3 g, 96% yield) as a colorless liquid. Rf¼0.25 (30% EtOAc/hexane);
25
[
a
]
ꢁ10.4 (c 0.65, CHCl3); IR (Neat):
n 3456, 2934, 1374, 1247,
D
850 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
3.87 (q, J¼6.4Hz, 1H,
CHCH3), 3.67e3.64 (m, 1H, OH), 3.62 (t, J¼5.2 Hz, 2H, CH2OH),
1.51e1.88 (m, 3H, CHAHBCH2), 1.40 (s, 3H, CCH3), 1.33 (s, 3H, CCH3),
1.23e1.32 (m, 1H, CHAHB), 1.20 (s, 3H, CCH3), 1.18 (d, J¼6.6 Hz, 3H,
CHCH3); 13C NMR (75 MHz, CDCl3):
d 106.6, 81.7, 79.8, 63.2, 31.2,
15% EtOAc/hexane to furnish the pure product 8 (8.0 g, 90% yield).
28.2, 26.7, 22.4, 13.5; MS (ESI): m/z 211 [MþNa]þ; HRMS: calcd for
10H20O3Na [MþNa]þ 211.1310, found: 211.1319.
25
Rf¼0.25 (15% EtOAc/hexane); [
a
]
ꢁ11.8 (c 1.1, CHCl3); IR (neat):
n
C
D
3467, 2985, 2635, 1376, 1217, 1105, 1054, 997 cmꢁ1
(300 MHz, CDCl3):
;
1H NMR
d
3.92 (q, J¼6.6Hz, 1H, CHCH3), 3.49 (d,
3.9. Ethyl (E)-2-methyl-5-[(4S,5R)-2,2,4,5-tetramethyl-1,3-
dioxolan-4-yl]-2-pentenoate (19)
J¼10.7 Hz, 1H, CHAHB), 3.25 (t, J¼10.7 Hz, 1H, CHAHB), 1.68e1.78 (br
s, 1H, OH), 1.42 (s, 3H, CCH3), 1.36 (s, 3H, CCH3), 1.24 (s, 3H, CCH3),
1.22 (d, J¼6.6 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d
107.3,
To a solution of oxalyl chloride (5.4 mL, 63.8 mmol) in CH2Cl2
(150 mL) at ꢁ78 ꢀC was added dimethylsulfoxide (6.5 mL, 83 mmol)
over 20 min. The resulting mixture was stirred for another 30 min
and then a solution of alcohol 18 (8.0 g, 42.5 mmol) in CH2Cl2
(40 mL) was added dropwise. The mixture was stirred for 1 h and
then triethylamine (35.8 mL, 255 mmol) was added dropwise. The
reaction mixture was allowed to warm to room temperature and
stirred for 30 min. After completion, the mixture was quenched
with water (200 mL) and the aqueous phase was extracted with
CH2Cl2 (2ꢂ200 mL). The combined organic layers were washed
with brine, dried over anhydrous Na2SO4 and concentrated under
reduced pressure to get crude aldehyde.
81.9, 78.3, 64.9, 28.2, 26.3, 20.6, 12.7.
3.7. Ethyl (E)-3-[(4S,5R)-2,2,4,5-tetramethyl-1,3-dioxolan-4-
yl]-2-propenoate (17)
To a solution of oxalyl chloride (6.35 mL, 75 mmol) in CH2Cl2
(150 mL) at ꢁ78 ꢀC was added dimethylsulfoxide (7.6 mL, 97.5 mmol)
over 20 min. The resulting mixture was stirred for another 30 min
and then a solution of alcohol 8 (8.0 g, 50 mmol) in CH2Cl2 (40 mL)
was added drop wise. The mixture was stirred for 30 min and trie-
thylamine (42.5 mL, 300 mmol) was added dropwise. The mixture

7544
J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
To the above aldehyde in benzene (200 mL) was added ethyl 2-
stir for 30 min at 0 ꢀC, before being quenched with sodium po-
tassium tartarate solution (40 mL). The mixture was then stirred at
room temperature until it becomes clear solution. The aqueous
layer was extracted with CH2Cl2 (3ꢂ50 mL) and the combined or-
ganic layers were dried over Na2SO4, concentrated in vacuo and
then purified by column chromatography using 16% EtOAc/hexanes
(triphenylphosphoranylidene)propanoate (23.1 g, 63.8 mmol) and
the mixture was heated under reflux for 24 h. After completion,
benzene was removed and the crude product was purified by silica
gel column chromatography using 10% EtOAc/hexane to afford the
pure unsaturated ester 19 (10.45 g, 91% yield). Rf¼0.35 (10% EtOAc/
25
hexane); [
a
]
D
ꢁ4.5 (c 1.05, CHCl3); IR (neat):
n
2983, 2935, 1711,
to afford the pure 22 (5.3 g, 90% yield) as light yellow oil. Rf¼0.34
25
1373, 1259, 1216, 1109, 997, 519 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
(16% EtOAc/hexane); [
a
]
ꢁ4.9 (c 0.8, CHCl3); IR (neat):
n
3378,
D
d
6.69 (t, J¼8.3 Hz, 1H, olefinic), 4.13 (q, J¼7.5Hz, 2H, CH2CH3), 3.84
2954, 2858, 1254, 1100 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 5.38 (t,
(q, J¼6.7Hz, 1H, CHCH3), 2.28e2.47 (m, 1H, CHAHB), 2.10e2.28 (m,
1H, CHAHB), 1.84 (s, 3H, CCH3), 1.55e1.70 (m, 1H, CHAHB), 1.38 (s, 3H,
CCH3), 1.33 (s, 3H, CCH3), 1.30 (t, J¼7.5 Hz, 3H, CH2CH3), 1.21 (m, 1H,
CHAHB), 1.20 (s, 3H, CCH3), 1.18 (d, J¼6.0 Hz, 3H, CHCH3); 13C NMR
J¼6.9 Hz, 1H, olefinic), 3.95 (s, 2H, CH2OH), 3.59 (q, J¼6.9Hz, 1H,
CHCH3), 2.12e2.23 (m, 1H, CHAHB), 2.02e2.09 (m, 1H, CHAHB), 2.0
(br s, 1H, OH), 1.67 (s, 3H, CCH3), 1.49e1.57 (m, 1H, CHAHB),
1.30e1.38 (m, 1H, CHAHB), 1.10 (d, J¼5.9, 3H, CHCH3), 1.09 (s, 3H,
CCH3), 0.91 (s, 9H, (CH3)3C), 0.09 (s, 6H, (CH3)2Si); 13C NMR
(75 MHz, CDCl3):
d 168.0, 142.2, 127.7, 106.6, 81.4, 79.7, 60.2, 33.3,
28.2, 26.7, 22.6, 22.3, 14.1, 13.3, 12.1.
(75 MHz, CDCl3): d 134.6, 126.3, 75.1, 74.2, 68.7, 35.8, 25.7, 23.1, 21.7,
20.7, 17.9, 13.3, ꢁ4.1, ꢁ5.0; MS (ESI): m/z 325 [MþNa]þ.
3.10. Ethyl (E,6S,7R)-6,7-dihydroxy-2,6-dimethyl-2-octenoate
(20)
3.13. (2S)-2-[(2R,5S)-5-((1R)-1-[1-(tert-Butyl)-1,1-
dimethylsilyl]oxyethyl)-5-methyltetrahydro-2-furanyl]pro-
pane-1,2-diol (7a)
Acetic acid (80%, 50 mL) was added to 19 (10.0 g, 37.0 mmol) at
room temperature and reaction mixture was stirred for 12 h. The
reaction mixture was quenched with saturated NaHCO3 and the
aqueous layer was extracted with EtOAc (5ꢂ150 mL). The combined
organic layers were washed with brine, dried over Na2SO4 and
concentrated under reduced pressure and the residue was purified
To a 100 mL two neck round bottom flask equipped with
a magnetic bar and a septum with N2 inlet was weighed 1.9 g of 4 A
ꢀ
molecular sieves (dry powder). To this was added dry CH2Cl2
(50 mL) and the solution was then cooled to ꢁ20 ꢀC. To the above
by column chromatography using 30% EtOAc/hexane to afford the
suspension was added Ti(OiPr)4 (5.1 mL, 17.2 mmol) followed by L-
25
pure diol 20 (8.1 g, 96% yield). Rf¼0.17 (30% EtOAc/hexane); [
a]
þ0.5 (c 1.05, CHCl3); IR (neat):
n
3428, 2980, 1706, 1274, 1094 cmꢁD1
;
diethyl tartrate (2.9 mL, 17.2 mmol) and the mixture was stirred
vigorously at ꢁ20 ꢀC for 30 min. A solution of allyl alcohol 22 (5.2 g,
17.2 mmol) in 20 mL CH2Cl2 was added to the above reaction
mixture and stirred for another 30 min and then TBHP (10.5 mL,
37.8 mmol, 3.6M solution in toluene) was added at ꢁ20 ꢀC. The
resulting mixture was then set for stirring at the same temperature
for 1 h and then at room temperature for another 2 h. The reaction
mixture was filtered and the residue was washed with CH2Cl2. The
filtrate and the washings were quenched with water (100 mL) at
0 ꢀC and then stirred for another 30 min. After, which a solution of
17 mL of 20% NaOH solution prepared from a satd NaCl was added
to the reaction mixture and the stirring was continued at rt for 12 h.
The organic layers were separated, dried over anhydrous Na2SO4
and concentrated in vacuo and then purified by column chroma-
tography using 20% EtOAc/hexane to afford the pure 7a (4.5 g, 83%
yield, Rf¼0.15 (20% EtOAc/hexane)) along with another di-
astereoisomer 7b (711 mg, 13%, Rf¼0.25 (20% EtOAc/hexane) as
1H NMR (300 MHz, CDCl3):
d
6.73 (t, J¼7.5 Hz, 1H, olefinic), 4.15 (q,
J¼6.7Hz, 2H, CH2CH3), 3.59 (q, J¼6.7Hz, 1H, CHCH3), 2.17e2.43 (m,
2H, CH2), 2.16 (br s, 1H, OH), 2.04 (br s, 1H, OH), 1.84 (s, 3H, CCH3),
1.60e1.76 (m, 1H, CHAHB), 1.38e1.47 (m, 1H, CHAHB), 1.30 (t,
J¼6.7 Hz, 3H, CH2CH3), 1.17 (s, 3H, CCH3), 1.15 (d, J¼6.0, 3H, CHCH3);
13C NMR (75 MHz, CDCl3):
d 168.2, 142.3, 127.6, 74.2, 74.3, 60.4, 33.0,
23.0, 22.7, 17.3, 14.1, 12.2; MS (ESI): m/z 253 [MþNa]þ; HRMS: calcd
for C12H22O4Na [MþNa]þ 253.1415, found: 253.1411.
3.11. Ethyl (E,6S,7R)-7-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-6-
hydroxy-2,6-dimethyl-2-octenoate (21)
tert-Butyldimethylsilyltrifluoromethane sulfonate (TBSOTf,
5.4 mL, 23.9 mmol) was added drop wise to a cooled solution (0 ꢀC)
of diol 20 (5.0 g, 21.7 mmol) and 2,6-lutidine (5.0 mL, 43.4 mmol) in
dry CH2Cl2 (100 mL). After 10 min, the reaction mixture was diluted
with CH2Cl2 (50 mL) and quenched with water and extracted with
CH2Cl2 (2ꢂ50 mL). The organic layer was dried over Na2SO4, con-
centrated in vacuo and the residue was purified by column chro-
matography using 10% EtOAc/hexane to afford the pure compound
21 (6.9 g, 93% yield). Rf¼0.22 (10% EtOAc/hexane); [
CHCl3); IR (neat):
1H NMR (300 MHz, CDCl3):
J¼6.9Hz, 2H, CH2CH3), 3.61 (q, J¼6.9Hz, 1H, CHCH3), 2.29e2.40 (m,
1H, CHAHB), 2.13e2.24 (m, 1H, CHAHB), 2.20 (br s, 1H, OH), 1.84 (s,
3H, CCH3), 1.58e1.67 (m, 1H, CHAHB), 1.36e1.45 (m, 1H, CHAHB), 1.30
(t, J¼6.9 Hz, 3H, CH2CH3), 1.11 (d, J¼5.9 Hz, 3H, CHCH3), 1.10 (s, 3H,
CCH3), 0.91 (s, 9H, (CH3)3C), 0.09 (s, 6H, (CH3)2Si); 13C NMR
a colorless liquid; [
a]
25 ꢁ7.4 (c 1.0, CHCl3); IR (neat):
n
3442, 2955,
1H NMR
D
2932, 2859, 1638, 1465, 1253, 1100, 833, 774 cmꢁ1
;
(500 MHz, CDCl3):
d
3.89 (t, J¼6.9 Hz,1H, OCH), 3.61 (q, J¼6.9Hz,1H,
CHCH3), 3.58 (d, J¼10.8 Hz, 1H, CHAHB), 3.33 (d, J¼10.8 Hz, 1H,
CHAHB), 2.46 (br s, 1H, OH), 2.23 (br s, 1H, OH), 1.74e1.99 (m, 3H,
CH2, HAHB), 1.56e1.63 (m, 1H, CHAHB), 1.12 (d, J¼5.9 Hz, 3H, CHCH3),
1.11 (s, 3H, CCH3), 1.10 (s, 3H, CCH3), 0.88 (s, 9H, (CH3)3C), 0.07 (s,
a
]
25 ꢁ5.0 (c 1.15,
D
n
2955, 2933, 2858, 1709, 1254, 1099, 834 cmꢁ1
;
d
6.71 (t, J¼5.9 Hz, 1H, olefinic), 4.16 (q,
3H, CH3Si), 0.06 (s, 3H, CH3Si); 13C NMR (75 MHz, CDCl3):
d 85.8,
83.4, 73.1, 67.4, 34.6, 26.1, 25.8, 21.0, 20.2, 18.7, 17.9, ꢁ4.0, ꢁ4.6; MS
(ESI): m/z 341 [MþNa]þ; HRMS: calcd for C16H34O4NaSi [MþNa]þ
341.2124, found: 341.2113.
(75 MHz, CDCl3):
d
168.1, 142.5, 127.6, 75.2, 74.0, 60.3, 34.5, 25.7,
3.14. tert-Butyl(dimethyl)[((1R)-1-(2S,5R)-2-methyl-5-[(2S)-2-
methyloxiran-2-yl]tetrahydro-2-furanylethyl)oxy]silane (23)
22.9, 22.8, 17.9, 14.2, 12.2, ꢁ4.1, ꢁ5.0; MS (ESI): m/z 367 [MþNa]þ;
HRMS: calcd for C18H36O4NaSi [MþNa]þ 367.2280, found: 367.2273.
To a stirred solution of the diol 7a (4.4 g, 13.8 mmol), triethyl-
amine (3.8 mL, 27.6 mmol) in dry CH2Cl2 (50 mL) at 0 ꢀC was added
p-toluenesulfonyl chloride (3.15 g, 16.6 mmol), DMAP (336 mg,
2.7 mmol) and dibutyltin oxide (669 mg, 2.7 mmol). The resulting
mixture was stirred at 0 ꢀC for 1 h. After complete conversion as
indicated by TLC, the mixture was quenched with water (20 mL),
extracted with CH2Cl2 (3ꢂ50 mL) and the combined organic layers
3.12. (E,6S,7R)-7-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-2,6-
dimethyl-2-octene-1,6-diol (22)
To a cooled (0 ꢀC) solution of 21 (6.8 g, 19.7 mmol) in dry CH2Cl2
(80 mL) was added DIBAL-H (43.4 mL, 43.4 mmol, 1M solution in
toluene) slowly over 15 min. The resulting mixture was allowed to

J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
7545
were dried over Na2SO4 and concentrated in vacuo to afford the
tosylate.
J¼6.7 Hz, 1H, OCH), 3.43 (q, J¼6.0 Hz, 1H, CHCH3), 3.21 (dd, J¼6.7,
9.0 Hz, 2H, CH2SO2), 1.52e2.02 (m, 6H, 3ꢂCH2), 1.09 (s, 3H, CCH3),
1.03 (s, 3H, CCH3), 1.01 (d, J¼6.0 Hz, 3H, CHCH3), 0.87 (s, 9H,
(CH3)3C), 0.05 (s, 3H, CH3Si), 0.03 (s, 9H, (CH3)3Si), 0.01 (s, 3H,
d 139.0, 133.4, 129.1, 128.0, 85.6,
82.7, 75.6, 73.3, 51.8, 35.8, 32.5, 26.1, 25.7, 22.9, 18.8, 18.3, 17.8, 2.2,
To a solution of crude tosylate in dry THF (60 mL) at 0 ꢀC was
added NaH (1.1 g, 27.6 mmol). The resulting mixture was stirred at
room temperature for 3e4 h. The mixture was quenched with
water (20 mL), extracted with EtOAc (3ꢂ50 mL) and the combined
organic layers were dried over Na2SO4, concentrated in vacuo and
then purified by column chromatography using 8% EtOAc/hexanes
CH3Si); 13C NMR (75 MHz, CDCl3):
ꢁ3.9, ꢁ4.9.
to afford the pure product 23 (3.9 g, 96% yield) as colorless liquid.
3.17. Ethyl (E,4S,6S,8S)-9-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-
4,6,8-trimethyl-2-nonenoate (26)
25
Rf¼0.3 (8% EtOAc/hexane); [
a
]
D
ꢁ7.4 (c 0.7, CHCl3); IR (neat):
n
2956, 2858, 1465, 1253, 1099 cmꢁ1 1H NMR (500 MHz, CDCl3):
;
d
3.84 (t, J¼7.1 Hz, 1H, OCH), 3.58 (q, J¼5.9 Hz, 1H, CHCH3), 2.60 (d,
To a stirred solution of IBX (2.9 g, 10.4 mmol) in DMSO (8 mL) at
25 ꢀC, was slowly added a solution of alcohol 25 (2.0 g, 6.94 mmol)
in CH2Cl2 (20 mL). The resulting mixture was stirred at 25 ꢀC for 3 h.
The solid was filtered and was washed with ether. The filtrate was
diluted with ether, washed with saturated aqueous NaHCO3 solu-
tion followed by water, brine and dried over Na2SO4. The solvent
was removed under reduced pressure to furnish the crude alde-
hyde. To a solution of aldehyde in CH2Cl2 (40 mL) was added
J¼4.7 Hz, 1H, CHAHB), 2.52 (d, J¼4.7 Hz, 1H, CHAHB), 1.93e2.0 (m,
1H, CHAHB), 1.80e1.88 (m, 1H, CHAHB), 1.65e1.73 (m, 1H, CHAHB),
1.55e1.64 (m, 1H, CHAHB), 1.31 (s, 3H, CCH3), 1.13 (d, J¼5.9 Hz, 3H,
CHCH3), 1.10 (s, 3H, CCH3), 0.88 (s, 9H, (CH3)3C), 0.06 (s, 3H, CH3Si),
0.05 (s, 3H, CH3Si); 13C NMR (75 MHz, CDCl3):
d 86.0, 80.5, 72.6,
57.2, 52.3, 35.4, 26.7, 25.7, 19.6, 18.2, 17.8, 17.5, ꢁ4.0, ꢁ4.9; MS (ESI):
m/z 323 [MþNa]þ; HRMS: calcd for C16H32O3NaSi [MþNa]þ
323.2018, found: 323.2006.
(ethoxycarbonylmethylene)triphenylphosphorane
(6.38
g,
18.3 mmol) and the resulting mixture was stirred for 12 h at room
temperature and then quenched with water and extracted with
CH2Cl2 (3ꢂ100 mL). The combined organic layers were washed
with water, followed by brine, dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude product was purified by silica gel
3.15. (2S)-2-[(2R,5S)-5-((1R)-1-[1-(tert-Butyl)-1,1-
dimethylsilyl]oxyethyl)-5-methyltetrahydro-2-furanyl]-4-
(phenylsulfonyl)butan-2-ol (24)
To a well-stirred solution of methyl phenyl sulphone (2.57 g,
16.5 mmol) in anhydrous THF (20 mL) at ꢁ78 ꢀC was added n-butyl
lithium (10.3 mL, 16.5 mmol, 1.6M solution in hexanes) dropwise
and stirred for 30 min at the same temperature. BF3$Et2O (0.93 mL,
7.2 mmol) was added to the above mixture and allowed to stir for
10 min and then a solution of epoxide 23 (2.0 g, 6.6 mmol) in dry
THF (15 mL) was added dropwise at ꢁ78 ꢀC. The mixture was
stirred for 4 h at ꢁ78 ꢀC and then warm to room temperature. After
completion, the reaction mixture was quenched with saturated
NH4Cl and the product was extracted with EtOAc (3ꢂ50 mL). The
combined organic layers were washed with brine and dried over
anhydrous Na2SO4 was and then purified by column chromatog-
raphy (EtOAc/hexane, 5%) to afford the pure product 24 (2.94 g, 97%
column chromatography (1:19 EtOAc/hexane) to afford the 26 in
25
(2.24 g, 91%) yield as colorless oil. Rf¼0.45 (5% EtOAc/hexane); [
a]
þ11.9 (c 1.0, CHCl3); IR (neat):
n
2957, 2857, 1723, 1256, 838 cmꢁD1
;
1H NMR (300 MHz, CDCl3):
d
6.86 (dd, J¼7.7, 15.6 Hz, 1H, olefinic),
5.77 (d, J¼15.6 Hz, 1H, olefinic), 4.21 (q, J¼7.1Hz, 2H, CH2CH3), 3.44
(dd, J¼5.2, 9.6 Hz, 1H, OCHAHB), 3.33 (dd, J¼6.2, 9.6 Hz, 1H,
OCHAHB), 2.31e2.49 (m, 1H, CH), 1.46e1.73 (m, 2H, 2ꢂCH), 1.33 (t,
J¼7.1 Hz, 3H, CH2CH3), 1.07e1.33 (m, 4H, 2ꢂCH2), 1.05 (d, J¼6.6 Hz,
3H, CHCH3), 0.85e0.95 (m, 15H, 2ꢂCH3, (CH3)3C), 0.03 (s, 6H,
(CH3)2Si); 13C NMR (75 MHz, CDCl3):
d 166.9, 155.1, 119.1, 68.1, 60.0,
43.4, 41.3, 33.9, 33.1, 27.7, 25.9, 20.4, 18.9, 18.3, 17.7, 14.2, ꢁ5.4; MS
(ESI): m/z 379 [MþNa]þ; HRMS: calcd for C20H40O3NaSi [MþNa]þ
379.2644, found: 379.2640.
yield) as a pale yellow liquid. Rf¼0.15 (5% EtOAc/hexane); [
(c 0.55, CHCl3); IR (neat):
NMR (500 MHz, CDCl3):
a
]
25 ꢁ8.7
D
n
3508, 2928, 2856, 1308, 834 cmꢁ1
;
1H
d
7.90 (d, J¼7.1 Hz, 2H, ArH), 7.53e7.70 (m,
3.18. Ethyl (4R,6S,8S)-9-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-
4,6,8-trimethylnonanoate (27)
3H, ArH), 3.75 (t, J¼7.1 Hz, 1H, CHCH2), 3.56 (q, J¼6.2 Hz, 1H,
CHCH3), 3.29 (dt, J¼4.5, 13.5 Hz, 1H, CHAHBSO2), 3.11 (dt, J¼4.5,
13.5 Hz, 1H, CHAHBSO2), 2.22 (br s, 1H, OH), 1.53e2.01 (m, 6H,
3ꢂCH2), 1.11 (s, 3H, CCH3), 1.09 (s, 3H, CCH3), 1.06 (d, J¼6.2 Hz, 3H,
CHCH3), 0.87 (s, 9H, (CH3)3C), 0.07 (s, 3H, CH3Si), 0.04 (s, 3H, CH3Si);
To a cooled solution of 26 (2.2 g, 6.17 mmol) and NiCl2.6H2O
(292 mg, 1.23 mmol) in MeOH (30 mL), was added NaBH4 (562 mg,
14.8 mmol) in small portions at 0 ꢀC. After complete addition of
NaBH4, the mixture was stirred for 1 h at room temperature. The
black precipitate formed was filtered and washed with MeOH. The
solvent was removed under reduced pressure and the residue was
diluted with water (40 mL) and extracted with ethyl acetate
(2ꢂ50 mL). The combined organic layers were washed with water,
brine and dried over anhydrous Na2SO4. Removal of the solvent
under reduced pressure and purification by silica gel column
chromatography using ethyl acetate and hexane (1:19) afforded the
13C NMR (75 MHz, CDCl3):
d 139.1, 133.6, 129.2, 127.9, 84.8, 84.1,
72.9, 72.0, 51.5, 34.2, 29.5, 25.7, 25.4, 23.6, 20.4,18.7,17.8, ꢁ4.1, ꢁ4.5;
MS (ESI): m/z 479 [MþNa]þ; HRMS: calcd for C23H40O5NaSiS
[MþNa]þ 479.2263, found: 479.2256.
3.16. tert-Butyl(dimethyl)[(1R)-1-((2S,5R)-2-methyl-5-(1S)-1-
methyl-3-(phenylsulfonyl)-1-[(1,1,1-trimethylsilyl)oxy]pro-
pyltetrahydro-2-furanyl)ethyl]oxysilane (2)
pure compound 27 (2.16 g, 98% yield) as a colorless liquid. Rf¼0.15
25
To a stirred solution of alcohol 24 (1.8 g, 3.9 mmol) and 2,6-
lutidine (1.0 mL, 8.58 mmol) in dry CH2Cl2 (20 mL) at ꢁ15 ꢀC was
added trimethylsilyl trifluoromethanesulfonate (TMSOTf, 0.80 mL,
4.3 mmol) dropwise. After 10 min, the mixture was diluted with
CH2Cl2 (20 mL) and quenched with water and extracted with
CH2Cl2 (2ꢂ40 mL). The organic layer was dried and concentrated in
vacuo and the residue was purified by column chromatography
(5% EtOAc/hexane); [
a]
ꢁ14.3 (c 1.25, CHCl3); IR (neat):
n
2957,
D
2929, 1723, 1256, 839 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 4.13 (q,
J¼7.3Hz, 2H, CH2CH3), 3.44 (dd, J¼5.1, 9.5 Hz,1H, OCHAHB), 3.34 (dd,
J¼6.5, 9.5 Hz,1H, OCHAHB), 2.22e2.31 (m, 2H, CH2CO),1.41e1.72 (m,
6H, alkyl chain), 1.27 (t, J¼7.3 Hz, 3H, CH2CH3), 1.20 (m, 1H, alkyl
chain), 0.95e1.13 (m, 2H, alkyl chain), 0.88 (s, 9H, (CH3)3C), 0.87 (d,
J¼7.3 Hz, 3H, CHCH3), 0.86 (d, J¼7.3 Hz, 3H, CHCH3), 0.84 (d,
J¼6.6 Hz, 3H, CHCH3), 0.02 (s, 6H, (CH3)2Si); 13C NMR (75 MHz,
using 20% EtOAc/hexane to afford the pure compound 2 (2.0 g, 98%
25
yield). Rf¼0.5 (20% EtOAc/hexane); [
a
]
D
ꢁ8.3 (c 1.0, CHCl3); IR
CDCl3): d 174.0, 68.3, 60.1, 44.0, 41.9, 33.0, 32.1, 29.7, 27.3, 25.9, 20.1,
(neat):
CDCl3):
n
d
2956, 2857, 1252, 1093, 836 cmꢁ1
7.90 (d, J¼7.5 Hz, 2H, ArH), 7.53e7.70 (m, 3H, ArH), 3.66 (t,
;
1H NMR (500 MHz,
18.9, 18.3, 17.3, 14.2, ꢁ5.3; MS (ESI): m/z 376 (MþNH4)þ; HRMS:
calcd for C20H42O3NaSi [MþNa]þ 381.2800, found: 381.2810.

7546
J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
3.19. Ethyl (4R,6S,8S)-9-hydroxy-4,6,8-trimethylnonanoate (6)
warmed to room temperature and then allowed to stir for 3 h. The
mixture was quenched with NaHCO3 solution and extracted with
EtOAc (3ꢂ50 mL). Removal of the solvent followed by purification
on silica gel column chromatography (20% EtOAc/hexane) gave the
To a stirred solution of silyl ether 27 (4.2 g,11.7 mmol) in dry THF
(30 mL) at 0 ꢀC was added drop wise a solution of TBAF (17.5 mL,
17.5 mmol) in THF. The resulting mixture was allowed to warm to rt
and stirred for 12 h. The reaction mixture was then quenched with
water and extracted with ethyl acetate (2ꢂ100 mL). The combined
organic extracts were dried over Na2SO4 and concentrated under
reduced pressure and the crude product was purified by silica gel
column chromatography (1.5:8.5, EtOAc/hexane) to afford the pure
desired product 30 (1.37 g, 94% yield) as a viscous liquid. Rf¼0.15
25
(20% EtOAc/hexane); [
a]
þ4.5 (c 1.0, CHCl3); IR (neat):
n
3351,
D
2929, 1427, 822, 740 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 7.64 (d,
J¼7.5 Hz, 2H, ArH), 7.63 (d, J¼7.5 Hz, 2H, ArH), 7.28e7.43 (m, 6H,
ArH), 3.52e3.70 (m, 2H, OCH2), 3.36e3.52 (m, 2H, OCH2), 1.14e1.79
(m, 6H, 2ꢂCH, 2ꢂCH2), 1.05 (s, 9H, (CH3)3C), 0.95 (d, J¼6.7 Hz, 3H,
CHCH3), 0.86 (d, J¼6.0 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
product 6 (2.76 g, 97% yield) as a colorless liquid. Rf¼0.22 (15%
25
EtOAc/hexane); [
a]
ꢁ17.0 (c 1.05, CHCl3); IR (neat):
n
3442, 2957,
d 135.6, 133.9,129.4,127.5, 68.7, 61.0, 41.1, 39.7, 33.0, 26.9, 26.8, 20.2,
D
2873, 1735, 1460, 1376, 1176, 1036 cmꢁ1; 1H NMR (300 MHz, CDCl3):
19.2, 17.6; MS (ESI): m/z 407 [MþNa]þ; HRMS: calcd for
d
4.15 (q, J¼7.5Hz, 2H, CH2CH3), 3.34e3.51 (m, 2H, OCH2), 2.32 (t,
C
24H36O2NaSi [MþNa]þ 407.2382, found: 407.2400.
J¼7.5 Hz, 2H, CH2CO), 1.43e1.75 (m, 5H, alkyl chain), 1.29e1.43 (m,
2H, alkyl chain), 1.28 (t, J¼7.5 Hz, 3H, CH2CH3), 0.98e1.17 (m, 2H,
alkyl chain), 0.93 (d, J¼6.7 Hz, 3H, CHCH3), 0.87 (d, J¼6.7 Hz, 6H,
3.22. 1-(tert-Butyl)-1,1-diphenylsilyl(2R,4S)-2,4-dimethyl-6-
[(1-phenyl-1H-1,2,3,4-tetraazol-5-yl)sulfanyl]hexyl ether (31)
2ꢂCHCH3); 13C NMR (75 MHz, CDCl3):
d 174.1, 68.0, 60.1, 44.0, 41.4,
32.8, 32.6, 31.9, 29.5, 27.2, 20.2, 19.0, 17.1, 14.1; MS (ESI): m/z 245
(MþH)þ; HRMS: calcd for C14H28O3Na [MþNa]þ 267.1936, found:
267.1947.
To a cooled (0 ꢀC) solution of alcohol 30 (1.3 g, 3.38 mmol), PPh3
(1.32 g, 5.07 mmol), and thiol (843 mg, 4.73 mmol) in 30 mL THF
was added diethyl azodicarboxylate (0.85 mL, 5.4 mmol) dropwise.
The reaction mixture was stirred for 2 h before being quenched
with saturated aqueous NaHCO3 solution, and extracted with EtOAc
(3ꢂ50 mL). The organic layers were combined and dried over an-
hydrous Na2SO4, filtered, and concentrated under reduced pres-
sure. The residue was purified on silica gel column chromatography
3.20. tert-Butyl[(2R,4S)-2,4-dimethyl-5-hexenyl]oxy-
diphenylsilane (29)
To a stirred solution of IBX (1.98 g, 7.08 mmol) in DMSO (10 mL)
was added dropwise a solution of alcohol 28 (1.75 g, 4.72 mmol) in
CH2Cl2 (25 mL). The resulting mixture was stirred at rt for 3 h. The
solid was filtered through a pad of Celite and washed with ether.
The filtrate was washed with saturated aqueous NaHCO3 solution,
water, brine and dried over Na2SO4. The solvent was removed un-
der reduced pressure and then the residue was purified by flash
column chromatography (1:9, EtOAc/hexane) to furnish the crude
aldehyde. To a stirred suspension of methyl(triphenyl)phospho-
nium iodide (7.62 g, 18.8 mmol) in dry THF (100 mL) at ꢁ78 ꢀC was
added n-BuLi (5.87 mL, 1.6 M in hexanes, 9.4 mmol) dropwise and
the resulting mixture was stirred for 30 min at the same temper-
ature. A solution of aldehyde in THF was slowly added to the above
reaction mixture and the mixture was stirred for 1 h at ꢁ78 ꢀC, then
warmed to room temperature and stirred for another 6 h. The re-
action mixture was quenched with saturated NH4Cl solution at 0 ꢀC
and then extracted with EtOAc (3ꢂ100 mL). The combined organic
layers were washed with water, brine, dried over Na2SO4 and
concentrated under reduced pressure. The crude mixture was pu-
rified by silica gel column chromatography (1:9 EtOAc/hexane) to
(10% EtOAc/hexane) to afford the desired product 31 (1.76 g, 96%
25
yield) as a viscous liquid. Rf¼0.35 (10% EtOAc/hexane); [
(c 0.55, CHCl3); IR (neat):
702 cmꢁ1 1H NMR (300 MHz, CDCl3):
a
]
þ10.5
D
n
2957, 2858, 1499, 1387, 1108, 822,
7.44e7.67 (m, 10H, ArH),
;
d
7.27e7.43 (m, 5H, ArH), 3.23e3.53 (m, 4H, 2ꢂCH2), 1.37e1.89 (m,
6H, 2ꢂCH, 2ꢂCH2), 1.03 (s, 9H, (CH3)3C), 0.94 (d, J¼6.4 Hz, 6H,
2ꢂCHCH3); 13C NMR (75 MHz, CDCl3):
d 154.3, 135.5, 133.9, 129.9,
129.7, 129.4, 127.5, 123.7, 68.6, 40.7, 35.9, 33.0, 31.2, 29.6, 26.8, 19.7,
19.2, 17.6; MS (ESI): m/z 567 [MþNa]þ; HRMS: calcd for
C
31H40N4ONaSiS [MþNa]þ 567.2589, found: 567.2586.
3.23. (3S,5R)-6-[1-(tert-Butyl)-1,1-diphenylsilyl]oxy-3,5-
dimethylhexyl(1-phenyl-1H-1,2,3,4-tetraazol-5-yl) sulfone (5)
To a stirred solution of sulphide 31 (1.7 g, 3.1 mmol) in CH2Cl2
(25 mL) at 0 ꢀC was added mCPBA (1.61 g, 9.3 mmol). The reaction
mixture was allowed to stir for 12 h at room temperature. After
completion of the reaction as indicated by TLC, the mixture was
quenched with aqueous NaHCO3 and the organic layer was
extracted with CH2Cl2 (3ꢂ30 mL). The combined organic layers
were dried over Na2SO4, concentrated under reduced pressure and
purified by chromatography on silica gel (5%, EtOAc/hexane) to
afford the compound 29 (1.48 g, 86% yield). Rf¼0.25 (10% EtOAc/
25
hexane); [
a]
þ4.1 (c 1.25, CHCl3); IR (neat):
n 3071, 2958, 2929,
D
2859, 1640, 1466, 1426, 1109, 910, 702, 504 cmꢁ1
(300 MHz, CDCl3):
;
1H NMR
7.62 (d, J¼7.5 Hz, 4H, ArH), 7.27e7.43 (m, 6H,
d
yield the corresponding sulphone 5 (1.66 g, 93% yield) as a colorless
25
ArH), 5.48e5.63 (m, 1H, olefinic), 4.77e4.97 (m, 2H, olefinic),
3.34e3.50 (m, 2H, OCH2), 2.07e2.25 (m, 1H, CHCH3), 1.59e1.76 (m,
1H, CHCH3), 1.30e1.46 (m, 2H, CH2), 1.04 (s, 9H, (CH3)3C), 0.97 (d,
J¼6.7 Hz, 3H, CHCH3), 0.91 (d, J¼6.7 Hz, 3H, CHCH3); 13C NMR
liquid. Rf¼0.55 (5% EtOAc/hexane); [
a]
þ5.6 (c 0.65, CHCl3); IR
D
(Neat):
CDCl3):
n
d
2957, 2857, 1341, 1152, 1109 cmꢁ1
7.54e7.77 (m, 9H, ArH), 7.28e7.47 (m, 6H, ArH), 3.53e3.77
;
1H NMR (300 MHz,
(m, 2H, CH2), 3.46 (dd, J¼3.0, 5.2 Hz, 2H, CH2), 1.82e2.0 (m,1H, alkyl
chain), 1.56e1.82 (m, 3H, alkyl chain), 1.22e1.49 (m, 2H, alkyl
chain), 1.04 (s, 9H, (CH3)3C), 0.95 (d, J¼6.0 Hz, 3H, CHCH3), 0.94 (d,
(75 MHz, CDCl3): d 144.6, 135.6, 134.0, 129.4, 127.5, 112.5, 69.2, 40.3,
35.4, 33.3, 26.8, 21.3, 19.3, 16.7.
J¼6.7 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d 153.4, 135.5,
3.21. (3S,5R)-6-[1-(tert-Butyl)-1,1-diphenylsilyl]oxy-3,5-
dimethylhexan-1-ol (30)
134.7, 133.8, 133.0, 131.3, 129.6, 129.5, 127.5, 125.0, 68.5, 54.0, 40.3,
32.9, 29.3, 28.1, 26.8, 19.6, 19.2, 17.5; MS (ESI): m/z 599 [MþNa]þ;
HRMS: calcd for C31H40N4O3NaSiS [MþNa]þ 599.2488, found:
599.2483.
To a stirred solution of alkene 29 (1.4 g, 3.82 mmol) in dry THF
(15 mL) at 0 ꢀC was added borane-dimethyl sulfide complex (2M
solution in THF, 2.1 mL, 4.2 mmol) dropwise and the resulting
mixture was stirred at room temperature for 4 h. After complete
conversion of the starting material as indicated by TLC, the mixture
was cooled to 0 ꢀC, and then treated with 1 M NaOH solution (76 mL)
followed by 30% H2O2 (25 mL) solution. The resulting mixture was
3.24. (3R,4S,5R,6R)-5-(Benzyloxy)-4,6-dimethylheptane-1,3,7-
triol (32)
To an ice cooled suspension of LAH (1.03 g, 27.1 mmol) in dry
THF (50 mL) was added a solution of lactone 10 (5.0 gm, 18.1 mmol)

J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
7547
in THF (25 mL) under nitrogen atmosphere. The reaction mixture
was stirred for 1 h at room temperature. After completion of the
reaction, it was quenched with saturated ammonium chloride so-
lution and the precipitate formed was filtered off on a pad of Celite
using EtOAc. The filtrate was dried over anhydrous Na2SO4 and
59.2, 49.0, 46.1, 38.0, 26.9, 26.7, 19.2, 19.0, 14.9, 13.1; MS (ESI): m/z
779 [MþNa]þ; HRMS: calcd for C48H60O4NaSi2 [MþNa]þ 779.3927,
found: 779.3937.
3.27. 5-(Benzyloxy)-1,7-di[1-(tert-butyl)-1,1-diphenylsilyl]
oxy-(3S,4S,5R,6R)-4,6-dimethylheptan-3-ol (35)
concentrated in vacuo to afford the triol 32 (4.5 g, 90% yield) as
25
a colorless viscous liquid; [
a
]
D
þ9.3 (c 0.95, CHCl3); IR (Neat):
n
3414, 2937, 2881, 1679, 754 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
To a stirred solution of keto compound 34 (5.0 g, 6.61 mmol)
in MeOH-THF (4:1, 60 mL) at 0 ꢀC was added NaBH4 (376 mg,
9.91 mmol) portion wise. The mixture was brought to room
temperature and the stirring was continued for 1 h. After com-
pletion of the reaction, it was quenched with Na2SO4 solution
(10 mL) at 0 ꢀC. The solvent was evaporated and the residue was
extracted with EtOAc. The combined organic layers were washed
with brine, and dried over Na2SO4. The solvent was evaporated to
dryness and the residue was purified by silica gel column chro-
matography to afford the desired products 35 (4.35 g, 87% yield,
Rf¼0.22 (10% EtOAc/hexane)) along with another diastereoisomer
d
7.26e7.38 (m, 5H, ArH), 4.67 (s, 2H, CH2Ph), 4.17e4.26 (m, 1H,
OCH), 3.70e3.80 (m, 3H, OCH2, OCH), 3.66 (dd, J¼4.5, 10.5 Hz, 1H,
OCHAHB), 3.51 (dd, J¼3.7, 7.5 Hz, 1H, OCHAHB), 1.94e2.07 (m, 1H,
CHCH3), 1.78e1.92 (m, 1H, CHCH3), 1.64e1.76 (m, 1H, CHAHB),
1.32e1.42 (m, 1H, CHAHB), 1.10 (d, J¼6.7 Hz, 3H, CHCH3), 1.0 (d,
J¼6.7 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d 137.5, 128.5,
128.0, 127.8, 88.0, 76.0, 70.3, 64.9, 61.6, 39.1, 37.7, 36.5, 14.9, 11.7; MS
(ESI): m/z 305 [MþNa]þ; HRMS: calcd for C16H26O4Na [MþNa]þ
305.1728, found: 305.1728.
3.25. (3R,4S,5R,6R)-5-(Benzyloxy)-1,7-di[1-(tert-butyl)-1,1-
diphenylsilyl]oxy-4,6-dimethylheptan-3-ol (33)
33 (450 mg, 9% yield, Rf¼0.3 (10% EtOAc/hexane)) as viscous
25
liquid; [
a
]
ꢁ1.4 (c 1.0, CHCl3); IR (neat):
n ;
3445 cmꢁ1 1H NMR
d 7.58e7.67 (m, 8H, ArH), 7.27e7.40 (m, 14H,
D
(300 MHz, CDCl3):
To a stirred solution of triol 32 (4.4 g, 15.6 mmol) and imidazole
(3.18 g, 46.8 mmol) in dry CH2Cl2 (50 mL) at 0 ꢀC was added
TBDPSCl (3.87 mL, 34.3 mmol) dropwise. The reaction mixture was
brought to rt and stirred for 2 h. After completion of the reaction as
indicated by TLC, it was quenched by NH4Cl solution and extracted
with CH2Cl2 (3ꢂ50 mL). The combined organic layers were dried
over Na2SO4, filtered and concentrated in vacuo. The residue was
purified by silica gel column chromatography (10%, EtOAc/hexanes)
ArH), 7.16e7.22 (m, 2H, ArH), 7.07e7.13 (m, 1H, ArH), 4.50 (ABq,
J¼11.0 Hz, 2H, CH2Ph), 3.94 (t, J¼8.0 Hz, 1H, OCH), 3.80e3.87 (m,
1H, OCH), 3.71e3.80 (m, 2H, OCH2), 3.68 (dd, J¼7.0, 10.0 Hz, 1H,
OCHAHB), 3.42 (t, J¼6.0 Hz, 1H, OCHAHB), 3.30 (br s, 1H, OH),
1.95e2.05 (m, 1H, CH3CH), 1.84e1.92 (m, 1H, CH3CH), 1.69e1.79
(m, 1H, CHAHB), 1.49e1.63 (m, 1H, CHAHB), 1.06 (s, 9H, (CH3)3C),
1.04 (s, 9H, (CH3)3C), 1.03 (d, J¼7.0 Hz, 3H, CHCH3), 0.90 (d,
J¼7.0 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d 138.5, 135.6,
to afford the pure disilyl ether 33 (10.9 g, 93% yield) as viscous
135.5, 133.8, 133.3, 129.6, 129.5, 128.2, 127.6, 127.5, 127.4, 127.3,
84.9, 74.4, 72.0, 65.5, 63.0, 40.8, 39.1, 35.3, 26.9, 26.8, 19.2, 19.0,
14.8, 13.6; MS (ESI): m/z 781 [MþNa]þ; HRMS: calcd for
25
liquid. Rf¼0.3 (10% EtOAc/hexane); [
a]
þ8.3 (c 1.0, CHCl3); IR
D
(neat):
n
3425 cmꢁ1; 1H NMR (500 MHz, CDCl3):
d 7.57e7.72 (m, 8H,
ArH), 7.27e7.42 (m,14H, ArH), 7.18e7.24 (m, 2H, ArH), 7.06e7.11 (m,
1H, ArH), 4.55 (ABq, J¼11.0 Hz, 2H, CH2Ph), 4.17e4.23 (m, 1H, OCH),
3.67e3.80 (m, 4H, 2ꢂOCH2), 3.49 (dd, J¼4.0, 7.0 Hz, 1H, OCH), 3.18
(br, s, 1H, OH), 1.98e2.10 (m, 1H, CH3CH), 1.81e1.86 (m, 1H, CH3CH),
1.69e1.79 (m, 1H, CHAHB), 1.34e1.47 (m, 1H, CHAHB), 1.06 (s, 9H,
(CH3)3C), 1.03 (s, 9H, (CH3)3C), 1.02 (d, J¼6.0 Hz, 3H, CHCH3), 1.0 (d,
C
48H62O4NaSi2 [MþNa]þ 781.4084, found: 781.4062.
3.28. (3S,4S,5R,6R)-5-(Benzyloxy)-4,6-dimethylheptane-1,3,7-
triol (36)
To a cooled (0 ꢀC), solution of disilylether 35 (4.3 g, 5.67 mmol)
in THF (15 mL) was added TBAF (17.0 mL, 17.0 mmol, 1 M solution in
THF) under nitrogen. After 15 min, the resulting mixture was
brought to rt and stirred for another 5 h. The reaction mixture was
quenched with ammonium chloride solution, extracted with EtOAc,
dried over Na2SO4 and concentrated in vacuo. The residue was
purified by column chromatography (EtOAc) to afford the triol 36
J¼6.0 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d 138.1, 135.7,
135.5, 134.7, 133.7, 133.6, 129.5, 128.3, 127.6, 86.2, 75.6, 67.8, 65.4,
61.8, 38.5, 38.3, 37.5, 26.9, 26.8, 19.2, 19.1, 14.8, 11.6; MS (ESI): m/z
781 [MþNa]þ; HRMS: calcd for C48H62O4NaSi2 [MþNa]þ 781.4084,
found: 781.4062.
3.26. (4R,5R,6R)-5-(Benzyloxy)-1,7-di[1-(tert-butyl)-1,1-
diphenylsilyl]oxy-4,6-dimethylheptan-3-one (34)
(1.48 g, 93% yield) as a viscous liquid. Rf¼0.35 (EtOAc); [
0.65, CHCl3); IR (neat):
3444, 2937, 2881, 1457 cmꢁ1
(300 MHz, CDCl3):
a
]
;
25 ꢁ5.7 (c
D
n
1H NMR
d
7.26e7.39 (m, 5H, ArH), 4.55e4.70 (m, 2H,
Dess-Martin periodinane (8.22 g, 19.3 mmol) was added to an
ice-cooled solution of disilyl ether 33 (10.5 g, 13.8 mmol) in CH2Cl2
(80 mL) under N2 atmosphere. After stirring for 10 min, it was
brought to room temperature and the stirring was continued for
another 3 h. The reaction mixture was diluted with ether and the
precipitate was filtered on a pad of Celite using ether as solvent.
The filterate was washed with aqueous NaHCO3 followed by brine
solution, and dried over anhydrous Na2SO4 and concentrated in
vacuo. The residue was purified by silica gel column chromatog-
raphy (8%, EtOAc/hexanes) to afford the pure keto compound 34
CH2Ph), 3.53e3.94 (m, 5H, 2ꢂOCH, OCH2, OCHAHB), 3.48 (t,
J¼5.4 Hz, 1H, OCHAHB), 2.32e3.0 (br s, 3H, 3ꢂOH), 1.88e2.08 (m,
2H, 2ꢂCHCH3), 1.52e1.84 (m, 2H, CH2), 1.09 (d, J¼7.1 Hz, 3H,
CHCH3), 0.93 (d, J¼6.9 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d
137.5, 128.5,128.0,127.9, 88.0, 75.0, 74.0, 65.2, 61.6, 41.9, 38.1, 35.0,
15.5,14.0; MS (ESI): m/z 305 [MþNa]þ; HRMS: calcd for C16H26O4Na
[MþNa]þ 305.1728, found: 305.1728.
3.29. (2R,3R,4R)-3-(Benzyloxy)-4-[(4S)-2,2-dimethyl-1,3-
dioxan-4-yl]-2-methylpentan-1-ol (4)
(9.5 g, 92% yield) as viscous liquid. Rf¼0.25 (8% EtOAc/hexane);
25
[
a
]
ꢁ17.8 (c 1.0, CHCl3); IR (neat):
n
1740 cmꢁ1
;
1H NMR
To a stirred solution of triol 36 (3.0 g, 10.6 mmol) and 2,2-
dimethoxypropane (2.63 mL, 21.2 mmol) in dry CH2Cl2 (40 mL)
at 0 ꢀC was added a catalytic amount of CSA (232 mg, 1.0 mmol),
and stirred at room temperature for 5 h. After completion of the
reaction, it was quenched with saturated aqueous NaHCO3 solu-
tion, extracted with CH2Cl2 and the combined organic layers were
washed with water, brine, and dried over Na2SO4. Removal of the
solvent in vacuo followed by purification on silica gel column
D
(300 MHz, CDCl3):
d 7.53e7.74 (m, 8H, ArH), 7.03e7.47 (m, 17H,
ArH), 4.32e4.48 (m, 2H, CH2Ph), 3.53e3.99 (m, 5H, 2ꢂOCH2, OCH),
2.90e3.08 (m, 1H, CHCO), 2.62e2.79 (m, 1H, CHAHB), 2.47e2.62
(m, 1H, CHAHB), 1.89e2.07 (m, 1H, CHCH3), 1.06 (s, 9H, (CH3)3C),
1.02 (d, J¼6.0 Hz, 3H, CHCH3), 0.98 (s, 9H, (CH3)3C), 0.96 (d,
J¼6.0 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
d 212.4, 138.5,
135.6, 135.5, 133.6, 129.5, 128.1, 127.6, 127.4, 127.3, 83.8, 74.4, 65.1,

7548
J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
chromatography (15% EtOAc/hexanes) afforded the pure com-
extracts were dried over Na2SO4, concentrated under reduced
pressure and the crude was purified by silica gel column chroma-
25
pound 4 (3.07 g, 90% yield). Rf¼0.3 (15% EtOAc/hexane); [
þ14.7 (c 0.65, CHCl3); IR (neat): 3469, 1379, 1038, 769,
575 cmꢁ1 1H NMR (300 MHz, CDCl3):
7.22e7.40 (m, 5H, ArH),
a
]
D
n
tography (1:9, EtOAc/hexane) to afford the pure alcohol 38 (247 mg,
25
;
d
97% yield) as a viscous liquid. Rf¼0.15 (10% EtOAc/hexane); [
ꢁ12.1 (c 1.35, CHCl3); IR (neat):
3461, 1339, 1031, 835 cmꢁ1
NMR (300 MHz, CDCl3):
a
;
]
1DH
4.61 (ABq, J¼11.3 Hz, 2H, CH2Ph), 3.74e3.95 (m, 3H, 2ꢂOCH,
OCHAHB), 3.41e3.67 (m, 3H, OCH2, OCHAHB), 2.58 (br s, 1H, OH),
1.84e2.07 (m, 2H, 2ꢂCHCH3), 1.49e1.65 (m, 1H, CHAHB), 1.41e1.47
(m, 1H, CHAHB), 1.38 (s, 3H, CCH3), 1.35 (s, 3H, CCH3), 0.99 (d,
J¼7.5 Hz, 3H, CHCH3), 0.96 (d, J¼7.5 Hz, 3H, CHCH3); 13C NMR
n
d
7.26e7.39 (m, 5H, ArH), 5.57 (dd, J¼8.8,
15.3 Hz, 1H, olefinic), 5.36e5.45 (m, 1H, olefinic), 4.58 (ABq,
J¼11.3 Hz, 2H, CH2Ph), 4.05e4.15 (m, 1H, OCH), 3.71e3.82 (m, 2H,
OCH, OCHAHB), 3.45 (dd, J¼4.8, 10.5 Hz, 1H, OCHAHB), 3.35 (dd,
J¼6.4, 10.5 Hz, 1H, OCHAHB), 3.24 (dd, J¼3.2, 7.2 Hz, 1H, OCHAHB),
2.41e2.50 (m, 1H, CHCH3), 1.81e2.02 (m, 5H, CH2, 2ꢂCHCH3,
CHAHB), 1.51e1.76 (m, 4H, CH2, CHCH3, CHAHB), 1.40 (s, 3H, CCH3),
1.36 (s, 3H, CCH3), 1.12 (d, J¼7.2 Hz, 3H, CHCH3), 0.91 (d, J¼7.2 Hz,
3H, CHCH3), 0.89 (d, J¼7.2 Hz, 3H, CHCH3), 0.87 (d, J¼7.2 Hz, 3H,
(75 MHz, CDCl3):
d 138.0, 128.4, 127.8, 127.7, 98.0, 84.5, 73.2, 69.5,
66.5, 59.9, 40.8, 36.3, 29.9, 28.7, 19.0, 15.7, 11.0; MS (ESI): m/z 345
[MþNa]þ; HRMS: calcd for C19H30O4Na [MþNa]þ 345.2041,
found: 345.2048.
3.30. (2R,4R,6E,8R,9R,10R)-9-(Benzyloxy)-10-[(4S)-2,2-
dimethyl-1,3-dioxan-4-yl]-2,4,8-trimethyl-6-undecenyloxy)
(tert-butyl)diphenylsilane (37)
CHCH3); 13C NMR (75 MHz, CDCl3):
d 138.9,133.6,128.2,128.1,127.6,
127.4, 98.2, 84.2, 74.0, 69.3, 68.1, 59.9, 40.6, 39.9, 39.5, 39.2, 33.1,
29.8, 26.7, 25.5, 20.5, 19.4, 19.2, 17.1, 10.9; MS (ESI): m/z 455
[MþNa]þ.
To a stirred solution of IBX (313 mg, 1.12 mmol) in DMSO (2 mL)
at rt was added drop wise a solution of alcohol 4 (240 mg,
0.74 mmol) in CH2Cl2 (8 mL). The resulting mixture was stirred for
3 h at the same temperature. The solid was filtered through a pad of
Celite and washed with ether. The filtrate was washed with satu-
rated aqueous NaHCO3 solution, water, brine and dried over
Na2SO4. The solvent was removed under reduced pressure and the
residue was purified by flash column chromatography (1:9, EtOAc/
hexane, Rf¼0.15) to furnish the crude aldehyde (230 mg,
0.71 mmol), which was used for the Julia olefination without fur-
ther purification.
To a solution of azeotropically dried sulfone 5 (576 mg,
1.0 mmol) in dry THF (10 mL) at ꢁ78 ꢀC was added KHMDS
(2.0 mL, 0.5M solution in toluene, 1.0 mmol) and the mixture was
stirred for 30 min. To this, a solution of the above aldehyde
(azeotropically dried with benzene) in dry THF (10 mL) was added
via cannula and the reaction mixture was slowly warm to room
temperature and stirred for 12 h. The reaction was quenched with
NH4Cl solution. The aqueous phase was extracted with EtOAc
(3ꢂ15 mL), and the combined organic layer was washed with
brine, dried over anhydrous Na2SO4, and concentrated in vacuo.
The crude product was purified by flash chromatography on silica
3.32. (3R,5R,7E,9R,10R,11R)-10-(Benzyloxy)-11-[(4S)-2,2-
dimethyl-1,3-dioxan-4-yl]-3,5,9-trimethyl-7-dodecen-2-one
(39)
To a stirred solution of IBX (145 mg, 0.52 mmol) in DMSO (2 mL)
at rt was added a solution of alcohol 38 (150 mg, 0.34 mmol) in
CH2Cl2 (8 mL). The resulting mixture was stirred for 3 h at the same
temperature. The solid was filtered through a pad of Celite and
washed with ether. The filtrate was washed with saturated aqueous
NaHCO3 solution, water, brine and dried over Na2SO4. The solvent
was removed under reduced pressure and the residue was purified
by flash column chromatography (5%, EtOAc/hexane) to furnish the
crude aldehyde, which was used for the Grignard reaction without
further purification.
To a stirred solution of above aldehyde in dry ether (10 mL) at
ꢁ78 ꢀC was added freshly prepared CH3MgI (0.3 mL, 2 M in ether,
0.6 mmol) and reaction was allowed to stir at the same temperature
for 1 h. After complete conversion of the starting material as in-
dicated by TLC, the mixture was quenched with NH4Cl solution and
extracted with EtOAc (3ꢂ15 mL). Removal of the solvent followed
by purification on silica gel column chromatography (10% EtOAc/
hexane, Rf¼0.15) gave the isomeric alcohol, which was used for the
oxidation reaction.
gel (5%, EtOAc/hexanes) to give the trans-olefin 37 (413 mg, 87%
25
yield) as a colorless liquid. Rf¼0.25 (5% EtOAc/hexane); [
a
]
D
ꢁ3.0
(c 0.9, CHCl3); IR (neat):
n
d
2958, 2929, 2861, 1377, 1103 cmꢁ1
7.57e7.75 (m, 5H, ArH), 7.20e7.45 (m,
;
1H
NMR (300 MHz, CDCl3):
To a stirred solution of the above alcohol in dry CH2Cl2 (5 mL) at
10H, ArH), 5.54 (dd, J¼8.3, 15.8 Hz, 1H, olefinic), 5.24e5.38 (m, 1H,
olefinic), 4.57 (ABq, J¼11.3 Hz, 2H, CH2Ph), 3.92e4.02 (m, 1H,
OCH), 3.66e3.84 (m, 2H, OCH, OCHAHB), 3.50 (dd, J¼5.2, 9.0 Hz,
1H, OCHAHB), 3.39 (dd, J¼6.7, 9.8 Hz, 1H, OCHAHB), 3.24 (dd, J¼3.7,
6.7 Hz, 1H, OCHAHB), 2.32e2.48 (m, 1H, CHCH3), 1.42e2.05 (m, 6H,
2ꢂCH2, 2ꢂCHCH3), 1.32 (s, 3H, CCH3), 1.25 (s, 3H, CCH3), 1.14e1.41
(m, 3H, CH2, CHCH3), 1.06 (d, J¼6.7 Hz, 3H, CHCH3), 1.04 (s, 9H,
(CH3)3C), 0.93 (d, J¼6.7 Hz, 3H, CHCH3), 0.84 (d, J¼6.7 Hz, 3H,
CHCH3), 0.81 (d, J¼6.7 Hz, 3H, CHCH3); 13C NMR (75 MHz, CDCl3):
0
ꢀC was added Dess-Martin periodinane (288 mg, 0.68 mmol)
under N2 atmosphere. After stirring for 10 min, it was brought to
room temperature and the stirring was continued for another 3 h.
The mixture was diluted with ether and the precipitate was filtered
on a pad of Celite using ether as a solvent. The filterate was washed
with water, NaHCO3, dried over anhydrous Na2SO4 and concen-
trated in vacuo. The residue was purified by silica gel column
chromatography (7%, EtOAc/hexane) to afford the pure keto com-
pound 39 (137 mg, 91% yield over three steps) as a colorless liquid.
25
d
139.0, 135.5, 134.7, 134.0, 133.8, 129.4, 128.4, 128.2, 127.5, 127.3,
Rf¼0.10 (7% EtOAc/hexane); [
a
]
D
ꢁ10.2 (c 0.5, CHCl3); IR (neat):
n
98.1, 84.2, 73.7, 69.4, 68.8, 60.0, 40.6, 40.5, 39.9, 39.4, 33.1, 30.5,
29.9, 29.6, 26.8, 20.1, 17.7, 11.1.
2960, 2925, 1713, 1459, 1374, 1175, 1106, 700 cmꢁ1
;
1H NMR
(300 MHz, CDCl3):
d
7.26e7.39 (m, 5H, ArH), 5.60 (dd, J¼8.3,15.4 Hz,
1H, olefinic), 5.30e5.44 (m, 1H, olefinic), 4.55 (ABq, J¼11.5 Hz, 2H,
CH2Ph), 4.01e4.11 (m, 1H, OCH), 3.74e3.88 (m, 2H, OCH, OCHAHB),
3.28 (dd, J¼3.5, 7.5 Hz, 1H, OCHAHB), 2.39e2.68 (m, 2H, 2ꢂCHCH3),
2.01 (s, 3H, CH3CO), 1.79e2.05 (m, 3H, CHCH3, CH2), 1.59e1.76 (m,
2H, CHCH3, CHAHB), 1.41 (s, 3H, CCH3), 1.36 (s, 3H, CCH3), 1.19e1.36
(m, 3H, CHAHB, CH2), 1.12 (d, J¼6.9 Hz, 3H, CHCH3), 1.08 (d, J¼6.9 Hz,
3H, CHCH3), 0.87 (d, J¼6.9 Hz, 3H, CHCH3), 0.86 (d, J¼6.9 Hz, 3H,
3.31. (2R,4R,6E,8R,9R,10R)-9-(Benzyloxy)-10-[(4S)-2,2-
dimethyl-1,3-dioxan-4-yl]-2,4,8-trimethyl-6-undecen-1-ol
(38)
To a stirred solution of silyl ether 37 (400 mg, 0.59 mmol) in dry
THF (5 mL) at 0 ꢀC was added drop wise a solution of TBAF (0.9 mL,
0.9 mmol) in THF. The resulting mixture was allowed to stir for 12 h
at rt upon completion, the mixture was then quenched with water
and extracted with ethyl acetate (3ꢂ10 mL). The combined organic
CHCH3); 13C NMR (75 MHz, CDCl3):
d 212.9, 138.9, 134.2, 128.2,
127.8, 127.5, 127.3, 98.0, 84.1, 73.7, 69.3, 59.9, 44.9, 40.6, 39.9, 39.8,
39.4, 30.9, 29.9, 29.6, 27.0, 19.7, 19.3, 19.1, 17.0, 11.0; MS (ESI): m/z

J.S. Yadav et al. / Tetrahedron 71 (2015) 7539e7549
7549
467 [MþNa]þ; HRMS: calcd for C28H44O4Na [MþNa]þ 467.3137,
Supplementary data
found: 467.3127.
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.08.011.
3.33. Ethyl (4R,6S,8S,9Z,12R,14R,16E,18R,19R,20R)-19-(benzy-
loxy)-20-[(4S)-2,2-dimethyl-1,3-dioxan-4-yl]-9-hydroxy-
4,6,8,12,14,18-hexamethyl-11-oxo-9,16-henicosadienoate (3)
References and notes
To a stirred solution of IBX (68 mg, 0.24 mmol) in DMSO (1 mL)
at rt, was added drop wise a solution of alcohol 6 (40 mg,
0.16 mmol) in CH2Cl2 (5 mL). The resulting mixture was stirred for
2 h at the same temperature. The solid was filtered through a pad of
Celite and washed with ether. The filtrate was washed with satu-
rated aqueous NaHCO3 solution, water, brine and dried over
Na2SO4. The solvent was removed under reduced pressure to fur-
nish the crude aldehyde, which was used for the aldol reaction
without further purification.
To a solution of azeotropically dried methyl ketone 39 (60 mg,
0.13 mmol) in dry THF (2 mL) at ꢁ78 ꢀC was added KHMDS
(0.26 mL, 0.5M solution in toluene, 0.13 mmol) and the mixture was
stirred for 30 min. To this, a solution of the above aldehyde
(azeotropically dried with benzene) in dry THF (1.5 mL) was added
via cannula and the resulting mixture was stirred for 4 h at the
same temperature. The reaction was quenched with NH4Cl solution
and the aqueous phase was extracted with EtOAc (3ꢂ5 mL). The
combined organic layers were washed with brine, dried over an-
hydrous Na2SO4, and concentrated in vacuo. The crude product was
purified by flash chromatography on silica gel (10%, EtOAc/hexanes)
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S.; Yadav, N. N.; Chary, D. N.; Ghamdi, A. K. Tetrahedron Lett. 2012, 53, 5952; (d)
Yadav, J. S.; Yadav, N. N. RSC Adv. 2013, 3, 4024; (e) Yadav, J. S.; Chary, D. N.;
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dron Asymmentry 2004, 1745.
to give the isomeric
oxidation reaction without further purification.
To a stirred solution of above -hydroxy ketone and Celite
b-hydroxy ketone, which was used for the PDC
b
(75 mg) in dry CH2Cl2 (3 mL) at 0 ꢀC was added PDC (188 mg,
0.5 mmol). After stirring for 10 min it was brought to room tem-
perature and the stirring was continued for another 12 h. The sol-
vent was removed under reduced pressure and the residue was
purified by silica gel column chromatography (5%, EtOAc/hexane)
to afford the pure diketo compound 3 (64 mg, 70% yield for three
25
steps) as pale yellow liquid. Rf¼0.15 (5% EtOAc/hexane); [
(c 0.7, CHCl3); IR (neat):
1097, 970, 757 cmꢁ1; 1H NMR (300 MHz, CDCl3):
a]
ꢁ7.9
D
n
2923, 2853, 1736, 1628, 1461, 1375, 1174,
7.27e7.41 (m, 5H,
d
ArH), 5.58 (dd, J¼8.3, 15.1 Hz, 1H, olefinic), 5.46 (s, 1H, olefinic),
5.27e5.42 (m, 1H, olefinic), 4.56 (ABq, J¼11.3 Hz, 2H, CH2Ph), 4.15
(q, J¼7.5 Hz, 2H, CH2CH3), 3.99e4.07 (m, 1H, OCH), 3.68e3.89 (m,
2H, OCH, OCHAHB), 3.28 (dd, J¼3.7, 6.7 Hz, 1H, OCHAHB), 1.77e2.55
(m, 7H, 2ꢂCH2, 3ꢂCHCH3), 1.41 (s, 3H, CCH3), 1.36 (s, 3H, CCH3), 1.26
(t, J¼7.5 Hz, 3H, CH2CH3), 1.13 (d, J¼6.7 Hz, 3H, CHCH3), 1.12 (d,
J¼6.7 Hz, 3H, CHCH3),1.01e1.76 (m,14H, alkyl chain), 0.78e0.93 (m,
12. Martin, T.; Rodriguez, C. M.; Martin, V. S. Tetrahedron: Asymmentry 1995, 1151.
13. Toyota, M.; Hirota, M.; Nishikawa, Y.; Fukumoto, K.; Ihara, M. J. Org. Chem. 1998,
63, 5895.
14. Colvin, E. W.; Robertson, A. D.; Wakharkar, S. J. Chem. Soc., Chem. Commun. 1983,
312.
15. Phillips, K. D.; Zemlicka, J.; Horowitz, J. P. Carbohydr. Res. 1973, 30, 281.
16. Satoh, T.; Nanba, K.; Suzuki, S. Chem. Pharm. Bull. 1971, 19, 817.
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Kocienski, P. J. Angew. Chem., Int. Ed. 2009, 48, 5022.
15H, alkyl chain); 13C NMR (75 MHz, CDCl3):
d 198.8, 198.3, 173.9,
139.1, 134.3, 128.2, 127.9, 127.6, 127.3, 98.1, 97.1, 84.2, 73.7, 69.4, 60.1,
60.0, 44.3, 44.1, 42.4, 41.0, 40.6, 40.3, 40.1, 39.4, 30.9, 30.4, 29.9, 27.9,
27.2, 26.6, 22.6, 19.5, 19.4, 19.3, 19.2, 18.9, 18.8, 18.3, 14.2, 11.1; MS
(ESI): m/z 707 [MþNa]þ; HRMS: calcd for C42H68O7Na [MþNa]þ
707.4862, found: 707.4872.
18. Gao, Y.; Nan, F.; Xu, X. Tetrahedron Lett. 2000, 41, 4811.
19. (a) Bucher, B.; Curran, D. P. Tetrahedron Lett. 2000, 41, 9617; (b) Martinelli, M. J.;
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Lett. 1999, 1, 447.
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Acknowledgements
R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26.
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N. N. Y thanks CSIR, New Delhi for the financial support in the
form of a fellowship.