Tetrahedron Letters
Enaminone ligand-assisted homo- and cross-coupling of terminal
alkynes under mild conditions
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Yunyun Liu , Chunping Wang, Xiaobo Wang, Jie-Ping Wan
College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper-catalyzed oxidative coupling reactions of terminal alkynes have been performed at room temper-
ature by using enaminone as effective ligand. Both symmetrical and unsymmetrical 1,3-diynes bearing
various functional groups have been synthesized in moderate to excellent yields via homo- and cross-
coupling reactions.
Received 5 March 2013
Revised 12 May 2013
Accepted 15 May 2013
Available online xxxx
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Terminal alkyne
Homo-coupling
Cross-coupling
Enaminone
Ligand
Conjugated 1,3-diynes are widely employed starting materials
in organic synthesis, including the synthesis of natural product,1–
coupling reaction,36,37 C–O coupling38,39 reaction, and Suzuki cou-
pling reaction.40 Based on our ongoing interests in the topic of
enaminone-type ligands promoted, transition metal-catalyzed C–
C bond formation reactions,41 we report herein the copper-cata-
lyzed, enaminone ligand-assisted homo- and cross-coupling reac-
tions of terminal alkynes under mild conditions.
Initially, the homo-coupling of phenylacetylene 1a yielding 1,4-
diphenylbuta-1,3-diyne 2a was selected as a model reaction. The
first entry was performed using CuBr2 as catalyst and enaminone
L1 as ligand in DMSO in the presence of 2 equiv of K2CO3, and corre-
sponding product 2a was obtained in 12% yield. After screening dif-
ferent inorganic and organic bases, we were pleased to find that the
entry using pyrrolidine exhibited significantly higher yield than
other bases (entries 1–8, Table 1). During the following experiments,
it has been found that the yield could be further improved when
dichloromethane was employed as solvent, while other solvents
such as toluene, DMF, ethyl lactate gave inferior results (entries 9–
12, Table 1). Interestingly, even though ligand L1 has been found
as generally efficient ligand in enaminone promoted coupling reac-
tions reported previously,35–39 p-nitrophenyl funtionalized enami-
none L2 was better ligand than L1, L3, L442,43 and other classical
3
polymer materials,4–6 pharmaceuticals,7,8 and many other func-
tional organic molecules.9,10 The dimerization coupling of two ter-
minal alkynes is the most straightforward method for the synthesis
of 1,3-diynes.11–14 Numerous efforts have been devoted to discov-
ering facile and simple catalyst systems for this kind of reactions
since the reports by Glaser15 and Hay.16 A general feature of most
reports on this oxidative coupling transformation is the utilization
of transition metal catalyst or co-catalysts such as Pd/Cu,17–21 Ag/
25
Cu,22 Ni/Cu,23,24 and Cu/Ti, and most of these reported catalytic
systems provide target diyne products with satisfactory results.
Among the efforts made for establishing economical approaches
of 1,3-diyne, reaction with copper as the only catalyst has drawn
considerable attention owing to the low cost of copper catalysts
and excellent reaction efficiency from these catalyzed reac-
tions.26–34 Most of the copper-catalyzed coupling protocols are
performed either at high temperature without ligand or under mild
reaction conditions with the assistance of a ligand. In several cases,
stoichiometric amount of copper was required. Therefore, develop-
ment of more efficient and atom economical approaches via
searching easily available and highly effective ligand remains as
desirable work. Enaminone derivatives that contain flexible N-
and O-chelating sites have been demonstrated as excellent ligands
in transition metal-catalyzed coupling reactions by this and other
groups, including Ullmann-type C–N coupling reaction,35 C–S
ligands such as L-proline L5 and 8-hydroxylquinoline L6 (entries
12–17, Table 1) in this reaction. Finally, other copper catalysts such
as CuBr, CuI, and Cu(OAc)2 were also respectively employed and
displayed no better effect than CuBr2 (entries 18–20, Table 1).
With the optimized conditions, we then investigated the homo-
coupling transformation using different terminal alkynes to dem-
onstrate the application scope of the present protocol.44 Results
obtained from entries using different alkyne substrates were
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Corresponding author. Tel./fax: +86 791 8812 0380.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
Liu, Yunyun
