Palladium-catalyzed acylation and/or homo-coupling of aryl- and alkyl-acetylenes

Article abstract of DOI:10.1016/j.tet.2011.07.032

Allyl or benzyl halides, through a Pd(0)-catalyzed reaction and under CO pressure, generate acyl-palladium/halides that, in the presence of a base and an aryl- and alkyl-acetylene, undergo nucleophilic acyl substitution giving conjugated acetylenic ketones. Diynes, resulting from alkyne/alkyne homo-coupling, were instead the main products in reactions performed without allyl or benzyl halides. Moreover, dimerization, trimerization, and cyclotrimerization reactions of acetylenes were observed in reaction carried out even without base.

Full text of DOI:10.1016/j.tet.2011.07.032

Tetrahedron 67 (2011) 7386e7391
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed acylation and/or homo-coupling of aryl- and alkyl-acetylenes
*
Serena Perrone, Fabio Bona, Luigino Troisi
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Allyl or benzyl halides, through a Pd(0)-catalyzed reaction and under CO pressure, generate acyl-palla-
dium/halides that, in the presence of a base and an aryl- and alkyl-acetylene, undergo nucleophilic acyl
substitution giving conjugated acetylenic ketones. Diynes, resulting from alkyne/alkyne homo-coupling,
were instead the main products in reactions performed without allyl or benzyl halides. Moreover, di-
merization, trimerization, and cyclotrimerization reactions of acetylenes were observed in reaction
carried out even without base.
Received 18 March 2011
Received in revised form 20 June 2011
Accepted 12 July 2011
Available online 22 July 2011
Keywords:
Palladium
Ó 2011 Elsevier Ltd. All rights reserved.
Acylation
Acetylenic ketones
Homo-coupling
Diynes
1. Introduction
The synthesis of acetylenic compounds, such as conjugated
acetylenic ketones has been rarely reported in the literature. A
Alkyne derivatives, such as diynes and conjugated acetylenic
ketones, are very interesting molecules in organic chemistry.
In particular diynes are a class of compounds that have an im-
portant role in the synthesis of natural products, polymer chem-
istry, supramolecular chemistry, and materials science because
they can be converted into various structural entities.1e4 In the past
years, several groups have developed homo-coupling reactions of
alkynes using various catalytic systems. An oxidative alkyne/alkyne
homo-coupling reaction is one of the most widely used procedures
for the synthesis of symmetrical diyne derivatives. Stoichiometric
amounts of copper salts5 or copper salts in catalytic amounts with
appropriate nitrogen bases in the presence of molecular oxygen6
have typically been used for the oxidative alkyne/alkyne homo-
coupling reactions. Oishi and co-workers showed that supported
copper hydroxide on titanium oxide, Cu(OH)x/TiO2, acted as an ef-
ficient heterogeneous catalyst for the oxidative alkyne/alkyne
homo-coupling.7 Recently, a catalytic system, which used Fe(acac)3
and a trace quantity of Cu(acac)2 as the co-catalyst and air as the
oxidant for the homo-coupling of terminal alkynes, has been de-
veloped.8 This catalytic system could also apply to the cross-
coupling reaction of two different terminal alkynes.8
general method, involving the alkylation of aldehydes with ethynyl
magnesium bromides and oxidation of propargylic alcohols to
conjugated ketones was used as shown in the Scheme 1.10
O
OH
R
EtMgBr
RCHO
MnO2
R'
R'
MgBr
R'
R'
R
Scheme 1. Alkylation of aldehydes with ethynyl magnesium bromides and oxidation
of the corresponding propargylic alcohols.
A direct ketone synthesis method through a nucleophilic sub-
stitution on the acyl chloride from ethynyl magnesium bromide in
the presence of Cu2Cl2 was also described (Scheme 2).11
O
R
RC(O)Cl
Cu2Cl2
MgBr
Ph
Ph
Scheme 2. Nucleophilic substitution on acyl chloride from ethynyl magnesium
bromide.
Alternatively, an acylation of terminal alkynes with acyl chlo-
rides, under copper and solvent-free conditions, using polystyrene-
supported palladium(0) complex,12 or a palladium-catalyzed car-
bonylative coupling of aryl iodides and phenylacetylene using
a mutiphase microflow system was re1ported (Scheme 3).13
Furthermore, a single example was reported where palladium,
in the form of a palladium/iminophosphine complex, was found to
catalyze the homo-coupling reaction of alkynylstannanes using
allyl acetate as an oxidant.9
O
Pd catalyst
CO
Ar
I
Ph
Ph
Ar
Scheme 3. Palladium-catalyzed carbonylative coupling of aryl iodides and
phenylacetylene.
* Corresponding author. Fax: þ39 0832 298701; e-mail address: luigino.troisi@
unisalento.it (L. Troisi).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.07.032

S. Perrone et al. / Tetrahedron 67 (2011) 7386e7391
7387
Recently, we have carried out several reactions involving palladium
catalysis. A series of different allyl or benzyl halides, through
a Pd(0)-catalyzed reaction and under CO pressure, generate an acyl-
palladium/halide intermediate (A). This last one has led to the
The same trend was found in a similar reaction carried out on
phenylacetylene and 3-chloro-2-methylpropene as the halide; after
a 36 h period, 5-methyl-1-phenyl-hex-4-en-1-yn-3-one (1b) and
1,4-diphenyl-1,3-butadiyne (2a) were obtained in 90% total yield
(Table 1, entry 3).
In the reaction with allyl chloride, p-methoxyphenylacetylene,
p-cyanophenylacetylene, 1,4-diethynylbenzene, treated under the
same conditions, led to the acetylenic ketones with E configuration,
1d, 1f, 1h, and trace amounts of the homo-coupling products 2b, 2c,
and 2d, respectively (Table 1, entries 5, 7, and 9).
synthesis of many differently substituted and functinalized b-lac-
tams in the presence of imines,14 or amides in the presence of
primary or secondary amines.15 Moreover, esters can be prepared
from alcohols and phenols using the same catalytic system
(Scheme 4).16
The reactions of terminal alkynes with benzyl chloride pro-
ceeded with lower yields than those ones with allyl chloride. Phe-
nylacetylene, p-methoxyphenylacetylene, p-cyanophenylacetylene,
and 1,4-diethynylbenzene, after a reaction time of 20e36 h, were
transformed into their corresponding diynes 2a, 2b, 2c, 2d and into
conjugated acetylenic ketones 1c,1e,1g, and 1i, respectively, in only
60e65% total yield (Table 1, entries 4, 6, 8, and 10).
Moreover, we verified that the aforementioned alkynes behaved
similarly with allyl and benzyl bromide and, in the absence of
significant differences, we considered it unnecessary to report this
data.
O
Ar'
N
Ar
Ar
N
Ar'
R
O
O
Pd(AcO)2, Ph3P
HN R'
R
X
PdX
N
Et3N, CO (400 psi)
THF, 110 °C
ROH
R'
A
X = Cl, Br
O
R
O
Aliphatic halides (Table 1, entry 11) and picolyl chlorides (Table
1, entries 12 and 13) instead did not lead to acylated compounds,
and therefore diyne 2a was the only product of the reactions.
Probably the palladium acyl chloride intermediate is not formed
from aliphatic and picolyl halides due to lack of unsaturation in the
alpha position, as in the first case, or because of the coordinating
effect of pyridine nitrogen, as in the second case.
Scheme 4. Acyl-palladium/halide in the synthesis of b-lactams, amides and esters.
With the aim of increasing the potential use of the acyl-palla-
dium/halide intermediate A, we have considered the possibility of
generating it in the presence of terminal alkynes, such as phenyl-
acetylene and the results of this investigation are reported herein.
Furthermore, the alkyl acetylenes reacted with the benzyl
chloride under the same reaction conditions. When hex-1-yne and
but-1-yne are reacted with benzyl chloride in the same reaction
conditions, they form, in 36 h, only the acetylenic ketone 1l or 1m
with a transformation yield of 30e32%, respectively. Not even
traces of the diyne have been observed (Table 1, entries 14 and 15).
Probably the decreased acidity of alkyl acetylenic hydrogen respect
to aryl acetylenic one could cause the low observed reactivity in
alkyne/alkyne homo-coupling.
However the same reactions, performed in a more polar solvent
(CH3CN) and with a stronger base than Et3N, such as NaOH, led to
an almost complete disappearance of the starting alkyne giving 1-
phenyl-oct-3-yn-2-one 1l (yield¼55%) and 1-phenyl-hex-3-yn-2-
one 1m (yield¼45%), respectively (Table 1, entries 16 and 17). Un-
der these conditions, small quantities of homo-coupling products
2. Results and discussion
Phenylacetylene, allyl chloride, Pd(AcO)2, Ph3P, and Et3N were
dissolved in THF and placed in an autoclave under CO pressure. The
reaction mixture was heated at 100 ꢀC for about 6 h. After this time,
GC analysis showed the formation of a new product in 41% total
yield. Purification by chromatography on silica gel of the crude
mixture afforded the acylation product 1a, E-1-phenylhex-4-en-1-
yn-3-one, in which the unsaturation was in the more stable posi-
tion conjugated to the carbonyl group. The homo-coupling product
of phenylacetylene, 2a, was found too. The yield and the product
distribution are reported in Table 1 (entry 1). Interestingly, a better
transformation yield (94%) and the same ratio (1a/2a 70:30) were
observed with longer reaction times (Table 1, entry 2).
Table 1
Acetylenic ketones and diynes synthesis
O
CO (400 psi), Et3N, 110 °C
Pd(AcO)2, Ph3P, THF
R
R' Cl
R
R
R
R'
1a-m
2a-f
Entry
RCCH
R0Cl
Time (h)
Total yielda (%)
Products distributionb (%)
1
2
O
Ph
1
2
3
6
36
36
41
94
PhCCeCCPh 2a (31)
2a (30)
(69)
1a
1b
Cl
1a (70)
PhCCH
O
O
Ph
Ph
90
65
2a (17)
Cl
(83)
4
PhCH2Cl
36
2a (41)
Ph
1c (59)
(continued on next page)

7388
S. Perrone et al. / Tetrahedron 67 (2011) 7386e7391
Table 1 (continued )
Entry
RCCH
R0Cl
Time (h)
Total yielda (%)
Products distributionb (%)
1
2
O
p-MeOPh
C l
5
36
85
MeOPhCCeCCPhOMe 2b (2)
(98)
1d
p-MeOPhCCH
O
6
7
PhCH2Cl
36
36
60
80
2b (10)
p-MeOPh
p-NCPh
Ph
(90)
1e
O
C l
NCPhCCeCCPhCN 2c (1)
(99)
(85)
1f
p-NCPhCCH
O
p-NCPh
8
9
PhCH2Cl
36
20
63
88
2c (15)
Ph
1g
O
p-HCCPh
C l
HCCPhCCeCCPhCCH 2d (5)
1h
(95)
p-HCCPhCCH
O
p-HCCPh
10
PhCH2Cl
20
60
2d (20)
Ph
1i
(80)
11
12
13
PhCCH
CH3CH2Cl
2-PyCH2Cl
4-PyCH2Cl
14
14
14
99
99
99
d
d
d
2a (100)
2a (100)
2a (100)
O
14
15
CH3(CH2)3CCH
CH3CH2CCH
PhCH2Cl
PhCH2Cl
36
36
30
32
CH3(CH2)3
CH3CH2
d
d
Ph
(100)
1l
O
Ph
1m
(100)
16c
17c
CH3(CH2)3CCH
CH3CH2CCH
PhCH2Cl
PhCH2Cl
10
10
95
95
1l (55)
1m (45)
CH3(CH2)3CCeCC(CH2)3CH3 2e (5)
CH3CH2CCeCCCH2CH3 2f (5)
a
Yield measured by GC analysis on the basis of the converted starting acetylene.
Product distribution measured by GC analysis or isolation of the product.
Reaction conditions: CH3CN as solvent and NaOH as base. Benzyl alcohol, 1-phenylhept-2-yne and phenylacetic acid were identified in the mixture, too.
b
c
2e and 2f together with other compounds resulting from nucleo-
philic substitution of OHꢁ on the benzyl chloride, such as benzyl
alcohol, 1-phenylhept-2-yne, and phenylacetic acid were identified
in the mixture, too.
According to our results, two possible mechanisms for Pd-
catalyzed acylation and homo-coupling reaction of terminal acet-
ylenes were proposed (Scheme 5).
palladium acyl chloride intermediate (A) would release the conju-
gated acetylenic ketone (1aem) and generate Pd(0).
Acetylide anion could also react with a second Pd-activated
molecule of alkyne to afford the homo-coupling product (2aef).
According to the suggested mechanism, carbon monoxide, allyl
and/or benzyl chloride seems unnecessary for the alkyne/alkyne
homo-coupling reaction. For this reason, we have performed dif-
ferent reactions without them. The results of this investigation are
summarized in Table 2.
In particular, a solution of phenylacetylene, Pd(AcO)2, PPh3, and
Et3N in THF heated at 110 ꢀC, after a 6 h period, provided 1,4-
diphenyl-1,3-butadiyne 2a, as shown in Scheme 5, together with
other products derived from dimerization (3a, 4a) and asymmet-
rical and symmetrical cyclotrimerization (5a, 6a), Table 2, entry 1.
Even p-methoxyphenylacetylene behaved similarly. The homo-
coupling, dimerization and cyclotrimerization products, 2b, 3b,
4b, 5b, and 6b were formed, respectively, under the same condi-
tions (Table 2, entry 2).
O
HCl
R
C
C
R"
R'Cl
CO
1a-m
Pd(0)
R
C
C Pd H
R'PdCl
O
R
C C
R'
PdCl
Et3N
A
R
C
CH
R C CH
Pd(0)
Hex-1-yne produced different results affording only dimeric
enynes 3d, 4d and cyclotrimers 5d, 6d. No homo-coupling product
was observed in this reaction, probably due to a lower acidity of the
acetylenic proton (Table 2, entry 4). Several new approaches to the
rhodium catalyzed dimerization17 and cobalt catalyzed cyclo-
trimerization of alkynes have been reported recently.18
H2
R
C
C
C
C R
2a-f
Scheme 5. Suggested mechanism for acetylenic ketones and diynes synthesis.
The importance of the acetylide anion formation to obtain the
diyne was put in evidence carrying out the same reactions
With the aid of the base (Et3N), terminal acetylene could lead to
the formation of acetylide anion. The next reaction with the

S. Perrone et al. / Tetrahedron 67 (2011) 7386e7391
7389
Table 2
1,3-Diynes, 1,3-enynes, and tri-substituted benzenes synthesis
R
R
R
R
Pd (AcO) , Ph P
2
3
R
R
R
R
R
R
Et N, THF, 110 °C
3
R
R
R
5a-d
6a-d
2a-d
3a-d
4a-d
Entry
RCCH
Time (h)
Total yielda (%)
Products distributiona (%)
2
3
4
5
6
1
2
3
4
PhCCH
6
6
6
15
6
6
95
90
98
40
90
79
98
2a (55)
2b (48)
3a (35)
3b (35)
4a (2)
4b (6)
5a (5)
5b (8)
6a (3)
6b (3)
p-MeOPhCCH
p-HCCPhCCH
CH3(CH2)3CCH
PhCCH
p-MeOPhCCH
p-HCCPhCCH
Mixture of polymers and traces of 2ce6c identified only by GCeMSc
d
d
d
3d (40)
3a (55)
3b (55)
4d (30)
4a (8)
4b (10)
5d (15)
5a (28)
5b (25)
6d (15)
6a (9)
6b (10)
5b
6b
7b
6
Mixture of polymers and traces of 2ce6c identified only by GCeMSc
a
Yield and product distribution measured by GC analysis.
Reactions performed without Et3N.
The mixture of polymers observed is due to the dimerization and trimerization of the starting materials on both sides of the molecules.
b
c
described above without Et3N. In all these cases, the homo-
coupling product was not found (Table 2, entries 5 and 6).
Analyzing the collected data we hypothesize that the activated
complex ReCCePdeH can be added to a second molecule of acet-
ylene generating the enynes 3aed and 4aed. These last ones,
through the catalysis of palladium, can further add a third molecule
of alkyne generating the two possible tri-substituted benzenes
5aed and 6aed, asymmetrical and symmetrical, respectively. In
addition, trace amounts of liner trimers were detected by GCeMS
analysis of the reaction mixture.
Finally, a distinctive trend was found in similar reactions carried
out on 1,4-diethynylbenzene with two acetylenic groups. Di-
merization and subsequent trimerization on both sides of the
molecule resulted in a mixture of high molecular weight polymers,
both in the presence (Table 2, entry 3) and absence of Et3N (Table 2,
entry 7). These polymers are currently analyzed in terms of struc-
ture and their properties will be evaluated.
as the solvent and TMS as an internal standard (
d
¼7.26 ppm for
1H spectra;
d
¼77.0 ppm for 13C spectra). The IR spectra were
recorded with an FT-IR spectrophotometer Digilab Scimitar Se-
ries FTS 2000. GCeMS analyses were performed with an Agilent
Technologies 6850 series II gas chromatograph (5% phenyl-
polymethylsiloxane capillary column, 30 m, 0.25 mm i.d.),
equipped with a 5973 Network mass-selective detector operating
at 70 eV. The electrospray ionization [HRMS (ESI)] experiments
were carried out in a hybrid QqTOF mass spectrometer (PE
SCIEXeQSTAR) equipped with an ion-spray ionization source. MS
(þ) spectra were acquired by direct infusion (5
m
L minꢁ1) of
Lꢁ1
a solution containing the appropriate sample (10 pmol
m
)
dissolved in a solution 0.1% acetic acid, methanol/water (50:50)
at the optimum ion voltage of 4800 V. The nitrogen gas flow was
set at 30 psi (pounds per square inch) and the potentials of the
orifice, the focusing ring and the skimmer were kept at 30, 50
and 25 V relative to ground, respectively. Melting points were
determined with an Electrothermal melting point apparatus and
are uncorrected. TLC was performed on Merck silica gel plates
with F-254 indicator; viewing was by UV light (254 nm). Column
chromatographies were performed on silica gel (63e200 mm)
using petroleum ether/diethyl ether (Et2O) mixture as eluent. All
reactions involving air-sensitive reagents were performed under
an atmosphere of nitrogen in oven-dried glassware by using
syringe/septum cap techniques.
3. Conclusions
In conclusion, we have discovered a simple and efficient method
for transforming terminal acetylenes into conjugated acetylenic
ketones, 1,3-diynes, 1,3-enynes, asymmetrical, and symmetrical tri-
substituted benzenes. The ability to modulate the formation of the
various unsaturated compounds, depending on the reaction con-
ditions, makes this synthetic methodology employable for a num-
ber of applications involving polymer chemistry, supramolecular
chemistry and materials science.
4.2. General procedure for the palladium-catalyzed acylation
and homo-coupling reaction of terminal alkynes
4. Experimental section
4.1. General
A solution of terminal alkyne (1.0 mmol), aliphatic or aryl ha-
lide (1.5 mmol), Pd(AcO)2 (4 mg, 0.02 mmol), PPh3 (21 mg,
0.08 mmol), and Et3N (202 mg, 2.0 mmol) in THF (15 mL) was
placed in a 45 mL autoclave. The autoclave was purged, pressur-
ized (400 psi CO) and then heated at 110 ꢀC, under magnetic
stirring, for 6e36 h. After this time, the solution was cooled to
room temperature and the solvent was removed under reduced
pressure to give a crude material. The crude mixture was then
purified by chromatography on silica gel (petroleum ether/Et2O
90:10) to afford, for each reaction shown in Table 1, the conjugated
acetylenic ketone 1aem and the corresponding diyne of the ter-
minal alkyne 2aef as pure compounds. The compounds 1c, 2a, 2e,
and 2f are commercially available. The compounds 1a,19 1l,20
1m,21 2b,22 2c,23 and 2d,24 are known and their characterization
data resulted in agreement with those reported in literature. The
Triethylamine, palladium(II) acetate, triphenylphosphine,
phenylacetylene, p-methoxyphenylacetylene, p-cyanophenylace-
tylene, and 1,4-diethynylbenzene, hex-1-yne, but-1-yne, allyl
chloride and bromide, benzyl chloride and bromide, 3-chloro-2-
methylpropene, chloroethane, 2-chloromethylpyridine, 4-
chloromethylpyridine, acetonitrile, and NaOH were of commer-
cial grade (Aldrich) and used without further purification. THF
was purified by distillation from sodium before use. Petroleum
ether refers to the 40e60 ꢀC boiling fraction. The 1H and the 13C
NMR spectra were recorded with a Bruker Avance 400 apparatus
(400.13 and 100.62 MHz, for 1H and 13C, respectively) with CDCl3

7390
S. Perrone et al. / Tetrahedron 67 (2011) 7386e7391
acetylenic ketones 1b, and 1dei are unknown and their full
characterization is reported below.
(triple bond), 1655 (C]O) cmꢁ1; GCeMS (70 eV): m/z (%)¼195 (45)
[M]þ, 166 (70), 154 (100), 140 (30), 127 (40); HRMS (ESI): calcd for
C13H10NO: (196.0763) [MþH]þ; found: (196.0765).
4.2.1. E-1-Phenylhex-4-en-1-yn-3-one (1a). Known product, the
following characterization data are in agreement with those repor-
ted in the literature.19 Yield: 49 mg (29%), yellow oil. Rf (petroleum
4.2.7. 4-(3-Oxo-4-phenylbut-1-ynyl)benzonitrile (1g). Yield: 132
mg (54%), light yellow solid with mp 80e81 ꢀC (n-hexane). Rf
(petroleum ether/Et2O 90:10): 0.45; 1H NMR (400.13 MHz, CDCl3):
ether/Et2O 90:10): 0.54; 1H NMR (400.13 MHz, CDCl3):
d¼2.02 (3H,
dd, J¼1.6, 6.9 Hz, CH3), 6.26 (1H, dq, J¼1.6,15.6 Hz, ]CHeC]O), 7.28
(1H, dq, J¼6.9, 15.6 Hz, ]CHeCH3), 7.39 (2H, t, J¼7.3 Hz, Ph), 7.45
(1H, t, J¼7.2 Hz, Ph), 7.59 (2H, d, J¼7.1 Hz, Ph) ppm; 13C NMR
d
¼3.94 (2H, s, CH2), 7.29e7.40 (5H, m, Ph), 7.51 (2H, d, J¼8.3 Hz, Ph),
7.64 (2H, d, J¼8.3 Hz, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
d¼52.1, 89.3, 90.0, 114.1, 117.8, 124.6, 127.6, 128.8, 129.8, 132.2, 133.0,
(100.62 MHz, CDCl3):
d
¼18.5, 86.1, 91.0, 120.1, 128.6, 130.5, 132.8,
133.3, 184.6 ppm; FTIR (CHCl3): 3027, 2930, 2855, 2223 (triple
bond), 1650 (C]O) cmꢁ1; GCeMS (70 eV): m/z (%)¼245 (25) [M]þ,
217 (70), 203 (40), 154 (100), 91 (60); HRMS (ESI): calcd for
C17H12NO: (246.0920) [MþH]þ; found: (246.0921).
133.9,149.5,178.3 ppm; FTIR (CHCl3): 3012, 2960, 2854, 2210 (triple
bond),1648 (C]O),1621,1310,1190 cmꢁ1; GCeMS (70 eV): m/z (%)¼
170 (38) [M]þ, 155 (9), 141 (58), 129 (100); HRMS (ESI): calcd for
C12H11O: (171.0810) [MþH]þ; found: (171.0811).
4.2.8. E-1-(4-Ethynylphenyl)hex-4-en-1-yn-3-one
(1h). Yield:
4.2.2. 5-Methyl-1-phenylhex-4-en-1-yn-3-one (1b). Yield: 138 mg
(75%), pale yellow oil. Rf (petroleum ether/Et2O 90:10): 0.52; 1H
163 mg (84%), orange solid with mp 95e96 ꢀC (n-hexane). Rf (pe-
troleum ether/Et2O 90:10): 0.46; 1H NMR (400.13 MHz, CDCl3):
NMR (400.13 MHz, CDCl3):
d
¼1.96 (3H, s, CH3), 2.27 (3H, s, CH3),
d
¼2.03 (3H, dd, J¼1.5, 6.9 Hz, ]CHCH3), 3.24 (1H, s, acetylenic H),
6.27 (1H, s, ]CH), 7.36 (2H, t, J¼7.1 Hz, Ph), 7.42 (1H, t, J¼7.1 Hz, Ph),
6.26 (1H, dq, J¼1.5, 15.6 Hz, COCH), 7.27 (1H, dq, J¼6.9, 15.6 Hz, ]
CHCH3), 7.49 (2H, d, J¼8.0 Hz, Ph), 7.54 (2H, d, J¼8.0 Hz, Ph) ppm;
7.56 (2H, d, J¼7.1 Hz, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼21.1, 27.8, 89.0, 90.3, 120.4, 126.1, 128.5, 130.3, 132.8, 158.0,
13C NMR (100.62 MHz, CDCl3):
d
¼18.5, 80.2, 82.7, 87.6, 89.9, 120.5,
176.4 ppm; FTIR (CHCl3): 3014, 2927, 2860, 2208 (triple bond), 1645
(C]O), 1604, 1269, 1221, 1120, 1048 cmꢁ1; GCeMS (70 eV): m/z
(%)¼184 (40) [M]þ, 179 (6), 102 (20), 129 (100); HRMS (ESI): calcd
for C13H13O: (185.0967) [MþH]þ; found: (188.0966).
124.3, 132.2, 132.6, 133.8, 149.6, 178.1 ppm; FTIR (CHCl3): 3012,
2960, 2855, 2207 (triple bond), 1650 (C]O) cmꢁ1; GCeMS (70 eV):
m/z (%)¼194 (69) [M]þ,165 (85),153 (100),139 (15),126 (60); HRMS
(ESI): calcd for C14H11O: (195.0811) [MþH]þ; found: (195.0810).
4.2.3. 1,4-Diphenylbut-3-yn-2-one (1c). Product commercially
available. Yield: 84 mg (38%), yellow oil. Rf (petroleum ether/Et2O
4.2.9. 4-(4-Ethynylphenyl)-1-phenylbut-3-yn-2-one
(1i). Yield:
117 mg (48%), dark yellow solid with mp 62e63 ꢀC (n-hexane). Rf
90:10): 0.56; 1H NMR (400.13 MHz, CDCl3):
d
¼3.94 (2H, s, CH2),
(petroleum ether/Et2O 90:10): 0.53; 1H NMR (400.13 MHz, CDCl3):
7.29e7.46 (10H, m, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼52.2,
d
¼3.23 (1H, s, acetylenic H), 3.93 (2H, s, CH2), 7.29e7.46 (9H, m, Ph)
87.7, 92.9, 119.8, 127.4, 128.1, 128.6, 128.7, 129.8, 130.8, 133.1,
185.2 ppm; FTIR (CHCl3): 3034, 2929, 2859, 2204 (triple bond),1702
(C]O), 1666 cmꢁ1; GCeMS (70 eV): m/z (%)¼220 (12) [M]þ, 192
(20), 129 (100), 91 (15); HRMS (ESI): calcd for C16H13O: (221.0966)
[MþH]þ; found: (221.0967).
ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼52.1, 80.4, 82.7, 89.0, 91.7,120.1,
124.7, 127.4, 128.7, 129.8, 132.2, 132.8, 133.1, 184.9 ppm; FTIR (CHCl3):
3034, 2929, 2860, 2200 (triple bond), 1665 (C]O) cmꢁ1; GCeMS
(70 eV): m/z (%)¼244 (45) [M]þ, 216 (55), 154 (71), 153 (100), 91 (35);
HRMS (ESI): calcd for C18H13O: (245.0967) [MþH]þ; found: (245.0969).
4.2.4. E-1-(4-Methoxyphenyl)hex-4-en-1-yn-3-one
166 mg (83%), yellow oil. Rf (petroleum ether/Et2O 90:10): 0.55; 1H
NMR (400.13 MHz, CDCl3):
(1d). Yield:
4.2.10. 1-Phenyloct-3-yn-2-one (1l). Known product, the following
characterization data are in agreement with those reported in the
literature.20 Yield: 104 mg (52%), yellow oil. Rf (petroleum ether/Et2O
d
¼2.02 (3H, dd, J¼1.5, 6.9 Hz, ]CHCH3),
3.85 (3H, s, OCH3), 6.26 (1H, dq, J¼1.5, 15.6 Hz, COCH), 6.90 (2H, d,
90:10): 0.57; 1H NMR (400.13 MHz, CDCl3):
d¼0.95 (3H, t, J¼6.5 Hz,
J¼8.9 Hz, Ph), 7.27 (1H, dq, J¼6.9, 15.6 Hz, ]CHCH3), 7.56 (2H, d,
CH3),1.33e1.36 (2H, m, CH3CH2), 1.43e1.46 (2H, m, CH3CH2CH2), 2.15
(2H, t, J¼6.6 Hz, CH2eCC), 3.65 (2H, s, CH2Ph), 7.10e7.16 (5H, m, Ph)
J¼8.9 Hz, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
¼18.1, 55.4,
d
85.5, 92.5, 113.7, 114.3, 131.2, 134.9, 150.0, 160.0, 172.0 ppm; FTIR
(CHCl3): 3009, 2927, 2855, 2210 (triple bond), 1650 (C]O),
1455 cmꢁ1; GCeMS (70 eV): m/z (%)¼200 (68) [M]þ, 185 (17), 172
(21), 159 (100),132 (48); HRMS (ESI): calcd for C13H13O2: (201.0916)
[MþH]þ; found: (201.0914).
ppm; 13C NMR (100.62 MHz, CDCl3):
d
¼13.5, 18.1, 21.9, 29.1, 43.0,
79.1, 91.7, 127.3, 129.1, 130.0, 135.1, 178.2 ppm; FTIR (CHCl3): 3020,
2927, 2860, 2210 (triple bond), 1655 (C]O), 1453 cmꢁ1; GCeMS
(70 eV): m/z (%)¼200 (65) [M]þ, 171 (20), 119 (21), 91 (100); HRMS
(ESI): calcd for C14H17O: (201.1279) [MþH]þ; found: (201.1278).
4.2.5. 4-(4-Methoxyphenyl)-1-phenylbut-3-yn-2-one
108 mg (54%), pale yellow oil. Rf (petroleum ether/Et2O 90:10):
(1e). Yield:
4.2.11. 1-Phenylhex-3-yn-2-one (1m). Knownproduct, the following
characterization data are in agreement with those reported in the
literature.21 Yield: 74 mg (43%), yellow oil. Rf (petroleum ether/Et2O
0.57; 1H NMR (400.13 MHz, CDCl3):
d
¼3.80 (3H, s, OCH3), 3.90 (2H,
s, CH2), 6.90 (2H, d, J¼8.9 Hz, Ph), 7.20e7.56 (7H, m, Ph) ppm; 13C
90:10): 0.47; 1H NMR (400.13 MHz, CDCl3):
d
¼1.20 (3H, t, J¼6.6 Hz,
CH3), 2.10(2H, q, J¼6.6Hz,CH3CH2), 3.63(2H, s,CH2Ph), 7.10e7.15 (5H,
m, Ph) ppm; 13C NMR (100.62 MHz, CDCl3):
NMR (100.62 MHz, CDCl3):
d¼48.1, 56.0, 86.8, 90.6, 114.1, 114.8,
127.1, 129.1, 129.3, 133.1, 135.2, 159.8, 181.0 ppm; FTIR (CHCl3): 3030,
2926, 2860, 2208 (triple bond), 1650 (C]O) cmꢁ1; GCeMS (70 eV):
m/z (%)¼250 (13) [M]þ, 222 (15), 159 (100), 91 (20); HRMS (ESI):
calcd for C17H15O2: (251.1073) [MþH]þ; found: (251.1076).
d¼11.5, 13.6, 43.5, 77.2,
91.5, 127.2, 129.0, 130.1, 135.2, 177.9 ppm; FTIR (CHCl3): 3021, 2928,
2857, 2209 (triple bond),1654 (C]O),1453 cmꢁ1; GCeMS (70 eV): m/
z (%)¼172 (40) [M]þ,143 (35),119 (20), 91 (100); HRMS (ESI): calcd for
C12H13O: (173.0966) [MþH]þ; found: (173.0964).
4.2.6. E-4-(3-Oxohex-4-en-1-ynyl)benzonitrile (1f). Yield: 154 mg
(79%), yellow solid, mp 127e128 ꢀC (petroleum ether). Rf (petro-
4.2.12. 1,4-Diphenylbuta-1,3-diyne (2a). Product commercially
available. Yield: 200 mg (99%, Table 1, entry 11), white solid, mp
85e87 ꢀC.
leum ether/Et2O 90:10): 0.49; 1H NMR (400.13 MHz, CDCl3):
d
¼2.04
(3H, d, J¼6.9 Hz, ]CHCH3), 6.28 (1H, d, J¼15.7 Hz, COCH), 7.30 (1H,
dq, J¼6.9, 15,7 Hz, ]CHCH3), 7.69 (4H, s, Ph) ppm; 13C NMR
(100.62 MHz, CDCl3):
133.1, 133.7, 150.4, 177.6 ppm; FTIR (CHCl3): 3030, 2926, 2856, 2225
d
¼18.6, 87.8, 88.8, 113.8, 117.9, 125.1, 132.2,
4.2.13. 1,4-Bis(4-methoxyphenyl)buta-1,3-diyne (2b). Known prod-
uct, the following characterization data are in agreement with

S. Perrone et al. / Tetrahedron 67 (2011) 7386e7391
7391
those reported in the literature.22 Yield: 16 mg (6%, Table 1, entry 6),
yellow solid, mp 138e140 ꢀC. 1H NMR (400.13 MHz, CDCl3):
¼3.83
(6 H, s, OCH3), 6.88 (4H, d, J¼8.6 Hz, Ph), 7.48 (4H, d, J¼8.6 Hz, Ph)
ppm; 13C NMR (100.62 MHz, CDCl3):
References and notes
d
1. Bohlmann, F.; Burkhart, F. T.; Zero, C. Naturally Occurring Acetylenes; Academic:
London, 1973.
2. Hansen, L.; Boll, P. M. Phytochemistry 1986, 25, 285e293.
3. Matsunaga, H.; Katano, M.; Yamamoto, H.; Fujito, H.; Mori, M.; Takata, K. Chem.
Pharm. Bull. 1990, 38, 3480e3482.
d
¼55.5, 73.2, 81.4, 114.2, 114.3,
134.3, 160.2 ppm; HRMS (ESI): calcd for C18H15O2: (263.1072)
[MþH]þ; found: (263.1070).
4. Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem. 2000, 112, 2740e2767.
5. Glaser, C. Ber. Dtsch. Chem. Ges. 1869, 2, 422e424.
4.2.14. 4,40-(Buta-1,3-diyne-1,4diyl)dibenzonitrile
(2c). Known
6. (a) Hay, A. S. J. Org. Chem. 1962, 27, 3320e3323; (b) Campbell, I. D.; Eglinton, G.
Org. Synth. 1965, 45, 39e42; (c) Li, J.; Jiang, H. Chem. Commun. 1999,
2369e2370; (d) Salazar, R.; Fomina, L.; Fomine, S. Polym. Bull. 2001, 47,
151e158; (e) Sharifi, A.; Mirzaei, M.; Naini-Jamal, M. R. J. Chem. Res. 2002,
628e630; (f) Yadav, J. S.; Reddy, B. V. S.; Reddy, K. B.; Gayathri, K. U.; Prasad, A.
R. Tetrahedron Lett. 2003, 44, 6493e6496; (g) Wang, L.; Yan, J.; Li, P.; Wang, M.;
Su, C. J. Chem. Res. 2005, 112e115; (h) Lu, X.; Zhang, Y.; Luo, C.; Wang, Y. Synth.
Commun. 2006, 36, 2503e2511; (i) Kamata, K.; Yamaguchi, S.; Kotani, M.;
Yamaguchi, K.; Mizuno, N. Angew. Chem. 2008, 120, 2441e2444; (j) Yamaguchi,
K.; Kamata, K.; Yamaguchi, S.; Kotani, M.; Mizuno, N. J. Catal. 2008, 258,
121e130.
product, the following characterization data are in agreement with
those reported in the literature.23 Yield: 23 mg (9%, Table 1, entry 8),
brown solid, mp 182e184 ꢀC. 1H NMR (400.13 MHz, CDCl3):
d¼7.48
(4H, d, J¼8.6 Hz, Ph), 7.61 (4H, d, J¼8.6 Hz, Ph) ppm; 13C NMR
(100.62 MHz, CDCl3):
d
¼74.5, 76.8, 112.3, 115.6, 127.0, 131.7,
133.0 ppm; HRMS (ESI): calcd for C18H9N2: (253.0765) [MþH]þ;
found: (253.0766).
7. Oishi, T.; Katayama, T.; Yamaguchi, K.; Mizuno, N. Chem.dEur. J. 2009, 15,
7539e7542.
8. Meng, X.; Li, C.; Han, B.; Wang, T.; Chen, B. Tetrahedron 2010, 66, 4029e4031.
9. Shirakawa, E.; Nakao, Y.; Murota, Y.; Hiyama, T. J. Organomet. Chem. 2003, 670,
132e136.
10. Jones, E. R. H.; Skattebol, L.; Whiting, M. C. J. Chem. Soc. 1956, 4765e4768.
11. Fukumaru, T.; Awata, H.; Hamma, N.; Komatsu, T. Agric. Biol. Chem. 1975, 39,
519e527.
12. Bakherad, M.; Keivanloo, A.; Bahramian, B.; Jajarmi, S. Synlett 2011, 311e314.
13. Rahman, M. T.; Fukuyama, T.; Kamata, N.; Sato, M.; Ryu, I. Chem. Commun. 2006,
2236e2238.
4.2.15. 1,4-Bis(4-ethynylphenyl)buta-1,3-diyne (2d). Known prod-
uct, the following characterization data are in agreement with
those reported in the literature.24 Yield: 30 mg (12%, Table 1, entry
10), white solid, mp 148e151 ꢀC. 1H NMR (400.13 MHz, CDCl3):
d
¼3.06 (2H, s, CCH), 7.40 (8H, s, Ph) ppm; 13C NMR (100.62 MHz,
CDCl3):
d
¼77.1, 77.3, 84.1, 85.0, 122.2, 132.3 ppm; HRMS (ESI): calcd
for C20H11: (251.0861) [MþH]þ; found: (251.0862).
14. (a) Troisi, L.; De Vitis, L.; Granito, C.; Pilati, T.; Pindinelli, E. Tetrahedron 2004, 60,
6895e6900; (b) Troisi, L.; Ronzini, R.; Granito, C.; Pindinelli, E.; Troisi, A.; Pilati,
T. Tetrahedron 2006, 62, 12064e12070; (c) Troisi, L.; Granito, C.; Pindinelli, E.
Tetrahedron 2008, 64, 11632e11640.
4.2.16. 4,6-Decadiyne (2e) and 3,5-octadiyne (2f). Products com-
mercially available; they were isolated in traces and identified only
by GCeMS.
15. Troisi, L.; Granito, C.; Rosato, F.; Videtta, V. Tetrahedron Lett. 2010, 51, 371e373.
16. Tommasi, S.; Perrone, S.; Rosato, F.; Salomone, A.; Troisi, L. Synthesis, submitted
for publication.
4.3. General procedure for the synthesis of 1,3-diynes, 1,3-
enynes and tri-substituted benzenes
1
7. Ardizzoia, G. A.; Brenna, S.; Cenini, S.; La Monica, G.; Ma sciocchi, N.; Maspero,
A. J. Mol. Catal. A: Chem. 2003, 333, 204e205.
18. (a) Hilt, G.; Vogler, T.; Hess, W.; Galbiati, F. Chem. Commun. 2005, 1474e1475;
(b) Hilt, G.; Hengst, C.; Hess, W. Eur. J. Org. Chem. 2008, 2293e2297.
19. Tolstikov, G. A.; Valitov, F. K.; Kuchin, A. V. Zh. Obshch. Khim. 1983, 53,
2284e2286.
20. Tanaka, M.; Kobayashi, T. Jpn. Kokai Tokkyo Koho 1985, 5.
21. (a) Bardone-Gaudemar, F. Ann. Chim. (Paris) 1958, 3, 52e107; (b) Manoiu, D.;
Manoiu, M.; Dinulescu, I. G.; Avram, M. Rev. Roum. Chim. 1985, 30, 223e227.
22. (a) Kakusawa, N.; Yamaguchi, K.; Kurita, J. J. Organomet. Chem. 2005, 690,
2956e2966; (b) Adimurthy, S.; Malakar, C. C.; Beifuss, U. J. Org. Chem. 2009, 74,
5648e5651.
23. Kumar, V.; Chipeleme, A.; Chibale, K. Eur. J. Org. Chem. 2008, 1, 43e46.
24. Guha, S.; Frazier, C. C.; Porter, P. L.; Kang, K.; Finberg, S. E. Opt. Lett. 1989, 14,
952e954.
25. Bassetti, M.; Pasquini, C.; Raneri, A.; Rosato, D. J. Org. Chem. 2007, 72,
4558e4561.
A solution of terminal alkyne (1.0 mmol), Pd(AcO)2 (4 mg,
0.02 mmol), PPh3 (21 mg, 0.08 mmol), and Et3N (202 mg, 2.0 mmol)
in THF (10 mL) was heated at reflux, under magnetic stirring for 6 h.
The solution was cooled to room temperature and the solvent was
removed under reduced pressure to give a crude material. The
crude mixture was then purified by chromatography on silica gel
(petroleum ether/Et2O 95:5) to afford, as shown in Table 2, 1,4-
dialkyl- and 1,4-diaryl-1,3-butadiynes 2aec together with di-
merization products 3aed and 4aed, asymmetrical and symmet-
rical cyclotrimerisation products 5aed and 6aed. The compounds
3a, and 6a, are commercially available. The compounds 3b,25 3d,26
4a,27 4b,28 4d,29 5a, 6a30 5b, 6b,30b,31 and 5d, 6d32 are known and
their characterization data resulted in agreement with those
reported in literature. Compounds 2ce6c were isolated in traces
and identified only by GCeMS.
26. (a) Ben-Efraim, D. A. Tetrahedron Lett. 1967, 11, 957e960; (b) Brown, H. C.; Bhat,
N. G.; Bassavaiah, D. Isr. J. Chem. 1984, 24, 72e75.
27. Singh, F. V.; Weber, M.; Guadagnin, R. C.; Stefani, H. A. Synlett 2008, 1889e1893.
28. Boese, W. T.; Goldman, A. S. Organometallics 1991, 10, 782e786.
29. Selimov, F. A.; Rutman, O. G.; Dzhemilev, U. M. Zh. Org. Khim. 1983, 19,
1853e1856.
30. (a) Geny, A.; Agenet, N.; Iannazzo, L.; Malacria, M.; Aubert, C.; Gandon, V. An-
gew. Chem., Int. Ed. 2009, 48, 1810e1813; (b) Cadierno, V.; Garcia-Garrido, S. E.;
Gimeno, J. J. Am. Chem. Soc. 2006, 128, 15094e15095.
Acknowledgements
31. Joosten, A.; Soueidan, M.; Denhez, C.; Harakat, D.; Helion, F.; Namy, J.-L.; Vasse,
J.-L.; Szymoniak, J. Organometallics 2008, 27, 4152e4157.
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1439e1442.
Thanks are due to the University of Salento and C.I.N.M.P.I.S
(Consorzio Interuniversitario Nazionale Metodologie e Processi
Innovativi di Sintesi) for financial support.