Palladium-Catalyzed C-N Bond Cleavage of 2 H-Azirines for the Synthesis of Functionalized α-Amido Ketones

Article abstract of DOI:10.1021/acs.joc.8b03193

A Pd-catalyzed ring-opening reaction of 2H-azirines with carboxylic acids was developed. This reaction undergoes nucleophilic addition between 2,3-diaryl-2H-azirines and carboxylic acids followed by C-N single-bond cleavage and a subsequent thermal rearrangement. This method enables the rapid construction of valuable α-amido ketone derivatives with high atomic efficiency and superb functional group tolerance.

Full text of DOI:10.1021/acs.joc.8b03193

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Article
Palladium-Catalyzed C-N Bond Cleavage of 2H-Azirines
for the Synthesis of Functionalized #-Amidoketones
Fen Xu, Xiao-Ju Si, Yuan-Yuan Song, Xing-Dong Wang, Chun-Sen Liu, Peng-Fei Geng, and Miao Du
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03193 • Publication Date (Web): 28 Jan 2019
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Palladium-Catalyzed C-N Bond Cleavage of
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2H-Azirines for the Synthesis of Functionalized
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α-Amidoketones
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Fen Xu,a,* Xiao-Ju Si, Yuan-Yuan Song, Xing-Dong Wang, Chun-Sen Liu,* Peng-Fei Geng, Miao Du*
a
College of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou
450002 (China). E-mail: fenxu_zzuli@163.com
TABLE OF CONTENTS
ABSTRACT: A Pd-catalyzed ring-opening reaction of 2H-azirines with carboxylic
acids was developed. This reaction undergoes nucleophilic addition between
2,3-diaryl-2H-azirines and carboxylic acids followed by C-N single bond cleavage
and a subsequent thermal rearrangement. This method enables the rapid construction
of valuable α-amidoketone derivatives with high atomic efficiency and superb
functional-group tolerance.
INTRODUCTION
The metal-catalyzed conversion of 2H-azirines has attracted considerable attention in
modern organic synthesis to build up highly complex molecular skeletons.1-6 Based on
their inherently high ring-strain energy,7-10 2H-azirines undergo various ring
expansion reactions, such as [3+2],11-17 [3+3],18-22 [3+2+2]23 cycloaddition with
unsaturated molecules, aza-Diels-Alder reactions,24 intramolecular rearrangement25
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and various nucleophilic addition reactions.26-30 Among these events, three general
models for the chemical bond cleavage of 2H-azirines have been well-established: i)
heterolytic C−N single-bond-cleavage mode to generate vinyl nitrenoid
intermediates,31,32 ii) transition-metal-assisted or visible light-induced C−C cleavage
mode to generate nitrile ylides,33 and iii) simultaneous cleavage of both C−C and
C−N mode to form carbenoid species34 (Scheme 1, a). Compared with the prevalence
of ring expansion via cycloaddition reactions, the exploration of new applications of
2H-azirines is highly desirable.
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Scheme 1. Representative applications of 2H-azirines.
The α-amidoketones are very important structural motifs that are widely found in
pharmaceuticals and several natural active molecules, such as herbicides, fungicides,
and enzyme inhibitors.35-37 They are also important synthetic intermediates, for
instance in the synthesis of N-heterocycles such as oxazoles,38 imidazoles39,
thiazoles40, and others. Therefore, considerable efforts have been devoted to their
synthesis.41-50 Nevertheless, some of these synthetic methods suffer from the
following drawbacks: the difficulties of preparing starting substrates, rigorous
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conditions, and/or limitations of the substrate scope. Therefore, new synthetic
methods featuring high atomic-efficiency and operational simplicity are still under
great demand. In this regard, method based on direct Pd-catalyzed ring-opening
reaction of methyleneaziridine with carboxylic acid has been applied to access
α-amidoketones51 (Scheme 1, b). However, this transformation was limited to the
synthesis of tertiary amide, and was also restricted by strict inert conditions and lack
of substrate variation. In view of high ring strain and the easy ring-opening nature of
2H-azirines, reaction of 2H-azirines with carboxylic acids was also developed.
However, the substrates were limited to amino-azirines52,53, 2-phenylazirine54,55 and
phosphorus substituted azirines.56,57 Very recently, Nakamura’s group described an
oxidative ring-opening reaction of aziridines with α-nitroesters using a cinchona
alkaloid amide/NiBr2 catalyst to construct α-amidoketones,58 whereas this process is
confined to low atomic-efficiency, and limited substrate scope. Nevertheless, despite
the potential interest of 2H-azirines, three-membered heterocycles directly substituted
with two aryl functional group, easily accessed from 1,2-diarylethan-1-one and
hydroxylamine,14 have received scarce attention. In this context, the development of
ring-opening reaction of 2,3-diaryl-2H-azirines with carboxylic acids is highly
demand. Key challenges in developing the proposed transformation include: (1)
poorer nucleophilicity of carboxyl group compared to nitrogen atom27,59 and Grignard
reagent,60 and (2) difficulty in controlling the desired thermal rearrangement. Herein,
we describe the discovery of the first Pd-catalyzed ring-opening reaction of
2,3-diaryl-2H-azirines with carboxylic acids in a step-economical fashion, affording
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α-amidoketones involving a C-N single bond cleavage and a subsequent thermal
rearrangement (Scheme 1, c).
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RESULTS AND DISCUSSION
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Initially, the reaction of 2-bromobenzoic acid 1a and 2,3-diphenyl-2H-azirine 2a was
investigated (Table 1). The desired product 3aa was obtained in 38% yield when the
reaction was proceeded using AgOAc and DMAP (4-dimethylaminopyridine) as
additives in the presence of Pd(OAc)2 in dioxane at 110 oC. Based on this preliminary
result, we first investigated the impact of Ag salts and discovered that the yield of 3aa
could be improved when AgPF6, AgOTf, and Ag2CO3 were employed (entries 2-4). In
contrast, low yields were obtained when AgOSO2CF3, AgOBz (Silver benzoate) and
AgCl were used (entries 5-7). It should be noted that the expected product 3aa was
obtained in 92% yield by using Ag-1 as the additive (entry 8). Furthermore, we
screened different solvents such as THF, CH3CN, toluene, EtOH, and tert-amyl
alcohol. However, none of these solvents gave better result than dioxane (entries
9-14). The yield was marginally decreased upon increasing the loading of Ag-1 from
10 mol% to 50 mol% (entry 15). To our disappointment, decreasing the reaction
temperature to 80 °C led to the expected product 3aa in 38% yield, while the reaction
afforded 3aa in trace at room temperature (entries 16-17). The control experiments
revealed that reaction efficiency was significantly decreased in absence of DMAP or
Ag-1 (entries 18-19). Therefore, the use of 10 mol% Pd(OAc), 10 mol% Ag salt, 100
mol% DMAP in the presence of Li2CO3 in dioxane at 110 °C for 18 h was found to be
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the best reaction conditions for the ring-opening reaction of 2H-aziridines with
carboxylic acids (entry 8).
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Table 1. Optimization of the reaction conditions.a
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Entry
Solvent
Ag salt
Yieldb
1
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
THF
AgOAc
AgPF6
AgOTf
Ag2CO3
AgOSO2CF3
AgOBz
AgCl
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92
N.D
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N.D
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Ag-1
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Ag-1
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19g
CH3CN
Toluene
DMF
Ag-1
Ag-1
Ag-1
EtOH
Ag-1
tert-amyl alcohol
dioxane
dioxane
dioxane
dioxane
dioxane
Ag-1
Ag-1
Ag-1
Ag-1
Ag-1
No
a
Reaction conditions: 1a (0.125 mmol), 2a (0.125 mmol), Pd(OAc)2 (10 mol%), DMAP (1 equiv),
Ag-1 (Chloro[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]silver) (10 mol%), and Li2CO3 (1
equiv) in dioxane (2 mL) at 110 C for 18 h. Isolated yields. 40 C. 80 C. e Ag-1 (50 mol%).
o
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c
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o
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Without DMAP. g Without Ag salt.
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With the optimized reaction conditions, the scope of the carboxylic acids for
Pd-catalyzed ring-opening reaction was investigated, as illustrated in Scheme 2.
Generally, various carboxylic acids furnished the expected products 3aa-3va with
moderate-to-good yields in this protocol. We observed that the electronic properties of
the substituents on the aromatic ring of benzoic acid have a decisive effect on the
reaction efficiency, as the substrates bearing electron-withdrawing groups (56-95%)
gave better yields than the one bearing electron-donating groups (43-70% yield). In
addition, substituents such as halides, nitro, alkyl, CF3, and ester, at different positions
of benzoic acid were well-tolerated, providing new opportunities for potential further
derivatization. In addition, the reaction efficiency was not very sensitive to the steric
hindrance of the substituents, wherein the substrates with two ortho-CF3 or
ortho-methyl substituents worked smoothly, affording the desired products 3la and
3pa in 48% and 70% yields, respectively. The structure of 3la was unambiguously
determined by single crystal X-ray crystallography and NMR (see Pages S5-S6 of the
Supporting Information). To our delight, the introduction of two or three
electron-withdrawing groups such as fluoro on the aromatic ring furnished the
expected products 3na and 3oa in 88% and 63% yields. Remarkably,
thiophene-2-carboxylic acid, furan-2-carboxylic acid, and nicotinic acid were also
amenable for the reactions (3ra-3ta). Most importantly, aliphatic carboxylic acids 1u
and 1v also performed well with good yields (3ua and 3va, 60% and 93%).
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Scheme 2. Pd-catalyzed ring-opening cascade of 2H-azirines with various carboxylic
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acids. a
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a Reaction Conditions: 1a-1v (0.125 mmol), 2a (0.125 mmol), Pd(OAc)2 (10 mol%), DMAP (1 equiv),
and Li2CO3 (1 equiv) in dioxane (2 mL) at 110 oC for 18 h. Yields are those of isolated products.
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Scheme 3. Substrate scope of 2H-azirines.a
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a Reaction Conditions: 1a (0.125 mmol), 2a-2g (0.125 mmol), Pd(OAc)2 (10 mol%), DMAP (1 equiv),
and Li2CO3 (1 equiv) in dioxane (2 mL) at 110 oC for 18 h. Yields are those of isolated products.
To assess the reaction generality, we next explored the scope of the reaction by
variation of the substitution patterns of 2H-azirines under the optimized conditions,
and the results are summarized in Scheme 3. We first sought to investigate the effect
of different substituents on the phenyl ring B of 2H-azirines. Substrates bearing
various electron-withdrawing groups, such as F, Cl, and Br, along with
electron-donating methoxy group, all generated the targeted α-aminoketones in
satisfying yields (3ab-3ae). The reaction of 3-phenyl-2-(p-tolyl)-2H-azirine 2f with
1a delivered the α-aminoketone 3af in lower yield than that observed with 2a-2e. As
for 2-(4-chlorophenyl)-3-phenyl-2H-azirine 2g and 2-phenyl-3-(p-tolyl)- 2H-azirine
2h, a chlorine atom and Me- group on the phenyl ring of 2H-azirines were well
tolerated, and the desired product 3ag and 3ah were obtained in 84% and 85% yields.
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We also carried out the reactions between various 2H-azirines and benzoic acid 1b
under optimal reaction conditions, in which moderate to good yields and high
efficiency were observed for substrates 2b, 2c, 2e, and 2f (Scheme 3, 3bb, 3bc, 3be,
and 3bf). To our delight, when 1 mmol scale of 1g and 2a were used in the reaction
under the optimized reaction conditions, 3ga was isolated in 67% yield (Scheme 4).
Scheme 4. Scale-up reaction
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Scheme 5. Mechanistic experiments.
To gain insights into the reaction mechanism, several control experiments were
performed (Scheme 5, and see Scheme S1-S4 in SI). First, control experiments were
conducted to investigate the transformation of 1a and 2a to 3aa. It was found that
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DMAP could promote the reaction, while no product was detected without Pd(OAc)2
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(Scheme 5, eq. a). Second, the reaction of 1a and 2a in the presence of 2 equiv of D2O
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at 110 C for 18 h furnished 3aa in 76% yield and HNMR analysis of the isolated
product revealed H/D exchange (22%) was observed at α-H of 3aa-d (Scheme 5, eq. b,
and see Figure S1 in SI). After that, we probed the electronic preference of this
cascade reaction via 2H-azirines competition experiments. The reaction between 2h
and 2b differing in electronic effects was conducted with 1a. The small difference is
perhaps due to the substrate structure (Scheme 5, eq. c).
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Scheme 6. Comparative trial experiment.
Scheme 7. Proposed mechanism.
The reaction of Pd(OAc)2 with 1 equiv of DMAP in the presence of
2,3-diphenyl-2H-azirine 2a at room temperature led to the formation of a stable Pd (0)
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complex I, which was determined by a single crystal X-ray analysis (Scheme 6, and
see Scheme S5 in SI). In the comparative trial using Pd (0) complex I as the catalyst
under the standard conditions, 3aa was isolated in 60% yield, suggesting that the
transformation is probably initiated by reducing of Pd (II) to Pd (0) species (see
Scheme S6 in SI). Based on the previous work23,51 and the above results, a proposed
catalytic cycle for Pd-catalyzed cascade nucleophilic addition/ring-opening reaction is
depicted in Scheme 7. Initially, Pd(II) salt is reduced to Pd(0) species. Coordination
and ligand exchange of Pd(0) complex with 2H-azirines and carboxylic acids are
followed by the nucleophilic addition of carboxylic acids to reactive unsaturated C-N
double bonds to generate intermediate B. The intermediate B subsequently undergoes
C-N single bond cleavage and a thermal rearrangement to generate the ring-opening
product C and releases the Pd(0) species. Key to the success of this catalytic cycle is
reduction of Pd(II) salt by DMAP, which probably facilitate ligand exchange and
nucleophilic addition.
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CONCLUSION
In summary, we have established the Pd-catalyzed cascade nucleophilic
addition/ring-opening reaction between 2,3-diaryl-2H-azirines and carboxylic acid
derivatives in a step-economical fashion. The reaction exhibited outstanding
functional-group compatibility with respect to both 2H-azirines and carboxylic acids,
allowing for the formation of functionalized α-amidoketones in good to excellent
yields (up to 95%). The notable features of this protocol comprise operational
simplicity, broad substrate scope, high atomic-efficiency, and mild conditions. From a
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mechanistic point of view, the Pd(II) complex is reduced to Pd(0) species and then
coordinated to the DMAP. This process probably facilitates ligand exchange and
nucleophilic addition. Further applications of this promising strategy are in progress
in our laboratory.
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EXPERIMENTAL SECTION
General Information. Unless otherwise noted, all the reactions were carried out in a
glassware under air condition. The commercially available chemicals and solvents
were used as received without further purification. 2H-Azirines were prepared
according to the published procedure.10,11,61,62 The reactions were monitored by TLC
using UV-light or by staining with iodine. Column chromatography was performed on
silica gel (200-300 mesh). Single-crystal X-ray data in this work were collected on an
Agilent Technologies SuperNova Single Crystal Diffractometer at different
temperatures equipped with graphite-monochromatic Mo Kα or Cu Kα radiation (λ =
0.71073 Å or 1.54184 Å). The structures were solved by SHELXS (direct methods)
and refined by SHELXL (full matrix least-squares techniques) in the Olex2 package.
All non-hydrogen atoms were refined with anisotropic displacement parameters.
Hydrogen atoms attached to carbon were placed in geometrically idealized positions
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and refined using a riding model. H, C, and F NMR were recorded on a 600 or
1
400 MHz Bruker NMR spectrometer in CDCl3 (7.26 ppm for H and 77.16 ppm for
13C) using tetramethylsilane (TMS) as the internal standard (s = singlet, d = doublet, t
= triplet, q = quartet, dd = doublet of doublets, m = multiplet). High-resolution mass
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spectra HRMS data were obtained with Micromass HPLC–Q–TOF mass
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spectrometer.
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Procedure for Cascade C-N Bond Cleavage of 2H-Azirines. A mixture of
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Pd(OAc)2 (2.8 mg, 0.0125 mmol), Ag-1 (Chloro[1,3-bis(2,6-diisopropylphenyl)
imidazole-2-ylidene]silver) (6.6 mg, 10 mol%), Li2CO3 (1 equiv), 2H-azirines (0.125
mmol), carboxylic acids (0.125 mmol), DMAP (1 equiv), and dioxane (2 mL) was
stirred at 110 C for 18 h. After cooling the reaction to room temperature, the solvent
was removed under vacuum and the residue was purified by silica gel
chromatography using ethyl acetate/petroleum ether (10:1~4:1) to afford desired
products.
Scale-up Synthesis. A mixture of Pd(OAc)2 (22.4 mg, 0.1 mmol), Ag-1 (52.8 mg, 10
mol%), Li2CO3 (1 equiv), 2H-azirines 2a (1 mmol, 193.3 mg), carboxylic acid 1g (1
mmol, 167.1 mg), DMAP (1 equiv), and dioxane (16 mL) was stirred at 110 C for 18
h. After cooling the reaction to room temperature, the solvent was removed under
vacuum and the residue was purified by silica gel chromatography using ethyl
acetate/petroleum ether (10:1~4:1) to afford desired product 3ga (241.5 mg, 67%
yield).
3-(4-fluorophenyl)-2-phenyl-2H-azirine (2b).14 White solid. Petroleum ether/ethyl
acetate = 10:1. 1H NMR (400 MHz, CDCl3) δ = 8.03 – 7.86 (m, 2H), 7.40 – 7.20 (m,
5H), 7.20 – 7.08 (m, 2H), 3.32 (s, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 165.6 (d,
J = 255.5 Hz), 162.5, 140.6, 132.2 (d, J = 9.3 Hz), 128.4, 127.2, 126.1, 120.5, 116.8
(d, J = 22.4 Hz), 34.6.
3-(4-bromophenyl)-2-phenyl-2H-azirine (2d).62 White solid. Petroleum ether/ethyl
acetate = 10:1. 1H NMR (400 MHz, CDCl3) δ = 7.80 (d, J=8.5, 2H), 7.73 (d, J=8.5,
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2H), 7.31 (m, 3H), 7.21 – 7.10 (m, 2H), 3.37 (s, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ = 163.1, 140.4, 132.7, 131.1, 128.4, 128.2, 127.3, 126.1, 123.0, 34.7.
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2-bromo-N-(2-oxo-1,2-diphenylethyl)benzamide (3aa). White solid (45.3 mg,
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isolated yield 92%). m.p 144.6-146.5. Petroleum ether/ethyl acetate = 4:1. H NMR
(400 MHz, CDCl3) δ = 8.02 (dd, J=5.2, 3.4, 2H), 7.62 (d, J=7.0, 1H), 7.58 (dd, J=7.9,
1.1, 1H), 7.56 – 7.51 (m, 2H), 7.51 – 7.46 (m, 2H), 7.42 (dd, J=10.6, 4.8, 2H), 7.37 –
7.30 (m, 3H), 7.30 – 7.24 (m, 2H), 6.76 (d, J=7.2, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ = 195.2, 166.5, 137.0, 136.8, 134.2, 133.9, 133.5, 131.5, 129.9, 129.2, 128.8,
128.5, 128.4, 127.5, 124.4, 119.6, 59.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H17BrNO2 , 394.0443, found 394.0420.
N-(2-oxo-1,2-diphenylethyl)benzamide (3ba). White solid (27.6 mg, isolated yield
1
70%). m.p 144.5-146.3. Petroleum ether/ethyl acetate = 10:1. H NMR (600 MHz,
CDCl3) δ 8.10 – 7.99 (m, 2H), 7.91 – 7.81 (m, 2H), 7.74 (d, J = 6.7 Hz, 1H), 7.57 –
7.47 (m, 4H), 7.43 (m, 3H), 7.32 (t, J = 7.6 Hz, 2H), 7.28 – 7.23 (m, 1H), 6.76 (d, J =
7.0 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ = 195.8, 166.3, 137.3, 134.2, 133.9,
133.9, 131.8, 129.3, 129.2, 128.8, 128.6, 128.4, 128.3, 127.2, 58.9. HRMS (ESI-TOF)
+
m/z: [M + H]+ Calcd for C21H18NO2 , 316.1338, found 316.1330.
4-methyl-N-(2-oxo-1,2-diphenylethyl)benzamide (3ca). White solid (19.7 mg,
isolated yield 48%). m.p 141.6-143.4. 1H NMR (400 MHz, CDCl3) δ = 8.06 – 7.99 (m,
2H), 7.75 (d, J=8.2, 2H), 7.69 (d, J=6.9, 1H), 7.57 – 7.51 (m, 1H), 7.50 – 7.45 (m,
2H), 7.42 (t, J=7.7, 2H), 7.35 – 7.29 (m, 2H), 7.28 – 7.20 (m, 3H), 6.75 (d, J=7.0, 1H),
2.39 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.9, 166.3, 149.8, 142.2, 137.4,
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134.4, 133.9, 131.0, 129.2, 129.2, 128.8, 128.39, 128.35, 127.2, 58.9, 21.5. HRMS
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+
(ESI-TOF) m/z: [M + H]+ Calcd for C22H20NO2 , 330.1494, found 330.1499.
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4-bromo-N-(2-oxo-1,2-diphenylethyl)benzamide (3da). White solid (34.0 mg,
isolated yield 69%). m.p 149.3-150.9. 1H NMR (400 MHz, CDCl3) δ = 8.05 – 7.96 (m,
2H), 7.78 – 7.67 (m, 3H), 7.61 – 7.51 (m, 3H), 7.45 (dt, J=15.4, 4.5, 4H), 7.37 – 7.29
(m, 2H), 7.29 – 7.24 (m, 1H), 6.72 (d, J=7.0, 1H). 13C{1H} NMR (101 MHz, CDCl3)
δ = 195.7, 171.1, 165.4, 137.1, 134.2, 134.0, 132.8, 131.8, 129.3, 129.2, 128.8, 128.6,
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+
128.4, 126.5, 59.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17BrNO2 ,
394.0443, found 394.0446.
4-chloro-N-(2-oxo-1,2-diphenylethyl)benzamide (3ea). White solid (24.5 mg,
1
isolated yield 56%). m.p 131.8-133.5. Petroleum ether/ethyl acetate = 4:1. H NMR
(400 MHz, CDCl3) δ = 8.09 – 7.97 (m, 2H), 7.78 (t, J=5.4, 2H), 7.71 (d, J=6.8, 1H),
7.54 (t, J=7.4, 1H), 7.50 – 7.38 (m, 6H), 7.33 (t, J=7.4, 2H), 7.30 – 7.23 (m, 1H), 6.72
(d, J=7.0, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.7, 165.3, 138.0, 137.1,
134.1, 134.0, 132.3, 129.3, 129.2, 128.9, 128.8, 128.6, 128.6, 128.4, 59.0. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C21H17ClNO2+, 350.0948, found 350.0943.
4-fluoro-N-(2-oxo-1,2-diphenylethyl)benzamide (3fa). White solid (32.1 mg, isolated
1
yield 77%). m.p 139.1-140.4. H NMR (400 MHz, CDCl3) δ = 8.07 – 7.98 (m, 2H),
7.91 – 7.81 (m, 2H), 7.68 (d, J=6.7, 1H), 7.58 – 7.52 (m, 1H), 7.50 – 7.39 (m, 4H),
7.38 – 7.29 (m, 2H), 7.29 – 7.24 (m, 1H), 7.17 – 7.06 (m, 2H), 6.73 (d, J=7.0, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ = 195.8, 186.2, 181.1 (d, J = 282.1 Hz) , 165.3,
138.1, 137.2, 134.0, 129.6 (d, J = 9.0 Hz), 129.3, 129.2, 128.8, 128.5, 128.4, 115.6 (d,
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J = 21.9 Hz), 59.0. 19F{1H} NMR (376 MHz, CDCl3) δ = -108.07. HRMS (ESI-TOF)
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+
m/z: [M + H]+ Calcd for C21H17FNO2 , 334.1243, found 334.1236.
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4-nitro-N-(2-oxo-1,2-diphenylethyl)benzamide (3ga). Yellow solid (42.8 mg, isolated
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yield 95%). m.p 186.4-187.9. H NMR (400 MHz, CDCl3) δ = 8.34 – 8.25 (m, 2H),
8.06 – 7.95 (m, 4H), 7.83 (d, J=6.7, 1H), 7.59 – 7.52 (m, 1H), 7.51 – 7.39 (m, 4H),
7.39 – 7.31 (m, 2H), 7.31 – 7.24 (m, 1H), 6.72 (d, J=6.9, 1H). C{1H} NMR (101
13
MHz, CDCl3) δ = 195.4, 164.3, 149.8, 139.5, 136.7, 134.2, 134.0, 129.4, 129.2, 128.9,
128.8, 128.4, 128.4, 123.8, 59.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H17N2O4 , 361.1188, found 361.1192.
3-methyl-N-(2-oxo-1,2-diphenylethyl)benzamide (3ha). White solid (17.7 mg,
isolated yield 43%). m.p 120.1-121.9. 1H NMR (400 MHz, CDCl3) δ = 8.05 – 8.00 (m,
2H), 7.71 (d, J=6.9, 1H), 7.68 – 7.61 (m, 2H), 7.56 –7.50 (m, 1H), 7.51 – 7.46 (m,
2H), 7.42 (dd, J=10.6, 4.7, 2H), 7.32 (m, 4H), 7.28 – 7.23 (m, 1H), 6.75 (d, J=7.1,
1H), 2.40 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.9, 166.5, 138.4, 137.3,
134.3, 133.9, 133.9, 132.5, 129.2, 129.2, 128.8, 128.5, 128.4, 128.4, 127.8, 124.2,
58.9, 21.3. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H20NO2 , 330.1494, found
+
330.1485.
3-chloro-N-(2-oxo-1,2-diphenylethyl)benzamide (3ia). White solid (32.8 mg, isolated
1
yield 75%). m.p 135.3-137.1. H NMR (400 MHz, CDCl3) δ = 8.06 – 7.98 (m, 2H),
7.83 (t, J=1.8, 1H), 7.77 – 7.67 (m, 2H), 7.52 (dd, J=4.9, 3.7, 1H), 7.50 – 7.36 (m,
6H), 7.36 – 7.30 (m, 2H), 7.29 – 7.23 (m, 1H), 6.72 (d, J=7.0, 1H). C{1H} NMR
13
(101 MHz, CDCl3) δ = 195.6, 165.0, 137.0, 135.8, 134.8, 134.2, 134.0, 131.8, 130.0,
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129.3, 129.2, 128.8, 128.6, 128.4, 127.6, 125.2, 59.0. HRMS (ESI-TOF) m/z: [M +
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7
+
H]+ Calcd for C21H17ClNO2 , 350.0948, found 350.0963.
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3-bromo-N-(2-oxo-1,2-diphenylethyl)benzamide (3ja). White solid (30.6 mg, isolated
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yield 62%). m.p 181.3-183.1. H NMR (400 MHz, CDCl3) δ = 8.08 – 7.95 (m, 3H),
7.76 (d, J=7.7, 1H), 7.71 (d, J=6.6, 1H), 7.63 (d, J=7.9, 1H), 7.54 (t, J=7.3, 1H), 7.51
– 7.39 (m, 4H), 7.38 – 7.23 (m, 4H), 6.72 (d, J=7.0, 1H). C{1H} NMR (101 MHz,
13
CDCl3) δ = 195.6, 164.9, 137.0, 135.9, 134.7, 134.1, 134.0, 130.5, 130.2, 129.3, 129.2,
128.8, 128.6, 128.4, 125.7, 122.8, 59.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H17BrNO2 , 394.0443, found 394.0442.
3-nitro-N-(2-oxo-1,2-diphenylethyl)benzamide (3ka). Yellow solid (41.4 mg, isolated
1
yield 92%). m.p 168.8-170.2. H NMR (400 MHz, CDCl3) δ = 8.68 (t, J=1.9, 1H),
8.36 (m, 1H), 8.23 – 8.14 (m, 1H), 8.06 – 7.99 (m, 2H), 7.85 (d, J=6.8, 1H), 7.65 (t,
J=8.0, 1H), 7.59 – 7.52 (m, 1H), 7.52 – 7.47 (m, 2H), 7.43 (dd, J=10.6, 4.8, 2H), 7.39
– 7.32 (m, 2H), 7.32 – 7.24 (m, 1H), 6.74 (d, J=6.9, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ = 195.3, 164.0, 148.3, 136.7, 135.7, 134.1, 134.0, 133.1, 129.8, 129.4, 129.2,
128.9, 128.8, 128.4, 126.3, 122.3, 59.3. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H17N2O4 , 361.1188, found 361.1189.
N-(2-oxo-1,2-diphenylethyl)-2,6-bis(trifluoromethyl)benzamide (3la). White solid
(27.1 mg, isolated yield 48%). m.p 135.9-137.4. 1H NMR (400 MHz, CDCl3) δ = 8.07
– 8.00 (m, 2H), 7.93 (d, J=8.0, 2H), 7.72 (t, J=8.0, 1H), 7.61 – 7.50 (m, 3H), 7.45 (t,
J=7.7, 2H), 7.42 – 7.36 (m, 3H), 7.25 (d, J=1.4, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ = 191.9, 164.2, 134.6, 133.6, 132.8, 130.4, 129.88 (dd, J = 8.4, 4.2 Hz),
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129.6, 129.3, 129.1, 128.9 (d, J = 5.6 Hz), 128.7, 126.8, 122.66 (dd, J = 277.6, 7.9 Hz),
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+
118.6, 79.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H16F6O2 , 452.1085,
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found 452.1082.
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2-nitro-N-(2-oxo-1,2-diphenylethyl)benzamide (3ma). Yellow solid (40.1 mg,
isolated yield 89%). m.p 154.2-156.0. 1H NMR (400 MHz, CDCl3) δ = 8.09 – 7.97 (m,
3H), 7.67 (t, J=7.5, 1H), 7.62 – 7.50 (m, 3H), 7.50 – 7.40 (m, 4H), 7.32 (m, 4H), 6.76
(d, J=7.1, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.2, 165.4, 163.7, 146.6,
136.5, 134.1, 134.0, 133.6, 132.4, 130.7, 129.3, 129.3, 128.8, 128.7, 128.4, 124.6,
+
59.1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17N2O4 , 361.1188, found
361.1183.
2,3-difluoro-N-(2-oxo-1,2-diphenylethyl)benzamide (3na). White solid (38.7 mg,
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isolated yield 88%). m.p 121.1-122.9. Petroleum ether/ethyl acetate = 4:1. H NMR
(400 MHz, CDCl3) δ = 8.25 (dd, J=9.9, 7.1, 1H), 8.02 (dd, J=5.2, 3.3, 2H), 7.78 (ddt,
J=8.1, 6.4, 1.7, 1H), 7.58 – 7.46 (m, 3H), 7.42 (dd, J=10.6, 4.8, 2H), 7.38 – 7.22 (m,
4H), 7.16 (tdd, J=8.1, 4.7, 1.4, 1H), 6.74 (dd, J=6.7, 1.7, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ = 195.0, 161.4, 150.63 (d, J = 249.3 Hz), 150.49 (d, J = 249.7 Hz),
136.8, 134.2, 133.9, 129.3, 128.98 (d, J = 40.5 Hz), 128.6, 128.4, 127.1, 126.35 (d, J
= 3.2 Hz), 124.43 (dd, J = 6.7, 4.5 Hz), 123.04 (d, J = 8.8 Hz), 120.47 (d, J = 17.2 Hz),
59.4. 19F{1H} NMR (376 MHz, CDCl3) δ -137.8 (d, J = 21.7 Hz), -138.9 (d, J = 21.7
+
Hz). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H16F2NO2 , 352.1149, found
352.1147.
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2,3,4-trifluoro-N-(2-oxo-1,2-diphenylethyl)benzamide (3oa). White solid (29.1 mg,
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isolated yield 63%). m.p 128.3-129.7. Petroleum ether/ethyl acetate = 4:1. H NMR
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(400 MHz, CDCl3) δ = 8.31 – 8.17 (m, 1H), 8.10 – 7.98 (m, 2H), 7.85 (m, 1H), 7.60 –
7.54 (m, 1H), 7.51 (dd, J=5.2, 3.3, 2H), 7.45 (dd, J=10.6, 4.8, 2H), 7.39 – 7.33 (m,
2H), 7.33 – 7.26 (m, 1H), 7.09 (m, 1H), 6.74 (dd, J=6.7, 1.7, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ = 195.0, 160.6, 153.31 (ddd, J = 256.6, 10.0, 3.5 Hz), 150.28 (ddd, J
= 252.4, 11.2, 3.7 Hz), 139.79 (ddd, J = 253.3, 17.0, 15.6 Hz), 136.7, 134.0, 134.0,
129.3, 129.2, 128.8, 128.6, 128.4, δ125.74 (ddd, J = 8.3, 4.1, 2.5 Hz), 118.44 (ddd, J
= 9.1, 3.6, 2.1 Hz), 112.74 (dd, J = 17.5, 3.5 Hz), 59.4. 19F{1H} NMR (376 MHz,
CDCl3) δ -127.93 (dd, J = 20.1, 11.3 Hz), -134.19 (dd, J = 21.8, 11.3 Hz), -159.45 (t,
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+
J = 21.0 Hz). HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H15F3NO2 , 370.1055,
found 370.1070.
2,6-dimethyl-N-(2-oxo-1,2-diphenylethyl)benzamide (3pa). White solid (30.0 mg,
1
isolated yield 70%). m.p 162.7-164.3. H NMR (400 MHz, CDCl3) δ = 8.05 (dd,
J=5.2, 3.3, 2H), 7.59 – 7.53 (m, 1H), 7.51 – 7.42 (m, 4H), 7.39 – 7.33 (m, 2H), 7.31
(dt, J=5.3, 2.1, 1H), 7.20 – 7.15 (m, 1H), 7.12 (d, J=7.5, 1H), 7.02 (d, J=7.6, 2H),
6.84 (d, J=7.7, 1H), 2.22 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.4, 169.3,
137.1, 136.9, 134.5, 134.2, 133.9, 129.3, 129.2, 128.9, 128.8, 128.5, 128.3, 127.5,
+
58.5, 19.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C23H22NO2 , 344.1651, found
344.1630.
Methyl 4-((2-oxo-1,2-diphenylethyl)carbamoyl)benzoate (3qa). White solid (36.9 mg,
isolated yield 79%). m.p 151.6-153.4. 1H NMR (400 MHz, CDCl3) δ = 8.14 – 8.06 (m,
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2H), 8.06 – 7.97 (m, 2H), 7.94 – 7.88 (m, 2H), 7.79 (d, J=6.9, 1H), 7.57 – 7.51 (m,
1H), 7.51 – 7.46 (m, 2H), 7.42 (dd, J=10.6, 4.8, 2H), 7.37 – 7.30 (m, 2H), 7.30 – 7.24
(m, 1H), 6.74 (d, J=7.0, 1H), 3.95 (d, J=7.9, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
= 195.6, 166.3, 165.5, 137.8, 137.0, 134.2, 134.0, 133.0, 129.8, 129.3, 129.2, 128.8,
128.6, 128.4, 127.3, 59.1, 52.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
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+
C23H20NO4 , 374.1392, found 374.1388.
N-(2-oxo-1,2-diphenylethyl)nicotinamide (3ra). White solid (17.8 mg, isolated yield
45%). m.p 122.1-123.9. 1H NMR (400 MHz, CDCl3) δ = 9.09 (d, J=1.7, 1H), 8.74 (dd,
J=4.9, 1.6, 1H), 8.18 (dt, J=8.0, 1.9, 1H), 8.01 (dd, J=5.2, 3.3, 2H), 7.82 (d, J=6.8,
1H), 7.58 – 7.51 (m, 1H), 7.49 (dd, J=5.3, 3.3, 2H), 7.43 (ddd, J=10.9, 5.9, 2.5, 3H),
13
7.38 – 7.31 (m, 2H), 7.31 – 7.27 (m, 1H), 6.73 (d, J=6.9, 1H). C{1H} NMR (101
MHz, CDCl3) δ = 195.4, 164.3, 152.0, 148.0, 136.8, 135.5, 134.1, 134.0, 129.8, 129.4,
129.2, 128.8, 128.7, 128.4, 123.6, 59.1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C20H17N2O2 , 317.1290, found 317.1272.
N-(2-oxo-1,2-diphenylethyl)thiophene-2-carboxamide (3sa). White solid (26.9 mg,
isolated yield 67%). m.p 139.1-140.4. 1H NMR (400 MHz, CDCl3) δ = 8.06 – 7.97 (m,
2H), 7.63 – 7.51 (m, 3H), 7.51 – 7.38 (m, 5H), 7.36 – 7.29 (m, 2H), 7.29 – 7.22 (m,
2H), 7.08 (dd, J=4.9, 3.8, 1H), 6.71 (d, J=7.0, 1H). 13C{1H} NMR (101 MHz, CDCl3)
δ = 195.6, 160.9, 144.5, 138.5, 137.1, 134.2, 133.9, 130.4, 129.3, 129.2, 128.8, 128.5,
128.4, 127.6, 58.8. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H16NO2S+,
322.0902, found 322.0882.
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N-(2-oxo-1,2-diphenylethyl)furan-2-carboxamide (3ta). White solid (18.3 mg,
isolated yield 48%). m.p 149.2-150.9. 1H NMR (400 MHz, CDCl3) δ = 8.05 – 7.98 (m,
2H), 7.85 (d, J=7.3, 1H), 7.58 – 7.51 (m, 1H), 7.51 – 7.38 (m, 5H), 7.37 – 7.29 (m,
2H), 7.29 – 7.22 (m, 1H), 7.11 (dd, J=3.5, 0.7, 1H), 6.71 (d, J=7.4, 1H), 6.49 (dd,
J=3.5, 1.8, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.4, 157.4, 147.7, 144.2,
137.1, 134.3, 133.9, 129.3, 129.2, 128.8, 128.5, 128.4, 114.7, 112.1, 58.2. HRMS
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(ESI-TOF) m/z: [M + H]+ Calcd for C19H16NO3 , 306.1130, found 306.1123.
N-(2-oxo-1,2-diphenylethyl)acetamide (3ua). White solid (19.0 mg, isolated yield
60%). m.p 143.1-144.8. 1H NMR (400 MHz, CDCl3) δ = 8.01 – 7.93 (m, 2H), 7.55 –
7.48 (m, 1H), 7.44 – 7.36 (m, 4H), 7.34 – 7.24 (m, 3H), 6.97 (d, J=6.7, 1H), 6.58 (d,
J=7.4, 1H), 2.05 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.9, 169.2, 137.3,
134.3, 133.8, 129.2, 129.1, 128.7, 128.4, 128.2, 58.5, 23.3. HRMS (ESI-TOF) m/z:
+
[M + H]+ Calcd for C16H16NO2 , 254.1181, found 254.1180.
2,2,2-trifluoro-N-(2-oxo-1,2-diphenylethyl)acetamide (3va). White solid (35.7 mg,
isolated yield 93%). m.p 167.2-168.9. 1H NMR (400 MHz, CDCl3) δ = 8.04 – 7.88 (m,
3H), 7.55 (t, J=7.4, 1H), 7.46 – 7.38 (m, 4H), 7.38 – 7.27 (m, 3H), 6.49 (d, J=7.0, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ = 193.7, 156.27 (q, J = 37.8 Hz), 147.1, 135.3,
134.4, 133.4, 129.5, 129.08 (d, J = 33.0 Hz), 129.2, 128.3, 115.65 (dd, J = 284.9, 15.0
Hz), 58.9. 19F{1H} NMR (376 MHz, CDCl3) δ = -75.73. HRMS (ESI-TOF) m/z: [M +
+
H]+ Calcd for C16H13F3NO2 , 308.0898, found 308.0896.
2-bromo-N-(2-(4-fluorophenyl)-2-oxo-1-phenylethyl)benzamide (3ab). White solid
(47.4 mg, isolated yield 92%). m.p 152.1-153.8. 1H NMR (400 MHz, CDCl3) δ = 8.06
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– 8.00 (m, 2H), 7.70 (d, J=6.8, 1H), 7.64 – 7.54 (m, 3H), 7.54 – 7.43 (m, 4H), 7.38 (td,
J=7.5, 1.2, 1H), 7.32 (dd, J=7.7, 1.8, 1H), 7.09 – 7.01 (m, 2H), 6.79 – 6.73 (m, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ = 195.1, 166.5, 162.62 (d, J = 248.1 Hz), 136.9,
134.1, 134.0, 134.0, 133.6, 132.75 (d, J = 3.1 Hz), 131.5, 130.24 (d, J = 8.4 Hz),
129.8, 129.03 (d, J = 32.8 Hz), 127.5, 119.6, 116.21 (d, J = 21.8 Hz), 58.4. 19F{1H}
NMR (376 MHz, CDCl3) δ = -112.85. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
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C21H16BrFNO2 , 412.0348, found 412.0356.
2-bromo-N-(2-(4-chlorophenyl)-2-oxo-1-phenylethyl)benzamide (3ac). White solid
(44.5 mg, isolated yield 83%). m.p 169.5-171.2. 1H NMR (400 MHz, CDCl3) δ = 8.02
(d, J=7.9, 2H), 7.73 (d, J=6.7, 1H), 7.64 – 7.52 (m, 3H), 7.46 (dd, J=7.6, 4.2, 4H),
7.40 – 7.26 (m, 4H), 6.74 (d, J=6.9, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 194.9,
166.5, 136.8, 135.4, 134.5, 134.2, 133.9, 133.6, 131.6, 129.9, 129.8, 129.4, 129.2,
128.9, 127.5, 119.6, 58.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H16BrClNO2 , 430.0032, found 430.0034.
2-bromo-N-(2-(4-bromophenyl)-2-oxo-1-phenylethyl)benzamide (3ad). White solid
(45.5 mg, isolated yield 77%). m.p 185.9-187.7. 1H NMR (400 MHz, CDCl3) δ = 8.04
– 7.94 (m, 2H), 7.69 (d, J=6.7, 1H), 7.62 – 7.50 (m, 3H), 7.49 – 7.41 (m, 4H), 7.41 –
7.32 (m, 3H), 7.29 (dd, J=7.8, 1.8, 1H), 6.70 (d, J=6.9, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ = 194.8, 166.5, 136.8, 135.9, 134.2, 133.9, 133.6, 132.4, 131.6, 130.1, 129.9,
129.2, 128.9, 127.5, 122.7, 119.6, 58.5. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H16Br2NO2 , 473.9527, found 473.9526.
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2-bromo-N-(2-(4-methoxyphenyl)-2-oxo-1-phenylethyl)benzamide (3ae). White
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solid (41.4 mg, isolated yield 78%). m.p 137.9-139.8. H NMR (400 MHz, CDCl3) δ
8
9
= 8.01 (dd, J=5.2, 3.4, 2H), 7.63 – 7.49 (m, 4H), 7.46 – 7.38 (m, 4H), 7.34 (td, J=7.5,
1.2, 1H), 7.30 – 7.24 (m, 2H), 6.88 – 6.82 (m, 1H), 6.70 (d, J=7.1, 1H), 3.76 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ = 195.3, 166.4, 159.6, 137.1, 134.3, 133.8, 133.5,
131.4, 129.9, 129.7, 129.2, 128.9, 128.8, 127.5, 119.6, 114.6, 58.6, 55.2. HRMS
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(ESI-TOF) m/z: [M + H]+ Calcd for C22H19BrNO3 , 424.0548, found 424.0544.
2-bromo-N-(2-oxo-2-phenyl-1-(p-tolyl)ethyl)benzamide (3af). White solid (23.0 mg,
isolated yield 45%). m.p 151.3-153.1. 1H NMR (400 MHz, CDCl3) δ = 7.92 (d, J=8.3,
2H), 7.64 (d, J=6.9, 1H), 7.58 (dd, J=7.9, 1.0, 1H), 7.54 (dd, J=7.6, 1.7, 1H), 7.51 –
7.45 (m, 2H), 7.37 – 7.29 (m, 3H), 7.29 – 7.24 (m, 2H), 7.22 (d, J=8.0, 2H), 6.73 (d,
J=7.2, 1H), 2.37 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ = 194.8, 166.4, 159.8,
145.0, 137.1, 133.5, 131.7, 131.4, 129.8, 129.5, 129.4, 129.2, 128.40, 128.38, 127.5,
+
119.6, 59.0, 21.7. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H19BrNO2 ,
408.0599, found 408.0593.
2-bromo-N-(1-(4-chlorophenyl)-2-oxo-2-phenylethyl)benzamide (3ag). White solid
(45.0 mg, isolated yield 84%). m.p 129.7-131.4. 1H NMR (400 MHz, CDCl3) δ = 7.95
(d, J=8.5, 2H), 7.57 (dd, J=15.2, 7.7, 3H), 7.46 (d, J=7.2, 2H), 7.39 (d, J=8.5, 2H),
7.34 (t, J=7.4, 3H), 7.31 – 7.26 (m, 2H), 6.70 (d, J=7.0, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ = 194.1, 166.5, 140.5, 136.9, 136.4, 133.6, 132.5, 131.6, 130.6, 129.9,
129.4, 129.2, 128.7, 128.4, 127.5, 119.6, 59.2. HRMS (ESI-TOF) m/z: [M + H]+
+
Calcd for C21H15BrClNO2 , 430.0032, found 430.0018.
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2-bromo-N-(2-oxo-1-phenyl-2-(p-tolyl)ethyl)benzamide (3ah). White solid (43.4 mg,
isolated yield 85%). m.p 116.9-118.5. 1H NMR (400 MHz, CDCl3) δ = 8.02 (d, J=7.5,
2H), 7.64 – 7.49 (m, 4H), 7.37 (ddd, J=16.6, 11.4, 7.3, 5H), 7.29 – 7.23 ( 1H), 7.13 (d,
J=7.9, 2H), 6.72 (d, J=7.2, 1H), 2.28 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ =
195.3, 166.4, 138.4, 137.1, 134.3, 133.8, 133.8, 133.5, 131.4, 129.9, 129.9, 129.2,
128.8, 128.3, 127.5, 119.6, 58.9, 21.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C22H19BrNO2+, 408.0599, found 408.0584.
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N-(2-(4-fluorophenyl)-2-oxo-1-phenylethyl)benzamide (3bb). White solid (34.2 mg,
isolated yield 82%). m.p 158.1-159.7. 1H NMR (400 MHz, CDCl3) δ = 8.00 (d, J=7.7,
2H), 7.85 (d, J=7.6, 2H), 7.79 (d, J=5.9, 1H), 7.60 – 7.38 (m, 8H), 7.00 (t, J=8.2, 2H),
6.73 (d, J=6.4, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 195.7, 166.4, 162.6 (d, J =
247.9 Hz), 134.1, 133.8, 133.24, 133.21, 131.9, 130.2 (d, J = 8.4 Hz), 129.2, 128.7,
128.6, 127.2, 116.2 (d, J = 21.7 Hz), 58.1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C21H17FNO2 , 334.1243, found 334.1237.
N-(2-(4-chlorophenyl)-2-oxo-1-phenylethyl)benzamide (3bc). White solid (26.2 mg,
isolated yield 60%). m.p 177.6-179.5. 1H NMR (400 MHz, CDCl3) δ = 8.00 (d, J=7.8,
2H), 7.84 (d, J=7.5, 2H), 7.79 (d, J=6.4, 1H), 7.60 – 7.49 (m, 2H), 7.44 (m, 6H), 7.29
(d, J=8.4, 2H), 6.71 (d, J=6.7, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ = 212.2,
195.5, 166.4, 157.6, 135.7, 134.5, 134.2, 133.9, 133.7, 131.9, 129.7, 129.5, 129.2,
+
128.9, 128.6, 127.2, 58.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H17ClNO2 ,
350.0948, found 350.0955.
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N-(2-(4-methoxyphenyl)-2-oxo-1-phenylethyl)benzamide (3be). White solid (41.1
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1
mg, isolated yield 95%). m.p 176.3-177.7. H NMR (400 MHz, CDCl3) δ = 8.07 –
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9
7.96 (m, 2H), 7.84 (dd, J=5.2, 3.3, 2H), 7.71 (d, J=6.8, 1H), 7.58 – 7.48 (m, 2H), 7.47
– 7.36 (m, 6H), 6.90 – 6.81 (m, 2H), 6.70 (d, J=7.0, 1H), 3.74 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ = 195.9, 166.3, 159.6, 134.3, 134.0, 133.8, 131.7, 129.6, 129.3,
129.2, 128.8, 128.6, 127.2, 114.7, 58.4, 55.2. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
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for C22H20NO3 , 346.1443, found 346.1433.
N-(2-oxo-2-phenyl-1-(p-tolyl)ethyl)benzamide (3bf). White solid (32.9 mg, isolated
1
yield 80%). m.p 213.3-214.9. H NMR (400 MHz, CDCl3) δ = 7.95 (d, J=8.1, 2H),
7.88 (d, J=7.7, 2H), 7.81 (d, J=6.8, 1H), 7.49 (tt, J=15.0, 7.3, 5H), 7.34 (t, J=7.5, 2H),
7.25 (t, J=7.4, 3H), 6.76 (d, J=7.0, 1H), 2.39 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ = 195.4, 166.3, 145.0, 137.6, 134.0, 131.7, 131.7, 129.5, 129.4, 129.2, 128.6,
128.34, 128.31, 127.2, 58.7, 21.7. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
+
C22H20NO2 , 330.1494, found 330.1494.
ACKNOWLEDGEMENTS
We are grateful to the support from the National Natural Science Foundation of China
(21701148, 21471134, and 21571158), the Key Research Project of University of
Henan Province (19zx004), and Universities in Henan Province (17A150053).
SUPPORTING INFORMATION STATEMENT
The Supporting Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.joc
.
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Copies of 1H, 13C, and 19F spectra for all products (PDF)
X-ray crystallographic data for product 3la (CIF)
X-ray crystallographic data for product 3va (CIF)
X-ray crystallographic data for product 3ah (CIF)
X-ray crystallographic data for product Pd (0) complex I (CIF)
AUTHOR INFORMATION
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Corresponding Author
*E-mail: fenxu_zzuli@163.com.
*E-mail: chunsenliu@zzuli.edu.cn.
*E-mail: dumiao@zzuli.edu.cn.
ORCID
Fen Xu: 0000-0002-5412-3060
Chun-Sen Liu: 0000-0002-5095-7359
Miao Du: 0000-0002-1029-1820
NOTES
The authors declare no competing financial interest.
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