Stereoselective total synthesis of (+)-strictifolione and (6R)-6[(E,4R,6R)-4,6-dihydro-10-phenyl-1-decenyl)-5,6-dihydro-2H-2-pyrone

Article abstract of DOI:10.1016/j.tetasy.2010.11.003

The stereoselective total synthesis of two naturally occurring α-pyrone derivatives, (+)-strictifolione and (6R)-6[(E,4R,6R)-4,6- dihydroxy-10-phenyl-1-decanyl]-5,6-dihydro-2H-2-pyrone has been accomplished involving the Sharpless kinetic resolution and o

Full text of DOI:10.1016/j.tetasy.2010.11.003

Tetrahedron: Asymmetry 21 (2010) 2762–2767
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective total synthesis of (+)-strictifolione and
(6R)-6[(E,4R,6R)-4,6-dihydro-10-phenyl-1-decenyl)-5,6-dihydro-2H-2-pyrone q
⇑
Biswanath Das , Boyapati Veeranjaneyulu, Penagaluri Balasubramanyam, Malampati Srilatha
Organic Chemistry 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:
The stereoselective total synthesis of two naturally occurring a-pyrone derivatives, (+)-strictifolione and
Received 1 September 2010
Accepted 8 November 2010
Available online 6 December 2010
(6R)-6[(E,4R,6R)-4,6-dihydroxy-10-phenyl-1-decanyl]-5,6-dihydro-2H-2-pyrone has been accomplished
involving the Sharpless kinetic resolution and olefin cross-metathesis as the key reactions.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Naturally occurring
a
-pyrones (6-substituted 5,6-dihydro-2H-
Retrosynthetic analysis (Scheme 1) suggests that compounds 1
and 2 can be obtained from two intermediates (3 and 5 for 1 and 4
and 5 for 2) by olefin cross-metathesis8 using Grubbs’ catalyst.
Compounds 3 and 4 can again be prepared from the aldehydes 6
pyran-2-ones or ,b-unsaturated d-lactones) are known to possess
a
various biological properties1 including antibacterial, antifungal,
antiviral, and cytotoxic activities.2 (+)-Strictifolione 1, a member of
this group, was isolated from Cryptocarya strictifolia and displayed
antifungal property.3 (6R)-6[(E,4R,6R)-4,6-Dihydro-10-phenyl-1-
decenyl)-5,6-dihydro-2H-2-pyrone 2, another related member,
was isolated from Ravensara crassifolia.4 The synthesis of both mole-
cules 15 and 26 has recently become an attractive target to organic
chemists. In continuation of our work7 on the synthesis of natural
and 7, respectively, while the compound 5 derives from
acid 8.
L-ascorbic
The synthesis of 1 was initiated (Scheme 2) from the readily
available aldehyde, phenyl propanal 6 that underwent 2C-Wittig
homologation with (carboethylmethylene) triphenyl phosphorane
to afford the
a,b-unsaturated ester 9. Reduction of 9 with DIBAL-
a
-pyrones we have synthesized these two compounds with a
H followed by treatment with allyl bromide and Zn produced the
racemic alcohol 11 in high yield. The Sharpless kinetic resolution9
of 11 using (+)-DIPT, Ti(OiPr)4 and TBHP afforded the chiral epoxy
alcohol 12 (ee 97%). The opening of the epoxide ring in 12 with
Red-Al gave the desired diol 3. The 1,3-anti relationship of the
two hydroxyl groups in 3 was established by analysis of the 13C
NMR spectrum of the corresponding acetonide (d 24.8 and 24.7
for the methyl groups and d 100.1 for the quaternary carbon).10
convenient approach which we would like to describe here.
O
OH
OH
O
The other fragment 5 was prepared from L-ascorbic acid 8
1
(Scheme 3) which was converted into the known hydroxyl ester
13 by a previously reported method.11 The hydroxyl group of 13
was subsequently removed to prepare the ester 15 by converting
the former into a xanthate ester 14 by treatment with CS2, NaH
and then with methyl iodide followed by reaction with tributyltin
hydride and AIBN. Reduction of ester 15 with DIBAL-H and subse-
quent Still–Gennari–Wittig reaction of the resulting aldehyde with
O
OH OH
O
2
(CF3CH2O)2P(O) CH2COOMe afforded the a,b-unsaturated ester 17.
This ester was cyclized with methanolic HCl to form the known
pyran derivative 1812 which underwent Swern oxidation followed
by Wittig reaction with triphenyl phosphonium methyl iodide to
give desired intermediate 5.
Compounds 3 and 5 were coupled (Scheme 4) by olefin cross-
metathesis reaction8 using Grubbs’ second generation catalyst to
produce the target molecule, (+)-strictifolione 1. The spectral data
q
Part 35 in series, ‘synthetic studies on natural products’.
Corresponding author.
E-mail address: biswanathdas@yahoo.com (B. Das).
⇑
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.11.003

B. Das et al. / Tetrahedron: Asymmetry 21 (2010) 2762–2767
2763
N
N
100.1 ppm
Cl
O
O
Ru
Cl
Ph
P(Cy)3
Grubbs' Catalyst
(II generation)
of the compound were found to be identical to those reported
earlier.3,5
reaction with (carboethylmethylene) triphenyl phosphorane. Ester
19 was then reduced with DIBAL-H to form the corresponding
aldehyde 20 which on treatment with allyl bromide and zinc affor-
ded the racemic alcohol 21. The Sharpless kinetic resolution of 21
with (ꢀ)-DIPT, Ti(OiPr)4 and TBHP resulted in the formation of the
chiral epoxy alcohol 22 (ee 97%). The epoxy ring of 22 was then
opened with Red-Al to afford the desired fragment 4. The 13C
NMR spectrum of the corresponding acetonide (d 24.7 and 24.6
for the methyl groups and d 100.1 for the quaternary carbon) sug-
gested the 1,3-anti relationship of the two hydroxyl groups present
in 4.10
100.1 ppm
O
O
Finally the olefin cross-metathesis reaction8 of 4 and 5 using
Grubbs’ second generation catalyst afforded the target compound
2 (Scheme 6). The spectral properties of the compound were sim-
ilar to those reported earlier.5,7
Compound 4 was prepared (Scheme 5) from the aldehyde, phe-
nyl pentanal 7 following a similar sequence of reactions as shown
above for the preparation of 3 from the aldehyde 6. Thus, com-
pound 7 was converted into the
a,b-unsaturated ester 19 by Wittig
O
O
O
R3
2 R3
R
R1 R2
R1
n
R4
R4
O
Ph
Ph
n
1, 2
3, 4
5
For 1 and 3 n=1, R1=R4=OH, R2=R3=H
For 2 and 4 n=3, R1=R4=H, R2=R3=OH
Ph
O
n
L-Ascorbic acid
6
7
n=1
n=2
8
Scheme 1.
OH
O
O
ii
iii
v
i
Ph
Ph
O
Ph
OEt
Ph
H
6
9
10
11
iv
OH OH
OH
O
Ph
Ph
3
12
Scheme 2. Reagents and conditions: (i) Ph3PCHCOOEt, CH2Cl2, rt, 8 h, 84%; (ii) DIBAL-H, toluene, ꢀ78 °C, 0.5 h, 78%; (iii) allyl bromide, Zn, THF, saturated NH4Cl, 0 °C to rt, 3 h,
93%; (iv) Ti(iOPr)4, (+)-DIPT, TBHP, CH2Cl2, ꢀ20 °C, 5 h, 45%; (v) Red-Al, THF, 0 °C to rt, 3 h, 77%.

2764
B. Das et al. / Tetrahedron: Asymmetry 21 (2010) 2762–2767
HO
O
O
O
O
O
O
O
O
Ref. 11
i
ii
HO
COOEt
SMe
S
COOEt
COOEt
HO
OH
O
14
15
HO
O
13
8
iii
O
O
O
O
O
Ref. 12
v
iv
O
O
HO
CHO
5
18
17
16
COOMe
Scheme 3. Reagents and conditions: (i) NaH, CS2, THF, 0 °C, 0.5 h, then add CH3I, 0 °C to rt 1 h, 89%; (ii) n-Bu3SnH, AIBN, toluene, reflux, 1 h, 87%; (iii) DIBAL-H, toluene,
ꢀ78 °C, 15 min, 79%; (iv) NaH, (CF3CH2O)2P(O)CH2COOMe, THF, ꢀ78 °C, 1 h, 83%; (v) (a) (COCl)2, DMSO, Et3N, CH2Cl2, ꢀ78 °C, 0.5 h, 90%; (b) triphenyl phosphonium methyl
iodide, n-BuLi, THF, ꢀ78 °C, 1 h, 75%.
O
O
OH
OH
O
OH
OH
Grubb's II catalyst
(15 mol%)
O
CH2Cl2
50ºC, 4 h, 66%
1
5
3
Scheme 4.
O
O
ii
i
Ph
H
Ph
Ph
OEt
O
20
19
7
iii
OH
OH
O
OH
OH
iv
v
Ph
Ph
Ph
22
21
4
Scheme 5. Reagents and conditions: (i) Ph3PCHCOOEt, CH2Cl2, rt, 8 h, 86%; (ii) DIBAL-H, toluene, ꢀ78 °C, 30 min, 78%; (iii) allyl bromide, Zn, THF, saturated NH4Cl, 0 °C to rt,
3 h, 92%; (iv) Ti (iOPr)4, (ꢀ)-DIPT, TBHP, CH2Cl2, ꢀ20 °C, 5 h, 46%; (v) Red-Al, THF, 0 °C to rt, 3 h, 74%.
O
O
OH
OH
OH
OH
O
Grubb's II catalyst
(15 mol%)
O
CH2Cl2
50 ºC, 4 h, 68%
4
2
5
Scheme 6.
3. Conclusion
4. Experimental
4.1. General
In conclusion, the stereoselective total synthesis of (+)-strictifo-
lione and (6R)-6[(E,4R,6R)-4,6-dihydro-10-phenyl-1-decenyl)-5,6-
dihydro-2H-2-pyrone has been achieved by employing Sharpless
kinetic resolution and olefin cross-metathesis reaction as the key
steps. The method can be conveniently utilized for the preparation
All commercially available reagents were used directly without
further purification unless otherwise stated. The solvents used
were all of AR grade and were distilled under a positive pressure
of dry nitrogen atmosphere where necessary. All reactions were
of different other related a-pyrone derivatives.

B. Das et al. / Tetrahedron: Asymmetry 21 (2010) 2762–2767
2765
performed in pre-dried apparatus unless otherwise stated. The
progress of the reactions was monitored by analytical thin-layer
chromatography (TLC) performed on Merck Silica Gel 60 F254
plates. Column chromatography was carried out using Silica Gel
60–120 mesh (Qingdao Marine Chemical, China). NMR spectra
were recorded on Gemini 200 MHz spectrometer with tetrameth-
ylsilane as an internal standard using CDCl3. The chemical shifts
are expressed as d values in parts per million (ppm) and the cou-
pling constants (J) are given in hertz (Hz). The IR spectra were re-
corded with Perkin–Elmer RX1 FT-IR spectrophotometer. ESIMS
were recorded with VG-Autospec micromass and HRMS with
QSTAR XL, Hybrid MS system (Applied Biosystems). Yields were
of purified compounds unless otherwise stated. Optical rotations
were measured with JASCO DIP 300 digital polarimeter at 25 °C.
stirring for 30 min allyl alcohol 11 (1.5 g, 7.42 mmol) in dry CH2Cl2
(10 mL) was added and stirring was continued for another 30 min
at the same temperature. Then TBHP (0.89 mL, 3.56 mmol) was
added and after stirring for another 5 h at the same temperature,
the reaction mixture was quenched by addition of water (15 mL).
It was allowed remain at room temperature by stirring for
30 min. After re-cooling at 0 °C, an aqueous solution of NaOH
(30% w/v, 10 mL saturated with brine) was added to it and the mix-
ture was stirred at 0 °C for 1 h. The reaction mixture was extracted
with ether (2 ꢁ 40 mL). The combined organic extracts were
washed with brine (2 ꢁ 20 mL), dried over anhydrous Na2SO4
and concentrated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 4:6) afforded pure (S)-1-
((2S,3S)-3-phenethyloxiran-2-yl)but-3-en-1-ol 12 (0.72 g, 45%) as
a colorless liquid; ½a D25
ꢂ
¼ ꢀ11:2 (c 1.0, CHCl3); IR:
m 3447, 1640,
4.1.1. (E)-Ethyl-5-phenylpent-2-enoate 9
1503, 1454 cmꢀ1 1H NMR (200 MHz, CDCl3): d 7.30–7.10 (5H,
;
To a stirred solution of phenyl propanal (2.0 g, 14.92 mmol) in
dry CH2Cl2 (20 mL) ethyl (triphenyl phosphorylidene) acetate
(6.23 g, 17.91 mmol) was added and the mixture was stirred at
ambient temperature for 8 h. It was then concentrated in vacuo.
The residue on purification by column chromatography (ethyl ace-
tate/hexane, 2:8) afforded pure (E)-ethyl-5-phenylpent-2-enoate 9
m), 5.77 (1H, m), 5.16–5.02 (2H, m), 3.69 (1H, m), 2.93 (1H, m),
2.87–2.62 (3H, m), 2.31–2.13 (2H, m), 1.90–1.79 (3H, m); 13C
NMR (50 MHz): d 141.1, 134.0, 129.9, 129.7, 126.2, 118.0, 68.2,
60.8, 54.7, 38.0, 33.2, 32.3; ESIMS: m/z 241 [M+Na]+; HRESIMS:
calcd for C14H18O2Na m/z 241.1204 [M+Na]+, found m/z 241.1212
[M+Na]+.
(2.55 g, 84%) as a colorless oil; IR:
m 1721, 1655, 1454, 1317,
1267 cmꢀ1 1H NMR (200 MHz, CDCl3): d 7.28–7.11 (5H, m), 6.94
;
4.1.4. (3S,5S)-1-Phenyloct-7-ene-3,5-diol 3
(1H, m), 5.81 (1H, m), 5.81 (1H, d, J = 14.0 Hz), 4.15 (2H, q,
J = 7.0 Hz), 2.74 (2H, t, J = 7.0 Hz), 2.55–2.46 (2H, m), 1.27 (3H, t,
J = 7.0 Hz); 13C NMR (50 MHz): d 166.9, 148.1, 140.8, 128.7,
128.5, 126.1, 121.9, 60.2, 34.0, 33.7, 14.1; ESIMS: m/z 205
[M+H]+, 227 [M+Na]+; HRESIMS: calcd for C13H17O2 m/z 205.1201
[M+H]+, found 205.1221 [M+H]+.
To a stirred solution of 12 (0.650 g, 2.98 mmol) in dry THF
(15 mL) under N2 atmosphere at 0 °C was added Red-Al solution
in toluene (65% w/v, 2.78 mL, 8.94 mmol) and reaction mixture
was stirred at room temperature for 3 h. The reaction mixture
was quenched with saturated NH4Cl solution (15 mL) at 0 °C and
then extracted with EtOAc (2 ꢁ 30 mL). The combined organic
extracts were washed with brine, dried over anhydrous Na2SO4,
and concentrated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 5:5) afforded pure
(3S,5S)-1-phenyloct-7-ene-3, 5-diol 3 (0.5 g, 77%) as a colorless
4.1.2. (E)-8-Phenylocta-1,5-diene-4-ol 11
To a stirred solution of compound 9 (2.5 g, 12.25 mmol) in dry
toluene (25 mL) at ꢀ78 °C DIBAL-H (1.0 M, 14.70 mL, 14.70 mmol)
was added dropwise and the mixture was stirred at that tempera-
ture for 30 min. The reaction mixture was then quenched by slow
addition of dry methanol (10 mL) and was brought to room tem-
perature. Saturated sodium potassium tartrate (10 mL) was added
and stirred for 1 h. Then the reaction mixture was diluted with
water (10 mL) and extracted with diethyl ether (2x50 mL). The or-
ganic layer was separated and dried over anhydrous Na2SO4 and
concentrated in vacuo. The crude aldehyde 10 (1.52 g, 78%) thus
obtained was used further without purification.
oil;
½
a 2D5
ꢂ
¼ þ4:1 (c 1.0, CHCl3); IR:
m 3370, 1641, 1496,
1454 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d 7.28–7.10 (5H, m), 5.77
(1H, m), 5.12–5.03 (2H, m), 3.99–3.84 (2H, m), 2.97 (2H, m), 2.78
(1H, m), 2.61 (1H, m), 2.21 (2H, t, J = 7.0 Hz), 1.81 (1H, m), 1.72
(1H, m), 1.58 (2H, t, J = 7.0 Hz); 13C NMR (50 MHz): d 142.1,
134.6, 128.2, 125.5, 118.0, 68.2, 68.0, 41.5, 38.8, 32.0, 29.3; ESIMS:
m/z 243 [M+Na]+; HRESIMS: calcd for C14H20O2Na m/z 243.1360
[M+Na]+, found m/z 243.1363 [M+Na]+.
The crude aldehyde 10 (1.40 g, 8.75 mmol) was dissolved in THF
(15 mL). Activated Zn (2.84 g, 43.75 mmol) and allyl bromide
(2.22 mL, 26.25 mmol) were added at 0 °C and stirred for 10 min.
To this mixture saturated NH4Cl solution (10 mL) was added
dropwise at 0 °C and the solution was stirred for 3 h at ambient
temperature. Then the reaction mixture was extracted with EtOAc
(2 ꢁ 15 mL). The organic layer was separated, dried over anhy-
drous Na2SO4 and concentrated in vacuo. The residue on purifica-
tion by column chromatography (ethyl acetate/hexane, 3:7)
afforded pure (E)-8-phenylocta-1,5-diene-4-ol 11 (1.64 g, 93%) as
4.1.5. (R)-Ethyl-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-
(methylthiocarbonothioyloxy)acetate 14
To a stirred suspension of NaH (60%, 0.431 g, 10.78 mmol) in
THF (10 mL) a solution of 13 (2.0 g, 9.8 mmol) in THF (10 mL)
was added dropwise at 0 °C under N2 atmosphere. After stirring
for 20 min, CS2 (2.07 mL, 29.41 mmol) was added and the reaction
mixture was stirred for 30 min. Then iodomethane (3.86 mL,
58.52 mmol) was added and stirring was continued for 1 h at the
same temperature. The reaction mixture was quenched with ice
and saturated NH4Cl (20 mL) at 0 °C and extracted with EtOAc
(2 ꢁ 40 mL). The combined organic extracts were washed with
brine, dried over anhydrous Na2SO4 and concentrated in vacuo.
The residue on purification by column chromatography (ethyl ace-
tate/hexane, 2:8) afforded pure (R)-ethyl-2-((S)-2,2-dimethyl-1,3-
dioxolan-4-yl)-2-(methylthiocarbonothioyloxy)acetate 14 (2.56 g,
a colorless liquid; IR:
m ;
3422, 1610, 1556, 1450 cmꢀ1 1H NMR
(200 MHz, CDCl3): d 7.24–7.11 (5H, m), 5.78–5.62 (2H, m), 5.45
(1H, m), 5.11–5.03 (2H, m), 4.03 (1H, m), 2.67 (2H, t, J = 7.0 Hz),
2.39–2.31 (2H, m), 2.28–2.17 (2H, m), 1.42 (1H, br s); 13C NMR
(50 MHz): d 141.7, 134.3, 132.9, 130.8, 128.3, 128.2, 125.9, 118.0,
71.2, 42.0, 35.5, 33.9; ESIMS: m/z 225 [M+Na]+; HRESIMS: calcd
for C14H18ONa m/z 225.1255 [M+Na]+, found m/z 225.1247
[M+Na]+.
89%) as a colorless liquid; ½a D25
ꢂ
¼ ꢀ15:2 (c 1.0, CHCl3); IR:
m 1742,
1589, 1458, 1372, 1202 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d 5.75
(1H, d, J = 6.0 Hz), 4.58 (1H, q, J = 6.0 Hz), 4.23 (2H, q, J = 7.0 Hz),
4.07 (1H, m), 3.92 (1H, m), 2.62 (3H, s), 1.41 (3H, s), 1.32 (3H, s),
1.28 (3H, t, J = 7.0 Hz); 13C NMR (50 MHz): d 215.5, 166.0, 110.4,
79.4, 74.7, 65.4, 61.6, 26.3, 25.6, 19.3, 14.3; ESIMS: m/z 317
[M+Na]+; HRESIMS: calcd for C11H18O5S2Na m/z 317.0488
[M+Na]+, found m/z 317.0508 [M+Na]+.
4.1.3. (S)-1-((2S,3S)-3-Phenethyloxiran-2yl) but-3-en-1-ol 12
To a suspension of powered molecular sieves (4 Å, 200 mg) in
dry CH2Cl2 (15 mL), Ti(OiPr)4 (1.1 mL, 3.71 mmol), and (+)-DIPT
(0.931 mL, 4.45 mmol) were added sequentially at ꢀ20 °C. After

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B. Das et al. / Tetrahedron: Asymmetry 21 (2010) 2762–2767
4.1.6. (R)-Ethyl-2-(2,2-dimethyl-1,3-dioxolan-4-yl)acetate 15
To a solution of 14 (2.5 g, 8.50 mmol) in dry toluene (25 mL)
was added catalytic amount of AIBN and tributyltin hydride
(2.97 mL, 11.05 mmol) at ambient temperature and then the mix-
ture was refluxed for 1 h. It was allowed to cool at room tempera-
ture, diluted with water (10 mL), and extracted with EtOAc
(2 ꢁ 30 mL). The combined organic extracts were washed with
brine (2 ꢁ 20 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. The residue on purification by column chromatography
(ethyl acetate/hexane, 2:8) afforded pure (R)-ethyl-2(2,2-di-
methyl-1,3-dioxolan-4-yl)acetate 15 (1.38 g, 87%) as a colorless li-
(0.142 g, 90%) was used directly after flash chromatography for
the next reaction.
To a stirred suspension of triphenyl phosphonium methyl io-
dide (0.678 g, 1.68 mmol) in dry THF (3 mL) at ꢀ78 °C, n-BuLi in
hexane (1.6 M, 0.98 mL, 1.57 mmol) was added dropwise under
N2 atmosphere and was allowed to room temperature. After
45 min the reaction mixture was again cooled to ꢀ78 °C and the
aldehyde obtained above, dissolved in dry THF (3 mL) was added
dropwise and stirred for another 45 min. The reaction mixture
was quenched with saturated NH4Cl solution (5 mL) at 0 °C and ex-
tracted with diethyl ether (2 ꢁ 10 mL). The combined organic ex-
tracts were washed with brine (2 ꢁ 10 mL), dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue on purification
by column chromatography (ethyl acetate/hexane, 2:8) afforded
pure (R)-5, 6-dihydro-6-vinylpyran-2-one 5 (0.104 g, 75%) as a pale
quid;
½
a 2D5
ꢂ
¼ ꢀ11:4 (c 1.0, CHCl3); IR:
m 1736, 1457, 1371,
1255 cmꢀ1
;
1H NMR (200 MHz, CDCl3): d 4.41 (1H, m), 4.19–4.08
(3H, m), 3.60 (1H, m), 2.68 (1H, dd, J = 12.0, 5.0 Hz), 2.43 (1H, dd,
J = 12.0, 7.0 Hz), 1.39 (3H, s), 1.32 (3H, s), 1.27 (3H, t, J = 7.0 Hz);
13C NMR (50 MHz): d 170.5, 109.1, 72.0, 69.1, 60.6, 38.9, 29.8,
25.4, 14.1; ESIMS: m/z 211 [M+Na]+; HRESIMS: calcd for
C9H16O4Na m/z 211.0941 [M+Na]+, found m/z 211.0935 [M+Na]+.
yellow liquid; ½a D25
ꢂ
¼ þ91:2 (c 0.8, CHCl3); IR:
m 1719, 1605, 1421,
1385, 1251 cmꢀ1; 1H NMR (200 MHz, CDCl3): d 6.84 (1H, m), 6.05–
5.86 (2H, m), 5.40 (IH, dd, J = 12.0, 2.0 Hz), 5.29 (1H, dd, J = 7.0,
2.0 Hz), 4.90 (1H, m), 2.51–2.38 (2H, m); 13C NMR (50 MHz): d
163.9, 144.7, 134.8, 121.6, 117.9, 77.8, 29.1; ESIMS: m/z 125
[M+H]+. Anal. Calcd for C7H8O2: C, 67.74; H, 6.45. Found: C,
67.65; H, 6.52.
4.1.7. (R,Z)-Methyl-4-(2,2-dimethyl-1,3-dioxaolan-4-yl)but-2-
enoate 17
To a stirred solution of compound 15 (1.2 g, 6.38 mmol) in dry
toluene (15 mL) at ꢀ78 °C DIBAL-H (1.2 M, 6.38 mL, 7.65 mmol)
was added dropwise and the mixture was stirred at that tempera-
ture for 15 min. The reaction mixture was then quenched by slow
addition of dry methanol (10 mL) and was brought to room tem-
perature. Saturated sodium potassium tartrate (10 mL) was added
and stirred for 1 h. Then the reaction mixture was diluted with
water (10 mL) and extracted with diethyl ether (2 ꢁ 30 mL). The
organic layer was separated and dried over anhydrous Na2SO4
and concentrated in vacuo. The crude aldehyde 16 (0.72 g, 79%)
thus obtained was used further without purification.
To a suspension of NaH (60%, 0.213 g, 5.34 mmol) under an N2
atmospherein dry THF (10 mL)was added bis-(2,2,2-trifluoroethyl)-
(methoxy-carbonyl methyl) phosphonate (1.23 mL, 5.83 mmol) at
0 °C. After the mixture was stirred for 30 min at the same tempera-
ture, the reaction mixture was cooled to ꢀ78 °C, and then a solution
of crude aldehyde (0.7 g, 4.86 mmol) in dry THF (10 mL) was added
dropwise. After stirring for 1 h, the reaction mixture was diluted
with 5 mL of ether and quenched by slow addition of 4 mL of water.
The reaction mixture was extracted with ether (2 ꢁ 30 mL). The
combined organic extracts were washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. The residue on puri-
fication by column chromatography (ethyl acetate/hexane, 2:8)
afforded pure (R,Z)-methyl-4-(2,2-dimethyl-1,3-dioxaolan-4-yl)-
4.1.9. (R)-5,6-Dihydro-6-((E,4S,6S)-4,6-dihydroxy-8-phenyloct-
1-enyl) pyran-2-one 1
A solution of compound 3 (0.399 g, 1.81 mmol) and compound
5 (0.045 g, 0.36 mmol) in dry CH2Cl2 (50 mL) was first bubbled
with an N2 flow, after which Grubbs’ second generation catalyst
(0.045 g, 0.054 mmol) was added at once and the resulting mixture
was heated under N2 at 50 °C for 4 h. After cooling the solvent was
evaporated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 5:5) afforded pure (R)-
5,6-dihydro-6-((E,4S,6S)-4,6-dihydroxy-8-phenyloct-1-enyl) pyr-
an-2-one 1 (0.052 g, 66%) as a white solid. The spectral data of
the compound were found to be identical to those reported
earlier.3,5
4.1.10. (E)-Ethyl-7-phenylhept-2-enoate 19
To a stirred solution of phenyl pentanal (2.0 g, 12.34 mmol) in
dry CH2Cl2 (20 mL) ethyl (triphenyl phosphorylidene) acetate
(5.15 g, 14.81 mmol) was added and the mixture was stirred at
ambient temperature for 8 h. It was then concentrated in vacuo.
The residue on purification by column chromatography (ethyl ace-
tate/hexane, 2:8) afforded pure (E)-ethyl-7-phenylhept-2-enoate
19 (2.46 g, 86%) as a colorless oil; IR:
m 1720, 1655, 1592, 1496,
but-2-enoate 17 (0.806 g, 83%) as a colorless oil; ½a D25
ꢂ
¼ þ1:7 (c
1368, 1263 cmꢀ1 1H NMR (200 MHz, CDCl3): d 7.28–7.07 (5H,
;
1.0, CHCl3); 1H NMR (200 MHz, CDCl3): d 6.34 (1H, m), 5.90 (1H, d,
J = 9.0 Hz), 4.21 (1H, m), 4.02 (1H, m), 3.72 (3H, s), 3.58 (1H, m),
3.02 (1H, m), 2.89 (1H, m), 1.42 (3H, m), 1.34 (3H, s); 13C NMR
(50 MHz): d 166.4, 144.9, 121.2, 108.9, 74.7, 68.6, 50.9, 32.6, 26.6,
25.4; ESIMS: m/z 223 [M+Na]+; HRESIMS: calcd for C10H16O4Na
m/z 223.0946 [M+Na]+, found m/z 223.0943 [M+Na]+.
m), 6.90 (1H, m), 5.76 (1H, d, J = 14.0 Hz), 4.12 (2H, q, J = 7.0 Hz),
2.61 (2H, t, J = 7.0 Hz), 2.21 (2H, q, J = 7.0 Hz), 1.71–1.60 (2H, m),
1.56–1.42 (2H, m), 1.26 (3H, t, J = 7.0 Hz); 13C NMR (50 MHz): d
166.9, 149.1, 142.2, 128.7, 128.6, 125.9, 121.2, 60.1, 36.0, 32.1,
31.0, 27.3, 14.0; ESIMS: m/z 233 [M+H]+; HRESIMS: calcd for
C
15H21O2 m/z 233.1541 [M+H]+, found m/z 233.1539 [M+H]+.
4.1.8. (R)-5,6-Dihydro-6-vinylpyran-2-one 5
4.1.11. (E)-10-Phenyldeca-1,5-dien-4-ol 21
To a solution of oxalyl chloride (0.16 mL, 1.87 mmol) in dry
CH2Cl2 (4 mL) at ꢀ78 °C, DMSO (0.28 mL, 4.0 mmol) was added
dropwise with stirring under an N2 atmosphere. After 15 min, com-
pound 18 (0.16 g, 1.25 mmol) dissolved in dry CH2Cl2 (3 mL) was
added into the reaction mixture and subsequently after stirring
for 0.5 h at ꢀ78 °C, Et3N (0.9 mL, 6.25 mmol) was added and the
mixture was stirred for another 0.5 h at 0 °C. The reaction mixture
was quenched with saturated NH4Cl solution (8 mL) at 0 °C and ex-
tracted with diethyl ether (2 ꢁ 10 mL). The combined organic ex-
tracts were washed with brine (2 ꢁ 10 mL), dried over anhydrous
Na2SO4, and concentrated in vacuo. The aldehyde, thus obtained
To a stirred solution of compound 19 (2.3 g, 9.91 mmol) in dry
toluene (20 mL) at ꢀ78 °C DIBAL-H (1.0 M, 11.89 mL, 11.89 mmol)
was added dropwise and the mixture was stirred at that tempera-
ture for 30 min. The reaction mixture was then quenched by the
slow addition of dry methanol (10 mL) and was brought to room
temperature. Saturated sodium potassium tartrate (10 mL) was
added and stirred for 1 h. Then the reaction mixture was diluted
with water (10 mL) and extracted with diethyl ether (2 ꢁ 40 mL).
The organic layer was separated and dried over anhydrous Na2SO4
and concentrated in vacuo. The crude aldehyde 20 (1.45 g, 78%)
thus obtained was used further without purification.

B. Das et al. / Tetrahedron: Asymmetry 21 (2010) 2762–2767
2767
The crude aldehyde (1.45 g, 7.73 mmol) was dissolved in THF
(15 mL). Activated Zn (2.5 g, 38.65 mmol) and allyl bromide
(1.96 mL, 23.19 mmol) are added at 0 °C and stirred for 10 min.
To this saturated NH4Cl solution (10 mL) was added dropwise at
0 °C and the solution was stirred for 3 h at ambient temperature.
Then the reaction mixture was extracted with EtOAc (2 ꢁ 15 mL).
The organic layer was separated, dried over anhydrous Na2SO4,
and concentrated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 3:7) afforded pure (E)-10-
phenyldeca-1,5-dien-4-ol 21 (1.63 g, 92%) as a colorless oil; 1H
NMR (200 MHz, CDCl3): d 7.28–7.07 (5H, m), 5.77 (1H, m), 5.60
(1H, m), 5.43 (1H, dd, J = 12.0, 7.0 Hz), 5.12–5.04 (2H, m), 4.03
(1H, q, J = 7.0 Hz), 2.60 (2H, t, J = 7.0 Hz), 2.30–2.21 (2H, m), 2.05
(2H, q, J = 7.0 Hz), 1.69–1.55 (2H, m), 1.50–1.36 (3H, m); 13C NMR
(50 MHz): d 142.8, 134.2, 132.2, 132.0, 128.2, 128.1, 125.3, 118.1,
71.9, 42.1, 36.0, 32.2, 31.0, 28.9; ESIMS: m/z 231 [M+H]+, 253
[M+Na]+; HRESIMS: calcd for C16H23O m/z 233.1541 [M+H]+, found
m/z 233.1539 [M+H]+.
and concentrated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 5:5) afforded pure (4R,6R)-
10-phenyldec-1-ene-4,6-diol 4 (0.48 g, 74%) as a colorless oil;
½
a 2D5
ꢂ
¼ ꢀ5:75 (c 1.0, CHCl3); IR:
m 3369, 1726, 1641, 1603, 1496,
1454, 1376 cmꢀ1 1H NMR (200 MHz, CDCl3): d 7.28–7.05 (5H,
;
m), 5.75 (1H, m), 5.15–5.03 (2H, m), 3.98–3.81 (2H, m), 2.60 (2H,
t, J = 7.0 Hz), 2.50 (1H, br s), 2.21 (2H, t, J = 7.0 Hz), 1.67–1.25
(9H, m); 13C NMR (50 MHz): d 142.7, 134.9, 128.2, 128.1, 125.9,
118.2, 69.1, 68.0, 42.0, 41.9, 37.1, 36.0, 31.4, 25.5; ESIMS: m/z
271 [M+Na]+; HRESIMS: calcd for C16H24O2Na m/z 271.1669
[M+Na]+, found m/z 271.1671 [M+Na]+.
4.1.14. (6R)-6[(E,4R,6R)-4,6-Dihydro-10-phenyl-1-decenyl)-5,6-
dihydro-2H-2-pyrone 2
A solution of compound 4 (0.449 g, 1.81 mmol) and compound
5 (0.045 g, 0.36 mmol) in dry CH2Cl2 (50 mL) was first bubbled
with N2 flow, after which Grubbs’ second generation catalyst
(0.045 g, 0.054 mmol) was added at once and the resulting mixture
was heated under N2 at 50 °C for 4 h. After cooling, the solvent was
evaporated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 5:5) afforded pure (6R)-
6[(E,4R,6R)-4,6-dihydro-10-phenyl-1-decenyl)-5,6-dihydro-2H-2-
pyrone 2 (0.061 g, 68%) as a colorless liquid. The spectral properties
of the compound were similar to those reported earlier.5,7
4.1.12. (R)-1-((2R,3R)-3-(4-phenylbutyl)oxiran-2-yl)but-3-en-1-
ol 22
To a suspension of powered molecular sieves (4 Å, 200 mg) in
dry CH2Cl2 (15 mL), Ti(OiPr)4 (0.97 mL, 3.26 mmol) and (ꢀ)-DIPT
(0.81 mL, 3.91 mmol) were added sequentially at ꢀ20 °C. After stir-
ring for 30 min allyl alcohol 21 (1.5 g, 6.52 mmol) in dry CH2Cl2
(15 mL) was added and stirring was continued for another
30 min at the same temperature. Then TBHP (4 M, 0.78 mL,
3.13 mmol) was added and after stirring for another 5 h at the
same temperature, the reaction mixture was quenched by the
addition of water (15 mL). It was allowed remain at room temper-
ature by stirring for 30 min. After re-cooling at 0 °C, an aqueous
solution of NaOH (30% w/v, 10 mL saturated with brine) was added
to it and the mixture was stirred at 0 °C for 1 h. The solvent was
removed under reduced pressure and the residue was extracted
with ether (3 ꢁ 40 mL). The combined organic extracts were
washed with brine (2 ꢁ 20 mL), dried over anhydrous Na2SO4
and concentrated in vacuo. The residue on purification by column
chromatography (ethyl acetate/hexane, 4:6) afforded pure (R)-1-
((2R,3R)-3-(4-phenylbutyl) oxiran-2-yl) but-3-en-1-ol 22 (0.73 g,
Acknowledgments
The authors thank the CSIR and UGC, New Delhi for financial
assistance.
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¼ þ4:8 (c 1.0, CHCl3); IR:
m 3423,
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4.1.13. (4R,6R)-10-Phenyldec-1-ene-4,6-diol 4
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To a stirred solution of 22 (0.650 g, 2.64 mmol) in dry THF
(15 mL) under N2 atmosphere at 0 °C was added a Red-Al solution
in toluene (65% w/v, 2.46 mL, 7.92 mmol) and the reaction mixture
was stirred at room temperature for 3 h. Then it was quenched
with saturated NH4Cl solution (15 mL) at 0 °C and then extracted
with EtOAc (2 ꢁ 30 mL). The combined organic extracts were
washed with brine (2 ꢁ 15 mL), dried over anhydrous Na2SO4,
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