Stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one by Prins reaction and olefin cross-metathesis

Article abstract of DOI:10.1016/j.tetasy.2008.12.004

Prins and olefin cross-metathesis reactions were used as the key steps for the stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-one. Removal of MOM protecting groups under

Full text of DOI:10.1016/j.tetasy.2008.12.004

Tetrahedron: Asymmetry 20 (2009) 184–191
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective total synthesis of (+)-strictifolione and (6R)-6-[(4R,6R)
-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-pyran-2-
one by Prins reaction and olefin cross-metathesis
*
Gowravaram Sabitha , Narjis Fatima, Peddabuddi Gopal, C. Nagendra Reddy, Jhillu S. Yadav
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Prins and olefin cross-metathesis reactions were used as the key steps for the stereoselective total syn-
thesis of (+)-strictifolione and (6R)-6-[(4R,6R)-4,6-dihydroxy-10-phenyldec-1-enyl]-5,6-dihydro-2H-
pyran-2-one. Removal of MOM protecting groups under neutral conditions using CeCl3ꢀ7H2O is an attrac-
tive addition to the present strategy.
Received 11 November 2008
Accepted 3 December 2008
Available online 12 January 2009
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
However, the retrosynthesis for target molecule 2 reveals that it
could be obtained by olefin cross-metathesis reaction of 9 and 8
a
-Pyrone derivatives (5,6-dihydro-2H-pyran-2-ones), isolated
followed by simple manipulations. Similarly 9, could in turn be ob-
tained from 10, was prepared via Prins route from 7.
from natural sources,1 have attracted much attention over the last
decade due to their medicinal potential2 as antiviral, antifungal,
antibacterial, antimalarial and antitumor compounds, as well as
plant growth inhibition. Strictifolione 1,3 a 6-substituted 5,6-dihy-
2. Results and discussion
dro-a-pyrone, has been isolated by Aimi et al. from the stem bark
The synthesis starts from the known homoallylic alcohol 7.11
The classical TFA-mediated Prins reaction between the known
homoallylic alcohol 7 and benzaldehyde 11, followed by hydro-
lysis of the resulting trifluoroacetate yielded the desired trisub-
stituted pyran. MOM protection of the resulting alcohol with
MOMCl in the presence of Hunig’s base afforded 6 in 90% yield.
The tetrahydropyran ring was opened in a different manner
using Li in liquid NH3 to furnish the key open chain compound
12. The primary alcohol was protected as tosyl derivative 13
and exposure to a base afforded epoxide 14. Opening of the
epoxide with vinyl magnesium bromide was unsuccessful, but
we were successful in opening of the epoxide with the Li acety-
lide to provide the homopropargylic alcohol 15 in 80% yield. Par-
tial reduction of the terminal triple bond using Lindlar’s catalyst
gave the required homoallylic alcohol 16. MOM deprotection un-
der neutral conditions12 using CeCl3ꢀ7H2O in CH3CN/MeOH (1:1)
afforded diol 4 (Scheme 2).
The other key intermediate 5 was synthesized starting from
homoallylic alcohol 8.13 Accordingly, the secondary hydroxyl was
protected as the silyl ether 17 with TBDMSCl and imidazole and
the primary THP ether was cleaved to furnish a free alcohol. Oxida-
tion using IBX in DMSO/CH2Cl2 furnished the aldehyde, which was
subjected directly to a homologation using Still–Gennari condi-
tions to give Z-unsaturated ester. Compound 18 was lactonized
using methanol in the presence of PTSA to afford vinyl lactone 5
in very good yield (Scheme 3).
of Cryptocarya strictifolia that grows in Indonesia, and has been
shown to display antifungal activity. Its structure was proposed
based on spectroscopic analysis. The absolute configuration of
strictifolione was confirmed by accomplishing its first total synthe-
sis as being (6R,40S,60S).4
Later, two more asymmetric syntheses5 and a formal synthesis
were reported.6 (6R)-6-[(4R,6R)-4,6-Dihydroxy-10-phenyldec-1-
enyl]-5,6-dihydro-2H-pyran-2-one 27 is also one such natural
product, isolated from Ravensara crassifolia by Hostetmann et al.
along with a structurally similar compound 3.8 The absolute con-
figuration of these 6-alkylated
a-pyrones from R. crassifolia was
determined by LC-NMR.9 To the best of our knowledge, only one
report has appeared with regard to the synthesis of 2.10 (see Fig. 1).
Within our recently initiated program on synthesis of bioactive
lactones where Prins and ring-closing metathesis (RCM) reactions
are used as one of the key steps,11 we decided to undertake a ster-
eoselective synthesis of 1 and 2 using Prins, olefin cross-metathesis
reactions and MOM deprotection as key steps. Retrosynthetic anal-
ysis revealed that target compound 1 could be obtained from 4 and
5 by olefin cross-metathesis using Grubbs’ catalyst. Compound 4,
could in turn be obtained from 6, was prepared via a Prins route
from 7. Vinyl lactone 5 could in turn be prepared from known
allylic alcohol 8 (Scheme 1).
* Corresponding author. Tel./fax: +91 40 27160512.
E-mail address: gowravaramsr@yahoo.com (G. Sabitha).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.12.004

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
185
O
OH OH
O
1
3
5
OH OH
OH
4
2'
2
6
O
O
O
O
6'
4'
1'
1
2
3
Figure 1.
O
R1
R4
R3
R2
O
1 and 2
+
n
4: n=1, R1 = H, R2 = OH, R3 = OH, R4 =H
5
9; n=3, R1 = OH, R2 = H, R3 = H, R4 = OMOM
+
4; n = 1, R = H
9; n = 3, R = MOM
OMOM
OH
OH
OBn
OTHP
Ph
OBn
O
n
8
7
6; n = 0
10; n = 4
Scheme 1. Retrosynthetic analysis for 1 and 2.
With the two key fragments 4 and 5 in hand, the next concern
was to couple them by olefin cross-metathesis reaction.14 Thus,
cross-coupling reaction of 4 and 5 using Grubbs’ second generation
catalyst in dichloromethane at 50 °C led to a target molecule 1 di-
rectly as a single cross-coupled product in 63% yield (Scheme 4).
The spectroscopic data of synthetic 1 are in good agreement with
that reported in the literature.
Next, the olefin cross-metathesis reaction14 of homoallyl alco-
hol 10 with the allyl alcohol 813 in the presence of Grubbs’ second
generation catalyst (10 mol %) in dichloromethane at room tem-
perature afforded a cross-coupling product 23 in 70% yield and
with excellent stereoselectivity (E/Z ratio of 20:1) as observed by
1H NMR spectroscopy. In this reaction, the formation of the homo
dimer of 10 was observed in very low yield as a by-product. The
two hydroxyl groups in 23 were protected as MOM ethers 24,
and subsequent removal of the THP group using PPTS methanol
gave primary alcohol 25. Oxidation using iodoxybenzoic acid
(IBX) in DMSO/DCM16 at room temperature, followed by chain
elongation using Still–Gennari Wittig reaction ((F3CCH2O)2POCH2-
Having achieved a synthesis of the target 1, we now undertook
the synthesis of 2, which also relies on the use of Prins, olefin cross-
metathesis reactions and MOM deprotection as key steps. The syn-
thesis of 2 commenced from the known homoallylic alcohol 7.11
Prins cyclization of 7 with 5-phenyl-1-pentanal 19 in the pres-
ence of TFA followed by hydrolysis of the resulting trifluoroacetate
yielded the desired trisubstituted pyran 20 (Scheme 5). The sec-
ondary hydroxyl group in 20 was protected as MOM ether 9 using
MOMCl and Hunig’s base in 95% yield. Compound 9, on debenzyla-
tion using Li in liquid NH3, gave primary alcohol 21. Alcohol 21 on
exposure to TPP, iodine, and imidazole in refluxing ethanol was
converted into the corresponding iodide 22 in 3 h, which on treat-
ment with Zn dust in Et2O/CH3CN (3:1) at 0 °C to rt, furnished the
key ring-opened homoallylic alcohol 23 with the required anti-1,3-
diol system. The anti relative stereochemistry of the 1,3-diol was
established by its conversion to the corresponding acetonide (PPTS,
2,2-dimethoxypropane, dry DCM, rt, 2 h, 95% yield). The anti rela-
tive configuration of the hydroxyl groups was confirmed by analy-
sis of the 13C NMR spectra (d = 25.08 and 24.85 ppm for the methyl
groups and 100.02 ppm for the quaternary center).15
COOMe, NaH, THF, ꢁ78 °C), afforded the
a,b-unsaturated ester 26
predominantly as the Z-isomer, established by 1H NMR
spectroscopy.
Finally, removal of the MOM protecting group and lactonization
were realized in a one-pot manner in the presence of CeCl3 ꢀ 7H2O
in MeOH/CH3CN (1:1)12 to furnish target molecule in 73% isolated
yield. Synthetic 1 was completely identical in all respects (mp, 1H,
13C NMR, and ½a 2D5
ꢂ
) with the natural one.
3. Conclusions
In conclusion, the total stereoselective synthesis of target mol-
ecules 1 and 2 has been accomplished. The highlights of the syn-
thesis are the successful utilization of the Prins reaction to
introduce the stereogenic centers at C40 and C60 and a cross-

186
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
OMOM
11
i) PhCHO , TFA, CH2Cl2
i) Li-liq NH3, dry THF
OH
OBn
-78 oC, 60%
ii) TsCl, Et3N, CH2Cl2
K2CO3, MeOH
r.t, 0.5 h, 59%
OBn
Ph
O
7
Bu2SnO(cat), 0 oC-r.t.
ii) MOMCl, Hunig's base,
6
0 oC-r.t., 2 h, 90%
2 h, 78%
MOMO
OH
OMOM
O
R1
LiC CH, DMSO
0 oC-r.t., 4 h, 80%
NaH, THF, r.t
1 h, 85%
12; R1 = OH
1
13
14
; R = OTs
MOMO
OH
MOMO
Pd/C, CaCO3, EtOAc,
H2,
Quinoline, r.t., 85%
16
15
OH OH
CeCl3·7H2O, CH3CN:MeOH (1:1)
ref lux, 12 h, 60%
4
Scheme 2.
i) IBX, DMSO/ Dry, CH2Cl2,
70%, r.t., 6 h
OTBS
OH
i) TBDMSCl, Imidazole
OTHP
OH
CH2Cl2,0 oC-r.t.,85%
ii) comm.NH4Cl,MeOH
reflux, 4 h, 60%
3
2
2
2
2
3
(CF CH O) P(O)CH CO CH ,
ii)
NaH, dry THF, 75%
17
8
O
OTBS
MeOH, PTSA
O
CO2Me
r.t., 2 h, 78%
18
5
Scheme 3.
O
OH
OH
O
Grubbs' II (15 mol%), CH2Cl2
50 oC, 4 h, 63%
OH OH
O
O
+
CH3
CH3
N
N
4
5
H3C
CH3
1
CH3
H3C
Cl
Ru
Cl
Ph
P
Scheme 4.

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
187
OR
19,
i) Ph-(CH2)4-CHO
CH2Cl2, rt, 4 h
TFA
i) Li in liq NH3
91%
OH
OBn
OBn
K2CO3, MeOH
r.t, 1 h, 65%
ii) MOMCl, Hunig's base,
CH2Cl2, 0 oC-r.t.,
4 h, 95%
ii) TPP, I2 ,imidazole
Ph
O
3
3
Et2O/CH3CN, (3:1) 0 oC-rt
7
20; R = H
R = MOM
9;
OH
OR
OTHP
OH
OMOM
Zn dust, EtOH,
92% 2 h
8
X
Ph
Grubbs' II,
O
Ph
3
10
CH3
CH3
N
N
21; R = MOM, X = OH
22; R = MOM, X = I
H3C
CH3
CH3
H3C
Cl
Ru
P
Cl
Ph
i) MOMCl, Hunig's base,
CH2Cl2, r.t., 86%, 4 h
OH
OMOM
OH
MOMO
OMOM
OMOM
Ph
3
Ph
3
ii) PPTS/MeOH
12 h, 81%
24; R2 = THP
25; R2 = H
23
CeCl3·7H2O
CH3CN/MeOH (1:1)
MOMO
3
OMOM
OMOM
i) IBX/DMSO/CH2Cl2 80%
2
Ph
(F3CCH2O)2POCH2COOMe
NaH, THF, -78 oC-rt
85%, 1 h
r.t., 12 h, 73%
CO2Me
26
Scheme 5.
metathesis (CM) reaction to control the (E)-double bond at C10–C20
and removal of MOM protecting groups under neutral conditions.
Further studies on the utility of the vinyl lactone for other mole-
cules are currently in progress and will be reported in due course.
(IICT, Hyderabad). Column chromatography was performed on sil-
ica gel (60–120 mesh) supplied by Acme Chemical Co., India. TLC
was performed on Merck 60 F-254 silica gel plates. Optical rota-
tions were measured with JASCO DIP-370 Polarimeter at 25 °C.
4. Experimental
4.1. General
4.1.1. (3S)-5-(Tetrahydro-2H-2-pyranyloxy)-1-penten-3-ol 8
A mixture of epoxy iodo compound (7.0 g, 22.4 mmol), NaI
(8.35 g, 56.08 mmol) and activated Zn dust (4.39 g, 67.73 mmol)
in methanol (30 mL) was refluxed under N2 atm for 3 h. The sol-
vent was removed under reduced pressure and the residue was
purified by silica gel column chromatography to afford the 8 as a
Reactions were conducted under N2 in anhydrous solvents such
as CH2Cl2, THF, and EtOAc. All reactions were monitored by TLC
(silica-coated plates and visualizing under UV light). Light petro-
leum ether (bp 60–80 °C) was used. Yields refer to chromatograph-
ically and spectroscopically (1H, 13C NMR) homogeneous material.
Air-sensitive reagents were transferred by syringe or double-ended
needle. Evaporation of solvents was performed at reduced pressure
on a Buchi rotary evaporator. 1H and 13C NMR spectra of samples in
CDCl3 were recorded on Varian FT-200 MHz (Gemini) and Bruker
UXNMR FT-300 MHz (Avance) spectrometers. Chemical shifts (d)
are reported relative to TMS (d = 0.0) as an internal standard. Mass
spectra were recorded in E1 conditions at 70 eV on an LC-MSD
(Agilent technologies) spectrometers. All high resolution spectra
were recorded on QSTAR XL hybrid ms/ms system (Applied Biosys-
tems/MDS sciex, foster city, USA), equipped with an ESI source
yellow liquid (9.6 g, 80%). ½a D25
ꢂ
¼ ꢁ9:6 (c 3.75, CHCl3) 1H NMR
(CDCl3, 300 MHz): d 5.92–5.80 (m, 1H), 5.31–5.06 (m, 2H), 4.60–
4.55 (m, 1H), 4.36–4.26 (m, 1H), 4.00H–4.34 (m, 4H), 2.74 (s, OH,
1H), 1.91–1.47 (m, 8H). 13C NMR (CDCl3, 50 MHz): 140.4, 114.2,
98.8, 71.9, 65.6, 62.1, 36.2, 30.4, 25.2, 19.3. ESIMS: 209 (M+Na).
4.1.2. (3S)-3-[1-(tert-Butyl)-1,1-dimethylsilyl]oxy-4-penten-1-
ol 17
To the THP ether (2.5 g, 7.81 mmol) in methanol (20 mL), com-
mercial NH4Cl (0.49 g, 9.36 mmol) was added and heated at reflux
for 4 h. Methanol was removed, diluted with water (15 mL), and
extracted with ether (3 ꢃ 25 mL). The combined ether extracts
were dried over Na2SO4. Evaporation of solvent, followed by

188
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
column chromatography (ethylacetate/pet ether, 4:6) furnished
ual mixture was taken in ether (35 mL) and washed with water
(2 ꢃ 10 mL), brine (1 ꢃ 10 mL), and dried over Na2SO4. Removal
of the solvent and purification by column chromatography of the
crude product afforded alcohol 12 (1.1 g, 60%) as a colorless liquid.
THP cleaved product (1.01 g, 60% yield). ½a D25
¼ þ1:9 (c 1.2, CHCl3).
ꢂ
1H NMR (CDCl3, 300 MHz): d 5.90–5.77 (m, 1H), 5.24–5.05 (m, 2H),
4.43–4.35 (m, 1H), 3.84–3.64 (m, 2H), 2.13 (br s, OH, 1H), 1.88–
1.62 (m, 2H), 0.92 (s, 9H), 0.06 (s, 6H). 13C NMR (CDCl3, 50 MHz):
d 140.6, 114.3, 73.1, 60.1, 39.1, 25.8, 18.1, ꢁ4.4. ESIMS: 239
(M+Na).
Rf = 0.5 (SiO2, 20% EtOAc in hexane). ½a D25
ꢂ
¼ þ41 (c 2.4, CHCl3); 1H
NMR (CDCl3, 300 MHz): d 7.31–7.13 (m, 5H), 4.69 (s, 2H), 4.02–3.80
(m, 2H), 3.65–3.55 (m, 1H), 3.48–3.38 (m, 4H), 3.24 (s, OH, 1H),
2.77–2.59 (td, 2H, J = 3.0, 6.0 Hz), 2.00–1.50 (m, 4H): 13C NMR
(CDCl3, 50 MHz): d: 141.76, 128.42, 128.23, 125.92, 96.50, 75.75,
68.51, 66.84, 55.97, 37.37, 36.81, 31.64 HRMS: calcd 277.1415
(M+Na), found 147.1423 (M+Na).
4.1.3. Methyl(2Z,5S)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-
2,6-heptadienoate 18
To a stirred suspension of NaH (1.06 g, 46.4 mmol) in dry THF
(40 mL) at 0 °C under nitrogen was added bis-(2,2,2-trifluoroethyl)
(methoxy-carbonylmethyl) phosphonate (8.09 g, 25.07 mmol) in
dry THF (20 mL). After the mixture was stirred for 30 min at 0 °C,
the reaction mixture was cooled to ꢁ78 °C, and then a solution of
aldehyde (5 g, 23.3 mmol) in dry THF (20 mL) was added dropwise.
After stirring for 1 h, the reaction mixture was diluted with 5 mL of
Et2O and quenched by the slow addition of 4 mL of H2O. The layers
were separated, and the aqueous phase was extracted with two
10 mL portions of Et2O. The organic extract was washed with brine
solution, dried over anhydrous Na2SO4, and concentrated in vacuo.
The crude product was purified by column chromatography on sil-
4.1.7. (2R)-2-[(2S)-2-(Methoxymethoxy)-4-phenylbutyl]
oxetane 14
To a stirred suspension of freshly activated sodium hydride
(0.32 g, 14.1 mmol) in dry THF (30 mL) at 0 °C, compound 13
(4 g, 9.45 mmol) in dry THF (10 mL) was added dropwise. After
completion of the reaction (3 h), the reaction mixture was
quenched with saturated aqueous NH4Cl solution and extracted
with EtOAc. The organic layer was washed with brine solution,
dried over anhydrous Na2SO4, and concentrated under reduced
pressure, purification by silica-gel column chromatography affor-
ica gel to give
a
,b-unsaturated ester 18 (4.7 g, 75%) as a viscous li-
ded 14 (1.9 g, 85%) as a viscous liquid. ½a D25
¼ þ12:3 (c 2.1, CHCl3).
ꢂ
quid. ½a 2D5
ꢂ
¼ ꢁ8:1 (c 0.5, CHCl3). 1H NMR (CDCl3, 300 MHz): d 6.30
1H NMR (CDCl3, 300 MHz): d 7.30–7.19 (m, 5H), 4.71 (s, 2H), 3.87–
3.75 (tt, J = 6.04, 12.08, 15.10 Hz, 1H), 3.43 (s, 3H), 3.05–2.97 (m,
1H), 2.81–2.60 (m, 2H), 2.50–2.46 (m, 1H), 1.98–1.57 (m, 4H). 13C
NMR (CDCl3, 50 MHz): d 141.86, 128.31, 128.2, 125.76, 95.7,
75.18, 55.59, 49.42, 47.29, 37.86, 36.7, 31.38. HRMS calcd
259.1310 (M+Na), found 259.1320 (M+Na).
(dt, J = 4.5, 6.7 Hz, 1H), 5.86–5.73 (m, 2H), 5.23–5.03 (qt, J = 2.2,
1.5 Hz, 2H), 4.27 (q, 1H), 3.69 (s, 3H), 2.86 (dt, J = 2.2, 1.5 Hz, 2H),
0.89 (s, 9H), 0.04 (s, 6H). 13C NMR (CDCl3, 50 MHz): d 158.8,
146.3, 120.5, 72.4, 51.0, 37.0, 29.6, 25.7, ꢁ4.7.
4.1.4. (6R)-6-Vinyl-5,6-dihydro-2H-2-pyranone 5
To a stirred solution of compound 18 (0.5 g, 1.96 mmol) in
MeOH was added a catalytic amount of PTSA under an N2 atmo-
sphere. After stirring for 3 h at room temperature, the reaction
mixture was quenched with solid NaHCO3 and filtered off, the sol-
vent was removed under reduced pressure and the residue was
purified by silica gel column chromatography to afford compound
5 as a yellow liquid (019 g, 80%). 1H NMR (CDCl3, 300 MHz): d
6.87–6.80 (m, 1H), 6.06–5.87 (m, 2H), 5.45–5.37 (t, 1H,
J = 1.1 Hz), 5.32–5.26 (t, 1H), 4.95–4.86 (m, 1H), 2.47–2.41 (m,
2H): 13C NMR (CDCl3, 50 MHz): d 163.7, 144.3, 134.8, 121.6,
117.8, 77.7, 29.3; HRMS: calcd 147.0429 (M+Na); found 147.0421
4.1.8. (4R,6S)-6-(Methoxymethoxy)-8-phenyl-1-octyn-4-ol 15
A lithium acetylide-EDA complex (0.33 g 19.4 mmol) was added
to a solution of epoxide 14 (2 g, 8.47 mmol) in dry DMSO (22 mL),
and the mixture was stirred overnight at room temperature. After
quenching with ice, 0.5 M H2SO4 was used to neutralize the basic
solution to pH 7. The solution was extracted with diethyl ether
(3 ꢃ 50 mL), dried over MgSO4, and concentrated in vacuo to give
15 (1.77 g, 80%) as a colorless oil. ½a D25
¼ þ40:7 (c 1.95, CHCl3).
ꢂ
1H NMR (CDCl3, 300 MHz): d 7.27–7.10 (m, 5H), 4.65 (s, 2H),
4.07–3.96 (m, 1H), 3.90–3.80 (m, 1H), 3.41 (s, 3H), 2.92 (br s, 1H,
OH), 2.70–2.61 (td, J = 2.83, 3.77 Hz, 2H), 2.40–2.33 (m, 2H), 1.96
(t, J = 2.6 Hz, 1H), 1.94–1.66 (m, 4H). 13C NMR (CDCl3, 50 MHz): d
141.6, 128.3, 128.1, 125.1, 96.4, 80.9, 75.6, 70.5, 66.4, 55.8, 40.2,
36.6, 31.6, 27.2. HRMS: calcd 285.1466 (M+Na), found 285.1478
(M+Na).
(M+Na). ½a 2D5
¼ þ95:2 (c 0.85, CHCl3).
ꢂ
4.1.5. (2R,4R,6S)-2-[(Benzyloxy)methyl]-4-(methoxymethoxy)-
6-phenyltetrahydro-2H-pyran 6
To a solution of hydroxyl compound (2.5 g, 8.38 mmol) in anhy-
drous DCM (10 mL) at 0 °C under nitrogen was added iPr2NEt
(6.54 g, 50.28 mmol) dropwise and after 5 min MOMCl (3.08 mL,
41.9 mmol) was added dropwise. After stirring for 2 h at room
temperature, the reaction mixture was diluted with water, satu-
rated aqueous NH4Cl, and brine solution, then dried over anhy-
drous Na2SO4. The residue was purified on silica gel column
chromatography to afford pure 6 as a clear colorless liquid
4.1.9. (4R,6S)-6-(Ethylperoxy)-8-phenyl-1-octen-4ol 16
To solution of alkyne 15 (10 g, 38.02 mmol) in EtOAc, 3 drops of
quinoline and Lindlar’s catalyst (Pd/BaSO4) were added and stirred
at room temperature under an H2 atm for 12 h. After completion of
the reaction, the reaction mixture was filtered and the solvent was
removed under reduced pressure. The crude product was purified
on silica gel column chromatography to afford compound 16 as a
(2.57 g, 90%).
½
a 2D5
ꢂ
¼ ꢁ13 (c 0.3, CHCl3). 1H NMR (CDCl3,
yellow liquid (8.46 g, 85%). ½a D25
ꢂ
¼ þ35:5 (c 1.6, CHCl3); 1H NMR
300 MHz): d 7.33–7.21 (m, 10H), 4.66 (s, 2H), 4.57 (s, 2H), 4.37
(m, 1H), 3.93–3.80 (m, 1H), 3.77–3.67 (m, 1H), 3.66–3.47 (m,
2H), 3.34 (s, 3H), 2.23–2.08 (tq, J = 2.6 Hz, 2H), 1.56–1.28 (m,
2H).13C NMR (CDCl3, 50 MHz): d 141.9, 137.5, 128.3, 128.2, 127.6,
127.5, 127.4, 125.9, 94.4, 77.8, 75.5, 73.4, 73.1, 73.0, 55.3, 40.5,
35.2. ESIMS: 365 (M+Na).
(CDCl3, 300 MHz): d 7.28–7.08 (m, 5H), 5.94–5.70 (m, 1H), 5.14–
5.03 (dt, 2H, J = 5.8, 11.7 Hz), 4.64 (s, 2H), 3.86 (td, 2H, J = 5.8,
11.7 Hz), 3.40 (s, 3H), 2.70–2.59 (m, 2H), 2.20 (td, 2H, J = 7.3, 5.8,
1.4 Hz), 1.99–1.55 (m, 4H); 13C NMR (CDCl3, 50 MHz): d 141.8,
134.8, 128.4, 128.2, 125.8, 117.5, 96.4, 75.7, 67.1, 55.8, 42.0, 40.8,
36.7, 31.6; HRMS: calcd 287.1623 (M+Na), found 287.1615 (M+Na).
4.1.6. (2S,4S)-4-(Ethylperoxy)-6-phenylhexane-1,2-diol 12
To a solution of lithium (0.13 g, 43.8 mmol) in liquid NH3
(25 mL) was added compound 6 (2.5 g, 7.3 mmol) in dry THF
(8 mL). The mixture was stirred for 2–3 h and quenched with solid
NH4Cl (1.36 g). Ammonia was allowed to evaporate and the resid-
4.1.10. (3S,5R)-1-Phenyl-7-octene-3,5-diol 4
To a stirred solution of compound 16 (0.3 g, 1.13 mmol) in a
mixture of MeOH (5 mL) and CH3CN (5 mL) was added CeCl3ꢀ7H2O
(cat.) under N2,12 then the mixture was stirred at rt for 12 h. The
mixture was quenched with solid NaHCO3 (0.5 g) and filtered,

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
189
the solvent was removed under reduced pressure and the residue
was purified by silica gel column chromatography (8:13 EtOAc/
hexane) to afford compound 4 as a yellow liquid (0.15 g, 60% yield),
1H NMR (CDCl3, 300 MHz): d 7.28–7.9 (m, 5H), 5.85–5.70 (m, 1H),
5.16–5.08 (m, 2H), 4.02–3.88 (m, 2H), 2.85–2.59 (m, 2H), 2.28–2.19
(m, 2H), 1.92–1.59 (m, 4H); 13C NMR (CDCl3, 50 MHz): d 141.9,
134.5, 128.3, 125.8, 118.2, 68.6, 68.1, 41.9, 39.0, 32.1; HRMS: calcd
243.1360 (M+Na), found 243.1371 (M+Na).
anhydrous Na2SO4 (2 g), and concentrated under vacuum to re-
move the solvent and the crude residue was purified by column
chromatography (2:23 EtOAc/hexane) to afford the MOM ether 9
(10.2 g, 95% yield) as a colorless oil. Rf = 0.4 (SiO2, 15% EtOAc in
hexane); ½a 2D5
ꢂ
¼ þ5:7 (c 1.02, CHCl3); 1H NMR (200 MHz, CDCl3):
d (ppm) = 7.32–7.02 (m, 10H), 4.62 (s, 2H), 4.54 (q, J = 11.0,
13.2 Hz, 2H), 3.75–3.57 (m, 1H), 3.55–3.19 (m, 7H), 2.60 (t,
J = 7.3 Hz, 2H), 2.03–1.84 (m, 2H), 1.73–1.05 (m, 8H); 13C NMR
(100 MHz, CDCl3): d (ppm) = 142.4, 138.2, 128.2, 128.1, 127.5,
127.4, 125.4, 94.2, 75.7, 74.9, 73.3, 73.1, 72.8, 55.2, 38.4, 35.9,
35.8, 35.3, 31.4, 25.2; IR (neat): 2927, 2857, 1602, 1494, 1452,
1369, 1102, 1038, 741, 699 cmꢁ1; HRMS(ESI): [M+Na]+ m/z calcd
for C25H34O4Na: 421.2354; found: 421.2341 (ꢁ3.2751 ppm error).
4.1.11. (6R)-6-[(E,4S,6S)-4,6-Dihydroxy-8-phenyl-1-octenyl]-
5,6-dihydro-2H-2-pyranone 1
A solution of compound 4 (0.152 g, 0.69 mmol) and compound
5 (0.438 g, 3.45 mmol) in dichloromethane (100 mL) was first bub-
bled with nitrogen flow, after which Grubbs type II catalyst
(0.089 g, 0.103 mmol) was added at once and the resulting mixture
heated under nitrogen at 50 °C for 4 h. After cooling and concentra-
tion, the solvent was removed and the crude mixture was purified
by flash chromatography (AcOEt/hexanes: 20/80) to give lactone 1
4.1.14. [(2R,4R,6R)-4-(Methoxymethoxy)-6-(4-phenylbutyl)
tetrahydro-2H-2-pyranyl]methanol 21
Lithium metal (500 mg, 71.6 mmol) was added to a stirred solu-
tion of freshly distilled ammonia (10 mL) and compound 9 (9.5 g,
23.8 mmol) in dry THF (50 mL) in a 250 mL two necked round bot-
tomed flask fitted with a cold finger condenser at ꢁ33 °C. The reac-
tion mixture was then stirred for another 10 min at ꢁ33 °C and
quenched by the addition of solid ammonium chloride (5 g) and
the ammonia was then allowed to evaporate. The residue left
was partitioned between water (5 mL) and ether (10 mL) and the
aqueous phase was extracted with ether. The combined organic
layers were washed with water (2 mL), brine (2 mL), dried over
anhydrous Na2SO4 (3 g), and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (1:4
EtOAc/hexane) to afford pure 21 (6.69 g, 91% yield) as a clear col-
(0.119 g, 63%) as a white solid. mp: 109–114 °C: ½a D37
¼ þ37:8 (c
ꢂ
0.5, CHCl3); 1H NMR (CDCl3, 300 MHz): d 7.29–7.07 (m, 5 H), 6.84
(ddd, 1H, J = 9.5, 4.4, 3.6 Hz), 6.00 (dt, 1H, J = 9.5, 2.2 Hz), 5.86
(ddt, 1H, J = 15.4, 7.3, 1.4 Hz), 5.6 (dd, 1H, J = 15.5, 6.5 Hz), 4.86
(m, 1H), 3.95 (m, 2H), 2.87–2.57 (m, 2H), 2.42–2.40 (m, 2H),
2.28–2.23 (m, 2H), 1.90–1.71 (m, 2H), 1.62 (t, 2H, J = 5.5 Hz) 13C
NMR (CDCl3, 50 MHz): d 163.8, 144.7, 141.8, 131.1, 129.9, 128.4,
128.3, 125.8, 121.5, 77.7, 68.7, 68.2, 42.1, 40.3, 38.9, 38.1, 29.7;
HRMS: calcd 339.1572 (M+Na), found 339.1573 (M+Na).
4.1.12. (2R,4R,6R)-2-[(benzyloxy)methyl]-6-(4-phenylbutyl)
tetrahydro-2H-4-pyranol 20
orless liquid. Rf = 0.4 (SiO2, 40% EtOAc in hexane); ½a D25
¼ þ3:0 (c
ꢂ
Trifluoroacetic acid (80.2 mL, 1041.6 mmol) was added slowly
to a solution of homoallylic alcohol 7 (10.0 g, 52.0 mmol) and 5-
phenyl-1-pentanal 19 (25.3 g, 156.0 mmol) in CH2Cl2 (200 mL) at
room temperature under a nitrogen atmosphere. The reaction mix-
ture was stirred for 4 h and then saturated aqueous sodium hydro-
gen carbonate solution (200 mL) was added and the pH adjusted to
>7 by the addition of triethylamine. The layers were then separated
and the aqueous layer was extracted with CH2Cl2 (4 ꢃ 60 mL). The
organic layers were combined, dried over anhydrous Na2SO4 (3 g),
and the solvent was removed under reduced pressure. The residue
was dissolved in methanol (75 mL) and stirred with potassium car-
bonate (14.4 g, 104 mmol) for 1 h. After removing MeOH under re-
duced pressure, water (50 mL) was added. The mixture was
extracted with dichloromethane (3 ꢃ 50 mL) and the combined or-
ganic layers were dried over anhydrous Na2SO4 (3 g) and the sol-
vent was removed under reduced pressure. Column
chromatography (1:4 EtOAc/hexane) afforded pure product 20
(11.9 g, 65% yield) as a colorless liquid. Rf = 0.4 (SiO2, 20% EtOAc
0.32, CHCl3); 1H NMR (200 MHz, CDCl3): d (ppm) = 7.30–7.02 (m,
5H), 4.63 (s, 2H), 3.78–3.23 (m, 8H), 2.60 (t, J = 7.2 Hz, 2H), 1.99–
1.76 (m, 2H), 1.73–1.08 (m, 8H); 13C NMR (75 MHz, CDCl3): d
(ppm) = 142.4, 128.3, 128.1, 125.6, 94.3, 75.9, 75.5, 72.8, 65.9,
55.2, 38.4, 35.8, 35.7, 34.2, 31.3, 25.0; IR (neat): 3462, 2930,
2856, 1603, 1494, 1453, 1374, 1101, 1037, 748, 700 cmꢁ1; HRMS
(ESI): [M+Na]+ m/z calcd for C18H28O4Na: 331.1885, found:
331.1882 (-0.9945 ppm error).
4.1.15. (2R,4R,6R)-2-(Iodomethyl)-4-(methoxymethoxy)-6-(4-
phenylbutyl)tetrahydro-2H-pyran 22
To a stirred solutionof 21(6.0 g, 19.4 mmol)in a mixtureof 45 mL
of dry ether and 15 mL of dry CH3CN was added TPP (7.6 g,
29.2 mmol), imidazole (3.31 g, 48.7 mmol), and iodine (5.91 g,
23.3 mmol) at 0 °C. The resulting mixture was stirred at room tem-
perature for 20 min, after which the solids were filtered and washed
with ether (15 mL). The filtrate was extracted with ether
(2 ꢃ 10 mL), washed with 10% aqueous Na2S2O3 solution (10 mL),
water (5 mL), brine (5 mL) solution, and dried over anhydrous
Na2SO4 (2 g). The residue was concentrated under reduced pressure.
Column chromatography (2:23 EtOAc/hexane) afforded pure prod-
uct 22 (7.49 g, 92% yield) as a colorless liquid. Rf = 0.4 (SiO2, 10%
EtOAc in hexane); 1H NMR (200 MHz, CDCl3): d (ppm) = 7.29–7.02
(m, 5H), 4.62 (s, 2H), 3.77–3.57 (m, 1H), 3.39–3.08 (m, 7H), 2.60 (t,
J = 6.8, 2H), 2.24–2.10 (m, 1H), 1.94–1.78 (m, 1H), 1.74–1.04 (m,
8H); IR (neat): 3024, 2935, 2854, 1602, 1495, 1452, 1369, 1147,
1099, 1039, 746, 700 cmꢁ1; ESI-MS: m/z 441 [M+Na]+.
in hexane); ½a 2D5
ꢂ
¼ þ10:0 (c 1, CHCl3); 1H NMR (300 MHz, CDCl3):
d (ppm) = 7.33–7.07 (m, 10H), 4.54 (q, J = 12.2, 15.2 Hz, 2H),
3.79–3.68 (m, 1H), 3.54–3.36 (m, 3H), 3.31–3.21 (m, 1H), 2.59 (t,
J = 7.3 Hz, 2H), 1.98–1.83 (m, 2H), 1.68–1.04 (m, 8H); 13C NMR
(75 MHz, CDCl3): d (ppm) = 142.5, 138.2, 128.3, 128.2, 127.6,
127.5, 125.5, 75.6, 74.9, 73.3, 73.1, 68.0, 40.9, 37.8, 35.8, 35.7,
31.4, 25.2; IR (neat): 3408, 2933, 2856, 1602, 1496, 1452, 1367,
1323, 1105, 1032, 741, 698 cmꢁ1; HRMS(ESI.): [M+Na]+ m/z calcd
for C23H30O3Na: 377.2092; found 377.2106; (+3.5396 ppm error).
4.1.13. (2R,4R,6R)-2-[(Benzyloxy)methyl]-4-(methoxymethoxy)
-6-(4-phenylbutyl)tetrahydro-2H-pyran 9
4.1.16. (5R,7R)-7-(Methoxymethoxy)-1-phenyl-9-decen-5-ol 10
A solution of compound 22 (6.0 g, 14.3 mmol) in ethanol
(50 mL) was added to zinc dust (18.6 g, 287.0 mmol) in a 250 mL
round bottomed flask. The reaction mixture was stirred at reflux
for 2 h and then Et2O (10 mL) and NH4Cl (3 g) were added to the
reaction mixture at 0 °C. The mixture was allowed to stir at room
temperature for 1 h and then filtered through Buckner funnel-flask
setup and the filtrate was concentrated under reduced pressure.
To alcohol 20 (9.5 g, 26.8 mmol) in anhydrous CH2Cl2 (50 mL) at
0 °C were added diisopropyl ethylamine (10.38 g, 80.5 mmol), cat-
alytic DMAP (10 mg) and MOMCl (4.2 g, 53.6 mmol) successively
and the mixture was stirred for 4 h at room temperature, quenched
by adding water (20 mL), and extracted with CH2Cl2 (3 ꢃ 20 mL).
The organic extracts were washed with brine (20 mL), dried over

190
G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
Column chromatography (3:22 EtOAc/hexane) afforded pure prod-
reduced pressure and the residue was purified by silica gel column
chromatography to afford compound 25 as a pale yellow liquid
(0.512 g, 81% yield). Rf = 0.3 (SiO2, 50% EtOAc in hexane);
uct 10 (3.8 g, 92% yield) as a colorless liquid. Rf = 0.4 (SiO2, 10%
EtOAc in hexane);
½
a 2D5
ꢂ
¼ ꢁ30:5 (c 1.4, CHCl3); 1H NMR
(300 MHz, CDCl3): d (ppm) = 7.23–7.02 (m, 5H), 5.82–5.66 (m,
1H), 5.11–5.01 (m, 2H), 4.66 (d, J = 6.7 Hz, 1H), 4.59 (d, J = 6.7 Hz,
1H), 3.89–3.75 (m, 2H), 3.38 (s, 3H), 2.60 (t, J = 7.5 Hz, 2H), 2.40–
2.19 (m, 2H), 1.76–1.20 (m, 8H). 13C NMR (75 MHz, CDCl3): d
(ppm) = 142.5, 134.2, 128.2, 128.1, 125.5, 117.4, 96.1, 75.1, 67.5,
55.6, 41.2, 39.3, 37.8, 35.8, 31.4, 25.3; IR (neat): 3462, 3025,
2933, 2856, 1641, 1602, 1494, 1449, 1372, 1213, 1149, 1098,
1036, 915, 750, 699 cmꢁ1; HRMS (ESI): [M+Na]+ m/z calcd for
C18H28O3Na: 315.1936, found: 315.1932; (ꢁ1.3158 ppm error).
½
a 2D5
ꢂ
¼ þ18:5 (c 1.3, CHCl3); 1H NMR (200 MHz, CDCl3):
d
(ppm) = 7.28–7.02 (m, 5H), 5.75–5.58 (m, 1H), 5.44–5.29 (m, 1H),
4.74–4.54 (m, 6H), 4.49–4.42 (m, 1H), 4.27–4.13 (m, 1H), 3.79–
3.58 (m, 4H), 3.39–3.30 (m, 9H), 2.60 (t, J = 8.0 Hz, 2H), 2.35–2.23
(m, 2H), 1.86–1.22 (m, 10H); 13C NMR (75 MHz, CDCl3):
d
(ppm) = 142.4, 132.2, 129.9, 128.2, 128.1, 125.5, 96.0, 95.8, 93.3,
75.4, 75.1, 74.6, 59.8, 55.5, 55.4, 40.1, 38.0, 37.8, 35.8, 34.9, 31.5,
24.5; IR (neat): 3477, 2928, 2854, 1448, 1376, 1213, 1035, 917,
750, 699 cmꢁ1; HRMS (ESI): [M+Na]+ m/z calcd for C25H42O7Na:
477.2828; found: 477.2834 (+1.2071 ppm error).
4.1.17. (3R,4E,7R,9R)-7-(Methoxymethoxy)-13-phenyl-1-
(tetrahydro-2H-2-pyranyloxy)-4-tridecene-3,9-diol 23
4.1.20. Methyl (2Z,5R,6E,9R,11R)-5,9,11-tri(methoxymethoxy)-
15-phenyl-2,6-pentadecadienoate 26
Grubbs’ second generation catalyst (0.145 g, 0.17 mmol,
10 mol %) was dissolved in 10 mL of CH2Cl2 and was added drop-
wise to a solution of compound 10 (1.0 g, 3.4 mmol) and com-
pound 8 (1.2 g, 6.8 mmol) in 100 mL of CH2Cl2 at 0 °C. After
completion of addition, reaction mixture was allowed to stir for
1 h. The solvent was removed under reduced pressure and the
crude product was purified by silica gel column chromatography
(11:9 EtOAc/hexane) to afford the pure product 23 (1.04 g, 68%
yield) as a colorless liquid. Rf = 0.2 (SiO2, 50% EtOAc in hexane);
To an ice-cooled solution of 2-iodoxybenzoic acid (0.446 g,
1.65 mmol) in dry DMSO (4.5 mL, 63.22 mmol) was added a solu-
tion of alcohol 25 (0.5 g, 1.10 mmol) in dry CH2Cl2 (10 mL). The
mixture was stirred at room temperature for 2 h and then filtered
through a Celite pad and washed with Et2O (15 mL). The combined
organic filtrates were washed with H2O (2 ꢃ 5 mL) and brine
(5 mL), dried over anhydrous Na2SO4 (2 g), and concentrated in va-
cuo. The unstable crude aldehyde product was used for further
½
a 2D5
ꢂ
¼ ꢁ18:0 (c 1, CHCl3); 1H NMR (200 MHz, CDCl3):
d
reaction. In a 50 mL round bottomed flask, NaH (0.0318 g,
(ppm) = 7.28–7.02 (m, 5H), 5.72–5.45 (m, 2H), 4.76–4.52 (m, 3H),
4.32–4.21 (m, 1H), 4.0–3.71 (m, 4H), 3.63–3.42 (m, 2H), 3.38 (s,
3H), 2.61 (t, J = 6.8 Hz, 2H), 2.42–2.14 (m, 2H), 1.88–1.24 (m,
16H); 13C NMR (75 MHz, CDCl3): d (ppm) = 142.6, 135.5, 128.3,
128.1, 126.4, 125.5, 98.8, 96.2, 75.4, 70.8, 67.6, 65.5, 62.1, 55.7,
41.2, 37.7, 37.3, 36.6, 35.9, 31.5, 30.4, 25.4, 25.2, 19.3; IR (neat):
3435, 2932, 1733, 1641, 1604, 1447, 1031, 910, 810, 754,
1.32 mmol) was taken and to it 4 mL of dry THF was added under
an N2 atmosphere. After 5 min, bis-(2,2,2-trifluoroethyl)(methoxy-
carbonyl methyl)] phosphonate (0.281 g, 0.884 mmol) in 2 mL of
dry THF was added at 0 °C. It was allowed to stir for 30 min. The
reaction mixture was cooled to ꢁ78 °C and the above crude alde-
hyde (0.4 g, 0.884 mmol) in dry THF (2 mL) was added over a per-
iod of 10 min after which the resulting mixture was stirred for 1 h
at ꢁ78 °C. The reaction mixture was quenched with saturated
NH4Cl (5 mL) and the product was extracted into ether
(2 ꢃ 10 mL). The organic layer was dried over anhydrous Na2SO4
(2 g) and evaporated in vacuo (water bath temperature should
not exceed 35 °C) and the product was purified using silica gel col-
umn chromatography (3:17 EtOAc/hexane) to afford (Z)-olefin es-
ter 26 as light yellow liquid (0.382 g, 85% yield). Rf = 0.3 (SiO2,
;
699 cmꢁ1 HRMS (ESI): [M+Na]+ m/z calcd for C26H42O6Na:
473.2879; found: 473.2883 [M+Na]+ (+0.8256 ppm error).
4.1.18. 2-[(3R,4E,7R,9R)-3,7,9-Tri(methoxymethoxy)-13-
phenyl-4-tridecenyl]oxytetrahydro-2H-pyran 24
To the diol 23 (0.785 g, 1.74 mmol) in anhydrous CH2Cl2
(15 mL) at 0 °C were added diisopropylethylamine (0.56 g,
6.1 mmol), a catalytic amount of DMAP (5 mg), and MOMCl
(0.4 g, 5.23 mmol) successively and the mixture was stirred for
4 h at room temperature, quenched by adding water (10 mL), and
extracted with CH2Cl2 (3 ꢃ 10 mL). The organic extracts were
washed with brine (10 mL), dried over anhydrous Na2SO4 (2 g),
and concentrated under vacuum to remove the solvent. The crude
residue was purified by column chromatography (1:4 EtOAc/hex-
ane) to afford compound 24 (0.8 g, 86% yield) as a colorless oil.
20% EtOAc in hexane); ½a D25
ꢂ
¼ þ15:0 (c 1.05, CHCl3); 1H NMR
(300 MHz, CDCl3): d (ppm) = 7.24–7.02 (m, 5H), 6.34–6.23 (m,
1H), 5.81 (d, J = 11.5 Hz, 1H), 5.72–5.59 (m, 1H), 5.42–5.29 (m,
1H), 4.69–4.52 (m, 6H), 4.51–4.41 (m, 1H), 4.14–4.04 (m, 1H),
3.76–3.58 (m, 4H), 3.35–3.29 (m, 9H), 2.95–2.86 (m, 2H), 2.60 (t,
J = 7.5 Hz, 2H), 2.33–2.25 (m, 2H), 1.68–1.22 (m, 8H); 13C NMR
(75 MHz, CDCl3): d (ppm) = 166.6, 145.9, 142.5, 132.0, 130.1,
128.3, 128.2, 125.6, 120.7, 96.1, 96.0, 93.5, 75.7, 75.2, 74.6, 55.6,
55.4, 51.0, 40.3, 38.2, 35.9, 35.1, 34.9, 31.6, 24.6; IR (neat): 2929,
1723, 1645, 1440, 1097, 1036, 917, 820, 749, 699 cmꢁ1; HRMS
(ESI): [M+Na]+ m/z calcd for C28H44O8Na: 531.2933; found:
531.2942 (+1.5272 ppm error).
Rf = 0.3 (SiO2, 20% EtOAc in hexane); ½a D25
¼ þ9:3 (c 1.2, CHCl3);
ꢂ
1H NMR (200 MHz, CDCl3): d (ppm) = 7.33–7.02 (m, 5H), 5.74–
5.54 (m, 1H), 5.41–5.26 (m, 1H), 4.78–4.51 (m, 6H), 4.49–4.41
(m, 1H), 4.19–4.04 (m, 1H), 3.90–3.56 (m, 4H), 3.52–3.30 (m,
11H), 2.60 (t, J = 7.3 Hz, 2H), 2.35–2.24 (m, 2H), 1.95–1.22 (m,
16H); 13C NMR (75 MHz, CDCl3): d (ppm) = 142.4, 132.6, 129.6,
128.2, 128.1, 125.5, 98.8, 96.0, 93.3, 75.0, 74.5, 73.9, 73.5, 63.9,
63.8, 62.1, 55.5, 55.2, 40.1, 38.1, 35.8, 35.0, 31.6, 30.6, 25.4, 24.5,
4.1.21. (6R)-6-[(E,4R,6R)-4,6-Dihydroxy-10-phenyl-1-decenyl]-
5,6-dihydro-2H-2-pyranone 2
To a stirred solution of compound 14 (0.3 g, 0.59 mmol) in a
mixture of MeOH (5 mL) and CH3CN (5 mL) was added CeCl3ꢀ7H2O
(cat.) under N2,12 then the mixture was stirred at rt for 12 h. The
mixture was quenched with solid NaHCO3 (0.5 g) and filtered.
The solvent was removed under reduced pressure and the residue
was purified by silica gel column chromatography (7:13 EtOAc/
hexane) to afford compound 2 as a white solid (0.148 g, 73% yield),
19.5; IR (neat): 2930, 1448, 1374, 1209, 980, 917, 751,700 cmꢁ1
;
HRMS (ESI): [M+Na]+ m/z calcd for C30H50O8Na: 561.3403; found:
561.3408 (+0.8215 ppm error).
4.1.19. (3R,4E,7R,9R)-3,7,9-Tri(methoxymethoxy)-13-phenyl-4-
tridecen-1-ol 25
To a stirred solution of compound 24 (0.750 g, 1.39 mmol) in
MeOH (15 mL) was added a catalytic amount of pyridinium p-tol-
uenesulfonate under a nitrogen atmosphere. After stirring for 12 h
at room temperature, the reaction mixture was quenched with so-
lid NaHCO3 (1 g) and filtered off, the solvent was removed under
mp: 64–66 °C. Rf = 0.2 (SiO2, 70% EtOAc in hexane); ½a D25
¼ þ52:5 (c
ꢂ
0.25, CHCl3); 1H NMR (200 MHz, CDCl3): d (ppm) = 7.27–7.01 (m,
5H), 6.88–6.78 (m, 1H), 6.01 (d, J = 9.8 Hz, 1H), 5.85 (ddd, J = 7.5,
7.5, 15.1 Hz, 1H), 5.64 (dd, J = 6.0, 15.1 Hz, 1H), 4.86 (q, J = 7.5,
14.3 Hz, 1H), 4.05–3.78 (m, 2H), 3.0 (br s, 2-OH), 2.60 (t,

G. Sabitha et al. / Tetrahedron: Asymmetry 20 (2009) 184–191
191
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Synthesis 2007, 24, 3886–3890.
9. Queiroz, E.-F.; Wolfender, J.-L.; Raoelison, G.; Hostettmann, K. Phytochem-Anal.
2003, 14, 34–39.
10. Krishna, P. R.; Srinivas, R. Tetrahedron Lett. 2007, 48, 2013–2015.
11. Sabitha, G.; Narjis, F.; Reddy, E. V.; Yadav, J. S. Tetrahedron Lett 2008, 48, 6087–
6089.
J = 7.5 Hz, 2H), 2.45–2.36 (m, 2H), 2.29–2.18 (m, 2H), 1.68–1.58 (m,
2H), 1.54–1.39 (m, 6H); 13C NMR (75 MHz, CDCl3): d (ppm) = 164.1,
144.7, 142.4, 131.4, 129.7, 128.3, 128.2, 125.6, 121.4, 77.8, 69.2,
68.2, 42.0, 40.3, 37.3, 35.8, 31.3, 29.7, 25.4; IR (neat): 3404, 2925,
2854, 1706, 1492, 1455, 1383, 1257, 1204, 1139, 1021, 971, 817,
749, 700 cmꢁ1; HRMS (ESI): [M+Na]+ m/z calcd for C21H28O4Na:
367.1909; found: 367.1925 (+4.2630 ppm error).
12. Sabitha, G.; Babu, R. S.; Gopal, P.; Yadav, J. S. in preparation.
13. (a) Garegg, P. J.; Samuelson, B. J. Chem. Soc., Chem. Commun. 1979, 978; (b)
Kang, S.-K.; Kim, S.-G.; Cho, D.-G.; Jeon, J.-H. Synth. Commun. 1993, 23, 681. The
known epoxy alcohol was converted into the corresponding iodide,13a which
on reductive elimination with Zn dust in refluxing ethanol13b afforded chiral
allylic alcohol 8.
Acknowledgments
N.F. thanks IICT, P.G. thanks CSIR, and C.N.R. thanks UGC New
Delhi for the award of Fellowship.
Zn dust,
OH
EtOH, reflux
95%, 30 min
O
O
TPP, I2
OTHP
I
OTHP
OTHP
HO
References
imidazole,
8
Et2O/CH3CN (3:1)
0 oC-rt, 20 min
90%
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