Pheromone synthesis. Part 257: Synthesis of methyl (2E,4Z,7Z)-2,4,7-decatrienoate and methyl (E)-2,4,5-tetradecatrienoate, the pheromone components of the male dried bean beetle, Acanthoscelides obtectus (Say)

Article abstract of DOI:10.1016/j.tet.2015.06.051

Tandem Dess-Martin oxidation/Wittig reaction of (2Z,5Z)-2,5-octadien-1-ol yielded methyl (2E,4Z,7Z)-2,4,7-decatrienoate, a newly discovered pheromone component of the male dried bean beetle, while that of (±)-2,3-dodecadien-1-ol gave (±)-methyl (E)-2,4,5-tetradecatrienoate, the racemate of the known and major pheromone component. Methyl (2E,4E,7Z)-2,4,7-decatrienoate was also synthesized, which is the methyl ester of an acid metabolite of a green alga. Reduction of 2,5-octadiyn-1-ol with Zn-Cu/EtOH cleanly gave (2Z,5Z)-2,5-octadien-1-ol.

Full text of DOI:10.1016/j.tet.2015.06.051

Accepted Manuscript
Pheromone synthesis. Part 257: Synthesis of methyl (2E,4Z,7Z)-2,4,7-decatrienoate
and methyl (E)-2,4,5-tetradecatrienoate, the pheromone components of the male
dried bean beetle, Acanthoscelides obtectus (Say)
Kenji Mori
PII:
S0040-4020(15)00935-7
10.1016/j.tet.2015.06.051
TET 26887
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 June 2015
Revised Date: 11 June 2015
Accepted Date: 12 June 2015
Please cite this article as: Mori K, Pheromone synthesis. Part 257: Synthesis of methyl (2E,4Z,7Z)-2,4,7-
decatrienoate and methyl (E)-2,4,5-tetradecatrienoate, the pheromone components of the male dried
bean beetle, Acanthoscelides obtectus (Say), Tetrahedron (2015), doi: 10.1016/j.tet.2015.06.051.
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ACCEPTED MANUSCRIPT
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ACCEPTED MANUSCRIPT
Pheromone synthesis. Part 257: Synthesis of methyl (2E,4Z,7Z)-2,4,7-decatrienoate and methyl
(E)-2,4,5-tetradecatrienoate, the pheromone components of the male dried bean beetle,
Acanthoscelides obtectus (Say)ꢀ
Kenji Mori*
Photosensitive Materials Research Center, Toyo Gosei Co., Ltd, 4-2-1 Wakahagi, Inzai-shi, Chiba
270-1609, Japan
ARTICLE INFO
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
Acanthoscelides obtectus (Say)
Alkadiene, (Z,Z)-skipped
Allene
Pheromone
Tandem Dess-Martin oxidation/ Wittig reaction
Zn-Cu/EtOH reduction
ABSTRACT
Tandem Dess-Martin oxidation/Wittig reaction of (2Z,5Z)-2,5-octadien-1-ol yielded methyl
(2E,4Z,7Z)-2,4,7-decatrienoate, a newly discovered pheromone component of the male dried bean
beetle, while that of (±)-2,3-dodecadien-1-ol gave (±)-methyl (E)-2,4,5-tetradecatrienoate, the
racemate of the known and major pheromone component. Methyl (2E,4E,7Z)-2,4,7-decatrienoate
was also synthesized, which is the methyl ester of an acid metabolite of a green alga. Reduction of
2,5-octadiyn-1-ol with Zn-Cu/EtOH cleanly gave (2Z,5Z)-2,5-octadien-1-ol.
ꢀ For Part 256, see Ref. 1.
* Tel.: +81 3 3816 6889; fax: + 81 3 3813 1516; e-mail address: kjk-mori@arion.ocn.ne.jp
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1. Introduction
In 1970 Horler isolated (-)-methyl (E)-2,4,5-tetradecatrienoate (1, Fig.1) as the male pheromone
of the dried bean beetle, Acanthoscelides obtectus (Say)[Coleoptera: Bruchidae].2 This chiral and
non-racemic allene attracted the attention of chemists, and a number of synthesis of (±)-, (R)- and
(S)-1 were reported to date as detailed in ref. 3 and references cited therein.
The absolute configuration of 1 was definitely determined as R (87% ee) by my synthesis of the
enantiomers of 13 followed by their GC comparison with the naturally occurring 1.4 Although (R)-1
was electroantennographically bioactive, it did not attract females, indicating that there must be
additional pheromone components. International cooperative investigations carried out by several
research groups culminated in the identification of two additional methyl esters 2 and 3 along with
three other active compounds.4 A mixture of all six components in natural proportions proved to be
behaviorally bioactive as the pheromone of the dried bean beetle.4 As reported previously,3 the
synthesis of 2 could be accomplished smoothly. However, the synthesis of 3, a new compound, was
not at all easy despite its seemingly simple structure, because of its high tendency to isomerize.
Fig. 1. Structures 1, 2 and 3 of the pheromone components of the male dried bean beetle,
Acanthoscelides obtectus, and structure 4 of a metabolite of the green alga, Cladophora columbiana.
The first objective of this paper is to report the synthesis of methyl (2E,4Z,7Z)-2,4,7-decatrienoate
(3) and its (2E,4E,7Z)-isomer (5). The latter is the esterification product of an acid metabolite 4 of
the green alga, Cladophora columbiana.5 The second objective is to describe a concise synthesis of
(±)-1 by modification of Landor's 1971 route.6 An attempted preparation of (S)-1 is also recorded.
2. Results and discussion
2.1. Attempted synthesis of 2 and 3 via organopalladium chemistry
As shown in Scheme 1, the pheromone components 2 and 3 seemed to be obtainable from
intermediates 8 and 11, which were to be prepared by either Sonogashira coupling7 or Heck reaction.8
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Scheme 1. Attempts to prepare 2 and 3 via organopalladium chemistry. Reagents: (a) PdCl2(Ph3P)2,
CuI, Et3N, THF (50% for 8); (b) H2, Pd/BaSO4, quinolone, MeOH (45%); (c) I2, morpholine, C6H6
(27%); (d) Pd(OAc)2, K2CO3, (n-Bu)4NCl, DMF.
Firstly, an attempt was made to execute the Sonogashira coupling between 1-heptyne (6) and
methyl β-iodoacrylate (7)9, which was successful to give the desired ester 8 in 50% yield. Semi-
hydrogenation of 8 was expected to give the pheromone component 2. Unfortunately, however,
hydrogenatgion of 8 over Pd/BaSO4 in the presence of quinoline in MeOH10 yielded the
over-reduction product 9 instead of the desired 2.
Secondly, the Sonogashira coupling of 1,4-heptadiyne (10)11 with methyl β-iodoacrylate (7) was
attempted employing PdClꢁ(Ph3P)2 and CuI as catalysts in the presence of Et3N in THF.
Unfortunately, the reaction gave only a dark and obscure mixture of products, and 11 could not be
secured. The next attempt was the Heck reaction of 1-iodo-1,4-heptadiyne (12) with methyl acrylate
(13). In this attempt, too, no useful product such as 11 could be obtained. It therefore seemed that
the presence of the skipped diyne system in 10 and 12 was the major reason for the failure to obtain 11.
Thus, organopalladium chemistry turned out to be of no use in this particular case.
2.2. Attempted application of the two successful routes for the synthesis of 1 and 2 to the
synthesis of 3
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In my previous synthesis of 1, organoselenium chemistry was successfully employed to introduce
the (E)-double bond at C-2 of 1.3 It was therefore expected that ester 15 (Scheme 2) would give
(2E,4Z,7Z)-3 via α-phenylselenenyl ester 16. The starting (3Z,6Z)-3,6-nonadien-1-ol (14) was
prepared by the known method.12 Its purity, however, was only 81% with 18% of the isomers of
nonen-1-ol, the over-reduction products generated in the course of the semi-hydrogenation of
3,6-nonadiyn-1-ol. The impure dienol 14 was then converted to methyl (4Z,7Z)-4,7-decadienoate
(15) after four synthetic operations: (i) tosylation, (ii) treatment with KCN, (iii) alkaline hydrolysis
with NaOH in refluxing aq. EtOH, and (iv) esterification with CH2N2. The resulting 15 was only
44% pure, contaminated with (4E,7Z)-isomer (20%) and others. Presumably, heating under alkaline
conditions to hydrolyze the nitrile group proceded with concomitant isomerization of the (Z)-double
bond at C-4 to give more stable (E)-isomer and also with conjugation of the two double bonds.
Scheme 2. Further unsuccessful attempts to prepare 3. Reagents: (a) TsCl, C5H5N, DMAP (87%);
(b) KCN, DMSO [quant. (77% purity)]; (c) NaOH, EtOH, H2O, reflux, 6 h (87%), (d) CH2N2, Et2O
{80% [44% of 15, 20% of (4E,7Z)-isomer, 28% of other isomers of 15 and 5% of dihydro
compounds]}; (e) KN(SiMe3)2, PhSeCl,THF (48%); (f) NaIO4, THF, H2O [45% (61% of 5, 3% of 3
and other isomers)]; (g) DMP, CH2Cl2; (h) TMSC≡CH, MeMgBr, THF; (i) K2CO3, MeOH (37%,
three steps); (j) MeC(OMe)3, EtCO2H, o-xylene, 145oC (1 h) and then 160-170oC (1 h) (85%); (k)
Al2O3 (basic Brockmann 1), o-xylene, 160oC (2 h) [41% (38% of 3, 21% of 19 and total 25% of
isomers of 3 with strong M+ at m/z = 180)].
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Subsequent phenylselenenylation of 15 gave crude 16, whose oxidative elimination with NaIO4
afforded the desired (2E.4Z,7Z)-3 only as a minor product (3% of the whole products), while the major
product (61% of the whole products) was (2E,4E,7Z)-5 generated by further isomerization of the
double bond at C-4. It therefore became clear that the organoselenium route was inadequate for the
synthesis of (2E,4Z,7Z)-3 due to unexpectedly facile isomerization of the trienoate system of 3.
In my previous synthesis of (2E,4Z)-2,3 methyl 3,4-decadienoate was subjected to Tsuboi's
interesting allene to conjugated diene rearrangement reaction13 to give the desired 2. The
rearrangement was thought to be applicable to the synthesis of (2E,4Z,7Z)-3 from allene 19, which
could be prepared from commercially available (Z)-3-hexen-1-ol (17) via acetylenic alcohol 18. The
alcohol 18 was synthesized by ethynylation of (Z)-3-hexenal, which was obtained by oxidation of 17
with Dess-Martin periodinane (DMP).14 Conversion of 18 to 19 was executed via orthoester Claisen
rearrangement employing methyl orthoacetate in the presence of propanoic acid. Thermal
rearrangement of allene 19 in the presence of Al2O3 indeed gave (2E,4Z,7Z)-3, but its purity was only
38% with recovered allene 19 (21%) and many other isomers of 3. It therefore became clear that a
new route to 3 must be explored.
2.3. Successful synthesis of methyl (2E,4Z,7Z)-decatrienoate (3) and its (2E,4E,7Z)-isomer (5)
A lesson learned from the failures as described above in 2.2. was the instability of the
2E,4Z,7Z-triene system of 3. To avoid isomerization of the double bond geometries, the following
two points seemed to be of importance: (i) preparation of pure (2Z,5Z)-2,5-octadien-1-ol (23) and (ii)
its one-pot conversion to (2E,4Z,7Z)-3 by a tandem oxidation/olefination process.
The starting material for the synthesis of 3 (Scheme 3) was commercially available
1-bromo-2-pentyne (20). Alkylation of the tetrahydropyranyl (THP) ether (21) of propargyl alcohol
with 20 was executed as reported by Kobayashi et al. to give 2,5-octadiyn-1-ol (22) in 90% yield after
deprotection.15
Reduction of 22 to (2Z,5Z)-2,5-octadien-1-ol (23) was then examined by employing various
different methods. Semi-hydrogenation of 22 to 23 was very sluggish when Lindlar catalyst16 was
employed in either hexane/THF or MeOH. Recently reported Kaneda's Pd/SiO2-DMSO catalyst17 in
hexane/THF did not work either (extremely sluggish rate of hydrogenation). When Cram's
Pd/BaSO4 catalyst was employed in MeOH containing quinoline,10 hydrogenation took place
smoothly at 0-5oC. The course of hydrogenation could be monitored by GC-MS. Hydrogenation
of the C-2 triple bond was almost four times more rapid than that of the C-5 triple bond, and the
desired (2Z,5Z)-23 was generated subsequently. The Z/E selectivity, however, was not so high,
giving 86% pure (2Z,5Z)-23 in 87% yield after distillation A number of by-products (Z/E-isomers
and over-reduced alken-1-ols) were present in the distilled product, (2E,5Z)-isomer having been the
major one (6.3%) as analyzed by GC-MS. The selectivity was worse when the hydrogenation was
carried out at room temperature (20-22oC), while no hydrogen uptake was observed at -78oC.
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Scheme 3. Synthesis of 3 and 5. Reagents: (a) EtMgBr, CuI, THF; (b) aq. HCl, MeOH (90%, two
steps); (c) H2, Pd/BaSO4, quinoline, MeOH [87% (86% purity)]; (d) Zn, Br(CH2)2Br, CuBr, LiBr,
EtOH, 100ꢂC (5-6 h), 80oC (16 h for 23 and 3 d for 25) [70% (99% purity) for (2Z,5Z)-23 and 73%
(98% purity) for (2E,5Z)-25]; (e) DMP, Ph3P=CHCO2Me, PhCO2H, DMSO, CH2Cl2 [71% (85%
purity) for 3 and 62% (75% purity) for 5]; (f) LiAlH4, THF (15%); (g) Zn, Br(CH2)2Br, EtOH, 100oC
(45 min) [50% (96.5% purity)].
Chemical reduction of 22 to 23 was also examined. Titanium (II)-based reduction as reported by
Kitching18 was not suitable for gram-scale preparation. Finally, the best reduction method was found
to be the classical one with Zn and EtOH as reported by Brandsma.19 When Zn activated with
Br(CH2)2Br was used in EtOH, 22 was reduced to give (Z)-2-octen-5-yn-1-ol (26) after refluxing for
45 min. Prolonged heating did not reduce the enyne 26 to 23. However, when Zn activated with
Br(CH2)2Br in hot EtOH was treated with CuBr and LiBr, the resulting Zn/Cu in EtOH [100oC (bath
temperature) for 6 h and 80oC (bath temperature) for 16 h] converted 22 to (2Z,5Z)-23 of 99% purity
in 70% yield after distillation. It thus became possible to obtain 99% pure (2Z,5Z)-23 in gram scale.
Chemical reduction with Zn/Cu in EtOH was better in selectivity than catalytic semi-hydrogenation
over Pd/BaSO4 catalyst in this particular case.
The final step was the tandem oxidation/olefination to convert (2Z,5Z)-23 to (2E,4Z,7Z)-3.
Tandem MnO2 oxidation/Wittig olefination as reported by Taylor20 was first applied to 23.
Unfortunately, however, the product was a messy mixture of unidentified esters. Barrett's DMP
oxidation/Wittig olefination method21 was then examined, and found to be successful. Treatment of
(2Z,5Z)-23 with Dess-Martin periodinane (DMP) and Ph3P=CHCO2Me in the presence of PhCO2H
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(acceleration catalyst for the Wittig reaction) in CH2Cl2/DMSO gave crude (2E,4Z,7Z)-3 in 71% yield.
The overall yield of 3 was 45% based on 20 (four steps). GC-MS analysis of the product revealed it
to be a mixture of 85% of (2E,4Z,7Z)-3, 6% of the (2Z,4Z,7Z)-isomer, and 2% of the
(2E,4E,7Z)-isomer. The product was rechromatographed repeatedly over SiO2, but the desired ester
3 could not be obtained in pure state. Even after fourth chromatographic purification, the purity
remained as 89%. Prof. W. Francke (Hamburg University) informed me that he could obtain pure
(2E,4Z,7Z)-3 after repeated SiO2/AgNO3 chromatography of my synthetic sample. The IR, 1H NMR
and MS spectra of the synthetic (2E,4Z,7Z)-3 coincided with those of the naturally occurring
pheromone component.
Similarly, methyl (2E,4E,7Z)-2,4,7-decatrienoate (5) was synthesized as follows.
2,5-Octadiyn-1-ol (22) was reduced with lithium aluminum hydride to give (E)-2-octen-5-yn-1-ol (24).
The yield (15%) of this step was quite poor, giving dark polymeric materials as the major products.
Reduction of 24 with Zn/Br(CH2)2Br/CuBr/LiBr in EtOH [100oC (bath temperature) for 5 h and 80oC
(bath temperature) for 3 d] gave (2E,5Z)-25 (96% purity) in 73% yield. This was subjected to
Barrett's tandem DMP oxidation/Wittig olefination to give 75% pure (2E,4E,7Z)-5 in 62% yield. The
overall yield of 5 was 6% based on 17 (five steps). The IR, 1H NMR and MS spectra of the synthetic
(2E,4E,7Z)-5 were consistent with the reported data5 of the methyl ester 5 derived from the naturally
occurring acid 4 isolated from the green alga Cladophora columbiana.
2.4. Concise synthesis of (±)-methyl (E)-2,4,5-tetradecatrienoate (1)
As to the synthesis of (R,E)-1, the major component, there is a problem due to the instability of the
conjugated allene system of 1. The pheromone 1 was reported to be unstable and readily polymerize
with a half-life of about 20 days at -13oC.2 The final step of the synthesis must therefore employ
mild conditions to avoid decomposition of 1. Of course the synthesis should be as concise as
possible.
Landor's first synthesis of (±)-1 in 1971 was a concise one [Fig. 2 (A)].6 The known
(±)-1-undecyn-3-ol (27) yielded (±)-1 after only five steps, although the yield of the each step was not
disclosed in their paper. The conciseness of their approach attracted my attention, because the
process might be improved by using contemporary synthetic methods.
Another interesting aspect of Landor's synthesis of (±)-1 is its modification to obtain optically
active 1 starting from the known optically active 273. Landor and co-workers were the first to find
out the reductive elimination of a tetrahydropyranyl(THP)oxy group from
4-(2-tetrahydropyranyloxy)-2-alkyn-1-ols to give allenic 2,3-alkadien-1-ols. They suggested a
concerted mechanism via intermediate A (Fig. 2).22-24 If this is the correct mechanism, (R)-28 should
afford (R)-29.
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Fig. 2. (A) Landor's 1971 synthesis of (±)-1 and (B) (C) Proposed mechanisms for conversion of
4-(2-tetrahydropyranyloxy-2-alkyn-1-ols (28 and 30) to 2,3-allenic alcohols (29 and 31).
A few years later, Olsson and Claesson discovered that (S)-30 gives the known (R)-31 upon
reduction with lithium aluminum hydride, and proposed trans-hydroalumination/anti-elimination
mechanism via intermediate B.25,26 Two later works supported the trans-addition/anti-elimination
mechanism.27,28 Chiral version of Landor's synthesis of (±)-1 will give an additional opportunity to
confirm the mechanism proposed by Olsson and Claesson, because the absolute configurations of
optically active 27 and 1 are well-established.3,29
The improved synthetic route to 1 is shown in Scheme 4. Methyl 4-(2-tetrahydropyranyloxy)-2-
dodecynoate (33) was chosen as the substrate for the reduction with lithium aluminum hydride.
Accordingly, the known (±)-1-undecyn-3-ol (27)6,29 was treated with 3,4-dihydro-2H-pyran (DHP)
and p-toluenesulfonic acid (TsOH) in diethyl ether to give (±)-32, which was converted to the
corresponding lithium acetylide by treatment with n-butyllithium in THF. Methoxycarbonylation of
the acetylide with ClCO2Me afforded (±)-33.
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Scheme 4. Synthesis of 1 to provide (±)-1 and (S,E)-1. [The depicted formulas show the synthesis of
(S,E)-1]. Reagents: (a) DHP, TsOH, Et2O [quant. for both (±)- and (R)-32]: (b) n-BuLi, ClCO2Me,
THF [91% for (±)-33; 77% for (R)-33]; (c) LiAlH4, Et2O [44% for (±)-29; 48% for (S)-29]; (d) DMP,
wet CH2Cl2 [71% for both (±)- and (S)-34]; (e) Ph3P=CHCO2Me, CH2Cl2 [39-44% for (±)-1, 71% for
(S)-1 of about 17% optical purity]; (d and e in tandem and one-pot manner21) DMP, Ph3P=CHCO2Me,
PhCO2H, DMSO, CH2Cl2 [27% for (±)-1 and 54% for (S)-1 of about 30% optical purity].
Reduction of (±)-33 with lithium aluminum hydride in diethyl ether was followed by
chromatographic purification and distillation of the product to give allenic alcohol (±)-29 in 44% yield.
Tandem and one-pot oxidation/Wittig olefination of (±)-29 was executed by treatment with
Dess-Martin periodinane (DMP) and Ph3P=CHCO2Me in the presence of PhCO2H in
CH2Cl2/DMSO.21 The product was purified by SiO2 chromatography (twice) to give (±)-1 in 27%
yield. Many by-products were generated at this final stage, including methyl 2,4,6-tetradecatrienoate.
Although the overall yield of the present four step-synthesis was only 11% based on (±)-27, this
synthesis is the shortest one to give (±)-1.
The final tandem oxidation/olefination could be executed separately. DMP oxidation of (±)-29
gave rather unstable (±)-34 in 71% yield. Its olefination with the Wittig reagent furnished (±)-1 in
39-44% yield (28-31% yield based on 29). In this particular case, the tandem procedure did not
increase the efficiency of the reactions presumably due to the instability of both (±)-34 and (±)-1.
Synthesis of optically active 1 was then attempted starting from (R)-27. Preparation of (R)-27
was executed by asymmetric acetylation of (±)-1-trimethylsilyl-1-undecyn-3-ol with vinyl acetate and
lipase PS to give its (R)-acetate and the recovered (S)-alcohol.3 In 2013, lipase PS coated with an
ionic liquid [IL1 : α-cetylpolyoxyethylene(19)ether sulfate] was reported by Itoh and his co-workers
to be more active than Amano's commercial lipase PS.30 Indeed, 250 mg of Itoh's IL l-coated lipase
PS was as active as 4.0 g of Amano's lipase PS in effecting the asymmetric acetylation of 4.4 g of the
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racemic alcohol under the conditions previously reported (3 days at 30oC).3 The (R)-acetate yields
(R)-alcohol 27 (97% ee)3 by treatment with potassium carbonate in methanol and water.3
The corresponding THP ether (R)-32, [α]D26 +103.1 (c 3.32, hexane), was treated with
n-butyllithium and ClCO2Me to give (R)-33, [α]D24 +115.4 (c 3.40, hexane), in 77% yield. This was
reduced with lithium aluminum hydride in diethyl ether to give (+)-29, [α]D23 +60.0 (c 3.47, hexane),
in 48% yield. The absolute configuration of (+)-29 was determined as S, because it gave (S,E)-1.
Since (R)-33 afforded (S)-(+)-29, the mechanism of the reaction must be as proposed by Olsson and
Claesson [Fig. 2 (C)].25,26
Finally, tandem oxidation/olefination21 of (S)-29 furnished (S,E)-1 in 54% yield. Its specific
rotation, however, was disappointingly small: [α]D24 +45.3 (c 1.18, hexane). Because the specific
rotation value of (R,E)-1 with 87% ee (determined by chiral GC) was [α]D24 -130.3 (c 2.23, hexane),3
the present (S,E)-1 was of only 30% optical purity. Extensive racemization must have taken place in
the course of the tandem oxidation/olefination process.
22
The two reactions were then executed separately. DMP oxidation of (S)-29 gave (S)-34, [α]D
23
+21.0 (c 1.04, hexane), in 71% yield. Its Wittig olefination furnished (S,E)-1 in 71% yield, [α]D
+25.2 (c 1.06, hexane). In this case, the optical purity of (S,E)-1 was about 17%. It therefore
became clear that the modified Landor process cannot be used for the synthesis of the naturally
occurring (R,E)-1 (87% ee) due to the racemization in the course of the final oxidation/olefination step
probably because of the stereochemical instability of (S)-34, although the process provides (S,E)-1 of
about 30% optical purity in 20% overall yield based on (R)-27 (four steps).
The best preparative methods for the racemate and enantiomers of 1 are those in ref. 3.cf. 31 In the
synthesis of (R)- and (S)-1, conditions which may cause racemization are carefully avoided by
generating the unstable conjugated allenic ester 1 at the final stage.3 Gratifyingly, a mixture of our
synthetic (R,E)-13, 23 and 3 together with other components attracted the dried bean beetles.4
3. Conclusions
Synthesis of methyl (2E,4Z,7Z)-2,4,7-decatrienoate (3), a new component of the male pheromone
of the dried bean beetle (Acanthoscelides obtectus), was accomplished by tandem DMP
oxidation/Wittig olefination of (2Z,5Z)-2,5-octadien-1-ol (23). Reduction of 2,5-octadiyn-1-ol (22)
with Zn/Cu in hot EtOH was the best method to secure 99% pure (2Z,5Z)-23. Similarly, methyl
(2E,4E,7Z)-2,4,7-decatrienoate (5) was synthesized by tandem DMP oxidation/Wittig olefination of
(2E,5Z)-2,5-octadien-1-ol (25), which was prepared by reduction of (E)-2-octen-5-yn-1-ol (24) with
Zn/Cu in hot EtOH. Catalytic semi-hydrogenation of 22 was found to be inferior in selectivity to the
Zn/Cu reduction in these particular cases.
The modified Landor's method was shown to be a method of choice for preparing (±)-methyl
(E)-2,4,5-tetradecatrenoate (1), the racemate of the major component (R,E)-1 of the male pheromone
of the dried bean beetle, although the method failed to give optically pure (S,E)-1. Stereochemical
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course of the allene formation step was shown to give (S)-allene 29 from (R)-acetylenic ester 33 in
accord with the mechanism proposed by Olsson and Claesson.25,26
4. Experimental
4.1. General
Boiling points are uncorrected values. Refractive indices were measured on an Atago EMT-1
refractometer. IR spectra were measured on a Jasco FT/IR-410 spectrometer. 1H NMR spectra
(400 MHz, TMS at δ = 0.00 as internal standard) and 13C NMR spectra (100 MHz, CDCl3 at δ = 77.0
as internal standard) were recorded on a Jeol JNM-AL 400 spectrometer. GC-MS were measured on
Agilent Technologies 5975 inert XL. HRMS were recorded on Jeol JMS-SX 102A or Waters Synapt
G2 HDMS. Column chromatography was carried out on Merck Kieselgel 60 Art 1.07734.
4.2. 2,5-Octadiyn-1-ol (22)
A solution of EtMgBr in Et2O (TCI, 3 M, 57 mL, 171 mmol) was added dropwise to a stirred
solution of 21 (23.8 g, 170 mmol) in dry THF (285 mL) under argon. When the exothermic reaction
with evolution of ethane ceased after 30 min at reflux, CuI (2.5 g, 13 mmol) was added to the solution.
Subsequently, a solution of 20 (Wako Chemical, 21.5 g, 154 mmol) in dry THF (20 mL) was added
dropwise over 30 min. The reaction was exothermic to raise the inner temperature to 45-47oC, and
solid MgBr2 separated from the solution. The mixture was stirred overnight, and then concentrated
in vacuo to remove Et2O and THF. The residue was diluted with ice and NH4Cl solution, and
extracted with Et2O. The Et2O solution was washed with brine, dried (MgSO4), and concentrated in
ν
vacuo to give 36.8 g (quant.) of the THP ether of 22 as an oil, max (film): 2941 (s), 2237 (w), 1120
(s), 1025 (s). This oil was dissolved into MeOH (300 mL) containing conc HCl (10 mL), and the
solution was stirred for 1 h at room temperature. It was then neutralized with solid NaHCO3, and
concentrated in vacuo. The residue was diluted with water, and extracted with Et2O. The Et2O
solution was washed with brine, dried (MgSO4), and concentrated in vacuo. The residue was
18
distilled to give 16.0 g (90%) of 22 as a colorless oil, bp 86-88oC/4 Torr; nD
max (film):
ν
= 1.4951;
3338 (br. s), 2977 (s), 2938 (m), 2920 (m), 2877 (m), 2259 (w), 1455 (m), 1415 (m), 1320 (s), 1115
(m), 1013 (s); δH (CDCl3): 1.13 (3H, t, J 7.2), 1.90-2.00 (1H, br.), 2.18 (2H, qt, J 7.2, 2.4), 3.19 (2H,
m), 4.27 (2H, t, J 2.4); GC-MS [column: HP-5MS, 5% phenylmethylsiloxane, 30 m x 0.25 mm i.d.,
carrier gas, He; press: 60.7 kPa; temp: 70-230oC (+10oC/min)]: tR 8.18 min (99.0%). MS (70 eV, EI):
m/z: 122 (5) [M+], 121 (7) [(M-1)+], 107 (18), 104 (79), 91 (69), 79 (40), 78 (38), 77 (100), 65 (30), 51
(24), 39 (26). HRMS calcd for C8H10O: 122.0732, found: 122.0731.
4.3. (2Z,5Z)-2,5-Octadien-1-ol (23)
~ 12 ~

ACCEPTED MANUSCRIPT
4.3.1. By catalytic hydrogenation. 5% Pd/BaSO4 (TCI, 1.15 g) was added to a solution of 22
(3.70 g, 30 mmol) and quinoline (1.0 mL) in MeOH (50 mL). The mixture was stirred vigorously at
0-5oC (ice-water) under H2 atmosphere (balloon). The H2 uptake ceased after 3.5 h. The mixture
was filtered through Celite, and the Celite layer was washed with Et2O. The filtrate and washings
were concentrated in vacuo, and the residue was dissolved in Et2O. The Et2O solution was
successively washed with dil HCl, NaHCO3 solution and brine, dried (MgSO4), and concentrated in
vacuo to give 3.34 g (87%) of 23. Distillation of a portion (2.32 g) of it gave 1.62 g of purified 23,
18
bp 59oC/1 Torr; nD =1.4698: max (film):3323 (br. s), 3013 (s), 2964 (s), 2933 (s), 2874 (s), 1650 (w),
ν
1462 (m), 1023 (s), 716 (m); δH (CDCl3): 0.98 (3H, t, J 7.6), 1.40 (1H, br. s), 2.07 (2H, dq, J 7.6, 7.6),
2.83 (2H, t, J 7.2), 4.24 (2H, br, s); 5.26-5.33 (1H, m), 5.39-5.45 (1H, m), 5.50-5.55 (1H, m),
5.55-5.65 (1H, m), GC-MS (same conditions as those for 22): tR 6.09 min (1.1%). 6.19 (1.6%), 6.27
(86.0%, 23), 6.31 (6.3%), 6.38 (3.3%). MS of (2Z,5Z)-23 (70 eV, EI): m/z: 124 (<1) [M-2)+ ], 108
(25), [M-H2O)+ ]: 93 (31), 79 (100), 77 (30), 70 (19), 67 (33), 55 (27), 41 (29). HRMS calcd for
C8H12 [(M-H2O)+]:108.0939, found: 108.0936. Column chromatography over SiO2 before
distillation did not improve the purity of the product.
4.3.2. By reduction with Zn/Cu in EtOH. Br(CH)2Br (0.8 mL) was added to powdered zinc
(Aldrich 209988, 14.0 g, 214 mmol) in anhydrous EtOH (20 mL) under argon. The mixture was
stirred and heated under reflux for 10 min. Then Br(CH2)2Br (0.8 mL) was added again, and the
mixture was stirred and heated under reflux for another 10 min. When the inner temperature dropped
to 50oC, CuBr (3.2 g, 22 mmol) and LiBr (4.8 g, 55 mmol) in dry THF (15 mL) were added to the
mixture with vigorous stirring. Subsequently, a solution of 22 (4.88 g, 40 mmol) in anhydrous EtOH
(10 mL) was added to the mixture, and the stirring and heating were continued for 6 h at 100oC and
then 16 h at 80oC under argon. After cooling, the mixture was diluted with NH4Cl solution and
thoroughly extracted with Et2O. The Et2O solution was washed with water and brine, dried (MgSO4),
and concentrated in vacuo. The residue was distilled to give 3.55 g (70%) of 23 as a colorless oil, bp
64-65oC/4 Torr; GC-MS (same conditions as those for 22): tR 6.25 min (98.9%, 23).
4.4. (Z)-2-Octen-5-yn-1-ol (26)
Br(CH2)2Br (0.4 mL) was added to powdered zinc (Aldrich 209988, 7.0 g, 107 mmol) in
anhydrous EtOH (10 mL) under argon. The mixture was stirred and heated under reflux for 10 min.
Then Br(CH2)2Br (0.4 mL) was added again and the mixture was stirred and heated under reflux for
another 10 min. After cooling to 40oC, a solution of 22 (2.44 g) in anhydrous EtOH (2.5 mL) was
added to the mixture, and the stirring and heating were continued for 45 min under reflux. After
cooling, the mixture was diluted with NH4Cl solution and thoroughly extracted with Et2O. The Et2O
solution was washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue
18
was distilled to give 1.24 g (50% ) of 26 as a colorless oil, bp 78-79oC/3 Torr; nD = 1.4822: max
ν
(film):3349 (br. s), 3026 (m), 2976 (s), 2937 (s), 2878 (s), 1657 (w), 1456 (m), 1422 (m), 1320
~ 13 ~

ACCEPTED MANUSCRIPT
(m),1290 (m), 1025 (s), 937 (w); δH (CDCl3): 1.11 (3H, t, J 7.2), 1.60-1.82 (1H, br.), 2.12-2.19 (2H,
m), 2.94-2.96 (2H, m), 4.22 (2H, d, J 5.2), 5.56-5.62 (1H, m), 5.64-5.70 (2H, m); GC-MS (same
conditions as those for 22): tR 7.14 min (96.5%). MS (70 eV, EI): m/z: 123 (2) [(M-1)+ ], 106 (47),
[(M-H2O)+ ], 95 (30), 91 (100), 79 (40), 78 (29), 77 (43), 70 (28), 65 (23), 57 (13), 53 (16), 41 (21), 39
(25), HRMS calcd for C8H10 [(M-H2O)+]: 106.0785, found: 106.0785.
4.5. Methyl (2E,4Z,7Z)-2,4,7-decatrienoate (3)
DMP (1.106 g, 2.6 mmol) was added in one portion to a stirred and ice-cooled solution of
(2Z,5Z)-23 (98.9% purity, 259 mg, 2 mmol), PhCO2H (490 mg, 4 mmol), Ph3P = CHCO2Me (1.39 g,
4 mmol) and DMSO (1.5 mL) in CH2Cl2 (7.5 mL) at 0-5oC. The ice-bath was removed after the
addition, and the mixture was stirred for 30 min at room temperature. The colorless mixture soon
turned yellow, and then darkened to give a dark red solution. It was cooled again at 0-5oC, and
saturated NaHCO3 solution (30 mL) was added to the mixture. After stirring for 1 h, the mixture was
diluted with Et2O and filtered through Celite. The Celite layer was washed with Et2O. The
combined filtrate and washings were washed with brine, dried (MgSO4), and concentrated in vacuo to
give 0.3 g of a dark oil. This was chromatographed over SiO2 (15 g). Elution with hexane/EtOAc
18
ν
(75 : 1) gave 264 mg (71%) of 85% pure (2E,4Z,7Z)-3 as a colorless oil, nD =1.5060: max
(film):3012 (m), 2964 (m), 2875 (m), 1721 (vs), 1638 (s), 1604 (m), 1435 (s), 1407 (m), 1311
(m),1268 (s), 1204 (m), 1170 (s), 1133 (m), 995 (m), 869 (m), 727 (m), 705 (m); δH (CDCl3): 0.99 (3H,
t, J 7.2), 2.09 (2H, dq, J 7.2, 7.2), 3.05 (2H, dd-like, J 7.2, 7.2), 3.76 (3H, s), 5.32 (1H, dt, J 10, 7),
5.45 (1H, dt J 10, 7), 5.80 (1H, dt, J 11, 7.6), 5.89 (1H, d, J 15), 6.13 (1H, dd, J 7, 7), 7.65 (1H, dd, J
15, 10); δC (CDCl3): 14.1, 20.5, 26.4, 51.5, 121.0, 125.0, 126.3, 133.2, 139.35, 139.37, 167.6; GC-MS
(same conditions as those for 22): tR 10.88 min [85.1%, (2E,4Z,7Z)-3], .10.98 [6.0%,
(2Z,4Z,7Z)-isomer], 11.36 [2.1%, (2E,4E,7Z)-isomer]. MS of 3 (70 eV, EI): m/z: 180 (5) [M+], 165
(2), 149 (14), 137 (16), 121 (53), 120 (38), 119 (36), 111 (55), 105 (40), 98 (28), 93 (34), 91 (88), 79
(100), 77 (46), 67 (21), 65 (20), 55 (29), 39 (22). The MS was identical with that of the naturally
occurring pheromone component. HRMS calcd for C11H16O2: 180.1150, found: 180.1158.
Attempted purification of 3 by repeated chromatography over SiO2 was fruitless. The purest 3
obtained was 89.1% pure with 6.2% of (2Z,4Z,7Z)- and 1.7% of (2E,4E.7Z)-isomers.
4.6. (E)-2-Octen-5-yn-1-ol (24)
A solution of 22 (3.66 g, 30 mmol) in dry THF (10 mL) was added dropwise to a stirred and
ice-cooled suspension of LiAlH4 (1.36 g, 36 mmol) in dry THF (20 mL) at 5-10oC. The mixture was
stirred for 3 h with ice-cooling. It gradually darkened in color. The reaction was then quenched by
slow addition of water with ice-cooling. Subsequently, the mixture was poured into ice and dil HCl
containing NH4Cl, and extracted with Et2O. The Et2O solution was successively washed with water,
NaHCO3 solution and brine, dried (MgSO4), and concentrated in vacuo. The dark-colored residual
~ 14 ~

ACCEPTED MANUSCRIPT
oil was chromatographed over SiO2 (40 g). Elution with hexane/EtOAc (10 : 1) gave 1.11 g of 24 as
an oil. This was distilled to give 552 mg (15%) of pure 24 as a colorless oil, bp 85-87oC/4 Torr;
19
ν
nD =1.4850: max (film):3333 (br. s), 2976 (s), 2937 (s), 2918 (s), 2878 (s), 1672 (w), 1456 (m),
1421 (m), 1322 (m), 1094 (m), 997 (s), 971 (s); δH (CDCl3): 1.14 (3H, t, J 7.6), 1.52 (1H, br),
2.17-2.23 (2H, m), 2.95 (2H, br, s-like), 4.15 (2H, br. s-like), 5.68-5.74 (1H, m), 5.88-5.94 (1H, m);
GC-MS (same conditions as those for 22): tR 7.39 min (93.0%, 24). MS (70 eV, EI): m/z: 123 (4)
[(M-1)+ ], 109 (30), 95 (75), 91 (69), 79 (100), 77 (75), 67 (34), 65 (30), 57 (37), 53 (23), 41 (27), 39
(32). HRMS calcd for C8H12O: 124.0888, found: 124.0882.
4.7. (2E,5Z)-2.5-Octadien-1-ol (25)
Br(CH2)2Br (0.1 mL) was added to powdered zinc (Aldrich 209988, 2.0 g, 31 mmol) in anhydrous
EtOH (3 mL) under argon. The mixture was stirred and heated under reflux for 10 min. Then
Br(CH2)2Br (0.1 mL) was added again, and the mixture was stirred and heated under reflux for another
10 min. After cooling to 50oC, a mixture of CuBr (0.3 g, 2 mmol) and LiBr (0.5 g, 6 mmol) in dry
THF (2 mL) was added to the mixture with vigorous stirring. Subsequently, a solution of 24 (310 mg,
2.5 mmol) in anhydrous EtOH (2 mL) was added to the mixture, and the stirring and heating were
continued for 5 h at 100oC and then 3 d for 80oC. After cooling, the mixture was diluted with NH4Cl
solution and thoroughly extracted with Et2O. The Et2O solution was washed with water and brine,
dried (MgSO4), and concentrated in vacuo to give 245 mg (73%) of (2E,5Z)-25 as a colorless oil,
20
ν
nD =1.4733: max (film):3334 (br. s), 3010 (m), 2963 (s), 2932 (s), 2837 (s), 1668 (w), 1461 (m),
1090 (m), 1005 (s), 970 (s); δH (CDCl3): 0.97 (3H, t J 7.6), 1.21 (1H, br. s), 2.05 (2H, dt, J 7.2, 7.6),
2.92 (2H, t-like, J 6.4), 3.74 (2H, br. s), 5.36 (1H, dt, J 10.8, 7.2), 5.50 (1H, dt, J 10.8, 7.2), 5.80 (1H, d,
J 15.6), 6.14 (1H, dt, J 15.6, 6.8); GC-MS (same conditions as those for 22): tR 6.31 min (98.4%, 25).
MS (70 eV, EI): m/z: 126 (<1) [M+ ], 108 (20), 98 (12), 95 (36), 93 (39), 91 (31), 84 (54), 83 (49), 82
(43), 79 (80), 77 (47), 70 (27), 67 (100), 57 (42), 55 (81), 53 (27), 51 (13), 43 (19), 41 (76), 39 (46), 31
(12). HRMS calcd for C8H14O: 126.1045, found: 126.1047.
4.8. Methyl (2E,4E,7Z)-2,4,7-decatrienoate (5)
DMP (1.206 g, 2.8 mmol) was added in one portion to a stirred and ice-cooled solution of
(2E,5Z)-25 (237 mg, 2 mmol), PhCO2H (492 mg, 4 mmol), Ph3P=CHCO2Me (1.39 g, 4 mmol) and
DMSO (1.5 mL) in CH2Cl2 (7.5 mL) at 0-5oC. After stirring for 30 min at room temperature, the
mixture was worked up as described for 3 in 4.5 to give 208 mg (62%) of 75.6% pure (2E,4E,7Z)-5,
16
ν
nD =1.5127; max (film):3014 (m), 2962 (s), 2935 (m), 2875 (m), 1720 (vs), 1641 (s), 1617 (m),
1435 (m), 1267 (s), 1203 (m), 1171 (m), 1138 (s), 1002 (m), 866 (w), 714 (m); δH (CDCl3): 0.97 (3H, t,
J 7.6), 2.04 (2H, quint-like J 6.4), 2.91 (2H, t, J 6.8), 3.74 (3H, s), 5.36 (1H, dt J 10.8, 6.8), 5.50 (1H,
dt, J 10.8, 6.8), 5.80 (1H, d, J 15.6), 6.12 (1H, dt, J 15.6, 9.2), 6.16 (1H, dt, J 15.6, 10.8), 7.27 (1H, dd,
J 10.8, 16.2); δC (CDCl3): 14.1, 20.5, 30.5, 51.4, 119.0, 124.4, 128.2, 133.8, 142.5, 145.0, 167.7;
~ 15 ~

ACCEPTED MANUSCRIPT
GC-MS (same conditions as those for 22): tR 10.69 min (4.4%, M+= 180, isomer of 5), 11.14 (9.2%,
strong M+ at 180, unidentified), 11.32 [6.9%, M+ =180, (2Z,4E,7Z)-isomer], 11.38 (75.6%, 5), 11.62
(1.4%, strong M+ at 180, unidentified). MS of 5 (70eV, EI): m/z: 180 (12) [M+], 149 (17), 138 (14),
137 (9), 133 (8), 124 (14), 121 (44), 120 (35), 119 (42), 111 (72), 105 (37), 98 (44), 93 (32), 91 (81),
81 (32), 79 (100), 77 (44), 68 (21), 67 (22), 66 (17), 65 (21), 59 (23), 55 (35), 53 (21), 39 (26). These
IR, 1H NMR and MS data are in good accord with the reported data.5 HRMS calcd for C11H16O2:
180.1150, found: 180.1148.
4.9. 1-Undecyn-3-ol THP ether (32)
4.9.1. Racemate. TsOH·H2O (200 mg, 1.2 mmol) was added
to a solution of (±)-27 (6.0 g, 35.7 mmol) and DHP (3.8 g, 45 mmol) in dry Et2O (60 mL) with
shaking in an ice-bath. After the initial exothermic reaction, the mixture was left to stand for 3 h at
room temperature. It was then diluted with Et2O, washed with aqueous K2CO3 solution and brine,
dried (MgSO4), and concentrated in vacuo to give 9.2 g (quant.) of (±)-32 as a colorless oil,
nD25=1.4544; IR νmax (film) cm-1: 3310 (m), 2926 (s), 2855 (s), 2111 (w), 1467 (m), 1455 (m), 1201
(m), 1118 (s), 1077 (m), 1022 (s), 974 (m), 871 (m), 656 (m), 625 (m); Different batches of (±)-32
showed different 1H NMR spectra due to their differences in diastereomeric ratios originating from the
stereogenic center in THP: δH (CDCl3): 0.88 (3H, t, J 7.2), 1.27 (8H, br. s), 1.40-1.65 (7H, m),
1.65-1.90 (5H, m), 2.368 (0.8H, d, J 2), 2.426 (0.2H, d, J2), 3.50-3.56 (1H, m), 3.81 (0.8H, m), 4.02
(0.2H, m), 4.38 (0.2H, m), 4.41 (0.8H, m), 4.75 (0.2H, t, J 3.2), 4.98 (0.8H, t, J 3.2). HRMS calcd
for C16H28O2Na [(M+Na)+]: 275.19815, found: 275.1981.
4.9.2. (R)-Isomer. Similarly, (R)-27 {2.10 g; [α]D25+13.8 (c 4.01, Et2O)} yielded 3.34 g (quant.) of
(R)-32 as an oil, nD26=1.4546; [α]D26+103.1 (c 3.32, hexane). Its IR and 1H NMR spectra were
identical with those of (±)-32.
4.10. Methyl 4-(2-tetrahydropyranyloxy)-2-dodecynoate (33)
4.10.1. Racemate. A solution of n-BuLi in hexane (1.6 M, 23.2 mL, 37 mmol) was added dropwise
to a stirred and cooled solution of (±)-32 (9.22 g, 36.6 mmol) in dry THF (30 mL) at -78 to -60oC
under argon. The slightly yellowish mixture was warmed to -15oC and then cooled again at -70oC.
A solution of ClCO2Me (3.78 g, 40 mmol) in dry THF (10 mL) was added dropwise to the stirred and
cooled mixture. The mixture was stirred for 1 h at -78oC and an additional 1 h at room temperature
until the colorless precipitates of LiCl separated. It was then quenched with aqueous NH4Cl solution,
and extracted with Et2O. The Et2O solution was washed successively with water and brine, dried
(MgSO4), and concentrated in vacuo. The residue (12.5 g) was chromatographed over SiO2 (100 g).
Elution with hexane/EtOAc (50:1) gave 10.4 g (91%) of (±)-33 as a colorless oil, nD26=1.4612; νmax
(film): 2927 (s), 2855 (s), 2235 (m), 1720 (s), 1456 (m), 1435 (m), 1252 (s), 1119 (m), 1022 (s), 973
(m), 751 (m). Different batches of (±)-33 showed different 1H NMR spectra due to their differences
in diastereomeric composition originating from the stereogenic center in THP. In one occasion the
~ 16 ~

ACCEPTED MANUSCRIPT
1H NMR spectrum of a single diastereomer of (±)-33 was observed: δH (CDCl3): 0.88 (3H, t, J 6.8),
1.21-1.35 (10H, br), 1.40-1.50 (2H, m), 1.50-1.70 (5H, m), 1.70-1.90 (3H, m), 3.52-3.60 (1H, m),
3.77 (3H, s), 3.95-4.03 (1H, m), 4.34 (1H, t, J 6.8), 4.75 (1H, t, J 3.2). Another diastereomer showed
the following signals: δH (CDCl3): 3.78 (3H, s, CO2CH3), 4.53 (1H, t, J 6.8 ), 4.92 (1H, t, J 3.2 );
GC-MS (same conditions as those for 22): tR 18.91 min [0.84%, a diastereomer of (±)-33],19.18 min
[98.69%, another diastereomer of (±)-33]. These two diastereomers showed slightly different MS.
MS(70 eV, EI) of (±)-33 with tR 18.91 min: m/z: 309 (<1) [M+-1], 210 (14), 209 (100) [M+-THPO],
177 (8), 149 (14), 107 (12), 93 (14), 85 (87) [THP], 79 (13), 67 (11), 55 (12), 41 (12); MS (70 eV, EI)
of (±)-33 with tR 19.18 min: m/z: 309 (<1) [M+-1], 210 (9), 209 (59), 177 (4), 149 (6), 114 (10), 107
(7), 93 (10), 85 (100), 79 (14), 67 (10), 55 (15), 41 (14). HRMS calcd for C18H30O4Na [(M+Na)+]:
333.2036, found: 333.2035.
4.10.2. (R)-Isomer. Similarly, (R)-32 (3.30 g) furnished 3.12 g (77%) of (R)-33 as an oil,
nD24=1.4628; [α]D24+115.4 (c 3.40, hexane); GC-MS (same conditions as for 22): tR 18.93 min
(87.6%), 19.10 min (13.4%). Its IR, 1H NMR and MS spectra were identical with those of (±)-33.
4.11
2,3-Dodecadien-1-ol (29)
4.11.1. Racemate. A solution of (±)-33 (10.3 g, 33 mmol) in dry Et2O (10 mL) was added dropwise
to the stirred and ice-cooled suspension of LiAlH4 (2.3 g, 60 mmol) in dry Et2O (80 mL) at 5-15oC.
After the addition, the mixture was stirred and heated under reflux for 2 h. After cooling, the excess
LiAlH4 was destroyed by successive addition of water (2 mL), 15% aqueous NaOH solution (2 mL),
and water (6 mL) to the stirred and ice-cooled reaction mixture. The mixture was stirred for 30 min
at room temperature, and filtered through Celite. The Celite layer was washed with Et2O. The
combined filtrate and washings were dried (MgSO4), and concentrated. The residue (4.0 g) was
chromatographed over SiO2 (80 g). Elution with hexane gave 0.83 g of hydrocarbons, and further
elution with hexane/EtOAc (50:1) gave 2.66 g (44%) of (±)-29, bp 104oC/2 Torr, nD26=1.4712; νmax
(film): 3325 (m, br), 2955 (s), 2925 (s), 2854 (s), 1964 (w), 1465 (m), 1013 (m), 870 (w), 722 (w); δH
(CDCl3): 0.88 (3H, t, J 7.2), 1.27 (10H, br. s), 1.40 (2H, dt, J 7.2, 6.8), 1.52 (1H, br.), 1.99-2.05 (2H,
m), 4.11 (2H, dd, J 7.2, 5.6), 5.26-5.36 (2H, m); GC-MS (same conditions as those for 22): tR 11.97
min (96.8%), MS (70 eV, EI): m/z: 180 (<1) [M+], 164 (1), 151 (1), 135 (4), 121 (6), 107 (8), 95 (14),
93 (16), 91 (13), 84 (86), 83 (90), 79 (40), 69 (43), 67 (40), 56 (60), 55 (100), 43 (40), 41 (52).
HRMS calcd for C12H22O: 182.1671, found: 182.1684.
4.11.2. (S)-Isomer. Similarly, 3.10 g (10 mmol) of (R)-33 was reduced with 0.76 g (20 mmol) of
LiAlH4 in Et2O (35 mL) to give 878 mg (48%) of (S)-29 as a colorless oil, nD23=1,4708; [α]D23+60.0
(c 3.47, hexane). Its IR, 1H NMR and MS spectra were identical with those of (±)-29, GC-MS (same
conditions as those for 22): tR 11.95 min (98.7%).
4.12. 2,3-Dodecadienal (34)
4.12.1 Racemate. DMP (870 mg, 2.1 mmol) was added portionwise to a stirred and
~ 17 ~

ACCEPTED MANUSCRIPT
ice-cooled solution of (±)-29 (259 mg, 1.4 mmol) in CH2Cl2 (6 mL) containing H2O (32 mg). After 5 min,
the ice-bath was removed, and the mixture was stirred for 1 h at room temperature to give a colorless
suspension of o-iodobenzoic acid. The reaction was quenched by adding Et2O and aqueous NaHCO3
solution. The mixture was then filtered through Celite, and the Celite layer was washed with Et2O.
The Et2O solution was separated from the aqueous filtrate, washed with brine, dried (MgSO4), and
concentrated in vacuo. The residue was chromatographed over SiO2 (4 g). Elution with
hexane/EtOAc (50:1) gave (±)-34 (184 mg, 71%) as a colorless oil, nD21=1.4778; νmax (film): 2926 (s),
2855 (s), 2720 (w), 1944 (m), 1692 (s), 1465 (m), 1168 (m), 1081 (m), 878 (m), 456 (m); δH (CDCl3):
0.88 (3H, t, J 7.2), 1.28 (10H, br. s), 1.47 (2H, dt, J 7.6, 7.2), 1.55 (1H, br. s), 2.15-2.22 (2H, m),
5.72-5.77 (1H, m), 5.78-5.83 (1H, m), 9.48 (1H, d, J 3.2); GC-MS (same conditions as those for 22):
tR 11.71 min (88.6%); MS (70eV, EI): m/z: 180 (5) [M+], 151 (2), 137 (7), 123 (23), 109 (13), 95 (31),
83 (42), 81 (100), 67 (23), 55 (27), 41 (32). This aldehyde was unstable and no good HRMS data
could be collected.
4.12.2. (S)-Isomer. Similarly, 583 mg (3.2 mmol) of (S)-29 was oxidizded with 2.40 g (5.66 mmol)
of DMP to give 410 mg (71%) of (S)-34 as a colorless oil, nD23=1,4771; [α]D22+21.0 (c 1.04, hexane).
Its IR, 1H NMR and MS spectra were identical with those of (±)-34.
4.13. Methyl (E)-2,4,5-tetradecatrienoate (1)
4.13.1. Racemate. (a) Tandem DMP oxidation/Wittig reaction. DMP (1.106 g, 2.6 mmol) was
added over 3 min to a stirred and ice-cooled solution of (±)-29 (364 mg, 2 mmol), PhCO2H (490 mg, 4
mmol) and Ph3P=CHCO2Me (1.385 g, 4 mmol) in CH2Cl2 (7.5 mL) and DMSO (1.5 mL) containing a
drop of H2O. The mixture was then stirred for 30 min at room temperature. Subsequently, the
mixture was diluted with aqueous NaHCO3 solution (30 mL), stirred for 30 min, and filtered through
Celite. The Celite layer was washed with Et2O. The Et2O solution was washed with brine, dried
(MgSO4), and concentrated in vacuo. The brown residue (1.4 g) was chromatographed over SiO2 (20
g). Elution with hexane/EtOAc (50:1) gave 277 mg of crude (±)-1. This was rechromatographed
over SiO2 (7 g). Elution with hexane/EtOAc (50:1) gave 130 mg (27%) of (±)-1 as the first fraction,
and 29 mg of the second fraction containing methyl 2,4,6-tetradecatrienoate (tentative) and (±)-1. In
another run, the yield was 118 mg (25%). Properties of (±)-1 as a slightly yellowish oil: nD25=1.4910,
νmax (film): 2926 (s), 2855 (s), 1943 (m), 1721 (s), 1630 (m), 1437 (m), 1306 (m), 1264 (m), 1242
(m), 1176 (m), 1139 (m), 984 (m), 882 (w), 858 (w); δH (CDCl3): 0.88 (3H, t, J 6.8), 1.22-1.36 (10H,
br), 1.36-1.50 (2H, m), 2.02-2.10 (2H, m), 3.74 (3H, s), 5.44 (1H, q, J 6.8), 5.85 (1H, dd, J 0.7, 15),
5.86-5.92 (1H, m), 7.14-7.26 (1H, m); GC-MS (same condition as those for 22): tR 15.91 min
(78.0%); MS (70 eV, EI) of (±)-1 : m/z: 236 (<1) [M+], 138 (52), 137 (28), 123 (13), 107 (25), 106 (23),
105 (21), 91 (25), 79 (100), 78 (35), 77 (22), 67 (14), 55 (11), 41 (16). HRMS calcd for C15H24O2:
236.1776, found: 236.1782. (b) Wittig reaction with (±)-34. The stabilized ylid Ph3P=CHCO2Me
(501 mg, 1.5 mmol) was added to a solution of (±)-34 (189 mg, 1.04 mmol) in dry CH2Cl2 (4 mL),
and the mixture was stirred for 1.5 h at room temperature under argon. The yellowish solution was
concentrated, and the residue was triturated with hexane/Et2O. The hexane/Et2O solution was
~ 18 ~

ACCEPTED MANUSCRIPT
separated from solid Ph3PO, and chromatographed over SiO2 (5 g). Elution with hexane/EtOAc
(50:1) gave 109 mg (44%) of (±)-1. In another run, the yield was 39%. Its spectral properties were
identical with those described above for (±)-1.
4.13.2. (S)-Isomer. (a) Tandem DMP oxidation/Wittig reaction. Similarly, 182 mg (1 mmol) of
(S)-29 was treated with DMP (700 mg, 1.65 mmol), PhCO2H (224 mg, 2 mmol) and Ph3P=CHCO2Me
(668 mg, 2 mmol) to give 128 mg (54%) of (S)-1 as a yellowish oil, nD23=1.4900, [α]D24 +45.3 (c 1.18,
hexane){about 30% optical purity, because (R)-1 of 87% ee showed [α]D24-130.3 (c 2.23, hexane)}3
Its IR, 1H NMR and MS spectra were identical with those of (±)-1. (b) Wittig reaction with (S)-34.
Similarly, 281 mg (1.56 mmol) of (S)-34 and 1.00 g (3 mmol) of Ph3P=CHCO2Me with 360 mg (3
mmol) of PhCO2H in CH2Cl2 (6 mL) gave 260 mg (71%) of (S)-1 as a yellowish oil, nD22=1.4933;
[α]D23+25.2 (c 1.06, hexane) (about 17% optical purity). Its IR, 1H NMR and MS spectra were
identical with those of (±)-1.
Acknowledgements
I thank Mr. M. Kimura (President, Toyo Gosei Co., Ltd) for his support. My thanks are due to
Prof. W. Francke (Hamburg University) for his suggestion to undertake the present work. I thank
Prof. T. Itoh (Tottori University) for his kind gift of IL1-coated lipase PD. Mr. Y. Shikichi (Toyo
Gosei Co., Ltd) is thanked for NMR and GC-MS measurements. Drs. T. Nakamura and Y. Hongo
(both at RIKEN) kindly executed the HRMS analysis, and Dr. T. Tashiro (Niigata University of
Pharmacy and Applied Life Sciences) prepared the Figures and the Schemes. I also thank Mr. A.
Nakanishi (T. Hasegawa Co. Ltd) for his kind gift of 1,4-heptadiyne.
Supplementary data
Supplementary data describing the experimental details of the unsuccessful routes shown in Schemes
1 and 2 can be found in the online version of this article at doi: 10.1016/j. tet. 2015.00.000.
References and notes
1. Mori, K.; Akasaka, K. Tetrahedron 2015, 71, 4102-4115.
2. Horler, D.F. J. Chem. Soc. C 1970, 859-862.
3. Mori, K. Tetrahedron 2012, 68, 1936-1946.
4. Vuts, J.; Francke. W.; Mori, K.; Zarbin, P.H.G.; Hooper, A.M.; Millar, J.G.; Pickett, J.A.; Tóth,
M.; Caulfield, J.C.; Woodcock, C.M.; Csonka, E.B.; Birkett, M.A. Eur. J. Org. Chem. in press.
5. Gerwick, W.H.; Proteau, P.J.; Nagle, D.G.; Wise, M.L.; Jiang, Z.D.; Bernart, M.W.; Hamberg, M.
Hydrobiologia 1993, 260/261, 653-665.
6. Landor, P.D.; Landor, S.R.; Mukasa, S. Chem. Commun. 1971, 1638-1639.
7. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467-4470.
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ACCEPTED MANUSCRIPT
8. Jeffery, T. Synthesis 1987, 70-71.
9. Garrais, S.; Turkington, Jr.; Goldring, W.P.D. Tetrahedron 2009, 65, 8418-8427.
10. Cram, D.J.; Allinger, N.L. J. Am. Chem. Soc. 1956, 78, 2518-2524.
11. Nakanishi, A.; Mori, K. Biosci. Biotechnol. Biochem. 2005, 69, 1007-1013.
12. Kajiwara, T.; Sekiya, J.; Odake, Y.; Hatanaka, A. Agric. Biol. Chem. 1977, 41, 1481-1484.
13. Tsuboi, S.; Masuda, T.; Takeda, A. J. Org. Chem. 1982, 47, 4478-4482.
14. Wavrin, L.; Viala, J. Synthesis 2002, 326-330.
15. Kobayashi, A.; Kubota, K.; Iwamoto, M.; Tamura, H. J. Agric. Food Chem. 1989, 37, 151-154.
16. Lindlar, H. Helv. Chim. Acta 1952, 35, 446-450.
17. Takahashi, Y.; Hashimoto, N.;Hara, T.; Shimazu, S.; Mitsudome, T.; Mizugaki, T.; Jitsukawa, K.;
Kaneda, K. Chem. Lett. 2011, 40, 405-407.
18. Hungerford, N.; Kitching, W. J. Chem. Soc., Perkin Trans. 1, 1998, 1839-1858.
19. Aerssens, M.H.P.J.; van der Heiden, R.; Heus, M.; Brandsma, L. Synth. Commun. 1990, 20,
3421-3425.
20. Wei, X.; Taylor, R.J.K. Tetrahedron Lett. 1998, 39, 3815-3818.
21. Barrett, A.G.M.; Hamprecht, D.; Ohkubo, M. J. Org. Chem. 1997, 62, 9376-9378.
22. Cowie, J.S.; Landor, P.D.; Landor, S.R. Chem. Commun. 1969, 541-542.
23. Cowie, J.S.; Landor, P.D.; Landor, S.R. J.Chem.Soc.,Perkin Trans.1, 1973 720-724.
24. Review on allene synthesis: Krause, N.; Hoffmann-Röder, A. Tetrahedron, 2004 66, 11671-11694.
25. Olsson, L.-I.; Claesson , A. Acta Chem.Scand.Ser B, 1977, 31, 614-618.
26. Claesson, A.; Olsson, L.-I. J.Am.Chem.Soc., 1979,101, 7302-7310.
27. Huguet, J.; Carmen Reyes, M. Tetrahedron Lett., 1990, 31, 4279-4280.
28. Van Brunt , M.P.; Standaert, R.F. Org.Lett., 2000, 2, 705-708.
29. Mori, K.; Nukada, T.; Ebata, T. Tetrahedron, 1981, 37, 1343-1347.
30. Yoshiyama, K.; Abe, Y.; Hayase, S.; Nokami, T.; Itoh, T. Chem.Lett., 2013 42, 663-665.
31. Boudouy, R.; Gore, J. Synthesis, 1974, 573-574.
Legends for Figures and Schemes
Fig. 1. Structures 1, 2 and 3 of the pheromone components of the male dried bean beetle,
Acanthoscelides obtectus, and structure 4 of a metabolite of the green alga, Cladophora columbiana.
Fig. 2. (A) Landor's 1971 synthesis of (±)-1 and (B) (C) Proposed mechanisms for conversion of
4-(2-tetrahydropyranyloxy-2-alkyn-1-ols (28 and 30) to 2,3-allenic alcohols (29 and 31).
Scheme 1. Attempts to prepare 2 and 3 via organopalladium chemistry. Reagents: (a) PdCl2(Ph3P)2,
CuI, Et3N, THF (50% for 8); (b) H2, Pd/BaSO4, quinolone, MeOH (45%); (c) I2, morpholine, C6H6
(27%); (d) Pd(OAc)2, K2CO3, (n-Bu)4NCl, DMF.
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ACCEPTED MANUSCRIPT
Scheme 2. Further unsuccessful attempts to prepare 3. Reagents: (a) TsCl, C5H5N, DMAP (87%);
(b) KCN, DMSO [quant. (77% purity)]; (c) NaOH, EtOH, H2O, reflux, 6 h (87%), (d) CH2N2, Et2O
{80% [44% of 15, 20% of (4E,7Z)-isomer, 28% of other isomers of 15 and 5% of dihydro
compounds]}; (e) KN(SiMe3)2, PhSeCl,THF (48%); (f) NaIO4, THF, H2O [45% (61% of 5, 3% of 3
and other isomers)]; (g) DMP, CH2Cl2; (h) TMSC≡CH, MeMgBr, THF; (i) K2CO3, MeOH (37%,
three steps); (j) MeC(OMe)3, EtCO2H, o-xylene, 145oC (1 h) and then 160-170oC (1 h) (85%); (k)
Al2O3 (basic Brockmann 1), o-xylene, 160oC (2 h) [41% (38% of 3, 21% of 19 and total 25% of
isomers of 3 with strong M+ at m/z = 180)].
Scheme 3. Synthesis of 3 and 5. Reagents: (a) EtMgBr, CuI, THF; (b) aq. HCl, MeOH (90%, two
steps); (c) H2, Pd/BaSO4, quinoline, MeOH [87% (86% purity)]; (d) Zn, Br(CH2)2Br, CuBr, LiBr,
EtOH, 100ꢂC (5-6 h), 80oC (16 h for 23 and 3 d for 25) [70% (99% purity) for (2Z,5Z)-23 and 73%
(98% purity) for (2E,5Z)-25]; (e) DMP, Ph3P=CHCO2Me, PhCO2H, DMSO, CH2Cl2 [71% (85%
purity) for 3 and 62% (75% purity) for 5]; (f) LiAlH4, THF (15%); (g) Zn, Br(CH2)2Br, EtOH, 100oC
(45 min) [50% (96.5% purity)].
Scheme 4. Synthesis of 1 to provide (±)-1 and (S,E)-1. [The depicted formulas show the synthesis of
(S,E)-1]. Reagents: (a) DHP, TsOH, Et2O [quant. for both (±)- and (R)-32]: (b) n-BuLi, ClCO2Me,
THF [91% for (±)-33; 77% for (R)-33]; (c) LiAlH4, Et2O [44% for (±)-29; 48% for (S)-29]; (d) DMP,
wet CH2Cl2 [71% for both (±)- and (S)-34]; (e) Ph3P=CHCO2Me, CH2Cl2 [39-44% for (±)-1, 71% for
(S)-1 of about 17% optical purity]; (d and e in tandem and one-pot manner21) DMP, Ph3P=CHCO2Me,
PhCO2H, DMSO, CH2Cl2 [27% for (±)-1 and 54% for (S)-1 of about 30% optical purity].
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Pheromone synthesis. Part 257: Synthesis of methyl (3E,4Z,7Z)-2,4,7-decatrienoate
and methyl (E)-2,4,5-tetradecatrienoate, the pheromone components of the male dried
bean beetle, Acanthoscelides obtectus (Say)
Kenji Mori
Supplementary Data
Experimental part related to Schemes 1 and 2
S1.
Methyl (E)-2-decen-4-ynoate (8)
A solution of 6 (1.00 g, 10.4 mmol) in Et3N (3 mL) was added to a stirred mixture of
PdCl2(Ph3P)2 (100 mg, 0.14 mmol) and 7 (2.10 g, 10 mmol) in dry THF (25 mL). CuI
(30 mg, 0.16 mmol) was added to the mixture which was stirred for 4 h at room
temperature under argon. The color of the mixture turned from yellow to red, and
Et3NHCl precipitated. The mixture was filtered through Celite, and the Celite layer
was washed with Et2O. The combined filtrate and washings were concentrated in
vacuo, and the residue was chromatographed over SiO2 (20 g). Elution with
hexane/EtOAc (50 : 1) gave 1.57 g (84%) of 8, which was distilled to give 934 mg
(50%) of pure 8 as an oil, bp 85oC/2 Torr; nD =1.4914; max (film): 2954 (s), 2933 (s),
19
ν
2861 (m), 2215 (m), 1726 (s), 1621 (s), 1459 (m), 1435 (m), 1305 (s), 1266 (s), 1219
(m), 1194 (m), 1176 (m), 1158 (s), 962 (m); δH (CDCl3): 0.91 (3H, t, J 7.2), 1.30-1.43
(2H, m), 1.56 (2H, m), 2.37 (2H, dt, J 2.4, 7.2); 3.75 (3H, s), 6.15 (1H, d, J 15.6), 6.76
(1H, dt, J 2.4, 15.6); GC-MS [column:HP-5MS, 5% phenylmethylsiloxane, 30 m x 0.25
mm i.d., carrier gas; He; press; 60.7 kPa; temp: 70-230oC (+10oC/min)]: tR 11.22 min
(98.6%); MS (70 eV, EI): m/z: 180 (2) [M+], 179 (3), 165 (76), 149 (60), 137 (46), 133
(44), 121 (61), 120 (47), 119 (63), 109 (65), 105 (91), 93 (65), 92 (56), 91 (93), 79 (100),
65 (45), 63 (45), 55 (38), 41 (33). HRMS calcd for C11H16O2: 180.1150, found:
180.1153.
S2.
Methyl (E)-2-decenoate (9)
5% Pd/BaSO4 (267 mg) was added to a solution of 8 (900 mg, 5 mmol) and
quinoline (0.3 mL) in MeOH (15 mL). The mixture was stirred vigorously under H2
(balloon) for 2 h at room temperature. Then the mixture was filtered through Celite,
~ 1 ~

ACCEPTED MANUSCRIPT
and the Celite layer was washed with Et2O. The filtrate was concentrated in vacuo,
and the residue was dissolved in Et2O. The Et2O solution was washed successively
with dil HCl, NaHCO3 solution and brine, dried (MgSO4), and concentrated in vacuo.
The residue was distilled to give 415 mg (45%) of 9 as a colorless oil, bp 85oC/2 Torr;
20
ν
nD =1.4472; max (film): 2954 (m), 2928 (s), 2856 (m), 1728 (s), 1658 (m), 1459 (m),
1436 (m), 1271(s), 1197 (s), 1170 (s), 1128 (m), 1041 (m), 980 (m); δH (CDCl3): 0.88
(3H, t, J 6.8), 1.29 (8H, br. s), 1.45 (2H, t-like, J 7.2), 2.19 (2H, q-like, J 6.8), 3.73 (3H,
s), 5.82 (1H, d, J 15.6), 6.97 (1H, dt, J 15.6, 6.8); GC-MS (same conditions as those for
8): tR 9.76 min (5.6%); 9.96 (9.7%), 10.62 (81.6%, 9); MS of 9 (70 eV, EI): m/z: 184 (1)
[M+], 153 (31), 152 (20), 141 (6), 123 (15), 113 (29), 110 (29), 101 (19), 100 (20), 96
(23), 87 (100), 84 (30), 81 (31), 74 (32), 69 (38), 55 (57), 43 (44), 41 (42). HRMS calcd
for C11H20O2: 184.1463, found: 184.1462.
S3.
1-Iodo-1,4-heptadiyne (12)
Iodine (15.2 g, 60 mmol) was dissolved in stirred and warmed benzene (170 mL) at
40oC. A solution of morpholine (15.7 g, 180 mmol) in benzene (20 mL) was added
dropwise to the above iodine solution with stirring to generate dark orange-colored
iodine-morpholine complex. After 10 min, a solution of 10 (5.0 g, 54.3 mmol) in
benzene (10 mL) was added to the stirred mixture, and the stirring was continued for 22
h at 45oC (bath temperature). After cooling, the precipitated morpholine hydroiodide
was removed by filtration through a glass filter under suction. The filter-cake was
washed with Et2O (25 mL x 3). The combined filtrate and washings were washed
successively with Na2S2O3 solution, NaHCO3 solution and brine, dried (MgSO4), and
concentrated in vacuo to give an oil (16.7 g). This was distilled to give 3.23 g (27%)
25
of 12 as a yellowish oil (The rest polymerized.), bp 72-73oC/4 Torr; nD =1.5080; max
ν
(film): 3295 (w), 2214 (w), 1318 (s), 1308 (s), 1134 (s); δH (CDCl3): 1.12 (3H, t, J 7.6),
2.14-2.21 (2H, m), 3.32 (2H, t, J 2.4); GC-MS (same conditions as those for 8): tR 8.33
min (81.3%, 12), 8.89 (14.3%, probably 1-iodo-1,2-heptadien-4-yne); MS of 12 (70 eV,
EI): m/z : 218 (100) [M+], 91 (58), 65 (58). HRMS calcd for C7H7I: 217.9592, found:
217.9588. Heck reaction of 12 with 13 gave black tar.
S4.
3,6-Nonadiyn-1-ol
This was prepared from 1-bromo-2-pentyne and 3-butyn-1-ol THP ether as reported
12
o
ν
by Kajiwara et al. as an oil, bp 101-102 C/3 Torr; max (film): 3366 (s), 2976 (s),
~ 2 ~

ACCEPTED MANUSCRIPT
2938 (s), 2919 (s), 2882 (s), 2213 (w), 1321 (s), 1045 (s); δH (CDCl3): 1.12 (3H, t, J 7.2),
2.14-2.21 (3H, m), 2.42-2.47 (2H, m), 3.12-3.15 (2H, m), 3.70 (3H, dt J 5.2, 6.0);
GC-MS (same conditions as those for 8): tR 9.12 min (98.3%); MS (70 eV, EI): m/z: 136
(1) [M+], 135 (5), 121 (18), 117 (11), 107 (20), 105 (28), 103 (21), 91 (100), 77 (62), 65
(23), 51 (18), 39 (15), 31(10).
S5.
(3Z,6Z)-3,6-Nonadien-1-ol (14)
5% Pd/BaSO4 (1.0 g) was added to a solution of 3,6-nonadiyn-1-ol (1.70 g, 12.5
mmol) and quinoline (0.7 mL) in MeOH (50 mL). The mixture was stirred vigorously
under H2 (balloon) at room temperature for 45 min until the exothermic H2 uptake
ceased. It was then filtered through Celite, and the Celite layer was washed with Et2O.
The filtrate was concentrated in vacuo. The residue was dissolved in Et2O. The Et2O
solution was washed with dil HCl, NaHCO3 solution and brine, dried (MgSO4), and
concentrated in vacuo. The residue was distilled to give 1.42 g (81%) of 14 as a
o
ν
colorless oil, bp 80-82 C/3 Torr; max (film): 3335 (m), 3011 (m), 2962 (s), 2932 (s),
2874 (m), 1655 (w), 1456 (m), 1049 (s), 968 (m), 720 (m); δH (CDCl3): 0.98 (3H, t, J
7.2), 1.92-2.14 (3H, m), 2.36 (2H, q J 7.2), 2.82 (2H, t, J 6.8), 3.65 (2H, t, J 6.8),
5.26-5.35 (1H, m), 5.35-5.50 (2H, m), 5.50-5.60 (1H, m); GC-MS (same conditions as
those for 8): tR 7.54 min (4.6%, nonen-1-ol isomer), 7.61 (80.8%, 14), 7.70 (7.2%,
nonen-1-ol isomer), 7.77 (6.2%, nonen-1-ol isomer); MS of 14 (70 eV, EI): m/z: 140
(<1) [M+], 122 (8), 107 (21), 93 (79), 91 (38), 81 (30), 79 (71), 77 (32), 67 (100), 55
(40), 41 (39), 39 (28), 31(13).
S6.
Methyl (4Z,7Z)-4,7-decadienoate (15)
S6.1. Tosylation of 14. TsCl (2.1 g, 11 mmol) was added to a stirred and ice-cooled
solution of 14 (1.40 g, 10 mmol) and DMAP (10 mg) in dry pyridine (7 mL). After 2 h
at 0-5oC, the mixture was worked up to give 2.54 g (87%) of the tosylate of 14 as a
ν
colorless oil, max (film): 3011 (m), 2962 (s), 2931 (s), 2873 (m), 1655 (w), 1599 (m),
1362 (s), 1189 (s), 966 (s), 909 (s), 816 (s), 664 (s), 555 (s).
S6.2. (4Z,7Z)-4,7-Decadienenitrile. Powdered KCN (2.50 g, 8.5 mmol) was added
to a solution of the above tosylate (2.50 g, 8.5 mmol) in dry DMSO (20 mL). The
mixture was stirred for 3 d at room temperature under argon. Work-up yielded 1.28 g
ν
(quant.) of the nitrile as a colorless oil, max (film): 3012 (m), 2963 (s), 2932 (s), 2873
~ 3 ~

ACCEPTED MANUSCRIPT
(m), 2246 (m), 1653 (w), 1456 (m), 1427 (m), 970 (m), 719 (m); GC-MS (same
conditions as those for 8): tR 9.11 min (0.9%, decenenitrile isomer), 9.22 (5.5%,
decenenitrile isomer), 9.27 (4.7%, decenenitrile isomer), 9.34 (76.8%, the desired
nitrile), 9.44 (4.6%, decenenitrile isomer), 9.49 (3.3%, isomer of the desired nitrile); MS
of the desired nitrile (70 eV, EI): m/z: 149 (6) [M+], 148 (14), 134 (14), 120 (63), 108
(14), 93 (27), 79 (94), 67 (100), 55 (51), 41 (38).
S6.3. (4Z,7Z)-4,7-Decadienoic acid. A solution of the above nitrile (1.25 g, 8.4
mmol) and NaOH (4.0 g, 100 mmol) in 99% EtOH (20 mL) and water (6 mL) was
stirred and heated under reflux for 6 h. Usual work-up gave 1.23 g (87%) of the acid
ν
as a colorless oil, max (film): ~3500- ~2500 (br, m), 3012 (s), 2963 (s), 1713 (s), 1413
(m), 1283 (m), 967 (m), 948 (m), 727 (m).
S6.4. Methyl (4Z,7Z)-4,7-decadienoate (15). A solution of the above acid (1.20 g, 7
mmol) in Et2O (10 mL) was treated with CH2N2 (prepared from 2.5 g of
N-methyl-N-nitrosourea) in Et2O (70 mL), and concentrated in vacuo. The residue
o
ν
was distilled to give 962 mg (80%) of 15 as a colorless oil, bp 82-85 C/3 Torr; max
(film): 3011 (m), 2961 (m), 2933 (m), 2873 (m), 1742 (s), 1654 (w), 1437 (m), 1199 (m),
1164 (m), 969 (w), 728 (w). Its 1H NMR spectrum was complicated due to the
extensive double bond isomerization and migration in the course of the nitrile
hydrolysis. GC-MS (same conditions as those for 8): tR 9.73 min (1%, decenoate
isomer), 9.81 (44%,15), 9.84 [20%, (4E,7Z)-isomer of 15], 9.89 (8%, (4Z,7E)-isomer of
15], 9.93 [4%, decenoate isomer), 9.99 [3%, (4E,7E)-isomer of 15], 10.40 [(6%,
(5Z,7Z)-conjugated isomer], 10.47 [11%, (5E,7Z)-conjugated isomer], 10.57 [0.5%,
(5Z,7E)-conjugated isomer], 10.63 [0.5%, (5E,7E)-conjugated isomer]. Accordingly,
the composition of the product was 44% of (4Z,7Z)-15, 31% of other E/Z-isomers of 15,
18% of the conjugated diene isomers with strong M+ at m/z 180, and 5% of decenoate
isomers. Assignments of E/Z geometries of the components are tentative and
speculative.
S7.
Methyl (2RS,4Z,7Z)-2-phenylselenenyl-4,7-decadienoate (16)
A solution of KN(SiMe3)2 (TCI, 0.5 M in toluene, 30 mL, 30 mmol) was added
dropwise to a stirred and cooled solution of crude 15 (887 mg, 4.9 mmol) in THF (20
mL) at -78 to -65oC under argon. The stirring was continued for 30 min at -78oC to
generate a pale orange-colored enolate solution. Then a red solution of PhSeCl (1.53 g,
~ 4 ~

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8 mmol) in THF (20 mL) was added dropwise at -78 to -65oC, and the mixture was
stirred for 30 min at -78 to -70oC. The reaction was quenched by the addition of
NH4Cl solution, and the mixture was extracted with Et2O. The Et2O solution was
washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue
was chromatographed over SiO2 (30 g). Elution with hexane/EtOAc (200 : 1) gave
Ph2Se2 (70 mg), and further elution with the same eluent gave 878 mg (48%) of 16 as a
ν
yellowish viscous oil, max (film): 3058 (w), 3010 (m), 2959 (s), 2930 (s), 2872 (m),
1732 (s), 1653 (w), 1578 (m), 1437 (m), 1250 (m), 1160 (m), 741 (s), 691 (s); δH
(CDCl3) (Major signals due to 16 are recorded.): 0.96 (3H, t, J 7.2), 1.90-2.10 (4H, m),
2.45-2.60 (1H, m), 2.60-2.80 (2H, m), 3.63 (3H, s), 5.10-5.55 (4H, m), 7.20-7.45 (3H,
m), 7.55-7.65 (1H, m), 7.65-7.70 (1H, d-like , J 6.8); GC-MS (same conditions as those
for 8): tR 19.26 min (58.3%, 16), 19.51 [7.6%, (4E,7Z)-isomer of 16]; Other isomers of
16 with (M+1)+=338 : 19.88 (4.5%), 20.17 (3.7%); Dihydro isomers of 16 with
(M+1)+= 340 : 19.20 (5.1%), 19.32 (7.9%), 19.40 (2.8%). MS of 16 (70 eV, EI): m/z:
338 (21) [(M+1)+], 243 (11), 181 (17), 169 (18), 157 (51), 149 (42), 138 (16), 121 (100),
120 (44), 93 (38), 91 (39), 79 (63), 77 (46), 67 (31), 55 (38), 41 (29).
S8.
Methyl (2E,4E,7Z)-2,4,7-decatrienoate (5)
A solution of 16 (474 mg, 1.4 mmol) in THF (16 mL) was added dropwise to a
stirred suspension of NaIO4 (2.14 g, 10 mmol) in water (10 mL) at room temperature.
The reaction was slightly exothermic. The mixture was stirred for 1 h at room
temperature, diluted with Na2CO3 solution, and extracted with Et2O. The Et2O
solution was washed with water and brine, dried (MgSO4), and concentrated in vacuo.
The residue was chromatographed over SiO2 (20 g). Elution with pentane/EtOAc (30 :
ν
1) gave 113 mg of crude 5 as a slightly yellowish oil, max (film): 3013 (m), 2960 (s),
2932 (s), 2873 (m), 1721 (s), 1643 (s), 1617 (m), 1435 (m), 1268 (s), 1139 (s), 1001
(m); δH (CDCl3) 0.85-0.92 (1.6 H, m, due to decadienoate isomers), 0.96 (3H, t, J 7.2),
1.25-1.40 (1.8H, m, due to decadienoate isomers), 2.00-2.10 (2H, m), 2.92 (2H, t, J 6.8),
3.74 (3H, s), 5.30-5.42 (1H, m), 5.43-5.56 (1H, m), 5.25-5.40 (1.4H, due to impurities),
6.05-6.24 (2H, m), 7.27 (1H, dd, J 10, 16); GC-MS (same conditions as those for 8): tR
10.38 (6.2%, decadienoate isomer), 10.43 (1.4%, decadienoate isomer), 10.51 (2.9%,
decadienoate isomer), 10.55 (9.8%, decadienoate isomer), 10.87 [3.0%, (2E,4Z,7Z)-3 =
natural component], 10.93 (2.0%, decadienoate isomer), 10.97 (1.7%, isomer of 3),
11.17 (1.8%, isomer of 3), 11.39 [60.8%, (2E,4E,7Z)-5], 11.49 (1.5%, isomer of 3),
11.86 (0.7%, isomer of 3 with a large M+ peak), 12.14 (1.8%, isomer of 3 with a large
~ 5 ~

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M+ peak). Use of Na2CO3 at the work-up stage might have caused the isomerization of
3 to 5. MS of 5 (70 eV, EI): m/z: 180 (13) [M+], 149 (19), 138 (14), 137 (9), 133 (10),
124 (14), 121 (45), 120 (34), 119 (45), 111 (77), 105 (39), 98 (42), 93 (30), 91 (87), 81
(33), 79 (100), 77 (48), 68 (21), 67 (21), 65 (22), 59 (21), 55 (32), 53 (22), 39 (27).
S9.
(Z)-3-Hexenal
According to Wavrin and Viala,14 DMP (10.0 g, 23.6 mmol) was added portionwise
to a stirred and ice-cooled solution of 17 (TCI, Z/E = 99.2 : 0.6 as analyzed by GC-MS,
2.0 g, 20 mmol) in CH2Cl2 (20 mL) at 0-5oC under argon. The mixture was stirred for
1 h at room temperature, and quenched by adding a solution of NaHCO3 and Na2S2O3.
After stirring for 10 min, the mixture was diluted with Et2O, and filtered through Celite.
The Celite layer was washed with Et2O. The Et2O layer of the filtrate was separated,
washed with brine, dried (MgSO4), and concentrated under atmospheric pressure. The
residue was diluted with dry C6H6, and concentrated under atmospheric pressure to give
a solution of (Z)-3-hexenal in C6H6 (ca. 10 mL). This was employed in the next step.
A small portion of the solution was further concentrated to give crude (Z)-3-hexenal,
+
ν
max (film): 2724 (w), 1725 (s), 1656 (m): MS (70 eV, EI): m/z: 98 (12) [M ], 83 (27),
80 (19), 69 (57), 55 (46), 41 (100), 39 (41).
S10. (±)-(Z)-5-Octen-1-yn-3-ol (18)
A solution of MeMgBr in Et2O (TCI, 3 M, 20 mL, 60 mmol) was added to a stirred
and cooled solution of TMSC ≡ CH (6.60 g, 66 mmol) in dry THF (30 mL) at -70oC
under argon. The mixture was stirred for 3 h at 30oC until the evolution of CH4 ceased.
Then a C6H6 solution (10 mL) of crude (Z)-3-hexenal prepared from 2.0 g of 17 was
added dropwise to the stirred and cooled solution of TMSC ≡ CMgBr at -78oC, and the
mixture was left to stand overnight. It was then poured into ice and NH4Cl solution,
and extracted with Et2O. The Et2O solution was washed with water and brine, dried
(MgSO4), and concentrated in vacuo to give crude TMS derivative of 18, MS (70 eV,
EI): m/z 181 (12) [M+-1], 127 (59), 99 (100), 75 (31), 73 (21), 70 (19). K2CO3 (4.0 g,
29 mmol) was added to a solution of the TMS derivative in MeOH (60 mL) and water
(2 mL), and the mixture was stirred for 1 h at 50oC. It was then concentrated in vacuo.
The residue was diluted with water, and extracted with Et2O. The Et2O solution was
washed with water and brine, dried (MgSO4), and concentrated in vacuo. The residue
was distilled to give 920 mg (37%, three steps) of 18 as a colorless oil, bp 60-62oC/5
~ 6 ~

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ν
Torr; max (film) ~3400 (br. s), 3303 (s), 3013 (m), 2965 (s), 2934 (m), 2875 (m), 2116
(w), 1654 (w), 1041 (s), 656 (s); δH (CDCl3): 0.98 (3H, t, J 7.6), 1.71 (1H, d, J 7.2),
2.10 (2H, dq, J 7.2, 7.2), 2.47 (1H, d, J 2.0), 2.50 (2H, dd, J 6.4, 7.2), 4.40 (1H, dt, J 2.0,
6.4), 5.41-5.48 (1H, m), 5.61-5.67 (1H, m); GC-MS (same conditions as those for 8): tR
5.02 min (90.3%); MS (70 eV, EI) : m/z: 124 (2) [M+], 123 (2), 109 (22), 95 (42), 91
(49), 70 (49), 69 (42), 67 (64), 55 (81), 41 (100), 39 (38).
S11. (±)-Methyl (7Z)-3,4,7-decatrienoate (19)
Propanoic acid (0.1 g) was added to a solution of (±)-18 (0.90 g, 7.3 mmol) in
methyl orthoacetate (20 mL), and the mixture was stirred and heated at 145oC (bath
temperature) for 1 h with distillative removal of the low bp materials. After cooling,
the mixture was concentrated in vacuo. The residue was diluted with methyl
orthoacetate (10 mL) and o-xylene (10 mL) containing propanoic acid (0.1 g), and
heated at 160-170oC (bath temperature) for 1 h. After cooling, the mixture was
concentrated in vacuo. The residue was distilled to give 1.11 g (85%) of (±)-19 as a
o
ν
colorless oil, bp 93-95 C/6 Torr; max (film) 3010 (m), 2964 (m), 2875 (m), 1967 (w),
1742 (s), 1653 (w), 1166 (s); δH (CDCl3): 0.96 (3H, t, J 7.2), 2.08-2.11 (2H, m),
2.73-2.76 (2H, m), 3.04 (2H, dd, J 2.4, 7.2), 3.70 (3H, s), 5.17-5.21 (1H, m), 5.24-5.28
(1H, m), 5.33-5.39 (1H, m), 5.41-5.48 (1H, m); GC-MS [same conditions as those for
8]: tR 9.58 min (12.7%, unidentified), 10.26 [0.8%, (7E)-isomer of 19], 10.33 (80.8%,
19). MS of 19 (70 eV, EI): m/z: 180 (4) [M+], 165 (3), 151 (9), 137 (7), 123 (23), 121
(32), 120 (22), 106 (50), 105 (42), 93 (54), 91 (100), 79 (66), 77 (38), 69 (28), 67 (29),
55 (24), 41 (62).
S12. Thermal isomerization of (±)-19 over basic alumina
Al2O3 (Aldrich 199443, basic Brockmann 1, 3.0 g) was placed in a 30 mL
round-bottomed flask, and heated at 200oC (bath temperature) for 2 h under reduced
pressure (4 Torr). After cooling, a solution of (±)-19 (1.02 g, 5.6 mmol) in o-xylene (6
mL) was added to Al2O3 which turned yellow in color, and the mixture was vigorously
stirred and heated at 160oC (bath temperature) for 2 h under argon. After cooling, the
mixture was filtered through a glass filter, and Al2O3 was washed with EtOAc (10 mL).
The combined filtrate and washings were concentrated in vacuo. The residue was
o
ν
distilled to give 0.423 g (41%) of a slightly yellowish oil, bp 100-102 C/5 Torr; max
(film): 3502 (w, due to 18), 3299 (w, due to 18), 3013 (s), 2964 (s), 2934 (s), 2874 (s),
~ 7 ~

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2113 (w, due to 18), 1967 (w, due to the recovered 19), 1741 (s, due to 19), 1720 (s),
1637 (s), 1603 (w), 1436 (m), 1268 (s), 1170 (s), 994 (m). The distillate was a mixture
containing 6% of 18, 21% of 19, 38% of (2E,4Z,7Z)-3 and total 25% of isomers of 3 as
revealed by GC analysis. GC-MS (same conditions as those for 8): tR 4.98 min (6.3%,
18), 10.31 (20.9%, 19), 10.88 [37.8%, (2E,4Z,7Z)-3], 11.64 (17.8%, an isomer of 3 with
strong M+ at m/z 180). MS of (2E,4Z,7Z)-3 (70 eV, EI): m/z: 180 (4) [M+], 165 (2),
149 (13), 137 (15), 121 (50), 120 (38), 119 (34), 111 (52), 105 (40), 98 (27), 93 (35), 91
(88), 79 (100), 77 (49), 67 (21), 65 (22), 55 (30), 39 (27). The MS was identical to
that of the naturally occurring pheromone component.
~ 8 ~