Electrochemical Oxidative Halogenation of N-Aryl Alkynamides for the Synthesis of Spiro[4.5]trienones

Article abstract of DOI:10.1021/acs.joc.0c02429

We developed a green method for the synthesis of spiro[4.5]trienones through an electrochemical oxidative halocyclization with N-aryl alkynamides. This reaction was conducted under metal-catalyst- and exogenous-oxidant-free conditions at room temperature.

Full text of DOI:10.1021/acs.joc.0c02429

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Electrochemical Oxidative Halogenation of N‑Aryl Alkynamides for
the Synthesis of Spiro[4.5]trienones
Ke Yu, Xianqiang Kong, Jiajun Yang, Guodong Li, Bo Xu,* and Qianjin Chen*
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ABSTRACT: We developed a green method for the synthesis of spiro[4.5]trienones through an electrochemical oxidative
halocyclization with N-aryl alkynamides. This reaction was conducted under metal-catalyst- and exogenous-oxidant-free conditions
at room temperature. Using readily available LiCl, LiBr, and LiI as the halogen source, a variety of dearomative halo-spirocyclization
products were obtained in good to excellent yields with a broad scope and functional group tolerance.
Scheme 1. Synthesis of Spiro[4.5]trienones
INTRODUCTION
■
Spirocyclic compounds are important structural motifs widely
existing in many natural products and bioactive molecules.1
Owing to their unique structure, they play a pivotal role in
organic synthesis.2 Consequently, great efforts have been
devoted to the construction of a spirocyclic framework.3 For
example, methods including dearomatization of phenol
derivatives,4 electrophilic ipso-cyclization,5 radical dearomati-
zation tandem reaction,6 etc.,7 have been established for the
synthesis of spiro[4.5]trienones. Moreover, the introduction of
halogen atoms into the framework of organic compounds can
greatly improve the pharmacological activities8 and act as a
versatile intermediate for further ample functionalization.9
Over the past decade, a variety of halogenated spiro[4.5]-
trienones have been constructed via alkymate or alkyamide
intramolecular ipso-cyclization and coupling with iodine
monochloride (ICl),10 I2,10a,b CuX (X = I, Br, SCN), and
electrophilic fluoride reagents,11 NXS,12 or hypervalent
iodine(III) reagent bis(trifluoroacetate) (PIFA)13 (Scheme
1a). Despite the remarkable achievement, these strategies
generally suffer from disadvantages such as exogenous
additives,13 stoichiometric oxidants,14 and harsh reaction
conditions.10c,11,12,13b Thus, the development of a green and
environmentally friendly approach under mild conditions for
the synthesis of halogenated spiro[4.5]trienones is still strongly
desirable.
Received: October 13, 2020
Electrochemistry has become a routine technique in organic
synthesis due to its convenience and environmental sustain-
ability as well as controllability simply by potential, current, or
total charge.15 Remarkable progress has been made to prompt
the investigations of reactions for C−C,16 C−O,17 C−N,18 and
C−X19 bond formation. In 2020, Guo’s group developed a
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A

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radical-initiated dearomative selenylative spirocyclization of
alkynes through a direct constant current electrolysis20
(Scheme 1b). Inspired by this and other electrochemical
dearomatization studies,21 we here for the first time report a
clean halogenation through an electrochemical dearomative
spirocyclization for the synthesis of spiro[4.5]trienones from
readily available halide salts (LiX, X = Cl, Br, I). The reaction
was conducted at room temperature without metal catalysts or
exogenous oxidants.
oxygen atom of the ketone group formed by dearomative
spirocyclization was derived from the methoxy group of 1a. No
desired product was observed without the electrolyte or
electricity (entries 16 and 17). In the end, we explored the
electrode materials for this electrochemical dearomatization
reaction. Pt (+)/Pt (−) and C (+)/Pt (−) electrodes both led
to decreased yields, while the Pt (+)/C (−) combination gave
a very similar yield (Table S1 in the Supporting Information).
With the optimized conditions in hand, we next investigated
the substrate scope of iodinated and brominated spiro[4,5]-
trienones (Scheme 2). First, the substitutes on the nitrogen
such as methyl, ethyl, benzyl, and isopropyl groups all showed
good tolerance with excellent yields of corresponding products
ranging from 75 to 92% (2a−d, 3a−d). It was pleasing to find
that the N-allyl group also applies to this reaction, and the
iodinated and brominated products could be obtained with
yields of 56 and 70%, respectively (2e, 3e). Sterically hindered
electron-withdrawing groups such as t-butyloxycarbonyl (Boc)
and benzyloxycarbonyl (Cbz) could take part in this
transformation with moderate yields (2f−g, 3f−g). Substrates
bearing ortho-methyl and two meta-methoxy groups on the N-
aryl ring also proceeded smoothly to give the desired products
(71−92%, 2h−i, 3h−i). Aryl substituents at the terminal
alkynes bearing halide (p-F, p-Cl, p-Br) groups were
successfully coupled with 1a with the yields of 70−90% (2j−
l, 3j−l). When strong electron-withdrawing groups (p-CF3, p-
CN) were installed, iodinated products were achieved in
moderate yields (2m−n), and brominated products gave high
yields (3m−n). In addition, methyl groups at different
positions of the aryl ring afforded a decreasing yield from
para to meta and to ortho due to the steric effect (2o−r, 3o−
r). Notably, heteroaromatic groups such as furan and
thiophene were also suitable for this reaction (2s−t, 3s−t).
Compared with iodination and bromination, there are very
few examples reporting the chlorination of spirocyclization in
the literature.10 We here further evaluated the scope and
generality of the chlorination of spiro[4,5]trienones (Scheme
3). Gratifyingly, when N was protected by electron-donating
groups or sterically hindered electron-withdrawing groups, the
corresponding products (4a−g) were obtained in moderate to
excellent yields (52−91%). However, the substrate of N-allyl
only gave a trace amount of the desired product (4e). It is
interesting to find that the substrate with ortho-methyl groups
on the aryl ring could get the desired chlorination product in
51% yield (4h), whereas substrates bearing two meta-methoxy
groups only afforded a chlorinated quinolinone product (4i′).
We speculate that this is due to the increased nucleophilicity of
the aromatic ring. Moreover, the aryl substitutes at the terminal
C−C triple bond showed good performance. Substrates with
electron-withdrawing (p-Br, p-CN) and -donating (p-methoxy,
p-methyl, o-methyl) groups were all tolerated under standard
reaction conditions (4j−n). Unfortunately, no desired product
was detected for the heterocycle furan group at the alkyne
(4o). Finally, the N-H-substituted substrate failed to afford the
desired halogenated products.
RESULTS AND DISCUSSION
■
Initially, we chose N-(4-methoxyphenyl)-N-methyl-3-phenyl-
propiolamide (1a) as the model substrate to explore the
reaction conditions in an undivided cell (Table 1). After
a
Table 1. Optimization of Reaction Conditions
a
b
entry
variation from standard conditions
yield (%)
a
1
2
3
4
5
6
none
86
52
45
78
74
70
CH3CN/H2O = 9:1
CH3CN/H2O = 5:1
CH3CN/DCE = 9:1
TBAI instead of LiI
KI instead of LiI
c
7
8
9
LiBr
LiCl
87
82
41
d
ce
,
KBr instead of LiBr
5 mA instead of 10 mA
15 mA instead of 10 mA
n-Bu4NPF6 instead of LiClO4
n-Bu4NClO4 instead of LiClO4
n-Bu4NBF4 instead of LiClO4
N2 atmosphere
f
10
11
12
13
14
15
16
17
NR
84
f
NR
NR
NR
f
d
76
d
no electrolyte
no electric current
NR
NR
d
a
Reaction conditions: graphite anode and cathode (52.5 mm × 8.0
mm × 1.5 mm), constant current = 10 mA, 1a (0.125 mmol), LiI
(0.25 mmol), LiClO4 (0.2 M), CH3CN (4 mL), room temperature,
undivided cell. Isolated yield. Product 3a. Product 4a. Constant
current = 8 mA. NR = no reaction.
b
c
d
e
f
optimizations, we found that 86% isolated yield of desired
product 2a could be obtained at 10 mA constant current in
CH3CN using graphite electrodes as both the cathode and
anode at room temperature (entry 1). A mixture of CH3CN
with H2O or dichloroethane (DCE) gave lower yields (entries
2−4). Alternative iodine sources such as tetrabutylammonium
iodide (TBAI) and potassium iodide (KI) were found less
efficient (entries 5 and 6). Furthermore, LiBr or LiCl was
found to be a good bromine or chloride source with yields as
high as 87 or 82%. However, KBr afforded an obviously
decreased yield (entries 7−9). Decreasing current to 5 mA led
to no reaction, while increasing to 15 mA resulted in a quite
close conversion (entries 10 and 11). Subsequently, replacing
the electrolyte of LiClO4 with n-Bu4NPF6, n-Bu4NClO4, or n-
Bu4NBF4 afforded no reaction (entries 12−14). The reaction
under a N2 atmosphere displayed a lower yield relative to the
air atmosphere (entry 15). This result indicated that the
We continued to investigate the spirocyclization reaction of
alkynamides with diphenyl selenium (Scheme 4). Both
electron-withdrawing and electron-donating groups performed
well under standard conditions (5a−e, 50−99%). Specifically,
N-H-substituted alkynamides and the terminal terminal alkyne
gave yields of 52 and 60%, respectively. Very recently, Guo and
co-workers20 reported the preparation of selenylated spiro-
[4,5]trienones using electrochemistry in a mixture of solvents
B
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a b c
, ,
Scheme 2. Substrate Scope of Electrochemical Synthesis of Iodinated and Brominated Spiro[4,5]trienones
a
Reaction conditions: graphite anode and cathode (52.5 mm × 8.0 mm × 1.5 mm), constant current = 10 mA, 1a (0.125 mmol), LiI or LiBr (0.25
b
mmol), LiClO4 (0.2 M), CH3CN (4 mL), room temperature, undivided cell, 2 h. Pt anode (52.5 mm × 8.0 mm × 1.5 mm), graphite cathode
(52.5 mm × 8.0 mm × 1.5 mm). 12 mA, 2 h.
c
CH3CN/HFIP. Therefore, we here only present a few
examples. Notably, diphenyldisulfane was also tried; however,
no desired product was obtained. Similar results have been
reported by Guo.20a
To evaluate the potential applicability of this electrochemical
oxidative halogenation protocol, a scale-up reaction was
conducted. As shown in Scheme 5, 4.0 mmol (1.06 g) of 1a
was electrolyzed at 40 mA for 10 h, and the corresponding
brominated product could be obtained with a yield of 80%
(1.05 g), indicating the potential industrial application
prospects of this method. Subsequently, we performed
derivatization experiments of product 2a. The Sonogashira
and Suzuki coupling reaction proceeded smoothly with desired
products 6a and 6b in excellent yields (Scheme S1 in the
Supporting Information).
To shed light on the reaction mechanism of this method, a
series of control experiments were carried out. When N-
methyl-N,3-diphenylpropiolamide 1b and N-(4-fluorophenyl)-
N-methyl-3-phenylpropiolamide 1c were chosen to react with
LiI, no reactions occurred under standard conditions. It should
be noted that coupling of alkynamides 1a with LiI gave a yield
of 86% under the same condition (Table 1, entry 1). The
above observation indicated that the methoxy group
contributed to the formation of ketones. Furthermore, in the
radical trapping experiments, by the addition of 3 equiv of
(2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO) or bu-
C
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a
Scheme 3. Substrate Scope of Electrochemical Synthesis of Chlorinated Spiro[4,5]trienones
a
Reaction conditions: graphite anode and cathode (52.5 mm × 8.0 mm × 1.5 mm), constant current = 8 mA, 1a (0.125 mmol), LiCl (0.25 mmol),
LiClO4 (0.2 M), CH3CN (4 mL), room temperature, undivided cell, 2 h.
tylated hydroxytoluene (BHT) into the reaction system, the
yields of iodinated and brominated products sharply decreased
and the chlorinated product was completely suppressed
(Schemes 5(b)2−3), suggesting that radical intermediates are
probably involved in this process.
G by intramolecular ispo-spirocyclization. The intermediate G
underwent the same process as path I to form 2a.
In summary, we have developed an environment-friendly
and operationally simple electrocatalytic protocol for the
synthesis of halogenated and selenylated spiro[4.5]trienones
under metal-catalyst- and oxidant-free conditions. With cheap
graphite electrodes and lithium salts, we can get a series of
dearomatization products. The gram-scale experiment shows
that this method has prospective applications.
Cyclic voltammograms of related compounds were inves-
tigated on the glassy carbon electrode. As shown in Figure 1,
LiI undergoes two oxidation processes at 0.44 and 0.76 V,
while an oxidation peak for reactant 1a is observed at 1.48 V.
Based on the above experiments and cyclic voltammetric
results, a plausible mechanism was proposed in Scheme 6.
First, the iodine anion lost electrons at the anode and became
iodine cation B. Then, iodine cation B reacted with 1a to form
cyclic iodonium C. Subsequently, C underwent thermody-
namically controlled ispo-electrophilic spirocyclization onto the
aromatic ring to give oxonium ion D, which was followed by
demethylation to the final product 2a. On the other hand,
iodine radical E might be produced by the iodine anion
oxidation in path II. After combining with 1a, vinyl radical
species F could be generated and converted into intermediate
EXPERIMENTAL SECTION
■
General Methods. Commercial reagents and solvents were
purchased and used without further purification. 1H NMR (600
MHz) and 13C NMR (150 MHz) spectra were recorded on a Bruker
NMR apparatus. The chemical shifts are reported in δ (ppm) values
(1H and 13C NMR relative to CHCl3, δ 7.26 ppm for 1H NMR and δ
77.0 ppm for 13C NMR). Alternatively, 1H NMR chemical shifts were
referenced to a tetramethylsilane signal (0 ppm). Multiplicities are
indicated by s (singlet), d (doublet), t (triplet), q (quartet), and m
(multiplet). Coupling constants (J) are reported in hertz (Hz). High
D
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a
Scheme 4. Substrate Scope of Electrochemical Synthesis of Selenylated Spiro[4,5]trienones
a
Reaction conditions: graphite anode and cathode (52.5 mm × 8.0 mm × 1.5 mm), constant current = 10 mA, 1 (0.125 mmol), PhSeSePh (0.25
mmol), LiClO4 (0.2 M), CH3CN (4 mL), room temperature, undivided cell, 1 h.
a
Scheme 5. Gram-Scale Reaction and Control Experiments
a
Reaction conditions: carbon felt as the anode and cathode (4.0 cm × 4.0 cm), constant current = 40 mA, 1a (4.0 mmol), LiBr (10.0 mmol),
LiClO4 (0.1 M), CH3CN (80 mL), room temperature, undivided cell, 10 h.
resolution mass spectrometry (HRMS) was performed on a Thermo
Scientific Q Exactive HF Orbitrap-FTMS apparatus.
extracted with DCM. The organic layer was washed with brine and
dried over Na2SO4. The obtained filtrate was concentrated under
vacuum. The residue was purified by flash column chromatography on
silica gel (PE/EtOAc = 5:1) to afford the desired N,3-
diphenylpropiolamide, which was used directly in the next step.
Under a N2 atmosphere, to a solution of N,3-diphenylpropiolamide
products (3.0 mmol) in anhydrous tetrahydrofuran (THF) or DCM
(20 mL) was added NaH (60%, 4.5 mmol, 1.5 equiv, 180 mg) at 0
°C. After the mixture was stirred for 10 min at the same temperature,
the corresponding halogenated hydrocarbon or acid chloride was
General Procedure for the Synthesis of N-Aryl Alkyna-
mides.22 To an ice-bath-cooled solution of the relative aniline (5.0
mmol, 1.0 equiv) in dichloromethane (DCM; 30 mL) was added 3-
phenylpropiolic acid (5.5 mmol, 1.1 equiv), and a mixture of N,N′-
dicyclohexylcarbodiimide (DCC; 7.5 mmol, 1.5 equiv, 1.5 g) and 4-
dimethyl- aminopyridine (DMAP; 0.5 mmol, 0.1 equiv, 60 mg) in
DCM (15 mL) was added dropwise. Then, the mixture was stirred at
room temperature overnight. The reaction was diluted with water and
E
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Na2SO4, and concentrated under vacuum. The residue was purified by
column chromatography on silica gel.
Procedures for the Gram-Scale Reaction. In an oven-dried
undivided bottle (100 mL) equipped with a stir bar, 1a (4 mmol),
LiBr (10 mmol), LiClO4 (0.1 M), and CH3CN (70 mL) were added.
The bottle was equipped with a carbon felt as the anode and cathode
(4.0 cm × 4.0 cm × 1 mm, approximately 3.0 cm immersed in the
solvent). The reaction mixture was stirred at room temperature with a
constant current of 40 mA for 10 h. When the reaction was finished,
the solvent was removed under vacuum. The residue was then
extracted with DCM and H2O, dried over Na2SO4, and concentrated.
The pure product was obtained by flash column chromatography on
silica gel.
3-Iodo-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2a).13a Eluent: petroleum ether/ethyl acetate (3:1). Yellow
solid, 86% yield (41 mg); 1H NMR (600 MHz, CDCl3) δ 7.40 (dt, J =
14.8, 7.1 Hz, 3H), 7.30 (d, J = 7.3 Hz, 2H), 6.53 (d, J = 9.8 Hz, 2H),
6.48 (d, J = 10.2 Hz, 2H), 2.97 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 183.7, 167.4, 157.9, 144.1, 133.3, 131.9, 130.1, 128.7, 127.7,
98.2, 70.4, 27.0.
Figure 1. Cyclic voltammograms of a 0.1 M LiClO4 solution in
CH3CN at room temperature; a 3 mm diameter glassy carbon
electrode was used as the working electrode and Ag/AgCl and a
carbon rod were used as the reference and counter electrode,
respectively. Scan rate: 0.1 V/s. (a) Black line: background, 0.1 M
LiClO4; (b) red line: 0.1 M LiClO4 + 10 mM LiI; (c) blue line: 0.1 M
LiClO4 + 10 mM 1a.
3-Iodo-1-ethyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione
(2b).6e Eluent: petroleum ether/ethyl acetate (3:1). Yellow solid, 82%
1
yield (40 mg); H NMR (600 MHz, CDCl3) δ 7.44−7.34 (m, 3H),
added and the mixture was stirred for 15 min at 0 °C and then
warmed up to room temperature. The reaction was diluted with water
and extracted with EtOAc. The organic layer was washed with brine,
dried over Na2SO4, filtered, and concentrated. The residue was
purified by column chromatography on silica gel.
7.29−7.25 (m, 2H), 6.57 (d, J = 10.1 Hz, 2H), 6.44 (d, J = 10.1 Hz,
2H), 3.42 (q, J = 7.2 Hz, 2H), 1.23 (t, J = 7.2 Hz, 3H). 13C{1H}
NMR (150 MHz, CDCl3) δ 184.0, 167.3, 157.8, 144.4, 132.8, 131.9,
130.0, 128.7, 127.8, 98.9, 70.8, 37.0, 15.2.
1-Benzyl-3-iodo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2c).11 Eluent: petroleum ether/ethyl acetate (4:1). Yellow
solid, 75% yield (43 mg); 1H NMR (600 MHz, CDCl3) δ 7.40 (t, J =
7.4 Hz, 1H), 7.35 (t, J = 7.4 Hz, 2H), 7.28 (tq, J = 4.8, 2.2, 1.6 Hz,
5H), 7.23−7.18 (m, 2H), 6.36 (d, J = 10.1 Hz, 2H), 6.26 (d, J = 10.1
Hz, 2H), 4.62 (s, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ 184.0,
167.6, 158.4, 144.2, 137.1, 132.4, 131.8, 130.1, 129.0, 128.6, 128.0,
127.8, 98.2, 70.82, 45.8.
3-Iodo-1-isopropyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2d).13b Eluent: petroleum ether/ethyl acetate (3:1). Yellow
solid, 78% yield (40 mg); 1H NMR (600 MHz, CDCl3) δ 7.44−7.33
(m, 3H), 7.27−7.22 (m, 2H), 6.61 (d, J = 10.1 Hz, 2H), 6.43 (d, J =
10.1 Hz, 2H), 3.50 (quint, J = 6.8 Hz, 1H), 1.46 (d, J = 6.9 Hz, 6H).
13C{1H} NMR (150 MHz, CDCl3) δ 183.9, 166.8, 157.2, 144.3,
132.7, 132.0, 130.0, 128.7, 127.8, 100.6, 71.6, 47.4, 20.9.
N-Methyl-N-phenylpropiolamide (2 mmol), boronic acid (2.4
mmol), Pd(OAc)2 (1 mol %), Ag2O (3.0 mmol), K2CO3 (4 mmol),
and CH3CN (12 mL) were added to a Schlenk tube. Then, the
solution was stirred at 70 °C in an oil bath for 12 h. After the reaction
was finished, the mixture was filtered, extracted with EtOAc, and
evaporated under vacuum. The residue was purified by flash column
chromatography on silica gel to afford the desired product.
General Procedure for Electrochemical Oxidative Halogen-
ation. An undivided cell was equipped with graphite electrodes as the
anode and cathode (52.5 mm × 8.0 mm × 1.5 mm) and connected to
an IKA power supply. Alkynamides (0.125 mmol), halogenated
lithium salt (0.25 mmol), and LiClO4 (0.2 M) were added into the
cell with a 4.0 mL solution of CH3CN. The mixture was electrolyzed
using a constant current of 10 mA at room temperature under
magnetic stirring. When the reaction was finished (witnessed by the
disappearance of 1), the solvent was removed under vacuum and then
extracted with DCM (3 × 5 mL), washed with brine, dried over
1-Allyl-3-iodo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione
(2e). Eluent: petroleum ether/ethyl acetate (5:1). Yellow solid, 56%
Scheme 6. Proposed Mechanism
F
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yield (28 mg); H NMR (600 MHz, CDCl3) δ 7.47−7.36 (m, 3H),
4H), 3.00 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.2, 166.8,
155.9, 143.3, 136.5, 133.7, 132.6, 128.7, 117.8, 114.0, 100.4, 70.2,
27.1. HRMS (ESI+) m/z calcd for C17H12O2N2I [M + H]+: m/z
402.9936; found: 402.9938.
3-Iodo-4-(4-methoxyphenyl)-1-methyl-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (2o).13a Eluent: petroleum ether/ethyl acetate (3:1).
Yellow solid, 88% yield (42 mg); 1H NMR (600 MHz, CDCl3) δ 7.35
(d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 6.51 (q, J = 10.3 Hz,
4H), 3.82 (s, 3H), 2.95 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ
183.9, 167.6, 160.9, 157.2, 144.6, 133.1, 129.2, 123.9, 114.1, 96.8,
70.2, 55.3, 26.9.
3-Iodo-1-methyl-4-(p-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2p).13a Eluent: petroleum ether/ethyl acetate (3:1). Yellow
solid, 90% yield (44 mg); 1H NMR (600 MHz, CDCl3) δ 7.25−7.07
(m, 4H), 6.59−6.40 (m, 4H), 2.96 (s, 3H), 2.36 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3) δ 183.8, 167.6, 157.9, 144.3, 140.4, 133.2,
129.4, 128.9, 127.6, 97.6, 70.4, 27.0, 21.4.
7.30−7.24 (m, 2H), 6.55 (d, J = 10.1 Hz, 2H), 6.42 (d, J = 10.1 Hz,
2H), 5.88−5.77 (m, 1H), 5.20−5.15 (m, 2H), 4.01 (d, J = 6.3 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 184.0, 167.3, 158.3, 144.3,
132.8, 132.8, 131.8, 130.1, 128. 7, 127.8, 119.1, 98.4, 70.8, 44.5.
HRMS (ESI+) m/z calcd for C18H15O2NI [M + H]+: m/z 404.0138;
found: 404.0142.
tert-Butyl 3-iodo-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-tri-
ene-1-carboxylate (2f). Eluent: petroleum ether/ethyl acetate (5:1).
Yellow solid, 35% yield (34 mg); 1H NMR (600 MHz, CDCl3) δ 7.41
(m, J = 7.4 Hz, 1H), 7.37 (m, J = 7.4 Hz, 2H), 7.11 (d, J = 7.0 Hz,
2H), 6.64 (d, J = 10.0 Hz, 2H), 6.35 (d, J = 10.0 Hz, 2H), 1.45 (s,
9H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.9, 164.8, 160.7, 147.4,
143.8, 132.0, 131.2, 130.3, 128.6, 128.1, 98.5, 85.0, 70.5, 27.8. HRMS
(ESI+) m/z calcd for C20H18O4NINa [M + Na]+: m/z 486.0170;
found: 486.0173.
Benzyl 3-iodo-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
1-carboxylate (2g). Eluent: petroleum ether/ethyl acetate (4:1).
Yellow solid, 42% yield (26 mg); 1H NMR (600 MHz, CDCl3) δ 7.44
(t, J = 7.4 Hz, 1H), 7.42−7.33 (m, 7H), 7.14 (d, J = 7.0 Hz, 2H), 6.62
(d, J = 10.0 Hz, 2H), 6.34 (d, J = 10.0 Hz, 2H), 5.30 (s, 2H). 13C{1H}
NMR (150 MHz, CDCl3) δ 183.6, 164.2, 161.6, 149.2, 142.9, 134.3,
132.3, 131.0, 130.4, 128.7, 128.6, 128.3, 128.0, 97.8, 70.6, 69.0.
HRMS (ESI+) m/z calcd for C23H16O4NINa [M + Na]+: m/z
520.0013; found: 520.0016.
3-Iodo-1-methyl-4-(m-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2q). Eluent: petroleum ether/ethyl acetate (3:1). Yellow solid,
1
85% yield (43 mg); H NMR (600 MHz, CDCl3) δ 7.30−7.19 (m,
2H), 7.12−7.05 (m, 2H), 6.53 (d, J = 10.2 Hz, 2H), 6.47 (d, J = 10.1
Hz, 2H), 2.97 (s, 3H), 2.35 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 183.8, 167.5, 158.172, 144.2, 138.4, 133.2, 131.8, 130.9,
128.6, 128.3, 124.7, 98.0, 70.4, 27.0, 21.4. HRMS (ESI+) m/z calcd
for C17H15O2NI [M + H]+: m/z 392.0137; found: 392.0142.
3-Iodo-1,6-dimethyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2h).12 Eluent: petroleum ether/ethyl acetate (4:1). Yellow
solid, 86% yield (46 mg); 1H NMR (600 MHz, CDCl3) δ 7.42 (t, J =
7.2 Hz, 1H), 7.38 (t, J = 7.5 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 6.49
(s, 2H), 6.34 (s, 1H), 2.87 (s, 3H), 1.77 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3) δ 184.5, 167.9, 157.9, 152.4, 144.3, 132.8, 132.1, 131.6,
130.3, 128.8, 127.4, 97.9, 72.6, 26.6, 17.7.
3-Iodo-7,9-dimethoxy-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (2i). Eluent: petroleum ether/ethyl acetate
(1:1). White solid, 71% yield (55 mg); 1H NMR (600 MHz, CDCl3)
δ 7.43−7.34 (m, 3H), 7.27−7.23 (m, 2H), 5.42 (s, 2H), 3.69 (s, 6H),
2.95 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 175.2, 166.8,
160.5, 153.3, 132.3, 130.0, 128.7, 127.8, 127.6, 111.1, 96.8, 70.6, 55.9,
26.5. HRMS (ESI+) m/z calcd for C18H17O4NI [M + H]+: m/z
438.0192; found: 438.0197.
3-Iodo-1-methyl-4-(o-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (2r).11 Eluent: petroleum ether/ethyl acetate (3:1). Yellow
solid, 63% yield (31 mg); 1H NMR (600 MHz, CDCl3) δ 7.32−7.28
(m, 1H), 7.25 (d, J = 8.1 Hz, 1H), 7.16 (t, J = 6.9 Hz, 1H), 6.87 (d, J
= 7.7 Hz, 1H), 6.62 (dd, J = 10.0, 3.0 Hz, 1H), 6.55−6.51 (m, 2H),
6.33 (dd, J = 10.0, 1.8 Hz, 1H), 3.02 (s, 3H), 2.24 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3) δ 183.6, 167.2, 159.3, 143.7, 143.5, 135.6,
133.6, 133.0, 130.8, 130.6, 129.8, 128.1, 125.5, 100.6, 72.0, 27.4, 20.1.
4-(Furan-3-yl)-3-iodo-1-methyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (2s). Eluent: petroleum ether/ethyl acetate (2:1). Yellow
1
solid, 61% yield (28 mg); H NMR (600 MHz, CDCl3) δ 8.13 (s,
1H), 7.47 (t, J = 1.8 Hz, 1H), 6.95 (d, J = 2.0 Hz, 1H), 6.60 (d, J =
10.1 Hz, 2H), 6.52 (d, J = 10.1 Hz, 2H), 2.94 (s, 3H). 13C{1H} NMR
(150 MHz, CDCl3) δ 183.9, 167.7, 148.5, 145.3, 143.6, 142.7, 133.0,
117.3, 108.4, 93.7, 69.0, 26.5. HRMS (ESI+) m/z calcd for
C14H11O3NI [M + H]+: m/z 367.9775; found: 367.9778.
4-(4-Fluorophenyl)-3-iodo-1-methyl-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2j).13a Eluent: petroleum ether/ethyl acetate (3:1).
Yellow solid, 89% yield (44 mg); 1H NMR (600 MHz, CDCl3) δ 7.33
(dd, J = 8.8, 5.2 Hz, 2H), 7.08 (t, J = 8.6 Hz, 2H), 6.51 (q, J = 10.3
Hz, 4H), 2.97 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.6,
167.3, 163.4 (d, J = 250.5 Hz), 156.8, 144.0, 133.4, 129.9 (d, J = 7.5
Hz), 127.8 (d, J = 4.5 Hz), 116.0 (d, J = 22.5 Hz), 98.7, 70.4, 27.1.
4-(4-Chlorophenyl)-3-iodo-1-methyl-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2k).13a Eluent: petroleum ether/ethyl acetate (3:1).
Yellow solid, 70% yield (33 mg); 1H NMR (600 MHz, CDCl3) δ 7.37
(d, J = 8.6 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H), 6.54−6.47 (m, 4H),
2.97 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.5, 167.2,
156.7, 143.9, 136.4, 133.5, 130.2, 129.1, 129.1, 98.9, 70.3, 27.1.
4-(4-Bromophenyl)-3-iodo-1-methyl-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2l).13a Eluent: petroleum ether/ethyl acetate (2:1).
Yellow solid, 82% yield (47 mg); 1H NMR (600 MHz, CDCl3) δ 7.52
(d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.6 Hz, 2H), 6.53−6.46 (m, 4H),
2.96 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.5, 167.2,
156.7, 143.8, 133.5, 132.1, 130.7, 129.3, 124.7, 98.9, 70.2, 27.1.
3-Iodo-1-methyl-4-(4-(trifluoromethyl)phenyl)-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (2m).13a Eluent: petroleum ether/ethyl
acetate (3:1). Yellow solid, 54% yield (30 mg); 1H NMR (600 MHz,
CDCl3) δ 7.67 (d, J = 8.2 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 6.57−
6.49 (m, 4H), 3.00 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ
183.3, 167.0, 156.5, 143.5, 135.5, 133.6, 132.1(d, J = 22.0 Hz), 128.3,
125.8 (q, J = 3.0 Hz), 123.5 (q, J = 271.5 Hz), 99.8, 70.3, 27.1.
4-(3-Iodo-1-methyl-2,8-dioxo-1-azaspiro[4.5]deca-3,6,9-trien-4-yl)-
benzonitrile (2n). Eluent: petroleum ether/ethyl acetate (2:1). White
solid, 51% yield (26 mg); 1H NMR (600 MHz, CDCl3) δ 7.74−7.64
(d, J = 12 Hz, 2H), 7.48−7.37 (d, J = 12 Hz, 2H), 6.56−6.47 (m,
3-Iodo-1-methyl-4-(thiophen-3-yl)-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (2t). Eluent: petroleum ether/ethyl acetate (2:1).
Yellow solid, 84% yield (51 mg); 1H NMR (600 MHz, CDCl3) δ 7.91
(dd, J = 2.9, 1.4 Hz, 1H), 7.55 (dd, J = 5.1, 1.4 Hz, 1H), 7.39 (dd, J =
5.1, 2.9 Hz, 1H), 6.62−6.47 (m, 4H), 2.94 (s, 3H). 13C{1H} NMR
(150 MHz, CDCl3) δ 183.9, 167.7, 151.3, 145.1, 133.1, 131.6, 127.0,
126.4, 126.2, 95.2, 69.5, 26.6. HRMS (ESI+) m/z calcd for
C14H11O2NIS [M + H]+: m/z 383.9544; found: 383.9550.
3-Bromo-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3a).13a Eluent: petroleum ether/ethyl acetate (3:1). White
1
solid, 87% yield (36 mg); H NMR (600 MHz, CDCl3) δ 7.40 (m,
4.3 Hz, 5H), 6.59−6.45 (m, 4H), 2.95 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3) δ 183.7, 165.8, 151.3, 144.1, 133.5, 130.3, 130.2, 128.8,
127.8, 119.9, 68.3, 26.7.
3-Bromo-1-ethyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3b). Eluent: petroleum ether/ethyl acetate (3:1). Yellow solid,
1
85% yield (39 mg); H NMR (600 MHz, CDCl3) δ 7.44−7.34 (m,
5H), 6.58 (d, J = 10.1 Hz, 2H), 6.47 (d, J = 10.1 Hz, 2H), 3.41 (q, J =
7.2 Hz, 2H), 1.24 (t, J = 6.0 Hz, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 183, 165.7, 151.2, 144.4, 132.9, 130.2, 130.2, 128.7, 127.8,
120.3, 68.8, 36.7, 15.2. HRMS (ESI+) m/z calcd for C17H15O2NBr
[M + H]+: m/z 344.0278; found: 344.0281.
1-Benzyl-3-bromo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3c).14 Eluent: petroleum ether/ethyl acetate (4:1). White
solid, 92% yield (39 mg); 1H NMR (600 MHz, CDCl3) δ 7.40 (t, J =
7.3 Hz, 1H), 7.36 (t, J = 7.5 Hz, 2H), 7.33−7.23 (m, 7H), 6.37 (d, J =
10.0 Hz, 2H), 6.28 (d, J = 10.0 Hz, 2H), 4.61 (s, 2H). 13C{1H} NMR
(150 MHz, CDCl3) δ 183.9, 166.0, 151.9, 144.3, 137.0, 132.6, 130.2,
130.0, 128.9, 128.7, 128.6, 128.1, 127.8, 119.9, 68.1, 45.5.
G
https://dx.doi.org/10.1021/acs.joc.0c02429
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
3-Bromo-1-isopropyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (3d). Eluent: petroleum ether/ethyl acetate (3:1). White
solid, 91% yield (40 mg); 1H NMR (600 MHz, CDCl3) δ 7.44−7.32
(m, 5H), 6.61 (d, J = 10.1 Hz, 2H), 6.46 (d, J = 10.1 Hz, 2H), 3.47
(quint, J = 6.8 Hz, 1H), 1.46 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (150
MHz, CDCl3) δ 183.900, 165.2, 150.5, 144.4, 132.9, 130.3, 130.1,
128.7, 127.8, 121.3, 69.5, 47.2, 20.8. HRMS (ESI+) m/z calcd for
C18H17O2NBr [M + H]+: m/z 358.0435; found: 358.0437.
3-Bromo-1-methyl-4-(4-(trifluoromethyl)phenyl)-1-azaspiro[4.5]-
deca-3,6,9-triene-2,8-dione (3m).13a Eluent: petroleum ether/ethyl
acetate (3:1). White solid, 98% yield (48 mg); H NMR (600 MHz,
1
CDCl3) δ 7.67 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H), 6.55 (s,
4H), 2.98 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.3, 165.3,
149.8, 143.5, 133.8, 132.1 (d, J = 33.0 Hz), 128.3, 125.8 (q, J = 3.0,
4.5 Hz), 123.5 (d, J = 271.5 Hz), 121.5, 68.2, 26.7.
4-(3-Bromo-1-methyl-2,8-dioxo-1-azaspiro[4.5]deca-3,6,9-trien-4-
yl)benzonitrile (3n). Eluent: petroleum ether/ethyl acetate (2:1).
White solid, 86% yield (38 mg); 1H NMR (600 MHz, CDCl3) δ 7.70
(d, J = 8.7 Hz, 1H), 7.54 (d, J = 8.7 Hz, 1H), 6.54 (s, 3H), 2.97 (s,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.1, 165.1, 149.3, 143.4,
134.7, 133.9, 132.6, 128.6, 122.0, 117.8, 114.1, 68.1, 26.8. HRMS (ESI
+) m/z calcd for C17H12O2N2Br [M + H]+: m/z 355.0075; found:
355.0077.
3-Bromo-4-(4-methoxyphenyl)-1-methyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3o).13a Eluent: petroleum ether/ethyl acetate
(3:1). White solid, 90% yield (40 mg); 1H NMR (600 MHz, CDCl3)
δ 7.47 (d, J = 8.9 Hz, 2H), 6.90 (d, J = 8.9 Hz, 2H), 6.53 (s, 4H), 3.83
(s, 3H), 2.93 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.8,
166.1, 161.0, 150.6, 144.7, 133.3, 129.3, 122.3, 118.3, 114.2, 68.1,
55.4, 26.5.
3-Bromo-1-methyl-4-(p-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3p).14 Eluent: petroleum ether/ethyl acetate (3:1). White
solid, 95% yield (41 mg); 1H NMR (600 MHz, CDCl3) δ 7.33 (d, J =
8.2 Hz, 2H), 7.24−6.99 (m, 2H), 6.68−6.28 (m, 4H), 2.94 (s, 3H),
2.36 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.8, 165.9,
151.3, 144.4, 140.6, 133.3, 129.5, 127.6, 127.2, 119.2, 68.3, 26.6, 21.4.
3-Bromo-1-methyl-4-(m-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (3q). Eluent: petroleum ether/ethyl acetate (3:1). White
solid, 86% yield (38 mg); 1H NMR (600 MHz, CDCl3) δ 7.29−7.25
(m, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.20 (s, 1H), 7.17 (d, J = 7.6 Hz,
1H), 6.59−6.46 (m, 4H), 2.95 (s, 3H), 2.35 (s, 3H). 13C{1H} NMR
(150 MHz, CDCl3) δ 183.8, 165.9, 151.6, 144.2, 138.5, 133.4, 131.1,
130.1, 128.6, 128.3, 124.7, 119.7, 68.4, 26.7, 21.4. HRMS (ESI+) m/z
calcd for C17H15O2NBr [M + H]+: m/z 344.0277; found: 344.0281.
3-Bromo-1-methyl-4-(o-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3r).14 Eluent: petroleum ether/ethyl acetate (3:1). White
solid, 77% yield (33 mg); 1H NMR (600 MHz, CDCl3) δ 7.31 (td, J =
7.5, 1.4 Hz, 1H), 7.26 (d, J = 7.7 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H),
6.92 (dd, J = 7.7, 1.3 Hz, 1H), 6.64 (dd, J = 10.0, 3.0 Hz, 1H), 6.55
(dd, J = 10.0, 1.8 Hz, 1H), 6.52 (dd, J = 10.0, 3.0 Hz, 1H), 6.34 (dd, J
= 10.0, 1.8 Hz, 1H), 3.01 (s, 3H), 2.24 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3) δ 183.5, 165.6, 152.5, 143.5, 143.3, 136.1, 133.9, 133.2,
130.7, 129.9, 128.7, 128.1, 125.4, 122.1, 69.9, 27.2, 20.0.
1-Allyl-3-bromo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (3e). Eluent: petroleum ether/ethyl acetate (4:1). White solid,
1
70% yield (31 mg); H NMR (600 MHz, CDCl3) δ 7.45−7.33 (m,
5H), 6.56 (d, J = 10.1 Hz, 2H), 6.45 (d, J = 10.1 Hz, 2H), 5.82 (ddt, J
= 16.7, 10.3, 6.3 Hz, 1H), 5.22−5.12 (m, 2H), 3.99 (d, J = 6.3 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.9, 165.6, 151.7, 144.3,
133.0, 132.6, 130.2, 130.1, 128.7, 127.8, 120.0, 119.2, 68.7, 44.2.
HRMS (ESI+) m/z calcd for C18H15O2NBr [M + H]+: m/z
356.0277; found: 356.0281.
tert-Butyl 3-bromo-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-
triene-1-carboxylate (3f). Eluent: petroleum ether/ethyl acetate
(4:1). White solid, 64% yield (34 mg); 1H NMR (600 MHz,
CDCl3) δ 7.43 (m, J = 7.9 Hz, 1H), 7.39 (m, J = 7.6 Hz, 2H), 7.20 (d,
J = 8.2 Hz, 2H), 6.67 (d, J = 9.8 Hz, 2H), 6.39 (d, J = 9.8 Hz, 2H),
1.47 (s, 9H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.8, 163.3,
154.4, 147.4, 143.7, 132.2, 130.4, 129.3, 128.6, 128.2, 120.0, 85.1,
68.6, 27.8. HRMS (ESI+) m/z calcd for C20H18O4NBrNa [M + Na]+:
m/z 438.0307; found: 438.0311.
Benzyl 3-bromo-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-tri-
ene-1-carboxylate (3g). Eluent: petroleum ether/ethyl acetate (5:1).
White solid, 71% yield (40 mg); 1H NMR (600 MHz, CDCl3) δ 7.44
(t, J = 7.4 Hz, 1H), 7.41−7.33 (m, 7H), 7.22 (d, J = 7.0 Hz, 2H), 6.64
(d, J = 10.0 Hz, 2H), 6.35 (d, J = 10.0 Hz, 2H), 5.30 (s, 2H). 13C{1H}
NMR (150 MHz, CDCl3) δ 183.6, 162.8, 155.2, 149.1, 142.9, 134.2,
132.6, 130.5, 129.1, 128.7, 128.7, 128.6, 128.3, 128.1, 119.4, 69.0,
68.5. HRMS (ESI+) m/z calcd for C23H16O4NBrNa [M + Na]+: m/z
472.0150; found: 472.0155.
3-Bromo-1,6-dimethyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (3h).12 Eluent: petroleum ether/ethyl acetate (3:1). White
solid, 89% yield (37 mg); 1H NMR (600 MHz, CDCl3) δ 7.46−7.35
(m, 5H), 6.53−6.48 (m, 2H), 6.38 (s, 1H), 2.86 (s, 3H), 1.76 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 184.4, 166.3, 152.6, 151.3,
144.4, 132.9, 132.2, 130.4, 129.9, 128.9, 127.5, 119.7, 70.4, 26.2, 17.7.
3-Bromo-7,9-dimethoxy-1-methyl-4-phenyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (3i). Eluent: petroleum ether/ethyl acetate
(1:1). White solid, 88% yield (49 mg); 1H NMR (600 MHz, CDCl3)
δ 7.46−7.32 (m, 5H), 5.42 (s, 2H), 3.70 (s, 6H), 2.94 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 175.2, 165.3, 153.6, 153.4,
130.5, 130.1, 128.7, 127.7, 118.6, 111.1, 68.7, 55.9, 26.1. HRMS (ESI
+) m/z calcd for C18H17O4NBr [M + H]+: m/z 390.0330; found:
390.0335.
3-Bromo-4-(furan-3-yl)-1-methyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (3s). Eluent: petroleum ether/ethyl acetate (2:1). White
1
solid, 65% yield (26 mg); H NMR (600 MHz, CDCl3) δ 8.07 (s,
1H), 7.47 (t, J = 1.7 Hz, 1H), 6.89 (dd, J = 2.0, 0.9 Hz, 1H), 6.62 (d, J
= 10.1 Hz, 2H), 6.53 (d, J = 10.1 Hz, 2H), 2.91 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3) δ 183.8, 165.8, 145.3, 143.7, 143.1, 142.5,
133.2, 116.4, 116.3, 108.3, 66.7, 26.1. HRMS (ESI+) m/z calcd for
C14H11O3NBr [M + H]+: m/z 319.9914; found: 319.9917.
3-Bromo-1-methyl-4-(thiophen-3-yl)-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (3t). Eluent: petroleum ether/ethyl acetate (2:1).
White solid, 87% yield (36 mg); 1H NMR (600 MHz, CDCl3) δ 7.96
(dd, J = 2.9, 1.4 Hz, 1H), 7.61 (dd, J = 5.2, 1.4 Hz, 1H), 7.40 (dd, J =
5.2, 2.9 Hz, 1H), 6.62 (d, J = 10.1 Hz, 2H), 6.56 (d, J = 10.2 Hz, 2H),
2.93 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.9, 166.0,
145.2, 144.9, 133.2, 130.4, 127.4, 126.4, 126.2, 117.1, 67.2, 26.2.
HRMS (ESI+) m/z calcd for C14H11O2NBrS [M + H]+: m/z
335.9683; found: 335.9688.
3-Chloro-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (4a).13a Eluent: petroleum ether/ethyl acetate (4:1). Yellow
solid, 82% yield (29 mg); 1H NMR (600 MHz, CDCl3) δ 7.51−7.44
(m, 2H), 7.45−7.35 (m, 3H), 6.54 (s, 4H), 2.94 (s, 3H). 13C{1H}
NMR (150 MHz, CDCl3) δ 183.7, 165.2, 147.3, 144.4, 133.5, 130.4,
129.3, 128.8, 128.5, 127. 8, 66.5, 26.4.
3-Bromo-4-(4-fluorophenyl)-1-methyl-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (3j). Eluent: petroleum ether/ethyl acetate (3:1).
1
White solid, 90% yield (39 mg); H NMR (600 MHz, CDCl3) δ
7.46−7.40 (m, 2H), 7.08 (t, J = 8.6 Hz, 2H), 6.53 (s, 4H), 2.95 (s,
3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.5, 163.5 (d, J = 250.5
Hz), 162.7, 150.2, 144.1, 133.6, 129.9 (d, J = 7.5 Hz), 126.2 (d, J =
4.5 Hz), 120.12, 116.1 (d, J = 21 Hz), 68.25, 26.67. HRMS (ESI+)
m/z calcd for C16H12O2NBrF [M + H]+: m/z 348.0027; found:
348.0030.
3-Bromo-4-(4-chlorophenyl)-1-methyl-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (3k).13a Eluent: petroleum ether/ethyl acetate (2:1).
White solid, 85% yield (39 mg); 1H NMR (600 MHz, CDCl3) δ 7.38
(s, 4H), 6.53 (s, 4H), 2.95 (s, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 183.5, 165.5, 150.0, 143.9, 136.5, 133.6, 129.2, 129.1, 128.5,
120.5, 68.2, 26.7.
3-Bromo-4-(4-bromophenyl)-1-methyl-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (3l).13a Eluent: petroleum ether/ethyl acetate (2:1).
White solid, 76% yield (39 mg); 1H NMR (600 MHz, CDCl3) δ 7.54
(d, J = 8.6 Hz, 2H), 7.31 (d, J = 8.6 Hz, 2H), 6.53 (d, J = 1.5 Hz, 4H),
2.95 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.4, 165.5,
150.1, 143.9, 133.6, 132.1, 129.3, 129.0, 124.9, 120.5, 68.1, 26.7.
3-Chloro-1-ethyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (4b). Eluent: petroleum ether/ethyl acetate (5:1). Yellow solid,
H
https://dx.doi.org/10.1021/acs.joc.0c02429
J. Org. Chem. XXXX, XXX, XXX−XXX

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1
91% yield (32 mg); H NMR (600 MHz, CDCl3) δ 7.47−7.36 (m,
128.6, 117.8, 114.1, 66.3, 26.5. HRMS (ESI+) m/z calcd for
C17H11O2N2Cl [M + H]+: m/z 311.0580; found: 311.0582.
3-Chloro-4-(4-methoxyphenyl)-1-methyl-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (4l).13a Eluent: petroleum ether/ethyl acetate
(5:1). White solid, 36% yield (13 mg); 1H NMR (600 MHz, CDCl3)
δ 7.56−7.54 (m, 2H), 6.91 (d, J = 9.0 Hz, 2H), 6.57−6.53 (m, 4H),
3.84 (s, 3H), 2.92 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ
183.8, 165.5, 161.0, 146.6, 145.0, 144.7, 133.3, 129.3, 126.7, 121.6,
114.3, 66.3, 55.4, 26.2.
5H), 6.59 (d, J = 6.2 Hz, 2H), 6.51 (d, J = 6.0 Hz, 2H), 3.40 (q, J =
7.2 Hz, 2H), 1.25 (t, J = 6.0 Hz, 3H). 13C{1H} NMR (150 MHz,
CDCl3) δ 183.9, 165.1, 147.2, 144.7, 133.0, 130.3, 129.3, 128.8, 127.8,
67.0, 36.5, 15.1. HRMS (ESI+) m/z calcd for C17H15O2NCl [M +
H]+: m/z 300.0782; found: 300.0786.
1-Benzyl-3-chloro-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (4c). Eluent: petroleum ether/ethyl acetate (4:1). White solid,
1
82% yield (37 mg); H NMR (600 MHz, CDCl3) δ 7.43−7.35 (m,
5H), 7.32−7.24 (m, 5H), 6.37 (d, J = 10.1 Hz, 2H), 6.31 (d, J = 10.1
Hz, 2H), 4.60 (s, 2H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.9,
165.4, 147.9, 144.5, 136.9, 132.7, 130.3, 129.1, 128.9, 128.7, 128.6,
128.5, 128.0, 127.9, 67.1, 45.2. HRMS (ESI+) m/z calcd for
C22H17O2NCl [M + H]+: m/z 362.0938; found: 362.0942.
3-Chloro-1-isopropyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (4d). Eluent: petroleum ether/ethyl acetate (5:1). white
solid, 76% yield (33 mg); 1H NMR (600 MHz, CDCl3) δ 7.44−7.37
(m, 5H), 6.61 (d, J = 10.1 Hz, 2H), 6.50 (d, J = 10.1 Hz, 2H), 3.46
(quint, J = 6.9 Hz, 1H), 1.47 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (150
MHz, CDCl3) δ 183.9, 164.6, 146.4, 144.7, 132.9, 130.2, 129.6, 129.4,
128.7, 127.8, 67.6, 47.0, 20.7. HRMS (ESI+) m/z calcd for
C18H17O2NCl [M + H]+: m/z 314.0938; found: 314.0942.
tert-Butyl 3-chloro-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-
triene-1-carboxylate (4f). Eluent: petroleum ether/ethyl acetate
(5:1). White solid, 52% yield (24 mg); 1H NMR (600 MHz,
CDCl3) δ 7.44 (m, J = 7.4 Hz, 1H), 7.39 (m, J = 7.5 Hz, 2H), 7.25 (d,
J = 9.8 Hz, 2H), 6.67 (d, J = 9.8 Hz, 2H), 6.41 (d, J = 9.8 Hz, 2H),
1.47 (s, 9H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.9, 162.8,
150.6, 147.4, 143.9, 132.3, 130.5, 128.7, 128.6, 128.2, 85.2, 67.0, 27.8.
HRMS (ESI+) m/z calcd for C20H18O4NClNa [M + Na]+: m/z
394.0813; found: 394.0817.
3-Chloro-1-methyl-4-(p-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (4m). Eluent: petroleum ether/ethyl acetate (5:1). White solid,
11% yield (4 mg); 1H NMR (600 MHz, CDCl3) δ 7.39 (d, J = 8.3 Hz,
2H), 7.18 (d, J = 8.0 Hz, 2H), 6.52 (d, J = 3.1 Hz, 4H), 2.91 (s, 3H),
2.36 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.8, 165.4,
147.2, 144.7, 140.8, 133.4, 132.4, 129.5, 127.6, 126.4, 66.5, 26.3, 21.4.
HRMS (ESI+) m/z calcd for C17H15O2NCl [M + H]+: m/z
300.0782; found: 300.0786.
3-Chloro-1-methyl-4-(o-tolyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (4n). Eluent: petroleum ether/ethyl acetate (5:1). White solid,
58% yield (25 mg); 1H NMR (600 MHz, CDCl3) δ 7.31 (td, J = 7.5,
1.3 Hz, 1H), 7.27 (d, J = 7.8 Hz, 1H), 7.16 (t, J = 7.5 Hz, 1H), 6.95
(d, J = 6.4 Hz, 1H), 6.68−6.46 (m, 3H), 6.38−6.31 (m, 1H), 3.00 (s,
3H), 2.24 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.5, 164.9,
148.6, 143.6, 143.4, 136.5, 134.0, 133.4, 130.7, 130.6, 129.9, 128.2,
127.7, 125.5, 68.2, 27.1, 19.9. HRMS (ESI+) m/z calcd for
C17H15O2NCl [M + H]+: m/z 300.0782; found: 300.0786.
1-Methyl-4-phenyl-3-(phenylselanyl)-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (5a).20a Eluent: petroleum ether/ethyl acetate (3:1).
Yellow solid, 95% yield (48 mg); 1H NMR (600 MHz, CDCl3) δ 7.39
(dd, J = 8.2, 1.3 Hz, 2H), 7.30−7.24 (m, 1H), 7.23−7.16 (m, 3H),
7.12 (t, J = 7.9 Hz, 4H), 6.52 (d, J = 10.2 Hz, 2H), 6.44 (d, J = 10.1
Hz, 2H), 2.92 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 184.0,
168.8, 154.2, 145.1, 133.9, 133.1, 131.2, 130.1, 129.4, 129.0, 128.2,
128.0, 127.9, 127.1, 69.1, 26.4.
Benzyl 3-chloro-2,8-dioxo-4-phenyl-1-azaspiro[4.5]deca-3,6,9-tri-
ene-1-carboxylate (4g). Eluent: petroleum ether/ethyl acetate (5:1).
1
White solid, 57% yield (29 mg); H NMR (600 MHz, CDCl3) δ
7.46−7.42 (m, 1H), 7.42−7.35 (m, 7H), 7.27 (d, J = 7.1 Hz, 2H),
6.63 (d, J = 10.0 Hz, 2H), 6.37 (d, J = 10.0 Hz, 2H), 5.30 (s, 2H).
13C{1H} NMR (150 MHz, CDCl3) δ 183.6, 162.2, 151.4, 149.1,
143.0, 134.2, 132.7, 130.7, 128.7, 128.4, 128.2, 128.1, 69.0, 66.9.
HRMS (ESI+) m/z calcd for C23H16O4NClNa [M + Na]+: m/z
428.0656; found: 428.0660.
3-Chloro-1,6-dimethyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-
2,8-dione (4h). Eluent: petroleum ether/ethyl acetate (4:1). White
solid, 51% yield (19 mg); 1H NMR (600 MHz, CDCl3) δ 7.53−7.49
(m, 2H), 7.44−7.37 (m, 3H), 6.55 (dd, J = 9.9, 1.7 Hz, 1H), 6.50 (d,
J = 9.9 Hz, 1H), 6.42 (t, J = 1.5 Hz, 1H), 2.85 (s, 3H), 1.76 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 184.5, 165.6, 153.0, 147.3,
144.7, 132.9, 132.2, 130.5, 129.0, 127.5, 68.6, 25.9, 17.8, 17.7. HRMS
(ESI+) m/z calcd for C17H15O2NCl [M + H]+: m/z 300.0782; found:
300.0786.
1-Benzyl-4-phenyl-3-(phenylselanyl)-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (5b).20a Eluent: petroleum ether/ethyl acetate (2:1).
Yellow solid, 99% yield (60 mg); 1H NMR (600 MHz, CDCl3) δ 7.40
(dd, J = 8.2, 1.3 Hz, 2H), 7.26 (tdt, J = 9.3, 6.5, 3.3 Hz, 5H), 7.23−
7.17 (m, 2H), 7.17−7.11 (m, 4H), 7.05−6.96 (m, 2H), 6.35 (d, J =
10.1 Hz, 2H), 6.22 (d, J = 10.1 Hz, 2H), 4.58 (s, 2H). 13C{1H} NMR
(150 MHz, CDCl3) δ 184.2, 168.9, 154.5, 145.2, 137.4, 133.9, 132.2,
130.9, 130.1, 129.3, 129.0, 128.9, 128.5, 128.1, 128.1, 128.0, 127.9,
127.1, 69.5, 45.2.
Benzyl 2,8-dioxo-4-phenyl-3-(phenylselanyl)-1-azaspiro[4.5]deca-
3,6,9-triene-1-carboxylate (5c). Eluent: petroleum ether/ethyl acetate
(4:1). Yellow solid, 50% yield (33 mg); 1H NMR (600 MHz, CDCl3)
δ 7.39−7.33 (m, 7H), 7.28 (s, 1H), 7.20 (q, J = 7.4 Hz, 3H), 7.11 (t, J
= 7.7 Hz, 2H), 6.94 (d, J = 8.1 Hz, 2H), 6.60 (d, J = 10.0 Hz, 2H),
6.27 (d, J = 10.0 Hz, 2H), 5.27 (s, 2H). 13C{1H} NMR (150 MHz,
CDCl3) δ 183.8, 165.9, 157.8, 149.5, 143.8, 134.6, 134.4, 132.1, 130.2,
130.0, 129.7, 129.2, 128.7, 128.6, 128.4, 128.4, 128.3, 128.1, 126.3,
69.2, 68.7. HRMS (ESI+) m/z calcd for C29H21O4NSeNa [M + Na]+:
m/z 550.0522; found: 550.0528.
3-Chloro-5,6,7-trimethoxy-1-methyl-4-phenylquinolin-2(1H)-one
(4i′). Eluent: petroleum ether/ethyl acetate (4:1). Yellow solid, 50%
1
yield (45 mg); H NMR (600 MHz, CDCl3) δ 7.36−7.32 (t, J = 6.0
Hz, 1H), 7.24 (t, J = 6.0 Hz, 2H), 7.19−7.11 (d, J = 6.0 Hz, 2H), 6.77
(s, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 3.87 (s, 3H), 3.32 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 154.6, 152.3, 150.7, 143.6,
136.1, 132.4, 130.1, 128.4, 120.3, 120.1, 109.0, 90.1, 82.1, 61.4, 61.3,
56.4, 35.1. HRMS (ESI+) m/z calcd for C19H19O4NCl [M + H]+: m/
z 360.0993; found: 360.0994.
1,6-Dimethyl-4-phenyl-3-(phenylselanyl)-1-azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (5d). Eluent: petroleum ether/ethyl acetate
(2:1). Yellow solid, 98% yield (51 mg); 1H NMR (600 MHz, CDCl3)
δ 7.38 (dd, J = 8.2, 1.3 Hz, 2H), 7.30−7.24 (m, 1H), 7.23−7.16 (m,
3H), 7.14−7.11 (m, 4H), 6.48 (d, J = 9.9 Hz, 1H), 6.45 (dd, J = 9.9,
1.6 Hz, 1H), 6.33 (t, J = 1.5 Hz, 1H), 2.81 (s, 3H), 1.76 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 184.7, 169.2, 154.5, 153.3,
145.3, 133.7, 132.6, 132.0, 131.0, 130.4, 129.6, 129.0, 128.3, 127.9,
127.7, 127.5, 71.1, 26.0, 17.8. HRMS (ESI+) m/z calcd for
C23H20O2NSe [M + H]+: m/z 422.0647; found: 422.0654.
7,9-Dimethoxy-1-methyl-4-phenyl-3-(phenylselanyl)-1-azaspiro-
[4.5]deca-3,6,9-triene-2,8-dione (5e). Eluent: petroleum ether/ethyl
4-(4-Bromophenyl)-3-chloro-1-methyl-1-azaspiro[4.5]deca-3,6,9-
triene-2,8-dione (4j).13a Eluent: petroleum ether/ethyl acetate (5:1).
White solid, 47% yield (21 mg); 1H NMR (600 MHz, CDCl3) δ 7.54
(d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 6.59−6.50 (m, 4H),
2.94 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 183.4, 164.9,
146.1, 144.2, 133.7, 132.2, 129.3, 129.0, 128.1, 124.9, 66.4, 26.4.
4-(3-Chloro-1-methyl-2,8-dioxo-1-azaspiro[4.5]deca-3,6,9-trien-4-
yl)benzonitrile (4k). Eluent: petroleum ether/ethyl acetate (5:1).
1
acetate (1:1). White solid, 90% yield (52 mg); H NMR (600 MHz,
1
White solid, 15% yield (6 mg); H NMR (600 MHz, CDCl3) δ 7.69
CDCl3) δ 7.45−7.40 (m, 2H), 7.25 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 7.8
Hz, 3H), 7.13 (t, J = 7.4 Hz, 2H), 7.05 (d, J = 7.0 Hz, 2H), 5.40 (s,
2H), 3.66 (s, 6H), 2.88 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ
175.3, 168.2, 157.1, 153.3, 134.0, 131.5, 129.3, 129.0, 128.5, 128.2,
(d, J = 8.5 Hz, 2H), 7.59 (d, J = 8.5 Hz, 2H), 6.56 (d, J = 10.1 Hz,
2H), 6.51 (d, J = 10.1 Hz, 2H), 2.94 (s, 3H). 13C{1H} NMR (150
MHz, CDCl3) δ 183.1, 164.4, 145.1, 143.6, 133.9, 133.7, 132.6, 130.8,
I
https://dx.doi.org/10.1021/acs.joc.0c02429
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
127.9, 127.9, 127.4, 112.0, 69.2, 55.9, 26.0. HRMS (ESI+) m/z calcd
for C24H22O4NSe [M + H]+: m/z 468.0702; found: 468.0709.
4-Phenyl-3-(phenylselanyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (5f).20a Eluent: petroleum ether/ethyl acetate (3:1). Yellow
solid, 52% yield (25 mg); 1H NMR (600 MHz, CDCl3) δ 7.37 (d, J =
8.0 Hz, 2H), 7.28−7.26 (m, 1H), 7.23−7.16 (m, 3H), 7.14−7.08 (m,
4H), 6.74 (s, 1H), 6.65 (d, J = 10.0 Hz, 2H), 6.32 (d, J = 10.0 Hz,
2H). 13C{1H} NMR (150 MHz, CDCl3) δ 184.1, 170.9, 157.6, 145.1,
133.7, 131.5, 131.0, 129.6, 129.6, 129.1, 128.2, 128.0, 127.9, 127.1,
65.1.
Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China; orcid.org/0000-
0001-9150-6178; Email: qianjinchen@dhu.edu.cn
Authors
Ke Yu − Key Laboratory of Science and Technology of Eco-
Textile, Ministry of Education, College of Chemistry,
Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China
Xianqiang Kong − Key Laboratory of Science and Technology
of Eco-Textile, Ministry of Education, College of Chemistry,
Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China
Jiajun Yang − Key Laboratory of Science and Technology of
Eco-Textile, Ministry of Education, College of Chemistry,
Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China
Guodong Li − Key Laboratory of Science and Technology of
Eco-Textile, Ministry of Education, College of Chemistry,
Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China
1-Methyl-3-(phenylselanyl)-1-azaspiro[4.5]deca-3,6,9-triene-2,8-
dione (5g). Eluent: petroleum ether/ethyl acetate (3:1). Yellow solid,
1
60% yield (27 mg); H NMR (600 MHz, CDCl3) δ 7.65 (d, J = 4.0
Hz, 2H), 7.44−7.37 (m, 3H), 6.44−6.39 (d, J = 8.0 Hz, 2H), 6.38−
6.32 (d, J = 8.0 Hz, 2H), 5.81 (s, 1H), 2.89 (s, 3H). 13C{1H} NMR
(150 MHz, CDCl3) δ 183.9, 168.5, 145.1, 138.6, 136.0, 133.4, 132.2,
130.0, 129.5, 124.8, 67.0, 26.2. HRMS (ESI+) m/z calcd for
C16H14O2NSe [M + H]+: m/z 332.0183; found: 332.0184.
1-Methyl-4-phenyl-3-(phenylethynyl)-1-azaspiro[4.5]deca-3,6,9-tri-
ene-2,8-dione (6a).13a Under a N2 atmosphere, to a solution of 2a
(0.15 mmol) and phenylacetylene (0.2 mmol) in Et3N (6 mL) and
THF (6 mL), PdCl2(PPh3)2 (0.005 mmol) and CuI (0.01 mmol)
were added. The reaction mixture was heated to 70 °C in an oil bath
and stirred overnight. Until the reaction was completed, the resulting
mixture was cooled to room temperature. Then the residue was
extracted with EtOAc, washed with brine, and dried over Na2SO4, and
the solvent was evaporated. The given residue was purified by flash
chromatography. Eluent: petroleum ether/ethyl acetate (5:1). Yellow
solid, 88% yield (80 mg); 1H NMR (600 MHz, CDCl3) δ 7.89 (d, J =
7.4 Hz, 2H), 7.55 (dt, J = 7.6, 2.1 Hz, 2H), 7.44−7.35 (m, 6H), 6.60
(s, 4H), 2.91 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3) δ 184.1,
167. 6, 153.6, 145.8, 132.9, 132.1, 131.2, 130.7, 129.3, 128.7, 128.4,
127.6, 122.2, 119.8, 100.4, 81.7, 66.2, 25.7.
3-(4-Methoxyphenyl)-1-methyl-4-phenyl-1 azaspiro[4.5]deca-
3,6,9-triene-2,8-dione (6b).1a 2a (0.15 mmol), 4-methoxyphenylbor-
onic acid (0.3 mmol), PdO(Ac)2 (0.015 mmol), and K2CO3 (0.30
mmol) were added in a Schlenk tube under a N2 atmosphere, then
DMF (3 mL) and H2O (0.75 mL) were added in the system. The
reaction mixture was stirred overnight at room temperature. Until the
reaction was completed, the resulting mixture was cooled to room
temperature. Then, the residue was extracted with EtOAc, washed
with brine, and dried over Na2SO4, and the solvent was evaporated.
The given residue was purified by flash chromatography. Eluent:
petroleum ether/ethyl acetate (6:1). White solid, 92% yield (50 mg);
1H NMR (600 MHz, CDCl3) δ 7.40 (d, J = 6.0 Hz, 2H), 7.34−7.24
(m, 4H), 7.14 (d, J = 7.2 Hz, 2H), 6.81 (d, J = 6.0 Hz, 2H), 6.60 (d, J
= 10.0 Hz, 2H), 6.48 (d, J = 10.0 Hz, 2H), 3.79 (s, 3H), 2.98 (s, 3H).
13C{1H} NMR (150 MHz, CDCl3) δ 184.3, 169.9, 159.8, 147.8,
146.0, 134.7, 133.1, 132.2, 130.9, 129.1, 128.7, 128.4, 122.9, 113.7,
67.0, 55.2, 26.2.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02429
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge the financial support from the Fundamental
Research Funds for the Central Universities (2232020A-09) as
well as the National Science Foundation of China (NSFC-
21804018) and Shanghai (19ZR1470800).
REFERENCES
■
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02429.
■
sı
Experimental procedure, compound characterization,
and NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Bo Xu − Key Laboratory of Science and Technology of Eco-
Textile, Ministry of Education, College of Chemistry,
Chemical Engineering and Biotechnology, Donghua
University, Shanghai 201620, China; orcid.org/0000-
0001-8702-1872; Email: bo.xu@dhu.edu.cn
Qianjin Chen − Key Laboratory of Science and Technology of
Eco-Textile, Ministry of Education, College of Chemistry,
J
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