D.-X. Liu et al. / Tetrahedron 70 (2014) 2416e2421
2417
oxidized into the corresponding 1,3-diynes? To explore the cata-
lytic activity of copper salt toward oxidative decarboxylative
speCsp homocoupling of aryl propiolic acid, we carried out the
reactions of aryl propiolic acids using CuI as catalyst and I as oxi-
dant without extra ligands under mild conditions and successfully
prepared a set of 1,4-diarylsubstituted 1,3-diynes in good to ex-
cellent yields, which will be described as follows.
acetylene18b,24 could be oxidized into 2a by O
similar reaction was carried out in pure O
yield (Table 1, entry 2)) was increased. Could the yield of the cou-
pling product be increased by using other oxidant agents? A range
of oxidants, such as benzoquinone (BQ), di-tert-butyl peroxide
2
in air. When the
, only the yield of 3a (40%
2
C
2
(DTBP), H
2
O
2
, K
2
S
2
O
8
, (NH
4
)S
2
O
8
, Cu(OAc)
2
, I
2
were therefore cho-
as a base, THF as
sen in the presence of CuI as a catalyst, K
a solvent at 60 C. As shown in Table 1 (entries 1e9), the oxidant
2
CO
3
ꢀ
2
was necessary for such a coupling reaction, and I could afford the
2
. Results and discussion
desirable product 2a in 92% yield. To find the most active ligand-
free catalyst system, several other Cu(I) or Cu(II) salts as catalysts
were used for the oxidative decarboxylative homocoupling of aryl
propiolic acid (Table 1, entries 10e16). It was found that CuI was the
best one (Table 1, entry 9) among those listed in Table 1. A blank
experiment confirmed that the yield of the product was only 3% in
the absence of the Cu catalyst (Table 1, entry 17). For a variety of
To screen out what copper salt could catalyze the oxidative
decarboxylative homocoupling of aryl propiolic acids, we firstly
carried out the reactions of phenyl propiolic acid (0.2 mmol), CuI
ꢀ
(
0.06 mmol), and K
2
CO
3
(0.4 mmol) in THF (2 mL) at 60 C in air for
2
4 h. A standard workup produced 1,4-diphenylbuta-1,3-diyne (2a)
in 2% yield and ethynylbenzene (3a) in 5% yield (Table 1, entry 1).
This result implied that CuI might initialize the decarboxylation of
phenyl propiolic acid and the in situ-formed Cu species of phenyl
other bases (e.g., Na
yields were observed (Table 1, entries 18e22) compared with that
using K CO . The solvent dependence of the decarboxylative
2 3 3 4 3
CO , K PO , KOH, NaHCO , and DBU), the lower
2
3
homocoupling reaction was observed. Five different solvents (THF,
toluene, DMF, DMSO, and MeCN) were employed to evaluate their
influence on the performance of the coupling reaction (Table 1,
entries 23e26). The catalyst did not work in toluene, but it showed
low activity in THF, DMF, or MeCN. Complete conversion of the 3-
phenyl propiolic acid into 1,4-diphenylbuta-1,3-diyne was ach-
Table 1
Optimizing the reaction conditions for the decarboxylative homocoupling reactions
of phenyl propiolic acida
ꢀ
ieved within 24 h at 60 C in DMSO (Table 1, entry 26). The in-
fluence of catalyst and oxidant loading on the reaction efficiency
was also studied. The yield of 2a was gradually reduced from 100%
ꢀ
Entry Cat.
Oxidant
Air
Base
Solvent T ( C) Yield (%) of
2
a/3a (%)b
to 81% when the catalyst loading was changed from 30 mol % to
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
MeCN
DMF
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
2/5
ꢀ
2
0 mol % in DMSO at 60 C (Table 2, entries 26e28). When the
O
2
2/40
0/55
6/21
3/31
3/33
22/16
8/22
92/0
3/0
62/0
trace/0
<1/0
87/0
2/0
dosage of I
be obtained in DMSO (Table 1, entry 29). The yield of 2a was de-
creased from 100% to 86% if the oxidant I loading was changed
2
was maintained at 55 mol %, the 100% yield of 2a could
BQ
H O
2 2
DTBP
2 2 8
K S O
2
from 55 mol % to 50 mol % (Table 1, entry 30). The reaction tem-
4 2 2 8
(NH ) S O
ꢀ
perature exerted great impact on this reaction. At 50 C, the 100%
Cu(OAc)
2
CuI
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
I
2
yield of 2a could also be obtained in the presence of 30 mol %
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
CuBr
CuCl
[Cu(MeCN)
catalyst in DMSO in 24 h (Table 2, entry 32), while the reaction
ꢀ
ꢀ
temperature was lowered to 45 C or 40 C, and its yield was de-
creased to 97% or 83% (Table 2, entries 33 and 34). Finally, we in-
]PF
4 6
Cu
Cu(acac)
Cu(OAc)
2
O
vestigated effects of the amount of K
The yield of 2a would be reduced when the dosage of K
the reaction time was shortened (Table 1, entries 35 and 36). In
addition, in this CuI/I catalytic system, the head-to-head
enyne (1,4-diphenylbut-1-en-3-yne) and head-to-tail enyne (2,4-
2
CO
3
and the reaction time.
2
2
2
CO or
3
CuCl
2
7/0
3/0
2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
KOH
DBU
55/19
81/3
43/34
12/40
83/0
98/0
91/0
0/0
2
3
Na
2
CO
3
diphenylbut-1-en-3-yne) byproducts were not observed by GC.
According to the aforementioned optimization experiments, the
optimal reaction conditions were identified as follows: 30 mol % of
NaHCO
3
K
3
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
K
2
PO
4
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2 3 2
CuI (as the catalyst), 2 equiv of K CO (as the base), 55 mol % I (as
an oxidant), and DMSO (as a solvent) with a reaction temperature
Toluene 60
ꢀ
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
60
60
60
60
60
55
50
45
40
50
50
100/0
95/0
81/0
100/0
86/0
100/0
100/0
97/0
83/0
91/0
92/0
of 50 C. With the optimized reaction conditions in hand, a variety
c
of aryl propiolic acids were chosen as the substrates in this oxida-
tive decarboxylative homocoupling reaction. As shown in Table 2,
the coupling reactions were performed well for all the substrates
examined, and the desired products were isolated in good to ex-
d
e
f
e
e
cellent yields. To our delight, both p-substituted electron-rich (Ar,
e
t
OMe, Bu) and electron-deficient (F, Br, COMe, CO
2
Me) of phenyl
e
e,g
e,h
propiolic acids could all afford the desired products in high yields
(87%e97%). As shown in entries 2e10, the electron-deficient p-
substituted phenyl propiolic acids were found to proceed in higher
yields than those with electron-donating substituent groups. For
example, lower yields (entries 4 and 5) were obtained for aryl
propiolic acids bearing electron-donating substituent groups rela-
tive to those of electron-withdrawing ones (entries 9 and 10). It
seemed that 4, or 3/5-substituents of benzene ring did not hamper
the decarboxylative homocoupling reaction (entries 3, 5 and 11).
However, this reaction was sensitive to the 2 or/and 6-substituent
a
Reaction conditions: phenyl propiolic acid (0.2 mmol), cat. (30 mmol%), oxidant
ꢀ
(
60 mol %), K
2
CO
3
(0.4 mmol), solvent (2 mL), 60 C, 24 h.
b
GC yields.
c
d
e
f
2
5 mmol% CuI.
0 mmol% CuI.
5 mol % of I
0 mol % of I
CO (0.3 mmol).
Reaction time¼20 h.
2
5
5
2
.
2
.
g
h
K
2
3