Palladium-Catalyzed Regioselective Coupling of Propargylic Substrates with Terminal Alkynes. Application to the Synthesis of 1,2-Dien-4-ynes

Article abstract of DOI:10.1016/S0040-4020(00)00115-0

The palladium-catalyzed reaction of propargyl halides, tosylates and acetates with terminal alkynes is reported. The best yields are obtained from propargyl chlorides and 1-alkynes (i) in the presence of amine (triethylamine, diisopropylamine) in benzene,

Full text of DOI:10.1016/S0040-4020(00)00115-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1851–1857
Palladium-Catalyzed Regioselective Coupling of Propargylic
Substrates with Terminal Alkynes. Application to the Synthesis
of 1,2-Dien-4-ynes
*
´
Sylvie Condon-Gueugnot and Gerard Linstrumelle
´
Laboratoire de Chimie, Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris Cedex 05, France
Received 21 June 1999; accepted 9 February 2000
Abstract—The palladium-catalyzed reaction of propargyl halides, tosylates and acetates with terminal alkynes is reported. The best yields
are obtained from propargyl chlorides and l-alkynes (i) in the presence of 2 equiv. of amine (triethylamine, diisopropylamine) in benzene,
toluene or ethylacetate (ii) or in pure diisopropylamine. Propargyl acetates undergo the cross coupling reaction with moderate to high yields
after modification of the general procedure. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Palladium(0) complexes are versatile catalysts for cross
coupling reactions and play an important role in organic
synthesis.1 In our laboratory, we had studied the preparation
of allenynes2 by reaction of allenic halides with terminal
alkynes in the presence of catalytic amounts of tetrakis[tri-
phenylphosphine]palladium and copper(I) iodide in diethyl-
amine at room temperature. A synthesis of allenynes3,4 was
also described by Tsuji from 2-alkynyl carbonates and
terminal acetylenes.5,6 Our interest in the development of
synthetic methods based on palladium catalysis7–10 stimu-
lated us to examine the reactivity of propargylic halides,
tosylates and acetates11 with terminal alkynes in the
presence of palladium-complexes. Usually propargylic
halides undergo 1,1 or 1,3 substitution reaction12–16 when
treated with organometallic compounds.
This paper deals with a systematic study of the effects of
reaction conditions which was carried out in order to
optimize and generalize this procedure.
We first decided to examine the reactivity of propargyl
halides under the standard reaction conditions reported
for the synthesis of enynes from alkenyl halides with
alkynes.7–10 Under these conditions, the reaction of 1-chloro-
2-octyne with trimethyl silylacetylene gave allenyne 2 in
moderate yield (Scheme 2).
The standard reaction chosen for the study is shown in
Scheme 3. Reaction conditions and yields are reported in
Table 1.
The cross coupling reaction of 1-chloro-2-octyne 1a with
1-heptyne was very sensitive to the nature of the amine
(2 equiv.) when performed in the presence of Pd(PPh3)4-
CuI as catalysts and benzene as solvent (entries 1–7). The
best results were obtained with diethylamine (60%), diiso-
propylamine (88%) and triethylamine (79%). With pyridine
(2 equiv.) or quinoline (2 equiv.), no allenyne was formed
and the starting materials were recovered after 6 h at 20ЊC.
We thus found a mild and convenient method17 for the
preparation of a large variety of substituted allenynes (1,1-
disubstituted, 1,3-disubstituted, tri- and tetrasubstituted
allenynes).
We have shown that this new procedure tolerates sensitive
functional groups and is highly regioselective: pure
allenynes were obtained without formation of 1,4-diyne
isomers. The reaction most likely proceeded via an organo-
palladium complex which arose by oxidative addition of
propargyl compound to the catalyst (Scheme 1) reaction
with the acetylide and subsequent reductive elimination to
give the allenyne.
Keywords: palladium-catalyzed; allene; propargyl halides.
* Corresponding author. Present address: Laboratoire d’Electrochimie,
`
Catalyse et Synthese Organique, CNRS, 2 rue Henri Dunant, 94320 Thiais,
France; Tel.: ϩ33-1-49-78-11-26; fax: ϩ33-1-49-78-11-48; e-mail:
Scheme 1.
sylvie.condon@glvt-cnrs.fr
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00115-0

1852
S. Condon-Gueugnot, G. Linstrumelle / Tetrahedron 56 (2000) 1851–1857
Scheme 2.
Scheme 3.
Table 1. Influence of the palladium catalyst, amine and solvent on the regioselective cross coupling reaction of 1-heptyne with primary propargyl halides 1a–c
Entry
Starting material
X
Catalysta
Amine (2 equiv.)
Solvent
Time (h)b
Isolated yield (%)c
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1c
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
OTs
OTs
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
n-Butylamine
Diethylamine
Diisopropylamine
Piperidine
Tri n-propylamine
N,N-Diisopropyl ethylamine
Triethylamine
Triethylamine
Triethylamine
Triethylamine
Triethylamine
–
–
–
–
–
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
THF
7
6
3
5d
60
88
8
12d
10
24
3
7
7
3
3
1.5
4
2
1
1
1
3.5
1
21d
14d
79
31
31
79
79
88
79
85.5
92 (0)e
88 (0)e
92 (0)e
15
9
Et2O
10
11
12
13
14
15
16
17
18
19
20
21
CH3C6H5
CH3CO2Et
Diisopropylamine
Triethylamine
Diisopropylamine
Diisopropylamine
Diisopropylamine
Diisopropylamine
C6H6
Pd(PPh3)4
Pd(PPh3)2Cl2
PdCl2ϩ2PPh3
Pd(C6H5CN)2Cl2ϩ2PPh3
Pd(OAc)2ϩ2PPh3
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
–
Triethylamine
–
Triethylamine
–
Diisopropylamine
C6H6
Diisopropylamine
51
3
2.5
25 (31)f
69 (71)f
a All reactions were performed with 0.1 equiv. of CuI catalyst.
b Reaction times were monitored by GC.
c 3 is a colourless liquid.
d Propargyl halide was not completely consumed after the reaction time indicated.
e Reaction performed in the absence of PPh3.
f In the presence of LiCl (2 equiv.).
Although the role of the amine is yet unclear, its participa-
tion in the formation of acetylide-copper12,13,18,19 is usually
retained.
takes place without palladium or without palladium-copper
salt catalysts. However, when the palladium(0) catalyst was
used alone, a small amount of cross coupling product was
observed (14% isolated yield). Other types of palladium
complexes were also tested. We found that PdCl2,
Pd(0Ac)2 or Pd(C6H5CN)Cl2 in the absence of triphenylpho-
sphine did not catalyze the coupling reaction (entries
15–17). An almost quantitative coupling was then obtained
by the addition of 2 equiv. of triphenylphosphine as ligand
for one equivalent of palladium. The possibility to prepare
in situ an efficient Pd(0) catalyst is interesting since success
in such catalyzed reactions depends on the quality of the
palladium(0) complex: thus, Pd(PPh3)4 had to be stored
under argon whereas the catalyst precursors PdCl2 or
Pd(0Ac)2 could be stored without any particular care.
Inspection of Table 1 shows the great influence of the
solvent when the reaction was performed with 2 equiv. of
triethylamine (entries 7–11). Acetonitrile, dichloromethane,
and N,N-dimethylformamide gave poor results (5–8%).
Benzene could be replaced by toluene or ethyl acetate
(entries 10–11). We also found that the preparation of
allenyne compounds from primary propargyl halides (or
tosylates) and 1-heptyne could be achieved in amine as a
solvent such as diisopropylamine or triethylamine (entries
12–13, 19, 21). Acceleration of the reaction was apparent by
using diisopropylamine (entries 3, 12).
The role of palladium(0) and copper(I) was evidenced in
diisopropylamine as solvent. It was found that no reaction
The nature of the leaving group was also very important.
Propargyl chlorides gave better results than propargyl

S. Condon-Gueugnot, G. Linstrumelle / Tetrahedron 56 (2000) 1851–1857
1853
Table 2. Regioselective synthesis of allenynes from propargyl acetates and 1-heptyne in refluxing THF
Entry
AcetatesϾ
R1
Conditions
Product N0
Time (h)
Isolated yielda (%)
R
R2
N0
1
2
3
4
C5H11
C4H9
C4H9
C4H9
H
Et
CH3
CH3
H
H
CH3
CH3
4a
4b
4c
4c
ZnCl2 (3 equiv.)
ZnCl2 (3 equiv.)
LiCl (2 equiv.)
ZnCl2 (3 equiv.)
5a
5b
5c
5c
7
4
6
3
52 (63)b
74
42
74.5 (68)b
a All products are oils.
b Reaction performed in the absence of CuI.
Table 3. Regioselective synthesis of functionalized 1,1-disubstituted allenynes from 1-chloro-2-octyne and terminal alkynes
Entry
R
Methoda
Time (h)
Product N0
Isolated yieldb (%)
1
2
3
4
5
6
7
8
Me3Si
Me3Si
A
B
A
B
A
B
A
B
3
0.5
3
2
4.5
1
6a
6a
6b
6b
6c
6c
6d
6d
60.5
84
69
69
53
80.5
29
73.5
(CH2)3CO2Me
(CH2)3CO2Me
(CH2)2OH
(CH2)2OH
CH2OH
3.5
1.5
CH2OH
a Method A: reaction performed in benzene with triethylamine (2 equiv.); method B: reaction performed in diisopropylamine.
b All products are oils.
tosylates or bromides (entries 12, 19, 21). In addition,
comparison of experiments carried out in pure diisopropyl-
amine with those in benzene-2 equiv. triethylamine
indicated that the reaction proceeded faster and with higher
yields in pure diisopropylamine (entries 7, 12, 18–21).
Table 3 illustrates the generality of the procedure for the
synthesis of 1,1-disubstituted allenes from 1-chloro-2-
octyne and functionalized terminal acetylenes. Satisfactory
results were obtained with both methods A (benzene-
2 equiv. of triethylamine) and B (diisopropylamine as
solvent). The use of method B for the preparation of
allenynols gave shorter reaction times and higher yields
(entries 5–8).
Propargyl acetates were unreactive; however, they could be
activated by the addition of zinc chloride or lithium chloride
as mentioned in the literature20,21 (Table 2).
Method B gave 1,3-disubstituted allenes (Scheme 4) in
moderate yields (25%, RˆC5H11; XˆCl). Another product,
N,N-diisopropyl-3-amino-1-octyne, was formed in 56%
yield by the reaction of diisopropylamine with the propargyl
halide. The yields of the coupling product was considerably
improved by slowly adding propargyl halide in benzene to
a mixture of terminal alkyne, Pd(PPh3)4 5%-CuI 10% in
diisopropylamine (Scheme 4). Our results are comparable
The best results were obtained with ZnCl2 in refluxing THF.
Secondary and tertiary propargyl acetates gave good yields
of coupling products, primary propargyl acetates were less
reactive. Interestingly, we observed that the reaction could
proceed without the presence of copper iodide. Presumably
zinc acetylide was formed in situ and then underwent cross
coupling reaction.
Scheme 4. Regioselective synthesis of 1,3-disubstituted allenes from 3-chloro-1-octyne.

1854
S. Condon-Gueugnot, G. Linstrumelle / Tetrahedron 56 (2000) 1851–1857
Table 4. Regioselective syntheses of tri- and tetrasubstituted allenes
Entry
Propargyl chlorides
R3
R
Conditionsa
Time (h)
Product N0
Yieldb (%)
R2
N0
1
2
H
H
H
H
Et
Et
Et
Et
9a
9a
9a
9a
9a
9b
9b
9b
9b
9b
C5H11
C5H11
C5H11
(CH2)3CO2Me
(CH2)2OH
C5H11
C5H11
C5H11
Method B
Method A
Et3N 2 equiv. in AcOEt
Method A
Method A
Method B
Method A
Et3N 2 equiv. in AcOEt
Method A
Method A
1
2
1.5
2
3
1
1.5
1
2.5
2
10a
10a
10a
10b
10c
10d
10d
10d
10e
10f
91
91.5
92
85
86
90
93
86
87
3
4
5
6
H
Et
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
7
8
(CH2)3CO2Me
(CH2)2OH
93.5
a Method A: reaction performed in benzene with triethylamine (2 equiv.); method B: reaction performed in diisopropylamine.
b Isolated yields, all products are oils.
with those of J. Gore and R. Baudouy22 for the synthesis of
n-tetradeca-4,5-dien-2-yn-1-ol, an intermediate in the
synthesis of an insect pheromone.
230–400 mesh). All glassware was oven-dried at 140ЊC
and all reactions were conducted under argon atmosphere.
Boiling points are uncorrected. Tetrahydrofuran was
distilled from sodium and benzophenone. Benzene and
toluene were distilled over CaH2. Ethyl acetate was used
without further purification. Diethylamine, n-butylamine,
and N,N-diisopropylamine, piperidine, tri-n-propylamine,
N,N-diisopropylethylamine were distilled over potassium
hydroxide. 2-octyn-1-ol,23 non-4-yn-3-ol,23 2-methyl-oct-
3-yn-2-ol23 and 1-bromo-2-octyne24 were prepared by
known procedures. PdCl2 and Pd(OAc)2 are commercial
´
The coupling reaction of secondary and tertiary propargyl
chlorides with terminal alkynes gave good yields of tri- and
tetrasubstituted allenes. The two methods are valuable for
the preparation of branched allenes. High yields were
obtained by using method A (Table 4). It is worth noting
that allenynols can be prepared by the two methods.
27
In summary, the procedure described herein provides an
interesting approach for the preparation of a large variety
of substituted allenes. The reaction proceeds cleanly under
mild conditions, tolerates sensitive functional groups and is
highly regioselective. From the results of this investigation,
it appears that different experimental conditions can be
proposed for the cross coupling. Generally the reaction
can be carried out in benzene, ethylacetate, and toluene,
with 2 equiv. of amine (diethylamine, triethylamine,
diisopropylamine), or in pure amine (triethylamine,
diisopropylamine). We have shown that PdCl2 and
Pd(OAc)2 can be used with triphenylphosphine instead of
Pd(PPh3)4. The nature of the propargyl halide is important.
Chlorides are the most appropriate but acetates can also be
used.
products. Pd(PPh3)4,25 Pd(C6H5CN)2Cl2,26 and Pd(PPh3)2Cl2
were prepared by known procedures. Lithium and zinc
chloride were dried at 200ЊC in high vacuum.
General procedure for the syntheses of allenynes from
propargyl halides
Method A. Under an argon atmosphere, to a degassed solu-
tion of propargyl halide (2.75 mmol) in 3 ml of benzene,
tetrakis[triphenylphosphine]palladium (0.05 equiv.) was
rapidly added at room temperature. After stirring for
5 min, a solution of alkyne (1.1–1.2 equiv.) in 2 ml of ben-
zene, copper iodide (0.1 equiv.) and triethylamine (2 equiv.)
was added successively. After the time indicated in Table 3
or 4, the reaction mixture was diluted with 1:1 ether/pentane
(20 ml), then the organic phase was washed twice with
saturated aqueous ammonium chloride solution (10 ml),
dried over magnesium sulfate and evaporated. The crude
product was purified by flash chromatography.
Experimental
General
Method B. Under an argon atmosphere, to a degassed solu-
tion of propargyl halide (2.75 mmol) in 3 ml of diisopropyl-
amine, tetrakis[triphenylphosphine]palladium (0.05 equiv.)
was rapidly added at room temperature. After stirring for
5 min, a solution of alkyne (1.1–1.2 equiv.) in 2 ml of diiso-
propylamine and copper iodide (0.1 equiv.) was added
successively. After the reaction time indicated in Table 3
or 4, the reaction mixture was diluted with 1:1 ether/pentane
(20 ml), then the organic phase was washed twice with
saturated aqueous ammonium chloride solution (10 ml),
1H and 13C spectra were recorded on a Bruker VM 250 or
AM 400 instrument (CDCl3, d (ppm), J (Hz)). Mass spectra
were determined on a Nermag R 10/10 instrument in a NH3
chemical ionisation mode. IR spectra were measured on a
Perkin Elmer 599 spectrophotometer (neat, cmϪ1). Purity
of products was determined by gas chromatographic
analyses performed on a Girdel equipped with capillary
column (SGE 50 QC2/BP5 0.25). Products were purified
by distillation or by column chromatography (silica gel 60

S. Condon-Gueugnot, G. Linstrumelle / Tetrahedron 56 (2000) 1851–1857
1855
dried over magnesium sulfate and evaporated. The crude
product was purified by flash chromatography.
hydroxide (10.40 g; 185 mmol) portionwise while keeping
temperature below Ϫ10ЊC. The mixture was stirred at
Ϫ5ЊC for 1 h and then poured into ice water (50 ml).
After vigorous shaking, the layers were separated and
the aqueous layer was extracted twice with small
portions of diethylether. The combined organic layers
were washed with brine and dried over MgSO4. After
the solvent was removed on a rotary evaporator, 7 g
(100%) of the title compound 1c was obtained without
further purification. IR (neat) cmϪ1: 2950, 2920, 2870,
2860, 2300, 2230, 1600, 1480, 1450, 1370, 1190, 1175;
1H NMR: d 7.80 (d, 2H, Jˆ8.3 Hz), 7.33 (d, 2H,
Jˆ8.3 Hz), 4.68 (t, 2H, Jˆ2.2 Hz), 2.45 (s, 3H), 2.05 (tt,
2H, Jˆ7.0 Hz, Jˆ2.2 Hz), 1.40–1.20 (m, 6H), 0.85 (t, 3H,
Jˆ6.6 Hz); 13C NMR: d 144.7, 133.1, 129.5, 127.8, 90.3,
71.6, 58.6, 30.6, 27.5, 21.8, 21.3, 18.3, 13.6; MS: m/z (%)
298 (100%, Mϩ18); 281 (Mϩ1).
General procedure for the preparation of allenynes 5
from propargyl acetates 4
Under an argon atmosphere, tetrakis[triphenylphosphine]-
palladium (0.05 equiv.) was added rapidly to a solution of
propargyl acetate (1 mmol) in 1 ml of tetrahydrofuran at
20ЊC. Then a solution of ZnCl2 (3 equiv.) in 2 ml of tetra-
hydrofuran was added and the mixture was stirred for 5 min
at 20ЊC. After the addition of diisopropylamine (2 equiv.)
and copper iodide (0.1 equiv.), the reaction mixture was
heated to refluxing tetrahydrofuran and a solution of alkyne
(1.4 equiv.) was added slowly (addition time: 1 h). After the
reaction time indicated in the Table 2, reaction mixture was
cooled with an ice bath, diluted in diethylether (20 ml) and
washed twice with an aqueous ammonium chloride solution
(10 ml). The organic layer was dried over magnesium sul-
fate and evaporated. The crude product was purified by flash
chromatography.
1-Acetoxy-2-octyne 4a. To a solution of 2-octyn-1-ol
(1.26 g; 10 mmol) in 1.7 ml of pyridine, acetic anhydride
(2.04 g; 20 mmol) was added at Ϫ10ЊC. The temperature
was allowed to rise to 0ЊC and the mixture was stirred for
12 h at 0ЊC. The reaction was quenched with water,
extracted with diethylether, and dried over MgSO4. After
removal of the solvent, reduced pressure fractional distilla-
tion afforded 1.54 g (91.5%) of 4a. Bp 103ЊC/15 mm Hg. IR
(neat) cmϪ1: 2960, 2920, 2860, 2220, 1745, 1380, 1220,
Procedure for the preparation of 1,3-disubstituted
allenes
Synthesis of 8a. To a mixture of tetrakis[triphenylphos-
phine]palladium (0.08 g; 0.069 mmol) and copper iodide
(0.026 g; 0.136 mmol) in 4 ml of diisopropylamine, at
room temperature, under an argon atmosphere, was added
a solution of 1-heptyne (0.16 g; 1.656 mmol) in 3 ml of
diisopropylamine and very slowly (addition time 40 min)
3-chloro-1-octyne 7a (0.20 g; 1.384 mmol) in solution in
4.5 ml of benzene. The reaction was stirred 20 min after
the end of the addition and then diluted in 20 ml of diethyl-
ether, washed twice with saturated aqueous ammonium
chloride solution (10 ml), dried over magnesium sulfate
and evaporated. Purification by column chromatography
(eluent: pentane) afforded 0.16 g (56.5%) of 8a.
1
1030; H NMR: d 4.66 (t, 2H, Jˆ2.2 Hz), 2.22 (tt, 2H,
Jˆ7.1 Hz, Jˆ2.2 Hz), 2.09 (s, 3H), 1.46–1.58 (m, 2H),
1.27–1.41 (m, 4H), 0.9 (t, 3H, Jˆ7.1 Hz); 13C NMR: d
170.0, 87.3, 73.7, 52.5, 30.8, 27.9, 21.9, 20.5, 18.5, 13.6;
MS: m/z (%) 186 (100%, Mϩ18); Anal. Calcd for C10H16O2:
C, 71.39; H, 9.58. Found: C, 71.28; H, 9.75.
3-Acetoxy-4-nonyne 4b. Following the same procedure
described above for the synthesis of 4a, non-4-yn-3-ol
(1.40 g; 10 mmol) was transformed into 4b (1.66 g;
91.5%) bp 92ЊC/15 mm Hg. IR (neat) cmϪ1: 2960, 2920,
1
2860, 2220, 1740, 1460, 1370, 1230, 1020; H NMR: d
5.31 (tt, 1H, Jˆ6.5 Hz, Jˆ2.0 Hz), 2.22 (td, 2H,
Jˆ6.9 Hz, Jˆ2.0 Hz), 2.08 (s, 3H), 1.75 (quin, 2H,
Jˆ7.1 Hz), 1.30–1.58 (m, 4H), 1.00 (t, 3H, Jˆ7.4 Hz),
0.91 (t, 3H, Jˆ7.1 Hz); 13C NMR: d 170.2, 86.2, 77.2,
65.7, 30.5, 28.3, 21.9, 21.1, 18.3, 13.6, 9.3; MS: m/z (%)
200 (Mϩ18), 183 (Mϩ1); %); Anal. Calcd for C11H18O2: C,
72.49; H, 9.95. Found: C, 72.63; H, 10.11.
1-Chloro-2-octyne 1a. This was obtained from 2-octyn-
1-ol according to the method described for the synthesis
of 1-chloro-2-heptyne.28 To a solution of alcohol (3.15 g;
25 mmol) and pyridine (0.29 g; 3.71 mmol) in 7 ml of
diethylether cooled at Ϫ20ЊC, was added thionylchloride
(3.75 g; 30 mmol) while keeping the temperature below
Ϫ20ЊC. The mixture was stirred for 12 h at room
temperature (20ЊC). The mixture was then cautiously
poured into a sodium hydrogen carbonate solution (2 g/
30 ml water) and extracted with diethylether (2×20 ml).
These extracts were combined, dried (MgSO4) and
evaporated. Reduced pressure fractional distillation
afforded 3 g (84%) of 1a, bp 45ЊC/3 mm Hg. IR (neat)
cmϪ1: 2960, 2920, 2860, 2230, 1470, 1260, 1150; 1H
NMR: d 4.15 (t, 2H, Jˆ2.5 Hz), 2.23 (tt, 2H, Jˆ6.9 Hz,
Jˆ2.5 Hz), 1.52 (quin, 2H, Jˆ7.2 Hz), 1.41–1.27 (m, 4H),
0.9 (t, 3H, Jˆ7.5 Hz); 13C NMR: d 87.5, 74.8, 31.1, 30.9,
28.0, 22.0, 18.6, 13.7; Anal. Calcd for C8H13Cl: C, 66.43;
H, 9.06. Found: C, 66.62; H, 9.10.
2-Acetoxy-2-methyl-3-octyne 4c. Based on a procedure
described by A. Hassner,29 to a mixture of 2-methyl-3-
octyn-2-ol (1 g; 7.00 mmol), triethylamine (1.73 g; 17.09
mmol) and 4-dimethylaminopyridine (52 mg; 0.43 mmol),
acetic anhydride (1.74 g; 17.09 mmol) was added dropwise.
The mixture was stirred for 14 h at room temperature,
hydrolyzed with saturated ammonium chloride solution,
extracted with diethylether and dried over MgSO4. Reduced
pressure fractional distillation afforded 1.11 g (85.5%) of
4c. Bp 77ЊC/15 mm Hg. IR (neat) cmϪ1: 2980, 2960,
1
2920, 2220, 1740, 1460, 1360, 1240, 1010; H NMR: d
2.20 (t, 2H, Jˆ6.9 Hz), 2.01 (s, 3H), 1.64 (s, 6H), 1.50–
1.58 (m, 4H), 0.9 (t, 3H, Jˆ7.1 Hz); 13C NMR: d 169.4,
84.6, 81.3, 72.6, 30.6, 29.3, 22.1, 21.6, 18.3, 13.6; MS: m/z
(%) 200 (Mϩ18), 183 (Mϩ1); 140 (100%); Anal. Calcd for
C11H18O2: C, 72.49; H, 9.95. Found: C, 72.42; H, 9.84.
1-Tosyloxy-2-octyne 1c. To a solution of p-toluene-
sulfonylchloride (5.24 g; 27.50 mmol) and 2-octyn-2-ol
(3.15 g; 25 mmol) in 40 ml of diethylether cooled at
Ϫ10ЊC, was added freshly fine powdered potassium

1856
S. Condon-Gueugnot, G. Linstrumelle / Tetrahedron 56 (2000) 1851–1857
3-Chloro-1-octyne 7a. This was obtained according to the
method described for the synthesis of 3-chloro-1-butene.30
A solution of triphenylphosphine (8.52 g; 32.50 mmol) and
1-octyn-3-ol (3.15 g; 25.00 mmol) in 12 ml of tetrachloro-
methane was stirred for 3 days at 20ЊC. The crude suspen-
sion was filtered through a short silica gel column and the
precipitate was rinsed with diethylether. The organic layers
were collected and the solvent removed. Purification by
column chromatography (eluent: pentane/ethylacetate:
98:2) afforded 2.52 g (70%) of 7a. IR (neat) cmϪ1: 3300,
(m, 4H), 0.89 (t, 3H, Jˆ6.8 Hz), 0.18 (s, 9H); 13C NMR:
d 214.0, 100.2, 96.5, 89.9, 76.8, 33.1, 31.0, 27.2, 22.4, 14.0,
Ϫ0.03; MS: m/z (%) 224 (100%, Mϩ18), 207 (Mϩ1); Anal.
Calcd for C13H22Si: C, 75.65; H, 10.74. Found: C, 75.60; H,
10.69.
3-Pentyl-deca-1,2-dien-4-yne 3. IR (neat) cmϪ1: 2960,
1
2920, 2860, 2220, 1940, 1460, 1380, 850; H NMR: d
4.91 (m, 2H), 2.34 (tt, 2H, Jˆ7.1 Hz, Jˆ1.1 Hz), 2.11 (tt,
2H, Jˆ7.5 Hz, Jˆ3 Hz), 1.45–1.70 (m, 4H), 1.20–1.45 (m,
8H), 0.83–1.00 (m, 6H); 13C NMR: d 213.4, 92.6, 89.9,
76.0, 75.2, 33.6, 31.1 (2C), 28.5, 27.3, 22.4, 22.2, 19.5,
14.0, 13.9; MS: m/z (%) 222 (Mϩ18), 205 (Mϩ1, 100%).
1
2960, 2920, 2860, 1460, 1380; H NMR: d 4.51 (td, 1H,
Jˆ6.7 Hz, Jˆ2.3 Hz), 2.60 (d, 1H, Jˆ2.3 Hz), 1.86–2.02
(m, 2H), 1.44–1.63 (m, 2H), 1.20–1.43 (m, 4H), 0.91 (t,
3H, Jˆ6.8 Hz); 13C NMR: d 82.1, 74.2, 47.9, 39.0, 31.0,
25.8, 22.5, 14.0.
5-Butyl-dodeca-3,4-dien-6-yne 5b. IR (neat) cmϪ1: 2960,
2920, 2860, 1945, 1940, 1460, 1380, 860; 1H NMR: d 5.28–
5.38 (m, 1H), 2.30 (td, 2H, Jˆ7.1 Hz, Jˆ0.9 Hz), 1.95–2.14
(m, 4H), 1.21–1.63 (m, 10H), 1.02 (t, 3H, Jˆ7.4 Hz), 0.84–
0.95 (m, 6H); 13C NMR: 208.1, 94.0, 91.1, 90.9, 76.5, 34.1,
31.1, 30.1, 28.6, 22.2, 22.1, 22.0, 19.6, 14.0, 13.9, 13.3; MS:
m/z (%) 236 (Mϩ18), 219 (Mϩ1, 100%); Anal. Calcd for
C16H26: C, 88.00; H, 12.00. Found: C, 88.12; H, 11.98.
3-Tosyloxy-1-octyne 7b. Following the same procedure
described above for the synthesis of 1c, 1-octyn-3-ol
(3.15 g; 24.96 mmol) was transformed into 7b (6.98 g;
100%). IR (neat) cmϪ1: 3300, 2960, 2920, 2860, 2120,
1
1600, 1360, 1170; H NMR: d 8.38 (d, 2H, Jˆ8.4 Hz),
7.34 (d, 2H, Jˆ8.2 Hz), 5.06 (td, 1H, Jˆ6.5 Hz,
Jˆ2.0 Hz), 2.46 (s, 3H), 2.40 (d, 1H, Jˆ2.3 Hz), 1.82 (m,
2H), 1.35–1.47 (m, 2H), 1.27–1.35 (m, 4H), 0.87 (t, 3H,
Jˆ6.8 Hz); 13C NMR: d 144.8, 133.8, 129.6, 128.0, 79.0,
76.1, 71.1, 35.5, 30.9, 24.1, 22.3, 21.6, 13.8; MS: m/z (%)
298 (100%, Mϩ18).
4-Butyl-1-methyl-undeca-2,3-dien-5-yne 5c. IR (neat)
1
cmϪ1: 2940, 2920, 2840, 1460, 1360; H NMR: d 2.29 (t,
2H, Jˆ7.1 Hz), 2.05 (t, 2H, Jˆ7.1 Hz), 1.71 (s, 6H), 1.23–
1.62 (m, 10H), 0.9 (t, 6H, Jˆ7.1 Hz); 13C NMR: d 205.6,
96.0, 89.7, 87.5, 76.8, 34.1, 30.9, 29.7, 28.3, 21.9, 21.6,
20.1, 19.2, 13.6, 13.5; MS: m/z (%) 236 (Mϩ18), 219
(Mϩ1, 100%); Anal. Calcd for C16H26: C, 88.00; H,
12.00. Found: C, 88.06; H, 12.02.
3-Chloro-4-nonyne 9a. Following the same procedure
described above for the synthesis of 3-chloro-1-octyne 7a,
non-4-yn-3-ol (2.00 g; 0.28 mmol) was transformed into 9a
(1.47 g; 64%), bp 47ЊC/6 mm Hg. IR (neat) cmϪ1: 2960,
2920, 2860, 2240, 1460; 1H NMR: d 4.53 (tt, 1H,
Jˆ6.3 Hz, Jˆ2.1 Hz), 2.24 (td, 2H, Jˆ6.9 Hz, Jˆ2.1 Hz),
1.87–2.00 (m, 2H), 1.31–1.60 (m, 4H), 1.08 (t, 3H,
Jˆ7.3 Hz), 0.91 (t, 3H, Jˆ7.1 Hz); 13C NMR: d 78.3,
87.1, 50.8, 32.8, 30.5, 21.8, 18.3, 13.4, 10.4; MS: m/z (%)
176 (Mϩ18), 158 (M); 81 (100%).
Methyl-7-pentyl-nona-7,8-dien-5-ynoate 6b. IR (neat)
1
cmϪ1: 2950, 2920, 2850, 1940, 1740, 1430, 1150, 850; H
NMR: d 4.89 (m, 2H), 3.68 (s, 3H), 2.44 (m, 4H), 2.08 (tt,
2H, Jˆ7.4 Hz, Jˆ3.0 Hz), 1.86 (quin, 2H, Jˆ7.2 Hz), 1.58–
1.40 (m, 2H), 1.33 (m, 4H), 0.90 (t, 3H, Jˆ6.8 Hz); 13C
NMR: 213.3, 173.3, 90.8, 89.5, 76.0, 69.0, 51.2, 33.3,
32.6, 30.9, 27.1, 23.7, 22.2, 18.8, 13.8; MS: m/z (%) 252
(100%, Mϩ18), 235 (Mϩ1).
2-Chloro-2-methyl-3-octyne 9b. Based on a procedure
described by Hennion and Boisselle31 which was modified
by replacing the mass of CuCl by the same mass of
CuCl2. To a mixture of CaCl2 (1.11 g; 10 mmol),
CuCl2 (0.8 g) and copper powder (10 mg; 0.16 mmol)
in concentrated hydrochloric acid (8.60 ml; 103 mmol),
2-methyl-3-octyn-2-ol (2.78 g; 19.86 mmol) was added
dropwise at 0ЊC. After stirring for 1 h at 20ЊC the
mixture was diluted in diethylether. The layers were
separated and the organic layer washed twice with
distilled water and dried over potassium carbonate. Distil-
lation under reduced pressure afforded 2.75 g (87%) of
9b with the presence of 8% of chloroallene isomer as
5-Pentyl-hepta-5,6-dien-3-yn-1-ol 6c. IR (neat) cmϪ1
:
1
3340, 2960, 2920, 2860, 1935, 1460, 1040, 850; H NMR:
d 4.90 (m, 2H), 3.74 (t, 2H, Jˆ6.2 Hz), 2.60 (tt, 2H,
Jˆ6.2 Hz, Jˆ1.2 Hz), 2.09 (tt, 2H, Jˆ7.4 Hz, Jˆ2.9 Hz),
1.80 (s, 1H), 1.44–1.57 (m, 2H), 1.24–1.40 (m, 4H), 0.89 (t,
3H, Jˆ6.8 Hz); 13C NMR: d 213.4, 89.4, 88.4, 77.1, 76.4,
60.9, 33.2, 30.9, 27.2, 23.7, 22.3, 13.9; MS: m/z (%) 196
(Mϩ18), 179 (100%, Mϩ1); Anal. Calcd for C12H18O: C,
80.85; H, 10.17. Found: C, 80.87; H, 10.13.
4-Pentyl-hexa-4,5-dien-2-yn-1-ol 6d. IR (neat) cmϪ1
:
determinated by GC, bp 35ЊC/2 mm Hg. IR (neat) cmϪ1
:
3330, 2940, 2920, 2840, 2200, 1930, 1020, 850; H NMR:
d 4.93 (m, 2H), 4.39 (t, 2H, Jˆ0.9 Hz), 2.10 (tt, 2H,
Jˆ7.4 Hz, Jˆ2.9 Hz), 1.63 (s, 1H), 1.43–1.58 (m, 2H),
1.24–1.38 (m, 4H), 0.90 (t, 3H, Jˆ6.8 Hz); 13C NMR: d
213.0, 89.4, 89.1, 80.8, 76.7, 51.4, 33.0, 31.0, 27.3, 22.4,
14.0; MS: m/z (%) 182 (Mϩ18, 100%), 165 (Mϩ1); Anal.
Calcd for C11H16O: C, 80.44; H, 9.81. Found: C, 80.31; H,
9.52.
1
1
2960, 2920, 2860, 2225, 1460, 1380; H NMR: d 2.22 (t,
2H, Jˆ7.0 Hz), 1.83 (s, 6H), 1.32–1.58 (m, 4H), 0.91 (t,
3H, Jˆ7.1 Hz); 13C NMR: 84.5, 83.1, 58.5, 34.9 (2C),
30.2, 21.6, 18.1, 13.3; MS: m/z (%) 161 (37Cl, Mϩ1),
159 (35Cl,Mϩ1); 123 (100%).
1-Trimethylsilyl-3-pentyl-penta-3,4-dien-1-yne 2. IR
(neat) cmϪ1: 2960, 2920, 2860, 2140, 1940, 1460, 1250,
1
850, 760; H NMR: d 4.93 (t, 2H, Jˆ2.9 Hz), 2.10 (tt,
Pentadeca-8,9-dien-6-yne 8a. IR (neat) cmϪ1: 2960, 2920,
2860, 1950, 1460, 1380, 870; 1H NMR: d 5.38 (m, 2H), 2.30
2H, Jˆ7.4 Hz, Jˆ2.9 Hz), 1.42–1.59 (m, 2H), 1.21–1.39

S. Condon-Gueugnot, G. Linstrumelle / Tetrahedron 56 (2000) 1851–1857
1857
3. For a review in allene chemistry see Bruneau, C.; Dixneuf, P. H.
In Comprehensive Organic Functional Group Transformations;
Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon:
New York; 1995; Vol. 2, pp 953–996.
(m, 2H), 2.05 (m, 2H), 1.20–1.65 (m, 12H), 0.90 (t, 6H,
Jˆ6.8 Hz); 13C NMR: d 211.9, 92.8, 90.8, 75.7, 73.3,
31.2, 31.0, 28.4 (2C), 28.2, 22.4, 22.2, 19.5, 14.0, 13.9;
MS: m/z (%) 222 (Mϩ18), 205 (Mϩ1).
4. For coupling with acetylen and diacetylen see Markl, G.;
Attenberger, P.; Kellner, J. Tetrahedron Lett. 1988, 29, 3651–
3654.
5. Mandai, M.; Nakata, T.; Murayama, H.; Yamaoki, H.; Ogawa,
M.; Kawada, M.; Tsuji, J. Tetrahedron Lett. 1990, 31, 7179–7180.
6. Mandai, M.; Murayama, H.; Nakata, T.; Yamaoki, H.; Ogawa,
M.; Kawada, M.; Tsuji, J. J. Organomet. Chem. 1991, 417, 305–
311.
Undeca-4,5-dien-2-yn-1-ol 8c. IR (neat) cmϪ1: 3340, 2960,
2920, 2860, 2210, 1940, 1460, 1380, 1010, 870; 1H NMR: d
5.40 (m, 2H), 4.38 (m, 2H), 2.06 (m, 2H), 1.69 (s, 1H),
1.20–1.53 (m, 6H), 0.90 (t, 3H, Jˆ6.9 Hz); 13C NMR: d
211.9, 93.5, 87.6, 79.1, 74.9, 51.5, 31.2, 28.4, 28.0, 22.4,
14.0; MS: m/z (%) 182 (Mϩ18), 164 (M), 107 (100%);
Anal. Calcd for C11H16O: C, 80.44; H, 9.81. Found: C,
80.37; H, 9.86.
7. Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1991, 32, 6109–
6112.
Methyl-7-butyl-undeca-7,8-dien-5-ynoate 10b. IR (neat)
8. Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett. 1993,
40, 6403–6406.
1
cmϪ1: 2960, 2920, 2860, 1945, 1740, 1430; H NMR: d
5.34 (m, 1H), 3.68 (s, 3H), 2.45 (t, 2H, Jˆ7.4 Hz), 2.39
(td, 2H, Jˆ7.4, 1.1 Hz), 1.97–2.12 (m, 4H), 1.85 (quin,
2H, Jˆ7.1 Hz), 1.26–1.54 (m, 4H), 1.02 (t, 3H, Jˆ7.4 Hz)
0.90 (t, 3H, Jˆ7.1 Hz); 13C NMR: d 208.0, 173.4, 94.0,
90.5, 89.3, 77.3, 51.3, 33.8, 32.6, 29.9, 23.9, 21.9, 21.8,
18.9, 13.7, 13.1; MS: m/z (%) 266 (Mϩ18), 249 (Mϩ1,
100%); Anal. Calcd for C16H24O2: C, 77.37; H, 9.74.
Found: C, 77.30; H, 9.76.
9. Crousse, B.; Alami, M.; Linstrumelle, G. Tetrahedron Lett.
1995, 36, 4245–4248.
10. Crousse, B.; Alami, M.; Linstrumelle, G. Tetrahedron Lett.
1997, 38, 5297–5300.
11. For a review in Palladium-catalyzed coupling of propargyl
compounds see Tsuji, J.; Mandai, T. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F., Stang, P. J., Eds.; 1998, pp
455–489.
12. Sevin, A.; Chodkiewicz, W.; Cadiot, P. Tetrahedron Lett.
1965, 24, 1953–1959.
13. Sevin, A.; Chodkiewicz, W.; Cadiot, P. Bull. Soc. Fr. Chim.
1974, 5/6, 913–917.
5-Butyl-nona-5,6-dien-3-yn-1-ol 10c. IR (neat) cmϪ1
:
1
3340, 2950, 2920, 2860, 1940, 1460, 1040; H NMR: d
5.30–5.42 (m, 1H), 3.73 (t, 2H, Jˆ6.2 Hz), 2.60 (td, 2H,
Jˆ6.2 Hz, Jˆ1.1 Hz), 1.98–2.15 (m, 4H), 1.75 (m, 1H),
1.26–1.55 (m, 4H), 1.02 (t, 3H, Jˆ7.4 Hz) 0.91 (t, 3H,
Jˆ7.1 Hz); 13C NMR: d 208.3, 94.4, 90.5, 87.2, 78.3,
61.1, 33.9, 30.0, 23.7, 22.1, 22.0, 13.9, 13.3; MS: m/z (%)
210 (Mϩ18), 193 (Mϩ1, 100%); Anal. Calcd for C13H20O:
C, 81.20; H, 10.48. Found: C, 81.15; H, 10.45.
´
14. Baudouy, R.; Gore, J. Bull. Soc. Fr. Chim. 1975, 9/10, 2153–
2158.
15. Vermeer, P.; Meijer, J.; Brandsma, L. Recl. Trav. Chim. 1975,
94, 112–114.
16. Ruitenberg, K.; Kleijn, H.; Elsevier, C. J.; Meijer, J.; Vermeer,
P. Tetrahedron Lett. 1981, 22, 1451–1452.
17. Preliminary report: Gueugnot, S.; Linstrumelle, G. Tetrahedron
Lett. 1993, 34, 3853–3856.
18. Baker, C. S. L.; Landor, P. D.; Landor, S. R. Proc. Chem. Soc.
1963, 340.
19. Baker, C. S. L.; Landor, P. D.; Landor, S. R. J. Chem. Soc.
1965, 4659–4664.
Methyl-7-butyl-9-deca-7,8-dien-5-ynoate 10e. IR (neat)
cmϪ1: 2960, 2940, 2860, 1740, 1440, 1360, 1160, 1220;
1H NMR: d 3.68 (s, 3H), 2.45 (t, 2H, Jˆ7.5 Hz), 2.38 (t,
2H, Jˆ6.9 Hz), 2.04 (t, 2H, Jˆ7.1 Hz), 1.85 (quin, 2H,
Jˆ7.3 Hz), 1.71 (s, 6H), 1.26–1.50 (m, 4H), 0.90 (t, 3H,
Jˆ7.1 Hz); 13C NMR: d 205.8, 175.8, 96.2, 88.1, 87.3,
77.8, 51.1, 34.0, 32.6, 29.7, 23.8, 21.6, 20.2, 18.8, 13.6;
MS: m/z (%) 266 (Mϩ18), 249 (Mϩ1, 100%); Anal.
Calcd for C16H24O2: C, 77.37; H, 9.74. Found: C, 77.02;
H, 9.48.
20. Elsevier, C. J.; Kleijn, H.; Ruitenberg, K.; Vermeer, P.
J. Chem. Soc., Chem. Commun. 1983, 1529–1530.
21. Elsevier, C. J.; Kleijn, H.; Boersma, J.; Vermeer, P. Organo-
metallics 1986, 5, 716–720.
´
22. Baudouy, R.; Gore, J. Synthesis 1974, 573–574.
23. Brandsma, L.; Verkruijsse, H. D. Preparative Acetylenic
Chemistry, Elsevier: Amsterdam, 1988.
24. Gueugnot, S.; Alami, M.; Linstrumelle, G.; Mambu, L.; Petit,
5-Butyl-7-methyl-octa-5,6-dien-3-yn-1-ol 10f. IR (neat)
cmϪ1: 3330, 2950, 2920, 2860, 1950, 1440, 1370, 1040,
840; 1H NMR: d 3.73 (t, 2H, Jˆ6.3 Hz), 2.59 (t, 2H,
Jˆ6.3 Hz), 2.05 (t, 2H, Jˆ7.2 Hz), 1.91 (s, 1H), 1.71
(s, 6H), 1.39 (m, 4H), 0.90 (t, 3H, Jˆ7.1 Hz); 13C NMR:
d 206.0, 96.7, 87.2, 85.8, 78.9, 61.0, 34.0, 29.8, 23.7,
21.8, 20.2, 13.7; MS: m/z (%) 210 (Mϩ18), 193 (Mϩ1,
100%).
ˆ
Y.; Larcheveque, M. Tetrahedron 1996, 52, 6635–6646.
25. Coulson, D. R. Inorg. Synth. 1972, 13, 121–124.
26. Kharasch, M. S.; Seyler, R. C.; Mayo, F. R. J. Am. Chem. Soc.
1938, 60, 882–884.
27. King, A. O.; Negishi, E. I. J. Org. Chem. 1978, 43, 358–360.
28. Brandsma, L.; Verkruijsse, H. D. Preparative Acetylenic
Chemistry, Elsevier: Amsterdam, 1971.
29. Hassner, A.; Krepski, L. R.; Alexanian, V. Tetrahedron 1978,
34, 2069–2076.
References
30. Snyder, E. J. J. Org. Chem. 1972, 37, 1466.
31. Hennion, G. F.; Boisselle, A. P. J. Org. Chem. 1961, 26, 725–
727.
1. Tamao, K. In Comprehensive Organic Synthesis, Trost, B. M.,
Fleming, I., Eds.; Pergamon: New York, 1991; 3, pp 435–480.
2. Jeffery-Luong, T.; Linstrumelle, G. Synthesis 1983, 1, 32–34.