Stereoselective synthesis of the C1-C8 subunit of peloruside A

Article abstract of DOI:10.1016/j.tet.2013.04.059

Two routes to the C1-C8 subunit of peloruside A are disclosed. The first route involving 14 steps exploits Krische's allylation, substrate controlled 1,3-asymmetric induction during bromohydrin formation from an alkene utilizing an intramolecular sulfinyl

Full text of DOI:10.1016/j.tet.2013.04.059

Tetrahedron 69 (2013) 4835e4844
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Stereoselective synthesis of the C1eC8 subunit of peloruside A
*
Sadagopan Raghavan , V. Vinoth Kumar
Division of Natural Product Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 March 2013
Received in revised form 4 April 2013
Accepted 15 April 2013
Available online 18 April 2013
Two routes to the C1eC8 subunit of peloruside A are disclosed. The first route involving 14 steps exploits
Krische’s allylation, substrate controlled 1,3-asymmetric induction during bromohydrin formation from
an alkene utilizing an intramolecular sulfinyl group as a nucleophile and Pummerer reaction as key steps.
The second, shorter, scalable route (seven steps) exploits catalytic asymmetric reactions including Ja-
cobsen’s hydrolytic kinetic resolution of an epoxide and Sharpless’ asymmetric dihydroxylation reaction
as the key steps.
Keywords:
Peloruside A
Ó 2013 Elsevier Ltd. All rights reserved.
Catalytic asymmetric synthesis
1,3-Asymmetric induction
Pummerer reaction
Sulfinyl group
1. Introduction
2. Results/discussion
Peloruside A 1, is a marine metabolite isolated from Mycale
hentscheli by Northcote and co-workers.1 Peloruside A is an ar-
chitecturally complex 16-membered macrolide. It possesses
potent taxol-like microtubule stabilizing activity,2 although
binding to tubulin at a site different from taxol.3 NMR studies
helped in establishing the relative stereochemistry of the ten
stereogenic centers and the absolute stereochemistry became
known with De Brabander’s synthesis.4 The structural com-
plexity, interesting biological activity, and scarcity in nature
have led to a considerable interest in peloruside from the syn-
thesis community.5e10
We envisioned the synthesis of (þ)-peloruside A 1, Scheme 1, by
coupling C1eC8 alkyne subunit 2 with the C9eC19 aldehyde sub-
unit 3,11 followed sequentially by, the oxidation of the ensuing
epimeric propargylic alcohols to a ketone, partial reduction of the
alkyne to a cis-alkene, diastereoselective dihydroxylation, ketal
formation, and lastly macrolactonization. The alkyne 2 was envis-
aged to be obtained from triflate 4 and TMS-acetylene. Triflate 4
was proposed to be obtained by stereoselective oxidative hetero-
functionalization of alkene 5 by taking advantage of its C5 stereo-
center. Compound 5 in turn can be traced to terminal alkene 6 and
cis-1,4-butene diol 7, Scheme 1.
The synthesis began with the oxidation of phenylthio ethanol 8
with IBX12 to phenylthio acetaldehyde 9 that on exposure to allyl-
tributyl tin following Keck’s protocol13 afforded homoallyl alcohol 6
(89.5% ee, 63% yield).14 Subsequently, alcohol 6 was obtained di-
rectly from phenylthio ethanol 8 and allyl acetate in a single step by
adopting Krische’s protocol15 in the presence catalyst 10, prepared
in situ using 5 mol % of (S)-BINAP, 3-nitrobenzoic acid, and 2.5 mol %
of [Ir(cod)Cl]2, in good yield, and selectivity (93.5% ee, 82% yield).16
Cross metathesis of 6 with an excess of cis-butene diol 7 using
Grubbs’ catalyst 11, furnished diol 12.17 Protection of diol 12 with
TBDPSeCl in the presence of imidazole furnished silyl ether 13
(P¼TBBPS). Selective oxidation of the sulfanyl group in 13 using
mCPBA at low temperature yielded an equimolar, inseparable, epi-
meric mixture of sulfoxide 5. Oxidative heterofunctionalization of
the alkene in 5 using N-bromosuccinimide as the electrophile and
the sulfinyl group as the intramolecular nucleophile furnished
bromohydrin 14 via substrate controlled asymmetric induction in-
volving putative transition states I and II, Scheme 2.18
It was intended to introduce the oxygen functionality at C2 by
intermolecular displacement of bromide by an oxygen nucleophile.
Toward this end, the carbinol in 14 was protected as its MOM-ether
15 employing standard conditions. Attempted displacement19 of
the bromide in 15 by an acetate using excess KOAc in DMF at 90 ꢀC
for 48 h furnished unreacted starting material while, treatment
with an excess of NaNO2 in DMSO at 100 ꢀC for 24 h afforded
a complex mixture of products. In parallel, the MOM-ether 15 was
subjected to Pummerer rearrangement20 by treatment with TFAA
* Corresponding author. E-mail addresses: sraghavan@iict.res.in, purush101@
yahoo.com (S. Raghavan).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.059

4836
S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
OP
O
OMe
OP
1
3
PO
18
3
1
O
OP OMe OP
O
5
OP
PO
15
18
OH
5
O
HO
11
9
15
13
H
HO
10
HO
13
7
OMe
8
3
MeO
2
OH
1
OH
3
5
S
OP
Ph
3
1
1
6
3
PO
O
S
PO
5
5
OP
OTf
PO
Ph
1
PO
HO
OH
5
4
7
P = Protecting group
Scheme 1. Retrosynthetic disconnection of peloruside A.
Scheme 2. Stereoselective synthesis of bromohydrin 14.
in the presence of triethylamine and the resulting intermediate 16
without isolation was hydrolyzed to yield an aldehyde that was
reduced in the same pot with NaBH4 to yield alcohol 17. Treatment
with triflic anhydride and 2,6-lutidine expecting to obtain triflate
18, instead yielded tetrahydrofuran 19 as the sole product by
intramolecular etherification, Scheme 3.
It was apparent from the formation of 19 that a nucleophilic
ether type protecting group at C3 was not suitable for the eventual
introduction of the alkyne moiety. The bromohydrin 14 was
therefore reacted with benzoic anhydride to afford benzoate 20,
Scheme 3. Again, attempted displacement of bromide in 20 with
KOAc in DMF at 90 ꢀC afforded unreacted starting material while,

S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
4837
a) MOM-Cl, iPr2NEt,
TBAI, CH2Cl2, 82%
or
OTBDPS
OP
KOAc,
DMF
Rec S M
O
S
14
Ph
OTBDPS
b) (PhCO)2O, Et3N
CH2Cl2, cat DMAP
83%
Br
NaNO2,
DMSO
Complex
mixture
15, P = MOM, via a
20
, P = OCOPh via b
TBDPSO
OMOM
TBDPSO
HO
OMOM
aq NaHCO3
NaBH4, 75%
TFAA, Et3N
CH2Cl2
S
15
Ph
OTBDPS
OTBDPS
CF3COO
16
17
Br
Br
TBDPSO
TfO
OMOM
O
Tf2O, 2,6-lutidine
CH2Cl2
TBDPSO
OTBDPS
OTBDPS
82%
18 Br
Not obtained
19 Br
Scheme 3. Attempted intermolecular displacement of bromide by an oxygen nucleophile.
attempted reaction with NaNO2 in DMSO at 100 ꢀC furnished
a complex mixture of products. Having failed to introduce an ox-
ygen functionality at C2 via an intermolecular reaction it was
thought fit to attempt an intramolecular displacement.
Proceeding, the MOM-ether 15 was subjected to selective
deprotection of the primary silyl ether using TBAF under buffered
conditions to afford bromohydrin 21. Epoxide formation proceeded
cleanly on treatment of 21 with anhydrous K2CO3 in a mixture of
acetonitrile and ethanol to yield 22. Treatment of 22 with 4-
hydrolysis of the intermediate and in situ reduction of the result-
ing aldehyde to afford alcohol 25. TBAF promoted deprotection of
the silyl ether yielded diol 26 that on treatment with an excess of
NaH and an equivalent of N-tosyl imidazole22 yielded epoxide 27.
Subjecting epoxide 27 to reaction with TMS-acetylide following
Yamaguchi’s protocol23 furnished alcohol 28 by a concomitant
desilylation, probably during work up. Protection of the alcohol as
its TBS ether using standard conditions yielded silyl ether 29,
Scheme 4, corresponding to the C1eC8 subunit of peloruside A.
Scheme 4. Synthesis of the C1eC8 subunit of peloruside A.
methoxybenzyl alcohol in the presence of catalytic amounts of
Sc(OTf)321 furnished tetrol derivative 23 via regioselective epoxide
opening. The hydroxy group in 23 was protected following the
standard protocol, to yield the MOM-ether 24. It only remained to
introduce the alkynyl residue. Toward this end, the compound 24
was subjected to Pummerer rearrangement followed by one-pot
The C1eC8 subunit was thus synthesized in 14 steps beginning
from phenylthio ethanol in 3.7% overall yield. Although the subunit
was successfully synthesized the route was not suitable for bringing
more material due to its length. We therefore sought an alternate
route to the C1eC8 fragment and we describe below its synthesis
by a shorter seven-step sequence, Scheme 5. (S)-Epichlorohydrin

4838
S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
Scheme 5. Alternate, short synthesis of the C1eC8 subunit.
30, obtained by hydrolytic kinetic resolution,24 was subjected to
BF3$OEt2 promoted opening by the lithio alkene, prepared from
iodo alkene 31, to furnish chlorohydrin 32.25 The iodo alkene 31
was prepared by hydrozirconation26 of propargyl ether 33 followed
by iodine quench. Protection of the carbinol as its pivalate 34 fol-
lowed by asymmetric dihydroxylation27 yielded diol 35 (>95% de,
74% yield). The hydroxy groups were protected employing usual
conditions as their MOM-ethers to afford compound 36. Exposure
of 36 to ethanolic KOH yielded epoxide 27 identical in all respects to
that obtained from diol 26. The epoxide 27 was elaborated to al-
kyne 29 as detailed earlier. The overall yield of 29 by the second
route was 22%.
(Et2O) were dried over CaH2 and distilled prior to use. 4 A molecular
ꢀ
sieves were flame dried and then cooled under high vacuum prior
to use. All reactions were monitored by E. Merck analytical thin-
layer chromatography (TLC) plates and analyzed with 254 nm UV
light and/or anisaldehydeesulfuric acid or potassium permanga-
nate or PMA treatment. Silica gel for column chromatography was
purchased from Acme (Silica Gel 60e120, 100e200 mesh). All 1H
and 13C NMR spectra were recorded in CDCl3 using Gemini 200,
Avance 300, Inova 400, Inova 500, Bruker 600 spectrometers.
Chemical shifts (
to residual CHCl3 as an internal reference (1H:
77.00 ppm). Coupling constants (J) are reported in Hertz (Hz).
d
) are reported in parts per million (ppm) relative
d
7.26 ppm, 13C:
d
Peak multiplicity is indicated as follows: s (singlet), d (doublet), t
(triplet), q (quartet), and m (multiplet). Enantiomeric excess were
recorded by Waters HPLC instrument. Mass spectra were recorded
using Waters Mass spectrometers. High resolution spectroscopies
(HRMS) were recorded using Applied Bio-Sciences HRMS spec-
trometer. All IR-spectra were recorded using Nexus 870-FT-IR
Thermo Nicolet spectrometer. The optical rotations were measured
on JASCO DIP-360 digital polarimeter.
3. Conclusion
In summary, we have disclosed two routes, one exploiting the
nucleophilic potential of the sulfinyl group for oxidative function-
alization of an alkene and the other utilizing the Sharpless asym-
metric dihydroxylation as key steps for introduction of the C2 and
C3 stereogenic centers in the C1eC8 subunit of peloruside A. The
second route is shorter, scalable, and is desirable.
4.2. Compound 6 using Keck’s protocol
4. Experimental section
4.1. General information
To a solution of 2-iodoxy benzoic acid (3.7 g, 14.4 mmol) in
DMSO (14 mL) was added a solution of phenylthio ethanol 8 (1.85 g,
12 mmol) in CH2Cl2 (60 mL) at rt and the mixture was stirred for
4 h. The precipitated solid was filtered, washed with CH2Cl2, and
the combined filtrates were washed with water, brine, dried over
anhydrous Na2SO4, and concentrated under reduced pressure. Pu-
rification of the crude residue via flash chromatography on silica gel
using 10% EtOAc/hexane (v/v) as the eluent afforded aldehyde 9
(1.64 g, 10.8 mmol) in 90% yield as a light yellow oil. TLC Rf¼0.40
All materials were used as received from a commercial supplier
without further purification. All anhydrous reactions were per-
formed using oven-dried or flame dried glassware, which was then
cooled under nitrogen gas. Tetrahydrofuran (THF), toluene was
distilled over Na/Ph2CO under nitrogen atmosphere. Dichloro-
methane (CH2Cl2), hexane, acetonitrile, dimethylsulfoxide, dime-
thylformamide, triethylamine (TEA), 2,6-lutidine, and diethyl ether
(10% EtOAc/hexanes). 1H NMR (300 MHz, CDCl3):
d
9.49 (t, J¼3.2 Hz,

S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
4839
1H), 7.47e7.15 (m, 5H), 3.53 (d, J¼3.2 Hz, 2H). A mixture of (S)-
3072, 2923, 1438, 1026, 917, 740, 691 cmꢁ1
CDCl3): d 7.64e7.62 (m, 8H), 7.44e7.28 (m, 12H), 7.12e6.96 (m, 5H),
.
1H NMR (300 MHz,
BINOL (286 mg, 1 mmol), Ti(iOPr)4 (0.15 mL, 0.5 mmol), and 2 g of
ꢀ
activated 4 A molecular sieves in anhydrous CH2Cl2 (20 mL) was
5.70 (dt, J¼15.3, 6.8 Hz, 1H), 5.51 (dt, J¼15.3, 4.7 Hz, 1H), 4.12 (d,
J¼4.7 Hz, 2H), 4.02e3.92 (m, 1H), 2.95 (d, J¼6.8 Hz, 2H), 2.48e2.31
stirred at rt for 3 h. The red-brown reaction mixture was cooled to
ꢁ10 ꢀC and a solution of the above aldehyde 9 (1.52 g, 10 mmol) in
anhydrous CH2Cl2 (10 mL) was added followed by allyl tri-n-
butyltin (3.72 mL, 12 mmol). After 16 h of stirring at the same
temperature the reaction mixture was quenched with aq saturated
NaHCO3 and stirred for further 1 h. The mixture was filtered
through a pad of Celite and washed with dichloromethane. The
layers were separated and the aq layer was extracted with
dichloromethane (3ꢂ50 mL). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4, and evaporated
under reduced pressure to provide the crude material, which was
purified by column chromatography using hexanes/EtOAc (9:1, v/v)
(m, 2H), 1.10 (s, 9H), 1.06 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 136.5,
135.8, 135.5, 133.9, 133.7, 132.3, 129.6, 129.5, 128.6, 127.6, 125.4,
125.3, 71.5, 64.2, 38.7, 37.9, 26.9, 26.8, 19.3, 19.2. MS (ESI) 723
[MþNa]þ. HRMS (ESI) m/z calcd for C44H52O2Si2SNa 723.31188;
found 723.31262.
4.6. Compound 5
To a solution of 13 (2.8 g, 4 mmol) in anhydrous CH2Cl2 (20 mL)
cooled at ꢁ23 ꢀC was added mCPBA (920 mg, 4 mmol) portionwise
over a 2 h period. After 1 h of further stirring, the reaction was
quenched with aq saturated sodium sulfite solution. The layers
were separated and aq layer was extracted with DCM (3ꢂ50 mL).
The combined organic layers were washed with water, aq saturated
NaHCO3, water, brine, dried over Na2SO4, and the solvent evapo-
rated. The crude product was purified by column chromatography
using hexanes/EtOAc (8:2, v/v) to provide 5 (2.44 g, 3.4 mmol) in
to afford 6 (1.22 g, 6.3 mmol) in 63% yield as a colorless oil. TLC
35
Rf¼0.25 (15% EtOAc/hexanes). [
a
]
D
¼þ18.5 (c 1, CHCl3). IR (KBr):
3471, 3072, 2923,1438,1026, 917, 740, 691 cmꢁ1. 1H NMR (300 MHz,
CDCl3): 7.38e7.12 (m, 5H), 5.88e5.72 (m, 1H), 5.13e5.06 (m, 2H),
3.74e3.66 (m, 1H), 3.09 (dd, J¼13.5, 4.5 Hz, 1H), 2.85 (dd, J¼13.5,
d
8.3 Hz, 1H), 2.39e2.23 (m, 2H). 13C NMR (75 MHz, CDCl3):
d 133.8,
129.7, 128.9, 126.3, 118.0, 68.7, 41.0, 40.2. MS (ESI) 233 [MþNa]þ.
HRMS (ESI) m/z calcd for C11H14O2NaS 233.06067; found
233.06098.
85% yield as an inseparable mixture of epimers in equimolar
35
amount. TLC Rf¼0.18 (20% EtOAc/hexanes). [
a
]
¼þ10.7 (c 1, CHCl3).
D
IR (KBr): 3072, 2923, 1438, 1026, 917, 740, 691 cmꢁ1
.
1H NMR
(300 MHz, CDCl3): 7.82e7.26 (m, 50H), 5.75e5.32 (m, 4H),
d
4.3. Compound 6 via Krische’s protocol
4.46e4.02 (m, 6H), 3.00e2.73 (m, 4H), 2.26e2.18 (m, 4H), 1.18e1.00
(m, 36H). MS (ESI) 717 [MþH]þ. HRMS (ESI) m/z calcd for
C44H53O3Si2S 717.3257; found 717.3230.
To a sealed tube charged with phenylthio ethanol 8 (760 mg,
5 mmol), [Ir(cod)Cl]2 (85 mg, 0.125 mmol), (S)-BINAP (155 mg,
0.25 mmol), Cs2CO3 (325.0 mg, 1 mmol), m-nitrobenzoic acid
(82.5 mg, 0.5 mmol) was added anhydrous THF (25.0 mL) followed
by allyl acetate (5.5 mL, 50 mmol). The reaction mixture was stirred
at 110 ꢀC for 30 h. The reaction mixture was allowed to cool to rt
and filtered through a small pad of silica gel. The organic layer was
evaporated under reduced pressure. The crude residue was purified
via column chromatography using hexanes/EtOAc (9:1, v/v) to
furnish 6 (800 mg, 4.1 mmol) in 82% yield as a colorless oil.
4.7. Compound 14
To a solution of sulfoxide 5 (2.15 g, 3 mmol) in anhydrous tol-
uene (12 mL) was added water (81
mL, 4.5 mmol) followed by
freshly recrystallized N-bromosuccinimide (0.64 g, 3.6 mmol)
portionwise over 30 min and the reaction mixture was stirred
further for 1 h at rt. The reaction was quenched by the addition of
an aq saturated NaHCO3 solution. The layers were separated and
the aq layer was extracted with ethylacetate (4ꢂ30 mL). The
combined organic layers were washed with brine and dried over
anhydrous Na2SO4. The organic layer was evaporated under re-
duced pressure to afford the crude product that was purified by
column chromatography using hexanes/EtOAc (8:2, v/v) as the el-
uent to afford bromohydrin 14 (1.8 g, 2.25 mmol) in 75% yield as
a viscous oil. The bulk sample was carried ahead to the next step
without separating epimeric sulfoxides. However, for character-
ization purposes a small sample was separated into individual
4.4. Compound 12
To a solution of 6 (1.55 g, 8 mmol) and cis-butene diol 7 (2.1 g,
24 mmol) in anhydrous CH2Cl2 (24 mL) was added Grubbs’ II gen-
eration catalyst 11 (680 mg, 0.8 mmol) and stirred at reflux tem-
perature. After 24 h, a second portion of catalyst 11 (680 mg,
0.8 mmol) was added and stirring continued for a further 24 h. The
volatiles were evaporated and the crude product was purified by
column chromatography using hexanes/EtOAc (6:4, v/v) to afford
epimeric sulfoxides. Less polar isomer: TLC Rf¼0.10 (20% EtOAc/
36
12 (1.1 g, 4.9 mmol) in 61% yield as a solid. Mp: 79 ꢀC. TLC Rf¼0.10
hexanes). [
a
]
D
¼ꢁ8.2 (c 1, CHCl3). IR (KBr): 3389, 3068, 2931, 2890,
35
(50% EtOAc/hexanes). [
a
]
D
¼þ25.0 (c 1, CHCl3). IR (KBr): 3471, 3072,
2857, 1427, 1109, 1024, 821, 743, 702, 609, 504 cmꢁ1
.
1H NMR
2923, 1438, 1026, 917, 740, 691 cmꢁ1
7.38e7.20 (m, 5H), 5.68e5.58 (m, 2H), 4.10e4.02 (m, 2H),
3.84e3.60 (m, 1H), 3.25 (dd, J¼13.6, 4.5 Hz, 1H), 2.82 (dd, J¼13.6,
8.3 Hz, 1H), 2.34e2.16 (m, 2H). 13C NMR (75 MHz, CDCl3):
135.3,
.
1H NMR (300 MHz, CDCl3):
(300 MHz, CDCl3): 7.76e7.58 (m, 8H), 7.52e7.2 (m, 17H),
d
d
4.36e4.20 (m, 2H), 4.05e3.82 (m, 3H), 3.19 (dd, J¼13.4, 7.9 Hz, 1H),
2.93 (dd, J¼13.4, 3.2 Hz, 1H), 2.38e2.20 (m, 1H), 2.12e1.96 (m, 1H),
d
1.10 (s, 9H), 0.99 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 142.6, 135.7,
132.6, 129.9, 129.0, 127.7, 126.5, 68.9, 63.1, 41.1, 38.7. MS (ESI) 247
[MþNa]þ. HRMS (ESI) m/z calcd for C12H16O2NaS 247.0768; found
247.0775.
135.6,135.4,133.2,132.8,130.5,129.8,129.7,128.9,127.6,123.6, 68.6,
66.6, 65.1, 60.9, 59.7, 39.4, 26.8, 26.7, 19.1. MS (ESI) 813 [MþH]þ.
HRMS (ESI) m/z calcd for C44H54O4Si2SBr 813.2464; found
813.2452. More polar isomer: TLC Rf¼0.09 (20% EtOAc/hexanes).
35
4.5. Compound 13
[a
]
¼þ27.2 (c 1, CHCl3). IR (KBr): 3384, 3068, 2932, 2890, 2857,
D
1427, 1387, 1109, 821, 743, 702, 609, 503 cmꢁ1. 1H NMR (300 MHz,
CDCl3): 7.78e7.62 (m, 8H), 7.46e7.28 (m, 17H), 4.67e4.57 (m, 1H),
To a solution of 12 (1.01 g, 4.5 mmol) and imidazole (1.28 g,
19.8 mmol) in anhydrous CH2Cl2 (22.5 mL) cooled at 0 ꢀC was
added TBDPSeCl (2.58 mL, 9.9 mmol). After 6 h the solvent was
evaporated to provide the crude compound, which was purified by
column chromatography using hexanes/EtOAc (9:1, v/v) to provide
pure 13 (2.96 g, 4.24 mmol) in 94% yield as a viscous oil. TLC
Rf¼0.26 (20% EtOAc/hexanes). [
d
4.20e4.10 (m, 1H), 3.98e3.76 (m, 3H), 3.23 (dd, J¼13.2, 5.8 Hz, 1H),
2.71 (dd, J¼13.2, 7.1 Hz, 1H), 2.05e1.80 (m, 2H), 1.10 (s, 9H), 1.01 (s,
9H). 13C NMR (75 MHz, CDCl3):
d 143.7, 135.9, 135.7, 135.4, 133.1,
132.7, 130.8, 129.9, 129.7, 129.1, 127.7, 123.6, 68.0, 66.8, 64.8, 64.6,
60.0, 40.4, 26.9, 26.6,19.3,19.1. MS (ESI) 813 [MþH]þ. HRMS (ESI) m/
z calcd for C44H54O4Si2SBr 813.2464; found 813.2473.
35
a]
¼ꢁ4.7 (c 1, CHCl3). IR (KBr):
D

4840
S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
4.8. Compound 15
4.10. Compound 19
To a solution of bromohydrin 14 (1.25 g, 1.5 mmol) in anhy-
drous CH2Cl2 (6 mL) cooled at 0 ꢀC was added diisopropylethyl-
amine (0.52 mL, 3 mmol), TBAI (58 mg, 0.15 mmol) followed by
Mom-Cl (0.17 mL, 2.25 mmol). After 16 h of stirring, the reaction
mixture was quenched by adding aq saturated NaHCO3. The layers
were separated and the aq layer was extracted with dichloro-
methane (3ꢂ10 mL). The combined organic layers were washed
with water, brine, dried over Na2SO4, and evaporated under re-
duced pressure. The resulting crude product was purified by col-
umn chromatography using hexanes/EtOAc (8:2, v/v) as the eluent
to furnish pure 15 (1.06 g, 1.22 mmol) in 82% yield as a viscous oil.
While the bulk sample was taken ahead without separating the
individual sulfoxides for characterization purposes a small sample
To a solution of 17 (75 mg, 0.1 mmol) in anhydrous CH2Cl2
(1 mL) cooled at ꢁ40 ꢀC was added anhydrous 2,6-lutidine (17
mL,
0.14 mmol) followed by triflic anhydride (20 mL, 0.12 mmol) and
the mixture stirred at the same temperature for 30 min. To the
reaction mixture anhydrous hexane (5 mL) was added and the
precipitated solid was filtered, washed with hexane, and the
combined filtrated were concentrated under reduced pressure. The
triflate was dissolved in anhydrous THF (1 mL). In another rb flask
containing a solution of TMS-acetylene (28 mL, 0.2 mmol) in an-
hydrous THF (2 mL) cooled at 0 ꢀC was added n-BuLi (0.08 mL,
0.2 mmol) and the mixture stirred for 30 min at the same tem-
perature. The resulting TMS-acetylide was added to the triflate
prepared above at ꢁ40 ꢀC dropwise and stirred further for 1 h at
same temperature. The reaction mixture was quenched by adding
aq NH4Cl solution at 0 ꢀC. The reaction mixture was diluted with
DCM and the layers were separated. The aq layer was extracted
with DCM (2ꢂ5 mL). The combined organic layers were washed
with water, brine, dried over anhydrous Na2SO4, and concentrated
to afford the crude product. Purification by column chromatogra-
phy using hexanes/EtOAc (9:1, v/v) as the eluent provided pure
was separated. Less polar isomer: TLC Rf¼0.16 (20% EtOAc/hex-
35
anes). [
a
]
¼ꢁ24.3 (c 1, CHCl3). IR (KBr): 3066, 2932, 2891, 2857,
D
1108, 1039, 821, 744, 701, 611, 503 cmꢁ1
.
1H NMR (600 MHz,
CDCl3):
d
7.73e7.60 (m, 8H), 7.48e7.25 (m, 17H), 4.37 (d, J¼7.2 Hz,
1H), 4.22e4.20 (m, 2H), 4.15e4.13 (m, 1H), 3.85e3.77 (m, 3H), 3.10
(s, 3H), 3.04 (dd, J¼13.2, 4.9 Hz, 1H), 2.84 (dd, J¼13.2, 5.2 Hz, 1H),
2.18e2.13 (m, 1H), 2.07e2.03 (m, 1H), 1.11 (s, 9H), 1.05 (s, 9H). 13C
NMR (75 MHz, CDCl3):
d
144.8, 135.8, 135.5, 133.2, 132.8, 130.6,
product 19 (57 mg, 0.082 mmol) in 82% yield as a viscous oil. TLC
34
129.8, 128.9, 127.7, 123.9, 96.5, 75.2, 66.7, 64.7, 64.6, 58.0, 55.8,
Rf¼0.20 (15% EtOAc/hexanes). [
a
]
¼ꢁ2.2 (c 1, CHCl3). IR (KBr)
D
38.1, 26.9, 26.7, 19.2, 19.1. MS (ESI) 857 [MþH]þ. HRMS (ESI) m/z
3069, 2933, 2858, 1428, 1262, 1108, 1005, 822, 704, 613, 505 cmꢁ1
.
calcd for C46H58O5Si2SBr 857.2726; found 857.2762. More polar
1H NMR (500 MHz, CDCl3):
d
7.73e7.62 (m, 8H), 7.47e7.36 (m,
34
isomer: TLC Rf¼0.15 (20% EtOAc/hexanes). [
a
]
¼þ19.2 (c 1, CHCl3).
12H), 4.61e4.55 (m, 1H), 4.47e4.43 (m, 1H), 4.18e4.12 (m, 1H), 3.95
(dd, J¼10.9, 4.9 Hz, 1H), 3.88 (dd, J¼10.9, 5.9 Hz, 1H), 3.80e3.74 (m,
2H), 2.11e2.04 (m, 1H), 1.88e1.80 (m, 1H), 1.08 (s, 9H), 1.07 (s, 9H).
D
IR (KBr): 3067, 2931, 2892, 2857, 1108, 1041, 821, 744, 702, 611,
504 cmꢁ1 1H NMR (500 MHz, CDCl3):
.
d
7.65e7.53 (m, 8H),
7.38e7.12 (m, 17H), 4.31 (d, J¼6.9 Hz, 1H), 4.15e4.06 (m, 3H),
3.78e3.69 (m, 3H), 3.02 (s, 3H), 2.95 (dd, J¼12.7, 5.0 Hz, 1H), 2.81
(dd, J¼12.7, 4.1 Hz, 1H), 2.09e2.05 (m, 1H), 2.01e1.96 (m, 1H), 1.04
13C NMR (75 MHz, CDCl3):
d 135.6, 133.0, 129.7, 127.7, 77.9, 76.1,
73.6, 65.5, 58.3, 39.3, 26.8, 26.7, 19.3, 19.0. MS (ESI) 711 [MþNa]þ.
HRMS (ESI) m/z calcd for C38H47O3BrNaSi2 709.21393; found
709.21568.
(s, 9H), 0.99 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 145.0, 135.5,
135.4, 133.4, 132.9, 130.6, 129.1, 127.7, 123.6, 96.3, 73.9, 66.6, 65.9,
64.7, 57.1, 56.2, 39.1, 27.0, 26.7, 19.5, 19.1. MS (ESI) 857 [MþH]þ.
HRMS (ESI) m/z calcd for C46H58O5Si2SBr 857.2726; found
857.2732.
4.11. Compound 20
To a solution of 14 (203 mg, 0.25 mmol) in anhydrous CH2Cl2
(1 mL) cooled at 0 ꢀC was added triethylamine (70
mL, 0.5 mmol),
4.9. Compound 17
catalytic amount of DMAP followed by benzoic anhydride (68 mg,
0.3 mmol), and the mixture stirred for 16 h at ambient temperature.
The reaction mixture was diluted with dichloromethane (5 mL),
successively washed with water, brine, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The resulting
crude product was purified by column chromatography using
hexanes/EtOAc (9:1, v/v) as the eluent to afford product 20 (192 mg,
To a solution of sulfoxide 15 (171 mg, 0.2 mmol) in anhydrous
CH2Cl2 (1 mL) cooled at 0 ꢀC was added Et3N (56
m
L, 0.4 mmol)
followed by TFAA (57
mL, 0.4 mmol). After 30 min of stirring,
when TLC examination revealed consumption of starting mate-
rial, aq saturated NaHCO3 (1 mL) was added followed by solid
NaBH4 (37 mg, 1.0 mmol) portionwise. After 30 min the reaction
mixture was diluted with dichloromethane (5 mL) and filtered
through a pad of Celite. The Celite pad was washed with
dichloromethane. The layers were separated and the aq layer was
extracted with dichloromethane (2ꢂ20 mL). The combined or-
ganic layers were washed with water, brine, dried over Na2SO4,
and evaporated under reduced pressure to afford the crude
product, which was purified by column chromatography using
hexanes/EtOAc (8:2, v/v) as the eluent to afford pure 17 (115 mg,
0.21 mmol) in 83% yield as a viscous oil. Less polar isomer: TLC
35
Rf¼0.13 (20% EtOAc/hexanes). [
a
]
¼ꢁ20.8 (c 1, CHCl3). IR (KBr)
D
2933, 2858, 1719, 1467, 1384, 1254, 1106, 1003, 833, 704, 613,
435 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
7.76e7.53 (m, 11H),
7.49e7.13 (m, 19H), 5.45 (td, J¼10.6, 3.0 Hz, 1H), 4.23e4.16 (m, 1H),
4.09e4.01 (m, 1H), 3.91e3.80 (m, 2H), 3.10 (dd, J¼13.6, 5.3 Hz, 1H),
2.81 (dd, J¼13.6, 4.5, 1H), 2.44e2.26 (m, 2H), 1.10 (s, 9H), 1.06 (s,
9H). 13C NMR (75 MHz, CDCl3):
d 165.1, 135.9, 135.8, 135.6, 133.1,
129.9, 129.8, 128.9, 128.2, 127.7, 123.9, 70.1, 66.6, 64.5, 63.7, 55.9,
0.15 mmol) in 75% yield as a viscous oil. TLC Rf¼0.15 (20% EtOAc/
37.6, 26.9, 26.7, 19.2, 19.1. MS (ESI) 939 [MþNa]þ. HRMS (ESI) m/z
35
hexanes). [
a
]
¼ꢁ9.2 (c 1, CHCl3). IR (KBr) 3541, 3302, 3030,
calcd for C51H58O5BrSSi2 917.27214; found 917.27496. More polar
D
35
2964, 2930, 1455, 1361, 1097, 1024, 740, 698, 636, 509 cmꢁ1
.
1H
isomer: TLC Rf¼0.12 (20% EtOAc/hexanes). [
a
]
D
¼þ15.7 (c 1, CHCl3).
NMR (300 MHz, CDCl3): 7.76e7.64 (m, 8H), 7.48e7.32 (m, 12H),
d
IR (KBr) 3063, 2935, 2859, 1720, 1463, 1426, 1269, 1108, 703,
4.61 (d, J¼7.0 Hz, 1H), 4.52 (d, J¼7.0 Hz, 1H), 4.22e4.18 (m, 1H),
4.08e3.96 (m, 2H), 3.85 (d, J¼6.0 Hz, 2H), 3.58 (dd, J¼11.9, 4.9 Hz,
1H), 3.52 (dd, J¼11.9, 3.9 Hz, 1H), 3.20 (s, 3H), 2.02e1.92 (m, 1H),
1.88e1.82 (m, 1H), 1.09 (s, 9H), 1.08 (s, 9H). 13C NMR (75 MHz,
502 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
7.76e7.23 (m, 30H),
5.46e5.39 (m, 1H), 4.55e4.42 (m, 2H), 3.76e3.63 (m, 2H), 3.03 (dd,
J¼12.8, 3.0 Hz, 1H), 2.81 (dd, J¼12.8, 9.0 Hz, 1H), 2.41e2.04 (m, 2H),
1.11 (s, 9H), 0.95 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 165.2, 136.0,
CDCl3):
d
135.8, 132.8, 129.8, 127.7, 96.6, 74.9, 70.9, 65.3, 64.8,
135.8, 135.4, 133.6, 132.6, 129.7, 129.1, 128.2, 127.7, 123.6, 69.6, 66.0,
65.5, 64.5, 55.3, 38.1, 26.9, 26.6, 19.5, 19.1. MS (ESI) 939 [MþNa]þ.
HRMS (ESI) m/z calcd for C51H58O5BrSSi2 917.27214; found
917.27475.
57.8, 56.0, 35.5, 27.0, 26.7, 19.2, 19.1. MS (ESI) 771 [MþNa]þ.
HRMS (ESI) m/z calcd for C40H53NaO5Si2Br 771.2512; found
771.2519.

S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
4841
4.12. Compound 21
4.14. Compound 23
To a solution of 15 (856 mg, 1 mmol) in anhydrous THF (3 mL)
To a solution of 22 (215 mg, 0.4 mmol) and p-methoxybenzyl
alcohol (116 mg, 0.48 mmol) in anhydrous CH2Cl2 cooled at 0 ꢀC
was added scandium triflate (10 mg, 0.02 mmol, 5 mol %) and the
mixture gradually allowed to equilibrate to rt over a 3 h period. The
volatiles were evaporated and the crude product was purified
by column chromatography using hexanes/EtOAc (7:3, v/v) as the
eluent to afford pure 23 (410 mg, 0.31 mmol) in 78% yield as a vis-
cooled at 0 ꢀC was added acetic acid (136
mL, 2.4 mmol) and TBAF
(2.4 mL, 1 M in THF, 2.4 mmol). The reaction mixture was stirred
gradually allowing it to warm to rt over 3 h. The solvent was
evaporated to provide the crude product, which was purified by
column chromatography using hexanes/EtOAc (7:3, v/v) as the
eluent to afford 21 (550 mg, 0.9 mmol) in 90% yield as a viscous oil.
35
Less polar isomer: TLC Rf¼0.12 (30% EtOAc/hexanes). [
a]
¼ꢁ29.8 (c
cous oil. Less polar isomer: TLC Rf¼0.11 (40% EtOAc/hexanes).
D
35
1, CHCl3). IR (KBr) 3390, 3067, 2932, 2891, 2857, 1428, 1106, 1033,
[a
]
¼ꢁ46.5 (c 1, CHCl3). IR (KBr) 3424, 3066, 2932, 1521, 1429,
D
916, 821, 744, 702, 610, 503 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
1389, 1247, 1106, 1032, 913, 745, 702, 504 cmꢁ1. 1H NMR (300 MHz,
CDCl3):
d
7.78e7.65 (m, 4H), 7.48e7.36 (m, 11H), 4.58 (d, J¼7.5 Hz, 1H),
d
7.74e7.60 (m, 4H), 7.47e7.31 (m, 11H), 7.21 (d, J¼9.1 Hz,
4.50e4.42 (m, 1H), 4.38 (d, J¼7.5 Hz, 1H), 4.32 (dt, J¼9.8, 3.0 Hz,
1H), 3.95 (dd, J¼11.3, 2.2 Hz, 1H), 3.90e3.84 (m, 2H), 3.13 (dd,
J¼14.3, 1.5 Hz, 1H), 2.99 (s, 3H), 2.58 (dd, J¼14.3, 4.5 Hz, 1H),
2.49e2.45 (m, 1H), 2.28e2.16 (m, 1H), 1.16 (s, 9H). 13C NMR
2H), 6.82 (d, J¼9.1 Hz, 2H), 4.44 (s, 2H), 4.40 (d, J¼6.8 Hz, 1H), 4.28
(d, J¼6.8 Hz,1H), 4.25e4.06 (m, 1H), 3.78 (s, 3H), 3.63e3.51 (m, 2H),
3.43e3.30 (m, 2H), 3.08 (s, 3H), 3.03 (dd, J¼13.6, 3.7 Hz, 1H), 2.74 (d,
J¼13.6, 5.2 Hz, 1H), 2.31 (ddd, J¼13.6, 9.0, 3.7 Hz, 1H), 1.90 (ddd,
J¼13.6, 9.0, 5.2 Hz, 1H), 1.10 (s, 9H). 13C NMR (75 MHz, CDCl3):
(75 MHz, CDCl3):
d 143.1, 135.6, 133.3, 132.7, 130.8, 129.8, 129.2,
127.7, 127.6, 123.4, 95.3, 73.3, 67.4, 63.7, 63.4, 57.1, 55.5, 35.7, 26.8,
d 159.1, 144.6, 135.8, 133.7, 132.8, 130.7, 129.8, 129.3, 127.6, 123.7,
19.1. MS (ESI) 641 [MþNa]þ. HRMS (ESI) m/z calcd for
113.6, 96.7, 76.5, 72.9, 71.5, 70.3, 66.1, 64.2, 55.7, 55.1, 38.3, 26.9,19.4.
C30H40O5SiSBr 619.1549; found 619.1551. More polar isomer: TLC
MS (ESI) 677 [MþH]þ. HRMS (ESI) m/z calcd for C38H49O7SiS
35
Rf¼0.11 (30% EtOAc/hexanes). [
a]
¼þ14.9 (c 1, CHCl3). IR (KBr)
677.2968; found 677.2968. More polar isomer: TLC Rf¼0.10 (40%
D
35
3392, 3068, 2931, 1452, 1428, 1387, 1147, 1107, 1033, 916, 744, 702,
EtOAc/hexanes). [
a]
¼þ37.1 (c 1, CHCl3). IR (KBr) 3429, 3067, 2858,
D
610, 503 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
7.78e7.64 (m, 4H),
1613, 1467, 1389, 1247, 1107, 1032, 821, 702, 611, 504 cmꢁ1. 1H NMR
(300 MHz, CDCl3): 7.78e7.66 (m, 4H), 7.53e7.32 (m, 11H), 7.12 (d,
7.52e7.28 (m, 11H), 4.54e4.28 (m, 3H), 4.07e4.02 (m, 1H),
3.84e3.54 (m, 3H), 3.26 (s, 3H), 3.01 (dd, J¼12.8, 4.5 Hz, 1H), 2.83
(dd, J¼12.8, 7.5 Hz, 1H), 2.04e1.91 (m, 2H), 1.11 (s, 9H). 13C NMR
d
J¼8.3 Hz, 2H), 6.79 (d, J¼8.3 Hz, 2H), 4.62e4.24 (m, 5H), 3.78 (s, 3H),
3.50e3.37 (m, 2H), 3.26e3.16 (m, 5H), 3.00 (d, J¼12.8, 3.0 Hz, 1H),
2.76 (dd, J¼12.8, 9.0 Hz, 1H),1.78e1.71 (m, 2H),1.10 (s, 9H). 13C NMR
(75 MHz, CDCl3):
d 144.0, 135.9, 135.8, 133.7, 132.8, 129.8, 129.7,
129.1, 127.6, 123.6, 96.5, 74.9, 66.1, 66.0, 63.2, 58.4, 56.1, 39.8, 26.9,
19.3. MS (ESI) 641 [MþNa]þ. HRMS (ESI) m/z calcd for
C30H40O5SiSBr 619.1549; found 619.1523.
(75 MHz, CDCl3): d 159.3, 144.4, 136.0, 135.9, 133.5, 133.3, 130.9,
129.5, 129.5, 127.9, 127.8, 124.1, 113.8, 96.8, 77.0, 73.1, 72.0, 70.7, 67.1,
64.2, 55.7, 55.3, 37.6, 27.1,19.3. MS (ESI) 677 [MþH]þ. HRMS (ESI) m/
z calcd for C38H49O7SiS 677.2968; found 677.2950.
4.13. Compound 22
4.15. Compound 24
To a solution of 22 (495 mg, 0.8 mmol) in the mixture of
ethanol (1.2 mL) and acetonitrile (1.2 mL) cooled at 0 ꢀC was
added K2CO3 (130 mg, 0.96 mmol). After 6 h, water was added and
the mixture extracted with ether (3ꢂ20 mL). The combined or-
ganic layers were washed with brine, dried over anhydrous
Na2SO4, and evaporated to provide the crude product, purification
by column chromatography using hexanes/EtOAc (7:3, v/v) as the
eluent afforded 22 (355 mg, 0.66 mmol) in 82% yield as a viscous
To a solution of 23 (170 mg, 0.25 mmol) in anhydrous CH2Cl2
i
(2 mL) cooled at 0 ꢀC was added Pr2NEt (90
m
L, 0.5 mmol) TBAI
(9 mg, 0.025 mmol) followed by Mom-Cl (25
mL, 0.38 mmol). After
7 h of stirring gradually allowing the mixture to warm to rt, the
reaction was quenched by adding saturated aq NaHCO3. The layers
were separated and the aq layer was extracted with dichloro-
methane (3ꢂ10 mL). The combined organic layers were succes-
sively washed with water, brine, dried over anhydrous Na2SO4, and
evaporated. The crude product was purified by column chroma-
tography using hexanes/EtOAc (8:2, v/v) as the eluent to afford pure
oil. Less polar isomer: TLC Rf¼0.11 (30% EtOAc/hexanes).
35
[
a
]
¼ꢁ16.4 (c 1, CHCl3). IR (KBr) 3065, 2932, 2893, 1470, 1394,
D
1148, 1105, 1029, 921, 821, 744, 702, 505 cmꢁ1. 1H NMR (400 MHz,
CDCl3):
1H), 4.47 (d, J¼6.6 Hz, 1H), 4.42e4.36 (m, 1H), 3.42e3.38 (m, 1H),
3.10 (s, 3H), 3.06 (dd, J¼13.2, 3.3 Hz, 1H), 2.88e2.82 (m, 1H), 2.80
(dd, J¼13.2, 5.5 Hz, 1H), 2.64 (t, J¼4.4 Hz, 1H), 2.46e2.45 (m, 1H),
2.31e2.26 (m, 1H), 2.10e2.04 (m, 1H), 1.12 (s, 9H). 13C NMR
d
7.72e7.61 (m, 4H), 7.44e7.36 (m, 11H), 4.74 (d, J¼6.6 Hz,
24 (150 mg, 0.21 mmol) in 84% yield as a viscous oil. Less polar
35
isomer: TLC Rf¼0.25 (30% EtOAc/hexanes). [
a]
¼ꢁ37.4 (c 1, CHCl3).
D
IR (KBr): 2927, 2856, 2100, 1727, 1617, 1465, 1368, 1254, 1217, 1102,
1032, 918, 803, 764, 506 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
7.74e7.60 (m, 4H), 7.47e7.31 (m, 11H), 7.23 (d, J¼9.1 Hz, 2H), 6.85
(75 MHz, CDCl3):
d
144.7, 135.8, 135.5, 133.4, 133.2, 130.7, 129.9,
(d, J¼9.1 Hz, 2H), 4.69e4.59 (m, 2H), 4.44e4.40 (m, 2H), 4.29e4.22
(m, 2H), 3.83e3.67 (m, 4H), 3.57e3.30 (m, 7H), 3.10 (dd, J¼12.8,
4.5 Hz, 1H), 3.01 (s, 3H), 2.87e2.80 (m, 1H), 2.26e1.91 (m, 2H), 1.10
129.1, 127.8, 127.7, 123.8, 95.5, 75.6, 67.0, 63.7, 55.6, 54.6, 43.5, 37.8,
26.9, 19.2. MS (ESI) 539 [MþH]þ. HRMS (ESI) m/z calcd for
C30H39O5SiS 539.2287; found 539.2308. More polar isomer: TLC
(s, 9H). 13C NMR (75 MHz, CDCl3):
d 159.1, 144.8, 136.0, 135.9, 133.4,
35
Rf¼0.10 (30% EtOAc/hexanes). [
a
]
¼þ29.2 (c 1, CHCl3). IR (KBr)
130.7, 129.9, 129.6, 129.2, 127.7, 127.6, 124.0, 113.6, 97.1, 96.9, 77.7,
75.0, 72.8, 69.4, 67.1, 64.5, 55.7, 55.6, 55.2, 37.4, 26.9, 19.2. MS (ESI)
721 [MþH]þ. HRMS (ESI) m/z calcd for C40H53O8SiS 721.3230; found
D
3066, 2932, 2857, 1638, 1428, 1396, 1105, 1029, 859, 744, 702,
505 cmꢁ1 1H NMR (400 MHz, CDCl3):
.
d
7.81e7.70 (m, 4H),
7.56e7.37 (m, 11H), 4.68 (d, J¼6.6 Hz, 1H), 4.60e4.55 (m, 1H), 4.48
(d, J¼6.6 Hz, 1H), 3.30e3.25 (m, 1H), 3.22 (s, 3H), 3.07 (dd, J¼12.1,
3.3 Hz, 1H), 2.94 (dd, J¼12.1, 8.8 Hz, 1H), 2.72e2.68 (m, 1H), 2.46 (t,
J¼4.4 Hz, 1H), 2.08e2.07 (m, 1H), 1.85e1.80 (m, 1H), 1.73e1.68 (m,
721.3197. More polar isomer: TLC Rf¼0.24 (30% EtOAc/hexanes).
35
[a
]
¼þ34.2 (c 1, CHCl3). IR (KBr): 2930, 2857, 1727, 1521, 1466,
D
1369, 1102, 1032, 702, 611, 407 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
7.81e7.61 (m, 4H), 7.53e7.34 (m, 11H), 7.12 (d, J¼9.1 Hz, 2H), 6.79
1H), 1.12 (s, 9H). 13C NMR (75 MHz, CDCl3):
d
144.7, 135.8, 135.1,
(d, J¼9.1 Hz, 2H), 4.65e4.27 (m, 6H), 3.80e3.74 (m, 4H), 3.58e3.45
(m, 2H), 3.37e3.25 (m, 3H), 3.18 (s, 3H), 3.14 (s, 3H), 2.83e2.71 (m,
1H), 1.77e1.64 (m, 2H), 1.11 (s, 9H). 13C NMR (75 MHz, CDCl3):
133.4, 132.5, 130.7, 129.9, 129.5, 129.0, 127.7, 127.4, 123.8, 95.5,
75.6, 66.9, 63.7, 55.6, 54.6, 43.5, 37.8, 26.9, 19.2. MS (ESI) 539
[MþH]þ. HRMS (ESI) m/z calcd for C30H39O5SiS 539.2287; found
539.2286.
d
159.0, 145.0, 136.0, 135.8, 134.0, 132.9, 130.5, 129.7, 129.1, 127.6,
127.4, 123.6, 113.6, 96.6, 77.6, 74.1, 72.8, 69.1, 66.2, 66.0, 55.9, 55.5,

4842
S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
55.1, 38.2, 26.9, 19.4. MS (ESI) 721 [MþH]þ. HRMS (ESI) m/z calcd for
1249, 1100, 1032, 918, 761 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 7.20
C40H53O8SiS 721.3230; found 721.3216.
(d, J¼8.9 Hz, 2H), 6.80 (d, J¼8.9 Hz, 2H), 4.76e4.63 (m, 4H),
4.46e4.42 (m, 2H), 3.90e3.79 (m, 4H), 3.62 (dd, J¼9.9, 3.9 Hz, 1H),
3.53 (dd, J¼9.9, 3.9 Hz, 1H), 3.31e3.28 (m, 7H), 3.03e3.01 (m, 1H),
2.72e2.69 (m, 1H), 2.43e2.40 (m, 1H), 1.88e1.84 (m, 1H), 1.64e1.60
4.16. Compound 25
To an ice cooled solution of sulfoxide 24 (144 mg, 0.2 mmol) in
(m, 1H). 13C NMR (75 MHz, CDCl3):
d 159.1, 130.0, 129.2, 113.6, 96.8,
anhydrous CH2Cl2 (1 mL) was added Et3N (56
m
L, 0.4 mmol) fol-
96.7, 77.7, 75.7, 72.9, 69.3, 55.7, 55.6, 55.1, 49.5, 46.6, 33.9. MS (ESI)
379 [MþNa]þ. HRMS (ESI) m/z calcd for C18H28O7Na 379.1732;
found 379.1748.
lowed by TFAA (57 L, 0.4 mmol). After complete consumption of
m
starting sulfoxide (30 min), the reaction was quenched using aq
saturated NaHCO3 (1 mL). Then solid NaBH4 (37 mg, 1.0 mmol) was
added portionwise. After 30 min the reaction mixture was diluted
with dichloromethane (5 mL) and filtered through a pad of Celite.
The filter pad was washed with dichloromethane. The layers were
separated and the aq layer was extracted with dichloromethane
(2ꢂ20 mL). The combined organic layers were washed successively
with water, brine, dried over anhydrous Na2SO4, and evaporated to
provide the crude product, which was purified by column chro-
matography using hexanes/EtOAc (8:2, v/v) as the eluent to afford
4.19. Compound 28
To a solution of TMS-acetylene (20
m
L, 0.14 mmol) in anhydrous
L, 2.4 M in
THF (1.4 mL) cooled at 0 ꢀC was added n-BuLi (59
m
hexane, 0.14 mmol) and stirred for 1 h at the same temperature. The
reaction mixture was cooled to ꢁ78 ꢀC and a solution of epoxide 27
(45 mg, 0.09 mmol) in anhydrous THF (1 mL) was added slowly
followed by BF3$OEt2 (15 mL, 0.14 mmol). Stirring was continued for
pure 25 (80 mg, 0.13 mmol) in 66% yield as a viscous oil. TLC Rf¼0.26
3 h at the same temperature before quenching with saturated aq
NH4Cl. The reaction mixture was diluted with ether and the layers
were separated. The aq layer was extracted with ether (2ꢂ5 mL).
The combined organic layers were washed with brine, dried over
anhydrous Na2SO4, and the solvent evaporated under reduced
pressure to afford the crude product. The crude mixture was pu-
rified by column chromatography using hexanes/EtOAc (85:15, v/v)
35
(30% EtOAc/hexanes). [
a
]
¼ꢁ5.2 (c 0.5, CHCl3). IR (KBr) 3459,
D
3063, 2935, 2859, 1463, 1426, 1269, 1108, 818, 703, 611, 502 cmꢁ1
.
1H NMR (500 MHz, CDCl3):
d
7.68e7.65 (m, 4H), 7.41e7.34 (m, 6H),
7.24 (d, J¼9.0 Hz, 2H), 6.82 (d, J¼9.0 Hz, 2H), 4.55e4.49 (m, 4H),
4.43e4.41 (m, 2H), 4.27e4.24 (m, 1H), 4.11e4.06 (m, 1H), 4.02e3.98
(m, 1H), 3.83 (dd, J¼10.0, 5.1 Hz, 1H), 3.78 (s, 3H), 3.69e3.59 (m,
3H), 3.28 (s, 3H), 3.27 (s, 3H), 2.20 (ddd, J¼13.8, 7.8, 1.9 Hz, 1H), 1.99
(ddd, J¼13.8, 8.4, 2.8 Hz, 1H), 1.05 (s, 9H). 13C NMR (75 MHz, CDCl3):
as the eluent to afford pure 28 (26.7 mg, 0.07 mmol) in 79% yield as
35
a viscous oil. TLC Rf¼0.28 (30% EtOAc/hexanes). [
a]
¼ꢁ17.3 (c 1,
D
d
159.1, 135.8, 135.6, 133.8, 133.5, 129.7, 129.2, 127.7, 113.6, 96.8, 77.6,
CHCl3). IR (KBr): 3421, 2895, 2860, 2172, 1613, 1465, 1585, 1216,
74.7, 72.9, 71.1, 69.5, 65.4, 55.7, 55.6, 55.2, 34.4, 26.9, 19.2. MS (ESI)
635 [MþNa]þ. HRMS (ESI) m/z calcd for C34H48O8NaSi 635.3016;
found 635.3026.
1033, 916, 702 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d
7.21 (d, J¼8.3 Hz,
2H), 6.83 (d, J¼8.3 Hz, 2H), 4.77 (d, J¼6.6 Hz,1H), 4.71e4.64 (m, 3H),
4.44 (s, 2H), 3.94e3.83 (m, 2H), 3.80 (s, 3H), 3.61 (dd, J¼10.0, 3.4 Hz,
1H), 3.53 (dd, J¼10.0, 6.2 Hz, 1H), 3.41e3.35 (m, 7H), 2.39e2.37 (m,
2H), 2.03e1.92 (m, 2H), 1.66e1.56 (m, 1H). 13C NMR (75 MHz,
4.17. Compound 26
CDCl3):
d 158.9, 129.7, 129.0, 113.4, 96.9, 96.7, 80.5, 77.1, 76.7, 72.8,
To a solution of 25 (85 mg, 0.14 mmol) in anhydrous THF
(0.75 mL) cooled at 0 ꢀC was added TBAF (0.2 mL, 1 M in THF,
0.2 mmol) and stirred at ambient temperature for 3 h. The solvent
was evaporated to afford the crude product, which was purified by
column chromatography using hexanes/EtOAc (8:2, v/v) as the el-
70.2, 69.1, 68.3, 55.7, 55.5, 54.9, 36.2, 27.0. MS (ESI) 405 [MþNa]þ.
HRMS (ESI) m/z calcd for C20H30O7Na 405.1889; found 405.1869.
4.20. Compound 29
uent to afford pure 26 (45 mg, 0.12 mmol) in 86% yield as a viscous
To solution of 28 (26.7 mg, 0.07 mmol) in anhydrous CH2Cl2
(1 mL) cooled at 0 ꢀC was added imidazole (11 mg, 0.17 mmol)
followed by TBS-Cl (13 mg, 0.086 mmol). After 3 h of stirring at rt
the volatiles were evaporated and the crude product was purified
by column chromatography using hexanes/EtOAc (8:2, v/v) as the
35
oil. TLC Rf¼0.08 (30% EtOAc/hexanes). [
a
]
¼ꢁ8.9 (c 0.5, CHCl3). IR
D
(KBr) 3645, 3443, 3069, 2960, 1590, 1369, 1107, 822, 703, 615,
505 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
7.24 (d, J¼8.3 Hz, 2H), 6.87
(d, J¼8.3 Hz, 2H), 4.83e4.63 (m, 4H), 4.46 (s, 2H), 4.01e3.82 (m, 2H),
3.80 (s, 3H), 3.67e3.45 (m, 3H), 3.42e3.30 (m, 8H), 1.96e1.85 (m,
eluent to afford pure 29 (45 mg, 0.064 mmol) in 91% yield as
33
1H), 1.79e1.69 (m, 1H). 13C NMR (75 MHz, CDCl3):
d
159.2, 129.9,
a viscous oil. TLC Rf¼0.20 (30% EtOAc/hexanes). [
a
]
¼ꢁ15.8 (c
D
129.3, 113.7, 96.9, 77.6, 76.9, 73.0, 70.3, 69.4, 66.6, 55.9, 55.7, 55.2,
33.7. MS (ESI) 397 [MþNa]þ. HRMS (ESI) m/z calcd for C18H30O8Na
397.18329; found 397.18417.
1.2, CHCl3). IR (KBr): 2933, 2858, 2175, 1513, 1465, 1429, 1248,
1105, 1033, 844, 762, 702, 610, 507 cmꢁ1 1H NMR (300 MHz,
CDCl3):
.
d
7.25 (d, J¼8.3 Hz, 2H), 6.86 (d, J¼8.3 Hz, 2H), 4.81 (d,
J¼6.8 Hz, 1H), 4.69 (d, J¼6.8 Hz, 1H), 4.66e4.65 (m, 2H), 4.46 (s,
2H), 4.00e3.92 (m, 1H), 3.89e3.78 (m, 5H), 3.63e3.60 (m, 2H),
3.38 (s, 3H), 3.36 (s, 3H), 2.42e2.37 (m, 2H), 2.07e1.98 (m, 1H),
1.97 (t, J¼2.3 Hz, 1H), 1.80e1.70 (m, 1H), 0.87 (s, 9H), 0.08 (s, 3H),
4.18. Compound 27
To a suspension of NaH (12 mg, 60% in Nujol, 0.3 mmol) in an-
hydrous THF (1 mL) cooled at 0 ꢀC was added a solution of 26
(45 mg, 0.12 mmol) in THF (0.5 mL) dropwise. The reaction was
stirred for 1 h and freshly prepared tosyl imidazole (29 mg,
0.13 mmol) was added at the same temperature. The reaction was
stirred for 1 h and quenched with saturated aq NH4Cl at 0 ꢀC. The
reaction mixture was diluted with ether, the layers were separated,
and the aq layer was extracted with ether (2ꢂ5 mL). The combined
organic layers were washed with brine and dried over anhydrous
Na2SO4. Removal of solvent under reduced pressure afforded the
crude product, which was purified by column chromatography
using hexanes/EtOAc (8:2, v/v) as the eluent to afford pure 27
0.05 (s, 3H). 13C NMR (125 MHz, CDCl3):
d 159.2, 130.3, 129.3,
113.7, 96.9, 96.6, 81.4, 77.3, 74.6, 73.0, 70.1, 69.9, 67.9, 55.9, 55.8,
55.2, 37.6, 27.3, 25.8, 18.0, ꢁ4.4, ꢁ4.6. MS (ESI) 519 [MþNa]þ.
HRMS (ESI) m/z calcd for C26H44O7NaSi 519.27485; found
519.27477.
4.21. Compound 31
To a solution of Cp2ZrCl2 (8.02 g, 27.5 mmol) in anhydrous THF
(75 mL) cooled at 0 ꢀC was added iBu2AlH (18.2 mL,1.5 M in toluene,
27.5 mmol) dropwise over 10 min. The resultant suspension was
stirred for 30 min at same temperature, followed by addition of
a solution of propargyl ether 33 (4.4 g, 25.0 mmol) in anhydrous
(45 mg, 0.09 mmol) in 76% yield as a viscous oil. TLC Rf¼0.20 (30%
33
EtOAc/hexanes). [
a
]
¼ꢁ26.4 (c 1, CHCl3). IR (KBr): 2934, 1513,
D

S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
4843
THF (15 mL). The mixture was warmed to rt, stirred for 1 h, and
4.24. Compound 35
then cooled to ꢁ78 ꢀC, followed by the addition of a solution of I2
(8.25 g, 32.5 mmol) in THF (37 mL). After 30 min the reaction
mixture was quenched with aq 1 N HCl. The layers were separated
and the aq layer extracted with ether (3ꢂ100 mL). The combined
organic layers were washed successively with aq saturated sodium
thiosulfate, NaHCO3, brine, dried over Na2SO4, and concentrated.
The crude product was purified by flash column chromatography
using hexanes/EtOAc (9:1, v/v) as the eluent to afford (E)-iodo al-
kene 31 (6.3 g, 21 mmol) in 84% yield as a colorless oil. TLC Rf¼0.18
(10% EtOAc/hexanes). IR (KBr): 2956, 2929, 2857, 1465, 1253, 1105,
To the mixture of K2CO3 (3.26 g, 24 mmol), potassium ferricyanide
(7.87 g, 24 mmol) in a mixture of distilled water (20 mL) and tert-
butanol (20 mL) was added potassium osmate (15 mg, 0.04 mmol)
and DHQD(PHAL) (32 mg, 0.04 mmol) and stirred for 30 min
resulting in an orange suspension. The reaction mixture was cooled
at 0 ꢀC and a solution of 33 (2.83 g, 8 mmol) in toluene (4 mL) was
added followed by the addition of methane sulfonamide (800 mg,
8 mmol). Stirring was continued for 20 h at the same temperature.
The reaction was quenched by addition of solid sodium sulfite and
stirred further for 1 h at rt. The layers were separated and the aq layer
was diluted with water to dissolve the salts and reextracted with
dichloromethane (5ꢂ60 mL). The combined organic layers were
dried over anhydrous Na2SO4 and evaporated under reduced pres-
sure to provide a crude product that was purified by column chro-
matography using hexanes/EtOAc (6:4, v/v) as the eluent to afford
1059, 835, 775 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d
7.18 (d, J¼7.9 Hz,
2H), 6.81 (d, J¼7.9 Hz, 2H), 6.59 (dt, J¼14.8, 5.9 Hz, 1H), 6.34 (d,
J¼14.8 Hz, 1H), 4.40 (s, 2H), 3.87 (d, J¼5.9 Hz, 2H), 3.78 (s, 3H). 13C
NMR (75 MHz, CDCl3):
d 159.1, 142.3, 129.6, 129.3, 113.7, 78.7, 71.8,
71.3, 55.1. Anal. Calcd for C11H13IO2: C, 43.44; H, 4.31. Found: C,
43.74; H, 3.85.
pure 35 (2.3 g, 5.9 mmol) in 74% yield as a viscous oil. TLC Rf¼0.12
33
4.22. Compound 32
(40% EtOAc/hexanes). [
a
]
¼ꢁ15.2 (c 1, CHCl3). IR (KBr): 3426, 2959,
D
.
2871, 1725, 1512, 1248, 1170, 1034, 820 cmꢁ1 1H NMR (500 MHz,
To a solution of vinyl iodide 31 (6.02 g, 20 mmol) (azeotropically
dried once with toluene (10 mL)) dissolved in anhydrous toluene
(80 mL) and cooled at ꢁ78 ꢀC was added n-BuLi (8 mL, 2.5 M in
hexane, 20 mmol) dropwise over 5 min. The colorless solution was
stirred for 30 min and a solution of 30 (2.05 mL, 26 mmol) in an-
hydrous toluene (5 mL) was added followed by BF3$OEt2 (2.7 mL,
22 mmol) giving a yellow solution. Stirring was continued at ꢁ78 ꢀC
for 1 h; then the reaction mixture was quenched by adding satu-
rated aq NaHCO3. After the mixture had attained rt, it was diluted
with ether (100 mL). The phases were separated and the aq phase
was extracted with ether (3ꢂ50 mL). The combined organic ex-
tracts were washed with brine, dried over anhydrous Na2SO4,
concentrated under reduced pressure, and the residue was purified
by column chromatography using hexanes/EtOAc (85:15, v/v) to
CDCl3):
d
7.20 (d, J¼7.9 Hz, 2H), 6.80 (d, J¼7.9 Hz, 2H), 5.17e5.12 (m,
1H), 4.45 (d, J¼10.8, 1H), 4.41 (d, J¼10.8 Hz, 1H), 3.79 (s, 3H),
3.73e3.64 (m, 3H), 3.58e3.48 (m, 3H),1.89e1.86 (m, 2H),1.20 (s, 9H).
13C NMR (75 MHz, CDCl3):
d 177.7,159.2,129.4,129.3,113.6, 72.9, 71.9,
71.5, 70.2, 68.6, 55.0, 45.6, 38.6, 34.6, 26.8. MS (ESI) 411 [MþNa]þ.
HRMS (ESI) m/z calcd for C19H29O6ClNa 411.1550; found 411.1568.
4.25. Compound 36
To a solution of diol 35 (1.94 g, 5 mmol) in anhydrous CH2Cl2
(20 mL) cooled at 0 ꢀC was added iPr2NEt (1.95 mL, 14 mmol), TBAI
(184.5 mg, 0.5 mmol) followed by Mom-Cl (0.9 mL, 12 mmol). After
12 h the reaction was quenched by adding aq NaHCO3. The layers
were separated and the aq layer was extracted with dichloro-
methane (3ꢂ20 mL). The combined organic layers were washed
with water, brine, dried over anhydrous Na2SO4, and evaporated
under reduced pressure to furnish crude product, which was pu-
rified by column chromatography using hexanes/EtOAc (8:2, v/v) as
afford 32 (3.3 g, 12.2 mmol) in 61% yield as a colorless oil. TLC
33
Rf¼0.20 (20% EtOAc/hexanes). [
a]
¼ꢁ6.8 (c 1, CHCl3). IR (KBr):
D
3421, 2933, 2861, 1611, 1512, 1247, 1033, 819, 572 cmꢁ1
.
1H NMR
(500 MHz, CDCl3):
d
7.21 (d, J¼9.7 Hz, 2H), 6.83 (d, J¼9.7 Hz, 2H),
5.71e5.68 (m, 2H), 4.42 (s, 2H), 3.92e3.82 (m, 2H), 3.84e3.80 (m,
4H), 3.58 (dd, J¼10.8, 3.9 Hz, 1H), 3.48 (dd, J¼10.8, 6.9 Hz, 1H),
the eluent to provide pure 36 (1.97 g, 4.15 mmol) in 83% yield as
33
a viscous oil. TLC Rf¼0.20 (30% EtOAc/hexanes). [
a]
¼ꢁ8.5 (c 1,
D
2.36e2.32 (m, 2H). 13C NMR (75 MHz, CDCl3):
d
158.6, 133.0, 129.7,
CHCl3). IR (KBr): 2958, 1727, 1513, 1250, 1154, 1103, 1033, 918,
128.8, 128.3, 113.5, 71.5, 70.3, 69.9, 54.9, 48.7, 36.9. MS (ESI) 293
[MþNa]þ. HRMS (ESI) m/z calcd for C14H19O3ClNa 293.09149; found
293.09125.
763 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
7.20 (d, J¼8.5 Hz, 2H), 6.80
(d, J¼8.5 Hz, 2H), 5.20e5.12 (m, 1H), 4.73 (d, J¼6.9 Hz, 1H),
4.64e4.61 (m, 2H), 4.57 (d, J¼6.9 Hz, 1H), 4.43 (s, 2H), 3.78e3.68
(m, 5H), 3.63e3.49 (m, 3H), 3.36e3.31 (m, 7H), 2.12e2.04 (m, 1H),
4.23. Compound 34
1.85e1.76 (m, 1H), 1.19 (s, 9H). 13C NMR (75 MHz, CDCl3):
d 177.4,
158.9, 129.8, 129.1, 113.5, 96.7, 96.6, 77.0, 74.0, 72.8, 69.5, 68.8, 55.7,
55.5, 54.9, 45.4, 38.6, 32.3, 26.8. MS (ESI) 499 [MþNa]þ. HRMS (ESI)
m/z calcd for C23H37O8ClNa 499.20692; found 499.20674.
To a cooled solution of 32 (2.7 g, 10 mmol) in anhydrous CH2Cl2
(30 mL) was added Et3N (2.1 mL, 15 mmol) followed by pivaloyl
chloride (1.47 mL, 12 mmol) and stirred for 4 h. Water was added to
destroy excess acid chloride. The layers were separated, the aq
layer was extracted with dichloromethane (2ꢂ40 mL). The com-
bined organic layers were washed with brine, dried over anhy-
drous Na2SO4, and evaporated to provide crude product, which
was purified by column chromatography using hexanes/EtOAc
4.26. Compound 27
To a solution of compound 36 (1.9 g, 4 mmol) in ethanol (12 mL)
was added crushed KOH (269 mg, 4.8 mmol) at 0 ꢀC. After 2 h, water
was added and the mixture extracted with ether (4ꢂ30 mL). The
combined organic layers were washed with brine, dried over an-
hydrous Na2SO4, and evaporated under reduced pressure to provide
the crude product that was purified by column chromatography
using hexanes/EtOAc (7:3, v/v) as the eluent to afford epoxide 27
(1.58 g, 3.6 mmol) in 90% yield as a viscous oil. All the physical data
were identical to the sample obtained from 26.
(8:2, v/v) as the eluent to afford pure 34 (3.25 g, 9.2 mmol) in 92%
33
yield as an oil. TLC Rf¼0.27 (20% EtOAc/hexanes). [
a
]
¼ꢁ6.2 (c 1,
D
CHCl3). IR (KBr): 2967, 2838, 1728, 1613, 1514, 1281, 1249, 1150,
1034, 822 cmꢁ1. 1H NMR
d
7.19 (d, J¼8.3 Hz, 2H), 6.81 (d, J¼8.3 Hz,
2H), 5.74e5.45 (m, 2H), 5.02e4.93 (m, 1H), 4.43 (d, J¼7.5 Hz, 1H),
4.37 (d, J¼7.5 Hz, 1H), 4.01 (d, J¼6.0 Hz, 1H), 3.90 (d, J¼6.0 Hz, 1H),
3.79 (s, 3H), 3.64e3.48 (m, 2H), 2.47e2.38 (m, 2H), 1.20 (s, 9H). 13C
NMR (75 MHz, CDCl3):
d
177.5, 159.3, 131.9, 129.7, 129.4, 129.2,
Acknowledgements
113.8, 78.8, 71.1, 70.4, 57.0, 55.2, 44.4, 38.9, 27.0. MS (ESI) 377
[MþNa]þ. HRMS (ESI) m/z calcd for C19H27O4ClNa 377.14901;
found 377.15029.
V.V.K. is thankful to the UGC, New Delhi, for a fellowship. Financial
assistance from the DST, New Delhi, is gratefully acknowledged. We

4844
S. Raghavan, V.V. Kumar / Tetrahedron 69 (2013) 4835e4844
Roulland, E.; Ermolenko, M. S. Org. Lett. 2005, 7, 2225; (i) Stocker, B. L.; Tees-
dale-Spittle, P.; Hoberg, J. O. Eur. J. Org. Chem. 2004, 330; (j) Engers, D. W.;
Bassindale, M. J.; Pagenkopf, B. L. Org. Lett. 2004, 6, 663; (k) Gurjar, M. K.;
Pedduri, Y.; Ramana, C. V.; Puranik, V. G.; Gonnade, R. G. Tetrahedron Lett. 2004,
45, 387; (l) Liu, B.; Zhou, W. S. Org. Lett. 2004, 6, 71; (m) Taylor, R. E.; Jin, M. Org.
Lett. 2003, 5, 4959; (n) Ghosh, A. K.; Kim, J.-H. Tetrahedron Lett. 2003, 44, 7659;
(o) Ghosh, A. K.; Kim, J.-H. Tetrahedron Lett. 2003, 44, 3967; (p) Paterson, I.;
DiFrancesco, E.; Kuehn, T. Org. Lett. 2003, 5, 599 For review, see: (a) Taylor, R. E.;
Zhao, Z.; Wuensch, S. C. R. Chim. 2008, 11, 1369; (b) Williams, D. R.; Nag, P. P.;
Zorn, N. Curr. Opin. Drug Discovery Dev. 2008, 11, 251.
thank Dr. B. Jagadeesh, Head, NMR center, for acquiring the NMR
spectra and Dr. R. Srinivas, Head, NCMS division, for acquiring the
mass spectra.
Supplementary data
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2013.04.059.
11. For the synthesis of the C9eC19 subunit of peloruside A see: Raghavan, S.;
Kumar, V. Vinoth Org. Biomol. Chem. 2013, 11, 2847.
12. Frigerio, M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537.
13. Keck, G. E.; Geraci, L. S. Tetrahedron Lett. 1993, 34, 7827.
References and notes
14. The enantiomer ratio was determined by chromatography using a chiral col-
umn; Chiralpak OD column, hexane/iPrOH¼99:1, flow rate 2.0 mL/min,
tminor¼13.2 min, tmajor¼14.6 min; ee¼89.5%.
1. West, L. M.; Northcote, P. T. J. Org. Chem. 2000, 65, 445.
2. Hood, K. A.; West, L. M.; Rouwe, B.; Northcote, P. T.; Berridge, M. V.; Wakefield,
S. J.; Miller, J. H. Cancer Res. 2002, 62, 3356.
ꢁ
15. Kim, I. S.; Ngai, M. Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14891.
16. The enantiomer ratio was determined by chromatography using a chiral col-
umn; Chiralpak OD column, hexane/iPrOH¼99:1, flow rate 2.0 mL/min,
tminor¼13.2 min, tmajor¼14.6 min; ee¼93.5%.
3. (a) Wilmes, A.; Bargh, K.; Kelly, C.; Nothcote, P. T.; Miller, J. H. Mol. Pharmaceutics
2007, 4, 269; (b) Hamel, E.; Day, W.; Miller, J. H.; Jung, M. K.; Northcote, P. T.; Ghosh,
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Miller, J. H.; Rouwe, B.; Gaitanos, T. N.; Hood, K. A.; Crume, K. P.; Backstrom, B. T.; La
Flamme, A. C.; Berridge, M. V.; Northcote, P. T. Apoptosis 2004, 9, 785.
4. Liao, X.; Wu, Y.; De Brabander, J. K. Angew. Chem., Int. Ed. 2003, 42, 1648.
5. Jin, M.; Taylor, R. E. Org. Lett. 2005, 7, 1303.
17. Blackwell, H. E.; O’Leary, D. J.; Chatterjee, A. K.; Washenfelder, R. A.; Bussmann,
D. A.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 58.
18. Raghavan, S.; Reddy, S. R. J. Org. Chem. 2003, 68, 5754.
19. Displacement was not attempted on bromohydrin 14 based on experience
gained from early trials on different bromohydrins that afforded a mixture of
epoxide and regioisomeric hydroxy acetates as
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