Sequentially Pd/Cu-Catalyzed Alkynylation-Oxidation Synthesis of 1,2-Diketones and Consecutive One-Pot Generation of Quinoxalines

Article abstract of DOI:10.1002/ejoc.201900783

We report a simple and efficient one-pot synthesis of 1,2-diketones by concatenation of two Pd/Cu-catalyzed processes: Pd⁰/Cu^I-catalyzed Sonogashira coupling of terminal alkynes with aryl (pseudo)halides furnishes internal alkynes, which are directly transformed by Pd^II/Cu^II-catalyzed Wacker-type oxidation with DMSO and oxygen as dual oxidants to furnish 1,2-diketones. With this efficient, catalyst economical process, various aryl iodides and triflates are efficiently transformed in high yields into symmetrically and unsymmetrically substituted 1,2-diketones with various functional groups. This process can be readily extended to a consecutive one-pot synthesis of quinoxalines in a diversity-oriented fashion.

Full text of DOI:10.1002/ejoc.201900783

A Journal of
Accepted Article
Title: Sequentially Pd/Cu-catalyzed Alkynylation-Oxidation Synthesis
of 1,2-Diketones and Consecutive One-Pot Generation of
Quinoxalines
Authors: Patrik Niesobski, Ivette Santana Martínez, Sebastian Kustosz,
and Thomas J. J. Müller
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900783
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900783
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10.1002/ejoc.201900783
European Journal of Organic Chemistry
COMMUNICATION
Sequentially Pd/Cu-catalyzed Alkynylation-Oxidation Synthesis of
1,2-Diketones and Consecutive One-Pot Generation of
Quinoxalines
Patrik Niesobski,[a] Ivette Santana Martínez,[a] Sebastian Kustosz,[a] and Thomas J. J. Müller*[a]
Dedication ((optional))
Abstract: We report a simple and efficient one-pot synthesis of 1,2-
diketones by concatenation of two Pd/Cu-catalyzed processes:
Pd(0)/Cu(I)-catalyzed Sonogashira coupling of terminal alkynes with
aryl (pseudo)halides furnishes internal alkynes, which are directly
transformed by Pd(II)/Cu(II)-catalyzed Wacker-type oxidation with
DMSO and oxygen as dual oxidants to furnish 1,2-diketones. With
this efficient, catalyst economical process, various aryl iodides and
triflates are efficiently transformed in high yields into symmetrically
and unsymmetrically substituted 1,2-diketones with various
functional groups. This process can be readily extended to a
consecutive one-pot synthesis of quinoxalines in a diversity-oriented
fashion.
Cu(II) catalysis - of alkynes with H2O[22] or DMSO[23] as a source
for oxygen is a very efficient method (Scheme 1A) and has
several advantages: the reaction proceeds without strong
oxidant, under mild and neutral conditions, and with clean
conversion in high efficiency. Nevertheless, these methods have
some drawbacks, such as starting materials' preparation and
relatively high catalyst loading.
Introduction
Diaryl 1,2-diketones, also known as benzil derivatives, are very
important structural moieties in natural products,[1] biologically
active compounds, such as antitumor agents,[2] as photoinitiators
in radical polymerization,[3] and acid corrosion inhibitors of mild
steel.[4] Moreover, 1,2-dicarbonyl derivatives can be broadly
utilized as building blocks for the synthesis of complex and
biologically active heterocyclic compounds, for instance
quinoxalines, imidazoles and oxazoles.[5]
Due to the increasing interest in 1,2-diketones in recent years,
many synthetic protocols for their preparation have been
reported. Among classical syntheses, e.g. the oxidation of
benzoin[6] or hydrobenzoin,[7] and several other methods,[8] 1,2-
diketones can be very easily and efficiently prepared from
alkynes,[9] which, in turn, are readily accessible by Sonogashira
coupling.[10] Besides inorganic reagents such as iodine,[11]
potassium permanganate,[12] sulfur trioxide,[13] potassium
peroxymonosulfate,[14] and cerium ammonium nitrate (CAN),[15]
diarylalkynes can be oxidized by palladium,[16] copper,[17] iron,[18]
ruthenium[19] or gold[20] catalysts with oxidants. However, these
methods are suffering from several drawbacks with respect to
toxicity, harsh conditions, high loadings of expensive metal
catalysts and the preparation and purification of starting
materials. The Wacker-type oxidation[21] - a bimetallic Pd(II) and
Pd0
CuI
PdII
CuII
Scheme 1. Synthesis of 1,2-diketones from internal alkynes as starting
material respectively intermediate.
Recently, an efficient one-pot synthesis of diaryl 1,2-diketones
from aryl iodides and arylalkynyl carboxylic acids was reported
using a Cu(I)/Cu(II) couple as the catalyst system (Scheme
1B).[24] This methodology combines decarboxylative coupling
and subsequent oxidation of the resulting diarylalkynes without
their isolation. Both processes are mediated by the copper
catalyst couple. However, this reaction is limited to aryl iodides,
needs aryl propiolic acids and a high catalyst loading.
Starting from terminal alkynes we developed sequentially metal-
catalyzed multicomponent reactions, particularly for synthesizing
heterocycles in a one-pot fashion.[25] As a key transformation,
Sonogashira coupling readily gives an access to alkynes,[26]
alkynones,[27] and butadiynes[28] as reactive functional groups
that are directly transformed into heterocycles and functional
materials.[29] As a consequence we now reasoned that in situ
generation of internal alkynes could excellently be concatenated
with their oxidation to benzil derivatives and, hence, a novel
[a]
M. Sc. P. Niesobski, M. Sc. I. Santana Martínez, B. Sc. S. Kustosz,
Prof. Dr. T. J. J. Müller
Department Institut für Organische Chemie und Makromolekulare
Chemie
Heinrich-Heine-Universität Düsseldorf
Universitätsstraße 1, D-40225 Düsseldorf, Germany
E-mail: ThomasJJ.Mueller@uni-duesseldorf.de
Homepage: www.orgchem.hhu.de
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201900783
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COMMUNICATION
entry to multicomponent synthesis. We herein report
a
heating at 150 °C for 20 h. DMSO was used as a solvent or
cosolvent and source of oxygen since no product was formed
from tolane with H2O (see Table S1, Supp Inf). In the
Sonogashira coupling step, in 1,4-dioxane the conversion is
complete after 10 minutes at room temperature and after
subsequent oxidation the benzil (3a) could be obtained in
excellent yield of 93% (condition A, Table 1), whereas in DMSO
the intermediate tolane is completely formed at 50 °C after 4
hours and subsequent oxidation furnished 3a in 87% yield
(condition B, Table 1). However, as for condition A, DMSO has
to be added for the oxidation step.
sequentially
palladium/copper-catalyzed
multicomponent
synthesis of diaryl 1,2-diketones as a consecutive one-pot
process (Scheme 1C). Conceptually this novel one-pot approach
is grounded on the Pd(0)/Cu(I)-catalyzed Sonogashira coupling
of aryl iodides or triflates with terminal alkynes, and without
further catalyst addition the modulation into the Wacker-type
Pd(II)/Cu(II)-system enabling the oxidation of the alkyne to the
1,2-dione with DMSO and oxygen via an ionic mechanistic
pathway in a one-pot fashion.[23]
For both optimized conditions A and B for the Sonogashira-
oxidation sequence with aryl iodides 1 and alkynes 2 , the scope
of the sequentially Pd-Cu-catalyzed pseudo-four-component
synthesis of 1,2-diketones 3, was screened and illustrated for 19
examples of benzil derivatives 3 that were obtained in 19–93 %
yield. As summarized in Table 1, various substituted iodo
benzene derivatives 1 were well tolerated in the reaction.
Results and Discussion
Indeed, after a thorough optimization of this sequentially Pd-Cu-
catalyzed one-pot coupling-oxidation process (for details see
Supp Inf), iodobenzene (1a) and phenylacetylene (2a) can be
transformed to benzil (3a) in the presence of catalytic amount of
tetrakis(triphenylphosphane)-palladium(0) and CuI as well as a
slight excess of triethylamine under an oxygen atmosphere and
Table 1. Scope of the coupling-oxidation sequence (condition A or B) with aryl iodides 1 and alkynes 2 furnishing 1,2 diketones 3.
Yield [%][a]
Entry
1
1/Ar1
2/Ar2
2a/Ph
3
3a
3b
3c
3d
3e
3f
condition A[b]
condition B[c]
1a/Ph
93
72
69
62
83
71
69
78
87
51
83
19
31
-
87
84
63
69
87
-
2
1b/4-O2NC6H4
1c/4-NCC6H4
1d/4-OHCC6H4
1e/4-ClC6H4
1f/4-BrC6H4
1g/4-MeC6H4
1a/Ph
2a/Ph
3
2a/Ph
4
2a/Ph
5
2a/Ph
6
2a/Ph
7
2a/Ph
3g
3h
3i
64
87
-
8
2b/4-MeOC6H4
2c/4-PhC6H4
2a/Ph
9
1a/Ph
10
11
12
13
14
15
16
1h/2-MeC6H4
1a/Ph
3j
70
86
26
2d/3-FC6H4
2e/4-pyridyl
2a/Ph
3k
3l
1a/Ph
[d]
1i/2-thiophenyl
1j/3-quinolinyl
1b/4-O2NC6H4
1c/4-NCC6H4
3m
3n
3o
3p
-
2a/Ph
66
77
54
2f/4-O2NC6H4
2g/4-NCC6H4
70
-
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COMMUNICATION
17
18
1k/4-MeOC6H4
1b/4-O2NC6H4
2b/4-MeOC6H4
2b/4-MeOC6H4
3q
3r
78
80
85
76
19[d]
1a/Ph
1,4-(diethynyl)benzene (2h)
-
62
3s
[a] Isolated yield after chromatography on silica gel. [b] Reaction conditions A: 1 (0.50 mmol), 2 (0.55 mmol), NEt3 (0.55 mmol), Pd(PPh3)4 (2 mol%), CuI
(4 mol%), 1,4-dioxane (0.5 mL), rt, 10 min. Then: DMSO (4.5 mL), 150 °C, 20 h, O2. [c] Reaction conditions B: 1 (0.50 mmol), 2 (0.55 mmol), NEt3 (0.55 mmol),
Pd(PPh3)4 (2 mol%), CuI (4 mol%), DMSO (5.0 mL), 50 °C, 4 h. Then: 150 °C, 20 h, O2. [d] For compound 2h 0.28 mmol were employed.
Aryl iodides 1 are equally tolerated for electron-withdrawing
groups (Table 1, entries 2-6, 15, 16 and 18) as well as for
electron-donating groups (Table 1, entries 7, 10 and 17).
Arylacetylenes 2 with electron-withdrawing groups (Table 1,
entries 11, 15 and 16), and electron-releasing groups (Table 1,
entries 8, 17 and 18) as well as biphenyl acetylene (Table 1,
entry 9) can be successfully employed. 1,4-Diethynylbenzene
(2h) was transformed into the corresponding tetraketone in
moderate yield (entry 19). 4-Pyridyl- and 2-thienyl derivatives
were obtained in low yields (Table 1, entries 12 and 13),
whereas for 3-iodoquinoline (1j) the corresponding 1,2-diketone
was isolated in moderate yield (Table 1, entry 14). In general the
yields for condition B are slightly higher in comparison to
condition A. However, all attempts to transform aliphatic alkynes
such as 1-hexyne, 3-butyne-1-ol, ethyl propiolate and
trimethylsilyl acetylene failed so far.
Alternative starting materials for aryl iodides were also
considered. With bromobenzene and phenylacetylene (2a),
decomposition was observed and benzil (3a) could only be
obtained in 41% yield (see Table S2, Supp Inf).
Aryl triflates, which can be readily prepared from the
corresponding phenols, have been tested. Fortunately, phenyl
triflate (4a) can be converted with phenylacetylene (2a) into
tolane in DMSO at 90 °C in 4 h and then oxidized under the
established conditions (150 °C, 20 h, O2) furnishing benzil (3a) in
an excellent yield of 94% (condition C, Table 2, entry 1). With
these optimized conditions for the Sonogashira coupling-
oxidation sequence with aryl triflates 4, we screened the scope
of the sequentially Pd-Cu-catalyzed pseudo-four-component
synthesis of 1,2-diketones 3, where the triflates 4 and alkynes 2
were varied. After isolation and purification, 12 examples of
benzyl derivatives 3 were obtained in 12–95 % yield (Table 2).
Table 2. Scope of the coupling-oxidation sequence (condition C) with aryl triflates 4 and alkynes 2 furnishing 1,2 diketones 3.[a]
Entry
1
4/Ar1
4a/Ph
2/Ar2
2a/Ph
3
Yield [%][b]
3a
3b
3c
3e
3g
3h
3k
3l
94
91
12
95
79
70
92
45
72
45
84
58
90
2
4b/4-O2NC6H4
4c/4-NCC6H4
4d/4-ClC6H4
4e/4-MeC6H4
4a/Ph
2a/Ph
3
2a/Ph
4
2a/Ph
5
2a/Ph
6
2b/4-MeOC6H4
2c/3-FC6H4
2d/4-pyridyl
2e/4-O2NC6H4
2b/4-MeOC6H4
2b/4-MeOC6H4
1,4-(diethynyl)benzene (2h)
2a/Ph
7
4a/Ph
8
4a/Ph
9
4b/4-O2NC6H4
4f/4-MeOC6H4
4b/4-O2NC6H4
4a/Ph
3o
3q
3r
10
11
12
13[c]
3s
3a
4g/Ph
[a] Reaction conditions C: 4 (0.50 mmol), 2 (0.55 mmol), NEt3 (0.55 mmol), Pd(PPh3)4 (2 mol%), CuI (4 mol%), DMSO (2.5 mL), 90 °C, 4 h. Then: 150 °C, 20 h,
O2. [b] Isolated yield after chromatography on silica gel. [c] 0.50 mmol of phenylnonaflate (4g).
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The aryl triflates 4 substituted with electron-withdrawing groups
(Table 2, entries 2, 4, 9 and 11) as well as electron-donating
groups (Table 2, entries 5 and 10) gave the corresponding 1,2-
diketones 3 in moderate to excellent yields. However, in the
case of p-cyano-substituted phenyl triflate 4c, the product could
only be isolated in very poor 12% yield (entry 3). Arylacetylenes
with electron-withdrawing groups (Table 2, entries 7 and 9) and
electron-donating group (Table 2, entries 6, 10 and 11) are well
tolerated. 1,4-Diethynylbenzene (2h) could be transformed to
the corresponding tetraketone in a moderate yield (Table 2,
entry 12). Compared to methods A and B with iodobenzene (1a)
(Table 1, entry 12), the 4-pyridyl-substituted alkyne 2d reacted
with phenyltriflate (4a) and the product was obtained in a
moderate yield of 45% (entry 8). Nonaflates (nonafluorobutane-
sulfonates) as C4 homologues of triflates have also been used
as a coupling partner.[30] Under the same conditions as for aryl
triflates, benzil (3a) could be obtained from phenylnonaflate (4g)
and phenylacetylene (2a) in an excellent yield of 90% (entry 13).
For illustration of the utility of this novel sequentially Pd/Cu-
catalyzed alkynylation-oxidation process a consecutive one-pot
coupling-oxidation-cyclocondensation synthesis was conceived.
Starting from aryl iodides 1 or triflates 4 and arylacetylenes 2 the
generated benzils were reacted in the same reaction vessel by
addition of 1,2-diamino derivatives 5 at 75 °C for after 4 to 8 h to
give quinoxalines 6, which have recently received considerable
interest as emission solvatochromic materials[31] and
aggregation-induced emissive chromophores.[32] After isolation
and purification 12 different quinoxalines 6 were obtained in 42–
87% yield (Table 3), where various substituted aryl iodides 1 or
triflates 4 and ortho-phenylene diamines 5 were well tolerated in
the reaction.
Table 3. Scope of the coupling-oxidation-cyclization sequence (via condition B or C) with aryl iodides 1 or aryl triflates 4, alkynes 2 and 1,2-diamino derivatives 5
furnishing quinoxalines 6.
Entry
1[b]
Substrate/Ar1/X
1a/Ph/I
2/Ar2
1,2-Diamino benzene derivative 5
o-phenylenediamine (5a)
6
Yield [%][a]
2a/Ph
6a
6a
6b
6c
6d
6e
6f
82
85
62
45
42
71
78
87
79
76
76
62
66
78
2[c]
4a/Ph/OTf
2a/Ph
o-phenylenediamine (5a)
3[c]
4b/4-O2NC6H4/OTf
1c/4-NCC6H4/I
4e/4-MeC6H4/OTf
1k/4-MeOC6H4/I
1b/4-O2NC6H4/I
4d/4-ClC6H4/OTf
4b/4-O2NC6H4/OTf
1k/4-MeOC6H4/I
1a/Ph/I
2f/4-O2NC6H4
2g/4-NCC6H4
2i/4-MeC6H4
2b/4-MeOC6H4
2b/4-MeOC6H4
2d/3-FC6H4
2f/4-O2NC6H4
2b/4-MeOC6H4
2a/Ph
o-phenylenediamine (5a)
4[b]
o-phenylenediamine (5a)
5[c]
o-phenylenediamine (5a)
6[b]
o-phenylenediamine (5a)
7[b]
o-phenylenediamine (5a)
8[c]
o-phenylenediamine (5a)
6g
6h
6i
9[c]
4,5-dichloro-o-phenylenediamine (5b)
4,5-dichloro-o-phenylenediamine (5b)
2,3-diaminonaphthalene (5c)
2,3-diaminonaphthalene (5c)
2,3-diaminonaphthalene (5c)
2,3-diaminonaphthalene (5c)
10[b]
11[b]
12[c]
13[c]
14[b,d]
6j
4a/Ph/OTf
2a/Ph
6j
4b/4-O2NC6H4/OTf
1k/4-MeOC6H4/I
2f/4-O2NC6H4
2b/4-MeOC6H4
6k
6l
[a] Isolated yield after chromatography on silica gel. [b] Reaction conditions: 1 (0.50 mmol), 2 (0.55 mmol), NEt3 (0. 55 mmol), Pd(PPh3)4 (2 mol%), CuI (4 mol%),
DMSO (5.0 mL), 50 °C, 4 h. Then: 150 °C, 20 h, O2. Then: 5 (0.75 mmol), 75 °C, 4 h. [c] Reaction conditions: 4 (0.50 mmol), 2 (0.55 mmol), NEt3 (0.55 mmol),
Pd(PPh3)4 (2 mol%), CuI (4 mol%), DMSO (2.5 mL), 90 °C, 4 h. Then: 150 °C, 20 h, O2. Then: 5 (0.75 mmol), 75 °C, 4 h. [d] The cyclization step was performed
in 8 h.
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10.1002/ejoc.201900783
European Journal of Organic Chemistry
COMMUNICATION
(100 mM, 4 x 25 mL). The aqueous layer was extracted again with ethyl
acetate (3 × 25 ml) before the combined organic layers were washed with
distillated water (3 x 25 mL) and brine (25 mL) and dried with anhydrous
sodium sulfate. After removal of the drying agent by filtration and solvent
by reduced pressure, the product mixture was adsorbed onto Celite® and
purified by column chromatography on silica gel to afford 3b (116 mg,
Conclusions
In summary, we have successfully developed a novel and facile
one-pot synthesis of diaryl 1,2-diketones from aryl iodides or
triflates and terminal alkynes, involving two distinct Pd/Cu-
catalyzed steps upon efficiently utilizing the bimetallic catalyst
system. First, tolanes are formed by Pd(0)/Cu(I)-catalyzed
Sonogashira coupling before 1,2-diketones are subsequently
formed by Pd(II)/Cu(II)-catalyzed Wacker-type oxidation with
DMSO and oxygen as dual oxidants The desired title
compounds are obtained in good yields and many functional
groups are well tolerated. In addition, quinoxalines can be
obtained in a consecutive one-pot fashion by subsequent
addition of 1,2-diamino phenylene derivatives. This versatile
entry to benzils can be readily extended to other consecutive
multicomponent syntheses of heterocycles that are currently
underway as mechanistic studies of the oxidation step.
1
454 µmol, 91% yield) as a yellow solid; mp 139 °C. H NMR (CDCl3, 300
MHz):  8.36 (d, J = 9.0 Hz, 2 H), 8.17 (d, J = 9.0 Hz, 2 H), 7.95–8.00 (m,
2 H), 7.71 (t, J = 7.4 Hz, 1 H), 7.55 (t, J = 7.7 Hz, 2 H). 13C NMR (CDCl3,
75 MHz):  124.3 (CH), 129.4 (CH), 130.2 (CH), 131.1 (CH), 132.5 (Cquat),
135.6 (CH), 137.5 (Cquat), 151.3 (Cquat), 192.2 (Cquat), 193.0 (Cquat). MS
(GC-MS, m/z (%)): 150 ([C7H4NO3]+, 2) 105 ([C7H5O]+, 100), 77 ([C6H5]+,
48), 51 ([C4H3]+, 13).
Typical procedure for the synthesis of compound 6g
Tetrakis(triphenylphosphane)palladium(0) (11.6 mg, 10.0 μmol, 2.00
mol%) and copper(I)iodide (3.80 mg, 20.0 μmol, 4.00 mol%) were placed
in a Schlenk tube and the atmosphere was evacuated and replaced by
argon three times. Then, 4-chlorophenyl triflate (130 mg, 500 µmol, 1.00
equiv), 1-ethynyl-3-fluorobenzene (66.1 mg, 550 µmol, 1.10 equivs) and
DMSO (2.5 mL) were added. After addition of triethylamine (55.7 mg, 550
µmol, 1.10 equivs), the reaction mixture was stirred for 4 hours at 90 °C.
Then at room temperature, the argon atmosphere was replaced by
oxygen by using a tube and the mixture stirred at 150 °C under oxygen
atmosphere for 20 h. At room temperature, 1,2-diaminobenzene (81.1
mg, 750 µmol, 1.50 equivs) was added and stirred at 75 °C under air
atmosphere to complete conversion (4 h, TLC control). After cooling to
room temperature, the reaction mixture was extracted with ethyl acetate
(25 mL) and aqueous sodium sulfite solution (100 mM, 4 x 25 mL). The
aqueous layer was extracted again with ethyl acetate (3 × 25 ml) before
the combined organic layers were washed with distillated water (3 x 25
mL) and brine (25 mL) and dried with anhydrous sodium sulfate. After
removal of the drying agent by filtration and solvent by reduced pressure,
the product mixture was adsorbed onto Celite® and purified by column
chromatography on silica gel to afford 6g (146 mg, 437 µmol, 87% yield)
as a yellow solid; mp 125–127 °C. 1H NMR (acetone-d6, 300 MHz): 
7.17–7.26 (m, 1 H), 7.3–7.47 (m, 5 H), 7.59 (d, J = 8.7 Hz, 2 H), 7.87–
7.91 (m, 2 H), 8.12–8.17 (m, 2 H). 13C NMR (acetone-d6, 75 MHz): 
116.5 (d, J(C, F) = 21.3 Hz, CH), 117.6 (d, J(C, F) = 22.9 Hz, CH), 127.0
(d, J(C, F) = 3.0 Hz, CH), 129.2 (CH), 130.1 (CH), 130.1 (CH), 130.9 (d,
J(C, F) = 8.3 Hz, CH), 131.3 (CH), 131.4 (CH), 132.5 (CH), 135.6 (Cquat),
138.9 (Cquat), 142.1 (d, J(C, F) = 10.3 Hz, Cquat), 142.5 (Cquat), 142.6
(Cquat), 152.8 (d, J(C, F) = 2.3 Hz, Cquat), 153.0 (Cquat), 163.4 (d, J(C, F) =
244.5 Hz, Cquat). 19F NMR (Acetone-d6, 565 MHz):  -114.39. MS (GC-
MS, m/z (%)): 334 ([M]+, 100) 299 ([C20H12FN2]+, 46), 197 ([C13H8FN]+,
32), 178 ([C13H8N3]+, 39), 102 ([C7H4N3]+, 15), 76 ([C6H4]+, 68). IR (ATR):
Experimental Section
Typical procedure for the synthesis of compound 3a with
iodobenzene (1a)
Tetrakis(triphenylphosphane)palladium(0) (11.6 mg, 10.0 μmol, 2.00
mol%) and copper(I)iodide (3.80 mg, 20.0 μmol, 4.00 mol%) were placed
in a Schlenk tube and the atmosphere was evacuated and replaced by
argon three times. Then, iodobenzene (102 mg, 500 µmol, 1.00 equiv),
phenylacetylene (56.2 mg, 550 µmol, 1.10 equivs) and 1,4-dioxane (0.5
mL) were added. After addition of triethylamine (55.7 mg, 550 µmol, 1.10
equivs), the reaction mixture was stirred for 10 min at room temperature.
Then, the argon atmosphere was replaced by oxygen by using a tube
before DMSO (4.5 mL) was added and the mixture stirred at 150 °C
under oxygen atmosphere for 20 h. After cooling to room temperature,
the reaction mixture was extracted with ethyl acetate (25 mL) and
aqueous sodium sulfite solution (100 mM, 4 x 25 mL). The aqueous layer
was extracted again with ethyl acetate (3 × 25 ml) before the combined
organic layers were washed with distillated water (3 x 25 mL) and brine
(25 mL) and dried with anhydrous sodium sulfate. After removal of the
drying agent by filtration and solvent by reduced pressure, the product
mixture was adsorbed onto Celite® and purified by column
chromatography on silica gel to afford 3a (98.0 mg, 466 µmol, 93% yield)
as a yellow solid; mp 94–95 °C. 1H NMR (CDCl3, 300 MHz):  7.52 (t, J =
7.6 Hz, 4 H), 7.67 (t, J = 7.4 Hz, 2 H), 7.95–8.01 (m, 4 H).13C NMR
(CDCl3, 75 MHz):  129.2 (CH), 130.1 (CH), 133.1 (Cquat) ,135.0 (CH),
194.7 (Cquat). MS (GC-MS, m/z (%)): 210 ([M]+, 2), 105 ([C7H5O]+, 100),
77 ([C6H5]+, 58), 51 ([C4H3]+, 25).
̃
[cm-1] 1538 (m), 1477 (m), 1341 (m), 1236 (m), 1092 (m), 993 (m), 856
(m), 837 (s), 795 (m), 764 (s), 748 (m), 715 (s), 681 (m). Anal. calcd. for
C20H12ClFN2 [334.8]: C 71.75, H 3.61, N 8.37; found: C 71.97, H 3.78, N
8.19.
Typical procedure for the synthesis of compound 3b with 4-
nitrophenyl triflate (4b)
Acknowledgments
Tetrakis(triphenylphosphane)palladium(0) (11.6 mg, 10.0 μmol, 2.00
mol%) and copper(I)iodide (3.80 mg, 20.0 μmol, 4.00 mol%) were placed
in a Schlenk tube and the atmosphere was evacuated and replaced by
argon three times. Then, 4-nitrophenyl triflate (136 mg, 500 µmol, 1.00
equiv), phenylacetylene (56.2 mg, 550 µmol, 1.10 equivs) and DMSO
(2.5 mL) were added. After addition of triethylamine (55.7 mg, 550 µmol,
1.10 equivs), the reaction mixture was stirred for 4 hours at 90 °C. Then
at room temperature, the argon atmosphere was replaced by oxygen by
using a tube and the mixture stirred at 150 °C under oxygen atmosphere
for 20 h. After cooling to room temperature, the reaction mixture was
extracted with ethyl acetate (25 mL) and aqueous sodium sulfite solution
The authors gratefully acknowledge the support by the Fonds
der Chemischen Industrie, Consejo Nacional de Ciencia y
Tecnología (CONACYT) and Universitad Autónoma del Estado
de México.
Keywords: one-pot catalysis • multicomponent reaction •
Sonogashira coupling • oxidation • 1,2-diketones
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10.1002/ejoc.201900783
European Journal of Organic Chemistry
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Entry for the Table of Contents (Please choose one layout)
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COMMUNICATION
A sequentially Pd/Cu-catalyzed
One-pot catalysis*
alkynylation-oxidation reaction
furnishes 1,2-diketones in a one-pot
fashion. This one-pot process can be
successfully concatenated with a
cyclocondensation to furnish a
consecutive multicomponent synthesis
of quinoxalines.
PdII
CuII
Pd0
CuI
Patrik Niesobski, Ivette Santana
Martínez, Sebastian Kustosz, and
Thomas J. J. Müller*
Page No. – Page No.
Pd0
CuI
PdII
Sequentially Pd/Cu-catalyzed
Alkynylation-Oxidation Synthesis of
1,2-Diketones and Consecutive One-
Pot Generation of Quinoxalines
CuII
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