Copper(i) chloride catalysed room temperature Csp-Csp homocoupling of terminal alkynes mediated by visible light

Article abstract of DOI:10.1039/c6cy01400c

We developed a technique mediated by visible light for the aerobic homocoupling of terminal alkynes to synthesize 1,3-conjugated diynes using a copper(i) chloride catalyst at room temperature. Compared with previously reported thermal processes, this photochemical method is simple, uses only mild reaction conditions, produces high yields and works well for substrates with electron-withdrawing groups without the need for bases/ligands, oxidants or palladium catalysts.

Full text of DOI:10.1039/c6cy01400c

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CopperIJI) chloride catalysed room temperature
Csp–Csp homocoupling of terminal alkynes
mediated by visible light†
Cite this: DOI: 10.1039/c6cy01400c
Received 3rd July 2016,
Accepted 30th August 2016
*
Arunachalam Sagadevan, Vaibhav Pramod Charpe and Kuo Chu Hwang
DOI: 10.1039/c6cy01400c
www.rsc.org/catalysis
We developed a technique mediated by visible light for the aerobic
homocoupling of terminal alkynes to synthesize 1,3-conjugated
diynes using a copperIJI) chloride catalyst at room temperature.
Compared with previously reported thermal processes, this
photochemical method is simple, uses only mild reaction
conditions, produces high yields and works well for substrates
with electron-withdrawing groups without the need for bases/li-
gands, oxidants or palladium catalysts.
(e.g. Cu) with the exclusion of palladium and bases/ligands
remains challenging.
Transition metal/organic dye based photoredox catalysis
initiated by visible light is now recognized as a powerful al-
ternative to metal-catalysed “thermal” reactions.12 This is be-
cause most of the reactions mediated by visible light are
performed at room temperature in the absence of ligands or
bases.12a Visible light is easier to handle than high-energy UV
light and complex organic molecules are more stable under
low-energy visible light irradiation. Photoredox Cu catalysts
have been used as an inexpensive catalytic system for C–C
coupling, atom transfer radical addition reactions,13 alkyne–
azide cycloaddition click reactions14 and Ullmann-type C–N
The discovery of mild and highly efficient methods for the
construction of 1,3-conjugated diynes and polyynes is a
central objective in organic synthesis.1 The 1,3-conjugated
diynes are important building blocks in numerous natural
products, pharmaceuticals and medicinally important
molecules, including anti-inflammatory, anticancer, anti-HIV
and antifungal drugs.1a,2 Conjugated diynes play an essential
part in the synthesis of functional organic molecules, such as
acetylenic oligomers, polymers and supramolecular materials
(Scheme 1).3
Glaser–Hay coupling was one of the earliest techniques of
synthesizing conjugated diynes through the homocoupling of
terminal alkynes4 and is still considered to be the classical
method.5 Many other processes have been developed, includ-
ing the use of Cu, Pd and bimetallic Pd/Cu, Ni/Cu catalyst
systems.6–10 Jia et al.11 reported the oxidative homocoupling
of terminal alkynes using CuIJI) or CuIJII) salts without any pal-
ladium or base. A dimethylsulfoxide solvent is necessary in
the homocoupling reaction (Scheme 2). However, this reac-
tion does not work at room temperature and is limited to
electron-rich terminal acetylenes. Despite the utility of such
processes, the development of an eco-friendly and green
method for the oxidative Csp–Csp homocoupling of terminal
alkynes at room temperature using an inexpensive catalyst
coupling reactions.15 We recently reported
a copperIJI)-
catalysed Sonogashira C–C cross-coupling reaction16 and oxi-
dative Csp–N cross-coupling reactions of terminal acetylenes
with anilines at room temperature mediated by visible
light,17 in which the key photocatalyst was copperIJI)-
phenylacetylide. We report here that copperIJI)-phenylacetylide
catalytically generated in situ can also catalyse the aerobic
Csp–Csp homocoupling reaction of terminal alkynes at room
temperature on irradiation with light from blue LEDs (see
Scheme 2). The unique features of our current work include:
(a) no base or ligand/additive is required; (b) the reaction
proceeds cleanly at room temperature; (c) there is a high re-
activity towards electron-withdrawing substituted aryl acety-
lenes and aliphatic alkynes; and (d) this protocol also
Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan,
Republic of China. E-mail: kchwang@mx.nthu.edu.tw
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c6cy01400c
Scheme 1 1,3-Diynes in natural and organic products.
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This result indicated that the concentration of terminal al-
kynes is crucial in the homocoupling reaction.
We also examined many other solvents, including metha-
nol, THF, dimethylsulfoxide and DMF. These solvents
afforded the homocoupling product, but did not give a com-
plete conversion (Table 1, entries 9–12). No reaction was ob-
served under solvent-free conditions (Table 1, entry 13). In
the screening of metal salts, CuX (X: Cl, Br, I) gave the
highest yield (98%) of desired product 2a (Table 1, entries 3,
5 and 6). When 2 mol% CuCl was used, the yield of product
2a decreased slightly to 80% (Table 1, entry 1). By contrast,
the CuIJII) salt did not catalyse the formation of the product in
any appreciable yield (Table 1, entries 7 and 8). Therefore the
key catalyst responsible for this reaction is most probably the
copperIJI)-related species. Control experiments showed that
with the exclusion of light, CuCl or O2, no (or only a trace
amount of) product was obtained (Table 1, entries 14–16).
We examined the reaction of various substituted aromatic
terminal alkynes under the optimized conditions. Excellent
yields were generally observed for substrates bearing
electron-donating and electron-neutral groups in a short pe-
riod of time (Table 2, 2a–2g). Alkynes containing the naph-
thalene moiety (1h) were also well tolerated in the reaction
and afforded product 2h in good yield.
The homocoupling reactions of electron-deficient aromatic
terminal alkynes are generally very difficult to accomplish be-
cause these groups have less π-basicity on the CC triple
bond and do not easily react when using a soft Lewis acid
such as CuIJI).18 However, the system reported here was more
effective for these substrates (1m–1t). The use of 5 mol%
CuCl was sufficient to promote the homocoupling reactions
and provided 1,3-diynes in good yields (82–93%) over a pe-
riod of 12–15 h (Table 2, 2m–2t). For halo-substituted aryl
acetylenes, F, Br and I afforded the corresponding products
in good to excellent yields (82–94%, Table 2, 2i–2l). Hetero-
arylalkynes (1u) and anisole-substituted aliphatic alkynes (1v)
can also effectively undergo homocoupling reactions to gen-
erate their corresponding products (2u and 2v) in very good
yields. Cyclohexylacetylene (1w) and 1-cyclohexenylacetylene
(1x) were also well tolerated in the reaction and produced
their corresponding products (2w and 2x) in good yields. The
homocoupling reaction of linear aliphatic alkynes was also
completed with 8 h of photoirradiation and a good yield was
obtained (2y–2dd). The current homocoupling reaction of a
broad range of electron-deficient phenylacetylenes/aliphatic
linear chain terminal alkynes provides a powerful method for
the synthesis of 1,3-conjugated diynes through a homo-
coupling reaction, which is either very difficult or not achiev-
able by previously reported thermal processes.11
Scheme 2 Comparison of previously reported thermal process and
the current CuCl-catalysed homocoupling of terminal alkynes medi-
ated by visible light.
provides a practical and mild synthetic approach to prepare
1,3-conjugated diynes under visible light irradiation.
We observed in an initial study that the presence of atmo-
spheric oxygen leads to the formation of the homocoupling
product exclusively through a Glaser–Hay coupling reaction.16
Based on this preliminary result, we further optimized the re-
action conditions using 5 mol% copperIJI) chloride without
any base in the presence of O2 under visible light irradiation.
The reaction yielded 55% of the desired homocoupling prod-
uct (Table 1, entry 1), indicating that a base is not required
for the observed reaction. CH3CN was found to be the most
efficient solvent in the solvent screening, providing the de-
sired product at 74% yield after 7 h of irradiation (Table 1,
entry 2). This might be because the polarity of CH3CN
matches well with that of the products and thus drives the re-
action forwards more efficiently. We observed a dramatic in-
crease in the homocoupling product yield to 98% on increas-
ing the concentration of terminal alkynes (Table 1, entry 3).
Table
1 Optimization studies for the homocoupling reaction of
phenylacetylene (1a)a
Entry
Catalyst (mol%)
Solvent
Yieldb
1
CuCl
CuCl
CuCl
CuCl (2)
CuBr
Cul
CuCl2
CuIJOAc)2
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CH3CN–MeOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
MeOH
THF
DMSO
DMF
Neat
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
55
74
98
80
98
98
Trace
nr
74
23
22
45
Trace
Trace
n.r
Trace
92
2c
3
4
5
6
7
8
9
10
11
12
13
14d
15e
16f
17g
18h
We also evaluated the green chemistry metrics11c of the
synthesis of the 1,3-diynes-(2g) on a preparative scale (see
ESI†). The green metrics values (E factor = 5.76, atom econ-
omy = 94%, atom efficiency = 82%, carbon efficiency = 100%
and reaction mass efficiency = 87%), the turnover number of
c. 17.6–20 and the turnover frequency of 2.8 h−1 indicated
that the current photochemical process is a very simple,
73
a
Reaction conditions: 1 M (1a) and 5 mol% catalyst in solvent. The
solution was irradiated with blue LEDs for 7 h in the presence of 1
b
atm O2 atmosphere (in balloon). Isolated yield (note: entry 4, 2
c
mol% catalyst used). 0.5 M of 1a was used in the reaction.
d
e
Reaction was conducted in the dark at RT. In the absence of CuCl
f
g
catalyst. In the absence of O2. 1 atm air (in balloon) was used in
the reaction. h Phenylacetylene-d1 was used as a substrate.
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Table 2 Results of CuCl-catalysed homocoupling reaction of terminal
acetylene (2a) mediated by visible lighta
Table 2 (continued)
2aa (91%, 8 h)
2bb (85%, 8 h)
2dd (86%, 8 h)
2a (98%, 7 h)
2c (98%, 7 h)
2e (95%, 7 h)
2b (99%, 7 h)
2d (98%, 7 h)
2f (94%, 7 h)
2cc (85%, 8 h)
a
Isolated yield after purification by column chromatography on
SiO2.
practical and eco-friendly method for the preparation of 1,3-
diynes, which makes this process a greener alternative to
existing thermal methodologies.6–11
2g (95%, 7 h)
2i (92%, 8 h)
2k (76%, 15 h)
2h (94%, 7 h)
2j (84%, 12 h)
A possible reaction mechanism for the CuCl-catalysed
homocoupling reaction mediated by visible light (λmax = 460
nm) is proposed in Scheme 3. The first step involves the for-
mation of the π–alkyne complex A, which makes the terminal
H of alkynes more acidic.18 In the next step, the irradiation
of the π–alkyne complex with visible light (λabs = 464 nm, see
Fig. 1) resulted in the in situ formation of copperIJI)
phenylacetylide B, as evidenced by the increase in the 480
nm absorption in the UV–visible absorption spectra (see
Fig. 1 and S1†). Thus irradiation of the π–alkyne complex
with visible light (λabs = 464 nm) is probably the key step in
the formation of the key catalyst, copperIJI)-phenylacetylide in
the absence of a base. Without photoirradiation, copperIJI)-
phenylacetylide could not be formed in the dark (thermal pro-
cess) and in the absence of base.17d Direct visible light excita-
tion of copperIJI)-phenylacetylide (λmax = 480 nm) leads to the
formation of a partial positive charge on the acetylene ligand
and a partial negative charge on the metal centre via ligand
to metal charge transfer.19 It is thought that the excited state
of copperIJI)-phenylacetylides undergoes facile intersystem
crossing16b,17,19 and hence C probably undergoes single
electron transfer to molecular oxygen to generate the super-
oxide17b,20 and electron-deficient CuIJII)-phenylacetylide D (see
EPR spectra in Fig. S1†). The dissociation of complex D leads
to the formation Csp–Csp homocoupling products and the
2l (85%, 12 h)
2n (82%, 15 h)
2m (93%, 12 h)
2o (88%, 15 h)
2p (86%, 15 h)
2r (88%, 15 h)
2t (85%, 12 h)
2q (82%, 15 h)
2s (87%, 12 h)
2u (88%, 10 h)
2v (86%, 10 h)
2w (88%, 8 h)
2y (90%, 8 h)
2x (84%, 8 h)
2z (88%, 8 h)
Scheme
3 Proposed mechanism for the CuCl-catalysed homo-
coupling of terminal alkynes mediated by visible light.
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1 UV–visible absorption spectra of in situ generated CuIJI)-
phenylacetylide (B) in CH3CN.
regeneration of CuCl. The proposed mechanism is supported
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copper(I)-phenylacetylide B (see Fig. 1).
Conclusions
We have successfully developed a novel homocoupling method
for terminal alkynes (including substrates with electron-
withdrawing groups) using CuCl as a catalyst and mediated by
visible light. This method can be used for the preparation of
1,3-conjugated diynes. This is the first example of the use of
visible light to initiate the Glasser homocoupling reaction of ter-
minal alkynes to synthesize 1,3-conjugated diynes at room tem-
perature using a CuCl catalyst in the absence of base/ligands
and expensive palladium catalysts. This mechanistic study illus-
trates that the π–alkyne complex A and copperIJI)-acetylides (al-
kyl and aryl, λmax = 425–490 nm) are the key light-absorbing spe-
cies and are responsible for the visible light-induced Csp–Csp
homocoupling of terminal alkynes. The cost-effective nature of
the catalyst, the absence of bases/ligands, the wide tolerance of
different functional groups (electron-withdrawing groups) and
the high reaction efficiency under low-energy visible light irradi-
ation make this process a green alternative to existing thermal
methodologies.
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Acknowledgements
This work was supported by the Ministry of Science and Tech-
nology, Taiwan.
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