Gold-Catalyzed Oxidation of Internal Alkynes into Benzils and its Application for One-Pot Synthesis of Five-, Six-, and Seven-Membered Azaheterocycles

Article abstract of DOI:10.1002/ejoc.201900108

Internal alkynes have been shown to undergo oxidation to substituted benzils (1,2-diarylethane-1,2-diones) by α-picoline N-oxide in the presence of Ph₃PAuNТf₂ (5 mol-%). In addition to the unsubstituted benzil, the method allows preparing, under markedly mild conditions (50 °C in chlorobenzene), various non-symmetrical products, including heteroaromatic versions thereof which are much more difficult to obtain otherwise. This gold(I)-catalyzed transformation was integrated into one-pot reaction sequence delivering a range of 5- to 7-membered ring systems (imidazoles, quinoxalines, 1,2,4-triazines, pyrazines, and 1,4-diazepines), thus linking these important heterocyclic motifs to the internal alkyne reagent space.

Full text of DOI:10.1002/ejoc.201900108

DOI: 10.1002/ejoc.201900108
Full Paper
Gold Catalysis
Gold-Catalyzed Oxidation of Internal Alkynes into Benzils and
its Application for One-Pot Synthesis of Five-, Six-, and Seven-
Membered Azaheterocycles
[a]
[a]
[a]
[a]
Alexey Yu. Dubovtsev* Dmitry V. Dar'in, Mikhail Krasavin, and Vadim Yu. Kukushkin*
Abstract: Internal alkynes have been shown to undergo oxid- versions thereof which are much more difficult to obtain other-
ation to substituted benzils (1,2-diarylethane-1,2-diones) by α- wise. This gold(I)-catalyzed transformation was integrated into
picoline N-oxide in the presence of Ph PAuNТf (5 mol-%). In one-pot reaction sequence delivering a range of 5- to 7-mem-
3
2
addition to the unsubstituted benzil, the method allows prepar- bered ring systems (imidazoles, quinoxalines, 1,2,4-triazines,
ing, under markedly mild conditions (50 °C in chlorobenzene), pyrazines, and 1,4-diazepines), thus linking these important
various non-symmetrical products, including heteroaromatic heterocyclic motifs to the internal alkyne reagent space.
Introduction
tionalizations of alkynes with N–O species continues to be of
great importance.
[
13]
Carbo- and heteroaromatic derivatives of the so-called benzils,
In particular, Li et al. reported the Au-catalyzed synthesis of
1
2
R C(=O)C(=O)R (IUPAC name: 1,2-diaryl(heteryl)ethane-1,2-
benzils and α-keto imides of limited scope from internal alkynes
1
2
diones; R /R = Ar, Het), are useful synthons for design of a
[
14]
by their oxidation with Ph S=O (Scheme 1a).
This method
2
wide range of heterocyclic systems.[1] Benzils also found an ap-
demonstrates good results for the oxidation of 4-RC H C≡ CPh
6
4
[
2]
plication as precursors for syntheses of chiral 1,2-diols, α-di-
(R = H, Me, Br, Ac; 80–98 %), but the yields drop to 74–75 %
[
3]
[4]
imine ligands, and N-heterocyclic carbenes. Attractiveness
for 4-MeO- or 2-F-substituted substrates. Furthermore, the best
results were obtained in refluxing 1,2-dichloroethane – a toxic
and possibly carcinogenic solvent that is no longer used by the
1
2
of R C(=O)C(=O)R is also driven by their occurrence in natural
products and, in particular, natural benzils – such as scandione
[
5]
and calophione A – had been the goal of total synthesis. Ow-
[
15]
pharmaceutical industry
– whereas the application of safer
[
6]
ing their carboxylesterase inhibition activity as well as anti-
solvents does not give satisfactory results. In a relevant Au-
involving synthesis (Scheme 1b), the neighboring ester group-
participated diketonization of o-alkynylbenzoates under the
[
7]
[8]
[9]
microbial, antitumor, and cytotoxic properties, benzils are
useful species from medicinal chemistry viewpoint.
Common routes to benzils include oxidation (or, in other
words, diketonization) of easily and/or commercially available
[
1a]
acetylenes using transition-metal species as activators. These
approaches to benzils are not free from substantial drawbacks
that include harsh conditions, high catalyst loading, use of toxic
or aggressive reagents and limited scope (see SI for detailed
literature survey on synthetic methods leading to benzils).
A logical alternative to the known metal-catalyzed methods
is the application of gold-based catalysts insofar as Au-involving
reactions (for reviews and works on Au-catalyzed conversions
[
10,11]
of acetylenes see references
conditions, in air and in the moistures atmosphere, and the Au-
) often proceed under mild
[
12]
catalysts are active at a very small catalyst load. Considering
the power of gold catalysis in achieving various synthetic goals,
development of new methods for Au-catalyzed O- and N-func-
[
a] Saint Petersburg State University,
Universitetskaya Nab. 7/9, 199034 Saint Petersburg, Russian Federation
E-mail: a.dubovtsev@spbu.ru (A.Yu.D.)
v.kukushkin@spbu.ru (V.Yu.K.)
http://chem.spbu.ru/ptchem.html
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201900108.
Scheme 1. Gold-catalyzed generation of 1,2-dicarbonyl compounds from
acetylenes.
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gold(I)/Selectfluor catalytic system[16] led to low yield of unsub-
stituted benzil (31 %). Noteworthy that all these methods were
not applied for hetaryl-substituted internal alkynes.
Table 1. Optimization of the reaction conditions.[a]
Notable results, particularly in the context of this work, were
obtained by Hashmi and co-workers who developed an Au-
catalyzed approach to glyoxals via oxidation of terminal alkynes
using pyridine N-oxide derivatives as convenient oxygen carri-
Time [h] Yield,[b]
%
Entry
Catalyst, mol % Acid, Equiv
MsOH, 1
Tf NH, 1
Solvent
[
17]
ers (Scheme 1c);
the method was extended to one-pot syn-
1
2
3
4
5
6
7
8
9
10
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
3
1.5
0
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
DMSO
THF
2
2
2
2
2
2
2
2
2
2
2
2
1
4
6
31
41
42
32
33
46
87
79
61
77
84
86
71
94
97
72
72
85
63
–
thesis of 2-substituted quinoxalines. Despite its superior effi-
ciency for the oxidation of terminal alkynes, the developed
method was not found suitable for internal acetylenes that of-
ten exhibit different reactivity (for general consideration see (i)
Results and Discussion).
2
TfOH, 1
None
TfOH, 0.5
TfOH, 1.5
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
TfOH, 2
In this project, we discovered that the application of the
[c]
[
18]
well-established Gagosz catalyst, Ph PAuNTf ,
as part of α-
3
2
picoline N-oxide/TfOH/Ph PAuNTf system can offer a facile ap-
3
2
1
1
PhMe
DCE
proach to oxidation (diketonization) of internal alkynes, which
complements Hashimi's oxidation of terminal alkynes. The ad-
vantages of our method for oxidation of internal alkynes
include mild reaction conditions, a wide scope of obtained
benzils (including non-symmetric, that are substantially more
difficult-to-obtain than the symmetric), a tolerance to functional
substituents, and the possibility for syntheses of heteroaromatic
1
2
1
3
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
1
4
15
[d]
1
6
48
[e]
1
7
1
1
8
6
6
6
1
9
1,2-diketones. An important feature of this approach is a possi-
20
bility of its extension to one-pot methodology for generation
of various azaheterocyclic systems. This Au -involving one-pot
[
a] All reactions were carried out on a 0.2 mmol scale (1 mL of solvent).
I
[b] 19F NMR yield. [c] Pyridine N-oxide was used instead α-picoline N-oxide.
synthetic strategy was applied for molecular design of various
[d] Room temperature. [e] Microwave irradiation (50 W) at 50 °C.
(
5-to-7)-membered heterocycles starting directly from internal
acetylenes. All our results are consequently disclosed in sections
that follow.
A common feature of the oxidation reactions involving N-
oxides is the formation of the respective free base in the reac-
[
21]
tion mixture,
which leads to deactivation of the gold cata-
[
22]
lyst. Thus, it was shown that using acid to scavenge the base
formed upon the transfer of oxygen from the N-oxide is critical
for gold-catalyzed oxidation of acetylenes with pyridine N-ox-
Results and Discussion
[
17]
(
i) Gold-Catalyzed Diketonization of Internal Alkynes. Both ides. Therefore, we first screened for the optimal acid compo-
internal and terminal alkynes possess the same carbon–carbon nent (1 equiv.) which would scavenge the pyridine base and re-
triple bond, but in many instances, their reactivities are differ- activate the catalyst. Between triflic acid and triflic imide which
ent. This is because some reactions with terminal alkynes pro- gave the best results, triflic acid (TfOH) was selected as more
ceed via intermediate generation of acetylide (e.g. nucleophilic readily available. It was further found that the acid/acetylene
additions) and this is not feasible for internal alkynes. On the ratio substantially affected the yield of the product. The yield
other hand, different steric/electronic properties of internal and of the benzil product steadily increased from 32 to 87 % when
terminal alkynes also affect an outcome of the reaction. While 0, 0.5, 1.5, and 2 equiv. of TfOH were employed in the reaction.
terminal alkynes are most frequently employed in oxidative Au-
Next, we tested the possibility of using a cheaper oxidizing
catalyzed transformations, regioselective oxidations of internal agent in this reaction and found that unsubstituted pyridine
alkynes (especially alkyl substituted) can be challenging, due to N-oxide also exhibited a high oxidative efficiency (79 %). The
their reduced reactivity and occurrence of side reactions (e.g. effect of the solvent was also examined and the best synthetic
[
19]
facile 1,2-CH insertions).
results were obtained in non-polar solvents (chlorobenzene,
[
20]
Recently we found
benzil (PhCOCOPh) to be a minor DCE, toluene). Chlorobenzene was chosen due to its lower tox-
[
23]
by-product of the reaction between diphenylacetylene and α- icity compared to 1,2-dichloroethane
and the possibility of
picoline N-oxide in the presence of Ph AuNTf . Considering the carrying out reactions over a wide range of temperatures in this
3
2
fact that such an oxidation has not been described for internal solvent. The yield was further improved (up to 97 %) by increas-
alkynes under gold-catalyzed conditions, we attempted to opti- ing the reaction time to 6 h. The reaction at r.t. was much
mize this reaction to increase its utility for the preparation of slower and the yield obtained after 48 h was somewhat lower
substituted benzils. Oxidation of 1-fluoro-4-(phenylethynyl)- (72 %). The reaction conducted under microwave irradiation
benzene (1a) to corresponding diketone 2a was chosen as a (50 °C, 50 W, 1 h) gave a similar result (Entry 17).
1
9
model reaction as it can be easily monitored by F NMR
Table 1).
Finally, we tested different catalyst loadings and found that
using 3 mol-% of the catalyst was sufficient for achieving a
(
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good product yield (85 %) whereas reducing the amount of the ceeded to increase the yield of 1-(4-nitrophenyl)-2-
catalyst to 1.5 mol-% led to a significant reduction of the yield. phenylethane-1,2-dione (2j) to 72 %. While moving from para-
Thus, the optimal results were obtained in the model reaction (1e) to meta- (1f), and then to ortho-methoxy-4-(phenylethy-
conducted in PhCl with 2 equiv. of TfOH, 2.5 equiv of α-picoline nyl)benzene (1g) as substrates for the oxidation, the yield of
N-oxide and 5 mol-% of Ph PAuNTf at 50 °C for 6 h.
the corresponding benzils slightly decreased. The reaction con-
3
2
(
ii) Scope of the Gold-catalyzed Oxidation. With the opti- ditions were also found applicable to the oxidation of heteroa-
mal conditions at hand, the substrate scope and limitations of ryl substituted acetylenes 1l–o. However, all attempts to em-
the developed approach were examined (Table 2). Excellent ploy alkyl-substituted internal acetylenes or 1-trimethylsilyl-2-
yields of substituted benzils 2 were obtained from unsubsti- phenylacetylene in the reaction failed and the desired diket-
tuted diphenylacetylene and diarylacetylenes bearing either ones were not obtained. This fact is probably related to the
electron-donating (Me, OMe) or electron-withdrawing (F, Br) facile 1,2-CH insertions in gold carbene intermediates.[19b–19d]
groups. Strong electron-withdrawing groups (CN, Ac) slightly The method is inapplicable for the oxidation of terminal alkynes
reduced the product yields. In the case of acetylene featuring and, e.g., phenylacetylene under the optimized conditions gave
1
a nitro group, the yield decreased significantly (44 %), most phenylglyoxal in only 22 % H NMR yield.
likely due to the lower electron density on the alkyne triple
It has been reported that a carbonyl group in the ortho-
bond. The decreased reactivity of electron-deficient substrates position of a phenylacetylene moiety can participate in the di-
[
16,24]
is documented in the literature as a common limitation of alk- ketonization.
We observed such a neighbouring group par-
[
1a]
yne oxidation methods. However, by increasing both the cat- ticipation when methyl 2-(phenylethynyl) benzoate (1p) was re-
alyst loading (10 mol-%) and the reaction time (24 h), we suc- acted under the optimized reaction conditions and 3-phenyl-
Table 2. Gold-catalyzed oxidation of internal alkynes into benzils.[a,b]
[
a] All reactions were carried out on a 0.5 mmol scale (2 mL of PhCl). [b] Isolated yield. [c] Ph
3
AuNTf
2
10 mol-%, 16 h.
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1H-isochromen-1-one (3) – and not diketone 2p – was obtained However, altogether these two gold-involving methods com-
as the major product (Scheme 2). Control experiments indicated prise a unified approach to the oxidation of both internal- and
that in the absence of both the N-oxide and TfOH, 1H-iso- terminal alkynes. Application of these two approaches to the
chromen-1-one 3 was formed in 31 % yield. However, using oxidation of internal- or terminal alkynes clearly illustrates how
only 1 equiv. TfOH (without added Ph PAuNTf and the N-ox- seemingly small modifications of the catalytic system (usage of
3
2
+
+
ide), the yield of 3 increased to 95 %. Similar 6-endo-dig gold- Ph PAuNTf /H instead of in situ generated Ph PAu species)
catalyzed and silver/p-TsA co-catalyzed cyclizations of ester 1p and the nature of nucleophilic oxygenation
to isocoumarin 3 had been previously reported.
3
2
3
[
26]
agent (replace-
[
25]
ment of quinoline- or Cl -pyridine oxides with more nucleo-
2
philic α-picoline oxide) lead to remarkable consequences and
allow the selective syntheses of different type 1,2-dicarbonyl
compounds.
(iv) Application of the Gold-catalyzed Diketonization for
One-pot Heterocycle Synthesis. With the Au-catalyzed proto-
col for oxidation of internal akynes at hand, we aimed to de-
velop a one-pot methodology toward various medicinally im-
[
27]
[28]
portant azaheterocycles (such as imidazole,
quinoxaline,
[
29]
[30]
[31]
1
,2,4-triazine,
pyrazine,
and 1,4-diazepine ). To this end,
1
,2-diaryl-1,2-ethandiones 2 (obtained by diketonization of in-
ternal alkynes 1) were not isolated and further reacted with
various mono- and bis-nucleophiles to give these heterocyclic
cores (Scheme 3).
Scheme 2. Generation of 3-phenyl-1H-isochromen-1-one (3).
The one-pot synthesis of imidazoles 4a –c was carried out in
To summarize sections (i) and (ii) one should indicate that if a sequential way by diketonization of diarylacetylenes 1 under
the Hashmi method, considered in Introduction, of the the optimized conditions followed by the addition of an alde-
(
Ph PAuCl/AgSbF )-catalyzed oxidation of alkynes is useful for hyde (1.2 equiv) with an excess amount of AcONH while in-
4
3 6
terminal alkynes, but unsuccessful for internal alkynes, our ap- creasing the reaction temperature in the second step. Thus,
proach utilizing the Gagosz catalyst (Ph PAuNTf ) is, on the con- 2,4,5-triaryl-1H-imidazoles 4a–c were obtained in good yields
3
2
trary, useful for internal alkynes but not for the terminal species. (Table 3). A similar one-pot approach was applied to the synthe-
Scheme 3. One-pot Synthesis of (5-to-7)-Membered Azaheterocycles. All reactions were carried out on a 0.25 mmol scale (2 mL of PhCl as solvent). Reaction
3
conditions: (a) α-picoline N-oxide (2.5 equiv.), TfOH (2 equiv.), Ph
(
(
3
PAuNTf
2
(5 mol-%), 50 °C, 6 h; (b) R CHO (1.2 equiv), AcONH
4
(5 equiv.), 120 °C, 24 h; (c) 7
(CH NH
2
1.1 equiv.), 110 °C, 18 h; (d) 8 (1.1 equiv), 90 °C, 10 h; (e) ethylenediamine diacetate (1.5 equiv.), α-picoline N-oxide (1.5 equiv), 110 °C, 24 h; (f) NH
1.5 equiv.), 110 °C, 24 h.
2
2
)
3
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Table 3. The scope of the one-pot azaheterocycle synthesis developed in this work.
sis of 3,5,6- triaryl-1,2,4-triazines 5a–c and 2,3-diarylquinoxal- portant five-, six-, and seven-membered azaheterocyclic motifs
ines 6a–e starting from amidrazones 7 and o-phenylene- from broadly available starting materials and, consequently, the
diamines 8, respectively. 2,3-Diarylpyrazines 9a–c were ob- method can be useful for combinatorial medicinal chemistry.
tained analogously starting from ethylenediamine diacetate,
but yields were lower (68–71 %). In this case, an additional
1
.5 equiv. of α-picoline N-oxide was required to oxidize interme-
Experimental Section
diate 5,6-dihydropyrazines 10. For preparation of 7-membered
azaheterocycles the method proved to be less efficient and 2,3-
Materials and methods
diaryl-6,7-dihydro-5H-1,4-diazepines 11a–b were obtained in NMR spectra were recorded at ambient temperature with a Bruker
1
only moderate yields (39–44 %). Overall, the above examples Avance III 400 instrument at 400.13 MHz ( H NMR), 376.50 MHz
1
9
13
(
F), and 100.61 MHz ( C NMR) in CDCl or [D ]DMSO. Chemical
demonstrated the applicability of this tandem one-pot route to
the synthesis of a broad variety of useful azaheterocycles.
3 6
1
shifts (δ) are given in ppm relative to resonances of solvents ( H:
δ = 7.26 for residual CHCl peak, δ = 2.50 for residual DMSO peak;
3
13
C: δ = 77.2 for CDCl , δ = 39.5 for [D ]DMSO). Mass-spectra were
3
6
recorded on Bruker MicroTOF (ESI) and Bruker maXis HRMS-ESI-
QTOF instruments. Chromatographic separation was carried out on
Conclusions
We have developed a facile gold-catalyzed method for the Macherey–Nagel silica gel 60 M (0.04–0.063 mm). Analytical TLC was
performed on unmodified Merck ready-to-use plates (TLC silica gel
0 F254); detection was achieved with a UV lamp. Melting points
were measured with Stuart smp30 apparatus. Ph PAuNTf was syn-
transformation of internal aryl- and heteroaryl-substituted alk-
ynes into the respective benzil (1,2-diaryl-1,2-ethandione) deriv-
atives. The protocol carries a number of advantages over the
previously described methods of the diketonization due to sig-
nificantly milder reaction conditions, higher product yields, and
a good substituent tolerance.
6
3
2
[
20]
thesized accordingly to our previously published protocol. Amid-
[
32]
razones 7 were prepared by the literature procedure.
The sol-
vents, diphenylacetylene, and other reagents were purchased from
commercial vendors and were used as received. Internal alkynes 2
were prepared by the Sonogashira coupling between aryl alkynes
We also found that our oxidation method can be applied for
syntheses of heteroaromatic benzils. The strongest point of our and aryl halides. Details of the syntheses and characterization of
synthetic scheme is its ability to construct a wide range of im- compounds 2 is provided in the SI.
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1
General Procedure A. Preparation of Benzil Derivatives 2: A so-
0.30 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 8.02
3
lution of trifluoromethanesulfonic acid (150 mg, 1.0 mmol, (d, J = 9.4 Hz, 1H, Ar), 7.92 (d, J = 7.2 Hz, 2H, Ar), 7.63–7.57 (m, 2H,
2
.0 equiv) in chlorobenzene (1.0 mL) was added to reaction flask Ar), 7.49 (t, J = 7.6 Hz, 2H, Ar), 7.12 (t, J = 7.5 Hz, 1H, Ar), 6.93 (d,
containing a solution of internal alkyne 1 (500 μmol, 1.0 equiv), α- J = 8.4 Hz, 1H, Ar), 3.55 (s, 3H, OMe); 13C NMR (100 MHz, CDCl ) δ
3
picoline N-oxide (136.4 mg, 1.25 mmol, 2.5 equiv) and Ph PAuNTf2 194.8, 193.6, 160.5, 136.6, 133.9, 133.1, 130.6, 129.4, 128.8, 124.0,
3
+
+
(
18.5 mg, 25 μmol, 5 mol-%) in chlorobenzene (1.0 mL). The result- 121.7, 112.5, 55.8; HRMS (ESI): m/z [M + Na] calcd. for C H NaO :
15 12 3
ing mixture was stirred at 50 °C for 6 h. After cooling, the solvent
was then removed in vacuo. The residue was purified by silica gel
chromatography eluting with EtOAc/hexane (gradient from 1:12 to
263.0679, found 263.0673.
-(4-Acetylphenyl)-2-phenylethane-1,2-dione (2h):[35] yellow
crystals (102 mg, 81 %); mp 77.0–78.0 °C (hexane/ethyl acetate); Rf
1
1
:4) to afford target benzils 2.
-(4-Fluorophenyl)-2-phenylethane-1,2-dione (2a):[33] yellow
crystals (107 mg, 94 %); mp 62.5–63.5 °C (hexane/ethyl acetate); R
1
0
.30 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 8.06 (s,
3
1
4H, Ar), 7.97 (d, J = 7.2 Hz, 2H, Ar), 7.68 (t, J = 7.5 Hz, 1H, Ar), 7.53
(t, J = 7.8 Hz, 2H, Ar), 2.65 (s, 3H, Me); 13C NMR (100 MHz, CDCl ) δ
f
3
1
0
8
.65 (hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 8.03–
197.3, 193.9, 193.7, 141.5, 136.1, 135.3, 132.9, 130.2, 130.1, 129.3,
3
+
+
.00 (m, 2H, Ar), 7.97 (d, J = 7.2 Hz, 2H, Ar), 7.65 (t, J = 7.4 Hz, 1H,
128.8, 27.1; HRMS (ESI): m/z [M + Na] calcd. for C H NaO :
16 12 3
13
Ar), 7.51 (t, J = 7.8 Hz, 2H, Ar), 7.18 (t, J = 8.6 Hz, 2H, Ar); C NMR
275.0679, found 275.0677.
-(2-Oxo-2-phenylacetyl)benzonitrile (2i):[34] yellow crystals
(
100 MHz, CDCl ) δ 194.2, 192.8, 166.7 (d, J = 258.2 Hz, CF), 135.1,
3
F
4
1
1
33.0, 132.8 (d, J = 9.8 Hz, CH), 130.0, 129.6 (d, J = 2.9 Hz, C),
F F
(
(
87.0 mg, 74 %); mp 108.0–109.0 °C (hexane/ethyl acetate); R 0.40
f
1
9
29.2, 116.5 (d, J = 22.2 Hz, CH); F NMR (376.5 MHz, CDCl ) δ
1
F
3
hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 8.09 (d, J =
3
+
+
–101.2; HRMS (ESI): m/z [M + Na] calcd. for C H FNaO : 251.0479,
14 9 2
8
.5 Hz, 2H, Ar), 7.97 (d, J = 7.2 Hz, 2H, Ar), 7.81 (d, J = 8.5 Hz, 2H,
found 251.0471.
13
Ar), 7.70 (t, J = 7.5 Hz, 1H, Ar), 7.54 (t, J = 7.8 Hz, 2H, Ar); C NMR
1
,2-Diphenylethane-1,2-dione (2b):[33] yellow crystals (101 mg,
(100 MHz, CDCl ) δ 193.1, 192.5, 136.0, 135.5, 132.9, 132.6, 130.3,
3
+
9
6 %); mp 94.5–95.5 °C (hexane/ethyl acetate); R 0.30 (hexane/ethyl
130.2, 129.3, 118.0, 117.7; HRMS (ESI): m/z [M + Na] calcd. for
C H NNaO : 258.0525, found 258.0516.
f
1
+
acetate, 12:1); H NMR (400 MHz, CDCl ) δ 7.99–7.97 (m, 4H, Ar),
3
15
9
2
13
7
.66 (t, J = 7.4 Hz, 2H, Ar), 7.51 (t, J = 7.8 Hz, 4H, Ar); C NMR
-(4-Nitrophenyl)-2-phenylethane-1,2-dione (2j):[34] yellow crys-
tals (56.2 mg, 44 %); mp 138.5–139.5 °C (hexane/ethyl acetate); Rf
1
(
[
100 MHz, CDCl ) δ 194.7, 135.0, 133.2, 130.0, 129.2; HRMS (ESI): m/z
3
+
+
M + Na] calcd. for C H NaO : 233.0573, found 233.0578.
1
14
10
2
0
.40 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 8.35
3
1
-(4-Bromophenyl)-2-phenylethane-1,2-dione (2c):[33] yellow
(d, J = 8.8 Hz, 2H, Ar), 8.17 (d, J = 8.8 Hz, 2H, Ar), 7.99 (d, J = 7.2 Hz,
1
3
crystals (134 mg, 93 %); mp 85.0–86.5 °C (hexane/ethyl acetate); R
2H, Ar), 7.71 (t, J = 7.5 Hz, 1H, Ar), 7.55 (t, J = 7.8 Hz, 2H, Ar);
C
f
1
0
.60 (hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 7.96
NMR (100 MHz, CDCl ) δ 193.0, 192.2, 151.3, 137.5, 135.6, 132.5,
3
3
+
(
d, J = 7.2 Hz, 2H, Ar), 7.85 (d, J = 8.6 Hz, 2H, Ar), 7.69–7.65 (m, 3H,
131.1, 130.2, 129.4, 124.3; HRMS (ESI): m/z [M + H] calcd. for
1
3
+
Ar), 7.52 (t, J = 7.8 Hz, 2H, Ar); C NMR (100 MHz, CDCl ) δ 194.0, C H NO : 256.0604, found 256.0603.
3
14 10
4
1
(
93.4, 135.2, 132.9, 132.6, 131.9, 131.4, 130.6, 130.1, 129.2; HRMS
-(2-(4-Methoxyphenyl)-2-oxoacetyl)benzonitrile (2k):[36] yellow
4
ESI): m/z [M + Na]+ calcd. for C H BrNaO : 310.9678, found
+
1
4
9
2
crystals (99.5 mg, 75 %); mp 134.5–136.0 °C (hexane/ethyl acetate);
3
10.9682.
1
R 0.50 (hexane/ethyl acetate, 2:1); H NMR (400 MHz, CDCl ) δ 8.08
f
3
1
-Phenyl-2-(4-tolyl)ethane-1,2-dione (2d):[34] yellow crystals
(d, J = 8.4 Hz, 2H, Ar), 7.95 (d, J = 8.9 Hz, 2H, Ar), 7.80 (d, J = 8.4 Hz,
1
3
(110 mg, 98 %); mp 30.0–30.5 °C (hexane/ethyl acetate); R 0.65
2H, Ar), 7.00 (d, J = 8.9 Hz, 2H, Ar), 3.90 (s, 3H, OMe); C NMR
f
1
(hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 7.97 (d, J = (100 MHz, CDCl ) δ 192.8, 191.6, 165.6, 136.3, 132.8, 132.7, 130.4,
3
3
+
7
.3 Hz, 2H, Ar), 7.87 (d, J = 8.2 Hz, 2H, Ar), 7.64 (t, J = 7.4 Hz, 1H,
125.7, 117.9, 117.8, 114.7, 55.9; HRMS (ESI): m/z [M + Na] calcd. for
C H NNaO : 288.0631, found 288.0637.
+
Ar), 7.50 (t, J = 7.7 Hz, 2H, Ar), 7.31 (d, J = 8.0 Hz, 2H, Ar), 2.43 (s,
16
11
3
3
1
H, Me); 13C NMR (100 MHz, CDCl ) δ 194.9, 194.4, 146.3, 134.9,
-Phenyl-2-(thiophen-2-yl)ethane-1,2-dione (2l):[37] brown crys-
3
1
33.2, 130.7, 130.1, 130.0, 129.9, 129.1, 22.0; HRMS (ESI): m/z [M +
tals (86.5 mg, 80 %), mp 61.5–62.5 °C (hexane/ethyl acetate); R 0.30
f
+
+
Na] calcd. for C H NaO : 247.0730, found 247.0742.
1
15
12
2
(
hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 8.04 (d, J =
3
1
-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (2e):[34] yellow
crystals (117 mg, 97 %); mp 62.0–63.0 °C (hexane/ethyl acetate); R
7.3 Hz, 2H, Ar), 7.83–7.79 (m, 2H, Ar), 7.65 (t, J = 7.4 Hz, 1H, Ar), 7.50
(t, J = 7.8 Hz, 2H, Ar), 7.18–7.16 (m, 1H, Ar); 13C NMR (100 MHz,
f
1
0
7
.35 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 7.98–
.93 (m, 4H, Ar), 7.64 (t, J = 7.4 Hz, 1H, Ar), 7.50 (t, J = 7.7 Hz, 2H,
CDCl ) δ 192.2, 185.7, 139.9, 137.0, 136.8, 135.0, 132.7, 130.3, 129.0,
3
3
+
+
128.9; HRMS (ESI): m/z [M + Na] calcd. for C H NaO S : 239.0137,
12 8 2
1
3
Ar), 6.97 (d, J = 8.9 Hz, 2H, Ar), 3.88 (s, 3H, OMe); C NMR (100 MHz,
CDCl ) δ 195.0, 193.3, 165.1, 134.8, 133.3, 132.5, 130.0, 129.1, 126.2,
found 239.0142.
-Phenyl-2-(pyridin-3-yl)ethane-1,2-dione (2m):[37] yellow crys-
3
1
+
+
1
2
14.5, 55.8; HRMS (ESI): m/z [M + Na] calcd. for C H NaO :
15 12 3
tals (59.1 mg, 56 %); mp 48.0–49.5 °C (hexane/ethyl acetate); R 0.30
f
63.0679, found 263.0676.
1
(
hexane/ethyl acetate, 2:1); H NMR (400 MHz, CDCl ) δ 9.16 (s, 1H,
3
1
-(3-Methoxyphenyl)-2-phenylethane-1,2-dione (2f):[34] yellow
Ar), 8.86 (d, J = 6.0 Hz, 1H, Ar), 8.29 (d, J = 8.0 Hz, 1H, Ar), 7.99 (d,
crystals (100 mg, 83 %); mp 90.5–91.5 °C (hexane/ethyl acetate); R
J = 7.2 Hz, 2H, Ar), 7.68 (t, J = 7.4 Hz, 1H, Ar), 7.53 (t, J = 7.8 Hz, 2H,
f
1
13
0
.45 (hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 7.97
Ar), 7.45–7.49 (m, 1H, Ar); C NMR (100 MHz, CDCl ) δ 193.0, 192.9,
3
3
(
d, J = 7.9 Hz, 2H, Ar), 7.66 (t, J = 7.4 Hz, 1H, Ar), 7.55–7.47 (m, 4H,
155.0, 151.5, 137.0, 135.4, 132.6, 130.2, 129.3, 128.8, 124.0; HRMS
+
+
Ar), 7.39 (t, J = 7.9 Hz, 1H, Ar), 7.20 (d, J = 10.7 Hz, 1H, Ar), 3.86 (s,
3
1
(ESI): m/z [M + H] calcd. for C H NO : 212.0706, found 212.0697.
13 10 2
H, OMe); 13C NMR (100 MHz, CDCl ) δ 194.6 (×2), 160.2, 135.0,
3
-Phenyl-2-(pyridin-2-yl)ethane-1,2-dione (2n):[37] yellow crystals
1
34.4, 133.2, 130.2, 130.0, 129.2, 123.4, 122.0, 113.0, 55.7; HRMS
(
55.9 mg, 53 %); mp 72.0–73.5 °C (hexane/ethyl acetate); R 0.40
f
ESI): m/z [M + Na]+ calcd. for C H NaO : 263.0679, found
+
(
1
1
5
12
3
(hexane/ethyl acetate, 2:1); H NMR (400 MHz, CDCl ) δ 8.66 (d, J =
3
2
63.0691.
-(2-Methoxyphenyl)-2-phenylethane-1,2-dione (2g):[34] yellow
crystals (94.9 mg, 79 %), mp 70.5–71.5 °C (hexane/ethyl acetate); Rf
4
.7 Hz, 1H, Ar), 8.20 (d, J = 7.9 Hz, 1H, Ar), 7.96–7.91 (m, 3H, Ar),
13
1
7.63 (t, J = 7.5 Hz, 1H, Ar), 7.53–7.48 (m, 3H, Ar); C NMR (100 MHz,
CDCl ) δ 196.2, 195.2, 151.8, 150.0, 137.4, 134.7, 133.3, 129.7, 129.0,
3
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Full Paper
1
2
28.2, 123.3; HRMS (ESI): m/z [M + H]+ calcd. for C H NO2+:
of diphenylacetylene (1b) (44.6 mg, 250 μmol, 1.0 equiv), α-picoline
N-oxide (68.2 mg, 625 μmol, 2.5 equiv) and Ph PAuNTf (9.24 mg,
1
3 10
12.0706, found 212.0705.
-Phenyl-2-(quinolin-3-yl)ethane-1,2-dione (2o):[36] yellow crys-
tals (99.2 mg, 76 %); mp 127.0–128.0 °C (hexane/ethyl acetate); R
3
2
12.5 μmol, 5 mol-%) in chlorobenzene (0.5 mL). The resulting mix-
ture was stirred at 50 °C for 6 h. Then amidrazone 7 (275 μmol,
1.1 equiv) and chlorobenzene (1.0 mL) were added. The resulted
mixture was stirred at 110 °C for 18 h. Upon cooling to r.t., the
solvent was removed in vacuo. The residue was purified by silica
gel chromatography eluted by EtOAc/hexane (gradient from 1:12 to
1:4) to afford target triazines 5.
1
f
1
0
.45 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 9.48
3
(d, J = 2.2 Hz, 1H, Ar), 8.72 (d, J = 1.5 Hz, 1H, Ar), 8.17 (d, J = 7.4 Hz,
1
7
H, Ar), 8.05–8.03 (m, 2H, Ar), 7.91–7.85 (m, 2H, Ar), 7.68 (t, J =
.4 Hz, 1H, Ar), 7.62 (t, J = 7.5 Hz, 1H, Ar), 7.53 (t, J = 7.8 Hz, 2H,
13
Ar); C NMR (100 MHz, CDCl ) δ 193.2, 192.9, 150.5, 149.3, 140.3,
3
3,5,6-Triphenyl-1,2,4-triazine (5a):[39] yellow crystals (68.8 mg,
1
35.3, 133.1, 132.8, 130.2, 129.82, 129.78. 129.3, 128.0, 126.7, 125.5;
+
+
HRMS (ESI): m/z [M + H] calcd. for C H NO : 262.0863, found
89 %); mp 144.0–145.0 °C (hexane/ethyl acetate); R 0.50 (hexane/
1
7
12
2
f
ethyl acetate, 4:1); 1H NMR (400 MHz, CDCl ) δ 8.69–8.67 (m, 2H,
2
62.0869.
3
-Phenyl-1H-isochromen-1-one (3)[25] was obtained from methyl
-(phenylethynyl) benzoate (1n) according to General Procedure
Ar), 7.69 (d, J = 7.2 Hz, 2H, Ar), 7.63 (d, J = 6.6 Hz, 2H, Ar), 7.58–7.56
3
2
(
m, 3H, Ar), 7.48–7.36 (m, 6H, Ar); 13C NMR (100 MHz, CDCl ) δ 161.4,
3
1
55.7, 155.6, 136.1, 135.7, 135.0, 131.7, 130.8, 130.0, 129.7, 129.6,
A as colorless crystals (106 mg, 95 %); mp 88.0–89.0 °C (hexane/
+
1
129.0, 128.7 (×2), 128.5; HRMS (ESI): m/z [M + H] calcd. for
C H N : 310.1339, found 310.1339.
ethyl acetate); R 0.45 (hexane/ethyl acetate, 4:1); H NMR (400 MHz,
f
+
21 16 3
CDCl ) δ 8.28 (d, J = 8.2 Hz, 1H, Ar), 7.85 (d, J = 6.5 Hz, 2H, Ar), 7.69
3
13
(
t, J = 8.1 Hz, 1H, Ar), 7.48–7.38 (m, 5H, Ar), 6.92 (s, 1H, CH);
C
3-(4-Methoxyphenyl)-5,6-diphenyl-1,2,4-triazine (5b): yellow
NMR (100 MHz, CDCl ) δ 162.3, 153.7, 137.6, 134.9, 132.0, 130.0, crystals (72.1 mg, 85 %); mp 161.0–162.0 °C (hexane/ethyl acetate);
3
1
1
29.7, 128.9, 128.2, 126.1, 125.3, 120.6, 101.9; HRMS (ESI): m/z [M + R 0.40 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 8.63
f
3
+
+
H] calcd. for C H O : 223.0754, found 223.0746.
(d, J = 9.0 Hz, 2H, Ar), 7.67 (d, J = 7.1 Hz, 2H, Ar), 7.61 (d, J = 6.4 Hz,
1
5 11 2
2
3
1
5
H, Ar), 7.44–7.34 (m, 6H, Ar), 7.07 (d, J = 9.0 Hz, 2H, Ar), 3.90 (s,
General Procedure B. Preparation of Imidazoles 4: A solution
of trifluoromethanesulfonic acid (75.0 mg, 500 μmol, 2.0 equiv) in
chlorobenzene (0.5 mL) was added to a flask containing a solution
of diphenylacetylene (1b) (44.6 mg, 250 μmol, 1.0 equiv), α-picoline
N-oxide (68.2 mg, 625 μmol, 2.5 equiv) and Ph PAuNTf (9.24 mg,
H, OMe); 13C NMR (100 MHz, CDCl ) δ 162.7, 161.2, 155.5, 155.0,
3
36.2, 135.8, 130.7, 130.2, 129.9, 129.5 (×2), 128.6 (×2), 127.4, 114.3,
+
+
5.5; HRMS (ESI): m/z [M + H] calcd. for C H N O : 340.1444,
22 18 3
found 340.1469.
3
2
1
2.5 μmol, 5 mol-%) in chlorobenzene (0.5 mL). The resulting mix-
ture was stirred at 50 °C for 6 h. Then a benzaldehyde (300 μmol,
.2 equiv), ammonium acetate (96.4 mg, 125 μmol, 5.0 equiv) and
chlorobenzene (1.0 mL) were added. The mixture was stirred at
20 °C for 24 h. After cooling, the solvent was then removed in
5
,6-Diphenyl-3-(4-(trifluoromethyl)phenyl)-1,2,4-triazine (5c):
yellow crystals (79.2 mg, 84 %); mp 151.0–152.0 °C (hexane/ethyl
acetate); R 0.50 (hexane/ethyl acetate, 4:1); H NMR (400 MHz,
CDCl ) δ 8.79 (d, J = 8.2 Hz, 2H, Ar), 7.83 (d, J = 8.3 Hz, 2H, Ar), 7.69
1
1
f
3
1
(d, J = 7.3 Hz, 2H, Ar), 7.64 (d, J = 6.8 Hz, 2H, Ar), 7.48–7.38 (m, 6H,
vacuo. The residue was purified by silica gel chromatography eluted
by EtOAc/hexane (1:4) to afford target imidazoles 4.
13
Ar); C NMR (100 MHz, CDCl ) δ 160.3, 156.3, 155.9, 138.3, 135.7,
3
135.4, 133.2 (q, J = 32.5 Hz, C), 130.0 (×2), 129.6, 128.8 (×2), 128.7,
F
19
,5-Diphenyl-2-(4-tolyl)-1H-imidazole (4a):[38] colorless crystals
125.9 (q, J = 3.7 Hz, CH), 125.5, 122.8;
δ –62.8; HRMS (ESI): m/z [M + H] calcd. for C H F N : 378.1213,
found 378.1223.
F NMR (376.5 MHz, CDCl )
4
F
3
+
+
(69.8 mg, 90 %); mp 231.5–232.0 °C (hexane/ethyl acetate); R 0.60
22 15 3 3
f
1
(hexane/ethyl acetate, 2:1); H NMR (400 MHz, [D ]DMSO) δ 12.59
6
(
7
1
br. s, 1H, NH), 7.98 (d, J = 8.1 Hz, 2H, Ar), 7.54–7.52 (m, 4H, Ar), 7.37–
General Procedure D. Preparation of Quinoxalines 6: A solution
of trifluoromethanesulfonic acid (75.0 mg, 500 μmol, 2.0 equiv) in
chlorobenzene (0.5 mL) was added to a flask containing a solution
of internal alkyne 1 (250 μmol, 1.0 equiv), α-picoline N-oxide
1
3
.28 (m, 8H, Ar), 2.35 (s, 3H, Me); C NMR (100 MHz, [D ]DMSO) δ
6
45.6, 137.6, 129.2, 128.3, 127.7, 125.1, 20.9; HRMS (ESI): m/z [M +
+
+
H] calcd. for C H N : 311.1543, found 311.1549.
22 19 2
2
-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (4b):[38] color-
(68.2 mg, 625 μmol, 2.5 equiv) and Ph PAuNTf (9.24 mg, 12.5 mmol,
3 2
less crystals (71.0 mg, 87 %); mp 233.0–234.0 °C (hexane/ethyl acet- 5 mol-%) in chlorobenzene (0.5 mL). The resulting mixture was
1
ate); Rf 0.35 (hexane/ethyl acetate, 2:1); H NMR (400 MHz,
stirred at 50 °C for 6 h. Then o-phenylenediamine 8 (275 μmol,
1.1 equiv) and chlorobenzene (1.0 mL) were added. The mixture
was stirred at 90 °C for 10 h. Upon cooling to r.t., the solvent was
[D ]DMSO) δ 12.51 (br. s, 1H, NH), 8.02 (d, J = 8.8 Hz, 2H, Ar), 7.53–
6
7
3
1
.51 (m, 4H, Ar), 7.36–7.29 (m, 6H, Ar), 7.04 (d, J = 8.8 Hz, 2H, Ar),
1
3
.82 (s, 3H, OMe); C NMR (100 MHz, [D ]DMSO) δ 159.4, 145.6, removed in vacuo. The residue was purified by silica gel chromatog-
6
+
28.4, 127.7, 126.7, 123.1, 114.1, 55.2; HRMS (ESI): m/z [M + H]
raphy eluting with EtOAc/hexane (gradient from 1:12 to 1:8) to af-
ford target quinoxalines 6.
+
calcd. for C H N O : 327.1492, found 327.1478.
22 19 2
2,3-Diphenylquinoxaline (6a):[40] colorless crystals (66.4 mg, 94 %);
2
-(4-Bromophenyl)-4,5-diphenyl-1H-imidazole (4c):[38] colorless
crystals (67.5 mg, 72 %), mp 243.0–244.5 °C (hexane/ethyl acetate); mp 129.5–130.5 °C (hexane/ethyl acetate); R
0.30 (hexane/ethyl
f
R 0.60 (hexane/ethyl acetate, 2:1); H NMR (400 MHz, [D ]DMSO) δ acetate, 8:1); 1H NMR (400 MHz, CDCl
1
) δ 8.20–8.18 (m, 2H, Ar),
7.79–7.76 (m, 2H, Ar), 7.54–7.52 (m, 4H, Ar), 7.39–7.32 (m, 6H, Ar);
f
6
3
1
2
2.77 (br. s, 1H, NH), 8.04 (d, J = 8.6 Hz, 2H, Ar), 7.68 (d, J = 8.6 Hz,
H, Ar), 7.55 (d, J = 7.2 Hz, 2H, Ar), 7.50 (d, J = 7.1 Hz, 2H, Ar), 7.44
1
3
C NMR (100 MHz, CDCl ) δ 153.6, 141.4, 139.3, 130.1, 130.0, 129.4,
3
+
+
(t, J = 7.4 Hz, 2H, Ar), 7.38 (t, J = 7.2 Hz, 1H, Ar), 7.30 (t, J = 7.4 Hz,
128.9, 128.4; HRMS (ESI): m/z [M + H] calcd. for C20H N :
15 2
1
3
2
H, Ar), 7.23 (t, J = 7.3 Hz, 1H, Ar); C NMR (100 MHz, [D ]DMSO)
283.1230, found 283.1231.
6
δ 144.4, 137.3, 135.0, 131.6, 130.9, 129.5, 128.6 (×2), 128.4, 128.2,
-(4-Methoxyphenyl)-3-phenylquinoxaline (6b):[40] yellow crys-
tals (66.4 mg, 85 %); mp 105.5–106.5 °C (hexane/ethyl acetate); Rf
2
+
1
27.9, 127.1, 127.0, 126.6, 121.4; HRMS (ESI): m/z [M + H] calcd. for
+
C H BrN : 375.0491, found 375.0496.
1
21
16
2
0
.45 (hexane/ethyl acetate, 4:1); H NMR (400 MHz, CDCl ) δ 8.17–
3
General Procedure C. Preparation of Triazines 5: A solution of
8.14 (m, 2H, Ar), 7.77–7.72 (m, 2H, Ar), 7.55–7.53 (m, 2H, Ar), 7.48
trifluoromethanesulfonic acid (75.0 mg, 500 μmol, 2.0 equiv) in (d, J = 8.8 Hz, 2H, Ar), 7.37–7.36 (m, 3H, Ar), 6.86 (d, J = 8.8 Hz, 2H,
chlorobenzene (0.5 mL) was added to a flask containing a solution
Ar), 3.82 (s, 3H, OMe); 13C NMR (100 MHz, CDCl ) δ 160.4, 153.6,
3
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Full Paper
1
9
1
1
53.2, 141.5, 141.2, 139.6, 131.6, 131.5, 130.0, 129.9, 129.7, 129.3, 115.5 (d, J = 21.7 Hz, CH); F NMR (376.5 MHz, CDCl ) δ –112.4;
F 3
+
+
+
29.2, 128.9, 128.5, 113.9, 55.4; HRMS (ESI): m/z [M + H] calcd. for HRMS (ESI): m/z [M + H] calcd. for C H FN : 251.0979, found
16
12
2
+
C H N O : 313.1335, found 313.1343.
251.0984.
-(4-Fluorophenyl)-3-phenylquinoxaline (6c):[40] yellow crystals General Procedure F. Preparation of Diazepines 11: A solution
65.3 mg, 87 %); mp 109.5–111.0 °C (hexane/ethyl acetate); R 0.30
of trifluoromethanesulfonic acid (75.0 mg, 500 μmol, 2.0 equiv) in
hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 8.19–8.15 chlorobenzene (0.5 mL) was added to a flask containing a solution
of internal alkyne 1 (250 μmol, 1.0 equiv), α-picoline N-oxide
m, 3H, Ar), 7.03 (t, J = 8.7 Hz, 2H, Ar); C NMR (100 MHz, CDCl ) δ (68.2 mg, 625 mmol, 2.5 equiv) and Ph PAuNTf (9.24 mg,
63.3 (d, J = 249.3 Hz, CF), 153.5, 152.5, 141.4, 141.3, 139.1, 135.3 12.5 mmol, 5 mol-%) in chlorobenzene (0.5 mL). The resulting mix-
21 17 2
2
(
(
(
(
f
1
3
m, 2H, Ar), 7.80–7.76 (m, 2H, Ar), 7.54–7.50 (m, 4H, Ar), 7.41–7.34
1
3
3
3
2
1
F
(
1
d, J = 3.4 Hz, C), 132.0 (d, J = 8.4 Hz, CH), 130.2 (×2), 129.9, 129.4,
ture was stirred at 50 °C for 6 h. 1,3-Diaminopropane (27.8 mg,
29.3, 129.1, 128.5, 115.6 (d, J = 21.7 Hz, CH); F NMR (376.5 MHz, 375 μmol, 1.5 equiv) and chlorobenzene (1.0 mL) were added. The
F
F
1
9
F
+
+
CDCl ) δ –112.3; HRMS (ESI): m/z [M + H] calcd. for C H FN
3
:
mixture was stirred at 110 °C for 24 h. Upon cooling to r.t., the
solvent was removed in vacuo. The residue was purified by silica
gel chromatography eluting with EtOAc/hexane (gradient from 1:4
to 1:2) to afford target diazepines 11.
3
20 14
2
01.1136, found 301.1129.
(6d):[36]
6
-Methyl-2,3-diphenylquinoxaline
yellow crystals
(67.4 mg, 91 %); mp 116.5–117.5 °C (hexane/ethyl acetate); R 0.30
f
hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 8.07 (d, J = 2,3-Diphenyl-6,7-dihydro-5H-1,4-diazepine (11a):[43] yellow crys-
1
(
3
8
7
.5 Hz, 1H, Ar), 7.96 (s, 1H, Ar), 7.60 (dd, J = 8.6, 1.7 Hz, 1H, Ar),
tals (27.3 mg, 44 %); mp 114.5–116.0 °C (hexane/ethyl acetate); R
f
.53–7.51 (m, 4H, Ar), 7.37–7.30 (m, 6H, Ar), 2.62 (s, 3H, Me); 13
C
1
0.35 (hexane/ethyl acetate, 2:1); H NMR (400 MHz, CDCl
) δ 7.62–
), 2.36 (p,
) δ 166.9, 136.3, 130.6,
3
3
NMR (100 MHz, CDCl ) δ 153.4, 152.7, 141.4, 140.6, 139.8, 139.4 (×2), 7.60 (m, 4H, Ar), 7.38–7.29 (m, 6H, Ar), 3.54 (br. s, 4H, CH
3
2
13
1
32.4, 130.0 (×2), 128.8 (×2), 128.7, 128.3 (×2), 128.1, 22.0; HRMS J = 6.8 Hz, 2H, CH
2
); C NMR (100 MHz, CDCl
+
+
+
(ESI): m/z [M + H] calcd. for C H N : 297.1386, found 297.1377.
128.7, 127.6, 49.1, 32.1; HRMS (ESI): m/z [M + H] calcd. for
21 17 2
+
-Chloro-2,3-diphenylquinoxaline (6e):[41] yellow crystals
C
17
H
17
N
2
: 249.1386, found 249.1375.
6
(71.2 mg, 90 %), mp 120.0–121.0 °C (hexane/ethyl acetate); R 0.40
2-(4-Fluorophenyl)-3-phenyl-6,7-dihydro-5H-1,4-diazepine
f
1
[43]
(
2
1
hexane/ethyl acetate, 8:1); H NMR (400 MHz, CDCl ) δ 8.18 (d, J = (11b):
yellow crystals (25.9 mg, 39 %); mp 76.5–78.0 °C (hexane/
3
1
.2 Hz, 1H, Ar), 8.11 (d, J = 8.9 Hz, 1H, Ar), 7.70 (dd, J = 8.9, 2.3 Hz,
ethyl acetate); R
f
0.35 (hexane/ethyl acetate, 2:1); H NMR (400 MHz,
) δ 7.62–7.58 (m, 4H, Ar), 7.39–7.30 (m, 3H, Ar), 6.99 (t, J =
H, Ar), 7.52 (d, J = 7.1 Hz, 4H, Ar), 7.40–7.32 (m, 6H, Ar); 13C NMR CDCl
3
1
3
(100 MHz, CDCl ) δ 154.4, 153.7, 141.6, 139.8, 138.9, 138.8, 135.8,
8.6 Hz, 2H, Ar), 3.52 (br. s, 4H, CH
2
), 2.35 (p, J = 6.7 Hz, 2H, CH
= 251.2 Hz, CF),
= 8.7 Hz, CH),
2
);
C
3
1
31.0, 130.5, 130.0, 129.9, 129.2, 129.1, 128.4 (×2), 128.2; HRMS (ESI):
NMR (100 MHz, CDCl
136.2, 132.5 (d, J = 3.2 Hz, C), 130.8, 129.7 (d, J
28.8, 127.5, 115.8 (d, J = 21.9 Hz, CF), 49.1, 49.0, 32.1; F NMR
) δ 166.6, 165.6, 164.2 (d, J
3 F
+
+
m/z [M + H] calcd. for C H ClN : 317.0840, found 317.0843.
F
F
2
0
14
2
1
9
1
(
F
General Procedure E. Preparation of Pyrazines 9: A solution of
trifluoromethanesulfonic acid (75.0 mg, 500 μmol, 2.0 equiv) in
chlorobenzene (0.5 mL) was added to a flask containing a solution
of internal alkyne 1 (250 μmol, 1.0 equiv), α-picoline N-oxide
+
376.5 MHz, CDCl ) δ –109.5; HRMS (ESI): m/z [M + H] calcd. for
3
+
C H FN : 267.1292, found 267.1288.
17
16
2
For compounds 2a–n, 3, 4a–c, 5a, 6a–e, 9a, and 11a,b the H, 13C
spectra and melting points are identical to those reported in the
literature.
1
(109 mg, 1.0 mmol, 4.0 equiv) and Ph PAuNTf (9.24 mg, 12.5 μmol,
3 2
5
mol-%) in chlorobenzene (0.5 mL). The resulting mixture was
stirred at 50 °C for 6 h. Ethylenediamine diacetate (67.6 mg,
75 μmol, 1.5 equiv) and chlorobenzene (1.0 mL) were added. The
resulting mixture was stirred at 110 °C for 24 h. Upon cooling to
3
Acknowledgments
r.t., the solvent was removed in vacuo. The residue was purified by AYuD thanks the Russian Science Foundation for support of
silica gel chromatography eluting with EtOAc/hexane (gradient
from 1:8 to 1:4) to afford target pyrazines 9.
these studies (grant 18-73-00026). We are much obliged to the
Center for Magnetic Resonance, Center for Chemical Analysis
,3-Diphenylpyrazine (9a):[42] orange crystals (41.2 mg, 71 %); mp and Material Research (both belonging to Saint Petersburg
2
1
2
16.5–117.5 °C (hexane/ethyl acetate); R 0.50 (hexane/ethyl acetate, State University) for physicochemical measurements.
f
1
:1); H NMR (400 MHz, CDCl ) δ 8.60 (s, 2H, Ar), 7.48–7.44 (m, 4H,
3
1
3
Ar), 7.35–7.28 (m, 6H, Ar); C NMR (100 MHz, CDCl ) δ 153.0, 142.2,
3
Keywords: Homogeneous catalysis · Heterocycles ·
+
1
38.7, 129.8, 128.8, 128.4; HRMS (ESI): m/z [M + H] calcd. for
+
Oxidation · Gold · Synthetic methods
C H N : 233.1073, found 233.1063.
16 13 2
2
-(4-Methoxyphenyl)-3-phenylpyrazine (9b): orange oil (45.9 mg,
1
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.8 Hz, 2H, Ar), 7.33–7.30 (m, 3H, Ar), 6.82 (d, J = 8.8 Hz, 2H, Ar),
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8
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6
Received: January 23, 2019
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Full Paper
Gold Catalysis
A. Yu. Dubovtsev,* D. V. Dar'in,
M. Krasavin,
V. Yu. Kukushkin* ............................ 1–10
Gold-Catalyzed Oxidation of Inter-
nal Alkynes into Benzils and its Ap-
plication for One-Pot Synthesis of
Five-, Six-, and Seven-Membered
Azaheterocycles
Internal alkynes have been shown to by α-picoline N-oxide in the presence
undergo oxidation to substituted of Ph PAuNТf (5 mol-%).
3
2
benzils (1,2-diarylethane-1,2-diones)
DOI: 10.1002/ejoc.201900108
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10
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim