M. Daryanavard et al.
Inorganic Chemistry Communications 122 (2020) 108274
coupling reaction of aryl halides with terminal alkynes (Scheme 1).
obtained using Pd(OAc)
ligand (The results were not reported in Table 1). However, Ni(acac)
the presence of (Ph P) py/CuI produced a considerable yield of the
2
or Ni(acac)
2
in the absence of (Ph
2
P)
2
py as the
2
in
2
. Experimental
.1. Materials and methods
, CuI, NiCl ·6H
2
2
Sonogashira coupling product in a short reaction time (Table 1, entry 6).
The Sonogashira coupling product yield increased with increasing
2
(
2 2
Ph P) py loading from 0.3 to 0.6 mol% (Table 1, entries 6,7) but did not
Ni(acac)
TBAB, aryl bromides, aryl chlorides, phenylacetylene, Et
CS CO , DMF (N,N-dimethylformamide), THF (tetrahydrofuran), DMSO
dimethylsulfoxide), CH Cl , toluene, EtOAc (ethyl acetate), n-heptane,
and MgSO were purchased from Merck Company, Germany in analyt-
ical grades. All chemicals were used as received without further purifi-
cation. (Ph P) py was synthesized according to our previous report
41].
The progress of the cross-coupling reactions was monitored using
thin layer chromatography (TLC) on the precoated silica gel fluorescent
54 nm (0.2 mm). The coupling products were characterized by their
2
2
2
O, NiCl
2
, Ni(OAc)
2
, Ni(cod)
2
, Pd(OAc)
2
,
significantly change with further loading (1.2 mol%) (Table 1, entry 8).
In the next step, the effect of tetrabutylammonium bromide (TBAB), the
so-called Jeffery condition [48,49], was investigated. While the yield of
the coupling product moderately increased with increasing TBAB from
0.3 to 0.6 mmol (Table 1, entries 9,10), it markedly increased using 1.5
mmol of TBAB (Table 1, entry 11). Further loading of TBAB up to 2
mmol led to a lower yield of the Sonogashira coupling product (Table 1,
entry 12).
3
N, KOH,
2
3
(
2
2
4
2
2
[
Furthermore, the various bases including Et
3
N, KOH, CS
NaO Bu were tested in the Sonogashira cross-coupling reaction and the
best performance was achieved using Et
N (Table 1, entries 11,13–15).
2 3
CO , and
t
2
3
melting points and NMR spectroscopy. NMR spectra of the products
were recorded on a Bruker Avance spectrometer at ambient temperature
The effect of solvent was also investigated on the Sonogashira cross-
coupling reaction. The Sonogashira coupling product was not
observed in both toluene and THF (Table 1, entries 16,17). Moreover,
the lower yield of the Sonogashira coupling product was obtained in
DMSO in comparison with DMF (Table 1, entry 18). The Sonogashira
cross-coupling reaction revealed higher yield and shorter reaction time
3
in CDCl .
2
.2. General procedure for the Sonogashira cross-coupling reaction
◦
◦
at 100 C compared to 120 and 80 C (Table 1, entries 19,20). Finally,
the optimal reaction conditions were examined in the absence of CuI as
the co-catalyst and consequently, the Sonogashira coupling product
yield was dramatically decreased (The result was not reported in
Table 1).
In a typical reaction, a suspension of aryl halide (1.0 mmol), phe-
nylacetylene (1.2 mmol), Et N (2.0 mmol), Ni(acac) (0.3 mol%),
Ph P) py (0.6 mol%), CuI (0.03 mol%), DMF (4 mL), and TBAB (1.5
3
2
(
2
2
mmol) were mixed in a reaction flask under a dry nitrogen atmosphere.
◦
The resulting mixture was stirred and heated at 100 C. The progress of
To evaluate the scope of this new protocol, the coupling reactions of
various aryl bromides and aryl chlorides with phenylacetylene were
investigated at the optimized reaction conditions (Tables 2 and 3).
Bromobenzene in coupling with phenylacetylene resulted in a high
yield of the Sonogashira coupling product (Table 2, entry 1). The
coupling of aryl bromides containing the electron-donating groups with
phenylacetylene gave good yields of the Sonogashira coupling products
the cross-coupling reaction was monitored by TLC. Upon completion of
the reaction, the mixture was cooled to room temperature, and the
organic phase was then extracted with CH
bined organic layers were dried over MgSO
2
Cl
2
(3 × 20 mL). The com-
4
, filtered, and evaporated to
dryness. The crude residue was purified by silica-gel chromatography
using EtOAc/n-heptane as the eluent. The Sonogashira coupling prod-
ucts were characterized using 1H and 13C NMR spectroscopy. The
(
Table 2, entries 1–4). However, the lower yield of the Sonogashira
spectral data of the known compounds are in agreement with those re-
coupling product was obtained using meta bromoanisole in comparison
with the para isomer (Table 2, entries 3,4). This result may be due to the
steric effect of the methoxy substituent in the meta position. A moderate
yield of the Sonogashira coupling product was obtained using 4-bromo-
N,N-dimethylaniline (Table 2, entry 5). Aryl bromides containing
electron-withdrawing groups effectively coupled with phenylacetylene
with excellent yields of the Sonogashira coupling products in the short
reaction times (Table 2, entries 6–9). The sterically hindered aryl bro-
mides such as 1-bromonaphthalene and 4-bromobiphenyl were also
suitable for this protocol and gave the high yields of the Sonogashira
coupling products (Table 2, entry 10,11).
ported previously [42–47].
3
. Results and discussion
The cross-coupling reaction of phenylacetylene with 4-bromoani-
sole, a relatively challenging test substrate due to its electron-poor na-
ture, was chosen as the model reaction to optimize the reaction
conditions. The results revealed that NiCl
the presence of (Ph P)
py/CuI were less effective (Table 1, entries 1–3).
Moreover, no Sonogashira coupling product was observed using Ni
2 2 2 2
·6H O, NiCl , and Ni(OAc) in
2
2
(
cod)
2
(Table 1, entry 4). Although Pd(OAc)
2
in the presence of
Chlorobenzene, 2-chlorotoluene, and 4-chloro-N,N-dimethylaniline
gave good yields of the Sonogashira coupling products in longer reac-
tion times compared with bromo analogous (Table 3, entries 1,2,5).
Morover, 4-chloroanisole led to a low yield of the Sonogashira coupling
product in a longer reaction time in comparison with 3-chloroanisole
(
Ph P)
2
2
py/CuI led to a complete conversion of aryl bromide, a moderate
yield of the Sonogashira coupling product was produced along with a
large amount of the undesired homocoupling product of phenyl-
acetylene (Table 1, entry 5). This result exhibits that Pd(OAc)
2
acts as a
C–H activating agent. Further, no Sonogashira coupling product was
2 2 2
Scheme 1. The Sonogashira cross-coupling reaction of aryl halides with terminal alkynes at the presence of Ni(acac) /(Ph P) py/CuI as a homogeneous catalyst.
2