Pheromone synthesis. Part 249: Syntheses of methyl (R,E)-2,4,5- tetradecatrienoate and methyl (2E,4Z)-2,4-decadienoate, the pheromone components of the male dried bean beetle, Acanthoscelides obtectus (Say)

Article abstract of DOI:10.1016/j.tet.2011.12.064

The enantiomers of methyl (E)-2,4,5-tetradecatrienoate (1), a component of the male pheromone of Acanthoscelides obtectus, were synthesized from the enantiomers of 1-undecyn-3-ol (6), which were obtained via asymmetric acetylation of (±)-1-trimethylsilyl-1-undecyn-3-ol (4) with vinyl acetate as catalyzed by lipase PS (Amano). The ortho ester Claisen rearrangement of 6 with triethyl orthoacetate was the key-step to generate the chiral allenic system. A new synthesis of (±)-1 was also executed starting from (±)-6. Three different syntheses of methyl (2E,4Z)-2,4-decadienoate (2), another component of the male pheromone of A. obtectus, were achieved by means of either palladium-catalyzed Heck reaction or a Claisen and an Al ₂O₃ catalyzed thermal rearrangements.

Full text of DOI:10.1016/j.tet.2011.12.064

Tetrahedron 68 (2012) 1936e1946
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Pheromone synthesis. Part 249: Syntheses of methyl (R,E)-2,4,5-
tetradecatrienoate and methyl (2E,4Z)-2,4-decadienoate, the pheromone
components of the male dried bean beetle, Acanthoscelides obtectus (Say)q
*
Kenji Mori
Photosensitive Materials Research Center, Toyo Gosei Co., Ltd, 4-2-1 Wakahagi, Inzai-shi, Chiba 270-1609, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The enantiomers of methyl (E)-2,4,5-tetradecatrienoate (1), a component of the male pheromone of
Acanthoscelides obtectus, were synthesized from the enantiomers of 1-undecyn-3-ol (6), which were
obtained via asymmetric acetylation of (ꢀ)-1-trimethylsilyl-1-undecyn-3-ol (4) with vinyl acetate as
catalyzed by lipase PS (Amano). The ortho ester Claisen rearrangement of 6 with triethyl orthoacetate
was the key-step to generate the chiral allenic system. A new synthesis of (ꢀ)-1 was also executed
starting from (ꢀ)-6. Three different syntheses of methyl (2E,4Z)-2,4-decadienoate (2), another compo-
nent of the male pheromone of A. obtectus, were achieved by means of either palladium-catalyzed Heck
reaction or a Claisen and an Al2O3 catalyzed thermal rearrangements.
Received 8 December 2011
Received in revised form 19 December 2011
Accepted 21 December 2011
Available online 3 January 2012
Dedicated to Professor Masanao Matsui, my
Dr. thesis advisor, on the occasion of his
94th birthday
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Acanthoscelides obtectus (Say)
Allene
Claisen rearrangement
Heck reaction
Lipase
Optically active allene
Pheromone
1. Introduction
hexane), respectively}, and confirmed the R configuration of the
natural pheromone.7 Since the magnitude of the specific rotation of
In 1970 Horler isolated (ꢁ)-methyl (E)-2,4,5-tetradecatrienoate
the natural (ꢁ)-1 was reported as ꢁ128, its enantiomeric purity was
speculated to be less than 100%.7 In 1981 when our previous syn-
thesis was completed, however, there was no good analytical
method available to determine the enantiomeric composition of
the natural pheromone.
23
{1, Fig. 1, [
a]
ꢁ128 (c 0.6, hexane)} as the male-produced phero-
D
mone of the dried bean beetle, Acanthoscelides obtectus (Say)
[COLEOPTERA: Bruchidae].2 This unique chiral and non-racemic
allene soon attracted the attention of synthetic chemists, and
Landor et al. were the first to announce the synthesis of (ꢀ)-1 in
1971.3 Since then a number of syntheses of (ꢀ)-, (R)-, and (S)-1 were
reported.4e10
In February 2011, Professor W. Francke (Hamburg University,
Germany) informed me that he, in cooperation with the groups of
ꢀ
J.A. Pickett (Rothamsted Research, UK) and M. Toth (Plant Protection
The absolute configuration of the naturally occurring (ꢁ)-1 was
Institute, Budapest, Hungary), reinvestigated the male pheromone
of A. obtectus, and found 1 and methyl (2E,4Z)-2,4-decadienoate (2)
to be bioactive as checked by electroantenographic detection (EAD).
He also proposed that he would analyze the enantiomeric compo-
sition of the natural 1, employing enantioselective GC analysis on
a cyclodextrin-based chiral stationary phase.11 Of course, avail-
ability of the enantiomers of 1 as the reference samples was pre-
requisite for the analysis. Because the pheromone 1 was reported to
be unstable and polymerize readily (half-life of natural 1 was about
20 d at ꢁ13 ꢂC),2 our samples prepared in 1981 were no more
useful. I therefore decided to prepare again the enantiomers of 1 by
determined as R by Pirkle and Boeder’s first synthesis of the
enantiomerically enriched (R)- and (S)-1 {[
a
]
D ꢁ98.3 (c 3.8, hexane)
and þ94.7 (c 3.3, hexane), respectively} in 1978.6 The second syn-
thesis of (R)- and (S)-1 gave enantiomerically more enriched
23
22
products {[
a
]
ꢁ162 (c 0.95, hexane) and [
a
]
þ160 (c 0.75,
D
D
q
For Part 248, see Ref. 1.
* Tel.: þ81 3 3816 6889; fax: þ81 3 3813 1516; e-mail address: kjk-mori@
arion.ocn.ne.jp
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.064

K. Mori / Tetrahedron 68 (2012) 1936e1946
1937
Scheme 1. Synthesis of the acetylenic alcohols (R)- and (S)-6 by lipase-catalyzed
asymmetric acetylation of (ꢀ)-4. Reagents and conditions: (a) HC^CTMS, n-BuLi,
THF, ꢁ78 ꢂC to room temperature (99%); (b) (i) Lipase PS on Celite 503 (pH 7.0), CH2]
CHOAc, (i-Pr)2O, 30 ꢂC, 3 d; (ii) SiO2 chromatographic separation [49% for (R)-5 and 36%
for (S)-4]; (c) K2CO3, MeOH, 33e40 ꢂC, 2e2.5 h [91% for (R)-6 and 83% for (S)-6].
Fig. 1. Structures 1 and 2 of the pheromone components of the male dried bean beetle,
Acanthoscelides obtectus, and the key-step (ortho ester Claisen rearrangement) to
prepare the chiral and non-racemic allene system of 1.
improving our 1981 synthesis. This paper describes the results of
my efforts along this line together with a new synthesis of (ꢀ)-1 and
three different syntheses of 2.
The overall yields of (R)- and (S)-6 based on nonanal (3) were 40
and 30%, respectively. The present enzymatic preparation of (R)-
and (S)-6 was far more efficient and easier than the classical res-
olution of (ꢀ)-6 as its half phthalate as reported in 1981.7
2. Results and discussion
Conversion of the acetylenic alcohol (R)-6 to the pheromone (R)-
1 is summarized in Scheme 2. The key ortho ester Claisen rear-
rangement with transfer of the central chirality at C-3 of (R)-6 into
the axial chirality of the allenic system of (R)-7 was executed by
heating a mixture of (R)-6 and triethyl orthoacetate in the presence
of propanoic acid at 145e150 ꢂC for 1e1.5 h with distillative re-
moval of the generated ethanol. Under these conditions, the con-
version of (R)-6 to (R)-7 was complete, although slight and partial
racemization also took place. The conditions (110 ꢂC for 7 h) pre-
viously reported7 was mild enough to avoid racemization, while the
product contained a substantial amount of ortho ester (R)-i.
Reduction of (R)-7 with lithium aluminum hydride gave (R)-8
without any event, although reduction of (ꢀ)-7 with the same re-
agent had been reported to give a poor yield of (ꢀ)-8, recom-
mending the use of diisobutylaluminum hydride.17 The
corresponding tosylate (R)-9 was converted to methyl ester (R)-12
via (R)-10 and (R)-11.7 Phenylselenenylation of (R)-12 at C-2 was
first attempted with excess lithium diisopropylamide [LiN(i-Pr)2]
and phenylselenenyl chloride. The product (R)-13, however, was
contaminated with the starting (R)-12. Chromatographic separa-
tion over silica gel of (R)-12 from (R)-13 was rather difficult.7 For-
tunately, use of potassium hexamethyldisilazide [KN(SiMe3)2]
solved the problem, and the desired (R)-13 could be secured
without contamination of (R)-12. Finally, selenide (R)-13 was oxi-
2.1. Synthesis of the enantiomers of methyl (E)-2,4,5-
tetradecatrienoate (1)
Examination of the five existing syntheses of (R)- and (S)-1 in-
dicated that the use of organocopper reagents led to partial race-
mization of intermediates.6,8,9 Although Franck-Neumann’s method
employing allene manganese complexes yielded both (R)- and (S)-1
of high enantiomeric purity,10 it was rather complicated due to the
formation and removal of the manganese coordination complexes.
Accordingly, ortho ester Claisen rearrangement as shown in Fig. 1
was again adopted as the key-step just like in our previous syn-
thesis to convert acetylenic alcohol A into allenic ester C via B.7
Scheme 1 shows the preparation of the enantiomers of 1-
undecyn-3-ol (6). Since the resolution of (ꢀ)-6 was quite cumber-
some by means of chemical derivatization followed by re-
crystallization or chromatographic separation,6,7 the enzymatic
method was adopted as reported by Anastasia and his co-
workers.12 They achieved lipase-catalyzed enantiomer separation
of (ꢀ)-1-trimethylsilyl(TMS)-1-alkyn-3-ols.12 By attaching a TMS
group at C-1, the enantioselectivity of asymmetric acetylation with
vinyl acetate and lipase could be improved to give optically active
and long-chain 1-alkyn-3-ols.12 Their results were later confirmed
by us13 and others.14
dized with sodium periodate to give the pheromone component
23
Nonanal (3) was treated with lithium trimethylsilylacetylide in
THF to give (ꢀ)-4 in 99% yield. Immobilized lipase PS (Amano) on
Celite 50315 was added to a stirred and warmed solution of (ꢀ)-4
and vinyl acetate in diisopropyl ether. The mixture was stirred for
3 d at 30 ꢂC, and filtered. After concentration of the filtrate, the
mixture was chromatographed over SiO2 to give acetate (R)-5 and
(R)-1, [
a
]
24 ꢁ130.3 (c 2.23, hexane) {Ref. 7 [
a]
ꢁ162 (c 0.95, hex-
D
D
ane)}. Its enantiomeric purity was determined as 74.7% ee by GC
analysis employing ChiramixÒ as the chiral stationary phase (see
Experimental 4.12.1). Another batch of (R)-13 prepared by
employing LiN(i-Pr)2 as the base yielded (R)-1 contaminated with
23
(R)-12 (1/12¼65.6:33.3), [
a
]
ꢁ117.1 (c 1.09, hexane). Due to the
D
23
the recovered alcohol (S)-4.12 Treatment of (R)-5 with potassium
contamination with (R)-12, [
a
]
ꢁ62.0, a smaller [
a] value was
D
D
14
carbonate in methanol furnished (R)-6, [
a]
þ14.5 (c 3.57, Et2O)
observed for the product. However, GC analysis of this batch of (R)-
D
22
{Ref. 12 [
a]
þ14.8 (c 1.04, Et2O)}. Similarly (S)-4 afforded (S)-6,
1 revealed its enantiomeric purity as 87.9% ee. Similarly, (S)-6
D
17
21
25
[
a]
ꢁ14.7 (c 3.48, Et2O) {Ref. 12 [
a
]
ꢁ15.0 (c 1.02, Et2O)}. The
afforded (S)-1, [
a]
D
þ122.8 (c 1.75, hexane). Since (S)-13 was pre-
D
D
enantiomeric purities of (R)- and (S)-6 were determined by GC
pared by using LiN(i-Pr)2 as the base, both (S)-13 and (S)-1 were
contaminated with (S)-12. The enantiomeric purity of (S)-1 was
analysis on a ChiramixÒ column16 as 97.4 and 97.5% ee, respectively.

1938
K. Mori / Tetrahedron 68 (2012) 1936e1946
recovered (S)-ii (33%) and other products with no allenic absorp-
tion (1960e1967 cmꢁ1) in their IR spectrum. In this particular case,
gold(I)-catalyzed propargyl Claisen rearrangement failed to give
the desired (S)-8.
2.2. Synthesis of ( )-methyl (E)-2,4,5-tetradecatrienoate (1)
Because the absolute configuration of the major enantiomer of
the natural pheromone (ꢁ)-1 was R, it would be advantageous to
prepare (R)-1 from (S)-6. Of course Mitsunobu inversion of (S)-6
affords (R)-6, the starting material for (R)-1. It was expected,
however, that SN20-type conversion of (S)-14 (Scheme 3) to (R)-16
might eventually lead to (R)-1, in view of the success of SN20-type
allene synthesis in the past.24,25 In order to explore this possibility,
a synthesis of (ꢀ)-1 was first executed starting from (ꢀ)-6 as shown
in Scheme 3. The key-step was the allene formation from mesylate
(ꢀ)-14 and acetylene 15 by the attack of a carbanion generated
from 15. The present allene formation reaction was reported pre-
viously by Boudouy and Gore under the Cadiot conditions (CuCl, t-
BuNH2, DMF) employing (ꢀ)-14 and propargyl alcohol.26
Scheme 2. Synthesis of (R)- and (S)-1. Reagents and conditions: (a) MeC(OEt)3, Et-
CO2H, 145e150 ꢂC, 1.5 h (83%); (b) LiAlH4, THF, 0e5 ꢂC, 1.5 h (98%); (c) TsCl, C5H5N,
DMAP, 0e5 ꢂC, 2.5 h (98%); (d) KCN, DMSO, room temperature, 4 d (93%); (e) NaOH,
EtOH, H2O, reflux, 7 h (89%); (f) CH2N2, Et2O (78%); (g) KN(SiMe3)2, PhSeCl, THF, ꢁ78 to
ꢁ70 ꢂC, 1 h (59%) or LiN(i-Pr)2, THF, ꢁ65 ꢂC, 1 h (49%); (h) NaIO4, THF, H2O, room
temperature, 2.5 h (74%); (i) EtOCH]CH2, room temperature, 5 h (5%); (j) [(Ph3PAu)3O]
BF4, CH2Cl2, room temperature, 6.5 h; then NaBH4, MeOH (0%).
94.4% ee. In this case, the Claisen rearrangement was executed by
heating at 110 ꢂC for 7 h. Apparently under the low temperature
conditions, the chirality transfer from (S)-6 to (S)-7 could be ach-
ieved more perfectly. Because the objective of the present work was
to supply reference samples to the GC analysis of the naturally
occurring pheromone (R)-1, the synthetic samples of 70e90% ee
could be utilized successfully. The overall yields of (R)- and (S)-1
based on (R)- and (S)-6 were 22 and 12% (eight steps).
These synthetic enantiomers of 1 enabled Professor Francke to
determine the enantiomeric purity of the naturally occurring (R)-1
as 87% ee (W. Francke, private communication, May 19, 2011). The
result added another example to known cases of enantiomerically
impure pheromones.18e20
In 2004, Sherry and Toste reported a new variant of propargyl
Claisen rearrangement under gold(I) catalysis at room tempera-
ture.21 Their procedure yielded, with remarkably efficient chirality
transfer (>90%), homoallenic alcohols after reduction with sodium
borohydride. The acetylenic alcohol (S)-6 was therefore converted
to vinyl ether (S)-ii by treatment with ethyl vinyl ether in the
presence of mercury(II) acetate.22,23 The transetherification pro-
ceeded in very poor yield (5%), presumably due to the presence of
the terminal alkyne group, which reacted with Hg2þ ion. Attempted
conversion of (S)-ii to (S)-8 under the reported condition with
Scheme 3. Synthesis of (ꢀ)-1. Reagents and conditions: (a) MsCl, C5H5N, DMAP, 0-5 ꢂC,
2 h (85%); (b) (i) 15, n-BuLi, CuBr$Me2S, THF, ꢁ78 ꢂC, 2 h; (ii) 46% HF aq, MeCN, room
temperature, 45 min (89%, two steps); (c) LiAlH4, THF, room temperature, 2.5 h (50%);
(d) DMP, CH2Cl2, 0 ꢂC to room temperature, 50 min (60%); (e) KCN, AcOH, MnO2, MeOH,
room temperature, 4 h (79%); (f) NaI, DMF, 50 ꢂC, 1.5 h (86%); (g) 20, Pd(OAc)2, K2CO3,
(n-Bu)4NCl, DMF, room temperature, 4.5 h (0%).
Treatment of (ꢀ)-6 with mesyl chloride and pyridine in the
presence of 4-dimethylaminopyridine (DMAP) gave crystalline
(ꢀ)-14, which was treated with the lithio salt of 15 in THF in the
presence of copper(I) bromide at ꢁ78 ꢂC to give (ꢀ)-16 after
21
gold catalyst [(Ph3PAu)3O]BF4 was unsuccessful, giving only the

K. Mori / Tetrahedron 68 (2012) 1936e1946
1939
deprotection of the TBS group with hydrofluoric acid. Reduction of
(ꢀ)-16 with lithium aluminum hydride furnished alcohol (ꢀ)-17.
DesseMartin periodinane (DMP) oxidized (ꢀ)-17 to aldehyde
(ꢀ)-18. Finally, aldehyde (ꢀ)-18 was treated with potassium
cyanide, manganese dioxide, and acetic acid in methanol27 to fur-
nish (ꢀ)-1. The overall yield of (ꢀ)-1 based on (ꢀ)-6 was 18% (six
steps).
Conversion of 14 to 16 was then carried out employing oily (S)-
27
26
14, [a
]
D
ꢁ49.4 (c 3.26, hexane). The generated 16 showed [
a]
D
ꢁ0.33 (c 3.19, hexane), indicating that extensive racemization took
place in the course of the reaction.28 The present (ꢁ)-16 eventually
afforded almost racemic 1, [
a
]
D
27 ꢁ0.12 (c 1.35, hexane). Attempted
synthesis of (R)-1 from (S)-14 via SN20 mechanism was thus proved
to be unsuccessful. Since Sarandeses and co-workers found that
organoindium reagents react with optically active propargylic es-
ters to give optically active allenes via SN20 mechanism under pal-
ladium catalysis, their conditions were also examined in the
present case of the reaction of (S)-14 with 15 to give no useful
results.14,25
Another attempt was made to prepare (ꢀ)-1 by means of
palladium-catalyzed Heck reaction29 between allenic iodide (ꢀ)-19
and methyl acrylate 20. Although the iodoallene (ꢀ)-19 could
be synthesized readily by treatment of (ꢀ)-14 with sodium iodide
in DMF, the attempted Heck reaction was unsuccessful, giving
a messy mixture of unsaturated esters including methyl 2,4,6-
tetradecatrienoate.
2.3. Synthesis of methyl (2E,4Z)-2,4-decadienoate (2) via three
different routes
Scheme 4. Synthesis of (2E,4Z)-2 via (Z)-23. Reagents and conditions: (a) I2, mor-
pholine, C6H6, 45 ꢂC, 21 h (79%); (b) (i) KO2CN]NCO2K, C5H5N, MeOH, AcOH, room
temperature, overnight; (ii) Me2NH, H2O, Et2O, room temperature, 5 h (67%); (c) (i)
(C6H11)2BH, THF, 0e5 ꢂC, 30 min, then room temperature, 1.5 h; (ii) AcOH, 50 ꢂC,
30 min (57%); (d) Pd(OAc)2, K2CO3, (n-Bu)4NCl, DMF, room temperature, 1 h (75%).
Palladium-catalyzed Heck reaction was employed to prepare
methyl (2E,4Z)-2,4-decadienoate (2), the second component of the
male dried bean beetle pheromone.29,30 Scheme 4 summarizes the
first attempt, which consists in the coupling of (Z)-1-iodo-1-
heptene (23) with methyl acrylate (20).
(Z)-1-Iodo-1-heptene (23) was synthesized in two different
ways. At first, 1-heptyne (21) was warmed with iodine and mor-
pholine in benzene at reflux to give 1-iodo-1-heptyne (22).31 Dii-
mide reduction of 22 gave in 67% yield a mixture of the desired (Z)-
23 (89.6%), its (E)-isomer (2.9%) and the over-reduction product 1-
iodoheptane (24, 0.9%) together with the recovered 22 (6.6%).31 In
the second route, hydroboration-protonolysis of 22 with dicyclo-
hexylborane followed by acetic acid furnished in 57% yield a mix-
ture of (Z)-23 (90.2%) and (E)-23 (2.5%) together with other
unidentified products.
The iodoalkene mixture containing 90.2% of (Z)-23 and 2.5% of
(E)-23 was allowed to react with methyl acrylate (20) in the pres-
ence of palladium(II) acetate, potassium carbonate, and tetrabuty-
lammonium chloride in DMF29 to give in 75% yield a mixture of the
desired (2E,4Z)-2 (82.1%) and its isomers [(2E,4E)-2 (12.8%), (2Z,4E)-
2 (3.9%), and (2Z,4Z)-2 (3.1%)]. Isomerization of the desired (2E,4Z)-
2 to other E/Z-isomers was an inevitable side-reaction of the
present Heck reaction owing to the gradual generation of palla-
dium(0) in the reaction mixture. Further attempts were therefore
made to obtain purer (2E,4Z)-2 (Scheme 5).
In the second attempt, as shown in the upper part of Scheme 5,
1-iodo-1-heptyne (22) was subjected to the Heck reaction with
methyl acrylate (20) under Jeffrey’s conditions,30 similar to those
employed for the coupling of (Z)-23 with 20. The reaction afforded
25 in 47% yield. The enyne ester 25 was thermally unstable, and its
purification by distillation caused severe decrease in its yield (47
into 27%). Hydroboration-protonolysis of 25 furnished (2E,4Z)-2
(98.3% purity) contaminated with 1.7% of (2E,4E)-2 in 23% yield
after chromatographic purification and distillation. The present
method provided (2E,4Z)-2 of a better purity (98.3%) than that
(82.1%) obtained by the first method.
Scheme 5. Syntheses of (2E,4Z)-2 via hydroboration-protonolysis of 25 and re-
arrangement of (ꢀ)-27. Reagents and conditions: (a) Pd(OAc)2, K2CO3, (n-Bu)4NCl, DMF,
room temperature, 4.5 h (47%, 29% after distillation); (b) (i) (C6H11)2BH, THF, 0e5 ꢂC for
30 min, then room temperature for 2 h; (ii) AcOH, 50 ꢂC, 140 min (23%); (c) (i) Me-
C(OMe)3, EtCO2H, 145 ꢂC, 1.5 h; (ii) EtCO2H, o-xylene, 160e170 ꢂC, 2 h (72e87%); (d)
basic Al2O3, o-xylene, 160 ꢂC, 2 h (55%).

1940
K. Mori / Tetrahedron 68 (2012) 1936e1946
Aiming a more efficient synthesis, the third attempt was made
mixture was quenched with ice and aqueous NH4Cl solution, and
extracted with hexane. The extract was washed with water and
brine, dried (MgSO4), and concentrated in vacuo to give a residual
oil (28.8 g). This was chromatographed over SiO2 (160 g). Elution
with hexane/EtOAc (20:1e15:1) gave 23.8 g (99%) of (ꢀ)-4 as
a colorless oil, n2D3¼1.4502; nmax (film): 3332 (m), 2956 (s), 2925
(s), 2856 (s), 2171 (m), 1250 (s), 1011 (m), 843 (s), 760 (m); dH
(CDCl3): 0.17 (9H, s), 0.88 (3H, t, J 6.8), 1.23e1.35 (10H, br),
1.40e1.47 (2H, m), 1.68e1.73 (2H, m), 1.79 (1H, br), 4.35 (1H, dt, J
6.0, 6.4); GCeMS [column: HP-5MS, 5% phenylmethylsiloxane,
30 mꢃ0.25 mm i.d.; carrier gas, He; press: 60.7 kPa, temp:
70e230 ꢂC (þ10 ꢂC/min)]: tR 13.18 min (99.3%); MS of (ꢀ)-4
(70 eV, EI): m/z 239 (1) [(Mꢁ1)þ], 225 (3), 207 (8), 167 (10), 127
(100), 99 (65), 75 (98), 73 (38). HRMS calcd for C13H25OSi
[(MꢁCH3)þ]: 225.1675, found: 225.1680.
to prepare (2E,4Z)-2 as shown in the lower part of Scheme 5. In
1982 Tsuboi et al. discovered a thermal rearrangement of 3,4-
allenic esters with alumina catalyst in aprotic solvents to give
(2E,4Z)-dienoic esters.32 Indeed, rearrangement of (ꢀ)-ethyl 3,4-
decadienoate to ethyl (2E,4Z)-2,4-decadienoate was established as
an Organic Syntheses procedure.33
Accordingly, (ꢀ)-ethyl 3,4-decadienoate (27) was prepared from
(ꢀ)-1-octyn-3-ol (26) by treatment with trimethyl orthoacetate in
the presence of propanoic acid followed by Claisen rearrangement
in o-xylene at 160e170 ꢂC. The key thermal rearrangement of
(ꢀ)-27 to (2E,4Z)-2 was executed in the presence of basic alumina
in o-xylene at 160 ꢂC for 2 h to give the pheromone component
(2E,4Z)-2 in 40e48% overall yield based on the commercially
available (ꢀ)-26 (two steps). The purity of (2E,4Z)-2 obtained by
this method was 85.9% with contaminating three isomers [(2E,4E)-
2 (7.3%), (2Z,4E)-2 (5.7%), and (2Z,4Z)-2 (1.2%)]. Consequently, the
present short and efficient route according to Tsuboi et al. was the
best one to prepare a substantial amount of (2E,4Z)-2, although the
second method (hydroboration-protonolysis) afforded (2E,4Z)-2
with a better purity.
4.3. Asymmetric acetylation of ( )-4 with vinyl acetate and
lipase PS (Amano)
4.3.1. Preparation of immobilized lipase PS on Celite 503.15 Lipase PS
(Amano, 9.0 g) and Celite 503 (30.0 g) were mixed thoroughly by
shaking in a 300 mL Erlenmeyer flask with a glass stopper. Phos-
phate buffer (pH 7.0, 1/15 M, 30 mL) was added portionwise to the
mixture, which was vigorously shaken to make it homogeneous. It
was then dried in vacuo for 1 d to give 53.0 g of immobilized lipase
PS, and kept in a refrigerator at 0e5 ꢂC.
3. Conclusion
The two pheromone components 1 and 2 of the male dried bean
beetle were synthesized.
Firstly, enzymatic resolution of (ꢀ)-1-trimethylsilyl-1-undecyn-
3-ol (4) very much facilitated the synthesis of methyl (R,E)-2,4,5-
tetradecatrienoate (1) and its (S)-isomer. Samples with
74.7e94.4% ee of the enantiomers of 1 were prepared, and
employed as reference samples for the determination of the en-
antiomeric purity of the naturally occurring (R)-1 to be 87% ee.
Secondly, a modified synthesis of (ꢀ)-1 was developed to give it in
18% overall yield (six steps) based on (ꢀ)-1-undecyn-3-ol (6).
Thirdly, three different routes were developed for the synthesis of
methyl (2E,4Z)-2,4-decadienoate (2). Alumina-catalyzed rear-
rangement of (ꢀ)-methyl 3,4-decadienoate (27) to 2 was simpler
and more efficient than other two methods based on palladium-
catalysis.
4.3.2. Asymmetric acetylation of (ꢀ)-4.12 Immobilized lipase PS
(15.0 g) was added to a solution of (ꢀ)-4 (15.0 g, 62.5 mmol) and
vinyl acetate (150 mL) in diisopropyl ether (350 mL). The sus-
pension was stirred at 30 ꢂC for 3 d, and then filtered. The filtrate
was concentrated in vacuo to give an oil (17.7 g). This was chro-
matographed over SiO2 (200 g). Elution with hexane/EtOAc (150:1
to 200:1) first gave (R)-5 (7.22 g) and then (S)-4 (5.39 g). The in-
termediate fractions were rechromatographed over SiO2 (50 g) to
give additional amounts of (R)-5 and (S)-4. The total yield of (R)-5
was 8.63 g (98% of the theoretical) and that of (S)-4 was 5.39 g
(72%). Properties of (R)-5: a colorless oil, n2D3¼1.4456; [
a
]
22 þ74.4 (c
D
22
13
3.12, CHCl3) {Ref. 12 [
a
]
þ67.7 (c 1, CHCl3)}; [
a
]
þ63.6 (c 3.32,
D
D
hexane); nmax (film): 2957 (s), 2927 (s), 2857 (m), 2179 (w), 1748
(s), 1467 (w), 1371 (m), 1250 (s), 1231 (s), 1019 (m), 845 (s), 761
(m); dH (CDCl3): 0.17 (9H, s), 0.88 (3H, t, J 6.8), 1.22e1.35 (10H, br),
1.41 (2H, m),1.73 (2H, m), 2.08 (3H, s), 5.38 (1H, t, J 6.8); GCeMS
[same conditions as those for (ꢀ)-4]: tR 14.08 min (99.6%); MS
(70 eV, EI): m/z 282 (1) [Mþ], 239 (37), 207 (40), 184 (16), 169 (15),
142 (13), 127 (40), 117 (100), 109 (29), 99 (13), 83 (13), 75 (60), 73
4. Experimental
4.1. General
Boiling points and a melting point are uncorrected values.
Refractive indices (nD) were measured on an Atago DMT-1 re-
fractometer. Optical rotations were measured on a Jasco P-1020
polarimeter. IR spectra were measured on a Jasco FT/IR-410
(93), 59 (13), 43 (38). HRMS calcd for C16H30O2Si: 282.2015, found:
23
282.2012. Properties of (S)-4: a colorless oil, n2D3¼1.4536; [
a]
D
spectrometer. 1H NMR spectra (400 MHz, TMS at
d
¼0.00 as in-
þ1.34 (c 3.16, CHCl3) {Ref. 12 [
a
]
25 þ1.2 (c 1, CHCl3)}; [
a
]
14 ꢁ5.22 (c
D
D
ternal standard) and 13C NMR spectra (100 MHz, CDCl3 at
d
¼77.0
3.68, hexane). Its IR, 1H NMR, and mass spectra were identical to
those of (ꢀ)-4. HRMS calcd for C13H25OSi [(MꢁCH3)þ]: 225.1675,
found: 225.1675.
as internal standard) were recorded on a Jeol JNM-AL 400 spec-
trometer. GCeMS were measured on Agilent Technologies 5975
inert XL. HRMS were recorded on Jeol JMS-SX 102A. Column
chromatography was carried out on Merck Kieselgel 60 Art
1.07734.
4.4. 1-Undecyn-3-ol (6)
4.4.1. (R)-Isomer. Potassium carbonate (11.6 g, 84 mmol) was
added to a solution of (R)-5 (9.65 g, 34.2 mmol) in MeOH (150 mL)
and water (5 mL). The mixture was stirred for 2.5 h at 33e35 ꢂC,
and concentrated in vacuo. The residue was diluted with water, and
extracted with Et2O. The extract was washed with water and brine,
dried (MgSO4), and concentrated in vacuo. The residue was distilled
to give 5.21 g (91%) of (R)-6 as a colorless oil, bp 94.0e94.5 ꢂC/
4.2. ( )-1-Trimethylsilyl-1-undecyn-3-ol (4)
A solution of n-BuLi in hexane (1.6 M, 81 mL, 130 mmol) was
added dropwise to a stirred and cooled solution of TMSC^CH
(12.3 g, 125 mmol) in dry THF (200 mL) at ꢁ75 ꢂC under Ar. The
mixture was stirred for 30 min with gradual raise of temperature
up to ꢁ10 ꢂC. It was then cooled again, and a solution of nonanal
(3, 14.2 g, 100 mmol) in dry THF (30 mL) was added dropwise to
the stirred and cooled mixture at ꢁ65 to ꢁ78 ꢂC. The stirring was
continued for 1 h at ꢁ78 ꢂC to room temperature. The reaction
14
22
4 Torr; n2D3¼1.4478; [
a
]
þ14.5 (c 3.57, Et2O) {Ref. 7 [
a
]
þ14.8 (c
D
D
1.04, Et2O)}; nmax (film): 3350 (m), 3311 (s), 2925 (s), 2856 (s), 2116
(w), 1466 (m), 1029 (m), 655 (m), 627 (m); dH (CDCl3): 0.88 (3H, t, J
7.2), 1.20e1.38 (10H, br), 1.40e1.50 (2H, m), 1.64e1.79 (2H, m), 2.00

K. Mori / Tetrahedron 68 (2012) 1936e1946
1941
(1H, br), 2.46 (1H, d, J 2); 4.37 (1H, dt J 2, 6); GCeMS [same con-
ditions as those for (ꢀ)-4]: tR 9.55 min (94.2%); MS (70 eV, EI): m/z
167 (<1) [(Mꢁ1)þ], 153 (<1), 121 (11), 107 (21), 97 (24), 93 (44), 83
(44), 79 (64), 71 (55), 70 (72), 57 (70), 55 (100), 43 (69), 41 (65), 39
(22). HRMS calcd for C10H17O [(MꢁCH3)þ]: 153.1279, found:
153.1274.
(S)-7 finally afforded (S)-1 with 94.4% ee. Racemization of (S)-7
could be avoided at a lower reaction temperature.
4.6. 3,4-Tridecadien-1-ol (8)
4.6.1. (R)-Isomer. A solution of (R)-7 (5.83 g, 24.5 mmol) in dry THF
(10 mL) was added dropwise to a stirred and ice-cooled suspension
of LiAlH4 (1.00 g, 26 mmol) in dry THF (40 mL) at 5e10 ꢂC. The
mixture was stirred for 1.5 h at 0e5 ꢂC. The excess LiAlH4 was then
destroyed by dropwise addition of water to the stirred and ice-
cooled mixture. Subsequently, the mixture was diluted with ice-
cooled dil. HCl and NH4Cl solution, and extracted with Et2O. The
Et2O solution was washed with water, NaHCO3 solution and brine,
dried (MgSO4), and concentrated in vacuo. The residue was chro-
matographed over SiO2 (60 g). Elution with hexane/EtOAc
(20:1e10:1) gave 4.71 g (98%) of (R)-8 as a colorless oil, n2D3¼1.4716;
4.4.2. (S)-Isomer. Potassium carbonate (7.0 g, 51 mmol) was added
to a solution of (S)-4 (8.30 g, 34.6 mmol) in MeOH (150 mL) and
water (5 mL). The mixture was stirred at 40 ꢂC for 2 h, and con-
centrated in vacuo. The residue was worked up in the same manner
as described above for (R)-6 to give 4.84 g (83%) of (S)-6 as a col-
orless oil, bp 97e98 ꢂC/5 Torr; n2D3¼1.4478; [
a]
17 ꢁ14.7 (c 3.48, Et2O)
D
{Ref. 7 [
a
]
21 ꢁ15.0 (c 1.02, Et2O)}. Its IR, 1H NMR, and mass spectra
D
were identical to those of (R)-6. GCeMS [same conditions as those
for (ꢀ)-4]: tR 9.57 min (95.0%). HRMS calcd for C10H17
O
21
20
[(MꢁCH3)þ]: 153.1279, found: 153.1278.
[a
]
ꢁ62.5 (c 3.15, Et2O) {Ref. 7 [
a
]
ꢁ66.3 (c 1.17, Et2O)}; nmax
D
D
(film): 3332 (m), 2955 (s), 2925 (s), 2854 (s), 1963 (w), 1466 (m),
1050 (m), 874 (m); dH (CDCl3): 0.88 (3H, t, J 6.8), 1.20e1.36 (10H, br),
1.36e1.45 (2H, m), 1.68 (1H, br), 1.95e2.02 (2H, m), 2.21e2.30 (2H,
m), 3.70 (2H, q-like, J 5.6 ), 5.05e5.20 (2H, m); GCeMS [same
conditions as those for (ꢀ)-4]: tR 9.51(2.5%), 13.28 min [97.5%, (R)-
8]; MS (70 eV, EI): m/z 196 (2) [Mþ], 178 (2), 166 (4), 153 (3), 135 (3),
124 (5), 121 (6), 109 (7), 107 (8), 98 (81), 97 (50), 83 (37), 81 (45), 80
(44), 79 (61), 69 (56), 68 (100), 67 (92), 55 (60), 41 (63). HRMS calcd
for C13H24O: 196.1827, found: 196.1823.
4.4.3. Enantioselective GC analysis of 6. Instrument: Agilent 7890;
column: ChiramixÒ 30 mꢃ0.25 mm i.d.; carrier gas: He; flow
rate: 0.7 mL/min; temp: 40e180 ꢂC (0.7 ꢂC/min); detector: FID;
injection port temp: 230 ꢂC; detector temp: 250 ꢂC; tR
129.56 min [(S)-6], 131.24 min [(R)-6]. Synthetic (R)-6: (S)-iso-
mer/(R)-isomer¼1.29:98.71. Enantiomeric purity¼97.4% ee. Syn-
thetic (S)-6: (S)-isomer/(R)-isomer¼98.73:1.27. Enantiomeric
purity¼97.5% ee.
4.5. Ethyl 3,4-tridecadienoate (7)
4.6.2. (S)-Isomer. In the same manner as described above, 3.10 g
(13 mmol) of (S)-7 was treated with 0.60 g (16 mmol) of LiAlH4 in
THF (33 mL) to give 2.10 g (82%) of (S)-8 as a colorless oil,
4.5.1. (R)-Isomer. Propanoic acid (0.15 g) was added to a solution
of (R)-6 (5.30 g, 31.5 mmol) in triethyl orthoacetate (38 mL), and
the solution was stirred and heated at 135 ꢂC for 1 h with dis-
tillative removal of EtOH. The mixture was cooled and concen-
trated in vacuo. The residue was diluted with Et2O. The Et2O
solution was washed with NaHCO3 solution and brine, dried
(MgSO4), and concentrated in vacuo. The residue was distilled to
give 6.26 g (83%) of (R)-7 as a colorless oil, bp 120e122 ꢂC/4 Torr;
21
24
n2D3¼1.4720; [
a
]
þ64.8 (c 3.20, Et2O) {Ref. 7 [
a
]
þ66.9 (c 1.20,
D
D
Et2O)}. Its IR, 1H NMR, and mass spectra were identical to those of
(R)-8. GCeMS [same conditions as those for (ꢀ)-4]: tR 9.52 (0.3%),
13.27 min [99.7%, (R)-8]. HRMS calcd for C13H24O: 196.1827, found:
196.1827.
4.7. 3,4-Tridecadienyl tosylate (9)
n2D3¼1.4542; [
a
]
16 ꢁ30.1 (c 3.64, Et2O); nmax (film): 2956 (m), 2926
D
(s), 2855 (m), 1967 (w), 1741 (s), 1242 (m), 1159 (s), 1040 (m); dH
(CDCl3): 0.88 (3H, t, J 6.8), 1.18e1.22 (1H, m), 1.23e1.34 (9H, br),
1.27 (3H, t, J 7.2), 1.35e1.45 (2H, m), 1.95e2.02 (2H, m), 3.01 (2H, q, J
7.2), 4.15 (2H, q, J 7.2), 5.16e5.25 (2H, m); GCeMS [same conditions
as those for (ꢀ)-4]: tR 13.97 [8.1%, ortho ester (R)-i], 14.70 min
[91.9%, (R)-7]; MS of (R)-i (70 eV, EI): m/z 281 (<1), 239 (2), 139 (2),
117 (C6H13Oþ2 , 100), 89 (46), 79 (18), 61 (35), 43 (46); MS of (R)-7
(70 eV, EI): m/z 238 (10) [Mþ], 209 (9), 193 (6), 181 (10), 167 (9), 150
(16), 140 (38), 139 (26), 125 (25), 112 (32), 111 (46), 98 (29), 83 (70),
81 (42), 79 (35), 67 (100), 55 (39), 41 (38). HRMS calcd for
C15H26O2: 238.1933, found: 238.1940. This batch of (R)-7 finally
yielded (R)-1 with 87.9% ee. When the Claisen rearrangement was
executed at 145e150 ꢂC at 1.5 h, the ortho ester (R)-i almost dis-
appeared, and (R)-7 was obtained in a better purity [(R)-7/(R)-
i¼96.7:1.8]. That batch of (R)-7 finally afforded (R)-1 with 74.7% ee.
This indicated that the attempt to force complete conversion of
(R)-i to (R)-7 by raising the reaction temperature caused partial
racemization of (R)-7. Enantiomer separation of 7 by GC was
unsuccessful.
4.7.1. (R)-Isomer. Tosyl chloride (5.25 g, 25 mmol) was added
portionwise to
a stirred and ice-cooled solution of (R)-8
(4.62 g, 23.6 mmol) in dry pyridine (30 mL) containing 4-
dimethylaminopyridine (DMAP, 50 mg) at 0e5 ꢂC. The mixture
was stirred for 2.5 h at 0e5 ꢂC, poured into ice-water, and extracted
with Et2O. The Et2O solution was washed with CuSO4 solution and
brine, dried (MgSO4), and concentrated in vacuo to give 7.80 g (98%)
of (R)-9 as a colorless oil; nmax (film): 2954 (m), 2925 (s), 2854 (m),
1964 (w), 1598 (m), 1364 (s), 1189 (s), 1177 (s), 972 (m), 915 (m), 814
(m), 664 (m), 573 (m), 555 (m); dH (CDCl3): 0.88 (3H, t, J 6.8),
1.20e1.40 (12H, br), 1.90e1.98 (2H, m), 2.28e2.35 (2H, m), 2.45 (3H,
s), 4.07 (2H, t, J 6.8), 4.92e5.06 (1H, m), 5.06e5.62 (1H, m), 7.34 (2H,
d, J 8.0), 7.79 (2H, d, J 8.0). This was employed in the next step
without further purification.
4.7.2. (S)-Isomer. In the same manner as described above, 2.00 g
(10 mmol) of (S)-8 gave 2.60 g (quant.) of (S)-9 as a colorless oil. Its
IR and 1H NMR spectra were identical to those of (R)-9. This was
employed in the next step without further purification.
4.5.2. (S)-Isomer. In the same manner as described above (S)-6
(3.00 g, 18 mmol) was stirred and heated with triethyl orthoacetate
(35 mL) in the presence of propanoic acid (0.12 g) at 110 ꢂC for 7 h
4.8. 4,5-Tetradecadienenitrile (10)
4.8.1. (R)-Isomer. Potassium cyanide (2.50 g, 38 mmol) was added
to a stirred solution of (R)-9 [7.80 g (crude), 23 mmol] in dry DMSO
(35 mL). The mixture was stirred for 4 d under Ar at room tem-
perature, then diluted with water, and extracted with Et2O. The
extract was washed with water and brine, dried (MgSO4), and
concentrated in vacuo to give 4.36 g (93%) of (R)-10 as an oil; nmax
to give 3.10 g (72%) of (S)-7 as a colorless oil, bp 124e135 ꢂC/5 Torr;
n2D3¼1.4540; [
a
]
þ29.8 (c 3.12, Et2O). Its IR, 1H NMR, and mass
21
D
spectra were identical to those of (R)-7. GCeMS [same conditions as
those for (ꢀ)-4]: tR 13.97 [8.3%, (S)-i], 14.70 min [89.8%, (S)-7].
HRMS calcd for C15H26O2: 238.1933, found: 238.1940. This batch of

1942
K. Mori / Tetrahedron 68 (2012) 1936e1946
23
(film): 2955 (s), 2925 (s), 2854 (s), 2247 (w),1964 (w),1341 (m), 722
(m); dH (CDCl3): 0.88 (3H, t, J 6.8), 1.20e1.35 (10H, br), 1.35e1.50
(2H, m), 1.98e2.05 (2H, m), 2.29e2.36 (2H, m), 2.41 (2H, t, J 6.8),
5.12e5.20 (1H, m), 5.22e5.30 (1H, m); GCeMS [same conditions as
those for (ꢀ)-4]: tR 9.52 (4.0%), 11.22 (3.9%), 14.65 [85.4%, (R)-10],
16.91 (1.4%), 17.00 min (3.1%); MS (70 eV, EI) of (R)-10: m/z 205 (<1)
[Mþ], 204 (3) [(Mꢁ1)þ], 190 (3), 176 (4), 162 (5), 148 (9), 134 (13),
120 (13), 107 (44), 106 (25), 79 (32), 67 (100), 55 (13), 41 (22). This
was employed in the next step without further purification.
a colorless oil, bp 102e103 ꢂC/1.5 Torr; nD23¼1.4621; [
a
]
þ61.7 (c
D
22
3.66, hexane) {Ref. 7 [
a]
þ63.3 (c 2.17, hexane)}. Its IR, 1H NMR,
D
and mass spectra were identical to those of (R)-12. GCeMS [same
conditions as those for (ꢀ)-4]: tR 14.98 min (96.9%). HRMS calcd for
C15H26O2: 238.1933, found: 238.1944.
4.11. Methyl 2-phenylseleno-4,5-tetradecadienoate (13)
4.11.1. (R)-Isomer employing KN(SiMe3)2. A solution of KN(SiMe3)2
in toluene (Tokyo Kasei, 0.5 M, 24 mL, 12 mmol) was added drop-
wise to a stirred and cooled solution of (R)-12 (714 mg, 3 mmol) in
dry THF (10 mL) at ꢁ78 to ꢁ65 ꢂC under Ar. After stirring for 30 min
at ꢁ78 ꢂC, a dark red solution of PhSeCl (997 mg, 5.2 mmol) in dry
THF (10 mL) was added dropwise to the stirred and cooled yellowish
solution of the K-enolate of (R)-12 at ꢁ78 to ꢁ65 ꢂC. The stirring was
continued for 1 h at ꢁ78 to ꢁ70 ꢂC. The reaction was quenched with
aqueous 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 orange-yellow residual oil
was chromatographed over SiO2 (30 g). Elution with hexane gave
Ph2Se2 (0.12 g). Further elution with hexane/EtOAc (200:1) fur-
nished 695 mg (59%) of (R)-13 as a yellow oil; nmax (film): 3058 (w),
2952 (s), 2925 (s), 2854 (s), 1962 (w), 1733 (s), 1436 (m), 1251 (m),
1224 (m), 1160 (m), 741 (m), 691 (m); dH (CDCl3): 0.88 (3H, t, J 7.2),
1.20e1.30 (10H, br),1.30e1.40 (2H, br),1.90e2.00 (2H, m), 2.40e2.50
(1H, m), 2.52e2.62 (1H, m), 3.62 (3H, s), 3.66e3.72 (1H, m),
5.05e5.15 (2H, m), 7.25e7.35 (3H, m), 7.57e7.62 (2H, m); GCeMS
[same conditions as those for (ꢀ)-4]: tR 28.06 min (98.6%); MS
(70 eV, EI): m/z 394 (21) [(Mþ1)þ], 295 (100), 293 (48), 237 (12), 177
(17),157 (36),137 (16), 121 (21), 107 (19), 95 (29), 93 (25), 91 (28), 79
(52), 77 (36). 67 (24), 53 (35), 44 (28). This was employed in the
next step without further purification to give (R)-1 with 74.7% ee.
4.8.2. (S)-Isomer. In the same manner as described above, 3.62 g
(10 mmol) of crude (S)-9 was treated with 1.3 g (20 mmol) of KCN
to give 2.08 g (99%) of crude (S)-10 as an oil. Its IR, 1H NMR, and
mass spectra were identical to those of (R)-10. GCeMS [same
conditions as those (ꢀ)-4]: tR 9.52 (2.0%), 13.26 (1.4%), 14.65 [89.6%,
(S)-10], 16.91 (1.5%), 17.00 min (3.4%).This was employed in the next
step without further purification.
4.9. 4,5-Tetradecadienoic acid (11)
4.9.1. (R)-Isomer. An aqueous solution of NaOH [10.0 g (250 mmol)
in 15 mL water] was added to a solution of (R)-10 (4.30 g, 21 mmol)
in 99% EtOH (50 mL). The mixture was stirred and heated at reflux
for 7 h, and concentrated in vacuo. The residue was diluted with
water, and extracted with Et2O to remove neutral impurities. The
aqueous layer was acidified with ice and dil. HCl (containing 30 mL
of concd HCl), and extracted with Et2O. The extract was washed
with water and brine, dried (MgSO4), and concentrated in vacuo.
The residue was chromatographed over SiO2 (50 g). Elution with
hexane/EtOAc (25:1) gave 3.54 g (75%) of (R)-11 as a colorless oil;
nmax (film): 3200 (m, br), 2956 (s), 2925 (s), 2855 (s), 2669 (m, br),
1964 (w), 1712 (s), 1436 (m), 1278 (m), 1250 (m), 936 (m, br), 875
(m); dH (CDCl3): 0.88 (3H, t, J 6.8), 1.20e1.35 (10H, br), 1.35e1.45
(2H, m), 1.92e2.05 (2H, m), 2.26e2.34 (2H, m), 2.47 (2H, t, J 6.4),
5.10e5.20 (2H, m); GCeMS [same conditions as those for (ꢀ)-4]: tR
15.50 min (99.8%); MS (70 eV, EI): m/z 224 (<1) [Mþ], 126 (100), 111
(6), 93 (16), 84 (41), 81 (68), 67 (31), 55 (19), 41 (24). This was
employed in the next step without further purification.
4.11.2. (R)-Isomer employing LiN(i-Pr)2. A solution of LiN(i-Pr)2 in
THF was prepared by adding a solution of n-BuLi in hexane (1.6 M,
14 mL, 22 mmol) to a stirred and cooled solution of (i-Pr)2NH
(2.35 g, 3.2 mL, 23 mmol) in dry THF (15 mL) at ꢁ78 ꢂC under Ar.
The mixture was stirred for 30 min at ꢁ78 ꢂC. Subsequently, a so-
lution of (R)-12 (1.428 g, 6 mmol) in dry THF (10 mL) was added
dropwise to the stirred and cooled solution of LiN(i-Pr)2 at ꢁ65 ꢂC.
The stirring was continued for 30 min at ꢁ65 ꢂC. A solution of
PhSeCl (1.15 g, 6 mmol) in dry THF (10 mL) was then added drop-
wise to the stirred and cooled solution of the Li-enolate at ꢁ65 ꢂC.
The stirring was continued for 1 h at ꢁ65 to ꢁ78 ꢂC. The reaction
was quenched with aqueous NH4Cl solution, and the mixture was
extracted with Et2O. The extract was washed with water and brine,
dried (MgSO4), and concentrated in vacuo. The residue was chro-
matographed over SiO2 (50 g). Elution with hexane gave Ph2Se2
(0.41 g). Further elution with hexane/EtOAc (200:1 to 25:1) gave
a mixture (1.91 g) of (R)-12 and (R)-13. This was rechromato-
graphed over SiO2 (35 g). Elution with hexane/EtOAc (200:1) gave
1.15 g (49%) of crude (R)-13 as a yellow oil. GCeMS analysis of this
oil revealed it to be a 65.6:33.3 mixture of (R)-13 and (R)-12. This
was employed for the next step, and yielded (R)-1 (87.9% ee) con-
taminated with (R)-12.
4.9.2. (S)-Isomer. In the same manner as described above, 2.06 g
(10 mmol) of (S)-10 afforded 2.00 g (89%) of (S)-11. Its IR, 1H NMR,
and mass spectra were identical to those of (R)-11. GCeMS [same
conditions as those (ꢀ)-4]: tR 15.44 min (100%). This was employed
in the next step without further purification.
4.10. Methyl 4,5-tetradecadienoate (12)
4.10.1. (R)-Isomer. A solution of (R)-11 (4.20 g, 19 mmol) in Et2O
(20 mL) was treated with CH2N2 in Et2O (prepared from 7.0 g of N-
nitroso-N-methylurea), and the product was purified by distillation
to give 3.54 g (78%) of (R)-12 as a colorless oil, bp 105e106 ꢂC/
2 Torr; n2D3¼1.4620; [
a]
23 ꢁ62.0 (c 3.51, hexane) {Ref. 7 [
a]
22 ꢁ63.3
D
D
(c 2.07, hexane)}; nmax (film): 2953 (s), 2925 (vs), 2854 (s), 1963 (w),
1743 (vs), 1437 (m),1252 (m), 1227 (m), 1200 (m),1161 (s), 1058 (w),
1032 (w), 996 (w), 875 (m), 721 (w); dH (CDCl3): 0.88 (3H, t, J 6.8),
1.20e1.35 (10H, br), 1.35e1.42 (2H, m), 1.92e2.00 (2H, m),
2.25e2.32 (2H, m), 2.43 (2H, t, J 6.8), 3.67 (3H, s), 5.13 (2H, quint-
like, J 4.8); GCeMS [same conditions as those for (ꢀ)-4]: tR
14.99 min (99.5%); MS (70 eV, EI): m/z 238 (4) [Mþ], 207 (3),164 (4),
149 (4), 140 (80), 121 (10), 111 (14), 98 (40), 81 (56), 80 (100), 79
(52), 67 (28), 55 (16), 41 (24). HRMS calcd for C15H26O2: 238.1933,
found: 238.1940.
4.11.3. (S)-Isomer employing LiN(i-Pr)2. In the same manner as de-
scribed above, 1.50 g (6.3 mmol) of (S)-12 gave 1.65 g (67%) of crude
(S)-13, whose GCeMS analysis revealed it to be a 64.5:33.3 mixture
of (S)-13 and (S)-12. This was employed for the next step, and
yielded (S)-1 (94.4% ee) contaminated with (S)-12.
4.12. Methyl 2,4,5-tetradecatrienoate (1)
4.10.2. (S)-Isomer. In the same manner as described above, (S)-11
(2.00 g, 8.9 mmol) was treated with CH2N2 in Et2O (prepared from
3.5 g of N-nitroso-N-methylurea) to give 1.50 g (71%) of (S)-12 as
4.12.1. (R)-Isomer from (R)-13 prepared by employing KN(SiMe3)2. A
solution of (R)-13 (670 mg, 1.7 mmol) in THF(16 mL) was added to

K. Mori / Tetrahedron 68 (2012) 1936e1946
1943
a suspension of NaIO4 (2.14 g, 10 mmol) in water (8 mL), and the
mixture was stirred for 2.5 h at room temperature. The mixture
became paste-like due to the precipitation of fine crystals of NaIO3.
It was then diluted with aqueous Na2CO3 solution, and extracted
with Et2O. The Et2O solution was washed with water and brine,
dried (MgSO4), and concentrated in vacuo. The residue was chro-
extracted with Et2O. The Et2O solution was washed with water and
brine, dried (K2CO3), and concentrated in vacuo. The residue was
chromatographed over SiO2 (10 g). Elution with hexane recovered
134 mg (33%) of (S)-ii. Further elution with hexane/EtOAc
(10:1) gave an oil without any IR absorption at 1960e1967 cmꢁ1
due to C]C]C, indicating the failure of the reaction.
matographed over SiO2 (30 g). Elution with hexane/EtOAc (50:1)
24
gave 297 mg (74%) of (R)-1 as a slightly yellow oil, n2D6¼1.5024; [
a]
4.14. 1-Ethynylnonyl methanesulfonate 14
D
ꢁ130.3 (c 2.23, hexane); nmax (film): 2952 (s), 2925 (s), 2855 (s),
1942 (m), 1721 (s), 1628 (s), 1458 (m), 1436 (m), 1306 (m), 1265 (s),
1240 (s), 1176 (m), 1138 (m), 984 (m); dH (CDCl3): 0.88 (3H, t, J 7),
1.22e1.36 (10H, br), 1.37e1.48 (2H, m), 2.02e2.10 (2H, m), 3.74 (3H,
s), 5.44 (1H, q, J 6), 5.85 (1H, dd, J 0.7, 15), 5.86e5.92 (1H, m),
7.14e7.27 (1H, m); dC (CDCl3): 14.1, 22.7, 28.1, 28.9, 29.1, 29.26,
29.35, 31.9, 51.5, 92.9, 93.0, 118.9, 143.0, 167.2, 211.6; GCeMS [same
conditions as those for (ꢀ)-4]: tR 16.05 min (98.3%); MS (70 eV, EI):
m/z 236 (2) [Mþ], 138 (52), 137 (29), 119 (13), 107 (22), 106 (21), 105
(21), 91 (26), 79 (100), 78 (34), 77 (22), 67 (15), 55 (11), 41 (17).
HRMS calcd for C15H24O2: 236.1776, found: 236.1775. Enantiose-
lective GC [instrument: Agilent 7890; column: ChiramixÒ
(30 mꢃ0.25 mm i.d.); column temp: 40e180 ꢂC (þ0.7 ꢂC/min);
carrier gas: He (flow rate, 0.7 mL/min); injection temp: 230 ꢂC;
detector temp: 250 ꢂC]: tR 171.2 [87.37%, (R)-1], 172.5 min [12.63%,
(S)-1]. Enantiomeric purity of the sample: 74.74 (ca.75)% ee. The
4.14.1. Racemate. Methanesulfonyl chloride (2.30 g, 20 mmol) and
DMAP (50 mg, 0.4 mmol) were added to a stirred and ice-cooled
solution of (ꢀ)-6 (1.68 g, 10 mmol) in dry C5H5N (5 mL). The mix-
ture was stirred for 2 h at 0e5 ꢂC. It was then poured into ice-water,
and extracted with hexane. The extract was washed with water, dil.
HCl, NaHCO3 solution and brine, dried (MgSO4), and concentrated
in vacuo. The solid residue of crude (ꢀ)-14 (2.09 g, 85%) was
recrystallized from EtOAc/hexane to give pure (ꢀ)-14 as colorless
rods, mp 44e45 ꢂC (Ref. 26 mp 40e41 ꢂC); nmax (Nujol): 3264 (m),
3020 (w), 2127 (w), 1469 (m), 1348 (s), 1332 (s), 1175 (s), 986 (m),
957 (m), 920 (s), 865 (s); dH (CDCl3): 0.88 (3H, t, J 6.8), 1.21e1.40
(10H, m), 1.45e1.55 (2H, m), 1.82e1.98 (2H, m), 2.70 (1H, d J 1.5),
3.13 (3H, s), 5.16 (1H, dt, J 1.5, 6.4); GCeMS [same conditions as
those for (ꢀ)-4]: tR 14.84 min (99.2%); MS (70 eV, EI): m/z 246 (<1)
[Mþ], 148 (4), 133 (13), 121 (19), 107 (25), 93 (52), 79 (100), 67 (25),
55 (34), 41 (36). HRMS (FAB, NaI matrix) calcd for C12H22O233NaS:
269.1187, found: 269.1189.
specific rotation of pure (R)-1 was therefore calculated as ꢁ174.
24
Another experiment gave 884 mg of (R)-10 with nD21¼1.5074, [
ꢁ122.7 (c 3.06, hexane).
a]
D
4.14.2. (S)-Isomer. In the same manner as described above (S)-6
4.12.2. (R)-Isomer from (R)-13 prepared by employing LiN(i-
Pr)2. Oxidation of crude (R)-13 [(R)-13/(R)-12¼65.6:33.3] (678 mg)
(2.1 g) gave 2.51 g (82%) of (S)-14 as an oil, n2D6¼1.4516; [
a
]
27 ꢁ49.4
D
(c 3.26, hexane). Its spectral data were identical to those of (ꢀ)-14.
HRMS (FAB, LiI matrix) calcd for C12H22O3LiS: 253.1450, found:
253.1458.
gave impure (R)-1 [(R)-1/(R)-12¼65.6:33.3] (312.5 mg), [
a
]
23 ꢁ117.1
D
(c 1.09, hexane). Enantioselective GC analysis of this impure (R)-1
showed its enantiomeric purity as 87.9% ee: tR 187.7 [93.95%, (R)-1],
189.1 min [6.05%, (S)-1]. Enantiomers of 12 could not be separated.
4.15. tert-Butyldimethylsilyl ether (15) of propargyl alcohol
4.12.3. (S)-Isomer from (S)-13 prepared by employing LiN(i-
Pr)2. Oxidation of crude (S)-13 [(S)-13/(S)-12¼64.5:33.3] (754 mg)
A solution of propargyl alcohol (5.61 g, 100 mmol) in DMF
(100 mL) was treated with TBSCl (16.6 g, 110 mmol) and imidazole
(16.4 g, 280 mmol) for 4 h at room temperature. Usual work-up and
distillation gave 15.8 g (93%) of 15 as a colorless oil, bp 73e74 ꢂC/
43 Torr; nmax (film): 3312 (m), 2956 (s), 2931 (s), 2887 (m), 2859 (s),
2121 (w), 1256 (m), 1098 (s), 838 (s), 779 (s).
gave impure (S)-1 [(S)-1/(S)-12¼64.5:33.3] (358.0 mg), [
a]
25 ꢁ122.8
D
(c 1.75, hexane). Enantioselective GC analysis of this impure (S)-1
revealed its enantiomeric purity as 94.4% ee [(S)-1/(R)-
1¼97.21:2.79]. The allenic ester 1 was unstable and polymerized
readily unless it was kept as a hexane solution.
4.16. ( )-4,5-Tetradecadien-2-yn-1-ol (16)
4.13. (S)-1-Ethynylnonyl vinyl ether (ii) and its attempted
conversion to (S)-8
A solution of n-BuLi in hexane (1.6 M, 8.25 mL, 13.2 mmol) was
added dropwise to a stirred and cooled mixture of 15 (2.04 g,
12 mmol) and CuBr$Me2S (246 mg, 1.2 mmol) in dry THF (30 mL) at
ꢁ78 ꢂC under Ar. The mixture was stirred for 30 min at ꢁ78 ꢂC to
give a clear and light-yellow solution. Subsequently, a solution of
(ꢀ)-14 (1.476 g, 66 mmol) in dry THF (10 mL) was added dropwise
to the mixture, and the resulting clear and yellow-colored solution
was stirred for 2 h at ꢁ78 ꢂC. It was then quenched by the addition
of NH4Cl solution, and extracted with Et2O. The extract was washed
with water and brine, dried (MgSO4), and concentrated in vacuo to
give 2.82 g of a mixture of (ꢀ)-16 and excess 15. This was dissolved
in MeCN (50 mL). Hydrofluoric acid (46% HF in H2O, 3 mL) was
added to the stirred solution and the stirring was continued for
45 min at room temperature. The mixture was diluted with ice-
water, and extracted with hexane. The extract was washed with
NaHCO3 solution and brine, dried (MgSO4), and concentrated in
vacuo to give an oil (1.34 g).This was chromatographed over SiO2
(20 g). Elution with hexane/EtOAc (100:1 to 10:1) gave 1.10 g (89%)
of (ꢀ)-16 as a colorless oil, n2D6¼1.5058; nmax (film): 3331 (m), 2955
(s), 2925 (s), 2855 (s), 2220 (w), 1950 (m), 1265 (m), 1015 (s), 865
(m), 724 (m), dH (CDCl3): 0.88 (3H, t, J 6.8), 1.21e1.40 (10H, br),
1.40e1.50 (2H, m),1.66 (1H, br), 2.02e2.10 (2H, m), 4.37 (2H, s), 5.36
Mercury(II) acetate (1.40 g, 4.4 mmol) was added to a solution of
(S)-6 (3.71 g, 22 mmol) in EtOCH]CH2 (65 mL), and the mixture
was stirred for 5 h at room temperature under Ar. It was then mixed
with 5% KOH aqueous solution (60 mL), and the organic layer was
separated. The aqueous layer was extracted with Et2O. The com-
bined organic solution was washed with water and brine, dried
(K2CO3), and concentrated in vacuo. The residue was chromato-
graphed over SiO2 (30 g). Elution with hexane gave 221 mg (5%) of
(S)-ii, and further elution with hexane/EtOAc (10:1) afforded 2.00 g
(54%) of the recovered (S)-8. Properties of (S)-ii: nmax (film): 3311
(m), 2925 (s), 2856 (s), 1638 (m), 1189 (s), 1057 (m), 821 (w);
GCeMS [same conditions as those for (ꢀ)-4]: tR 10.01 min (73%);
MS (70 eV, EI): m/z 194 (<1) [Mþ], 151 (2), 137 (4),123 (10),109 (18),
95 (100), 81 (86), 67 (63), 55 (52), 41 (49), 29 (16).
The gold catalyst [(Ph3PAu)3O]BF4 (Aldrich, 151 mg, 0.1 mmol,
5 mol % to ii) was added to a solution of (S)-ii (403 mg, 2.08 mmol)
in dry CH2Cl2 (2 mL). The yellowish solution was stirred for 6.5 h at
room temperature under Ar. Then NaBH4 (100 mg, 2.6 mmol) and
MeOH (2 mL) were added and the dark colored mixture was stirred
for 30 min at room temperature. It was diluted with water, and

1944
K. Mori / Tetrahedron 68 (2012) 1936e1946
(1H, m), 5.42 (1H, dt, J 6.8, 6.4); GCeMS [same conditions as those
for (ꢀ)-4]: tR 15.47 min (99.1%); MS (70 eV, EI): m/z 206 (<1) [Mþ],
131 (4), 124 (5), 117 (5), 108 (35), 107 (34), 103 (6), 91 (26), 79 (100),
77 (33), 67 (12), 55 (9), 41 (17). HRMS calcd for C14H22O: 206.1671,
conditions as those for (ꢀ)-4]: tR 11.95 (7.6%, unidentified impurity),
16.03 min [89.5%, (ꢀ)-1]. HRMS calcd for C15H24O2: 236.1776,
found: 236.1775.
When (S)-14 was employed as the starting material, an oily 1,
found: 206.1674.
[
a
]
27 ꢁ0.12 (c 1.35, hexane), was obtained, indicating racemization
D
20
When (S)-14 was employed, an oily 16, [
a]
ꢁ0.33 (c 3.29,
in the course of the synthesis, particularly at the stage of conversion
D
hexane), was obtained.
of (S)-14 to (R)-16.
4.17. ( )-2,4,5-Tetradecatrien-1-ol (17)
4.20. ( )-1-Iodo-1,2-undecadiene (19)
A solution of (ꢀ)-16 (1.00 g, 4.9 mmol) in dry THF (5 mL) was
added dropwise to a stirred and ice-cooled suspension of LiAlH4
(250 mg, 6.6 mmol) in dry THF (10 mL). The mixture was stirred for
2.5 h at room temperature. The excess LiAlH4 was then destroyed
by adding water with ice-cooling. The mixture was acidified with
dil. HCl/NH4Cl solution, and extracted with Et2O. The extract was
washed with water, NaHCO3 solution and brine, dried (MgSO4), and
concentrated in vacuo. The residue was chromatographed over SiO2
(20 g). Elution with hexane/EtOAc (10:1) gave (ꢀ)-17 (0.51 g, 50%)
as a colorless oil, n2D6¼1.5060; nmax (film): 3338 (m), 2955 (s), 2925
(s), 2854 (s), 1946 (w), 1643 (w), 1465 (m), 1097 (w), 1004 (w), 967
(m); dH (CDCl3): 0.88 (3H, t, J 6.8), 1.20e1.35 (10H, br), 1.35e1.45
(2H, m), 1.90e2.05 (3H, m), 4.16 (2H, d, J 6), 5.30e5.35 (1H, m),
5.73e5.83 (2H, m), 6.04e6.11 (1H, m); GCeMS [same conditions as
those for (ꢀ)-4]: tR 15.09 min (95.2%); MS (70 eV, EI): m/z 208 (1)
[Mþ], 190 (12), 133 (12), 124 (8), 119 (15), 110 (57), 105 (36), 96 (20),
95 (55), 91 (98), 82 (92), 81 (75), 79 (100), 67 (88), 55 (62), 41 (55).
HRMS calcd for C14H24O: 208.1827, found: 208.1823.
Sodium iodide (5.01 g, 33 mmol) was added to a stirred solution
of (ꢀ)-14 (4.30 g, 17.5 mmol) in DMF (30 mL). The mixture was
stirred and heated at 50 ꢂC for 1.5 h. The initial homogeneous so-
lution turned to a suspension of solid NaOMs. It was cooled, diluted
with water, and extracted with hexane. The extract was washed
with water and brine, dried (MgSO4), and concentrated in vacuo.
The residue was distilled to give 4.09 g (86%) of (ꢀ)-19 as a slightly
yellowish oil, bp 107e109 ꢂC/4 Torr; nD23¼1.5044; nmax (film): 3038
(w), 2954 (s), 2925 (s), 2854 (s), 1944 (w), 1464 (m), 1377 (w), 1165
(m), 1103 (w), 835 (w), 601 (m); dH (CDCl3): 0.88 (3H, t, J 6.8),
1.20e1.38 (10H, br), 1.40e1.51 (2H, m), 2.05e2.15 (2H, m), 5.09 (1H,
dd, J 6.8, 12), 5.65e5.68 (1H, m); GCeMS [same conditions as those
for (ꢀ)-4]: tR 13.12 min (88.0%); MS (70 eV, EI): m/z 278 (<1) [Mþ],
180 (100), 124 (5), 109 (4), 95 (17), 81 (21), 67 (19), 55 (15), 41 (18).
HRMS calcd for C11H19I: 278.0531, found: 278.0531.
4.21. 1-Iodo-1-heptyne (22)
When (S)-14 was employed as the starting material, an oily 17,
Iodine (35.7 g, 140.6 mmol) was dissolved in stirred and
warmed benzene (350 mL) at 40 ꢂC. A solution of morpholine
(35 mL, 402 mmol) in benzene (45 mL) was added dropwise to the
above iodine solution with stirring to generate dark orange-colored
iodineemorpholine complex. After 10 min, a solution of 21 (9.01 g,
93.9 mmol) in benzene (10 mL) was added to the mixture, and
stirring was continued for 21 h at 45 ꢂC. After cooling, the pre-
cipitated morpholine hydroiodide was removed by filtration
through a glass filter under suction. The filter-cake was washed
with Et2O (50 mLꢃ3). The combined filtrate and washings were
washed successively with Na2S2O3 solution, NaHCO3 solution and
brine, dried (MgSO4), and concentrated in vacuo. The residue was
distilled to give 16.04 g (79%) of 22 as a colorless oil, bp 53e54 ꢂC/
2 Torr; n2D8¼1.5088; nmax (film): 2956 (s), 2931 (s), 2859 (s), 2186
(w), 1465 (m), 1427 (m), 1378 (m), 728 (m); dH (CDCl3): 0.90 (3H, t, J
6.8), 1.28e1.40 (4H, m), 1.52 (2H, quint-like, J 7.2), 2.35 (2H, t, J 7.2);
GCeMS [same conditions as those for (ꢀ)-4]: tR 7.10 min (99.6%);
MS (70 eV, EI): m/z 222 (48) [Mþ], 165 (54), 95 (100), 67 (79), 55
(62), 41 (41). HRMS calcd for C7H11I: 221.9905, found: 221.9905.
27
[
a]
ꢁ0.10 (c 1.60, hexane), was obtained.
D
4.18. ( )-2,4,5-Tetradecatrienal (18)
DesseMartin periodinane (933 mg, 2.2 mmol) was added por-
tionwise to a stirred and ice-cooled solution of (ꢀ)-17 (312 mg,
1.5 mmol) in dry CH2Cl2 (20 mL) at 0e5 ꢂC. The homogeneous so-
lution was stirred for 45 min at room temperature to give a sus-
pension of colorless crystals of o-iodobenzoic acid. The reaction was
quenched by adding a solution of NaHCO3 and Na2S2O3, and
extracted with CH2Cl2. The CH2Cl2 solution was washed with
NaHCO3 solution and brine, dried (MgSO4), and concentrated in
vacuo. The residue was chromatographed over SiO2 (10 g). Elution
with hexane/EtOAc (50:1) gave 185 mg (60%) of (ꢀ)-18 as a slightly
yellowish oil; nmax (film): 2955 (s), 2925 (s), 2855 (s), 2719 (w),
2208 (w), 1940 (m), 1685 (s), 1607 (m), 1465 (m), 1150 (m), 1132 (m),
972 (m); dH (CDCl3): 0.88 (3H, t, J 7.2), 1.20e1.40 (10H, br), 1.40e1.50
(2H, m), 2.08e2.15 (2H, m), 5.42e5.53 (1H, dt, J 6, 6), 6.00e6.06
(1H, m), 6.15 (1H, dd, J 8, 15), 7.02 (1H, dd, J 8, 15), 9.52 (1H, d, J 8);
GCeMS [same conditions as those for (ꢀ)-4]: tR 14.97 min (91.9%);
MS (70 eV, EI): m/z 206 (9) [Mþ],177 (2),163 (3),149 (5),135 (6),121
(15), 108 (66), 107 (64), 91 (23), 79 (100), 67 (18), 55 (14), 41 (25).
This was employed in the next step without further purification.
4.22. (Z)-1-Iodo-1-heptene (23)
4.22.1. Reduction with diimide. To a stirred and ice-cooled mixture
of 22 (8.0 g, 36 mmol), yellow-colored KO2CN]NCO2K (14.9 g,
72 mmol), C5H5N (17 mL), and MeOH (50 mL), AcOH (9.0 mL,
158 mmol) was added dropwise over 2 h at 5e10 ꢂC. The mixture
was stirred for 4 h at room temperature. An additional amount
(12.0 g, 62 mmol) of KO2CN]NCO2K (CAUTION. This reagent once
exploded when stored in a refrigerator.) was added to the mixture.
AcOH (7.2 mL, 126 mmol) was then added dropwise to the mixture,
and the stirring was continued overnight. The reaction was
quenched by acidification with 5% HCl (70 mL) and the mixture was
extracted with pentane. The extract was washed with water,
NaHCO3 solution and brine, dried (MgSO4), and concentrated by
fractional distillation using a Vigreux column under atmospheric
pressure. The residue was dissolved in Et2O (50 mL). A 50% aqueous
solution (15 mL) of Me2NH was added to the Et2O solution, and the
mixture was stirred for 5 h at room temperature. It was then
4.19. ( )-Methyl 2,4,5-tetradecatrienoate (1)
A mixture of (ꢀ)-18 (180 mg, 0.9 mmol), MnO2 [Aldrich (217646,
activated), 1.5 g], KCN (300 mg, 4.6 mmol), and AcOH (150 mg,
2.5 mmol) in MeOH (8 mL) was stirred for 4 h at room temperature.
It was then filtered through Celite, and the Celite layer was washed
with Et2O. The combined filtrate and washings were concentrated
in vacuo. The residue was diluted with water, and extracted with
Et2O. The extract was washed with water and brine, dried (MgSO4),
and concentrated in vacuo. The residue was chromatographed over
SiO2 (10 g). Elution with hexane/EtOAc (50:1) gave 142 mg (79%) of
(ꢀ)-1 as a slightly yellowish oil, n2D8¼1.4994. Its IR, 1H NMR, and
mass spectra were identical with those of (R)-1;GCeMS [same

K. Mori / Tetrahedron 68 (2012) 1936e1946
1945
washed with water, 5% HCl, NaHCO3 solution and brine, dried
(MgSO4), and concentrated by fractional distillation (Vigreux col-
umn) under atmospheric pressure. The residue was distilled to give
5.43 g (67%) of (Z)-23 as an oil, bp 47e48 ꢂC/3 Torr; nD27¼1.5005;
nmax (film): 3067 (w), 2956 (s), 2856 (s), 1608 (m), 1296 (m), 1277
(s), 1233 (m), 688 (s), 627 (m), ; dH (CDCl3): 0.90 (3H, t, J 7.2),
1.25e1.38 (4H, m), 1.43 (2H, quint-like, J 7.8), 2.10e2.17 (2H, m),
6.13e6.20 (2H, m); GCeMS [same conditions as those for (ꢀ)-4]: tR
6.65 [89.6%, (Z)-23], 6.86 [2.9%, (E)-23], 7.07 (6.6%, 22), 7.23 min
(0.9%, 24); MS of (Z)-23 (70 eV, EI): m/z 224 (88) [Mþ], 167 (21), 154
(49), 127 (5), 97 (26), 55 (100), 41 (40). HRMS calcd for C7H13I:
224.0062, found: 224.0059. Without treatment with Me2NH, the
product contained ca. 10% of 24.
(2Z,4Z)-2 (2.1%), (2E,4Z)-2 (68.9%),(2Z,4E)-2 (3.1%), and (2E,4E)-2
(25.6%).When the reaction was continued for 3 h, the product was
a mixture of (2Z,4Z)-2 (2.7%), (2E,4Z)-2 (65.0%), (2Z,4E)-2 (2.6%),
and (2E,4E)-2 (24.9%). Pd(0) equilibrates (2E,4Z)-2 to give 2.6e2.7:1
ratio of (2E,4Z)-2 nd (2E,4E)-2.
4.24. Methyl (E)-2-decen-4-ynoate (25)
A mixture of K2CO3 (10.35 g, 75 mmol), (n-Bu)4NCl (8.34 g,
30 mmol), and 20 (27 mL, 25.9 g, 301 mmol) in DMF (5 mL) was
stirred for 10 min at room temperature to dissolve (n-Bu)4NCl. Then
Pd(OAc)2 (330 mg, 1.47 mmol) was added to the mixture, which
was stirred for 5 min under Ar to give a yellow suspension. A so-
lution of 22 (8.30 g, 37 mmol) in DMF (20 mL) was added dropwise
over 10 min to the stirred mixture under Ar at room temperature.
The reaction was exothermic, and the mixture turned dark brown
in color. Stirring was continued for 4.5 h at room temperature. It
was then worked up in the same manner as described for 2, and the
residue (8.30 g) was chromatographed over SiO2 (70 g). Elution
with hexane and hexane/EtOAc (50:1) gave 3.16 g (47%) of 25,
which was distilled to give pure 25 (1.93 g, 29%), bp 98e99 ꢂC/
3 Torr; n2D7¼1.4864; nmax (film): 2956 (s), 2933 (s), 2860 (m), 2215
(m), 1727 (s), 1621 (m), 1459 (m), 1434 (m), 1304 (s), 1267 (m), 1158
(s), 962 (m), 860 (w); dH (CDCl3): 0.91 (3H, t, J 7.2), 1.28e1.42 (4H,
m), 1.50e1.60 (2H, quint-like, J 6.8), 2.37 (2H, dt, J 1.6, 7.2), 3.75 (3H,
s), 6.15 (1H, d, J 16), 6.76 (1H, dt, J 16, 2.4); GCeMS [same conditions
as for (ꢀ)-4]: tR 11.24 min (97.3%) (After distillation, an unidentified
compound was detected at tR 13.03 min, and the purity dropped to
87.9% with 10.9% of the unknown compound.); MS (70 eV, EI): m/z
180 (3) [Mþ], 179 (3), 165 (74), 149 (60), 137 (46), 134 (43), 121 (60),
120 (45), 119 (59), 109 (63), 105 (83), 93 (63), 92 (59), 91 (89), 79
(100), 63 (47), 55 (38), 41 (36). HRMS calcd for C11H16O2: 180.1150,
found: 180.1153.
4.22.2. Reduction via hydroboration-protonolysis. Borane-dimethyl
sulfide complex (4.25 mL, 5.47 g, 72 mmol) was added dropwise to
a stirred and ice-cooled solution of cyclohexene (11.8 g, 144 mmol)
in dry THF (70 mL) at 0e5 ꢂC to give colorless crystals of dicyclo-
hexylborane. A solution of 22 (8.0 g, 36 mmol) in THF (10 mL) was
added dropwise to the stirred and ice-cooled suspension of dicy-
clohexylborane, and the mixture was stirred at 0e5 ꢂC for 30 min,
and for 1.5 h at room temperature to give a homogeneous solution.
AcOH (10 mL) was then added dropwise, and the mixture was
stirred at 50 ꢂC for 30 min. It was cooled, poured into ice and NaOH
aqueous solution (2 M, 200 mL), and extracted with pentane. The
pentane solution was washed with water and brine, dried (MgSO4),
and concentrated by fractional distillation (Vigreux column) under
atmospheric pressure. The residue was distilled to give 4.57 g (57%)
of (Z)-23 as a colorless oil, bp 52e56 ꢂC/5 Torr; nD27¼1.5001. A sub-
stantial amount of high bp oil resulting from dicyclohexylborane
remained in the distillation flask. The spectral data (IR, 1H NMR, and
MS) of (Z)-23 was identical to those of (Z)-23 obtained by diimide
reduction except that the present sample contained neither 21 nor
24. GCeMS [same conditions as those for (ꢀ)-4]: tR 6.64 [90.2%, (Z)-
23], 6.91 min [2.5%, (E)-23]. The product contained several un-
identified impurities at tR¼3.6 (0.7%), 6.3 (4.3%), 9.0 (0.3%), 9.8
(0.5%), 10.2 (1.1%), and 10.4 min (0.4%).
4.25. Methyl (2E,4Z)-2,4-decadienoate (2) via hydroboration-
protonolysis
Borane-dimethyl sulfide complex (1.2 mL, 1.52 g, 20 mmol) was
added dropwise to a stirred and ice-cooled solution of cyclohexene
(3.28 g, 40 mmol) in dry THF (20 mL) at 0e5 ꢂC under Ar. Stirring
was continued for 30 min at 0e5 ꢂC to give colorless crystals of
dicyclohexylborane. A solution of 25 (1.84 g, 10.2 mmol) in dry THF
(5 mL) was added dropwise to the stirred and ice-cooled suspen-
sion of dicyclohexylborane, and the mixture was stirred for 30 min
at 0e5 ꢂC and for 2 h at room temperature to give a homogeneous
solution. AcOH (3 mL) was then added dropwise, and the mixture
was stirred and heated at 50 ꢂC for 140 min. It was cooled, poured
into ice and K2CO3 (13 g) in water (100 mL), and extracted with
hexane. The hexane solution was washed with water and brine,
dried (MgSO4), and concentrated in vacuo. The residue (4.82 g) was
chromatographed over SiO2 (60 g). Elution with hexane/EtOAc
(50:1) gave 1.68 g (90%) of crude 2. This was distilled to furnish
427 mg (23%) of pure 2 as a colorless oil, bp 99e100 ꢂC/5 Torr;
n2D7¼1.4834. Its IR, 1H and 13C NMR, and mass spectra were identical
to those of 2 prepared from 23 and 20. GCeMS [same conditions as
those for (ꢀ)-4]: tR 10.38 (7.41%, dicyclohexyl ether), 10.98 [82.81%,
(2E,4Z)-2], 11.38 [1.38%, (2E,4E)-2], 12.04 min [2.20%, unidentified].
(2E,4Z)-2/(2E,4E)-2¼98.3:1.7.
4.23. Methyl (2E,4Z)-2,4-decadienoate (2) via Heck reaction
Palladium(II) acetate (136 mg, 0.6 mmol) was added to a mix-
ture of 20 (8.66 g, 100 mmol), (Z)-23 (2.24 g, 10 mmol), K2CO3
(2.77 g, 20 mmol), and (n-Bu)4NCl (2.21 g, 8 mmol) in DMF (40 mL).
The mixture was vigorously stirred under argon for 1 h at room
temperature. The reaction was slightly exothermic, and the initially
yellow-colored mixture turned brown after 1 h. It was diluted with
Et2O (50 mL), and filtered through Celite. The filter-cake was
washed with Et2O. The combined Et2O solution was washed with
water and brine, dried (MgSO4), and concentrated in vacuo. The
residue was chromatographed over SiO2 (30 g). Elution with hex-
ane gave the recovered 23 (0.31 g). Further elution with hexane/
EtOAc (50:1) furnished 1.27 g (75% or 82% based on the consumed
23) of 2 as a colorless oil, n2D7¼1.4825; nmax (film): 3011 (w), 2954
(s), 2929 (s), 2858 (m), 1721 (vs), 1639 (s), 1605 (w), 1435 (m), 1308
(m), 1269 (vs), 1172 (s), 1140 (s), 998 (m), 869 (m); dH (CDCl3): 0.89
(3H, t, J 7.2), 1.25e1.35 (4H, m), 1.38e1.47 (2H, quint-like, J 7.2), 2.30
(2H, q-like, J 7.2), 3.75 (3H, s), 5.85e5.92 (2H, m), 6.08e6.18 (1H, q-
like J 9), 7.58e7.66 (1H, m); dC (CDCl3): 14.0, 22.5, 28.3, 29.1, 31.4,
51.1, 120.7, 126.4, 139.8, 141.9, 167.8; GCeMS [same conditions as
those for (ꢀ)-4]: tR 10.75 [3.1%, (2Z,4Z)-2], 10.98 [82.1%, (2E,4Z)-2],
11.02 [3.9% (2Z,4E)-2], 11.38 min [12.8%, (2E,4E)-2]; MS of (2E,4Z)-2
(70 eV, EI): m/z 182 (20) [Mþ], 151 (9), 139 (7), 122 (6), 111 (100), 97
(9), 93 (9), 81 (29), 79 (24), 67 (18), 55 (10), 41 (13). HRMS calcd for
C11H18O2: 182.1307, found: 182.1306.
4.26. ( )-Methyl 3,4-decadienoate (27)
Propanoic acid (0.30 g) was added to a solution of (ꢀ)-26
(12.6 g, 100 mmol) in methyl orthoacetate (100 g, 833 mmol), and
the mixture was stirred and heated at 145 ꢂC (bath temperature)
for 1.5 h with distillative removal of the low bp materials
(<100 ꢂC) through a Vigreux column to give a mixture of a mixed
The isomeric ratio of the four isomers of 2 fluctuates. Even when
the reaction was stopped after 30 min, the product was a mixture of

1946
K. Mori / Tetrahedron 68 (2012) 1936e1946
ortho ester containing (ꢀ)-26 and the allenic ester (ꢀ)-27. After
cooling, the mixture was concentrated in vacuo. The residue (ca.
30 g) was dissolved in o-xylene (150 mL) containing 0.30 g of
propanoic acid. The mixture was stirred and heated at 160e170 ꢂC
(bath temperature) for 2 h with removal of low bp materials
through a Vigreux column. After cooling, the mixture was con-
centrated in vacuo. The residue was distilled to give 13.1 g-15.8 g
(72e87%) of (ꢀ)-27 as a colorless oil, bp 136e138 ꢂC/41 Torr or
87e90 ꢂC/3 Torr; nD21¼1.4596; nmax (film): 2929 (s), 2857 (m), 1966
(w), 1744 (vs), 1437 (m), 1334 (m), 1248 (m), 1164 (s), 1027 (w), 872
(m), 728 (w); dH (CDCl3): 0.89 (3H, t, J 7.2), 1.26e1.36 (4H, br m),
1.36e1.50 (2H, m), 1.96e2.08 (2H, m), 3.01e3.05 (2H, m), 3.70 (3H,
s), 5.14e5.26 (2H, m); GCeMS [same conditions as those for
(ꢀ)-4]: tR 10.31 min (96.8%); MS (70 eV, EI): m/z 182 (4) [Mþ], 167
(4),151 (3), 139 (6), 126 (54), 125 (29), 111 (31), 97 (100), 84 (93), 79
(47), 67 (83), 59 (30), 41 (29). HRMS calcd for C11H18O2: 182.1307,
found: 182.1305.
preparation of 2. Dr. S. Tamogami (T. Hasegawa Co., Ltd) kindly
carried out the enantioselective GC analysis of 1 and 6. Dr. T. Tashiro
(RIKEN) prepared the Figure and the Schemes. Mr. Y. Shikichi (Toyo
Gosei Co., Ltd) is thanked for NMR and GCeMS measurements. Drs.
T. Nakamura and Y. Hongo (both at RIKEN) kindly executed the
HRMS analysis. Lipase PS was given to me by Dr. Y. Hirose of Amano
Enzyme Inc.
References and notes
1. Shikichi, Y; Mori, K. Biosci. Biotechnol. Biochem., in press.
2. Horler, D. F. J. Chem. Soc. C 1970, 859e862.
3. Landor, P. D.; Landor, S. R.; Mukasa, S. J. Chem. Soc., Chem. Commun. 1971,
1638e1639.
4. Mori, K. In; ApSimon, J., Ed. The Total Synthesis of Natural Products; Wiley: New
York, NY, 1981; Vol. 4, pp 55e57.
5. Mori, K. In; ApSimon, J., Ed. The Total Synthesis of Natural Products; Wiley: New
York, NY, 1992; Vol. 9, pp 212e215.
6. Pirkle, W. H.; Boeder, C. W. J. Org. Chem. 1978, 43, 2091e2093.
7. Mori, K.; Nukada, T.; Ebata, T. Tetrahedron 1981, 37, 1343e1347.
8. Oehlschlager, A. C.; Czyzewska, E. Tetrahedron Lett. 1983, 24, 5587e5590.
9. Fujisawa, T.; Iida, S.; Sato, T. Tetrahedron Lett. 1984, 25, 4007e4010.
10. Franck-Neunann, M.; Martina, D.; Neff, D. Tetrahedron: Asymmetry 1998, 9,
697e708.
4.27. Methyl (2E,4Z)-2,4-decadienoate (2) via isomerization of
( )-27
Aluminum oxide (Aldrich 199443, basic Brockmann 1, 30 g) was
placed in a 300 mL round-bottomed flask, and heated at 200 ꢂC
(bath temperature) for 2 h under reduced pressure (5 Torr). After
cooling, a solution of (ꢀ)-27 (9.20 g, 51 mmol) in o-xylene (60 mL)
was added to Al2O3, and the mixture was vigorously stirred and
heated at 160 ꢂC (bath temperature) for 2 h under argon. Vigorous
stirring was essential to convert (ꢀ)-27 to 2 within 2 h at 160 ꢂC.
After cooling, the mixture was filtered through a glass filter, and
Al2O3 was washed with EtOAc (50 mL). The combined filtrate and
washings were concentrated in vacuo. The residue was distilled to
give 5.06 g (55%) of 2 as a colorless oil, bp 80e82 ꢂC/2e3 Torr or
93e96 ꢂC/5 Torr; n2D1¼1.4902. Its IR, 1H NMR, and mass spectra were
identical to those of 2 prepared by other routes. GCeMS [same
conditions as those for (ꢀ)-4]: tR 10.75 [1.1%, (2Z,4Z)-2], 10.99
[85.9%, (2E,4Z)-2], 11.03 [5.7%, (2Z,4E)-2], 11.38 min [7.3%, (2E,4E)-
2]. In other experiments, the isomeric ratios were 0.4:86.4:5.3:7.9
and 1.3:83.3:8.7:6.7%.
11. Mori, K. In Methods in Chemical Ecology: Chemical Methods; Millar, J. G., Haynes,
K. F., Eds.; Kluwer: Norwell, MA, 1998; Vol. 1, pp 295e338.
12. Allevi, P.; Ciuffreda, P.; Anastasia, M. Tetrahedron: Asymmetry 1997, 8, 93e99.
13. Masuda, Y.; Mori, K. Eur. J. Org. Chem. 2005, 4789e4800.
14. Kato, T.; Ishigami, K.; Akasaka, K.; Watanabe, H. Tetrahedron 2009, 65,
6953e6958.
15. Bovara, R.; Carrea, G.; Ferrara, L.; Riva, S. Tetrahedron: Asymmetry 1991, 2,
931e938.
16. Tamogami, S.; Awano, K.; Amaike, M.; Takagi, Y.; Kitahara, T. Flavour Fragrance J.
2001, 16, 349e352.
17. Kocienski, P. J.; Cernigliaro, G.; Feldstein, G. J. Org. Chem. 1977, 42, 353e355.
18. Mori, K. Bioorg. Med. Chem. 2007, 15, 7505e7523.
19. Mori, K. Chirality 2011, 23, 449e462.
20. Mori, K. Chim. Oggi/Chem. Today 2011, 29, 40e43.
21. Sherry, B. D.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 15978e15979.
ꢀ
22. Garayalde, D.; Gomez-Bengoa, E.; Huang, X.; Goeke, A.; Nevado, C. J. Am. Chem.
Soc. 2010, 132, 4720e4730.
23. Grissom, J. W.; Klingberg, D.; Huang, D.; Slattery, B. J. J. Org. Chem. 1997, 62,
603e626.
ꢀ
24. Rona, P.; Crabbe, P. J. Am. Chem. Soc. 1968, 90, 4733e4734.
25. Riverios, R.; Rodríguez, D.; Sestelo, J. P.; Sarandeses, R. A. Org. Lett. 2006, 8,
1403e1406.
26. Boudouy, R.; Gore, J. Synthesis 1974, 573e574.
27. Corey, E. J.; Gilman, N. W.; Ganem, B. E. J. Am. Chem. Soc. 1968, 90, 5616e5617.
28. Claesson, A.; Olsson, L.-I. J. Chem. Soc., Chem. Commun. 1979, 524e525.
29. Jeffery, T. Tetrahedron Lett. 1985, 26, 2667e2670.
30. Jeffery, T. Synthesis 1987, 70e71.
Acknowledgements
I thank Mr. M. Kimura (President, Toyo Gosei Co., Ltd) for his
support. My thanks are due to Prof. W. Francke (Hamburg Univer-
sity) for his suggestion to undertake the present work, and also to
Prof. S. Tsuboi (Okayama University) for his advice concerning the
€
31. Luthy, C.; Konstantin, P.; Untch, K. G. J. Am. Chem. Soc. 1978, 100, 6211e6217.
32. Tsuboi, S.; Masuda, T.; Takeda, A. J. Org. Chem. 1982, 47, 4478e4482.
33. Tsuboi, S.; Masuda, T.; Mimura, S.; Takeda, A. Organic Syntheses; Wiley:
New York, NY, 1993; Collect. Vol. 8; 251e254.