Phosphine-Catalyzed [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates with Isoxazole-Based Alkenes

Article abstract of DOI:10.1021/acs.joc.0c01948

A phosphine-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with 3-methyl-4-nitro-5-styrylisoxazoles has been developed to afford various multifunctional isoxazoles in moderate to good yields with moderate to excellent diastereoselectivities. With a spirocyclic chiral phosphine as the catalyst, up to 89% ee was obtained.

Full text of DOI:10.1021/acs.joc.0c01948

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Article
Phosphine-Catalyzed [3 + 2] Annulation of Morita−Baylis−Hillman
Carbonates with Isoxazole-Based Alkenes
Jianning Liao, Jipan Dong, Jiaqing Xu, Wei Wang, Yongjun Wu, Yuxia Hou,* and Hongchao Guo*
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ABSTRACT: A phosphine-catalyzed [3 + 2] annulation of
Morita−Baylis−Hillman (MBH) carbonates with 3-methyl-4-
nitro-5-styrylisoxazoles has been developed to afford various
multifunctional isoxazoles in moderate to good yields with
moderate to excellent diastereoselectivities. With a spirocyclic
chiral phosphine as the catalyst, up to 89% ee was obtained.
thiourea-catalyzed [4 + 2] annulation of chromone-based
oxindoles,11 cinchona-derived squaramide/base-catalyzed [2 +
2 + 2] annulation of β-dicarbonyl compounds and β-
nitroalkenes,12 trienamine-mediated [4 + 2]-cycloaddition,13
and base-promoted [3 + 2] annulation of 1,4-dithiane-2,5-
diol.14 With these synthetic reactions, diverse carbocyclic and
heterocyclic compounds have been prepared. However,
application of 4-nitro-5-styrylisoxazoles in nucleophilic phos-
phine catalysis has not been explored.
INTRODUCTION
■
The isoxazole and its derivatives are significant scaffolds in
natural products which exhibit versatile biological and
pharmaceutical activities along with low toxicity.1 Many
compounds bearing the isoxazole scaffold display various
bioactivities such as antitumor, antiproliferative, neuroprotec-
tive, antiviral, herbicidal, insecticidal, and fungicidal activities.1
As shown in Figure 1, leflunomide is a dehydrogenase inhibitor
Nucleophilic phosphine catalysis has had huge success in the
past two decades and has become a powerful tool for synthesis
of carbo- and heterocyclic compounds.15 Since Lu reported the
seminal work on phosphine-catalyzed [3 + 2] annulation of
allenoates with electron-deficient alkenes,16 the nucleophilic
phosphine-catalyzed [3 + 2] annulation reactions of zwitter-
ionic species (which are catalytically formed by the
nucleophilic addition to precursors) with various dipolarphiles
have extensively been studied, including activated alkenes,17
imines,18 dipoles,19 and other types of dipolarphiles.20 Among
them, activated alkenes are the most intensively studied
reaction partners which can act as C2 synthons and therefore
can be used to construct all-carbon ring structures. Despite the
progress, novel activated alkenes that bearing diverse structures
and electronic properties are still highly desired to be
investigated in phosphine-catalyzed reactions to enrich the
synthetic strategy as well as providing new synthetic routes to
diverse new compounds. Considering the electron-deficient
property of 4-nitro-5-styrylisoxazoles, we envision that this
type of alkenes can be utilized in phosphine-catalyzed [3 + 2]
Figure 1. Examples of bioactive compounds containing 5-cyclo-
pentylisoxazole Scaffold.
used in adults for the treatment of active moderate-to-severe
rheumatoid arthritis. Compound I has antitumor activity.
Isoxaben is an herbicide. Encouraged by bioactivity of
isoxazole derivatives, they have become a popular synthetic
target over the years.2
As one type of electron-deficient alkenes, 4-nitro-5-
styrylisoxazoles, in which alkenes are installed on a 4-
nitroisoxazole ring, have attracted much attention in various
transformations for synthesis of isoxazole derivatives with
structural diversity. They have extensively been applied in
many annulation reactions such as 1,3-dipolar [3 + 2]
cycloaddition of azomethine ylides,3 [3 + 2] cycloaddition of
tosylmethyl isocyanide,4 N-heterocyclic carbene-catalyzed [3 +
2]5 and [4 + 2]6 annulation reactions of enals, L-proline-
catalyzed one-pot three-component aza-Diels−Alder reac-
tions,7 phase-transfer-catalyzed enantioselective cyclopropana-
tion8 and [4 + 2] annulation,9 quinine-catalyzed [3 + 2]
annulation of 3-isothiocyanato oxindoles,10 quinidine-derived
Received: August 11, 2020
Published: January 5, 2021
https://dx.doi.org/10.1021/acs.joc.0c01948
© 2021 American Chemical Society
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The Journal of Organic Chemistry
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Article
annulation to construct biologically important isoxazole
derivatives. As part of our continuing efforts on cycloaddition
reactions,21 we herein reported a phosphine-catalyzed [3 + 2]
annulation of 4-nitro-5-styrylisoxazoles with MBH carbonates
to afford isoxazole derivatives (Scheme 1).
9). A lower temperature resulted in lower reactivity and did
not provide better diastereoselectivity (entry 10).
With the optimal reaction conditions in hand, we set out to
explore the scope of MBH carbonates by evaluating the
reaction between (E)-3-methyl-4-nitro-5-styrylisoxazole (2a)
and various MBH carbonates (1) bearing diverse substituents
with different electronic properties (Table 2). We were pleased
Scheme 1. Phosphine-Catalyzed [3 + 2] Annulation of 4-
Nitro-5-styrylisoxazoles with MBH Carbonates
a
Table 2. Scope of MBH Carbonates 1
b
c
Initially, 3-methyl-4-nitro-5-styrylisoxazole 1a and MBH
carbonate 2a were chosen as the model substrates to
investigate the reaction. As shown in Table 1, various
entry
R in 1
Ph (1a)
3-FC6H4 (1b)
3
yield (%)
dr
1
2
3
4
5
6
7
8
3aa
3ba
3ca
3da
3ea
3fa
3ga
3ha
3ia
95
87
90
24
81
80
66
82
83
75
67
30
99
98
91
trace
98
trace
85
15:1
9:1
4-FC6H4 (1c)
13:1
10:1
10:1
10:1
8:1
10:1
15:1
8:1
8:1
6:1
10:1
15:1
15:1
a
Table 1. Optimization of the Reaction Conditions
2-ClC6H4 (1d)
3-ClC6H4 (1e)
4-ClC6H4 (1f)
3,5-Cl2C6H3 (1g)
3-BrC6H4 (1h)
4-BrC6H4 (1i)
3-CF3C6H4 (1j)
3-NO2C6H4 (1k)
4-NO2C6H4 (1l)
3-MeOC6H4 (1m)
4-MeOC6H4 (1n)
4-i-PrC6H4 (1o)
2-MeC6H4 (1p)
4-MeC6H4 (1q)
1-naphthyl (1r)
2-naphthyl (1s)
2-furyl (1t)
9
b
c
entry
cat.
PPh3
Ph2PMe
PhPMe2
n-Bu3P
PhPMe2
PhPMe2
PhPMe2
PhPMe2
PhPMe2
PhPMe2
solvent
T (°C) time (h) yield (%)
dr
10
11
12
13
14
15
16
17
18
19
3ja
3ka
3la
1
2
3
4
5
6
7
8
9
DCM
DCM
DCM
DCM
CHCl3
DCE
toluene
THF
DMF
DCM
rt
rt
rt
rt
rt
rt
rt
rt
rt
0
72
72
12
72
24
12
24
24
72
48
0
25
95
87
49
98
53
84
0
3:1
15:1
10:1
10:1
10:1
9:1
3ma
3na
3oa
3pa
3qa
3ra
3sa
3ta
15:1
10:1
15:1
18:1
d
20
69
10
67
15:1
a
a
Unless indicated otherwise, reactions of 1 (0.15 mmol) and 2a (0.1
mmol) were carried out at room temperature in the presence of
catalyst (0.02 mmol) in 2 mL of the DCM. Isolated yield.
Determined by H NMR analysis. The reaction was carried out at
Unless indicated otherwise, reactions of 1a (0.15 mmol) and 2a
(0.10 mmol) were carried out at room temperature in the presence of
b
b
catalyst (0.02 mmol) in 2 mL of the solvent. Isolated yield.
c
d
1
c
1
Determined by H NMR analysis.
70 °C in 2 mL of the DCE.
phosphines, solvents, and temperatures were carefully exam-
ined to determine the optimal reaction conditions. The weak
nucleophilic Ph3P did not promote the reaction, and no
product was observed (entry 1). With moderate nucleophilic
Ph2PMe as the catalyst, the desired [3 + 2] cycloadduct was
obtained in 25% yield (entry 2). The PhPMe2 turned out to be
the most efficient catalyst, leading to the corresponding [3 + 2]
cycloadduct 3aa in 95% yield with 15:1 diastereomeric ratio
(entry 3). The strong nucleophilic n-Bu3P was also a suitable
catalyst, giving the product in 87% yield with 10:1 dr (entry 4).
With the use of PhPMe2 as the catalyst, we then examined the
effect of different solvents on the reaction, including CHCl3,
1,2-dichloroethane (DCE), toluene, THF, and DMF (entries
5−9). Among them, DCE proved to be a compatible solvent
while the product 3aa was obtained in 98% yield (entry 6), but
the diastereomeric ratio was not as good as in DCM (entry 6
vs 3). Solvents such as CHCl3, THF, and toluene were also
feasible but afforded the product in lower yields (entries 5, 7,
and 8), compared with DCM and DCE. When chloroform was
used as a solvent, the yield of the reaction decreased, which
might be due to the relative strong polarity of chloroform
(entry 5). A strong polar solvent like DMF completely
suppressed the reaction, producing no desired product (entry
to find that most of the MBH carbonates were efficiently
transformed into the corresponding cycloadducts in good to
excellent yields with 6:1−18:1 diastereomeric ratio (entries 1−
20). It was also found that the reactivity of the reaction was
greatly influenced by the substituent on the benzene ring of the
MBH carbonates. Generally, MBH carbonates bearing meta-
and para-substituted phenyl groups smoothly underwent
cycloadditions with compound 2a to afford the desired
cycloadducts in good to excellent yields and diastereoselectiv-
ities (for examples, see entries 2, 3, 5, 6, 8, 9, 13, 14, 15, and
17). MBH carbonates bearing ortho-substituted phenyl groups
exhibited sluggish results due to steric hindrance (entry 4 and
entry 16). When the benzene ring is substituted with an
electron-withdrawing group, the yield of the reaction is lower
than the substrate which is substituted with an electron-
donating group because the electron-donating group increases
the activity of the phosphine ylide intermediate. The
cycloadduct was obtained in much lower yield and
diastereoselectivity when the nitro group was in the para-
position of the benzene ring for the MBH carbonate, compared
with results of meta-substituted one (entry 11 vs 12). 1-
Naphthyl-substituted MBH carbonate did not afford the
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corresponding product under optimal conditions, while the 2-
naphthyl-substituted one gave the desired product in good
yield with good diastereoselectivity, indicating a significant
influence of steric hindrance on reactivity of the substrates
(entries 18 and 19). The 2-methyl-subsituted substrate and the
2-chloro-substituted substrate did not work for the same
reason (entries 4, 16). MBH carbonate having heteroaryl
group also worked in this reaction to produce the
corresponding product in high yield with good diastereose-
lectivitiy (entry 20).
to be suitable in the reaction with good yield and
diastereoselectivity (entry 16). The relative configuration of
the [3 + 2] cycloaddition products was established by X-ray
crystallographic analysis of the cycloadduct 3an.
In order to synthesize chiral isoxazole derivatives, we next
investigate chiral phosphine-catalyzed [3 + 2] annulation of 4-
nitro-5-styrylisoxazoles with MBH carbonates (Table 4).
Table 4. Screening the Reaction Conditions for Asymmetric
a
Variant
The scope of 3-methyl-4-nitro-5-styrylisoxazoles was also
carefully examined under the optimal conditions (Table 3). No
a
Table 3. Scope of 3-Methyl-4-nitro-5-styrylisoxazoles 2
b
c
entry
R in 2
3
yield (%)
dr
1
2
3
4
5
6
7
8
4-FC6H4 (2b)
2-ClC6H4 (2c)
3-ClC6H4 (2d)
4-ClC6H4 (2e)
4-BrC6H4 (2f)
4-NO2C6H4 (2g)
2-MeC6H4 (2h)
3-MeC6H4 (2i)
4-MeC6H4 (2j)
2-MeOC6H4 (2k)
3-MeOC6H4 (2l)
4-MeOC6H4 (2m)
2-naphthyl (2n)
3-thienyl (2o)
3-furyl (2p)
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao
3ap
3aq
82
75
82
81
82
52
65
96
91
99
99
86
87
90
65
80
15:1
12:1
7:1
11:1
15:1
6:1
b
c
d
entry
Px
solvent
time (h)
yield (%)
ee (%)
dr
e
1
2
3
4
5
6
7
8
9
P1
P2
P3
P4
P4
P4
P4
P4
P4
P4
DCM
DCM
DCM
DCM
CHCl3
DCE
toluene
AcOEt
THF
72
72
72
72
48
48
48
48
48
72
NR
15
NR
20
25
22
14
22
trace
13
70
2:1
88
87
89
84
80
11:1
10:1
6:1
1:1
1:1
6:1
15:1
12:1
15:1
15:1
10:1
8:1
15:1
>20:1
15:1
9
10
11
12
13
14
15
f
10
DCE
77
15:1
a
Unless indicated otherwise, reactions of 1a (0.06 mmol) and 2a
(0.05 mmol) were carried out at toom temperature in the presence of
b
chiral phosphine (0.01 mmol) in 1 mL of solvent. Isolated yield.
d
c
d
Determined by chiral HPLC analysis. Determined by 1H NMR
16
Ethyl (2q)
e
f
a
analysis. No reaction. The reaction was performed at 80 °C.
Unless indicated otherwise, reactions of 1a (0.15 mmol) and 2 (0.1
mmol) were carried out at toom temperature in the presence of
b
PPhMe2 (0.02 mmol) in 2 mL of the DCM. Isolated yield.
Three commercially available chiral phosphines including P1,
P2, and P3 were first tried. Unfortunately, cyclic chiral
phosphine P1 and bifunctional chiral phosphine P3 did not
promote the reaction (entries 1 and 3). Delightedly, spirocyclic
chiral phosphine P2 catalyzed the reaction of MBH carbonate
1a and alkene 2a to give the cycloadduct 3aa in 70% ee, albeit
with poor 15% yield (entry 2). On the basis of this result, chiral
phosphine P4, which is an analogue of P2, was examined. An
improved 88% ee was obtained, but the yield still remained at
low 20% (entry 4). With the use of chiral phosphine P4 as the
catalyst, several solvents were screened (entries 5−9).
However, the yields could not be increased and enantiose-
lectivity remained nearly same as that obtained with DCM as
solvent. After the reaction temperature was increased to 80 °C,
both the yield and enantioselectivity decreased (entry 10). It
indicated that the catalytic activity of these two chiral
phosphines P2 and P4 were not high enough to promote
this reaction for full conversion. New highly reactive chiral
phosphines are needed for the current reaction.
c
d
1
Determined by H NMR analysis. The reaction was carried out at
70 °C in 2 mL of the DCE.
matter the substitution pattern and electronic property of the
aryl group in the 3-methyl-4-nitro-5-styrylisoxazole, the
reactions proceeded smoothly and furnished the desired
products in moderate to good yields with good to excellent
diastereomeric ratios (Table 3, entries 1−12). Like the MBH
carbonates, when the substituent was at the ortho position of
the benzene ring of the substrates 2, generally, the reactions
gave relatively lower yields of the corresponding products due
to the steric hindrance (Table 3, entries 2, 7). However, the
reaction of 2-methoxyphenyl-substituted 3-methyl-4-nitro-5-
styrylisoxazole gave the corresponding cycloadduct 3ak in
excellent yield (Table 3, entry 10). The NO2-containing
substrate was not very reactive in the reaction, and the
corresponding product was obtained in lower yield with lower
diastereoselectivity because the nitro group deactivates the 3-
methyl-4-nitro-5-styrylisoxazoles (entry 6). The 2-naphthyl
and heteroaryl such as 3-thienyl- and 3-furyl-substituted 4-
nitro-5-styrylisoxazoles also performed the reaction, leading to
the corresponding products in good yields with good to
excellent diastereoselectivities (entries 13−15). To our delight,
alkyl-substituted 3-methyl-4-nitro-5-styrylisoxazole was proved
To demonstrate the practicability of the reaction, a scale-up
reaction of 3-methyl-4-nitro-5-styrylisoxazoles 1a with MBH
carbonate 2a was carried out, and the desired product 3aa was
obtained in 94% yield with 15:1 dr (Scheme 2). Further
derivations of the cycloadducts were also performed. In the
presence of SnCl2, the 4-nitroisoxazole group of 3aa could be
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transfer and elimination of tertiary phosphine give the product
3aa. Due to the hindrance between the benzene ring of 3-
methyl-4-nitro-5-styrylisoxazoles and the benzene ring of MBH
carbonate, nucleophilic addition reaction of the ylide A to
carbon−carbon double bond occurs to favor that the two
phenyl groups of the intermediate B locate on the opposite
sides. The intramolecular annulation results in a favorable trans
configuration of the carboxyl group and the phenyl group.
Scheme 2. Scale-up Reaction and Further Transformations
CONCLUSION
■
In conclusion, we developed a new [3 + 2] annulation reaction
of Morita−Baylis−Hillman carbonates with isoxazole-based
alkenes. In this reaction, a new type of olefin is used. The
corresponding cycloadducts were provided under mild
conditions in typically good to excellent yields with good to
excellent diastereoselectivities. The reaction could be per-
formed on hundreds of milligrams scale, and further trans-
formations of the cycloadducts were feasible, showing the
reaction will be a useful method for the construction of
biologically important isoxazole derivatives.
EXPERIMENTAL SECTION
■
reduced to afford the product 4 in 45% yield with >20:1 dr.
Treatment of the product 3aa with bromine in CCl4 produced
the derivative 5 in 65% yield with >20:1 dr. Interestingly,
compound 5 was produced by a rearrangement during the
reaction. A plausible mechanism of this reaction is described in
the Supporting Information. The relative configuration of
brominated product 5 was established by X-ray crystallo-
graphic analysis.
General Information. All reactions were performed under Ar
atmosphere in oven-dried glassware with magnetic stirring. Unless
otherwise stated, all reagents were purchased from commercial
suppliers and used without further purification. All solvents were
purified and dried according to standard methods prior to use.
Organic solutions were concentrated under reduced pressure on a
rotary evaporator or an oil pump. Reactions were monitored by thin-
layer chromatography (TLC) on silica gel precoated glass plates.
Chromatograms were visualized by fluorescence quenching with UV
light at 254 nm. Flash column chromatography was performed using
flash silica gel (200−300 mesh). 1H and 13C NMR spectra were
recorded in CDCl3 using 300 MHz NMR and 600 MHz instrument
(referenced internally to Me4Si). 1H NMR data are reported as
follows: chemical shift, multiplicity (s = singlet; d = doublet; q =
quartet; m = multiplet; br = broad), coupling constant (Hz), and
integral. Data for 13C NMR spectra are reported in terms of chemical
shift. Accurate mass measurements were performed using an
instrument with the ESI-Linear ion trap-MS technique.
On the basis of previous work,15 a plausible mechanism is
described in Scheme 3. The reaction is initiated by the
Scheme 3. Plausible Reaction Mechanism for the
Annulation
General Procedure for Phosphine-Catalyzed [3 + 2]
Annulation. Under Ar atmosphere, at 25 °C, to a mixture of 3-
methyl-4-nitro-5-alkenyl-isoxazoles 2 (0.1 mmol, 1 equiv) and MBH
carbonate 1 (0.15 mmol, 1.5 equiv) in DCM (2 mL) was added via
syringe. Then the reaction solution was vigorously stirred at 25 °C
and monitored by TLC. After the reaction was complete, the mixture
was directly purified by column chromatography on silica gel with
petroleum ether/EtOAc (10:1) as the eluent to furnish the
corresponding product.
General Procedure for the Scaled-up Annulation Reaction.
An oven-dried 100 mL of Schlenk tube was charged with 3-methyl-4-
nitro-5-alkenylisoxazoles 2a (0.46 g, 2 mmol), MBH carbonate 1a
(0.88 g, 3 mmol) and PPhMe2 (0.4 mmol) in 20 mL of DCM for 12 h
under Ar atmosphere at 25 °C. The mixture was concentrated to
dryness. The residue was purified by flash column chromatography
with petroleum ether/EtOAc (10:1) as the eluent to afford the
product 3aa (0.76 g, 94% yield, 15:1 dr).
Further Transformations of the Products. SnCl2 (1.5 mmol,
283 mg) was add to the solution of 3aa (0.3 mmol, 120 mg) in THF
(7 mL). Then 36% HCl solution (0.35 mL) was dropwise added to it.
After being stirred at room temperature for 4 h, the mixture was
poured in an ice-cold solution of 10% NaOH (10 mL) and extracted
with ethyl acetate. The combined organic layers were dried over
Na2SO4 and concentrated. The residue was purified by flash column
chromatography (petroleum ether/EtOAc = 5:1) to afford the
product 4 (44.8 mg, 45% yield, > 20:1 dr).
nucleophilic attack of the phosphine catalysis to MBH
carbonate 1a, which is followed by the release of CO2 and t-
BuOH to generate phosphorus ylide A. Nucleophilic attack of
ylide A to 3-methyl-4-nitro-5-styrylisoxazoles occurred to form
the intermediate B. The configuration in which the two
benzene rings of intermediate B are on opposite sides is
relatively stable. The intramolecular cyclization of intermediate
B leads to the cyclic intermediate C. Subsequent proton
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1
At 0 °C, the bromine (0.3 mmol, 48 mg) was add to the solution of
3aa (0.1 mmol, 40 mg) in CCl4 (2 mL), After being stirred at 0 °C for
36 h, the mixture was concentrated. The residue was purified by flash
column chromatography (petroleum ether: EtOAc = 5:1) to afford
the product 5 (34.5 mg, 65% yield, > 20:1 dr).
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.37−7.30 (m, 3H), 7.26−7.23 (m, 2H), 7.19−7.15 (m, 3H), 7.09−
7.02 (m, 2H). 4.57 (dt, J = 8.7, 2.6 Hz, 1H), 4.51 (dt, J = 9.0, 2.7 Hz,
1H), 4.37 (t, J = 8.9 Hz, 1H), 3.68 (s, 3H), 2.56 (s, 3H); 13C{1H}
NMR (75 MHz, CDCl3) δ 172.3, 163.5, 155.8, 144.6, 142.8, 139.4,
137.1, 134.3, 129.8, 128.9, 128.5, 127.6, 127.4, 127.1, 127.0, 126.8,
124.9, 55.3, 55.13, 55.07, 51.5, 27.4, 11.3; IR (film) νmax 2360, 1719,
1598, 1521, 1474, 1436, 1418, 1378, 1364, 1275, 1197, 1155, 1101,
981, 887, 829, 788, 694, 572, 513, 441 cm−1; HRMS (ESI-Linear ion
Characterization Data for Phosphine-Catalyzed [3 + 2]
Annulation Products 3. Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-
4,5-diphenylcyclopent-2-ene-1-carboxylate (3aa). Yellow oil (38.4
mg, 95% yield). It was purified by flash column chromatography
1
−
trap) m/z [M − H]− calcd for C23H18ClN2O5 437.0910, found
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.36−7.28 (m, 5H), 7.25−7.14 (m, 5H), 7.02 (t, J = 2.2 Hz, 1H),
4.62 (dt, J = 8.6, 2.8 Hz, 1H), 4.51 (dt, J = 9.0, 2.8 Hz, 1H), 4.43 (d, J
= 8.8 Hz, 1H), 3.66 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3) δ 172.8, 163.8, 155.7, 144.1, 140.7, 139.7, 137.6, 128.8, 128.5,
127.5, 127.1, 126.9, 126.7, 55.8, 55.4, 55.0, 51.4, 11.4; IR (film) νmax
2990, 2360, 1719, 1601, 1521, 1455, 1436, 1418, 1378, 1365, 1331,
1302, 1239, 1197, 1142, 1100, 828, 766, 698, 565, 507 cm−1; HRMS
437.0913.
Methyl 5-(4-Chlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3fa). Yellow oil (35 mg,
80% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.40−7.27 (m, 5H), 7.21−7.09 (m, 4H), 7.03 (t, J = 2.2 Hz, 1H),
4.59 (dt, J = 8.7, 2.7 Hz, 1H), 4.50 (dt, J = 9.0, 2.8 Hz, 1H), 4.38 (t, J
= 8.9 Hz, 1H), 3.67 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3) δ 172.4, 163.6, 155.7, 144.5, 139.5, 139.3, 137.2, 133.0,
128.84, 128.75, 128.6, 128.1, 127.6, 126.8, 55.2, 55.1, 55.0, 51.4, 11.3;
IR (film) νmax 2953, 1720, 1601, 1522, 1491, 1436, 1417, 1378, 1365,
1302, 1239, 1197, 1142, 1093, 1015, 887, 829, 767, 698, 554, 507
cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
+
(ESI-Linear ion trap) m/z [M + H]+ calcd for C23H21N2O5
405.1445, found 405.1450.
Methyl 5-(3-Fluorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3ba). Yellow oil (37.1 mg,
87% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
−
7.48−7.35 (m, 2H), 7.22−7.11 (m, 3H), 7.09 (t, J = 2.7 Hz, 1H),
(7.04−6.96 (m, 4H), 4.60 (dt, J = 8.7, 2.7 Hz, 1H), 4.51 (dt, J = 9.0,
2.7 Hz, 1H), 4.39 (d, J = 8.9 Hz, 1H), 3.67 (s, 3H), 2.55 (s, 3H);
13C{1H} NMR (75 MHz, CDCl3) δ 172.4, 164.3(C−F, 1JC−F = 246.8
C23H18ClN2O5 437.0910, found 437.0912.
Methyl 5-(3,5-Dichlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
4-phenylcyclopent-2-ene-1-carboxylate (3ga). Yellow oil (31.2 mg,
66% yield). It was purified by flash column chromatography
1
1
Hz), 163.6, 161.0(C−F, JC−F = 246.8 Hz), 155.7, 144.6, 143.4 (C−
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
3
F,3JC−F = 7.0 Hz), 143.3(C−F, JC−F = 7.0 Hz), 139.5, 137.1, 130.2
7.40−7.27 (m, 4H), 7.19−7.12 (m, 3H), 7.06 (m, 2H), 4.52 (ddt, J =
11.4, 9.1, 2.9 Hz, 2H), 4.33 (t, J = 8.8 Hz, 1H), 3.71 (s, 3H), 2.57 (s,
3H); 13C{1H} NMR (75 MHz, CDCl3) δ 171.9, 163.3, 155.8, 145.2,
144.2, 139.1, 136.6, 135.0, 128.9, 128.6, 127.8, 127.6, 127.3, 127.1,
126.8, 125.8, 125.4, 55.1, 54.92, 54.88, 51.6, 11.3; IR (film) νmax 2954,
2359, 1720, 1589, 1569, 1521, 1435, 1418, 1378, 1364, 1274, 1241,
1198, 1142, 1098, 859, 829, 798, 764, 686, 516, 430 cm−1; HRMS
3
3
(C−F, JC−F = 8.3 Hz),130.1(C−F, JC−F = 8.3 Hz), 128.9, 127.6,
3
3
126.8, 122.40(C−F, JC−F = 3.0 Hz),122.36(C−F, JC−F = 3.0 Hz),
2
2
114.3(C−F, JC−F = 21.4 Hz), 114.0(C−F, JC−F = 21.4 Hz), 113.8
2
2
(C−F, JC−F = 21.8 Hz), 113.5(C−F, JC−F = 21.8 Hz), 55.4(C−F,
3JC−F = 1.9 Hz), 55.3(C−F, 3JC−F = 1.9 Hz), 55.2, 55.0, 51.4, 11.3; IR
(film) νmax 2360, 1719, 1600, 1490, 1450, 1418, 1378, 1364, 1272,
1244, 1197, 1142, 1101, 983, 873, 830, 766, 695, 573, 474 cm−1;
−
(ESI-Linear ion trap) m/z [M − H]− calcd for C23H17Cl2N2O5
−
HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for C23H18FN2O5
471.0520, found 471.0522.
421.1205, found 421.1207.
Methyl 5-(3-Bromophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3ha). Yellow oil (39.5 mg,
82% yield). It was purified by flash column chromatography
Methyl 5-(4-Fluorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3ca). Yellow oil (37.9 mg,
90% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.42−7.29 (m, 5H), 7.21−7.19 (m, 4H), 7.04 (t, J = 2.2 Hz, 1H),
4.55 (dt, J = 8.6, 2.6 Hz, 1H), 4.50 (dt, J = 9.0, 2.8 Hz, 1H), 4.37 (t, J
= 8.8 Hz, 1H), 3.68 (s, 3H), 2.56 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3) δ 172.3, 163.5, 155.8, 144.6, 143.1, 139.4, 137.1, 130.4, 130.2,
130.1, 129.9, 128.9, 128.5, 127.7, 127.1, 126.8, 125.4, 122.5, 55.2,
55.11, 55.07, 51.5, 11.4; IR (film) νmax 3735, 2953, 2360, 1719, 1600,
1522, 1436, 1378, 1274, 1197, 1142, 1103, 1073, 997, 888, 829, 786,
695, 571, 517, 435 cm−1; HRMS (ESI-Linear ion trap) m/z [M −
7.41−7.29 (m, 3H), 7.22−7.11 (m, 4H), 7.04−6.96 (m, 3H), 4.60
(dt, J = 8.7, 2.7 Hz, 1H), 4.51 (dt, J = 9.0, 2.7 Hz, 1H), 4.39 (d, J =
8.9 Hz, 1H), 3.67 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR (75 MHz,
1
CDCl3) δ 172.5, 163.7, 163.4(C−F, JC−F = 245.7 Hz), 160.1(C−F,
3
1JC−F = 245.7 Hz), 155.7, 144.2, 139.6, 137.4, 136.51(C−F, JC−F
=
=
3
3
3.4 Hz), 136.46 (C−F, JC−F = 3.4 Hz), 128.8, 128.3(C−F, JC−F
8.2 Hz), 128.2(C−F, 3JC−F = 8.2 Hz), 127.6, 126.8, 115.6(C−F, 2JC−F
= 21.6 Hz), 115.3(C−F, 2JC−F = 21.6 Hz), 55.4, 55.0, 54.9, 51.4, 11.3;
IR (film) νmax 2360, 1719, 1601, 1559, 1510, 1437, 1378, 1329, 1273,
1197, 1142, 1103, 1015, 981, 887, 766, 698, 669, 564, 514 cm−1;
−
H]− calcd for C23H18BrN2O5 481.0405, found 481.0410.
Methyl 5-(4-Bromophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3ia). Yellow oil (40.0 mg,
83% yield). It was purified by flash column chromatography
−
HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for C23H18FN2O5
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
421.1205, found 421.1208.
7.51−7.40 (m, 2H), 7.39−7.27 (m, 3H), 7.21−7.15 (m, 2H), 7.08−
6.99 (m, 3H), 4.59 (dt, J = 8.7, 2.7 Hz, 1H), 4.50 (dt, J = 9.0, 2.8 Hz,
1H), 4.47 (t, J = 8.9 Hz, 1H), 3.67 (s, 3H), 2.55 (s, 3H); 13C{1H}
NMR (75 MHz, CDCl3) δ 172.4, 163.6, 155.7, 144.5, 139.8, 139.5,
137.2, 131.7, 128.9, 128.5, 127.6, 126.8, 121.1, 55.12, 55.10, 55.08,
51.5, 11.3; IR (film) νmax 2953, 1720, 1601, 1523, 1437, 1378, 1302,
1239, 1197, 1142, 1098, 1073, 1011, 887, 767, 698, 674, 554, 506
cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
Methyl 5-(2-Chlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3da). Yellow oil (10.5 mg,
24% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.39−7.30 (m, 5H), 7.29 (s, 1H), 7.20 (ddd, J = 7.7, 4.8, 2.9 Hz, 3H),
7.09 (t, J = 2.3 Hz, 1H), 5.19 (s, 1H), 4.59 (dt, J = 8.7, 2.6 Hz, 1H),
4.39 (d, J = 10.7 Hz, 1H), 3.69 (s, 3H), 2.57 (s, 3H); 13C{1H} NMR
(75 MHz, CDCl3) δ 172.9, 163.6, 155.6, 144.7, 139.7, 136.9, 132.9,
129.4, 128.8, 128.3, 127.5, 127.2, 127.1, 126.9, 55.1, 51.5, 11.3; IR
(film) νmax 2359, 1719, 1601, 1521, 1475, 1437, 1378, 1287, 1249,
1198, 1143, 1101, 1038, 981, 888, 757, 698, 572, 513, 469 cm−1;
−
C23H18BrN2O5 481.0405, found 481.0411.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-4-phenyl-5-(3-
(trifluoromethyl)phenyl)cyclopent-2-ene-1-carboxylate (3ja). Yel-
low oil (35.4 mg, 75% yield). It was purified by flash column
+
HRMS (ESI-Linear ion trap) m/z [M + H]+ calcd for C23H20ClN2O5
1
chromatography (petroleum ether/EtOAc = 10:1): H NMR (300
439.1055, found 439.1049.
MHz, CDCl3) δ 7.57−7.32 (m, 7H), 7.19 (dd, J = 7.8, 1.7 Hz, 2H),
7.09 (t, J = 2.2 Hz, 1H), 4.65 (dt, J = 8.7, 2.7 Hz, 1H), 4.55 (dt, J =
8.9, 2.7 Hz, 1H), 4.40 (t, J = 8.8 Hz, 1H), 3.67 (s, 3H), 2.56 (s, 3H);
Methyl 5-(3-Chlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3ea). Yellow oil (35.4 mg,
81% yield). It was purified by flash column chromatography
2094
https://dx.doi.org/10.1021/acs.joc.0c01948
J. Org. Chem. 2021, 86, 2090−2099

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
13C{1H} NMR (75 MHz, CDCl3) δ 172.2, 163.5, 155.8, 144.9, 141.7,
139.3, 136.9, 130.1, 129.1, 128.9, 127.7, 126.8, 124.1 (q, J = 3.8 Hz),
123.7 (q, J = 3.7 Hz), 55.5, 55.00, 54.96, 51.5, 11.3; IR (film) νmax
2360, 1719, 1602, 1522, 1437, 1418, 1379, 1364, 1328, 1252, 1196,
1166, 1125, 1073, 904, 830, 803, 766, 699, 668, 515 cm−1; HRMS
127.5, 126.9, 126.5, 55.3, 55.2, 51.3, 33.3, 23.53, 23.49, 11.4; IR (film)
νmax 2961, 2360, 1719, 1600, 1521, 1436, 1418, 1378, 1364, 1275,
1253, 1197, 1142, 1098, 1056, 1019, 887, 828, 764, 698, 669, 567
cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
−
C26H25N2O5 445.1769, found 445.1768.
−
(ESI-Linear ion trap) m/z [M − H]− calcd for C24H18F3N2O5
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-4-phenyl-5-(p-tolyl)-
cyclopent-2-ene-1-carboxylate (3qa). Yellow oil (40.9 mg, 98%
yield). It was purified by flash column chromatography (petroleum
ether/EtOAc = 10:1): 1H NMR (300 MHz, CDCl3) δ 7.40−7.29 (m,
3H), 7.23−7.17 (m, 2H), 7.14−7.03 (m, 4H). 6.99 (t, J = 2.2 Hz,
1H), 4.60 (dt, J = 8.5, 2.8 Hz, 1H), 4.49 (dt, J = 9.0, 2.9 Hz, 1H),
4.45−4.36 (m, 1H), 3.67 (s, 3H), 2.55 (s, 3H), 2.32 (s, 3H); 13C{1H}
NMR (75 MHz, CDCl3) δ 173.0, 163.9, 155.7, 143.8, 139.8, 137.8,
137.7, 136.7, 129.2, 128.8, 127.5, 126.9, 126.5, 55.38, 55.36, 55.1,
51.3, 20.8, 11.4; IR (film) νmax 2952, 2360, 1719, 1600, 1520, 1436,
1418, 1377, 1364, 1325, 1300, 1238, 1196, 1141, 1098, 886, 829, 766,
698, 549, 508 cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]−
471.1173, found 471.1172.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-(3-nitrophenyl)-4-
phenylcyclopent-2-ene-1-carboxylate (3ka). Yellow oil (30 mg,
67% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
8.15 (dt, J = 6.8, 2.3 Hz, 1H), 8.06 (q, J = 1.5 Hz, 1H), 7.56−7.50 (m,
2H), 7.42−7.30 (m, 3H), 7.21 (dq, J = 8.2, 2.5, 1.8 Hz, 2H), 7.12 (t, J
= 2.2 Hz, 1H), 4.68 (dt, J = 8.7, 2.6 Hz, 1H), 4.59 (dt, J = 8.9, 2.7 Hz,
1H), 3.68 (s, 3H), 2.56 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ
171.8, 163.3, 155.8, 148.2, 145.4, 142.9, 139.1, 136.5, 132.9, 129.6,
129.0, 127.8, 126.8, 122.3, 121.9, 55.3, 55.0, 54.9, 51.6, 11.3; IR (film)
νmax 2359, 1719, 1602, 1529, 1437, 1378, 1352, 1304, 1252, 1198,
1142, 1101, 982, 905, 805, 767, 698, 572, 512 cm−1; HRMS (ESI-
−
calcd for C24H21N2O5 417.1456, found 417.1458.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-(naphthalen-2-yl)-4-
phenylcyclopent-2-ene-1-carboxylate (3sa). Yellow oil (38.6 mg,
85% yield). It was purified by flash column chromatography
+
Linear ion trap) m/z [M + H]+ calcd for C23H20N3O7 450.1296,
found 450.1293.
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-(4-nitrophenyl)-4-
phenylcyclopent-2-ene-1-carboxylate (3la). Yellow oil (13.4 mg,
30% yield). It was purified by flash column chromatography
7.86−7.75 (m, 3H), 7.62 (d, J = 1.8 Hz, 1H), 7.53−7.45 (m, 2H),
7.42−7.30 (m, 4H), 7.28−7.21 (m, 2H), 7.11−7.05 (m, 1H). 4.83
(ddd, J = 6.8, 5.0, 2.3 Hz, 1H), 4.57−4.51 (m, 2H), 3.63 (s, 3H), 2.54
(s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 163.9, 155.7,
144.2, 139.7, 138.1, 137.7, 133.1, 132.5, 128.8, 128.6, 127.6, 127.5,
127.4, 126.9, 125.9, 125.5, 124.4, 55.8, 55.3, 55.2, 51.4, 11.4; IR (film)
νmax 2953, 2359, 1719, 1599, 1522, 1436, 1397, 1365, 1300, 1241,
1197, 1141, 1103, 977, 909, 888, 829, 799, 698, 650, 507, 472, 415
cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
8.25−8.12 (m, 2H), 7.45−7.31 (m, 5H), 7.20−7.15 (m, 2H), 7.11 (t,
J = 2.2 Hz, 1H), 4.70 (dt, J = 8.9, 2.7 Hz, 1H), 4.58 (dt, J = 9.0, 2.7
Hz, 1H), 4.41 (t, J = 9.0 Hz, 1H), 3.68 (s, 3H), 2.56 (s, 3H); 13C{1H}
NMR (75 MHz, CDCl3) δ 171.7, 163.3, 155.8, 148.2, 147.0, 145.4,
139.1, 136.5, 129.0, 127.8, 127.7, 126.7, 123.9, 55.4, 55.1, 54.9, 51.6,
11.3; IR (film) νmax 2359, 1720, 1601, 1522, 1436, 1418, 1378, 1365,
1332, 1301, 1238, 1194, 1141, 1101, 884, 830, 789, 763, 698, 564,
446 cm−1; HRMS (ESI-Linear ion trap) m/z [M + Na]+ calcd for
−
C27H21N2O5 453.1456, found 453.1458.
Methyl 5-(Furan-2-yl)-3-(3-methyl-4-nitroisoxazol-5-yl)-4-phe-
nylcyclopent-2-ene-1-carboxylate (3ta). Yellow oil (27.1 mg, 69%
yield). It was purified by flash column chromatography (petroleum
ether/EtOAc = 10:1): 1H NMR (500 MHz, CDCl3) δ 7.25 (m, 4H),
7.12 (m, 2H), 6.20 (dd, J = 3.3, 1.9 Hz, 1H), 6.01 (dd, J = 3.3, 0.8 Hz,
1H), 4.56 (dt, J = 8.4, 2.6 Hz, 1H), 4.49 (t, J = 8.4 Hz, 1H), 4.39 (dt,
J = 8.5, 2.6 Hz, 1H), 3.63 (s, 3H), 2.45 (s, 3H); 13C{1H} NMR (126
MHz, CDCl3) δ 172.0, 162.9, 155.1, 151.6, 143.7, 141.3, 138.9, 134.4,
128.1, 126.9, 126.4, 109.5, 105.9, 53.9, 51.0, 50.8, 48.2, 10.7; IR (film)
νmax 2953, 1721, 1602, 1522, 1436, 1418, 1377, 1365, 1339, 1256,
1211, 1196, 1143, 1099, 1013, 830, 765, 739, 702 cm−1; HRMS (ESI-
+
C23H19N3NaO7 472.1115, found 472.1122.
Methyl 5-(3-Methoxyphenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
4-phenylcyclopent-2-ene-1-carboxylate (3ma). Yellow oil (42.9
mg, 99% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.39−7.29 (m, 3H), 7.24−7.17 (m, 3H), 7.00 (t, J = 2.2 Hz, 1H),
6.82−6.65 (m, 3H), 4.59 (ddd, J = 8.5, 3.2, 2.3 Hz, 1H), 4.48 (dt, J =
8.9, 2.9 Hz, 1H), 4.45−4.35 (m, 1H), 3.77 (s, 3H), 3.67 (s, 3H), 2.55
(s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.9, 163.8, 159.5,
155.7, 144.0, 142.4, 139.7, 137.6, 129.6, 128.8, 127.5, 126.9, 119.0,
112.9, 112.1, 55.7, 55.2, 55.1, 54.8, 51.4, 11.4; IR (film) νmax 2953,
2359, 1719, 1600, 1521, 1455, 1377, 1284, 1197, 1154, 1043, 982,
874, 766, 697, 565, 509, 477 cm−1; HRMS (ESI-Linear ion trap) m/z
−
Linear ion trap) m/z [M − H]− calcd for C21H18N2O6 393.1092,
found 393.1103.
Methyl 4-(4-Fluorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-5-
phenylcyclopent-2-ene-1-carboxylate (3ab). Yellow oil (34.6 mg,
82% yield). It was purified by flash column chromatography
−
[M − H]− calcd for C24H21N2O6 433.1405, found 433.1403.
Methyl 5-(4-Methoxyphenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
4-phenylcyclopent-2-ene-1-carboxylate (3na). Yellow oil (42.5
mg, 98% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.36−7.22 (m, 4H), 7.15 (tt, J = 5.5, 2.4 Hz, 3H), 7.04 (t, J = 8.6 Hz,
2H), 6.97 (t, J = 2.2 Hz, 1H), 4.60 (dt, J = 8.7, 2.7 Hz, 1H), 4.48 (dt,
J = 9.1, 2.7 Hz, 1H), 4.36 (t, J = 8.9 Hz, 1H), 3.66 (s, 3H), 2.55 (s,
3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.5, 163.8, 163.6 (C−F,
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.40−7.29 (m, 3H), 7.23−7.15 (m, 2H), 7.13−7.05 (m, 2H), 6.98 (t,
J = 2.2 Hz, 1H), 6.88−6.80 (m, 2H), 4.58 (ddd, J = 8.5, 3.3, 2.3 Hz,
1H), 4.48 (ddd, J = 9.0, 3.3, 2.2 Hz, 1H), 4.39 (dd, J = 9.1, 8.5 Hz,
1H), 3.79 (s, 3H), 3.67 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR (75
MHz, CDCl3) δ 173.0, 163.9, 158.5, 155.7, 143.7, 139.8, 137.9, 132.8,
128.8, 127.8, 127.5, 126.9, 113.9, 55.4, 55.1, 54.9, 54.8, 51.3, 11.4; IR
(film) νmax 2360, 1719, 1600, 1513, 1436, 1418, 1377, 1365, 1303,
1274, 1177, 1098, 1033, 980, 887, 829, 765, 698, 565, 518 cm−1;
1
1JC−F = 246.9 Hz), 160.3(C−F, JC−F = 246.9 Hz), 155.7, 143.7,
140.6, 137.9, 135.54(C−F, 3JC−F = 3.4 Hz), 135.50(C−F, 3JC−F = 3.4
2
Hz), 128.6, 128.5, 127.2, 126.6, 115.9 (C−F, JC−F = 21.5 Hz),
2
115.6(C−F, JC−F = 21.5 Hz), 55.6, 55.5, 54.3, 51.4, 11.3; IR (film)
νmax 2359, 1720, 1601, 1522, 1436, 1378, 1365, 1274, 1197, 1159,
1142, 1100, 1015, 911, 887, 830, 794, 698, 669, 547, 520 cm−1;
−
−
HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for C24H21N2O6
433.1405, found 433.1404.
HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for C23H18FN2O5
421.1205, found 421.1208.
Methyl 5-(4-Isopropylphenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
4-phenylcyclopent-2-ene-1-carboxylate (3oa). Yellow oil (40.5
mg, 91% yield). It was purified by flash column chromatography
Methyl 4-(2-Chlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-5-
phenylcyclopent-2-ene-1-carboxylate (3ac). Yellow oil (32.8
mg,75% yield). It was purified by flash column chromatography
1
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.38−7.30 (m, 3H), 7.15−7.13 (m, 4H), 7.07 (d, J = 8.2 Hz, 2H),
6.98 (t, J = 2.2 Hz, 1H), 4.62 (dt, J = 8.5, 2.8 Hz, 1H), 4.46 (dt, J =
8.9, 2.8 Hz, 1H), 4.37 (t, J = 8.7 Hz, 1H), 3.67 (s, 3H), 2.94−2.80 (m,
1H), 2.56 (s, 3H), 1.24 (d, J = 6.9 Hz, 6H); 13C{1H} NMR (75 MHz,
CDCl3) δ 173.1, 163.9, 155.7, 147.5, 143.7, 139.9, 138.0, 137.8, 128.7,
7.47−7.40 (m, 1H), 7.36−7.24 (m, 6H), 7.18−7.12 (m, 2H), 6.99 (t,
J = 2.2 Hz, 1H), 5.01 (dt, J = 8.4, 2.6 Hz, 1H), 4.67 (dt, J = 8.3, 2.5
Hz, 1H), 4.35 (t, J = 8.4 Hz, 1H), 3.67 (s, 3H), 2.56 (s, 3H); 13C{1H}
NMR (75 MHz, CDCl3) δ 173.0, 163.7, 155.5, 143.1, 140.7, 138.3,
137.8, 133.0, 129.5, 128.8, 128.5, 128.4, 127.4, 127.1, 126.7, 55.7,
2095
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J. Org. Chem. 2021, 86, 2090−2099

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
54.3, 51.7, 51.4, 11.3; IR (film) νmax 2360, 1720, 1600, 1559, 1476,
1418, 1378, 1333, 1275, 1197, 1101, 1051, 1036, 981, 888, 829, 698,
566, 524, 461 cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]−
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-phenyl-4-(m-tolyl)-
cyclopent-2-ene-1-carboxylate (3ai). Yellow oil (40.1 mg, 96%
yield). It was purified by flash column chromatography (petroleum
ether/EtOAc = 10:1): 1H NMR (300 MHz, CDCl3) δ 7.37−7.15 (m,
7H), 7.01 (dd, J = 7.3, 5.2 Hz, 3H), 4.61 (ddd, J = 8.5, 3.3, 2.3 Hz,
1H), 4.49 (ddd, J = 9.1, 3.4, 2.2 Hz, 1H), 4.41 (dd, J = 9.1, 8.5 Hz,
1H), 3.66 (s, 3H), 2.55 (s, 3H), 2.36 (s, 3H); 13C{1H} NMR (75
MHz, CDCl3) δ 172.9, 163.9, 155.7, 144.3, 140.8, 139.7, 138.5, 137.4,
128.6, 128.5, 128.3, 127.6, 127.1, 126.7, 124.0, 55.8, 55.3, 54.9, 51.3,
21.1, 11.4; IR (film) νmax 2359, 1720, 1601, 1522, 1436, 1418, 1378,
1365, 1332, 1301, 1238, 1194, 1141, 1101, 884, 830, 789, 763, 698,
564, 446 cm−1; HRMS (ESI-Linear ion trap) m/z [M + Na]+ calcd
−
calcd for C23H18ClN2O5 437.0910, found 437.0910.
Methyl 4-(3-Chlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-5-
phenylcyclopent-2-ene-1-carboxylate (3ad). Yellow oil (35.9 mg,
82% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.33−7.25 (m, 5H), 7.23−7.12 (m, 3H), 7.08 (ddd, J = 5.6, 4.3, 1.7
Hz, 1H), 6.96 (t, J = 2.2 Hz, 1H), 4.6 (dt, J = 8.6, 2.7 Hz, 1H), 4.5
(dt, J = 9.0, 2.7 Hz, 1H). 4.37 (t, J = 8.9 Hz, 1H), 3.66 (s, 3H), 2.56
(s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.3, 163.7, 155.8,
143.1, 141.7, 140.4, 138.2, 134.7, 130.1, 128.6, 127.8, 127.3, 127.12,
127.08, 126.6, 125.1, 55.8, 55.2, 54.5, 51.4, 11.3; IR (film) νmax 2360,
1720, 1598, 1521, 1474, 1418, 1332, 1274, 1252, 1142, 1079, 981,
881, 829, 788, 764, 696, 564, 447, 419 cm−1; HRMS (ESI-Linear ion
+
for C24H22N2NaO5 441.1421, found 441.1426.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-phenyl-4-(p-tolyl)-
cyclopent-2-ene-1-carboxylate (3aj). Yellow oil (38.0 mg, 91%
yield). It was purified by flash column chromatography (petroleum
ether/EtOAc = 10:1): 1H NMR (300 MHz, CDCl3) δ 7.33−7.26 (m,
3H), 7.20−7.12 (m, 4H), 7.09 (d, J = 8.1 Hz, 2H), 7.00 (t, J = 2.2 Hz,
1H), 4.60 (ddd, J = 8.6, 3.2, 2.2 Hz, 1H), 4.52−4.44 (m, 1H), 4.44−
4.34 (m, 1H), 3.66 (s, 3H), 2.55 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR
(75 MHz, CDCl3) δ 173.0, 163.9, 155.7, 144.4, 140.8, 137.4, 137.2,
136.7, 129.4, 128.5, 127.1, 126.8, 126.7, 55.8, 55.4, 54.7, 51.3, 20.7,
11.4; IR (film) νmax 2953, 2360, 1720, 1601, 1521, 1436, 1418, 1378,
1365, 1330, 1302, 1239, 1197, 1142, 1100, 887, 829, 764, 698, 669,
564, 514 cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
−
trap) m/z [M − H]− calcd for C23H18ClN2O5 437.0910, found
437.0911.
Methyl 4-(4-Chlorophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-5-
phenylcyclopent-2-ene-1-carboxylate (3ae). Yellow oil (35.4 mg,
81% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.35−7.27 (m, 5H), 7.14 (d, J = 8.4 Hz, 4H), 6.96 (dd, J = 4.9, 2.7
Hz, 1H), 4.6 (dt, J = 8.6, 2.7 Hz, 1H), 4.5 (dt, J = 9.0, 2.8 Hz, 1H),
4.36 (t, J = 8.9 Hz, 1H), 3.66 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR
(75 MHz, CDCl3) δ 172.4, 163.7, 155.7, 143.3, 140.5, 138.2, 138.1,
133.5, 129.0, 128.6, 128.3, 127.2, 126.6, 55.7, 55.3, 54.4, 51.4, 11.3; IR
(film) νmax 2360, 1719, 1602, 1522, 1492, 1456, 1418, 1378, 1275,
1256, 1197, 1142, 1101, 1015, 829, 764, 750, 698, 669, 511 cm−1;
HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
−
C24H21N2O5 417.1456, found 417.1456.
Methyl 4-(2-Methoxyphenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
5-phenylcyclopent-2-ene-1-carboxylate (3ak). Yellow oil (42.9
mg, 99% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
−
7.32−7.23 (m, 5H), 7.18−7.11 (m, 2H), 7.08 (t, J = 2.2 Hz, 1H),
7.00 (td, J = 7.5, 0.9 Hz, 1H), 6.81 (dd, J = 6.4, 2.5 Hz, 1H), 4.81 (dt,
J = 8.0, 2.5 Hz, 1H), 4.61 (dt, J = 7.8, 2.3 Hz, 1H), 4.33 (t, J = 7.9 Hz,
1H), 3.67 (s, 3H), 3.60 (s, 3H), 2.58 (s, 3H); 13C{1H} NMR (75
MHz, CDCl3) δ 174.8, 163.9, 156.4, 155.3, 144.1, 141.4, 137.4, 128.6,
128.4, 127.4, 126.9, 126.8, 120.6, 110.1, 55.8, 54.6, 53.5, 51.3, 49.6,
11.3; IR (film) νmax 2360, 1719, 1599, 1519, 1493, 1437, 1378, 1333,
1244, 1194, 1142, 1097, 1028, 887, 829, 756, 698, 669, 564, 485
cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
C23H18ClN2O5 437.0910, found 437.0912.
Methyl 4-(4-Bromophenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-5-
phenylcyclopent-2-ene-1-carboxylate (3af). Yellow oil (39.5 mg,
82% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.51−7.45 (m, 2H), 7.32−7.26 (m, 3H), 7.11 (ddd, J = 8.4, 7.3, 1.8
Hz, 4H), 6.96 (t, J = 2.2 Hz, 1H), 4.6 (dt, J = 8.6, 2.7 Hz, 1H), 4.5
(dt, J = 9.0, 2.8 Hz, 1H), 4.36 (t, J = 8.8 Hz, 1H), 3.66 (s, 3H), 2.55
(s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.4, 163.7, 155.7,
143.2, 140.5, 138.7, 138.1, 131.9, 128.6, 127.2, 126.6, 121.5, 55.8,
55.2, 54.4, 51.4, 11.3; IR (film) νmax 2953, 2360, 1720, 1601, 1522,
1456, 1378, 1365, 1274, 1197, 1100, 1011, 981, 887, 764, 698, 556,
511 cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for
−
C24H21N2O6 433.1405, found 433.1404.
Methyl 4-(3-Methoxyphenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
5-phenylcyclopent-2-ene-1-carboxylate (3al). Yellow oil (42.9 mg,
99% yield): 1H NMR (300 MHz, CDCl3) δ 7.28 (td, J = 8.0, 4.1 Hz,
4H), 7.20−7.11 (m, 2H), 7.00 (t, J = 2.1 Hz, 1H), 6.87−6.69 (m,
3H), 4.60 (ddd, J = 8.4, 3.4, 2.3 Hz, 1H), 4.48 (ddd, J = 9.0, 3.4, 2.1
Hz, 1H), 4.44−4.36 (m, 1H), 3.80 (s, 3H), 3.66 (s, 3H), 2.55 (s,
3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 163.8, 159.8, 155.7,
144.0, 141.3, 140.7, 137.6, 129.8, 128.5, 127.1, 126.7, 119.2, 113.0,
112.5, 55.8, 55.1, 55.0, 54.9, 51.4, 11.4; IR (film) νmax 2953, 2359,
1720, 1600, 1521, 1488, 1378, 1365, 1323, 1287, 1243, 1194, 1101,
1042, 877, 829, 781, 697, 566, 467 cm−1; HRMS (ESI-Linear ion
−
C23H18BrN2O5 481.0405, found 481.0408.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-4-(4-nitrophenyl)-5-
phenylcyclopent-2-ene-1-carboxylate (3ag). Yellow oil (23.3 mg,
52% yield). It was purified by flash column chromatography
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
8.22 (d, J = 8.7 Hz, 2H), 7.44−7.35 (m, 2H), 7.33−7.27 (m, 3H),
7.18−7.09 (m, 2H), 6.97 (t, J = 2.2 Hz, 1H), 4.7 (dt, J = 8.6, 2.6 Hz,
1H), 4.60 (dt, J = 9.0, 2.6 Hz, 1H), 4.39 (t, J = 8.9 Hz, 1H), 3.67 (s,
3H), 2.55 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 171.8, 163.5,
155.8, 147.3, 147.0, 141.9, 140.10 139.0, 128.7, 127.9, 127.4, 126.5,
124.1, 124.0, 55.7, 55.0, 54.5, 51.5, 11.3; IR (film) νmax 2368, 1732,
1611, 1542, 1423, 1454, 1365, 1331, 1308, 1267, 1143, 1124, 1156,
812, 800, 734, 712, 634, 532, 488 cm−1; HRMS (ESI-Linear ion trap)
−
trap) m/z [M − H]− calcd for C24H21N2O6 433.1405, found
433.1403.
Methyl 4-(4-Methoxyphenyl)-3-(3-methyl-4-nitroisoxazol-5-yl)-
5-phenylcyclopent-2-ene-1-carboxylate (3am). Yellow oil (37.3
mg, 86% yield). It was purified by flash column chromatography
1
−
m/z [M − H]− calcd for C23H18N3O7 448.1223, found 448.1153.
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
7.33−7.26 (m, 3H), 7.16 (dd, J = 8.0, 1.5 Hz, 2H), 7.14−7.09 (m,
2H), 6.98 (t, J = 2.2 Hz, 1H), 6.91−6.83 (m, 2H), 4.60 (dt, J = 8.6,
2.7 Hz, 1H), 4.44−4.41 (m, 1H), 4.41−4.31 (m, 1H), 3.80 (s, 3H),
3.65 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 173.0,
163.9, 158.9, 155.7, 144.5, 140.8, 137.3, 131.8, 128.5, 128.0, 127.1,
126.7, 114.2, 55.7, 55.6, 54.9, 54.4, 51.3, 11.4; IR (film) νmax 2360,
1719, 1602, 1514, 1378, 1365, 1274, 1251, 1178, 1101, 1033, 830,
764, 749, 699 cm−1; HRMS (ESI-Linear ion trap) m/z [M − H]−
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-phenyl-4-(o-tolyl)-
cyclopent-2-ene-1-carboxylate (3ah). Yellow oil (27.1 mg, 65%
yield). It was purified by flash column chromatography (petroleum
ether/EtOAc = 10:1): 1H NMR (300 MHz, CDCl3) δ 7.33−7.23 (m,
5H), 7.21−7.10 (m, 4H), 6.98 (t, J = 2.2 Hz, 1H), 4.8 (dt, J = 8.7, 2.6
Hz, 1H), 4.58 (dt, J = 8.7, 2.6 Hz, 1H), 4.43 (t, J = 8.7 Hz, 1H), 3.66
(s, 3H), 2.54 (s, 3H), 2.10 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3)
δ 173.2, 163.8, 155.6, 144.8, 140.8, 138.0, 137.3, 135.0, 130.5, 128.5,
127.4, 127.2, 127.1, 126.7, 126.6, 56.0, 54.7, 51.3, 51.2, 19.0, 11.3; IR
(film) νmax 2360, 1719, 1601, 1559, 1495, 1456, 1418, 1378, 1274,
1195, 1155, 1112, 1097, 886, 758, 698, 669, 565, 523, 459 cm−1;
−
calcd for C24H21N2O6 433.1405, found 433.1404.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-4-(naphthalen-2-yl)-5-
phenylcyclopent-2-ene-1-carboxylate (3an). Yellow solid (39.4
mg, 87% yield). It was purified by flash column chromatography
(petroleum ether/EtOAc = 10:1): mp = 134−137 °C; 1H NMR (300
−
HRMS (ESI-Linear ion trap) m/z [M − H]− calcd for C24H22N2O5
417.1456, found 417.1458.
2096
https://dx.doi.org/10.1021/acs.joc.0c01948
J. Org. Chem. 2021, 86, 2090−2099

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
MHz, CDCl3) δ 7.90−7.78 (m, 3H), 7.65 (s, 1H), 7.55−7.47 (m,
2H), 7.37−7.30 (m, 3H), 7.29 (d, J = 2.4 Hz, 1H), 7.24−7.17 (m,
2H), 7.10 (t, J = 2.1 Hz, 1H), 4.68 (ddt, J = 14.9, 8.9, 3.0 Hz, 2H),
4.54 (t, J = 8.8 Hz, 1H), 3.69 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR
(75 MHz, CDCl3) δ 172.8, 163.9, 155.7, 144.1, 140.7, 137.7, 137.0,
133.1, 132.5, 128.8, 128.6, 127.4, 127.23, 127.17, 126.7, 126.2, 125.9,
125.8, 124.7, 56.0, 55.2, 55.1, 51.4, 11.4; IR (film) νmax 2967, 2343,
1733, 1578, 1512, 1423, 1388, 1354, 1306, 1245, 1188, 1132, 1112,
967, 912, 875, 832, 797, 688, 634, 511, 456, 413 cm−1; HRMS (ESI-
MHz, CDCl3) δ 166.9, 165.5, 155.1, 150.3, 133.8, 131.1, 130.9, 129.8,
128.7, 127.9, 127.4, 127.3, 126.8, 70.7, 61.6, 56.8, 53.1, 11.0; IR (film)
νmax 3028, 2352, 1723, 1612, 1487, 1423, 1345, 1311, 1259, 1123,
1103, 1091, 1056, 1023, 956, 768, 697, 641, 534, 478 cm−1; HRMS
+
(ESI-Linear ion trap) m/z [M + Na]+ calcd for C23H18Br2N2NaO5
582.9475, found 582.9479.
ASSOCIATED CONTENT
* Supporting Information
■
sı
−
Linear ion trap) m/z [M − H]− calcd for C27H21N2O5 453.1456,
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01948.
found 453.1456.
Methyl 3-(3-Methyl-4-nitroisoxazol-5-yl)-5-phenyl-4-(thiophen-
3-yl)cyclopent-2-ene-1-carboxylate (3ao). Yellow oil (36.9 mg,
90% yield). It was purified by flash column chromatography
1H NMR and 13C{1H} NMR spectra and single-crystal
data of 3an and 5 (PDF)
1
(petroleum ether/EtOAc = 10:1): H NMR (300 MHz, CDCl3) δ
Accession Codes
7.38−7.33 (m, 1H), 7.31 (t, J = 2.0 Hz, 1H), 7.29−7.26 (m, 2H),
7.15 (t, J = 2.0 Hz, 1H), 7.13 (t, J = 1.5 Hz, 1H), 7.10−7.06 (m, 1H),
7.02 (t, J = 2.0 Hz, 1H), 6.98 (dd, J = 5.0, 1.3 Hz, 1H), 4.65−4.53 (m,
2H), 4.51−4.37 (m, 1H), 3.65 (s, 3H), 2.69−2.63 (m, 1H), 2.56 (s,
3H); 13C{1H} NMR (75 MHz, CDCl3) δ 173.0, 163.8, 155.7, 143.7,
140.7, 140.1, 137.1, 128.5, 127.1, 126.8, 126.7, 125.9, 121.2, 55.7,
54.1, 51.4, 50.3, 11.3; IR (film) νmax 2953, 2360, 1719, 1600, 1520,
1496, 1436, 1378, 1364, 1332, 1302, 1244, 1194, 1141, 1099, 829,
785, 763, 698, 651, 565 cm−1; HRMS (ESI-Linear ion trap) m/z [M
− H]− calcd for C21H18N2O5S− 410.0936, found 409.0863.
Methyl 4-(Furan-3-yl)-3-(3-methyl-4-nitroisoxazol-5-yl)-5-phe-
nylcyclopent-2-ene-1-carboxylate (3ap). Yellow oil (25.5 mg, 65%
yield). It was purified by flash column chromatography (petroleum
ether/EtOAc = 10:1): 1H NMR (300 MHz, CDCl3) δ 7.43 (t, J = 1.7
Hz, 1H), 7.35−7.31 (m, 2H), 7.30−7.27 (m, 3H), 7.17−7.10 (m,
2H), 6.96 (t, J = 1.8 Hz, 1H), 6.35 (dd, J = 1.8, 0.9 Hz, 1H), 4.61−
4.53 (m, 1H), 4.45−4.40 (m, 2H), 3.66 (s, 3H), 2.58 (s, 3H);
13C{1H} NMR (75 MHz, CDCl3) δ 173.0, 163.8, 155.7, 143.8, 143.4,
CCDC 1969108−1969109 contain the supplementary crys-
tallographic 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
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Yuxia Hou − Department of Chemistry, China Agricultural
University, Beijing 100193, China; Email: houyuxia@
cau.edu.cn
Hongchao Guo − Department of Chemistry, China
Agricultural University, Beijing 100193, China;
orcid.org/0000-0002-7356-4283; Email: hchguo@
cau.edu.cn
140.7, 138.7, 137.1, 128.5, 127.1, 126.7, 123.9, 108.9, 55.7, 53.6, 51.4,
45.9, 11.3; IR (film) νmax 2953, 2359, 1720, 1602, 1522, 1455, 1378,
1271, 1238, 1142, 1103, 1026, 982, 874, 830, 785, 698, 660, 601, 568
cm−1; HRMS (ESI-Linear ion trap) m/z [M + H]+ calcd for
Authors
Jianning Liao − Department of Chemistry, China Agricultural
University, Beijing 100193, China
Jipan Dong − Department of Chemistry, China Agricultural
University, Beijing 100193, China
Jiaqing Xu − Department of Chemistry, China Agricultural
University, Beijing 100193, China
+
C21H19N2O6 395.1238, found 395.1243.
Methyl 4-Ethyl-3-(3-methyl-4-nitroisoxazol-5-yl)-5-phenylcyclo-
pent-2-ene-1-carboxylate (3aq). Yellow oil (28.5 mg, 80% yield). It
was purified by flash column chromatography (petroleum ether/
1
EtOAc = 10:1): H NMR (400 MHz, CDCl3) δ 7.27 (m, 3H), 7.09
(m, 2H), 6.97 (s, 1H), 4.48 (dt, J = 7.5, 2.2 Hz, 1H), 4.07 (t, J = 7.5
Hz, 1H), 3.61 (s, 3H), 3.19 (qt, J = 7.2, 2.3 Hz, 1H), 2.56 (s, 3H),
1.67 (td, J = 7.3, 1.2 Hz, 2H), 0.98(t, J = 7.4 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 174.8, 164.2, 155.8, 145.3, 141.8, 136.3, 128.6,
127.1, 126.8, 56.0, 52.5, 51.6, 51.4, 27.1, 11.6, 11.5; IR (film) νmax
2962, 1720, 1599, 1520, 1495, 1455, 1436, 1418, 1377, 1365, 1248,
1196, 1143, 1119, 1089, 829, 751, 701 cm−1; HRMS (ESI-Linear ion
Wei Wang − College of Public Health, Zhengzhou University,
Zhengzhou 450001, China
Yongjun Wu − College of Public Health, Zhengzhou
University, Zhengzhou 450001, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01948
+
trap) m/z [M - H]+ calcd for C19H20N2O5 355.1299, found
355.1307.
Notes
Characterization Data for the Products of Further Trans-
formations. Methyl 3-(4-Amino-3-methylisoxazol-5-yl)-4,5-diphe-
nylcyclopent-2-ene-1-carboxylate (4). Yellow oil (16.8 mg, 45%
yield). It was purified by flash column chromatography (petroleum
The authors declare no competing financial interest.
The paper is associated with the “The New Golden Age of
Organophosphorus Chemistry“ collection, published in the
November 20, 2020, issue of J. Org. Chem.
1
ether/EtOAc = 5:1): H NMR (300 MHz, CDCl3) δ 7.36−7.28 (m,
5H), 7.27−7.17 (m, 5H), 7.10−7.03 (m, 1H), 4.49 (d, J = 9.4 Hz,
2H), 3.65 (s, 3H), 3.34 (t, J = 9.4 Hz, 1H), 2.15 (s, 3H), 1.86 (s, 2H);
13C{1H} NMR (75 MHz, CDCl3) δ 164.3, 155.0, 154.3, 145.0, 142.5,
141.4, 137.9, 128.6, 128.4, 127.02, 126.97, 126.8, 126.6, 122.1, 56.3,
55.1, 53.8, 51.2, 8.9; IR (film) νmax 3029, 2359, 1717, 1602, 1495,
1436, 1354, 1300, 1244, 1197, 1149, 1100, 1077, 1031, 912, 764, 698,
642, 528, 489 cm−1; HRMS (ESI-Linear ion trap) m/z [M + H]+
ACKNOWLEDGMENTS
■
This work was supported by the Natural Science Foundation
of China (Nos. 21572264, 21871293 and 22071264) and
Chinese Universities Scientific Fund (Nos. 2018TC052,
2018TC055 and 2019TC085).
+
calcd for C23H23N2O3 375.1703, found 375.1709.
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(s, 1H), 5.67 (s, 1H), 3.91 (s, 3H), 2.43 (s, 3H); 13C{1H} NMR (75
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