Synthesis of 2,3,4-Trisubstituted 2-Cyclopentenones via Sequential Functionalization of 2-Cyclopentenone

Article abstract of DOI:10.1021/acs.joc.1c01039

The synthesis of differently substituted 2,3,4-triarylcyclopent-2-en-1-ones from 2-cyclopentenone via sequential functionalization of a novel 2,4-dibromo-3-(4-methoxyphenyl) cyclopent-2-en-1-one intermediate has been developed. The process provides access

Full text of DOI:10.1021/acs.joc.1c01039

pubs.acs.org/joc
Note
Synthesis of 2,3,4-Trisubstituted 2‑Cyclopentenones via Sequential
Functionalization of 2‑Cyclopentenone
Tarak N. Gowala, Pankaj Chaudhari, Jagadish Pabba, Krishna Sawant, Sitaram Pal,* and Sujit K. Ghorai*
Cite This: J. Org. Chem. 2021, 86, 10812−10818
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: The synthesis of differently substituted 2,3,4-
triarylcyclopent-2-en-1-ones from 2-cyclopentenone via sequential
functionalization of a novel 2,4-dibromo-3-(4-methoxyphenyl)
cyclopent-2-en-1-one intermediate has been developed. The
process provides access to selective arylation at C-4 and C-2
with a broader substrates scope, which includes heteroaryl and
alkyl substitution at C-2.
ubstituted cyclopentenones are highly versatile building
blocks for the synthesis of bioactive natural products,
we report a convenient and general synthesis of differently
substituted 2,3,4-triaryl 2-cyclopentenones via sequential
functionalization of easily available 2-cyclopentenone.
S
pharmaceuticals, agrochemicals, and synthetic materials.1
Substituted 2-cyclopentenones have gained importance in
recent times because of their multiple functional centers along
with pre-established dense substituents.2 These are also useful
intermediates for the synthesis of rocaglaol and flavaglines
group of natural products and their analogues.3 There is an
ample number of methods available for the synthesis of mono-
or diarylcyclopentenones, most commonly via Pauson-Khand
and Nazarov reaction.4 However, only a few reports are
available for the synthesis of triaryl 2-cyclopentenones,
especially where all the aryl substituents are different. The
first synthesis of differently substituted 2,3,4-triaryl cyclo-
pentenone was reported in the year 2004 by Thede et al. via
formation of 3,4-diaryl cyclopentenones-5-ethylcarboxylate
from diaryl-α-bromoketones and allyldienetriphenylphosphor-
ane.5 Barluenga and co-workers have demonstrated the use of
nickel(0)-catalyzed [3+2] cyclization reaction of chromium
alkenyl(methoxy)carbene complexes for the construction of
3,4-diphenyl-2-tributylstannyl-cyclopent-2-en-1-one, which
was finally converted to 2,3,4-triaryl cyclopentenones.6
Recently, Basmadjian’s group published differently substituted
2,3,4-triaryl 2-cyclopentenones by using gold(I)-catalyzed
intramolecular alkyne-ether cyclization as the key step.7
However, starting materials used in these processes are quite
complex and with a limited substrate scope. Importantly, all of
these methods for the construction of cyclopentanone
derivatives are rely on cyclization of the highly functionalized
starting material as a key step (Scheme 1), which is often low
yielding and catalyzed by expensive metal catalysts. For the
construction of the rocaglaol basic cage, which is the lead for
our current agrochemical research project, we needed access to
differently substituted 2,3,4-triaryl 2-cyclopentenones. To the
best of our knowledge, the synthesis of 2,3,4-triaryl 2-
cyclopentenones from 2-cyclopentenone is not known. Herein,
We commenced our studies with 3-(4-methoxyphenyl)-
cyclopent-2-en-1-one (2), which was prepared in a single step
from 2-cyclopentenone in 68% yield via the Heck reaction
following our previously reported condition.8 Our initial plan
was two sequential brominations, each followed by arylation at
the C-2 and C-4 position of 2 to afford the desired 2,3,4-triaryl
2-cyclopentenones (Scheme 2). Selective C-2 bromination was
achieved with NBS in the presence of pyridine-N-oxide in
acetonitrile at 0 °C to afford bromo compound 3 in 85% yield.
Then we tried α-arylation of 2-bromo-3-(4-methoxyphenyl)
cyclopent-2-en-1-one (3) via Suzuki coupling with (2-
benzyloxyphenyl)boronic acid using PdCl2(PPh3)2 as a catalyst
reported for a similar moiety.5 However, the yield obtained for
desired coupling product 4 was not satisfactory (30%).
Therefore, we quickly screened a few Pd catalysts under
different conditions.9 The best yields were obtained with
Pd(PPh3)4 (5.0 mol %) using of 3.0 equiv of Na2CO3 in a
toluene and water mixture (4:1) at 110 °C (Scheme 2).
Next, we planned the synthesis of 2,3,4-trisubstituted
derivatives (11), starting from C-4 bromo intermediate 5.
However, our attempts to brominate the C-4 position of
compound 4 to prepare 5 under various conditions were
unsuccessful.
At this point, we decided to explore the feasibility of
reversing the proposed reaction sequence, i.e., the first
Received: May 3, 2021
Published: July 13, 2021
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818
© 2021 American Chemical Society
10812

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
triggered a new idea that if we can use the dibromo
intermediate instead of monobromo so that we can reduce
one step in the synthetic scheme. Therefore, we optimized the
di bromination of 2 with excess NBS (2.2 equiv) to afford
dibromo cyclopentenone 6 in 80% yield (Scheme 3).9 Next,
we explored C-4 arylation of dibromo-2-cyclopentenone 6. We
expected that treatment of excess arylmagnesium bromide
would in situ convert 6 to the corresponding cyclo-
pentadieneone intermediate 9, following which, upon the
1,4-addition of an aryl moiety, would afford aryl addition
product 8. To our delight, treatment of 6 with excess PhMgBr
and Cu(I)Br·Me2S at −78 °C in THF afforded desired phenyl
addition product 8a in 62% yield (Scheme 3).9
Scheme 1. Previous Work in the Context of Present Work
To generalize the reaction, we then treated dibromo-2-
cyclopentenone 6 with two other aryl Grignard reagents 4-
fluorophenylmagnesium bromide and 4-methylphenylmagne-
sium bromide solutions under the optimized condition and
afforded the desired products 8b and 8c in 54% and 58%
yields, respectively (Scheme 3).
After successful synthesis of 3,4-diaryl-2-bromo-cyclopente-
none 8, the feasibility of C-2 arylation by Suzuki coupling with
2-(benzyloxy)phenylboronic acid was explored. Our previously
optimized condition9 for the synthesis of 4 was proven to be
the best for this coupling as well. The reaction of 8a with (2-
benzyloxyphenyl)boronic acid in the presence Pd(PPh3)4 (5.0
mol %) and Na2CO3 in toluene and water mixture (4:1) at 110
°C furnished the desired triarylcyclopentenone 11a in 58%
yield (Table 1; entry 1). Several other arylboronic acids were
conveniently reacted with 8 under the same reaction condition
to afford the desired 2,3,4-triaryl-2-cyclopentenones (11b−
11h) in moderate to good yields. The scope of aryl boronic
acids for C-4 aryl substitution on Suzuki coupling was briefly
examined. Aryl boronic acid bearing an electron-withdrawing
or electron-donating aryl group was found equally efficient
toward the coupling reaction and afforded a comparable yield
(Table 1, entry 1 vs entry 4, entry 2 vs entry 5, and entry 6 vs
entry 7). Notably, boronic acid having a free hydroxyl group
was well tolerated in the reaction condition (Table 1, entry 8).
introduction of the aryl moiety at the C-4 position via
bromination, then the introduction of aryl at the C-2 position.
During the initial attempts for C-4 bromination of 3-(4-
methoxyphenyl)cyclopent-2-en-1-one (2), a substantial
amount of dibromo 6 was obtained as a side product, which
a
Scheme 2. Initial Approach Toward the Synthesis of 2,3,4-Trisubstituted Cyclopent-2-en-1-ones
a
Reagents and conditions: (a) NBS (1.2 equiv), AIBN (0.2 equiv), CHCl3, 80 °C, 2 h; (b) NBS (1.2 equiv), Bn2O2 (0.2 equiv), CHCl3 80 °C, 2 h;
(c) NBS (1.2 equiv), AIBN (0.2 equiv), ACN, 80 °C, 2 h; (d) bromohydantoin (0.6 equiv), AIBN (0.2 equiv), CHCl3, 80 °C, 2 h; (e)
bromohydantoin (0.6 equiv), Bn2O2 (0.2 equiv), CHCl3, 80 °C, 2 h.
10813
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Scheme 3. Synthesis of 2-Bromo-3-(4-methoxyphenyl)-4-aryl-cyclopent-2-en-1-ones 8a−c
Table 1. Synthesis of 2,3,4-Trisubstituted Cyclopent-2-en-1-ones 11a−l
a
b
2-Bromo 3,4-biaryl cyclopent-2-en-1-one 8a (1.46 mmol) and boronic acid (1.89 mmol) were used for the reaction. Standard conditions were
c
performed in a microwave reactor at 120 °C, 1−2 h. Reaction conditions: Pd(tBu3P)2 (5.0 mol %), CsF (2.0 equiv), THF (10 mL), 65 °C, 12 h.
However, highly electron-rich 2,4,6-trimethoxybenzene bor-
onic acid failed to give the desired coupling product under
optimal conditions (Table 1, entry 9). It seems 10g underwent
a proto deborylation reaction due to its rich electronic nature,
which was indicated by the formation of 1,3,5-trimethox-
ybenzene as a major byproduct.10
Importantly, the reaction is not limited to simple aryl
boronic acids. Alkyl boronic acid (Table 1, entry 10) and
heteroaryl boronic acid (Table 1, entry 11) also underwent a
coupling reaction to give the desired products in moderate
yields. However, 2-furyl boronic acid provided only a trace
amount (<5%) of the desired coupled product under the
optimized condition (Table 1, entry 12). However, in the
presence of cat. Pd(tBu3P)2 (5 mol %), CsF (2.0 equiv) in
THF at 65 °C, 2-furyl boronic acid successfully reacted with 8a
to afford the desired coupling product 11l (Table 1, entry 12)
though in a moderate yield (35%).9 In general, the time
required for these coupling reactions was 12−18 h. It is worth
mentioning that the reaction time could be reduced to 1−2 h
without compromising the yield under microwave irradiation
(Table 1, entry 1−3).
10814
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
2,4-Dibromo-3-(4-methoxyphenyl)cyclopent-2-en-1-one (6). To
a stirred solution of 3-(4-methoxyphenyl)cyclopent-2-en-1-one (2)
(5.0 g, 26.59 mmol) in chloroform (150 mL) under a nitrogen
atmosphere were added NBS (58.58 mmol) and AIBN (5.31 mmol),
and the solution was heated at 80 °C for 6 h. The reaction mixture
was cooled to an ambient temperature, quenched with water (100
mL), and extracted with DCM (3 × 150 mL). The combined organic
layer was washed with brine (1 × 100 mL), dried over anhydrous
Na2SO4, and filtered and the volatiles were evaporated. The crude
product was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:9) to afford 6 as a pale-yellow solid: 7.30 g, 80% yield;
mp 122−124 °C; IR (KBr) cm−1 2932, 2837, 1720, 1606, 1508, 1260,
1240, 1174, 1018, 937, 839; 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J
= 8.6 Hz, 2H), 7.04 (d, J = 8.6 Hz, 2H), 5.57 (dd, J = 6.60, 1.34 Hz,
1H), 3.90 (s, 3H), 3.38 (dd, J = 19.44, 6.60 Hz, 1H), 3.13 (dd, J =
19.44, 1.34 Hz, 1H); 13C{1H} NMR(101 MHz, CDCl3) δ 195.5,
165.4, 162.1, 130.5, 124.0, 123.0, 114.1, 55.5, 44.3, 43.6; HRMS (EI)
m/z [M + H]+ calcd for C12H11Br2O2 344.9127, found 344.9125.
General Procedure for the Synthesis of 2-Bromo-3-(4-
methoxyphenyl)-4-aryl-cyclopent-2-en-1-one 8a−c. To a
stirred solution of Cu (I)Br·Me2S (5.20 mmol) in THF (15 mL)
under a nitrogen atmosphere at −78 °C was added the appropriate
arylmagnesium bromide in THF solution (4.33 mmol) dropwise
(exotherm observed), and the reaction mixture was stirred for 1 h at
the same temperature. 2,4-Dibromo-3-(4-methoxyphenyl)cyclopent-
2-en-1-one (6) (1.0 g, 2.89 mmol) in THF (5 mL) was then added to
the reaction dropwise at −78 °C over a period of 20 min (exotherm
observed), and the reaction was brought to an ambient temperature
slowly. The reaction mixture was quenched with saturated NH4Cl at 0
°C and extracted with AcOEt (3 × 100 mL). The combined organic
layer was washed with brine (1 × 50 mL), dried over anhydrous
Na2SO4, and filtered and the volatiles were removed under reduced
pressure. The crude product was purified by flash chromatography on
silica gel (AcOEt/cyclohexane, 1:4) to give 8a−c.
In summary, we have demonstrated a convenient and
general route to the construction of differently substituted
2,3,4-triarylcyclopent-2-en-1-ones from 2-cyclopentenone via
synthesis of a novel building block, 2,4-dibromo-3-(4-
methoxyphenyl)cyclopent-2-en-1-one. The strategy is also
suitable for the synthesis of 2-heteroaryl-3,4-diaryl- and 2-
alkyl-3,4-diaryl-2-cyclopentenones. Further functionalization of
2,3,4-triarylcyclopent-2-en-1-ones to generate a library of
rocaglaol analogues toward the optimization of agrochemical
lead is in progress in our laboratory.
EXPERIMENTAL SECTION
■
General. Unless otherwise indicated, all reactions were carried out
under an inert atmosphere of a nitrogen and in oven-dried flasks.
Materials were purchased from commercial sources and used without
additional purification. Anhydrous tetrahydrofuran and toluene were
obtained via passage through an activated alumina column. All heating
1
reactions were carried out using Heidolph heating blocks. H NMR
and 13C{1H} NMR spectra were recorded on a Bruker Avance II-400
spectrometer in CDCl3 or DMSO-d6 solution with tetramethylsilane
as the internal standard. Chemical shift values (δ) are given in parts
per million. The HRMS analyses were performed on an Agilent
QTOF 6520 mass spectrometer and LCMS on a THERMO MSQ
PLUS mass spectrometer. Melting points were determined with an
SRS-OptiMelt digital melting point apparatus and were uncorrected.
Column chromatographic purifications were performed on a
CombiFlash Rf (Teledyne Isco) with silica gel using the mobile
phase indicated.
2-Bromo-3-(4-methoxyphenyl)cyclopent-2-en-1-one (3). To a
stirred solution of 3-(4-methoxyphenyl)cyclopent-2-en-1-one (2)
(1.0 g, 5.32 mmol) and pyridine-N-oxide (5.85 mmol) in CH3CN
(30 mL) was added NBS (6.38 mmol) at 0 °C. The stirring was
continued at the same temperature for 1 h. The reaction mixture was
quenched with water (30 mL) and extracted with DCM (3 × 50 mL).
The combined organic layer was washed with brine (30 mL), dried
over anhydrous Na2SO4, filtered, and evaporated under reduced
pressure. The crude product was purified by flash chromatography on
silica gel (AcOEt/cyclohexane, 1:9) to provide 3 as a pale-yellow
solid: 1.20 g, 85% yield; mp 99−101 °C; IR (KBr) cm−1 2934, 2914,
2-Bromo-3-(4-methoxyphenyl)-4-phenyl-cyclopent-2-en-1-one
(8a): 620 mg, 62% yield; pale-yellow gummy solid; IR (film) cm−1
3011, 2931, 1713, 1698, 1605, 1587, 1504, 1450, 1255, 1180, 1028,
1
938, 835; H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.6 Hz, 2H),
7.28−7.18 (m, 3H), 7.13−7.11 (m, 2H), (d, J = 8.6 Hz, 2H), 4.62
(dd, J = 7.34, 1.96 Hz, 1H), 3.80 (s, 3H), 3.21 (dd, J = 18.89, 7.40 Hz,
1H), 2.57 (dd, J = 18.89, 2.02 Hz, 1H); 13C{1H} NMR (101 MHz,
CDCl3) δ 200.8, 170.0, 161.3, 141.8, 130.6, 129.1, 127.2, 127.1, 125.4,
121.4, 113.8, 55.3, 48.0, 43.6; HRMS (EI) m/z [M + H]+ calcd for
C18H16BrO2 343.0328, found 343.0329.
1
2840, 1730, 1604, 1584, 1508, 1460, 1323, 1180, 1026, 931, 842; H
NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.80 Hz, 2H), 7.00 (d, J =
8.93 Hz, 2H), 3.88 (s, 3H) 3.10−3.08 (m, 2H) 2.69−2.66 (m, 2H);
13C{1H} NMR (101 MHz, CDCl3) δ 201.7, 166.4, 161.9, 129.8,
2-Bromo-4-(4-fluorophenyl)-3-(4-methoxyphenyl)cyclopent-2-
en-1-one (8b): 545 mg, 54% yield; pale-yellow gummy solid; IR
(film) cm−1 3010, 2839, 1712, 1697, 1605, 1587, 1504, 1454, 1254,
1178, 1028, 835; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.6 Hz,
2H), 7.07- 7.05 (m, 2H), 6.95−6.86 (m, 4H), 4.61 (dd, J = 7.40, 1.90
Hz, 1H), 3.81 (s, 3H), 3.20 (dd, J = 18.89, 7.40 Hz, 1H), 2.52 (dd, J =
18.89, 2.02 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 200.4,
126.3, 119.5, 114.0, 55.5, 32.3, 30.3; HRMS (EI) m/z [M + H]+ calcd
for C12H12BrO2 267.0022, found 267.0015.
2-(2-Benzyloxyphenyl)-3-(4-methoxyphenyl)cyclopent-2-en-1-
one (4). To a stirred solution of 2-bromo-3-(4-methoxyphenyl)
cyclopent-2-en-1-one (3) (1.0 g, 3.75 mmol) in toluene and water
(8:2) mixed solvents (10 mL) were added (2-benzyloxyphenyl)-
boronic acid (5.62 mmol) and Na2CO3 (11.25 mmol). The mixture
was degassed with nitrogen for 10 min followed by the addition of
Pd(PPh3)4 (0.187 mmol) and stirred at 100 °C for 14 h. The reaction
mixture was cooled to an ambient temperature, diluted with water (30
mL), and extracted with AcOEt (3 × 50 mL). The combined organic
layer was washed with brine (1 × 30 mL), dried over anhydrous
Na2SO4, and filtered, and the volatiles were evaporated. The crude
was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:4) to get 4 as a white solid: 800 mg, 58% yield; mp
152−154 °C; IR (KBr) cm−1 2956, 2926, 1692, 1604, 1594, 1514,
1354, 1260, 1178, 1045, 1030, 941, 842; 1H NMR (400 MHz,
CDCl3) δ 7.55−7.29 (m, 3H), 7.28−7.24 (m, 3H), 7.14−7.10 (m,
3H), 7.01 (t, J = 7.24 Hz, 1H), 6.96 (d, J = 8.01 Hz, 1H), 6.78 (d, J =
8.00 Hz, 2H), 4.97 (br s, 1H), 4.90 (br s, 1H), 3.81 (s, 3H), 3.07 (br
d, J = 5.38 Hz, 2H), 2.70−2.68 (m, 2H); 13C{1H} NMR (101 MHz,
CDCl3) δ 207.7, 167.3, 161.0, 156.2,137.2, 135.9, 131.1, 129.4, 129.3,
128.5, 128.3, 127.5, 127.1, 123.1, 121.3, 113.7, 112.9, 70.1, 55.3, 34.6,
29.0; HRMS (EI) m/z [M + H]+ calcd for C25H23O3 371.1648, found
371.1639.
1
1
168.9, 163.0 (C−F, JC−F = 246.10 Hz), 161.4 (C−F, JC−F = 246.10
Hz), 160.5, 137.5, 130.5, 128.7 (C−F, 3JC−F = 8.09 Hz), 128.6 (C−F,
3JC−F = 8.09 Hz), 125.2, 121.6, 116.1 (C−F, 2JC−F = 21.69 Hz), 115.9
2
(C−F, JC−F = 21.69 Hz), 113.9, 55.3, 47.2, 43.5; HRMS (EI) m/z
[M + H]+ calcd for C18H15BrFO2 361.0239, found 361.0230.
2-Bromo-3-(4-methoxyphenyl)-4-(p-tolyl)cyclopent-2-en-1-one
(8c): 600 mg, 58% yield, pale-yellow gummy solid; IR (film) cm−1
3012, 2928, 1715, 1698, 1605, 1584, 1500, 1450, 1255, 1028, 940,
835; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.93 Hz, 2H), 7.05−
6.98 (m, 4H), 6.86 (br d, J = 8.80 Hz, 2H), 4.59−4.57 (m, 1H), 3.79
(s, 3H), 3.18 (dd, J = 18.89, 7.40 Hz, 1H), 2.56−2.51 (m, 1H), 2.26
(s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 200.8, 169.2, 161.3,
138.8, 136.8, 130.6, 129.8, 127.0, 125.5, 121.3, 113.8, 55.3, 47.6, 43.7,
26.9; HRMS (EI) m/z [M + H]+ calcd for C19H18BrO2 357.0484,
found 357.0471.
General Procedure for the Synthesis of 11a−l. Method A. To
a stirred solution of 2-bromo-3-(4-methoxyphenyl)-4-aryl-cyclopent-
2-en-1-one 8 (1.46 mmol) in toluene and water (8:2) mixed (5 mL)
were added appropriate arylboronic acid (1.89 mmol) and Na2CO3
10815
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(4.38 mmol), and the reaction mixture was degassed with nitrogen for
10 min. To the above mixture was added Pd(PPh3)4 (0.073 mmol),
and the solution was stirred at 100 °C for 12−18 h. The reaction
mixture was cooled to an ambient temperature. All volatiles were
evaporated under reduced pressure and then diluted with water (15
mL) and extracted with AcOEt (3 × 30 mL). The combined organic
layer was washed with brine (1 × 30 mL), dried over anhydrous
Na2SO4, and filtered and all volatiles were evaporated. The crude was
purified by flash chromatography on silica gel (AcOEt/cyclohexane,
1:3) to afford the corresponding coupling product.
Method B. To a stirred solution of 2-bromo-3-(4-methoxyphenyl)-
4-aryl-cyclopent-2-en-1-one 8 (1.46 mmol) in THF (10 mL) were
added appropriate arylboronic acid (1.89 mmol) and CsF (2.96
mmol), and the mixture was degassed with nitrogen for 10 min. To
the above mixture was added Pd(tBu3P)2 (0.073 mmol), and the
mixture was stirred at 65 °C for 12 h. The reaction mixture was
cooled to an ambient temperature. All volatiles were evaporated under
reduced pressure, diluted with water (15 mL), and extracted with
AcOEt (3 × 30 mL). The combined organic layer was washed with
brine (1 × 30 mL) and dried over anhydrous Na2SO4, and the
volatiles were evaporated. The crude was purified by flash
chromatography on silica gel (AcOEt/cyclohexane, 1:2) to afford
the corresponding coupling product.
2-(2-Benzyloxyphenyl)-3-(4-methoxyphenyl)-4-phenyl-cyclo-
pent-2-en-1-one (11a). The reaction was performed with 500 mg
(1.46 mmol) of 8a, following general method A. The crude product
was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:3) to afford 11a as a white solid: 380 mg, 58%
yield; mp 65−67 °C; IR (KBr) cm−1 2835, 1693, 1602, 1514, 1454,
1348, 1253, 1180, 1029, 837; 1H NMR (400 MHz, DMSO-d6) δ 7.33
(br d, J = 5.62 Hz, 5H), 7.26−7.20 as(m, 5H), 7.11 (br d, J = 7.21 Hz,
2H), 7.03−6.86 (m, 4H) 6.70 (br d, J = 8.68 Hz, 2H), 5.15−4.82 (m,
3H), 3.63 (s, 3H), 3.13 (brdd, J = 18.58 Hz, 7.34 Hz, 1H), 2.21 (br d,
J = 18.71 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 206.1,
168.7, 160.5, 157.1, 114.2, 137.7, 137.4, 130.7, 130.4, 129.8, 129.0,
128.8, 128.2, 127.5, 126.9, 126.7, 123.7, 121.3, 114.0, 112.9, 70.2,
55.5, 46.0, 45.9; HRMS (EI) m/z [M + H]+ calcd for C31H27O3
447.1960, found 447.1926.
2-(2-Benzyloxyphenyl)-3-(4-methoxyphenyl)-4-(p-tolyl)-
cyclopent-2-en-1-one (11b). The reaction was performed with 520
mg (1.46 mmol) of 8c, following general method A. The crude
product was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:3) to give 11b as a white solid: 370 mg, 55% yield; mp
70−72 °C; IR (KBr) cm−1 2840, 1702, 1600, 1530, 1454, 1348, 1253,
1180, 1040, 830; 1H NMR (400 MHz, DMSO-d6) δ 7.34 (br s, 4H),
7.24−7.18 (m, 5H), 7.06−6.86 (m, 5H), 6.78 (br d, J = 7.46 Hz, 1H),
6.70 (br d, J = 8.56 Hz, 2H), 5.13−4.76 (m, 3H), 3.64 (s, 3H), 3.11
(brdd, J = 18.58, 7.34 Hz, 1H), 2.22−2.16 (m, 1H), 2.14 (s, 3H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 204.6, 167.4, 158.9, 155.5
2-(2-Benzyloxy-4-fluoro-phenyl)-3-(4-methoxyphenyl)-4-phenyl-
cyclopent-2-en-1-one (11d). The reaction was performed with 500
mg (1.46 mmol) of 8a, following general method A. The crude
product was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:3) to give 11d as a pale-yellow solid: 440 mg, 65%
yield; mp 64−66 °C; IR (KBr) cm−1 2930, 1697, 1593, 1514, 1496,
1417, 1339, 1256, 1180, 1153, 1026, 968; 1H NMR (400 MHz,
DMSO-d6) δ 7.34 (br s, 4H), 7.30−7.18 (m, 5H), 7.13−6.95 (m,
4H), 6.90−6.78 (m, 2H), 6.74 (br d, J = 8.68 Hz, 2H), 5.17−4.82 (m,
3H), 3.66 (s, 3H), 3.14 (br dd, J = 18.40, 7.03 Hz, 1H), 2.34−2.19
(m, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 205.1, 168.4, 163.5
1
1
(C−F, JC−F = 244.40 Hz), 161.1 (C−F, JC−F = 244.40 Hz), 159.7,
3
157.4, 143.2, 136.0, 130.5 (2C−F, JC−F = 8.80 Hz), 129.7, 128.2,
2
128.0, 127.4, 126.6, 126.4, 125.9, 118.9, 113.2, 106.9 (C−F, JC−F
=
=
2
2
21.30 Hz), 106.7 (C−F, JC−F = 21.30 Hz), 100.6 (C−F, JC−F
2
27.60 Hz), 100.4 (C−F, JC−F = 27.60 Hz), 69.8, 54.7, 45.1, 44.9;
HRMS (EI) m/z [M + H]+ calcd for C31H26FO3 465.1860, found
465.1879.
2-(2-Benzyloxy-4-fluoro-phenyl)-3-(4-methoxyphenyl)-4-(p-
tolyl)cyclopent-2-en-1-one (11e). The reaction was performed with
520 mg (1.46 mmol) of 8c, following general method A. The crude
product was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:3) to afford 11e as a yellow solid: 418 mg, 60% yield;
mp 72−74 °C; IR (KBr) cm−1 2920, 2362, 1697, 1593, 1508, 1458,
1340, 1256, 1180, 1155, 1026, 837; 1H NMR (400 MHz, DMSO-d6)
δ 7.34 (br s, 4H), 7.28−7.11 (m, 4H), 7.05−6.96 (m, 2H), 6.96−6.84
(m, 2H), 6.82−6.68 (m, 4H), 5.15−4.77 (m, 3H), 3.66 (s, 3H),
3.19−3.05 (m, 1H), 2.32−2.11 (m, 4H); 13C{1H} NMR (101 MHz,
1
DMSO-d6) δ 205.6, 169.0, 163.9 (C−F, JC−F = 244.10 Hz), 161.5
1
(C−F, JC−F = 244.10 Hz), 160.1, 157.8, 140.5, 136.4, 135.3, 131.4
3
(2C−F, JC−F = 9.1 Hz), 130.2, 129.2, 128.4, 127.8, 126.9, 126.8,
2
126.4, 119.3, 113.6, 107.3 (C−F, JC−F = 19.14 Hz), 107.1 (C−F,
2JC−F = 19.14 Hz), 101.0 (C−F, 2JC−F = 21.30 Hz), 100.8 (C−F, 2JC−F
= 21.30 Hz), 70.1, 55.1, 45.4, 45.1, 20.5; HRMS (EI) m/z [M + H]+
calcd for C32H28FO3 479.2016, found 479.2036.
2,3-Bis(4-methoxyphenyl)-4-phenyl-cyclopent-2-en-1-one (11f).
The reaction was performed with 500 mg (1.46 mmol) of 8a,
following general method A. The crude product was purified by flash
chromatography on silica gel (AcOEt/cyclohexane, 1:3) to get 11f as
a pale-yellow solid: 350 mg, 65% yield; mp 82−84 °C; IR (KBr) cm−1
2845, 1706, 1602, 1535, 1450, 1348, 1253, 1040, 850; 1H NMR (400
MHz, CDCl3) δ 7.18−7.14 (m, 4H), 7.10−7.05 (m, 5H), 6.82 (d, J =
7.84 Hz, 2H), 6.56 (d, J = 8.03 Hz, 2H), 4.46 (dd, J = 7.40, 2.02 Hz,
1H), 3.74 (s, 3H), 3.62 (s, 3H), 3.12 (dd, J = 18.83, 7.46 Hz, 1H),
2.49 (dd, J = 18.77, 2.14 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3)
δ 207.0, 168.6, 160.3, 159.3, 143.0, 139.2, 130.9, 130.7, 129.0, 127.4,
127.2, 126.8, 124.6, 114.0, 113.6, 55.2, 55.1, 46.9, 46.0; HRMS (EI)
m/z [M + H]+ calcd for C25H23O3 371.1641, found 371.1469.
2-(4-Chlorophenyl)-3-(4-methoxyphenyl)-4-phenyl-cyclopent-2-
en-1-one (11g). The reaction was performed with 500 mg (1.46
mmol) of 8a, following general method A. The crude product was
purified by flash chromatography on silica gel (AcOEt/cyclohexane,
1:3) to afford 11g as a pale-yellow solid: 340 mg, 62% yield; mp 78−
80 °C; IR (KBr) cm−1 2833, 1690, 1602, 1516, 1460, 1348, 1250,
1180, 1029, 830; 1H NMR (400 MHz, CDCl3) δ 7.35−7.33 (m, 2H),
7.28−7.24 (m, 4H), 7.18−7.11 (m, 5H), 6.67 (d, J = 7.40 Hz, 2H),
4.57 (dd, J = 7.40, 2.02 Hz, 1H), 3.72 (s, 3H), 3.22 (dd, J = 18.89,
7.40 Hz, 1H), 2.60 (dd, J = 18.83, 2.08 Hz, 1H); 13C{1H} NMR (101
MHz, CDCl3) δ 206.3, 170.2, 160.6, 142.5, 138.4, 133.9, 131.1, 130.9,
130.7, 129.0, 128.8, 127.4, 126.9, 126.6, 113.8, 55.2, 47.0, 46.0;
HRMS (EI) m/z [M + H]+ calcd for C24H20ClO2 375.1146; found
375.1143.
139.5, 135.9, 134.1, 129.1, 128.8, 128.2, 128.0, 127.2, 126.6, 126.6,
125.8, 125.3, 122.2, 119.7, 116.8, 112.4, 111.3, 68.5, 53.9, 44.3, 44.1,
19.3; HRMS (EI) m/z [M + H]+ calcd for C32H29O3 461.2111, found
461.2106.
2-(2-Benzyloxyphenyl)-4-(4-fluorophenyl)-3-(4-methoxyphenyl)-
cyclopent-2-en-1-one (11c). The reaction was performed with 525
mg (1.46 mmol) of 8b, following general method A. The crude
product was purified by flash chromatography on silica gel (AcOEt/
cyclohexane, 1:3) to get 11c as a brown solid: 420 mg, 62% yield; mp
131−133 °C; IR (KBr) cm−1 2830, 1691, 1598, 1587, 1510, 1440,
1
1342, 1257, 1238, 1182, 844; H NMR (400 MHz, DMSO-d6) δ
7.38−7.17 (m, 9H), 7.12−6.87 (m, 5H), 6.73−6.69 (m, 3H), 5.16−
4.70 (m, 3H), 3.65 (s, 3H), 3.12 (brdd, J = 18.52, 7.40 Hz, 1H), 2.19
(br d, J = 18.71 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
2-(2-Hydroxyphenyl)-3-(4-methoxyphenyl)-4-phenyl-cyclopent-
2-en-1-one (11h). The reaction was performed with 500 mg (1.46
mmol) of 8a, following general method A. The crude product was
purified by flash chromatography on silica gel (AcOEt/cyclohexane,
1:3) to give 11h as brown solid: 270 mg, 52% yield; mp 192−194 °C;
IR (KBr) cm−1 3157, 2837, 2647, 1798, 1662, 1600, 1564, 1450,
1346, 1261, 1185, 1031, 839; 1H NMR (400 MHz, DMSO-d6) δ 9.34
(br s, 1H), 7.31−7.14 (m, 8H), 6.96 (br d, J = 7.09 Hz, 1H), 6.88−
1
206.0, 168.5, 162.2 (C−F, JC−F = 244.40 Hz), 160.6, 159.8 (C−F,
1JC−F = 244.40 Hz), 157.0, 140.3, 137.6, 137.4, 130.7, 130.4, 129.9,
129.3 (C−F, 3JC−F = 7.90 Hz), 129.2 (C−F, 3JC−F = 7.90 Hz), 128.8,
2
128.4, 128.3, 127.2, 126.7, 123.6, 121.4, 115.8 (C−F, JC−F = 21.19
2
Hz), 115.6 (C−F, JC−F = 21.19 Hz), 114.1, 112.9, 70.2, 55.6, 45.8,
45.1; HRMS (EI) m/z [M + H]+ calcd for C31H26FO3 465.1865,
found 465.1853.
10816
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
6.84 (m, 2H), 6.71 (d, J = 8.80 Hz, 2H), 4.86 (br d, J = 5.99 Hz, 1H),
3.65 (s, 3H), 3.14 (dd, J = 18.52, 7.52 Hz, 1H), 2.30−2.25 (m, 1H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 206.3, 168.9, 160.4, 155.6,
144.4, 137.7, 131.2, 130.5, 129.5, 129.2, 127.7, 127.4, 126.9, 121.2,
119.5, 116.0, 113.9, 55.5, 45.9, 41.0; HRMS (EI) m/z [M + H]+ calcd
for C24H21O3 357.1490, found 357.1496.
Authors
Tarak N. Gowala − Syngenta Biosciences Pvt. Ltd., Santa
Monica Works, North Goa, Goa, India 403110
Pankaj Chaudhari − Syngenta Biosciences Pvt. Ltd., Santa
Monica Works, North Goa, Goa, India 403110
Jagadish Pabba − Syngenta Biosciences Pvt. Ltd., Santa
Monica Works, North Goa, Goa, India 403110
Krishna Sawant − Syngenta Biosciences Pvt. Ltd., Santa
Monica Works, North Goa, Goa, India 403110
2-Cyclopropyl-3-(4-methoxyphenyl)-4-phenyl-cyclopent-2-en-1-
one (11j). The reaction was performed with 500 mg (1.46 mmol) of
8a, following general method A. The crude product was purified by
flash chromatography on silica gel (AcOEt/cyclohexane, 1:3) to get
11j as pale-yellow gummy mass: 250 mg, 56% yield; IR (film) cm−1
2852, 1688, 1605, 1514, 1348, 1263, 1200, 1039, 839; 1H NMR (400
MHz, CDCl3) δ 7.37 (d, J = 8.80 Hz, 2H), 7.28−7.02 (m, 5H), 6.82
(d, J = 8.68 Hz, 2H), 4.34 (d, J = 6.60 Hz, 1H), 3.77 (s, 3H), 3.00
(dd, J = 18.83, 7.34 Hz, 1H), 2.44−2.33 (m, 1H), 1.71−1.68 (m, 1H),
1.10−1.06 (m, 1H), 1.02−0.98 (m, 1H), 0.92- 0.88 (m, 1H), 0.72−
0.69 (m, 1H); 13C{1H} NMR(101 MHz, CDCl3) δ 208.2, 170.0,
160.0, 143.0, 139.7, 130.0, 128.8, 127.7, 127.4, 126.6, 113.6, 55.2,
46.7, 45.9, 8.3, 6.6, 5.5; HRMS (EI) m/z [M + H]+ calcd for
C21H21O2 305.1541, found 305.1533.
3-(4-Methoxyphenyl)-4-phenyl-2-(3-pyridyl)cyclopent-2-en-1-
one (11k). The reaction was performed with 500 mg (1.46 mmol) of
8a, following general method A. The crude product was purified by
flash chromatography on silica gel (AcOEt/cyclohexane, 1:3) to
afford the desired product 11k as a brown solid: 240 mg, 48%; yield;
mp 80−82 °C; IR (KBr) cm−1 2835, 1693, 1602, 1514, 1454, 1348,
1253, 1180, 1029, 837; 1H NMR (400 MHz, DMSO-d6) δ 8.52 (br d,
J = 3.67 Hz, 1H), 8.36 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.43 (dd, J =
7.89, 4.95 Hz, 1H), 7.25−7.22 (m, 4H), 7.17 (d, J = 8.80 Hz, 2H),
7.16−7.12 (m, 1H), 6.77 (d, J = 8.93 Hz, 2H), 4.89 (dd, J = 7.15, 1.77
Hz, 1H), 3.67 (s, 3H), 3.27−3.19 (m, 1H), 2.45−2.39 (m, 1H)
;13C{1H} NMR (101 MHz, DMSO-d6) δ 205.8, 171.7, 160.6, 150.3,
149.0, 143.2, 137.6, 136.3, 130.9, 130.1, 129.2, 128.0, 127.0, 126.6,
124.0, 114.3, 55.6, 46.4, 45.9; HRMS (EI) m/z [M + H]+ calcd for
C23H20NO2 342.1488, found 342.1488.
2-(2-Furyl)-3-(4-methoxyphenyl)-4-phenyl-cyclopent-2-en-1-one
(11l). The reaction was performed with 500 mg (1.46 mmol) of 8a,
following general method B. The crude product was purified by flash
chromatography on silica gel (AcOEt/cyclohexane, 1:2) to afford 11l
as a pale-yellow gummy solid: 170 mg, 35% yield; IR (film) cm−1
2832, 1695, 1600, 1512, 1455, 1340, 1252, 1180, 1029, 837; 1H NMR
(400 MHz, CDCl3) δ 7.26−7.23 (m, 1H), 7.16−7.07 (m, 7H), 6.95
(d, J = 3.30 Hz, 1H), 6.69−6.66 (m, 2H), 6.41 (dd, J = 3.36, 1.77 Hz,
1H), 4.42 (dd, J = 7.40, 2.02 Hz, 1H) 3.69 (s, 3H), 3.12 (dd, J =
18.89, 7.52 Hz, 1H), 2.50 (dd, J = 18.83, 2.20 Hz, 1H); 13C{1H}
NMR (101 MHz, CDCl3) δ 204.8, 160.4, 146.3, 142.5, 142.1, 130.8,
130.4, 128.9, 127.5, 127.4, 126.9, 113.5, 113.3, 111.9, 11.3, 55.1, 47.8,
46.1; HRMS (EI) m/z [M + H]+ calcd for C22H19O3 331.1328, found
331.1328.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01039
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We would like to thank Syngenta Biosciences Pvt. Ltd. for
providing the facility to pursue the current research. A special
thanks goes to Dr. Bhanu Manjunath, Director, Syngenta
Biosciences Pvt. Ltd. for his continuous encouragement and
support. The analytical department is thanked for timely
analytical support. T.G. would like to thank the Department of
Chemistry, Mangalore University.
REFERENCES
■
(1) (a) Roberts, S. M.; Santoro, M. G.; Sickle, E. S. The Emergence
of the Cyclopentenone Prostaglandins as Important, Biologically
Active Compounds. J. Chem. Soc. Perkin Trans. I 2002, 1735−1742.
(b) Weidler, M.; Rether, J.; Anke, T.; Erkel, G.; Sterner, O. New
Bioactive Cyclopentenone Derivatives as Inhibitors of the IL-6
Dependent Signal Transduction. J. Antibiot. 2001, 54, 679−681.
(c) Feng, Z.; Leutou, A. S.; Yang, G.; Nenkep, V. N.; Siwe, X. N.;
Choi, H. D.; Kang, J. S.; Son, B. W. Bioactive Cyclopentenone
Derivatives from Marine Isolates of Fungi. Bull. Korean Chem. Soc.
2009, 30, 2345−2350. (d) Shi, H.; Yu, S.; Liu, D.; van Ofwegen, L.;
Proksch, P.; Lin, W. Sinularones A−I, New Cyclopentenone and
Butenolide Derivatives from a Marine Soft Coral Sinulariasp. and
Their Antifouling Activity. Mar. Drugs 2012, 10, 1331−1344.
(e) Quesnel, Y.; Bidois-Sery, L.; Poirier, J.-M.; Duhamel, L. A
Convenient Synthesis of 2-Chlorophenyl Methylidene-5,5-dimethyl-
cyclopentanone, a Key Intermediate for a Potent Fungicide against
Botrytis Cinera. J. Org. Chem. 1998, 63, 3793−3794. (f) Shirinyan, V.
Z.; Markosyan, A. I.; Baryshnikova, M. A.; Yaminova, L. V.; L’vov, A.
G.; Gabrielyan, S. A. Synthesis and Antiproliferative Activity
Evaluation of Aryl(Hetaryl)Cyclopentenone Analogs of Combretas-
tatin A-4. Pharm. Chem. J. 2018, 51, 867−872.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01039.
(2) (a) Ohashi, M.; Taniguchi, T.; Ogoshi, S. Nickel-Catalyzed
Formation of Cyclopentenone Derivatives via the Unique Cyclo-
addition of α, β-Unsaturated Phenyl Esters with Alkynes. J. Am. Chem.
Soc. 2011, 133, 14900−14903. (b) Wang, M.; Han, F.; Yuan, H.; Liu,
Q. Tandem Nazarov Cyclization-Halovinylation of Divinyl Ketones
Under Vilsmeier Conditions: Synthesis of Highly Substituted
Cyclopentadienes. Chem. Commun. 2010, 46, 2247−2249. (c) Jang,
Y.; Lindsay, V. N. G. Synthesis of Cyclopentenones with Reverse
Pauson-Khand Regiocontrol via Ni-catalyzed C-C Activation of
Cyclopropanone. Org. Lett. 2020, 22, 8872−8876. (d) Lee, Y. H.;
Denton, E. H.; Morandi, B. Modular Cyclopentenone Synthesis
through the Catalytic Molecular Shuffling of Unsaturated Acid
Chlorides and Alkynes. J. Am. Chem. Soc. 2020, 142, 20948−20955.
(3) Ribeiro, N.; Thuaud, F.; Nebigil, C.; Desaubry, L. Recent
Advances in the Biology and Chemistry of the Flavaglines. Bioorg.
Med. Chem. 2012, 20, 1857−1864.
■
sı
Optimization tables, additional experimental procedure,
analytical data, and copies of spectra (1H NMR spectra
and 13C{1H} NMR spectra) (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Sitaram Pal − Syngenta Biosciences Pvt. Ltd., Santa Monica
Works, North Goa, Goa, India 403110; orcid.org/0000-
0003-3187-4475; Email: sitaram.pal@syngenta.com
Sujit K. Ghorai − Syngenta Biosciences Pvt. Ltd., Santa
Monica Works, North Goa, Goa, India 403110;
orcid.org/0000-0003-0816-2787; Email: sujit.ghorai@
syngenta.com
(4) (a) Santelli, M.; Doucet, H.; Fall, Y. Selective Heck reaction of
Aryl Bromides with Cyclopent-2-en-1-one or cyclohex-2-en-1-one.
Tetrahedron 2009, 65, 489−495. (b) Wu, X.; Zhou, J. Selective
Arylation at the Vinylic Site of Cyclic Olefins. Chem. Commun. 2013,
10817
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
49, 4794−4796. (c) Chen, P.-h.; Sieber, J.; Senanayake, C. H.; Dong,
G. Rh-catalyzed reagent-free ring expansion of cyclobutenones and
benzocyclobutenones. Chem. Sci. 2015, 6, 5440−5445. (d) Barluenga,
J.; Alvarez-Fernandez, A.; Suarez-Sobrino, A. L.; Tomas, M. Regio-
and Stereoselective Synthesis of Cyclopentenones: Intermolecular
Pseudo-Pauson−Khand Cyclization. Angew. Chem., Int. Ed. 2012, 51,
183−186. (e) Vinogradov, M. G.; Turova, O. V.; Zlotin, S. G.
Nazarov reaction: current trends and recent advances in the synthesis
of natural compounds and their analogs. Org. Biomol. Chem. 2017, 15,
8245−8269.
(5) Thede, K.; Diedrichs, N.; Ragot, J. P. Stereoselective Synthesis of
( )-Rocaglaol Analogues. Org. Lett. 2004, 6, 4595−4597.
(6) Barluenga, J.; Barrio, P.; Riesgo, L.; Lopez, L. A.; Tomas, M. A
General and Regioselective Synthesis of Cyclopentenone Derivatives
through Nickel(0)-Mediated [3+2] Cyclization of Alkenyl Fischer
Carbene Complexes and Internal Alkynes. J. Am. Chem. Soc. 2007,
129, 14422−14426.
(7) Basmadjian, C.; Zhao, Q.; Desaubry, L. Exploratory Studies
Toward a Synthesis of Flavaglines. A Novel Access to a Highly
Substituted Cyclopentenone Intermediate. Tetrahedron Lett. 2015, 56,
727−730.
(8) Gowala, T.; Pabba, J. Selective Heck Reaction of Electron-rich
Aryl Bromides with Cyclic Alkenones. Tetrahedron Lett. 2015, 56,
1801−1804.
(9) Optimization studies are described in the Supporting
Information.
(10) Ahn, S. - J.; Lee, C. - Y.; Kim, N. - K.; Cheon, C.- H. Metal-Free
Protodeboronation of Electron-Rich Arene Boronic Acids and Its
Application to ortho-Functionalization of Electron-Rich Arenes Using
a Boronic Acid as a Blocking Group. J. Org. Chem. 2014, 79, 7277−
7285.
10818
https://doi.org/10.1021/acs.joc.1c01039
J. Org. Chem. 2021, 86, 10812−10818