Pd-catalyzed regio and stereocontrolled mono and bis-coupling reactions of 1-bromo-6-chlorohexa-1,3,5-triene: synthesis of a naturally occurring tetraenynone

Article abstract of DOI:10.1016/j.tet.2009.01.037

The synthesis of new 1,6-dihalogenohexatrienes is described. The chemoselectivity of pallado-catalyzed cross-coupling reaction is studied and a short synthesis, by Negishi and Sonogashira reactions, of a natural product is described.

Full text of DOI:10.1016/j.tet.2009.01.037

Tetrahedron 65 (2009) 1967–1970
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Tetrahedron
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Pd-catalyzed regio and stereocontrolled mono and bis-coupling
reactions of 1-bromo-6-chlorohexa-1,3,5-triene: synthesis of a
naturally occurring tetraenynone
*
´ ˆ
´
´
Wissam Bentoumi, Jerome Helhaik, Gerard Ple, Yvan Ramondenc
Universite´ et INSA de Rouen, CNRS, UMR 6014 C.O.B.R.A.-IRCOF, 1 rue Tesnie`re, 76821 Mont Saint-Aignan Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of new 1,6-dihalogenohexatrienes is described. The chemoselectivity of pallado-catalyzed
cross-coupling reaction is studied and a short synthesis, by Negishi and Sonogashira reactions, of
a natural product is described.
Received 24 October 2008
Received in revised form 6 January 2009
Accepted 7 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 14 January 2009
1. Introduction
co-workers6 have used reagents for preparing fluorescent trans-
membrane probes of lipid bilayers. Other 1,6-bis-stannylated
Numerous natural products, with generally interesting biological
properties, have in their structure a stereodefined polyenic conju-
gated chain.1 For example, we can quote the large variety of all-trans
heptatrienamides containing acetylenic linkages, isolated from
plants of the Asteraceae family, and which have shown insecticidal
and physiological properties;2 Scyphostatine, extracted from the
mycelium of Dasyscyphus mollissimus, which inhibits the activity of
the enzyme sphingomylinase, is responsible of the formation of
ceramides at the human ones3 or Ansatrienine A, an antibiotic mac-
rolide, whichpossessantibacterial,antifungalorantitumouractivity.4
To synthesize polyenic systems, many strategies have been de-
veloped: for example, Wittig and Horner–Wadsworth–Emmons
olefinations or Mac Murry olefination. However, the control of the
stereochemistry of each formed double bond remains a challenge.
One of the challenges today in this area is to design and develop
systems have been developed by Bru¨ckner7 and more recently
hetero-bis-metalated by Coleman.8
During our work on the 1,6-dibromohexa-1,3,5-triene, we have
shown that the monocoupling reactions on stereomer (E,E,E) were
not selective and were accompanied by a significant quantity of
dicoupled product.9 To correct this lack of selectivity, we decided to
develop a new non-symmetrical dihalogenated reagent having one
atom of bromine and one atom of chlorine. This difference has
allowed us to increase chemoselectivity, especially in pallado-cat-
alyzed cross-coupling reaction.
Aftera studyof thesecoupling reactions,we have developed arapid
synthesis of a natural compound, the (6E,8E,10E)-heptadeca-1,6,8,10-
tetraen-4-yn-3-one, owning stimulating and diuretic properties. This
compound is contained in severalplants of the Ombellifer familyas the
common falcaire10 (falcaria vulgaris) and several species of seseli.11
Ph3P+CH2Cl, Cl-
Cl
tBuOK
Br
O
Br
+
Cl
Br
THF, -78 °C
90 min at 20 °C
1a
1b
67%
55 : 45
Scheme 1.
new synthons allowing access to those trienic compounds with
excellent stereoselectivity. In 1994, our team5 has described the
2. Results and discussion
u
,u
0-dibromo-1,3,5-hexatriene. This reagent, by double Negishi
2.1. Synthesis and reactivity of the 1-bromo-6-
chlorohexatriene
cross-coupling reaction, has given product with retention config-
uration of every double bond. In 2003, Amat-Guerri and
1-Bromo-6-chlorohexa-1,3,5-triene
1
has been prepared
according to a Wittig reaction with the (2E,4E)-5-bromopenta-2,4-
dienal.12 It was obtained as a mixture of 1E,3E,5E 1a and 1E,3E,5Z 1b
stereomers in similar proportions with 67% yield (Scheme 1).
* Corresponding author. Tel.: þ33 235 522 449; fax: þ33 235 522 962.
E-mail address: yvan.ramondenc@univ-rouen.fr (Y. Ramondenc).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.037

1968
W. Bentoumi et al. / Tetrahedron 65 (2009) 1967–1970
Pd(PPh3)4
THF, 25 °C
chemoselective pallado-catalyzed coupling reactions. In the first
Br
R
+
RMCl
Cl
Cl
step, the alkyl chain is introduced according to a selective
monopallado-catalyzed coupling reaction (Negishi coupling re-
action), on the bromine atom. Then, the acetylenic part is inserted
on the chloro trienic system according to a Sonogashira coupling
reaction (Scheme 3). To our knowledge, only one synthesis of
compound 8 has been described in the literature. In 1966, Bohl-
mann and co-workers10 have reported their synthesis, performed
in five steps with an overall yield of 22%.
Access to hexylchlorotriene 4 is done according to a Negishi
coupling reaction by a quick addition of an excess of organozinc
reagent on bromochlorohexatriene 1a, with a catalytic quantity of
tetrakistriphenylphosphine palladium complex in THF at room
temperature. Hexylchlorotriene 4 was obtained after purification
by flash chromatography in 85% yield.
1
2
3
R = n-Pent, M = Zn, R = Ph, M = Zn or Mg
Scheme 2.
After separation by chromatography, they are purified by sub-
limation. To study the chemoselectivity of pallado-catalyzed cross-
coupling reactions, depending on the nature of the halogen,
1-bromo-6-chlorohexa-1,3,5-triene 1 was involved in coupling re-
actions with an excess of pentyl- and phenylzinc chloride 2a and 2b
or phenylmagnesium bromide 2c (Scheme 2).
In all cases, we observed exclusively a monocoupling reaction on
the bromide atom. We never observed any product resulting from
Table 1
Monocoupling reaction results from 1 and organometallic reagent via Scheme 2
Entry
1-Bromo-6-
chlorohexatriene
Organometallic
reagent
Single coupled
1H NMR, J (Hz)
product: yielda (%)
1
2
3
4
5
6
1a
1a
1a
1b
1b
1b
2a: n-PentZnCl
2b: PhZnCl
2c: PhMgCl
2a: n-PentZnCl
2b: PhZnCl
3aa: 63
3ab: 43
3ab: 54
3ba: 45
3bb: 54
3bb: 62
J1–2¼13.1; J5–6¼14.6
J1–2¼13.2; J3–4¼14.7; J5–6¼15.8
J1–2¼6.5; J3–4¼15.1; J5–6¼13.0
J1–2¼7.2; J3–4¼15.1; J5–6¼15.8
2c: PhMgCl
a
Yield after purification.
a coupling reaction on the chlorine atom. These coupling reactions
between bromochlorohexatrienes 1 and organozinc chlorides 2a,
2b and phenylmagnesium bromide (2c) are chemoselective and
provide exclusively monocoupled products 3, under friendly con-
ditions, with acceptable yields. These coupling reactions occurred
with a total retention of configuration whatever the starting isomer
of 1 (for 3aa and 3ab: we observed by 1H NMR the following values
J1–2¼13.1 and 13.2 Hz and J5–6¼14.6 and 15.8 Hz; for 3ba and 3bb,
similarly J1–2¼6.5 and 7.2 Hz and J5–6¼13.0 and 15.8 Hz, Table 1).
Sonogashira13 coupling reaction of hexylchlorotriene 4 with the
trimethylsilylacetylene, under Linstrumelle and Alami14 conditions,
gives compound 5 in 80% yield. Under classic conditions of
deprotection (potassium carbonate in methanol), alkyne 6 is iso-
lated. Then, alcohol 7, precursor of the natural compound 8, is
obtained by condensation of lithium acetylide with acrolein. In the
last step, the MnO2 oxidation of alcohol 7 gives the natural product
8 (Scheme 4).
3. Conclusion
2.2. Synthesis of a natural product
In this paper, we report the first synthesis of a new dihalo-
genated conjugated trienic system, 1-bromo-6-chlorotriene 1. This
reagent has been used in pallado-catalyzed cross-coupling
reactions with organozinc or organomagnesium compounds and
has shown a total chemoselectivity. In application, we have
performed an original and rapid synthesis of a natural compound,
the (6E,8E,10E)-heptadeca-1,6,8,10-tetraen-4-yn-3-one. The conju-
gated trienic system has been introduced in a one-step procedure
and the chemoselectivity of the coupling reactions has permitted to
introduce successively the alkyl and then the alkyne groups. This
synthesis was realized in a five-step procedure, with an overall
yield of 43%.
The originality of our synthesis lies in the introduction of the
(E,E,E) trienic system in a one-step procedure, using the in-
termediate (1E,3E,5E)-1-bromo-6-chlorohexa-1,3,5-triene (1a), via
O
Negishi
coupling
Br
Cl
Sonogashira
coupling
Scheme 3.
SiMe3
Cl
H
SiMe3
(a)
Cl
Br
(b)
5
1a
4
(c)
O
OH
H
(e)
(d)
6
7
8
Scheme 4. (a) C6H13ZnCl, Pd(PPh3)4 (6%), THF, 30 min, rt, 85%; (b) Pd(PhCN)2Cl2 (6%), CuI (10%), piperidine, 80%; (c) K2CO3, MeOH, 90%; (d) BuLi (1 equiv), THF, 90 min, 0 ꢀC at rt;
addition of acrolein at ꢁ78 ꢀC, 67%; (e) MnO2, THF, 94%.

W. Bentoumi et al. / Tetrahedron 65 (2009) 1967–1970
1969
4. Experimental
4.1. General
4.4. Coupling reaction
To a solution of triene 1 (400.00 mg, 2.07 mmol) and Pd(PPh3)4
(143.00 mg, 0.12 mmol) in anhydrous THF (10 mL) under an argon
atmosphere was added the alkylzinc chloride 2 solution previously
prepared. The resulting mixture was stirred for 30 min at 25 ꢀC and
then with a solution of NaHCO3 (5%) and extracted three times with
diethyl ether. The combined organic layers were dried over MgSO4
and concentrated under vacuum. The crude product was purified
by column chromatography (SiO2, pentane) to give chlorotriene 3
(349.00 mg, 1.75 mmol).
Melting points were determined on a Reichert-Jung micro-
scope apparatus. The 1H and 13C NMR spectra were recorded on
a Bruker AC 300 (300 MHz 1H, 75 MHz 13C) instrument. CDCl3 or
C6D6 was used as solvent. Microanalyses were performed on
a
Carlo Erba CHNOS 1160 apparatus. The IR spectra were
obtained as potassium bromide pellets with a Perkin Elmer
Paragon 500 spectrometer. Absorption bands are given in cmꢁ1
.
Mass spectra were recorded with a Jeol JMS-AX500 spectrometer
or an ATI Unicam Automass, under electron impact conditions
(EI) at 70 eV ionizing potential, fitted (or not) with a GC-mass
coupling.
4.4.1. (1E,3E,5E)-1-Chloroundeca-1,3,5-triene (3aa)
1H NMR (CDCl3)
d
0.85 (t, 3H, J¼7.0 Hz, H11), 1.20 at 1.50 (m, 6H,
H
10, H9, H8), 2.05 (dt, 2H, J7–6¼6.8 Hz and J7–8¼7.1 Hz, H7), 5.74 (dt,
1H, J6–5¼15.1 Hz and J6–7¼6.8 Hz, H6), 6.01 (m, 2H, H3 and H4), 6.11
(d, 1H, J1–2¼13.5 Hz, H1), 6.18 (dd, 1H, J5–6¼14.6 Hz and J5–4¼9.6 Hz,
H5), 6.33 (dd, 1H, J2–3¼10.5 Hz and J2–1¼13.1 Hz, H2).
4.2. 1-Bromo-6-chlorohexa-1,3,5-triene (1)
To a solution of chloromethyltriphenylphosphonium chloride
(2.76 g, 10.00 mmol) in THF (50 mL) at ꢁ78 ꢀC under an argon at-
mosphere was slowly added t-BuOK (1.24 g, 11.00 mmol) in THF
(6 mL). After 1 h stirring at ꢁ78 ꢀC, (2E,4E)-5-bromopentadienal
(1.16 g, 7.20 mmol) in THF (6 mL) was slowly added. The mixture
was stirred at room temperature for 1 h 30 min and the reaction
mixture was quenched with a 5% aqueous solution of NaHCO3
(20 mL). The organic layer was extracted with pentane and then
dried over anhydrous MgSO4 and concentrated by rotary evapora-
tion. The brown residue was washed with pentane (6ꢂ5 mL) to
remove triphenylphosphine oxide and the crude product was fur-
ther purified by silica gel column chromatography (pentane/Et2O:
98/2) to give (0.93 g, 4.80 mmol) a mixture of two isomers 1a and
1b in the same ratio. Yield 67%.
4.4.2. (1Z,3E,5E)-1-Chloroundeca-1,3,5-triene (3ba)
1H NMR (C6D6)
d
0.80 (t, 3H, J¼7.0 Hz, H11), 1.07 at 1.30 (m, 6H,
H
10, H9, H8), 1.83 (dt, 2H, J7–6¼6.8 Hz and J7–8¼7.1 Hz, H7), 5.52 (d,
1H, J1–2¼6.5 Hz, H1), 5.52 (dt, 1H, J6–5¼13.0 Hz and J6–7¼6.8 Hz, H6),
5.87 (m, 2H, H2 and H5), 6.03 (dd, 1H, J3–2¼10.1 Hz and J3–4¼15.1 Hz,
H3), 6.56 (dd, 1H, J4–3¼14.7 Hz and J4–5¼10.5 Hz, H4). 13C NMR
(C6D6):
d
14.4 (C11), 23.0 (CH2), 29.3 (CH2), 31.8 (CH2), 33.2 (CH2),
117.7 (CH), 124.2 (CH), 130.4 (CH), 130.9 (CH), 136.8 (CH), 137.9 (CH).
ꢃ
ꢃ
MS (EI) m/z: 184–186 (Mþ , 22%, 8%), 91 (84%), 77 (C6Hþ5 , 100%).
4.4.3. (1E,3E,5E)-1-Chloro-6-phenylhexa-1,3,5-triene (3ab)
1H NMR (C6D6)
d
5.89 (dd, 1H, J¼10.2 and 15.8 Hz, H5), 5.93 (d,
1H, J1–2¼13.2 Hz, H1), 6.10 (dd, 1H, J4–3¼14.7 Hz and J4–5¼10.2 Hz,
H4), 6.45 (d, 1H, J6–5¼15.8 Hz, H6), 6.53 (dd, 1H, J2–1¼13.2 Hz and
J2–3¼10.9 Hz, H2), 6.67 (dd, 1H, J3–2¼10.9 Hz and J3–4¼14.7 Hz, H3),
The two isomers 1a (1E,3E,5E) and 1b (1E,3E,5Z) were separated
by sublimation at 18 mmHg. Isomer 1b (1E,3E,5Z) was sublimed at
35 ꢀC, after that, isomer 1a (1E,3E,5E) was sublimed at 45 ꢀC.
7.13 at 7.36 (m, 5H, Harom). 13C NMR (CDCl3):
d 121.3 (CHCl), 126.9,
128.3, 128.8, 129.0, 129.1, 129.2, 134.2, 134.3, 137.5 (C). MS (EI) m/z:
ꢃ
ꢃ
190–192 (Mþ , 48%, 17%), 155 (Mþ ꢁCl, 100%), 115 (28%), 91 (32%), 77
4.2.1. Isomer 1a (1E,3E,5E)
ꢃ
(C6Hþ5 , 45%).
Yield after sublimation: 38%, white solid. Mp 90 ꢀC. 1H NMR
(C6D6):
d
5.39 (dd, 2H, J3–4¼13.2 Hz and J3–2¼J4–5¼9.8 Hz, H3 and
4.4.4. (1Z,3E,5E)-1-Chloro-6-phenylhexa-1,3,5-triene (3bb)
H4), 5.71 (d,1H, J6–5¼13.2 Hz, H6), 5.83 (d,1H, J1–2¼13.2 Hz, H1), 6.10
1H NMR (C6D6)
d
5.90 (d, 1H, J1–2¼7.2 Hz, H1), 6.25 (dd, 1H,
(dd, 1H, J5–6¼13.2 Hz and J5–4¼9.8 Hz, H5), 6.38 (dd, 1H, J2–1
¼
J2–1¼7.2 Hz and J2–3¼10.9 Hz, H2), 6.44 (dd, 1H, J4–3¼15.1 Hz and
J4–5¼10.9 Hz, H4), 6.36 (d, 1H, J6–5¼15.8 Hz, H6), 6.87 (dd, 1H,
J5–4¼10.9 Hz and J5–6¼15.8 Hz, H5), 7.03 (dd, 1H, J3–2¼10.9 Hz and
J3–4¼15.1 Hz, H3), 7.27 at 7.49 (m, 5H, Harom). MS (EI) m/z: 190–192
13.2 Hz and J2–3¼9.8 Hz, H2). 13C NMR (C6D6):
d
110.2 (C1), 122.3
(C6), 129.2 (C3), 130.4 (C4), 133.4 (C5), 137.3 (C2). IR: 1597, 980,
ꢃ
742 cmꢁ1. MS (EI) m/z: 192–194–196 (Mþ , 32%, 44%, 12%), 157–159
ꢃ
ꢃ
ꢃ
(Mþ ꢁCl, 9%, 9%), 113–115 (Mþ ꢁBr, 41%, 14%), 77 (C6Hþ6 , 100%).
Anal. Calcd for C6H6BrCl (191.93): C 37.25, H 3.13; found: C 37.26, H
3.02.
ꢃ
ꢃ
ꢃ
(Mþ , 25%, 9%), 155 (Mþ ꢁCl, 100%), 115 (32%), 91 (45%), 77 (C6H5þ
,
56%).
4.4.5. (1E,3E,5E)-1-Chlorododeca-1,3,5-triene (4)
4.2.2. Isomer 1b (1E,3E,5E)
Yield: 85%, yellow oil. 1H NMR (CDCl3):
d
0.86 (t, 3H, J¼6.5 Hz,
Yield after sublimation: 30%, white solid. Mp 40 ꢀC. 1H NMR
H
12), 1.16 at 1.41 (m, 8H, H11, H10, H9, H8), 2.09 (q, 2H, J7–8
¼
(CDCl3):
d
6.04 (d, 1H, J6–5¼7.2 Hz, H6), 6.20 (m, 2H, H3 and H5), 6.35
J7–6¼6.9 Hz, H7), 5.69 (dt, 1H, J6–5¼15.5 Hz and J6–7¼6.8 Hz, H6),
5.95 (m, 2H, H3, H4), 6.05 (d, 1H, J1–2¼13.2 Hz, H1), 6.11 (dd, 1H,
J5–6¼15.1 Hz and J5–4¼10.2 Hz, H5), 6.37 (dd, 1H, J2–1¼13.2 Hz and
(d, 1H, J1–2¼13.5 Hz, H1), 6.57 (dd, 1H, J4–3¼13.2 Hz and J4–5¼9.8 Hz,
H4), 6.75 (dd,1H, J2–1¼13.2 Hz and J2–3¼9.8 Hz, H2). 13C NMR (C6D6):
d
111.3 (C1),120.5 (C6),126.9 (C4),129.5 (C5),132.7 (C3),137.7 (C2). IR:
J2–3¼10.9 Hz, H2). 13C NMR (CDCl3):
d
14.5 (C12), 23.0 (CH2), 29.3
ꢃ
1597, 980, 742 cmꢁ1. MS (EI) m/z: 192–194–196 (Mþ , 32%, 44%,
(CH2), 29.5 (CH2), 32.1 (CH2), 33.3 (CH2), 119.8 (CH), 126.3 (CH),
130.1 (CH), 134.3 (CH), 134.4 (CH), 137.6 (CH). IR: 2956, 2852, 1686,
ꢃ
ꢃ
12%), 157–159 (Mþ –Cl, 9%, 9%), 113–115 (Mþ ꢁBr, 41%, 14%), 77
ꢃ
(C6Hþ6 , 100%). Anal. Calcd for C6H6BrCl (191.93): C 37.25, H 3.13;
ꢃ
1462, 1377, 990, 754 cmꢁ1. MS (EI) m/z: 198–200 (Mþ , 54%, 18%),
found: C 37.28, H 3.06.
ꢃ
ꢃ
114–116 (Mþ ꢁC6H13, 12%, 4%), 91 (69%), 77 (C6H6þ , 100%). Anal.
Calcd for C12H19Cl (198.12): C 72.52, H 9.57; found: C 72.47, H 9.28.
4.3. Preparation of alkylzinc chloride solution
4.4.6. Trimethyl-(3E,5E,7E)-tetradeca-3,5,7-trien-1-ynylsilane (5)
To a stirred solution of chlorotriene 4 (154.90 mg, 0.78 mmol),
PdCl2(PhCN)2 (17.90 mg, 0.05 mmol) and CuI (14.85 mg,
0.08 mmol) in piperidine (2 mL) under an argon atmosphere was
slowly added, at room temperature trimethylsilylacetylene
To a stirred solution of zinc dichloride (1.5 equiv) in anhydrous
THF was slowly added at 0 ꢀC a 2 M THF solution of alkylmagne-
sium bromide. The resulting white mixture was stirred for 2 h at
room temperature to give a 0.5 M solution of alkylzinc chloride 2.

1970
W. Bentoumi et al. / Tetrahedron 65 (2009) 1967–1970
(92.00 mg, 0.93 mmol) in piperidine (1 mL). The resulting black
mixture was stirred for 4 h at room temperature and the reaction
mixture was treated with a saturated aqueous solution of NH4Cl.
The aqueous layer was extracted with ether (3ꢂ10 mL). The
combined organic layers were washed successively with aqueous
HCl (0.2 M, 15 mL), NaHCO3 (10 mL) and H2O (2ꢂ10 mL), dried over
MgSO4 and concentrated under vacuum. The residue was purified
by column chromatography (SiO2, pentane) to give pure compound
5 (163.80 mg, 0.62 mmol).
Yield: 80%, yellow solid. 1H NMR (CDCl3):
d
0.86 (t, 3H, J¼6.5 Hz,
H
17), 1.18 at 1.24 (m, 8H, H16, H15, H14, H13), 2.09 (q, 2H, J12–13
¼
J12–11¼6.9 Hz, H12), 2.65 (1H, OH), 5.00 (d, 1H, J3–2¼3.4 Hz, H3), 5.15
0
(d, 1H, J1 –2¼10.2 Hz, H1 ), 5.44 (d, 1H, J1–2¼17.0 Hz, H1), 5.56 (d, 1H,
0
J6–7¼15.5 Hz, H6), 5.80 (dt, 1H, J11–10¼15.1 Hz and J11–12¼6.8 Hz,
0
H
11), 5.95 (ddd, 1H, J2–1¼17.0 Hz, J2–1 ¼10.2 Hz and J2–3¼3.4 Hz, H2),
6.02 (dd, 1H, J10–11¼15.5 Hz and J10–9¼10.2 Hz, H10), 6.12 (dd, 1H,
J8–9¼15.5 Hz and J8–7¼10.9 Hz, H8), 6.26 (dd, 1H, J9–8¼15.5 Hz and
J9–10¼10.2 Hz, H9), 6.60 (dd, 1H, J7–6¼15.5 Hz and J7–8¼10.9 Hz, H7).
Yield: 80%, yellow oil. 1H NMR (CDCl3):
d
0.18 (9H, s, CH3), 0.86
13C NMR (CDCl3):
d
14.3(C17), 22.8, 27.1, 29.1, 29.3, 31.9 (C16, C15, C104
,
(3H, t, J14–13¼6.5 Hz, H14),1.18 at 1.24 (8H, m, H13, H12, H11, H10), 2.09
(2H, q, J9–10¼J9–8¼6.9 Hz, H9), 5.55 (d, 1H, J3–4¼15.5 Hz, H3), 5.78
(dt, 1H, J8–7¼15.2 Hz and J8–9¼6.7 Hz, H8), 5.98 at 6.16 (m, 2H, H5,
H6), 6.26 (dd, 1H, J7–8¼14.7 Hz and J7–6¼10.0 Hz, H7), 6.62 (dd, 1H,
C
13), 33.2 (C12), 63.8 (C3), 86.1 (C4), 90.6 (C5), 109.2 (C6), 114.8 (C1,1 ),
129.3 (C10), 130.2 (C8), 136.2 (C9), 137.2 (C2), 138.4 (C11), 142.9 (C7).
ꢃ
IR: 3620, 2210, 1640, 1615, 1405 cmꢁ1. MS (EI) m/z: 244 (Mþ , 20%),
ꢃ
ꢃ
226 (Mþ ꢁH2O, 100%), 163 (Mþ ꢁC5H5O, 40%), 85 (C6H1þ3, 60%). Anal.
J4–3¼15.5 Hz and J4–5¼10.4 Hz, H4). 13C NMR (CDCl3):
d
0.5 (SiCH3),
Calcd for C17H24O (244.18): C 83.55, H 9.90; found: C 83.60, H 9.54.
14.6 (CH3), 22.5 (CH2), 28.8 (CH2), 29.0 (CH2), 31.6 (CH2), 32.8 (C9),
97.8 (C1), 105.5 (C2), 110.3 (C3), 129.9 (C4), 130.6 (C5), 136.5 (C6),
138.7 (C7), 143.6 (C8). IR: 2958, 2926, 2854, 2114, 1250, 994,
4.4.9. (6E,8E,10E)-Heptadeca-1,6,8,10-tetraen-4-yn-3-one (8)
A solution of alcohol 7 (125.00 mg, 0.51 mmol) and MnO2
(436.00 mg, 5.10 mmol) in THF (8 mL) under argon was stirred
overnight. The reaction mixture was filtered on Celite and the
solvent was removed under vacuum. The crude product was puri-
fied by column chromatography (SiO2, pentane) to give pure
compound 8 (116 mg, 0.48 mmol).
ꢃ
ꢃ
844 cmꢁ1. MS (EI) m/z: 260 (Mþ , 15%), 245 (Mþ ꢁCH3), 73
(Si(CH3)þ3 , 100%). Anal. Calcd for C17H28Si (260.20): C 78.38, H 10.83;
found: C 78.63, H 10.68.
4.4.7. (3E,5E,7E)-Tetradeca-3,5,7-trien-1-yne (6)15
To a solution of trienyne silane 5 (163.80 mg, 0.63 mmol) in
degassed MeOH (2 mL) and under an argon atmosphere was added
K2CO3 (100.00 mg, 0.69 mmol). The reaction mixture was stirred at
room temperature for 4 h. Diethylether was added and the organic
layer washed with water (2ꢂ5 mL), dried over MgSO4 and the
solvent was removed under vacuum. The crude product was puri-
fied by column chromatography (SiO2, pentane) to give pure
compound 6 (106.60 mg, 0.56 mmol).
Yield: 94%, yellow oil. 1H NMR (CDCl3):
d
0.86 (t, 3H, J17–16
¼
6.5 Hz, H17), 1.18 at 1.24 (m, 8H, H16, H15, H14, H13), 2.09 (q, 2H,
J12–13¼J12–11¼6.9 Hz, H12), 5.65 (d, 1H, J6–7¼15.5 Hz, H6), 5.86 (dt,
1H, J11–10¼15.5 Hz and J11–12¼10.2 Hz, H11), 6.14 (3H, m, H8, H10, H2),
0
6.45 (3H, m, H9, H1, H1 ), 6.90 (dd, 1H, J7–6¼15.5 Hz and
J7–8¼10.1 Hz, H7). 13C NMR (CDCl3):
d
14.5 (C17), 22.9, 29.3, 29.4, 32.1
(C13, C14, C15, C16), 33.5 (C12), 89.3 (C5), 93.4 (C4), 106.9 (C6), 129.1
(C10), 130.3 (C8), 133.1 (C1), 138.4 (C2), 139.9 (C9), 141.3 (C11), 149.1
(C7), 179.1 (C3). IR: 2270, 1648, 1400, 995, 940 cmꢁ1. MS (EI) m/z:
Yield: 90%, yellow oil. 1H NMR (CDCl3):
d
0.86 (t, 3H, J14–13
¼
ꢃ
ꢃ
ꢃ
6.5 Hz, H14), 1.18 at 1.24 (m, 8H, H13, H12, H11, H10), 2.09 (q, 2H,
J9–10¼J9–8¼6.9 Hz, H9), 3.03 (d, 1H, J1–3¼2.2 Hz, H1), 5.51 (dd, 1H,
J3–4¼15.4 Hz and J3–1¼2.2 Hz, H3), 5.80 (dt, 1H, J8–7¼15.0 Hz and
J8–9¼6.9 Hz, H8), 6.05 (dd, 1H, J6–5¼14.6 Hz and J6–7¼10.0 Hz, H6),
6.12 (dd, 1H, J5–6¼14.6 Hz and J5–4¼10.6 Hz, H5), 6.28 (dd, 1H,
J7–8¼15.0 Hz and J7–6¼10.0 Hz, H7), 6.66 (dd, 1H, J4–3¼15.4 Hz and
242 (Mþ , 40%), 214 (Mþ ꢁCO, 100%), 187 (Mþ ꢁC3H3O, 40%), 85
(C6Hþ13, 60%). Anal. Calcd for C17H22O (242.17): C 84.24, H 9.15;
found: C 84.35, H 9.30.
References and notes
J4–5¼10.0 Hz, H4). 13C NMR (CDCl3):
d
14.2 (C14), 22.7, 29.0, 29.2, 31.8
1. Thirsk, C.; Whiting, A. J. Chem. Soc., Perkin Trans. 1 2002, 999–1023.
2. Rossi, R.; Carpita, A.; Lippolis, V. Synth. Commun. 1991, 21, 333–349.
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4. Sugita, M.; Natori, Y.; Sueda, N.; Sueda, N.; Furihata, K.; Seto, H.; Otake, N.
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5. (a) Soullez, D. Ph.D. Dissertation, Rouen University, 1994; (b) Soullez, D.; Ple´, G.;
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(C10, C11, C12, C13), 33.1 (C9), 79.8 (C2), 83.5 (C1), 108.7 (C3), 129.1 (C6),
130.0 (C5), 136.4 (C7), 138.5 (C8), 143.7 (C4). IR: 3308, 3018–2926–
ꢃ
2854, 2092, 1458, 1376, 992 cmꢁ1. MS (EI) m/z: 188 (Mþ , 80%), 117
ꢃ
(69%),103 (Mþ ꢁC6H13,100%), 77 (C6H6þ, 80%). Anal. Calcd for C14H20
(188.16): C 89.28, H 10.71; found: C 89.48, H 10.75.
´
Ple, G.; Soullez, D.; Duhamel, P.; Duhamel, L. French Patent 2,726,266, 1996;
4.4.8. (6E,8E,10E)-Heptadeca-1,6,8,10-tetraen-4-yn-3-ol (7)
To a solution of trienyne 6 (181.00 mg, 0.96 mmol) in THF (5 mL)
and under an argon atmosphere at 0 ꢀC, 2.5 M n-BuLi (0.38 mL,
0.96 mmol) was added dropwise at this temperature, and the
mixture was stirred for 1 h at room temperature. Then the solution
was cooled at ꢁ78 ꢀC and acrolein (43.00 mg, 0.76 mmol) in THF
(3 mL) was added dropwise at this temperature. The reaction
mixture was stirred for 1 h at room temperature, quenched with
10 mL of NH4Cl and was extracted with diethyl ether. The organic
layer was dried over MgSO4 and the solvent was removed under
vacuum. The crude product was purified by column chromato-
graphy (SiO2, pentane) to give pure compound 7 (157.50 mg,
0.64 mmol).
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´
N.; Ramondenc, Y.; Ple, G. Eur. J. Org. Chem. 2001, 561–574.
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Zdero, C.; Suwita, A. Chem. Ber. 1975, 108, 2818–2821.
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411–412.
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