Palladium-Catalyzed Denitrogenative Synthesis of Aryl Ketones from Arylhydrazines and Nitriles Using O2 as Sole Oxidant

Article abstract of DOI:10.1021/acs.joc.6b02697

An efficient and simple palladium-catalyzed approach for the synthesis of aryl ketones from low-cost nitriles and arylhydrazines using molecular oxygen (O₂) as sole oxidant via C-N bond cleavage is reported. Various aryl ketones were synthesized in moderate to good yields under mild conditions. A possible mechanism involving the Pd^II/Pd⁰ catalytic cycle process is depicted, and a cationic palladium intermediate was detected by ESI-MS.

Full text of DOI:10.1021/acs.joc.6b02697

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Note
Palladium-Catalyzed Denitrogenative Synthesis of Aryl Ketones
from Arylhydrazines and Nitriles Using O2 as Sole Oxidant
Xu Wang, Yubing Huang, Yanli Xu, Xiaodong Tang, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 20 Jan 2017
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Palladium-Catalyzed Denitrogenative Synthesis of
Aryl Ketones from Arylhydrazines and Nitriles Using
O2 as Sole Oxidant
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Xu Wang, Yubing Huang, Yanli Xu, Xiaodong Tang, Wanqing Wu* and Huanfeng
Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
P. R. China
Fax: (+86) 20ꢀ87112906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
Abstract: An efficient and simple palladiumꢀcatalyzed approach for the synthesis of
aryl ketones from lowꢀcost nitriles and arylhydrazines using molecular oxygen (O2) as
sole oxidant via CꢀN bond cleavage is reported. Various aryl ketones were synthesized
in moderate to good yields under mild conditions. A possible mechanism involving
the PdII/Pd0 catalytic cycle process is depicted, and a cationic palladium intermediate
was detected by ESIꢀMS.
Aryl ketones represent an important class of organic building block since numerous
compounds of fragrances, natural products and pharmaceuticals containing this
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structural motif.1 Classically, aryl ketones were synthesized by FriedelꢀCrafts
acylation, and stoichiometric amounts of Lewis acids were required.2 In recent years,
many novel strategies were developed to afford aryl ketone derivatives,3ꢀ8,15ꢀ24 among
them, the insertion of nitrile groups is a useful route to synthesize aryl ketones from
arylpalladium species, since they provide unique organic transformations which are
not readily available by classic methods (Scheme 1). For example, Lu3 and Larock4 et
al. respectively reported the synthesis of aryl ketones via palladiumꢀcatalyzed
insertion of nitriles by using arylboronic acids as aryl sources. In 2010, benzoic acids
have been proven to be useful as precursors of arylpalladium species for ketone
synthesis by Larhed and coꢀworkers.5 Similarly, Larhed,6 Deng7 and Wang8
independently developed the addition of aryl sulfinic acids or their salts to nitriles via
arylpalladium complexes. Despite of these contributions, they often suffered from
some drawbacks (e.g., substrate availability, functional group compatibility, unstable
nature of the substrates and toxic byꢀproducts, etc.) as a result of limited application.
Thus, there is still a room for broadening the scope of more environmentally friendly
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and more economic “green” arylation reagents to achieve aryl ketone derivatives.
Scheme 1. Palladium-Catalyzed Synthesis of Ketones from Nitriles
.
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In addition, arylhydrazines are used as organic synthesis blocks9 and important
identification reagents10 due to their high reactivity, low cost and easy availability.
However, to date, relatively little attention has been paid to utilize arylhydrazines as
aryl sources by denitrogenation,11 which is due to a high dissociation energy required
in direct activation of the CꢀN bond.12 Generally, the methods for activating
arylhydrazine CꢀN bond include the conversions to N’ꢀtosylarylhydrazines13 or
diazonium salts14. Nevertheless, most of these approaches often face significant
limitations, such as instability, substrate availability, involvement of multistage
synthesis and harsh reaction conditions. Therefore, the development of the “green”
and atom economy of the arylhydrazine CꢀN bond cleavage process is always needed.
Herein, we describe a palladiumꢀcatalyzed denitrogenative synthesis of aryl ketones
from arylhydrazines and nitriles via CꢀN bond cleavage using molecular oxygen as
oxidant, which generates nitrogen and water as the only byꢀproducts.
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To identify suitable conditions for the reaction, a series of catalysts, ligands,
additives and solvents were screened, and the results were shown in Table 1. Initially,
hydrazine (1a, 0.3 mmol) was treated with benzonitrile (2a, 0.2 mmol) in the presence
of Pd(OAc)2 (10 mol %), 1,10ꢀphenanthroline (phen; 10 mol %) and H2O (2 equiv) in
o
dioxane at 100 C under oxygen atmosphere for 24 h, and the desired benzophenone
product 3aa was observed in 22% yield (entry 1). Subsequently, various additives
were tested and TFA provided the best result (entries 2ꢀ5). Several different ligands
were also evaluated, and 2,2'ꢀbipyridine was found to improve the efficiency of the
reaction, affording 3aa in 76% yield (entries 6ꢀ9). The examination of different
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palladium salts revealed that Pd(OAc)2 was the most suitable catalyst for this reaction
system (entries 10ꢀ13). However, the use of toluene, DMSO or DMF as solvent was
proven to be disadvantageous to the reaction, as the yields were significantly
decreased (entries 14ꢀ16). Notably, when the initial substrate ratio was changed, the
yield of 3aa enhanced from 76% to 93% (entries 6 vs. 17). Moreover, lowering the
reaction temperature to 90 oC did not affect the reaction efficiency (entries 17 vs. 18).
Hence, 1a (0.2 mmol), 2a (0.3 mmol), Pd(OAc)2 (10 mol %), 2,2'ꢀbipyridine (10
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mol %), H2O (2 equiv) and TFA (2 equiv) in dioxane (2 mL) at 90 C under oxygen
atmosphere was chosen as the optimized conditions.
Table 1. Optimization of Reaction Conditionsa
entry
catalyst
ligand
Phen
additivec
–
solvent
yield (%)b
22
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Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
Phen
AgOAc
Cu(OAc)2
K2S2O8
TFA
<5
Phen
<5
Phen
17
Phen
49
Bipyridine
Neocuproine
PPh3
TFA
76
TFA
42
TFA
n.d.
n.d.
DPPP
TFA
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PdCl2
Pd(dba)2
Bipyridine
Bipyridine
Bipyridine
Bipyridine
Bipyridine
Bipyridine
Bipyridine
Bipyridine
Bipyridine
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
DMSO
7
n.d.
n.d.
<5
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17d
18e
PdBr2
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PdCl2(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
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PhCl
n.d.
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DMF
1,4ꢀDioxane
1,4-Dioxane
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92 (88)f
aAll reactions were carried out under the following conditions: 1a (0.3 mmol), 2a (0.2
mmol), Pd catalyst (10 mol %), ligand (10 mol %), solvents (2 mL) and H2O (2 equiv), 100
oC, 24 h, under O2. Bipyridine = 2,2'ꢀBipyridine. n.d. = not detected. bGC yield based on 2a
using dodecane as internal standard. c2.0 equiv. d1a (0.2 mmol), 2a (0.3 mmol), 24 h, GC
yield based on 1a using dodecane as internal standard. e90 oC. fIsolated yield.
With the optimal reaction conditions in hand, we started to investigate the scope
and limitation of this reaction. Typical results are shown in Table 2 and Table 3. We
first investigated the substrate scope of benzonitriles with hydrazine (1a, Table 2). To
our delight, a series of functional groups were participated well under the optimized
reaction conditions and gave the corresponding aryl ketones in excellent yields
(3abꢀ3ah). The benzonitriles 2bꢀ2d possessing electronꢀdonating group, such as
4ꢀmethyl, 4ꢀmethoxy and 1,3ꢀmethylenedioxy at the aryl ring could transfer to the
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desired products 3abꢀ3ad in 70%ꢀ76% yields, and some substrates bearing an
electronꢀwithdrawing group, including 4ꢀfluoro, 4ꢀacetyl, 2ꢀchloro and
4ꢀtrifluoromethyl at the benzene ring also reacted smoothly and afforded the desired
products 3aeꢀ3ah in 70ꢀ87% yields.
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Table 2. Synthesis of Aryl Ketones from Phenylhydrazine and Arylnitrilesa,b
aReaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), Pd(OAc)2 (10 mol %), 2,2'ꢀbipyridine (10
mol %), dioxane (2 mL), TFA (2 equiv) and H2O (2 equiv), 90 oC, 24 h, under O2. bIsolated yields.
Subsequently, to expand the scope of this method, a wide range of aromatic
hydrazines and substituted nitriles were examined (Table 3). It was found that most
aromatic hydrazines with various functional groups including methyl, dimethyl
methoxy, fluoro, chloro, bromo, cyano and trifluoromethyl were successfully
transformed to the desired aryl ketones in moderate to good yields (3baꢀ3la). The
reactions of aromatic hydrazines with electronꢀwithdrawing substituents at the
benzene ring gave the corresponding products in higher yields, and the yields were
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markedly lower with methoxy groups (3hb, 3hh and 3hj). Nitriles bearing a
heterocyclic substituent such as 2ꢀfuronitrile also gave the desired products in 51%
and 68% yields (3bi, 3ei). To our delight, the aliphatic nitrile substrates could be
converted to the desired aryl ketone products (3hmꢀ3ho) in moderate yields.
Unfortunately, the aliphatic hydrazines were not applicable for this reaction under the
current conditions, since the aliphatic hydrazines presumably are not conducive to the
formation of intermediate C (Scheme 4). In addition, 2ꢀnaphthylhydrazine was well
tolerated in this reaction system, with 3ib, 3ic and 3ik obtained in 42%, 55% and 60%
yields, respectively. When the orthoꢀposition of arylhydrazine was substituted with a
fluoro or dimethyl group, the yield of products 3ka and 3la decreased dramatically to
62% and 57%, which was probably due to the ortho steric hindrance. It is worth
noting that the ability to incorporate the halogen substituents (R = F, Cl, Br) into the
product makes this process have potential applications in further functionalization. To
our surprise, the reaction of hydrazine (0.6 mmol) with cinnamonitrile (0.2 mmol)
produced the dihydropyrazole derivative 4al in 41% yield under the standard
conditions.
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Table 3. Synthesis of Aryl Ketones from Arylhydrazines and Nitrilesa
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aReaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), Pd(OAc)2 (10 mol %), 2,2'ꢀbipyridine
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(10 mol %), dioxane (2 mL), TFA (2 equiv) and H2O (2 equiv), 90 C, 24 h, under O2.
bIsolated yields. cUnder air.
Fortunately, the reaction could be scaled up to 10 mmol under the standard
conditions and produced the desired product 3aa in 82% yield (Scheme 2).
Scheme 2. Gram Scale Experiment
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In order to investigate the mechanism of this reaction, a series of control
experiments were conducted (Scheme 3). When the reaction was carried out under a
nitrogen atmosphere, the corresponding aryl ketone 3aa was not obtained (Scheme
3a), which indicated that the reaction required the presence of oxygen. Next, some
control reactions with other oxidants under a nitrogen atmosphere were
performed to test the role of oxygen. We found that although some oxidants did
produce the desired product 3aa, the yields were inferior to that obtained with oxygen
as oxidant (Scheme 3b). The 18Oꢀlabeling experiment was also performed to get more
insights into this reaction process (Scheme 3c), indicating that the oxygen atom in the
ketone molecule was derived from H2O. Furthermore, the technology ESIꢀMS was
used to monitor the reaction between hydrazine and benzonitrile, and the result shows
that cationic palladium complex B (m/z = 472.0769) was detected in the reaction
mixture (Scheme 3d). When 1,10ꢀphen was used as the ligand, the ESIꢀMS(+) could
also detect a similar cationic palladium complex (m/z = 496.0762) in the reaction
mixture (Scheme 3e). This result demonstrated that the reaction might go through a
cationic palladium intermediate process.
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Scheme 3. Control Experiments
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On the basis of the above results and previous reports,11 we proposed a plausible
reaction mechanism for this transformation detailed in Scheme 4. The first step is the
formation of the palladiaziridine intermediate A via the metathesis of phenyl
hydrazide with L2Pd(II)X2 (X = OAc). Subsequently, the coordination of the nitrile
group with A forms complex B, and B undergoes the oxidative addition of L2Pd(0) to
afford the two palladium(II) centered intermediate C through CꢀN bond cleavage.
Next, cracking of the intermediate C gives the complex D and the palladiaziridine
complex G, which would be decomposed into L2Pd(0), nitrogen gas, and water by
oxygen. And then 1,2ꢀaddition of the coordinated aryl group to the nitrile group
generates the ketimine intermediate E. Protonation of ketimine intermediate E by the
acid affords the ketimine F and Pd(II) species. Finally, the hydrolysis of the ketimine
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F under acidic conditions would release the desired aryl ketone products and
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regenerate Pd(II) species to resume the catalytic cycle.
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Scheme 4. Possible Reaction Mechanism
In conclusion, we have successfully developed a novel method to synthesize a
series of aryl ketone derivatives from arylhydrazines and inexpensive nitriles via a
palladiumꢀcatalyzed CꢀN bond cleavage reaction. Taking into account the
combination of some desirable features, such as readily accessible starting materials,
operational simplicity, molecular oxygen as the sole oxidant, good tolerance to
scaleꢀup synthesis, as well as nontoxic gaseous N2 as the byꢀproducts, this
costꢀeffective method will provide a new arena of aryl ketone synthesis for both
academia and industry.
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EXPERIMENTAL SECTION
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General Information: NMR spectra were obtained using a 400 spectrometer (1H at
400 MHz, and 13C at 101 MHz). Chemical shifts for 1H NMR spectra are reported in
parts per million (ppm) from tetramethylsilane with the solvent resonance as the
internal standard (CDCl3: δ 7.26 ppm). Chemical shifts for 13C NMR spectra are
reported in parts per million (ppm) from tetramethylsilane with the solvent as the
internal standard (CDCl3: δ 77.0 ppm). IR spectra were obtained either as potassium
bromide pellets or as liquid films between two potassium bromide pellets with a
spectrometer. GC−MS was obtained using electron ionization. HRMS was obtained
with a LCMSꢀITꢀTOF mass spectrometer. Unless stated otherwise, commercial
reagents were used without further purification. All reagents were weighed and
handled in air at room temperature.
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Typical Procedure for Palladium(II)-Catalyzed Denitrogenative Reactions: The
reaction mixture of arylhydrazines 1 (0.2 mmol), nitriles 2 (0.3 mmol), Pd(OAc)2 (10
mol %), 2,2'ꢀbipyridine (10 mol %), TFA (2 equiv) and H2O (2 equiv) were added to
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1,4ꢀdioxane (2 mL). The mixture was stirred at 90 C for 24 h under O2, and
monitored periodically by TLC. Upon completion, the reaction mixture was diluted
with water (30 mL) and extracted with ethyl acetate (3 × 30 mL). The combined
organic layers were washed with water and brine, dried over Na2SO4 and filtered. The
solvent was removed under vacuum. The residue was purified by flash column
chromatography to afford aryl ketones 3.
Procedure for Large Scale Reaction: The reaction mixture of arylhydrazine 1a
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(10 mmol), nitrile 2a (15 mmol), Pd(OAc)2 (10 mol %), 2,2'ꢀbipyridine (10 mol %),
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TFA (2 equiv) and H2O (2 equiv) were added to 1,4ꢀdioxane (20 mL). The mixture
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was stirred at 90 C for 24 h under O2, and monitored periodically by TLC. Upon
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completion, the reaction mixture was diluted with water (30 mL) and extracted with
ethyl acetate (3 × 30 mL). The combined organic layers were washed with water and
brine, dried over Na2SO4 and filtered. The solvent was removed under vacuum. The
residue was purified by flash column chromatography to afford aryl ketones 3aa.
Benzophenone (3aa)15: Purified via flash column chromatography with 40% ethyl
acetate/petroleum ether, yielding 88% (32.0 mg) as a white solid: 47ꢀ49 oC. 1H NMR
(400 MHz, CDCl3, δ ppm) 7.81 (d, J = 7.6 Hz, 4H), 7.59 (t, J = 7.1 Hz, 2H), 7.48 (t, J
= 7.3 Hz, 4H); 13C NMR (101 MHz, CDCl3, δ ppm) 196.8, 137.6, 132.4, 130.1, 128.1.
IR (KBr, cm–1): 3060, 1659, 1599, 1313, 1150, 700. HRMS (ESI) m/z: calcd for
C13H10NaO [M + Na]+ 205.0624; found 205.0625.
Phenyl(p-tolyl)methanone (3ab)6: Purified via flash column chromatography with
40% ethyl acetate/petroleum ether, yielding 76% (29.8 mg) as a white solid: 55ꢀ57 oC.
1H NMR (400 MHz, CDCl3, δ ppm) 7.77 (d, J = 7.5 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H),
7.56 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 2.43 (s, 3H);
13C NMR (101 MHz, CDCl3, δ ppm) 196.4, 143.1, 137.9, 134.9, 132.1, 130.2, 129.8
128.9, 128.1, 21.6. IR (KBr, cm–1): 3050, 1653, 1603, 1312, 1176, 694. HRMS (ESI)
m/z: calcd for C14H12NaO [M + Na]+ 219.0780; found 219.0783.
(4-Methoxyphenyl)(phenyl)methanone (3ac)6: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 72% (30.5 mg) as a
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yellow solid: 61ꢀ63 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 7.83 (d, J = 8.2 Hz, 2H),
7.75 (d, J = 7.6 Hz, 2H), 7.55 (d, J = 7.2 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 6.96 (d, J =
8.2 Hz, 2H), 3.89 (s, 3H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.5, 163.2, 138.3,
132.5, 131.9, 130.2, 129.7, 128.2, 113.6, 55.5. IR (KBr, cm–1): 2922, 1650, 1598,
1259, 1027, 746. HRMS (ESI) m/z: calcd for C14H12NaO2 [M + Na]+ 235.0730;
found 235.0728.
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Benzo[d][1,3]dioxol-5-yl(phenyl)methanone (3ad)20: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 70% (31.6 mg) as a
yellow oil. 1H NMR (400 MHz, CDCl3, δ ppm) 7.74 (d, J = 7.8 Hz, 2H), 7.56 (t, J =
7.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.0 Hz,
1H), 6.05 (s, 2H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.1, 151.5, 147.9, 138.1,
131.9, 131.8, 129.6, 128.2, 126.8, 109.9, 107.7, 101.8. IR (KBr, cm–1): 2918, 1648,
1602, 1266, 1035, 748. HRMS (ESI) m/z: calcd for C14H10NaO3 [M + Na]+ 249.0522;
found 249.0526.
(4-Fluorophenyl)(phenyl)methanone (3ae)15: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 87% (34.9 mg) as a
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white solid: 47ꢀ48 C. H NMR (400 MHz, CDCl3, δ ppm) 7.87ꢀ7.81 (m, 2H),
7.80ꢀ7.73 (m, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.15 (t, J = 8.6
Hz, 2H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.2, 166.5 (d, J = 252.6 Hz), 137.5,
133.80 (d, J = 3.1 Hz), 132.6 (d, J = 9.1 Hz), 132.4, 129.8, 128.3, 115.4 (d, J = 2.1
Hz). IR (KBr, cm–1): 3060, 1649, 1585, 1283, 1091, 731. HRMS (ESI) m/z: calcd for
C13H9FNaO [M + Na]+ 223.0530; found 223.0527.
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1-(4-Benzoylphenyl)ethanone (3af)18: Purified via flash column chromatography
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82ꢀ84 C. H NMR (400 MHz, CDCl3, δ ppm) 8.04 (d, J = 8.3 Hz, 2H), 7.84 (d, J =
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8.3 Hz, 2H), 7.78 (d, J = 7.3 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H),
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2.65 (s, 3H); C NMR (101 MHz, CDCl3, δ ppm) 197.5, 195.9, 141.3, 139.6, 136.9,
133.1, 130.1, 130.0, 128.5, 128.2, 26.9. IR (KBr, cm–1): 3055, 1656, 1601, 1269,
1016, 736. HRMS (ESI) m/z: calcd for C15H12NaO2 [M + Na]+ 247.0730; found
247.0727.
(2-Chlorophenyl)(phenyl)methanone (3ag)20: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 70% (30.2 mg) as a
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white solid: 46ꢀ47 C. H NMR (400 MHz, CDCl3, δ ppm) 7.82 (d, J = 7.8 Hz, 2H),
7.59 (t, J = 7.3 Hz, 1H), 7.50ꢀ7.33 (m, 6H); 13C NMR (101 MHz, CDCl3, δ ppm)
195.3, 138.7, 136.5, 133.7, 1313, 131,2, 130.1, 129.1, 128.6, 126.7. IR (KBr, cm–1):
3063, 1671, 1592, 1286, 1058, 744. HRMS (ESI) m/z: calcd for C13H9ClNaO [M +
Na]+ 239.0234; found 239.0237.
Phenyl(4-(trifluoromethyl)phenyl)methanone (3ah)16: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 79% (39.5 mg) as a
white solid: 108ꢀ110 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 7.82 (d, J = 7.8 Hz, 2H),
7.59 (t, J = 7.3 Hz, 1H), 7.50ꢀ7.33 (m, 6H); 13C NMR (101 MHz, CDCl3, δ ppm)
195.5, 140.8, 136.8, 133.7 (q, J = 32 Hz), 133.0, 130.1, 130.0, 128.5, 125.3 (q, J = 3.7
Hz), 122.3 (q, J = 273 Hz). IR (KBr, cm–1): 2972, 1653, 1605, 1272, 1067, 696.
HRMS (ESI) m/z: calcd for C14H9F3NaO [M + Na]+ 273.0498; found 273.0496.
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(4-Chlorophenyl)(phenyl)methanone (3ak)6: Purified via flash column
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yellow solid: 75ꢀ77 C. H NMR (400 MHz, CDCl3, δ ppm) 7.83ꢀ7.71 (m, 4H),
7.63ꢀ7.57 (m, 1H), 7.54ꢀ7.42 (m, 4H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.5,
138.9, 137.3, 135.9, 132.6, 131.5, 129.9, 128.7, 128.4. IR (KBr, cm–1): 2958, 1726,
1655, 1272, 1082, 695. HRMS (ESI) m/z: calcd for C13H9ClNaO [M + Na]+ 239.0234;
found 239.0233.
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(4-Bromophenyl)(phenyl)methanone (3ba)6: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 81% (41.9 mg) as a
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yellow solid: 79ꢀ80 C. H NMR (400 MHz, CDCl3, δ ppm) 7.78ꢀ7.76 (m, 2H),
7.68ꢀ7.58 (m, 5H), 7.50ꢀ7.46(m, 2H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.5,
137.2, 136.3, 132.6, 131.6, 131.5, 129.9, 128.4, 127.5. IR (KBr, cm–1): 2923, 1651,
1586, 1268, 1067, 746. HRMS (ESI) m/z: calcd for C13H9BrNaO [M + Na]+
282.9729; found 282.9727.
(4-Chlorophenyl)(phenyl)methanone (3ca)6: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 79% (34.1 mg) as a
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yellow solid: 75ꢀ77 C. H NMR (400 MHz, CDCl3, δ ppm) 7.79ꢀ7.66 (m, 4H), 7.56
(t, J = 7.4 Hz, 1H), 7.48ꢀ7.36 (m, 4H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.1,
138.6, 137.0, 135.7, 132.4, 131.24, 129.7, 128.4, 128.2. IR (KBr, cm–1): 2364, 1650,
1585, 1273, 1093, 743. HRMS (ESI) m/z: calcd for C13H9ClNaO [M + Na]+ 239.0234;
found 239.0236.
(3,5-Dimethylphenyl)(phenyl)methanone (3da)19: Purified via flash column
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chromatography with 40% ethyl acetate/petroleum ether, yielding 84% (35.2 mg) as a
yellow solid: 58ꢀ60 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 7.80 (d, J = 7.5 Hz, 2H),
7.58 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.41 (s, 2H), 7.22 (s, 1H), 2.38 (s,
6H); 13C NMR (101 MHz, CDCl3, δ ppm) 197.1, 137.9, 137.8, 137.7, 134.1, 132.2,
130.0, 128.2, 127.8, 21.2. IR (KBr, cm–1): 2920, 1658, 1598, 1315, 1022, 725.
HRMS (ESI) m/z: calcd for C15H15O [M + H]+ 211.1117; found 211.1113.
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(3,5-Dimethylphenyl)(p-tolyl)methanone (3db): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 80% (35.8 mg) as a
yellow oil. 1H NMR (400 MHz, CDCl3, δ ppm) 7.71 (d, J = 7.3 Hz, 2H), 7.37 (s, 2H),
7.27 (d, J = 7.7 Hz, 2H), 7.20 (s, 1H), 2.43 (s, 3H), 2.36 (s, 6H); 13C NMR (101 MHz,
CDCl3, δ ppm) 196.9, 143.0, 138.1, 137.8, 135.2, 133.8, 130.2, 128.9, 127.7, 21.6,
21.2. IR (KBr, cm–1): 1663, 1614, 1384, 1135, 756. HRMS (ESI) m/z: calcd for
C16H16NaO [M + Na]+ 247.1093; found 247.1095.
Phenyl(p-tolyl)methanone (3ea)6: Purified via flash column chromatography with
40% ethyl acetate/petroleum ether, yielding 85% (37.2 mg) as a white solid: 55ꢀ57 oC.
1H NMR (400 MHz, CDCl3, δ ppm) 7.80ꢀ7ꢀ77 (m, 2H), 7.75ꢀ7.69 (m, 2H), 7.60ꢀ7.55
(m, 1H), 7.51ꢀ7.44 (m, 2H), 7.28 (d, J = 7.9 Hz, 2H), 2.44 (s, 3H); 13C NMR (101
MHz, CDCl3, δ ppm) 196.5, 143.2, 138.0, 134.9, 132.2, 130.3, 129.9, 129.0, 128.2,
21.7. IR (KBr, cm–1): 2959, 1655, 1587, 1272, 1082, 749. HRMS (ESI) m/z: calcd for
C14H12NaO [M + Na]+ 219.0780; found 219.0776.
di-p-Tolylmethanone (3eb)7: Purified via flash column chromatography with 40%
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ethyl acetate/petroleum ether, yielding 72% (30.2 mg) as a white solid: 89ꢀ91 C. H
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NMR (400 MHz, CDCl3, δ ppm) 7.69 (d, J = 8.0 Hz, 4H), 7.26 (d, J = 7.9 Hz, 4H),
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2.42 (s, 6H); C NMR (101 MHz, CDCl3, δ ppm) 196.2, 142.9, 135.3, 130.2, 128.9,
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21.6. IR (KBr, cm–1): 1644, 1605, 1272, 1116, 746. HRMS (ESI) m/z: calcd for
C15H15O [M + H]+ 211.1117; found 211.1118.
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(4-Fluorophenyl)(p-tolyl)methanone (3ee)7: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 80% (34.2 mg) as a
yellow solid: 92ꢀ94 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 7.82 (dd, J = 8.7, 5.5 Hz,
2H), 7.68 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.14 (t, J = 8.6 Hz, 2H), 2.44
13
(s, 3H); C NMR (101 MHz, CDCl3, δ ppm) 194.9, 165.2 (d, J = 252.0 Hz), 143.3,
134.8, 134.1 (d, J = 2.6 Hz), 132.5 (d, J = 9.1 Hz), 130.1, 129.0, 115.3 (d, J = 21.9
Hz). IR (KBr, cm–1): 1647, 1268, 753. HRMS (ESI) m/z: calcd for C14H11FNaO [M +
Na]+ 237.0686; found 237.0687.
Benzo[d][1,3]dioxol-5-yl(p-tolyl)methanone (3ed): Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 80% (30.2 mg) as a
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yellow oil. H NMR (400 MHz, CDCl3, δ ppm) 7.66 (d, J = 7.6 Hz, 2H), 7.40ꢀ7.31
(m, 2H), 7.27 (d, J = 6.7 Hz, 2H), 6.85 (d, J = 8.0 Hz, 1H), 6.05 (s, 2H), 2.43 (s, 3H);
13C NMR (101 MHz, CDCl3, δ ppm) 194.9, 151.3, 147.8, 142.7, 135.3, 132.2, 129.9,
128.9, 126.5, 109.9, 107.6, 101.8, 21.6. IR (KBr, cm–1): 2920, 1652, 1606, 1270,
1038, 752. HRMS (ESI) m/z: calcd for C15H12NaO3 [M + Na]+ 263.0679; found
263.0683.
(4-Bromophenyl)(furan-2-yl)methanone (3bi)21: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 51% (25.4 mg) as a
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yellow oil. 1H NMR (400 MHz, CDCl3, δ ppm) 7.88 (d, J = 8.1 Hz, 2H), 7.71 (s, 1H),
7.65 (d, J = 8.1 Hz, 2H), 7.27 (s, 1H), 6.66ꢀ6.55 (m, 1H); 13C NMR (101 MHz,
CDCl3, δ ppm) 181.2, 152.2, 147.2, 135.9, 131.7, 130.9, 127.7, 120.5, 112.4. IR (KBr,
cm–1): 2921, 1641, 1582, 1294, 1069, 753. HRMS (ESI) m/z: calcd for C11H7BrNaO2
[M + Na]+ 272.9522; found 272.9518.
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Furan-2-yl(p-tolyl)methanone (3ei)15: Purified via flash column chromatography
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with 40% ethyl acetate/petroleum ether, yielding 68% (25.3 mg) as a yellow oil. H
NMR (400 MHz, CDCl3, δ ppm) 7.89 (d, J = 7.7 Hz, 2H), 7.69 (s, 1H), 7.29 (d, J =
7.8 Hz, 2H), 7.22 (d, J = 3.4 Hz, 1H), 6.62ꢀ6.52 (m, 1H), 2.43 (s, 3H); 13C NMR (101
MHz, CDCl3, δ ppm) 182.2, 152.5, 146.8, 143.4, 134.6, 129.5, 129.1, 120.1, 112.1,
21.6. IR (KBr, cm–1): 2922, 1641, 1562, 1298, 1020, 752. HRMS (ESI) m/z: calcd for
C12H10NaO2 [M + Na]+ 209.0573; found 209.0578.
4-Benzoylbenzonitrile (3ja)18: Purified via flash column chromatography with
40% ethyl acetate/petroleum ether, yielding 72% (29.8 mg) as a white solid: 110ꢀ112
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oC. H NMR (400 MHz, CDCl3, δ ppm) 7.90ꢀ7.85 (m, 2H), 7.82ꢀ7.73 (m, 4H),
7.67ꢀ7.61 (m, 1H), 7.55ꢀ 7.48 (m, 2H); 13C NMR (101 MHz, CDCl3, δ ppm) 195.0,
141.3, 136.4, 133.3, 132.2, 130.2, 130.0, 128.6, 118.0, 115.7. IR (KBr, cm–1 ): 2920,
1764, 1652, 1248, 1056, 750. HRMS (ESI) m/z: calcd for C14H10NO [M + H]+
208.0757; found 208.0754.
p-Tolyl(4-(trifluoromethyl)phenyl)methanone (3fb)7: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 82% (43.3 mg) as a
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yellow solid: 135ꢀ137 C. H NMR (400 MHz, CDCl3, δ ppm) 7.87 (d, J = 8.0 Hz,
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2H), 7.79ꢀ7.64 (m, 4H), 7.30 (d, J = 7.7 Hz, 2H), 2.45 (s, 3H); 13C NMR (101 MHz,
CDCl3, δ ppm) 195.2, 144.1, 141.1, 134.1, 133.5 (q, J = 33 Hz), 130.3, 130.0, 129.2,
125.3 (q, J = 3.9 Hz), 123.3(q, J = 272 Hz), 21.7. IR (KBr, cm–1): 1645, 1267, 1128,
750. HRMS (ESI) m/z: calcd for C15H11F3NaO [M + Na]+ 287.0654; found 287.0656.
1-(4-(4-(Trifluoromethyl)benzoyl)phenyl)ethanone (3ff)16: Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 75% (43.8
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mg) as a yellow solid: 124ꢀ126 C. H NMR (400 MHz, CDCl3, δ ppm) 8.07 (d, J =
7.9 Hz, 2H), 7.89 (t, J = 9.7 Hz, 4H), 7.78 (d, J = 7.8 Hz, 2H), 2.67 (s, 3H); 13C NMR
(101 MHz, CDCl3, δ ppm) 197.3, 194.8, 140.3, 140.1, 140.0, 139.9, 139.8, 130.1 (q, J
= 33 Hz), 128.3, 125.5 (q, J = 3.7 Hz), 122.2 (q, J = 274 Hz), 26.9. IR (KBr, cm–1):
2922, 1645, 1523, 1264, 1064, 748. HRMS (ESI) m/z: calcd for C16H11F3NaO2 [M +
Na]+ 315.0603; found 315.0607.
Bis(4-fluorophenyl)methanone (3ge)19: Purified via flash column chromatography
with 40% ethyl acetate/petroleum ether, yielding 71% (30.9 mg) as a white solid:
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106ꢀ108 C. H NMR (400 MHz, CDCl3, δ ppm) 7.89ꢀ7.71 (m, 4H), 7.15 (t, J = 8.1
Hz, 4H); 13C NMR (101 MHz, CDCl3, δ ppm) 193.7, 166.4 (d, J = 252.7 Hz), 133.71
(d, J = 3.1 Hz), 132.47 (d, J = 9.2 Hz), 115.5 (d, J = 2.2 Hz). IR (KBr, cm–1): 1647,
1595, 1267, 1149, 755. HRMS (ESI) m/z: calcd for C13H8F2NaO [M + Na]+ 241.0435;
found 241.0437.
(4-Methoxyphenyl)(p-tolyl)methanone (3hb)7: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 47% (21.2 mg) as a
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yellow solid: 85ꢀ87 C. H NMR (400 MHz, CDCl3, δ ppm) 7.85ꢀ7.77 (m, 2H), 7.68
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(d, J = 8.1 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H),
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2.44 (s, 3H); C NMR (101 MHz, CDCl3, δ ppm) 195.4, 163.0, 142.6, 135.5, 132.4,
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HRMS (ESI) m/z: calcd for C15H14NaO2 [M + Na]+ 249.0886; found 249.0887.
(4-Methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone (3hh)17: Purified via
flash column chromatography with 40% ethyl acetate/petroleum ether, yielding 42%
(23.5 mg) as a yellow solid: 118ꢀ120 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 7.83 (t,
J = 8.3 Hz, 4H), 7.74 (d, J = 7.9 Hz, 2H), 6.98 (d, J = 8.5 Hz, 2H), 3.90 (s, 3H); 13C
NMR (101 MHz, CDCl3, δ ppm) 194.3, 163.7, 141.5, 133.1, 132.6, 129.6 (q, J = 32
Hz), 128.7, 125.26 (q, J = 3.8 Hz), 122.3 (q, J = 273 Hz), 113.8, 55.6. IR (KBr, cm–1):
2921, 1645, 1602, 1264, 1032, 755. HRMS (ESI) m/z: calcd for C15H11F3NaO2 [M +
Na]+ 303.0603; found 303.0606.
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(4-Methoxyphenyl)(4-nitrophenyl)methanone (3hj)17: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 40% (20.5 mg) as a
white solid: 122ꢀ124 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.33 (d, J = 8.7 Hz, 2H),
7.88 (d, J = 8.7 Hz, 2H), 7.81 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 3.91 (s,
3H); 13C NMR (101 MHz, CDCl3, δ ppm) 193.5, 164.0, 149.6, 143.8, 132.7, 130.3,
129.0, 123.5, 114.0, 55.6. IR (KBr, cm–1): 2922, 1641, 1594, 1263, 1111, 741. HRMS
(ESI) m/z: calcd for C14H11NNaO4 [M + Na]+ 280.0580; found 280.0587.
1-(4-Methoxyphenyl)-2-phenylethanone (3hm)6: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 52% (23.5 mg) as a
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white solid: 76ꢀ77 C. H NMR (400 MHz, CDCl3, δ ppm) 8.06ꢀ7.96 (m, 2H),
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7.37ꢀ7.22 (m, 5H), 7.02ꢀ6.84 (m, 2H), 4.24 (s, 2H), 3.84 (s, 3H); 13C NMR (101 MHz,
CDCl3, δ ppm) 196.2, 163.6, 135.1, 131.0, 129.7, 129.4, 128.7, 126.8, 113.8, 55.5,
45.3. IR (KBr, cm–1): 3022, 1671, 1594, 1318, 1166, 707. HRMS (ESI) m/z: calcd for
C15H14NaO2 [M + Na]+ 249.0886; found 249.0883.
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1-(4-Methoxyphenyl)pentan-1-one (3hn)7: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 47% (18.1 mg) as a
yellow oil. 1H NMR (400 MHz, CDCl3, δ ppm) 7.92 (d, J = 8.9 Hz, 2H), 6.91 (d, J =
8.9 Hz, 2H), 3.84 (s, 3H), 2.88 (t, J = 7.4 Hz, 2H), 1.75ꢀ1.63 (m, 2H), 1.44ꢀ1.32 (m,
2H), 0.93 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3, δ ppm) 199.2, 163.3,
130.2, 130.1, 113.7, 55.4, 38.0, 26.8, 22.5, 13.9. IR (KBr, cm–1): 2952, 1674, 1597,
1457, 1170, 754. HRMS (ESI) m/z: calcd for C12H16NaO2 [M + Na]+ 215.1043; found
215.1039.
1-(4-Methoxyphenyl)dodecan-1-one (3ho)22: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 46% (26.7 mg) as a
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white solid: 55ꢀ57 C. H NMR (400 MHz, CDCl3, δ ppm) 7.94 (d, J = 8.9 Hz, 2H),
6.92 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H), 2.90 (t, J = 7.5 Hz, 2H), 1.79ꢀ1.66 (m, 2H),
1.39ꢀ1.23 (m, 16H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3, δ ppm)
199.3, 163.3, 130.3, 130.2, 113.7, 55.4, 38.3, 31.9, 29.6, 29.5, 29.4, 29.3, 29.2, 24.7,
22.7, 14.1. IR (KBr, cm–1): 2971, 1676, 1599, 1317, 1172, 724. HRMS (ESI) m/z:
calcd for C19H30NaO2 [M + Na]+ 313.2138; found 313.2141.
Naphthalen-2-yl(p-tolyl)methanone (3ib)15: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 55% (27.0 mg) as a
yellow solid: 85ꢀ87 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.26 (s, 1H), 7.92 (d, J =
11.2 Hz, 4H), 7.79 (d, J = 7.7 Hz, 2H), 7.58 (dd, J = 15.4, 8.0 Hz, 2H), 7.32 (d, J =
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7.8 Hz, 2H), 2.47 (s, 3H); 13C NMR (101 MHz, CDCl3, δ ppm) 196.5, 143.2, 139.0,
135.2, 135.1, 132.3, 131.5, 130.3, 129.3, 129.0, 128.2, 128.1, 127.8, 126.7, 125.8,
21.7. IR (KBr, cm–1): 3190, 1663, 1615, 1385, 1137, 751. HRMS (ESI) m/z: calcd for
C18H14NaO [M + Na]+ 269.0937; found 269.0940.
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(4-Methoxyphenyl)(naphthalen-2-yl)methanone (3ic)15: Purified via flash
column chromatography with 40% ethyl acetate/petroleum ether, yielding 42% (22.0
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mg) as a yellow solid: 88ꢀ90 C. H NMR (400 MHz, CDCl3, δ ppm) 8.24 (s, 1H),
8.00ꢀ7.80 (m, 6H), 7.62ꢀ7.53 (m, 2H), 7.00 (d, J = 8.0 Hz, 2H), 3.91 (s, 3H); 13C
NMR (101 MHz, CDCl3, δ ppm) 195.6, 163.3, 135.5, 135.0, 132.6, 132.3, 131.1,
130.5, 129.3, 128.1, 128.0, 127.8, 126.7, 125.9, 113.6, 55.5. IR (KBr, cm–1): 1663
1613, 1384, 1138, 773. HRMS (ESI) m/z: calcd for C18H14NaO2 [M + Na]+ 285.0886;
found 285.0889.
(4-Chlorophenyl)(naphthalen-2-yl)methanone (3ik)8: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 60% (27.1 mg) as a
yellow solid: 122ꢀ124 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 8.23 (s, 1H), 8.00ꢀ7.88
(m, 4H), 7.82 (d, J = 8.1 Hz, 2H), 7.64ꢀ7.55(m, 2H), 7.50 (d, J = 8.0 Hz, 2H); 13C
NMR (101 MHz, CDCl3, δ ppm) 138.9, 136.2, 135.4, 134.5, 133.6, 132.3, 131.7,
131.5, 129.4, 128.7, 128.5, 128.4, 127.9, 126.9, 125.6. IR (KBr, cm–1): 1660, 1616,
1384, 1136, 753. HRMS (ESI) m/z: calcd for C17H11ClNaO [M + Na]+ 289.0391;
found 289.0389.
(2-Fluorophenyl)(phenyl)methanone (3ka)23: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 62% (24.8 mg) as a
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colorless oil. H NMR (400 MHz, CDCl3, δ ppm) δ 7.82 (d, J = 8.2 Hz, 2H),
7.59ꢀ7.42 (m, 5H), 7.26ꢀ7.22 (m, 1H), 7.13 (t, J = 9.0 Hz, 1H); 13C NMR (101 MHz,
CDCl3, δ ppm) 193.6, 160.1(d, J = 2501.0 Hz),, 137.4, 133.4, 133.1 (d, J = 8.3 Hz),
130.8 (d, J = 2.9 Hz), 129.8, 128.5, 127.1 (d, J = 14.9 Hz), 124.3 (d, J = 3.6 Hz),
116.4, 116.3(d, J = 21.6 Hz). IR (KBr, cm–1): 2926, 1668, 1594, 1451, 1165, 771.
HRMS (ESI) m/z: calcd for C13H9FNaO [M + Na]+ 223.0530; found 223.0534.
(2,6-Dimethylphenyl)(phenyl)methanone (3la)24: Purified via flash column
chromatography with 40% ethyl acetate/petroleum ether, yielding 57% (23.9 mg) as a
yellow solid: 62ꢀ64 oC. 1H NMR (400 MHz, CDCl3, δ ppm) 7.80 (d, J = 7.3 Hz, 2H),
7.58 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.25ꢀ7.20 (m, 1H), 7.07 (d, J = 7.6
Hz, 2H), 2.12 (s, 6H); 13C NMR (101 MHz, CDCl3, δ ppm) 200.5, 139.7, 137.1,
134.2, 133.7, 129.4, 128.9, 128.7, 127.6, 19.4. IR (KBr, cm–1): 2927, 1665, 1599,
1449, 1162, 755. HRMS (ESI) m/z: calcd for C15H14NaO [M + Na]+ 233.0937; found
233.0943.
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Procedure for product 4al: The reaction mixture of arylhydrazines 1a (0.6 mmol),
cinnamonitrile 2l (0.2 mmol), Pd(OAc)2 (10 mol %), 2,2'ꢀbipyridine (10 mol %), TFA
(2 equiv) and H2O (2 equiv) were added to 1,4ꢀdioxane (2 mL). The mixture was
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stirred at 90 C for 24 h under air, and monitored periodically by TLC. Upon
completion, the reaction mixture was diluted with water (30 mL) and extracted with
ethyl acetate (3 × 30 mL). The combined organic layers were washed with water and
brine, dried over Na2SO4 and filtered. The solvent was removed under vacuum. The
residue was purified by flash column chromatography to afford dihydropyrazole
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derivative 4al.
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1,3,5-Triphenyl-4,5-dihydro-1H-pyrazole (4al)9e: Purified via flash column
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chromatography with 40% ethyl acetate/petroleum ether, yielding 41% (24.4 mg) as a
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yellow solid: 137ꢀ139 C. H NMR (400 MHz, CDCl3, δ ppm) 7.72ꢀ7.54 (m, 2H),
7.29 (dd, J = 12.3, 4.7 Hz, 3H), 7.24 (d, J = 5.0 Hz, 5H), 7.09 (dd, J = 8.3, 7.5 Hz,
2H), 7.02ꢀ6.97 (m, 2H), 6.70 (t, J = 7.2 Hz, 1H), 5.18 (dd, J = 12.4, 7.3 Hz, 1H), 3.75
(dd, J = 17.1, 12.4 Hz, 1H), 3.05 (dd, J = 17.1, 7.3 Hz, 1H); 13C NMR (101 MHz,
CDCl3, δ ppm) 146.7, 144.9, 142.6, 132.8, 129.1, 128.9, 128.6, 128.5, 127.6, 125.8,
125.7, 119.1, 113.4, 64.6, 43.6. IR (KBr, cm–1 ): 3041, 2920, 1594, 1494, 1451, 1385,
1260, 1109, 872, 806, 753, 690. HRMS (ESI) m/z: calcd for C21H18N2Na [M + Na]+
321.1362; found 321.1359.
ASSOCIATED CONTENT
Supporting Information
The NMR and HRMS spectral data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
jianghf@scut.edu.cn; cewuwq@scut.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful to the National Program on Key Research Project (2016YFA0602900),
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the National Natural Science Foundation of China (21420102003, 21490572,
21672072), Pearl River S&T Nova Program of Guangzhou (201610010160) and the
Fundamental Research Funds for the Central Universities (2015ZY001) for financial
support.
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REFERENCES
(1) (a) Boger, D. L.; Hong, J.; Hikota, M.; Ishida, M. J. Am. Chem. Soc. 1999, 121,
2471. (b) Reux, B.; Nevalainen, T.; Raitio, K. H.; Koskinen, A. M. Bioorg. Med.
Chem. 2009, 17, 4441. (c) Wang, W.; Zeng, Y. H.; Osman, K.; Shinde, K.; Rahman,
M.; Gibbons, S.; Mu, Q. J. Nat. Prod. 2010, 73, 1815. (d) Chong, Y. M.; Yin, W. F.;
Ho, C. Y.; Mustafa, M. R.; Hadi, A. H. A.; Awang, K.; Narrima, P.; Koh, C.ꢀL.;
Appleton, D. R.; Chan, K.ꢀG. J. Nat. Prod. 2011, 74, 2261.
(2) (a) Calloway, N. O. Chem. Rev. 1935, 17, 392. (b) Gore, P. H. Chem. Rev. 1955,
55, 229.
(3) (a) Zhao, B.; Lu, X. Tetrahedron Lett. 2006, 47, 6765. (b) Zhao, B.; Lu, X. Org.
Lett. 2006, 8, 5987.
(4) (a) Zhou, C.; Larock, R. C. J. Am. Chem. Soc. 2004, 126, 2302. (b) Zhou, C.;
Larock, R. C. J. Org. Chem. 2006, 71, 3551.
(5) Lindh, J.; Sjöberg, P. J. R.; Larhed, M. Angew. Chem. Int. Ed. 2010, 49, 7733.
(6) Behrends, M.; Sävmarker, J.; Sjöberg, P. J. R.; Larhed, M. ACS Catal. 2011, 1,
1455.
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6
(7) Liu, J.; Zhou, X.; Rao, H.; Xiao, F.; Li, C.ꢀJ.; Deng, G.ꢀJ. Chem. Eur. J. 2011, 17,
7996.
7
8
9
(8) Miao, T.; Wang, G.ꢀW. Chem. Commun. 2011, 47, 9501.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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50
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53
54
55
56
57
58
59
60
(9) (a) Tomakinian, T.; Guillot, R.; Kouklovsky, C.; Vincent, G. Chem. Commun. 2016,
52, 5443. (b) Wei, W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.; Wang, H. Chem.
Commun. 2015, 51, 768. (c) Senadi, G. C.; Hu, W. P.; Lu, T. Y.; Garkhedkar, A. M.;
Vandavasi, J. K.; Wang, J. J. Org. Lett. 2015, 17, 1521. (d) Wu, Q.; Liu, P.; Pan, Y.ꢀM.;
Xu, Y.ꢀ L.; Wang, H.ꢀS. RSC Adv. 2012, 2, 10167. (e) Wang, X.; Pan, Y.ꢀM.; Huang,
X.ꢀC.; Mao, Z.ꢀY.; Wang, H.ꢀS. Org. Biomol. Chem. 2014, 12, 2028.
(10) Yao, P. Appl. Organometal. Chem. 2014, 28, 194.
(11) (a) Zhu, M.ꢀK.; Zhao, J.ꢀF.; Loh, T.ꢀP. Org. Lett. 2011, 13, 6308. (b) Chen, Y.;
Guo, S.; Li, K.; Qu, J.; Yuan, H.; Hua, Q.; Chen, B. Adv. Synth. Catal. 2013, 355, 711.
(c) Peng, Z.; Hu, G.; Qiao, H.; Xu, P.; Gao, Y.; Zhao, Y. J. Org. Chem. 2014, 79, 2733.
(d) Xu, W.; Hu, G.; Xu, P.; Gao, Y.; Yin, Y.; Zhao, Y. Adv. Synth. Catal. 2014, 356,
2948. (e) Zhao, Y.; Song, Q. Chem. Commun. 2015, 51, 13272.
(12) Ouyang, K.; Hao, W.; Zhang, W. X.; Xi, Z. Chem. Rev. 2015, 115, 12045.
(13) (a) Liu, J.ꢀB.; Yan, H.; Chen, H.ꢀX.; Luo, Y.; Weng, J.; Lu, G. Chem. Commun.
2013, 49, 5268. (b) Barluenga, J.; Valdés, C. Angew. Chem., Int. Ed. 2011, 50, 7486.
(14) (a) Roglans, A.; PlaꢀQuintana, A.; MorenoꢀMañas, M. Chem. Rev. 2006, 106,
4622. (b) Zhao, X.; Zhang, Y.; Wang, J. Chem. Commun. 2012, 48, 10162. (c) Felpin,
F. X.; NassarꢀHardy, L.; Callonnec, F. L.; Fouquet, E. Tetrahedron. 2011, 67, 2815. (d)
Taylor, J. G.; Moro, A. V.; Correia, C. R. D. Eur. J. Org. Chem. 2011, 1403.
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(15) Rao, M. L.; Venkatesh, V.; Banerjee, D. Tetrahedron 2007, 63, 12917.
(16) Neumann, H.; Brennführer, A.; Beller, M. Chem. Eur. J. 2008, 14, 3645.
(17) Ito, K.; Tamashima, H.; Iwasawa, N.; Kusama, H. J. Am. Chem. Soc. 2011, 133,
3716.
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53
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55
56
57
58
59
60
(18) Li, X.; Zou, G. Chem. Commun. 2015, 51, 5089.
(19) Zhou, Q.; Wei, S.; Han, W. J. Org. Chem. 2014, 79, 1454.
(20) EkoueꢀKovi, K.; Xu, H.; Wolf, C. Tetrahedron Lett. 2008, 49, 5773.
(21) Lerebours, R.; CamachoꢀSoto, A.; Wolf, C. J. Org. Chem. 2005, 70, 8601.
(22) Parella, R.; Kumar, N. A.; Babu, S. A. Tetrahedron Lett. 2013, 54, 1738.
(23) Liu, Y.; Meng, G.; Liu, R.; Szostak, M. Chem. Commun. 2016, 52, 6841.
(24) O’Keefe, B. M.;, Simmons, N.; Martin, S. F. Org. Lett. 2008, 10, 5301.
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