Copper (II) catalyzed homocoupling and heterocoupling of terminal alkynes

Article abstract of DOI:10.1016/j.tetlet.2019.03.057

Cu(OTf)₂ catalyzed homo– and heterocoupling of aromatic and aliphatic terminal alkynes has been developed. Symmetric and unsymmetric 1,3-diynes have been synthesized in good yields under an aerobic condition in the presence of an organic base D

Full text of DOI:10.1016/j.tetlet.2019.03.057

Accepted Manuscript
Copper (II) Catalyzed Homocoupling and Heterocoupling of Terminal Alkynes
Maria Katrina Holganza, Leslie Trigoura, Suzanne Elfarra, Yoona Seo, Jeremy
Oiler, Yalan Xing
PII:
S0040-4039(19)30286-2
https://doi.org/10.1016/j.tetlet.2019.03.057
TETL 50698
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
6 February 2019
12 March 2019
22 March 2019
Please cite this article as: Holganza, M.K., Trigoura, L., Elfarra, S., Seo, Y., Oiler, J., Xing, Y., Copper (II) Catalyzed
Homocoupling and Heterocoupling of Terminal Alkynes, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/
j.tetlet.2019.03.057
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Maria Katrina Holganza, Leslie Trigoura, Suzanne Elfarra, Yoona Seo, Jeremy Oiler, Yalan Xing*

1
Tetrahedron Letters
Copper (II) Catalyzed Homocoupling and Heterocoupling of Terminal Alkynes
Maria Katrina Holganza, Leslie Trigoura, Suzanne Elfarra, Yoona Seo, Jeremy Oiler, Yalan Xing*
Department of Chemistry, William Paterson University, 300 Pompton Rd, Wayne, NJ 07470, US
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Cu(OTf)2 catalyzed homo- and heterocoupling of aromatic and aliphatic terminal alkynes has
been developed. Symmetric and unsymmetric 1,3-diynes have been synthesized in good yields
under an aerobic condition in the presence of an organic base DBU. This reaction features mild
conditions, a wide substrate scope, and excellent functional group compatibility.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
homocoupling
heterocoupling
Glaser reaction
1,3-diynes
1. Introduction
2. Results
Initially, phenyl acetylene was chosen to serve as a model
substrate for the study of the homocoupling of terminal alkynes
(Table 1). We first screened several copper catalysts including
CuBr2, CuBr, CuI, Cu(OAc)2, and Cu(OTf)2 in the presence of 1
equiv. of a base DBU at room temperature. The reaction was
exposed to air and acetone was employed as the solvent. To our
delight, the desired homocoupling product was obtained in 92%
yield when Cu(OTf)2 was used as the catalyst (entry 5). The
oxygen present in the air was proved to be an effective oxidant
for this coupling reaction. Different bases were then utilized to
further optimize the reaction yield (entry 6-8). However, Et3N
and pyridine gave lower yields (78% and 80%) of the coupling
product and inorganic base K2CO3 did not produce any desired
product. Next, we decided to investigate the solvent effect of this
transformation. THF, 1,4-dioxane, dichloromethane, and
acetonitrile were employed as the solvent in the presence of the
optimal copper catalyst and base (entry 9-12). It was found that
acetone was the best solvent among all the solvents we tested for
this transformation.
Petroleum-derived alkynes are readily available starting
materials and building blocks for organic synthesis. Conjugated
1,3-diynes are essential structural motifs found in many natural
3
products1, bio-active compounds2， and functional materials .
Therefore, coupling of terminal alkynes to access 1,3-diynes is of
great significance to the synthetic community. Classic methods
5
for terminal alkyne coupling include Glaser4, Eglington , and
6
Hay protocols . Significant efforts have been made to develop
more efficient and sustainable approaches to improve the
originally used palladium/copper bi-catalyst system for oxidative
coupling of terminal alkynes. Single transition metal catalysts
such as Pd7, Cu8, Ni9, Co10, and Ti11 have been employed in
alkyne coupling. However, there are still challenges in this field
such as the use of expensive and toxic palladium catalysts,
requirement of complex ligands, external oxidants, and harsh
reaction conditions.
Our research group has been interested in the development of
green and sustainable synthetic methods for useful
transformations of alkynes12. Herein, we wish to report our recent
study on the synthesis of symmetric and unsymmetric 1,3-diynes
by Cu(OTf)2 catalyzed homo- and heterocoupling of terminal
alkynes in the presence of DBU under ambient conditions. As a
comparatively cheaper and easily accessible metal, Cu (I) and (II)
salts attracted considerable attentions due to their high catalytic
efficiency.13 Balaraman and Kesavan reported a homo- and
hetero-coupling of terminal alkynes utilizing 10 mol% of
Cu(OAc)2·H2O as the catalyst, stoichiometric amount of
piperidine as the base, and CH2Cl2 as the sovlent.13a In
comparison, our work was able to improve the efficiency and
sustainability of the coupling by lowering the catalyst loading of
the Cu(II) salts to 5 mol% and using a halogen-free solvent.
Table 1. Optimization of copper catalyzed homocoupling of
phenylacetylene.a
Entry Solvent
Catalyst
Base
Isolated
yield
1
2
3
Acetone
Acetone
Acetone
CuBr2
CuBr
CuI
DBU
DBU
DBU
35%
9%
10%

2
Tetrahedron
4
Acetone
Acetone
Acetone
Acetone
Acetone
THF
Cu(OAc)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
DBU
DBU
Et3N
trace
92%
78%
0%
Table 3. Substrate scope of heterocoupling of terminal alkynes
5
6
7
K2CO3
8
pyridine 80%
9
DBU
DBU
53%
10
1,4-
Trace
Dioxane
11
12
CH2Cl2
CH3CN
Cu(OTf)2
Cu(OTf)2
DBU
DBU
70%
75%
a Reaction conditions: phenylacetylene 1a (1 equiv.), catalyst (5
mol%), base (1 equiv.), room temperature, open flask, 2-5 hours.
With the optimal reaction conditions in hands, the
homocoupling and heterocoupling reactions of a variety of
substrates were conducted to investigate the substrate scope and
limitations as well as the functional group compatibility of this
reaction (Table 2). All the reactions were conducted at room
temperature within a short period of time (2-5 hours). First, the
homocoupling of terminal alkynes bearing different functional
groups was conducted using our optimal reaction conditions.
Aromatic terminal alkynes (2a-2l) and aliphatic terminal alkynes
(2m-2n) both resulted in good to excellent yields (63% – 92%).
To our delight, it was observed that both electron withdrawing
and donating groups were compatible with the reaction
conditions. For instance, electron withdrawing groups on the
phenyl rings such as Br (2b), Cl (2c-2e), F (2f-2h), and ester (2j)
were tolerated well and resulted in good yields. Terminal alkyne
substrates containing electron donating groups (2i, 2k, and 2l)
also produced the coupling products in good yields. Substituents
at para-position of the phenyl ring (2d and 2h) provide the
coupling products in slightly higher yields than that of meta- (2c
and 2g) and ortho-positions. It was also found that aliphatic
terminal alkynes (2m-2n) resulted in lower yields in comparison
to the aromatic alkynes.
After observing excellent yields in the homocoupling
reactions of a variety of terminal alkyne substrates, the reaction
conditions were applied to the heterocoupling reaction of several
terminal alkynes. As shown in Table 3, unsymmetric 1,3-diynes
were synthesized in 68-86% percent yields. Phenylacetylene was
cross-coupled with several other aromatic terminal alkynes
bearing both electron-withdrawing and electron-donating groups
in good yields (3ai, 3aj, 3ab, and 3ak). Good yield was also
achieved in the coupling of an aromatic substrate containing an
electron withdrawing group to an aromatic substrate containing
an electron donating group (3id). Additionally, the
heterocoupling of an aromatic terminal alkyne and an aliphatic
terminal alkyne (3ln) was tested and a lower yield (68%) was
observed, as expected.
Table 2. Substrate scope of homocoupling of terminal alkynes
4. Conclusion
In summary, we have developed an efficient homo- and
heterocoupling of terminal aromatic and aliphatic alkynes under
open-air conditions. Readily available and inexpensive copper
(II) salt Cu(OTf)2 was found to smoothly catalyze the coupling
reaction in the presence of an organic base DBU. Symmetric and
unsymmetric 1,3-diynes with a wide substrate scope were
prepared in good to excellent yields and within a short reaction
time. Mild conditions, easy accessibility of the catalyst, and
excellent functional group compatibility make this method an
attractive protocol for the synthesis of complex 1,3-diynes.
Acknowledgments
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for support (or
partial support) of this research. The authors also would like to
thank the Research Release Time awards of William Paterson

3
University and the Center for Research, College of Science and
Health, William Paterson University of New Jersey.
submitted along with the manuscript and graphic files to the
appropriate editorial office.
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4
Tetrahedron
 Mild reaction conditions
 Open to air
 Excellent functional group
compatibility
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