Copper-Catalyzed 1,1-Alkylmonofluoroalkylation of Terminal Alkynes with Diazo Compounds and 2-Fluoro-1,3-dicarbonyl Compounds: Access toward (E)-β-Monofluoroalkyl-β,γ-unsaturated Esters or Ketones

Article abstract of DOI:10.1021/acs.joc.1c00789

An efficient copper-catalyzed three-component 1,1-alkylmonofluoroalkylation of terminal alkynes, diazo compounds, and 2-fluoro-1,3-dicarbonyl compounds for the synthesis of (E)-β-monofluoroalkyl-β,γ-unsaturated esters or ketones has been developed. The methodology features a broad substrate scope, an inexpensive and easily available catalytic system, and excellent selectivity with good yields. The mechanism of the tandem Cu-catalyzed cross-coupling and nucleophilic addition of allenes has been investigated.

Full text of DOI:10.1021/acs.joc.1c00789

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Article
Copper-Catalyzed 1,1-Alkylmonofluoroalkylation of Terminal
Alkynes with Diazo Compounds and 2‑Fluoro-1,3-dicarbonyl
Compounds: Access toward (E)‑β-Monofluoroalkyl-β,γ-unsaturated
Esters or Ketones
Yunhe Lv,* Weiya Pu, Xueli Zhu, Chen Chen, and Shanshan Wang
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ABSTRACT: An efficient copper-catalyzed three-component 1,1-
alkylmonofluoroalkylation of terminal alkynes, diazo compounds,
and 2-fluoro-1,3-dicarbonyl compounds for the synthesis of (E)-β-
monofluoroalkyl-β,γ-unsaturated esters or ketones has been
developed. The methodology features a broad substrate scope, an
inexpensive and easily available catalytic system, and excellent
selectivity with good yields. The mechanism of the tandem Cu-
catalyzed cross-coupling and nucleophilic addition of allenes has been investigated.
Scheme 1. 1,1-Difunctionalization of Alkynes through Allene
Strategy
INTRODUCTION
■
Alkynes are ubiquitous motifs in organic synthesis. Their
accessibility and broad functionalization potential have fueled
persistent efforts aimed at developing new methods enabling
their conversion into high-value added chemicals.1 As a result of
these efforts, the difunctionalization of alkynes has emerged as a
powerful new approach for the synthesis of a vast array of
chemicals, especially multisubstituted alkenes. In this context,
1,2-difunctionalization of alkynes always occupies a leading
position regardless of whether transition-metal-catalyzed or
metal-free-catalyzed reactions are used. In contrast, the 1,1-
difunctionalization of alkynes is considerably less established
than the 1,2-difunctionalization. Although remarkable progress
has been made by Iwasawa,2 Takai,3 Zhu,4 Chirik,5 Sawamura,6
Wang,7 Yin,8 Song,9 Marder,10 Martin,11 and Engle,12 the
selective one-pot multicomponent tandem reactions for 1,1-
difunctionalization of terminal alkynes are still highly demanded
and challenging. They are mainly limited to two-component,
three-component reactions with two of the components being
the same coupling partner, or two-step operation. Recently, the
1,1-difunctionalization of alkynes through an allene strategy has
been a focus of interest. Diazo compounds represent privileged
motifs that have been extensively utilized in this field. For
instance, in 2016, the Jiang group independently reported a
novel synergistic rhodium/copper catalyzed three-component
coupling of terminal alkynes and α-diazo ketones (Scheme
1a).13 A copper-catalyzed 1,1-difunctionalization of the terminal
alkynes with diazo esters and sulfonyl hydrazides was developed
by Wang and co-workers (Scheme 1a).14 We have recently
reported a copper-catalyzed 1,1-arylalkylation of terminal
alkynes with diazo esters and organoboronic acids (Scheme
1b).15a Although the cross-coupling of alkyl chlorides with
Received: April 5, 2021
Published: July 27, 2021
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a
terminal alkynes to in situ generate allenes is difficult, a new
approach has been developed through the use of a copper-
catalyzed 1,1-difunctionalization of alkynes with α-haloaceta-
mides and organoboronic acids, terminal alkynes, or fluoromal-
onate derivatives (Scheme 1b).15b,d However, except for the
above-mentioned transformations, the three-component selec-
tive 1,1-difunctionalizations of other types of alkynes have been
scarcely explored due to the competition of 1,2-difunctionaliza-
tion and the cross-coupling reactions of any two of the three
components. Therefore, the development of a novel 1,1-
difunctionalization of alkynes by using one-pot multicomponent
reactions is still highly desired.
The methods for the introduction of fluorine or fluorine-
containing groups into organic molecules have attracted
considerable attention in drug design and screening because of
the unique properties of fluorinated compounds.16 Although
significant advancements have been made in fluorination,17
trifluoromethylation,18 and difluoroalkylation,19 only a few
monofluoroalkylations are available due to the lack of
monofluoroalkylation reagents,20 which are particularly used
for the construction of tertiary fluorides.21 Thus, practical and
efficient approaches to obtain fluorinated compounds from
readily available monofluoroalkylation reagents are still
required. Inspired by our preliminary study on the gem-
difunctionalization of alkynes,15 we envisioned the feasibility
of a copper-catalyzed 1,1-alkylmonofluoroalkylation of alkynes
with diazo compounds and appropriate monofluoroalkylation
reagents under suitable conditions. Herein, we report a novel
copper-catalyzed three-component 1,1-alkylmonofluoro-
alkylation of terminal alkynes through the trapping of an in
situ-generated allene intermediate with 2-fluoro-1,3-dicarbonyl
compounds, wherein a broad substrate scope and excellent
selectivity have been demonstrated (Scheme 1c).
Table 1. Optimization of Reaction Conditions
b
entry
catalyst
base
solvent
T (°C)
yields (%)
1
2
3
4
5
6
7
8
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCl
CuBr
none
CuI
CuI
CuI
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K3PO4
Et3N
K2CO3
K2CO3
K2CO3
none
dioxane
THF
80
80
80
80
80
80
80
80
80
80
80
40
60
77
81
79
86
55
62
66
trace
trace
0
CH3CN
acetone
acetone
acetone
acetone
acetone
acetone
acetone
acetone
acetone
acetone
9
10
11
12
13
0
15
32
K2CO3
K2CO3
a
Reactions were carried out with 1a (0.5 mmol), 2a (0.6 mmol), 3a
(0.75 mmol), catalyst (10 mol %), and base (0.75 mmol) in 1.0 mL of
solvent in a N2 atmosphere at 80 °C (an oil bath) for 2.0 h, unless
b
noted otherwise. Yield of the isolated product.
hindrance had no obvious effect on the reaction. Other electron-
withdrawing groups, such as para-bromo and COOMe
ethynylbenzenes, produced 4h and 4i in 76 and 70% yields,
respectively. Alkynes bearing electron-donating functional
groups on the aromatic rings were also efficiently transformed
into desired 1,1-alkylmonofluoroalkylation products 4j−4q in
good yields with exclusive regioselectivities. In addition, alkynes
bearing a thiophene or pyridine moiety underwent a 1,1-
alkylmonofluoroalkylation reaction to give corresponding
products 4r−4t in 45−77% yields. Alkyl propargyl ethers 1u,
N-propargyl amides 1v, and conjugated enynes 1w underwent
this 1,1-alkylmonofluoroalkylation reaction to provide corre-
sponding products 4u−4w in 70−75% yields, respectively. The
nonactivated aliphatic alkynes 1x−1z also provided desired
product 4x−4z in 35−40% yields. To demonstrate the potential
application of this reaction, the late-stage modification of
biologically relevant compounds containing alkyne groups was
conducted. Subjecting the citronellol-derived alkyne 1aa to the
optimized reaction conditions produced 4aa in 85% yield.
Alkyne derived from D,L-α-tocopherol 1ab was readily trans-
formed into the desired product 4ab in 70% yield. In addition,
this 1,1-alkylmonofluoroalkylation reaction could also be
extended to the purine-based alkyne derivative. It should be
noted that only E isomers were isolated, and no Z-isomer was
observed in all cases.
Dimethyl and diethyl 2-fluoromalonate are useful
monofluoroalkylation reagents for the incorporation of
polyfunctional fluorinated building blocks into organic mole-
cules. However, to our knowledge, other fluoromalonate
derivatives as monofluoroalkylation reagents are exceedingly
rare.22 Further exploration of the versatility and efficiency of
monofluoroalkylation reagents is still highly desired. Encour-
aged by the broad alkyne scope, various 2-fluoro-1,3-dicarbonyl
compounds as monofluoroalkylation reagents were examined
next (Table 3). A treatment of diethyl 2-fluoromalonate with 1a
and 2a under optimized reaction conditions gave product 5b in a
78% yield. When N,N-diethyl-2-fluoro-3-oxobutanamide and 2-
fluoro-1-morpholinobutane-1,3-dione were subjected to opti-
RESULTS AND DISCUSSION
■
Initially, ethynylbenzene 1a, ethyl 2-diazoacetate 2a, and
dimethyl 2-fluoromalonate 3a were chosen as the model
substrates for the optimization of the reaction conditions
(Table 1). The reaction system was first subjected to conditions
similar to those reported by our group for the 1,1-
difunctionalization of alkynes, and desired product 4a was
obtained in a 77% yield (Table 1, entry 1). To our delight, the
yield increased to 86% when the reaction was performed in
acetone, and other solvents such as THF and CH3CN were also
effective (Table 1, entries 2−4). Encouraged by this result, we
surveyed other bases, such as Na2CO3, K3PO4, and Et3N, and
the results demonstrated that K2CO3 was still the best choice
(Table 1, entries 5−7). Unfortunately, other catalysts, such as
CuCl and CuBr, were unsuitable for the reaction (Table 1,
entries 8 and 9). Control experiments indicated that none of the
1,1-alkylmonofluoroalkylation products was obtained in the
absence of CuI or K2CO3 (Table 1, entries 10 and 11). In
addition, decreasing the reaction temperature resulted in
significantly lower yields (Table 1, entries 12 and 13).
The scope of the 1,1-alkylmonofluoroalkylation was then
investigated under optimized reaction conditions, and the
results are summarized in Table 2. The reaction of ethyl 2-
diazoacetate, dimethyl 2-fluoromalonate, and a variety of
terminal alkynes produced desired 1,1-alkylmonofluoro-
alkylation products 4 in 35−91% yields. The ortho-, meta-, and
para-fluoro, chloro ethynylbenzenes underwent this 1,1-
alkylmonofluoroalkylation reaction to provide the correspond-
ing 4b−4g products in similar yields, which suggested that steric
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a
Table 2. Scope of Alkynes in the 1,1-Alkylmonofluoroalkylation
a
Reactions were carried out with 1 (0.5 mmol), 2a (0.6 mmol), 3a (0.75 mmol), CuI (10 mol %), and K2CO3 (0.75 mmol) in acetone (1.0 mL) in
a N2 atmosphere at 80 °C (an oil bath) for 2.0 h. The percentage is the yield of the isolated product.
mized reaction conditions, desired products 5c and 5d were
obtained in 56% and 70% yields, respectively. Surprisingly,
deacetylated product 5e was obtained in a 70% yield when the
reaction of 1a with 2a and ethyl 2-fluoro-3-oxobutanoate 3e was
performed under optimized reaction conditions. Moreover, 2-
fluoro-3-oxo-N-phenylbutanamide 3f, which is easily synthe-
sized from 3-oxo-N-phenylbutanamide and selectfluor,23 could
smoothly proceed with the 1,1-arylalkylation reaction to
produce product 5f by removing the acetyl group. 2-Fluoro-
acetoacetamides with either electron-donating or electron-
withdrawing functional groups on the aromatic rings could
also be converted to products 5g−5j in good yields. To obtain
some undeacetylated products, the reaction conditions were
further optimized. To our satisfaction, when replacing K2CO3
with K3PO4, desired products 5k−5p were obtained in 52−78%
yields. The configuration of 5m (CCDC 1972687) was further
confirmed to be the 1,1-alkylmonofluoroalkylated compound by
an X-ray crystallographic analysis (see the Supporting
Information). We next examined the substrate scope of diazo
compounds. The reactions of methyl aryldiazoacetates and 2-
diazo-1-phenylethanone were inferior to ethyl 2-diazoacetate
under identical conditions. When the reaction was performed in
THF, methyl aryldiazoacetates were shown to be suitable
substrates, affording the corresponding products (6b and 6c) in
39% and 40% yield, respectively. 2-Diazo-1-phenylethanone was
also converted to the 1,1-alkylmonofluoroalkylation products 6d
and 6d′ in 1,4-dioxane. The formation of 6d′ is probably
attributed to further isomerization of 6d in the presence of a
base.13
To further extend the practicality of this method, the large-
scale reaction (2 and 5 mmol) was conducted. As shown in
Scheme 2, the corresponding product 4a was isolated in 81%
and 75% yield, respectively. To demonstrate the synthetic
applications, further transformations of the 1,1-
alkylmonofluoroalkylation products have been performed.
Densely substituted furans are privileged motifs in natural
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a
Table 3. Scope of Monofluoroalkylation Reagents and Diazo Compounds in 1,1-Alkylmonofluoroalkylation
a
Reactions were carried out with 1a (0.5 mmol), 2 (0.6 mmol), 3 (0.75 mmol), CuI (10 mol %), and K2CO3 (0.75 mmol) in acetone (1.0 mL) in a
b
N2 atmosphere at 80 °C (an oil bath) for 2.0 h. The percentage is the yield of the isolated product. K3PO4 (0.25 mmol) was used instead of
K2CO3, 0.5 h. K3PO4 (0.75 mmol) was used instead of K2CO3. THF (1.0 mL) was used instead of acetone, 100 °C (an oil bath), 0.5 h. 1,4-
Dioxane (1.0 mL) was used instead of acetone, 100 °C (an oil bath), 0.5 h.
c
d
e
Scheme 2. Large-Scale Reaction and Further Transformations of Product 5
products, synthetic pharmaceuticals, and agrochemicals.24 To
our delight, 5d, 5l, and 5m could be converted to
tetrasubstituted furan 7a−7c in 50−85% yields by treatment
with TfOH in toluene.
Subsequently, we performed some control experiments to
elucidate the reaction mechanism (Scheme 3). The reaction of
ethyl 4-phenylbut-3-ynoate 8 or ethyl 4-phenylbuta-2,3-
dienoate 9 with dimethyl 2-fluoromalonate under the standard
reaction conditions generated product 4a in 68% and 70% yield,
respectively, indicating that 8 and 9 were the intermediates for
this transformation (Scheme 3a,b).25 Interestingly, without the
copper catalyst, product 4a was obtained in a similar yield in the
reaction of 8 and 9 with 3a. These result further indicated that
the nucleophilic addition of allenes as key intermediates should
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Scheme 3. Control Experiments
be involved. Furthermore, the addition of 2,2,6,6-tetramethyl-1-
piperidinyloxyl (TEMPO) or 2,6-ditert-butyl-4-methylphenol
(BHT) into the model reaction mixture did not obviously
decrease the yield of 4a, which indicated that a radical process
was excluded in this reaction (Scheme 3c).
Therefore, we propose a plausible mechanistic pathway based
on the experimental results in Scheme 4. Initially, a treatment of
type C−C bond cleavage reactions of products 5k-5p under the
conditions of K2CO3. The high stereoselectivity may be
explained on the basis of the nucleophilic addition of
intermediate 8: the monofluoroalkyl group prefers nucleophilic
addition from the opposite side of the phenyl to avoid steric
interactions.28
CONCLUSIONS
■
Scheme 4. Plausible Mechanistic Pathway
In conclusion, this paper describes a simple and practical copper-
catalyzed three-component 1,1-alkylmonofluoroalkylation of
terminal alkynes, diazo esters or diazo ketones, and 2-fluoro-
1,3-dicarbonyl compounds for the first time. The broad
substrate scope, inexpensive and easily available catalytic system,
and excellent selectivity make the proposed procedure very
attractive for the synthesis of (E)-β-monofluoroalkyl-β,γ-
unsaturated esters or ketones bearing quaternary C−F centers.
We have prepared a variety of monofluoroalkylation reagents
that will play an important role in the incorporation of
polyfunctional fluorinated building blocks into organic mole-
cules. Mechanistic investigations indicate that an in situ-
generated allene intermediate was trapped by 2-fluoro-1,3-
dicarbonyl compounds. Further studies are ongoing in our
laboratory.
EXPERIMENTAL SECTION
■
General Information. All deuterated solvents were purchased from
1
Cambridge Isotope Laboratories. H NMR, 13C{1H} NMR and 19F
NMR spectra were recorded at 25 °C on a Bruker Advance 400
̈
spectrometer (1H: 400 MHz, 13C{1H}:100 MHz, and 19F:376 MHz).
1H NMR chemical shifts were determined relative to internal (CH3)4Si
(TMS) at δ 0.00 ppm or to the signal of the residual protonated solvent:
CDCl3 at δ 7.26 ppm. 13C{1H} NMR chemical shifts were determined
relative to the signal of the solvent: CDCl3 at δ 77.00 ppm. Data for 1H,
13C{1H}, 19F NMR were recorded as follows: chemical shift (δ, ppm),
multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, q =
quartet, dd = doublet of doublets, dt = doublet of triplets), integration,
and coupling constants (Hz). High-resolution mass data were recorded
on a Waters LCT PremierxeTM (USA). Single-crystal X-ray diffraction
was carried out on a Bruker Smart Apex II diffractometer system.
Materials and Methods. Unless otherwise stated, starting
materials were purchased from Aldrich or Energy-Chemical Limited
and used as supplied without further purification. Solvents were used
directly without further purification. The following starting materials
CuI with K2CO3 generates copper acetylide, which reacts with
ethyl 2-diazoacetate to afford copper carbene A. Then a
migratory insertion of the alkynyl group into the copper carbene
gives intermediate B, and subsequent protonation leads to
intermediate 8 and regenerates the Cu(I) catalyst.26 After
rearrangement, 8 can be transformed to intermediate 9,26c,27
which was trapped by dimethyl 2-fluoromalonate to afford
product 4a in the presence of K2CO3. Deacetylated products
5e−5j were formed probably via the subsequent retro-Claisen-
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were prepared according to the procedures described previously in the
literature: 825a and 9.29 The alkynes 1,1-alkylmonofluoroalkylation
reactions were performed under nitrogen atmosphere in flame-dried
flasks. All reactions were monitored by thin layer chromatography
(TLC) with Taizhou GF254 silica gel coated plates. Flash column
chromatography was carried out using 200−300 mesh silica gel at
increased pressure.
General Procedure for Preparation of 2b and 2c (2b as an
Example). Following the general procedure described previously in the
literature,30 to a mixture of methyl 2-phenylacetate (0.72 mL, 5 mmol)
and tosyl azide (1.73 mL, 7.5 mmol) in anhydrous CH3CN (12.5 mL)
was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (1.12 mL, 7.5
mmol). The reaction mixture was stirred at room temperature for
overnight. Upon complete consumption of the starting materials, the
reaction mixture was quenched with saturated aqueous solution of
NH4Cl (3.0 mL), extracted with CH2Cl2 (3 × 10 mL), washed with
brine (3 × 5 mL), dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified by flash
chromatography to give compound 2b (0.79 g, 90%).
General Procedure for Preparation of 2d. Following the general
procedure described previously in the literature,31 to a mixture of 1,3-
diphenylpropane-1,3-dione (1.12 g, 5 mmol) and tosyl azide (1.15 mL,
5.0 mmol) in EtOH (5.0 mL) was added MeNH2 solution (40% aq.
solution, 6.0 mmol). The reaction mixture was stirred at room
temperature for 25 min. The solvent was removed in vacuo at 35 °C.
The crude product was purified by a flash chromatography using
EtOAc/hexane as eluent to provide desired products 2d (0.64 g, 88%).
General Procedure for Preparation of 3c, 3d, 3f−3j (3f as
Example). Following the general procedure described previously in the
literature,23 to a solution of 3-oxo-N-phenylbutanamide (0.35 g, 2.0
mmol) in PEG-400 (6 mL) at room temperature was added selectfluor
(0.78 g, 2.2 mmol) in one portion. The reaction mixture was well stirred
at 60 °C (an oil bath) for 8.0 h. After completion of the reaction (TLC
monitoring), the mixture was quenched by water and extracted with
diethyl ether (15 mL × 4). The solvent was removed under reduced
pressure, and the residue was purified by a short flash silica gel column
chromatography to give compound 3f (0.34 g, 87%).
General Procedure for 1,1-Alkylmonofluoroalkylation of
Terminal Alkynes (4a as an Example). To a solution of the ethyl
2-diazoacetate 2a (66 μL, 0.6 mmol) in acetone (1.0 mL) was added the
ethynylbenzene 1a (57 μL, 0.50 mmol), dimethyl 2-fluoromalonate 3a
(117.3 mg, 0.75 mmol), CuI (9.5 mg, 0.05 mmol), and K2CO3 (103.6
mg, 0.75 mmol) under N2 in screw-cap test tube. The reaction mixture
was stirred at 80 °C (an oil bath) for 2.0 h. After the reaction finished,
the reaction mixture was cooled to room temperature and quenched by
water. The mixture was extracted with EtOAc (3.0 mL × 3), the
combined organic phases were dried over anhydrous Na2SO4, and the
solvent was evaporated under vacuum. The residue was purified by
column chromatography to give the corresponding products 4a (146.0
mg, 86%).
General Procedure for Synthesis of Tetrasubstituted Furan
7a−7c (7a as an Example). To a 10 mL screw capped vial equipped
with a magnetic stirring bar was added compound 5d (113 mg, 0.3
mmol), TfOH (27 μL, 0.3 mmol), and toluene (0.6 mL). The reaction
tube was sealed with a Teflon screw cap. The reaction mixture was
vigorously stirred at 80 °C (an oil bath) for 2.0 h. The mixture was
allowed to cool to room temperature. Triethylamine (42 μL) was
added, and the product 7a (91.0 mg, 85%) was isolated by flash
chromatography.
Control Experiment (Scheme 3a). To a solution of 8 (94.0 mg, 0.5
mmol) in acetone (1.0 mL) was added 3a (117.3 mg, 0.75 mmol), CuI
(9.5 mg, 0.05 mmol), and K2CO3 (103.6 mg, 0.75 mmol) under N2 in
screw-cap test tube. The reaction mixture was stirred at 80 °C (an oil
bath) for 2.0 h. After the reaction finished, the reaction mixture was
cooled to room temperature and quenched by water. The mixture was
extracted with EtOAc (3.0 mL × 3), the combined organic phases were
dried over anhydrous Na2SO4, and the solvent was evaporated under
vacuum. The residue was purified by column chromatography to give
the corresponding products 4a (115.0 mg, 68%). This results suggested
that 8 might be the active intermediate.
To a solution of 8 (94.0 mg, 0.5 mmol) in acetone (1.0 mL) was
added 3a (117.3 mg, 0.75 mmol) and K2CO3 (103.6 mg, 0.75 mmol)
under N2 in screw-cap test tube. The reaction mixture was stirred at 80
°C (an oil bath) for 2.0 h. After the reaction finished, the reaction
mixture was cooled to room temperature and quenched by water. The
mixture was extracted with EtOAc (3.0 mL × 3), the combined organic
phases were dried over anhydrous Na2SO4, and the solvent was
evaporated under vacuum. The residue was purified by column
chromatography to give the corresponding products 4a (123.5 mg,
73%).
Control Experiment (Scheme 3b). To a solution of 9 (94.0 mg, 0.5
mmol) in acetone (1.0 mL) was added 3a (117.3 mg, 0.75 mmol), CuI
(9.5 mg, 0.05 mmol), and K2CO3 (103.6 mg, 0.75 mmol) under N2 in
screw-cap test tube. The reaction mixture was stirred at 80 °C (an oil
bath) for 2.0 h. After the reaction finished, the reaction mixture was
cooled to room temperature and quenched by water. The mixture was
extracted with EtOAc (3.0 mL × 3), the combined organic phases were
dried over anhydrous Na2SO4, and the solvent was evaporated under
vacuum. The residue was purified by column chromatography to give
the corresponding products 4a (118.0 mg, 70%). This results suggested
that 9 might be the active intermediate.
To a solution of 9 (94.0 mg, 0.5 mmol) in acetone (1.0 mL) was
added 3a (117.3 mg, 0.75 mmol), and K2CO3 (103.6 mg, 0.75 mmol)
under N2 in screw-cap test tube. The reaction mixture was stirred at 80
°C (an oil bath) for 2.0 h. After the reaction finished, the reaction
mixture was cooled to room temperature and quenched by water. The
mixture was extracted with EtOAc (3.0 mL × 3), the combined organic
phases were dried over anhydrous Na2SO4, and the solvent was
evaporated under vacuum. The residue was purified by column
chromatography to give the corresponding products 4a (126.7 mg,
75%). This results suggested that the nucleophilic addition of allenes as
key intermediates should be involved.
Control Experiment (Scheme 3c). To a solution of the ethyl 2-
diazoacetate 2a (66 μL, 0.6 mmol) in acetone (1.0 mL) was added the
ethynylbenzene 1a (57 μL, 0.50 mmol), dimethyl 2-fluoromalonate 3a
(117.3 mg, 0.75 mmol), CuI (9.5 mg, 0.05 mmol), K2CO3 (103.6 mg,
0.75 mmol), and TEMPO (156.0 mg, 1.0 mmol) under N2 in screw-cap
test tube. The reaction mixture was stirred at 80 °C (an oil bath) for 2.0
h. After the reaction finished, the reaction mixture was cooled to room
temperature and quenched by water. The mixture was extracted with
EtOAc (3.0 mL × 3), the combined organic phases were dried over
anhydrous Na2SO4, and the solvent was evaporated under vacuum. The
residue was purified by column chromatography to give the
corresponding products 4a (122.0 mg, 72%).
To a solution of the ethyl 2-diazoacetate 2a (66 μL, 0.6 mmol) in
acetone (1.0 mL) was added the ethynylbenzene 1a (57 μL, 0.50
mmol), dimethyl 2-fluoromalonate 3a (117.3 mg, 0.75 mmol), CuI (9.5
mg, 0.05 mmol), K2CO3 (103.6 mg, 0.75 mmol), and BHT (220.0 mg,
1.0 mmol) under N2 in screw-cap test tube. The reaction mixture was
stirred at 80 °C (an oil bath) for 2.0 h. After the reaction finished, the
reaction mixture was cooled to room temperature and quenched by
water. The mixture was extracted with EtOAc (3.0 mL × 3), the
combined organic phases were dried over anhydrous Na2SO4, and the
solvent was evaporated under vacuum. The residue was purified by
column chromatography to give the corresponding products 4a (127.0
mg, 75%).
(E)-3-Ethyl 1,1-dimethyl 2-benzylidene-1-fluoropropane-1,1,3-
tricarboxylate 4a. Yellow oil (146.0 mg, 86%). Petroleum ether/
ethyl acetate = 30/1 as eluent for column chromatography. 1H NMR
(400 MHz, CDCl3): δ 7.36−7.27 (m, 5H), 7.11 (s, 1H), 4.13 (q, 2H, J
= 7.2 Hz), 3.87 (s, 6H), 3.46 (d, 2H, J = 2.0 Hz), 1.24 (t, 3H, J = 7.2
Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 170.5, 165.5 (d, J = 26.0
Hz), 135.1, 133.6 (d, J = 11.0 Hz), 128.4, 128.3, 127.9, 127.1 (d, J = 20.0
Hz), 94.8 (d, J = 201.0 Hz), 60.9, 53.5, 33.7 (d, J = 5.0 Hz), 13.9. 19F
NMR (376 MHz, CDCl3): δ −159.9. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C17H20FO6 339.1244; Found 339.1246.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(2-fluorobenzylidene)-
propane-1,1,3-tricarboxylate 4b. Yellow oil (160.5 mg, 90%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 7.33−7.28 (m,
10048
https://doi.org/10.1021/acs.joc.1c00789
J. Org. Chem. 2021, 86, 10043−10054

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
2H), 7.14−7.05 (m, 3H), 4.12 (q, 2H, J = 7.2 Hz), 3.89 (s, 6H), 3.43 (d,
2H, J = 1.6 Hz), 1.23 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.3, 165.4 (d, J = 25.0 Hz), 160.0 (d, J = 247.0 Hz), 130.0,
129.9 (d, J = 3.0 Hz), 129.4 (d, J = 21.0 Hz), 127.1 (dd, J1 = 3.0 Hz, J2 =
11.0 Hz), 123.9 (d, J = 4.0 Hz), 122.9 (d, J = 15.0 Hz), 115.5 (d, J = 21.0
Hz), 94.7 (d, J = 201.0 Hz), 61.0, 53.6, 33.9 (d, J = 5.0 Hz), 13.9. 19F
NMR (376 MHz, CDCl3): δ −160.4, −113.6. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C17H19F2O6 357.1150; Found 357.1146.
8.0 Hz), 7.04 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz), 3.87 (s, 6H), 3.42 (d, 2H,
J = 1.6 Hz), 1.24 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.3, 165.3 (d, J = 25.0 Hz), 134.0, 132.5 (d, J = 12.0 Hz),
131.5, 130.1, 127.9 (d, J = 20.0 Hz), 122.1, 94.7 (d, J = 202.0 Hz), 61.0,
53.6, 33.7 (d, J = 5.0 Hz), 14.0. 19F NMR (376 MHz, CDCl3): δ −160.1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H19BrFO6 417.0349,
419.0329; Found 417.0352, 419.0341.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(4-(methoxycarbonyl)-
benzylidene)propane-1,1,3-tricarboxylate 4i. Yellow oil (138.6 mg,
70%). Petroleum ether/ethyl acetate = 30/1 as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 8.02 (d, 2H, J = 8.4
Hz), 7.37 (d, 2H, J = 8.4 Hz), 7.15 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz), 3.92
(s, 3H), 3.89 (s, 6H), 3.45 (d, 2H, J = 2.0 Hz), 1.25 (t, 3H, J = 7.2 Hz).
13C{1H} NMR (100 MHz, CDCl3): δ 170.2, 166.4, 165.3 (d, J = 25.0
(E)-3-Ethyl 1,1-dimethyl 2-(2-chlorobenzylidene)-1-fluoropro-
pane-1,1,3-tricarboxylate 4c. Yellow oil (152.6 mg, 82%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 7.41−7.35 (m, 2H), 7.28−7.25 (m, 2H),
7.14 (s, 1H), 4.11 (q, 2H, J = 7.2 Hz), 3.89 (s, 6H), 3.36 (d, 2H, J = 2.0
Hz), 1.23 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ
170.0, 165.1 (d, J = 26.0 Hz), 133.4 (d, J = 3.0 Hz), 131.3, 131.2, 129.6,
129.2, 128.9, 128.7, 126.5, 94.4 (d, J = 200.0 Hz), 60.7, 53.3, 33.5 (d, J =
6.0 Hz), 13.7. 19F NMR (376 MHz, CDCl3): δ −160.8. HRMS (ESI-
TOF) m/z: [M + Na]+ Calcd for C17H18ClFNaO6 395.0674; Found
395.0690.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(3-fluorobenzylidene)-
propane-1,1,3-tricarboxylate 4d. Yellow oil (160.2 mg, 90%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 7.34−7.29 (m,
1H), 7.08−6.98 (m, 4H), 4.15 (q, 2H, J = 7.2 Hz), 3.88 (s, 6H), 3.44 (d,
2H, J = 2.0 Hz), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.4, 165.5 (d, J = 25.0 Hz), 162.7 (d, J = 245.0 Hz), 137.4
(d, J = 8.0 Hz), 132.6 (dd, J1 = 2.0 Hz, J2 = 11.0 Hz), 130.0 (d, J = 9.0
Hz), 128.4 (d, J = 20.0 Hz), 124.4 (d, J = 3.0 Hz), 115.5 (d, J = 22.0 Hz),
114.9 (d, J = 21.0 Hz), 94.8 (d, J = 202.0 Hz), 61.2, 53.7, 33.8 (d, J = 5.0
Hz), 14.1. 19F NMR (376 MHz, CDCl3): δ −112.7, −160.3. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C17H19F2O6 357.1150; Found
357.1139.
Hz), 139.8, 132.6 (d, J = 12.0 Hz), 129.5, 129.4, 128.8 (d, J = 20.0 Hz),
128.4, 94.6 (d, J = 202.0 Hz), 61.0, 53.6, 52.0, 33.7 (d, J = 4.0 Hz), 13.9.
19F NMR (376 MHz, CDCl3): δ −160.4. HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C19H21FNaO8 419.1118; Found 419.1123.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(2-methoxybenzylidene)-
propane-1,1,3-tricarboxylate 4j. Yellow oil (143.6 mg, 78%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 7.31−7.25 (m,
2H), 7.14 (s, 1H), 6.94−6.86 (m, 2H), 4.13 (q, 2H, J = 7.2 Hz), 3.88 (s,
6H), 3.80 (s, 3H), 3.43 (d, 2H, J = 2.4 Hz), 1.24 (t, 3H, J = 7.2 Hz).
13C{1H} NMR (100 MHz, CDCl3): δ 170.9, 165.7 (d, J = 26.0 Hz),
157.2, 130.4 (d, J = 11.0 Hz), 129.5 (d, J = 14.0 Hz), 126.8, 126.6, 124.1,
120.2, 110.6, 95.1 (d, J = 200.0 Hz), 60.8, 55.4, 53.5, 34.0 (d, J = 5.0
Hz), 14.0. 19F NMR (376 MHz, CDCl3): δ −159.8. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C18H22FO7 369.1350; Found 369.1342.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(4-methylbenzylidene)-
propane-1,1,3-tricarboxylate 4k. Yellow oil (149.5 mg, 85%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
(E)-3-Ethyl 1,1-dimethyl 2-(3-chlorobenzylidene)-1-fluoropro-
chromatography. H NMR (400 MHz, CDCl3): δ 7.18 (d, 2H, J =
pane-1,1,3-tricarboxylate 4e. Yellow oil (169.2 mg, 91%). Petroleum
8.4 Hz), 7.15 (d, 2H, J = 8.0 Hz), 7.06 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz),
3.86 (s, 6H), 3.46 (d, 2H, J = 1.2 Hz), 2.33 (s, 3H), 1.24 (t, 3H, J = 7.2
Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 170.5, 165.5 (d, J = 26.0
Hz), 137.7, 133.5 (d, J = 11.0 Hz), 132.1, 128.9, 128.3, 126.3 (d, J = 21.0
Hz), 94.8 (d, J = 200.0 Hz), 60.8, 53.4, 33.6 (d, J = 4.0 Hz), 20.9, 13.9.
19F NMR (376 MHz, CDCl3): δ −159.8. HRMS (ESI-TOF) m/z: [M +
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 7.31−7.28 (m, 3H), 7.17 (d, 1H, J = 3.6
Hz), 7.06 (s, 1H), 4.15 (q, 2H, J = 7.2 Hz), 3.88 (s, 6H), 3.43 (d, 2H, J =
1.2 Hz), 1.26 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ
170.3, 165.4 (d, J = 26.0 Hz), 136.9, 134.3, 132.3 (d, J = 11.0 Hz), 129.7,
128.5 (d, J = 20.0 Hz), 128.5, 128.0, 126.6, 94.7 (d, J = 201.0 Hz), 61.1,
53.6, 33.8 (d, J = 4.0 Hz), 14.0. 19F NMR (376 MHz, CDCl3): δ −160.4.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H19ClFO6 373.0854;
Found 373.0851.
Na]+ Calcd for C18H21FNaO6 375.1220; Found 375.1234.
(E)-3-Ethyl 1,1-dimethyl 2-(4-ethylbenzylidene)-1-fluoropropane-
1,1,3-tricarboxylate 4l. Yellow oil (133.7 mg, 73%). Petroleum ether/
ethyl acetate = 30/1 as eluent for column chromatography. 1H NMR
(400 MHz, CDCl3): δ 7.21 (d, 2H, J = 8.4 Hz), 7.18 (d, 2H, J = 8.0 Hz),
7.06 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz), 3.87 (s, 6H), 3.47 (d, 2H, J = 1.2
Hz), 2.64 (q, 2H, J = 7.6 Hz), 1.26−1.21 (m, 6H). 13C{1H} NMR (100
MHz, CDCl3): δ 170.6, 165.6 (d, J = 26.0 Hz), 144.1, 133.6 (d, J = 11.0
Hz), 132.4, 128.5, 127.8, 126.3 (d, J = 20.0 Hz), 94.9 (d, J = 200.0 Hz),
60.8, 53.4, 33.7 (d, J = 5.0 Hz), 28.4, 15.3, 13.9. 19F NMR (376 MHz,
CDCl3): δ −159.8. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C19H23FNaO6 389.1376; Found 389.1369.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(4-fluorobenzylidene)-
propane-1,1,3-tricarboxylate 4f. Yellow oil (156.8 mg, 88%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 7.28 (dd, 2H, J1 =
5.2 Hz, J2 = 8.4 Hz), 7.07−7.02 (m, 3H), 4.15 (q, 2H, J = 7.2 Hz), 3.88
(s, 6H), 3.43 (d, 2H, J = 1.6 Hz), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 170.4, 165.4 (d, J = 26.0 Hz), 162.2 (d, J =
247.0 Hz), 132.6 (d, J = 11.0 Hz), 131.1 (d, J = 3.0 Hz), 130.3 (d, J = 8.0
Hz), 127.2 (d, J = 21.0 Hz), 115.3 (d, J = 21.0 Hz), 94.8 (d, J = 201.0
Hz), 61.0, 53.5, 33.6 (d, J = 4.0 Hz), 13.9. 19F NMR (376 MHz,
CDCl3): δ −113.4, −160.0. HRMS (ESI-TOF) m/z: [M + H]+ Calcd
for C17H19F2O6 357.1150; Found 357.1141.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(4-propylbenzylidene)-
propane-1,1,3-tricarboxylate 4m. Yellow oil (136.8 mg, 72%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 7.21 (d, 2H, J =
8.0 Hz), 7.16 (d, 2H, J = 8.0 Hz), 7.06 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz),
3.86 (s, 6H), 3.48 (d, 2H, J = 1.6 Hz), 2.57 (t, 2H, J = 7.6 Hz), 1.67−
1.58 (m, 2H), 1.24 (t, 3H, J = 7.2 Hz), 0.93 (t, 3H, J = 7.6 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 170.5, 165.5 (d, J = 26.0 Hz), 142.5, 133.5,
133.4, 132.3, 128.4 (d, J = 2.0 Hz), 126.2 (d, J = 20.0 Hz), 94.9 (d, J =
201.0 Hz), 60.7, 53.3, 37.5, 33.7 (d, J = 4.0 Hz), 24.2, 13.9, 13.5. 19F
NMR (376 MHz, CDCl3): δ −159.8. HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C20H25FNaO6 403.1533; Found 403.1536.
(E)-3-Ethyl 1,1-dimethyl 2-(4-chlorobenzylidene)-1-fluoropro-
pane-1,1,3-tricarboxylate 4g. Yellow oil (150.8 mg, 81%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 7.33 (d, 2H, J = 8.4 Hz), 7.23 (d, 2H, J =
8.4 Hz), 7.06 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz), 3.88 (s, 6H), 3.43 (d, 2H,
J = 1.6 Hz), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.4, 165.4 (d, J = 26.0 Hz), 133.9, 133.6, 132.5 (d, J = 11.0
Hz), 129.8, 128.6, 127.8 (d, J = 20.0 Hz), 94.7 (d, J = 201.0 Hz), 61.0,
53.6, 33.7 (d, J = 5.0 Hz), 14.0. 19F NMR (376 MHz, CDCl3): δ −160.1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H19ClFO6 373.0854;
Found 373.0847.
(E)-3-Ethyl 1,1-dimethyl 2-(4-butylbenzylidene)-1-fluoropro-
pane-1,1,3-tricarboxylate 4n. Yellow oil (151.8 mg, 77%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 7.21 (d, 2H, J = 8.0 Hz), 7.16 (d, 2H, J =
8.0 Hz), 7.06 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz), 3.86 (s, 6H), 3.48 (d, 2H,
J = 1.6 Hz), 2.60 (t, 2H, J = 7.6 Hz), 1.60−1.55 (m, 2H), 1.37−1.31 (m,
2H), 1.24 (t, 3H, J = 7.2 Hz), 0.92 (t, 3H, J = 7.6 Hz). 13C{1H} NMR
(E)-3-Ethyl 1,1-dimethyl 2-(4-bromobenzylidene)-1-fluoropro-
pane-1,1,3-tricarboxylate 4h. Yellow oil (158.4 mg, 76%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 7.48 (d, 2H, J = 8.4 Hz), 7.17 (d, 2H, J =
10049
https://doi.org/10.1021/acs.joc.1c00789
J. Org. Chem. 2021, 86, 10043−10054

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(100 MHz, CDCl3): δ 170.5, 165.5 (d, J = 25.0 Hz), 142.7, 133.5, 133.4,
132.3, 128.3 (d, J = 9.0 Hz), 126.3 (d, J = 21.0 Hz), 94.9 (d, J = 200.0
Hz), 60.7, 53.3, 35.1, 33.7 (d, J = 4.0 Hz), 33.3, 22.1, 13.9, 13.7. 19F
NMR (376 MHz, CDCl3): δ −159.8. HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C21H27FNaO6 417.1689; Found 417.1678.
MHz, CDCl3): δ −160.4. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C16H19FNO6 340.1196; Found 340.1186.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(2-methoxyethylidene)-
propane-1,1,3-tricarboxylate 4u. Yellow oil (108.5 mg, 71%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 6.12 (t, 1H, J = 6.0
Hz), 4.11−4.03 (m, 4H), 3.80 (s, 6H), 3.29 (s, 3H), 3.28 (s, 2H), 1.21
(t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 169.7, 165.3
(d, J = 26.0 Hz), 132.1 (d, J = 11.0 Hz), 127.2 (d, J = 20.0 Hz), 94.5 (d, J
= 200.0 Hz), 68.7, 61.0, 58.3, 53.4, 33.0 (d, J = 4.0 Hz), 14.0. 19F NMR
(376 MHz, CDCl3): δ −159.8. HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C13H19FNaO7 329.1013; Found 329.1005.
(E)-3-Ethyl 1,1-dimethyl 2-(2-((tert-butoxycarbonyl)amino)-
ethylidene)-1-fluoropropane-1,1,3-tricarboxylate 4v. Yellow oil
(137.0 mg, 70%). Petroleum ether/ethyl acetate = 30/1 as eluent for
column chromatography. 1H NMR (400 MHz, CDCl3): δ 6.04 (t, 1H, J
= 7.2 Hz), 4.83 (s, 1H), 4.12 (d, 2H, J = 7.2 Hz), 3.87−3.76 (m, 8H),
3.33 (s, 2H), 1.42 (s, 9H), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100
MHz, CDCl3): δ 170.0, 165.3 (d, J = 26.0 Hz), 155.7, 131.6 (d, J = 11.0
Hz), 127.5 (d, J = 19.0 Hz), 94.6 (d, J = 201.0 Hz), 79.5, 61.2, 53.6, 38.3,
32.6 (d, J = 3.0 Hz), 28.3, 14.1. 19F NMR (376 MHz, CDCl3): δ −159.4.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H27FNO8 392.1721;
Found 392.1711.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(2-methylallylidene)propane-
1,1,3-tricarboxylate 4w. Yellow oil (113.2 mg, 75%). Petroleum ether/
ethyl acetate = 30/1 as eluent for column chromatography. 1H NMR
(400 MHz, CDCl3): δ 6.39 (s, 1H), 5.04 (s, 1H), 4.92 (s, 1H), 4.08 (q,
2H, J = 7.2 Hz), 3.80 (s, 6H), 3.44 (s, 2H), 1.80 (s, 3H), 1.20 (t, 3H, J =
7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 170.6, 165.6 (d, J = 26.0
Hz), 139.8, 135.2 (d, J = 10.0 Hz), 125.5 (d, J = 20.0 Hz), 116.9, 94.8 (d,
J = 201.0 Hz), 60.8, 53.4, 33.6 (d, J = 5.0 Hz), 22.6, 14.0. 19F NMR (376
MHz, CDCl3): δ −160.1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C14H20FO6 303.1244; Found 303.1240.
(E)-3-Ethyl 1,1-dimethyl 2-(4-(tert-butyl)benzylidene)-1-fluoro-
propane-1,1,3-tricarboxylate 4o. Yellow oil (155.7 mg, 79%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 7.37 (d, 2H, J =
8.4 Hz), 7.23 (d, 2H, J = 8.4 Hz), 7.06 (s, 1H), 4.15 (q, 2H, J = 7.2 Hz),
3.87 (s, 6H), 3.48 (d, 2H, J = 2.0 Hz), 1.31 (s, 9H), 1.25 (t, 3H, J = 7.2
Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 170.7, 165.7 (d, J = 26.0
Hz), 151.1, 133.5 (d, J = 11.0 Hz), 132.2, 128.4, 126.4 (d, J = 20.0 Hz),
125.3, 95.0 (d, J = 200.0 Hz), 60.9, 53.5, 34.5, 33.9 (d, J = 5.0 Hz), 31.3,
14.0. 19F NMR (376 MHz, CDCl3): δ −159.7. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C21H27FNaO6 417.1689; Found 417.1680.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(4-pentylbenzylidene)-
propane-1,1,3-tricarboxylate 4p. Yellow oil (142.9 mg, 70%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 7.20 (d, 2H, J =
8.0 Hz), 7.16 (d, 2H, J = 8.0 Hz), 7.06 (s, 1H), 4.14 (q, 2H, J = 7.2 Hz),
3.87 (s, 6H), 3.48 (d, 2H, J = 1.6 Hz), 2.59 (t, 2H, J = 7.6 Hz), 1.62−
1.59 (m, 2H), 1.32−1.23 (m, 7H), 0.89 (t, 3H, J = 6.8 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 170.7, 165.6 (d, J = 25.0 Hz), 142.9, 133.7,
133.6, 132.4, 128.4 (d, J = 11.0 Hz), 126.3 (d, J = 20.0 Hz), 95.0 (d, J =
201.0 Hz), 60.9, 53.5, 35.5, 33.8 (d, J = 4.0 Hz), 31.3, 30.9, 22.4, 14.0,
13.9. 19F NMR (376 MHz, CDCl3): δ −159.7. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C22H29FNaO6 431.1846; Found 431.1841.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(4-methoxybenzylidene)-
propane-1,1,3-tricarboxylate 4q. Yellow oil (119.8 mg, 65%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 7.24 (d, 2H, J =
8.8 Hz), 7.01 (s, 1H), 6.88 (d, 2H, J = 8.4 Hz), 4.15 (q, 2H, J = 7.2 Hz),
3.87 (s, 6H), 3.81 (s, 3H), 3.46 (d, 2H, J = 1.6 Hz), 1.25 (t, 3H, J = 7.2
Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 170.8, 165.8 (d, J = 26.0
Hz), 159.4, 133.4 (d, J = 10.0 Hz), 130.1, 127.6, 125.5 (d, J = 21.0 Hz),
113.9, 95.2 (d, J = 200.0 Hz), 61.0, 55.2, 53.6, 33.9 (d, J = 4.0 Hz), 14.1.
19F NMR (376 MHz, CDCl3): δ −159.4. HRMS (ESI-TOF) m/z: [M +
(E)-3-Ethyl 1,1-dimethyl 2-butylidene-1-fluoropropane-1,1,3-tri-
carboxylate 4x. Yellow oil (61.0 mg, 40%). Petroleum ether/ethyl
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 5.99 (t, 1H, J = 7.2 Hz), 4.11 (q, 2H, J = 7.2 Hz), 3.83
(s, 6H), 3.29 (s, 2H), 2.13−2.07 (m, 2H), 1.49−1.40 (m, 2H), 1.24 (t,
3H, J = 7.2 Hz), 0.91 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.3, 165.8 (d, J = 26.0 Hz), 135.6 (d, J = 11.0 Hz), 125.0
(d, J = 19.0 Hz), 95.1 (d, J = 199.0 Hz), 60.9, 53.4, 32.7 (d, J = 4.0 Hz),
30.3, 21.9, 14.1, 13.7. 19F NMR (376 MHz, CDCl3): δ −159.3. HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C14H21FNaO6 327.1220; Found
327.1219.
H]+ Calcd for C18H22FO7 369.1350; Found 369.1342.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(thiophen-2-ylmethylene)-
propane-1,1,3-tricarboxylate 4r. Yellow oil (77.5 mg, 45%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 7.36 (d, 1H, J =
4.8 Hz), 7.19 (s, 1H), 7.13 (d, 1H, J = 3.6 Hz), 7.06−7.04 (m, 1H), 4.16
(q, 2H, J = 7.2 Hz), 3.86 (s, 6H), 3.69 (d, 2H, J = 1.2 Hz), 1.25 (t, 3H, J
= 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 169.8, 165.5 (d, J =
26.0 Hz), 137.6, 130.1, 127.3, 127.2, 125.8 (d, J = 13.0 Hz), 123.8 (d, J =
19.0 Hz), 94.8 (d, J = 202.0 Hz), 61.1, 53.6, 34.4 (d, J = 4.0 Hz), 14.1.
19F NMR (376 MHz, CDCl3): δ −159.7. HRMS (ESI-TOF) m/z: [M +
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-pentylidenepropane-1,1,3-
tricarboxylate 4y. Yellow oil (60.5 mg, 38%). Petroleum ether/ethyl
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 5.99 (t, 1H, J = 7.2 Hz), 4.11 (q, 2H, J = 7.2 Hz), 3.83
(s, 6H), 3.29 (s, 2H), 2.15−2.09 (m, 2H), 1.42−1.28 (m, 4H), 1.24 (t,
3H, J = 7.2 Hz), 0.89 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.3, 165.8 (d, J = 26.0 Hz), 135.8 (d, J = 10.0 Hz), 124.8
(d, J = 20.0 Hz), 95.1 (d, J = 199.0 Hz), 60.9, 53.4, 32.7 (d, J = 4.0 Hz),
30.8, 28.1, 22.3, 14.1, 13.9. 19F NMR (376 MHz, CDCl3): δ −159.2.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C15H23FNaO6 341.1376;
Found 341.1373.
Na]+ Calcd for C15H17FNaO6S 367.0628; Found 367.0622.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(thiophen-3-ylmethylene)-
propane-1,1,3-tricarboxylate 4s. Yellow oil (132.5 mg, 77%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
chromatography. 1H NMR (400 MHz, CDCl3): δ 7.35 (s, 1H),
7.32−7.30 (m, 1H), 7.09−7.08 (m, 1H), 7.01 (s, 1H), 4.16 (q, 2H, J =
7.2 Hz), 3.86 (s, 6H), 3.54 (d, 2H, J = 1.6 Hz), 1.25 (t, 3H, J = 7.2 Hz).
13C{1H} NMR (100 MHz, CDCl3): δ 170.3, 165.4 (d, J = 26.0 Hz),
135.8, 128.2, 127.6 (d, J = 12.0 Hz), 125.7, 125.5, 125.0, 94.9 (d, J =
201.0 Hz), 60.9, 53.4, 34.1 (d, J = 5.0 Hz), 13.9. 19F NMR (376 MHz,
CDCl3): δ −159.4. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C15H17FNaO6S 367.0628; Found 367.0622.
(E)-3-Ethyl 1,1-dimethyl 2-(cyclopropylmethylene)-1-fluoropro-
pane-1,1,3-tricarboxylate 4z. Yellow oil (53.0 mg, 35%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 5.36 (d, 1H, J = 10.0 Hz), 4.14 (q, 2H, J =
7.2 Hz), 3.83 (s, 6H), 3.41 (s, 2H), 1.54−1.48 (m, 1H), 1.25 (t, 3H, J =
7.2 Hz), 0.89−0.84 (m, 2H), 0.53−0.49 (m, 2H). 13C{1H} NMR (100
MHz, CDCl3): δ 170.5, 165.8 (d, J = 26.0 Hz), 139.5 (d, J = 11.0 Hz),
122.6 (d, J = 20.0 Hz), 94.9 (d, J = 200.0 Hz), 60.9, 53.4, 33.1 (d, J = 4.0
Hz), 14.1, 10.9, 7.6. 19F NMR (376 MHz, CDCl3): δ −158.9. HRMS
(ESI-TOF) m/z: [M + Na]+ Calcd for C14H19FNaO6 325.1063; Found
325.1066.
(E)-3-Ethyl 1,1-dimethyl 2-(2-((3,7-dimethyloct-6-en-1-yl)oxy)-
ethylidene)-1-fluoropropane-1,1,3-tricarboxylate 4aa. Yellow oil
(182.8 mg, 85%). Petroleum ether/ethyl acetate = 20/1 as eluent for
column chromatography. 1H NMR (400 MHz, CDCl3): δ 6.16 (t, 1H, J
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(pyridin-2-ylmethylene)-
propane-1,1,3-tricarboxylate 4t. Yellow oil (78.0 mg, 46%).
Petroleum ether/ethyl acetate = 20/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 8.55 (s, 2H), 7.64
(d, 1H, J = 7.6 Hz), 7.32−7.29 (m, 1H), 7.09 (s, 1H), 4.15 (q, 2H, J =
7.2 Hz), 3.89 (s, 6H), 3.45 (s, 2H), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 170.2, 165.3 (d, J = 25.0 Hz), 149.5, 149.0,
135.7, 131.1, 130.1 (d, J = 12.0 Hz), 129.5 (d, J = 21.0 Hz), 123.2, 94.6
(d, J = 202.0 Hz), 61.2, 53.7, 33.8 (d, J = 5.0 Hz), 14.0. 19F NMR (376
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= 6.0 Hz), 5.08 (t, 1H, J = 7.2 Hz), 4.13−4.08 (m, 4H), 3.82 (s, 6H),
3.45−3.41 (m, 2H), 3.31 (s, 2H), 2.00−1.92 (m, 2H), 1.66 (s, 3H),
1.63−1.49 (m, 5H), 1.40−1.28 (m, 2H), 1.23 (t, 3H, J = 7.2 Hz), 1.19−
1.10 (m, 1H), 0.87 (d, 3H, J = 6.4 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 169.7, 165.4 (d, J = 26.0 Hz), 132.6 (d, J = 10.0 Hz), 131.1,
126.8 (d, J = 20.0 Hz), 124.7, 94.6 (d, J = 200.0 Hz), 69.2, 67.2, 61.0,
53.4, 37.2, 36.6, 33.1 (d, J = 4.0 Hz), 29.5, 25.6, 25.4, 19.5, 17.6, 14.1.
19F NMR (376 MHz, CDCl3): δ −159.7. HRMS (ESI-TOF) m/z: [M +
CDCl3): δ −157.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H24FNNaO5 400.1536; Found 400.1528.
(E)-Diethyl 3-benzylidene-2-fluoropentanedioate 5e. Yellow oil
(103.0 mg, 70%). Petroleum ether/ethyl acetate = 30/1 as eluent for
column chromatography. 1H NMR (400 MHz, CDCl3): δ 7.37−7.27
(m, 5H), 6.96 (d, 1H, J = 2.0 Hz), 5.46 (d, 1H, J = 47.2 Hz), 4.32−4.23
(m, 2H), 4.17 (q, 2H, J = 7.2 Hz), 3.36 (dd, 2H, J1 = 16.8 Hz, J2 = 27.6
Hz), 1.32 (t, 3H, J = 7.2 Hz), 1.26 (t, 3H, J = 7.2 Hz). 13C{1H} NMR
(100 MHz, CDCl3): δ 170.5, 167.9 (d, J = 27.0 Hz), 135.1, 134.7 (d, J =
10.0 Hz), 128.5 (d, J = 1.0 Hz), 128.3, 127.9 (d, J = 18.0 Hz), 127.9,
91.1 (d, J = 184.0 Hz), 61.7, 60.9, 32.9 (d, J = 3.0 Hz), 14.0, 13.9. 19F
NMR (376 MHz, CDCl3): δ −184.2. HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C16H19FNaO4 317.1165; Found 317.1160.
H]+ Calcd for C22H36FO7 431.2445; Found 431.2441.
(E)-3-Ethyl 1,1-dimethyl 1-fluoro-2-(2-((2,5,7,8-tetramethyl-2-
(4,8,12-trimethyltridecyl)chroman-6-yl)oxy)ethylidene)propane-
1,1,3-tricarboxylate 4ab. Yellow oil (246.1 mg, 70%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
(E)-Ethyl 3-benzylidene-4-fluoro-5-oxo-5-(phenylamino)-
NMR (400 MHz, CDCl3): δ 6.43 (t, 1H, J = 6.0 Hz), 4.36 (dd, 2H, J1 =
1.6 Hz, J2 = 5.6 Hz), 4.08 (q, 2H, J = 7.2 Hz), 3.86 (s, 6H), 3.32 (s, 2H),
2.57 (t, 2H, J = 6.8 Hz), 2.16 (s, 3H), 2.11 (s, 3H), 2.08 (s, 3H), 1.83−
1.73 (m, 2H), 1.56−1.51 (m, 2H), 1.40−1.20 (m, 19H), 1.16−1.06 (m,
6H), 0.88−0.84 (m, 12H). 13C{1H} NMR (100 MHz, CDCl3): δ 169.6,
165.4 (d, J = 25.0 Hz), 148.0, 131.9 (d, J = 12.0 Hz), 127.7, 126.6, 126.4,
125.8, 123.0, 117.6, 94.6 (d, J = 201.0 Hz), 74.8, 69.6, 61.1, 53.6, 40.0
(d, J = 5.0 Hz), 39.3, 37.6, 37.4 (d, J = 7.0 Hz), 37.3 (d, J = 5.0 Hz), 33.2,
32.8 (d, J = 1.0 Hz), 32.7 (d, J = 2.0 Hz), 31.2 (d, J = 5.0 Hz), 28.0, 24.8
(d, J = 1.0 Hz), 24.4, 23.8, 22.7, 22.6, 21.0 (d, J = 1.0 Hz), 20.6, 19.7 (d, J
= 7.0 Hz), 19.6 (d, J = 4.0 Hz), 14.1, 12.9, 12.0, 11.8. 19F NMR (376
MHz, CDCl3): δ −159.7. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C41H66FO8 705.4742; Found 705.4746.
(E)-3-Ethyl 1,1-dimethyl 2-(2-(6-chloro-9H-purin-9-yl)-
ethylidene)-1-fluoropropane-1,1,3-tricarboxylate 4ac. Yellow oil
(173.5 mg, 81%). Petroleum ether/ethyl acetate = 5/1 as eluent for
column chromatography. 1H NMR (400 MHz, CDCl3): δ 8.74 (s, 1H),
8.25 (s, 1H), 6.26 (t, 1H, J = 7.2 Hz), 5.03 (d, 2H, J = 7.2 Hz), 4.16 (q,
2H, J = 7.2 Hz), 3.83 (s, 6H), 3.56 (s, 2H), 1.27 (t, 3H, J = 7.2 Hz).
13C{1H} NMR (100 MHz, CDCl3): δ 169.4, 164.9 (d, J = 26.0 Hz),
pentanoate 5f. Yellow oil (133.0 mg, 78%). Petroleum ether/ethyl
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 8.20 (d, 1H, J = 4.0 Hz), 7.61 (d, 2H, J = 8.0 Hz),
7.38−7.29 (m, 7H), 7.16 (t, 1H, J = 7.6 Hz), 7.04 (d, 1H, J = 2.4 Hz),
5.58 (d, 1H, J = 48.0 Hz), 4.16 (q, 2H, J = 7.2 Hz), 3.42 (dd, 2H, J1 =
16.0 Hz, J2 = 72.4 Hz), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100
MHz, CDCl3): δ 171.0, 165.7 (d, J = 21.0 Hz), 136.8, 135.2, 135.2,
135.1, 129.1, 128.7 (d, J = 1.0 Hz), 128.5, 128.0, 125.0, 120.0, 93.9 (d, J
= 189.0 Hz), 61.3, 33.9 (d, J = 2.0 Hz), 14.1. 19F NMR (376 MHz,
CDCl3): δ −179.4. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H20FNNaO3 364.1325; Found 364.1315.
(E)-Ethyl 3-benzylidene-5-((4-chlorophenyl)amino)-4-fluoro-5-
oxopentanoate 5g. Yellow oil (152.0 mg, 81%). Petroleum ether/
ethyl acetate = 30/1 as eluent for column chromatography. 1H NMR
(400 MHz, CDCl3): δ 8.32 (d, 1H, J = 4.4 Hz), 7.57 (d, 2H, J = 8.8 Hz),
7.38−7.30 (m, 7H), 7.03 (d, 1H, J = 2.4 Hz), 5.57 (d, 1H, J = 48.0 Hz),
4.16 (q, 2H, J = 7.2 Hz), 3.41 (dd, 2H, J1 = 16.4 Hz, J2 = 70.8 Hz), 1.24
(t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 171.1, 165.8
(d, J = 21.0 Hz), 135.3 (d, J = 10.0 Hz), 135.3, 135.0, 130.0, 129.1, 128.7
(d, J = 1.0 Hz), 128.4, 128.1, 127.9 (d, J = 17.0 Hz), 121.2, 93.8 (d, J =
188.0 Hz), 61.3, 33.8 (d, J = 2.0 Hz), 14.0. 19F NMR (376 MHz,
CDCl3): δ −179.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C20H19ClFNNaO3 398.0935; Found 398.0926.
152.0, 151.7, 151.1, 145.0, 131.5, 131.0 (d, J = 20.0 Hz), 127.0 (d, J =
12.0 Hz), 94.1 (d, J = 203.0 Hz), 61.6, 53.8, 41.7, 32.9 (d, J = 3.0 Hz),
14.1. 19F NMR (376 MHz, CDCl3): δ −160.3. HRMS (ESI-TOF) m/z:
[M + H]+ Calcd for C17H19ClFN4O6 429.0977; Found 429.0974.
(E)-Triethyl 2-benzylidene-1-fluoropropane-1,1,3-tricarboxylate
5b. Yellow oil (142.8 mg, 78%). Petroleum ether/ethyl acetate = 30/
1 as eluent for column chromatography. 1H NMR (400 MHz, CDCl3):
δ 7.37−7.27 (m, 5H), 7.10 (s, 1H), 4.37−4.29 (m, 4H), 4.13 (q, 2H, J =
7.2 Hz), 3.45 (d, 2H, J = 2.0 Hz), 1.34 (t, 6H, J = 7.2 Hz), 1.24 (t, 3H, J
= 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 170.6, 165.2 (d, J =
26.0 Hz), 135.4, 133.6 (d, J = 11.0 Hz), 128.5, 128.4, 127.9, 127.4 (d, J =
21.0 Hz), 94.9 (d, J = 200.0 Hz), 62.9, 60.9, 33.9 (d, J = 4.0 Hz), 14.0,
13.9. 19F NMR (376 MHz, CDCl3): δ −159.9. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C19H23FNaO6 389.1376; Found 389.1370.
(E)-Ethyl 3-benzylidene-4-(diethylcarbamoyl)-4-fluoro-5-oxohex-
anoate 5c. Yellow oil (101.5 mg, 56%). Petroleum ether/ethyl acetate
(E)-Ethyl 3-benzylidene-4-fluoro-5-oxo-5-(p-tolylamino)-
pentanoate 5h. Yellow oil (138.5 mg, 78%). Petroleum ether/ethyl
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 8.14 (d, 1H, J = 4.8 Hz), 7.48 (d, 2H, J = 8.4 Hz),
7.36−7.28 (m, 5H), 7.15 (d, 2H, J = 8.4 Hz), 7.03 (d, 1H, J = 2.8 Hz),
5.57 (d, 1H, J = 47.6 Hz), 4.16 (q, 2H, J = 7.2 Hz), 3.41 (dd, 2H, J1 =
16.4 Hz, J2 = 73.6 Hz), 2.33 (s, 3H), 1.24 (t, 3H, J = 7.2 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 171.0 (d, J = 1.0 Hz), 165.6 (d, J = 21.0
Hz), 135.2 (d, J = 3.0 Hz), 135.1, 134.7, 134.2, 129.6, 128.7 (d, J = 1.0
Hz), 128.4, 128.2 (d, J = 17.0 Hz), 128.0, 120.0, 94.0 (d, J = 189.0 Hz),
61.2, 33.9 (d, J = 3.0 Hz), 20.9, 14.1. 19F NMR (376 MHz, CDCl3): δ
−179.4. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H22FNNaO3
378.1481; Found 378.1479.
1
= 30/1 as eluent for column chromatography. H NMR (400 MHz,
(E)-Ethyl 3-benzylidene-4-fluoro-5-((4-methoxyphenyl)amino)-5-
CDCl3): δ 7.37−7.27 (m, 5H), 6.81 (s, 1H), 4.18−4.08 (m, 2H), 3.80−
3.74 (m, 1H), 3.58−3.53 (m, 1H), 3.45 (d, 1H, J = 16.8 Hz), 3.28−3.18
(m, 2H), 3.08 (dd, 1H, J1 = 1.6 Hz, J2 = 16.8 Hz), 2.24 (d, 3H, J = 3.6
Hz), 1.26−1.15 (m, 9H). 13C{1H} NMR (100 MHz, CDCl3): δ 199.1
(d, J = 30.0 Hz), 171.0, 165.3 (d, J = 21.0 Hz), 135.2, 133.9, 133.8, 128.5
(d, J = 4.0 Hz), 128.3, 128.0, 102.3 (d, J = 197.0 Hz), 61.0, 42.1 (d, J =
8.0 Hz), 40.8, 34.1 (d, J = 4.0 Hz), 26.0, 14.0, 13.9 (d, J = 2.0 Hz), 12.1.
19F NMR (376 MHz, CDCl3): δ −157.3. HRMS (ESI-TOF) m/z: [M +
oxopentanoate 5i. Yellow oil (126.1 mg, 68%). Petroleum ether/ethyl
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 8.17 (s, 1H), 7.52 (d, 2H, J = 8.8 Hz), 7.36−7.22 (m,
5H), 7.03 (d, 1H, J = 2.4 Hz), 6.88 (d, 2H, J = 8.8 Hz), 5.57 (d, 1H, J =
48.0 Hz), 4.16 (q, 2H, J = 7.2 Hz), 3.79 (s, 3H), 3.41 (dd, 2H, J1 = 16.4
Hz, J2 = 72.8 Hz), 1.24 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.9, 165.5 (d, J = 21.0 Hz), 156.8, 135.1, 135.0 (d, J = 10.0
Hz), 129.8, 128.7 (d, J = 2.0 Hz), 128.4, 128.2 (d, J = 17.0 Hz), 127.9,
121.7, 114.1, 93.9 (d, J = 189.0 Hz), 61.2, 55.4, 33.8, 14.0. 19F NMR
(376 MHz, CDCl3): δ −179.5. HRMS (ESI-TOF) m/z: [M + Na]+
Calcd for C21H22FNNaO4 394.1431; Found 394.1421.
(E)-Ethyl 3-benzylidene-5-((2,4-dimethylphenyl)amino)-4-fluoro-
5-oxopentanoate 5j. Yellow oil (129.1 mg, 70%). Petroleum ether/
ethyl acetate = 30/1 as eluent for column chromatography. 1H NMR
(400 MHz, CDCl3): δ 7.99 (d, 1H, J = 4.8 Hz), 7.75 (d, 1H, J = 8.8 Hz),
7.37−7.29 (m, 5H), 7.06−7.03 (m, 3H), 5.62 (d, 1H, J = 48.0 Hz),
4.20−4.14 (m, 2H), 3.42 (dd, 2H, J1 = 16.4 Hz, J2 = 78.8 Hz), 2.30 (s,
3H), 2.28 (s, 3H), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.9, 165.8 (d, J = 20.0 Hz), 135.3 (d, J = 16.0 Hz), 134.9
Na]+ Calcd for C20H26FNNaO4 386.1744; Found 386.1736.
(E)-Ethyl 3-benzylidene-4-fluoro-4-(morpholine-4-carbonyl)-5-
oxohexanoate 5d. Yellow oil (132.0 mg, 70%). Petroleum ether/
1
ethyl acetate = 30/1 as eluent for column chromatography. H NMR
(400 MHz, CDCl3): δ 7.38−7.30 (m, 5H), 6.86 (s, 1H), 4.17−4.11 (m,
2H), 3.80−3.52 (m, 8H), 3.44 (d, 1H, J = 17.2 Hz), 3.03 (dd, 1H, J1 =
1.6 Hz, J2 = 16.8 Hz), 2.36 (d, 3H, J = 3.6 Hz), 1.24 (t, 3H, J = 7.2 Hz).
13C{1H} NMR (100 MHz, CDCl3): δ 198.9 (d, J = 30.0 Hz), 171.1,
164.5 (d, J = 21.0 Hz), 134.9, 134.5 (d, J = 8.0 Hz), 128.6, 128.4, 128.2,
127.8 (d, J = 21.0 Hz), 102.3 (d, J = 196.0 Hz), 66.6, 66.4, 61.1, 46.8 (d,
J = 9.0 Hz), 43.0, 34.0 (d, J = 5.0 Hz), 26.1, 14.0. 19F NMR (376 MHz,
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(d, J = 11.0 Hz), 131.9, 131.2, 129.1, 128.7 (d, J = 1.0 Hz), 128.5, 128.5,
128.4, 128.0, 127.4, 122.8, 94.2 (d, J = 188.0 Hz), 61.2, 33.9, 20.9, 17.5,
14.1. 19F NMR (376 MHz, CDCl3): δ = −179.5. HRMS (ESI-TOF) m/
z: [M + Na]+ Calcd for C22H24FNNaO3 392.1638; Found 392.1630.
(E)-Diethyl 2-acetyl-3-benzylidene-2-fluoropentanedioate 5k.
Yellow oil (87.5 mg, 52%). Petroleum ether/ethyl acetate = 30/1 as
200.9 (d, J = 27.0 Hz), 171.4, 163.1 (d, J = 22.0 Hz), 135.6, 135.2, 134.3
(d, J = 8.0 Hz), 131.9, 131.3, 129.6, 128.5 (d, J = 4.0 Hz), 128.2, 128.1,
128.0, 127.3, 122.9, 100.9 (d, J = 196.0 Hz), 61.3, 33.6 (d, J = 6.0 Hz),
26.3, 20.9, 17.5, 14.1. 19F NMR (376 MHz, CDCl3): δ −157.4. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd for C24H27FNO4 412.1924; Found
412.1932.
1
eluent for column chromatography. H NMR (400 MHz, CDCl3): δ
(E)-Trimethyl 2-benzylidene-1-fluoro-3-phenylpropane-1,1,3-tri-
carboxylate 6b. Yellow oil (78.0 mg, 39%). Petroleum ether/ethyl
7.37−7.25 (m, 5H), 7.04 (s, 1H), 4.31 (q, 2H, J = 7.2 Hz), 4.15 (q, 2H, J
= 7.2 Hz), 3.50−3.35 (m, 2H), 2.41 (d, 3H, J = 5.6 Hz), 1.33 (t, 3H, J =
7.2 Hz), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ
200.4 (d, J = 29.0 Hz), 170.9, 165.2 (d, J = 26.0 Hz), 135.2, 133.3 (d, J =
10.0 Hz), 128.4, 128.4, 127.9, 127.0 (d, J = 22.0 Hz), 99.6 (d, J = 198.0
Hz), 62.8, 61.0, 33.5 (d, J = 6.0 Hz), 25.5, 14.0, 13.9. 19F NMR (376
MHz, CDCl3): δ −161.1. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for
C18H21FNaO5 359.1271; Found 359.1266.
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 7.36−7.30 (m, 4H), 7.25−7.19 (m, 6H), 7.11 (s, 1H),
5.15 (s, 1H), 3.89 (s, 3H), 3.70 (s, 3H), 3.53 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3): δ 171.4, 165.9 (d, J = 25.0 Hz), 165.6 (d, J = 26.0
Hz), 135.6, 135.3, 134.6, 134.5, 132.3, 132.0, 129.7 (d, J = 3.0 Hz),
128.5 (d, J = 4.0 Hz), 128.0, 127.2, 95.5 (d, J = 200.0 Hz), 53.8, 53.4,
52.3, 50.3 (d, J = 3.0 Hz). 19F NMR (376 MHz, CDCl3): δ −160.4.
HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H21FNaO6 423.1220;
Found 423.1212.
(E)-Ethyl 3-benzylidene-4-fluoro-5-oxo-4-(phenylcarbamoyl)-
hexanoate 5l. Yellow oil (138.0 mg, 72%). Petroleum ether/ethyl
1
acetate = 30/1 as eluent for column chromatography. H NMR (400
(E)-Trimethyl 2-benzylidene-3-(2-chlorophenyl)-1-fluoropro-
pane-1,1,3-tricarboxylate 6c. Yellow oil (86.8 mg, 40%). Petroleum
MHz, CDCl3): δ 8.66 (d, 1H, J = 2.8 Hz), 7.59 (d, 2H, J = 8.0 Hz),
7.37−7.14 (m, 9H), 4.18 (q, 2H, J = 7.2 Hz), 3.52−3.33 (m, 2H), 2.49
(d, 3H, J = 4.4 Hz), 1.26 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 200.3 (d, J = 28.0 Hz), 171.6, 163.1 (d, J = 22.0 Hz), 136.8,
135.1, 134.8, 134.7, 129.1, 128.5, 128.1, 127.6 (d, J = 22.0 Hz), 125.1,
120.0, 100.8 (d, J = 196.0 Hz), 61.4, 33.7 (d, J = 6.0 Hz), 26.3, 14.1. 19F
NMR (376 MHz, CDCl3): δ −156.7. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C22H23FNO4 384.1611; Found 384.1611.
(E)-Ethyl 3-benzylidene-4-((4-chlorophenyl)carbamoyl)-4-fluoro-
5-oxohexanoate 5m. White solid (162.5 mg, 78%). Petroleum ether/
ethyl acetate = 30/1 as eluent for column chromatography. Mp: 117−
118 °C. 1H NMR (400 MHz, CDCl3): δ 8.82 (d, 1H, J = 2.8 Hz), 7.56
(d, 2H, J = 8.8 Hz), 7.37−7.24 (m, 7H), 7.17 (s, 1H), 4.17 (q, 2H, J =
7.2 Hz), 3.52−3.33 (m, 2H), 2.48 (d, 3H, J = 4.4 Hz), 1.26 (t, 3H, J =
7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 200.3 (d, J = 28.0 Hz),
171.7, 163.1 (d, J = 22.0 Hz), 135.4, 134.9, 134.8 (d, J = 8.0 Hz), 130.0,
129.0, 128.5, 128.4, 128.1, 127.3 (d, J = 22.0 Hz), 121.2, 100.6 (d, J =
197.0 Hz), 61.4, 33.6 (d, J = 6.0 Hz), 26.3, 14.0. 19F NMR (376 MHz,
CDCl3): δ −156.8. HRMS (ESI-TOF) m/z: [M + H]+ Calcd for
C22H22ClFNO4 418.1221; Found 418.1225.
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 7.60−7.57 (m, 1H), 7.34−7.19 (m, 8H),
7.12 (d, 1H, J = 1.6 Hz), 5.41 (s, 1H), 3.91 (s, 3H), 3.64 (s, 3H), 3.56 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3): δ 170.5, 165.8 (d, J = 25.0
Hz), 165.4 (d, J = 26.0 Hz), 135.9 (d, J = 8.0 Hz), 135.4, 135.0, 134.0,
131.4 (d, J = 5.0 Hz), 130.1, 129.8, 129.2, 128.9, 128.3 (d, J = 5.0 Hz),
128.2, 126.7, 95.7 (d, J = 199.0 Hz), 53.8, 53.4, 52.4, 48.4 (d, J = 3.0
Hz). 19F NMR (376 MHz, CDCl3): δ −159.3. HRMS (ESI-TOF) m/z:
[M + Na]+ Calcd for C22H20ClFNaO6 457.0830; Found 457.0839.
(E)-Dimethyl 2-fluoro-2-(4-oxo-1,4-diphenylbut-1-en-2-yl)-
malonate 6d and (E)-Dimethyl 2-fluoro-2-(4-oxo-1,4-diphenylbut-
1-en-2-yl)malonate 6d′. Yellow oil (64.8 mg, 35%). Petroleum ether/
ethyl acetate = 50/1 as eluent for column chromatography. 1H NMR
(400 MHz, CDCl3): δ 8.00 (d, 2H, J = 7.6 Hz), 7.94 (d, 2H, J = 7.2 Hz),
7.59−7.55 (m, 2H), 7.49−7.43 (m, 4H), 5.27−5.18 (m, 1H), 3.83 (s,
3H), 3.59 (s, 3H), 3.78−3.55 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3): δ 197.4, 196.1, 165.7 (d, J = 25.0 Hz), 165.5 (d, J = 25.0 Hz),
135.7, 135.6, 133.7, 133.6, 128.8, 128.7, 128.7, 128.2, 93.5 (d, J = 207.0
Hz), 53.5 (d, J = 34.0 Hz), 45.3 (d, J = 20.0 Hz), 36.7 (d, J = 4.0 Hz). 19F
NMR (376 MHz, CDCl3): δ −169.3. HRMS (ESI-TOF) m/z: [M +
H]+ Calcd for C21H20FO5 371.1295; Found 371.1291.
(E)-Ethyl 3-benzylidene-4-fluoro-5-oxo-4-(p-tolylcarbamoyl)-
hexanoate 5n. Yellow oil (148.9 mg, 75%). Petroleum ether/ethyl
1
Ethyl 2-(5-methyl-4-(morpholine-4-carbonyl)-2-phenylfuran-3-
acetate = 30/1 as eluent for column chromatography. H NMR (400
yl)acetate 7a. Yellow oil (91.0 mg, 85%). Petroleum ether/ethyl
MHz, CDCl3): δ 8.55 (d, 1H, J = 2.8 Hz), 7.46 (d, 2H, J = 8.4 Hz),
7.37−7.14 (m, 8H), 4.17 (q, 2H, J = 7.2 Hz), 3.51−3.32 (m, 2H), 2.49
(d, 3H, J = 4.4 Hz), 2.32 (s, 3H), 1.26 (t, 3H, J = 7.2 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 200.4 (d, J = 28.0 Hz), 171.5, 162.9 (d, J =
22.0 Hz), 135.2, 134.8, 134.7, 134.6, 134.2, 129.6, 128.5 (d, J = 3.0 Hz),
128.1, 127.7 (d, J = 22.0 Hz), 120.1, 100.8 (d, J = 197.0 Hz), 61.3, 33.7
(d, J = 6.0 Hz), 26.3, 20.9, 14.1. 19F NMR (376 MHz, CDCl3): δ
−156.7. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H24FNNaO4
420.1587; Found 420.1581.
1
acetate = 15/1 as eluent for column chromatography. H NMR (400
MHz, CDCl3): δ 7.52 (d, 2H, J = 7.6 Hz), 7.39 (t, 2H, J = 7.6 Hz), 7.30
(t, 1H, J = 7.2 Hz), 4.14 (q, 2H, J = 7.2 Hz), 3.89−3.61 (m, 10H), 2.33
(s, 3H), 1.25 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ
171.1, 165.2, 149.7, 148.2, 130.1, 128.6, 127.8, 126.3, 118.5, 113.6, 66.8,
60.9, 47.8, 42.3, 29.8, 14.2, 13.0. HRMS (ESI-TOF) m/z: [M + H]+
Calcd for C20H24NO5 358.1654; Found 358.1646.
Ethyl 2-(5-methyl-2-phenyl-4-(phenylcarbamoyl)furan-3-yl)-
acetate 7b. White solid (54.5 mg, 50%). Petroleum ether/ethyl
acetate = 20/1 as eluent for column chromatography. Mp: 113−114 °C.
1H NMR (400 MHz, CDCl3): δ 9.74 (s, 1H), 7.69 (d, 2H, J = 8.0 Hz),
7.61 (d, 2H, J = 8.0 Hz), 7.45 (t, 2H, J = 7.6 Hz), 7.36 (t, 3H, J = 7.6
Hz), 7.12 (t, 1H, J = 7.6 Hz), 4.36 (q, 2H, J = 7.2 Hz), 3.77 (s, 2H), 2.62
(s, 3H), 1.37 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ
173.8, 162.4, 156.0, 149.5, 138.7, 129.9, 129.0, 128.7, 128.1, 126.3,
124.0, 120.5, 119.8, 110.9, 62.2, 31.2, 14.2, 13.5. HRMS (ESI-TOF) m/
z: [M + H]+ Calcd for C22H22NO4 364.1549; Found 364.1554.
Ethyl 2-(4-((4-chlorophenyl)carbamoyl)-5-methyl-2-phenylfur-
an-3-yl)acetate 7c. White solid (71.5 mg, 60%). Petroleum ether/
ethyl acetate = 20/1 as eluent for column chromatography. Mp: 146−
148 °C. 1H NMR (400 MHz, CDCl3): δ 9.94 (s, 1H), 7.66 (d, 2H, J =
8.8 Hz), 7.61 (d, 2H, J = 7.6 Hz), 7.45 (t, 2H, J = 7.6 Hz), 7.36 (t, 1H, J
= 7.6 Hz), 7.31 (d, 2H, J = 8.4 Hz), 4.36 (q, 2H, J = 7.2 Hz), 3.75 (s,
2H), 2.61 (s, 3H), 1.38 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz,
CDCl3): δ 174.1, 162.4, 156.4, 149.7, 137.4, 129.8, 128.9, 128.8, 128.7,
128.2, 126.4, 120.9, 120.3, 110.7, 62.4, 31.2, 14.2, 13.5. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C22H21ClNO4 398.1159; Found
398.1163.
(E)-Ethyl 3-benzylidene-4-fluoro-4-((4-methoxyphenyl)-
carbamoyl)-5-oxohexanoate 5o. Yellow oil (132.0 mg, 64%).
Petroleum ether/ethyl acetate = 30/1 as eluent for column
1
chromatography. H NMR (400 MHz, CDCl3): δ 8.51 (d, 1H, J =
3.2 Hz), 7.49 (d, 2H, J = 8.8 Hz), 7.35−7.26 (m, 5H), 7.21 (s, 1H), 6.88
(d, 2H, J = 8.8 Hz), 4.17 (q, 2H, J = 7.2 Hz), 3.79 (s, 3H), 3.51−3.32
(m, 2H), 2.48 (d, 3H, J = 4.4 Hz), 1.26 (t, 3H, J = 7.2 Hz). 13C{1H}
NMR (100 MHz, CDCl3): δ 200.4 (d, J = 27.0 Hz), 171.6, 162.8 (d, J =
22.0 Hz), 156.9, 135.2, 134.7 (d, J = 9.0 Hz), 129.8, 128.5 (d, J = 3.0
Hz), 128.1, 127.8, 127.6, 121.8, 114.2, 100.8 (d, J = 196.0 Hz), 61.3,
55.5, 33.7 (d, J = 6.0 Hz), 26.3, 14.1. 19F NMR (376 MHz, CDCl3): δ
−156.6. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H24FNNaO5
436.1536; Found 436.1535.
(E)-Ethyl 3-benzylidene-4-((2,4-dimethylphenyl)carbamoyl)-4-
fluoro-5-oxohexanoate 5p. Yellow oil (135.7 mg, 66%). Petroleum
1
ether/ethyl acetate = 30/1 as eluent for column chromatography. H
NMR (400 MHz, CDCl3): δ 8.37 (d, 1H, J = 2.8 Hz), 7.68 (d, 1H, J =
8.8 Hz), 7.37−7.23 (m, 6H), 7.02 (d, 2H, J = 6.0 Hz), 4.17 (q, 2H, J =
7.2 Hz), 3.51−3.32 (m, 2H), 2.50 (d, 3H, J = 4.4 Hz), 2.30 (s, 3H), 2.27
(s, 3H), 1.26 (t, 3H, J = 7.2 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ
10052
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J. Org. Chem. 2021, 86, 10043−10054

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(4) Tong, S.; Piemontesi, C.; Wang, Q.; Wang, M.-X.; Zhu, J. Silver-
Catalyzed Three-Component 1,1-Aminoacylation of Homopropargyl-
amines: α-Additions for Both Terminal Alkynes and Isocyanides.
Angew. Chem., Int. Ed. 2017, 56, 7958−7962.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00789.
■
sı
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Diboration of Terminal Alkynes: Scope, Mechanism, and Synthetic
Applications. J. Am. Chem. Soc. 2017, 139, 3868−3875.
Single-crystal X-ray crystallography data for product 5m;
1H NMR, 13C NMR, and 19F NMR spectra for
compounds 4−7 (PDF)
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1,1-Diborylalkenes through a Brønsted Base Catalyzed Reaction
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Accession Codes
CCDC 1972687 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
Yunhe Lv − College of Chemistry and Chemical Engineering,
Anyang Normal University, Anyang 455000, P. R. China;
orcid.org/0000-0001-5804-7475; Email: luyh086@
nenu.edu.cn
■
(10) Liu, X.; Ming, W.; Luo, X.; Friedrich, A.; Maier, J.; Radius, U.;
Santos, W. L.; Marder, T. B. Regio- and Stereoselective Synthesis of 1,1-
Diborylalkenes via Brønsted Base-Catalyzed Mixed Diboration of
Alkynyl Esters and Amides with BpinBdan. Eur. J. Org. Chem. 2020,
2020, 1941−1946.
Authors
Weiya Pu − College of Chemistry and Chemical Engineering,
Anyang Normal University, Anyang 455000, P. R. China
Xueli Zhu − College of Chemistry, Zhengzhou University,
Zhengzhou 450001, P. R. China
Chen Chen − College of Chemistry and Chemical Engineering,
Anyang Normal University, Anyang 455000, P. R. China
Shanshan Wang − College of Chemistry and Chemical
Engineering, Anyang Normal University, Anyang 455000, P.
R. China
(11) Gu, Y.; Duan, Y.; Shen, Y.; Martin, R. Stereoselective Base-
Catalyzed 1,1-Silaboration of Terminal Alkynes. Angew. Chem., Int. Ed.
2020, 59, 2061−2065.
(12) Gao, Y.; Wu, Z.-Q.; Engle, K. M. Synthesis of Stereodefined 1,1-
Diborylalkenes via Copper-Catalyzed Diboration of Terminal Alkynes.
Org. Lett. 2020, 22, 5235−5239.
(13) Wang, N.-N.; Huang, L.-R.; Hao, W.-J.; Zhang, T.-S.; Li, G.; Tu,
S.-J.; Jiang, B. Synergistic Rhodium/Copper Catalysis: Synthesis of 1,3-
Enynes and N-Aryl Enaminones. Org. Lett. 2016, 18, 1298−1301.
(14) Sun, Q.; Li, L.; Liu, L.; Yang, Y.; Zha, Z.; Wang, Z. Copper-
Catalyzed 1,1-Difunctionalization of Terminal Alkynes: a Three-
Component Reaction for the Construction of Vinyl Sulfones. Sci.
China: Chem. 2019, 62, 904−908.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00789
Notes
The authors declare no competing financial interest.
(15) (a) Lv, Y.; Pu, W.; Liu, X.; Sun, J.; Cui, M. Copper-Catalyzed 1,1-
Arylalkylation of Terminal Alkynes with Diazo Esters and Organo-
boronic Acids. Chem. Commun. 2019, 55, 13446−13449. (b) Lv, Y.; Pu,
W.; Shi, L. Copper-Catalyzed Regio- and Stereoselective 1,1-
Dicarbofunctionalization of Terminal Alkynes. Org. Lett. 2019, 21,
6034−6039. (c) Lv, Y.; Wang, Y.; Pu, W.; Zhu, X.; Wu, N.; Zhao, Y.
Copper-Catalyzed 1,1-Alkynylalkylation of Alkynes: Access toward
Conjugated Enynes. Org. Chem. Front. 2020, 7, 2752−2756. (d) Lv, Y.;
Pu, W.; Wang, X. Ligand-Free Copper-Catalyzed Regio- and Stereo-
selective 1,1-Alkylmonofluoroalkylation of Terminal Alkynes. Chem.
Commun. 2020, 56, 12933−12936.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the National Natural Science
Foundation of China (21801008), the Training Plan for
Young Backbone Teachers in Universities of Henan Province
(2020GGJS185), the Henan Key Laboratory of New Optoelec-
tronic Functional Materials, the Jilin Provincial Key Laboratory
of Organic Functional Molecular Design & Synthesis
(130028911), and the Science & Technology Foundation of
Anyang City for their financial support.
(16) (a) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Fluorine
in Medicinal Chemistry. Chem. Soc. Rev. 2008, 37, 320−330. (b) Zhou,
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