Synthesis of α-Amidoketones through the Cascade Reaction of Carboxylic Acids with Vinyl Azides under Catalyst-Free Conditions

Article abstract of DOI:10.1021/acs.joc.0c01871

An efficient synthesis of α-amidoketone derivatives through the cascade reactions of carboxylic acids with vinyl azides is presented. Compared with literature protocols, notable features of this new method include catalyst-free conditions, broad substrate scope, good tolerance of a wide range of functional groups, and high efficiency. In addition, the synthetic potential of this method as a tool for late-stage modification was convincingly manifested by its application in the structural elaborations of a number of carboxylic acid drug molecules.

Full text of DOI:10.1021/acs.joc.0c01871

pubs.acs.org/joc
Article
Synthesis of α‑Amidoketones through the Cascade Reaction of
Carboxylic Acids with Vinyl Azides under Catalyst-Free Conditions
Cai Gao, Qianting Zhou, Li Yang, Xinying Zhang,* and Xuesen Fan*
Cite This: https://dx.doi.org/10.1021/acs.joc.0c01871
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: An efficient synthesis of α-amidoketone derivatives
through the cascade reactions of carboxylic acids with vinyl azides
is presented. Compared with literature protocols, notable features
of this new method include catalyst-free conditions, broad
substrate scope, good tolerance of a wide range of functional
groups, and high efficiency. In addition, the synthetic potential of
this method as a tool for late-stage modification was convincingly
manifested by its application in the structural elaborations of a
number of carboxylic acid drug molecules.
preparation method of α-amidoketone derivatives via a Pd-
catalyzed ring-opening reaction of methylene aziridines using
carboxylic acids as an efficient coupling partner (Scheme 1a).5a
In addition, Xu et al. reported an alternative method for this
purpose via a Pd-catalyzed coupling reaction of 2H-azirines
with carboxylic acids (Scheme 1b).5b Very recently, Majee et
al. reported an elegant self-catalyzed rapid synthesis of α-
amidoketones from the reaction of 3-aryl-2H-azirines with
INTRODUCTION
■
α-Amidoketone derivatives have attracted considerable atten-
tion because they are not only the essential motifs of a plethora
of pharmaceutically active compounds but also the indis-
pensable intermediates that are widely used in organic
synthesis.1,2 Due to their importance, a number of methods
for the preparation of α-amidoketone derivatives have been
developed, which mainly include condensation of ketone-
derived nitrones with N-methyl carboximidoyl chloride
followed by hydrolytic workup,3a aza-benzoin condensation
of aldehydes with N-acylimines promoted by organocata-
lysts,3b−d Rh-catalyzed denitrogenative hydration of N-
sulfonyl-1,2,3-triazoles,3e the radical cascade reaction of
alkynes with N-fluoroarylsulfonimides and alcohols,3f the
Dakin−West reaction of α-aminoacids with acid anhydrides,
Rh-catalyzed hydroformylation of vinyl ester followed by
condensation with primary amines and rearrangement, the Ru-
catalyzed cascade reaction of 1,2-azidoalcohols, and Cu-
catalyzed condensation of N-alkoxylbenzamids with 2H-
azirines. Although these literature methods are generally
efficient and reliable, some of them still suffer from the use
of expensive transition-metal catalysts, harsh reaction con-
ditions, poor atom economy, and/or limited substrate scope.
Therefore, the search for more general, efficient, and
sustainable methods for the preparation of α-amidoketone
derivatives is highly desirable.
Scheme 1. Synthesis of α-Amidoketones Starting from
Carboxylic Acids
Received: August 3, 2020
Meanwhile, carboxylic acids are among the most abundant
naturally occurring compounds. In addition, they are relatively
cheap, easy-to-handle, and versatile in terms of reaction
patterns. Therefore, carboxylic acids are ideal starting materials
for the preparation of various classes of fine chemicals.4 In this
regard, Yamamoto et al. have developed an efficient
https://dx.doi.org/10.1021/acs.joc.0c01871
© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
carboxylic acids (Scheme 1c).5c Inspired by these elegant
pioneering studies and as a continuation of our own interest in
the economical construction of nitrogen-containing bio-
logically attractive compounds,6 especially using vinyl azides
as convenient three-atom synthons,7,8 we have studied the
reaction of vinyl azides with carboxylic acids. From this
reaction, we successfully developed a highly efficient and
general synthesis of α-amidoketones under catalyst-free
conditions (Scheme 1d). Herein, we wish to report our results
in this regard.
preliminary result, we then tried different solvents such as
toluene, dichloromethane (DCM), 1,2-dichloroethane (DCE),
acetone, 2,2,2-trifluoroethanol (THF), dioxane, CH3CN, and
tetrafluoroethylene (TFE) to improve the reaction efficiency
(entries 2−9). Gratifyingly, the reaction carried out in DCE
afforded 3a in an enhanced yield of 49% (entry 4). This study
showed that the reaction temperature also played an important
role. To be specific, reducing the reaction temperature from 90
to 80 °C resulted in an obvious decline in the yield of 3a
(entry 10 vs 4). On the other hand, when the reaction
temperature was increased from 90 to 100, 110, or 120 °C, the
yield of 3a could be improved from 49 to 61, 71, or 70%
(entries 11−13 vs 4). Subsequent optimization in terms of
reaction time showed that prolonging the reaction period from
6 to 8 or 10 h could increase the yield from 71 to 74 or 76%
(entries 14 and 15 vs 12). It was also demonstrated that raising
the molar ratio of 1a to 2a from 1.2:1 to 1.5:1 did not lead to a
substantial improvement in the yield of 3a (entry 16).
RESULTS AND DISCUSSION
■
Initially, (1-azidovinyl)benzene (1a) was treated with benzoic
acid (2a) in methanol at 90 °C for 6 h. From this reaction, the
desired N-(2-oxo-2-phenylethyl)benzamide (3a) was obtained
in a yield of 12% (Table 1, entry 1). Encouraged by this
a
Table 1. Optimization Study for the Formation of 3a
With the establishment of the optimal reaction conditions,
the substrate generality of this novel synthesis of α-
amidoketones was explored. First, the scope of vinyl azides
(1) was tested using 2a as a model substrate. The results
included in Table 2 demonstrated that 1-phenyl-substituted
vinyl azides with either an electron-donating group (EDG)
such as methyl, tert-butyl, or methoxy, or an electron-
withdrawing group (EWG) such as fluoro, chloro, bromo,
trifluoromethyl, or phenyl attached on the para-site of the 1-
phenyl ring took part in this reaction smoothly to give the
corresponding products 3b−3i in yields ranging from 66 to
82%. It is worth noting herein that this reaction was
compatible with substrates bearing a reactive formyl or acetoxy
unit to give 3j and 3k in reasonably good yields. For substrates
bearing a meta-methyl, ortho-methyl, or 3,4-dimethoxy-
substituted phenyl moiety, the corresponding reactions took
place to give 3l, 3m, and 3n. Furthermore, 2-naphthyl-
substituted vinyl azide reacted with 2a to afford 3o.
Interestingly, vinyl azides bearing a heterocyclic unit such as
2-thienyl or 3-pyridinyl could also participate in this reaction to
give 3p and 3q. In addition to aromatic moieties, an alkyl unit-
substituted vinyl azide, 2-azidodec-1-ene, was found to be also
suitable for this reaction to afford 3r in 66% yield.
b
entry
solvent
T (°C)
time (h)
yield (%)
1
2
3
4
5
6
7
8
MeOH
toluene
DCM
DCE
acetone
THF
dioxane
CH3CN
TFE
DCE
DCE
DCE
DCE
90
90
90
90
90
90
90
90
6
6
6
6
6
6
6
6
6
6
6
6
6
8
10
10
12
18
35
49
25
12
trace
40
trace
33
61
71
70
74
76
77
9
90
80
10
11
12
13
14
15
100
110
120
110
110
110
DCE
DCE
DCE
c
16
a
Conditions: 1a (0.36 mmol), 2a (0.3 mmol), solvent (2 mL), sealed
tube. Isolated yield. Conditions: 1a (0.45 mmol), 2a (0.3 mmol).
b
c
a b
,
Table 2. Scope of Substrate 1
a
b
Conditions: 1 (0.36 mmol), 2a (0.3 mmol), DCE (2 mL), 110 °C, sealed tube, 10 h. Isolated yield.
B
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a b
,
Table 3. Scope of Substrate 2
a
b
Conditions: 1a (0.36 mmol), 2 (0.3 mmol), DCE (2 mL), 110 °C, sealed tube, 10 h. Isolated yield.
Next, the generality of carboxylic acids (2) was explored
using 1a as a model substrate, and the results were listed in
Table 3. First, a number of aromatic carboxylic acids were
tried. It was thus observed that 2 bearing a 4-methyl, 4-tert-
butyl, 4-methoxy, 4-fluoro, 4-chloro, 4-bromo, 4-iodo, 4-
trifluoromethyl, 4-nitro, or 3-chloro-substituted phenyl ring
as the R2 moiety reacted with 1a smoothly to give 3s−3ab in
moderate to good yields. It is worth noting herein that even
the iodo unit could remain intact under the reaction
conditions, demonstrating remarkable advantages of this
novel method and allowing for versatile structural elaborations
of the products. Surprisingly, 2 bearing an ortho-halide-
substituted phenyl ring gave the corresponding products in
higher efficiency than their para- or meta-substituted counter-
parts, most likely due to the stronger acidity of ortho-
substituted benzoic acids. In addition, 2,4,6-trimethylbenzoic
acid and 1-naphthoic acid reacted with 1a smoothly to give 3af
and 3ag. Gratifyingly, furan-2-carboxylic acid and thiophene-2-
carboxylic acid showed excellent efficiency to afford 3ah and
3ai, while nicotinic acid and coumarin-3-carboxylic acid gave
their products 3aj and 3ak in moderate yields. Interestingly,
some alkenyl and alkynyl acids such as cinnamic acid, 2-
phenylacrylic acid, and 3-phenylpropiolic acid were found to
be also viable substrates to give 3al, 3am, and 3an. In addition,
the suitability of aliphatic carboxylic acids such as formic acid,
acetic acid, pivalic acid, hexanoic acid, cyclohexanecarboxylic
acid, and adamantane-1-carboxylic acid was also tested. It
turned out that the reactions of these aliphatic carboxylic acids
with 1a took place as efficiently as those of their aromatic
counterparts to afford 3ao−3at. Interestingly, aliphatic
carboxylic acids containing an EWG or an EDG on the α-
position of the carboxyl group, such as 2-cyanoacetic acid and
acetylglycine, showed moderate to good efficiency to give 3au
and 3av. On the other hand, trifluoroacetic acid and
trichloroacetic acid failed to give the corresponding α-
amidoketone products. In these cases, 1a underwent a
rearrangement to afford N-phenylacetamide. As described in
the Introduction section, Majee et al. developed a self-
catalyzed rapid synthesis of α-amidoketones from the reaction
of 3-aryl-2H-azirines with carboxylic acids.5c Despite being
highly facile, convenient, and catalyst-free, Majee’s method is
viable to formic acid, difluoroacetic acid, trichloroacetic acid,
bromoacetic acid, propiolic acid, and phenylpropiolic acid but
not applicable for more common carboxylic acids such as
acetic acid, benzoic acid, propionic acid, and pivalic acid.
Therefore, it might be reasonable to suggest that our method
could be considered as complementary to Majee’s method in
terms of the scope of acid substrates. By the way, the structure
of 3w was unambiguously established by single-crystal X-ray
crystallography (see the Supporting Information).
To further explore the generality of this α-amidoketone-
forming reaction and investigate its synthetic potential as a tool
for late-stage modifications, some carboxylic acid drug
molecules such as dehydrocholic acid, 18β-glycyrrhetinic
acid, adapalene, fenbufen, probenecid, oxaprozin, ibuprofen,
etodolac, indometacin, and sulindac were tried to react with
1a. It was thus found that all of them were compatible with the
reaction conditions to give the corresponding products 3aw−
C
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
a b
,
Table 4. Structural Elaboration of Carboxylic Acid Drug Molecules
a
b
Conditions: 1a (0.36 mmol), 2 (0.3 mmol), DCE (2 mL), 110 °C, sealed tube, 10 h. Isolated yield.
3bf in moderate to good yields. Interestingly, an estrone-
derived carboxylic acid substrate was found to be also suitable
for this reaction to give 3bg. Notably, the presence of a free
hydroxyl group in glycyrrhetinic acid did not affect the reaction
efficiency in the formation of 3ax (Table 4). These results
demonstrated that this newly found transformation is a highly
general and versatile synthetic approach toward α-amidoke-
tone derivatives under catalyst- and metal-free conditions.
To gain some insight into the mechanism of this reaction, a
set of competition experiments were performed. First, 1-
phenylvinyl azide bearing an EDG or an EWG on the phenyl
ring was reacted with 2a (Scheme 2a). It turned out that the
para-OMe-substituted substrate 1d reacted with 2a slightly
faster than its CF3-substituted analogue 1h. Second, the
benzoic acid derivative (2) bearing an EDG or an EWG on the
phenyl ring was reacted with 1a (Scheme 2b). It was thus
found that the para-CF3-substituted substrate 2i reacted with
1a three times faster than its OMe-substituted analogue 2d.
Based on the above described experimental results and
literature reports,5 a plausible mechanism accounting for the
formation of 3 is proposed in Scheme 3. Initially, the vinyl
Scheme 3. Plausible Mechanism Accounting for the
Formation of 3
azide (1) is decomposed under the reaction conditions to give
an azirine intermediate A. A then reacts with the carboxylic
acid (2) to give an aziridine species B. Finally, the unstable
aziridine B undergoes a thermal rearrangement to give the α-
amidoketone product 3.
To illustrate the usefulness of the products obtained above,
the following transformations were conducted. First, 3a was
treated with H2SO4 in Ac2O.1c From this reaction, 2,5-
diphenyloxazole (4) was obtained in 88% yield (Scheme 4).
Scheme 2. Mechanistic Studies
Scheme 4. Structural Elaborations of 3
D
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
7.40−7.51 (m, 6H), 4.92 (d, J = 4.4 Hz, 2H). 13C{1H} NMR (100
MHz, CDCl3) δ 194.4, 167.4, 134.4, 134.2, 133.9, 131.7, 128.9, 128.6,
128.0, 127.2, 46.9. HRMS (ESI) m/z: [M + Na]+ calcd for
C15H13NNaO2 262.0838; found, 262.0832.
N-(2-Oxo-2-(p-Tolyl)Ethyl)Benzamide (3b). Eluent: petroleum
Second, 3a was treated with phenol under the promotion of
tetrabutyl ammonium iodide (TBAI) and tert-butyl hydro-
peroxide (TBHP) to afford α-phenoxylated amidoketone (5)
in 70% yield.9 Third, 3bb, the α-amidoketone derivative of
oxaprozin, was treated with H2SO4 in Ac2O to afford a
structurally and biologically attractive bisoxazole derivative (6)
with good efficiency.10
Finally, to check the suitability of this protocol for large-scale
synthetic missions, 6 mmol of 1a was treated with 5 mmol of
2a under the standard reaction conditions (Scheme 5). It
turned out that the corresponding reaction proceeded
smoothly to afford 3a in 66% yield.
+
ether/ethyl acetate (5:1). Yellowish solid (54.7 mg, 72%), mp:
1
107−109 °C. H NMR (400 MHz, CDCl3) δ 7.87−7.91 (m, 4H),
7.48−7.53 (m, 1H), 7.39−7.45 (m, 3H), 7.28 (d, J = 8.0 Hz, 2H),
4.90 (d, J = 4.4 Hz, 2H), 2.41 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 193.9, 167.4, 145.2, 134.0, 131.9, 131.7, 129.6, 128.6, 128.1,
127.2, 46.8, 21.8. HRMS (ESI) m/z: [M + Na]+ calcd for
+
C16H15NNaO2 276.0995; found, 276.0991.
N-(2-(4-(tert-Butyl)Phenyl)-2-Oxoethyl)Benzamide (3c). Eluent:
petroleum ether/ethyl acetate (5:1). White solid (72.6 mg, 82%),
mp: 138−139 °C. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.4 Hz,
2H), 7.88−7.90 (m, 2H), 7.49−7.52 (m, 3H), 7.42−7.46 (m, 3H),
4.93 (d, J = 4.0 Hz, 2H), 1.35 (s, 9H). 13C{1H} NMR (150 MHz,
CDCl3) δ 193.9, 167.4, 158.2, 134.0, 131.9, 131.7, 128.6, 128.0, 127.2,
125.9, 46.8, 35.3, 31.0. HRMS (ESI) m/z: [M + Na]+ calcd for
Scheme 5. Gram-Scale Synthesis of 3a
+
C19H21NNaO2 318.1465; found, 318.1448.
N-(2-(4-Methoxyphenyl)-2-Oxoethyl)Benzamide (3d). Eluent:
petroleum ether/ethyl acetate (5:1). White solid (56.5 mg, 70%),
1
mp: 106−107 °C. H NMR (400 MHz, CDCl3) δ 7.99−8.03 (m,
2H), 7.87−7.90 (m, 2H), 7.51−7.55 (m, 1H), 7.44−7.48 (m, 2H),
7.36 (br s, 1H), 6.97−7.00 (m, 2H), 4.90 (d, J = 4.0 Hz, 2H), 3.89 (s,
3H). 13C{1H} NMR (150 MHz, CDCl3) δ 192.6, 167.4, 164.4, 134.0,
131.7, 130.4, 128.6, 127.4, 127.2, 114.2, 55.6, 46.5. HRMS (ESI) m/z:
CONCLUSIONS
■
To conclude, we have developed a convenient and efficient
method for the synthesis of α-amidoketones through an
unprecedented cascade reaction of vinyl azides with carboxylic
acids. Using this method, a library of diversely substituted α-
amidoketone derivatives was obtained in good to excellent
yields. In addition, the synthetic potential of this method as a
tool for late-stage modification was well showcased by its
application on a number of complex carboxylic acid drug
molecules. With notable advantages such as catalyst-free
conditions, good tolerance of sensitive functional groups,
broad scope of both coupling partners, simple operation, and
high efficiency, this method is expected to find wide
applications in related areas.
+
[M + Na]+ calcd for C16H15NNaO3 292.0944; found, 292.0940.
N-(2-(4-Fluorophenyl)-2-Oxoethyl)Benzamide (3e). Eluent: pe-
troleum ether/ethyl acetate (5:1). White solid (55.5 mg, 72%), mp:
1
154−156 °C. H NMR (400 MHz, CDCl3) δ 8.03−8.08 (m, 2H),
7.87−7.90 (m, 2H), 7.53 (tt, J1 = 7.2 Hz, J2 = 2.0 Hz, 1H), 7.44−7.48
(m, 2H), 7.33 (br s, 1H), 7.16−7.21 (m, 2H), 4.92 (d, J = 4.4 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 192.8, 167.4, 166.4
(d,1JC‑F = 254.9 Hz), 133.8, 131.8, 130.9 (d,4JC‑F = 3.3 Hz), 130.8
(d,3JC‑F = 8.9 Hz), 128.7, 127.2, 116.2 (d,2JC‑F = 21.8 Hz), 46.8. 19F
NMR (565 MHz, CDCl3) δ −102.78. HRMS (ESI) m/z: [M + Na]+
+
calcd for C15H12FNNaO2 280.0744; found, 280.0735.
N-(2-(4-Chlorophenyl)-2-Oxoethyl)Benzamide (3f). Eluent: petro-
leum ether/ethyl acetate (5:1). White solid (63.1 mg, 77%), mp:
1
EXPERIMENTAL SECTION
150−152 °C. H NMR (400 MHz, CDCl3) δ 7.94−7.97 (m, 2H),
■
7.86−7.88 (m, 2H), 7.43−7.55 (m, 5H), 7.31 (br s, 1H), 4.92 (d, J =
4.0 Hz, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ 193.3, 167.4,
140.8, 133.8, 132.7, 131.9, 129.40, 129.37, 128.7, 127.2, 46.9. HRMS
General Experimental Information. Commercial reagents were
used without further purification. Vinyl azides (1)11 were prepared
based on literature procedures. Melting points were recorded with a
micro melting point apparatus and uncorrected. The 1H nuclear
magnetic resonance (NMR) spectra were recorded at 400 or 600
MHz. The 13C NMR spectra were recorded at 100 or 150 MHz. The
19F NMR spectra were recorded at 376 MHz or 565 MHz. Chemical
shifts were expressed in parts per million (δ) and were reported as s
(singlet), d (doublet), t (triplet), q (quartet), dd (doublet of doublet),
m (multiplet), br s (broad singlet), etc. The coupling constant J was
given in Hz. High-resolution mass spectra (HRMS) were obtained via
electrospray ionization (ESI) mode using a micrOTOF mass
spectrometer. The conversion of starting materials was monitored
by thin-layer chromatography (TLC) using silica gel plates (silica gel
60 F254 0.25 mm), and components were visualized by observation
under UV light (254 and 365 nm).
Experimental Procedures and Spectroscopic Data. General
Synthetic Procedure for the Preparation of 3 and Spectroscopic
Data of 3a−3bg. To a reaction tube equipped with a stir bar were
charged with vinyl azides (1, 0.36 mmol), carboxylic acids (2, 0.3
mmol), and DCE (2 mL). The tube was then sealed and stirred at 110
°C (oil bath) under air for 10 h. Upon completion, it was cooled to
room temperature and concentrated under a reduced pressure. The
residue was purified by silica gel chromatography using petroleum
ether/ethyl acetate as an eluent to afford product 3.
N-(2-Oxo-2-Phenylethyl)Benzamide (3a). Eluent: petroleum
ether/ethyl acetate (5:1).12 White solid (54.5 mg, 76%), mp: 123−
124 °C (lit.12 124−125 °C). 1H NMR (400 MHz, CDCl3) δ 7.98 (d,
J = 7.6 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H),
+
(ESI) m/z: [M + Na]+ calcd for C15H12ClNNaO2 296.0449; found,
296.0444.
N-(2-(4-Bromophenyl)-2-Oxoethyl)Benzamide (3g). Eluent: pe-
troleum ether/ethyl acetate (5:1). White solid (74.2 mg, 78%), mp:
1
149−150 °C. H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz,
4H), 7.65 (d, J = 8.4 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.2
Hz, 2H), 7.31 (br s, 1H), 4.91 (d, J = 4.0 Hz, 2H). 13C{1H} NMR
(150 MHz, CDCl3) δ 193.5, 167.4, 133.8, 133.1, 132.4, 131.9, 129.6,
129.5, 128.7, 127.2, 46.8. HRMS (ESI) m/z: [M + Na]+ calcd for
+
C15H12BrNNaO2 339.9944; found, 339.9926.
N-(2-Oxo-2-(4-(Trifluoromethyl)Phenyl)Ethyl)Benzamide (3h).
Eluent: petroleum ether/ethyl acetate (5:1). White solid (60.8 mg,
66%), mp: 167−168 °C. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J =
8.0 Hz, 2H), 7.87−7.89 (m, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.53−7.56
(m, 1H), 7.47 (t, J = 6.8 Hz, 2H), 7.27 (s, 1H), 4.99 (d, J = 4.4 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 193.6, 167.5, 137.0, 135.5
(q,2JC‑F = 32.7 Hz), 133.7, 131.9, 128.7, 128.4, 127.2, 126.1 (q,3JC‑F
=
3.3 Hz), 123.4 (q,1JC‑F = 271.2 Hz), 47.2. 19F NMR (376
MHz,CDCl3) δ −63.27. HRMS (ESI) m/z: [M + Na]+ calcd for
+
C16H12F3NNaO2 330.0712; found, 330.0709.
N-(2-([1,1’-Biphenyl]-4-yl)-2-Oxoethyl)Benzamide (3i). Eluent:
petroleum ether/ethyl acetate (3:1). Yellow solid (64.3 mg, 68%),
1
mp: 168−170 °C. H NMR (400 MHz, CDCl3) δ 8.07−8.09 (m,
2H), 8.88−8.91 (m, 2H), 7.71 (m, 2H), 7.60−7.63 (m, 2H), 7.50−
7.54 (m, 1H), 7.37−7.49 (m, 6H), 4.97 (d, J = 4.4 Hz, 2H). 13C{1H}
NMR (100 MHz, CDCl3) δ 193.9, 167.5, 146.9, 139.5, 133.9, 133.1,
E
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
131.8, 129.1, 128.7, 128.64, 128.57, 127.6, 127.3, 127.2, 47.0. HRMS
13C{1H} NMR (100 MHz, CDCl3) δ 193.7, 167.5, 154.5, 149.4,
135.3, 133.7, 131.9, 130.0, 128.7, 127.2, 123.9, 47.0. HRMS (ESI) m/
+
(ESI) m/z: [M + Na]+ calcd for C21H17NNaO2 338.1151; found,
+
z: [M + H]+ calcd for C14H13N2O2 241.0972; found, 241.0972.
338.1138.
N-(2-(4-Formylphenyl)-2-Oxoethyl)Benzamide (3j). Eluent: petro-
leum ether/ethyl acetate (1:1). Orange solid (46.4 mg, 58%), mp:
120−122 °C. 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 8.18 (d, J
= 8.4 Hz, 2H), 8.02−8.04 (m, 2H), 7.87−7.89 (m, 2H), 7.54 (tt, J1 =
7.2 Hz, J2 = 2.0 Hz, 1H), 7.45−7.49 (m, 2H), 7.29 (br s, 1H), 5.00 (d,
J = 4.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.0, 191.4,
167.5, 139.8, 138.5, 133.7, 132.0, 130.1, 128.7, 128.6, 127.2, 47.3.
N-(2-Oxodecyl)Benzamide (3r). Eluent: petroleum ether/ethyl
acetate (5:1). White solid (54.5 mg, 66%), mp: 89−90 °C. H NMR
1
(400 MHz, CDCl3) δ 7.81−7.83 (m, 2H), 7.49−7.53 (m, 1H), 7.41−
7.45 (m, 2H), 7.08 (br s, 1H), 4.33 (d, J = 4.4 Hz, 2H), 2.50 (t, J =
7.6 Hz, 2H), 1.61−1.66 (m, 2H), 1.28 (d, J = 6.8 Hz, 10H), 0.88 (t, J
= 6.8 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 205.8, 167.3,
133.8, 131.7, 128.6, 127.1, 49.6, 40.4, 31.8, 29.3, 29.2, 29.1, 23.8, 22.6,
+
HRMS (ESI) m/z: [M + Na]+ calcd for C16H13NNaO3 290.0788;
+
14.1. HRMS (ESI) m/z: [M + Na]+ calcd for C17H25NNaO2
found, 290.0777.
298.1778; found, 298.1767.
4-(Benzoylglycyl)Phenyl Acetate (3k). Eluent: petroleum ether/
ethyl acetate (1:1). White solid (59.7 mg, 67%), mp: 145−147 °C. 1H
NMR (400 MHz, CDCl3) δ 8.02−8.05 (m, 2H), 7.86−7.89 (m, 2H),
7.49−7.53 (m, 1H), 7.42−7.46 (m, 2H), 7.36 (br s, 1H), 7.22−7.26
(m, 2H), 4.91 (d, J = 4.4 Hz, 2H), 2.32 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 193.1, 168.7, 167.4, 155.2, 133.9, 131.9, 131.8, 129.7,
128.6, 127.2, 122.3, 46.8, 21.1. HRMS (ESI) m/z: [M + Na]+ calcd
4-Methyl-N-(2-Oxo-2-Phenylethyl)Benzamide (3s). Eluent: petro-
leum ether/ethyl acetate (5:1). White solid (53.2 mg, 70%), mp:
122−124 °C. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0 Hz,
1
2H), 7.79 (d, J = 8.0 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 7.6
Hz, 2H), 7.25−7.29 (m, 3H), 4.95 (d, J = 4.4 Hz, 2H), 2.41 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 194.4, 167.4, 142.2, 134.4,
134.3, 131.1, 129.3, 129.0, 128.0, 127.2, 46.9, 21.5. HRMS (ESI) m/z:
+
+
[M + Na]+ calcd for C16H15NNaO2 276.0995; found, 276.0988.
for C17H15NNaO4 320.0893; found, 320.0884.
N-(2-Oxo-2-(m-Tolyl)Ethyl)Benzamide (3l). Eluent: petroleum
ether/ethyl acetate (5:1). White solid (57.7 mg, 76%), mp: 105−
4-(tert-Butyl)-N-(2-Oxo-2-Phenylethyl)Benzamide (3t). Eluent:
petroleum ether/ethyl acetate (5:1). Yellowish solid (70.8 mg,
1
1
106 °C. H NMR (400 MHz, CDCl3) δ 7.87−7.90 (m, 2H), 7.80−
80%), mp: 136−137 °C. H NMR (400 MHz, CDCl3) δ 8.04 (d, J
7.83 (m, 2H), 7.50−7.54 (m, 1H), 7.43−7.47 (m, 3H), 7.36−7.41
(m, 2H), 4.93 (d, J = 4.0 Hz, 2H), 2.42 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 194.5, 167.4, 138.9, 135.0, 134.4, 134.0, 131.8, 128.9,
128.6, 128.5, 127.2, 125.2, 46.9, 21.3. HRMS (ESI) m/z: [M + Na]+
= 7.6 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.64 (t, J = 7.6 Hz, 1H),
7.47−7.54 (m, 4H), 7.30 (br s, 1H), 4.97 (d, J = 4.0 Hz, 2H), 1.35 (s,
9H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.4, 167.4, 155.3, 134.4,
134.3, 131.1, 129.0, 128.0, 127.0, 125.6, 46.9, 35.0, 31.2. HRMS (ESI)
m/z: [M + Na]+ calcd for C19H21NNaO2+ 318.1465; found, 318.1454.
4-Methoxy-N-(2-Oxo-2-Phenylethyl)Benzamide (3u). Eluent: pe-
troleum ether/ethyl acetate (3:1).12 Yellowish solid (59.7 mg, 74%),
mp: 133−135 °C (lit.12 133−134 °C). 1H NMR (600 MHz, CDCl3)
δ 8.04 (d, J = 7.2 Hz, 2H), 7.85−7.87 (m, 2H), 7.65 (t, J = 7.2 Hz,
1H), 7.53 (t, J = 7.8 Hz, 2H), 7.21 (br s, 1H), 6.95−6.97 (m, 2H),
4.96 (d, J = 4.2 Hz, 2H), 3.87 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 194.5, 166.9, 162.4, 134.4, 134.3, 129.0, 128.0, 126.2, 113.8,
+
calcd for C16H15NNaO2 276.0995; found, 276.0994.
N-(2-Oxo-2-(o-Tolyl)Ethyl)Benzamide (3m). Eluent: petroleum
ether/ethyl acetate (5:1). White solid (45.6 mg, 60%), mp: 107−
108 °C. 1H NMR (400 MHz, CDCl3) δ 7.88−7.91 (m, 2H), 7.80 (d,
J = 8.0 Hz, 2H), 7.52 (tt, J1 = 7.2 Hz, J2 = 2.4 Hz, 1H), 7.44−7.47 (m,
3H), 7.29−7.34 (m, 3H), 4.86 (d, J = 4.4 Hz, 2H), 2.58 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 197.0, 167.4, 139.7, 134.1,
134.0, 132.8, 132.5, 131.8, 128.9, 128.6, 127.2, 126.2, 48.3, 21.8.
+
HRMS (ESI) m/z: [M + Na]+ calcd for C16H15NNaO2 276.0995;
+
55.4, 46.9. HRMS (ESI) m/z: [M + Na]+ calcd for C16H15NNaO3
found, 276.0996.
292.0944; found, 292.0935.
N-(2-(3,4-Dimethoxyphenyl)-2-Oxoethyl)Benzamide (3n). Elu-
ent: petroleum ether/ethyl acetate (3:1). Yellowish solid (59.2 mg,
66%), mp: 151−152 °C. 1H NMR (600 MHz, CDCl3) δ 7.89 (d, J =
7.2 Hz, 2H), 7.66 (d, J = 8.4 Hz, 1H), 7.51−7.54 (m, 2H), 7.46 (t, J =
7.2 Hz, 2H), 7.38 (br s, 1H), 6.93 (d, J = 8.4 Hz, 1H), 4.91 (d, J = 3.6
Hz, 2H), 3.95 (d, J = 8.4 Hz, 6H). 13C{1H} NMR (150 MHz,
CDCl3) δ 192.7, 167.4, 154.2, 149.3, 134.0, 131.7, 128.6, 127.5, 127.1,
122.8, 110.4, 109.9, 56.2, 56.1, 46.5. HRMS (ESI) m/z: [M + Na]+
4-Fluoro-N-(2-Oxo-2-Phenylethyl)Benzamide (3v). Eluent: petro-
leum ether/ethyl acetate (5:1). White solid (57.8 mg, 75%), mp:
124−126 °C (lit.13 122−126 °C). H NMR (400 MHz, CDCl3) δ
1
8.03 (d, J = 8.0 Hz, 2H), 7.90 (dd, J1 = 8.4 Hz, J2 = 5.6 Hz, 2H), 7.65
(t, J = 7.2 Hz, 1H), 7.53 (t, J = 8.0 Hz, 2H), 7.29 (br s, 1H), 7.14 (t, J
= 8.4 Hz, 2H), 4.95 (d, J = 4.0 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3) δ 194.3, 166.3, 164.9 (d,1JC‑F = 250.7 Hz), 134.34, 134.32,
130.1 (d,4JC‑F = 2.8 Hz), 129.5 (d,3JC‑F = 8.6 Hz), 129.0, 128.0, 115.7
(d,2JC‑F = 21.7 Hz), 46.9. 19F NMR (376 MHz, CDCl3) δ −107.76.
+
calcd for C17H17NNaO4 322.1050; found, 322.1039.
+
HRMS (ESI) m/z: [M + Na]+ calcd for C15H12FNNaO2 280.0744;
N-(2-(Naphthalen-2-yl)-2-Oxoethyl)Benzamide (3o). Eluent: pe-
troleum ether/ethyl acetate (3:1). Brown solid (59.8 mg, 69%), mp:
117−118 °C. 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 8.04 (dd,
J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.87−7.93 (m,
4H), 7.51−7.65 (m, 3H), 7.44−7.48 (m, 2H), 7.39 (br s, 1H), 5.08
(d, J = 4.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.2,
167.5, 136.1, 134.0, 132.5, 131.8, 131.7, 130.1, 129.8, 129.1, 128.9,
128.7, 127.9, 127.2, 123.2, 47.0. HRMS (ESI) m/z: [M + Na]+ calcd
Found 280.0743.
4-Chloro-N-(2-Oxo-2-Phenylethyl)Benzamide (3w). Eluent: pe-
troleum ether/ethyl acetate (5:1). White solid (59.0 mg, 72%), mp:
1
139−140 °C. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.6 Hz,
2H), 7.83 (d, J = 8.4 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.53 (t, J = 7.6
Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.29 (br s, 1H), 4.95 (d, J = 4.4 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.2, 166.3, 138.1, 134.4,
134.3, 132.3, 129.1, 128.9, 128.6, 128.0, 46.9. HRMS (ESI) m/z: [M
+
for C19H15NNaO2 312.0995; found, 312.0987.
+
+ Na]+ calcd for C15H12ClNNaO2 296.0449; found, 296.0442.
N-(2-Oxo-2-(Thiophen-2-yl)Ethyl)Benzamide (3p). Eluent: petro-
leum ether/ethyl acetate (3:1). White solid (55.9 mg, 76%), mp:
4-Bromo-N-(2-Oxo-2-Phenylethyl)Benzamide (3x). Eluent: petro-
1
149−150 °C. H NMR (400 MHz, CDCl3) δ 7.85−7.88 (m, 3H),
leum ether/ethyl acetate (5:1). White solid (69.4 mg, 73%), mp:
1
7.72 (dd, J1 = 5.2 Hz, J2 = 0.8 Hz, 1H), 7.50−7.53 (m, 1H), 7.44 (t, J
= 6.8 Hz, 2H), 7.29 (br s, 1H), 7.17−7.19 (m, 1H), 4.88 (d, J = 4.8
Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 187.4, 167.4, 140.9,
150−151 °C. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0 Hz,
2H), 7.76 (d, J = 8.4 Hz, 2H), 7.65 (t, J = 7.2 Hz, 1H), 7.60 (d, J = 8.0
Hz, 2H), 7.53 (t, J = 7.6 Hz, 2H), 7.31 (br s, 1H), 4.95 (d, J = 4.0 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.1, 166.4, 134.4, 134.3,
132.7, 131.9, 129.1, 128.8, 128.0, 126.6, 46.9. HRMS (ESI) m/z: [M
134.7, 133.8, 132.7, 131.8, 128.65, 128.57, 127.2, 46.9. HRMS (ESI)
+
m/z: [M + Na]+ calcd for C13H11NNaO2S
268.0403; found,
+
268.0396.
+ Na]+ calcd for C15H12BrNNaO2 339.9944; found, 339.9929.
N-(2-Oxo-2-(Pyridin-3-yl)Ethyl)Benzamide (3q). Eluent: petrole-
um ether/ethyl acetate (1:2). White solid (37.5 mg, 52%), mp: 127−
128 °C. 1H NMR (400 MHz, CDCl3) δ 9.23 (d, J = 1.6 Hz, 1H), 8.84
(dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 1H), 8.28 (dt, J1 = 8.0 Hz, J2 = 2.0 Hz,
1H), 7.87−7.89 (m, 2H), 7.53 (tt, J1 = 7.2 Hz, J2 = 2.0 Hz, 1H),
7.43−7.49 (m, 3H), 7.37 (br s, 1H), 4.97 (d, J = 4.8 Hz, 2H).
4-Iodo-N-(2-Oxo-2-Phenylethyl)Benzamide (3y). Eluent: petro-
leum ether/ethyl acetate (3:1). White solid (63.5 mg, 58%), mp:
1
171−173 °C. H NMR (400 MHz, CDCl3) δ 8.01−8.03 (m, 2H),
7.80−7.82 (m, 2H), 7.60−7.67 (m, 3H), 7.52 (t, J = 7.6 Hz, 2H),
7.31 (br s, 1H), 4.94 (d, J = 4.0 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3) δ 194.2, 166.6, 137.9, 134.4, 134.3, 133.3, 129.0, 128.8, 128.0,
F
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
+
98.9, 46.9. HRMS (ESI) m/z: [M + Na]+ calcd for C15H12INNaO2
NMR (100 MHz, CDCl3) δ 194.1, 169.6, 134.4, 134.3, 133.8, 133.7,
387.9805; found, 387.9806.
131.0, 130.2, 129.0, 128.4, 128.0, 127.3, 126.5, 125.52, 125.47, 124.8,
+
N-(2-Oxo-2-Phenylethyl)-4-(Trifluoromethyl)Benzamide (3z).
Eluent: petroleum ether/ethyl acetate (2:1). White solid (64.5 mg,
70%), mp: 171−173 °C. 1H NMR (600 MHz, CDCl3) δ 8.04 (d, J =
7.2 Hz, 2H), 8.00 (d, J = 7.2 Hz, 2H), 7.74 (d, J = 7.8 Hz, 2H), 7.66−
7.67 (m, 1H), 7.55−7.56 (m, 2H), 7.36 (br s, 1H), 4.98 (d, J = 3.0
Hz, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ 194.0, 166.1, 137.2,
134.5, 134.2, 133.5 (q,2JC‑F = 32.9 Hz), 129.1, 128.0, 127.7, 125.7
(q,3JC‑F = 4.5 Hz), 123.7 (q,1JC‑F = 271.4 Hz), 46.9. 19F NMR (565
MHz, CDCl3) δ −62.95. HRMS (ESI) m/z: [M + Na]+ calcd for
46.9. HRMS (ESI) m/z: [M + Na]+ calcd for C19H15NNaO2
312.0995; found, 312.0985.
N-(2-Oxo-2-Phenylethyl)Furan-2-Carboxamide (3ah). Eluent:
petroleum ether/ethyl acetate (5:1). Yellowish solid (58.4 mg,
1
85%), mp: 138−139 °C. H NMR (600 MHz, CDCl3) δ 8.00 (d, J
= 7.2 Hz, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.46−7.51 (m, 4H), 7.15 (d, J
= 3.6 Hz, 1H), 6.51 (q, J = 1.8 Hz, 1H), 4.92 (d, J = 4.8 Hz, 2H).
13C{1H} NMR (150 MHz, CDCl3) δ 193.9, 158.4, 147.7, 144.3,
134.4, 134.2, 128.9, 128.0, 114.5, 112.1, 46.1. HRMS (ESI) m/z: [M
+
+
+ Na]+ calcd for C13H11NNaO3 252.0631; found, 252.0628.
C16H12F3NNaO2 330.0712; found, 330.0701.
4-Nitro-N-(2-Oxo-2-Phenylethyl)Benzamide (3aa). Eluent: petro-
N-(2-Oxo-2-Phenylethyl)Thiophene-2-Carboxamide (3ai). Elu-
ent: petroleum ether/ethyl acetate (5:1). Yellowish solid (69.1 mg,
94%), mp: 140−141 °C. 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J =
8.0 Hz, 2H), 7.62−7.66 (m, 2H), 7.50−7.53 (m, 3H), 7.19 (br s, 1H),
7.10 (t, J = 4.4 Hz, 1H), 4.94 (d, J = 4.0 Hz, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ 194.1, 161.9, 138.3, 134.3, 130.4, 129.0, 128.6,
128.0, 127.8, 46.8. HRMS (ESI) m/z: [M + Na]+ calcd for
C13H11NNaO2S+ 268.0403; found, 268.0403.
leum ether/ethyl acetate (2:1). White solid (58.8 mg, 69%), mp:
1
170−172 °C. H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.4 Hz,
2H), 8.05 (t, J = 7.0 Hz, 4H), 7.68 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.6
Hz, 2H), 7.39 (br s, 1H), 4.98 (d, J = 3.6 Hz, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ 193.8, 165.3, 149.9, 139.4, 134.6, 134.1, 129.1,
128.4, 128.1, 123.9, 47.0. HRMS (ESI) m/z: [M + Na]+ calcd for
+
C15H12N2NaO4 307.0689; found, 307.0685.
3-Chloro-N-(2-Oxo-2-Phenylethyl)Benzamide (3ab). Eluent: pe-
N-(2-Oxo-2-Phenylethyl)Nicotinamide (3aj). Eluent: petroleum
ether/ethyl acetate (1:1). Brown solid (37.5 mg, 52%), mp: 129−130
troleum ether/ethyl acetate (5:1). White solid (62.3 mg, 76%), mp:
1
1
134−135 °C. H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.0 Hz,
°C. H NMR (400 MHz, CDCl3) δ 9.12 (d, J = 1.6 Hz, 1H), 8.76
2H), 7.88 (s, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H),
7.52 (q, J = 7.6 Hz, 3H), 7.40 (t, J = 7.6 Hz, 1H), 7.31 (br s, 1H),
4.95 (d, J = 4.0 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.1,
166.1, 135.7, 134.9, 134.4, 134.3, 131.8, 130.0, 129.0, 128.0, 127.6,
(dd, J1 = 4.4 Hz, J2 = 1.2 Hz, 1H), 8.19 (dt, J1 = 8.4 Hz, J2 = 1.6 Hz,
1H), 8.02−8.05 (m, 2H), 7.66 (t, J = 7.6 Hz, 1H), 7.54 (t, J = 7.6 Hz,
2H), 7.40−7.43 (m, 2H), 4.98 (d, J = 4.0 Hz, 2H). 13C{1H} NMR
(150 MHz, CDCl3) δ 194.0, 165.6, 152.5, 148.3, 135.1, 134.4, 134.2,
129.6, 129.1, 128.0, 123.5, 46.8. HRMS (ESI) m/z: [M + H]+ calcd
125.2, 46.9. HRMS (ESI) m/z: [M
+
Na]+ calcd for
+
+
C15H12ClNNaO2 296.0449; found, 296.0441.
for C14H13N2O2 241.0972; found, 241.0980.
2-Chloro-N-(2-Oxo-2-Phenylethyl)Benzamide (3ac). Eluent: pe-
2-Oxo-N-(2-Oxo-2-Phenylethyl)-2H-Chromene-3-Carboxamide
(3ak). Eluent: petroleum ether/ethyl acetate (1:1). Brown solid (37.8
mg, 41%), mp: 192−193 °C. 1H NMR (400 MHz, CDCl3) δ 9.67 (br
s, 1H), 8.93 (s, 1H), 8.03−8.05 (m, 2H), 7.62−7.71 (m, 3H), 7.52 (t,
J = 7.2 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H),
4.98 (d, J = 4.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.4,
161.8, 161.1, 154.6, 148.5, 134.7, 134.2, 134.0, 129.9, 128.9, 128.0,
125.3, 118.6, 118.3, 116.8, 47.0. HRMS (ESI) m/z: [M + Na]+ calcd
troleum ether/ethyl acetate (5:1). White solid (73.7 mg, 90%), mp:
1
100−102 °C. H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.6 Hz,
2H), 7.73 (d, J = 7.2 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 8.0
Hz, 2H), 7.42−7.44 (m, 2H), 7.32−7.40 (m, 2H), 4.99 (d, J = 4.4 Hz,
2H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.8, 166.5, 134.5, 134.3,
131.6, 131.1, 130.4, 130.3, 129.00, 128.0, 127.1, 47.1. HRMS (ESI)
+
m/z: [M + Na]+ calcd for C15H12ClNNaO2 296.0449; found,
+
296.0439.
for C18H13NNaO4 330.0737; found, 330.0730.
2-Bromo-N-(2-Oxo-2-Phenylethyl)Benzamide (3ad). Eluent: pe-
troleum ether/ethyl acetate (5:1). White solid (86.5 mg, 91%), mp:
104−106 °C. H NMR (600 MHz, CDCl3) δ 8.01 (d, J = 7.2 Hz,
N-(2-Oxo-2-Phenylethyl)Cinnamamide (3al). Eluent: petroleum
ether/ethyl acetate (5:1). Yellowish solid (56.5 mg, 71%), mp: 133−
134 °C. 1H NMR (600 MHz, CDCl3) δ 8.00 (d, J = 7.8 Hz, 2H), 7.69
(d, J = 16.2 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 7.47−7.52 (m, 4H),
7.34−7.36 (m, 3H), 6.98 (br s, 1H), 6.62 (d, J = 15.6 Hz, 1H), 4.92
(d, J = 4.2 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.4,
166.0, 141.6, 134.8, 134.4, 134.2, 129.8, 129.0, 128.8, 128.0, 127.9,
1
2H), 7.59−7.65 (m, 3H), 7.51 (t, J = 7.8 Hz, 2H), 7.36 (t, J = 7.2 Hz,
1H), 7.27−7.30 (m, 1H), 7.24 (br s, 1H), 4.97 (d, J = 4.2 Hz, 2H).
13C{1H} NMR (150 MHz, CDCl3) δ 193.7, 167.6, 137.2, 134.3,
133.5, 131.5, 129.7, 129.0, 128.0, 127.6, 119.6, 47.0. HRMS (ESI) m/
z: [M + Na]+ calcd for C15H12BrNNaO2+ 339.9944; found, 339.9936.
2-Iodo-N-(2-Oxo-2-Phenylethyl)Benzamide (3ae). Eluent: petro-
leum ether/ethyl acetate (4:1). White solid (96.4 mg, 88%), mp:
+
120.2, 46.8. HRMS (ESI) m/z: [M + Na]+ calcd for C17H15NNaO2
288.0995; found, 288.0983.
N-(2-Oxo-2-Phenylethyl)-2-Phenylacrylamide (3am). Eluent: pe-
troleum ether/ethyl acetate (5:1). Orange solid (54.1 mg, 68%), mp:
77−79 °C. 1H NMR (400 MHz, CDCl3) δ 7.95−7.97 (m, 2H),
7.59−7.63 (m, 1H), 7.36−7.50 (m, 7H), 6.84 (br s, 1H), 6.20 (d, J =
0.8 Hz, 1H), 5.69 (d, J = 0.8 Hz, 1H), 4.85 (d, J = 4.4 Hz, 2H).
13C{1H} NMR (150 MHz, CDCl3) δ 194.0, 167.4, 144.4, 136.8,
134.4, 134.2, 129.0, 128.8, 128.7, 128.2, 128.0, 122.6, 46.8. HRMS
1
107−108 °C. H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.6 Hz,
2H), 7.85 (d, J = 7.6 Hz, 1H), 7.62 (t, J = 7.2 Hz, 1H), 7.45−7.52 (m,
3H), 7.36 (t, J = 7.6 Hz, 1H), 7.08 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 2H),
4.94 (d, J = 4.4 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.8,
169.3, 141.6, 140.0, 134.3, 131.3, 129.0, 128.5, 128.2, 128.0, 92.7,
+
46.9. HRMS (ESI) m/z: [M + Na]+ calcd for C15H12INNaO2
+
387.9805; found, 387.9805.
(ESI) m/z: [M + Na]+ calcd for C17H15NNaO2 288.0995; found,
2,4,6-Trimethyl-N-(2-Oxo-2-Phenylethyl)Benzamide (3af). Elu-
ent: petroleum ether/ethyl acetate (5:1). White solid (63.3 mg,
75%), mp: 148−150 °C. 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J =
7.6 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 6.86 (s,
2H), 6.74 (br s, 1H), 4.98 (d, J = 4.4 Hz, 2H), 2.31 (s, 6H), 2.29 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.0, 170.9, 138.7,
134.41, 134.38, 134.3, 129.0, 128.3, 128.0, 46.4, 21.1, 19.2. HRMS
288.0989.
N-(2-Oxo-2-Phenylethyl)-3-Phenylpropiolamide (3an). Eluent:
petroleum ether/ethyl acetate (3:1). Yellow solid (69.5 mg, 88%),
mp: 147−149 °C. H NMR (600 MHz, CDCl3) δ 7.98 (dd, J1 = 8.4
Hz, J2 = 1.2 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.54−7.55 (m, 2H),
7.49 (t, J = 7.8 Hz, 2H), 7.40−7.42 (m, 1H), 7.34 (t, J = 7.2 Hz, 2H),
7.21 (br s, 1H), 4.86 (d, J = 4.2 Hz, 2H). 13C{1H} NMR (100 MHz,
CDCl3) δ 193.3, 153.4, 134.3, 134.2, 132.6, 130.2, 129.0, 128.6, 128.0,
120.1, 85.5, 82.7, 46.7. HRMS (ESI) m/z: [M + Na]+ calcd for
1
+
(ESI) m/z: [M + Na]+ calcd for C18H19NNaO2 304.1308; found,
304.1300.
+
N-(2-Oxo-2-Phenylethyl)-1-Naphthamide (3ag). Eluent: petrole-
um ether/ethyl acetate (5:1). Yellowish solid (78.0 mg, 90%), mp:
C17H13NNaO2 286.0838; found, 286.0835.
N-(2-Oxo-2-Phenylethyl)Formamide (3ao). Eluent: petroleum
ether/ethyl acetate (1:1). Yellowish solid (36.7 mg, 75%), mp: 74−
1
124−126 °C. H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.0 Hz,
1
1H), 8.03 (d, J = 8.0 Hz, 2H), 7.93 (d, J = 8.4 Hz, 1H), 7.87 (d, J =
8.0 Hz, 1H), 7.73 (d, J = 6.8 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.45−
7.58 (m, 5H), 7.14 (br s, 1H), 5.04 (d, J = 4.4 Hz, 2H). 13C{1H}
75 °C. H NMR (600 MHz, CDCl3) δ 8.36 (s, 1H), 7.98 (d, J = 7.2
Hz, 2H), 7.64 (t, J = 7.8 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 6.92 (br s,
1H), 4.82 (d, J = 4.2 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ
G
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
193.6, 161.3, 134.3, 134.2, 129.0, 128.0, 45.0. HRMS (ESI) m/z: [M
6H), 1.62 (td, J1 = 14.4 Hz, J2 = 4.4 Hz, 1H), 1.21−1.50 (m, 7H),
1.08 (s, 3H), 0.88 (d, J = 6.4 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 212.0, 209.2, 208.8, 194.4, 173.6, 134.4, 134.1, 128.9, 127.9,
56.9, 51.7, 49.0, 46.8, 46.4, 45.6, 45.5, 45.0, 42.8, 38.6, 36.5, 36.0,
35.6, 35.2, 33.5, 31.1, 27.6, 25.1, 21.9, 18.8, 11.9. HRMS (ESI) m/z:
+
+ Na]+ calcd for C9H9NNaO2 186.0525; found, 186.0527.
N-(2-Oxo-2-Phenylethyl)Acetamide (3ap). Eluent: petroleum
ether/ethyl acetate (1:1). Yellowish solid (35.1 mg, 66%), mp: 85−
86 °C. 1H NMR (400 MHz, CDCl3) δ 7.97−7.99 (m, 2H), 7.62 (tt, J1
= 7.6 Hz, J2 = 1.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 6.75 (br s, 1H),
4.78 (d, J = 4.4 Hz, 2H), 2.11 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 194.3, 170.4, 134.4, 134.2, 128.9, 127.9, 46.6, 23.0. HRMS
+
[M + Na]+ calcd for C32H41NNaO5 542.2877; found, 542.2869.
(2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bR)-10-Hydroxy-
2,4a,6a,6b,9,9,12a-Heptamethyl-13-Oxo-N-(2-Oxo-2-Phenylethyl)-
1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-Icosahydro-
picene-2-Carboxamide (3ax). Eluent: petroleum ether/ethyl acetate
+
(ESI) m/z: [M + Na]+ calcd for C10H11NNaO2 200.0682; found,
200.0680.
1
(1:1). Yellowish solid (142.6 mg, 81%), mp: 143−145 °C. H NMR
N-(2-Oxo-2-Phenylethyl)Pivalamide (3aq). Eluent: petroleum
ether/ethyl acetate (3:1). Brown oil (50.6 mg, 77%). 1H NMR
(400 MHz, CDCl3) δ 7.97−7.99 (m, 2H), 7.60−7.64 (m, 1H), 7.50
(t, J = 7.6 Hz, 2H), 6.82 (br s, 1H), 4.74 (d, J = 4.4 Hz, 2H), 1.28 (s,
9H). 13C{1H} NMR (150 MHz, CDCl3) δ 194.5, 178.7, 134.5, 134.1,
128.9, 127.9, 46.5, 38.8, 27.6. HRMS (ESI) m/z: [M + Na]+ calcd for
(400 MHz, CDCl3) δ 7.97−8.00 (m, 2H), 7.61 (t, J = 7.2 Hz, 1H),
7.49 (t, J = 8.0 Hz, 2H), 6.86 (t, J = 4.4 Hz, 1H), 5.78 (s, 1H), 4.77
(qd, J1 = 12.8 Hz, J2 = 4.0 Hz, 2H), 3.23 (dd, J1 = 11.2 Hz, J2 = 5.2
Hz, 1H), 2.77−2.81 (m, 1H), 2.35 (s. 1H), 2.26 (dd, J1 = 13.2 Hz, J2
= 3.2 Hz, 1H), 1.58−2.08 (m, 10H), 1.40−1.46 (m, 8H), 1.18−1.25
(m, 4H), 1.12 (d. J = 5.2 Hz, 6H), 0.96−1.05 (m, 5H), 0.81 (d, J =
0.4 Hz, 6H), 0.70 (d, J = 11.2 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3) δ 200.1, 194.6, 176.2, 169.0, 134.5, 134.1, 128.9, 128.6, 128.0,
78.6, 61.8, 54.9, 47.9, 46.3, 45.4, 43.8, 43.2, 41.6, 39.2, 39.1, 37.5,
37.1, 32.8, 31.9, 31.5, 29.6, 28.4, 28.2, 27.3, 26.5, 26.4, 23.4, 18.7,
+
C13H17NNaO2 242.1151; found 242.1152.
N-(2-Oxo-2-Phenylethyl)Hexanamide (3ar). Eluent: petroleum
ether/ethyl acetate (3:1). Yellowish solid (43.4 mg, 62%), mp: 69−71
1
°C. H NMR (400 MHz, CDCl3) δ 7.97−8.00 (m, 2H), 7.60−7.64
(m, 1H), 7.50 (t, J = 7.6 Hz, 2H), 6.65 (br s, 1H), 4.78 (d, J = 4.0 Hz,
2H), 2.31 (t, J = 8.0 Hz, 2H), 1.66−1.73 (m, 2H), 1.32−1.37 (m,
4H), 0.89−0.92 (m, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ
194.5, 173.4, 134.4, 134.1, 128.9, 127.9, 46.4, 36.5, 31.5, 25.4, 22.4,
+
17.5, 16.4, 15.7. HRMS (ESI) m/z: [M + H]+ calcd for C38H54NO4
588.4047; found, 588.4030.
6-(3-((3r,5r,7r)-Adamantan-1-yl)-4-Methoxyphenyl)-N-(2-Oxo-2-
Phenylethyl)-2-Naphthamide (3ay). Eluent: petroleum ether/ethyl
+
13.9. HRMS (ESI) m/z: [M + Na]+ calcd for C14H19NNaO2
1
acetate (3:1). Brown solid (87.3 mg, 55%), mp: 200−202 °C. H
256.1308; found, 256.1306.
N-(2-Oxo-2-Phenylethyl)Cyclohexanecarboxamide (3as). Eluent:
NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 8.00−8.05 (m, 3H), 7.93−
7.98 (m, 3H), 7.79 (dd, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 7.60−7.63 (m,
2H), 7.47−7.54 (m, 4H), 6.98 (d, J = 8.4 Hz, 1H), 5.00 (d, J = 4.4
Hz, 2H), 3.88 (s, 3H), 2.19 (s, 6H), 2.11 (s, 3H), 1.80 (s, 6H).
13C{1H} NMR (100 MHz, CDCl3) δ 194.4, 167.5, 158.9, 140.9,
139.0, 135.4, 134.4, 134.3, 132.6, 131.4, 130.6, 129.4, 129.0, 128.6,
128.1, 127.6, 126.6, 126.0, 125.7, 124.7, 124.0, 112.1, 55.2, 47.1, 40.7,
37.24, 37.17, 29.2. HRMS (ESI) m/z: [M + Na]+ calcd for
petroleum ether/ethyl acetate (3:1). Yellowish solid (50.7 mg, 69%),
1
mp: 111−113 °C. H NMR (400 MHz, CDCl3) δ 7.97−7.99 (m,
2H), 7.62 (tt, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H),
6.63 (br s, 1H), 4.76 (d, J = 4.4 Hz, 2H), 2.25 (tt, J1 = 12.0 Hz, J2 =
3.6 Hz, 1H), 1.93 (dd, J1 = 13.2 Hz, J2 = 1.6 Hz, 2H), 1.80−1.84 (m,
2H), 1.67−1.71 (m, 1H), 1.50 (qd, J1 = 12.0 Hz,J2 = 3.2 Hz, 2H),
1.21−1.36 (m, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 194.6,
176.3, 134.5, 134.1, 128.9, 127.9, 46.3, 45.3, 29.7, 25.75, 25.72.
+
C36H35NNaO3 552.2509; found, 552.2503.
4-([1,1’-Biphenyl]-4-yl)-4-Oxo-N-(2-Oxo-2-Phenylethyl)-
Butanamide (3az). Eluent: petroleum ether/ethyl acetate (3:1). Pink
solid (75.7 mg, 68%), mp: 169−171 °C. 1H NMR (400 MHz,
CDCl3) δ 8.06 (d, J = 8.4 Hz, 2H), 7.96−7.98 (m, 2H), 7.67 (d, J =
8.4 Hz, 2H), 7.59−7.63 (m, 3H), 7.47 (q, J = 8.4 Hz, 4H), 7.37−7.41
(m, 1H), 6.88 (br s, 1H), 4.79 (d, J = 4.4 Hz, 2H), 3.43 (t, J = 6.4 Hz,
2H), 2.80 (t, J = 6.8 Hz, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ
198.4, 194.2, 172.3, 145.9, 139.9, 135.3, 134.5, 134.1, 128.98, 128.95,
128.7, 128.3, 128.0, 127.30, 127.27, 46.6, 33.9, 30.1. HRMS (ESI) m/
+
HRMS (ESI) m/z: [M + Na]+ calcd for C15H19NNaO2 268.1308;
found, 268.1303.
(3R,5R,7R)-N-(2-Oxo-2-Phenylethyl)Adamantane-1-Carboxa-
mide (3at). Eluent: petroleum ether/ethyl acetate (3:1). Yellowish
solid (58.8 mg, 66%), mp: 127−128 °C. 1H NMR (400 MHz,
CDCl3) δ 7.97−8.00 (m, 2H), 7.60−7.64 (m, 1H), 7.50 (t, J = 7.2
Hz, 2H), 6.78 (br s, 1H), 4.74 (d, J = 4.4 Hz, 2H), 2.07 (s, 3H), 1.94
(d, J = 2.8 Hz, 6H), 1.71−1.79 (m, 6H). 13C{1H} NMR (150 MHz,
CDCl3) δ 194.7, 178.2, 134.5, 134.1, 128.9, 127.9, 46.3, 40.8, 39.2,
+
z: [M + Na]+ calcd for C24H21NNaO3 394.1414; found, 394.1403.
+
36.5, 28.1. HRMS (ESI) m/z: [M + Na]+ calcd for C19H23NNaO2
4-(N,N-Dipropylsulfamoyl)-N-(2-Oxo-2-Phenylethyl)Benzamide
320.1621; found 320.1612.
2-Cyano-N-(2-Oxo-2-Phenylethyl)Acetamide (3au). Eluent: pe-
(3ba). Eluent: petroleum ether/ethyl acetate (1:1). Yellowish solid
1
(88.1 mg, 73%), mp: 108−109 °C. H NMR (400 MHz, CDCl3) δ
troleum ether/ethyl acetate (5:1). Yellowish solid (47.3 mg, 78%),
7.99−8.01 (m, 4H), 7.87 (d, J = 8.4 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H),
7.51 (t, J = 8.0 Hz, 3H), 4.95 (d, J = 4.8 Hz, 2H), 3.09 (t, J = 7.6 Hz,
4H), 1.50−1.59 (m, 4H), 0.87 (t, J = 7.6 Hz, 6H). 13C{1H} NMR
(100 MHz, CDCl3) δ 194.0, 166.0, 143.0, 137.3, 134.32, 134.26,
129.0, 127.98, 127.95, 127.2, 49.9, 46.9, 21.9, 11.1. HRMS (ESI) m/z:
[M + Na]+ calcd for C21H26N2NaO4S+ 425.1505; found, 425.1496.
3-(4,5-Diphenyloxazol-2-yl)-N-(2-Oxo-2-Phenylethyl)-
Propanamide (3bb). Eluent: petroleum ether/ethyl acetate (1:1).
White solid (82.4 mg, 67%), mp: 105−106 °C. 1H NMR (400 MHz,
CDCl3) δ 7.95 (d, J = 7.2 Hz, 2H), 7.63−7.65 (m, 2H), 7.54−7.59
(m, 3H), 7.45 (d, J = 7.6 Hz, 2H), 7.28−7.36 (m, 6H), 7.08 (br s,
1H), 4.78 (d, J = 4.4 Hz, 2H), 3.24 (t, J = 7.6 Hz, 2H), 2.91 (t, J = 7.6
Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.2, 171.5, 162.3,
145.5, 135.1, 134.4, 134.1, 132.5, 129.0, 128.9, 128.7, 128.6, 128.5,
128.1, 127.98, 127.97, 126.5, 46.6, 32.8, 24.0. HRMS (ESI) m/z: [M
1
mp: 156−157 °C. H NMR (400 MHz, CDCl3) δ 7.97−7.99 (m,
2H), 7.66 (t, J = 7.6 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.14 (br s,
1H), 4.80 (d, J = 4.4 Hz, 2H), 3.50 (s, 2H). 13C{1H} NMR (150
MHz, CDCl3) δ 193.0, 161.1, 134.6, 134.0, 129.1, 128.0, 114.2, 46.8,
+
25.9. HRMS (ESI) m/z: [M + Na]+ calcd for C11H10N2NaO2
225.0634; found 225.0634.
2-Acetamido-N-(2-Oxo-2-Phenylethyl)Acetamide (3av). Eluent:
petroleum ether/ethyl acetate (1:2). White solid (38.6 mg, 55%), mp:
1
177−178 °C. H NMR (400 MHz, CDCl3) δ 7.96−7.98 (m, 2H),
7.63 (tt, J1 = 7.6 Hz, J2 = 2.0 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.15
(br s, 1H), 6.56 (br s, 1H), 4.78 (d, J = 4.4 Hz, 2H), 4.08 (d, J = 5.2
Hz, 2H), 2.08 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 193.8,
170.8, 169.2, 134.30, 134.27, 129.0, 128.0, 46.4, 43.1, 23.0. HRMS
+
(ESI) m/z: [M + Na]+ calcd for C12H14N2NaO3 257.0897; found
+
+ H]+ calcd for C26H23N2O3 411.1703; found, 411.1690.
257.0893.
2-(4-Isobutylphenyl)-N-(2-Oxo-2-Phenylethyl)Propanamide
(3bc). Eluent: petroleum ether/ethyl acetate (5:1). White solid (85.3
mg, 88%), mp: 81−82 °C. 1H NMR (600 MHz, CDCl3) δ 7.92−7.93
(m, 2H), 7.59 (t, J = 7.8 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.26 (d, J
= 8.4 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 6.51 (br s, 1H), 4.64−4.77
(m, 2H), 3.67 (q, J = 7.2 Hz, 1H), 2.46 (d, J = 6.6 Hz, 2H), 1.83−
1.89 (m, 1H), 1.56 (d, J = 7.2 Hz, 3H), 0.91 (d, J = 6.6 Hz, 6H).
(R)-4-((5S,8R,9S,10S,13R,14S,17R)-10,13-Dimethyl-3,7,12-Trioxo-
hexadecahydro-1H-Cyclopenta[a]Phenanthren-17-yl)-N-(2-Oxo-2-
Phenylethyl)Pentanamide (3aw). Eluent: petroleum ether/ethyl
1
acetate (1:1). White solid (101.3 mg, 65%), mp: 189−190 °C. H
NMR (400 MHz, CDCl3) δ 7.97−7.99 (m, 2H), 7.62 (t, J = 7.2 Hz,
1H), 7.50 (t, J = 7.6 Hz, 2H), 6.67 (t, J = 4.0 Hz, 1H), 4.77 (d, J = 4.4
Hz, 2H), 2.82−2.95 (m, 3H), 2.11−2.46 (m, 10H), 1.81−2.04 (m,
H
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
13C{1H} NMR (150 MHz, CDCl3) δ 194.2, 174.6, 140.8, 138.2,
2,5-Diphenyloxazole (4). Eluent: petroleum ether/ethyl acetate
(5:1). Yellowish solid (389.1 mg, 88%), mp: 73−74 °C. H NMR
(400 MHz, CDCl3) δ 8.08−8.11 (m, 2H), 7.69−7.72 (m, 2H), 7.40−
7.49 (m, 6H), 7.32 (tt, J1 = 7.2 Hz, J2 = 2.0 Hz, 1H). 13C{1H} NMR
(100 MHz, CDCl3) δ 161.2, 151.3, 130.3, 129.0, 128.9, 128.5, 128.1,
127.5, 126.3, 124.2, 123.5. HRMS (ESI) m/z: [M + H]+ calcd for
C15H12NO+ 222.0913; found, 222.0914.
1
134.4, 134.1, 129.7, 128.9, 127.9, 127.4, 46.7, 46.5, 45.1, 30.2, 22.4,
+
18.5. HRMS (ESI) m/z: [M + Na]+ calcd for C21H25NNaO2
346.1778; found, 346.1766.
2-(1,8-Diethyl-1,3,4,9-Tetrahydropyrano[3,4-b]Indol-1-yl)-N-(2-
Oxo-2-Phenylethyl)Acetamide (3bd). Eluent: petroleum ether/ethyl
1
acetate (3:1). White solid (87.3 mg, 72%), mp: 195−196 °C. H
NMR (600 MHz, CDCl3) δ 9.51 (s, 1H), 7.97 (d, J = 7.8 Hz, 2H),
7.62 (t, J = 7.8 Hz, 1H), 7.49 (t, J = 7.8 Hz, 3H), 7.34 (d, J = 7.8 Hz,
1H), 7.03 (t, J = 7.2 Hz, 1H), 6.97 (d, J = 7.2 Hz, 1H), 4.74 (qd, J1 =
19.2 Hz, J2 = 4.8 Hz, 2H), 4.11 (t, J = 5.4 Hz, 2H), 3.06 (d, J = 15.6
Hz, 1H), 2.97 (d, J = 15.6 Hz, 1H), 2.79−2.92 (m, 4H), 2.11−2.17
(m, 1H), 2.00−2.06 (m, 1H), 1.30 (t, J = 7.8 Hz, 3H), 0.89 (t, J = 7.8
Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 194.0, 171.4, 136.0,
134.8, 134.4, 134.2, 129.0, 128.0, 126.9, 126.3, 120.2, 119.5, 115.9,
108.1, 75.6, 60.8, 46.5, 44.6, 31.0, 24.1, 22.3, 13.9, 7.8. HRMS (ESI)
Synthesis of N-(2-Oxo-1-Phenoxy-2-Phenylethyl)Benzamide (5)
from 3a. To a solution of N-(2-oxo-2-phenylethyl)benzamide (3a,
120 mg, 0.5 mmol) in ethyl acetate (3 mL) were added with phenol
(236 mg, 2.5 mmol), TBAI (37 mg, 0.1 mmol), and TBHP (0.23 mL,
1.75 mmol, 70% aqueous solution).9 The resulting mixture was stirred
at 80 °C (oil bath) for 20 min. Upon completion, it was cooled to
room temperature, quenched with a saturated aqueous solution of
Na2S2O3 (10 mL), and extracted with ethyl acetate. The organic layer
was dried over anhydrous Na2SO4, filtered, and concentrated under a
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel with petroleum ether/ethyl acetate (20:1) to give
5.
+
m/z: [M + Na]+ calcd for C25H28N2NaO3 427.1992; found,
427.1977.
2-(1-(4-Chlorobenzoyl)-5-Methoxy-2-Methyl-1H-Indol-3-yl)-N-(2-
Oxo-2-Phenylethyl)Acetamide (3be). Eluent: petroleum ether/ethyl
acetate (1:1). Yellowish solid (109.5 mg, 77%), mp: 108−109 °C. 1H
NMR (600 MHz, CDCl3) δ 7.90 (d, J = 7.8 Hz, 2H), 7.70 (d, J = 8.4
Hz, 2H), 7.58 (t, J = 7.2 Hz, 1H), 7.44−7.48 (m, 4H), 6.99−6.71 (m,
2H), 6.81 (t, J = 4.2 Hz, 1H), 6.71 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H),
4.70 (d, J = 4.2 Hz, 2H), 3.83 (s, 3H), 3.72 (s, 2H), 2.38 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 193.9, 170.2, 168.3, 156.3,
N-(2-Oxo-1-Phenoxy-2-Phenylethyl)Benzamide (5). Eluent: pe-
troleum ether/ethyl acetate (20:1). White solid (115.9 mg, 70%), mp:
1
150−151 °C. H NMR (600 MHz, CDCl3) δ 8.04 (d, J = 7.8 Hz,
2H), 7.87 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 9.0 Hz, 1H), 7.62 (t, J = 7.2
Hz, 1H), 7.53 (t, J = 7.2 Hz, 1H), 7.43−7.49 (m, 4H), 7.30−7.34 (m,
3H), 7.23 (d, J = 8.4 Hz, 2H), 7.05 (t, J = 7.2 Hz, 1H). 13C{1H}
NMR (150 MHz, CDCl3) δ 191.3, 167.3, 155.7, 134.5, 133.5, 133.2,
132.4, 129.9, 129.5, 129.0, 128.8, 127.4, 122.9, 116.7, 76.1. HRMS
139.4, 136.1, 134.3, 134.1, 133.8, 131.3, 131.1, 130.4, 129.2, 128.9,
127.9, 115.2, 112.9, 112.4, 100.9, 55.7, 46.4, 32.1, 13.5. HRMS (ESI)
+
(ESI) m/z: [M + Na]+ calcd for C21H17NNaO3 354.1101; found,
+
m/z: [M + Na]+ calcd for C27H23ClN2NaO4 497.1239; found,
354.1110.
Synthesis of 4,5-Diphenyl-2-(2-(5-Phenyloxazol-2-yl)Ethyl)-
Oxazole (6) from 3bb. To a round-bottom flask equipped with a
stir bar were added 3-(4,5-diphenyloxazol-2-yl) -N-(2-oxo-2-
phenylethyl)propanamide (3bb, 205 mg, 0.5 mmol) and acetic
anhydride (1 mL) followed by dropwise addition of conc. H2SO4 (10
μL, 0.18 mmol) with stirring.1c It was then stirred at 90 °C (oil bath)
under air and monitored by TLC. Upon completion, it was cooled to
room temperature and diluted with water and DCM. The organic
layer was separated and washed with saturated sodium bicarbonate,
brine, and then dried over sodium sulfate, filtered, and concentrated
under a reduced pressure. The crude mixture was purified on a silica
gel column, eluting with petroleum ether/ethyl acetate (5:1) to yield
6.
497.1230.
(E)-2-(5-Fluoro-2-Methyl-1-(4-(Methylsulfinyl)Benzylidene)-1H-
Inden-3-yl)-N-(2-Oxo-2-Phenylethyl)Acetamide (3bf). Eluent: petro-
leum ether/ethyl acetate (1:3). Yellow solid (110.7 mg, 78%), mp:
169−170 °C. 1H NMR (600 MHz, CDCl3) δ 7.81 (dd, J1 = 8.4 Hz, J2
= 1.2 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 7.8 Hz, 2H), 7.48
(t, J = 7.8 Hz, 1H), 7.35 (t, J = 8.4 Hz, 2H), 7.07−7.10 (m, 2H),
6.83−6.86 (m, 2H), 6.46 (td, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 4.63 (d, J
= 4.8 Hz, 2H), 3.52 (s, 2H), 2.71 (s, 3H), 2.17 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3) δ 194.1, 169.5, 163.4 (d,1JC‑F = 245.1 Hz),
146.6 (d,3JC‑F = 8.7 Hz), 145.5, 141.6, 139.5, 138.7, 134.3, 134.1,
132.5 (d,4JC‑F = 2.1 Hz), 130.3, 129.6 (d,4JC‑F = 2.1 Hz), 128.9, 128.6,
127.9, 123.85, 123.77 (d,3JC‑F = 8.9 Hz), 111.0 (d,2JC‑F = 23.0 Hz),
106.2 (d,2JC‑F = 23.0 Hz), 46.5, 43.8, 33.5, 10.6. 19F NMR (565
MHz,CDCl3) δ −112.45. HRMS (ESI) m/z: [M + Na]+ calcd for
4,5-Diphenyl-2-(2-(5-Phenyloxazol-2-yl)Ethyl)Oxazole (6). Elu-
ent: petroleum ether/ethyl acetate (5:1). Yellowish solid (147.0 mg,
75%), mp: 108−110 °C. 1H NMR (600 MHz, CDCl3) δ 7.64 (d, J =
7.2 Hz, 2H), 7.57 (m, 4H), 7.27−7.37 (m, 9H), 7.25 (s, 1H), 3.41 (t,
J = 13.2 Hz, 4H). 13C{1H} NMR (150 MHz, CDCl3) δ 162.4, 161.5,
151.4, 145.6, 135.3, 132.5, 129.0, 128.9, 128.7, 128.6, 128.5, 128.3,
128.14, 128.05, 128.0, 126.5, 124.1, 122.0, 25.8, 25.7. HRMS (ESI)
+
C28H24FNNaO3S 496.1353; found, 496.1346.
(8R,9S,13S,14S)-13-Methyl-17-Oxo-N-(2-Oxo-2-Phenylethyl)-
7,8,9,11,12,13,14,15,16,17-Decahydro-6H-Cyclopenta[a]-
Phenanthrene-3-Carboxamide (3bg). Eluent: petroleum ether/ethyl
acetate (1:1). White solid (89.7 mg, 72%), mp: 177−178 °C. H
NMR (400 MHz, CDCl3) δ 8.03−8.06 (m, 2H), 7.64−7.67 (m, 3H),
7.54 (t, J = 7.6 Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.26 (br s, 1H),
4.97 (d, J = 4.0 Hz, 2H), 2.97−3.01 (m, 2H), 2.45−2.56 (m, 2H),
2.36 (td, J1 = 10.8 Hz, J2 = 3.6 Hz, 1H), 1.98−2.21 (m, 4H), 1.62−
1.68 (m, 2H), 1.47−1.58 (m, 4H), 0.93 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3) δ 194.4, 167.4, 143.9, 137.1, 134.4, 134.3, 131.3, 129.0,
128.0, 127.9, 125.7, 124.4, 50.5, 47.9, 46.9, 44.6, 37.9, 35.8, 31.6, 29.3,
26.3, 25.6, 21.6, 13.8. HRMS (ESI) m/z: [M + Na]+ calcd for
1
+
m/z: [M + H]+ calcd for C26H21N2O2 393.1598; found, 393.1601.
Gram-Scale Preparation of 3a. To a reaction tube equipped with
a stir bar were charged (1-azidovinyl)benzene (1a, 0.87 g, 6 mmol),
benzoic acid (2a, 0.61 g, 5 mmol), and DCE (20 mL). The tube was
then sealed and stirred at 110 °C (oil bath) under air for 10 h. Upon
completion, it was cooled to room temperature and concentrated
under a reduced pressure. The residue was purified by silica gel
chromatography using petroleum ether/ethyl acetate (5:1) as an
eluent to afford product 3a (0.813 g, 66%).
+
C27H29NNaO3 438.2040; found, 438.2026.
Mechanism Studies. To a reaction tube equipped with a stir bar
were charged 1-(1-azidovinyl)-4-methoxybenzene (1d, 52.5 mg, 0.3
mmol), 1-(1-azidovinyl)-4-(trifluoromethy)benzene (1h, 64.0 mg, 0.3
mmol), benzoic acid (2a, 36.6 mg, 0.3 mmol), and DCE (3 mL). The
tube was then sealed and stirred at 110 °C (oil bath) under air for 10
h. Upon completion, it was cooled to room temperature and
concentrated under a reduced pressure. The residue was purified by
silica gel chromatography using petroleum ether/ethyl acetate (5:1)
as an eluent to afford N-(2-(4-methoxyphenyl)-2-oxoethyl)- benza-
mide (3d, 29.9 mg, 37%) and N-(2-oxo-2-(4-(trifluoromethyl)-
phenyl)ethyl)benzamide (3h, 22.1 mg, 24%). Thus, the ratio of 3d
to 3h was calculated as about 1.5:1.
Structural Elaborations of 3. Synthesis of 2,5-Diphenyloxazole
(4) from 3a. To a round-bottom flask equipped with a stir bar were
added N-(2-oxo-2-phenylethyl) benzamide (3a, 478 mg, 2 mmol) and
acetic anhydride (5 mL) followed by dropwise addition of conc.
H2SO4 (50 μL, 0.9 mmol) with stirring.1c It was then stirred at 90 °C
(oil bath) under air and monitored by TLC. Upon completion, it was
cooled to room temperature and diluted with water and DCM. The
organic layer was separated and washed with saturated sodium
bicarbonate, brine, and then dried over sodium sulfate, filtered, and
concentrated under a reduced pressure. The crude mixture was
purified on a silica gel column, eluting with petroleum ether/ethyl
acetate (5:1) to yield 4.
I
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
To a reaction tube equipped with a stir bar were charged 4-
methoxybenzoic acid (2d, 45.6 mg, 0.3 mmol), 4-(trifluoromethyl)-
benzoic acid (2i, 57.0 mg, 0.3 mmol), (1-azidovinyl)benzene (1a,
43.5 mg, 0.3 mmol), and DCE (3 mL). The tube was sealed and
stirred at 110 °C (oil bath) under air for 10 h. Upon completion, it
was cooled to room temperature and concentrated under a reduced
pressure. The residue was purified by silica gel chromatography using
petroleum ether/ethyl acetate (5:1) as an eluent to afford 4-methoxy-
N-(2-oxo-2-phenylethyl)benzamide (3u, 13.7 mg, 17%) and N-(2-
oxo-2- phenylethyl)-4-(trifluoromethyl)benzamide (3z, 48.8 mg,
53%). Thus, the ratio of 3u to 3z was calculated as about 1:3.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the National Natural Science
Foundation of China (NSFC) (21572047), Program for
Innovative Research Team in Science and Technology in
Universities of Henan Province (20IRTSTHN005), Key
Project of Science and Technology of Henan Province
(192102310412), and 111 Project (D17007) for financial
support.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01871.
■
REFERENCES
(1) (a) Biala
sı
■
̷
s, A.; Grembecka, J.; Krowarsch, D.; Otlewski, J.;
Potempa, J.; Mucha, A. Exploring the Sn Binding Pockets in
Gingipains by Newly Developed Inhibitors: Structure-Based Design,
Chemistry, and Activity. J. Med. Chem. 2006, 49, 1744−1753. (b) El-
Dahshan, A.; Al-Gharabli, S. I.; Radetzki, S.; Al-Tel, T. H.; Kumar, P.;
Rademann, J. Flexible, Polymer-Supported Synthesis of Sphingosine
Derivatives Provides Ceramides with Enhanced Biological Activity.
Bioorg. Med. Chem. 2014, 22, 5506−5512. (c) Robles, A. J.;
McCowen, S.; Cai, S.; Glassman, M.; Ruiz, F., II; Cichewicz, R. H.;
McHardy, S. F.; Mooberry, S. L. Structure−Activity Relationships of
New Natural Product-Based Diaryloxazoles with Selective Activity
against Androgen Receptor-Positive Breast Cancer Cells. J. Med.
Chem. 2017, 60, 9275−9289.
Copies of the NMR spectra of all products and the X-ray
crystal structure and data of 3w (CCDC 2010162)
(PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Xinying Zhang − Henan Key Laboratory of Organic Functional
Molecules and Drug Innovation, Collaborative Innovation
Center of Henan Province for Green Manufacturing of Fine
Chemicals, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, School of Chemistry and
Chemical Engineering, Henan Normal University, Xinxiang,
Henan 453007, China; orcid.org/0000-0002-3416-4623;
Email: xinyingzhang@htu.cn
(2) (a) Griesbeck, A. G.; Heckroth, H. Stereoselective Synthesis of
2-Aminocyclobutanols via Photocyclization of α-Amido Alkylaryl
Ketones: Mechanistic Implications for the Norrish/Y ang Reaction. J.
Am. Chem. Soc. 2002, 124, 396−403. (b) Nicolaou, K. C.; Hao, J.;
Reddy, M. V.; Rao, P. B.; Rassias, G.; Snyder, S. A.; Huang, X.; Chen,
D. Y. K.; Brenzovich, W. E.; Giuseppone, N.; Giannakakou, P.;
O’Brate, A. Chemistry and Biology of Diazonamide A: Second Total
Synthesis and Biological Investigations. J. Am. Chem. Soc. 2004, 126,
12897−12906. (c) Frantz, D. E.; Morency, L.; Soheili, A.; Murry, J.
A.; Grabowski, E. J. J.; Tillyer, R. D. Synthesis of Substituted
Imidazoles via Organocatalysis. Org. Lett. 2004, 6, 843−846.
(d) Chen, W.; Cui, J.; Zhu, Y.; Hu, X.; Mo, W. DBU-Promoted
Cyclization of ortho-(3-Hydroxy-1- alkynyl)benzamide: Synthesis of
trans-3,4-Dihydroisoquinolin-1(2H)-ones and (E)-4-(1- Alkenyl)-
isoquinolin-1(2H)-ones. J. Org. Chem. 2012, 77, 1585−1591.
(e) Viviano, M.; Milite, C.; Rescigno, D.; Castellano, S.; Sbardella,
G. A Continuous-flow Synthesis of 1,4-Benzo- diazepin-5-ones,
Privileged Scaffolds for Drug Discovery. RSC Adv. 2015, 5, 1268−
1273. (f) Zhou, R.-R.; Cai, Q.; Li, D.-K.; Zhuang, S.-Y.; Wu, Y.-D.;
Wu, A.-X. Acid-Promoted Multicomponent Tandem Cyclization to
Synthesize Fully Substituted Oxazoles via Robinson−Gabriel-Type
Reaction. J. Org. Chem. 2017, 82, 6450−6456. (g) Dowling, M. S.;
Jiao, W.; Hou, J.; Jiang, Y.; Gong, S. Modular Synthesis of 3,6-
Disubstituted-1,2,4-triazines via the Cyclodehydration of β-Keto-N-
acylsulfonamides with Hydrazine Salts. J. Org. Chem. 2018, 83, 4229−
4238.
Xuesen Fan − Henan Key Laboratory of Organic Functional
Molecules and Drug Innovation, Collaborative Innovation
Center of Henan Province for Green Manufacturing of Fine
Chemicals, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, School of Chemistry and
Chemical Engineering, Henan Normal University, Xinxiang,
Henan 453007, China; orcid.org/0000-0002-2040-6919;
Email: xuesen.fan@htu.cn
Authors
Cai Gao − Henan Key Laboratory of Organic Functional
Molecules and Drug Innovation, Collaborative Innovation
Center of Henan Province for Green Manufacturing of Fine
Chemicals, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, School of Chemistry and
Chemical Engineering, Henan Normal University, Xinxiang,
Henan 453007, China
Qianting Zhou − Henan Key Laboratory of Organic Functional
Molecules and Drug Innovation, Collaborative Innovation
Center of Henan Province for Green Manufacturing of Fine
Chemicals, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, School of Chemistry and
Chemical Engineering, Henan Normal University, Xinxiang,
Henan 453007, China
Li Yang − Henan Key Laboratory of Organic Functional
Molecules and Drug Innovation, Collaborative Innovation
Center of Henan Province for Green Manufacturing of Fine
Chemicals, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, School of Chemistry and
Chemical Engineering, Henan Normal University, Xinxiang,
Henan 453007, China
(3) (a) Wilde, M. M. D.; Gravel, M. Bis(amino)cyclopropenylidene
(BAC) Catalyzed Aza-Benzoin Reaction. Org. Lett. 2014, 16, 5308−
5311. (b) Zheng, G.; Li, Y.; Han, J.; Xiong, T.; Zhang, Q. Radical
Cascade Reaction of Alkynes with N-Fluoroarylsulfonimides and
Alcohols. Nat. Commun. 2015, 6, 7011−7042. (c) Wende, R. C.;
Seitz, A.; Niedek, D.; Schuler, S. M. M.; Hofmann, C.; Becker, J.;
Schreiner, P. R. T. The Enantioselective Dakin−West Reaction.
Angew. Chem., Int. Ed. 2016, 55, 2719−2723. (d) Holthusen, K.;
̀
Leitner, W.; Francio, G. Synthesis of α-Amidoketones from Vinyl
Esters via a Catalytic/Thermal Cascade Reaction. J. Org. Chem. 2016,
81, 4823−4828. (e) Kim, Y.; Pak, H. K.; Rhee, Y. H.; Park, J. Catalytic
Transformation of Esters of 1,2-Azido Alcohols into α-Amido
Ketones. Chem. Commun. 2016, 52, 6549−6552. (f) Wu, F.; Zhang,
M.; Zhou, W.; Chen, W.; Liu, M.; Wu, H. Copper(I)- Catalyzed N−
O Bond Formation through Vinyl Nitrene Mediated Pathway under
Mild Conditions. J. Org. Chem. 2018, 83, 5999−6005.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01871
J
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(4) (a) Zhang, M.; Xie, J.; Zhu, C. A General Deoxygenation
Approach for Synthesis of Ketones from Aromatic Carboxylic Acids
and Alkenes. Nat. Commun. 2018, 9, 3517−3527. (b) Shi, X.; Chen,
X.; Wang, M.; Zhang, X.; Fan, X. Regioselective Synthesis of Acylated
N-Heterocycles via the Cascade Reactions of Saturated Cyclic Amines
with 2-Oxo-2-arylacetic Acids. J. Org. Chem. 2018, 83, 6524−6533.
(c) Shi, X.; He, Y.; Zhang, X.; Fan, X. FeCl3−Catalyzed Cascade
Reactions of Cyclic Amines with 2-Oxo-2-arylacetic Acids toward
Furan-2(5H)-one Fused N,O-Bicyclic Compounds. Adv. Synth. Catal.
2018, 360, 261−266. (d) Zhao, Y.- L.; Tang, Y.-Q.; Fei, X.-H.; Yang,
F.-F.; Cao, Z.-X.; Duan, D.-Z.; Zhao, Q.-J.; Yang, Y.-Y.; Zhou, M.; He,
B. Direct C(sp3)−H Acyloxylation of Indolin-3-ones with Carboxylic
Acids Catalysed by KI. Green Chem. 2020, 22, 2354−2358.
(e) Cianfanelli, M.; Olivo, G.; Milan, M.; Gebbink, R. J. M. K.;
Ribas, X.; Bietti, M.; Costas, M. Enantioselective C−H Lactonization
of Unactivated Methylenes Directed by Carboxylic Acids. J. Am.
Chem. Soc. 2020, 142, 1584−1593. (f) Uttry, A.; van Gemmeren, M.
Direct C(sp3)−H Activation of Carboxylic Acids. Synthesis 2020, 52,
479−488.
(5) (a) Oh, B. H.; Nakamura, I.; Yamamoto, Y. Palladium-Catalyzed
Ring-Opening Reaction of Methyleneaziridines with Carboxylic
Acids: Synthesis of α-Amidoketones. J. Org. Chem. 2004, 69, 2856−
2858. (b) Xu, F.; Si, X.-J.; Song, Y.-Y.; Wang, X.-D.; Liu, C.-S.; Geng,
P.-F.; Du, M. Palladium-Catalyzed C−N Bond Cleavage of 2H-
Azirines for the Synthesis of Functionalized α-Amido Ketones. J. Org.
Chem. 2019, 84, 2200−2208. (c) De, A.; Santra, S.; Zyryanov, G. V.;
Majee, A. Self-Catalyzed Rapid Synthesis of N-Acylated/N-Formy-
lated α-Aminoketones and N-Hydroxymethylated Formamides from
3-Aryl-2H-Azirines and 2-Me/Ph-3-Aryl-2H- Azirines. Org. Lett. 2020,
22, 3926−3930.
(6) (a) Wang, Z.; Chen, G.; Zhang, X.; Fan, X. Synthesis of 3-
Acylquinolines Through Cu-catalyzed Double C(sp3)−H Bond
Functionalization of Saturated Ketones. Org. Chem. Front. 2017, 4,
612−616. (b) Li, B.; Zhang, B.; Zhang, X.; Fan, X. Regio-Selective
Synthesis of Diversely Substituted Benzo[a]carbazoles Through
Rh(III)-Catalyzed Annulation of 2-Arylindoles with α-Diazo Carbon-
yl Compounds. Chem. Commun. 2017, 53, 1297−1300. (c) Xu, Y.; Li,
B.; Zhang, X.; Zhang, X.; Fan, X. One-Pot Synthesis of Fused N,O-
Heterocycles through Rh(III) Catalyzed Cascade Reactions of
Aromatic/Vinylic N-Alkoxy-Amides with 4-Hydroxy-2- Alkynoates.
Adv. Synth. Catal. 2018, 360, 2613−2620. (d) Xu, Y.; Zhang, L.; Liu,
M.; Zhang, X.; Fan, X. Synthesis of Benzoazepine Derivatives via
Rh(III)-Catalyzed Inert C(sp2)−H Functionalization and [4 + 3]
Annulation. Org. Biomol. Chem. 2019, 17, 8706−8710. (e) Gao, C.;
Ben Li; Geng, X.; Zhou, Q.; Zhang, X.; Fan, X. Two Birds With One
Stone: One-pot Simultaneous Synthesis of 2,2,2-Trifluoroethylphe-
nanthridines and Benzochromenones Featuring the Utilization of the
Byproduct of Togni’s Reagent. Green Chem. 2019, 21, 5113−5117.
(f) Guo, C.; Li, Bin.; Liu, H.; Zhang, X.; Zhang, X.; Fan, X. Synthesis
of Fused or Spiro Polyheterocyclic Compounds via the Dehydrogen-
ative Annulation Reactions of 2-Arylindazoles with Maleimides. Org.
Lett. 2019, 21, 7189−7193. (g) Xu, Y.; Shen, M.; Zhang, X.; Fan, X.
Selective Synthesis of Pyrazolo[1,2-a]pyrazolones and 2-Acylindoles
via Rh(III)-Catalyzed Tunable Redox-Neutral Coupling of 1-Phenyl-
pyrazolidinones with Alkynyl Cyclobutanols. Org. Lett. 2020, 22,
4697−4702, DOI: 10.1021/acs.orglett.0c01475.
Synthesis of Functionalized Phenathridine-6-carbonitriles via Copper-
catalyzed Annulation of Vinyl Azides and NaN3 in the Presence of
PhI(OAc)2. ChemistrySelect 2018, 3, 7354−7357. (c) Wang, X.; Li, Y.;
Qiu, G.; Wu, J. Synthesis of 6-(Sulfonylmethyl)phenanthridines
Through a Reaction of Aryldiazonium Tetrafluoroborates, Sulfur
Dioxide, and Vinyl Azides. Org. Chem. Front. 2018, 5, 2555−2559.
(d) Ning, Y.; Mekareeya, A.; Babu, K. R.; Anderson, E. A.; Bi, X.
Silver- Catalyzed C- to N-Center Remote Arene Migration. ACS
Catal. 2019, 9, 4203−4210. (e) Mulina, O. M.; Zhironkina, N. V.;
Paveliev, S. A.; Demchuk, D. V.; Terent’ev, A. O. Electrochemically
Induced Synthesis of Sulfonylated N-Unsubstituted Enamines from
Vinyl Azides and Sulfonyl Hydrazides. Org. Lett. 2020, 22, 1818−
1824. (f) More, A. A.; Szpilman, A. M. Indium(III) Catalyzed
Reactions of Vinyl Azides and Indoles. Org. Lett. 2020, 22, 3759−
3764. (g) Qin, C.; Feng, P.; Ou, Y.; Shen, T.; Wang, T.; Jiao, N.
Selective Csp2-Csp Bond Cleavage: The Nitrogenation of Alkynes to
Amides. Angew. Chem., Int. Ed. 2013, 52, 7850−7854.
(9) Xu, W.; Nachtsheim, B. J. TBAI-Catalyzed Oxidative Cross-
Coupling of Phenols and 2-Amino- acetophenones. Org. Lett. 2015,
17, 1585−1588.
(10) (a) Allred, T. K.; Manoni, F.; Harran, P. G. Exploring the
Boundaries of “Practical”: De Novo Syntheses of Complex Natural
Product- Based Drug Candidates. Chem. Rev. 2017, 117, 11994−
12051. For some interesting bisoxazole derivatives, see: (b) Anderson,
Z. J.; Fox, D. J. Total Synthesis of the Azolemycins. Org. Biomol.
Chem. 2016, 14, 1450−1454. (c) Knowles, R. R.; Carpenter, J.;
Blakey, S. B.; Kayano, A.; Mangion, I. K.; Sinz, C. J.; MacMillan, D.
W. C. Total Synthesis of Diazonamide A. Chem. Sci. 2011, 2, 308−
311.
(11) Qin, H.-T.; Wu, S.-W.; Liu, J.-L.; Liu, F. Photoredox-Catalysed
Redox-Neutral Trifluoromethylation of Vinyl Azides for the Synthesis
of α-Trifluoromethylated Ketones. Chem. Commun. 2017, 53, 1696−
1699.
(12) Moriya, T.; Takabe, S.; Maeda, S.; Matsumoto, K.; Takashima,
K.; Mori, T.; Takeyama, S. Synthesis and Hypolipidemic Activities of
5-Thienyl-4-oxazoleacetic Acid Derivatives. J. Med. Chem. 1986, 29,
333−341.
́
(13) Galvez, A. O.; Schaack, C. P.; Noda, H.; Bode, J. W.
Chemoselective Acylation of Primary Amines and Amides with
Potassium Acyltrifluoroborates under Acidic Conditions. J. Am. Chem.
Soc. 2017, 139, 1826−1829.
(7) (a) Ni, H.; Zhang, G.; Yu, Y. Vinyl Azides as Versatile Synthons
for the Synthesis of Nitrogen-containing Heterocycles. Curr. Org.
Chem. 2015, 19, 776−789. (b) Fu, J.; Zanoni, G.; Anderson, E. A.; Bi,
X. α-Substituted Vinyl Azides: an Emerging Functionalized Alkene.
Chem. Soc. Rev. 2017, 46, 7208−7228. (c) Hayashi, H.; Kaga, A.;
Chiba, S. Application of Vinyl Azides in Chemical Synthesis: A Recent
Update. J. Org. Chem. 2017, 82, 11981−11989. (d) Yan, J.; Ji, X.;
Hua, S.; Wang, J. Recent Advances of α-Aryl Vinyl Azides in Nitrogen
Heterocycle Synthesis. Chin. J. Org. Chem. 2018, 38, 791−801.
(8) (a) Jie, L.; Wang, L.; Xiong, D.; Yang, Z.; Zhao, D.; Cui, X.
Synthesis of 2-Arylindoles through Pd(II)-Catalyzed Cyclization of
Anilines with Vinyl Azides. J. Org. Chem. 2018, 83, 10974−10984.
(b) Zhou, B.; Zheng, L.; Xu, Z.; Jin, H.; Wu, Q.; Li, T.; Liu, Y.
K
https://dx.doi.org/10.1021/acs.joc.0c01871
J. Org. Chem. XXXX, XXX, XXX−XXX