An alternative synthesis of (8E,10Z)-tetradeca-8,10-dienal, sex pheromone of horse-chestnut leafminer (Cameraria ohridella)

Article abstract of DOI:10.1016/j.tet.2008.12.044

The stereoselective synthesis of the sex pheromone of horse-chestnut leafminer was efficiently carried out using methodology based on the Pd(0)-catalyzed cross-coupling of 1-pentynylmagnesium bromide with the corresponding vinyl iodides as the key step.

Full text of DOI:10.1016/j.tet.2008.12.044

Tetrahedron 65 (2009) 1648–1654
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An alternative synthesis of (8E,10Z)-tetradeca-8,10-dienal, sex pheromone of
horse-chestnut leafminer (Cameraria ohridella)
*
Jacek Grodner
Institute of Industrial Organic Chemistry, 6 Annopol St., 03-236 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 August 2008
Received in revised form 26 November 2008
Accepted 11 December 2008
Available online 24 December 2008
The stereoselective synthesis of the sex pheromone of horse-chestnut leafminer was efficiently carried
out using methodology based on the Pd(0)-catalyzed cross-coupling of 1-pentynylmagnesium bromide
with the corresponding vinyl iodides as the key step.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Sex pheromone
Cross-coupling reaction
Dienal
Natural product synthesis
1. Introduction
drawback of the Wittig reaction-based process is the high cost of
removal of triphenylphosphine oxide (the main by-product of the
(8E,10Z)-Tetradeca-8,10-dienal (1) was identified by Svatos
et al.1 as the female sex pheromone of the horse-chestnut leaf-
miner, Cameraria ohridella (Lepidoptera, Gracillariidae). This insect
is an economically important defoliating pest of horse-chestnuts
(Aesculus hippocastanum L.) and it is found throughout Europe.
The reported synthetic routes to 12,4,5 are based on the C–C bond
forming strategy with different carbon chain units. The first syn-
thesis of (8E,10Z)-tetradeca-8,10-dienal was achieved by Svatos
et al.2 by employing the C7þC2þC5 strategy. The key intermediate
for the synthesis, the (E)-14-(tert-butoxy)tetradec-6-en-4-yne, was
prepared by Sonogashira cross-coupling3 of (E)-9-(tert-butoxy)-1-
iodonon-1-ene (prepared in five steps from heptane-1,7-diol) with
1-pentyne. A Sonogashira protocol,2 involving the reaction of
a terminal alkyne with an organic halide in the presence of a cata-
lytic amount of Pd–phosphine complex and CuI as well as amine
base and benzene as the solvent, generally offered acceptable re-
sults at a relatively small scale. The use of the toxic solvent makes
this process much less attractive for large-scale preparation.
The improved procedures for the synthesis of the pheromone C.
ohridella, reported both by Francke et al.4 (C7þC3þC4 strategy) and
Szocs et al.5 (C8þC2þC4 strategy), employ the Wittig reaction as
the key step. However, such a process does not afford a product of
high enough chemical or isomeric purity. Another important
Wittig reaction), especially on the industrial process scale.
In 2007 Christmann et al.6 reported a short synthesis of alde-
hyde 1 (over four steps) using a combination of two Wittig re-
actions. The shortcoming of the Wittig reaction, especially
a relatively low isomeric purity of the product (ca. 90%), makes this
method a less desirable alternative, considering the potential
commercial application. It should be noted that in all published up-
to-date synthetic routes toward pheromone 1 that expensive
chromatographic purification is necessary for most of the isolated
compounds. Thus, the development of an expeditious, cost-effec-
tive, and operationally simple synthetic approach is necessary. A
particular incentive for this work is that this pheromone is in-
creasingly used for large-scale field tests.
We report herein a new stereoselective synthesis for (8E,10Z)-
tetradeca-8,10-dienal (1, C5þC5þC4 strategy), which successfully
overcomes the major limitations of the strategies published pre-
viously and which can be scaled up easily. The stereospecific in-
troduction of double bonds in this synthesis was achieved by the
methodology based on the Pd(0)-catalyzed cross-coupling between
suitable haloalkene and the known7 1-pentynylmagnesium bro-
mide. This type of cross-coupling8 was also used for the preparation
of a key compound in Svatos’s strategy,2 (E)-14-(tert-butoxy)tet-
radec-6-en-4-yne (13). In addition, we synthesized the (8E,10Z)-
tetradeca-8,10-dien-1-ol (precursor of the title pheromone, 18), by
a simple methodology based on the stereoselective dehydration of
* Tel.: þ48 22 8111231 261.
a
-alkynediols with potassium hydrogen sulfate.9
E-mail address: grodner@ipo.waw.pl
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.044

J. Grodner / Tetrahedron 65 (2009) 1648–1654
1649
O
1
O
O
OtBu
OH
OH
7
13
17
OtBu
I
O
O
ClMg
Cl
I
12
16
5
OH
O
OtBu
11
I
Cl
O
6
2
O-THP
14
OH
Cl
Cl
Cl
OH
9
Scheme 1. Retrosynthetic analysis of aldehyde 1 of the female-produced contact sex pheromone of the horse-chestnut leafminer, C. ohridella.
The retrosynthetic analysis of pheromone 1 (with part of the
different disconnection strategies realized in this paper) is shown
in Scheme 1.
Thus, starting with commercial 5-chloro-1-pentyne and diiso-
butyl aluminum hydride (DIBAH) in hexane we prepared the cor-
responding alkenyl diisobutylalane,10 which without isolation was
iodinated to give (E)-vinyl iodide 2 in a high stereoisomeric purity
(>99%, GC). Iodide 2 reacts efficiently with 1-pentynylmagnesium
bromide (generated in situ from magnesium, ethyl bromide, and 1-
pentyne) and 3% Pd(PPh3)4 inTHF below 15 ꢀC for 1 h, to give chloro-
enyne 3 in 89% yield. Chloro-enyne 3 showed a high stereoisomeric
purity (>99%) established by 1H NMR spectroscopy and GC analysis.
Iodination of chloride 3 in methyl ethyl ketone with NaI gave crude
compound 5, which was used without further purification in the
next step.
2. Results and discussion
2.1. Synthesis of pheromone 1 employing the C5DC5DC4
strategy
Scheme 2 summarizes the coupling of individual building blocks
to construct intermediate with the carbon skeleton of target
pheromone and its further conversion to the final aldehyde 1.
b
a
Cl
I
Cl
Cl
2
3
c
c
b
Cl
Cl
I
I
I
HO
O
5
4
d,e
O
O
g
f
MgCl
O
6
O
O
O
7
h
O
O
8
i
1
Scheme 2. Synthesis of 1 employing the C5þC5þC4 strategy; (a) 1. DIBAH, hexane, 50 ꢀC; 2. I2, THF, ꢁ40 ꢀC (63%, two steps); (b) n-PrC^CMgBr, 3 mol % Pd(PPh3)4, THF (89% for 3;
99% for 5); (c) NaI, CH3COC2H5 (90% for 4; 95% for 5); (d) PCC, CH2Cl2; (e) HOCH2CH2CH2OH, TsOH, toluene (47%, two steps); (f) Mg, C2H5I, THF; (g) CuBr, THF, ꢁ20 ꢀC/10 ꢀC (80%);
(h) 1. dicyclohexylborane, THF, 2. glacial AcOH, 3. 6 N NaOH, 4. 30% H2O2 (83%); (i) HCO2H–CCl3CH3 (72%).

1650
J. Grodner / Tetrahedron 65 (2009) 1648–1654
In an alternative approach, enyne 5 was prepared by iodination
the E-iodo-alkenes compared to their Z-counterparts.18 Enyne 13
was successfully used by Svatos et al.2 during the synthesis of
pheromone 1 (over four steps).
of chloride 2, followed by the reported cross-coupling reaction.8
The coupling reaction between di-iodide 4 and 1-pentynylmagne-
sium bromide proceeded quantitatively with an exclusive attack at
the alkenyl iodide.11 The overall yield for the two-step sequence
was ca. 90%. The crude iodide 5 was coupled with the Grignard
reagent, prepared from 2-(3-chloropropyl)-1,3-dioxane (6) in THF,
under copper(I) catalysis to afford enyne 7 in 80% yield and stereo-
isomeric purity of >99%. Chloride 6 was prepared by the oxidation
of 4-chloro-1-butanol with pyridinium chlorochromate (PCC),
followed by the protection of crude intermediate aldehyde as
1,3-dioxane derivative using 1,3-propanediol–p-toluenesulfonic
acid, under conditions of continuous removal of the water–toluene
azeotrope.12 The yield of 6 was 47% (over two steps). The selective
hydroboration of acetylene group in enyne 7 with dicyclohexyl-
borane and successive protonolysis of the vinyl–boron intermediate
with acetic acid and treatment with alkaline H2O2 gave diene 8 in
83% yield. The stereoisomeric purity of 8 was ca. 98%. Compound 8
was directly converted to the final aldehyde 1 (in 72% yield) by
treatment with anhydrous formic acid and 1,1,1-trichloroethane
(1:1) at 45 ꢀC (using a method reported by Normant et al.13).
Pheromone 1 partially isomerized (w2%) under these vigorous
conditions. Spectroscopic data of aldehyde 1 were in full accordance
with those in the literature.2,4,6 This aldehyde had similar stereo-
isomeric purity (ca. 95%) with the title pheromone prepared by
Svatos et al.2 Aldehyde 1 and propheromone 8 were tested suc-
cessfully in a separate biological investigation.14
2.3. Precursor of the target pheromone ((8E,10Z)-tetradeca-
8,10-dien-1-ol, 18)
The synthesis of (8E,10Z)-tetradeca-8,10-dien-1-ol (18), the
precursor of pheromone 1,2 was accomplished starting from the
readily available alkyne 1416 (Scheme 4). Thus, the transmetallation
of alkyne 14 with n-butyllithium, followed by the treatment with
pentanal led to the corresponding alcohol 15 in 84% yield. Alcohol
15 was converted into the free diol 16 by treatment with p-tolue-
nesulfonic acid in methanol. a-Alkynediol 16 was dehydrated with
potassium hydrogen sulfate9 by distillation under reduced pressure
(vacuum oven, 155–165 ꢀC/0.2 mmHg). Enynol 17 was obtained in
40% yield and its analysis (by GC) indicated that it exists as mixture
of 10Z and 10E isomers in a ratio of 81:19, which was also confirmed
by the 1H NMR spectrum. Dienol 18 was obtained in 71% yield by
the reduction of enyne 17 with an excess of lithium tetrahydro-
aluminate (LAH) in a mixture of diglyme and THF19 at 117–121 ꢀC
for 29 h. The GC and 1H NMR analyses of alcohol 18 indicated
a 67:33 ratio of isomers (i.e., 10Z-isomer and the respective 10E-
isomer). The latter can be removed as a THP ether derivative by
Diels–Alder reaction with tetracyanoethylene.4
2.2. Synthesis of the key intermediate 13 according to
3. Conclusion
C7DC2DC5 strategy
The work described herein establishes a different/improved ap-
proach to the synthesis of sex pheromone of C. ohridella and its
precursors using the Pd(0)-catalyzed cross-coupling of 1-pentynyl-
magnesium bromide with suitable vinyl iodides. The high yield and
stereoselectivity in addition to the mild reaction conditions make
the present process [both variantsdthe (C5þC5þC4) approach as
well as Svatos’s strategy] useful for the synthesis of the title phero-
mone. Moreover, the variant of the synthesis using the (C5þC5þC4)
strategy is arguably more straightforward than other reported
methods (minimal number of steps using less expensive raw
materials). Furthermore, this strategy could serve as a general
methodology for the synthesis of the E–Z dienic pheromoneswith an
aldehyde function. The protected aldehyde (acetal 8, propher-
omone) obtained by applying this methodology could be a useful
tool for the study of a controlled release of the pheromone into the
environment.12
Vinyl iodide 12, which finally was converted to the key synthon
13 by mentioned earlier cross-coupling reaction with 1-pentynyl-
magnesium bromide, was synthesized in a simple three-step re-
action sequence from 7-chloroheptan-1-ol15 (Scheme 3). Protection
of the hydroxyl group in chlorohydrin 9 as the tert-butyl ether
followed by the ethynylation of chloride 10 using a procedure
previously developed in our laboratory16 gave terminal alkyne 11 in
ca. 70% yield (over two steps). Alkyne 11 was readily converted to
vinyl iodide 12 by treatment with diisobutyl aluminum hydride
(DIBAH) in hexane, followed by the iodination.17 The stereoisomeric
purity of vinyl iodide 12 was ca. 94%. The Pd(0)-catalyzed cross-
coupling of iodide 12 with 1-pentynylmagnesium bromide gave
key intermediate 13 in 94% yield. The small increase (ca. 4%) of the
stereoisomeric purity of product was noted, in comparison to the
starting iodide 12. It may be explained by the higher reactivity of
a
b
HO
tBu-O
tBu-O
Cl
tBu-O
Cl
9
10
d
c
tBu-O
I
11
12
1
13
Scheme 3. Synthesis of the key intermediate 13 according to C7þC2þC5 strategy; (a) isobutylene, Amberlyst H-15, hexane (84%); (b) LiC^CH$EDA, DMA, ꢁ5 ꢀC/ rt, (82%); (c) 1.
DIBAH, hexane, 53 ꢀC, 2. I2, THF, ꢁ47 ꢀC (61%, two steps); (d) n-PrC^CMgBr, 3 mol % Pd(PPh3)4, THF (94%).

J. Grodner / Tetrahedron 65 (2009) 1648–1654
1651
b
a
THP-O
HO
THP-O
14
15
OH
c
d
HO
16
17
OH
1
HO
18
THP =
O
Scheme 4. Synthesis of precursor 18; (a) 1. n-BuLi, THF, ꢁ30 ꢀC/0 ꢀC, 2. pentanal, THF, ꢁ25 ꢀC (84%, two steps); (b) TsOH, MeOH (85%); (c) KHSO4, Bu¨chi B-580 vacuum oven
155–165 ꢀC/0.2 mmHg (40%); (d) LAH, diglyme–THF, 117–121 ꢀC for 29 h (71%).
4. Experimental
4.1. General
CH2CH]C), 3.54 (t, 2H, J¼6.5, CH2Cl), 6.10 (dt, H, J¼1.2, 14.2,
ꢂ
CH]CH), 6.49 (dt, H, J¼7.0, 14.4, CH]CH); HRMS (EI): [M]þ m/z
229.93557, calcd for C5H385ClI 229.93593.
All anhydrous solvents and reagents were prepared from re-
agent grade materials using conventional methods.20 The reactions
of air- and moisture-sensitive materials were carried out in a flame-
dried glassware under an argon atmosphere. The transfer of air-
and water-sensitive solutions was done using hypodermic syringes.
Column chromatography was performed using Merck Silica gel 60
(0.04–0.063 mm). Thin-layer chromatography was performed on
Alufolien with Merck Silica gel 60 F254. IR spectra were measured
using FT/IR-420 ‘Jasco’ instrument (neat, cmꢁ1). 1H NMR spectra
were recorded using Varian 200 MHz spectrometer for solutions in
CDCl3 (internal TMS). 13C NMR spectra were obtained on a Varian
200 MHz spectrometer operating at 50.2 MHz, unless otherwise
4.3. (E)-10-Chlorodec-6-en-4-yne (3)
A solution of pentynylmagnesium bromide in THF (100 mL) was
prepared7 from magnesium (1.37 g, 0.056 g-atoms), ethyl bromide
(4.6 mL, 6.7 g, 61 mmol), and 1-pentyne (5 mL, 3.5 g, 52 mmol),
which was added over 15 min to a stirred mixture of vinyl iodide 2
(9.2 g, 40 mmol) and tetrakis(triphenylphosphine)palladium (1.4 g,
1.2 mmol, 3 mol % catalyst) in THF (60 mL) at 5 ꢀC. The mixture was
stirred for 1 h at 14 ꢀC, quenched with 20% aqueous ammonium
chloride (100 mL), and organic layer was separated. The aqueous
layer was extracted with petroleum ether (3ꢃ120 mL). The com-
bined organic extracts were washed with 20% aqueous ammonium
chloride (2ꢃ120 mL), brine (2ꢃ120 mL), and dried over anhydrous
magnesium sulfate. The solution was filtered, the filtrate was con-
centrated in vacuo, and the residue was purified by distillation
under reduced pressure (Bu¨chi B-580 vacuum oven, 95–110 ꢀC/
0.4 mmHg) to give enyne 3 (6.1 g; 89%) as a colorless oil (GC purity
95%). IR: 2220 (C^C), 956 (CH]CH trans); 1H NMR: 1.02 (t, 3H,
J¼7.4, CH3), 1.48–1.70 (m, 2H, CH3CH2), 1.76–2.06 (m, 2H,
CH2CH2Cl), 2.22–2.40 (m, 4H, CH2C^CCH]CHCH2), 3.57 (t, 2H,
J¼6.5, CH2Cl), 5.55 (m, H, J¼15.8, CH]CH), 6.03 (dt, H, J¼7.1, 15.8,
noted. Chemical shifts (d) are reported in parts per million and
coupling constants in hertz. Mass spectra were measured on an API
365 or AMD M-40W spectrometer. The purity of the synthesized
compounds was estimated by GC method, using a Varian STAR
3400 CX chromatograph equipped with a flame ionization detector
(250 ꢀC), injector ‘on column’ (230 ꢀC), and a capillary column: DB1
(30 m, 0.53 mm i.d., 0.25 mm), the inert carrier gas was nitrogen.
The oven temperature was ꢁp1rogrammed from 90 ꢀC (held for
3 min) to 180 ꢀC at 20 ꢀC min (held for 0 min) and then temper-
ature was ramped to 230 ꢀC at 5 ꢀC minꢁ1 (held for 10 min). 7-
Chloroheptan-1-ol (10) and 9-(2-tetrahydropyranyloxy)-1-nonyne
(15) were prepared according to Ref. 16.
ꢂ
35
CH]CH); HRMS (EI): [M]þ m/z 170.08632, calcd for C10
H Cl
15
170.08623.
4.4. (E)-1,5-Diiodo-1-pentene (4)
4.2. (E)-1-Iodo-5-chloro-1-pentene (2)10
To a solution of compound 2 (13.9 g, 60.3 mmol) in 2-butanone
(180 mL), the anhydrous sodium iodide (24 g, 160 mmol) was
added at room temperature. The reaction mixture was heated un-
der gentle reflux for 7 h and then stirred at room temperature
overnight. The mixture was cooled (0 ꢀC) and hexane (350 mL) was
added to precipitate the inorganic salts, which were filtered off
using a sintered glass funnel. The filtrate was concentrated in vacuo
and pentane (200 mL) was added to precipitate the residual in-
organic salts. The solution was filtered, the filtrate was concen-
trated in vacuo to afford the iodide 4 (17.5 g; 90%) as a colorless oil,
which was used without further purification. IR: 941 (CH]CH
trans); 1H NMR: 1.80–2.02 (m, 2H, CH2CH2I), 2.08–2.30 (m, 2H,
CH]CHCH2), 3.18 (t, 2H, J¼6.7, CH2I), 6.11 (dt, H, J¼1.3, 14.4,
A solution of diisobutyl aluminum hydride (1 M in hexane,
100 mL, 100 mmol) was added to a solution of 1-chloro-4-pentyne
(10 g, 97.5 mmol) in hexane (50 mL) at room temperature. The
mixture was heated at 50 ꢀC for 2 h, cooled to ꢁ40 ꢀC, and THF
(50 mL) was added, followed by a dropwise addition of a solution of
iodine (25.4 g, 100 mmol) in THF (90 mL). The mixture was warmed
to ꢁ10 ꢀC and quenched with 5% sulfuric acid (90 mL). The organic
layer was separated, washed with saturated aqueous sodium
thiosulfate, brine, and dried over anhydrous magnesium sulfate.
The solution was filtered, the filtrate was evaporated, and the res-
idue was distilled under reduced pressure using a Bu¨chi B-580
vacuum oven (125–140 ꢀC/2 mmHg) to afford vinyl iodide 2 (14.2 g;
63%) as a colorless oil (GC purity 96%). IR: 947 (CH]CH trans); 1H
NMR: 1.72–2.04 (m, 2H, CH2CH2Cl), 2.24 (dq, 2H, J¼1.2, 7.2,
ꢂ
CH]CH), 6.47 (dt, H, J¼7.2, 14.4, CH]CH); HRMS (EI): [M]þ m/z
321.87081, calcd for C5H8I2 321.87155.

1652
J. Grodner / Tetrahedron 65 (2009) 1648–1654
4.5. (E)-10-Iododec-6-en-4-yne (5) from chlorodecenyne (3)
4.8. 2-(7E-Tridecen-9-ynyl)-1,3-dioxane (7)
To a solution of compound 3 (5.8 g, 34 mmol) in 2-butanone
(90 mL), the anhydrous sodium iodide (10.4 g, 69 mmol) was added
at room temperature. The reaction mixture was heated under
gentle reflux for 9 h and then stirred at room temperature over-
night. Hexane (150 mL) was added to the cooled mixture (0 ꢀC) to
precipitate inorganic salts, which were filtered off using sintered
glass funnel. The filtrate was concentrated in vacuo and additional
pentane (150 mL) was added to precipitate the residual inorganic
salts. The solution was filtered again and the filtrate was concen-
trated in vacuo to afford iodide 5 (8.5 g; 95%) as a colorless oil,
which was used without purification in the next step. IR: 2220
(C^C), 952 (CH]CH trans); 1H NMR: 0.99 (t, 3H, J¼7.3, CH3), 1.44–
1.66 (m, 2H, CH3CH2), 1.80–1.98 (m, 2H, CH2CH2I), 2.12–2.34 (m, 4H,
CH2C^CCH]CHCH2), 3.18 (t, 2H, J¼6.8, CH2I), 5.46–5.62 (m, H,
To a solution of magnesium (1.35 g, 0.056 g-atoms) in THF
(12 mL), were added freshly distilled 2-(3-chloropropyl)-1,3-di-
oxane 6 (0.35 mL) and ethyl iodide (0.17 mL, 0.33 g, 2.1 mmol)
under argon. The mixture was gently refluxed until the reaction
started. The additional portions of freshly distilled 2-(3-chloro-
propyl)-1,3-dioxane 6 (7.1 mL, 8.25 g, 50.5 mmol) were added at
a rate sufficient to maintain a gentle reflux (the mixture was heated
to reflux if needed). After complete addition, the mixture was
stirred at 60 ꢀC until all magnesium was consumed, and then
cooled to room temperature to give a Grignard reagent solution.
The Grignard reagent solution was diluted with THF (25 mL) and
the solution was added dropwise over 35 min to a stirred mixture
of (E)-10-iododec-6-en-4-yne 5 (8.4 g, 32 mmol) and cuprous(I)
bromide (0.64 g) in THF (135 mL) at ꢁ20 ꢀC. The mixture was stir-
red at ꢁ15 ꢀC for 15 min and was allowed to warm up gradually to
10 ꢀC and stirred for 30 min. Subsequently, the reaction mixture
was cooled to ꢁ5 ꢀC and quenched with saturated aqueous am-
monium chloride (80 mL). The organic layer was separated and the
aqueous layer was extracted with ether (150 mL). The combined
organic solutions were washed with saturated aqueous ammonium
chloride (2ꢃ150 mL), brine (2ꢃ100 mL), and dried over anhydrous
magnesium sulfate. The solution was filtered, and the filtrate was
concentrated in vacuo. The residue was partially purified by dis-
tilling off the volatile impurities (Bu¨chi B-580 vacuum oven, 60–
70 ꢀC/0.05 mmHg). The crude product was purified by column
chromatography on silica-gel (9:1 hexane–ether) to give enyne 7
(6.75 g, 80%) as a colorless oil (GC purity 98%). IR: 2210 (C^C), 1146
(C–O), 958 (CH]CH trans); 1H NMR: 0.99 (t, 3H, J¼7.3, CH3), 1.16–
1.68 (m, 13H, 6CH2 and OCH2CHHCH2O), 1.94–2.20 (m, 3H,
CH2CH]C and OCH2CHHCH2O), 2.26 (dt, 2H, J¼1.9, 7.2, CH2C^C),
3.66–3.86 (m, 2H, OCH2), 4.02–4.18 (m, 2H, OCH2), 4.50 (t, H, J¼5.1,
CH2OCHOCH2), 5.45 (dt, 1H, J¼1.7, 15.8, CH]CH), 6.04 (dt, 1H, J¼6.9,
15.6, CH]CH); 13C NMR: 13.72 (CH3), 21.51 (CH2), 22.44 (CH2),
24.04 (CH2), 26.03 (CH2), 28.87 (CH2), 29.13 (CH2), 29.42 (CH2),
33.08 (CH2), 35.36 (CH2), 67.07 (2CH2O), 79.50 (C^C), 88.69 (C^C),
102.57 (CH]CH), 110.00 (HC]CH), 143.46 (CHO2); HRMS (EI):
ꢂ
CH]CH), 5.97 (dt, H, J¼7.2, 15.7, CH]CH); HRMS (EI): [M]þ m/z
262.02161, calcd for C10H15I 262.02185.
4.6. (E)-10-Iododec-6-en-4-yne (5) from diiodopentene (4)
A solution of pentynylmagnesium bromide in THF (150 mL),
prepared7 from magnesium (2.03 g, 0.083 g-atoms), ethyl bromide
(6.6 mL, 9.6 g, 88 mmol), and 1-pentyne (7.4 mL, 5.1 g, 75 mmol),
was added over 20 min to a stirred mixture of vinyl iodide 4
(17.48 g, 54.3 mmol) and tetrakis(triphenylphosphine)palladium
(1.75 g, 1.5 mmol, 3 mol % catalyst) in THF (75 mL) at 5 ꢀC. The
mixture was stirred for 1 h at 10 ꢀC, then quenched with 20%
aqueous ammonium chloride (140 mL), and the organic layer was
separated. The aqueous layer was extracted with petroleum ether
(3ꢃ150 mL). The combined organic solutions were washed with
20% aqueous ammonium chloride (2ꢃ200 mL) and brine (200 mL).
The organic layer was concentrated and 300 mL of pentane was
added to the residue. The mixture was washed with 20% aqueous
ammonia (2ꢃ100 mL), 20% aqueous ammonium chloride
(2ꢃ150 mL), water (150 mL), and dried with magnesium sulfate.
Finally, the mixture was filtered through a charcoal plug and con-
centrated under reduced pressure. The crude enyne 5 (14.1 g, 99%)
was used in the next step without further purification.
ꢂ
[M]þ m/z 264.20953, calcd for C17H28O2 264.20893.
4.7. 2-(3-Chloropropyl)-1,3-dioxane (6)
4.9. 2-((7E,9Z)-trideca-7,9-dienyl)-1,3-dioxane (8)
A solution of freshly distilled 90% 4-chloro-1-butanol (25 g,
207 mmol) in dichloromethane (200 mL) was added slowly (over
To a stirred and cooled suspension of dicyclohexylborane in THF
(70 mL), freshly prepared from boron–dimethyl sulfide complex
(2 mol Lꢁ1, 16.2 mL) and cyclohexene (6.8 mL, 5.52 g, 67.2 mmol),
the solution of enyne 7 (6.67 g, 25.3 mmol) in THF (84 mL) was
added dropwise at 0 ꢀC (ice bath). The reaction mixture was kept at
room temperature for 4 h, diluted with glacial acetic acid (8.4 mL),
and then heated at 60 ꢀC for 5 h. The oxidation of the resulting
dicyclohexylborinate was achieved by treatment with aqueous 6 N
sodium hydroxide (33.6 mL), followed by the dropwise addition of
30% hydrogen peroxide (8.4 mL) at 30 ꢀC. The mixture was stirred
for additional 30 min and product was extracted with hexane
(4ꢃ120 mL). The combined extracts were washed with brine and
dried over anhydrous magnesium sulfate. The solution was filtered,
the filtrate evaporated, and the volatile impurities were distilled off
(Bu¨chi B-580 vacuum oven, 70–76 ꢀC/0.05 mmHg). The residue was
purified by column chromatography on silica-gel (hexane–ether,
9:1) to yield diene 8 (5.6 g; 83%) as a colorless oil (GC purity 95%).
IR: 1146 (C–O), 984, 947 (cis,trans-conjugated diene); 1H NMR: 0.92
(t, 3H, J¼7.5, CH3), 1.20–1.68 (m, 13H, 6CH2 and OCH2CHHCH2O),
1.96–2.24 (m, 5H, 2CH2CH]C and OCH2CHHCH2O), 3.66–3.86 (m,
2H, OCH2), 4.00–4.20 (m, 2H, OCH2), 4.50 (t, H, J¼5.2, CH2O-
CHOCH2), 5.30 (dt, H, J¼7.5, 10.8, CH]C), 5.64 (dt, 1H, J¼7.1, 14.8,
CH]C), 5.95 (br t,1H, J¼10.8, CH]C), 6.29 (ddq,1H, J¼1.2,11.0,15.0,
CH]C); 13C NMR: 13.94 (CH3), 23.06 (CH2), 24.07 (CH2), 26.02
1.5 h) to
a suspension of pyridinium chlorochromate (93 g,
431 mmol) in dichloromethane (200 mL). The mixture was stirred
for 3.5 h at room temperature and diluted with anhydrous ether
(500 mL), filtered through a pad of CeliteÔ and neutral alumina.
The residue (black gum) was triturated with ether (3ꢃ100 mL,
anhydrous). The combined etheral solutions were concentrated to
give crude aldehyde (17.8 g) as a pale yellow, fragrant liquid.
To a solution of the crude aldehyde (17.7 g, 166 mmol) dissolved
in toluene (600 mL), the trimethylene glycol (15 mL) was added,
followed by p-toluenesulfonic acid (0.2 g). The resulting mixture
was stirred under gentle reflux with a water-separator for 16 h and
then cooled to room temperature. The reaction mixture was
washed with saturated aqueous sodium bicarbonate (350 mL),
water (3ꢃ350 mL), dried with magnesium sulfate, filtered, and the
filtrate evaporated in vacuo. The residue was distilled under re-
duced pressure (Bu¨chi B-580 vacuum oven, 125–140 ꢀC/5 mmHg)
to give acetal 6 (16 g, 47%) as a colorless oil (GC purity 95%). IR: 1146
(C–O); 1H NMR: 1.27–1.42 (m, H, OCH2CHHCH2O), 1.67–2.21 (m, 5H,
2CH2 and OCH2CHHCH2O), 3.56 (t, 2H, J¼6.5, CH2Cl), 3.67–3.84 (m,
2H, OCH2), 4.02–4.18 (m, 2H, OCH2), 4.56 (t, H, J¼4.9, CH2O-
CHOCH2); HRMS (EI): [MꢁH]þ m/z 163.05185, calcd for C7H12O325Cl
163.05258.

J. Grodner / Tetrahedron 65 (2009) 1648–1654
1653
(CH2), 29.25 (CH2), 29.43 (CH2), 29.49 (CH2), 29.90 (CH2), 33.00
(CH2), 35.38 (CH2), 67.05 (2CH2O), 102.58 (CHO2), 125.84 (CH]CH),
128.94 (CH]CH), 129.99 (HC]CH), 134.74 (CH]CH); HRMS (EI):
vacuum oven, 70–86 ꢀC/0.05 mmHg). The residue was purified by
column chromatography on silica-gel (hexane–ethyl acetate, 80:1)
to give vinyl iodide 12 (5.15 g; 61%) as a colorless oil (GC purity
90%). 1H NMR: 1.18 (s, 9H, tBu), 1.24–1.62 (m, 10H, 5CH2), 2.04 (br q,
2H, J¼6.8, CH2CH]C), 3.32 (t, 2H, J¼6.6, CH2OR), 5.96 (dt, H, J¼1.4,
ꢂ
[M]þ m/z 266.22507, calcd for C17H30O2 266.22458.
ꢂ
4.10. (8E,10Z)-Tetradeca-8,10-dienal (1)
14.2, CH]CH), 6.51 (dt, H, J¼7.2, 14.2, CH]CH); HRMS (EI): [M]þ
m/z 324.09448, calcd for C13H25OI 324.09502.
Anhydrous formic acid (6 mL) was added dropwise (under argon
atmosphere) to a stirred and cooled solution of acetal 8 (1.78 g,
6.7 mmol) in dry 1,1,1-trichloroethane (6 mL) at 0 ꢀC (ice bath). The
emulsion was stirred at 45 ꢀC (oil bath) for 5 h, and the reaction
mixture was cooled and poured into cold water (120 mL). Sub-
sequent standard work-up and purification by column chroma-
tography on silica-gel (0.3% triethylamine in benzene–hexane, 1:1)
afforded dienal 1 (1 g, 72%) as a colorless oil (GC purity 94%). IR:
1727 (C]O), 984, 949 (cis,trans-conjugated diene); 1H NMR: 0.92
(t, 3H, J¼7.3, CH3), 1.20–1.74 (m, 10H, 5CH2), 2.00–2.22 (m, 4H,
2CH2CH]C), 2.42 (dt, 2H, J¼1.9, 7.4, CH2CHO), 5.31 (dt, H, J¼7.6,
10.8, CH]C), 5.64 (dt, H, J¼7.2, 14.9, CH]C), 5.96 (t, H, J¼10.8,
CH]C), 6.30 (ddq, H, J¼1.0, 10.8, 14.9, CH]C), 9.77 (t, H, J¼1.9,
CHO); 13C NMR: 13.95 (CH3), 22.18 (CH2), 23.06 (CH2), 29.06 (CH2),
29.16 (CH2), 29.32 (CH2), 29.92 (CH2), 32.91 (CH2), 44.05 (CH2),
126.00 (CH]CH), 128.87 (CH]CH), 130.19 (CH]CH), 134.48
(HC]CH), 203.07 (CHO); HRMS (EI): [M]þꢂ m/z 208.32507, calcd for
C14H24O 208.32458.
4.14. (E)-14-(tert-Butoxy)tetradec-6-en-4-yne (13)
A solution of 1-pentynylmagnesium bromide in THF (45 mL),
prepared7 from magnesium (0.59 g, 0.025 g-atoms), ethyl bromide
(1.95 mL, 2.83 g, 26 mmol), and 1-pentyne (2.15 mL, 1.49 g,
22 mmol), was added over 15 min to a stirred mixture of vinyl io-
dide 12 (5.1 g, 15.7 mmol) and tetrakis(triphenylphosphine)palla-
dium (533 mg, 0.46 mmol, 3 mol % catalyst) in THF (20 mL) at 5 ꢀC.
The mixture was stirred for 1 h at 14 ꢀC, then quenched with 20%
aqueous ammonium chloride (50 mL), and organic layer was sep-
arated. The aqueous layer was extracted with petroleum ether
(3ꢃ60 mL). The combined extracts were washed with 20% aqueous
ammonium chloride (2ꢃ100 mL), brine (2ꢃ100 mL), and dried over
anhydrous magnesium sulfate. The solution was filtered and the
filtrate was evaporated in vacuo. The purification of the residue by
column chromatography on silica-gel (40:1 hexane–ether) gave the
corresponding enyne 13 (3.9 g, 94%) as a colorless oil (GC purity
94%). IR: 2220 (C^C), 1083 (C–O), 955 (CH]CH trans); 1H NMR:
t
4.11. 1-Chloro-7-(tert-butoxy)heptane (10)
0.99 (t, 3H, J¼7.3, CH3), 1.18 (s, 9H, Bu), 1.24–1.66 (m, 12H, 6CH2),
2.07 (br q, 2H, J¼6.6, CH2CH]C), 2.26 (dt, 2H, J¼2.0, 7.0, CH2C^C),
3.32 (t, 2H, J¼6.6, CH2OR), 5.44 (dt, H, J¼1.6, 15.8, CH]CH), 6.05 (dt,
H, J¼7.2, 15.6, CH]CH); 13C NMR: 13.73 (CH3), 21.53 (CH2), 22.46
(CH2), 26.36 (CH2), 27.76 (3CH3), 28.98 (CH2), 29.25 (CH2), 29.50
(CH2), 30.85 (CH2), 33.13 (CH2), 61.79 (CH2O), 72.60 (OC(CH3)3),
79.52 (C^C), 88.69 (C^C), 109.97 (CH]CH), 143.56 (HC]CH);
HRMS (ESI): [MþNa]þ m/z 287.2349, calcd for C18H32ONa 287.2345.
Compound 10 was prepared from chloroheptanol 9 (11.3 g,
75 mmol), 2-methylpropene, and Amberlyst H-15 (2.0 g) using
a reported procedure.21 The yield was 84% (13.0 g); bp 62–64 ꢀC/
0.05 mmHg (lit.17 bp 65 ꢀC/0.03 mmHg). IR: 1083 (C–O), 726, 650
t
(C–Cl); 1H NMR: 1.18 (s, 9H, Bu), 1.06–1.90 (m, 10H, 5CH2), 3.33 (t,
2H, J¼6.4, CH2OR), 3.53 (t, 2H, J¼6.9, CH2Cl).
4.12. 9-(tert-Butoxy)non-1-yne (11)
4.15. 1-(2-Tetrahydropyranyloxy)-10-hydroxytetradec
-8-yne (15)
To a cooled (ꢁ5 ꢀC) suspension of lithium acetylide–ethyl-
enediamine complex (4.7 g, 52 mmol) in dry DMA (40 mL) under
argon 1-chloro-7-(tert-butoxy)heptane 10 (4.1 g, 19.8 mmol) was
added dropwise over 75 min. The mixture was stirred for 18 h at
room temperature, poured into iced water, and extracted with
petroleum ether. The combined organic extracts were washed with
brine, dried over anhydrous magnesium sulfate, filtered, and the
filtrate concentrated in vacuo. The residue was purified by column
chromatography on silica-gel (25:1 hexane–ether) to give the
known alkyne 11 (3.2 g; 82%)17 as a colorless oil (GC purity 95%). IR:
To
a stirred solution of n-BuLi (1.4 M in hexane, 14 mL,
19.6 mmol) was added dropwise the solution of 9-(2-tetrahydro-
pyranyloxy)-1-nonyne 14 (3.6 g, 16 mmol) in dry THF (32 mL) over
15 min at ꢁ30 ꢀC. The mixture was warmed to 0 ꢀC, stirred for
15 min, cooled to ꢁ30 ꢀC and the solution of pentanal (2.2 mL, 1.8 g,
20.9 mmol) in dry THF (7 mL) was added and stirring continued for
60 min at ꢁ25 ꢀC. The reaction mixture allowed to warm up to
room temperature, stirred for 2 h, then poured into cold water
(50 mL), and extracted with hexane (3ꢃ70 mL). The combined ex-
tracts were washed with brine (2ꢃ100 mL), dried over anhydrous
magnesium sulfate, filtered, and the filtrate was concentrated un-
der reduced pressure. The residue was purified by column chro-
matography on silica-gel (hexane–ether, 2:1) to give tetradecynol
15 (4.2 g, 84%) as a colorless oil (GC purity 94%). IR: 3436 (OH), 2213
(C^C); 1H NMR: 0.92 (t, 3H, J¼7.0, CH3), 1.20–1.96 (m, 22H, 11CH2),
2.14–2.26-(m, 2H, CH2C^C), 3.28–3.96 (m, 4H, 2 ꢀCH2), 4.26–4.40
(m, 1H, CHOH), 4.58 (dd, 1H, J¼2.7, 4.1, OCHO); 13C NMR: 14.21
(CH3), 18.82 (CH2), 19.85 (CH2), 22.56 (CH2), 25.67 (CH2), 26.26
(CH2), 27.57 (CH2), 28.73 (CH2), 28.88 (CH2), 29.07 (CH2), 29.83
(CH2), 30.94 (CH2), 38.10 (CH2), 62.52 (CHOH), 62.90 (CH2O), 67.79
(CH2O), 81.61 (C^C), 85.56 (C^C), 99.02 (CHO2); HRMS (ESI):
[MþNa]þ m/z 333.2414, calcd for C19H34O3Na 333.2400.
t
2120 (C^CH), 1085 (C–O); 1H NMR (200 MHz): 1.18 (s, 9H, Bu),
1.22–1.64 (m, 10H, 5CH2), 1.93 (t, 1H, J¼2.6, C^CH), 2.18 (dt, 2H,
J¼2.6, 7.0, CH2C^C), 3.32 (t, 2H, J¼6.6, CH2O).
4.13. (E)-9-(tert-Butoxy)-1-iodonon-1-ene (12)
To a solution of alkyne 11 (5.12 g, 26.1 mmol) in hexane (5 mL),
was added the diisobutyl aluminum hydride (1 M in hexane, 27 mL,
27 mmol) at room temperature. The mixture was heated to 53 ꢀC
for 2 h, then cooled to ꢁ47 ꢀC, and THF (12.5 mL) was added, fol-
lowed by a dropwise addition of solution of iodine (6.6 g, 26 mmol)
in THF (12.5 mL). The mixture was slowly warmed to room tem-
perature (30 min) and hydrolyzed with 5% sulfuric acid (25 mL).
The organic layer was separated and the aqueous layer was
extracted with ether (25 mL). The combined extracts were washed
with saturated aqueous sodium bicarbonate (35 mL), saturated
aqueous sodium thiosulfate (35 mL), brine (35 mL), and dried over
anhydrous magnesium sulfate. The solution was filtered, the filtrate
evaporated, and the volatile impurities removed (Bu¨chi B-580
4.16. 10-Hydroxytetradec-8-yn-1-ol (16)
A solution of compound 15 (4 g, 13 mmol) in methanol (30 mL)
was treated with p-toluenesulphonic acid (92 mg) and stirred at
room temperature for 5 h. The saturated aqueous sodium

1654
J. Grodner / Tetrahedron 65 (2009) 1648–1654
bicarbonate (1.3 mL) was added and stirring continued for 15 min
at room temperature. Methanol was removed under reduced
pressure and the residue was treated with ether (80 mL). The
precipitated solids were filtered off and the organic layer was
separated. The aqueous layer was extracted with ether (3ꢃ10 mL).
The combined extracts were washed with brine, dried over anhy-
drous magnesium sulfate, filtered, and the filtrate was concentrated
in vacuo. The crude product was purified by column chromatog-
raphy on silica-gel (hexane–ethyl acetate, 2:1) to give diol 16 (2.5 g;
85%) as a colorless oil (GC purity 96%). IR: 3348 (OH), 2229 (C^C);
1H NMR: 0.92 (t, 3H, J¼7.1, CH3), 1.20–1.80 (m, 16H, 8CH2), 2.20 (dt,
2H, J¼2.0, 6.8, CH2C^C), 3.64 (t, 2H, J¼6.5, CH2OH), 4.34 (tt, 1H,
J¼2.0, 6.5, CHOH); 13C NMR: 14.03 (CH3), 18.63 (CH2), 22.39 (CH2),
25.57 (CH2), 27.39 (CH2), 28.50 (CH2), 28.67 (CH2), 28.80 (CH2),
32.64 (CH2), 37.93 (CH2), 62.72 (CHOH), 62.95 (CH2OH), 81.50
(C^C), 85.34 (C^C); HRMS (ESI): [MþNa]þ m/z 249.1832, calcd for
C14H26O2Na 249.1825.
was filtered and the filtrate was concentrated in vacuo. Residue was
purified by column chromatography on silica-gel (hexane–ethyl
acetate, 2:1) to give dienol 18 (74 mg, 71%) as a colorless oil. GC
analysis indicated that compound 18 has 67% stereoisomeric pu-
rity.23 IR: 3330 (C–O), 982, 947 (cis,trans-conjugated diene); 1H
NMR: 0.92 (t, 3H, J¼7.2, CH3), 1.20–1.70 (m, 12H, 6CH2), 1.92–2.24
(m, 4H, 2CH2CH]C), 3.64 (t, 2H, J¼6.5, CH2OH), 5.32 (dt, H, J¼7.4,
10.6, CH]C), 5.66 (dt, H, J¼7.2, 15.1, CH]C), 5.97 (br t, H, J¼10.7,
CH]C), 6.30 (ddq, H, J¼1.2,10.9,15.1, CH]C); 13C NMR: 13.79 (CH3),
22.90 (CH2), 25.69 (CH2), 29.17 (CH2), 29.28 (CH2), 29.33 (CH2),
29.75 (CH2), 32.77 (CH2), 32.84 (CH2), 63.06 (CH2OH), 125.71
(CH]CH), 128.76 (CH]CH), 129.92 (CH]CH), 134.57 (HC]CH);
HRMS (ESI): [MþNa]þ m/z 233.1875, calcd for C14H26ONa 233.1881.
Acknowledgements
This work was partially supported by the Polish State Committee
for Scientific Research, project No. 6T09 2003 C/06263.
4.17. 10(Z)-Tetradecen-8-yn-1-ol (17)
A mixture of diol 16 (0.45 g, 2 mmol) and potassium hydrogen
sulfate (100 mg) was distilled using Bu¨chi B-580 vacuum oven
(temperature 155–165 ꢀC, pressure 0.2 mmHg, time 40 min). The
distillate was diluted with ether (20 mL), washed with saturated
aqueous sodium bicarbonate (10 mL), and dried over anhydrous
magnesium sulfate. The solution was filtered and the filtrate was
evaporated to give enynol 17 (165 mg, 40%) as a colorless oil. The GC
analysis indicates that compound 17 has 81% stereoisomeric pu-
rity.22 IR: 3341 (OH), 2215 (C^C), 730 (CH]CH cis); 1H NMR: 0.93
(t, 3H, J¼7.3, CH3), 1.20–1.76 (m, 12H, 6CH2), 2.24–2.37 (m, 4H,
CH2C^CCH]CHCH2), 3.64 (t, 2H, J¼6.3, CH2OH), 5.42–5.48 (m, 1H,
CH]CH), 5.82 (dt, 1H, J¼7.4, 10.8, CH]CH); 13C NMR: 13.77 (CH3),
19.49 (CH2), 22.18 (CH2), 25.66 (CH2), 28.79 (2CH2), 28.94 (CH2),
32.09 (CH2), 32.73 (CH2), 63.02 (CH2OH), 77.48 (C^C), 94.31 (C^C),
109.92 (CH]CH), 143.19 (HC]CH); HRMS (ESI): [MþNa]þ m/z
231.1718, calcd for C14H24ONa 231.1725.
References and notes
1. Svatos, A.; Kalinova, B.; Hoskovec, M.; Kindl, J.; Hovorka, O.; Hrdy, I. Tetrahedron
Lett. 1999, 40, 7011–7014.
2. Hoskovec, M.; Saman, D.; Svatos, A. Collect. Czech. Chem. Commun. 2000, 65,
511–523.
3. Sonogashira, K.; Tohda, T.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467–4470.
4. Francke, W.; Franke, S.; Bergman, J.; Tolasch, T.; Subchev, M.; Mircheva, A.;
Toshova, T.; Svatos, A.; Kalinova, B.; Karpati, Z.; Szocs, G.; To´th, M. Z. Naturforsch.
2002, 57c, 739–752.
5. Szocs, G.; Karpati, Z.; Nagy, Z.; Saly, K.; Sebestyen, A.; Nemesto´thy, K.; Ujvary, I.
IOBS Working Group Meeting in Erice, Sicily, Sep 22–27, 2002 (http://phero.
net/iobc/sicily/abs/szocs.pdf).
6. Figueiredo, R. M.; Berner, R.; Julis, J.; Liu, T.; Turp, D.; Christmann, M. J. Org.
Chem. 2007, 72, 640–642.
7. Baylis, Ch. J.; Odle, S. W.; Tyman, J. H. P. J. Chem. Soc., Perkin Trans. 1 1981,
132–141.
8. Negishi, E.; Kotora, M.; Xu, C. J. Org. Chem. 1997, 62, 8957–8960.
9. Cardillo, G.; Cugola, A.; Orena, M.; Sandri, S. Gazz. Chim. Ital. 1982, 112, 231–233.
10. Solladie, G.; Kovenski, J.; Colobert, F. Tetrahedron: Asymmetry 1993, 4, 2173–
2178.
11. Jabri, N.; Alexakis, A.; Normant, J. F. Bull. Soc. Chim. Fr. 1983, 321–332.
12. Scheurer, A. Ger. Pat. DE 10 2004 048 082 A1, 2006; Chem. Abstr. 2006, 144,
345102.
4.18. (8E,10Z)-Tetradeca-8,10-dien-1-ol (18)
Lithium tetrahydroaluminate (100 mg, 2.6 mmol) was added in
portions to an ice-cooled mixture of dry diglyme (1.2 mL) and THF
(0.15 mL) under argon atmosphere. When the vigorous foaming
had subsided the solution of enynol 17 (104 mg, 0.5 mmol) in
diglyme (0.3 mL) was added to the thick slurry. Following the initial
foaming, the mixture was heated at 117–121 ꢀC (oil bath) for 29 h.
The mixture was cooled to 0 ꢀC and the hexane (8 mL) was added,
followed by a cautious dropwise addition of water (0.2 mL), fol-
lowed by 20% sodium hydroxide (0.16 mL), and water (0.75 mL).
The mixture was stirred for 15 min to allow the precipitate to
granulate, then the hexane layer was decanted, and the solid resi-
due was rinsed several times with of hexane (4ꢃ5 mL). The com-
bined hexane solutions were washed with water (3ꢃ5 mL), brine
(10 mL), and dried over anhydrous magnesium sulfate. The solution
13. Gardette, M.; Alexakis, A.; Normant, J. F. Tetrahedron 1984, 40, 2740–2750.
´
14. Grodner, J.; Jab1on´ ski, T.; Kolk, A.; Przybysz, E.; Slusarski, S. Pestycydy/Pesticides
2008, 3–4, 5–13.
15. This reagent can be purchased from Narchem Corporation or prepared by
monochlorination of 1,7-heptanediol.
16. Karpin´ ska, M.; Lewandowska, M.; Grodner, J. Pol. J. Chem. 2004, 78, 937–942.
17. Tellier, F.; Sauvetre, R.; Normant, J. F. J. Organomet. Chem. 1989, 364, 17–28.
18. Jabri, N.; Alexakis, A.; Normant, J. F. Tetrahedron Lett. 1981, 22, 959–964.
19. McElfresh, J. S.; Millar, J. G.; Rubinoff, D. J. Chem. Ecol. 2001, 27, 791–806.
20. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.;
Pergamon Press: Oxford, 1988.
21. Alexakis, A.; Gardette, M.; Colin, S. Tetrahedron Lett. 1988, 29, 2951–2954.
22. 1H NMR spectra for enynol 17 contain additional signals of its E-counterpart (in
ratio 1:4): 0.90 (t, 3H, J¼7.5, CH3), 2.03–2.09 (m, 2H, CH2CH]C), 2.19–2.23 (m,
2H, CH2C^C), 5.45–5.48 (m, H, CH]CH), 6.05 (dt, H, J¼7.0, 15.5, CH]CH).
23. 1H NMR spectra for dienol 18 contain additional signals of its E-counterpart:
0.90 (t, 3H, J¼7.2, CH3), 1.92–2.24 (m, 4H, 2CH2CH]CH), 5.34–5.76 (m, 2H,
CH]CH), 5.86–6.08 (m, 2H, CH]CH).