Stereoselective total synthesis of (+)-varitriol

Article abstract of DOI:10.1016/j.tet.2010.08.068

Stereoselective total synthesis of (+)-varitriol, an antitumor natural product, was accomplished by two versatile strategies starting from the commercially available d-(-)-ribose and ethyl (S)-lactate. The key steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and Diels-Alder reaction.

Full text of DOI:10.1016/j.tet.2010.08.068

Tetrahedron 66 (2010) 8527e8535
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective total synthesis of (þ)-varitriol
*
B. Srinivas, R. Sridhar, K. Rama Rao
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Uppal Road, Hyderabad, Andhra Pradesh 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 May 2010
Received in revised form 27 August 2010
Accepted 27 August 2010
Available online 25 September 2010
Stereoselective total synthesis of (þ)-varitriol, an antitumor natural product, was accomplished by two
versatile strategies starting from the commercially available
D
-(ꢀ)-ribose and ethyl (S)-lactate. The key
steps involved in the synthesis of the target molecule are epoxidation, cyclization, dihydroxylation and
DielseAlder reaction.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Natural products
Varitriol
D
-(ꢀ)-ribose
Ethyl (S)-lactate
Propargyl alcohol
1. Introduction
In the present investigation, we have made an attempt to
install the required stereocenters from the commercially available
Marine fungiareanimportantsourceofmarinenaturalproducts.1
Amongst them, (þ)-varitriol 1 isolated from the fungus Emericella
variecolor has shown increased potency toward the renal, breast
and CNS cancer cell lines.2 The fascinating biological activities of
(þ)-1 have attracted the attention of the synthetic community.
To date, several total syntheses of (þ) and (ꢀ)-1 have been
completed. Jennings and Clemens3a reported the total synthesis of
(ꢀ)-1 using cross metathesis to link the carbohydrate and aromatic
moieties. Subsequently, the Taylor group3b also achieved the syn-
thesis of (ꢀ)-1 by applying HornereWadswortheEmmons (HWE)
and RambergeBacklund reaction. Both these groups started their
D
-(ꢀ)-ribose. We envisioned that the furanoside part of the natural
(þ)-1 can be derived from -(ꢀ)-ribose and the aromatic moiety
D
from propargyl alcohol.
OMe OH
O
synthesis with
D
-(ꢀ)-ribose to construct the furanoside part,
HO
(+)-varitriol 1
OH
though, Jennings et al., emphasized the need for the use of
expensive
L
-(þ)-ribose for obtaining the natural (þ)-varitriol. The
first total synthesis of (þ)-1, was reported by Shaw et al.,3c utilizing
methyl
a,D-mannopyranoside to construct the carbohydrate por-
tion of the molecule which was later combined with the aromatic
moiety by cross metathesis. Gracza et al.,3d reported the synthesis
of (þ)-1 by applying KocienskieJulia olefination of sulfonyl furan
derivative with substituted benzaldehyde. A recent report by Ghosh
and Pradhan,3e depicted the synthesis of both (þ) and (ꢀ)-1 and
their epimers utilizing Heck reaction to couple the olefinic sugar
moiety with the aromatic triflate. By the time this work is being
submitted, some more reports for the synthesis of (þ)-1 have also
appeared in literature.3f,g Furthermore, synthetic analogues of
(þ)-1 were also reported by various approaches.3h,i
2. Results and discussion
The synthesis of the furanoside part of (þ)-1 was initiated from
-(ꢀ)-ribose and the sequence of reactions are depicted in
D
Scheme 1. 2,3-O-Isopropylidene-D-ribofuranose 2 (synthesized
from
D
-(ꢀ)-ribose4) was treated with excess MeMgI to yield 3,5
which upon oxidative cleavage with NaIO4 gave a lactol. Wittig
olefination using carbethoxymethylene triphenylphosphorane
resulted in a,b
-unsaturated ester 4 with predominant Z selectivity6
in 44% yield (Z/E, 2:1). Both the isomers were separable by silica gel
column chromatography and the ester 4 was subjected to reduction
with DIBAL-H to provide precursor 6 in 75% yield. Compound 6 was
subjected to epoxidation with m-CPBA to furnish a mixture of
* Corresponding author. E-mail address: kakulapatirama@gmail.com (K.R. Rao).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.068

8528
B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
epoxide and cyclic diol. Although, pure epoxide could not be
purified from this reaction mixture, it cyclized to form diols 7 and 8
during chromatography. These diols are obtained in 55% yield in the
ratio of 1:1.7 Subsequently, we also attempted to cyclize crude
epoxide using CSA but no significant improvement in the yields of
the diols could be noticed. Then, the allylic alcohol 6 was subjected
to Sharpless epoxidation8 to give a diol, which is identical in all
respects to 8 formed by the reaction of m-CPBA. The stereochem-
istry of 8 having been established, the other isomer 7, which is of
the right stereochemical configuration for the synthesis of (þ)-1
was advanced further for cross metathesis reaction.
As depicted in Scheme 2, the protected lactaldehyde 9 (obtained
from ethyl (S)-lactate9) was subjected to olefination reaction
using StilleGennari procedure10 to afford the corresponding
a,
b-unsaturated ester 10 with prominent Z-stereochemistry in 77%
yield. Compound 10 on reduction with DIBAL-H gave corresponding
alcohol 11 (85%), which was later oxidized under Swern reaction
conditions to give the corresponding aldehyde. Wittig olefination
reactionwith stabilized Ph3P]CHCO2Et ylide afforded12 (78%) with
predominant trans-selectivity. DIBAL-H reduction of 12 followed by
Sharpless epoxidation11 gave 14 in 75% yield. Initially, we had pro-
posed to synthesize the dihydrofuran12 ring by opening the epoxide
HO
OH
OH
O
OH
O
OH
CO2Et
O
OH
a
b
c
HO
CO2Et
O
O
O
O
O
O
5
4
2
3
O
OH
O
OH
O
H
H
H
H
O
O
OH
OH
OH
OH
d
CH2OH
CH2OH
O
O
O
O
O
O
6
8
7
e
O
H
OH
H
O
OH
OH
CH2OH
O
O
O
O
8
Scheme 1. Reagents and conditions: (a) (i) CH3MgI, Et2O, 0 ꢁC-rt, 3 h (71%); (b) (i) NaIO4, THF/H2O (9:1), 0 ꢁC-rt, 3 h, (77%); (ii) Ph3P]CHCO2Et, cat. PhCO2H, toluene, 90 ꢁC, 4 h (65%
of 4 and 5) (Z/E, 2:1); (c) DIBAL-H, CH2Cl2, 0 ꢁC, 3 h (75%); (d) m-CPBA, CH2Cl2, 0 ꢁC-rt, 24 h, silicagel, (27.5% of 7 and 27.5% of 8); (e) (ꢀ)-DIPT, Ti(OiPr)4, TBHP, CH2Cl2, ꢀ20 ꢁC, 10 days
(47%).
Since the key intermediate 7 formed from
D
-(ꢀ)-ribose for cross
after deprotection of silyl ether, however, desilylation of 14 with
TBAF gave a mixture of dihydrofurans 15 and 16 (75:25) along with
small amounts of the uncyclized compound. Therefore, we treated
the reaction mixture with CSA to ensure the complete cyclization
and the major diol 15 was separated in 68% yield.
metathesis reaction is only to an extent of 27.5% in the mixture of
diols (7 and 8), we also explored the synthesis of the furanoside
moiety starting from ethyl (S)-lactate, a commercially available
synthon, as shown below.
CHO
OR
9
a
OR
c
CO2Et
b
OR
OR
d
CO2Me
OH
12
10
11
R = TBDPS
H
H
H
H
O
O
e
OR
OH
O
OH
OH
OR
OH
f
OH
+
OH
16
15
14
13
minor
major
Scheme 2. Reagents and conditions: (a) (F3CCH2O)2POCH2CO2Me, NaH, THF, ꢀ78 ꢁC, 3 h (77%); (b) DIBAL-H, CH2Cl2, 0 ꢁC, 2 h (85%); (c) (i) (COCl)2 DMSO, Et3N, CH2Cl2, ꢀ78 ꢁC, 1 h
(80%); (ii) Ph3P]CHCO2Et, benzene, rt, 6 h (78%); (d) DIBAL-H, CH2Cl2, 0 ꢁC, 4 h (82%); (e) (ꢀ)-DET, Ti(OiPr)4, cumene hydroperoxide, CH2Cl2, ꢀ20 ꢁC, 3 h (75%); (f) (i) TBAF, THF, 0 ꢁ
C
to rt, 24 h; (ii) cat. CSA, CH2Cl2, 6 h (68%).

B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
8529
Our next goal was the dihydroxylation13 of the double bond of
1
O
H
O
H
O
15 to introduce hydroxyl groups with high diastereoselectivity for
an efficient varitriol synthesis. Initially the diol 15 was protected
with acetonide and dihydroxylation was carried out using OsO4
in the presence of NMO to yield the secondary diol 19a as an
inseparable mixture. To explore the separation of this diol, it was
again protected with acetonide but to our dismay the corre-
sponding diols 20x and 20y were found to be formed in poor dia-
stereoselectivity (70:30). Therefore, we attempted to improve the
diastereoselectivity by changing the protective group of the diol 15
with TBS followed by dihydroxylation (19b) and acetonide pro-
tection, which gave 21 with maximum diastereoselectivity (95:5).
This may be not only due to 2,5-syn hydrogens, but also due to
bulkiness of TBS substituent, dictating the approach of OsO4 from
the more sterically accessible top face (Fig. 1). Due to clarity of
proton interactions, the stereochemistry of the major diastereomer
20x was assigned by the key NOE correlations (Fig. 2). The H-6
of CH3 proton has shown NOE correlation with H-4, which is syn to
H
O
6
2
5
7
3
4
H
H
O
α
β
Fig. 2. NOESY correlations for compound 20x
reaction in the next step. With the successful synthesis of
furanoside moiety, we proceeded further with the synthesis of
the aromatic part.
Scheme 5 depicts the synthetic sequence developed for the
synthesis of aromatic part. Initially, propargyl alcohol was protected
as PMB ether 2415 and was converted to 25 in excellent yield by
deprotonating acetylenic protonwith n-BuLi followed by quenching
with ethyl chloroformate.16 The required 1-methoxy cyclohexa-1,
4-diene was prepared from anisole by Birch reduction,17 which on
treating with dienophile 25 in the presence of catalytic amount of
dichloromaleic anhydride in a sealed tube at 180 ꢁC for 7 h gave
adduct 26 in 75% yield.18 Deprotection of PMB group of 26 un-
expectedly led to the formation of lactone 27. To overcome this
drawback, the ester 26 was initially subjected to reduction with
DIBAL-H in CH2Cl2 to obtain primary alcohol 28, which was pro-
tected as TBS ether to get 29 (90%). Next, the cleavage of the PMB
ether was carried out using DDQ in CH2Cl2 and pH 7 buffer to furnish
the alcohol 30 (72%), which on DesseMartin periodinane19 (DMP)
oxidation followed by Wittig olefination with Ph3PCH3Br gave aro-
matic fragment 32 in 70% yield.
With the two fragments 23 and 32 in hand, merging of the two
olefins was carried out with Grubbs cross metathesis20 reaction.
Treatment of 23 and 32 with the Grubbs second generation catalyst
in CH2Cl2 provided the protected varitriol in 55% yield. Depro-
tection of TBS and acetonide groups with 1 N HCl in THF resulted
in the target compound (þ)-varitriol 1 in 70% yield (Scheme 6).
All the analytical data were in close agreement with the reported
values.2a,3a
H-3, whereas both H-3 and H-4 correlated with a-CH3 of the ace-
tonide ring. H-2 and H-5 protons correlated with each other and
H-2 correlated with H-7. All these correlations confirmed stereo-
chemistry of the compound 20x (Scheme 3).
O
O Os O
H
O
H
R
O
OR
OR
Fig. 1. Attack of OsO4.
The diol, 7 or 22 (7 obtained from
D
-(ꢀ)-ribose or 22 from
ethyl (S)-lactate) was treated with TPP, imidazole and iodine in
toluene at 50 ꢁC to afford 23 in 75% yield (Scheme 4).14 Since this
compound showed exactly opposite sign of optical rotation
compared with Jenning’s molecule,3a we concluded that product
23 is of the right configuration required for the cross metathesis
H
H
H
H
H
H
H
H
O
OR
OR1
O
O
OR
OR1
OR
OR1
O
OR
OR1
c
d
HO
OH
O
O
O
O
15
19
x
y
x y
:
ratio
a
b
17. R, R1 = C(CH3)2
19a. R, R1 = C(CH3)2
20. R, R1 = C(CH3)2
70: 30
15
1
1
1
19b
. R, R = TBS
18
21
. R, R = TBS
. R, R = TBS
>95: 5
H
H
H
H
O
O
OTBS
OH
OH
e
OTBS
O
O
O
O
21x
22
Scheme 3. Reagents and conditions: (a) 2,2 DMP, cat. CSA, CH2Cl2, 2 h (87%); (b) TBSOTf, 2,6-lutidine, CH2Cl2, 0 ꢁC-rt, 12 h (72%); (c) OsO4, NMO, acetone:water (4:1), 0 ꢁC, 15 h
(70%); (d) 2,2 DMP, cat. CSA, acetone, 6 h (85% of 21x); (e) TBAF, THF, rt 12 h (68%).

8530
B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
H
H
H
H
O
O
OH
OH
OH
OH
H
H
O
a
(or)
O
O
O
O
O
O
22
7
23
Scheme 4. Reagents and conditions: (a) TPP, I2, imidazole, toluene, 50 ꢁC, 30 min (75%).
OMe
OMe
O
CO2Et
OPMB
CO2Et
OPMB
b
c
a
CH2OPMB
O
24
25
26
27
OMe
OMe
OMe
OMe
OTBS
OPMB
OTBS
OH
g
OTBS
H
d
h
OH
OPMB
e
f
26
29
30
28
O
31
OMe
OTBS
32
Scheme 5. Reagents and conditions: (a) n-BuLi, ClCO2Et, THF, ꢀ78 ꢁC-rt, 45 min (92%); (b) 1-methoxy cyclohexa-1,4-diene, dichloromaleic anhydride, neat, 180 ꢁC, 7 h (75%);
(c) DDQ, CH2Cl2/buffer pH¼7 (18:2), 0 ꢁC-rt, 3 h (75%); (d) DIBAL-H, CH2Cl2, 0 ꢁC, 4 h (85%); (e) TBDMS/Cl, imidazole, DMAP, CH2Cl2, 0 ꢁC-rt, 4 h (90%); (f) DDQ, CH2Cl2/buffer pH¼7
(18:2), 0 ꢁC-rt, 2 h (72%); (g) DMP, CH2Cl2, 0 ꢁC-rt, 1 h (87%); (h) n-BuLi, Ph3PCH3Br, THF, 0 ꢁC-rt, 2 h (70%).
OMe OTBS
H
H
O
a
1
+
O
O
32
23
Scheme 6. Reagents and conditions: (a) (i) Grubbs second generation catalyst, CH2Cl2, reflux, 18 h (55%); (ii) 1 M HCl, THF, rt, 3 h, (70%).
3. Conclusion
F254 to a thickness of 0.5 mm (Merck). Column chromatography was
performed on silica gel (60e120 mesh) using ethyl acetate, hexane,
In summary, the stereoselective total synthesis of (þ)-varitriol
was accomplished by two different protocols starting from the
commercially available
highly diastereocontrolled routes illustrate the utility of epoxida-
tion, cyclization, dihydroxylation, and cross metathesis strategy for
the natural (þ)-varitriol. The synthesis of other potential analogues
is in progress.
dichloromethane, and acetone as the eluents. Optical rotation values
were recorded on Horiba high sensitive polarimeter and IR spectra
were recorded with a PerkineElmer FT-IR spectrophotometer. 1H
NMR spectra were recorded with 200, 300, 400, 500 MHz and 13C
NMR spectra were recorded with 75 MHz spectrometer using tri-
methylsilane as an internal standard in CDCl3. Mass spectra were
obtained on Finnigan MAT1020B or micromass VG 70e70H spec-
trometer operating at 70 eV using a direct inlet system. All high
resolution mass spectra (HRMS) were recorded on QSTAR XL hybrid
MS/MS system equipped with an ESI source (IICT, Hyderabad).
D
-(ꢀ)-ribose and ethyl (S)-lactate. The
4. Experimental section
4.1. General
4.1.1. (R)-1-((4R,5S)-5-((S)-1-Hydroxyethyl)-2,2-dimethyl-1,3-dioxo-
lan-4-yl)ethane-1,2-diol (3). To a solution of MeMgI [prepared from
Mg (5.3 g, 221.1 mmol) and MeI (13.8 mL, 221.1 mmol)] in anhydrous
Solvents were dried and purified by conventional methods prior
to use. The progress of all the reactions was monitored by thin-layer
chromatography (TLC)using glassplates precoated with silicagel-60
ether (110 mL) was added 2,3-O-isopropylidene-D-ribofuranose

B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
8531
2 (4.2 g, 22.1 mmol) in ether (15 mL) at 0 ꢁC and reaction mixturewas
slowly warmed to rt and stirred for 3 h. The reaction mixture was
quenched with saturated aqueous NH4Cl (25 mL) and extracted with
EtOAc (2ꢂ45 mL). The combined organic layers were washed with
brine, dried over Na2SO4, and concentrated under reduced pressure.
The crude residue was purified by column chromatography to afford
3 (3.23 g, 71%) as white solid; Rf (80% EtOAc/hexane) 0.4; mp
ESI-MS: m/z 225 [MþNa]þ; HRMS (ESI): [MþNa]þ, found 225.1111.
C10H18O4Na requires 225.1102.
4.1.4. (S)-1-((3aR,4R,6S,6aS)-2,2,6-Trimethyltetrahydrofuro[3,4-d]
[1,3]dioxol-4-yl)ethane-1,2-diol (7). To a stirred solution of the allyl
alcohol 6 (0.35 g, 1.73 mmol) in CH2Cl2 (15 mL) m-CPBA (1.06 g,
4.33 mmol, 70% purity) was added slowly at 0 ꢁC. Then the reaction
mixture was warmed to rt and stirred until the starting material
disappeared. Later, the reaction mixture was quenched with satu-
rated NaHCO3 (5 mL) solution and extracted with CH2Cl2 (2ꢂ5 mL).
Thelayerswere separatedand the aqueous layer was again extracted
with EtOAc (10 mL) and the combined organic layers were washed
with saturated brine, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified by column chromatog-
71e72 ꢁC; [
a
]
D
28þ26.2 (c 0.01, CHCl3); IR (KBr):
n
3320, 2933, 2930,
2873, 1375, 1247, 1221, 1073, 1044, 877 cmꢀ1
;
1H NMR (500 MHz,
CDCl3):
3.59e3.74 (1H, m, CH2OH), 3.75e4.15 (5H, m, CH2OH, CHOH, CH3CH
(CH)2O2C(CH3)2), 4.47 (br s, OH); 13C NMR (75 MHz, CDCl3):
20.5,
d
1.22e1.40 (9H, m, 3ꢂCH3), 2.13 (br s, OH), 2.96 (br s, OH),
d
25.3, 27.8, 64.2, 65.8, 69.5, 77.2, 81.5, 108.6; ESI-MS: m/z 229
[MþNa]þ; HRMS (ESI): [MþNa]þ, found 229.1207. C9H18O5Na
requires 229.1202.
raphy to furnish the diol 7 (0.1 g, 27.5%) as pale yellow liquid; Rf (70%
28
EtOAc/hexane) 0.5; [
a]
ꢀ31.2 (c 0.005, CHCl3); IR (neat):
n 3416,
D
4.1.2. (Z)-Ethyl3-((4R,5S)-5-((S)-1-hydroxyethyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)acrylate (4). To a solution of triol 3 (3.1 g, 15 mmol) in
THF/H2O (9:1, 30 mL) was added NaIO4 (3.86 g,18 mmol) at 0 ꢁC and
stirred for 3 h at rt. The reaction mixture was quenched with sat-
urated Na2S2O3 (10 mL) and extracted with EtOAc (2ꢂ15 mL).
Combined organic layers were washed with brine, dried over
Na2SO4, and concentrated under reduced pressure to generate the
lactol (2.01 g, 77%) as pale yellow liquid; Rf (25% EtOAc/hexane) 0.4,
which was used as such for further reaction. To a solution of the
lactol (2 g, 11.4 mmol) in toluene (20 mL) was added carbethoxy-
methylene triphenylphosphorane (6 g, 17.2 mmol) and catalytic
benzoic acid. The mixture was stirred at 90 ꢁC for 4 h. The reaction
was allowed to reach rt and quenched with saturated aqueous
solution of NaCl and NaHCO3. The layers were partitioned and the
aqueous phase was extracted with EtOAc (2ꢂ10 mL). The combined
organic layers were filtered and the solvent was removed under
reduced pressure. The residue was purified by column chroma-
2981, 2932, 1378, 1212, 1075, 865 cmꢀ1; 1H NMR (300 MHz, CDCl3):
1.31 (3H, d, J 6.7 Hz, CH3),1.34 (3H, s, CH3),1.53 (3H, s, CH3), 2.31 (br
d
s, OH), 2.54 (br s, OH), 3.73e3.79 (3H, m, CHOH, CH2OH), 3.91e3.96
(1H, m, furanoside), 3.96e4.06 (1H, m, furanoside), 4.25 (1H, dd,
J 5.2, 6.7 Hz, furanoside), 4.70 (1H, dd, J 4.5, 6.7 Hz, furanoside); 13C
NMR (75 MHz, CDCl3):
d 18.8, 25.4, 27.3, 64.6, 71.1, 80.8, 82.0, 85.5,
85.7,114.8; ESI-MS: m/z 241 [MþNa]þ; HRMS (ESI): [MþNa]þ, found
241.1157. C10H18O5Na requires 241.1152.
4.1.5. (R)-1-((3aR,4S,6S,6aS)-2,2,6-Trimethyltetrahydrofuro[3,4-d]
28
[1,3]dioxol-4-yl)ethane-1,2-diol (8). Rf (70% EtOAc/hexane) 0.4; [
þ9.54 (c 0.011, CHCl3); IR (neat):
1059, 901 cmꢀ1; 1H NMR (300 MHz, CDCl3):
a]
D
n
3515, 2976, 2937, 1378, 1211, 1111,
1.15 (3H, d, J 6.7 Hz,
d
CH3CH), 1.30 (3H, s, CH3), 1.49 (3H, s, CH3), 2.76 (br s, OH), 3.30 (br s,
OH), 3.68e3.84 (2H, m, CHOH, CH2OH), 3.90 (1H, dd, J 3.7, 6.0 Hz,
CH2OH), 4.03e4.10 (1H, m, furanoside), 4.29 (1H, q, J 6.7 Hz, fu-
ranoside), 4.48 (1H, d, J 6.0 Hz, furanoside), 4.76 (1H, dd, J 3.7,
tography to give 4 (1.23 g, 44% yield) as pale yellow liquid; Rf (25%
6.0 Hz, furanoside); 13C NMR (75 MHz, CDCl3):
63.4, 70.9, 78.8, 79.5, 81.0, 86.5, 112.6.
d 16.8, 24.5, 26.0,
28
EtOAc/hexane) 0.6; [
a
]
ꢀ104.7 (c 0.02, CHCl3); IR (neat):
n
2981,
1H NMR (300 MHz,
1.17 (3H, d, J 6.7 Hz, CH3), 1.23 (3H, t, J 6.7 Hz, OCH2CH3),
D
2935, 1741, 1377, 1208, 1167, 1076, 866 cmꢀ1
CDCl3):
;
d
4.1.6. (S,Z)-Methyl4-(tert-butyldiphenylsilyloxy)pent-2-enoate
(10). To a stirred suspension of NaH (1.13 g, 28.3 mmol) in dry THF
(50 mL) at 0 ꢁC under nitrogen was added bis-(2,2,2-trifluoroethyl)
(methoxy-carbonylmethyl) phosphonate (6.91 g, 21.7 mmol) in dry
THF (20 mL) very slowly and stirred for 30 min. Later, the reaction
mixture was cooled to ꢀ78 ꢁC and a solution of aldehyde 9 (5.9 g,
18.9 mmol) in dry THF (15 mL) was added drop wise. After stirring
for 3 h at ꢀ78 ꢁC the reaction mixture was quenched with saturated
NH4Cl solution (20 mL) and stirred at rt for 30 min. The two layers
were separated and the aqueous layer was extracted with ether
(2ꢂ35 mL). The combined organic layers were washed with brine,
dried over Na2SO4, and the solvent was removed under reduced
pressure. The residue was purified by column chromatography to
1.32 (3H, s, CH3), 1.44 (3H, s, CH3), 2.87 (br s, OH), 3.62e3.73 (1H, m,
CH3CHOH), 4.08 (1H, dd, J 6.0, 7.5 Hz, CHOC(CH3)2), 4.13 (2H, q, J
6.7 Hz, OCH2CH3), 5.44e5.51 (1H, m, CHOC(CH3)2), 5.93 (1H, dd, J
1.5, 12.0 Hz, CH]CHCO2Et), 6.21 (1H, dd, J 8.3, 11.3 Hz, CH]
CHCO2Et); 13C NMR (75 MHz, CDCl3):
d 14.0, 19.6, 25.3, 27.8, 61.0,
66.4, 74.6, 82.8, 109.1, 121.7, 146.5, 166.9; ESI-MS: m/z 245 [MþH]þ;
HRMS (ESI): [MþNa]þ, found 267.1259. C12H20O5Na requires
267.1255.
4.1.3. (Z)-3-((4R,5S)-5-((S)-1-Hydroxyethyl)-2,2-dimethyl-1,3-dioxo-
lan-4-yl)prop-2-en-1-ol (6). To a solution of cis ester 4 (0.97 g,
3.9 mmol) in CH2Cl2 (10 mL) at 0 ꢁC was slowly added DIBAL-H
(7 mL, 20% solution in toluene, 9.9 mmol) and the mixture was
stirred for 3 h at 0 ꢁC. The reaction mixture was quenched with
saturated aqueous sodium potassium tartrate (4 mL) and the stir-
ring was continued for 1 h at rt. The organic layer was separated
and the aqueous layer was extracted with CH2Cl2 (2ꢂ5 mL). The
combined organic layers were washed with brine, dried over
Na2SO4, and concentrated under reduced pressure. The crude
product obtained was purified by column chromatography result-
afford the ester 10 (5.35 g, 77%) as colorless liquid; Rf (5% EtOAc/
28
hexane) 0.6; [
a
]
þ45.6 (c 0.011, CHCl3); IR (neat):
n
3068, 2934,
1H NMR (200 MHz,
1.05 (9H, s, C(CH3)3), 1.23 (3H, d, J 5.8 Hz, CH3), 3.50 (3H, s,
D
2893, 2858, 1723, 1197, 1110, 1071, 700 cmꢀ1
CDCl3):
;
d
OCH3), 5.31e5.51 (2H, m, CH3CH, olefin), 6.21 (1H, dd, J 8.0, 11.7 Hz,
olefin), 7.21e7.40 (6H, m, ArH), 7.53e7.67 (4H, m, ArH); 13C NMR
(75 MHz, CDCl3):
d 19.1, 23.2, 26.9, 50.9, 66.6, 116.4, 127.3, 127.4,
129.5, 134.0, 134.1, 135.72, 137.76, 153.8, 165.8; ESI-MS: m/z 391
[MþNa]þ; HRMS (ESI): [MþNa]þ, found 391.1711. C22H28O3NaSi
requires 391.1705.
ing in allyl alcohol 6 (0.6 g, 75%) as colorless oil; Rf (50% EtOAc/
28
hexane) 0.4; [
a
]
þ31.6 (c 0.012, CHCl3); IR (neat):
n 3385, 2985,
D
2932, 1376, 1217, 1063, 1015, 872 cmꢀ1; 1H NMR (300 MHz, CDCl3):
1.26 (3H, d, J 6.0 Hz, CH3CH), 1.35 (3H, s, CH3), 1.45 (3H, s, CH3),
d
4.1.7. (S,Z)-4-(tert-Butyldiphenylsilyloxy)pent-2-en-1-ol (11). To a sol-
ution of ester 10 (4.5 g, 12.2 mmol) in CH2Cl2 (40 mL) at 0 ꢁC under
nitrogen, wasslowlyaddedDIBAL-H(21.7mL,20% solutionintoluene,
30.5 mmol) and the mixture was stirred for 2 h at 0 ꢁC. The reaction
mixture was quenched with saturated aqueous sodium potassium
tartrate (10 mL) and later stirring was continued for 1 h at rt.
3.68e3.80 (1H, m, CH3CHOH), 3.84 (1H, dd, J 6.0, 9.0 Hz, CHOC
(CH3)2), 3.97 (1H, dd, J 6.4, 12.2 Hz, CH2OH), 4.22 (1H, dd, J 7.9,
11.8 Hz, CH2OH), 5.05 (1H, dd, J 5.8, 9.6 Hz, CHOC(CH3)2), 5.62 (1H, t,
J 10.7 Hz, olefin), 5.83e5.97 (1H, m, olefin); 13C NMR (75 MHz,
CDCl3):
d 20.8, 25.7, 28.3, 57.2, 65.7, 73.7, 82.3, 109.0, 130.6, 131.5;

8532
B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
The organic layer was separated and the aqueous layer was extracted
with CH2Cl2 (2ꢂ20 mL). The combined organic layers were washed
with brine, dried over Na2SO4, and concentrated under reduced
pressure. The crude product obtained was purified by column chro-
CH]CHCH2OH), 7.26e7.40 (6H, m, ArH), 7.58e7.69 (4H, m, ArH);
13C NMR (75 MHz, CDCl3):
19.2, 24.6, 27.0, 63.2, 65.9, 96.2, 126.2,
127.4, 127.6, 129.4, 129.5, 132.7, 134.1, 134.4, 135.9, 136.0, 136.1; ESI-
MS: m/z 389 [MþNa]þ; HRMS (ESI): [MþNa]þ, found 389.2638.
C23H30O2NaSi requires 389.2634.
d
matography to give the alcohol 11 (3.53 g, 85%) as colorless oil; Rf (15%
28
EtOAc/hexane) 0.4; [
a
]
þ20.6 (c 0.015, CHCl3); IR (neat):
n
3345,
1H NMR
1.04 (9H, s, C(CH3)3), 1.19 (3H, d, J 6.0 Hz, CH3),
D
3069, 3018, 2962, 2932, 2858, 1108, 1080, 703 cmꢀ1
(300 MHz, CDCl3):
;
4.1.10. ((2R,3R)-3-((S,Z)-3-(tert-Butyldiphenylsilyloxy)but-1-enyl)ox-
ꢀ
d
iran-2-yl)methanol (14). Crushed and activated 4 A molecular
3.56e3.72 (2H, m, CH3CH, CH2OH), 4.45e4.57 (1H, m, CH2OH),
5.23e5.34 (1H, m, olefin), 5.54 (1H, dd, J 9.8,11.3 Hz, olefin), 7.29e7.45
sieves were added to a stirred solution of CH2Cl2 (35 mL) under
nitrogen. The flask was cooled to ꢀ20 ꢁC, Ti(OiPr)4 (1.54 mL,
5.2 mmol) and (ꢀ)-DET (1 mL, 6.16 mmol) were added and stirred
for 15 min. The allylic alcohol 13 (1.6 g, 4.37 mmol) in CH2Cl2 (5 mL)
was added and stirred at the same temperature for 20 min and then
cumene hydroperoxide (1.36 mL, 7.86 mmol) was added slowly.
After the addition, the reaction was maintained at the same tem-
perature with stirring for 3 h. Tartaric acid aqueous solution (15% w/
v) was added at rt and stirring was continued until clear phases
were reached (1 h). The phases were separated and the aqueous
phase was extracted with CH2Cl2. The combined organic phases
were washed with brine, concentrated, and diluted with Et2O fol-
lowed by the addition of precooled 10% (w/v) aqueous NaOH so-
lution. The two-phase mixture was stirred vigorously for 15 min at
0 ꢁC. The organic phase was separated and the aqueous phase was
extracted with CH2Cl2. The combined organic phases were washed
with brine and concentrated under reduced pressure. The crude
product obtained was purified by silica gel column chromatography
(6H, m, ArH),7.60e7.69(4H, m, ArH);13CNMR(75MHz, CDCl3):
d19.2,
24.7, 27.0, 58.3, 65.7, 96.2, 127.3, 127.4, 127.6, 129.7, 134.0, 134.1, 135.8,
136.0, 136.1; ESI-MS: m/z 363 [MþNa]þ; HRMS (ESI): [MþNa]þ, found
363.1745. C21H28O2NaSi requires 363.1756.
4.1.8. (S,2E,4Z)-Ethyl 6-(tert-butyldiphenylsilyloxy)hepta-2,4-dien-
oate (12). To a stirredsolution of oxalyl chloride (1.3 mL,15 mmol) in
CH2Cl2 (30 mL) at ꢀ78 ꢁC under nitrogen DMSO (2.1 mL, 30 mmol)
was added and stirred for 15 min followed by the addition of com-
pound 11 (3.4 g, 10 mmol) in CH2Cl2 (10 mL). The contents were
stirred for 1 h at ꢀ78 ꢁC. The reaction mixture was quenched with
Et3N (8.4 mL, 60 mmol) and diluted with CH2Cl2 (20 mL) and then
allowed the reaction mixture to come to rt. The reaction was then
diluted with water(40 mL) and the aqueous layerwas extractedwith
CH2Cl2 (2ꢂ15 mL). The combined organic layers were washed with
water, brine, dried (Na2SO4), and concentrated. The residue was
passed through a pad of silica gel to give the corresponding aldehyde
(2.7 g, 80%), which was used as such for further reaction. To a solu-
tion of the aldehyde (2.65 g, 7.84 mmol) in benzene (25 mL) was
added ethoxycarbonylmethylene triphenylphosphorane (3.27 g,
9.4 mmol) and the mixture was stirred at rt for 6 h and quenched
with saturated aqueous solution of NaCl. The layers were partitioned
and the aqueous phase was extracted with EtOAc (2ꢂ15 mL). The
combined organic layers were washed with brine, dried over
Na2SO4, and concentrated under reduced pressure. The residue was
to furnish the epoxide 14 (1.25 g, 75%) as colorless oil; Rf (30%
28
EtOAc/hexane) 0.4; [
a
]
þ39.4 (c 0.01, CHCl3); IR (neat):
n
3428,
1H NMR (300 MHz,
1.02 (9H, s, C(CH3)3), 1.24 (3H, d, J 6.0 Hz, CH3CH),
D
2962, 2931, 2894, 2858, 1109, 1080, 703 cmꢀ1
CDCl3):
;
d
2.67e2.73 (1H, m, epoxide), 3.07 (1H, dd, J 2.2, 9.0 Hz, epoxide),
3.19e3.32 (1H, m, CH2OH), 3.60 (1H, d, J 12.8 Hz, CH2OH), 4.58e4.70
(1H, m, CH3CH), 4.87 (1H, dd, J 9.0, 11.3 Hz, olefin), 5.75 (1H, dd,
J 9.0, 11.3 Hz, olefin), 7.28e7.44 (6H, m, ArH), 7.59e7.69 (4H, m,
ArH); 13C NMR (75 MHz, CDCl3):
d 19.1, 24.5, 26.8, 51.1, 59.5, 61.0,
purified by column chromatography to give 12 (2.49 g, 78% yield) as
65.9, 124.7, 127.3, 127.6, 129.5, 129.6, 133.9, 135.7, 135.9, 140.9; ESI-
MS: m/z 405 [MþNa]þ; HRMS (ESI): [MþNa]þ, found 405.1857.
C23H30O3NaSi requires 405.1861.
28
pale yellow liquid; Rf (5% EtOAc/hexane) 0.5; [
CHCl3); IR (neat):
1136, 1110, 1084, 1041, 704 cmꢀ1; 1H NMR (400 MHz, CDCl3):
a
]
þ59.6 (c 0.013,
D
n
3068, 2965, 2933, 2895, 2859, 1715, 1266, 1180,
1.04
d
(9H, s, C(CH3)3), 1.22 (3H, d, J 5.8 Hz, CH3), 1.26 (3H, t, J 6.5 Hz,
OCH2CH3), 4.13 (2H, q, J 6.5 Hz, OCH2CH3), 4.71e4.80 (1H, m, CH3CH),
5.67 (1H, d, J 15.3 Hz, CH]CHCO2Et), 5.75e5.89 (2H, m, olefin), 7.04
(1H, dd, J 10.9, 15.3 Hz, CH]CHCO2Et), 7.26e7.41 (6H, m, ArH),
4.1.11. (R)-1-((2S,5S)-5-Methyl-2,5-dihydrofuran-2-yl)ethane-1,2-
diol (15). To a stirred cold solution (0 ꢁC) of the starting material 14
(4.25 g, 11.1 mmol) in THF (110 mL) under nitrogen, TBAF (27.8 mL,
1 M in THF, 27.8 mmol) was added slowly. The mixture was allowed
to warm up to rt and was monitored by TLC (24 h). The reaction was
quenched with saturated NH4Cl solution (25 mL), extracted with
EtOAc (2ꢂ25 mL), and concentrated under reduced pressure. The
crude product was filtered through a short silica gel column and
concentrated. To a solution of this product in CH2Cl2 (55 mL)
camphorsufonic acid (1 g, 4.45 mmol) was added. The mixture was
stirred at rt and monitored by TLC (6 h). The reaction mixture was
quenched with saturated aqueous NaHCO3 solution (5 mL), the
organic layer was separated and the aqueous layer was extracted
with EtOAc (3ꢂ15 mL). The combined organic phases were washed
with brine, dried over Na2SO4, and the solvent was removed under
reduced pressure. The residue was purified by silica gel column
7.56e7.68 (4H, m, ArH); 13C NMR (75 MHz, CDCl3):
d 14.4, 19.2, 24.6,
27.1, 59.9, 66.0, 96.2, 122.5, 124.6, 127.6, 127.6, 129.7, 133.5, 133.9,
135.7, 135.8, 138.5, 143.3, 165.9; ESI-MS: m/z 431 [MþNa]þ; HRMS
(ESI): [MþNa]þ, found 431.2016. C25H32O3NaSi requires 431.2018.
4.1.9. (S,2E,4Z)-6-(tert-Butyldiphenylsilyloxy)hepta-2,4-dien-1-ol
(13). To a solution of unsaturated ester 12 (2.25 g, 5.51 mmol) in
CH2Cl2 (20 mL) at 0 ꢁC under nitrogen was slowly added DIBAL-H
(9.8 mL, 20% solution in toluene, 13.7 mmol) and the mixture was
stirred for 4 h at the same temperature. The reaction was quenched
with saturated aqueous sodium potassium tartrate (5 mL) and the
stirring was continued for 1 h. The organic layer was separated and
the aqueous layer was extracted with CH2Cl2 (2ꢂ10 mL). The
combined organic layers were washed with brine, dried over
Na2SO4, and concentrated under reduced pressure. The crude
product obtained was purified by column chromatography to give
chromatography to afford the diol 15 (1 g, 68%) as yellow liquid; Rf
28
(90% EtOAc/hexane) 0.5; [
a]
ꢀ5.8 (c 0.012, CHCl3); IR (neat):
n
D
3387, 2971, 2927, 2868, 1067 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
1.28 (3H, d, J 6.7 Hz, CH3CH), 1.85 (br s, OH), 2.79 (br s, OH), 3.57
the allyl alcohol 13 (1.65 g, 82%) as colorless oil; Rf (30% EtOAc/
(1H, dd, J 5.2, 9.8 Hz, CH2OH), 3.61e3.76 (2H, m, CH2OH, CHOH),
4.70e4.78 (1H, m, CHeCHOH), 4.84e4.95 (1H, m, CH3CH),
28
hexane) 0.5; [
a]
þ48.1 (c 0.01, CHCl3); IR (neat):
n
3393, 3069,
1H NMR
1.02 (9H, s, C(CH3)3), 1.20 (3H, d, J 6.0 Hz,
D
2962, 2930, 2893, 2857, 1109, 1080, 989, 702 cmꢀ1
(300 MHz, CDCl3):
;
5.80e5.92 (2H, m, olefin); 13C NMR (75 MHz, CDCl3):
74.2, 82.2, 86.9, 126.5, 132.7; EIMS: m/z 144.
d 22.1, 63.4,
d
CH3CH), 3.96 (2H, d, J 5.2 Hz, CH3CH, CH2OH), 4.60e4.73 (1H, m,
CH2OH), 5.48 (1H, t, J 9.8 Hz, olefin), 5.55e5.66 (1H, m, CH]
CHCH2OH), 5.75 (1H, t, J 11.3 Hz, olefin), 5.85 (1H, dd, J 11.3, 15.1 Hz,
4.1.12. (R)-2,2,3,3,8,8,9,9-Octamethyl-5-((2S,5S)-5-methyl-2,5-dihy-
drofuran-2-yl)-4,7-dioxa-3,8-disiladecane (18). To solution of
a

B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
8533
compound 15 (0.49 g, 3.4 mmol) in CH2Cl2 (5 mL) 2,6-lutidine
(2.37 mL, 20.4 mmol) and TBSOTf (2.34 mL, 10.2 mmol) were added
sequentially at 0 ꢁC under nitrogen atmosphere. After stirring for 12 h
at rt, the reaction mixture was quenched with saturated aqueous
NaHCO3 (5 mL)and extractedwith EtOAc (2ꢂ5 mL). The extracts were
washed with saturated aqueous CuSO4 solution (2ꢂ5 mL), water,
brine, dried over Na2SO4, and concentrated under reduced pressure.
The resulting crude product was purified by column chromatography
to furnish 18 (0.91 g, 72%) as pale yellow liquid; Rf (3% EtOAc/hexane)
(0.51 g, 1.14 mmol) in dry THF (10 mL) under nitrogen, TBAF was
added (4.1 mL, 1 M THF solution, 4.11 mmol) at 0 ꢁC. The reaction
mixture was warmed to rt and stirred until the starting material
disappeared. The organic layer was washed with water, brine, dried
over Na2SO4, and concentrated. The residue was purified by column
chromatography to get the diol 22 (0.169 g, 68%) as pale yellow
28
liquid; Rf (80% EtOAc/Hexane) 0.5; [
(neat):
(300 MHz, CDCl3):
a
]
þ4.38 (c 0.01, CHCl3); IR
D
n
3420, 2981, 2932, 1377, 1211, 1074, 864 cmꢀ1
;
1H NMR
d
1.24 (3H, d, J 6.7 Hz, CH3CH), 1.28 (3H, s, CH3),
0.5; [
a
]
28 ꢀ27.08 (c 0.012, CHCl3); IR (neat):
n
2942, 2866, 1463, 1143,
d 0.07 (12H, d, J 6.0 Hz,
1.47 (3H, s, CH3), 3.56 (1H, dd, J 6.7, 11.3 Hz, CH2OH), 3.62e3.77 (3H,
m, CHOH, CH2OH, furanoside), 3.83e3.93 (1H, m, furanoside), 4.01
(br s, OH), 4.18 (1H, dd, J 4.5, 6.7 Hz, furanoside), 4.66 (1H, dd, J 4.5,
D
1069, 883 cmꢀ1; 1H NMR (300 MHz, CDCl3):
4ꢂCH3), 0.89(18H, d,J 4.3 Hz,2ꢂC(CH3)3),1.24(3H, d,J6.4Hz, CH3CH),
3.41e3.51 (1H, m, CHOTBS), 3.57 (1H, dd, J 5.8,10.3 Hz, CH2OTBS), 3.76
(1H, dd, J 3.3, 10.3 Hz, CH2OTBS), 4.54e4.64 (1H, m, CHCHOTBS),
4.79e4.90 (1H, m, CH3CH), 5.75 (1H, dd, J 1.5, 5.6 Hz, olefin), 5.88 (1H,
6.7 Hz, furanoside); 13C NMR (75 MHz, CDCl3):
d 18.8, 25.3, 27.3,
63.4, 71.9, 80.3, 81.7, 84.2, 85.8, 114.6; ESI-MS: m/z 241 [MþNa]þ;
HRMS (ESI): [MþNa]þ, found 241.1048. C10H18O5Na requires
241.1051.
dd, J 1.5, 6.0 Hz, olefin); 13C NMR (75 MHz, CDCl3):
22.7, 26.1, 26.2, 65.8, 77.8, 81.9, 86.4, 96.2,128.4,131.9;ESI-MS:m/z395
[MþNa]þ; HRMS (ESI): [MþNa]þ, found 395.2401. C19H40O3NaSi2
requires 395.2413.
d
ꢀ5.1, ꢀ4.4, ꢀ3.8,
4.1.16. (3aS,4S,6R,6aR)-2,2,4-Trimethyl-6-vinyltetrahydrofuro[3,4-d]
[1,3]dioxole (23). To a stirred solution of compound 22 (0.122 g,
0.55 mmol) in toluene (5 mL) was added TPP (0.44 g, 1.67 mmol)
followed by imidazole (0.145 g, 2.23 mmol) at 50 ꢁC. After 5 min
iodine (0.497 g, 1.95 mmol) in toluene (5 mL) was added at the
same temperature. After 30 min, the reaction mixture was cooled to
rt and quenched with aqueous sodium hydroxide (0.156 g in 5 mL
H2O, 3.91 mmol). The mixture was stirred until virtually all the red
deposits were dissolved. The aqueous layer was separated and
extracted with EtOAc (10 mL). The organic layer was washed with
saturated aqueous Na2S2O3 (5 mL), NaHCO3 (5 mL), water, brine,
dried over Na2SO4, and concentrated under reduced pressure. The
crude product obtained was purified by column chromatography to
4.1.13. (3aR,4R,6S,6aS)-4-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-
2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxole (20x). Prepared as
28
described for 21x. Rf (10% EtOAc/hexane) 0.4; [
CHCl3); IR (neat):
861 cmꢀ1; 1H NMR (500 MHz, CDCl3):
a]
ꢀ2.1 (c 0.009,
D
n
2985, 2934, 1376, 1254, 1213, 1157, 1077,
1.28 (3H, d, J 6.4 Hz, CH3),
d
1.34 (3H, s, CH3), 1.37 (3H, s, CH3), 1.46 (3H, s, CH3), 1.53(3H, s, CH3),
3.82e3.88 (2H, m, CH2O, furanoside), 3.97 (1H, qd, J 6.4, 4.7 Hz,
furanoside), 4.07e4.13 (2H, m, CHO, CH2O), 4.26 (1H, dd, J 6.9,
4.7 Hz, furanoside), 4.67 (1H, dd, J 6.9, 4.1 Hz, furanoside); 13C NMR
(CDCl3, 75 MHz):
d 19.0, 25.1, 25.4, 26.5, 27.6, 66.8, 75.9, 80.6, 82.3,
84.6, 86.0, 109.7, 114.6; ESI-MS: m/z 281 [MþNa]þ; HRMS (ESI):
afford the pure olefin 23 (0.077 g, 75%) as colorless oil; Rf (15%
28
[MþNa]þ, found 281.1366. C13H22O5Na requires 281.1364.
EtOAc/hexane) 0.6; [
a
]
D
þ17.8 (c 0.009, CHCl3); IR (neat):
n 2923,
2853, 1461,1375, 1247, 1158, 1076 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 1.29 (6H, d, J 6.2 Hz, CH3CH, CH3), 1.51 (3H, s, CH3), 3.86e3.97 (1H,
4.1.14. (R)-2,2,3,3,8,8,9,9-Octamethyl-5-((3aR,4S,6S,6aS)-2,2,6-tri-
methyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-4,7-dioxa-3,8-dis-
iladecane (21x). To a stirred solution of the olefin 18 (0.79 g,
2.12 mmol) in acetone/water (4:1, 10 mL) mixture, OsO4 catalytic
(0.15 mL) and NMO (0.637 g, 5.3 mmol) were added at 0 ꢁC and
stirred for 15 h at the same temperature. The reaction mixture was
quenched with Na2SO3 (2.5 g) and the solvent was evaporated. The
residue was diluted with EtOAc (10 mL) and filtered through a small
pad of Celite. The aqueous layer was extracted with EtOAc
(2ꢂ5 mL). The combined organic layers were washed with brine,
dried over Na2SO4, and concentrated. The residue was purified by
column chromatography to afford unseparable mixture of diols 19b
(0.6 g, 70%) as yellow liquid; Rf (50% EtOAc/hexane) 0.5. To a solu-
tion of the diol 19b (0.6 g, 1.47 mmol) in acetone (5 mL) at rt was
added 2,2-dimethoxypropane (0.27 mL, 2.21 mmol) followed by
catalytic camphorsulfonic acid (0.07 g, 0.3 mmol). After 6 h of
stirring, the reaction mixture was concentrated, quenched with
NaHCO3 (3 mL), extracted with CH2Cl2 (2ꢂ5 mL), and concentrated.
The crude product was purified by column chromatography to give
m, furanoside), 4.15e4.26 (2H, m, furanoside), 4.37 (1H, dd, J 5.0,
6.7 Hz, furanoside), 5.18 (1H, d, J 10.5 Hz, CH]CH2), 5.34 (1H, d, J
17.1 Hz, CH]CH2), 5.87 (1H, ddd, J 6.0, 10.5, 16.9 Hz, CH]CH2); 13
C
NMR (75 MHz, CDCl3):
d 19.0, 25.5, 27.4, 80.1, 84.8, 85.4, 86.2, 114.8,
116.9, 136.1; EIMS: m/z 184 [M]þ.
4.1.17. Ethyl 4-(4-methoxybenzyloxy)but-2-ynoate (25). To a stirred
solution of alkyne 24 (3.2 g, 18.18 mmol) in THF (60 mL) at ꢀ78 ꢁC
under N2 atmosphere was added n-BuLi (1.6 M in hexane, 17 mL,
27.2 mmol) drop wise and stirred for 20 min. Then, ethyl chlor-
oformate (5.2 mL, 54.5 mmol) was added and the solution was
warmed to rt and stirred for 45 min and quenched with a saturated
NaHCO3 solution (15 mL). The aqueous layer was extracted with
Et2O (2ꢂ15 mL). The organic layers were combined, dried over
Na2SO4, and concentrated under reduced pressure. Flash column
chromatography afforded the pure alkynoate 25 (4.14 g, 92%) as
pale yellow liquid; Rf (5% EtOAc/hexane) 0.4; IR (neat):
2840, 2236, 1713, 1513, 1250, 1090, 1057 cmꢀ1; 1H NMR (200 MHz,
CDCl3): 1.33 (3H, t, J 6.8 Hz, CH3), 3.79 (3H, s, OCH3), 4.16e4.29
(4H, m, 2ꢂOCH2), 4.53 (2H, s, OCH2Ph), 6.83 (2H, d, J 9.0 Hz, ArH),
7.24 (2H, d, J 8.3 Hz, ArH); 13C NMR (75 MHz, CDCl3):
13.8, 55.0,
n 2939,
the pure compound 21x (0.55 g, 85%) as yellow liquid; Rf (5% EtOAc/
d
28
hexane) 0.4; [
a
]
ꢀ12.5 (c 0.016, CHCl3); IR (neat):
n
2932, 2859,
0.06 (12H,
D
1254, 1086, 836, 778 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
d
d, J 4.5 Hz, 4ꢂCH3), 0.88 (18H, d, J 4.5 Hz, 2ꢂC(CH3)3), 1.27 (6H, t, J
6.0 Hz, 2ꢂCH3), 1.47 (3H, s, CH3), 3.48e3.61 (2H, m, CHOTBS,
CH2OTBS), 3.72e3.83 (2H, m, CH2OTBS, furanoside), 3.87(1H, dd, J
3.0, 4.5 Hz, furanoside), 4.05 (1H, t, J 6.7 Hz, furanoside), 4.69 (1H,
56.1, 61.9, 71.5, 78.0, 83.1, 113.7, 128.6, 129.6, 152.9, 159.4; EIMS: m/z
248 [M]þ.
4.1.18. Ethyl 2-methoxy-6-((4-methoxybenzyloxy)methyl)benzoate
(26). A neat solution of 1-methoxy cyclohexa-1,4-diene (3.19 g,
29.0 mmol), which is obtained by Birch reduction and alkynoate 25
(3.6 g, 14.5 mmol) and a catalytic amount of dichloromaleic anhy-
dride (5 mg) were heated at 180 ꢁC for 7 h in a sealed tube. Later, the
reaction mixture was cooled to rt, diluted with EtOAc (35 mL) and
washed with aqueous 10% NaHCO3 solution followed by brine. The
organic layer was dried over anhydrous Na2SO4 and the solvent was
dd, J 3.7, 6.7 Hz, furanoside); 13C NMR (75 MHz, CDCl3):
d
ꢀ5.49,
ꢀ5.41, ꢀ4.58, ꢀ4.52, 18.1, 18.4, 25.6, 25.8, 25.9, 27.5, 29.6, 64.8, 72.8,
79.7, 80.1, 84.5, 85.9, 114.3; ESI-MS: m/z 447 [MþH]þ; HRMS (ESI):
[MþNa]þ, found 469.1267. C22H46O5NaSi2 requires 469.1262.
4.1.15. (R)-1-((3aR,4R,6S,6aS)-2,2,6-Trimethyltetrahydrofuro[3,4-d]
[1,3]dioxol-4-yl)ethane-1,2-diol (22). To a solution of compound 21x

8534
B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
evaporated to give the crude product, which was purified by col-
umn chromatography to yield 26 (3.59 g, 75%) as pale yellow liquid;
3.49 (1H, t, J 5.8 Hz, CH2OH), 3.83 (3H, s, OCH3), 4.61 (2H, d, J 5.8 Hz,
OCH2), 4.90 (2H, s, OCH2), 6.81 (1H, d, J 7.8 Hz, ArH), 6.95 (1H, d, J
7.8 Hz, ArH), 7.23 (1H, t, J 7.8 Hz, ArH); 13C NMR (75 MHz, CDCl3):
Rf (15% EtOAc/hexane) 0.4; IR (neat):
n
2937, 2841, 1724, 1588, 1512,
1.34
1467,1250, 1112,1066,1031 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
d
ꢀ5.2, 26.0, 55.5, 56.4, 64.3, 96.2, 110.3, 122.3, 126.9, 129.2, 142.9,
(3H, t, J 7.5 Hz, CH3), 3.79 (3H, s, OCH3), 3.84 (3H, s, OCH3), 4.32 (2H,
q, J 7.5 Hz, OCH2), 4.43 (2H, s, OCH2), 4.57 (2H, s, OCH2), 6.86 (3H, d, J
8.3 Hz, ArH), 7.02 (1H, d, J 7.5 Hz, ArH), 7.27 (2H, t, J 8.3 Hz, ArH),
156.9; ESI-MS: m/z 305 [MþNa]þ; HRMS (ESI): [MþNa]þ, found
305.1556. C15H26O3NaSi requires 305.1548.
7.33 (1H, d, J 7.5 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d
14.0, 55.1,
4.1.22. 2-((tert-Butyldimethylsilyloxy)methyl)-3-methoxy-
55.9, 61.0, 69.4, 71.8, 110.6, 113.6, 120.3, 122.8, 129.3, 130.0, 130.3,
137.2, 156.5, 159.0, 167.5; ESI-MS: m/z 353 [MþNa]þ; HRMS (ESI):
[MþNa]þ, found 353.1362. C19H22O5Na requires 353.1364.
benzaldehyde (31). To a solution of compound 30 (0.2 g, 0.7 mmol)
in dry CH2Cl2 (4 mL) under nitrogen at
0
ꢁC, was added
DesseMartin periodinane (0.451 g, 1.06 mmol), the solution was
warmed to rt and stirred for 1 h. Later the reaction mixture was
quenched with saturated NaHCO3 (5 mL) and saturated Na2S2O3
(5 mL). The aqueous phase was extracted with CH2Cl2 (5 mL) and
washed with water, brine, dried over Na2SO4, and concentrated
under reduced pressure. The crude product obtained was purified
by the column chromatography to furnish the aldehyde 31 (0.172 g,
4.1.19. (2-Methoxy-6-((4-methoxybenzyloxy)methyl)phenyl)metha-
nol (28). To a stirred solution of 26 (3.2 g, 9.69 mmol) in dry CH2Cl2
(30 mL) under nitrogen atmosphere DIBAL-H (17.2 mL, 20% solution
in toluene, 24.2 mmol) was added drop wise at 0 ꢁC and stirred for
4 h at the same temperature. The reaction mixture was quenched
with saturated sodium potassium tartrate (10 mL) and the aqueous
phase was extracted with CH2Cl2 (2ꢂ15 mL). The combined organic
layers were washed with brine, dried (Na2SO4), and concentrated.
The crude residue was purified by silica gel chromatography to
furnish 28 (2.37 g, 85%) as yellow liquid; Rf (25% EtOAc/hexane) 0.4;
87%) as colorless liquid; Rf (7% EtOAc/hexane) 0.5; IR (neat):
2890, 2855, 1693, 1586, 1465, 1257, 1064, 838, 774 cmꢀ1 1H NMR
(300 MHz, CDCl3):
n 2936,
;
d
0.04 (6H, s, 2ꢂCH3), 0.86 (9H, s, C(CH3)3), 3.87
(3H, s, OCH3), 5.09 (2H, s, OCH2), 7.07 (1H, d, J 7.1 Hz, ArH), 7.35 (1H,
t, J 7.7 Hz, ArH), 7.50 (1H, d, J 7.7 Hz, ArH), 10.50 (1H, s, CHO); 13C
IR (neat):
n
3455, 3000, 2937, 2839, 1610, 1587, 1513, 1466, 1256,
2.80 (br s, OH),
NMR (75 MHz, CDCl3):
d
ꢀ5.3, 18.2, 25.7, 54.6, 55.9, 115.6, 120.0,
1066, 1035,1006 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
128.7, 131.6, 136.2, 156.7, 192.6; ESI-MS: m/z 319 [MþK]þ.
3.78 (3H, s, OCH3), 3.86 (3H, s, OCH3), 4.47 (2H, s, OCH2), 4.55 (2H, s,
OCH2), 4.67 (2H, s, OCH2), 6.77e6.90 (4H, m, ArH), 7.14e7.28 (3H, m,
4.1.23. tert-Butyl(2-methoxy-6-vinylbenzyloxy)dimethylsilane
(32). To a stirred solution of Ph3PCH3Br (0.516 g, 1.4 mmol) in THF
(7 mL) under nitrogen, n-BuLi (1.6 M in hexane, 0.67 mL,1.07 mmol)
was added at 0 ꢁC, brought to rt and stirred for 30 min. Then the
reaction mixture was cooled to 0 ꢁC, aldehyde 31 (0.15 g,
0.53 mmol) in THF (2 mL) was added, warmed to rt and stirred for
2 h. The reaction mixture was quenched with water (5 mL) and
extracted with ether (2ꢂ5 mL). The combined organic layers were
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure. The crude product obtained was purified by
column chromatography to afford the olefin 32 (0.1 g, 70%) as
ArH); 13C NMR (75 MHz, CDCl3):
d 55.0, 55.5, 56.0, 70.6, 71.9, 110.8,
113.7, 122.1, 128.5, 128.4, 128.5, 129.4,137.6, 157.8, 159.1; ESI-MS: m/z
311 [MþNa]þ; HRMS (ESI): [MþNa]þ, found 311.1258. C17H20O4Na
requires 311.1254.
4.1.20. tert-Butyl(2-methoxy-6-((4-methoxybenzyloxy)methyl)ben-
zyloxy)dimethylsilane (29). To a stirred solution of 28 (2.1 g,
7.29 mmol) in dry CH2Cl2 (20 mL) under N2 atmosphere were added
imidazole (1.18 g,18.2 mmol) followed by catalytic amount of DMAP
(10 mg) and TBDMSCl (1.31 g, 8.75 mmol) at 0 ꢁC. The resulting
mixture was stirred for 4 h at rt. The reaction mixture was
quenched with water (10 mL) and extracted with CH2Cl2
(2ꢂ10 mL). The organic layer was washed with brine, dried over
anhydrous Na2SO4, and concentrated under reduced pressure. The
crude product obtained was purified by silica gel column chroma-
tography to afford the TBS ether 29 (2.63 g, 90%) as pale yellow
colorless liquid; Rf (5% EtOAc/hexane) 0.4; IR (neat):
2855, 1575, 1468, 1256, 1067, 838, 775 cmꢀ1 1H NMR (400 MHz,
CDCl3):
n 2953, 2891,
;
d
0.11 (6H, s, 2ꢂCH3), 0.95 (9H, s, C(CH3)3), 3.88 (3H, s,
OCH3), 4.87 (2H, s, OCH2), 5.37 (1H, dd, J 1.4, 10.9 Hz, olefin), 5.72
(1H, dd, J 1.4, 17.5 Hz, olefin), 6.80 (1H, d, J 8.0 Hz, ArH), 7.14e7.27
(3H, m, olefin, ArH); 13C NMR (75 MHz, CDCl3):
d
ꢀ5.2, 18.4, 25.9,
liquid; Rf (5% EtOAc/hexane) 0.5; IR (neat):
n
2952, 2892, 2855, 1513,
0.0
55.5, 55.9, 109.8, 115.9, 118.3, 126.3, 128.5, 135.0, 139.6, 157.3; ESI-
MS: m/z 301 [MþNa]þ; HRMS (ESI): [MþNa]þ, found 301.1592.
C16H26O2NaSi requires 301.1599.
1466, 1252, 1068, 839, 776 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
d
(6H, s, 2ꢂCH3), 0.85 (9H, s, C(CH3)3), 3.79 (3H, s, OCH3), 3.81 (3H, s,
OCH3), 4.47 (2H, s, OCH2), 4.63 (2H, s, OCH2), 4.75 (2H, s, OCH2), 6.76
(1H, d, J 8.3 Hz, ArH), 6.82 (2H, d, J 6.9 Hz, ArH), 7.06 (1H, d, J 7.7 Hz,
4.1.24. (þ)-Varitriol (1). To oven-dried 25 mL two necked round-
bottom flask fitted with a reflux condenser was added Grubbs
second generation catalyst (10 mg, 0.01 mmol) under argon at-
mosphere followed by dry degassed CH2Cl2 (1 mL). The compound
23 (25 mg, 0.13 mmol) in CH2Cl2 (2 mL) was added followed by 32
(50 mg, 0.18 mmol) in CH2Cl2 (2 mL). The solution was refluxed for
18 h and later the reaction mixture was cooled slowly to rt. The
organic solvent was evaporated under reduced pressure and puri-
fied by column chromatography to give the protected varitriol
(32 mg, 55%) as pale yellow oil; Rf (20% EtOAc/hexane) 0.5. Later
a solution of protected varitriol (23 mg, 0.05 mmol) in THF (3 mL)
was stirred with 1 M HCl (3 mL) for 3 h at rt. The reaction mixture
was quenched with Na2CO3 and the resulting mixture was extrac-
ted with EtOAc (3ꢂ5 mL). The extracts were combined, dried
(Na2SO4), and concentrated under reduced pressure. The crude
product obtained was purified by column chromatography to result
ArH), 7.16e7.29 (3H, m, ArH); 13C NMR (75 MHz, CDCl3):
d
ꢀ5.3,
18.3, 25.9, 55.1, 55.5, 55.6, 69.1, 72.0, 110.0, 113.7, 120.7, 126.9, 128.5,
129.2, 130.4, 139.5, 157.1, 159.0; ESI-MS: m/z 425 [MþNa]þ; HRMS
(ESI): [MþNa]þ, found 425.2112. C23H34O4NaSi requires 425.2124.
4.1.21. (2-((tert-Butyldimethylsilyloxy)methyl)-3-methoxyphenyl)
methanol (30). To a stirred solution of 29 (1.8 g, 4.47 mmol) in
CH2Cl2/buffer solution (pH¼7) [prepared from NaH2PO4 and
Na2HPO4] (18:2 mL) was added DDQ (1.52 g, 6.71 mmol) at 0 ꢁC. The
reaction mixture was warmed to rt and stirring was continued for
2 h. The mixture was quenched with saturated NaHCO3 (10 mL) and
filtered through a small pad of Celite. The aqueous layer was
extracted with CH2Cl2 (2ꢂ10 mL). The combined organic layers
were washed with water, brine, dried over anhydrous Na2SO4, and
concentrated under reduced pressure. The crude product was pu-
rified by column chromatography to afford the alcohol 30 (0.9 g,
in natural (þ)-varitriol 1 (10 mg, 70%) as colorless oil; Rf (30% ac-
28
72%) as pale yellow liquid; Rf (15% EtOAc/hexane) 0.5; IR (neat):
3438, 2932, 2890, 2856, 1588, 1466, 1257, 1041, 838, 777 cmꢀ1 1H
NMR (500 MHz, CDCl3):
0.09 (6H, s, 2ꢂCH3), 0.89 (9H, s, C(CH3)3),
n
etone/dichloromethane) 0.3; [
a]
þ18.1 (c 0.005, MeOH); [lit.2a
D
25
;
[a
]
þ18.5 (c 2.30, MeOH)]; IR (neat):
n 3353, 2922, 1576, 1361,
D
d
1256, 1086 cmꢀ1 1H NMR (500 MHz, CD3COCD3):
; d 1.27 (3H, d, J

B. Srinivas et al. / Tetrahedron 66 (2010) 8527e8535
8535
4. (a) Kaskar, B.; Heise, G. L.; Michalak, R. S.; Vishnuvajjala, B. R. Synthesis 1990,
1031e1032; (b) Levene, P. A.; Tipson, R. S. J. Biol. Chem. 1936, 115, 731e747.
5. (a) Kinoshita, M.; Arai, M.; Tomooka, K.; Nakata, M. Tetrahedron Lett. 1986, 27,
1811e1814; (b) Srihari, P.; Kumar, B. P.; Subbarayudu, K.; Yadav, J. S. Tetrahedron
Lett. 2007, 48, 6977e6981.
6. (a) Argyropoulos, N. G.; Panagiotidis, T. D.; Gallos, J. K. Tetrahedron: Asymmetry
2006, 17, 829e836; (b) Harcken, C.; Martin, S. F. Org. Lett. 2001, 3, 3591e3593.
7. (a) Freeman, F.; Robarge, K. D. Tetrahedron Lett. 1985, 26, 1943e1946; (b) Shoji,
M.; Akiyama, N.; Tsubone, K.; Lash, L. L.; Sanders, J. M.; Swanson, G. T.; Sakai, R.;
Shimamoto, K.; Oikawa, M.; Sasaki, M. J. Org. Chem. 2006, 71, 5208e5220.
8. Katsuki, T.; Lee, A. W. M.; Martin, P. Ma. V. S.; Masamune, S.; Sharpless, K. B.;
Tuddenham, D.; Walker, F. J. J. Org. Chem. 1982, 47, 1373e1378.
5.7 Hz, CH3CH), 3.62 (1H, t, J 4.8 Hz, OH), 3.70 (1H, q, J 5.7 Hz,
CHOH), 3.80e3.85 (4H, m, OCH3, CHCH3), 3.91 (1H, q, J 3.8 Hz,
CHOH), 4.03 (1H, d, J 4.8 Hz, OH), 4.24 (1H, br s, OH), 4.29 (1H, t, J
4.8 Hz, CHeCH]CHeAr), 4.71 (2H, d, J 4.8 Hz, CH2OH), 6.20 (1H, dd,
J 6.7, 15.4 Hz, olefin), 6.89 (1H, d, J 7.7 Hz, ArH), 7.09e7.15 (2H, m,
olefin, ArH), 7.22 (1H, t, J 7.7 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d
19.4, 55.3, 56.0, 76.4, 77.1, 80.0, 85.2, 110.6, 119.2, 127.9, 129.3,
129.4, 132.4, 138.9, 158.8; ESI-MS: m/z 303 [MþNa]þ; HRMS (ESI):
[MþNa]þ, found 303.1212. C15H20O5Na requires 303.1208.
9. (a) Takashima, Y.; Kaneko, Y.; Kobayashi, Y. Tetrahedron 2010, 66, 197e207; (b)
Georges, Y.; Ariza, X.; Garcia, J. J. Org. Chem. 2009, 74, 2008e2012.
10. (a) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405e4408; (b) Sabitha, G.;
Sudhakar, K.; Reddy, N. M.; Rajkumar, M. Tetrahedron Lett. 2005, 46, 6567e6570.
11. (a) Garcia, C.; Martin, T.; Martin, V. S. J. Org. Chem. 2001, 66, 1420e1428; (b)
Ramana, C. V.; Salian, S. R.; Gurjar, M. K. Tetrahedron Lett. 2007, 48, 1013e1016.
12. (a) Pradilla, R. F.; Castellanos, A.; Osante, I.; Colomer, I.; Sanchez, M. I. J. Org.
Chem. 2009, 74, 170e181; (b) Pradilla, R. F.; Castellanos, A. Tetrahedron Lett.
2007, 48, 6500e6504.
Acknowledgements
We thank CSIR, New Delhi, India, for fellowships to B.S and R.S.
References and notes
13. (a) Berry, C. R.; Hsung, R. P.; Antoline, J. E.; Petersen, M. E.; Challeppan, R.;
Nielson, J. A. J. Org. Chem. 2005, 70, 4038e4042; (b) Trost, B. M.; Kallander, L. S.
J. Org. Chem. 1999, 64, 5427e5435; (c) Ainai, T.; Wang, Y.-G.; Tokoro, Y.;
Kobayashi, Y. J. Org. Chem. 2004, 69, 655e659.
14. (a) Garegg, P. G.; Samuclson, B. Synthesis 1979, 813e814; (b) Ghosh, S.;
Shashidhar, J.; Dutta, S. K. Tetrahedron Lett. 2006, 47, 6041e6044.
15. Sridhar, R.; Srinivas, B.; Rama Rao, K. Tetrahedron 2009, 65, 10701e10708.
16. (a) Ding, F.; Jennings, M. P. J. Org. Chem. 2008, 73, 5965e5976; (b) Guo, H.;
Mortensen, M. S.; O’Doherty, G. A. Org. Lett. 2008, 10, 3149e3152.
17. (a) Birch, A. J.; Dastur, K. P. Tetrahedron Lett. 1972, 13, 4195e4196; (b) Birch, A. J.;
Dastur, K. P. J. Chem. Soc., Perkin Trans. 1 1973, 1650e1652.
1. (a) Faulkner, D. J. Nat. Prod. Rep. 2000, 17, 1e6; (b) Faulkner, D. J. Nat. Prod. Rep.
2000, 17, 7e55; (c) Faulkner, D. J. Nat. Prod. Rep. 1999, 16, 155e198; (d) Brase, S.;
Encinas, A.; Keck, J.; Nising, C. F. Chem. Rev. 2009, 109, 3903e3990.
2. (a) Malmstrom, J.; Christophersen, C.; Barrero, A. F.; Oltra, J. E.; Justicia, J.;
Rosales, A. J. Nat. Prod. 2002, 65, 364e367; (b) Mayer, A. M. S.; Gustafson, K. R.
Eur. J. Cancer 2004, 40, 2676e2704.
3. (a) Clemens, R. T.; Jennings, M. P. Chem. Commun. 2006, 2720e2721; (b)
McAllister, G. D.; Robinson, J. E.; Taylor, R. J. K. Tetrahedron 2007, 63,
12123e12130; (c) Kumar, V.; Shaw, A. K. J. Org. Chem. 2008, 7526e7531; (d)
Palik, M.; Karlubikova, O.; Lasikova, A.; Kozisek, J.; Gracza, T. Eur. J. Org. Chem.
2009, 709e715; (e) Ghosh, S.; Pradhan, T. K. J. Org. Chem. 2010, 75, 2107e2110;
(f) Brichacek, M.; Batory, L. A.; McGrath, N. A.; Njardarson, J. T. Tetrahedron
2010, 66, 4832e4840; (g) Palik, M.; Karlubikova, O.; Lackovicova, D.; Lasikova,
A.; Gracza, T. Tetrahedron 2010, 66, 5244e5249; (h) Nagarapu, L.; Paparaju, V.;
Satyender, A. Bioorg. Med. Chem. Lett. 2008, 18, 2351e2354; (i) Senthilmurugan,
A.; Aidhen, I. S. Eur. J. Org. Chem. 2010, 555e564.
18. (a) Yadav, J. S.; Srihari, P. Tetrahedron: Asymmetry 2004, 15, 81e89; (b) Yoshino,
T.; Ng, F.; Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 14185e14191.
19. (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155e4156; (b) Dess, D. B.;
Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277e7287.
20. Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003,
125, 11360e11370.