Stereoselective total synthesis of (S)-Virol C and (S)-1-dehydroxyvirol A

Article abstract of DOI:10.1016/j.tet.2005.03.014

A stereoselective total synthesis of (S)-Virol C and (S)-1-dehydroxyvirol A has been developed, based upon the selective and sequential substitution of the two trimethylsilyl groups of readily available 1,4-bis(trimethylsilyl)-1,3- butadiyne.

Full text of DOI:10.1016/j.tet.2005.03.014

Tetrahedron 61 (2005) 4551–4556
Stereoselective total synthesis of (S)-Virol C and
(S)-1-dehydroxyvirol A
a
b
a
Vito Fiandanese,a, Daniela Bottalico, Cosimo Cardellicchio, Giuseppe Marchese
*
and Angela Punzia
a
`
Dipartimento di Chimica, Universita di Bari, via E. Orabona 4, 70126 Bari, Italy
bC.N.R. ICCOM, Sezione di Bari, via E. Orabona 4, 70126 Bari, Italy
Received 17 December 2004; revised 16 February 2005; accepted 3 March 2005
Available online 23 March 2005
Abstract—A stereoselective total synthesis of (S)-Virol C and (S)-1-dehydroxyvirol A has been developed, based upon the selective and
sequential substitution of the two trimethylsilyl groups of readily available 1,4-bis(trimethylsilyl)-1,3-butadiyne.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
connection with our ongoing work, we report here the
total synthesis of (S)-Virol C3,5,6 1 and (S)-1-dehydroxyvirol
A 2, a Virol A derivative.4
Water hemlock, Cicuta virosa (Umbelliferae), is a well-
known toxic plant widely distributed in temperate regions.
The main toxic component of the plant is cicutoxin,1 a
chemical belonging to the class of conjugated polyacetyl-
enes, which was shown to induce tonic and clonic
convulsion and respiratory paralysis by acting directly on
the central nervous system. Recently, cicutoxin and related
polyacetylenic alcohols, congeners of cicutoxin, such as
isocicutoxin, Virol A and Virol C have been isolated from
C. virosa and their stereostructures elucidated on the basis
of spectroscopic analysis.2 Some of these cicutoxin
analogues have been synthesized by stereoselective
routes3–6 to confirm their stereochemistry and to obtain
supply of these compounds for pharmacological study.
2. Results and discussion
We have recently reported a straightforward and general
route to a variety of unsymmetrical conjugated diynes,
based upon the selective and sequential substitution of the
trimethylsilyl groups of the readily available 1,4-bis(tri-
methylsilyl)-1,3-butadiyne with alkyl, aryl and vinyl
groups.7 We have successfully applied the above method-
ology to the synthesis of polyacetylenic compounds, such as
dihydroxerulin and xerulin, potent inhibitors of the
biosynthesis of cholesterol,8 and of Montiporic acids A
and B, bioactive metabolites from Montipora digitata,
possessing antibacterial and cytotoxic properties.9 In
Our overall retrosynthesis is summarized in Schemes 1
and 2. In the case of (S)-Virol C the stereogenic center can
be obtained by enantioselective chemical reduction of the
carbonyl group of the polyunsaturated compound 3. The
double disconnection of the C3–C4 and C7–C8 bonds of
compound 3 affords the conjugated diyne 4, which, after
appropriate desilylation reactions, can be subjected to
coupling reactions involving, respectively, an alkylation
reaction with the halide 6, followed by a coupling reaction
with the keto vinyl derivative 5.
In a similar manner, in the case of (S)-1-dehydroxyvirol A,
the stereogenic center can be obtained by enantioselective
chemical reduction of the carbonyl group of the poly-
unsaturated compound 7. The double disconnection of the
Keywords: Silicon and compounds; Polyacetylenes; Coupling reactions;
Enantioselective reductions.
*
Corresponding author. Tel.: C39 080 544 2075; fax: C39 080 544 2129;
e-mail: fianda@chimica.uniba.it
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.014

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V. Fiandanese et al. / Tetrahedron 61 (2005) 4551–4556
Scheme 1.
Scheme 2.
C3–C4 and C7–C8 bonds of compound 7 can lead to the same
conjugated diyne 4, which can be subjected to an alkylation
reaction with the halide 9, followed by a coupling reaction
with the keto dienyl derivative 8.
Accordingly, the synthesis of (S)-Virol C started with the
preparation of the basic fragment 5. This compound was
obtained in 97% yield by a simple acylation reaction10 of
Scheme 3.
Scheme 4.

V. Fiandanese et al. / Tetrahedron 61 (2005) 4551–4556
4553
(E)-1-bromo-2-trimethylsilylethene 10 with the octanoyl
chloride–AlCl3 complex, as a mixture of compound 5a (the
(E)-bromovinylketone) and compound 5b (the (E)-chloro-
vinylketone) (Scheme 3).
and Pd(PPh3)47,15 affording the polyunsaturated ketone 7 in
69% yield. Finally, the enantioselective reduction of the
carbonyl group of compound 7 with borane catalyzed by
(R)-12 completed the sequence leading to (S)-1-dehydroxy-
virol A 2 in 54% yield (84% ee). It is noteworthy that as a
chiral reagent for the enantioselective reduction was
selected as catalyst the oxazaborolidine that afforded the
higher enantiomeric enrichments. Indeed, several attempts
were performed with the (S)-BINAL-H16 reagent, obtaining
higher yields (in the range 76–97%), but lower ee (in the
range 38–70%) for compounds 1 and 2.
Then, the total synthesis of (S)-Virol C was performed as
depicted in Scheme 4. To obtain compound 11,3 the diyne 4
was selectively desilylated with MeLi–LiBr complex
affording the lithium salt of the mono-silylated terminal
diyne11 which was alkylated with 3-iodo-1-propanol tetra-
hydropyranyl ether 6. Subsequent desilylation reaction with
K2CO3 in MeOH led to terminal diyne 113 (56% yield)
which was subjected to a Pd(II)-catalyzed cross-coupling
reaction12 with the halovinylketone 5 to give the conjugated
enediyne 3 in 64% yield. The CBS (Corey, Bakshi, Shibata)
enantioselective reduction of the carbonyl group of
compound 3 with borane catalyzed by (R)-2-methyloxaza-
borolidine 12,13 followed by the deprotection reaction with
p-toluenesulfonic acid completed the sequence leading to
(S)-Virol C 1 (52% yield, 83% ee).
In conclusion, we believe that our synthetic approach to
both compounds 1 and 2 compares favorably with other
synthetic procedures as far as number of steps and chemical
yields. A special advantage of our strategy is represented by
the possibility of starting from a common intermediate and
of employing the same reaction sequence. Moreover, in
principle, both stereogenic centers can be obtained by the
same chiral reagent used in both opposite configurations.
Taking also into account the ready availability of the
starting materials, the mild reaction conditions and the
experimental simplicity of the operations involved we
believe that our approach is very useful.
3. Experimental
The synthesis of (S)-1-dehydroxyvirol A 2 was realized
employing the same synthetic approach. Thus, the basic
fragment 8 was synthesized in 87% yield and with a high
stereoselectivity (R97%) by a simple acylation reaction of
(1E,3E)-1-iodo-4-trimethylsilylbuta-1,3-diene 1314 with the
hexanoyl chloride–AlCl3 complex (Scheme 5).
Macherey–Nagel silica gel (60, particle size 0.040–
0.063 mm) for column chromatography and Macherey–
Nagel aluminum sheets with silica gel 60 F254 for TLC were
used. GC analysis was performed on a Varian 3900 gas
chromatograph equipped with a J & W capillary column
(DB-1301, 30 m!0.25 mm id). GC/mass-spectrometry
analysis was performed on a Shimadzu GCMS-QP5000
gas chromatograph-mass spectrometer equipped with a
Zebron capillary column (methyl polysiloxane, 30 m!
1
0.25 mm id). H-NMR spectra were recorded in deutero-
chloroform on a Bruker AM 500 spectrometer. 13C NMR
spectra were recorded in deuterochloroform or acetone-d6
on a Bruker AM 500 spectrometer. IR spectra were recorded
on a Perkin–Elmer FT-IR 1710 spectrometer. Elemental
analyses were recorded on a Carlo Erba EA 1108 elemental
analyzer. Optical rotations were measured at 589 nm with a
Perkin–Elmer 343 polarimeter. Enantiomeric excesses were
Scheme 5.
The total synthesis of (S)-1-dehydroxyvirol A was per-
formed as depicted in Scheme 6. Compound 14 was
obtained in 60% yield according to our reported procedure,8
then coupled directly with the iododerivative 8 in the
presence of a K2CO3/MeOH and a catalytic amount of AgCl
Scheme 6.

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V. Fiandanese et al. / Tetrahedron 61 (2005) 4551–4556
evaluated using HPLC with a Chiralcel OD-H column
(Daicel) on an Agilent 1100 instrument. Melting points
(uncorrected) were determined on a Reichert Microscope.
Solvents were dried before use as follows: methylene
chloride was distilled over phosphorus pentoxide, N,N-di-
methylformamide was distilled over molecular sieves and
tetrahydrofuran was distilled from sodium. (R)-2-Methyl-
CBS-oxazaborolidine 12 and 1,4-bis(trimethylsilyl)-1,3-
butadiyne 47 were purchased from Aldrich.
vinylic H of 5a), 7.24 (d, JZ13.5 Hz, vinylic H of 5b),
6.74 (d, JZ14.0 Hz, vinylic H of 5a), 6.47 (d, JZ13.5 Hz,
vinylic H of 5b), 2.46 (t, JZ7.4 Hz, 2H), 1.58–1.50 (m, 2H),
1.27–1.16 (m, 8H), 0.82 (t, JZ6.9 Hz, 3H).
5a. MS m/z 153 (23), 150 (56), 148 (60), 135 (65), 133 (62),
107 (15), 105 (14), 83 (14), 69 (23), 57 (31), 55 (46), 43
(53), 42 (27), 41 (100%).
5b. MS m/z 153 (17), 106 (24), 104 (76), 91 (32), 89 (100),
69 (15), 61 (19), 57 (15), 55 (25), 53 (11), 43 (44), 42 (22),
41 (84%).
3.1. Synthesis of (S)-Virol C
3.1.1. 2-(Hepta-4,6-diynyloxy)-tetrahydro-2H-pyran
(11).3 MeLi–LiBr complex (1.5 M) in ether (6.83 mL,
10.24 mmol) was added, under nitrogen, to a THF solution
(18 mL) of 1,4-bis(trimethylsilyl)-1,3-butadiyne 4 (1.80 g,
9.3 mmol) at room temperature. After complete desilylation
(5 h), the reaction mixture was cooled to K80 8C and
HMPA (3.24 mL, 18.60 mmol) was added. A solution of 6
(2.51 g, 9.3 mmol) in THF (18 mL) was slowly dropped at
the same temperature, then the mixture was slowly brought
to room temperature. After reaction completion (18 h),
the mixture was quenched with a saturated aqueous solution
of NaCl (100 mL), and extracted with ethyl acetate (3!
50 mL). The organic extracts were washed with a saturated
aqueous solution of NaCl (3!50 mL), dried over Na2SO4
and concentrated under vacuum. After percolation on florisil
column (20% ethyl acetate/petroleum ether) the residue was
dissolved in methanol (18 mL) and K2CO3 (1.54 g,
11.15 mmol) was added at room temperature. The reaction
mixture was stirred for 1.5 h, then concentrated under
vacuum. A saturated aqueous solution of NaCl (100 mL)
was added, then the reaction mixture extracted with ethyl
acetate (3!50 mL). The organic extracts were washed with
a saturated aqueous solution of NaCl (3!50 mL), dried
over Na2SO4 and concentrated under vacuum. The residue
was purified by column chromatography (10% ethyl acetate/
petroleum ether) leading to the title compound 11 as a pale
yellow oil (1.0 g, 56% yield).
3.1.3. (9E)-17-(Tetrahydropyranyl-2-oxy)-eptadec-9-en-
11,13-diyn-8-one (3). A solution of diyne 11 (0.774 g,
4.03 mmol) in THF (20 mL) was added at room tempera-
ture, under nitrogen, to a stirred mixture of 5 (0.90 g,
4.03 mmol), PdCl2(PPh3)2 (0.060 g, 0.08 mmol), CuI
(0.031 g, 0.16 mmol) and Et3N (0.84 mL, 6.05 mmol) in
THF (20 mL). After reaction completion (2 h), the mixture
was quenched with a saturated aqueous solution of NaCl
(50 mL), and extracted with ethyl acetate (3!50 mL). The
organic extracts were washed with a saturated aqueous
solution of NaCl (3!50 mL), dried over Na2SO4 and
concentrated under vacuum. The residue was purified by
column chromatography (10% ethyl acetate/petroleum
ether) leading to compound 3 as a pale yellow oil
(0.887 g, 64% yield). [Found: C, 76.75; H, 9.43.
C22H32O3 requires C, 76.70; H, 9.36%]; nmax (neat) 2929,
2856, 2229, 1692, 1589, 1465, 1455, 1440, 1383, 1368,
1354, 1201, 1136, 1122, 1076, 1035, 958 cmK1; dH
(500 MHz, CDCl3) 6.55 (d, JZ16.0 Hz, 1H), 6.49 (d, JZ
16.0 Hz, 1H), 4.52–4.49 (m, 1H), 3.80–3.69 (m, 2H), 3.45–
3.35 (m, 2H), 2.44 (t, JZ7.4 Hz, 2H), 2.42 (t, JZ7.0 Hz,
2H), 1.82–1.69 (m, 3H), 1.66–1.58 (m, 1H), 1.56–1.40 (m,
6H), 1.25–1.13 (m, 8H), 0.79 (t, JZ7.0 Hz, 3H); dC
(125.7 MHz, CDCl3) 198.6, 139.0, 121.7, 98.6, 88.4, 83.5,
72.0, 65.4, 65.0, 62.0, 41.1, 31.5, 30.4, 29.0, 28.9, 28.1,
25.3, 23.8, 22.4, 19.3, 16.5, 13.9; MS m/z 259 (8), 217 (7),
203 (5), 189 (26), 176 (18), 161 (9), 147 (7), 145 (7), 143
(6), 131 (9), 129 (9), 115 (19), 85 (100), 77 (11), 67 (30), 57
(60), 55 (49), 43 (82), 41 (88%).
The spectral data of compound 11 are in accordance with
the literature.3
3.1.2. (1E)-1-Bromodec-1-en-3-one (5a) and (1E)-1-
chlorodec-1-en-3-one (5b). A CH2Cl2 solution (10 mL) of
freshly distilled octanoyl chloride (1.09 g, 6.7 mmol) was
added, under nitrogen, to a cold (0 8C) suspension of
anhydrous AlCl3 (0.89 g, 6.7 mmol) in 10 mL of CH2Cl2.
The resulting mixture was stirred for 10 min at 0 8C, then a
solution of (E)-1-bromo-2-trimethylsilylethene 10 (1.0 g,
5.58 mmol) in 10 mL of CH2Cl2 was added dropwise. After
complete addition, the reaction mixture was stirred at 0 8C
for 1 h, quenched with a saturated aqueous solution of
NH4Cl (50 mL), and extracted with ethyl acetate (3!
50 mL). The organic extracts were dried over Na2SO4 and
concentrated under vacuum. The residue was purified by
column chromatography (5% ethyl acetate/petroleum ether)
leading to a 80:20 mixture of (1E)-1-bromodec-1-en-3-one
5a and (1E)-1-chlorodec-1-en-3-one 5b (1.21 g, 97% yield)
as a colorless oil. The mixture of 5a and 5b was employed
for the preparation of compound 3.
3.1.4.
(10S)-(8E)-Heptadec-8-en-4,6-diyn-1,10-diol
(Virol C) 1.3,5 0.61 mL (0.61 mmol) of a 1.0 M THF
solution of BH.3THF were added at room temperature, under
nitrogen, to 0.10 mL (0.10 mmol) of a 1.0 M solution of
(R)-2-methyl-CBS-oxazaborolidine in toluene and stirred
for 5 min. A solution of 0.175 g of ketone 3 (0.51 mmol) in
2.5 mL of THF was dropped, then the reaction mixture was
stirred for 1 h. After addition of 20 mL of water, the mixture
was extracted with ethyl acetate (3!20 mL). The organic
extracts were dried over Na2SO4 and concentrated under
vacuum. The residue was purified by percolation on florisil
column (10% ethyl acetate/petroleum ether), dissolved in
CH3OH (2 mL), then p-toluenesulfonic acid monohydrate
(0.019 g, 0.1 mmol) was added at room temperature. After
reaction completion (1 h), the mixture was quenched with
water (20 mL), and extracted with ethyl acetate (3!
20 mL). The organic extracts dried over Na2SO4 and
concentrated under vacuum. The residue was percolated
on florisil (50% ethyl acetate/petroleum ether) affording
0.070 g of Virol C (52% yield, 83% ee determined by
5a)C(5b. dH (500 MHz, CDCl3) 7.47 (d, JZ14.0 Hz,

V. Fiandanese et al. / Tetrahedron 61 (2005) 4551–4556
4555
HPLC, hexane/2-propanol 90/10, 0.5 mL/min), [a]DZ
C6.4 (cZ0.81, CH3OH), lit.2 [a]DZC6.4 (cZ0.82,
CH3OH). After crystallization from diethyl ether/hexane,
Virol C 1 was obtained as a white solid (mp 56–58 8C).
[Found: C, 77.79; H, 9.95. C17H26O2 requires C, 77.82; H,
9.99%]; nmax (KBr) 3318, 3235, 2954, 2931, 2853, 2237,
(2 h), the mixture was quenched with a saturated aqueous
solution of NH4Cl (50 mL), and extracted with ethyl acetate
(3!50 mL). The organic extracts were washed with water
(3!50 mL), dried over Na2SO4 and concentrated under
vacuum. The residue was purified by column chromato-
graphy (10% ethyl acetate/petroleum ether) leading to
0.807 g of compound 7 (69% yield). After crystallization
from hexane, the title compound was obtained as a white
solid (mp 65–67 8C). [Found: C, 84.35; H, 9.20. C17H22O
requires C, 84.25; H, 9.15%]; nmax (KBr) 3041, 2960, 2932,
2871, 2219, 1682, 1593, 1575, 1460, 1335, 1126, 1072,
1005 cmK1; dH (500 MHz, CDCl3) 7.07 (dd, JZ15.3,
11.3 Hz, 1H), 6.68 (dd, JZ15.3, 11.3 Hz, 1H),), 6.18 (d,
JZ15.3 Hz, 1H), 5.96 (d, JZ15.3 Hz, 1H), 2.49 (t, JZ
7.5 Hz, 2H), 2.28 (t, JZ6.9 Hz, 2H), 1.60–1.49 (m, 4H),
1.31–1.18 (m, 4H), 0.95 (t, JZ7.4 Hz, 3H), 0.83 (t, JZ
7.0 Hz, 3H); dC (125.7 MHz, CDCl3) 200.2, 141.6, 140.0,
131.3, 118.8, 88.0, 81.1, 73.4, 65.2, 40.9, 31.3, 23.8, 22.3,
21.6, 13.8, 13.3; MS m/z 242 (MC, 4), 213 (4), 185 (11), 171
(9), 157 (7), 152 (9), 143 (7), 128 (26), 115 (18), 95 (8), 91
(7), 77 (8), 71 (12), 65 (7), 63 (8), 55 (14), 51 (9), 43 (100),
41 (34%).
1622, 1463, 1423, 1133, 1061, 1037, 1017, 961, 725 cmK1
;
dH (500 MHz, CDCl3) 6.24 (dd, JZ15.9, 5.8 Hz, 1H), 5.69
(dd, JZ15.9, 1.4 Hz, 1H), 4.13 (dq, JZ1.4, 5.8 Hz, 1H),
3.71 (t, JZ6.5 Hz, 2H), 2.43 (t, JZ6.5 Hz, 2H), 1.87 (br s,
2H), 1.76 (quintet, JZ6.5 Hz, 2H), 1.53–1.45 (m, 2H),
1.37–1.18 (m, 10H), 0.85 (t, JZ6.9 Hz, 3H); dC
(125.7 MHz, CDCl3) 148.9, 108.5, 83.5, 74.7, 73.3, 72.1,
65.5, 61.3, 36.9, 31.8, 30.9, 29.4, 29.2, 25.2, 22.6, 16.1,
14.1; MS m/z 217 (1), 191 (1), 177 (2), 163 (6), 145 (2), 135
(8), 127 (10), 115 (9), 107 (8), 91 (15), 77 (13), 57 (100), 55
(21), 43 (45), 41 (32%).
3.2. Synthesis of 1-dehydroxyvirol A
3.2.1. 1-Trimethylsilyl-1,3-heptadiyne (14). This com-
pound was prepared in 60% yield (yellow oil) according to
our reported procedure.8 [Found: C, 73.00; H, 9.88.
C10H16Si requires C, 73.10; H, 9.81%]; nmax (neat) 2964,
2937, 2902, 2875, 2227, 2109, 1460, 1251, 1181, 846, 761,
630 cmK1; dH (500 MHz, CDCl3) 2.23 (2H, t, JZ7.2 Hz),
1.53 (2H, sextet like JZ7.2 Hz) 0.97 (3H, t, JZ7.2 Hz),
0.16 (9H, s); dC (125.7 MHz, CDCl3) 88.4, 83.0, 80.1, 65.5,
21.6, 21.2, 13.5, K0.3; MS m/z 164 (MC, 7), 150 (15), 149
(100), 121 (6), 120 (7), 107 (7), 105 (7), 93 (5), 91 (7), 83
(11), 79 (9), 77 (6), 73 (3), 69 (4), 67 (7), 53 (10), 43 (25%).
3.2.4. (6S)-(7E,9E)-Heptadeca-7,9-dien-11,13-diyn-6-ol
(1-dehydroxyvirol A) 2.4 0.50 mL (0.50 mmol) of a THF
solution (1.0 M) of BH3. THF were added at room
temperature, under nitrogen, to 0.083 mL (0.083 mmol) of
a toluene solution (1.0 M) of (R)-2-methyl-CBS-oxaza-
borolidine and stirred for 5 min. A solution of 0.10 g of
ketone 7 (0.413 mmol) in 2 mL of THF was dropped, then
the reaction mixture was stirred for 1 h. After addition of
20 mL of water, the mixture was extracted with ethyl acetate
(3!20 mL). The organic extracts were dried over Na2SO4
and concentrated under vacuum. The residue was purified
by column chromatography (10% ethyl acetate/petroleum
ether) leading to 0.055 g (54% yield) of dehydroxyvirol A 2
as a pale yellow oil (84% ee determined by HPLC, hexane/
2-propanol 97/3, 0.5 mL/min). [a]DZC16.5 (cZ0.60,
CH3OH), lit.4 [a]DZC15.4 (cZ0.67, CH3OH). [Found:
C, 83.59; H, 9.85. C17H24O requires C, 83.55; H, 9.90%];
nmax (neat) 3366, 3024, 2959, 2931, 2864, 2228, 2136, 1636,
1588, 1459, 1383, 985 cmK1; dH (500 MHz, CDCl3) 6.63
(dd, JZ15.6, 10.9 Hz, 1H), 6.22 (dd, JZ15.3, 10.9 Hz, 1H),
5.80 (dd, JZ15.3, 6.4 Hz, 1H), 5.57 (d, JZ15.6 Hz, 1H),
4.14 (q, JZ6.4 Hz, 1H), 2.27 (t, JZ7.0 Hz, 2H), 1.79 (br s,
1H), 1.59–1.44 (m, 4H), 1.35–1.20 (m, 6H), 0.96 (t, JZ
7.4 Hz, 3H), 0.85 (t, JZ6.9 Hz, 3H); dC (125.7 MHz,
acetone-d6) 145.7, 143.3, 128.7, 109.7, 86.1, 77.3, 75.4,
71.9, 66.3, 38.3, 32.7, 26.0, 23.5, 22.6, 21.9, 14.5, 13.8; MS
m/z 215 (3), 202 (2), 201 (2), 187 (2), 173 (8), 145 (9), 131
(85), 129 (6), 128 (8), 117 (9), 115 (15), 105 (6), 99 (7), 95
(9), 91 (13), 77 (11), 71 (22), 55 (12), 43 (100), 41 (29%).
3.2.2. (1E,3E)-1-Iodo-deca-1,3-dien-5-one (8). A CH2Cl2
solution (10 mL) of freshly distilled hexanoyl chloride
(0.894 g, 6.64 mmol) was added, under nitrogen, to a cold
(0 8C) suspension of anhydrous AlCl3 (0.885 g, 6.64 mmol)
in 10 mL of CH2Cl2. The resulting mixture was stirred for
10 min at 0 8C, then a solution of (1E,3E)-1-iodo-4-
trimethylsilylbutadiene 13 (1.395 g, 5.53 mmol) in 14 mL
of CH2Cl2 was added dropwise. After complete addition, the
reaction mixture was stirred at 0 8C for 2 h, quenched with
0.1 N HCl (50 mL), and extracted with ethyl acetate (3!
50 mL). The organic extracts were washed with water (3!
50 mL), dried over Na2SO4 and concentrated under vacuum.
The residue was purified by percolation on florisil column
(10% ethyl acetate/petroleum ether) affording 1.343 g of
compound 8 (87% yield), which was immediately employed
for the preparation of compound 7. dH (500 MHz, CDCl3)
7.11 (dd, JZ14.4, 11.2 Hz, 1H), 6.95 (dd, JZ15.4, 11.2 Hz,
1H), 6.93 (d, JZ14.4 Hz, 1H), 6.12 (d, JZ15.4 Hz, 1H),
2.47 (t, JZ7.4 Hz, 2H), 1.55 (quintet, JZ7.4 Hz, 2H),
1.30–1.17 (m, 4H), 0.83 (t, JZ7.0 Hz, 3H).
3.2.3. (7E,9E)-Heptadeca-7,9-dien-11,13-diyn-6-one (7).
To a solution of iodide 8 (1.343 g, 4.83 mmol) in anhydrous
DMF (12 mL) at room temperature, under nitrogen, were
successively added Pd(PPh3)4 (0.278 g, 0.24 mmol), AgCl
(0.138 g, 0.96 mmol) and K2CO3 (5.332 g, 38.64 mmol).
The resulting mixture was stirred for 5 min, then MeOH
(1.236 g, 38.64 mmol), was added followed by a solution of
the diyne 14 (0.792 g, 4.82 mmol) in anhydrous DMF
(12 mL). The reaction mixture was warmed to 40 8C and
stirred at the same temperature. After reaction completion
Acknowledgements
This work was financially supported in part by the Ministero
`
dell’Istruzione, dell’Universita e della Ricerca (M.I.U.R.),
Rome, and the University of Bari (National Project
‘Stereoselezione in Sintesi Organica. Metodologie ed
Applicazioni’).

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V. Fiandanese et al. / Tetrahedron 61 (2005) 4551–4556
Holland, J. P.; Howard, J. A. K.; Lin, Z.; Marder, T. B.;
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