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atmosphere, 3 h). Thus, in the absence of 3, phenyl acetylene 1a
was dimerised to give the diyne 5a in 75% yield. Further
different temperatures (Table 2). On close inspection of Table 2
one can see quite clearly that the presence of either unidentate
addition of PPh
3
(9 mol%) enhances the yield of the diyne to
3 3
(Ph P and (o-tol) P) or bidentate ligands (dppp and dppf) serves
9
8%. We turned our attention to the alkyl substituted acetylenes
to reduce the formation of the enyne side products. The
employment of unidentate ligands results in generally higher
selectivity for the diyne product, a trend which is observed at
and found that the enyne side products 6–8 were much more
prominent. Four general Pd-catalysts were screened, employing
1
-heptyne 1b as our benchmark substrate (Table 1). The
each temperature. Overall, it was found that additional Ph
3
P
production of enyne side products varies according to choice of
catalyst. Decreasing the reaction temperature to room tem-
perature substantially reduces the formation of enynes 6–8
provided reproducibly higher yields of the diyne products.
On mechanistic grounds an oxidant should not be required.
To address whether O acts as an oxidant, the reaction was
2
(
compare entries 4 & 5, Table 1). To our delight carrying out the
conducted under strictly anhydrous conditions (solvents were
degassed using freeze–pump–thaw cycles) under an argon
atmosphere using our standard conditions at 25 °C
reaction at 25 °C with additional PPh resulted in suppression of
3
the enynes (entry 6, Table 1). It should be noted that these
reactions do not proceed in the absence of triethylamine.
We were intrigued by the effect of additional ligand and thus
carried out investigations with other chelating phosphines, in
[PdCl
Et N/CH
> 92% yield. Thus the reaction does not require the presence of
2
(PPh
3
3 2 3
) ] (3 mol%), CuI (3 mol%), PPh (9 mol%) in dry
3
CN (2.5+1.5, v/v)). The reaction gave the diyne 5b in
the presence of [PdCl
2
(PPh
3
)
2
] as the catalyst, at a variety of
2
O . Using these standard conditions, a range of terminal alkynes
were evaluated for homocoupling (Table 3). The yields for the
Table 3 Dimerization of various terminal alkynes using optimised
other alkyl acetylenes 1c–1e were essentially quantitiative
a
conditions
(
1
entries 2–5, Table 3). Dimerisation of trimethylsilyl acetylene
f, pent-5-yn-1-ol 1g, ethyl but-4-yne carboxylate 1h and
propargyl alcohol 1i all resulted in homocoupling to give the
diynes 5f–i in good yields (entries 6–9, Table 3). Enynes 6–8
were not observed in these reactions. Switching to propargyl
acetate 1j and propargyl phenylsulfone 1k resulted in no
reaction (entries 10,11, Table 3). It is plausible that 1j and 1k
oxidatively adds to palladium, possibly resulting in allene
formation/decomposition. The cyclic alkynols 1l, 1m and 1n
couple efficiently using our reaction conditions (entries 12–14,
Table 3). The latter example demonstrates that structurally
complex terminal alkynes can be dimerised in good yield.
In summary, our method for the dimerisation of alkynes is
efficient for the synthesis of a variety of diynes at room
temperature. The method is tolerant to a range of functional
groups and does not require the addition of stoichiometric
Entry
1
Alkyne
Diyne (%)b
1a
1b
> 97 (98) 5a
2
3
> 99 (96) 5b
> 99 (96) 5c
1c
4
1d
> 99 (94) 5d
reagents, such as I
bromoacetate. Our reactions show that terminal alkynes readily
dimerise under seemingly standard conditions (Et N, CH CN,
cat. CuI and cat. [PdCl (PPh ] at reflux) for the Sonogashira
2
, chloroacetone, allyl bromide or ethyl
5
6
7
1e
1f
> 97 (98) 5e
(80) 5f
3
3
2
3 2
)
cross-coupling reaction. Detailed mechanistic studies are cur-
rently being pursued to understand this process more fully.
1
0
1g
(80) 5g
Future studies will address cross-dimerisation possibilities.
We are indebted to Dr G. C. Lloyd-Jones (University of
Bristol) and Professor R. J. K. Taylor (York) for valuable
comments and mechanistic insights. Johnson Matthey PLC
provided a generous loan of Pd salts. IJSF acknowledges the
University of York for financial support in the form of an IRPF
grant.
8
9
1h
1i
(80) 5h
> 97 (98) 5i
1
0
1
1j
0 5j
Notes and references
1
K. Sonogashira, in Comprehensive Organic Synthesis, Vol. 3, Perga-
mon Press, 1990, p. 521.
1
1k
0 5k
2
L. R. Marrison, PhD Thesis, Manchester Metropolitan University, UK,
1
998; L. R. Marrison, J. M. Dickinson and I. J. S. Fairlamb, Bioorg.
1
1
2
3
1l
(95) 5l
Med. Chem. Lett., 2002, 12, 3509; L. R. Marrison, J. M. Dickinson, R.
Ahmed and I. J. S. Fairlamb, Tetrahedron Lett., 2002, 43, 8853.
E. V. Tretyakov, D. W. Knight and S. F. Vasilevsky, J. Chem. Soc.,
Perkin Trans. 1, 1999, 3713.
4 (a) R. J. K. Taylor, in Organocopper Reagents: A Practical Approach,
Oxford University Press, 1994; (b) P. Siemsen, R. C. Livingston and F.
Diederich, Angew. Chem., Int. Ed., 2000, 39, 2632.
3
1m
(95) 5m
5
6
7
A. S. Hay, J. Org. Chem., 1962, 27, 3320; E. Valenti, M. A. Pericas and
F. Serratosa, J. Am. Chem. Soc., 1990, 112, 7405.
K. Sonogashira, Y. Tohda and N. Hagihara, Tetrahedron Lett., 1975, 16,
14
1n
(82) 5n
4
467.
R. Rossi, A. Carpita and C. Bigelli, Tetrahedron Lett., 1985, 26.
a
8 A. Lei, M. Srivastava and X. Zhang, J. Org. Chem., 2002, 67, 1969.
Reaction conditions: 2.0 mmol of alkyne, Et
PdCl (3 mol%), PPh
4 h. Determined by GC analysis (hexadecane standard) (values in
parenthesis are isolated yields after flash chromatography).
3
N (2.5 mL), CH
3
CN (1.5
9
M. Vlasa, I. Ciocan-Tarta, F. Margineanu and I. Oprean, Tetrahedron,
1996, 52, 1337.
mL), CuI (3 mol%), (PPh
2
)
3 2
2
3
(9 mol%), at 25 °C for
b
1
0 B. M. Trost, M. T. Sorum, C. Chan, A. E. Harms and G. Rühter, J. Am.
Chem. Soc., 1997, 119, 698.
CHEM. COMMUN., 2003, 632–633
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