Synthesis of (4: E,6 Z,10 Z)-hexadeca-4,6,10-trien-1-ol and (4 E,6 E,10 Z)-hexadeca-4,6,10-trien-1-ol, the pheromone components of cocoa pod borer moth Conopomorpha cramerella

Article abstract of DOI:10.1039/c7ra04027j

A concise and efficient synthesis of the pheromone components of the cocoa pod borer moth, namely (4E,6Z,10Z)-hexadeca-4,6,10-trien-1-ol and (4E,6E,10Z)-hexadeca-4,6,10-trien-1-ol, starting from commercially available materials, was reported. The overall yield was 30.4% and 27.4%, respectively. The stereoselective formation of (E,Z)- or (E,E)-conjugated double bond relied on Sonogashira coupling with (E)-5-bromopent-4-en-1-ol prepared from (E)-5-bromopent-4-enal and the stereoselective hydrogenation of the enyne, while the 10Z-double bond was formed by Wittig reaction from 4-hydroxybutanal and n-hexyltriphenylphosphonium bromide.

Full text of DOI:10.1039/c7ra04027j

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Synthesis of (4E,6Z,10Z)-hexadeca-4,6,10-trien-1-
ol and (4E,6E,10Z)-hexadeca-4,6,10-trien-1-ol, the
pheromone components of cocoa pod borer moth
Conopomorpha cramerella
Cite this: RSC Adv., 2017, 7, 35575
Fei Huang, Yushun Zhang, Yun Yao, Wanqiu Yang* and Yunhai Tao *a
b
a
a
c
A concise and efficient synthesis of the pheromone components of the cocoa pod borer moth, namely
(4E,6Z,10Z)-hexadeca-4,6,10-trien-1-ol and (4E,6E,10Z)-hexadeca-4,6,10-trien-1-ol, starting from
commercially available materials, was reported. The overall yield was 30.4% and 27.4%, respectively. The
Received 9th April 2017
Accepted 10th July 2017
stereoselective formation of (E,Z)- or (E,E)-conjugated double bond relied on Sonogashira coupling with
(
E)-5-bromopent-4-en-1-ol prepared from (E)-5-bromopent-4-enal and the stereoselective
DOI: 10.1039/c7ra04027j
hydrogenation of the enyne, while the 10Z-double bond was formed by Wittig reaction from 4-
hydroxybutanal and n-hexyltriphenylphosphonium bromide.
rsc.li/rsc-advances
Introduction
(4E,6Z,10Z)-Hexadeca-4,6,10-trien-1-ol
(1a),
(4E,6E,10Z)-
hexadeca-4,6,10-trien-1-ol (2a), and their acetates (1b and 2b)
are the pheromone components of cocoa pod borer moth
(
Conopomorpha cramerella, Lepidoptera: Gracillariidae) which is
Fig. 1 Structure of the pheromone components of the cocoa pod
borer moth Conopomorpha cramerella.
the most important pest damaging cocoa plantations in
Southeast Asia. The life cycle of the insect starts once the egg is
1
laid on the pod surface of the cocoa plant (this cycle lasts for 2–7
days). Then, the larval stage is characterized by the formation of
tunnels at the pod surface that reaches the sclerotic layer of the
husk to reach food, causing scarication and sticking of the
beans. Damage to the funicles of the pods results in beans that
are deformed and under-sized, signicantly reducing the
quality and thus the value of the processed beans. Insect
feeding in the pods also causes a change of the color of the
beans into yellow or uneven and premature ripening, which do
chlorides, and applied this new method to prepare 1a with an
overall yield of 51%. Yet, the preparation of 1,5-diynes was
4
complicated, and this compound could not be used as the
starting material of isomer 2a. The general utilization of
insecticides is limited by their high cost, environmentally
unfriendliness and the development of insecticide-resistance.
Considerable efforts have been made for the development and
evaluation of new integrated pest management techniques,
such as the usage of pheromone compounds (Fig. 1).
2
not match with the ripeness standards for harvesting. Conse-
1
quently, the production losses can exceed 50% of the crop.
Previously, we reported the efficient syntheses of (5Z,7E)-
dodecadien-1-ol, (7Z,11Z,13E)-hexadecatrienal, (8E,10Z)-tetra-
decadienal, and (9Z,11E)-hexadecadienal from (4Z,6E)-7-
In 1986 Beevor et al. isolated and identied the pheromone
components of the insect, and synthesized those compounds
1
using a long and non-stereospecic route. In 1992 Yen et al.
5
bromohepta-4,6-dienal (3a), and developed an useful
reported a shorter synthesis for the pheromone components, in
5
c
3
compound, namely (E)-5-bromopent-4-enal (4a). As a part of
an ongoing investigation, we reported herein a concise and
stereoselective synthesis of 1a and 2a from 4a, which success-
fully overcame the major limitations of the previous strategies
published.
eight steps and with an overall yield of 32%. Later, Pereira and
Cabezas reported a new method for the synthesis of 1,5-diynes
using the reaction of 1,3-dilithiopropyne with propargyl
a
School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR
China. E-mail: cloudsea2000@sina.com; Fax: +86-871-67429991; Tel: +86-871-
6
5031119
Results and discussion
b
Kunming Biohome Technology Co. Ltd., Kunming 650501, PR China
c
Compound 4a was prepared by the tandem addition reaction of
Department of Chemical Science and Technology, Kunming University, Kunming
6
50214, PR China
2
acrolein with acetylene using Pd(OAc) as catalyst. Previously, Lu
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Scheme 1 Pd(II)-catalyzed coupling reaction of lithium bromide,
acetylene, and acrolein.
6
et al. reported the preparation of 3a. By repeating the reported
strategy, we found that the method was efficient only in small
scale. In the large-scale preparations, 4a was produced in consid-
erable amount as a by-product. Based on this result, we optimized Scheme 2 Possible mechanisms for Pd(II)-catalyzed coupling reaction
of halide, acetylene, and acrolein.
the experimental conditions to afford uniquely 4a (Scheme 1).
We studied the effect of different reaction conditions on the
ratio of 3a and 4a. The reaction time, reactant concentration
acetylene pressure, a high acrolein concentration obviously
increased the selectivity of the reaction.
and temperature were tested (Table 1). A high concentration of
acrolein (a decrease of the quantity of HOAc and H O) did not
2
We studied further the effect of different counter ions and
increase the total conversion rate, but it resulted in a better
selectivity of the reaction (Table 1, entries 1–3). Increasing the
temperature resulted in a better selectivity of the reaction, but it
decreased the total conversion rate (Table 1, entries 3–5),
because acrolein and the two products were not stable at high
temperature. When the reaction time was prolonged, signi-
cant improvements were observed in terms of conversion rate
and selectivity (Table 1, entries 4, 6, and 7). Lower acetylene
pressure allowed a better selectivity, but it did not affect
strongly the total conversion rate (Table 1, entries 7–9). These
results showed the same trend in both large-scale and small-
scale preparation. Previously, Lu et al. explained the forma-
ꢀ
ꢀ
reactants on the products distribution (Table 2). Br and Cl ions
allowed satisfying total conversion rate and selectivity (Table 2,
ꢀ
entries 1–3). In contrast, I ion resulted in poor total conversion
rate and selectivity (Table 2, entry 4). The results indicated that
a difference in the electron-deciency of the alkenes could have
a striking effect on the products distribution. The total conver-
sion rate and the selectivity of the reaction were in agreement
with the electrophilicity of the alkenes (enal or enone > acrolein
dimethyl acetal > allyl bromide or allyl alcohol) (Table 2, entries
5
–10). However, crotonaldehyde resulted in poor total conversion
rate and selectivity, which probably resulted from the steric
6
hindrance of the CH group. The reaction with acrolein dimethyl
tion of 3a (Scheme 2, path a). First, transhalopalladation of
3
acetal afforded a mixture, because acrolein dimethyl acetal and
acetylene lead to the (E)-vinylpalladium intermediate 5, which
was inserted by a second molecule of acetylene to form (E,Z)-
dienylpalladium 6. Aer the insertion of acrolein, (2-oxoalkyl)
palladium intermediate 7 underwent protonolysis (path a) to
afford 3a. We suggest an explanation of the formation of 4a
based on the path a (Scheme 2, path b). (E)-Vinylpalladium
intermediate 5 could react with acrolein to give (2-oxoalkyl)
palladium intermediate 8, which underwent protonolysis to
afford 4a. The crucial factors that decided which path to go were
the acetylene pressure and the acrolein concentration. At a xed
the products 3g and 4g were partially hydrolyzed by acetic acid.
The reaction with allyl bromide gave 3h and 4h aer 12 h reac-
tion, as did the corresponding reaction with allyl alcohol resulting
in 3j and 4j, but these chemicals were completely converted into
3i and 4i aer 24 h reaction. These results could be explained by
the fact that both Br and OH groups were good leaving groups,
7
supporting a b-heteroatom elimination.
Both pheromone components of the cocoa pod borer moth
were synthesized by an efficient and stereoselective route
a
Table 1 Optimization of Pd(II)-catalyzed coupling reaction of lithium bromide, acetylene, and acrolein
Yield (%)
ꢀ1
ꢁ
Entry
HOAc/H
2
O (mol mol
)
Reaction time (h)
Temp. ( C)
Acetylene pressure (atm)
3a
4a
1
2
3
4
5
6
7
8
9
4.5/3
3/2
24
24
24
24
24
48
72
72
72
5
5
5
25
45
25
25
25
25
1
1
1
1
1
1
1
0.8
1.2
16
18
15
21
35
38
31
59
73
70
73
1.5/1
1.5/1
1.5/1
1.5/1
1.5/1
1.5/1
1.5/1
3.2
1.0
0.8
1.2
1.3
0.5
3.3
a
2
Pd(OAc) (1 mmol), LiBr (1 mol), and acrolein (1.2 mol).
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Table 2 Pd(II)-catalyzed coupling reaction of halides, acetylene, and
a
electron-deficient alkenes
Entry MX
R
1
R
2
E
Product (yield, %)
Scheme 4 Synthetic route of the target compounds. Reagents and
ꢁ
conditions: (a) NaBH
Et
d) LiAlH
4
, CH
3
OH, 0 C, 3 h; (b) alkyne 7, Pd(PPh
3
)
4
, CuI,
1
2
3
4
5
6
7
8
n-Bu
4
NBr
NCl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH
H
CHO
CHO
CHO
CHO
COCH
COC
CHO
CH(OMe)
3a (2.6)
3b (2.8)
3b (0.9)
3c (2.2)
3d (2.3)
3e (2.4)
3f (1.1)
3a (7.6)
4a (71)
2
NH, rt, 12 h; (c) Zn, 1,2-dibromoethane, LiBr, CuBr, EtOH, reflux, 4 h;
, diglyme, reflux, 24 h.
n-Bu
LiCl
LiI
LiBr
LiBr
LiBr
LiBr
4
4b (73)
4b (69)
4c (25)
4d (56)
4e (65)
4f (68)
4a (21)
4g (19)
4h (traces)
4i (9.5)
(
4
3
Enal 11 was prepared by oxidation of enol 10 using pyridinium
2
H
5
9
b
3
chlorochromate in dichloromethane in 86% yield. The alde-
hydic carbonyl group was converted into the carbon–carbon
triple bond via the standard Corey–Fuchs protocol. Enal 11
reacted with carbon tetrabromide and triphenylphosphine in
2
3
g (6.8)
3h (traces)
i (12)
9
LiBr
H
H
CH
2
Br
3
10
dichloromethane to afford dibromoolen 12 in 87% yield.
Subsequently, dibromoolen 12 was converted cleanly and
rapidly into enyne 13 in 91% yield by treatment with 2 equiva-
lents of n-butyllithium followed by aqueous work-up.
1
0
1
LiBr
LiBr
H
H
H
CH
2
OH
3j (traces)
i (15)
3k (8.3)
4j (traces)
4i (12)
4k (14)
3
10
1
CH
3
CHO
On the other hand, reduction of enal 4a to enol 14 was ach-
(1 mmol), halides (1 mol), and electron-decient alkenes (1.2 ieved in 86% yield by treatment with an excess of sodium boro-
a
Pd(OAc)
2
ꢁ
mol), HOAc (1.5 mol), H
2 h.
2
O (1 mol), acetylene pressure (0.8 atm), 25 C,
hydride in methanol, without affecting the double bonds. The
Sonogashira coupling of enol 14 with enyne 13 using Pd(PPh as
catalyst in dry diethylamine at room temperature gave enynol 15
7
3 4
)
11
in 83% yield. The Sonogashira coupling maintained the excel-
lent isomeric purity owing to the moderate conditions used.
Enynol 15 was hydrogenated using Zn to form trienol 1a in 82%
(Schemes 3 and 4). Preparation of the key intermediate 13
involved the following ve steps. Hydration of 2,3-dihydrofuran
in wet acid according to our improved method based on the
literature to afforded 4-hydroxybutanal (9b) in 84% yield.
Construction of the 10Z-double bond relied on Wittig reaction.
To ensure the cis selectivity of the Wittig olenation, potassium
bis(trimethylsilyl) amide was selected as the base. The ylide was
12
yield and with a high isomeric purity (>98%, GC). The reduction
of enynol 15 with LiAlH provided the corresponding trienol 2a in
4% yield and with a high isomeric purity (>98%, GC).
8
4
13
7
prepared from n-hexyltriphenylphosphonium bromide by Conclusions
treatment with potassium bis(trimethylsilyl) amide in dry THF
ꢁ
In conclusion, preparation of (E)-5-bromopent-4-enal (4a) was
optimized. (4E,6Z,10Z)-Hexadeca-4,6,10-trien-1-ol (1a) and
at ꢀ78 C. Subsequently, the ylide reacted with aldehyde 9b to
9
afford enol 10 in 78% yield and with 98% isomeric purity (GC).
(4E,6E,10Z)-hexadeca-4,6,10-trien-1-ol (2a) were prepared ster-
eoselectively in 8 steps starting from commercially available
materials with an overall yield of 30.4% and 27.4%, respectively.
The stereoselective formation of (E,Z)- or (E,E)-conjugated
double bond relied on the Sonogashira coupling with (E)-5-
bromopent-4-en-1-ol (14) prepared from 4a and stereoselective
hydrogenation of (Z)-undec-5-en-1-yne (13), while the 10Z-
double bond was formed by the Wittig reaction of 4-hydrox-
ybutanal and n-hexyltriphenylphosphonium bromide. (E)-5-
Bromopent-4-enal (4a) may be used in biologically active natural
products including insect pheromones.
Experimental
General
Scheme 3 Synthetic route of key intermediate 13. Reagents and
conditions: (a) HCl/H
bromide, KN[Si(Me)
h; (d) PPh , CBr , CH
2
O, rt, 5 h; (b) n-hexyltriphenylphosphonium
ꢁ
All reagents used in reactions were obtained commercially in
, 0 C, rt, 12 h; (e) n-BuLi, THF, ꢀ50 C, 2 h. China. All anhydrous solvents were dried and puried by
3
]
2
, THF, ꢀ78 C, 12 h; (c) PCC/Celite, CH
2
ꢁ
2
Cl , rt,
ꢁ
5
3
4
2
Cl
2
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standard techniques just before use. All nonaqueous reactions solution of aldehyde 9b (17.6 g, 0.2 mol) in dry THF (200 mL)
were performed under an inert atmosphere (nitrogen) with rigid was added dropwise to the above mixture over 1 h, maintaining
ꢁ
exclusion of moisture from reagents, and all reaction vessels the temperature below ꢀ70 C. The resulting yellow solution
1
were oven dried. H NMR spectra were recorded on Bruker- was allowed to slowly warm up to room temperature over
Ascend 400 spectrometer at 400 MHz. Chemical shis are re- a period of 10 h. Then the reaction mixture was quenched with
ported in parts per million (ppm) relative to TMS. Data are re- a saturated solution of NH
ported as follows: chemical shi, multiplicity (s ¼ singlet, d ¼ THF, the reaction mixture was extracted with EtOAc (300 mL ꢂ
doublet, t ¼ triplet, q ¼ quartet), coupling constants, and 3). The extract was washed with H O and brine, dried over
, and then concentrated. The residue was puried
4
Cl. Aer the complete evaporation of
2
1
3
2 4
integration. C NMR were recorded on Bruker-Ascend 400 Na SO
spectrometer at 100 MHz. Chemical shis are reported in parts through a silica gel column (eluent: 10 : 1 petroleum ether/ethyl
1
per million measured relative to TMS. In preparation of (E)-5- acetate) to afford enol 10 as a colorless oil (24.3 g, 78%). H NMR
bromopent-4-enal (4a), some reaction conditions may be (400 MHz, CDCl ) (d, ppm): 5.45–5.37 (m, 2H, Z–CH]CH), 3.67
3
different from those cited in the text (small scale) since they (t, J ¼ 6.42 Hz, 2H, CH
have been chosen for large scale reactions. 2H, ]CHCH ), 1.65 (m, 2H, CH
.91 (t, 3H, J ¼ 7.5 Hz, –CH
ppm): 131.2, 129.2, 62.9, 33.0, 32.2, 30.1, 27.6, 24.0, 23.1, 14.5.
2
OH), 2.14 (m, 2H, ]CHCH
2
), 2.06 (m,
–),
3 3
); C NMR (100 MHz, CDCl ) (d,
2
2
3
), 1.40–1.29 (m, 6H, –CH
2
1
0
(
E)-5-Bromopent-4-enal (4a)
Acetylene (passed through concentrated sulfuric acid) was
tardily passed through a mixture of Pd(OAc) (1122 mg, 5
mmol), LiBr (261 g, 3 mol), and acrolein (168 g, 3 mol) in HOAc Enol 10 (15.6 g, 0.1 mol) was stirred at room temperature for 5 h
500 mL) and H O (100 mL) at room temperature for 72 h. The with a slurry of pyridinium chlorochromate (32.3 g, 0.15 mol)
reaction mixture was poured into a saturated aqueous solution and Celite (32.3 g) in CH Cl (200 mL). The mixture was then
(
Z)-Dec-4-enal (11)
2
(
2
2
2
of Na CO and then extracted with CH Cl (500 mL ꢂ 3). The diluted with CH Cl and ltered through Celite. The lter cake
2
3
2
2
2
2
extract was washed with water, dried over Na SO , and then was washed with CH Cl (200 mL ꢂ 2). The extract was washed
2
4
2
2
2 4
concentrated by evaporation. The residue was puried through with water, dried over Na SO , and then concentrated. The
a silica gel column (eluent: 20 : 1 petroleum ether/ethyl acetate) residue was puried through a silica-gel column (eluent: 25 : 1
to afford enal 4a as a colorless oil (337 g, 69%, isomeric purity > petroleum ether/ethyl acetate) to afford enal 11 as a colorless oil
1
1
9
9%, GC). H NMR (300 MHz, CDCl
3
) (d, ppm): 9.76 (s, 1H, (13.3 g, 86%). H NMR (400 MHz, CDCl
), 2.44 1H, Z–CH]CH), 5.35 (m, 1H, Z–CH]CH), 2.51 (m, 2H,
m, 2H, CH2); C NMR (75 MHz, CDCl ) (d, ppm): 202.1, 131.5, CH CHO), 2.39 (m, 2H, CH CH CHO), 2.06 (m, 2H, ]CHCH –),
3
) (d, ppm): 9.79, 5.46 (m,
CHO), 6.15–6.12 (m, 2H, CH]CH), 2.55–2.50 (m, 2H, CH
2
1
3
(
1
9
3
2
2
2
2
13
+
30.8, 42.9, 21.3; EI-MS (m/z): 164/162 (M ), 121/119, 108/106, 1.40–1.29 (m, 6H, –CH –), 0.91 (t, 3H, J ¼ 7.5 Hz, –CH );
C
2
3
5/93, 83, 65, 55.
NMR (100 MHz, CDCl ) (d, ppm): 202.7, 132.1, 127.4, 44.2, 31.9,
3
29.6, 27.6, 23.0, 20.5, 14.5.
4-Hydroxybutanal (9b)
(
Z)-1,1-Dibromoundeca-1,5-diene (12)
Aer adding concentrated hydrochloric acid (2.0 g, 20 mmol)
and H O (10.8 g, 0.6 mol) to CH Cl (600 mL), 2,3-dihydrofuran A solution of enal 11 (10.8 g, 80 mmol) in CH Cl (240 mL) was
2
2
2
2
2
ꢁ
(
28 g, 0.4 mol) was added to the mixture. The resulting mixture cooled to 0 C and triphenylphosphine (63 g, 240 mmol) was
was stirred for 5 h at room temperature, neutralized with added to the reaction mixture. A solution of carbon tetra-
Na CO , dried over Na SO , and then concentrated to afford 4- bromide (39.8 g, 120 mmol) in CH Cl (120 mL) was added
2
3
2
4
2
2
hydroxybutanal (9b) as a colorless oil (29.6 g, 84%). The product dropwise, then the reaction mixture was allowed to warm up
was directly used for the Wittig reaction without further puri- slowly to room temperature, and stirred overnight. Aer
1

cation. Tetrahydrofuran-2-ol (9a): H NMR (CDCl , 400 MHz) removal of CH Cl by evaporation, petroleum ether (200 mL ꢂ
3
2
2
(
2
d, ppm): 5.55–5.50 (m, 1H, CHOH), 3.95–3.81 (m, 2H, OCH ), 2) was added to precipitate triphenylphosphine oxide. The
2
1
3
.09–2.01 (m, 1H, CH ), 2.0–1.8 (m, 3H, CH CH ); C NMR mixture was ltered and the solvent was removed. The residue
2 2 2
(
2
3
CDCl , 100 MHz) (d, ppm): 100.3/98.6, 67.6/67.4, 33.5/32.6, was puried through a silica gel column (eluent: petroleum
1
1
3.8. 4-Hydroxybutanal (9b): H NMR (CDCl
3
, 400 MHz) (d, ether) to afford diene 12 (21.6 g, 87%) as a colorless oil. H NMR
OH), 2.51–2.48 (400 MHz, CDCl ),
) (d, ppm): 6.44 (t, J ¼ 6.83 Hz, 1H, CH]CBr
); C NMR (CDCl , 100 5.49 (m, 1H, Z–CH]CH), 5.37 (m, 1H, Z–CH]CH), 2.23–2.19
ppm): 9.75 (s, 1H, CHO), 3.70–3.64 (m, 2H, CH
2
3
2
1
3
(
m, 2H, CH
MHz) (d, ppm): 203.0, 66.4, 41.4, 23.0; EI-MS (m/z): 87.0 (M ꢀ 1), (m, 4H, ]CH–CH
1.1.
2
CHO), 2.0–1.8 (m, 2H, CH
2
3
+
2
2 2
CH –CH]), 2.06 (m, 2H, ]CHCH –), 1.43–
1
3
7
1.32 (m, 6H, –CH –), 0.92 (t, 3H, J ¼ 7.5 Hz, –CH ); C NMR (100
2
3
MHz, CDCl ) (d, ppm): 138.6, 132.1, 127.9, 89.32, 33.5, 31.9,
3
(
Z)-Dec-4-en-1-ol (10)
29.9, 27.6, 25.9, 23.0, 14.5.
Potassium bis(trimethylsiyl)amide (300 mL, 0.3 mol, 1 M in
THF) was added dropwise over 30 min to a suspension of n-
(
Z)-Undec-5-en-1-yne (13)
hexylphosphonium bromide (128 g, 0.3 mol) in dry THF (600 A solution of diene 12 (15.5 g, 50 mmol) in dry THF (200 mL) was
ꢁ
ꢁ
mL) at 0 C under nitrogen. The resulting orange solution was cooled to ꢀ70 C under nitrogen. Aer a solution of n-BuLi (44
ꢁ
ꢁ
further stirred for 1 h at 0 C and then cooled to ꢀ78 C. A mL, 110 mmol, 2.5 M solution in hexane) was slowly added to
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ꢁ
the reaction mixture, the mixture was stirred at ꢀ70 C for 2 h reaction mixture was reuxed for 4 h and then quenched with
and then allowed to warm up to room temperature. The reaction a saturated solution of NH Cl. The organic phase was washed
4
mixture was quenched with a saturated solution of NH Cl, and with brine, dried over Na SO , and concentrated. The residue
4
2
4
the organic phase was washed with brine, dried over Na SO , was puried through a silica-gel column (eluent: 8 : 1 petroleum
2
4
and then concentrated. The residue was puried through ether/ethyl acetate) to afford trienol 1a as a colorless oil (981 mg,
1
a silica gel column (eluent: petroleum ether) to afford enyne 13 82%). H NMR (400 MHz, CDCl
3
) (d, ppm): 6.30 (ddd, 1H, J ¼
) (d, 15.0, 11.0, 1.0 Hz, CH]CH), 5.95 (dd, 1H, J ¼ 11.0, 10.7 Hz,
ppm): 5.53–5.42 (m, 2H, Z–CH]CH), 2.34–2.25 (m, 4H, ]CH– CH]CH), 5.62 (dt, 1H, J ¼ 15.0, 7.5 Hz, CH]CH), 5.26–5.43 (m,
CH CH –C^), 2.08 (m, 2H, ]CHCH OH), 2.19 (m, 4H, ]
–), 2.00 (s, 1H, ^CH), 3H, CH]CH), 3.61 (t, 2H, J ¼ 6.5 Hz, CH
CH–CH CH –C]), 2.14 (m, 2H, CH ), 2.05 (m, 2H, CH ), 1.66
1
as a colorless oil (6.83 g, 91%). H NMR (400 MHz, CDCl
3
2
2
2
2
1
3
1
.41–1.30 (m, 6H, –CH –), 0.93 (t, 3H, J ¼ 7.5 Hz, –CH );
C
2
3
2
2
2
2
NMR (100 MHz, CDCl ) (d, ppm): 132.1, 127.8, 84.6, 68.7, 31.9, (m, 2H, CH ), 1.18–1.40 (m, 6H, –CH –), 0.90 (t, 3H, J ¼ 7.3 Hz,
3
2
2
1
3
29.8, 27.7, 26.8, 23.0, 19.3, 14.5.
–CH ); C NMR (100 MHz, CDCl ) (d, ppm): 134.5, 131.5, 129.9,
3 3
129.2, 128.9, 126.4, 62.8, 32.5, 31.8, 29.7, 29.5, 27.9, 27.5, 27.2,
(
E)-5-Bromopent-4-en-1-ol (14)
23.0, 14.4.
A solution of enal 4a (16.3 g, 100 mmol) and sodium borohy-
dride (2.27 g, 60 mmol) in methanol (500 mL) was stirred for 3 h (4E,6E,10Z)-Hexadeca-4,6,10-trien-1-ol (2a)
ꢁ
at 0 C. The reaction mixture was quenched with diluted HCl
Lithium tetrahydroaluminate (950 mg, 25 mmol) was added in
followed by evaporation of methanol. The reaction mixture was
portions to an ice-cooled mixture of dry diglyme (12 mL) and
THF (1.5 mL) under nitrogen atmosphere. When the vigorous
foaming had subsided, the solution of enynol 15 (1172 mg, 5
mmol) in diglyme (3 mL) was added to the thick slurry.
Following the initial foaming, the reaction mixture was heated
then extracted with EtOAc (100 mL ꢂ 2). The extract was washed
2 4
with water and brine, dried over Na SO , and then concen-
trated. The residue was puried through a silica-gel column
eluent: 8 : 1 petroleum ether/ethyl acetate) to afford enol 14 as
a colorless oil (14.2 g, 86%). H NMR (400 MHz, CDCl ) (d, ppm):
.76 (s, 1H, CHO), 6.15–6.12 (m, 2H, CH]CH), 2.55–2.50 (m,
2 2 3
H, CH ), 2.44 (m, 2H, CH ); C NMR (100 MHz, CDCl ) (d,
ppm): 202.1, 131.5, 130.8, 42.9, 21.3.
4E,10Z)-Hexadeca-4,10-dien-6-yn-1-ol (15)
(
1
3
ꢁ
ꢁ
at 117–121 C for 24 h. The mixture was cooled to 0 C and
petroleum ether (100 mL) was added followed by a cautious and
dropwise addition of water (2 mL). Then, 20% (w/w) NaOH
9
2
1
3
solution (1.6 mL) and H O (8 mL) were added to the reaction
2
mixture. The mixture was stirred for 15 min to allow the
precipitate to granulate, then the petroleum ether layer was
(
A solution enol 14 (3.3 g, 20 mmol) and enyne 13 (3.0 g, 20 decanted, and the solid residue was rinsed with petroleum ether
mmol) in dry diethylamine (40 mL) was degassed with a stream (50 mL ꢂ 3). The combined organic phases were washed with
of nitrogen for 20 min. Aer subsequent addition of Pd(PPh
3
)
4
2 4
water and brine, dried over Na SO , and then concentrated. The
(
1155 mg, 1 mmol) and CuI (209 mg, 1.1 mmol), the reaction residue was puried through a silica-gel column (eluent: 8 : 1
mixture was degassed for an additional 10 min. The reaction petroleum ether/ethyl acetate) to afford trienol 2a as a colorless
1
mixture was stirred overnight and ltered through Celite. The oil (875 mg, 74%). H NMR (400 MHz, CDCl
) (d, ppm): 5.98–6.07
3

lter cake was washed with CH Cl (50 mL ꢂ 2). Aer concen- (m, 2H, E–CH]CH), 5.53–5.63 (m, 2H, E–CH]CH), 5.45–5.37 (m,
2
2
tration of the combined organic phase, the residue was puried 2H, Z–CH]CH), 3.60 (t, 2H, J ¼ 6.5 Hz, CH
through a silica-gel column (eluent: 10 : 1 petroleum ether/ethyl CH–CH CH –C]), 2.15 (m, 2H, CH ), 2.04 (m, 2H, CH
), 1.18–1.40 (m, 6H, –CH
–), 0.90 (t, 3H, J ¼ 7.3 Hz, –CH
C NMR (100 MHz, CDCl ) (d, ppm): 132.3, 131.7, 131.5, 130.2,
), 5.51 (d, 1H, J ¼ 16.0 Hz, ^CH]CH), 129.3, 126.7, 62.7, 32.8, 32.1, 31.6, 29.6, 29.4, 27.7, 27.3, 23.0, 14.3.
.48–5.40 (m, 2H, Z–CH]CH), 3.66 (t, 2H, J ¼ 6.4 Hz), 2.34–2.27
OH), 2.21 (m, 4H, ]
), 1.66 (m,
);
2
2
2
2
2
1
acetate) to afford enynol 15 as a colorless oil (3.89 g, 83%). H 2H, CH
2
2
3
1
3
NMR (400 MHz, CDCl
3
) (d, ppm): 6.07 (td, 1H, J ¼ 7.05 Hz, J ¼
3
1
5
(
(
6.0 Hz, CH]CH–CH
2
m, 4H, ]CH–CH CH –C^), 2.22–2.17 (m, 2H, CH ), 2.08–2.03
2 2 2
Acknowledgements
m, 2H, CH ), 1.70–1.61 (m, 2H, CH ), 1.40–1.31 (m, 6H, –CH –),
2
2
2
1
3
0
.91 (t, 3H, J ¼ 7.4 Hz, –CH
3
); C NMR (100 MHz, CDCl
3
) (d,
This work was nancially supported by the National Natural
Science Foundation of China (No. 21362018 and 81460525), the
Yunnan Applied Basic Research Project (No. 2014FB117), and
the Science and Technology Foundation of Yunnan University
ppm): 142.8, 131.9, 128.1, 110.9, 89.0, 79.5, 62.5, 32.1, 31.9, 29.8,
2
9.6, 27.7, 27.1, 23.0, 20.2, 14.5.
(
4E,6Z,10Z)-Hexadeca-4,6,10-trien-1-ol (1a)
(No. 2011YB12).
A mixture of Zn powder (13.8 g, 200 mmol) and 1,2-dibromo-
ethane (1.88 g, 10 mmol) in ethanol (20 mL) was heated until
a vigorous reaction occurred. The mixture was again treated
Notes and references
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1 P. S. Beevor, A. Cork, D. R. Hall, B. F. Nesbitt, R. K. Day and
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ꢁ
10 min. The mixture was then cooled to 50 C followed by
addition of a mixture of LiBr (4.34 g, 50 mmol) and CuBr (2.87 g,
0 mmol) in THF (10 mL) within 3 min. Aer addition of
a solution of enynol 15 (1172 mg, 5 mmol) in THF (10 mL), the
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M. J. Mamat, Management of the Cocoa Pod Borer, The
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2
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