pubs.acs.

org/joc Article

1
O2 Mediated Conversion of β‑Enaminonitriles to α‑Keto Amides
Photosensitized by Recyclable H2TPP in Visible Light
Rohit Kumar, Nitika Grover, and Nidhi Jain*
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ABSTRACT: We report a one-step approach for the conversion of

β-enaminonitriles to synthetically versatile α-keto amides in
Downloaded via INDIAN INST OF TECH ROORKEE on April 22, 2024 at 07:36:18 (UTC).

moderate to high yields under visible light irradiation photo-

sensitized by porphyrins. The method is mild, cost-effective, and
sustainable and requires air as the sole reagent/oxidant. The
reaction is believed to proceed via an ene-type pathway initiated by
1
O2, followed by dehydration, imine hydrolysis, and subsequent
nucleophilic substitution of the cyanide group by amine. The
method offers a broad substrate scope and has also been extended
for synthesis of α-keto esters with aliphatic alcohols as nucleophiles.
The porphyrin recovered after the reaction can be reused multiple
times.

■ INTRODUCTION
Molecular oxygen (3O2) is a paramagnetic biradical molecule
that plays a vital role in sustaining life on Earth. Because of its
ground-state electronic configuration, most chemical reactions
involving 3O2 are spin-forbidden, which reduces its reactivity
and therefore its applicability in driving synthetic reactions.1
The excited state of oxygen which is the more reactive singlet
oxygen form, 1O2 (1Δg), exhibits antiparallel spin in the same
antibonding orbital that can be accessed by altering its
electronic configuration.2 Photosensitization is one of the
most common techniques for generating 1O2, where a
photosensitizer absorbs visible light and undergoes intersystem
crossing (ISC), transferring its energy to the surrounding 3O2
to generate the reactive 1O2.3 Porphyrin and its analogs
represent a unique class of organic photosensitizers that can
generate 1O2 with a high quantum yield under white light
irradiation.4 Furthermore, the 1O2 quantum yield and excited
triplet state lifetime can be tuned by peripheral and core
functionalization of tetrapyrroles.5 While porphyrin-based
photosensitizers are extensively used in photodynamic therapy,
their application in mediating synthetic organic transforma-
tions still holds massive exploratory potential.6
The high reactivity of singlet oxygen makes it unarguably a
sustainable reagent in organic synthesis.7 The pioneer work of
Foote and Wexler, and Corey and Taylor describes various
classes of reactions involving singlet oxygen, including
oxidation at the heteroatom, [4 + 2] and [2 + 2]
cycloadditions, and Schenck−ene reactions.8 The seminal
work on photolysis of enamine and enaminones in the
presence of singlet oxygen was reported in the 1970s, in
which the oxidative cleavage of the C�C bond of enamines to
generate two carbonyl compounds was demonstrated. This was
later followed by many similar reports.9 Generally, in the
presence of conventional oxidants, such as potassium
permanganate10 and H2O2,11 enamines form amides. However,
an alternative reactivity pattern is observed with electron-
deficient enamines in the presence of 1O2. In 2014, Fan and Li
demonstrated a ruthenium and visible-light-promoted reaction
of enamino ketones with methanol in the presence of air to
yield quaternary amino acid derivatives. This involved an ene-
type pathway with 1O2, followed by 1,2-acyl migration
(Scheme 1i).12a Similar transformation of enamino ketones
was separately documented using the platinum complex as well
as chlorophyll in visible light (Scheme 1ii and iii).12bc A recent
article from Wu and co-workers demonstrated a Lewis acid-
mediated reaction of electron-deficient enamines with 1O2,
resulting in the formation of pyrrolin-4-ones (Scheme 1iv).13
Despite considerable progress in enamine chemistry, the
reactivity of β-enaminonitriles remains elusive and little
explored especially with singlet oxygen. Continuing our efforts
in 1O2-mediated transformations in visible light,14 we explored
the reactivity of β-enaminonitriles (1) as substrates and free-
base meso-tetraphenylporphyrin as the photosensitizer since it
is the simplest, cheapest, and readily available porphyrin.4bc We
envisaged that the double bond reactivity and good leaving
Received: December 26, 2023
Revised: February 24, 2024
Accepted: March 5, 2024
Published: March 19, 2024

© 2024 American Chemical Society https://doi.org/10.1021/acs.joc.3c02965

4722 J. Org. Chem. 2024, 89, 4722−4732
The Journal of Organic Chemistry
Scheme 1. Reaction of Electron-Deficient Enamino Ketones
with Singlet Oxygen in Visible Light
group ability of the cyanide group in β-enaminonitriles might
foster unique and useful synthetic ability in visible light.
■ RESULTS AND DISCUSSION
We started our investigation with a reaction of 3-(methyl-
amino)-3-phenylacrylonitrile (1a) in the presence of a catalytic
amount of 5,10,15,20-tetraphenylporphyrin H2TPP in CH3CN
at room temperature in open air. Pleasantly, irradiation of
enamine 1a under a 10 W green LED (λmax = 522 nm) for 20 h
gave N-methyl-2-oxo-2-phenylacetamide (2a) in 72% yield
(Table 1, entry 1). The conventional methods to access α-keto
amides include oxidative amidation of terminal alkynes,
oxidation of α-methylene group of amides, and oxidative
coupling of aldehydes and isocyanides.15 However, most of
these methods suffer from moisture sensitivity, formation of
undesired self-coupled products, and foul-smelling reactants
like isocyanides. Direct photochemical conversion of β-
enaminonitriles to α-keto amides under mild conditions
looked promising and straightforward. Hence, we decided to
optimize the reaction conditions to improve the product yield.
Cognizant of the broad absorption range (400−700 nm) of
porphyrin derivatives, we decided to use white light for the
reaction. In a white CFL lamp, a substantial increase in the
yield was observed, and 92% of 2a was isolated (Table 1, entry
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2). Since H2TPP has little solubility in CH3CN, other solvents,
such as CHCl3, CH2Cl2, toluene, N,N-dimethylformamide
(DMF), and dimethyl sulfoxide (DMSO), were screened, in
which it has higher solubility. While lower yields were obtained
in CHCl3, CH2Cl2, and toluene (Table 1, entries 3−5), no
product formation occurred in more polar solvents like DMF
and DMSO (Table 1, entries 6 and 7). Further, in polar protic
solvents like MeOH (Table 1, entry 8), the reaction did not
take place at all, suggesting CH3CN to be the medium of
choice for the transformation. The yield of the reaction
increased slightly when molecular oxygen was employed
instead of air (Table 1, entry 9). Enamine 1a remained
unreacted when the reaction was performed under an inert
nitrogen atmosphere (Table 1, entry 10). Control experiments
in the absence of photocatalyst as well as under thermal
heating were performed, but the unreacted starting material
was recovered in either case (Table 1, entries 11−13). These
findings clearly indicate the crucial role of oxygen, light, and
the photocatalyst in the reaction.
It was found that the product yield was nearly the same
when Ru(bpy)3Cl2·6H2O was used instead of H2TPP (see the
Supporting Information (SI), Table S1, entry 1). Reaction in
the presence of other photocatalysts, such as eosin-Y, Rose
Bengal, Ir(ppy)3, (Mes-Acr)+(ClO4)−, and rhodamine-B, gave
lower product yields (see the SI, Table S1, entries 2−6).
Further, the reaction did not proceed in a blue LED having
λmax = 457 nm (Table 1, entry 14).
It is well-known that peripheral substitution on porphyrin
alters its photophysical properties. To determine the
substituent effect on the catalytic efficiency of porphyrin,
various mixed meso-substituted porphyrins were screened, and
2a was isolated in 81−88% yields under the optimized reaction
conditions (see the SI, Table S2, entries 2−6). As expected, no
product formation was observed with CuTPP and NiTPP as
catalysts (see the SI, Table S2, entries 7 and 8). Recycling
photocatalysts is environmentally and economically advanta-
geous as it minimizes waste generation and the constant needs
to procure new catalysts. To this end, we recovered and reused
H2TPP up to five consecutive cycles (see the SI, Figure S3).
The porphyrin remained stable after the reaction and no
substantial decrease in the yield of 2a was observed. Since
H2TPP is metal-free, cheap, reusable, and atom-economical, it
was chosen for further reactions.
With the optimized reaction conditions in hand, we
surveyed various β-enaminonitriles to analyze the scope of
the test reaction (Scheme 2). A reaction of 3-phenyl-3-
(phenylamino)acrylonitrile (1b) yielded 2b in 71% yield. The
para-methoxy-, para-bromo-, and para-fluoro-substituted 3-
phenyl-3-(phenylamino)acrylonitrile afforded the correspond-
ing products 2c, 2d, and 2e in 77, 75, and 61% yields,
respectively. The meta-bromo- and meta-chloro-substituted β-
enaminonitriles furnished the corresponding products 2f and
2g in 71 and 69% yields, respectively. Substituents at the ortho-
position of the phenyl ring (bromo, chloro, and methyl) gave
the corresponding products 2h−2j in moderate yields (65−
73%). 3,4-Disubstitution on the N-phenyl ring lowered the
yield. For example, compounds 2k and 2l were obtained in 63
and 69% yields when 3-(3,4-dimethylphenylamino)-3-phenyl-
acrylonitrile (1k) and 3-(3,4-dimethoxylphenylamino)-3-phe-
nylacrylonitrile (1l) were subjected to optimized reaction
conditions. Overall, we observed that the electronic nature of
the substituent on the N-phenyl ring did not exert a substantial
effect on reaction progress. The molecular structure of 2k was
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The Journal of Organic Chemistry
Table 1. Optimized Reaction Conditionsa
entry photocatalyst
c
1 H2TPP
2 H2TPP
3 H2TPP
4 H2TPP
5 H2TPP
6 H2TPP
7 H2TPP
8 H2TPP
9d H2TPP
10e H2TPP
11 - CH3CN
12f H2TPP
13g H2TPP
14h H2TPP
a
Reaction conditions: 1a (0.2 mmol) and photocatalyst (2.0 mol %) in solvent (2.0 mL) irradiated with white light under air atmosphere for 20 h.
b
Isolated yield. cUnder green LED irradiation. dUnder O2. eUnder a N2 atmosphere. fIn heating (up to 75 °C). gIn the dark. hUnder blue LED
irradiation.
confirmed by single-crystal X-ray diffraction (SCXRD) analysis
(see the SI, Figure S2). Next, we investigated the reactivity of
different N-alkyl enaminonitriles. A slight reduction in isolated
yields was observed when enaminonitriles were substituted
with longer alkyl chains, such as butyl, hexyl, octyl, hexadecyl,
and octadecyl (2m−2q), respectively. On the contrary, the size
of the cyclic alkyl ring did not impact the reaction rate, and
similar yields were obtained for the products 2r−2t. When the
reaction was scaled to a gram level using 10.0 mmol of 1a, we
successfully obtained the desired product 2a in 81% yield (1.32
g). To further understand the scope of the reaction, various
aryl enaminonitriles (1u−1z) with substitution in the aryl ring
were explored. It was observed that meta- and ortho-substituted
derivatives gave lower product yields compared to para-
substitution on the aryl ring. For example, 87% yield was
observed for 2v, which had a para-Cl substitution, whereas
meta-Cl- and ortho-Cl-substituted keto amides, 2y and 2z, were
obtained in 72 and 65% yields, respectively.
Mechanistic Studies. Control experiments were per-
formed to get some insight into the reaction mechanism. As
discussed in Table 1, the reaction did not work in the absence
of light, photocatalyst, and oxygen/air. To determine if the
dioxygen activation under visible light conditions took place
via SET from the photocatalyst to form O2•− or involved
reactive 1O2 through an energy transfer (ET) pathway,
quenchers were added. It was observed that the addition of
2.0 equiv of TEMPO did not inhibit the reaction, and 80% of
2a was isolated (see the SI, Scheme S1). This suggested that
free-radical species were not formed in the reaction. Further,
the reaction was found to quench completely on addition of
2.0 equiv of 1,3-diphenylisobenzofuran (DPBF) and high-
resolution mass spectrometry (HRMS) of this reaction mixture
exhibited a peak corresponding to 1,2-phenylenebis-
(phenylmethanone) (3), confirming the formation of 1O2 in
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solvent yieldb [%]
CH3CN 72
CH3CN 92
CHCl3 73
CH2Cl2 65
toluene 64
DMF NR
DMSO NR
MeOH NR
CH3CN 96
CH3CN NR
NR
CH3CN NR
CH3CN NR
CH3CN NR
the reaction (see the SI, Scheme S2, Figure S4). Next, the
fluorescence (FL) emission quenching experiments of H2TPP
were performed. It was observed that the emission intensity
did not change when 1a at varied concentrations was
introduced into the N2-saturated solution of H2TPP. However,
a dramatic quenching in the FL intensity was observed when a
solution of H2TPP was saturated with oxygen or air (see the
SI, Figure S5). The results pointed out toward the interaction
of visible-light-excited photocatalyst with dioxygen instead of
enamine. Electron spin resonance (ESR) measurements (see
the SI, Figure S6) showed a sharp signal for the 1O2-TEMP
adduct when a solution of H2TPP and TEMP was irradiated
with a white LED. The signal disappeared upon addition of 1a,
indicating the interaction of 1O2 with enamine in acetonitrile
(ACN). DMPO instead of TEMP gave no superoxide anion
(O2•−) signal, regardless of the addition of 1a. Control
experiment with air-saturated ACN solution of H2TPP (0.6
mM) and TEMP (0.6 mM) in the dark did not show any signal
in ESR. Further, cyclic voltammetry (CV) results also ruled out
the possibility of SET since the redox potential of 1a (E1a+/1a =
1.39 V vs SCE) is higher than the excited state potential of
TPP (ETPP*/TPP− = 0.81 V vs SCE) and it is not possible to go
through an oxidative quenching cycle with TPP (ETPP+/TPP =
0.95 V vs SCE)12a (see the SI, Figure S7). All of these
experiments revealed that O2 interacted directly with H2TPP
and initiated the reaction via 1O2 generation and not via a
superoxide anion. Based on the experimental evidence and
literature reports,4,12,16 a plausible mechanism has been
proposed in Scheme 3. On absorbing visible light, H2TPP
gets excited to its singlet excited state (1H2TPP*) and loses
energy instantaneously via intersystem crossing (ISC) to
generate a triplet excited state (3H2TPP*). The O2 in the
reaction mixture undergoes intermolecular energy transfer with
3
H2TPP*, resulting in the formation of reactive 1O2 and
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Scheme 2. Substrate Scopec,c

a
Reaction Conditions: 1 (0.2 mmol), H2TPP (2.0 mol %), CH3CN (2.0 mL), 27 W white CFL, rt, air, 20 h; bGram-scale synthesis. cIsolated
yields.

Scheme 3. Proposed Reaction Mechanism
regenerating ground-state H2TPP. This is followed by an ene-
type reaction between 1a and 1O2, resulting in the formation of
intermediate I.12 Dehydration of I gives an imine intermediate
II, confirmed by HRMS analysis of the reaction mixture (see
4725
the SI, Scheme S3, Figure S8). The hydrolysis of II generates
2-oxo-2-phenylacetylcyanide intermediate III. Subsequent
nucleophilic substitution of the CN group in III by the
amine group results in the formation of product 2a. The in situ
Fourier transform infrared (FTIR) studies also pointed out
toward the formation of imine intermediate II and diketo
intermediate III. The band at 1651 cm−1 corresponding to
C�N stretching of imine II initially increased and then
decreased with time as the reaction progressed and II was
consumed. Similarly, bands at 1680 and 1716 cm −1
corresponding to intermediate III appeared initially and then
decreased with time.16j The formation of intermediate III was
also confirmed by the crossover experiment using methanol
(4.0 equiv) as the external nucleophile, which competed with
the internally available amine (see the SI, Scheme S4). The α-
keto ester 4a was isolated as the major product in this case,
suggesting III to be the intermediate which upon nucleophilic
substitution yielded 2. The mechanism is distinctively different
from the previously reported C�C bond cleavage reactions of
enamines by singlet oxygen.9a
Taking a lead from the cross-nucleophile experiment, other
aliphatic alcohols were examined. As expected, the reaction was
facile with other alcohols and α-keto esters were obtained in
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moderate yields. The reaction of 1a with methanol yielded 4a
in 58% yield. With ethanol, n-butanol, and iso-butanol, the
corresponding products 4b−4d were isolated in 60, 52, and
48% yields, respectively. Alcohols with longer alkyl chains
(hexanol and dodecanol) gave the corresponding products 4e
and 4f in 52 and 44% yields, respectively. Further with
ethoxyethanol, 4g was obtained in 54% yield (Scheme 4).
Scheme 4. Substrate Scope with Aliphatic Alcoholsa,b
a
Reaction conditions: 1a (0.2 mmol), H2TPP (2.0 mol %), ROH (0.8
mmol), CH3CN (2.0 mL), 27 W white CFL, rt, air, 20 h; bIsolated
yields.
■ CONCLUSIONS
In conclusion, we report a facile conversion of β-enaminoni-
triles to α-keto amides and α-keto esters by singlet oxygen in
visible light photosensitized by H2TPP. The products are
obtained in moderate to high yields under mild conditions,
with reusability of H2TPP up to five cycles. Fluorescence, ESR,
and control experiments suggest the reaction to follow an ene-
type pathway initiated by photochemically activated oxygen,
followed by subsequent nucleophilic substitution of cyanide by
amine/alcohol as the nucleophile. The mechanism is distinctly
different from the previously reported singlet oxygen-mediated
oxidative cleavage at the double bond, generating two
carbonyls.9a The findings in this work offer immense
exploratory scope toward the use of 1O2 as a reagent in
enamine chemistry for accessing useful synthetic building
blocks in a mild and sustainable manner.
■ EXPERIMENTAL SECTION
General Information. The commercially available analytical
grade reagents were used directly without additional purification.
Dry solvents were used for the reaction and column chromatography.
The progress of the reactions was monitored using thin-layer
chromatography carried out on 0.25 mm Merck silica plates (60F-
254). UV light (λmax = 254 nm) was used as a visualizing agent and
iodine vapor as a staining agent. Merck silica gel with particle sizes
60−120 and 100−200 mesh was used as the stationary phase, while
an appropriate amount of hexane and ethyl acetate was used as the
eluent (mobile phase) in column chromatography. 1H NMR spectra
were recorded at 500 MHz and 13C NMR at 125 MHz using CDCl3
as the solvent. The splitting pattern of the peaks in 1H NMR is
mentioned as singlet (s), doublet (d), triplet (t), broad singlet (bs),
and multiplet (m). The chemical shifts and coupling constants are
reported as parts per million (ppm) and hertz (Hz), respectively, in
1
H NMR. High-resolution mass spectra were recorded on a mass
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spectrometer using electrospray ionization time-of-flight (ESI-TOF)
reflection experiments. Data collection and refinement single-crystal
X-ray data of compounds were collected on a Bruker APEX-II CCD
diffractometer using graphite-monochromated Mo Kα radiation (λ =
0.71073 Å). EPR spectra were obtained using a Bruker A300-9.5/12/
S/W instrument.
General Procedure for the Synthesis of Starting Materials
1.17 A mixture of α-cyanoketone (1.0 equiv, 5.0 mmol), amine (2.0
equiv, 10.0 mmol), and acetic acid (600.5 mg, 2.0 equiv, 10.0 mmol)
was heated in an oil bath at 80 °C under a nitrogen atmosphere until
thin-layer chromatography (TLC) indicated the complete consump-
tion of α-cyanoketone. The reaction was allowed to cool to room
temperature. The resulting mixture was quenched with water (20 mL)
and extracted with ethyl acetate (2 × 30 mL). The combined organic
layers were dried over Na2SO4, filtered, concentrated, and purified
through column chromatography to afford the desired product 1 as a
mixture of cis and trans isomers. 1b−1d and 1j−1l are known
compounds. Their synthesis was confirmed by spectroscopic analysis,
which was in agreement with the literature data.17 1a, 1e−1i, and
1m−1z are new compounds, synthesized using the above procedure
and characterized by NMR and HRMS.
General Procedure for the Synthesis of Compounds 2. To
an oven-dried reaction tube, β-enaminonitriles 1 (0.2 mmol) and
H2TPP (2.46 mg, 2.0 mol %) were mixed in ACN (2.0 mL) and
irradiated under a 27 W white CFL lamp at room temperature for 20
h. After completion, as observed by TLC, the reaction mixture was
concentrated under reduced pressure and purified by column
chromatography using a mixture of hexane and ethyl acetate as the
eluent to afford the desired product 2.
General Procedure for the Synthesis of Compounds 4. To
an oven-dried reaction tube, β-enaminonitriles 1 (1.0 equiv, 0.2
mmol), aliphatic alcohol (4.0 equiv, 0.8 mmol), and H2TPP (2.46 mg,
2.0 mol %) were mixed in ACN (2.0 mL) and irradiated under a 27 W
white CFL lamp at room temperature for 20 h. After completion, as
observed by TLC, the reaction mixture was concentrated under
reduced pressure and purified by column chromatography using a
mixture of hexane and ethyl acetate as the eluent to afford the desired
product 4.
Procedure for the Gram-Scale Synthesis of 2a. To an oven-
dried 100 mL round-bottom flask, 3-(methylamino)-3-phenylacrylo-
nitrile 1a (1.58 g, 1.0 equiv, 10 mmol) and H2TPP (123.0 mg, 5.0 mol
%) were mixed in ACN (80 mL) and irradiated under a 27 W white
CFL lamp at room temperature for 72 h. After completion, as
observed by TLC, the reaction mixture was quenched with water (150
mL) and extracted with ethyl acetate (2 × 200 mL). The combined
organic layers were dried over Na2SO4, filtered, concentrated, and
purified through column chromatography to afford the desired
product 2a in 81% yield (1.32 g).
Physical Properties and Characterization Data of the
Synthesized Compounds. 3-(Methylamino)-3-phenylacrylonitrile
(1a). Yellow liquid, (640.7 mg, 81% yield), (minor/major = 1:7.7),
hexane/EtOAc (85:15); 1H NMR (500 MHz, CDCl3): major
isomer: δ 7.53−7.51 (m, 2H), 7.45−7.37 (m, 3H, peaks of two
isomers overlapped), 4.59 (br s, 1H), 3.97 (s, 1H, peaks of two
isomers overlapped), 2.82 (d, J = 5.5, 3H), ppm; minor isomer: δ
7.45−7.37 (m, 5H, peaks of two isomers overlapped), 4.84 (br s, 1H),
3.96 (s, 1H, peaks of two isomers overlapped), 3.13 (d, J = 5.0, 3H)
ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer: δ 163.5,
135.9, 130.5, 128.9, 127.9, 121.9, 60.9, 30.7 ppm; HRMS (ESI/TOF-
Q) m/z: [M + H]+ Calcd for C10H11N2 159.0917; found 159.0926.
3-(4-Fluorophenylamino)-3-phenylacrylonitrile (1e)**. Brown
solid, (810.0 mg, 68% yield), (minor/major = 1:2.0), hexane/
EtOAc (95:5); M.P.: 126−128 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.68 (dd, J = 7.5, 1.0 Hz, 1H), 7.52−7.46 (m, 1H,
peaks of two isomers overlapped), 7.40−7.30 (m, 4H, peaks of two
isomers overlapped), 7.08 (t, J = 8.5, 1H), 6.93 (br s, 1H), 6.85 (t, J =
8.5, 2H), 4.40 (s, 1H) ppm; minor isomer: δ 7.52−7.46 (m, 1H,
peaks of two isomers overlapped), 7.40−7.30 (m, 2H, peaks of two
isomers overlapped), 7.20−7.17 (m, 2H), 6.75−6.72 (m, 4H), 6.00
(br s, 1H), 4.50 (s, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3):
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major isomer + minor isomer: δ 161.0, 160.5 (d, JC−F = 244.7 Hz),
160.1, 159.5 (d, JC−F = 242.4 Hz), 136.1 (d, JC−F = 2.7 Hz), 135.2,
134.9 (d, JC−F = 3.0 Hz), 134.4, 131.1, 130.7, 129.1, 128.9, 128.2,
128.2, 126.1 (d, JC−F = 8.2 Hz), 124.1 (d, JC−F = 8.1 Hz), 120.9, 118.8,
116.7 (d, JC−F = 22.6 Hz), 115.9 (d, JC−F = 22.6 Hz), 71.0, 66.5 ppm;
HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for C15H12N2F
239.0979; found 239.0985.
3-(3-Bromophenylamino)-3-phenylacrylonitrile (1f)**. Off white
solid, (1077.0 mg, 72% yield), (minor/major = 1:1.72), hexane/
EtOAc (95:5); M.P.: 105−108 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.62 (d, J = 6.5, 2H), 7.49−7.42 (m, 1H, peaks of
two isomers overlapped), 7.37−7.42 (m, 2H, peaks of two isomers
overlapped), 7.29−7.25 (m, 1H), 7.07 (t, J = 7.5, 3H), 6.90 (br s,
1H), 4.69 (s, 1H) ppm; minor isomer: δ 7.49−7.42 (m, 2H, peaks of
two isomers overlapped), 7.40 (d, J = 7.0, 1H), 7.37−7.42 (m, 3H,
peaks of two isomers overlapped), 7.20 (t, J = 8.0, 1H), 6.96 (t, J =
8.0, 1H), 6.59 (dd, J = 8.0, 1.0, 1H), 6.30 (br s, 1H), 4.47 (s, 1H)
ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer + minor
isomer: δ 159.8, 159.1, 141.5, 140.6, 134.8, 134.0, 131.1, 131.0, 131.0,
130.1, 129.0, 129.0, 128.3, 128.3, 128.1, 126.4, 125.9, 124.4, 123.1,
122.5, 121.6, 120.6, 120.1, 118.4, 73.1, 68.0 ppm; HRMS (ESI/TOF-
Q) m/z: [M + H]+ Calcd for C15H12N2Br 299.0178; found 299.0189.
3-(3-Chlorophenylamino)-3-phenylacrylonitrile (1g)**. White
solid, (917.0 mg, 72% yield), (minor/major = 1:1.72), hexane/
EtOAc (95:5); M.P.: 100−104 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.68 (dd, J = 7.0, 1.0 Hz, 1H), 7.52−7.47 (m, 1H,
peaks of two isomers overlapped), 7.44−7.41 (m, 1H), 7.39−7.35 (m,
2H, peaks of two isomers overlapped), 7.31 (t, J = 8.0, 1H), 7.09−
7.03 (m, 1H, peaks of two isomers overlapped), 6.94 (dd, J = 8.0, 1.0
Hz, 1H), 6.90 (br s, 1H), 6.73 (t, J = 2.0, 1H), 4.52 (s, 1H) ppm;
minor isomer: δ 7.52−7.47 (m, 1H, peaks of two isomers
overlapped), 7.39−7.35 (m, 3H, peaks of two isomers overlapped),
7.21 (t, J = 1.5, 1H), 7.17−7.15 (m, 1H), 7.09−7.03 (m, 1H, peaks of
two isomers overlapped), 6.56 (dd, J = 8.0, 2.0 Hz, 2H), 5.96 (br s,
1H), 4.77 (s, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): major
isomer + minor isomer: δ 159.7, 159.2, 141.4, 140.4, 135.5, 135.0,
134.7, 134.0, 131.3, 131.1, 130.9, 130.0, 129.2, 129.1, 128.4, 128.1,
125.7, 123.7, 123.2, 121.6, 121.2, 120.4, 119.73, 118.3, 73.5, 68.6
ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for C15H12N2Cl
255.0684; found 255.0691.
3-(2-Bromophenylamino)-3-phenylacrylonitrile (1h)**. White
solid, (957.3 mg, 64% yield), (minor/major = 1:1.02), hexane/
EtOAc (95:5); M.P.: 95−100 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.74 (dd, J = 7.0, 2.0 Hz, 2H), 7.65 (dd, J = 8.0, 1.0
Hz, 2H), 7.56−7.49 (m, 3H, peaks of two isomers overlapped), 7.43−
7.32 (m, 3H, peaks of two isomers overlapped), 6.88 (br s, 1H), 4.67
(s, 1H) ppm; minor isomer: δ 7.56−7.49 (m, 1H, peaks of two
isomers overlapped), 7.43−7.32 (m, 4H, peaks of two isomers
overlapped), 7.08 (td, J = 7.0, 1.5 Hz, 1H), 6.97 (t, J = 8.0, 1H), 6.85
(td, J = 8.0, 1.0 Hz, 1H), 6.50 (d, J = 8.0, 1H), 6.05 (br s, 1H), 4.60
(s, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer +
minor isomer: δ 159.5, 158.8, 138.3, 137.4, 135.0, 134.3, 133.8,
133.1, 131.3, 131.0, 129.2, 129.1, 128.6, 128.4, 128.0, 127.8, 126.9,
125.0, 124.8, 123.5, 120.4, 118.4, 118.1, 116.0, 74.3, 68.8 ppm;
HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for C15H12N2Br
299.0178; found 299.0188.
3-(2-Chlorophenylamino)-3-phenylacrylonitrile (1i)**. Off white
solid, (776.9 mg, 61% yield), (minor/major = 1:1.25), hexane/EtOAc
(95:5); M.P.: 87−90 °C; 1H NMR (500 MHz, CDCl3): major
isomer: δ 7.73 (dd, J = 8.0, 1.5 Hz, 2H), 7.53−7.43 (m, 2H, peaks of
two isomers overlapped), 7.42−7.33 (m, 3H, peaks of two isomers
overlapped), 7.30 (dd, J = 8.0, 1.0 Hz, 2H), 6.08 (br s, 1H), 4.60 (s,
1H) ppm; minor isomer: δ 7.53−7.43 (m, 2H, peaks of two isomers
overlapped), 7.42−7.33 (m, 4H, peaks of two isomers overlapped),
6.95−6.90 (m, 3H), 6.50−6.48 (m, 1H), 4.72 (s, 1H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): major isomer + minor isomer: δ 159.4,
158.7, 137.0, 136.1, 135.1, 134.4, 131.3, 131.0, 130.6, 129.9, 129.2,
129.1, 128.4, 128.0, 127.9, 127.7, 127.1, 126.4, 125.5, 124.5, 124.4,
123.2, 120.3, 118.1, 74.4, 69.0 ppm; HRMS (ESI/TOF-Q) m/z: [M +
H]+ Calcd for C15H12N2Cl 255.0684; found 255.0695.
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3-(Butylamino)-3-phenylacrylonitrile (1m). Red liquid, (801.1
mg, 80% yield), (minor/major = 1:5.0), hexane/EtOAc (90:10); 1H
NMR (500 MHz, CDCl3): major isomer: δ 7.54−7.52 (m, 2H),
7.46−7.38 (m, 3H, peaks of two isomers overlapped), 4.37 (br s, 1H),
4.01 (s, 1H), 3.10−3.06 (m, 2H), 1.66−1.56 (m, 2H, peaks of two
isomers overlapped), 1.46−1.37 (m, 2H, peaks of two isomers
overlapped), 0.98−0.91 (m, 3H, peaks of two isomers overlapped)
ppm; minor isomer: δ 7.46−7.38 (m, 5H, peaks of two isomers
overlapped), 4.72 (br s, 1H), 3.94 (s, 1H), 3.44−3.43 (m, 2H), 1.66−
1.56 (m, 2H, peaks of two isomers overlapped), 1.46−1.37 (m, 2H,
peaks of two isomers overlapped), 0.98−0.91 (m, 3H, peaks of two
isomers overlapped) ppm; 13C{1H} NMR (125 MHz, CDCl3): major
isomer: δ 162.5, 136.0, 130.3, 128.8, 127.8, 122.0, 60.7, 43.7, 30.3,
20.3, 13.8 ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for
C13H17N2 201.1386; found 201.1394.
3-(Hexylamino)-3-phenylacrylonitrile (1n). Brown liquid, (879.1
mg, 77% yield), (minor/major = 1:4.2), hexane/EtOAc (90:10); 1H
NMR (500 MHz, CDCl3): major isomer: δ 7.54−7.52 (m, 2H),
7.49−7.38 (m, 3H, peaks of two isomers overlapped), 4.36 (br s, 1H),
4.01 (s, 1H), 3.09−3.05 (m, 2H), 1.67−1.56 (m, 2H, peaks of two
isomers overlapped), 1.42−1.32 (m, 6H, peaks of two isomers
overlapped), 0.92−0.83 (m, 3H, peaks of two isomers overlapped)
ppm; minor isomer: δ 7.86 (d, J = 6.5 Hz, 1H), δ 7.58 (d, J = 6.5 Hz,
1H), 7.49−7.38 (m, 3H, peaks of two isomers overlapped), 4.73 (br s,
1H), 3.95 (s, 1H), 3.43−3.37 (m, 2H), 1.67−1.56 (m, 2H, peaks of
two isomers overlapped), 1.42−1.32 (m, 6H, peaks of two isomers
overlapped), 0.92−0.83 (m, 3H, peaks of two isomers overlapped)
ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer: δ 162.5,
136.0, 130.3, 128.8, 127.8, 122.0, 60.6, 44.0, 31.5, 28.2, 26.7, 22.6,
14.0 ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for C15H21N2
229.1699; found 229.1708.
3-(Octylamino)-3-phenylacrylonitrile (1o). Red liquid, (935.8 mg,
73% yield), (minor/major = 1:5.0), hexane/EtOAc (90:10); 1H NMR
(500 MHz, CDCl3): major isomer: δ 7.53−7.52 (m, 2H), 7.46−7.38
(m, 3H, peaks of two isomers overlapped), 4.38 (br s, 1H), 4.01 (s,
1H), 3.08−3.05 (m, 2H), 1.67−1.58 (m, 2H, peaks of two isomers
overlapped), 1.42−1.28 (m, 10H, peaks of two isomers overlapped),
0.90−0.88 (m, 3H, peaks of two isomers overlapped) ppm; minor
isomer: δ 7.46−7.38 (m, 5H, peaks of two isomers overlapped), 4.73
(br s, 1H), 3.94 (s, 1H), 3.43−3.42 (m, 2H), 1.67−1.58 (m, 2H,
peaks of two isomers overlapped), 1.42−1.28 (m, 10H, peaks of two
isomers overlapped), 0.90−0.88 (m, 3H, peaks of two isomers
overlapped) ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer:
δ 162.5, 136.0, 130.3, 128.8, 127.8, 121.9, 60.7, 44.0, 31.8, 29.3, 29.2,
28.3, 27.1, 22.7, 14.1 ppm; HRMS (ESI/TOF-Q) m/z: [M + Na]+
Calcd for C17H24NaN2 279.1832; found 279.1847.
3-(Hexadecylamino)-3-phenylacrylonitrile (1p)*. Pale yellow
solid, (1234.8 mg, 67% yield), hexane/EtOAc (95:5); M.P.: 50−52
°C; 1H NMR (500 MHz, CDCl3): major isomer δ 7.55−7.53 (m,
2H), 7.44−7.43 (m, 3H), 4.29 (br s, 1H), 4.03 (s, 1H), 3.10−3.06
(m, 2H), 1.68−1.62 (m, 2H), 1.39−1.26 (m, 26H), 0.89−0.86 (m,
3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer: δ
162.4, 136.0, 130.3, 128.8, 127.8, 121.9, 60.8, 44.0, 32.0, 29.8 (for
2C), 29.7 (for 2C), 29.7 (for 2C), 29.6, 29.6, 29.4, 29.3, 28.3, 27.1,
22.8, 14.2 ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for
C25H41N2 369.3264; found 369.3281.
3-(Octadecylamino)-3-phenylacrylonitrile (1q). Off white solid,
(1269.3 mg, 64% yield), (minor/major = 1:5.0), hexane/EtOAc
(95:5); M.P.: 50−52 °C; 1H NMR (500 MHz, CDCl3): major
isomer: δ 7.55−7.53 (m, 2H), 7.48−7.38 (m, 3H, peaks of two
isomers overlapped), 4.31 (br s, 1H), 4.03 (s, 1H), 3.09−3.06 (m,
2H), 1.68−1.60 (m, 2H, peaks of two isomers overlapped), 1.38−1.26
(m, 30H, peaks of two isomers overlapped), 0.89−0.86 (m, 3H, peaks
of two isomers overlapped) ppm; minor isomer: δ 7.48−7.38 (m,
5H, peaks of two isomers overlapped), 4.70 (br s, 1H), 3.95 (s, 1H),
3.42−3.37 (m, 2H), 1.68−1.60 (m, 2H), 1.38−1.26 (m, 30H, peaks
of two isomers overlapped), 0.89−0.86 (m, 3H, peaks of two isomers
overlapped) ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer:
δ 162.7, 136.1, 130.5, 128.9, 127.9, 121.9, 61.1, 44.1, 32.1, 29.8 (for
4C), 29.8 (for 3C), 29.8, 29.7, 29.6, 29.5, 29.4, 28.4, 27.2, 22.8, 14.3
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The Journal of Organic Chemistry
ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for C27H45N2
397.3577; found 397.3590.
3-(Cyclopentylamino)-3-phenylacrylonitrile (1r). Red liquid,
(796.1 mg, 75% yield), (minor/major = 1:5.2), hexane/EtOAc
(90:10); 1H NMR (500 MHz, CDCl3): major isomer: δ 7.51−7.50
(m, 2H), 7.47−7.37 (m, 3H, peaks of two isomers overlapped), 4.43
(br s, 1H), 4.03 (s, 1H), 3.73−3.68 (m, 1H, peaks of two isomers
overlapped), 2.03−2.00 (m, 2H, peaks of two isomers overlapped),
1.72−1.60 (m, 4H, peaks of two isomers overlapped), 1.58−1.52 (m,
2H, peaks of two isomers overlapped) ppm; minor isomer: δ 7.47−
7.37 (m, 5H, peaks of two isomers overlapped), 4.70 (br s, 1H), 3.94
(s, 1H), 3.73−3.68 (m, 1H, peaks of two isomers overlapped), 2.03−
2.00 (m, 2H, peaks of two isomers overlapped), 1.72−1.60 (m, 4H,
peaks of two isomers overlapped), 1.58−1.52 (m, 2H, peaks of two
isomers overlapped) ppm; 13C{1H} NMR (125 MHz, CDCl3): major
isomer: δ 161.8, 136.0, 130.1, 128.6, 127.8, 122.0, 61.1, 54.8, 32.7,
24.0 ppm; HRMS (ESI/TOF-Q) m/z: [M + Na]+ Calcd for
C14H16NaN2 235.1206; found 235.1205.
3-(Cyclohexylamino)-3-phenylacrylonitrile (1s). Pale yellow solid,
(848.0 mg, 75% yield), (minor/major = 1:3.1), hexane/EtOAc
(90:10); M.P.: 90−95 °C; 1H NMR (500 MHz, CDCl3): major
isomer: δ 7.53−7.52 (m, 2H), 7.46−7.38 (m, 3H, peaks of two
isomers overlapped), 4.26 (br s, 1H), 4.06 (s, 1H), 3.24−3.19 (m,
1H), 2.07−2.04 (m, 2H, peaks of two isomers overlapped), 1.78−1.62
(m, 3H, peaks of two isomers overlapped), 1.42−1.20 (m, 5H, peaks
of two isomers overlapped) ppm; minor isomer: δ 7.46−7.38 (m,
5H, peaks of two isomers overlapped), 4.63 (br s, 1H), 3.94 (s, 1H),
3.67−3.65 (m, 1H), 2.07−2.04 (m, 2H, peaks of two isomers
overlapped), 1.77−1.62 (m, 3H, peaks of two isomers overlapped),
1.42−1.20 (m, 5H, peaks of two isomers overlapped) ppm; 13C{1H}
NMR (125 MHz, CDCl3): major isomer: δ 161.2, 136.3, 130.2,
128.7, 127.9, 122.1, 60.6, 52.2, 32.0, 25.6, 24.6 ppm; HRMS (ESI/
TOF-Q) m/z: [M + Na]+ Calcd for C15H18NaN2 249.1362; found
249.1369.
3-(Cyclopropylamino)-3-phenylacrylonitrile (1t)*. Orange solid,
(635.6 mg, 69% yield), hexane/EtOAc (90:10); M.P.: 62−64 °C; 1H
NMR (500 MHz, CDCl3): major isomer: δ 7.52−7.50 (m, 2H),
7.44−7.37 (m, 3H), 4.65 (br s, 1H), 4.52 (s, 1H), 2.46−2.45 (m,
1H), 0.85−0.82 (m, 2H), 0.64−0.61 (m, 2H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): major isomer: δ 163.1, 135.4, 130.4, 128.8,
127.8, 121.7, 63.2, 25.1, 7.4 ppm; HRMS (ESI/TOF-Q) m/z: [M +
Na]+ Calcd for C12H13N2 185.1073; found 185.1075.
3-(Methylamino)-3-(p-tolyl)acrylonitrile (1u). Brown solid, (732.0
mg, 85% yield), (minor/major = 1:6.2), hexane/EtOAc (85:15);
M.P.: 100−102 °C; 1H NMR (500 MHz, CDCl3): major isomer: δ
7.43−7.41 (m, 2H), 7.22−7.18 (m, 2H, peaks of two isomers
overlapped), 4.54 (br s, 1H), 3.97−3.95 (m, 1H, peaks of two isomers
overlapped), 2.84−2.81 (m, 3H), 2.37 (s, 3H, peaks of two isomers
overlapped) ppm; minor isomer: δ 7.28−7.26 (m, 2H), 7.22−7.18
(m, 2H, peaks of two isomers overlapped), 4.80 (br s, 1H), 3.97−3.95
(m, 1H, peaks of two isomers overlapped), 3.14−3.13 (m, 3H), 2.37
(s, 3H, peaks of two isomers overlapped) ppm; 13C{1H} NMR (125
MHz, CDCl3): major isomer: δ 163.6, 140.5, 132.9, 129.4, 127.7,
122.2, 60.1, 30.5, 21.4 ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+
Calcd for C11H13N2 173.1073; found 173.1074.
3-(4-Chlorophenyl)-3-(methylamino)acrylonitrile (1v). Brown
solid, (751.3 mg, 78% yield), (minor/major = 1:6.2), hexane/
EtOAc (82:18); M.P.: 107−112 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.49 (d, J = 7.5 Hz, 2H), 7.40 (d, J = 7.5 Hz, 2H),
4.44 (br s, 1H), 4.03 (s, 1H), 2.85 (d, J = 4.0 Hz, 3H) ppm; minor
isomer: δ 7.40−7.37 (m, 2H, peaks of two isomers overlapped), 7.33
(d, J = 7.5 Hz, 2H), 4.75 (br s, 1H), 3.96 (s, 1H), 3.13 (d, J = 4.0 Hz,
3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer: δ
162.4, 136.4, 134.1, 129.3, 129.0, 121.8, 60.8, 30.6 ppm; HRMS (ESI/
TOF-Q) m/z: [M + H]+ Calcd for C10H10ClN2 193.0527; found
193.0534.
3-(4-Fluorophenyl)-3-(methylamino)acrylonitrile (1w). Brown
solid, (660.7 mg, 75% yield), (minor/major = 1:7.7), hexane/
EtOAc (85:15); M.P.: 88−90 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.54−7.52 (m, 2H), 7.12−7.06 (m, 2H, peaks of two
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isomers overlapped), 4.49 (br s, 1H), 4.00 (s, 1H), 2.84 (d, J = 5.0
Hz, 3H) ppm; minor isomer: δ 7.39−7.37 (m, 2H), 7.12−7.06 (m,
2H, peaks of two isomers overlapped), 4.78 (br s, 1H), 3.94 (s, 1H),
3.12 (d, J = 5.0 Hz, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3):
major isomer: δ 163.8 (d, 1JC−F = 248.9 Hz), 162.5, 131.9 (d, 4JC−F =
3.1 Hz), 130.0 (d, 3JC−F = 8.6 Hz), 121.8, 115.9 (d, 2JC−F = 21.7 Hz),
60.9, 30.6; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for
C10H10FN2 177.0823; found 177.0827.
3-(3-Methoxyphenyl)-3-(methylamino)acrylonitrile (1x). Brown
solid, (724.7 mg, 77% yield), (minor:major = 1:6.2), hexane/EtOAc
(80:20); M.P.: 65−70 °C; 1H NMR (500 MHz, CDCl3): major
isomer: δ 7.32 (t, J = 7.5 Hz, 1H), 7.10−7.06 (m, 2H, peaks of two
isomers overlapped), 6.98−6.96 (m, 1H, peaks of two isomers
overlapped), 4.56 (br s, 1H), 3.98 (s, 1H, peaks of two isomers
overlapped), 3.82 (s, 3H, peaks of two isomers overlapped), 2.83 (d, J
= 5.0 Hz, 3H) ppm; minor isomer: δ 7.10−7.06 (m, 1H, peaks of two
isomers overlapped), 6.98−6.89 (m, 3H, peaks of two isomers
overlapped), 4.81 (br s, 1H), 3.98 (s, 1H, peaks of two isomers
overlapped), 3.82 (s, 3H, peaks of two isomers overlapped), 3.14 (d, J
= 5.0 Hz, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): major
isomer: δ 163.3, 159.6, 136.9, 129.9, 122.0, 120.0, 116.3, 113.2, 60.2,
55.4, 30.5 ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for
C11H13N2O 189.1022; found 189.1028.
3-(3-Chlorophenyl)-3-(methylamino)acrylonitrile (1y). Brown
solid, (674.3 mg, 70% yield), (minor/major = 1:6.7), hexane/
EtOAc (82:18); M.P.: 121−124 °C; 1H NMR (500 MHz, CDCl3):
major isomer: δ 7.49−7.82 (m, 4H, peaks of two isomers
overlapped), 4.45 (br s, 1H), 4.04 (s, 1H), 2.86 (d, J = 5.0 Hz,
3H) ppm; minor isomer: δ 7.49−7.82 (m, 4H, peaks of two isomers
overlapped), 4.75 (br s, 1H), 3.99 (s, 1H), 3.14 (d, J = 5.0 Hz, 3H)
ppm; 13C{1H} NMR (125 MHz, CDCl3): major isomer: δ 161.9,
137.6, 134.9, 130.7, 130.3, 127.9, 126.5, 121.1, 62.2, 30.8 ppm;
HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for C10H10ClN2
193.0527; found 193.0537.
3-(2-Chlorophenyl)-3-(methylamino)acrylonitrile (1z)*. White
solid, (587.6 mg, 61% yield), hexane/EtOAc (82:18); M.P.: 148−
151 °C; 1H NMR (500 MHz, CDCl3): major isomer: δ 7.45 (dd, J =
8.0, 1.0 Hz, 1H), 7.41 (dd, J = 7.5, 2.0 Hz, 1H), 7.37 (dd, J = 8.0, 2.0
Hz, 1H), 7.33 (td, J = 8.0, 1.0 Hz, 1H), 4.37 (br s, 1H), 4.15 (s, 1H),
2.88 (d, J = 5.5 Hz, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3):
major isomer: δ 161.0, 134.8, 132.3, 131.3, 130.7, 130.3, 127.3, 120.6,
63.7, 30.7 ppm; HRMS (ESI/TOF-Q) m/z: [M + H]+ Calcd for
C10H10ClN2 193.0527; found 193.0538.
N-Methyl-2-oxo-2-phenylacetamide (2a).18a Pale yellow solid,
(30.0 mg, 92% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.34−8.32 (m, 2H), 7.63−7.60 (m, 1H), 7.47 (t, J = 8.0
Hz, 2H), 7.13 (br s, 1H), 2.96 (d, J = 5.0 Hz, 3H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 187.9, 162.6, 134.6, 133.5, 131.4, 128.7,
26.2 ppm; HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for
C9H8NO2 162.0555; found 162.0555.
2-Oxo-N,2-diphenylacetamide (2b).18b Pale yellow solid, (31.9
mg, 71% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.99 (br s, 1H), 8.41 (dd, J = 8.5, 1.0 Hz, 2H), 7.71 (d,
J = 7.5 Hz, 2H), 7.65 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 8.0 Hz, 2H),
7.40 (t, J = 8.0 Hz, 2H), 7.20 (t, J = 7.5 Hz, 1H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): δ 187.6, 159.1, 136.8, 134.8, 133.2, 131.6, 129.4,
128.7, 125.4, 120.1 ppm; HRMS (ESI/TOF-Q) m/z: [M − H]−
Calcd for C14H10NO2 224.0712; found 224.0713.
N-(4-Methoxyphenyl)-2-oxo-2-phenylacetamide (2c).18b Yellow
solid, (39.3 mg, 77% yield), hexane/EtOAc (90:10); 1H NMR (500
MHz, CDCl3): δ 8.91 (br s, 1H), 8.40 (d, J = 8.0 Hz, 2H), 7.66−7.61
(m, 3H), 7.50 (t, J = 8.0 Hz, 2H), 6.92 (d, J = 9.0 Hz, 2H), 3.81 (s,
3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 187.8, 158.9, 157.2,
134.7, 133.4, 131.6, 130.0, 128.7, 121.7, 114.5, 55.6 ppm; HRMS
(ESI/TOF-Q) m/z: [M − H]− Calcd for C15H12NO3 254.0817;
found 254.0820.
N-(4-Bromophenyl)-2-oxo-2-phenylacetamide (2d).18b Yellow
solid, (45.6 mg, 75% yield), hexane/EtOAc (95:5); 1H NMR (500
MHz, CDCl3): δ 9.00 (br s, 1H), 8.39 (d, J = 7.5 Hz, 2H), 7.66 (t, J =
7.5 Hz, 1H), 7.60 (d, J = 8.5 Hz, 2H), 7.51 (t, J = 7.5 Hz, 4H) ppm;
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13
C{1H} NMR (125 MHz, CDCl3): δ 187.2, 159.0, 135.9, 134.9,
133.1, 132.4, 131.6, 128.8, 121.6, 118.2 ppm; HRMS (ESI/TOF-Q)
m/z: [M − H]− Calcd for C14H9BrNO2 301.9817; found 301.9817.
N-(4-Fluorophenyl)-2-oxo-2-phenylacetamide (2e).18c Pale yel-
low solid, (29.7 mg, 61% yield), hexane/EtOAc (95:5); 1H NMR
(500 MHz, CDCl3): δ 8.95 (br s, 1H), 8.41 (dd, J = 8.5, 1.0 Hz, 2H),
7.69−7.65 (m, 3H), 7.52 (t, J = 8.0 Hz, 2H), 7.10 (t, J = 8.5 Hz, 2H)
ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 187.4, 160.9 (d, JC−F =
243.7 Hz), 158.9, 134.9, 133.2, 132.9 (d, JC−F = 2.7 Hz), 131.7, 128.8,
121.8 (d, JC−F = 8.0 Hz), 116.2 (d, JC−F = 22.5 Hz) ppm; 19F{1H}
NMR (564.6 MHz, CDCl3): δ −116.3 ppm; HRMS (ESI/TOF-Q)
m/z: [M − H]− Calcd for C14H9FNO2 242.0618; found 242.0609.
N-(3-Bromophenyl)-2-oxo-2-phenylacetamide (2f).18b White
solid, (43.2 mg, 71% yield), hexane/EtOAc (95:5); 1H NMR (500
MHz, CDCl3): δ 8.98 (br s, 1H), 8.41 (dd, J = 8.0, 1.0 Hz, 2H), 8.01
(d, J = 2.0 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.57 (dd, J = 8.0, 1.0 Hz,
2H), 7.52 (t, J = 8.0 Hz, 2H), 7.33 (dd, J = 8.0, 0.5 Hz, 1H), 7.26 (t, J
= 8.0 Hz, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 187.0,
158.9, 138.0, 135.0, 133.0, 131.7, 130.7, 128.8, 128.5, 123.1, 123.0,
118.6 ppm; HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for
C14H9BrNO2 301.9817; found 301.9811.
N-(3-Chlorophenyl)-2-oxo-2-phenylacetamide (2g).18j White
solid, (35.8 mg, 69% yield), hexane/EtOAc (95:5); 1H NMR (500
MHz, CDCl3): δ 8.99 (br s, 1H), 8.41 (d, J = 7.5, Hz, 2H), 7.87 (t, J =
2.0 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5, 3H), 7.32 (t, J =
8.0 Hz, 2H), 7.18 (dd, J = 8.0, 1.0 Hz, 1H) ppm; 13C{1H} NMR (125
MHz, CDCl3): δ 187.1, 159.0, 137.9, 135.1, 135.0, 133.0, 131.7,
130.4, 128.8, 125.6, 120.2, 118.1 ppm; HRMS (ESI/TOF-Q) m/z:
[M − H]− Calcd for C14H9ClNO2 258.0322; found 258.0310.
N-(2-Bromophenyl)-2-oxo-2-phenylacetamide (2h).18k Pale yel-
low solid, (40.7 mg, 67% yield), hexane/EtOAc (95:5); 1H NMR
(500 MHz, CDCl3): δ 9.59 (br s, 1H), 8.50 (d, J = 8.0 Hz, 1H), 8.43
(d, J = 8.0 Hz, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H),
7.52 (t, J = 8.0 Hz, 2H), 7.38 (t, J = 8.0 Hz, 1H), 7.06 (t, J = 8.0 Hz,
1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 186.8, 158.9, 134.9,
134.8, 133.1, 132.8, 131.6, 128.8, 128.6, 126.3, 121.5, 114.4 ppm;
HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for C14H9BrNO2
301.9817; found 301.9809.
N-(2-Chlorophenyl)-2-oxo-2-phenylacetamide (2i).18j Pale yellow
solid, (33.7 mg, 65% yield), hexane/EtOAc (95:5); 1H NMR (500
MHz, CDCl3): δ 9.58 (br s, 1H), 8.52 (dd, J = 8.0, 1.5 Hz, 1H), 8.43
(dd, J = 8.0, 1.5 Hz, 2H), 7.69−7.65 (m, 1H), 7.52 (t, J = 8.0 Hz,
2H), 7.44 (dd, J = 8.0, 1.0 Hz, 2H), 7.36−7.33 (m, 1H), 7.15−7.12
(m, 1H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 186.9, 159.0,
134.9, 133.7, 133.1, 131.6, 129.6, 128.9, 128.0, 125.8, 124.0, 121.3
ppm; HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for C14H9ClNO2
258.0322; found 258.0312.
2-Oxo-2-phenyl-N-(o-tolyl)acetamide (2j).18b Off white solid,
(35.0 mg, 73% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz,
CDCl3): δ 8.93 (br s, 1H), 8.44 (d, J = 8.5, Hz, 2H), 8.12 (d, J = 8.0
Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5, 2H), 7.29 (t, J = 8.0
Hz, 1H), 7.25 (d, J = 7.5 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 2.38 (s,
3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 187.6, 158.9, 134.7,
133.1, 131.5, 130.7, 128.7, 128.6, 127.0, 125.7, 121.7, 17.6 ppm;
HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for C15H12NO2
238.0868; found 238.0859.
N-(3,4-Dimethylphenyl)-2-oxo-2-phenylacetamide (2k).18c Yel-
low solid, (31.9 mg, 63% yield), hexane/EtOAc (90:10); 1H NMR
(500 MHz, CDCl3): δ 8.86 (br s, 1H), 8.42 (d, J = 8.0 Hz, 2H), 7.65
(t, J = 7.5 Hz, 1H), 7.51 (t, J = 8.0 Hz, 3H), 7.42 (d, J = 8.5 Hz, 1H),
7.15 (d, J = 8.5 Hz, 1H), 2.29 (s, 3H), 2.26 (s, 3H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 187.7, 159.0, 137.5, 134.6, 134.5, 133.8,
133.2, 131.5, 130.2, 128.6, 121.3, 117.5, 20.0, 19.4 ppm; HRMS (ESI/
TOF-Q) m/z: [M − H]− Calcd for C16H14NO2 252.1025; found
252.1023.
N-(3,4-Dimethoxyphenyl)-2-oxo-2-phenylacetamide (2l).18b Yel-
low solid, (39.3 mg, 69% yield), hexane/EtOAc (90:10); 1H NMR
(500 MHz, CDCl3): δ 8.91 (br s, 1H), 8.41 (d, J = 8.0 Hz, 2H), 7.66
(t, J = 7.5 Hz, 1H), 7.52−7.50 (m, 3H), 7.10 (d, J = 8.5 Hz, 1H), 6.87
(d, J = 8.5 Hz, 1H), 3.93 (s, 3H), 3.89 (s, 3H) ppm; 13C{1H} NMR
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(125 MHz, CDCl3): δ 187.7, 158.8, 149.4, 146.7, 134.8, 133.3, 131.6,
130.4, 128.7, 112.2, 111.5, 104.5, 56.3, 56.2 ppm; HRMS (ESI/TOF-
Q) m/z: [M − H]− Calcd for C16H14NO4 284.0923; found 284.0922.
N-Butyl-2-oxo-2-phenylacetamide (2m).18d Yellow liquid, (33.6
mg, 82% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.34 (d, J = 8.0 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H), 7.48
(t, J = 7.5 Hz, 2H), 7.11 (br s, 1H), 3.40 (q, J = 7.0 Hz, 2H), 1.63−
1.57 (m, 2H), 1.44−1.37 (m, 2H), 0.96 (t, J = 7.5 Hz, 3H) ppm;
13
C{1H} NMR (125 MHz, CDCl3): δ 188.1, 161.9, 134.5, 133.5,
131.4, 128.6, 39.3, 31.5, 20.2, 13.9 ppm; HRMS (ESI/TOF-Q) m/z:
[M − H]− Calcd for C12H14NO2 204.1025; found 204.1032.
N-Hexyl-2-oxo-2-phenylacetamide (2n).18d Yellow viscous liquid,
(37.3 mg, 80% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.32 (d, J = 8.0 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.46 (t, J
= 7.5 Hz, 2H), 7.14 (br s, 1H), 3.37 (q, J = 7.0 Hz, 2H), 1.61−1.56
(m, 2H), 1.37−1.24 (m, 6H), 0.88 (t, J = 6.0 Hz, 3H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 188.1, 161.9, 134.5, 133.5, 131.3, 128.6,
39.6, 31.5, 29.4, 26.7, 22.7, 14.1 ppm; HRMS (ESI/TOF-Q) m/z: [M
− H]− Calcd for C14H18NO2 232.1338; found 232.1331.
N-Octyl-2-oxo-2-phenylacetamide (2o).18e Yellow liquid, (39.7
mg, 76% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.34 (d, J = 8.0 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H), 7.48
(t, J = 7.5 Hz, 2H), 7.08 (br s, 1H), 3.38 (q, J = 6.5 Hz, 2H), 1.63−
1.58 (m, 2H), 1.37−1.25 (m, 10H), 0.89−0.87 (m, 3H) ppm;
13
C{1H} NMR (125 MHz, CDCl3): δ 188.1, 161.9, 134.5, 133.6,
131.4, 128.6, 39.7, 31.9, 29.5, 29.4, 29.3, 27.1, 22.8, 14.3 ppm; HRMS
(ESI/TOF-Q) m/z: [M − H]− Calcd for C16H22NO2 260.1651;
found 260.1652.
N-Hexadecyl-2-oxo-2-phenylacetamide (2p).18f White solid,
(58.9 mg, 79% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz,
CDCl3): δ 8.34 (d, J = 7.5 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.47 (t, J
= 7.5 Hz, 2H), 7.10 (br s, 1H), 3.40−3.36 (m, 2H), 1.63−1.57 (m,
2H), 1.34−1.21 (m, 24H), 0.89−0.84 (m, 5H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): δ 188.1, 161.9, 134.5, 133.6, 131.4, 128.7, 39.6,
32.1, 29.9 (for 2C), 29.8(for 2C), 29.8 (for 2C), 29.7, 29.7, 29.5, 29.5,
29.4, 27.1, 22.9, 14.3 ppm; HRMS (ESI/TOF-Q) m/z: [M − H]−
Calcd for C24H38NO2 372.2903; found 372.2891.
N-Octadecyl-2-oxo-2-phenylacetamide (2q).18g White solid,
(57.4 mg, 71% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz,
CDCl3): δ 8.34 (d, J = 8.0 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.48−
7.45 (m, 2H), 7.11 (br s, 1H), 3.38 (q, J = 6.5 Hz, 2H), 1.63−1.57
(m, 2H), 1.40−1.25 (m, 30H), 0.88 (t, J = 7.0 Hz, 3H) ppm;
13
C{1H} NMR (125 MHz, CDCl3): δ 188.1, 161.9, 134.5, 133.6,
131.4, 128.6, 39.6, 32.1, 29.9 (for 4C), 29.8 (for 3C), 29.8, 29.7, 29.7,
29.5, 29.5, 29.4, 27.1, 22.9, 14.3 ppm; HRMS (ESI/TOF-Q) m/z: [M
− H]− Calcd for C26H42NO2 400.3216; found 400.3207.
N-Cyclopentyl-2-oxo-2-phenylacetamide (2r).18h Yellow oil,
(46.1 mg, 88% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.32−8.30 (m, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.45 (t, J =
7.5 Hz, 2H), 7.07 (br s, 1H), 4.27 (dd, J = 14.0, 7.0 Hz, 1H), 2.08-
2.01(m, 2H), 1.75−1.60 (m, 4H), 1.54−1.47 (m, 2H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 188.2, 161.5, 134.4, 133.5, 131.3, 128.6,
51.3, 33.0, 23.9 ppm; HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd
for C13H14NO2 216.1025; found 216.1017.
N-Cyclohexyl-2-oxo-2-phenylacetamide (2s).18d Colorless liquid,
(39.7 mg, 86% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.32 (d, J = 7.5 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.46 (t, J
= 8.0 Hz, 2H), 6.99 (br s, 1H), 3.87−3.81 (m, 1H), 1.99−1.97 (m,
2H), 1.76−1.74 (m, 2H), 1.65−1.62 (m, 1H), 1.43−1.36 (m, 2H),
13.0−1.16 (m, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ
188.3, 161.0, 134.4, 133.6, 131.3, 128.6, 48.6, 32.8, 25.5, 24.9 ppm;
HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for C14H16NO2
230.1181; found 230.1175.
N-Cyclopropyl-2-oxo-2-phenylacetamide (2t).18d Colorless oil,
(33.6 mg, 89% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.34 (d, J = 7.0 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.47 (t, J
= 8.0 Hz, 2H), 7.14 (br s, 1H), 2.89−2.83 (m, 1H), 0.90−0.86 (m,
2H), 0.66−0.63 (m, 2H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ
187.8, 163.3, 134.5, 133.3, 131.3, 128.6, 22.7, 6.6 ppm; HRMS (ESI/
https://doi.org/10.1021/acs.joc.3c02965
J. Org. Chem. 2024, 89, 4722−4732
The Journal of Organic Chemistry
TOF-Q) m/z: [M − H]− Calcd for C11H10NO2 188.0712; found
188.0714.
N-Methyl-2-oxo-2-(p-tolyl)acetamide (2u).18a Yellow solid, (32.9
mg, 93% yield), hexane/EtOAc (90:10); 1H NMR (500 MHz,
CDCl3): δ 8.26 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.14 (br
s, 1H), 2.95 (d, J = 5.0 Hz, 3H), 2.42 (s, 3H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): δ 187.4, 162.9, 145.7, 131.5, 131.0, 129.4, 26.1,
22.0 ppm; HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for
C10H10NO2 176.0712; found 176.0722.
2-(4-Chlorophenyl)-N-methyl-2-oxoacetamide (2v).18a White
solid, (34.3 mg, 87% yield), hexane/EtOAc (90:10); 1H NMR (500
MHz, CDCl3): δ 8.33 (dd, J = 8.5, 2.0 Hz, 2H), 7.45−7.44 (m, 2H),
7.15 (br s, 1H), 2.96 (d, J = 5.0 Hz, 3H) ppm; 13C{1H} NMR (125
MHz, CDCl3): δ 186.4, 162.3, 141.2, 132.7, 131.8, 128.9, 26.1 ppm;
HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for C9H7ClNO2
196.0166; found 196.0168.
2-(4-Fluorophenyl)-N-methyl-2-oxoacetamide (2w).18a White
solid, (29.7 mg, 82% yield), hexane/EtOAc (90:10); 1H NMR (500
MHz, CDCl3): δ 8.44 (dd, J = 8.5, 5.5 Hz, 2H), 7.13 (t, J = 8.5 Hz,
3H), 2.96 (d, J = 5.5 Hz, 3H) ppm; 13C{1H} NMR (125 MHz,
CDCl3): δ 185.9, 166.8 (d, JC−F = 256.8 Hz), 162.4, 134.4 (d, JC−F =
9.5 Hz), 130.0 (d, JC−F = 2.7 Hz), 115.9 (d, JC−F = 21.6 Hz), 26.2
ppm; 19F{1H} NMR (564.6 MHz, CDCl3): δ −102.1 ppm; HRMS
(ESI/TOF-Q) m/z: [M − H]− Calcd for C9H7FNO2 180.0461;
found 180.0459.
2-(3-Methoxyphenyl)-N-methyl-2-oxoacetamide (2x).18i Yellow
liquid, (29.7 mg, 77% yield), hexane/EtOAc (88:12); 1H NMR (500
MHz, CDCl3): δ 7.99 (d, J = 7.5 Hz, 1H), 7.85 (s, 1H), 7.39 (t, J =
7.5 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.08 (br s, 1H), 3.86 (s, 3H),
2.97 (d, J = 4.5 Hz, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ
187.6, 162.7, 159.6, 134.6, 129.6, 124.1, 121.5, 114.8, 55.5, 26.1 ppm;
HRMS (ESI/TOF-Q) m/z: [M − H]− Calcd for C10H10NO3
192.0661; found 192.0664.
2-(3-Chlorophenyl)-N-methyl-2-oxoacetamide (2y). Yellow
liquid, (28.4 mg, 72% yield), hexane/EtOAc (90:10); 1H NMR
(500 MHz, CDCl3): δ 8.33 (s, 1H), 8.27 (d, J = 8.0 Hz, 1H), 7.58 (d,
J = 7.5 Hz, 1H), 7.42 (t, J = 7.5 Hz, 1H), 7.12 (br s, 1H), 2.97 (d, J =
5.0 Hz, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 186.5, 162.1,
134.8, 134.7, 134.3, 131.0, 129.9, 129.4, 26.1 ppm; HRMS (ESI/
TOF-Q) m/z: [M − H]− Calcd for C9H7ClNO2 196.0166; found
196.0169.
2-(2-Chlorophenyl)-N-methyl-2-oxoacetamide (2z).18i Brown
viscous liquid, (25.7 mg, 65% yield), hexane/EtOAc (90:10); 1H
NMR (500 MHz, CDCl3): δ 7.69−7.68 (m, 1H), 7.48−7.43 (m, 2H),
7.38−7.34 (m, 1H), 7.01 (br s, 1H), 2.98 (d, J = 5.5 Hz, 3H) ppm;
13
C{1H} NMR (125 MHz, CDCl3): δ 189.9, 161.7, 134.0, 133.0,
132.9, 131.1, 130.3, 126.5, 26.1 ppm; HRMS (ESI/TOF-Q) m/z: [M
− H]− Calcd for C9H7ClNO2 196.0166; found 196.0168.
Methyl 2-Oxo-2-phenylacetate (4a).19 Colorless liquid, (19.0 mg,
58% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz, CDCl3): δ
8.01 (d, J = 8.0 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz,
2H), 3.98 (s, 3H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ 186.2,
164.2, 135.1, 132.6, 130.2, 129.1, 52.9 ppm; HRMS (ESI/TOF-Q)
m/z: [M + H]+ Calcd for C9H9O3 165.0546; found 165.0558.
Ethyl 2-Oxo-2-phenylacetate (4b).19 Colorless liquid, (21.4 mg,
60% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz, CDCl3): δ
8.01 (d, J = 7.5 Hz, 2H), 7.65 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz,
2H), 4.45 (q, J = 7.0 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 186.5, 164.0, 135.0, 132.6, 130.0, 129.0,
62.4, 14.2 ppm; HRMS (ESI/TOF-Q) m/z: [M + Na]+ Calcd for
C10H10NaO3 201.0522; found 201.0524.
Butyl 2-Oxo-2-phenylacetate (4c).19 Colorless liquid, yield (21.4
mg, 52% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz,
CDCl3): δ 8.00 (d, J = 7.0 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.51
(t, J = 7.5 Hz, 2H), 4.40 (t, J = 6.5 Hz, 2H), 1.79−1.74 (m, 2H),
1.49−1.42 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): δ 186.7, 164.2, 135.0, 132.7, 130.2, 129.1, 66.3,
30.7, 19.2, 13.8 ppm; HRMS (ESI/TOF-Q) m/z: [M + Na]+ Calcd
for C12H14NaO3 229.0835; found 229.0835.
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Isobutyl 2-Oxo-2-phenylacetate (4d).19 Colorless liquid, (19.8
mg, 48% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz,
CDCl3): δ 8.00 (d, J = 8.5 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.52
(t, J = 7.5 Hz, 2H), 4.18 (d, J = 6.5 Hz, 2H), 2.13−2.05 (m, 1H), 1.01
(d, J = 6.5 Hz, 6H) ppm; 13C{1H} NMR (125 MHz, CDCl3): δ
186.7, 164.2, 135.0, 132.7, 130.1, 129.1, 72.3, 27.9, 19.2 ppm; (ESI/
TOF-Q) m/z: [M + Na]+ Calcd for C12H14NaO3 229.0835; found
229.0838.
Hexyl 2-Oxo-2-phenylacetate (4e).19 Colorless liquid, (24.4 mg,
52% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz, CDCl3): δ
8.00 (d, J = 7.5 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz,
2H), 4.39 (t, J = 6.5 Hz, 2H), 1.81−1.79 (m, 2H), 1.43−1.39 (m, J =
2H), 1.34−1.28 (m, 4H), 0.89 (t, J = 6.5 Hz, 3H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 186.6, 164.1, 135.0, 132.6, 130.1, 129.0,
66.5, 31.4, 28.5, 25.5, 22.6, 14.1 ppm; (ESI/TOF-Q) m/z: [M + Na]+
Calcd for C14H18NaO3 257.1148; found 257.1152.
Dodecyl 2-Oxo-2-phenylacetate (4f). Colorless liquid, (28.0 mg,
44% yield), hexane/EtOAc (98:2); 1H NMR (500 MHz, CDCl3): δ
8.00 (d, J = 8.0 Hz, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz,
2H), 4.38 (t, J = 6.5 Hz, 2H), 1.80−1.75 (m, 2H), 1.42−1.38 (m,
2H), 1.33−1.25 (m, 16H), 0.88 (t, J = 6.5 Hz, 3H) ppm; 13C{1H}
NMR (125 MHz, CDCl3): δ 186.6, 164.2, 135.0, 132.7, 130.1, 129.0,
66.5, 32.01, 29.8, 29.8, 29.7, 29.6, 29.5, 29.3, 28.6, 25.9, 22.8, 14.2
ppm; (ESI/TOF-Q) m/z: [M + Na]+ Calcd for C20H30NaO3
341.2087; found 341.2092.
2-Ethoxyethyl 2-Oxo-2-phenylacetate (4g). Pale Yellow liquid,
(24.0 mg, 54% yield), hexane/EtOAc (95:5); 1H NMR (500 MHz,
CDCl3): δ 8.06 (d, J = 7.0 Hz, 2H), 7.68 (t, J = 7.5 Hz, 1H), 7.53 (t, J
= 7.5 Hz, 2H), 4.57 (t, J = 5.0 Hz, 2H), 3.78 (t, J = 5.0 Hz, 2H), 3.59
(q, J = 7.0 Hz, 2H), 1.25 (t, J = 7.0 Hz, 3H) ppm; 13C{1H} NMR
(125 MHz, CDCl3): δ 186.4, 164.0, 135.1, 132.7, 130.3, 129.0, 68.0,
66.9, 65.2, 15.3 ppm; (ESI/TOF-Q) m/z: [M + Na]+ Calcd for
C12H14NaO4 245.0784; found 245.0783.
■ ASSOCIATED CONTENT
Data Availability Statement
The data underlying this study are available in the published
article and its online Supporting Information.
*
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.3c02965.
Experimental procedures, mechanistic studies, crystallo-
graphic data of compound 2k, and copies of NMR of all
synthesized compounds (PDF)
Accession Codes
CCDC 2296097 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
■ AUTHOR INFORMATION
Corresponding Author
Nidhi Jain − Department of Chemistry, Indian Institute of
Technology, New Delhi 110016, India; orcid.org/0000-
0001-8645-430X; Email: njain@chemistry.iitd.ac.in
Authors
Rohit Kumar − Department of Chemistry, Indian Institute of
Technology, New Delhi 110016, India
Nitika Grover − Department of Chemistry, Indian Institute of
Technology, New Delhi 110016, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.3c02965
https://doi.org/10.1021/acs.joc.3c02965
J. Org. Chem. 2024, 89, 4722−4732
The Journal of Organic Chemistry
Notes
The authors declare no competing financial interest.
The major/minor ratio is based on the integration of 1H NMR
data of β-enaminonitrile. The olefinic proton in the range 3.8−
5.1 ppm has been used to determine the ratio of cis/trans
isomers.
■ ACKNOWLEDGMENTS
The authors are grateful to CSIR (02/0415/21/EMR-II) and
DST (CRG/2021/000729) for the financial support. The
authors thank DST-FIST for funding the ESI-HRMS instru-
ment and the SCXRD and CRF facility at IIT Delhi. N.G.
thanks DST/INSPIRE/04/2021/001724 for funding.
■
**13
ADDITIONAL NOTES
C NMR of both isomers was reported together as there
was a major overlap of peaks between them.
* Synthesis of Alkaloid Frameworks. Angew. Chem., Int. Ed. 2021, 60,
The exact amount of minor isomer could not be determined
by 1H NMR as it was present in traces. However, its presence
was evident from the few additional peaks seen in the aliphatic
region in the 13C NMR spectrum.
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