Visible-Light-Induced Photocatalytic Oxidative Decarboxylation of Cinnamic Acids to 1,2-Diketones

Article abstract of DOI:10.1021/acs.joc.1c00322

A concerted metallophotoredox catalysis has been realized for the efficient decarboxylative functionalization of α,β-unsaturated carboxylic acids with aryl iodides in the presence of perylene bisimide dye to afford 1,2-diketones.

Full text of DOI:10.1021/acs.joc.1c00322

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Article
Visible-Light-Induced Photocatalytic Oxidative Decarboxylation of
Cinnamic Acids to 1,2-Diketones
Shiv Chand, Anand Kumar Pandey, Rahul Singh, and Krishna Nand Singh*
Cite This: J. Org. Chem. 2021, 86, 6486−6493
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ABSTRACT: A concerted metallophotoredox catalysis has been realized for the efficient decarboxylative functionalization of α,β-
unsaturated carboxylic acids with aryl iodides in the presence of perylene bisimide dye to afford 1,2-diketones.
Scheme 1. Synthesis of 1,2-Diketones
INTRODUCTION
■
1,2-Diketones constitute an important class of privileged
structures with key applications in the synthesis of bioactive
molecules and natural products.1,2 Such motifs manifest in vital
molecules with antitumor activities3 and photochemical
properties.4 Besides their uses as ligands5 and versatile building
blocks to medicinal molecules,6 the 1,2-diketones have also
been exploited as pioneers to accomplish N-heterocyclic
carbenes.7 Thus, the synthesis of 1,2-diketones has garnered
a great deal of interest, and different strategies for their
preparation have emerged (Scheme 1). The existing strategies
to synthesize 1,2-diketones are mainly comprised of the
oxidation of different substrates, such as olefins,8 α-hydroxy
ketones,9 methylene ketones,10 alkynes,11 and aryl propiolic
acids as a terminal alkyne surrogate,12 among which the use of
an alkyne appears to be the most practical. Different transition
metals, such as Pd,13 Ru,14 Au,15a,d Hg,15e and Cu,16 are
prominent amid the consortium of catalysts employed in the
synthesis of 1,2-diketones with oxidants such as DMSO, oxone,
K2S2O8, TBHP, and Ph2SO. Despite many advantages, the
availability and prior synthesis of the reactants in the
aforementioned strategies are incommodious. The use of
toxic and rare metal catalysts and reagents and at times higher
temperatures further endorse the need for the development of
a novel and inclusive synthetic strategy for 1,2-diketones.
Decarboxylative cross-coupling has recently come up as a
powerful advancement in the formation of carbon−carbon or
carbon−heteroatom bonds in organic synthesis.17 The
carboxylic acids are easily available, stable, nontoxic, easy to
store and handle, far less air and moisture sensitive in
comparison to typical cross-coupling organometallic reagents,
and give CO2 as the only byproduct. Cinnamic acids are
especially important as they are commercially available in a
great structural diversity and are readily prepared.18 As a part
of our current research endeavor exploiting the use of cinnamic
acids in lieu of alkene and alkyne analogues,19 the exploration
of a proficient decarboxylative strategy involving cinnamic
Received: February 9, 2021
Published: April 14, 2021
https://doi.org/10.1021/acs.joc.1c00322
© 2021 American Chemical Society
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Article
a
acids under visible light photoredox catalysis to afford the 1,2-
diketones was envisioned. In this context, Lee et al. have
reported a decarboxylative cross-coupling of aryl propiolic
acids with aryl iodides, followed by oxidation to the title
products (cf. Scheme 1).12a
Table 1. Optimization of the Reaction Conditions
The substrate scope limitation at the propiolic acid end,
however, imposed restrictions, and an alternative approach
employing the cinnamic acid derivatives was thought to be
worthwhile. The last few decades have witnessed a
rejuvenation of photoredox catalysis to ensure sustainable
synthesis under mild conditions.20 The activation of traditional
inert substrates to reactive intermediates at room temperature
upon merely an exposure to visible light has influenced several
cross-coupling reactions that otherwise require a high energy
influx to overcome the activation barrier. While the approach
offers an eco-safe and efficient tool in organic synthesis, it has
been largely dependent on expensive ruthenium and iridium
complexes for catalysis. Organic dyes present a cost-effective
alternative, yet have a restricted range of redox potentials
under visible-light irradiation.21 A recent report by Sun et al.
uncovered the synthesis of 1,2-diketones via the visible-light
photooxidation of alkynes using eosin-Y as a photocatalyst.22
Aryl halides act as an efficient aryl source for cross-coupling
reactions due to their commercial accessibility.23 However, the
high reduction potential of aryl halides restricts its synthetic
appositeness for the photoredox catalysis. Inspired by the Z-
yield
b
entry
catalyst
CuI
CuBr
CuCl
CuCl2·2H2O
CuBr2
Cu(OAc)2
Cu(OAc)2·
H2O
photocatalyst
PDI
base
Et3N
solvent
(%)
1
2
3
4
5
6
7
8
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
trace
22
36
86
18
26
50
45
PDI
PDI
PDI
PDI
PDI
PDI
PDI
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
9
FeCl3
CoCl2·6H2O PDI
PDI
Et3N
Et3N
Et3N
-
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
THF
DCM
DMF
DMSO
Toluene
CH3CN
35
20
38
0
46
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
NiCl2·6H2O
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
PDI
PDI
PDI
PDI
PDI
PDI
PDI
PDI
PDI
PDI
PDI
PDI
PDI
NaOH
K2CO3
KOtBu
DBU
DABCO
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
0
79
75
70
75
48
42
37
30
46
̈
scheme of biological photosynthesis, Konig et al. have
disclosed the photocatalytic applicability of N,N′-bis(2,6-
diisopropylphenyl)-3,4,9,10-perylenetetracarboxylic diimide
(PDI) to overcome this limitation by engaging two successive
photoexcitations of PDI in a single catalytic cycle.24
In view of the above, we herein disclose an efficient visible-
light-promoted decarboxylative functionalization of cinnamic
acids with aryl iodides in the presence of PDI, CuCl, TBHP,
and Et3N to afford the 1,2-diketones with ample substrate
scope and functional group compatibility (cf. Scheme 1, our
approach).
rhodamine B
base
eosin-Y
eosin-B
rose bengal
25
26
27
CuCl
CuCl
CuCl
Et3N
Et3N
Et3N
CH3CN
CH3CN
CH3CN
70
62
35
a
Reaction conditions are as follows: 1a (1.0 mmol), 2a (1.0 mmol),
photocatalyst (2.0 mol %), catalyst (20 mol %), base (1.0 equiv),
RESULTS AND DISCUSSION
c
■
oxidant (3.0 equiv), and solvent (2.0 mL) in an open vessel with 470
b
To conceive of our idea for the synthesis of 1,2-diketones, an
archetypal reaction employing equimolar quantities of
cinnamic acid (1a) and iodobenzene (2a) was meticulously
investigated by varying different parameters, such as visible
light, the photocatalyst, the catalyst, the base, the oxidant, and
the solvent. The findings are given in Table 1. Under the initial
reaction stipulations, comprising PDI (2.0 mol %), TBHP (3.0
equiv), and Et3N (1.0 equiv) in acetonitrile, a trace of the
desired product benzil (3a) was observed when equimolar
amounts (1.0 mmol) of 1a and 2a were irradiated using blue
LED (470 nm) light at room temperature for 10 h (Table 1,
entry 1). Retaining all the parameters of entry 1, some copper
salts, viz. CuI, CuBr, CuCl, CuCl2·2H2O, CuBr2, Cu(OAc)2,
and Cu(OAc)2·H2O, were then added to envisage the
likelihood of metallophotoredox catalysis to effect the chosen
transformation (Table 1, entries 2−8, respectively). Out of the
different trials, the use of CuCl (20 mol %) gave rise to the
best surge in the product yield (86%; Table 1, entry 4). Some
other transition metal salts, viz. FeCl3, CoCl2·6H2O, and NiCl2·
6H2O, were also examined, but they all proved mediocre
(Table 1, entries 9−11, respectively). Notably, when the
reaction was carried out in the absence of a base, no product
was formed at all (Table 1, entry 12). Bases such as NaOH,
K2CO3, and KOtBu were also tested as a part of the
nm blue LED irradiation at rt for 10 h. Isolated yield after column
c
chromatography. Only TBHP (3.0 equiv., 70 wt % in H2O) could
work out of different oxidants screened, including K2S2O8, DTBP,
TBHP, and O2 (balloon).
optimization progression (Table 1, entries 13−15, respec-
tively), but only NaOH could provide somewhat appreciable
product yield (Table 1, entry 13) while the others remained
futile (Table 1, entries 14 and 15). However, when DBU or
DABCO was employed as base, it led to a substantially higher
product yield (Table 1, entries 16 or 17, respectively);
however, it did not surpass that of Et3N. Subsequently, while
maintaining other parameters of entry 4 as such, the effect of
different solvents was investigated (Table 1, entries 18−23).
Whereas DCE and THF provided considerably high product
yields (Table 1, entries 18 and 19, respectively), the use of
DCM, DMF, DMSO, and toluene led to much lower yields
(Table 1, entries 20−23, respectively). Furthermore, some
other organic dyes viz. rhodamine B base, eosin-Y, eosin-B, and
rose bengal, were also assessed for their redox activity under
visible light; however, none of them could match the efficacy of
PDI (Table 1, entries 24−27, respectively). Chloro- or bromo-
benzene, when tried in the place of 2a, did not work.
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After establishing the optimized conditions, the scope and
generality of the approach were explored using different
cinnamic acids and iodoarenes (Table 2). A diverse range of
Scheme 2. Control Experiments
Table 2. Substrate Scope for the Synthesis of 1,2-
a b
,
Diketones
tional heating at 120 °C for 16 h in the absence of a
photocatalyst, which could provide only a trace of the desired
product 3a. Control experiments were also executed to observe
if stilbene was an intermediate in the reaction pathway.
Although the direct oxidation of stilbene under the optimized
reaction conditions afforded the desired diketone product, no
stilbene was formed when the reaction was carried in the
absence of TBHP with the rest of the conditions intact, and
cinnamic acid (1a) remained unconsumed. Thus, the
possibility of a stilbene intermediate in the reaction pathway
remains faint. However, the reaction of phenylpropiolic acid 5a
with iodobenzene 2a under the standard conditions gave rise
to the 1,3-dialkyne product (6a) rather than the 1,2-diketone
product.
Based on control experiments, product isolation, and
literature precedent,24,25 a plausible mechanism involving the
metallophotoredox decarboxylative synthesis of 1,2-diketones
is outlined in Scheme 3.
a
Reaction conditions are as follows: 1 (1.0 mmol), 2 (1.0 mmol), PDI
(2.0 mol %), CuCl (20 mol %), Et3N (1.0 equiv), TBHP (3.0 mmol,
70 wt % in H2O), and CH3CN (2.0 mL) in an open vessel irradiated
The low-valent Cu(I) is initially oxidized by TBHP to
Cu(II)−OH. The first excitation of PDI by irradiation
undergoes a reductive quenching by triethylamine to form a
radical anion PDI•− and an oxidized Et3N•+. Afterward, the
further irradiation of PDI•− produces the species PDI•−*,
which then reduces the iodobenzene 2a to the radical
precursor PhI•−, followed by its fragmentation to form a
phenyl radical. The phenyl radical next is added to the
cinnamate to form the intermediate A,26 which is oxidized by
Cu(II)−OH to form the intermediate B with the revival of
Cu(I) for the next catalytic cycle. The hydroxylation of B gives
the intermediate C, which decarboxylates in the presence of
Et3N•+ to form the intermediate D26d and then affords the
intermediate E via a radical coupling with t-butyl peroxy
radical. The Kornblum−DeLaMare rearrangement of E affords
the α-hydroxy ketone F, which is eventually oxidized by TBHP
to the 1,2-diketone 3a.
b
with 470 nm blue LED at rt for 10 h. Isolated yield after column
chromatography.
both the reactants with different electron-withdrawing and
electron-donating substituents, such as CH3, Cl, Br, F, OMe,
NO2, CN, CF3, and COOMe, participated nicely in the
reaction to afford the desired products 3a−3z in reasonably
high yields. As such, no explicit electronic effect from the
substituent was observed, but the steric influence of the ortho-
substitution somewhat impeded the reaction. An archetypal
polycyclic substrate 1-iodonaphthalene also worked well under
the established conditions to afford the anticipated product 3n
(68%).
To gain insight into the reaction mechanism, some control
experiments were carried out, which are shown in Scheme 2.
The presence of radical trapping agents such as TEMPO
(2,2,6,6-tetramethylpiperidin-1-yl)oxyl and 2,6-di-tert-butyl-4-
methylphenol (BHT) under standard conditions suppressed
the reaction, thereby implying a radical pathway. The
involvement of an aryl radical in the mechanistic pathway
was further confirmed by the formation of the adduct 2,2,6,6-
tetramethyl-1-phenoxypiperidine 4a, which was detected by
HRMS. The reaction was further carried out under conven-
CONCLUSIONS
■
In conclusion, an oxidative decarboxylative functionalization of
cinnamic acids has been realized with aryl iodides using a
catalytic combination of copper chloride and N,N′-bis(2,6-
diisopropylphenyl)-3,4,9,10-perylenetetracarboxylic diimide
under visible-light irradiation.
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crude product was purified by column chromatography using ethyl
acetate/hexane (v/v = 1:50) as the eluent to afford the product 3.
1,2-Diphenylethane-1,2-dione (3a).15a Purification by column
chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow solid
(181 mg, 86% yield): mp 92−93 °C; 1H NMR (500 MHz, CDCl3) δ
7.98 (d, J = 7.0 Hz, 4H), 7.67 (t, J = 7.5 Hz, 2H), 7.53 (t, J = 7.5 Hz,
4H); 13C{1H} NMR (126 MHz, CDCl3) δ 194.7, 135.0, 133.1, 130.0,
129.2; HRMS (ESI) m/z [M + H]+ Calcd for C14H11O2 211.0754,
found 211.0762.
Scheme 3. Plausible Reaction Mechanism
1-Phenyl-2-(p-tolyl)ethane-1,2-dione (3b).13a Purification by
column chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow
1
solid (197 mg, 88% yield): mp 91−92 °C; H NMR (500 MHz,
CDCl3) δ 7.98 (d, J = 8.0 Hz, 2H), 7.88 (d, J = 8.0 Hz, 2H), 7.67 (t, J
= 7.5 Hz, 1H), 7.52 (t, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.44
(s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 194.9, 194.4, 146.4,
134.9, 133.2, 130.7, 130.2, 130.0, 129.9, 129.1, 22.1; HRMS (ESI) m/
z [M + H]+ Calcd for C15H13O2 225.0910, found 225.0913.
1-Phenyl-2-(m-tolyl)ethane-1,2-dione (3c).14c Purification by
column chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow
1
solid (166 mg, 74% yield): mp 88−89 °C; H NMR (500 MHz,
CDCl3) δ 7.98 (d, J = 7.5 Hz, 2H), 7.78 (d, J = 11.5 Hz, 2H), 7.66 (t,
J = 7.0 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H), 7.48 (d, J = 7.5 Hz, 1H),
7.41 (t, J = 7.5 Hz, 1H), 2.41 (s, 3H); 13C{1H} NMR (126 MHz,
CDCl3) δ 195.0, 194.9, 139.2, 135.9, 135.0, 133.2, 133.2, 130.4, 130.1,
129.2, 129.1, 127.4, 21.4; HRMS (ESI) m/z [M + H]+ Calcd for
C15H13O2 225.0910, found 225.0913.
1-Phenyl-2-(o-tolyl)ethane-1,2-dione (3d).14c Purification by
column chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow
solid (108 mg, 48% yield): mp 56−57 °C; H NMR (500 MHz,
1
EXPERIMENTAL SECTION
■
General Information. 1H, 13C{1H}, and 19F spectra were
recorded on a JEOL ECZ 500R FT NMR spectrometer (1H NMR
at 500 MHz, 13C {1H} NMR at 126 MHz, and 19F NMR at 471
MHz). Chemical shifts for the protons are reported in parts per
million downfield from tetramethylsilane and are referenced to the
residual deuterium in the solvent (1H NMR, CDCl3 at 7.26 ppm),
whereas those for the carbons are reported in parts per million
downfield from tetramethylsilane and are referenced to the carbon
resonance of the solvent peak (13C{1H} NMR, CDCl3 at 77.160
ppm). NMR data are represented as follows: chemical shift,
multiplicity (s = singlet, d = doublet, t = triplet and m = multiplet),
coupling constant (J) (Hz), and integration. Mass spectra were
recorded on a Sciex X500R QTOF mass spectrometer. Analytical thin
layer chromatography (TLC) was performed on Merck Kieselgel 60
GF254 plates (thickness 0.25 mm). TLC visualization was performed
with a 254 nm UV lamp and by staining in an I2 chamber. Organic
CDCl3) δ 7.98 (d, J = 7.5 Hz, 2H), 7.68−7.64 (m, 2H), 7.54−7.48
(m, 3H), 7.36 (d, J = 7.5 Hz, 1H), 7.28 (d, J = 7.5 Hz, 1H), 2.71 (s,
3H); 13C{1H} NMR (126 MHz, CDCl3) δ 196.9, 195.0, 141.5, 134.8,
133.9, 133.3, 133.2, 132.7, 132.0, 130.1, 129.2, 126.2, 22.1; HRMS
(ESI) m/z [M + H]+ Calcd for C15H13O2 225.0910, found 225.0913.
1-(2-Chlorophenyl)-2-phenylethane-1,2-dione (3e).16a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
Yellow oil (112 mg, 46% yield); 1H NMR (500 MHz, CDCl3) δ 8.00
(d, J = 7.5 Hz, 2H), 7.92 (d, J = 7.5 Hz, 1H), 7.68 (t, J = 7.0 Hz, 1H),
7.55 (t, J = 7.0 Hz, 3H), 7.46 (t, J = 8.0 Hz, 2H); 13C{1H} NMR (126
MHz, CDCl3) δ 193.8, 192.2, 134.7, 134.7, 134.2, 134.0, 132.6, 132.3,
130.7, 130.4, 129.0, 127.5; HRMS (ESI) m/z [M + H]+ Calcd for
C14H10ClO2 245.0364, found 245.0367.
1-(3-Chlorophenyl)-2-phenylethane-1,2-dione (3f).27 Purification
by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow solid (132 mg, 54% yield): mp 91−92 °C; H NMR (500
MHz, CDCl3) δ 7.98 (d, J = 7.5 Hz, 3H), 7.85 (d, J = 8.0 Hz, 1H),
7.70 (t, J = 7.5 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.5 Hz,
2H),7.47 (t, J = 8.0 Hz, 1H); 13C{1H} NMR (126 MHz, CDCl3) δ
193.8, 193.1, 135.6, 135.3, 134.9, 134.7, 132.8, 130.5, 130.1, 129.7,
129.3, 128.3; HRMS (ESI) m/z [M + H]+ Calcd for C14H10ClO2
245.0364, found 245.0373.
solutions were concentrated under reduced pressure using a Buchi
̈
rotary evaporator. Purification of the crude products was carried out
by column chromatography using silica gel 100−200 mesh. All the
reactions were carried out in open vessel using oven-dried glassware.
Yield refers to the isolated analytically pure material. Visible-light
irradiation was performed using a SP-01-B4 Blue (470 nm) LUXEON
Rebel LED on a SinkPAD-II 20 mm Star Base - 70 lm at 700 mA to
the reaction mixture contained in a borosilicate glass vessel, and the
distance from the light source to the irradiation vessel was 2 cm.
Materials. All the cinnamic acids and iodoarenes were purchased
from Sigma-Aldrich, whereas N,N′-bis(2,6-diisopropylphenyl)-
3,4,9,10-perylenetetracarboxylic diimide (PDI) was procured from
TCI Chemicals. All other chemicals were used as such without any
further purification. Solvents were purified by standard methods.
General Experimental Procedure for the Synthesis of 1,2-
Diketones 3. A mixture of cinnamic acid 1 (1.0 mmol), aryl iodide 2
(1.0 mmol), CuCl (20 mol %), Et3N (1.0 mmol), TBHP (3.0 mmol,
70 wt % in H2O), PDI (2.0 mol %), and CH3CN (2.0 mL) contained
in a 25 mL borosilicate RB flask was irradiated by Luxeon rebel Blue
LED (470 nm) while stirring at room temperature for 24 h. After the
completion of the reaction (monitored through TLC), the mixture
was quenched using a saturated aqueous solution of sodium
bicarbonate (15 mL) and then extracted with ethyl acetate (2 × 15
mL). The combined organic phase was dried over anhydrous Na2SO4,
filtered, and concentrated under reduced pressure. The resulting
1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (3g).16a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow solid (151 mg, 62% yield): mp 76−77 °C; H NMR (500
MHz, CDCl3) δ 7.97−7.92 (m, 4H), 7.69−7.66 (m, 1H), 7.54−7.49
(m, 4H); 13C{1H} NMR (126 MHz, CDCl3) δ 194.0, 193.2, 141.8,
135.2, 132.9, 131.5, 131.4, 130.1, 129.6, 129.2; HRMS (ESI) m/z [M
+ H]+ Calcd for C14H10ClO2 245.0364, found 245.0370.
1-(4-Bromophenyl)-2-phenylethane-1,2-dione (3h).15a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow solid (199 mg, 69% yield): mp 78−79 °C; H NMR (500
MHz, CDCl3) δ 7.97 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 8.0 Hz, 2H),
7.67 (d, J = 8.0 Hz, 3H), 7.54 (t, J = 7.5 Hz, 2H); 13C{1H} NMR
(126 MHz, CDCl3) δ 194.0, 193.4, 135.2, 132.9, 132.6, 131.9, 131.4,
130.7, 130.1, 129.2; HRMS (ESI) m/z [M + H]+ Calcd for
C14H10BrO2 288.9859, found 288.9869.
1-(4-Fluorophenyl)-2-phenylethane-1,2-dione (3i).15a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow solid (130 mg, 57% yield): mp 61−62 °C; H NMR (500
MHz, CDCl3) δ 8.03−8.00 (m, 2H), 7.98 (d, J = 7.5 Hz, 2H), 7.68 (t,
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J = 7.0 Hz, 1H), 7.53 (t, J = 8.0 Hz, 2H), 7.20 (t, J = 8.5 Hz, 2H);
13C{1H} NMR (126 MHz, CDCl3) δ 194.2, 192.9, 167.9 (C−F, 1JC−F
= 258.9 Hz), 135.1, 133.0, 132.9 (C−F, 3JC−F = 9.9 Hz), 130.1, 129.7
2.44 (s, 3H), 2.40 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ
195.2, 194.6, 146.3, 139.1, 135.8, 133.3, 130.8, 130.4, 130.2, 129.9,
129.0, 127.4, 22.1, 21.4; HRMS (ESI) m/z [M + H]+ Calcd for
C16H15O2 239.1067, found 239.1068.
4
2
(C−F, JC−F = 8.9 Hz), 129.2, 116.6 (C−F, JC−F = 22.7 Hz); 19F
NMR (471 MHz, CDCl3) δ −101.1; HRMS (ESI) m/z [M + H]+
Calcd for C14H10FO2 229.0659, found 229.0659.
1-(4-Fluorophenyl)-2-(4-methoxyphenyl)ethane-1,2-dione
(3r).11a Purification by column chromatography (ethyl acetate/
hexane, v/v = 1:50). Yellow solid (178 mg, 69% yield): mp 63−64
°C; 1H NMR (500 MHz, CDCl3) δ 8.03−8.00 (m, 2H), 7.95 (d, J =
9.0 Hz, 2H), 7.19 (t, J = 8.5 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 3.89
(s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 193.2, 192.8, 167.9,
165.8 (C−F, 1JC−F = 267.5 Hz), 132.9 (C−F, 3JC−F = 37.2 Hz), 132.6,
1-(4-Methoxyphenyl)-2-phenylethane-1,2-dione (3j).13a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow oil (213 mg, 89% yield); H NMR (500 MHz, CDCl3) δ
7.98−7.94 (m, 4H), 7.66 (t, J = 7.0 Hz, 1H), 7.51 (t, J = 7.5 Hz, 2H),
6.99 (d, J = 9.0 Hz, 2H), 3.89 (s, 3H); 13C{1H} NMR (126 MHz,
CDCl3) δ 194.7, 193.1, 164.9, 134.6, 133.1, 132.3, 129.8, 128.8, 126.0,
114.3, 55.5; HRMS (ESI) m/z [M + H]+ Calcd for C15H13O3
241.0859, found 241.0862.
4
2
129.9 (C−F, JC−F = 8.0 Hz), 126.1, 116.5 (C−F, JC−F = 84.3 Hz),
114.6, 55.8; 19F NMR (471 MHz, CDCl3) δ −101.6; HRMS (ESI)
m/z [M + H]+ Calcd for C15H12FO3 259.0765, found 259.0764.
1-(4-Fluorophenyl)-2-(p-tolyl)ethane-1,2-dione (3s).13a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1-(4-Nitrophenyl)-2-phenylethane-1,2-dione (3k).15a Purification
by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
1
Yellow solid (160 mg, 66% yield): mp 78−79 °C; H NMR (500
Yellow solid (156 mg, 61% yield): mp 126−127 °C; H NMR (500
MHz, CDCl3) δ 8.03−8.00 (m, 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.32
(d, J = 8.0 Hz, 2H), 7.20 (t, J = 8.0 Hz, 2H), 2.44 (s, 3H); 13C{1H}
NMR (126 MHz, CDCl3) δ 194.0, 193.1, 167.9 (C−F, 1JC−F = 258.2
MHz, CDCl3) δ 8.36 (d, J = 9.0 Hz, 2H), 8.18 (d, J = 9.0 Hz, 2H),
7.99 (d, J = 7.0 Hz, 2H), 7.72 (t, J = 7.5 Hz, 1H), 7.56 (t, J = 8.0 Hz,
2H); 13C{1H} NMR (126 MHz, CDCl3) δ 193.0, 192.2, 151.3, 137.4,
135.6, 132.5, 131.1, 130.2, 129.4, 124.3; HRMS (ESI) m/z [M + H]+
Calcd for C14H10NO4 256.0604, found 256.0610.
Hz), 146.5, 132.9 (C−F, 4JC−F = 9.8 Hz), 130.6, 130.2 (C−F, 3JC−F
=
34.8 Hz), 129.8, 116.6 (C−F, 2JC−F = 18.6 Hz), 22.1; 19F NMR (471
MHz, CDCl3): δ −101.5; HRMS (ESI) m/z [M + H]+ Calcd for
C15H12FO2 243.0816, found 243.0826.
4-(2-Oxo-2-phenylacetyl)benzonitrile (3l).16a Purification by
column chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow
1-(4-Methoxyphenyl)-2-(p-tolyl)ethane-1,2-dione (3t).27 Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
solid (113 mg, 48% yield): mp 111−112 °C; H NMR (500 MHz,
CDCl3) δ 8.10 (d, J = 8.0 Hz, 2H), 7.98 (d, J = 7.0 Hz, 2H), 7.83 (d, J
= 8.5 Hz, 2H), 7.72 (t, J = 7.5 Hz, 1H), 7.56 (t, J = 7.5 Hz, 2H);
13C{1H} NMR (126 MHz, CDCl3) δ 193.1, 192.5, 136.0, 135.5,
132.9, 132.6, 130.3, 130.2, 129.3, 118.0, 117.7; HRMS (ESI) m/z [M
+ H]+ Calcd for C15H10NO2 236.0706, found 236.0715.
1
Yellow solid (231 mg, 91% yield): mp 106−107 °C; H NMR (500
MHz, CDCl3) δ 7.95 (d, J = 8.5 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H),
7.31 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H), 3.88 (s, 3H), 2.43
(s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 194.7, 193.5, 165.1,
146.1, 132.5, 131.8, 130.9, 130.2, 129.8, 114.5, 55.8, 22.1; HRMS
(ESI) m/z [M + H]+ Calcd for C16H15O3 255.1016, found 270.1026.
1,2-Di-p-tolylethane-1,2-dione (3u).27 Purification by column
chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow solid
(200 mg, 84% yield): mp 103−104 °C; 1H NMR (500 MHz, CDCl3)
δ 7.87 (d, J = 8.5 Hz, 4H), 7.31 (d, J = 8.0 Hz, 4H), 2.43 (s, 6H);
13C{1H} NMR (126 MHz, CDCl3) δ 194.7, 146.2, 130.9, 130.2,
129.9, 22.1; HRMS (ESI) m/z [M + H]+ Calcd for C16H15O2
239.1067, found 239.1059.
1-(4-Nitrophenyl)-2-(p-tolyl)ethane-1,2-dione (3m).11e Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow solid (140 mg, 52% yield): mp 145−146 °C; H NMR (500
MHz, CDCl3) δ 8.35 (d, J = 8.5 Hz, 2H), 8.16 (d, J = 8.5 Hz, 2H),
7.88 (d, J = 7.5 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H);
13C{1H} NMR (126 MHz, CDCl3) δ 192.7, 192.4, 151.3, 147.1,
137.6, 131.1, 130.3, 130.1, 124.2, 22.1; HRMS (ESI) m/z [M + H]+
Calcd for C15H12NO4 270.0761, found 270.0767.
1-(Naphthalen-1-yl)-2-phenylethane-1,2-dione (3n).13a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1-(2-Chlorophenyl)-2-(p-tolyl)ethane-1,2-dione (3v).28 Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
Yellow solid (177 mg, 68% yield): mp 100−101 °C; H NMR (500
1
Yellow solid (131 mg, 51% yield): mp 66−67 °C; H NMR (500
MHz, CDCl3) δ 9.31 (d, J = 8.5 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H),
8.04 (d, J = 7.0 Hz, 2H), 7.96−7.91 (m, 2H), 7.77 (t, J = 7.5 Hz, 1H),
7.68−7.62 (m, 2H), 7.54−7.48 (m, 3H); 13C{1H} NMR (126 MHz,
CDCl3) δ 197.3, 194.7, 136.1, 135.2, 134.9, 134.2, 133.5, 131.1, 130.2,
129.6, 129.2, 128.9, 128.8, 127.3, 126.1, 124.6; HRMS (ESI) m/z [M
+ H]+ Calcd for C18H13O2 261.0910, found 261.0921.
MHz, CDCl3) δ 7.94 (d, J = 8.0 Hz, 2H), 7.91 (d, J = 7.5 Hz, 1H),
7.55 (t, J = 7.0 Hz, 1H), 7.45 (t, J = 7.0 Hz, 2H), 7.34 (d, J = 7.5 Hz,
2H), 2.46 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 193.9, 192.0,
145.9, 134.6, 134.1, 132.3, 130.7, 130.5, 130.2, 129.8, 127.5, 22.1;
HRMS (ESI) m/z [M + H]+ Calcd for C15H12ClO2 259.0520, found
259.0522.
Methyl 4-(2-Oxo-2phenylacetyl)benzoate (3o).27 Purification by
column chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow
1-(4-Chlorophenyl)-2-(p-tolyl)ethane-1,2-dione (3w).16a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
solid (177 mg, 66% yield): mp 71−72 °C; H NMR (500 MHz,
1
Yellow solid (168 mg, 65% yield): mp 116−117 °C; H NMR (500
CDCl3) δ 8.17 (d, J = 8.0 Hz, 2H), 8.05 (d, J = 8.0 Hz, 2H), 7.99 (d, J
= 7.5 Hz, 2H), 7.70 (t, J = 7.0 Hz, 1H), 7.56 (t, J = 7.5 Hz, 2H), 3.96
(s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 193.9, 193.8, 166.0,
136.2, 135.5, 135.3, 132.9, 130.2, 130.1, 129.9, 129.3, 52.8; HRMS
(ESI) m/z [M + H]+ Calcd for C16H13O4 269.0808, found 269.0805.
1-Phenyl-2-(3-(trifluoromethyl)phenyl)ethane-1,2-dione (3p).14c
Purification by column chromatography (ethyl acetate/hexane, v/v =
MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz, 2H), 7.86 (d, J = 7.5 Hz, 2H),
7.49 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 7.5 Hz, 2H), 2.44 (s, 3H);
13C{1H} NMR (126 MHz, CDCl3) δ 193.7, 193.4, 146.6, 141.6,
131.6, 131.3, 130.5, 130.2, 129.9, 129.5, 22.1; HRMS (ESI) m/z [M +
H]+ Calcd for C15H12ClO2 259.0520, found 259.0528.
1-(4-Bromophenyl)-2-(p-tolyl)ethane-1,2-dione (3x).29 Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
1
1:50). Yellow solid (156 mg, 56% yield): mp 69−70 °C; H NMR
1
Yellow solid (217 mg, 72% yield): mp 93−94 °C; H NMR (500
(500 MHz, CDCl3) δ 8.28 (s, 1H), 8.16 (d, J = 8.0 Hz, 1H), 8.00 (d, J
= 8.0 Hz, 2H), 7.92 (d, J = 7.5 Hz, 1H), 7.71−7.65 (m, 2 H), 7.58 (t,
J = 8.0 Hz, 2H); 13C{1H} NMR (126 MHz, CDCl3) δ 193.5, 192.8,
135.4, 133.7, 133.3, 132.8, 132.4 (C−F, 1JC−F = 124.8 Hz), 131.3 (C−
MHz, CDCl3) δ 7.86 (d, J = 8.5 Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H),
7.65 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.44 (s, 3H);
13C{1H} NMR (126 MHz, CDCl3) δ 193.7, 193.6, 146.6, 132.5,
132.0, 131.4,130.5, 130.2, 129.9, 22.1; HRMS (ESI) m/z [M + H]+
Calcd for C15H12BrO2 303.0015, found 303.0022.
3
2
F, JC−F = 9.9 Hz), 130.2, 129.9, 129.3, 126.6, (C−F, JC−F = 12.2
Hz); 19F NMR (471 MHz, CDCl3) δ −62.8; HRMS (ESI) m/z [M +
H]+ Calcd for C15H10F3O2 279.0627, found 279.0630.
4-(2-Oxo-2-(p-tolyl)acetyl)benzonitrile (3y). Purification by col-
umn chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow solid
(137 mg, 55% yield): mp 154−156 °C; 1H NMR (500 MHz, CDCl3)
δ 8.09 (d, J = 8.5 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 8.5
Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H); 13C{1H} NMR (126
MHz, CDCl3) δ 192.9, 192.7, 147.1, 136.2, 132.9, 130.3, 130.3, 130.2,
1-(m-Tolyl)-2-(p-tolyl)ethane-1,2-dione (3q).13a Purification by
column chromatography (ethyl acetate/hexane, v/v = 1:50). Yellow
solid (186 mg, 78% yield): mp 61−62 °C; H NMR (500 MHz,
CDCl3) δ 7.87 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 10.0 Hz, 2H), 7.47 (d,
J = 7.5 Hz, 1H), 7.40 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 7.5 Hz, 2H),
1
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The Journal of Organic Chemistry
pubs.acs.org/joc
Article
130.1, 117.9, 117.8, 22.1; HRMS (ESI) m/z [M + H]+ Calcd for
C16H12NO2 250.0863, found 250.0871.
and Aβ-Induced Neurotoxicity. Med. Chem. Res. 2017, 26, 3057−
3071. (c) Cumming, J. N.; Smith, E. M.; Wang, L.; Misiaszek, J.;
Durkin, J.; Pan, J.; Iserloh, U.; Wu, Y.; Zhu, Z.; Strickland, C.; Voigt,
J.; Chen, X.; Kennedy, M. E.; Kuvelkar, R.; Hyde, L. A.; Cox, K.;
Favreau, L.; Czarniecki, M. F.; Greenlee, W. J.; McKittrick, B. A.;
Parker, E. M.; Stamford, A. W. Structure Based Design of
Iminohydantoin BACE1 Inhibitors: Identification of an Orally
Available, Centrally Active BACE1 Inhibitor. Bioorg. Med. Chem.
Lett. 2012, 22, 2444−2449. (d) Al-kahraman, Y. M. S. A.; Yasinzai,
M.; Singh, G. S. Evaluation of Some Classical Hydrazones of Ketones
and 1,2-Diketones as Antileishmanial, Antibacterial and Antifungal
Agents. Arch. Pharmacal Res. 2012, 35, 1009−1013.
(2) (a) Yan, Q.; Ma, X.; Banwell, M. G.; Ward, J. S. Total Synthesis
of the Marine Alkaloid Discoipyrrole C via the MoOPH-Mediated
Oxidation of a 2,3,5-Trisubstituted Pyrrole. J. Nat. Prod. 2017, 80,
3305−3313. (b) Luan, Y.; Wei, H.; Zhang, Z.; Che, Q.; Liu, Y.; Zhu,
T.; Mandi, A.; Kurtan, T.; Gu, Q.; Li, D. Eleganketal A, A Highly
Oxygenated Dibenzospiroketal from the Marine-Derived Fungus
Spicaria elegans KLA03. J. Nat. Prod. 2014, 77, 1718−1723. (c) Shen,
Y.; Feng, Z.-M.; Jiang, J.-S.; Yang, Y.-N.; Zhang, P.-C. Dibenzoyl and
Isoflavonoid Glycosides from Sophora flavescens: Inhibition of the
Cytotoxic Effect of D-Galactosamine on Human Hepatocyte HL-
7702. J. Nat. Prod. 2013, 76, 2337−2345.
(3) Mousset, C.; Giraud, A.; Provot, O.; Hamze, A.; Bignon, J.; Liu,
J.-M.; Thoret, S.; Dubois, J.; Brion, J.-D.; Alami, M. Synthesis and
Antitumor Activity of Benzils Related to Combretastatin A-4. Bioorg.
Med. Chem. Lett. 2008, 18, 3266−3271.
(4) (a) Huang, S.; Gao, T.; Bi, A.; Cao, X.; Feng, B.; Liu, M.; Du, T.;
Feng, X.; Zeng, W. Revealing Aggregation-Induced Emission Effect of
Imidazolium Derivatives and Application for Detection of Hg2+. Dyes
Pigm. 2020, 172, 107830. (b) Kawai, S.; Yamaguchi, T.; Kato, T.;
Hatano, S.; Abe, J. Entropy-Controlled Thermal Back-Reaction of
Photochromic [2.2] paracyclophane-Bridged Imidazole Dimer. Dyes
Pigm. 2012, 92, 872−876. (c) Ren, H.; Li, J.; Zhang, T.; Wang, R.;
Gao, Z.; Liu, D. Synthesis and Properties of Novel Perylenebisimide-
Cored Dendrimers. Dyes Pigm. 2011, 91, 298−303.
1-(2-Methoxyphenyl)-2-phenylethane-1,2-dione (3z).15a Purifica-
tion by column chromatography (ethyl acetate/hexane, v/v = 1:50).
Yellow oil (127 mg, 53% yield); 1H NMR (500 MHz, CDCl3) δ 8.04
(d, J = 7.0 Hz, 1H), 7.94 (d, J = 7.5 Hz, 2H), 7.63 (q, J = 7.5 Hz, 2H),
7.51 (t, J = 7.5 Hz, 2H), 7.15 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.5 Hz,
1H), 3.57 (s, 3H); 13C{1H} NMR (126 MHz, CDCl3) δ 194.7, 193.6,
160.5, 136.5, 133.9, 133.0, 130.7, 129.4, 128.8, 124.0, 121.7, 112.4,
55.7; HRMS (ESI) m/z [M + H]+ Calcd for C15H13O3 241.0859,
found 241.0867.
1,4-Diphenylbuta-1,3-diyne (6a).30 Purification by column
chromatography (ethyl acetate/hexane, v/v = 1:50). White solid
(180 mg, 89%): mp 86−87 °C; 1H NMR (500 MHz, CDCl3) δ 7.54
(d, J = 7.5 Hz, 4H), 7.39−7.33 (m, 6H); 13C{1H} NMR (126 MHz,
CDCl3) δ 132.6, 129.4, 128.6, 121.9, 81.7, 74.1; HRMS (ESI) m/z
[M + H]+ Calcd for C16H11 203.0855, found 203.0859.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00322.
■
sı
1
copies of H, 13C{1H}, and 19F NMR spectra for all
compounds (PDF)
FAIR data, including the primary NMR FID files, for
compounds 3a−3z and 6a (ZIP)
AUTHOR INFORMATION
Corresponding Author
■
Krishna Nand Singh − Department of Chemistry, Institute of
Science, Banaras Hindu University, Varanasi 221005, India;
orcid.org/0000-0001-9147-5463; Email: knsingh@
bhu.ac.in, knsinghbhu@yahoo.co.in
(5) (a) van Velzen, N. J. C.; Harder, S. Deca-Arylsamarocene: An
Unusually Inert Sm(II) Sandwich Complex. Organometallics 2018, 37,
2263−2271. (b) Cesari, C.; Sambri, L.; Zacchini, S.; Zanotti, V.;
Mazzoni, R. Microwave-Assisted Synthesis of Functionalized Shvo-
Type Complexes. Organometallics 2014, 33, 2814−2819. (c) Liu, S.;
Senocak, A.; Smeltz, J. L.; Yang, L.; Wegenhart, B.; Yi, J.; Kenttamaa,
H. I.; Ison, E. A.; Abu-Omar, M. M. Mechanism of MTO-Catalyzed
Deoxydehydration of Diols to Alkenes Using Sacrificial Alcohols.
Organometallics 2013, 32, 3210−3219.
Authors
Shiv Chand − Department of Chemistry, Institute of Science,
Banaras Hindu University, Varanasi 221005, India
Anand Kumar Pandey − Department of Chemistry, Institute
of Science, Banaras Hindu University, Varanasi 221005,
India
Rahul Singh − Department of Chemistry, Institute of Science,
Banaras Hindu University, Varanasi 221005, India
(6) (a) Wang, G.; Wang, J.; He, D.; Li, X.; Li, J.; Peng, Z. Synthesis
and Biological Evaluation of Novel 1,2,4-Triazine Derivatives Bearing
Carbazole Moiety as Potent α-Glucosidase Inhibitors. Bioorg. Med.
Chem. Lett. 2016, 26, 2806−2809. (b) Scott, J. D.; Li, S. W.; Brunskill,
A. P. J.; Chen, X.; Cox, K.; Cumming, J. N.; Forman, M.; Gilbert, E. J.;
Hodgson, R. A.; Hyde, L. A.; Jiang, Q.; Iserloh, U.; Kazakevich, I.;
Kuvelkar, R.; Mei, H.; Meredith, J.; Misiaszek, J.; Orth, P.; Rossiter, L.
M.; Slater, M.; Stone, J.; Strickland, C. O.; Voigt, J. H.; Wang, G.;
Wang, H.; Wu, Y.; Greenlee, W. J.; Parker, E. M.; Kennedy, M. E.;
Stamford, A. W. Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-
Dioxide Derivative Verubecestat (MK-8931)-Aβ-Site Amyloid Pre-
cursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of
Alzheimer’s Disease. J. Med. Chem. 2016, 59, 10435−10450.
(c) Hicks, L. D.; Hyatt, J. L.; Moak, T.; Edwards, C. C.; Tsurkan,
L.; Wierdl, M.; Ferreira, A. M.; Wadkins, R. M.; Potter, P. M. Analysis
of the Inhibition of Mammalian Carboxylesterases by Novel
Fluorobenzoins and Fluorobenzils. Bioorg. Med. Chem. 2007, 15,
3801−3817.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00322
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are thankful to the SERB, New Delhi (file no.CRG/2019/
003649) for financial assistance. S.C. is grateful to the CSIR,
New Delhi, for SRF, and A.K.P. to the DST, New Delhi, for an
INSPIRE fellowship.
REFERENCES
■
(1) (a) Fan, T.-Y.; Wu, W.-Y.; Yu, S.-P.; Zhong, Y.; Zhao, C.; Chen,
M.; Li, H.-M.; Li, N.-G.; Chen, Z.; Chen, S.; Sun, Z.-H.; Duan, J.-A.;
Shi, Z.-H. Design, Synthesis and Evaluation of 2-Amino-imidazol-4-
one Derivatives as Potent β-Site Amyloid Precursor Protein Cleaving
Enzyme 1 (BACE-1) Inhibitors. Bioorg. Med. Chem. Lett. 2019, 29,
126772. (b) Kucukkilinc, T. T.; Yanghagh, K. S.; Ayazgok, B.;
Roknipour, M. A.; Moghadam, F. H.; Moradi, A.; Emami, S.; Amini,
M.; Irannejad, H. Synthesis and Neuroprotective Activity of Novel
1,2,4-Triazine Derivatives with Ethyl Acetate Moiety Against H2O2
(7) (a) Miera, G. G.; Martínez-Castro, E.; Martín-Matute, B.
Acceptorless Alcohol Dehydrogenation: OH vs NH Effect in
Bifunctional NHC-Ir(III) Complexes. Organometallics 2018, 37,
636−644. (b) Gupta, S. K.; Sahoo, S. K.; Choudhury, J. Dramatic
Effect of Ancillary NHC Ligand in the Highly Selective Catalytic
Oxidative Carbon-Carbon Multiple Bond Cleavage. Organometallics
6491
https://doi.org/10.1021/acs.joc.1c00322
J. Org. Chem. 2021, 86, 6486−6493

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
2016, 35, 2462−2466. (c) Liu, X.; Chen, W. Pyridazine-Based N-
Heterocyclic Carbene Complexes and Ruthenium-Catalyzed Oxida-
tion Reaction of Alkenes. Organometallics 2012, 31, 6614−6622.
(8) (a) Song, T.; Ma, Z.; Ren, P.; Yuan, Y.; Xiao, J.; Yang, Y. A
Bifunctional Iron Nanocomposite Catalyst for Efficient Oxidation of
Alkenes to Ketones and 1,2-Diketones. ACS Catal. 2020, 10, 4617−
4629. (b) Schmidt, B.; Krehl, S.; Hauke, S. Assisted Tandem Catalytic
Cross Metathesis−Oxidation: In One Flask from Styrenes to 1,2-
Diketones and Further to Quinoxalines. J. Org. Chem. 2013, 78,
5427−5435. (c) Su, Y.; Sun, X.; Wu, G.; Jiao, N. Catalyst-Controlled
Highly Selective Coupling and Oxygenation of Olefins: A Direct
Approach to Alcohols, Ketones, and Diketones. Angew. Chem., Int. Ed.
2013, 52, 9808−9812.
(9) (a) Rong, Z.-Q.; Pan, H.-J.; Yan, H.-L.; Zhao, Y. Enantioselective
Oxidation of 1,2-Diols with Quinine-Derived Urea Organocatalyst.
Org. Lett. 2014, 16, 208−211. (b) Su, Y.; Zhang, L.; Jiao, N.
Utilization of Natural Sunlight and Air in the Aerobic Oxidation of
Benzyl Halides. Org. Lett. 2011, 13, 2168−2171. (c) Chen, C.-T.;
Kao, J.-Q.; Salunke, S. B.; Lin, Y.-H. Enantioselective Aerobic
Oxidation of α-Hydroxy-Ketones Catalyzed by Oxidovanadium (V)
Methoxides Bearing Chiral, N-Salicylidene-tert-butylglycinates. Org.
Lett. 2011, 13, 26−29.
(10) (a) Hu, B.; Zhou, P.; Zhang, Q.; Wang, Y.; Zhao, S.; Lu, L.;
Yan, S.; Yu, F. Metal-Free Oxidative Thioesterification of Methyl
Ketones with Thiols/Disulfides for the Synthesis of α-Ketothioesters.
J. Org. Chem. 2018, 83, 14978−14986. (b) Chebolu, R.; Bahuguna,
A.; Sharma, R.; Mishra, V. K.; Ravikumar, P. C. An Unusual
Chemoselective Oxidation Strategy by an Unprecedented Exploration
of an Electrophilic Center of DMSO: A New Facet to Classical
DMSO Oxidation. Chem. Commun. 2015, 51, 15438−15441.
(11) (a) Vishwakarma, R. K.; Kumar, S.; Sharma, A. K.; Singh, R.;
Singh, K. N. An Efficient Synthesis of 1,2-Diketones by Oxidative
Cross-coupling of Alkynes and Aryl Triazenes using Copper Catalysis.
ChemistrySelect. 2019, 4, 4064−4067. (b) Zhou, J.; Tao, X.-Z.; Dai, J.-
J.; Li, C.-G.; Xu, J.; Xu, H.-M.; Xu, H.-J. Electrochemical Synthesis Of
1,2-Diketones from Alkynes under Transition-Metal-Catalyst-Free
Conditions. Chem. Commun. 2019, 55, 9208−9211. (c) Yang, W.;
Chen, Y.; Yao, Y.; Yang, X.; Lin, Q.; Yang, D. ICl/AgNO3 Co-
Catalyzed Radical Oxidation of Diaryl- and Alkylarylalkynes into 1,2-
Diketones. J. Org. Chem. 2019, 84, 11080−11090. (d) Kim, S. W.;
Um, T.-W.; Shin, S. Metal-Free Iodine-Catalyzed Oxidation of
Ynamides and Diaryl Acetylenes into 1,2-Diketo Compounds. J.
Org. Chem. 2018, 83, 4703−4711. (e) Chen, M.; Zhao, Q.; She, D.-B.;
Yang, M.-Y.; Hui, H.-H.; Huang, G.-S. Microwave-Assisted Efficient
Oxidation of Internal Alkynes to 1,2-Diaryldiketones with DMSO/I2.
Proc. - Indian Acad. Sci., Chem. Sci. 2008, 120, 347−351.
(12) (a) Min, H.; Palani, T.; Park, K.; Hwang, J.; Lee, S. Copper-
Catalyzed Direct Synthesis of Diaryl 1,2-Diketones from Aryl Iodides
and Propiolic Acids. J. Org. Chem. 2014, 79, 6279−6285. (b) Park, K.;
Lee, S. Transition Metal-Catalyzed Decarboxylative Coupling
Reactions of Alkynyl Carboxylic Acids. RSC Adv. 2013, 3, 14165−
14182.
(13) (a) Matsuda, T.; Oyama, S. Synthesis of Unsymmetrical Benzils
via Palladium-Catalysed α-Arylation−Oxidation of 2-Hydroxyaceto-
phenones with Aryl Bromides. Org. Biomol. Chem. 2020, 18, 3679−
3683. (b) Cotugno, P.; Monopoli, A.; Ciminale, F.; Milella, A.; Nacci,
A. Palladium-Catalyzed Cross-Coupling of Styrenes with Aryl Methyl
Ketones in Ionic Liquids: Direct Access to Cyclopropanes. Angew.
Chem., Int. Ed. 2014, 53, 13563−13567. (c) Ren, W.; Xia, Y.; Ji, S. J.;
Zhang, Y.; Wan, X.; Zhao, J. Wacker-Type Oxidation of Alkynes into
1,2-Diketones Using Molecular Oxygen. Org. Lett. 2009, 11, 1841−
1844.
(14) (a) Yusubov, M. S.; Nemykin, V. N.; Zhdankin, V. V.
Transition Metal-Mediated Oxidations Utilizing Monomeric Iodosyl-
and Iodylarene Species. Tetrahedron 2010, 66, 5745−5752.
(b) Yusubov, M. S.; Zagulyaeva, A. A.; Zhdankin, V. V. Iodine(V)/
Ruthenium(III)-Cocatalyzed Oxidations: A Highly Efficient Tandem
Catalytic System for the Oxidation of Alcohols and Hydrocarbons
with Oxone. Chem. - Eur. J. 2009, 15, 11091−11094. (c) Ren, W.; Liu,
J.; Chen, L.; Wan, X. Ruthenium Catalyzed Alkyne Oxidation with
Part-Per-Million Catalyst Loadings. Adv. Synth. Catal. 2010, 352,
1424−1428.
(15) (a) Dubovtsev, A. Y.; Shcherbakov, N. V.; Dar'in, D. V.;
Kukushkin, V. Y. Nature of the Nucleophilic Oxygenation Reagent Is
Key to Acid-Free Gold-Catalyzed Conversion of Terminal and
Internal Alkynes to 1,2-Dicarbonyls. J. Org. Chem. 2020, 85, 745−757.
(b) Xu, C. F.; Xu, M.; Jia, Y.-X.; Li, C.-Y. Gold-Catalyzed Synthesis of
Benzil Derivatives and α-Keto Imides via Oxidation of Alkynes. Org.
Lett. 2011, 13, 1556−1559. (c) Dubovtsev, A. Y.; Dar’in, D. V.;
Krasavin, M.; Kukushkin, V. Y. Gold-Catalyzed Oxidation of Internal
Alkynes into Benzils and its Application for One-Pot Synthesis of
Five-, Six-, and Seven-Membered Azaheterocycles. Eur. J. Org. Chem.
2019, 2019, 1856−1864. (d) Dubovtsev, A. Y.; Dar’in, D. V.;
Kukushkin, V. Y. Three-Component [2 + 2+1] Gold(I)-Catalyzed
Oxidative Generation of Fully Substituted 1,3-Oxazoles Involving
Internal Alkynes. Adv. Synth. Catal. 2019, 361, 2926−2935. (e) Jung,
M. E.; Deng, G. Synthesis of α-Diketones from Alkylaryl- and
Diarylalkynes Using Mercuric Salts. Org. Lett. 2014, 16, 2142−2145.
(16) (a) Lu, Y.; Luo, M.-J.; Hu, M.; Li, Y.; Li, J.-H. Dimethyl
Sulfoxide as an Oxygen Atom Source Enabled Tandem Conversion of
2-Alkynyl Carbonyls to 1,2-Dicarbonyls. Adv. Synth. Catal. 2020, 362,
1846−1850. (b) Zhou, P.-J.; Li, C.-K.; Zhou, S.-F.; Shoberu, A.; Zou,
J.-P. Copper-Catalyzed TEMPO Oxidative Cleavage of 1,3-Diketones
and β-Keto Esters for the Synthesis of 1,2-Diketones and α-Keto
Esters. Org. Biomol. Chem. 2017, 15, 2629−2637. (c) Zhu, X.; Li, P.;
Shi, Q.; Wang, L. Thiyl Radical Catalyzed Oxidation of Diarylalkynes
to α-Diketones by Molecular Oxygen under Visible-Light Irradiation.
Green Chem. 2016, 18, 6373−6379.
(17) (a) Liu, P.; Zhang, G.; Sun, P. Transition metal-free
decarboxylative alkylation reactions. Org. Biomol. Chem. 2016, 14,
10763−10777. (b) Weaver, J. D.; Recio, A., III; Grenning, A. J.;
Tunge, J. A. Transition Metal-Catalyzed Decarboxylative Allylation
and Benzylation Reactions. Chem. Rev. 2011, 111, 1846−1913.
(c) Rodríguez, N.; Goossen, L. J. Decarboxylative coupling reactions:
a modern strategy for C−C-bond formation. Chem. Soc. Rev. 2011, 40,
5030−5048.
(18) (a) Gao, B.; Xie, Y.; Yang, L.; Huang, H. Copper-catalyzed
decarboxylative cross-coupling of cinnamic acids and ACCN via single
electron transfer. Org. Biomol. Chem. 2016, 14, 2399−2402.
(b) Borah, A. J.; Yan, G. Decarboxylative functionalization of
cinnamic acids. Org. Biomol. Chem. 2015, 13, 8094−8115.
(19) (a) Sharma, A. K.; Jaiswal, A.; Singh, K. N. Cu-Catalysed
Oxidative Amidation of Cinnamic Acids/Arylacetic Acids with 2°
Amines: An Efficient Synthesis of α-Ketoamides. Org. Biomol. Chem.
2019, 17, 9348−9351. (b) Kumar, S.; Singh, R.; Singh, K. N.
Palladium Catalyzed C−C and C−N Bond Formation via ortho C−H
Activation and Decarboxylative Strategy: A Practical Approach
towards N-Acylated Indoles. Adv. Synth. Catal. 2018, 360, 422−426.
(c) Singh, R.; Allam, B. K.; Singh, N.; Kumari, K. K.; Singh, S. K.;
Singh, K. N. A Direct Metal-Free Decarboxylative Sulfono
Functionalization (DSF) of Cinnamic Acids to α,β-Unsaturated
Phenyl Sulfones. Org. Lett. 2015, 17, 2656−2659. (d) Guntreddi, T.;
Vanjari, R.; Singh, K. N. Elemental Sulfur Mediated Decarboxylative
Redox Cyclization Reaction of o-Chloronitroarenes and Arylacetic
Acids. Org. Lett. 2015, 17, 976−978.
(20) (a) Guo, Y.-Q.; Wang, R.; Song, H.; Liu, Y.; Wang, Q. Visible-
Light-Induced Deoxygenation/Defluorination Protocol for Synthesis
of γ,γ-Difluoroallylic Ketones. Org. Lett. 2020, 22, 709−713. (b) Xia,
P.-J.; Song, D.; Ye, Z.-P.; Hu, Y.-Z.; Xiao, J.-A.; Xiang, H.-Y.; Chen,
X.-Q.; Yang, H. Photoinduced Single-Electron Transfer as an
Enabling Principle in the Radical Borylation of Alkenes with
NHC−Borane. Angew. Chem., Int. Ed. 2020, 59, 6706−6710.
(c) Lee, J.; Hong, B.; Lee, A. Visible-Light-Promoted, Catalyst-Free
Gomberg−Bachmann Reaction: Synthesis of Biaryls. J. Org. Chem.
2019, 84, 9297−9306. (d) Xu, J.-H.; Wu, W.-B.; Wu, J. Photoinduced
DivergentAlkylation/Acylation of Pyridine N-Oxides with Alkynes
under Anaerobic and Aerobic Conditions. Org. Lett. 2019, 21, 5321−
5325.
6492
https://doi.org/10.1021/acs.joc.1c00322
J. Org. Chem. 2021, 86, 6486−6493

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(21) (a) Pagire, S. K.; Kumagai, N.; Shibasaki, M. The Different
Faces of [Ru(bpy)3Cl2] and fac[Ir(ppy)3] Photocatalysts: Redox
Potential Controlled Synthesis of Sulfonylated Fluorenes and
Pyrroloindoles from Unactivated Olefins and Sulfonyl Chlorides.
Org. Lett. 2020, 22, 7853−7858. (b) Wang, X.; Xia, C.; Wu, L.
Visible-Light-Promoted Photoredox Dehydrogenative Coupling of
Phosphines and Thiophenols. Org. Lett. 2020, 22, 7373−7377.
(c) Lyu, X.-L.; Huang, S.-S.; Song, H.-J.; Liu, Y.-X.; Wang, Q.-M.
Visible-Light-Induced Copper-Catalyzed Decarboxylative Coupling of
Redox-Active Esters with N-Heteroarenes. Org. Lett. 2019, 21 (14),
5728−5732. (d) Chand, S.; Pandey, A. K.; Singh, R.; Kumar, S.;
Singh, K. N. Eosin-Y-Catalyzed Photoredox C-S Bond Formation:
Easy Access to Thioethers. Chem. - Asian J. 2019, 14, 4712−4716.
(e) Wei, X.-J.; Boon, W.; Hessel, V.; Noel, T. Visible-Light
Photocatalytic Decarboxylation of α,β-Unsaturated Carboxylic
Acids: Facile Access to Stereoselective Difluoromethylated Styrenes
in Batch and Flow. ACS Catal. 2017, 7, 7136−7140.
(28) Li, Z.; Yin, J.; Wen, G.; Li, T.; Shen, X. Copper-mediated
aerobic oxidative cleavage of α,β-unsaturated ketones to 1,2-diketone.
RSC Adv. 2014, 4, 32298−32302.
(29) Gujjarappa, R.; Vodnala, N.; Putta, V. P. R. K.; Reddy, V. G.;
Malakar, C. C. Conversion of Alkynes into 1,2-Diketones using HFIP
as Sacrificial Hydrogen Donor and DMSO as Dihydroxylating Agent.
Tetrahedron Lett. 2020, 61, 1515885−1515893.
(30) Cao, W.; Niu, S.-L.; Shuai, L.; Xiao, Q. Copper-catalysed three-
component carboiodination of arynes: expeditious synthesis of o-
alkynyl aryl iodides. Chem. Commun. 2020, 56, 972−975.
(22) Liu, X.; Cong, T.; Liu, P.; Sun, P. Synthesis of 1,2-Diketones via
a Metal-Free, Visible-Light-Induced Aerobic Photooxidation of
Alkynes. J. Org. Chem. 2016, 81, 7256−7261.
(23) (a) Singh, J.; Sharma, S.; Sharma, A. Photocatalytic Carbon-
ylation Strategies: A Recent Trend in Organic Synthesis. J. Org. Chem.
2021, 86, 24−48. (b) Ding, T.-H.; Qu, J.-P.; Kang, Y.-B. Visible-
Light-Induced, Base-Promoted Transition-Metal-Free Dehalogena-
tion of Aryl Fluorides, Chlorides, Bromides, and Iodides. Org. Lett.
2020, 22, 3084−3088. (c) Wu, W.; Cui, E.; Zhang, Y.; Zhang, C.;
Zhu, F.; Tung, C.-H.; Wang, Y. Involving Single-Atom Silver (0) in
Selective Dehalogenation by AgF under Visible-Light Irradiation. ACS
Catal. 2019, 9, 6335−6341.
(24) Ghosh, I.; Ghosh, T.; Bardagi, J. I.; König, B. Reduction of Aryl
Halides by Consecutive Visible Light-Induced Electron Transfer
Processes. Science 2014, 346, 725−728.
(25) (a) Sasaki, Y.; Kato, H.; Kudo, A. [Co(bpy)3]3+/2+ and
[Co(phen)3]3+/2+ Electron Mediators for Overall Water Splitting
under Sunlight Irradiation Using Z-Scheme Photocatalyst System. J.
Am. Chem. Soc. 2013, 135, 5441−5449. (b) Ramanan, C.; Smeigh, A.
L.; Anthony, J. E.; Marks, T. J.; Wasielewski, M. R. Competition
between Singlet Fission and Charge Separation in Solution-Processed
Blend Films of 6,13-Bis(triisopropylsilylethynyl)pentacene with
Sterically-Encumbered Perylene-3,4:9,10-bis(dicarboximide)s. J. Am.
Chem. Soc. 2012, 134, 386−397. (c) Shirman, E.; Ustinov, A.; Ben-
Shitrit, N.; Weissman, H.; Iron, M. A.; Cohen, R.; Rybtchinski, B.
Stable Aromatic Dianion in Water. J. Phys. Chem. B 2008, 112, 8855−
8858. (d) Tauber, M. J.; Kelley, R. F.; Giaimo, J. M.; Rybtchinski, B.;
Wasielewski, M. R. Electron Hopping in π-Stacked Covalent and Self-
Assembled Perylene Diimides Observed by ENDOR Spectroscopy. J.
Am. Chem. Soc. 2006, 128, 1782−1783. (e) Gosztola, D.; Niemczyk,
M. P.; Svec, W.; Lukas, A. S.; Wasielewski, M. R. Excited Doublet
States of Electrochemically Generated Aromatic Imide and Diimide
Radical Anions. J. Phys. Chem. A 2000, 104, 6545−6551.
(26) (a) Zhang, J.; Xiao, D.; Tan, H.; Liu, W. Highly Selective
Synthesis of 2-tert-Butoxy-1-Arylethanones via Copper(I)-Catalyzed
Oxidation/tert-Butoxylation of Aryl Olefins with TBHP. J. Org. Chem.
2020, 85, 3929−3935. (b) Li, X.; Wang, M.; Wang, Z.; Wang, L.
Synthesis of Vinyl Sulfones through Visible Light-Induced Decarbox-
ylative Sulfonylation of Cinnamic Acids with Disulfides. Asian J. Org.
Chem. 2019, 8, 1426−1435. (c) Kaur, P.; Kumar, V.; Kumar, R.
Recent Advances in Decarboxylative C-C Bond Formation using
Direct or in situ Generated Alkenyl Acids. Catal. Rev.: Sci. Eng. 2020,
62, 118−161. (d) Miyake, Y.; Nakajima, K.; Nishibayashi, Y. Visible
Light-Mediated Oxidative Decarboxylation of Arylacetic Acids into
Benzyl Radicals: Addition to Electron-Deficient Alkenes by using
Photoredox Catalysts. Chem. Commun. 2013, 49, 7854−7856.
(27) Kumar, Y.; Jaiswal, Y.; Kumar, A. Two-Step One-Pot Synthesis
of Unsymmetrical (Hetero)Aryl 1,2-Diketones by Addition Oxygen-
ation of Potassium Aryltrifluoroborates to (Hetero)Arylacetonitriles.
Eur. J. Org. Chem. 2018, 2018, 494−505.
6493
https://doi.org/10.1021/acs.joc.1c00322
J. Org. Chem. 2021, 86, 6486−6493