Ruthenium-catalyzed synthesis of 1,2-diketones from alkynes

Article abstract of DOI:10.1002/ejoc.201402447

The ruthenium-catalyzed synthesis of 1,2-diketones through the oxidation of alkynes by using sodium hypochlorite has been investigated. RuO₄ was generated in situ from inexpensive RuCl₃·xH₂O, and NaOCl as the oxidant demonstrated high performance at room temperature in the solvent diethyl carbonate. A variety of diketones were prepared in good yields by using this environmentally friendly procedure.

Full text of DOI:10.1002/ejoc.201402447

FULL PAPER
DOI: 10.1002/ejoc.201402447
Ruthenium-Catalyzed Synthesis of 1,2-Diketones from Alkynes
Yanan Miao,[a] Antoine Dupé,[a] Christian Bruneau,*[a] and Cédric Fischmeister*[a]
Keywords: Synthetic methods / Oxidation / Ruthenium / Alkynes / Green chemistry
The ruthenium-catalyzed synthesis of 1,2-diketones through
the oxidation of alkynes by using sodium hypochlorite has
been investigated. RuO4 was generated in situ from inexpen-
sive RuCl3·xH2O, and NaOCl as the oxidant demonstrated
high performance at room temperature in the solvent diethyl
carbonate. A variety of diketones were prepared in good
yields by using this environmentally friendly procedure.
1990,[9,10] and recently FeCl3 (5 mol-%)/H2O2 was found to
be an efficient catalyst for a room-temperature oxidation of
electron-rich diarylalkynes.[11] Recently, an interesting cop-
per catalyst was disclosed that operates under mild condi-
tions with O2/H2O as the oxidant. However, the use of Se-
lectfluor to generate the active catalyst might hamper this
approach.[12] Ruthenium catalysts, in particular RuO4, play
a major role in oxidation catalysis.[13] In fact, with regard
to the oxidation of alkynes to diketones, a survey of the
literature shows that the RuO4/NaIO4 oxidation of an alk-
yne to a diketone is the most widespread procedure,[14] de-
spite the requirement of a highly toxic solvent (CCl4) and
oxidant. For these reasons, decreasing the environmental
impact of Ru-catalyzed oxidation reactions is of great inter-
est. In 2010, Wan reported a very efficient catalyst that was
composed of [RuCl2(p-cymene)]2 (0.001 mol-%)/I2 (10 mol-
%) and used tert-butyl hydroperoxide (TBHP) as the oxi-
dant.[15] However, this system required several hours in di-
oxane at 80 °C. Later, the same group reported a room-
temperature catalytic process that consisted of a complex
mixture of [RuCl2(p-cymene)]2, 2,2,6,6-tetramethyl-1-piper-
idinyloxy (TEMPO), Oxone, and NaHCO3 in nitromethane
and water as the reaction media.[16]
Introduction
1,2-Diketones are useful building blocks in organic syn-
thesis, especially the synthesis of heterocyclic compounds
of biological interest.[1] 1,2-Dicarbonyl compounds are also
precursors for the syntheses of N-heterocyclic carbenes
(NHC), a prominent class of ligands in organometallic
chemistry and catalysis.[2] During the past 15 years, many
examples of catalytic syntheses of 1,2-diketones have
emerged, and in particular the oxidation of internal alkynes
has received the most attention, because a wide variety of
these substrates can be obtained through Sonogashira
cross-coupling reactions. These catalytic methods demon-
strate undeniable progress, as these protocols are environ-
mentally more friendly than stoichiometric oxidation proto-
cols that employ, for instance, thallium, manganese, chro-
mium, or mercury salts.[3]
A variety of transition metals have been used for the oxi-
dation of alkynes into 1,2-diketones. Rhenium-[4] and palla-
dium-catalyzed[5] processes that employ either hydrogen
peroxide, dioxygen, sulfoxides, or pyridine N-oxide as the
oxidant have been reported. These catalysts generally per-
form very well with diarylalkynes, but their procedures re-
quire high catalyst loadings (5–10 mol-%) and/or high tem-
peratures (60–140 °C).[6] An interesting Au/Ag catalytic sys-
tem that uses diphenyl sulfoxide as the oxidant was recently
reported as an efficient system for the synthesis of benzil
derivatives and α-oxo imides.[7] However, the best results
were obtained in refluxing dichloroethane, a solvent that is
no longer used by the pharmaceutical industry.[8] Iron cata-
lysts have been reported since Sawyer’s early work in
All these examples demonstrate that the oxidation of alk-
ynes to 1,2-diketones still suffers in many cases from harsh
conditions, high catalyst loadings, and the use of oxidants
and solvents that have a high environmental impact.
Herein, we present our studies that are aimed at decreasing
the environmental impact of the ruthenium-catalyzed oxi-
dation of alkynes. In particular, we have focused on the use
of carbonate solvents and sodium hypochlorite as the oxi-
dant.
[a] UMR CNRS 6226-Université de Rennes1, Institut des Sciences
Chimiques de Rennes, Organometallics: Materials and
Catalysis, Centre for Catalysis and Green Chemistry,
Campus de Beaulieu, Avenue du général Leclerc, 35042 Rennes
Cedex, France
Results and Discussion
In our ongoing efforts on the subject of sequential trans-
formation reactions that involve an initial metathesis trans-
formation, we have been investigating tandem metathesis/
oxidation reactions. Although our initial goals were not
E-mail: cedric.fischmeister@univ-rennes1.fr
christian.bruneau@univ-rennes1.fr
http://scienceschimiques.univ-rennes1.fr/catalyse/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402447.
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Y. Miao, A. Dupé, C. Bruneau, C. Fischmeister
FULL PAPER
achieved, we observed, as reported by Dragojlovic,[17] that performed (see Table 1, Entry 9). As expected, the reaction
dimethyl carbonate (DMC), a solvent recently introduced rate decreased, but benzoic acid was still detected. Decreas-
as a greener alternative to toluene and dichloromethane in ing the catalyst loading or altering the concentration of the
olefin metathesis transformations,[18,19] was truly compati- reagents did not suppress the formation of benzoic acid
ble with the oxidants in our studies.[20] This is especially either (see Table 1, Entries 10–12).
highlighted by the high yielding oxidative cleavage of an
alkene to an aldehyde, a reaction that is usually carried out
in CCl4/H2O (see Scheme 1).
Table 1. Oxidation of tolane.[a]
Entry
Solvent
NaOCl
[equiv.]
t
[h]
Conversion
[%][b]
Yield [%]
[c]
1
2
DMC
DMC
DMC
H2O
DEC
DEC
DEC
DEC
DEC
DEC
DEC
DEC
DEC
4
3
3
4
4
2
3
3
3
3
3
3
3
4
4
4
4
4
4
4
2
8
Ͼ98[d]
76
65
69
34
51
3[e]
4[f]
5
0
0
Ͼ98[d]
46
86
6
7
8
n.d.[g]
86
Scheme 1. Oxidative cleavage of alkene in DMC/H2O.
Ͼ98[d]
Ͼ98
46
82
9[h]
10[j]
11[k]
12[l]
13[m]
n.d.[g,i]
86
As a result, we turned our attention to the RuCl3·xH2O-
catalyzed oxidation of diphenylacetylene (tolane) and em-
ployed DMC as the solvent (see Scheme 2). NaOCl was ini-
tially determined to be the “greenest” oxidant that can be
used without special equipment,[21] as H2O2 is not an ap-
propriate oxidant to generate RuO4 from RuCl3·xH2O.
5.5
2
2
Ͼ98[d]
62
39
59
0
83
0
2
[a] 1 (0.5 mmol), RuCl3·3H2O (0.5 mol-%), [1] = 0.1 m, room temp.,
argon. [b] Monitored by GC with hexadecane as the internal stan-
dard. [c] Isolated yields. [d] 1 was not detected by GC analysis.
[e] Buffer solution was Na2HPO4/NaOH (pH = 12). [f] No reac-
tion. [g] n.d. = not determined. [h] T = 5 °C. [i] Benzoic acid was
detected. [j] RuCl3·3H2O (0.1 mmol-%). [k] [1] = 0.5 m. [l] [1] =
0.02 m. [m] No catalyst.
Scheme 2. RuCl3·xH2O/NaOCl oxidation of tolane (1).
Despite the accessibility and low cost of RuCl3·xH2O,
several ruthenium catalyst precursors, which include olefin
metathesis catalysts, were evaluated to improve the catalytic
performance. As shown in Table 2, none of the examined
precursors yielded improved results. Of note, the complex
[RuCl2(p-cymene)]2, which afforded the best results under
Wan’s conditions,[16] did not reach the level of performance
of RuCl3·xH2O.
Initial attempts were carried out in DMC with a low cat-
alyst loading of RuCl3·xH2O (0.5 mol-%) and 4 equiv. of
sodium hypochlorite. Under these conditions, the reaction
proceeded with full conversion, but diketone 2 was isolated
in only 69% yield (see Table 1, Entry 1). Careful analysis of
the reaction mixture showed the presence of benzoic acid,
a side product that was previously encountered in several
studies of the oxidation of alkynes, including an early report
of the oxidation of an alkyne by using RuO2/NaOCl/CCl4/
H2O.[22] Reducing the excess amount of oxidant did not ef-
fectively suppress the formation of benzoic acid. In addition
to benzoic acid, the dichloro derivative PhClC=CClPh was
also detected by GC–MS analysis. The formation of a
chlorinated product is often encountered when NaOCl is
used, but this issue can be resolved by using a buffered solu-
tion with a pH Ͼ 10.[23] Indeed, when the reaction media
was buffered at pH = 12, the formation of the chlorinated
product was suppressed, and the yield of 2 increased (see
Table 1, Entries 2 and 3). Water was not a suitable solvent
for this reaction (see Table 1, Entry 4), but the replacement
of dimethyl carbonate with diethyl carbonate (DEC) re-
sulted in a reduction in the amount of the benzoic acid
side product to give 2 in 86 and 82% yield after 4 and 2 h,
respectively, at room temperature (see Table 1, Entries 7 and
8). Interestingly, no chlorinated product was formed when
Table 2. Screening of catalyst precursors.[a]
Entry
Catalyst
Conversion [%][b] Yield [%][c]
1
2
3
4
5
6
7
8
RuCl3·xH2O
Ͼ98[d]
90
82
79
[e]
[Ru(COD)Cl2]n
[e]
Ru(dppe)2Cl2
[RuCl2(p-cymene)]2
73[f]
Ͼ98[d]
77
n.d.[g]
74
[h]
RuCl2(p-cymene)PPh3
RuCl2(PCy3)2(=CHPh)[e]
RuCl2(SIMes)(PCy3)(=CHPh)[e]
IrCl3·3H2O
68
79
90
68
0
n.d.[g]
0
[a] 1 (0.5 mmol), catalyst (0.5 mol-%), NaOCl (3 equiv.), DEC
(5 mL), room temp., 2 h. [b] Determined by GC analysis with
hexadecane as the internal standard. [c] Isolated yield. [d] 1 was not
detected by GC analysis. [e] COD = 1,5-cyclooctadiene, dppe = 1,2-
bis(diphenylphosphino)ethane, Cy = cyclohexyl, Mes = 2,4,6-
trimethylphenyl. [f] After 6 h. [g] n.d.
[h] 0.25 mol-%.
=
not determined.
The scope of the reaction was then explored with a vari-
diethyl carbonate was used as the solvent. Further optimi- ety of internal alkynes that were easily prepared by using a
zation attempts were carried out to improve the selectivity palladium-catalyzed Sonogashira coupling reaction. In par-
of the reaction. Hence, low-temperature experiments were ticular, the effects of steric and electronic parameters were
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Ruthenium-Catalyzed Synthesis of 1,2-Diketones from Alkynes
evaluated. Good yields were obtained by using diphenyl- strate. The situation was somewhat different with substrates
acetylene derivatives that were substituted with an electron- that contained an electron-withdrawing group. In these
donating group, which included a sterically hindered sub- cases (see Table 3, Entries 3–9), despite almost full conver-
sion, the 1,2-diketones were isolated in moderate to good
Table 3. Scope of the reaction.[a]
yields. These results can be rationalized by mechanistic con-
siderations (see below). However, the lower reactivity of
alkynes with electron-withdrawing substituents is a general
problem that is observed in the oxidation of alk-
ynes.[5,11,14d,16] Likewise, aliphatic alkynes usually display
lower reactivity to lead to modest yields.
On the basis of the mechanism for the oxidation of alk-
enes, it is generally accepted that the RuO4 oxidation of
alkynes to 1,2-diketones involves a [3+2] cycloaddition.[13b]
This hypothesis was confirmed in 2000 by Che et al. who
presented the first evidence for a [3+2] cycloaddition in the
oxidation of an alkyne by using a cis-dioxoruthenium(VI)
complex.[24] In 2004, Yang et al. proposed a mechanism for
the oxidation of alkynes to acids, in which the generated
1,2-diketone undergoes a Baeyer–Villiger-type oxidation by
using peroxymonosulfate to give an acid anhydride, which
upon hydrolysis leads to
a
carboxylic acid (see
Scheme 3).[25]
Scheme 3. Suggested mechanism for the formation of carboxylic
acids from diketones.
On the basis of these investigations, a tentative mecha-
nism for the RuCl3·xH2O/NaOCl oxidation of alkynes is
proposed (see Scheme 4). A [3+2] cycloaddition between
the in situ generated RuO4 and the alkyne generates
metallacycle B, which undergoes a rapid electrocyclic frag-
mentation to give the desired 1,2-diketone C and RuO2.
Similar to Yang’s mechanism (see Scheme 3), the cleavage
of the diketone by using NaOCl proceeds through a nucleo-
philic addition of the hypochlorite ion to the carbonyl func-
tional group to afford intermediate D. A Baeyer–Villiger-
type rearrangement further leads to acid anhydride E and
subsequently to the corresponding carboxylic acid. How-
ever, a test showed that benzil (2) was indeed converted into
benzoic acid upon reaction with NaOCl under basic condi-
tions with or without RuO4.[26,27] These reactions were,
however, very slow and could not account for the total for-
mation of benzoic acid. Hence, other pathway(s) were con-
sidered, such as pathway II. Here, ruthenacycle B undergoes a
Baeyer–Villiger-type rearrangement followed by the ad-
dition of NaOCl to afford F and subsequently furnish an-
hydride E. Both mechanisms I and II are in agreement with
the experimental results, as the nucleophilic addition of
NaOCl to a carbonyl or alkenyl group should be facilitated
by an electron-withdrawing substituent on the aromatic ring
(R1 in Scheme 4) and, hence, lead to larger amounts of
benzoic acid derivatives.
[a] Alkyne (0.5 mmol), RuCl3·3H2O (0.5 mol-%), NaOCl (3 equiv.),
DEC (5 mL), room temp., 4 h. [b] Monitored by GC. [c] Isolated
yield. [d] 8 h.
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5073

Y. Miao, A. Dupé, C. Bruneau, C. Fischmeister
FULL PAPER
Scheme 4. Proposed mechanism for 1,2-diketone formation.
General Procedure A. Preparation of Internal Alkynes through Sono-
gashira Coupling Reaction: A mixture of phenylacetylene (561.3 mg,
Conclusions
We have demonstrated that the ruthenium-catalyzed oxi-
dation of alkynes to 1,2-diketones could be performed un-
der environmentally friendly experimental conditions. In
particular, the use of NaOCl as a unique oxidant along with
the low catalyst loading of inexpensive RuCl3·xH2O en-
abled the room-temperature synthesis of a variety of 1,2-
diketones in diethyl carbonate. As encountered in most
transition-metal-catalyzed oxidations of alkynes, the reac-
tion performed particularly well when diarylalkynes with
electron-rich substituents were employed, but performance
dropped when electron-poor or aliphatic alkynes were em-
ployed. Despite this limitation, we believe that this protocol
exhibits both a favorable balance between cost and environ-
mental impact as well as good yields. Given the strengthen-
5.5 mmol, 1.1 equiv.),
a
halobenzene derivative (5 mmol,
1.0 equiv.), PdCl2(PPh3)2 (35.1 mg, 1 mol-%), and PPh3 (26.23 mg,
2 mol-%) in NEt3 (20 mL) was stirred at room temperature under
argon for 5 min. CuI (9.5 mg, 1 mol-%) was added, the reaction
vessel was sealed, and the mixture stirred at 60 °C overnight. The
reaction mixture was filtered, and the filtrate was washed with
Et2O. The combined organic layers were washed with saturated
NH4Cl solution, HCl (1 n), NaOH (1 n), and brine and then dried
with MgSO4. After filtration, the solvent was removed in vacuo.
The residue was purified by silica gel chromatography to afford the
pure alkynes.
General Procedure B. Oxidation of Alkynes: A dry Schlenk tube
was loaded with DEC (5 mL), hexadecane (gas chromatography
standard, 20 μL) and the substrate (0.5 mmol). RuCl3·3H2O
(0.5 mol-% in solution) and NaOCl (13 wt.-% solution, 3 equiv.)
ing of regulations with regard to the use of toxic reagents were subsequently added. The mixture was stirred at 25 °C (regu-
lated oil-bath temperature) and monitored by gas chromatography.
The reaction was quenched by the addition of a saturated aqueous
solution of Na2SO3, and the resulting mixture was extracted with
ethyl acetate (4ϫ 10 mL). The combined organic layers were dried
with Na2SO4 and then concentrated, and the residue was purified
by chromatography on a silica gel column (mixture of ethyl acetate
and petroleum ether).
and waste treatments, this protocol appears an interesting
alternative to the widespread oxidation process that em-
ploys NaIO4 in carbon tetrachloride.
Experimental Section
General Methods: All reactions were conducted under argon and
by using standard Schlenk tube techniques, unless otherwise men-
tioned. DMC and DEC were distilled and stored over molecular
sieves (4 Å) prior to use. NEt3 was degassed. Organic reagents were
obtained from commercial sources and used as received.
RuCl3·xH2O was purchased from Umicore Precious Metals. NMR
spectroscopic data were recorded with a Bruker 400 MHz spec-
trometer, unless otherwise noted. The data are reported in ppm
relative to the residual solvent CHCl3 for 1H NMR (δ = 7.26 ppm)
Procedure for the Oxidation of Benzil (2): In the first experiment, a
dry Schlenk tube was loaded with DEC (5 mL), hexadecane (gas
chromatography standard, 20 μL), and 2 (0.5 mmol). Then, NaOCl
(13 wt.-% solution, 3 equiv.) was added. The mixture was stirred at
25 °C (regulated oil.bath temperature) for 4 h. The reaction was
quenched by the addition of a saturated aqueous solution of
Na2SO3, and the resulting mixture was extracted with ethyl acetate
(4ϫ 10 mL). The combined organic layers were dried with Na2SO4.
Conversions were below 6%. The aqueous phase was acidified to
and CDCl3 for 13C NMR (δ = 77.0 ppm). Coupling constants are pH = 4 by the addition of HCl (1 n) and then extracted with
reported in Hz. A GC-2014 Shimadzu gas chromatograph (Equity-
5, 30 mϫ0.25 mm) was used to monitor the reactions. LRMS were
recorded with a GC–MS Shimadzu QP2010S apparatus. The prod-
ucts were purified by chromatography on a silica gel column using
mixtures of petroleum ether and ethyl acetate as the eluent.
EtOAc. No benzoic acid was detected in this organic phase. A sec-
ond experiment was carried out by combining RuCl3·3H2O
(0.5 mol-%) and NaOCl (3 equiv.) in DEC (5 mL) at room temp.
for 2 h. Compound 2 (1 equiv.) was then added, and the reaction
mixture was stirred at room temp. for 2 h. Again, conversions
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Ruthenium-Catalyzed Synthesis of 1,2-Diketones from Alkynes
were below 5%, and only trace amounts of benzoic acid were de-
tected.
1-[4-(2-Phenylethynyl)phenyl]ethanone (10): Compound 10 was pre-
pared according to general procedure A to give a white solid (95%
yield). NMR spectroscopic data are consistent with reported
data.[7] 1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.3 Hz, 2
H), 7.61 (d, J = 8.3 Hz, 2 H), 7.58–7.53 (m, 2 H), 7.40–7.35 (m, 3
H), 2.62 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 197.2,
136.2, 131.7, 131.6, 128.8, 128.4, 128.3, 128.2, 122.7, 92.7, 88.6,
26.6 ppm. LRMS: calcd. for C16H12O [M]+· 220; found 220.
Characterization Data
1-Methoxy-4-(phenylethynyl)benzene (3): Compound 3 was pre-
pared according to general procedure A to give a yellow solid (88%
yield). NMR spectroscopic data are consistent with reported
data.[28] 1H NMR (400 MHz, CDCl3): δ = 7.51 (dd, J = 8.0, 2.0 Hz,
2 H), 7.47 (d, J = 8.4 Hz, 2 H), 7.35–7.30 (m. 3 H), 6.88 (d, J =
8.8 Hz, 2 H), 3.83 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ
= 159.6, 133.0, 131.4, 128.3, 127.9, 123.6, 115.4, 114.0, 89.4, 88.1,
55.3 ppm. LRMS: calcd. for C15H12O [M]+· 208; found 208.
[4-(2-Phenylethynyl)phenyl] Acetate (11): Compound 11 was pre-
pared according to general procedure A to give a white solid (89%
yield). NMR spectroscopic data are consistent with reported
data.[28] 1H NMR (400 MHz, CDCl3): δ = 7.56–7.52 (m, 4 H),
7.37–7.32 (m, 3 H), 7.10 (d, J = 8.4 Hz, 2 H), 2.31 (s, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 169.1, 150.5, 132.7, 131.6, 128.3,
128.3, 123.1, 121.7, 121.0, 89.4, 88.5, 21.1 ppm. LRMS: calcd. for
C16H12O2 [M]+· 236; found 236.
1-Methoxy-2-(phenylethynyl)benzene (4): Compound 4 was pre-
pared according to general procedure A to give a yellow oil (70%
yield). NMR spectroscopic data are consistent with reported
data.[28] 1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 6.8 Hz, 2
H), 7.50 (dd, J = 7.6, 1.2 Hz, 1 H), 7.40–7.25 (m, 4 H), 6.96–6.90
(m, 2 H), 3.92 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
159.9, 133.5, 131.6, 129.7, 128.2, 128.0, 123.5, 120.4, 112.4, 110.7,
93.4, 85.7, 55.8 ppm. LRMS: calcd. for C15H12O [M]+· 208; found
208.
Hex-1-yn-1-ylbenzene (12): Compound 12 was prepared according
to general procedure A to give a light yellow oil (81% yield). NMR
spectroscopic data are consistent with reported data.[28] 1H NMR
(400 MHz, CDCl3): δ = 7.43 (d, J = 6.1 Hz, 2 H), 7.32–7.22 (m, 3
H), 2.44 (t, J = 6.9 Hz, 2 H), 1.68–1.60 (m, 2 H), 1.58–1.45 (m, 2
H), 0.99 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (101 MHz, CDCl3):
δ = 131.5, 128.1, 127.4, 124.1, 90.4, 80.5, 30.8, 22.0, 19.1, 13.6 ppm.
LRMS: calcd. for C12H14 [M]+· 158; found 158.
Ethyl 4-(Phenylethynyl)benzoate (5): Compound 5 was prepared ac-
cording to general procedure A to give a yellow solid (90% yield).
NMR spectroscopic data are consistent with reported data.[28] 1
H
NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.3 Hz, 2 H), 7.59 (d,
J = 8.3 Hz, 2 H), 7.56–7.54 (m, 2 H), 7.41–7.31 (m, 3 H), 4.39 (q, J
= 7.1 Hz, 2 H), 1.41 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 166.1, 131.7, 131.5, 129.9, 129.4, 128.7, 128.4, 127.8,
122.7, 92.2, 88.7, 61.1, 14.3 ppm. LRMS: calcd. for C17H14O2
[M]+· 250; found 250.
1,2-Diphenylethane-1,2-dione (2): Compound 2 was prepared ac-
cording to general procedure B to give a yellow solid (82% yield).
NMR spectroscopic data are consistent with reported data.[5a,10b,15]
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 7.3 Hz, 4 H), 7.67
(t, J = 7.4 Hz, 2 H), 7.52 (m, 4 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 194.7, 135.0, 133.2, 130.0, 129.2 ppm. LRMS: calcd.
for C14H10O2 [M]+· 210; found 210.
4-(Phenylethynyl)benzonitrile (6): Compound 6 was prepared ac-
cording to general procedure A to give a white solid (83% yield).
NMR spectroscopic data are consistent with reported data.[28] 1
H
1-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (13): Compound 13
was prepared according to general procedure B to give a yellow oil
(83% yield). NMR spectroscopic data are consistent with reported
data.[15] 1H NMR (400 MHz, CDCl3): δ = 7.96 (m, 4 H), 7.63 (m,
1 H), 7.50 (m, 2 H), 6.98 (d, J = 8.1 Hz, 2 H), 3.88 (s, 3 H) ppm.
13C NMR (101 MHz, CDCl3): δ = 194.8, 193.2, 165.0, 134.7, 133.3,
132.4, 129.9, 129.9, 126.2, 114.4, 55.7 ppm. LRMS: calcd. for
C15H12O3 [M]+· 240; found 240.
NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.5 Hz, 2 H), 7.61 (d,
J = 8.5 Hz, 2 H), 7.58–7.51 (m, 2 H), 7.39–7.36 (m, 3 H) ppm. 13
C
NMR (101 MHz, CDCl3): δ = 132.1, 132.0, 131.8, 129.1, 128.5,
128.2, 122.2, 118.5, 111.5, 93.8, 87.7 ppm. LRMS: calcd. for
C15H9N [M]+· 203; found 203.
2-(Phenylethynyl)benzonitrile (7): Compound 7 was prepared ac-
cording to general procedure A to give a yellow oil (82% yield).
NMR spectroscopic data are consistent with reported data.[28] 1
H
1-(2-Methoxyphenyl)-2-phenylethane-1,2-dione (14): Compound 14
was prepared according to general procedure B to give a yellow
solid (71% yield). NMR spectroscopic data are consistent with re-
ported data.[5a] 1H NMR (400 MHz, CDCl3): δ = 8.02 (dd, J = 7.6,
2.1 Hz, 1 H), 7.91 (d, J = 7.6 Hz, 2 H), 7.60–7.58 (m, 2 H), 7.52–
7.45 (m, 2 H), 7.15–7.10 (m, 1 H), 6.93 (d, J = 8.4 Hz, 1 H), 3.56
(s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 194.8, 193.5,
160.4, 136.5, 133.7, 132.9, 130.4, 129.2, 128.6, 123.8, 121.5, 112.3,
55.6 ppm. LRMS: calcd. for C15H12O3 [M]+· 240; found 240.
NMR (400 MHz, CDCl3): δ = 7.69–7.54 (m, 5 H), 7.47–7.32 (m, 4
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 132.6, 132.3, 132.1,
132.0, 129.2, 128.4, 128.2, 127.2, 122.0, 117.5, 115.3, 96.0,
85.6 ppm. LRMS: calcd. for C15H9N [M]+· 203; found 203.
1-Chloro-4-(phenylethenyl)benzene (8): Compound 8 was prepared
according to general procedure A to give a white solid (81% yield).
NMR spectroscopic data are consistent with reported data.[28] 1
H
NMR (400 MHz, CDCl3): δ = 7.55–7.50 (m, 2 H), 7.46 (d, J =
8.5 Hz, 2 H), 7.37–7.31 (m, 5 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 134.2, 132.8, 131.6, 128.7, 128.5, 128.4, 122.9, 121.8,
90.3, 88.2 ppm. LRMS: calcd. for C14H935Cl [M]+ 212; found 212;
calcd. for C14H937Cl [M]+· 214; found 214 (C14H935Cl/C14H937Cl:
2.8).
Ethyl 4-(2-Oxo-2-phenylacetyl)benzoate (15): Compound 15 was
prepared according to general procedure B to give a yellow solid
(63% yield). NMR spectroscopic data are consistent with reported
data.[5a] 1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 8.4 Hz, 2
H), 8.03 (d, J = 8.4 Hz, 2 H), 7.97 (dd, J = 7.3, 1.6 Hz, 2 H), 7.68
(m, 1 H), 7.53 (m, 2 H), 4.11 (q, J = 7.1 Hz, 2 H), 1.41 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 193.8, 193.7,
165.4, 136.0, 135.7, 135.1, 132.7, 130.0, 129.9, 129.7, 129.1, 61.6,
14.2 ppm. LRMS: calcd. for C17H14O4 [M]+· 282; found 282.
1-Nitro-4-(phenylethynyl)benzene (9): Compound 9 was prepared
according to general procedure A to give a yellow solid (85%
yield). NMR spectroscopic data are consistent with reported
data.[28] 1H NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 8.8 Hz, 2
H), 7.66 (d, J = 8.8 Hz, 2 H), 7.58–7.55 (m, 2 H), 7.45–7.35 (m, 3 4-(2-Oxo-2-phenylacetyl)benzonitrile (16): Compound 16 was pre-
H) ppm. 13C NMR (101 MHz, CDCl3): δ = 147.0, 132.2, 131.8,
130.3, 129.3, 128.5, 123.6, 122.1, 94.7, 87.5 ppm. LRMS: calcd. for
C14H9NO2 [M]+· 223; found 223.
pared according to general procedure B to give a yellow solid (61%
yield). NMR spectroscopic data are consistent with reported
data.[16] 1H NMR (400 MHz, CDCl3): δ = 8.08 (d, J = 8.5 Hz, 2
Eur. J. Org. Chem. 2014, 5071–5077
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5075

Y. Miao, A. Dupé, C. Bruneau, C. Fischmeister
FULL PAPER
H), 7.987 (dd, J = 7.3, 1.6 Hz, 2 H), 7.81 (d, J = 8.5 Hz, 2 H), 7.70
(m, 1 H), 7.54 (m, 2 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
193.0, 192.4, 135.9, 135.4, 132.7, 132.4, 130.2, 130.0, 129.2, 117.9,
117.5 ppm. LRMS: calcd. for C15H9NO2 [M]+· 235; found 235.
eur et de la Recherche for their support. We thank the Fondation
Rennes 1 for a grant to Y. M. The authors also thank the ADEME
(Agence de l’Environnement et de la Maîtrise de l’Energie) and the
Région Bretagne for a Ph.D. grant to A. D.
2-(2-Oxo-2-phenylacetyl)benzonitrile (17): Compound 17 was pre-
pared according to general procedure B to give a yellow solid (42%
yield). NMR spectroscopic data are consistent with reported da-
ta.[5a] 1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.0 Hz, 2 H),
7.94–7.88 (m, 2 H), 7.80–7.60 (m, 3 H), 7.55 (m, 2 H) ppm. 13C
NMR (101 MHz, CDCl3): δ = 192.1, 191.2, 135.6, 135.3, 135.1,
134.0, 132.7, 132.5, 132.3, 130.2, 129.2, 117.0, 112.0 ppm. LRMS:
calcd. for C15H9NO2 [M]+· 235; found 235.
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1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (18): Compound 18
was prepared according to general procedure B to give a yellow
solid (79% yield). NMR spectroscopic data are consistent with re-
ported data.[16] 1H NMR (400 MHz, CDCl3): δ = 7.98–7.92 (m, 4
H), 7.67 (m, 1 H), 7.65–7.44 (m, 2 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 193.9, 193.1, 141.6, 135.0, 132.8, 131.3, 131.2, 129.9,
129.4, 129.1 ppm. LRMS: calcd. for C14H935ClO2 [M]+ 244; found
244; calcd. for C14H937ClO2 [M]+· 246; found 246 (C14H935ClO2/
C14H937ClO2: 3.0).
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1-(4-Nitrophenyl)-2-phenylethane-1,2-dione (19): Compound 19 was
prepared according to general procedure B to give a yellow solid
(53% yield). NMR spectroscopic data are consistent with reported
data.[16] 1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 8.8 Hz, 2
H), 8.17 (d, J = 8.8 Hz, 2 H), 7.99 (d, J = 7.3 Hz, 2 H), 7.71 (m, 1
H), 7.55 (m, 2 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 192.8,
192.0, 151.2, 137.3, 135.4, 132.4, 130.9, 130.0, 129.2, 124.1 ppm.
LRMS: calcd. for C14H9NO4 [M]+· 255; found 255.
1-(4-Acetylphenyl)-2-phenylethane-1,2-dione (20): Compound 20
was prepared according to general procedure B to give a yellow
solid (83% yield). NMR spectroscopic data are consistent with re-
ported data.[7] 1H NMR (400 MHz, CDCl3): δ = 8.07 (m, 4 H),
7.98 (d, J = 7.2 Hz, 2 H), 7.69 (t, J = 7.4 Hz, 1 H), 7.53 (dd, J =
7.4, J = 7.4 Hz, 2 H), 2.66 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 197.2, 193.7, 193.6, 141.3, 136.0, 135.1, 132.7, 130.1,
130.0, 129.1, 128.7, 26.9 ppm. LRMS: calcd. for C16H12O3 [M]+·
252; found 252.
4-(2-Oxo-2-phenylacetyl)phenyl Acetate (21): Compound 21 was
prepared according to general procedure B to give a yellow solid
(64% yield). NMR spectroscopic data are consistent with reported
data.[29] 1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.4 Hz, 2
H), 7.96 (d, J = 7.2 Hz, 2 H), 7.66 (t, J = 7.6 Hz, 1 H), 7.52 (m, 2
H), 7.28–7.23 (m, 2 H), 2.33 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 194.2, 193.1, 168.5, 155.7, 134.9, 132.8, 131.6, 130.5,
129.9, 129.0, 122.3, 21.1 ppm. LRMS: calcd. for C16H12O4 [M]+·
268; found 268.
1-Phenylhexane-1,2-dione (22): Compound 22 was prepared accord-
ing to general procedure B to give a yellow oil (33% yield). NMR
spectroscopic data are consistent with reported data.[5a] 1H NMR
(400 MHz, CDCl3): δ = 7.97 (d, J = 7.8 Hz, 2 H), 7.62 (m 1 H),
7.50–7.45 (m, 2 H), 2.87 (t, J = 7.4 Hz, 2 H), 1.68 (m, 2 H), 1.39
(m, 2 H), 0.94 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 203.5, 192.6, 134.5, 132.0, 130.1, 128.8, 38.5, 24.9,
22.3, 13.8 ppm. LRMS: calcd. for C12H14O2 [M]+· 190; found 190.
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1
cle): H and 13C NMR spectra.
Acknowledgments
The authors are grateful to the Centre National de la Recherche
Scientifique (CNRS) and the Ministère de l’Enseignement Supéri-
5076
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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[26] See Experimental Section for details.
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Published Online: July 7, 2014
Eur. J. Org. Chem. 2014, 5071–5077
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5077