Two-Step One-Pot Synthesis of Unsymmetrical (Hetero)Aryl 1,2-Diketones by Addition-Oxygenation of Potassium Aryltrifluoroborates to (Hetero)Arylacetonitriles

Article abstract of DOI:10.1002/ejoc.201701625

An efficient one-pot two-step procedure for the synthesis of unsymmetrical (hetero)aryl 1,2-diketones has been developed. The reaction proceeds through a palladium-catalyzed nucleophilic addition of potassium aryltrifluoroborates to aliphatic nitriles followed by a copper-catalyzed aerobic benzylic C–H oxygenation using molecular oxygen as a green oxidant. This represents the first example of the direct synthesis of unsymmetrical diaryl 1,2-diketones from arylacetonitriles. This method utilizes inexpensive, stable, nontoxic, and readily available starting materials, is highly effective in the presence of both electron-rich and electron-poor nitriles and aryltrifluoroborates, and tolerates a wide variety of functional groups. The synthetic utility of this transformation was shown by increasing the scale of the reaction and by carrying out the one-pot protocol for the preparation of quinoxaline and benzimidazole derivatives. A plausible reaction mechanism has also been proposed.

Full text of DOI:10.1002/ejoc.201701625

DOI: 10.1002/ejoc.201701625
Full Paper
Synthetic Methods
Two-Step One-Pot Synthesis of Unsymmetrical (Hetero)Aryl
1,2-Diketones by Addition-Oxygenation of Potassium
Aryltrifluoroborates to (Hetero)Arylacetonitriles
Yogesh Kumar,[a] Yogesh Jaiswal,[a] and Amit Kumar*[a]
Abstract: An efficient one-pot two-step procedure for the syn- method utilizes inexpensive, stable, nontoxic, and readily avail-
thesis of unsymmetrical (hetero)aryl 1,2-diketones has been de- able starting materials, is highly effective in the presence of
veloped. The reaction proceeds through a palladium-catalyzed both electron-rich and electron-poor nitriles and aryltrifluoro-
nucleophilic addition of potassium aryltrifluoroborates to ali- borates, and tolerates a wide variety of functional groups. The
phatic nitriles followed by a copper-catalyzed aerobic benzylic synthetic utility of this transformation was shown by increasing
C–H oxygenation using molecular oxygen as a green oxidant. the scale of the reaction and by carrying out the one-pot proto-
This represents the first example of the direct synthesis of un- col for the preparation of quinoxaline and benzimidazole deriv-
symmetrical diaryl 1,2-diketones from arylacetonitriles. This atives. A plausible reaction mechanism has also been proposed.
Introduction
diketones.[13] A large drawback, however, involves the depend-
ency of these strategies on elaborate substrates, which are not
cost effective or easy to prepare. Thus, it is desirable to develop
an improved method for the synthesis of 1,2-diketones that ful-
fills the following criteria: (a) uses safe and cost-effective start-
ing materials to avoid any tedious preparations, (b) considers
atom economy, (c) uses a benign oxidant, and (d) employs an
operationally mild method, which can easily be scaled up to
gram levels.
Functionalized organic molecules are important because of
their unique electronic features and wide applications to many
areas of science. Among these molecules, diaryl 1,2-diketones
have attracted the attention of the organic chemistry commu-
nity because they are a key structural motif in numerous natural
and bioactive compounds.[1,2] 1,2-Dicarbonyl compounds also
serve as useful building blocks in organic synthesis and are ex-
tensively used in the preparation of a broad range of versatile
heterocyclic compounds, such as imidazoles,[3] quinoxalines,[4]
triazines[5] and indolone-N-oxides,[6] through standard func-
tional group transformations. In addition, these scaffolds, nota-
bly benzil derivatives, are employed in a number of interesting
applications, such as photosensitive agents in photocurable
coatings,[7] corrosion inhibitors of mild steel,[8] and inhibitors of
carboxylesterase enzymes.[9] Some of the derivatives also show
good antitumor activity.[10] As a consequence of their diverse
applications, several classical and modern synthetic protocols,
which use various precursors such as olefins,[11] both α-halo
and α-hydroxy,[12] and alkynes[13] along with different oxidants,
have been developed for their preparation.[14]
By pursuing these challenges, we envisioned that cost-effec-
tive and commercially available phenylacetonitrile, in which a
phenyl ring is attached at the α-position to the cyano group,
may serve as an ideal starting material for the synthesis of 1,2-
diketones. In recent years, nitriles and their derivatives have
been extensively used for the synthesis of diverse heterocyclic
compounds, as they are inexpensive, stable, nontoxic, and
abundant in nature (Scheme 1a–c).[15–19] Nitriles may also serve
as useful building blocks in organic synthesis. Aromatic nitriles
have often been employed in the synthesis of aryl ketone deriv-
atives and α-keto esters through the addition of arylpalladium
species to the cyano group.[17b–17e,19a,19b] Compared with aro-
matic nitriles, aliphatic nitriles have been less explored because
of their inert nature. The presence of a methylene group adja-
cent to a nitrile makes a venerable precursor by serving as a
pronucleophile, such as an α-carbanion or metallated nitrile.
Recently, Lee et al. and Wang and co-workers reported an
elegant method to synthesize 1,2-diketones from the reaction
of alkynyl carboxylic acids with aryl halides or arylbronic
acids.[13c,13e] Among these precursors, alkynes have been most
extensively used as the key material for the synthesis of 1,2-
Despite tremendous progress, arylacetonitriles have never
been used as the starting material for the direct synthesis of
diaryl 1,2-diketones. With this understanding and our interest
in copper-catalyzed oxidative functionalizations of benzylic
C–H bonds for the synthesis of functionalized organic mol-
ecules,[20] we herein report a general and practical one-pot pro-
cedure for the synthesis of unsymmetrical 1,2-diketones 3. The
reaction between arylacetonitriles 1 and potassium aryltri-
[a] Department of Chemistry, Indian Institute of Technology Patna,
Bihta 801103, Bihar, India
E-mail: amitkt@iitp.ac.in
amitktiitk@gmail.com
https://jabapyne09.wixsite.com/mysite/home
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201701625.
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Table 1. Optimization of the reaction conditions.[a]
.
Entry
1
Reaction conditions
% Yield 3a[b]
Pd(TFA)2, L1, TFA, EtOH, 100 °C,
60
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(OAc)2, L1, TFA, EtOH, 100 °C,
2
54
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L1, TFA, THF/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L1, TFA, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L2, TFA, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L3, TFA, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L4, TFA, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L1, CSA, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L1, CH3SO3H, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L4, TFA, EtOH/H2O, 100 °C,
then K2CO3, DMF, 50 °C, 4 h
3
62
4
69
5
42
6
60
Scheme 1. Reactions of nitriles with organoboron reagent (FG = functional
group).
7
48
8
78, 70[c]
42
fluoroborates 2 proceeds through a Pd-catalyzed nucleophilic
addition reaction followed by a Cu-catalyzed/O2 benzylic C–H
oxygenation without the need to isolate the deoxybenzoin in-
termediate (Scheme 1d). The present method is characterized
by a two-step sequence that is carried out in a one-pot manner.
9
10
11
12
13
14
0
Pd(TFA)2, L1, CSA, EtOH/H2O, 100 °C,
then Cu(OAc)2, DMF, 50 °C, 24 h
44
Pd(TFA)2, L1, CSA, ETOH/H2O, 100 °C,
then Cu(OAc)2, Na2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L1, CSA, EtOH/H2O, 100 °C,
then CuBr2, K2CO3, DMF, 50 °C, 4 h
Pd(TFA)2, L1, CSA, EtOH/H2O, 100 °C,
then Cu(OAc)2, K2CO3, DMSO, 50 °C, 4 h
50
29
Results and Discussion
50
The one-pot procedure is an important and prevalent tech-
nique in synthetic organic chemistry, as it satisfies the demands
of green and sustainable chemistry by reducing reaction time,
cost, and undesired chemical waste.[15d,16a,18a] Because of its
widespread use and low toxicity, copper-catalyzed aerobic
benzylic C–H oxygenation reactions are an efficient method for
the synthesis of complex functionalized organic molecules.[21]
Taking these facts into consideration, we began our investiga-
tion by selecting 2-phenylacetonitrile (1a) and potassium
phenyltrifluoroborate (2a) as model substrates to optimize the
reaction conditions (Table 1). In a general procedure, 1a and 2a
were treated with Pd(TFA)2 (TFA = trifluoroacetic acid, 5 mol-
%), 2,2′-bipyridine (L1, 10 mol-%), and trifluoroacetic acid
(2.0 equiv.) in ethanol at 100 °C for 20 min under microwave
(MW) irradiation.[22] The crude mixture was then treated with
Cu(OAc)2 (5 mol-%) and K2CO3 (5 mol-%) in N,N-dimethylform-
amide (DMF, 1.5 mL), and the reaction was further stirred at
50 °C for 4 h under O2 (1 atm)[23] to afford diaryl 1,2-diketone
3a in 60 % yield (Table 1, Entry 1). Pleased with the initial result,
we proceeded to extensively screen other reaction parameters
such as the metal catalyst, ligand, solvent, and additive to im-
prove the efficacy of the transformation (Table 1).
[a] Reagents and conditions: 1a (0.25 mmol), 2a (0.375 mmol), Pd catalyst
(5 mol-%), ligand (10 mol-%), and additive (2 equiv.) in solvent (2.0 mL) under
MW irradiation at 100 °C for 20 min. Then, the crude mixture was treated
with the Cu salt (5 mol-%) and base (5 mol-%) in DMF (1.5 mL), and the
resulting mixture was stirred at 50 °C for 4 h under O2 (1 atm). [b] Yields of
the products were determined upon completion of the two-step reaction.
[c] Reaction was performed under thermal conditions at 100 °C for 8 h fol-
lowed by the addition of the Cu salt and base in DMF (1.5 mL). The resulting
mixture was then stirred at 50 °C for 4 h under O2 (1 atm).
ing Information). Several different ligands (i.e., L1–L4) were also
screened, and 2,2′-bipyridine (L1) was found to improve the
efficiency of the transformation and afford 3a in 69 % yield
(Table 1, Entries 4–7). Subsequently, a series of additives were
examined, as this variable was observed to be critical to the
outcome of the reaction (Table 1, Entries 7–9). The use of ( )-
camphor-10-sulfonic acid (CSA) as an additive produced the de-
Among the various catalysts that were tested (Table 1, En- sired product 3a in 78 % yield (Table 1, Entry 8), but it is note-
tries 1–7), Pd(TFA)2 and Cu(OAc)2 were most effective for the worthy that deoxybenzoin (2aa) was obtained in 15 % yield
addition of potassium phenyltrifluoroborate to the arylnitrile when the reaction was performed in the absence of ( )-
and the benzylic oxidation of the corresponding intermediate, camphor-10-sulfonic acid (for more details, see Supporting In-
respectively (Table 1, Entry 8). An investigation of the effect of formation). Furthermore, when the same reaction was per-
the solvent revealed that the EtOH/H2O (1:1) mixture gave the formed under thermal conditions at 100 °C for 8 h, instead of
best result (Table 1, Entry 3 vs. 4; for more details, see Support- under microwave irradiation, the desired product 3a was iso-
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lated in 70 % yield (Table 1, Entry 8). Finally, when the reaction properties of the aromatic ring of the arylacetonitriles and
was performed in the absence of the copper salt, no desired potassium aryltrifluoroborates have a minimal effect on the
product was obtained (Table 1, Entry 10).
product yields. Arylacetonitriles 1 that contain electron-rich
groups such as methyl, methoxy, and 3,4-dioxy or electron-neu-
tral groups such as naphthyl and phenyl at the ortho-, meta-,
or para-positions were tolerated and afforded the correspond-
ing 1,2-diketones 3b–3i in yields that ranged from 63 to 83 %.
The structure of product 3g was confirmed by single-crystal X-
ray analysis.[24]
The examined arylacetonitriles that contain halogens such as
fluoro, chloro, 1,2 dichloro, and bromo groups at different posi-
tions of the phenyl ring also afforded the corresponding prod-
uct in moderate to good yields (Table 2, compounds 3j–3q, 56–
75 % yield) and provided an opportunity for further synthetic
We next examined the effect of the base on the reaction
efficiency and found that the yield of 1,2-diketone 3a decreased
dramatically in the absence of base (Table 1, Entry 11). Chang-
ing the base (Table 1, Entry 12, see Supporting Information)
was not productive. The exact role of the base in this oxidative
transformation, however, is currently unclear. Hence, the reac-
tion conditions reported in Table 1, Entry 8 were considered as
optimized for the one-pot synthesis of the diaryl 1,2-diketones.
These conditions were then applied to the synthesis of various
unsymmetrical diaryl 1,2-diketones, that is, by using the two-
step one-pot strategy.
As shown in Table 2, this cross-coupling oxidative transfor- elaboration. Notably, the introduction of strong electron-with-
mation has good functional group tolerance, and the electronic drawing groups, including nitro, ester, and trifluoromethyl
Table 2. Scope of substrates for addition-oxygenation reaction.[a,b]
[a] For reagents and conditions, see Table 1, Entry 8 (bpy = 2,2′-bipyridine). [b] Yields of the products were determined upon completion of the two-step
reaction and are given in parentheses.
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groups, did not hamper the overall product yields (Table 2, the reaction with 3-phenylpropanenitrile (1n) and 2-cyclo-
compounds 3r–3t, 58–79 % yield). The substrate scope of this hexenylacetonitrile (1o), but unfortunately these substrates
addition-oxygenation transformation was further extended to were completely inert under optimized reaction conditions.
the synthesis of heteroaryl 1,2-diketones derivatives (Table 2,
compounds 3u–3y), which were afforded in a range of 40–74 %
yield.[25]
Fortunately, when the reaction was carried out with 10 mmol
of phenylacetonitrile 1a under standard reaction conditions, the
desired diphenyl 1,2-diketone 3a was isolated in 70 % yield,
Similarly, the scope of the arylacetonitriles and arylboronic which is not a substantial decrease. This result highlights the
acids was also examined (Table 3). The results reveal that a robustness of this one-pot strategy for the synthesis of 1,2-
broad range of arylboronic acids that contain electron-donating diketones from commercially available starting materials
(i.e., tert-butyl, methyl, and methoxy), electronically neutral (i.e., (Scheme 2).
naphthyl), and electron-withdrawing (i.e., chloro, acetyl, and
bromo) groups were tolerated to afford the corresponding
product in moderate to good yields (Table 3, compounds 4a–
4h, 52–74 % yield). The presence of a strong electron-withdraw-
ing group (i.e., CF3) on the aromatic ring dramatically decreased
the yield of product 4i to 40 %. Importantly, heterocyclic deriva-
tives of boronic acids such as furyl and thiophenyl compounds
smoothly underwent the reaction with arylacetonitrile deriva-
tives to give the desired heteroaryl 1,2-diketones 4j and 4k in
28 and 48 % yield, respectively. Similarly, 3-indoleacetonitrile
Scheme 2. Gram-scale experiment.
To propose a possible reaction mechanism for this transfor-
(1l) and N-ethyl-3-indoleacetonitrile (1m) underwent the reac- mation, a series of control experiments were carried out. From
tion with an arylboronic acid that contains a fluoro and chloro the results, we believe that either in situ generated diphenyl-
group, respectively, at the para-position to give the correspond- ethanimine (2ab) or deoxybenzoin (2aa) might be the potential
ing heterocyclic 1,2-diketone derivatives (Table 3, compounds intermediate that is subjected to the optimized reaction condi-
4l and 4m, 59 and 68 % yield, respectively). Thus, the outcome tions. However, the desired product was isolated in only 38 %
of the transformation is independent of the nature of substitu- yield when the reaction was carried out with 2ab (Scheme 3a).
ents on the arylboronic acids and arylacetonitriles. We also tried Gratifyingly, when 2aa was subjected to the similar conditions,
Table 3. Scope of arylacetonitriles and arylboronic acids.[a,b]
[a] Reaction was performed with arylboronic acids (0.75 mmol) and KF·2H2O (1.0 mmol), instead of potassium aryltrifluoroborates, under similar conditions
as mentioned in Table 1, Entry 8. [b] Yields of the products were determined upon completion of the two-step reaction and given in parentheses.
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Scheme 3. Mechanistic studies.
the desired product was procured in 70 % yield (Scheme 3a). uct as confirmed by NMR analysis (see Supporting Information).
These results clearly support 2aa as the possible intermediate Because the radical scavenger had an apparent effect on the
of this oxidative transformation.
outcome of the reaction, a radical intermediate may be involved
in this transformation.
To evaluate any electronic effects from the presence of a
substituent on the arylacetonitrile ring [electron-withdrawing
groups (EWGs) and electron-donating groups (EDGs)], a series
of competition experiments between 1e and 1j were carried
out under standard reaction conditions. Equimolar amounts of
electron-rich 1e and electron-poor 1j was treated with 2a un-
der the optimized conditions, and purification by column chro-
matography led to the isolation of the desired products 3e and
3j in 36 and 52 % yield, respectively (3e/3j, 1:1.44, Scheme 3b).
The results indicate that substrates that have EWGs on the aro-
matic ring oxidize faster than those that contain EDGs.
Furthermore, when the reaction was carried out under nitro-
gen or in the open air, the corresponding diaryl 1,2-diketone
3a was either not obtained or produced in only a moderate
yield (Scheme 3c). The use of an alternate oxidant such as
K2S2O8 afforded the desired product 3a, albeit in low yield
(Scheme 3c). These experimental outcomes indicate that the
reaction requires the presence of molecular oxygen.
Taking the above results and previous reports into considera-
tion,[15–20] we then proposed a possible reaction mechanism
(Scheme 4). First, arylpalladium species A is generated by trans-
metalation with the potassium aryltrifluoroborate.[16c,19d–19f]
Nitrile 1a then coordinates with the vacant site of the Pd metal
to form intermediate B, in which an intramolecular migration
of the aryl group from the Pd center to the carbon atom forms
imine palladium species C. Finally, the protonolysis of C fol-
lowed by acidic hydrolysis gives 2aa and regenerates the PdII
catalyst. Next, intermediate 2aa coordinates with the CuII cata-
lyst to form species D, which undergoes an aerobic oxidation
in the presence of molecular oxygen to generate benzylic radi-
cal F. The formation of the TEMPO adduct from the addition
of the radical scavenger further supports the formation of the
benzylic radical. Benzylic radical F is further transformed into
peroxy species G, which finally undergoes secondary hydrogen
abstraction of the benzylic proton followed by elimination of
the CuII salt to produce the corresponding 1,2-diketone 3a.
Quinoxaline and benzimidazole derivatives are important
Next, the reaction was performed in the presence of a radical
scavenger such as (2,2,6,6-tetramethylpiperidin-1-yl)oxyl
(TEMPO) or 2,6-di-tert-butyl-4-methylphenol (BHT, Scheme 3d heterocyclic compounds that are ubiquitous in many bioactive
and e). The desired 1,2-diketone was obtained in a trace molecules.[3,4] Hence, we considered the present optimized
amount, and TEMPO adduct 5 was identified as the major prod- strategy for the concise synthesis of quinoxaline and benzimid-
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Scheme 4. Proposed reaction mechanism.
Scheme 5. One-pot synthesis of quinoxaline and benzimidazole derivatives.
azole derivatives, in which a 1,2-diketone is a key intermediate In addition, this method was successfully applied to the one-
(Scheme 5a). Upon the completion of the addition reaction, pot synthesis of quinoxaline and benzimidazole derivatives,
the crude mixture of 2aa was treated under standard reaction which are important structural units that are found in medici-
conditions along with the addition benzene-1,2-diamine (6, nally active compounds. Further synthetic applications are cur-
Scheme 5). The desired 2,3-diphenylquinoxaline (7) was isolated rently under investigation in our laboratory.
as a major product in good yield (74 %) in the one-pot fashion
from phenylacetonitrile (1a). Similarly, the treatment of the
crude mixture of 1,2-diphenylethanone (2aa) with 6 in the
Experimental Section
open air in the presence of I2/dimethyl sulfoxide (DMSO) af-
forded the corresponding benzimidazole 8 in good yield (72 %,
Scheme 5b).
General Methods: All reagents and solvents were purchased from
commercial sources and used without further purification. The
progress of all reactions was monitored by TLC analysis, and the
developed plates were exposed to UV light and/or an iodine cham-
ber to visualize the spots. Column chromatography was performed
with silica gel [ethyl acetate/hexane (in different ratios) for the sol-
vent system]. FTIR spectra were recorded in the attenuated total
reflectance (ATR) mode, and the band frequencies were recorded
in units of cm–1. The 1H NMR (400 MHz) and 13C NMR (100 MHz)
spectroscopic data were recorded in CDCl3 or [D6]DMSO as the sol-
vent at 25 °C. Chemical shifts (in ppm) for the 1H NMR data were
reported by using tetramethylsilane (δ = 0 ppm) as an internal stan-
dard in CDCl3 (residual CHCl3, δ = 7.26 ppm) or [D6]DMSO (residual
[D5]DMSO, δ = 2.50 ppm). The following abbreviations were used
to define the multiplicity of each signal: s (singlet), d (doublet), t
(triplet), m (multiplet), dd (doublet of doublets), td (triplet of dou-
blets), and br. s (broad singlet). The coupling constants were re-
Conclusions
In summary, we have developed a general and practical proto-
col for the synthesis of unsymmetrical (hetero)aryl 1,2-diket-
ones by using a two-step sequence in a one-pot manner and
starting from arylacetonitriles. The proposed mechanism pro-
ceeds through a palladium-catalyzed nucleophilic addition re-
action followed by a copper-catalyzed benzylic C–H oxygen-
ation. The exclusivity of this method lies in (a) its use of aryl-
acetonitriles and potassium aryltrifluoroborates as venerable
and nontoxic starting materials, (b) its step economy approach,
(c) its capacity for scale up, and (d) its broad substrate scope. ported in units of Hz. Chemical shifts (ppm) for the 13C NMR spec-
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troscopic data were reported by using the center of the CDCl3 (δ =
194.9, 194.7, 139.0, 135.8, 134.9, 133.1, 133.0, 130.2, 129.9, 129.0,
77.0 ppm) or [D6]DMSO (δ = 39.5 ppm) signal as the internal stan- 128.9, 127.3, 21.3 ppm.
dard. HRMS data were performed in the ESI mode by using a Q-
1-Phenyl-2-p-tolylethane-1,2-dione (3c):[13c] Employing GP-A and
a reaction time of 7 h afforded 3c (70 mg, 63 % yield) as a yellow
TOF (positive ion) instrument. Microwave reactions were carried out
with Initiator 2.5 Microwave Synthesizers from Biotage, Uppsala,
Sweden. Melting points were recorded with an automated melting
point apparatus.
solid; m.p. 93–95 °C; Rf = 0.7 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
3050, 2918, 1669, 1604, 1215, 1174 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.97 (d, J = 8.0 Hz, 2 H), 7.87 (d, J = 8.0 Hz, 2 H), 7.65 (t, J =
8.0 Hz, 1 H), 7.51 (t, J = 8.0 Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 2.44
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.8, 194.3, 146.2,
134.8, 133.1, 130.6, 130.0, 129.9, 129.8, 129.0, 21.9 ppm.
General Procedure A (GP-A) for the Preparation of Di(Hetero)-
Aryl 1,2-Diketones: Arylacetonitrile 1a–1y (0.5 mmol), potassium
aryltrifluoroborate 2a (0.75 mmol), Pd(TFA)2 (8.3 mg, 5.0 mol-%),
2,2′-bipyridine (7.8 mg, 10.0 mol-%), ( )-camphor-10-sulfonic acid
(232.0 mg, 2.0 equiv.), and EtOH/H2O (1:1, 2.0 mL) were placed in
5 mL microwave vial. The reaction vial was sealed and subjected to
microwave irradiation at 100 °C for 20 min. Upon completion of the
reaction (progress monitored by TLC analysis), the reaction mixture
was evaporated under reduced pressure, and the crude residue was
dissolved in DMF (3.0 mL) and then treated with Cu(OAc)2 (4.5 mg,
5.0 mol-%) and K2CO3(3.5 mg, 5.0 mol-%) in a 25 mL round-bottom
flask. The reaction flask was sealed with a rubber septum and then
degassed and refilled with O2. Under O2, the mixture was heated
at 50 °C with a preheated oil bath until the reaction reached com-
pletion (progress monitored by TLC analysis). The reaction mixture
was extracted with ethyl acetate (3 × 15 mL). The combined organic
layers were washed with brine solution (15 mL), dried with anhy-
drous Na2SO4, and then filtered. The filtrate was concentrated in
vacuo to give the crude residue, which was purified by silica gel
column chromatography (hexanes/EtOAc, 98:02) to afford the corre-
sponding product 3a–3y.
1-(3-Methoxyphenyl)-2-phenylethane-1,2-dione (3d):[13e] Em-
ploying GP-A and a reaction time of 14 h afforded 3d (70 mg, 72 %
yield) as a yellow oil; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
3067, 2964, 1674, 1594, 1253, 1037 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.97 (d, J = 8.0 Hz, 2 H), 7.66 (t, J = 8.0 Hz, 1 H), 7.54–7.47 (m,
4 H), 7.40 (t, J = 8.0 Hz, 1 H), 7.21 (d, J = 8.0 Hz, 1 H), 3.87 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.53, 194.5, 160.1, 134.9,
134.3, 133.0, 130.1, 129.9, 129.0, 123.3, 121.9, 112.8, 55.6 ppm.
1-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (3e):[13c] Em-
ploying GP-A and a reaction time of 14 h afforded 3e (86 mg, 71 %
yield) as a yellow oil; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
1
3064, 2937, 1677, 1594, 1509, 1258, 1150, 1023, 833 cm–1. H NMR
(400 MHz, CDCl3): δ = 7.96 (t, J = 8.0 Hz, 4 H), 7.64 (t, J = 8.0 Hz, 1
H), 7.50 (t, J = 8.0 Hz, 2 H), 6.97 (d, J = 8.0 Hz, 2 H), 3.88 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 194.9, 193.2, 165.0, 134.7, 133.2,
132.4, 129.9, 129.0, 126.1, 114.4, 55.7 ppm.
1-(2-Methoxyphenyl)-2-phenylethane-1,2-dione (3f):[13e] Em-
ploying GP-A and a reaction time of 14 h afforded 3f (90 mg, 75 %
General Procedure B (GP-B) for the Preparation of Di(Hetero)-
Aryl 1,2-Diketones: Arylacetonitrile 1a–1y (0.5 mmol), arylboronic
acid 2b (0.75 mmol), KF·2H2O (1.0 mmol), Pd(TFA)2 (8.3 mg, 5.0 mol-
%), 2,2′-bipyridine (7.8 mg, 10.0 mol-%), ( )-camphor-10-sulfonic
acid (232.0 mg, 2.0 equiv.), and EtOH/H2O (1:1, 2.0 mL) were placed
in 5 mL microwave vial. The reaction vial was sealed and subjected
to microwave irradiation at 100 °C for 20 min. Upon completion of
the reaction (progress monitored by TLC analysis), the reaction mix-
ture was evaporated under reduced pressure, and the crude residue
was dissolved in DMF (3.0 mL) and then treated with Cu(OAc)2
(4.5 mg, 5.0 mol-%) and K2CO3 (3.5 mg, 5.0 mol-%) in a 25 mL
round-bottom flask. The reaction flask was sealed with a rubber
septum and then degassed and refilled with O2. Under O2, the mix-
ture was heated at 50 °C with a preheated oil bath until the reaction
reached completion (progress monitored by TLC analysis). The reac-
tion mixture was extracted with ethyl acetate (3 × 15 mL). The com-
bined organic layers were washed with brine solution (15 mL), dried
with anhydrous Na2SO4, and then filtered. The filtrate was concen-
trated in vacuo to give the crude residue, which was purified by
silica gel column chromatography (hexanes/EtOAc, 98:02) to afford
the corresponding product 4a–4m.
yield) as a yellow oil; R = 0.4 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
f
1
3067, 2948, 1682, 1657, 1596, 1483, 1267, 1206, 1018, 877 cm–1. H
NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.0 Hz, 1 H), 7.92 (d, J =
8.0 Hz, 2 H), 7.60 (q, J = 8.0 Hz, 2 H), 7.49 (t, J = 8.0 Hz, 2 H), 7.12
(t, J = 8.0 Hz, 1 H), 6.93 (d, J = 8.0 Hz, 1 H), 3.55 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 194.7, 193.6, 160.5, 136.5, 133.8, 132.9,
130.6, 129.4, 128.7, 123.9, 121.6, 112.4, 55.7 ppm.
1-(Benzo[d][1,3]dioxol-5-yl)-2-phenylethane-1,2-dione (3g):[26a]
Employing GP-A and a reaction time of 18 h afforded 3g (105 mg,
83 % yield) as a yellow solid; m.p. 118–120 °C; Rf = 0.4 (hexanes/
EtOAc, 9.8:0.2). IR (ATR): ν = 3061, 2914, 1671, 1599, 1441, 1242,
˜
1
1037, 924 cm–1. H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 4.0 Hz,
2 H), 7.64 (t, J = 8.0 Hz, 1 H), 7.51–7.46 (m, 4 H), 6.85 (d, J = 8.0 Hz,
1 H), 6.07 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.6, 192.8,
153.5, 148.7 134.8, 133.1, 129.9, 129.0, 127.9, 127.8, 108.4, 108.3,
102.3 ppm.
1-(Naphthalen-2-yl)-2-phenylethane-1,2-dione (3h):[14e] Employ-
ing GP-A and a reaction time of 6 h afforded 3h (105 mg, 81 %
yield) as a brown solid; m.p. 82–84 °C; Rf = 0.7 (hexanes/EtOAc,
9.8:0.2). IR (ATR): ν = 3058, 1663, 1624, 1596, 1447, 1173, 760 cm–1
.
Benzil (3a):[13c] Employing GP-A and a reaction time of 4 h afforded
3a (82 mg, 78 % yield) as a yellow solid: m.p. 94–96 °C; Rf = 0.7
˜
1H NMR (400 MHz, CDCl3): δ = 8.42 (s, 1 H), 8.11 (d, J = 8.0 Hz, 1 H),
8.04 (d, J = 8.0 Hz, 2 H), 7.97 (d, J = 8.0 Hz, 1 H), 7.91 (t, J = 8.0 Hz,
2 H), 7.66 (q, J = 8.0 Hz, 2 H), 7.54 (q, J = 8.0 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 194.7, 136.4, 134.9, 133.6, 133.2, 132.4, 130.4,
130.0, 129.9, 129.6, 129.2, 129.1, 128.0, 127.2, 123.7 ppm.
(hexanes/EtOAc, 9.8:0.2). IR (ATR): ν = 3063, 1669, 1595, 1449, 1210,
˜
1
873 cm–1. H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.0 Hz, 4 H),
7.66 (t, J = 8.0 Hz, 2 H), 7.51 (t, J = 8.0 Hz, 4 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 194.6, 134.9, 133.0, 129.9, 129.0 ppm.
1-Phenyl-2-m-tolylethane-1,2-dione (3b):[13c] Employing GP-A
and a reaction time of 7 h afforded 3b (74 mg, 66 % yield) as a
yellow solid; m.p. 56–58 °C; Rf = 0.7 (hexanes/EtOAc, 9.8:0.2). IR
1-(Biphenyl-4-yl)-2-phenylethane-1,2-dione (3i):[13c] Employing
GP-A and a reaction time of 6 h afforded 3i (112 mg, 78 % yield) as
a yellow solid; m.p. 103–105 °C; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR
(ATR): ν = 3058, 2923, 1668, 1599, 1231, 1162 cm–1
.
1H NMR
(ATR): ν = 3058, 1668, 1599, 1447, 1212, 1173, 879, 741 cm–1 1H
.
˜
˜
(400 MHz, CDCl3): δ = 7.97 (d, J = 8.0 Hz, 2 H), 7.77 (m, 2 H), 7.66
(t, J = 8.0 Hz, 1 H), 7.51 (t, J = 8.0 Hz, 2 H), 7.47 (m, 1 H), 7.40 (d,
J = 8.0 Hz, 1 H), 2.41 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.0 Hz, 2 H), 8.02 (d, J =
8.0 Hz, 2 H), 7.75 (t, J = 8.0 Hz, 2 H), 7.67–7.63 (m, 3 H), 7.55–7.42
(m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.6, 194.2, 147.6,
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© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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139.5, 134.9, 133.1, 131.7, 130.5, 130.0, 129.1, 128.7, 127.7,
127.4 ppm.
1-(4-Bromophenyl)-2-phenylethane-1,2-dione (3p):[26b] Employ-
ing GP-A and a reaction time of 5 h afforded 3p (88 mg, 61 % yield)
as a yellow solid; m.p. 82–84 °C; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR
1-(4-Fluorophenyl)-2-phenylethane-1,2-dione (3j):[13c] Employ-
ing GP-A and a reaction time of 5 h afforded 3j (64 mg, 56 % yield)
as a yellow solid; m.p. 66–68 °C; Rf = 0.5 (hexanes/EtOAc, 9.8:0.2). IR
(ATR): ν = 3086, 3061, 1666, 1580, 1397, 1209, 1176, 1070, 832 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.0 Hz, 2 H), 7.84 (d, J =
8.0 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 3 H), 7.52 (t, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 193.9, 193.3, 135.1, 132.8, 132.5,
131.8, 131.3, 130.5, 130.0, 129.1 ppm.
(ATR): ν = 3067, 1671, 1596, 1508, 1303, 1234, 1212, 1156, 843 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 8.04–8.00 (m, 2 H), 7.97 (d, J = 8.0 Hz,
2 H), 7.67 (t, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.0 Hz, 2 H), 7.19 (t, J =
8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.1, 192.7,
168.08 and 165.51 [d, J(C,F) = 257.0 Hz], 135.0, 132.9, 132.80 and
1-(2-Bromophenyl)-2-phenylethane-1,2-dione (3q):[26b] Employ-
ing GP-A and a reaction time of 5 h afforded 3q (109 mg, 72 %
132.70 [d, J(C,F) = 10.0 Hz], 129.9, 129.52 and 129.49 [d, J(C,F)
3.0 Hz], 129.1, 116.52 and 116.30 [d, J(C,F) = 22.0 Hz] ppm.
=
yield) as a yellow oil; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
3061, 1674, 1585, 1430, 1248, 1203, 1026, 860 cm–1
.
1H NMR
(400 MHz, CDCl3): δ = 8.07 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0 Hz,
1 H), 7.65 (t, J = 8.0 Hz, 2 H), 7.54 (t, J = 8.0 Hz, 2 H), 7.47 (t, J =
8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.2, 191.5, 136.1,
134.5, 134.4, 133.8, 132.7, 132.6, 130.4, 128.9, 127.9, 121.8 ppm.
1-(2-Fluorophenyl)-2-phenylethane-1,2-dione (3k):[26b] Employ-
ing GP-A and a reaction time of 5 h afforded 3k (71 mg, 62 % yield)
as a yellow solid; m.p. 62–64 °C; Rf = 0.5 (hexanes/EtOAc, 9.8:0.2). IR
(ATR): ν = 3069, 2923, 1677, 1608, 1486, 1450, 1259, 1198, 879 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 8.06 (t, J = 8.0 Hz, 1 H), 7.97 (d, J =
8.0 Hz, 2 H), 7.66 (q, J = 8.0 Hz, 2 H), 7.53 (t, J = 8.0 Hz, 2 H), 7.35
(t, J = 8.0 Hz, 1 H), 7.13 (t, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 193.1, 191.9, 164.18 and 161.62 [d, J(C,F) = 256.0 Hz],
136.92 and 136.83 [d, J(C,F) = 9.0 Hz], 134.7, 132.06 and 132.04 [d,
1-(4-Nitrophenyl)-2-phenylethane-1,2-dione (3r):[13c] Employing
GP-A and a reaction time of 4 h afforded 3r (98 mg, 79 % yield) as
a yellow solid; m.p. 140–142 °C; Rf = 0.5 (hexanes/EtOAc, 9.7:0.3). IR
(ATR): ν = 3108, 1674, 1660, 1591, 1524, 1345, 1203, 838 cm–1 1H
.
˜
NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 8.0 Hz, 2 H), 8.17 (d, J =
J(C,F) = 2.0 Hz], 130.83 and 130.82 [d, J(C,F) = 1.0 Hz], 129.9, 129.0, 8.0 Hz, 2 H), 7.99 (d, J = 8.0 Hz, 2 H), 7.71 (t, J = 8.0 Hz, 1 H), 7.55
125.01 and 124.98 [d, J(C,F) = 3.0 Hz], 122.43 and 122.32 [d, J(C,F)
11.0 Hz], 116.79 and 116.58 [d, J(C,F) = 21.0 Hz] ppm.
=
(t, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 192.9, 192.1,
151.2, 137.3, 135.5, 132.4, 131.0, 130.1, 129.3, 124.1 ppm.
1-(3-Fluorophenyl)-2-phenylethane-1,2-dione (3l):[13f] Employ-
ing GP-A and a reaction time of 5 h afforded 3l (82 mg, 72 % yield)
Methyl 4-(2-Oxo-2-phenylacetyl)benzoate (3s):[13c] Employing
GP-A and a reaction time of 4 h afforded 3s (98 mg, 79 % yield) as
as a brown solid; m.p. 98–100 °C; Rf = 0.5 (hexanes/EtOAc, 9.8:0.2).
a yellow solid; m.p. 64–66 °C; Rf = 0.5 (hexanes/EtOAc, 9.7:0.3). IR
1
1
IR (ATR): ν = 3069, 1668, 1585, 1450, 1234, 1148, 832 cm–1. H NMR (ATR): ν = 3065, 2955, 1726, 1665, 1435, 1277, 1206, 1109 cm–1. H
˜
˜
(400 MHz, CDCl3): δ = 7.97 (d, J = 8.0 Hz, 2 H), 7.75–7.66 (m, 3 H),
NMR (400 MHz, CDCl3): δ = 8.16 (d, J = 8.0 Hz, 2 H), 8.04 (d, J =
7.55–7.49 (m, 3 H), 7.37 (t, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 193.7, 193.1, 164.12 and 161.64 [d, J(C,F) = 248.0 Hz],
8.0 Hz, 2 H), 7.97 (d, J = 8.0 Hz, 2 H), 7.67 (t, J = 8.0 Hz, 1 H), 7.52
(t, J = 8.0 Hz, 2 H), 3.95 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
135.1, 135.01 and 134.94 [d, J(C,F) = 7.0 Hz], 132.7, 130.86 and 130.79 δ = 193.8, 193.7, 165.9, 136.1, 135.3, 135.2, 132.7, 130.1, 130.0, 129.8,
[d, J(C,F) = 7.0 Hz], 130.0, 129.1, 126.03 and 126.00 [d, J(C,F) = 3.0 Hz],
129.1, 52.6 ppm.
122.14 and 121.93 [d, J(C,F) = 21.0 Hz], 116.24 and 116.02 [d, J(C,F)
22.0 Hz] ppm.
=
1-Phenyl-2-[4-(trifluoromethyl)phenyl]ethane-1,2-dione
(3t):[13c] Employing GP-A and a reaction time of 5 h afforded 3t
(80 mg, 58 % yield) as a yellow solid; m.p. 58–60 °C; Rf = 0.5 (hex-
1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (3m):[13e] Employ-
ing GP-A and a reaction time of 4 h afforded 3m (90 mg, 74 %
yield) as a yellow solid; m.p. 73–75 °C; Rf = 0.6 (hexanes/EtOAc,
anes/EtOAc, 9.8:0.2). IR (ATR): ν = 3064, 1668, 1599, 1328, 1176,
˜
1
1117, 1070 cm–1. H NMR (400 MHz, CDCl3): δ = 8.11 (d, J = 8.0 Hz,
9.8:0.2). IR (ATR): ν = 3094, 1702, 1663, 1583, 1209, 1090, 835 cm–1
.
2 H), 7.98 (d, J = 8.0 Hz, 2 H), 7.78 (d, J = 8.0 Hz, 2 H), 7.68 (t, J =
8.0 Hz, 1 H), 7.53 (t, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 193.5, 193.0, 135.85 [q, J(C,F) = 33 Hz], 135.6, 135.3, 132.6, 130.2,
130.0, 129.2, 126.05 [q, J(C,F) = 4 Hz], 123.35 [q, J(C,F) = 271.0 Hz] ppm.
˜
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.0 Hz, 2 H), 7.93 (d, J =
8.0 Hz, 2 H), 7.67 (t, J = 8.0 Hz, 1 H), 7.54–7.48 (m, 4 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 193.9, 193.1, 141.6, 135.1, 132.8, 131.4,
131.2, 129.9, 129.5, 129.1 ppm.
1-(1H-Indol-3-yl)-2-phenylethane-1,2-dione (3u):[25b] Employing
1-(2-Chlorophenyl)-2-phenylethane-1,2-dione (3n):[13c] Employ- GP-A and a reaction time of 16 h afforded 3u (70 mg, 56 % yield)
ing GP-A and a reaction time of 5 h afforded 3n (92 mg, 75 % yield)
as a brown solid; m.p. 196–198 °C; Rf = 0.3 (hexanes/EtOAc, 8.0:2.0).
as a yellow oil; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν = 3067,
IR (ATR): ν = 3236, 2924, 1665, 1620, 1513, 1439, 1261, 1154,
˜
˜
1
2923, 1674, 1595, 1253, 1206, 860 cm–1. H NMR (400 MHz, CDCl3): 789 cm–1
.
1H NMR (400 MHz, [D6]DMSO): δ = 12.44 (s, 1 H), 8.23–
δ = 8.04 (d, J = 8.0 Hz, 2 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.67 (t, J =
8.0 Hz, 1 H), 7.54 (t, J = 8.0 Hz, 3 H), 7.44 (t, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 193.7, 192.1, 134.6, 134.5, 134.0,
133.9, 132.5, 132.1, 130.5, 130.2, 128.9, 127.4 ppm.
8.22 (m, 1 H), 8.18 (s, 1 H), 7.97 (d, J = 8.0 Hz, 2 H), 7.74 (t, J =
8.0 Hz, 1 H), 7.62–7.55 (m, 3 H), 7.33–7.31 (m, 2 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 194.5, 189.0, 138.5, 137.5, 135.2, 133.4,
130.2, 129.6, 125.5 124.3, 123.3, 121.6, 113.2, 113.0 ppm.
1-(3,4-Dichlorophenyl)-2-phenylethane-1,2-dione (3o):[26b] Em-
ploying GP-A and a reaction time of 5 h afforded 3o (98 mg, 71 %
yield) as a yellow solid; m.p. 92–94 °C; Rf = 0.6 (hexanes/EtOAc,
1-(1-Ethyl-1H-indol-3-yl)-2-phenylethane-1,2-dione (3v): Em-
ploying GP-A and a reaction time of 16 h afforded 3v (102 mg, 74 %
yield) as a brown oil; R = 0.4 (hexanes/EtOAc, 8.5:1.5). IR (ATR): ν =
˜
f
9.8:0.2). IR (ATR): ν = 3086, 1660, 1580, 1389, 1201, 1173, 907 cm–1
.
3065, 2984, 1671, 1620, 1523, 1393, 1203, 750 cm–1
.
1H NMR
˜
1H NMR (400 MHz, CDCl3): δ = 8.07 (s, 1 H), 7.96 (d, J = 8.0 Hz, 2 H),
7.80 (d, J = 8.0 Hz, 1 H), 7.68 (t, J = 8.0 Hz, 1 H), 7.59 (d, J = 8.0 Hz, 1 H), 7.63 (t, J = 8.0 Hz, 1 H), 7.50 (t, J = 8.0 Hz, 2 H), 7.41–7.38 (m,
1 H), 7.53 (t, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 3 H), 4.21 (q, J = 8.0 Hz, 2 H), 1.52 (t, J = 8.0 Hz, 3 H) ppm. 13C NMR
193.1, 191.8, 139.7, 135.3, 133.9, 132.6, 131.5, 131.2, 130.0, 129.2, (100 MHz, CDCl3): δ = 193.8, 187.6, 137.9, 136.9, 134.3, 133.5, 130.4,
(400 MHz, CDCl3): δ = 8.49 (s, 1 H), 8.11 (d, J = 8.0 Hz, 2 H), 7.87 (s,
128.8 ppm.
128.8, 126.6, 124.1, 123.5, 122.9, 113.0, 110.1, 42.1, 15.0 ppm. HRMS
Eur. J. Org. Chem. 2018, 494–505
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Full Paper
(ESI/Q-TOF): calcd. for C18H16NO2 [M + H]+ 278.1176; found
278.1174.
1-(4-Bromophenyl)-2-(4-fluorophenyl)ethane-1,2-dione (4e):[4a]
Employing GP-B and a reaction time of 4 h afforded 4e (105 mg,
69 % yield) as a yellow solid; m.p. 152–154 °C; Rf = 0.4 (hexanes/
1-Phenyl-2-(pyridin-3-yl)ethane-1,2-dione (3w):[26c] Employing
GP-A and a reaction time of 16 h afforded 3w (51 mg, 48 % yield)
EtOAc, 9.8:0.2). IR (ATR): ν = 3094, 1666, 1594, 1309, 1156, 838 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.0 Hz, 2 H), 7.84 (d, J =
8.0 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H), 7.20 (t, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 192.8, 192.0, 168.18 and 165.61 (d,
J = 257.0 Hz), 132.86 and 132.76 (d, J = 10.0 Hz), 132.5, 131.6, 131.3,
130.7, 129.30 and 129.27 (d, J = 3.0 Hz), 116.59 and 116.37 (d, J =
22.0 Hz) ppm.
as a yellow oil; Rf = 0.3 (hexanes/EtOAc, 6.0:4.0). IR (ATR): ν = 3058,
˜
1
1738, 1671, 1583, 1417, 1214, 874 cm–1. H NMR (400 MHz, CDCl3):
δ = 9.18 (s, 1 H), 8.88 (d, J = 8.0 Hz, 1 H), 8.32 (d, J = 8.0 Hz, 1 H),
8.00 (d, J = 8.0 Hz, 2 H), 7.70 (t, J = 8.0 Hz, 1 H), 7.56–7.49 (m, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 192.8, 192.5, 154.5, 151.1,
137.2, 135.3, 132.5, 130.1, 129.2, 128.9, 124.0 ppm.
1,2-Di-p-tolylethane-1,2-dione (4f):[4a] Employing GP-B and a re-
action time of 9 h afforded 4f (82 mg, 69 % yield) as a yellow solid;
1-Phenyl-2-(pyridin-2-yl)ethane-1,2-dione (3x):[26d] Employing
GP-A and a reaction time of 16 h afforded 3x (42 mg, 40 % yield)
m.p. 100–102 °C; Rf = 0.4 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν = 2920,
˜
as a yellow oil; Rf = 0.3 (hexanes/EtOAc, 8.0:2.0). IR (ATR): ν = 3054,
1662, 1607, 1364, 1225, 1173, 886, 740 cm–1
.
1H NMR (400 MHz,
˜
1
1734, 1670, 1596, 1428, 1202, 880 cm–1. H NMR (400 MHz, CDCl3):
CDCl3): δ = 7.86 (d, J = 8.0 Hz, 4 H), 7.30 (d, J = 8.0 Hz, 4 H), 2.43
(s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.5, 146.1, 130.7,
130.0, 129.7, 21.9 ppm.
1-(4-Methoxyphenyl)-2-p-tolylethane-1,2-dione (4g):[4a] Employ-
ing GP-B and a reaction time of 16 h afforded 4g (82 mg, 65 %
yield) as a yellow solid; m.p. 106–108 °C; Rf = 0.3 (hexanes/EtOAc,
δ = 8.68–8.67 (m, 1 H), 8.20 (t, J = 8.0 Hz, 1 H), 7.95–7.73 (m, 3 H),
7.66–7.63 (m, 1 H), 7.53–7.51 (m, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 196.2, 194.9, 151.7, 149.9, 137.3, 134.7, 133.2, 129.6,
128.9, 128.2, 123.2 ppm.
1-Phenyl-2-(thiophen-2-yl)ethane-1,2-dione (3y):[26d] Employing
GP-A and a reaction time of 16 h afforded 3y (42 mg, 43 % yield)
9.7:0.3). IR (ATR): ν = 2971, 2839, 1655, 1600, 1571, 1264, 1219, 1167,
˜
as a yellow oil; Rf = 0.3 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν = 2923,
1028, 882, 740 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J =
˜
1678, 1649, 1507, 1409, 1212, 1009 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 8.05 (d, J = 8.0 Hz, 2 H), 7.85 (d, J = 4.0 Hz, 1 H), 7.81 (d, J =
4.0 Hz, 1 H), 7.67 (t, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.0 Hz, 2 H), 7.19 (t,
J = 4.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 192.1, 185.6,
139.9, 136.9, 136.8, 134.9, 132.6, 130.3, 129.0, 128.9 ppm.
8.0 Hz, 2 H), 7.86 (d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 6.97
(d, J = 8.0 Hz, 2 H), 3.88 (s, 3 H), 2.43 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 194.6, 193.4, 164.9, 146.0, 132.4, 130.8, 130.0,
129.7, 126.2, 114.3, 55.6, 21.9 ppm.
1-(4-Chlorophenyl)-2-(naphthalen-2-yl)ethane-1,2-dione
(4h):[4b] Employing GP-B and a reaction time of 4 h afforded 4h
(102 mg, 69 % yield) as a yellow solid; m.p. 118–120 °C; Rf = 0.4
1-(4-tert-Butylphenyl)-2-phenylethane-1,2-dione (4a):[13c] Em-
ploying GP-B and a reaction time of 4 h afforded 4a (82 mg, 62 %
yield) as a yellow oil; R = 0.4 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
f
(hexanes/EtOAc, 9.8:0.2). IR (ATR): ν = 3062, 1662, 1587, 1400, 1093,
˜
2965, 1668, 1600, 1448, 1219, 1109, 882 cm–1
.
1H NMR (400 MHz,
1
818, 747 cm–1. H NMR (400 MHz, CDCl3): δ = 8.40 (s, 1 H), 8.09 (d,
CDCl3): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.91 (d, J = 8.0 Hz, 2 H), 7.65
(t, J = 8.0 Hz, 1 H), 7.54–7.49 (m, 4 H), 1.34 (s, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 194.8, 194.3, 159.1, 134.8, 133.1, 130.5, 129.9,
129.0, 126.1, 35.4, 31.0 ppm.
J = 8.0 Hz, 1 H), 7.98 (d, J = 8.0 Hz, 3 H), 7.92 (t, J = 8.0 Hz, 2 H),
7.66 (t, J = 8.0 Hz, 1 H), 7.57 (t, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.0 Hz,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.0, 193.2, 141.6, 136.5,
133.7, 132.3, 131.5, 131.3, 130.1, 130.0, 129.7, 129.5, 129.3, 128.0,
127.3, 123.7 ppm.
1-(Naphthalen-1-yl)-2-phenylethane-1,2-dione (4b):[13e] Employ-
ing GP-B and a reaction time of 4 h afforded 4b (82 mg, 63 % yield)
as a yellow solid; m.p. 86–88 °C; Rf = 0.4 (hexanes/EtOAc, 9.8:0.2). IR
1-p-Tolyl-2-[4-(trifluoromethyl)phenyl]ethane-1,2-dione (4i):
Employing GP-B and a reaction time of 16 h afforded 4i (59 mg,
40 % yield) as a yellow solid; m.p. 101–104 °C; Rf = 0.4 (hexanes/
(ATR): ν = 3055, 2920, 1668, 1602, 1448, 1225, 1170, 889 cm–1 1H
.
˜
EtOAc, 9.8:0.2). IR (ATR): ν = 2923, 1664, 1605, 1325, 1173, 1123 cm–1
.
NMR (400 MHz, CDCl3): δ = 9.31 (d, J = 8.0 Hz, 1 H), 8.13 (d, J =
8.0 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 2 H), 7.96–7.91 (m, 2 H), 7.75 (t, J =
8.0 Hz, 1 H), 7.68–7.62 (m, 2 H), 7.54–7.48 (m, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 197.2, 194.6, 136.0, 135.1, 134.8, 134.1, 133.4,
131.0, 130.1, 129.5, 129.1, 128.8, 128.7, 127.1, 126.0, 124.5 ppm.
˜
1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 8.0 Hz, 2 H), 7.87 (d, J =
8.0 Hz, 2 H), 7.77 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 2.45
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 193.3, 193.2, 146.7,
135.8 [q, J(C,F) = 33.0 Hz], 135.7, 130.23, 130.2, 130.1, 129.9, 126.0 [q,
J(C,F) = 4.0 Hz], 123.4 [q, J(C,F) = 272.0 Hz], 22.0 ppm. HRMS (ESI/Q-
TOF): calcd. for C16H11F3NaO2 [M + Na]+ 315.0603; found 315.0638.
1-(3-Chlorophenyl)-2-phenylethane-1,2-dione (4c):[13c] Employ-
ing GP-B and a reaction time of 4 h afforded 4c (90 mg, 74 % yield)
as a yellow solid; m.p. 90–92 °C; Rf = 0.4 (hexanes/EtOAc, 9.8:0.2). IR
1-(Furan-2-yl)-2-phenylethane-1,2-dione (4j):[26d] Employing
GP-B and a reaction time of 4 h afforded 4j (28 mg, 28 % yield) as
(ATR): ν = 3068, 2920, 1668, 1594, 1429, 1206, 1177, 902, 727 cm–1
.
˜
1H NMR (400 MHz, CDCl3): δ = 7.98–7.96 (m, 3 H), 7.84 (d, J = 8.0 Hz,
1 H), 7.68 (t, J = 8.0 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.53 (t, J =
8.0 Hz, 2 H), 7.46 (t, J = 8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 193.6, 193.0, 135.5, 135.2, 134.8, 134.5, 132.7, 130.4, 130.0, 129.6,
129.1, 128.1 ppm.
a yellow oil; Rf = 0.3 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν = 3130,
˜
1
2923, 1658, 1458, 1228, 1018, 785 cm–1. H NMR (400 MHz, CDCl3):
δ = 8.04 (d, J = 8.0 Hz, 2 H), 7.77 (s, 1 H), 7.67 (t, J = 8.0 Hz, 1 H),
7.52 (t, J = 8.0 Hz, 2 H), 7.40 (s, 1 H), 6.63 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 191.5, 180.4, 149.2, 134.9, 132.6, 130.2, 128.9,
123.3, 112.9 ppm.
1-(4-Acetylphenyl)-2-phenylethane-1,2-dione (4d):[13c] Employ-
ing GP-B and a reaction time of 4 h afforded 4d (65 mg, 52 % yield)
as a yellow solid; m.p. 74–76 °C; Rf = 0.4 (hexanes/EtOAc, 9.0:1.0). IR
1-(2-Bromophenyl)-2-(thiophen-2-yl)ethane-1,2-dione (4k): Em-
ploying GP-B and a reaction time of 4 h afforded 4k (62 mg, 48 %
(ATR): ν = 3055, 2926, 1684, 1675, 1597, 1258, 1209, 882 cm–1
.
1H yield) as a yellow oil; Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR (ATR): ν =
˜
˜
NMR (400 MHz, CDCl3): δ = 8.06 (s, 4 H), 7.97 (d, J = 8.0 Hz, 2 H),
7.68 (t, J = 8.0 Hz, 1 H), 7.53 (t, J = 8.0 Hz, 2 H), 2.65 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 197.2, 193.8, 193.6, 141.3, 136.0,
135.2, 132.7, 130.1, 130.0, 129.2, 128.7, 27.0 ppm.
3104, 2923, 1681, 1649, 1406, 1209, 1051, 730 cm–1
.
1H NMR
(400 MHz, CDCl3): δ = 8.00 (d, J = 4.0 Hz, 1 H), 7.86 (d, J = 4.0 Hz,
1 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.46 (t, J =
8.0 Hz, 2 H), 7.25 (d, J = 4.0 Hz, 1 H) ppm. 13C NMR (100 MHz,
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CDCl3): δ = 192.7, 182.8, 139.2, 136.7, 136.2, 134.0, 133.7, 132.2,
128.8, 127.7, 121.5 ppm. HRMS (ESI/Q-TOF): calcd. for C12H8BrO2S
[M + H]+ 294.9426; found 294.9422.
1-(4-Fluorophenyl)-2-(1H-indol-3-yl)ethane-1,2-dione (4l):[25a]
Employing GP-B and a reaction time of 16 h afforded 4l (79 mg,
59 % yield) as a yellow solid; m.p. 100–102 °C; Rf = 0.4 (hexanes/
the reaction (progress monitored by TLC analysis), the mixture was
extracted with ethyl acetate (3 × 15 mL). The combined organic
layers were washed with brine solution (15 mL), dried with anhy-
drous Na2SO4, and filtered. The filtrate was concentrated in vacuo
to give the crude residue, which was purified by silica gel column
chromatography (hexanes/EtOAc, 98:02) to afford products 3e
(36 % yield) and 3j (52 % yield) in a ratio of 1:1.4.
EtOAc, 8.0:2.0). IR (ATR): ν = 3395, 2926, 1665, 1623, 1594, 1442,
˜
1241, 1151, 1025, 1002, 753 cm–1
.
1H NMR (400 MHz, [D6]DMSO):
Experimental Procedures for Radical Capture Experiments with
TEMPO: Phenylacetonitrile (1a, 30.0 mg, 0.25 mmol), potassium
aryltrifluoroborate 2a (69.0 mg, 0.375 mmol), Pd(TFA)2 (4.2 mg,
5.0 mol-%), 2,2′-bipyridine (3.9 mg, 10.0 mol-%), CSA (116.0 mg,
2.0 equiv.), and EtOH/H2O (1:1, 1.0 mL) were placed in a 2 mL micro-
wave vial. The reaction vial was sealed and then subjected to micro-
wave irradiation at 100 °C for 20 min. Upon completion of the reac-
tion (progress monitored by TLC analysis), the mixture was concen-
trated under reduced pressure. The crude residue was dissolved in
DMF (1.5 mL) and then treated with Cu(OAc)2 (2.3 mg, 5.0 mol-%),
K2CO3 (1.7 mg, 5.0 mol-%), and TEMPO (78.0 mg, 2.0 equiv.) in a
25 mL round-bottom flask. The reaction flask was sealed with a
rubber septum and then degassed and refilled with O2. Under O2,
the mixture was heated at 50 °C with a preheated oil bath for 4 h.
Upon completion of the reaction (progress monitored by TLC analy-
sis), the mixture was extracted with ethyl acetate (3 × 15 mL). The
combined organic layers were washed with brine solution (15 mL),
dried with anhydrous Na2SO4, and filtered. The filtrate was concen-
trated in vacuo to give the crude residue, which was purified by
silica gel column chromatography (hexanes/EtOAc, 99:01) to afford
product 3a in a trace amount along with 1,2-diphenyl-2-(2,2,6,6-
tetramethylpiperidin-1-yloxy)ethanone (5, 28 mg, 32 % yield) as a
yellow wax. Data for 5:[4a] Rf = 0.6 (hexanes/EtOAc, 9.8:0.2). IR (ATR):
δ = 12.44 (s, 1 H), 8.23–8.20 (m, 2 H), 8.07 (t, J = 8.0 Hz, 2 H), 7.57
(d, J = 4.0 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 2 H), 7.33–7.31 (m, 2 H) ppm.
13C NMR (100 MHz, [D6]DMSO): δ = 197.6, 193.3, 172.26 and 169.74
[d, J(C,F) = 252.0 Hz], 143.4, 142.2, 138.17 and 138.07 [d, J(C,F)
=
10.0 Hz], 134.97 and 134.95 [d, J(C,F) = 2.0 Hz], 130.3, 129.1, 128.1,
126.4, 121.71 and 121.49 [d, J(C,F) = 22.0 Hz], 117.99 and 117.70 [d,
J(C,F) = 29.0 Hz] ppm.
1-(4-Chlorophenyl)-2-(1-ethyl-1H-indol-3-yl)ethane-1,2-dione
(4m): Employing GP-B and a reaction time of 16 h afforded 4m
(82 mg, 68 % yield) as a brown oil; Rf = 0.4 (hexanes/EtOAc, 8.5:1.5).
IR (ATR): ν = 3059, 2981, 1678, 1620, 1519, 1393, 1193, 1089,
˜
747 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.47–8.46 (m, 1 H), 8.06
(d, J = 8.0 Hz, 2 H), 7.89 (s, 1 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.41–7.38
(m, 3 H), 4.22 (q, J = 8.0 Hz, 2 H), 1.54 (t, J = 8.0 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 192.3, 186.7, 140.9, 138.0, 136.9, 131.9,
131.8, 129.1, 126.7, 124.2, 123.6, 122.9, 112.9, 110.2, 42.2, 15.0 ppm.
HRMS (ESI/Q-TOF): calcd. for C18H15ClNO2 [M + H]+ 312.0786; found
312.0791.
Experimental Procedure for the Gram-Scale Synthesis of Di-
phenyl 1,2-Diketones: Phenylacetonitrile (1a, 1.17 g, 10 mmol),
potassium aryltrifluoroborate 2a (15 mmol, 2.76 g), Pd(TFA)2
(161.2 mg, 5.0 mol-%), 2,2′-bipyridine (156.2 mg, 10.0 mol-%), CSA
(4.64 g, 2.0 equiv.), EtOH (20.0 mL), and H2O (20.0 mL) were placed
in a 100 mL round-bottom flask. The flask was sealed with a rubber
septum and then heated at 100 °C for 8 h. Upon completion of the
reaction (progress was monitored by TLC analysis), the mixture was
concentrated under reduced pressure. The crude residue was dis-
solved in DMF (60.0 mL) then and treated with Cu(OAc)2 (92.0 mg,
5.0 mol-%) and K2CO3 (78.0 mg, 5.0 mol-%) in a 250 mL round-
bottom flask. The reaction flask was sealed with a rubber septum
and then degassed and refilled with O2. Under O2, the mixture was
heated at 50 °C with a preheated oil bath for 5 h. Upon completion
of the reaction (progress monitored by TLC analysis), the mixture
was extracted with ethyl acetate (3 × 50 mL). The combined organic
layers were washed with brine solution (100 mL), dried with anhy-
drous Na2SO4, and filtered. The filtrate was concentrated in vacuo
to give the crude residue, which was purified by silica gel column
chromatography (hexanes/EtOAc, 98:02) to afford product 3a
(1.47 g, 70 % yield).
ν = 3054, 2928, 1670, 1446, 1415, 1270, 1084, 765 cm–1 1H NMR
.
˜
(400 MHz, CDCl3): δ = 8.12 (d, J = 8.0 Hz, 2 H), 7.57–7.53 (m, 3 H),
7.43 (t, J = 8.0 Hz, 2 H), 7.30 (t, J = 8.0 Hz, 2 H), 7.24 (t, J = 8.0 Hz,
1 H), 6.04 (s, 1 H), 1.49 (s, 4 H), 1.33 (d, J = 17.0 Hz, 2 H), 1.23 (s, 6
H), 1.04 (s, 3 H), 0.85 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
198.1, 137.6, 135.0, 132.7, 129.1, 128.1, 127.3, 127.0, 92.9, 59.8, 59.6,
40.0, 33.4, 33.1, 20.1, 20.0, 16.8 ppm.
Experimental Procedure for the One-Pot Synthesis of Quinoxal-
ine: Phenylacetonitrile (1a, 0.5 mmol), potassium aryltrifluoroborate
2a (0.75 mmol), Pd(TFA)2 (8.3 mg, 5.0 mol-%), 2,2′-bipyridine
(7.8 mg, 10.0 mol-%), CSA (232.0 mg, 2.0 equiv.), and EtOH/H2O (1:1,
2.0 mL) were placed in a 5 mL microwave vial. The reaction vial was
sealed and then subjected to microwave irradiation at 100 °C for
20 min. Upon completion of the reaction (progress monitored by
TLC analysis), the mixture was concentrated under reduced pres-
sure. The crude mixture was dissolved in DMF (3.0 mL) and then
treated with Cu(OAc)2 (4.5 mg, 5.0 mol-%), K2CO3 (3.5 mg, 5.0 mol-
%), and benzene-1,2-diamine (68.0 mg, 1.25 equiv.) in a 25 mL
round-bottom flask. The reaction flask was sealed with a rubber
septum and then degassed and refilled with O2. Under O2, the mix-
ture was heated at 50 °C with a preheated oil bath for 12 h. Upon
completion of the reaction (progress monitored by TLC analysis),
the reaction mixture was extracted with ethyl acetate (3 × 15 mL).
Experimental Procedures for Competition Experiment between
1e and 1j: 2-(4-Methoxyphenyl)acetonitrile (1e, 39.0 mg,
0.25 mmol), 2-(4-nitrophenyl)acetonitrile (1j, 41.0 mg, 0.25 mmol),
potassium aryltrifluoroborate 2a (69.0 mg, 0.375 mmol), Pd(TFA)2
(4.2 mg, 5.0 mol-%), 2,2′-bipyridine (3.9 mg, 10.0 mol-%), CSA
(116.0 mg, 2.0 equiv.), and EtOH/H2O (1:1, 1.0 mL) were placed in a The combined organic layers were washed with brine solution
2 mL microwave vial. The reaction vial was sealed and subjected to
microwave irradiation at 100 °C for 20 min. Upon completion of
the reaction (progress monitored by TLC analysis), the mixture was
(15 mL), dried with anhydrous Na2SO4, and filtered. The filtrate was
concentrated in vacuo to give the crude residue, which was was
purified by silica gel column chromatography (hexanes/EtOAc,
concentrated under reduced pressure. The crude residue was dis- 95:05) to afford 2,3-diphenylquinoxaline (7, 104 mg, 74 % yield) as
solved in DMF (1.5 mL) and then treated with Cu(OAc)2 (2.3 mg,
5.0 mol-%) and K2CO3 (1.7 mg, 5.0 mol-%) in a 25 mL round-bottom
flask. The reaction flask was sealed with a rubber septum and then
degassed and refilled with O2. Under O2, the mixture was heated
at 50 °C with a preheated oil bath for 14 h . Upon completion of
a white solid.[4a] M.p. 120–122 °C; Rf = 0.3 (hexanes/EtOAc, 9.5:0.5).
IR (ATR): ν = 3052, 2975, 1739, 1345, 1215, 756 cm–1 1H NMR
(400 MHz, CDCl3): δ = 8.20–8.18 (m, 2 H), 7.79–7.77 (m, 2 H), 7.54–
7.52 (m, 4 H), 7.36–7.35 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 153.5, 141.3, 139.1, 130.0, 129.9, 129.2, 128.8, 128.3 ppm.
.
˜
Eur. J. Org. Chem. 2018, 494–505
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Experimental Procedure for the One-Pot Synthesis of Benzimid-
azole: Phenylacetonitrile (1a, 0.5 mmol), potassium aryltrifluoro-
borate 2a (0.75 mmol), Pd(TFA)2 (8.3 mg, 5.0 mol-%), 2,2′-bipyridine
(7.8 mg, 10.0 mol-%), CSA (232.0 mg, 2.0 equiv.), and EtOH/H2O (1:1,
2.0 mL) were placed in a 5 mL microwave vial. The reaction vial was
sealed and then subjected to microwave irradiation at 100 °C for
20 min. Upon completion of the reaction (progress monitored by
TLC analysis), the mixture was concentrated under reduced pres-
sure. The crude mixture was dissolved in DMSO (5.0 mL) and then
treated with iodine (7.0 mg, 10 mol-%), benzene-1,2-diamine (6,
60.0 mg, 1.1 equiv.), and anhydrous Na2SO4 (355.0 mg, 5.0 equiv.)
in a 25 mL round-bottom flask at 120 °C for 14 h under open air.
Upon completion of the reaction (progress monitored by TLC analy-
sis), the mixture was extracted with ethyl acetate (3 × 15 mL). The
combined organic layers were washed with brine solution (15 mL),
dried with anhydrous Na2SO4, and filtered. The filtrate was concen-
trated in vacuo to give the crude residue, which was purified by
silica gel column chromatography (hexanes/EtOAc, 80:20) to afford
2-phenyl-1H-benzo[d]imidazole (8, 70 mg, 72 % yield) as a white
solid.[3a] M.p. 298–300 °C; Rf = 0.3 (hexanes/EtOAc, 7.0:3.0). IR (ATR):
[5]
[6]
[7]
[8]
[9]
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[10]
[11]
ν = 3049, 2923, 1736, 1442, 1409, 1274, 970, 740 cm–1 1H NMR
.
˜
(400 MHz, [D6]DMSO): δ = 12.89 (br. s, 1 H), 8.19 (d, J = 8.0 Hz, 2
H), 7.61–7.50 (m, 5 H), 7.23–7.21 (m, 2 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 151.7, 130.6, 130.3, 129.4, 126.9, 122.6, 115.8,
115.4 ppm.
Acknowledgments
This work was supported by the Council of Scientific and Indus-
trial Research (CSIR) [02(0229)/15/EMR-II], New Delhi and the
Indian Institute of Technology Patna. Y. K. and Y. J. thank the
Indian Institute of Technology (IIT) Patna for the Institute Re-
search Fellowship. We also acknowledge IIT Patna for providing
the NMR facilities and the Sophisticated Analytical Instrument
Facility-Central Drug Research Institute (SAIF-CDRI), Lucknow
for the HRMS facilities.
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Keywords: Synthetic methods · Ketones · Boron ·
Nucleophilic addition · Oxidation · Arenes
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Received: November 23, 2017
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