Synthesis of difluoroalkyl-γ-butyrolactones from iododifluoromethyl ketones and 4-pentenoic acids

Article abstract of DOI:10.1016/j.cclet.2015.07.007

A convenient and efficient approach for difluoroalkyl-containing γ-butyrolactones via the radical addition reaction of iododifluoromethyl ketones with 4-pentenoic acids initiated by AIBN in CH₃CN at 60 °C was reported. Various difluoroalkyl-containing δ-valerolactones were also synthesized under this reaction conditions.

Full text of DOI:10.1016/j.cclet.2015.07.007

Chinese Chemical Letters 26 (2015) 1381–1384
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Synthesis of difluoroalkyl-
g-butyrolactones from iododifluoromethyl
ketones and 4-pentenoic acids
a
a
Jie-Xiong Wang a, Jing-Jing Wu a,b, , Heng Chen , Shao-Wu Zhang , Fan-Hong Wu
*
a,**
a School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 201814, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201814, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A convenient and efficient approach for difluoroalkyl-containing
g-butyrolactones via the radical
Received 4 May 2015
addition reaction of iododifluoromethyl ketones with 4-pentenoic acids initiated by AIBN in CH3CN at
Received in revised form 18 June 2015
Accepted 24 June 2015
Available online 8 July 2015
60 8C was reported. Various difluoroalkyl-containing d-valerolactones were also synthesized under this
reaction conditions.
ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
g-Butyrolactones
Difluoromethylene
Fluorine-containing lactone
Radical reaction
1. Introduction
In recent years, our laboratory has been devoted to prepare
polyfluoroalkyl-containing lactones from the free radical additions
The
g
-butyrolactone is a characteristic skeletal core present in a
of polyfluoroalkyl iodides and 5-hexenoic acids/4-pentenoic acid
initiated by Na2S2O4 [22,23] and Pd(PPh3)4 [24]. As part of our
continued interest in expanding the structural diversity of the
fluoroalkyl-containing lactones, herein, we reported our new
results regarding the synthesis of difluoroalkyl-containing
large amount of natural products and biological compounds
including pharmaceuticals and agrochemicals, such as ascorbic
acid [1], sex pheromones [2], plant growth regulator karrikin [3]
and anti-HIV nucleoside
b-FddA [4]. Development of efficient
methods for the synthesis of various functionalized lactones has
attracted extensive attention [5–9].
g-butyrolactones via the free radical addition of iododifluoro-
methyl ketones to 4-pentenoic acids initiated by 2,2-azobisiso-
As we know, the introduction of fluorine-containing groups
into organic molecules could alter their properties and bioactiv-
butyronitrile (AIBN) in CH3CN at 60 8C (Scheme 1).
ities [10–14]. The synthesis of fluorine-containing g-butyrolac-
tones is of current interests [15–19]. Despite this interest, general
2. Experimental
synthetic methods for the incorporation of the gem-difluoro-
All reagents were of analytical grade, and obtained from
commercial suppliers and used without further purification. All
NMR spectra were recorded on a Bruker Avance 500 (resonance
frequencies 500 MHz for 1H and 126 MHz for 13C) equipped with a
5 mm inverse broadband probe head with z-gradients at 295.8 K
with standard Bruker pulse programs. The samples were dissolved
in 0.6 mL CDCl3 (99.8% D.TMS). Chemical shifts were given in
methylene group into
desirable [20,21]. Pohmakotr et al. have disclosed the synthesis
of gem-difluoromethylenated spiro- -butyrolactones by using
g-butyrolactones are still highly
g
PhSCF2Si(CH3)3 as a gem-difluoromethylenating building block
[20]. 4,5-Allenoic acids reacted with selectfluor to provide the
desired 1,1-difluoroallyl
group [21].
g-butyrolactones was reported by Zhao’s
values of
dH and dC referenced to residual solvent signals (dH 7.26
for 1H, C 77.0 for 13C in CDCl3). The 19F NMR spectra were obtained
d
using a 500 spectrometer (471 MHz) using trifluorotoluene as
external standard. High resolution mass spectra (HRMS) were
recorded on a Bruker solan X 70 FT-MS (samples was dissolved in
CH3OH and the ion source was ESI), and the energy was 22.5 eV at
MS/MS. Melting points are uncorrected.
*
Corresponding author at: School of Chemical and Environmental Engineering,
Shanghai Institute of Technology, Shanghai 201814, China.
**
Corresponding author.
E-mail addresses: wujj@sit.edu.cn (J.-J. Wu), wfh@sit.edu.cn (F.-H. Wu).
http://dx.doi.org/10.1016/j.cclet.2015.07.007
1001-8417/ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

1382
J.-X. Wang et al. / Chinese Chemical Letters 26 (2015) 1381–1384
5-(2,2-Difluoro-3-(4-fluorophenyl)-3-oxopropyl)dihydro-
furan-2(3H)-one (3ba): Yellow oil liquid, yield: 73%. 1H NMR
(500 MHz, CDCl3):
d 8.17–7.17 (m, 4H), 4.90–4.86 (m, 1H), 2.83–
2.71 (m, 1H), 2.62–2.50 (m, 4H), 2.10–2.01(m, 1H); 13C NMR
20
(126 MHz, CDCl3):
d
186.9 (t,
J
= 31.3 Hz), 176.1, 166.6 (d,
C–F
4
30
1JC–F = 258.1 Hz), 133.2 (dt, JC–F = 9.4 Hz,
J
= 3.1 Hz), 127.8,
C–F
10
2
118.4 (t,
J
= 255.1 Hz), 116.1 (d, JC–F = 22.1 Hz), 74.4 (t,
C–F
300
200
JC–F = 22.4 Hz), 28.8, 28.4; 19F NMR
Scheme 1. Synthesis of difluoroalkyl-containing g-butyrolactones.
JC–F = 4.2 Hz), 39.1(t,
(471 MHz, CDCl3):
2
d
ꢁ98.2 (AB, JF–F = 298.4 Hz, 2F), ꢁ101.6 (s,
1F). HRMS calcd. for C13H11F3O3: 272.0660, found: 272.0647.
5-(2,2-Difluoro-3-(4-fluorophenyl)-3-oxopropyl)-3,3-
2.1. Preparation of iododifluoromethyl ketones 1a–d
dimethyldihydrofuran-2(3H)-one (3bb): Yellow oil liquid, yield:
65%. 1H NMR (500 MHz, CDCl3):
d 8.18–4.78(m, 4H), 4.83–4.78 (m,
The iododifluoromethyl ketones 1a–d were prepared according
to the reported procedure [25–27]. As shown in Scheme 2, the
intermediates enols were obtained from the reaction of trifluor-
omethyl ethyl acetate and ketones. The enols reacted with
Selectfluor1 to form fluorinated gem-diols, which then reacted
with I2 to afford iododifluoromethyl ketones 1a–d using the
trifluoroacetate release conditions (Scheme 2).
1H), 2.81–2.51 (m, 2H), 2.36–1.89 (m, 2H), 1.33–1.29 (m, 6H); 13
C
0
NMR (126 MHz, CDCl3):
d
186.9 (t, 2 JC–F = 31.1 Hz), 181.0, 166.6 (d,
4
30
1JC–F = 258.3 Hz), 133.2 (dt, JC–F = 9.7 Hz,
J
= 3.0 Hz), 127.8,
C–F
10
2
118.2 (t,
J
= 255.0 Hz), 116.1 (d, JC–F = 22.0 Hz), 70.8 (t,
C–F
300
200
JC–F = 3.8 Hz), 44.1, 40.0, 39.4 (t, JC–F = 22.4 Hz), 24.8, 24.0;
19F NMR (471 MHz, CDCl3):
d
ꢁ98.1(AB, JF–F = 298.4 Hz, 2F),
2
ꢁ101.6 (s, 1F). HRMS calcd. for C15H15F3O3: 300.0973, found:
300.0939.
2.2. General procedure for the synthesis of compounds 3
5-(2,2-Difluoro-3-(4-methoxyphenyl)-3-oxopropyl)dihydro-
furan-2(3H)-one (3ca): White solid, yield: 84%, mp: 80.8–81.4 8C.
To
a
solution of iododifluoromethyl ketones 1a–d
1H NMR (500 MHz, CDCl3):
d
8.12–6.98 (m, 4H), 4.90–4.83(m, 1H),
3.91(s, 3H), 2.79–2.72 (m, 1H), 2.58–2.50 (m, 4H), 2.08–2.04 (m,
1H); 13C NMR (126 MHz, CDCl3): 186.8 (t, 2JC–F = 30.6 Hz), 176.3,
164.8, 124.2, 115.4 (t, 1JC–F = 254.9 Hz), 114.1, 74.7 (t,
(1.5 mmol) in acetonitrile (10 mL) was added 4-pentenoic
acids (1 mmol) and AIBN (33 mg, 20 mmol%) at room tempera-
ture, the mixture was then heated to 60 8C and stirred for
14–16 h (TLC). After the completion of reaction, the reaction
was quenched with H2O. The mixture was extracted with ethyl
acetate (3 ꢀ 10 mL). The combined organic layers were washed
with brine, dried over anhydrous Na2SO4, and concentrated
under reduced pressure. The residue was purified by flash
column chromatography using petroleum ether/EtOAc (10:1) as
eluent to afford the corresponding difluoroalkyl-containing
lactones 3.
d
30
20
J
= 3.8 Hz), 55.6, 39.4 (t,
J
= 22.2 Hz), 28.9, 28.5; 19F NMR
C–F
C–F
(471 MHz, CDCl3):
14H14F2O4: 284.0860, found: 284.0932.
5-(2,2-Difluoro-3-(4-methoxyphenyl)-3-oxopropyl)-3,3-
dimethyldihydrofuran-2(3H)-one (3cb): White solid, yield: 71%,
mp: 81.4–82.1 8C. 1H NMR (500 MHz, CDCl3):
8.10–6.95 (m, 4H),
d
ꢁ96.9 to ꢁ98.8 (m, 2F). HRMS calcd. for
C
d
4.81–4.76 (m, 1H), 3.88 (s, 3H), 2.78–2.47 (m, 2H), 2.33–1.86 (m,
2H), 1.27–1.26 (m, 6H); 13C NMR (126 MHz, CDCl3):
d 186.8 (t,
3
5-(2,2-Difluoro-3-oxo-3-phenylpropyl)dihydrofuran-2(3H)-
one (3aa): White solid, yield: 82%, mp: 49.5–50.7 8C. 1H NMR
2JC–F = 30.4 Hz), 181.1, 164.8, 132.8 (t, JC–F = 3.0 Hz), 124.2, 118.4
1
30
(t, JC–F = 254.9 Hz), 114.1, 80.0 (t,
J
= 4.2 Hz), 55.6, 44.2, 40.0,
C–F
20
(500 MHz, CDCl3):
d
8.13–7.51 (m, 5H), 4.90–4.86 (m, 1H), 2.85–
39.6 (t,
J
= 22.2 Hz), 24.9, 24.1; 19F NMR (471 MHz, CDCl3):
d
C–F
2.74 (m, 1H), 2.62–2.48 (m, 4H), 2.10–2.01(m, 1H); 13C NMR
ꢁ97.7 to ꢁ97.9 (m, 2F). HRMS calcd. for C16H18F2O4: 312.1173,
found: 312.1245.
5-(2,2-Difluoro-3-(4-methoxyphenyl)-3-oxopropyl)-3-methyl-
dihydrofuran-2(3H)-one (3cc): White solid, yield: 79%, mp: 81.7–
82.1 8C. 1H NMR (500 MHz, CDCl3):
d 8.12–6.97(m, 4H), 4.92–4.70
2
(126 MHz, CDCl3):
d
188.5 (t, JC–F = 30.8 Hz), 176.1, 134.6, 131.5,
3
1
130.2 (t, JC–F = 3.0 Hz), 128.8, 118.2 (t, JC–F = 255.1 Hz), 74.5 (t,
30
20
J
= 4.2 Hz), 39.3 (t,
J
= 22.4 Hz), 28.8, 28.4; 19F NMR
C–F
C–F
2
(471 MHz, CDCl3):
for C13H12F2O3:254.0755, found: 254.0762.
d
ꢁ98.4 (AB, JF–F = 296.3 Hz, 2F). HRMS calcd.
(m, 0.5H + 0.5H), 3.90 (s, 3H), 2.78–2.47 (m, 4H), 2.32–2.13 (m, 1H),
5-(2,2-Difluoro-3-oxo-3-phenylpropyl)3,3-dimethyldihydro-
furan-2(3H)-one (3ab): White solid, yield: 70%, mp: 57.3–58.1 8C.
1.31 (d, 1.5H, J = 7.9 Hz), 1.29 (d, 1.5H, J = 7.5 Hz); 13C NMR
(126 MHz, CDCl3):
(s, 0.5C), 164.8, 132.8, 124.2, 118.4 (t, 1JC–F = 254.9 Hz), 114.1, 72.4
d
186.8 (t, 2JC–F = 30.4 Hz), 179.1 (s, 0.5C), 178.6
1H NMR (500 MHz, CDCl3):
d 8.13–7.51(m, 5H), 4.84–4.79 (m, 1H),
30
30
2.84–2.72 (m,1H), 2.58–2.51(m, 1H), 2.37–2.33 (m, 1H), 1.94–1.90
(t,
J
J
= 4.2 Hz, 0.5C), 72.3 (t,
= 22.6 Hz, 0.5C), 39.1 (t,
J
= 4.2 Hz, 0.5C), 55.6, 39.4 (t,
= 23.0 Hz, 0.5C), 38.0 (s, 0.5C),
C–F
C–F
20
20
(m, 1H), 1.31–1.29 (m, 6H); 13C NMR (126 MHz, CDCl3):
d
188.5
J
C–F
C–F
2
(t, JC–F = 30.7 Hz),181.0, 134.6, 131.4, 130.2, 128.8, 118.2 (t,
36.1 (s, 0.5C), 35.5 (s, 0.5C), 33.7 (s, 0.5C), 15.6 (s, 0.5C), 14.9 (s,
0.5C); 19F NMR (471 MHz, CDCl3):
30
1JC–F = 254.9 Hz), 70.8 (t,
J
= 4.3 Hz), 44.1, 40.0, 39.5 (t,
d
ꢁ96.8 to ꢁ99.1 (m, 1F), 97.8 (s,
C–F
20
J
= 22.7 Hz), 24.9, 24.1; 19F NMR (471 MHz, CDCl3):
(AB, JF–F = 296.6 Hz, 2F). HRMS calcd. for C15H16F2O3:282.1068,
d
ꢁ98.4
1F). HRMS calcd. for C15H16F2O4: 298.1017, found: 298.0905.
5-(2,2-Difluoro-3-oxo-3-(thiophen-2-yl)propyl)dihydrofuran-
2(3H)-one (3da): White solid, yield: 80%, mp: 71.6–72.3 8C. 1H
C–F
2
found: 282.0958.
NMR (500 MHz, CDCl3):
d 8.04–7.21 (m, 3H), 4.86–4.83 (m, 1H),
2.80–2.69 (m, 1H), 2.60–2.48 (m, 4H), 2.08–1.99 (m, 1H); 13C NMR
2
(126 MHz, CDCl3):
d
181.8 (t, JC–F = 30.4 Hz), 171.6, 137.5, 137.0,
3
1
136.2 (t, JC–F = 4.6 Hz), 129.0, 117.7 (t, JC–F = 254.6 Hz), 74.4 (t,
30
20
J
= 3.8 Hz), 39.3 (t,
J
= 22.5 Hz), 28.8, 28.4; 19F NMR
2
C–F
C–F
(471 MHz, CDCl3):
for C11H10F2O3S:260.0318, found: 260.0391.
d
ꢁ99.4 (AB, JF–F = 284.7 Hz, 2F). HRMS calcd.
5-(2,2-Difluoro-3-oxo-3-(thiophen-2-yl)propyl)-3,3-dimethyld-
ihydrofuran-2(3H)-one (3db): White solid, yield: 71%, mp: 95.9–
97.0 8C. 1H NMR (500 MHz, CDCl3):
d
8.05–7.22 (m, 3H), 4.82–4.76
(m, 1H), 2.79–2.68 (m, 1H), 2.57–2.46 (m, 1H), 2.35–2.32 (m, 1H),
1.93–1.88 (m, 1H), 1.30–1.28 (m, 6H); 13C NMR (126 MHz, CDCl3):
Scheme 2. Synthesis of iododifluoromethyl ketones 1a–d.
d

J.-X. Wang et al. / Chinese Chemical Letters 26 (2015) 1381–1384
1383
181.9 (t, 2JC–F = 30.4 Hz), 181.0, 137.5, 137.0, 136.2 (t, 3JC–F = 5.1 Hz),
Table 1
Optimization of reaction conditions for the synthesis of compound 3aa.a
1
30
128.9, 117.7 (t, JC–F = 254.6 Hz), 70.4 (t,
J
= 4.2 Hz), 44.0, 40.0,
C–F
20
O
= 22.5 Hz), 24.8, 24.1; 19F NMR (471 MHz, CDCl3):
d
O
39.5 (t,
J
C–F
2
O
I
Initiator, Solvent
Temperature, 14-16 h
COOH
O
ꢁ99.3 (AB, JF–F = 289.4 Hz, 2F). HRMS calcd. for C13H14F2O3S:
288.0632, found: 288.0708.
F
F
F
F
3aa
1a
2a
5-(2,2-Difluoro-3-oxo-3-(thiophen-2-yl)propyl)-3-methyldihy-
drofuran-2(3H)-one (3dc): White solid, yield: 66%, mp: 54.4–
Entry
Initiator (mmol%)
Solvent
Temperature
Yield
(%)b
55.0 8C. 1H NMR (500 MHz, CDCl3):
d
8.04–7.21(m, 3H), 4.92–4.69
(8C)
(m, 0.5H + 0.5H), 2.80–2.45 (m, 4H), 2.31–2.14 (m,1H), 1.30 (d, 1.5H,
1
2
Pd(PPh3)4 (20)
Na2S2O4/NaHCO3 (20)
Pd(OAc)2 (20)
NiCl2 (20)
Neat
60
60
60
60
60
60
60
60
60
60
60
60
60
40
25
70
80
N.R.
43
J = 7.9 Hz), 1.29 (d, 1.5H, J = 7.0 Hz); 13C NMR (126 MHz, CDCl3):
d
CH3CN + H2O
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
DMF
181.9 (t, 2JC–F = 31.5 Hz), 179.0 (s, 0.5C),178.6 (s, 0.5C), 137.5, 137.0,
136.2 (t, 3JC–F = 4.6 Hz), 129.0, 117.7 (t, 1JC–F = 254.6 Hz, 0.5C), 117.6
3
N.R.
N.R.
N.R.
N.R.
70
4
1
30
5
Ni(acac)2 (20)
Cu0 (20)
(t, JC–F = 254.6 Hz, 0.5C), 72.1 (t,
J
J
= 4.0 Hz, 0.5C), 72.0 (t,
C–F
0
30
6
= 4.3 Hz, 0.5C), 39.4 (t, 2 JC–F = 22.6 Hz), 37.9 (s, 0.5C), 36.0 (s,
C–F
7
AIBN (20)
0.5C), 35.5 (s, 0.5C), 33.6 (s, 0.5C), 15.6 (s, 0.5C), 14.8 (s, 0.5C); 19F
8
AIBN (20)
76
NMR (471 MHz, CDCl3):
d
ꢁ98.5 to ꢁ100.0 (m, 1F), ꢁ98.7 to ꢁ100.4
9
AIBN (20)
DMSO
41
11
12
13
14
15
16
17
18
AIBN (20)
THF
54
(m, 1F); HRMS calcd. for C12H12F2O3S: 274.0475, found: 274.0544.
6-(2,2-Difluoro-3-oxo-3-phenylpropyl)tetrahydro-2H-pyran-
2-one (3ad): Light white oil, yield: 77%. 1H NMR (500 MHz, CDCl3):
AIBN (20)
1,4-Dioxane
CH3CN
46
AIBN (20)
94
AIBN (10)
CH3CN
84
d
8.12–7.51 (m, 5H), 4.41–4.36 (m, 1H), 3.17–3.05 (m, 1H), 3.00–
AIBN (20)
CH3CN
48
AIBN (20)
CH3CN
10
2.89 (m, 1H), 2.46–2.42 (m, 2H), 1.95–1.87 (m, 3H), 1.81–1.78 (m,
1H); 13C NMR (126 MHz, CDCl3):
d
188.5 (t, 2JC–F = 30.9 Hz), 179.0,
AIBN (20)
CH3CN
95
AIBN (20)
CH3CN
73
1
134.6, 131.6, 130.2, 128.8, 118.8 (t, JC–F = 256.2 Hz), 44.5 (t,
20
a
= 22.2 Hz), 39.7, 32.9, 24.8, 22.1; 19F NMR (471 MHz, CDCl3):
d
Reaction condition: 1a (1.5 mmol), 2a (1.0 mmol), organic solvent = 10 mL.
Yields determined by GC analysis and based on 2a.
J
C–F
b
2
ꢁ98.80 (AB, JF–F = 291.6 Hz, 2F). HRMS calcd. for C14H14F2O3:
268.0911, found: 268.0803.
6-(2,2-Difluoro-3-(4-fluorophenyl)-3-oxopropyl)tetrahydro-2H-
pyran-2-one (3bd): Yellow oil liquid, yield: 69%. 1H NMR
yield of 3aa (entry 14). In addition, the raising of the reaction
temperature did not promoted the reaction (entries 15 and 16).
The reaction proceeded less efficiently when the reaction
temperature was decreasing (entries 17 and 18).
Having established the optimized method, we next probe the
generality and scope of this radical addition reaction. Several
iododifluoromethyl ketones and different 4-pentenoic acids were
examined under the optimized reaction conditions (Scheme 3). In
most cases, the radical addition reaction proceeded smoothly to
(500 M Hz, CDCl3):
d 8.13–7.15 (m, 4H), 4.38–4.32 (m, 1H), 3.08–
3.05 (m, 1H), 2.93–2.86 (m, 1H), 2.43–2.42 (m, 2H), 1.89–1.73 (m,
2
4H); 13C NMR (126 MHz, CDCl3):
d
186.9 (t, JC–F = 30.5 Hz), 179.4,
0
0
166.5 (d, 1 JC–F = 258.2 Hz), 133.2 (d, 3 JC–F = 9.0 Hz), 127.9, 118.8 (t,
20
200
1JC–F = 256.1 Hz), 116.1 (t,
39.7, 32.9, 24.8, 22.0; 19F NMR (471 MHz, CDCl3):
J
= 22.1 Hz), 44.2(t, JC–F = 21.9 Hz),
C–F
d
ꢁ97.38 to ꢁ99.28
(m, 2F), ꢁ99.6 (s, 1F). HRMS calcd. for C14H13F3O4: 286.0817, found:
286.0832.
furnish the difluoroalkyl-containing
g-butyrolactones in good
yields, and no primary adduct -iodo(perfluoroalkyl)-alkanoic acid
b
3. Results and discussion
was observed. When 2-methylpent-4-enoic acid was used as
substrate to react with 2,2-difluoro-2-iodo-1-(4-methoxypheny-
l)ethanone, a mixture of trans- and cis-isomers of the correspond-
On the basis of previous literature, introduction of difluor-
omethylene group into organics could be accomplished by the
radical addition of iododifluoromethyl ketones to alkenes initiated
by Pd(PPh3)4 [28], Cu catalyst [29] and UV irradiation [30].
Therefore, we tried to use iododifluoromethyl ketones as the
difluoromethyl radicals in this reaction. The iododifluoromethyl
ketones in this communication were prepared by using release/
halogenation protocol reported by Colby [27]. Initially, we carried
out the reaction of 2,2-difluoro-2-iodo-1-phenylethanone 1a with
4-pentenoic acid 2a in the presence of Pd(PPh3)4 at room
temperature under solvent-free condition [28]. However, the
reaction hardly proceeded and a large amount (70%) of the starting
materialwasrecoveredalongwiththeformationof thesideproduct
2,2-difluoro-1-phenylethanone without any desired product 3a
(Table 1, entry 1). The result might be ascribed to the substrate
specificity of iododifluoromethyl ketone. When Na2S2O4/NaHCO3
ing difluoroalkyl-containing
g-butyrolactone was obtained in
almost a 1:1 ratio (determined by 1H NMR), and the two isomers
could not be separated due to their similarity in affinity to
chromatographic silica gel.
were used as initiators, the product difluoroalkyl-g-butyrolactone
3a was obtained in moderate yield under the reported reaction
condition [22] by using CH3CN/H2O as solvent at 60 8C (entry 2),
whereas Pd, Ni or Cu catalyst still afford no desire product in
ClCH2CH2Cl (entries 3–6). As AIBN provided a relatively higher yield
of 3a than Na2S2O4/NaHCO3 (entry 7 vs. entry 2), we chose AIBN as
the initiator for further optimization of reaction conditions.
Next, the influence of solvents on the model reaction was
investigated (entries 8–13). CH3CN promoted the reaction much
more efficiently and gave a high yield of the product 3aa (entry 13).
Decreasing the amount of AIBN to 10 mmol% led to a decrease in
Scheme 3. Reactions scope of iododifluoromethyl ketones and 4-pentenoic acids.

1384
J.-X. Wang et al. / Chinese Chemical Letters 26 (2015) 1381–1384
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4. Conclusion
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We are grateful for financial supports from the National Natural
Science Foundation of China (Nos. 21472126, 21172148,
21302128).