Synthesis of fluoroalkyl-δ-lactones from polyfluoroalkyl iodides and 5-hexenoic acids

Article abstract of DOI:10.1016/j.jfluchem.2007.12.004

The polyfluoroalkyl-lactonization of 5-hexenoic acids with the polyfluoroalkyl iodides initiated by sodium dithionite was carried out in aqueous acetonitrile, providing an efficient method for the synthesis of fluorine-containing δ-valerolactones. Formati

Full text of DOI:10.1016/j.jfluchem.2007.12.004

Available online at www.sciencedirect.com
Journal of Fluorine Chemistry 129 (2008) 280–285
www.elsevier.com/locate/fluor
Synthesis of fluoroalkyl-d-lactones from polyfluoroalkyl
iodides and 5-hexenoic acids
Xiang Fang a, Qi Ying a, Yang Chen a, Xueyan Yang a,
Xianjin Yang a,b, Fanhong Wu a,b,
*
a Laboratory for Advanced Material and Institute of fine chemicals, School of Chemistry and Molecular Engineering,
East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Received 3 December 2007; received in revised form 27 December 2007; accepted 27 December 2007
Available online 4 January 2008
Abstract
The polyfluoroalkyl-lactonization of 5-hexenoic acids with the polyfluoroalkyl iodides initiated by sodium dithionite was carried out in aqueous
acetonitrile, providing an efficient method for the synthesis of fluorine-containing d-valerolactones. Formation of RfCH2CH CH(CH2)2COOH
appeared to be unexpected minor product in sulfinatodehalogenation reagents.
# 2008 Elsevier B.V. All rights reserved.
Keywords: 5-Hexenoic acids; Polyfluoroalkyl iodide; d-valerolactone; Sodium dithionite; Polyfluoroalkyl-lactonization
1. Introduction
The addition reaction of polyfluoroalkyl iodides with
unsaturated compounds, such as olefins and alkynes, initiated
by sulfinatodehalogenation reagents (sodium dithionite) has
been thoroughly studied in our laboratory [6]. Herein we
extended our research to 5-hexenoic acids, the corresponding
polyfluoroalkylated d-valerolactones were obtained as the
major products and the unexpected elimination products were
obtained as minor products under the same reaction conditions.
The detailed experimental results and analysis are described
here.
Functionalized valerolactones are present in a large amount
of natural products and biologically active compounds such as
compactin, mevinclin and close relatives, collectively the
mevinic acids [1] and artemisinin, which is used to treat multi-
drug resistant strains of falciparum malaria [2]. Introduction of
fluorine into lactones is of great interest to synthetic chemists
due to two facts. First, fluorination of natural products and
drugs has demonstrated significant improvements of activities
and properties. Second, functionalized lactones have been
found as substructures in a variety of biologically active natural
products including flavor components, sex attractant pher-
omones of different insects, plant-growth regulators, alkaloids,
macrocyclic antibiotics, and lignanlactones [3,4]. Brace
described that thermally-induced reaction of C6F13I to 5-
hexenoic acid in ethyl acetate at 175–200 8C (bis-tert-butyl
peroxide) afforded 6-(perfluorohexyl)-5-hydroxyhexanoic acid
d-lactone in 60% yield [5].
2. Results and discussion
Free radical-induced reaction of RfI (n-C6F13) to 5-hexenoic
acid gave the primary adduct RfCH2CHI(CH2)3COOH (6da) in
excellent yield, using AIBN [7] copper powder [8] and
sulfuroxy-acid salts [6b] as initiator. Base induced SN2 internal
reaction of b-iodo(perfluoroalkyl)-alkanoic acid (6da) would
assume a conformation in which the carboxylate anion
approaches the back side of the CHI in order to smoothly
displace the iodide ion and form a d-valerolactone (3da), also
base induced a likely possible dehydrohalogenation of the
adduct would give the a,b olefin (5da) by attack of the proton
adjacent to the strong electron withdrawing perfluoroalkyl (Rf)
group [9] or give the b,g olefin (4da) by attack of the proton
* Corresponding author at: Laboratory for Advanced Material and Institute of
fine chemicals, School of Chemistry and Molecular Engineering, East China
University of Science and Technology, 130 Meilong Road, Shanghai 200237,
China. Tel.: +86 21 64253530.
E-mail address: wfh@ecust.edu.cn (F. Wu).
0022-1139/$ – see front matter # 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.12.004

X. Fang et al. / Journal of Fluorine Chemistry 129 (2008) 280–285
281
the expected complexity and shifts. The doublet of triplet at
2.79 ppm could be interpreted as arising from a 18.1 Hz
coupling of H6 with F7 and 7.0 Hz coupling of H6 with the
proton H5 (Table 1).
In order to obtain the d-valerolactone in one-pot, the
polyfluoroalkylation-lactonization reaction in the presence of
different bases and solvents was investigated. The results were
summarized in Table 2. At room temperature the adduct 6da
could not be converted completely even in different bases
(Table 2, entries 1–5). While with high temperature, the adduct
6da disappeared (Table 2, entries 6–8). It was found that the
mixture at reflux overnight after the addition reaction at 0 8C in
aqueous acetonitrile solution (CH3CN/H2O = 3:1 (v/v)) gave
the best results, with 3da in 68% yield and 4da in 30% yield
(Table 2, entry 7).
Scheme 1.
adjacent to the carboxyl group (Scheme 1). The reduction of
polyfluoroalkyl adduct had been reported by Qiu and Burton
[10]. A mixture of corresponding reduction product and b,g
olefin product was formed in a variety of solvents.
When RfI reacted with 5-hexenoic acid and analogues with a
substituent at the C-2 position, separation of 3 and 4 proved
troublesome, which result in the 50–88% of GC yields of 3
while the actual isolated yields were much low, only 16–27%
(Scheme 2 and Table 3). The reason was the tailing effect of 4
and the mixture of most 3 and 4 was obtained when the crude
product was purified by column chromatography. The
elimination products without substituent were obtained in very
small amount with 1.7:1–5.5:1 E:Z-isomers and the elimination
products with a substituent at the C-2 position could not be
separated sufficiently.
Base induced reaction of intermediate adduct 6da was
attempted under various conditions. With K2CO3 in stronger
coordinating solvent DMF, a mixture of C6F13CH CH(CH2)3
COOH 5da and C6F13CH2CH CH(CH2)2COOH 4da was
obtained, in poorly coordinating solvent acetonitrile solution,
only 4da was obtained. In sodium dithionite reagents, 3da was
obtained as major product and only 4da was obtained as minor
product.
Identification of 3da as d-lactone was based on its infrared
spectrum which showed the carbonyl frequency at 1740 cmÀ1
The results indicated that for 2-substituted 5-hexenoic acids
2b or 2c, a mixture of trans-/cis-isomers was obtained. Analysis
of the crude product by 1H NMR spectroscopy and integration
of signals attributed to proton on C-3 indicated the trans/cis
ratio of almost 1:1. The NMR signal of the proton on C-3
exhibited a multiplet in lower field for trans-isomer than for cis-
isomer [6d].
1
[11] and H NMR spectrum, which showed the anticipated
multi-pattern for H5 at 4.77–4.71 ppm. 13C NMR spectrum of
5da showed the anticipated three line pattern for C6 of 5da at
118.7 ppm showing 23.2 Hz coupling with CF2 group, 13C
NMR spectrum for C6 of 4da at 35.5 ppm with J = 22.6 Hz.
1
Also H NMR spectrum of 4da showed proton resonances of
Table 1
1H NMR, 13C NMR and IR spectra of d-valerolactone 3da and olefins 5da, 4da
d (ppm)
J (Hz)
n (cmÀ1
)
H5
4.77–4.71
1740
C6
C5
37.8
74.0
21.1
H6
6.43–6.36
H5
C6
C5
5.70–5.61
118.7
23.2
136.9
H6
2.79
JH–F = 18.1, JH–H = 7.0
1715
H5
H4
C6
C5
5.78–5.72
5.53–5.46
35.5
22.6
118.9

282
X. Fang et al. / Journal of Fluorine Chemistry 129 (2008) 280–285
Table 2
The fluoroalkylation of 5-hexenoic acid initiated by sodium dithionite
Entry
Base
Solvent
Temperature (8C)
Yielda
6da
3da
5da
4da
1
2
3
4
5
6
7
8
–
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
DMF/H2O
R.T.
R.T.
R.T.
0
51
42
20
59
20
0
20
31
33
20
20
3
21
24
41
19
22
48
30
41
NaHCO3
K2CO3
NaOH
NaOH
NaOH
NaOH
NaOH
R.T.
0–80
0–80
R.T.–80
20
47
DMF/H2O
CH3CN/H2O
CH3CN/H2O
0
68
55
0
a
Determined by GC.
Scheme 2.
All d-valerolactones exhibited a typical AB pattern signal in
the 19F NMR spectra. For example, 19F NMR of 3aa exhibited
two doublets of multiplets at À117.5 ppm and at À118.3 ppm.
The lower field signal is a doublet of doublet of doublet with
J = 267.9, 28.2, 9.4 Hz. The higher field signal is also a doublet
of doublet of doublet with J = 267.9, 28.2, 9.4 Hz.
potassium bromide pellet. High-resolution mass spectra were
carried out on a Finnigan GC-MS-4021 spectrometer. 1H NMR
(500 MHz) and 13C (125.8 MHz) spectra were recorded on a
Bruker AC-500 spectrometer with Me4Si as internal standard.
19F NMR spectra were obtained on Bruker AC-500 (470 MHz)
spectrometer in CDCl3 with CFCl3 as external standard,
downfield shifts being designated as negative. All chemical
shifts (d) are expressed in ppm, coupling constants (J) are given
in Hz.
In conclusion, a convenient and efficient method of
polyfluoroalkyl-lactonization by the reaction of 5-hexenoic
acids with polyfluoroalkyl iodides initiated by sodium dithionite
has been developed through sequential radical polyfluoroalk-
ylation and nucleophilic cyclization, and unexpected
RfCH2CH CH(CH2)2COOH were obtained as minor products.
3.1. General procedure for the reaction of 5-hexenoic acids
with polyfluoroalkyl iodides
3. Experimental
5-Hexenoic acid (2 mmol) was dissolved in aqueous sodium
hydroxide solution freshly prepared from 100 mg sodium
hydroxide in 1 mL water and stirred while acetonitrile (3 mL)
and RfI (2.2 mmol) was added. To the solution was added
All melting points were uncorrected. IR spectra were
measured on a Nicolet Magna IR-550 spectrometer using
Table 3
Data of the reaction of RfI 1 with 5-hexenoic acids 2
Entry
Substance
R
Rf
Product
Yield of 3 (%)a
Yield of 3 (%)b
Yield of 4 (%)a
E:Z of 4
1
2
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2c
H
C2F5
3aa
3ba
3ca
3da
3ab
3bb
3cb
3db
3ac
3bc
3cc
3dc
88
64
51
60
56
59
67
50
71
62
80
82
24
22
20
22
19
18
20
18
20
20
16
27
10
32
39
35
39
37
28
43
22
34
17
13
3:1c
H
ClC2F4
ClC4F8
C6F13
C2F5
2.5:1c
1.7:1c
5.5:1c
3
H
4
H
5
Et
Et
Et
Et
Bn
Bn
Bn
Bn
6
ClC2F4
ClC4F8
C6F13
C2F5
7
8
9
10
11
12
ClC2F4
ClC4F8
C6F13
a
Determined by GC.
Isolated yields.
Based on 19F and 13C NMR.
b
c

X. Fang et al. / Journal of Fluorine Chemistry 129 (2008) 280–285
283
sodium dithionite (440 mg) and sodium bicarbonate (210 mg).
The mixture was stirred at 0 8C for 2–5 h to complete the
reaction; after at reflux overnight the mixture was treated with
about 10 mL of water and extracted with 3 Â 5 mL of ether.
The combined organic layer was washed with saturated brine
solution and dried over anhydrous sodium sulfate. After
evaporation of ether, the crude product was subjected to column
chromatography to give the pure product.
(t, J = 22.8 Hz), 29.1. 19F NMR (CDCl3, 470 MHz) (E-isomer)
d À71.5 (2F, s), À114.1 (2F, t, J = 16.5 Hz); (Z-isomer) d À72.0
(2F, s), À115.3 (2F, t, J = 16.5 Hz). EI-MS (m/z) 251 (M + 2+,
2), 249 (M+, 6), 192 (39), 60 (100). HRMS cacld for
C8H9O2F4Cl: 248.0227, found: 248.0225.
3.1.5. 5-(2,2,3,3,4,4,5,5-Octafluoro-5-chloropentyl)-d-
valerolactone (3ca)
Colorless oil; IR (cmÀ1, KBr) 2959, 1741 (d-lactone), 1186,
1
841, 697. H NMR (CDCl3, 500 MHz) d 4.77–4.71 (1H, m),
3.1.1. 5-(2,2,3,3,3-Pentafluoropropyl)-d-valerolactone
(3aa)
2.70–2.56 (2H, m), 2.53–2.47 (1H, m), 2.45–2.30 (1H, m),
2.15–2.08 (1H, m), 2.03–1.89 (2H, m), 1.73–1.63 (1H, m). 13
C
Colorless oil; IR (cmÀ1, KBr) 2932, 1743 (d-lactone), 1197,
1
719. H NMR (CDCl3, 500 MHz) d 4.75–4.68 (1H, m), 2.70–
NMR (CDCl3, 125.8 MHz) d 170.9, 126.2–103.6 (4C, m), 74.1,
37.8 (t, J = 20.4 Hz), 30.0, 29.2, 18.9. 19F NMR (CDCl3,
470 MHz) d À69.0 (2F, t, J = 13.4 Hz), À112.9 (1F, ddd, JF–
F = 272.6 Hz, JF–H = 28.2 Hz, JF–H = 14.1 Hz), À114.2 (1F,
ddd, JF–F = 272.6 Hz, JF–H = 28.2 Hz, JF–H = 14.1 Hz), À120.8
(2F, s), À123.9 (2F, s). EI-MS (m/z) 350 (M + 2+, 2), 348 (M+,
6), 306 (20), 304 (61), 99 (100). HRMS cacld for C10H9O2F8Cl:
348.0163, found: 348.0163.
2.53 (1H, m), 2.55–2.45 (1H, m), 2.38–2.27 (1H, m), 2.14–2.08
(1H, m), 2.02–1.92 (2H, m), 1.73–1.64 (2H, m). 13C NMR
(CDCl3, 125.8 MHz) d 170.8, 126.5–113.3 (2C, m), 74.0, 37.6 (t,
J = 21 Hz), 29.8, 29.1, 19.0. 19F NMR (CDCl3, 470 MHz) d
À86.8 (3F, s), À117.5 (1F, ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz,
J
F–H = 9.4 Hz), À118.3 (1F, ddd, JF–F = 267.9 Hz, JF–H
=
28.2 Hz, JF–H = 9.4 Hz). EI-MS (m/z) 232 (M+, 100), 188
(21). HRMS cacld for C8H9O2F5: 232.0523, found: 232.0523.
3.1.6. 7,7,8,8,9,9,10,10,10-Nonafluorodec-4-enoic acid
(4ca)
3.1.2. 7,7,8,8,8-Pentafluorooct-4-enoic acid (4aa)
Colorless oil; IR (cmÀ1, KBr) 2932, 1716, 1200, 1119, 715.
1H NMR (CDCl3, 500 MHz) d 5.71–5.62 (1H, m), 5.48–5.35
(1H, m), 2.68 (2H, td, J = 17.4 Hz, J = 7.0 Hz), 2.46–2.27 (4H,
m). 13C NMR (CDCl3, 125.8 MHz) d (E-isomer) 179.7, 136.7,
119.0, 124.6–113.2 (2C, m), 35.2 (t, J = 22.4 Hz), 34.0, 28.1;
(Z-isomer) 181.1, 134.9, 118.2, 124.6–113.2 (2C, m), 34.4, 31.1
(t, J = 22.1 Hz), 29.1. 19F NMR (CDCl3, 470 MHz) d (E-
isomer) À85.8 (3F, s), À118.2 (2F, t, J = 16.5 Hz); (Z-isomer)
À86.4 (3F, s), À119.3 (2F, t, J = 18.8 Hz). EI-MS (m/z) 232
(M+, 8), 212 (22), 192 (29), 60 (100). HRMS cacld for
C8H9O2F5: 232.0523, found: 232.0515.
Colorless oil; IR (cmÀ1, KBr) 2962, 1716, 1236, 1134, 798.
1H NMR (CDCl3, 500 MHz) d 5.72–5.64 (1H, m), 5.49–5.37
(1H, m), 2.73 (2H, td, J = 17.5 Hz, J = 6.9 Hz), 2.42–2.38 (4H,
m). 13C NMR (CDCl3, 125.8MHz) d (E-isomer) 179.4, 137.0,
118.8, 122.1–109.0 (4C, m), 35.4 (t, J = 22.5 Hz), 34.0, 28.2;
(Z-isomer) 180.1, 135.1, 118.2, 122.1–109.0 (4C, m), 34.3, 31.3
(t, J = 22.2 Hz), 29.1. 19F NMR (CDCl3, 470MHz) d (E-isomer)
À82.0 (2F, s), À114.5 (2F, t, J = 14.1 Hz), À125.0 (2F, s),
À127.1 (2F, s); (Z-isomer) À82.0 (2F, s), À115.6 (2F, t,
J = 14.1Hz), À125.5 (2F, s), À127.1 (2F, s). EI-MS (m/z) 350
(M + 2+, 2), 348 (M+, 6), 60 (100). HRMS cacld for
C10H9O2F8Cl: 348.0163, found: 348.0163.
3.1.3. 5-(2,2,3,3-Tetrafluoro-3-chloropropyl)-d-
valerolactone (3ba)
3.1.7. 5-(2,2,3,3,4,4,5,5,6,6,7,7,7-Tridecafluoroheptyl)-d-
valerolactone (3da)
Colorless oil; IR (cmÀ1, KBr) 2973, 1724 (d-lactone), 1259,
1155, 1052, 939, 767. 1H NMR (CDCl3, 500 MHz) d 4.76–4.70
(1H, m), 2.71–2.58 (2H, m), 2.54–2.47 (1H, m), 2.43–2.31 (1H,
m), 2.15–2.08 (1H, m), 2.03–1.90 (2H, m), 1.73–1.63 (1H, m).
13C NMR (CDCl3, 125.8 MHz) d 170.9, 123.9 (tt, J = 298.6 Hz,
J = 37.0 Hz), 116.6 (tt, J = 256.3 Hz, J = 33.8 Hz), 74.3, 37.4
(t, J = 21.4 Hz), 29.7, 29.0, 18.9. 19F NMR (CDCl3, 470 MHz) d
White solid; m.p. 56–57 8C. IR (cmÀ1, KBr) 2920, 1740 (d-
lactone), 1252, 1144, 699. 1H NMR (CDCl3, 500 MHz) d 4.77–
4.71 (1H, m), 2.70–2.58 (2H, m), 2.55–2.48 (1H, m), 2.46–2.31
(1H, m), 2.13–2.08 (1H, m), 2.03–1.93 (2H, m), 1.73–1.63 (1H,
m). 13C NMR (CDCl3, 125.8 MHz) d 170.8, 122.6–106.0 (6C,
m), 74.0, 37.8 (t, J = 21.1 Hz), 29.8, 29.2, 19.0. 19F NMR
(CDCl3, 470 MHz) d À81.9 (3F, t, J = 11.8 Hz), À113.1 (1F,
ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz), À114.3
(1F, ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz),
À122.9 (2F, s), À124.0 (2F, s), À124.8 (2F, s), À127.3 (2F,
s). EI-MS (m/z) 432 (M+, 2), 388 (100). HRMS cacld for
C12H9O2F13: 432.0395, found: 432.0394.
À72.8 (2F, s), À112.8 (1F, ddd, JF–F = 258.5 Hz, JF–H
=
28.2 Hz, JF–H = 9.4 Hz), À114.2 (1F, ddd, JF–F = 258.5 Hz, JF–
H = 28.2 Hz, JF–H = 9.4 Hz). EI-MS (m/z) 250 (M + 2+, 7), 248
(M+, 21), 206 (30), 204 (100). HRMS cacld for C8H9O2F4Cl:
248.0227, found: 248.0228.
3.1.4. 8-Chloro-7,7,8,8-tetrafluorooct-4-enoic acid (4ba)
1
Colorless oil; IR (cmÀ1, KBr) 2926, 1714, 1256, 1152. H
3.1.8. 7,7,8,8,9,9,10,10,11,11,12,12,12-
Tridecafluorododec-4-enoic acid (4da)
7,7,8,8,9,9,10,10,11,11,12,12,12-tridecafluorododec-5-
enoic acid (5da)
Colorless oil; IR (cmÀ1, KBr) 2938, 1715, 1241, 1144, 709.
1H NMR (CDCl3, 500 MHz) d 6.43–6.36 (1H, m), 5.78–5.72
NMR (CDCl3, 500 MHz) d 5.77–5.69 (1H, m), 5.54–5.46 (1H,
m), 2.80 (2H, td, J = 17.6Hz, J = 6.7 Hz), 2.51–2.38 (4H, m).
13C NMR (CDCl3, 125.8 MHz) (E-isomer) d 179.3, 136.5,
119.4, 126.8–115.5 (2C, m), 35.1 (t, J = 22.9 Hz), 34.0, 28.1;
(Z-isomer) 181.0, 134.7, 118.8, 126.8–115.5 (2C, m), 34.3, 31.0

284
X. Fang et al. / Journal of Fluorine Chemistry 129 (2008) 280–285
(0.7H, m), 5.70–5.61 (1H, m), 5.53–5.46 (0.7H, m), 2.79 (1.4H,
td, J = 18.1 Hz, J = 7.0 Hz), 2.49–2.46 (2H, m), 2.45–2.38
(3.4H, m), 2.32–2.26 (1.4H, m), 1.86–1.79 (2H, m). 13C NMR
(CDCl3, 125.8 MHz) 4da d 180.1, 136.9, 118.7 (t, J = 23.2 Hz),
121.4–106.9 (6C, m), 33.7, 31.8, 23.6; 5da d 179.8, 142.4 (t,
J = 8.9 Hz), 118.9, 121.4–106.9 (6C, m), 35.5 (t, J = 22.6 Hz),
34.0, 28.2. 19F NMR (CDCl3, 470 MHz) 4da d À82.1 (3F, t,
J = 9.9 Hz), À112.7 (2F, s), À122.9 (2F, s), À124.2 (2F, s),
À124.8 (2F, s), À127.4 (2F, s); 5da d À82.1 (3F, t, J = 9.9 Hz),
À114.6 (2F, s), À123.2 (2F, s), À124.4 (2F, s), À124.8 (2F, s),
À127.4 (2F, s). EI-MS (m/z) 432 (M+, 14), 412 (76), 392 (100).
HRMS cacld for C12H9O2F13: 432.0395, found: 432.0396.
4.76-4.68 (1H, m), 2.71–2.55 (1H, m), 2.46–2.36 (2H, m),
2.19–2.05 (2H, m), 2.01–1.91 (1H, m), 1.77–1.58 (3H, m), 0.98
(3H, t, J = 7.5 Hz). 13C NMR (CDCl3, 125.8 MHz) d 171.2,
121.1–114.1 (4C, m), 73.2, 40.9, 36.4 (t, J = 21.0 Hz), 28.7,
23.8, 21.6, 10.0. 19F NMR (CDCl3, 470 MHz) d À69.0 (2F, t,
J = 12.7 Hz), À112.5 to À114.7 (2F, m), À120.8 (2F, s),
À123.9 (2F, s). EI-MS (m/z) 376 (M+, 2), 350 (30), 348 (100).
HRMS cacld for C12H13O2F8Cl: 376.0476, found: 376.0476.
3.1.12. 2-Ethyl-5-(2,2,3,3,4,4,5,5,6,6,7,7,7-
tridecafluoroheptyl)-d-valerolactone (3db)
White solid; m.p. 60–61 8C. IR (cmÀ1, KBr) 2981, 1728 (d-
lactone), 1206, 1146, 702, 659. 1H NMR (CDCl3, 500 MHz) d
4.76–4.68 (0.5H + 0.5H, m), 2.71–2.56 (0.5H + 0.5H, m),
2.47–2.25 (1H + 1H, m), 2.22–2.06 (1H + 1H, m), 2.01–1.87
(1H, m), 1.81–1.56 (0.5H + 1H + 1H, m), 1.54–1.45 (0.5H, m),
1.01 (1.5H, t, J = 7.4 Hz), 0.98 (1.5H, t, J = 7.0 Hz). 13C NMR
(CDCl3, 125.8 MHz) d cis 174.7, 120–108 (6C, m), 71.4, 40.1,
37.3 (t, J = 21.0 Hz), 28.2, 24.4, 23.3, 12.1; trans 172.9, 120–
108 (6C, m), 74.8, 42.6, 38.1 (t, J = 20.8 Hz), 30.4, 29.8, 25.5,
11.7. 19F NMR (CDCl3, 470 MHz) d À81.7 (3F, t, J = 9.4 Hz),
À112.4 to À114.6 (2F, m), À122.7 (2F, s), À123.8 (2F, s),
À124.5 (2F, s), 127.1 (2F, q, J = 9.4 Hz). EI-MS (m/z) 460 (M+,
3), 432 (100). HRMS cacld for C14H13O2F13: 460.0708, found:
460.0703.
3.1.9. 2-Ethyl-5-(2,2,3,3,3-pentafluoropropyl)-d-
valerolactone (3ab)
Colorless oil; IR (cmÀ1, KBr) 2970, 1742 (d-lactone), 1196,
795, 719. 1H NMR (CDCl3, 500 MHz)
d 4.74–4.66
(0.6H + 0.4H, m), 2.65–2.51 (0.6H + 0.4H, m), 2.48–2.34
(1.2H, m), 2.34–2.23 (0.8H, m), 2.21–2.06 (1.2H + 0.8H, m),
2.01–1.86 (1.2H, m), 1.80–1.53 (0.6H + 0.8H + 0.8H, m), 1.52–
1.44 (0.6H, m), 1.01 (1.2H, t, J = 7.5 Hz), 0.98 (1.8H, t,
J = 7.5 Hz). 13C NMR (CDCl3, 125.8 MHz) d cis 172.9, 123.9–
119.8 (2C, m), 74.8, 42.6, 37.9 (t, J = 20.9 Hz), 30.3, 25.4, 24.4,
11.7; trans 174.7, 117.5–113.6 (2C, m), 71.4, 40.1, 37.1 (t,
J = 21.1 Hz), 28.1, 25.4, 23.3, 12.2. 19FNMR(CDCl3, 470 MHz)
d cis À86.8 (3F, s), À116.7 (1F, ddd, JF–F = 267.9 Hz, JF–
H = 28.2 Hz, JF–H = 9.4 Hz), À118.4 (1F, ddd, JF–F = 267.9 Hz,
3.1.13. 2-Benzyl-5-(2,2,3,3,3-pentafluoropropyl)-d-
valerolactone (3ac)
J
F–H = 28.2 Hz, JF–H = 9.4 Hz); trans À86.8 (3F, s), À116.9 (1F,
ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz), À118.5
(1F, ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz). EI-
MS (m/z) 260 (M+, 2), 232 (100). HRMS cacld for C10H13O2F5:
260.0836, found: 260.0836.
Colorless oil; IR (cmÀ1, KBr) 2932, 1741 (d-lactone), 1198,
1096, 746, 702. 1H NMR (CDCl3, 500 MHz) d 7.33–7.29
(2.5H, m), 7.25–7.18 (2.5H, m), 4.72–4.65 (0.5H, m), 4.64–
4.57 (0.5H, m), 3.40 (0.5H, dd, J = 13.7 Hz, J = 4.0 Hz), 3.34
(0.5H, dd, J = 13.9 Hz, J = 4.4 Hz), 2.88–2.74 (1H, m), 2.71–
2.63 (1H, m), 2.62–2.48 (1H, m), 2.36–2.17 (1H, m), 2.11–1.95
(1H + 0.5H, m), 1.92–1.85 (0.5H, m), 1.78–1.68 (0.5H, m),
1.68–1.53 (0.5H + 1H, m). 13C NMR (CDCl3, 125.8 MHz) d cis
171.7, 138.4, 129.2, 128.6, 126.7, 120.1–118.3 (2C, m), 74.4,
42.5, 37.5, 37.2 (t, J = 21.0 Hz), 29.5, 24.8; trans 173.6, 138.6,
129.1, 128.6, 126.7, 118.0–116.2 (2C, m), 70.8, 39.9, 36.7, 36.3
(t, J = 21.2 Hz), 27.2, 22.3. 19F NMR (CDCl3, 470 MHz) d cis
3.1.10. 2-Ethyl-5-(2,2,3,3-tetrafluoro-3-chloropropyl)-d-
valerolactone (3bb)
White solid; m.p. 50–51 8C. IR (cmÀ1, KBr) 2972, 1725 (d-
lactone), 1153, 1097, 939. 1H NMR (CDCl3, 500 MHz) d 4.74–
4.66 (0.5H + 0.5H, m), 2.70–2.56 (0.5H + 0.5H, m), 2.44–2.30
(1H + 1H, m), 2.18–2.06 (1H + 1H, m), 2.0–1.91 (1H, m),
1.76–1.56 (0.5H + 1H + 1H, m), 1.50–1.45 (0.5H, m), 1.01
(1.5H, J = 7.5 Hz), 0.98 (1.5H, J = 7.5 Hz). 13C NMR (CDCl3,
125.8 MHz) d cis 172.3, 125.4–120.8 (2C, m), 74.5, 42.0, 37.2
(t, J = 21.3Hz), 29.6, 24.8, 22.6, 11.0; trans 174.2, 120.6–116.0
(2C, m), 71.1, 39.4, 36.3 (t, J = 21.4Hz), 27.5, 24.8, 23.8, 11.5.
19F NMR (CDCl3, 470 MHz) d cis À72.7 (2F, s), À112.6 (1F,
ddd, JF–F = 258.5 Hz, JF–H = 30.6 Hz, JF–H = 7.1 Hz), À114.3
(1F, ddd, JF–F = 258.5 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz);
trans À72.7 (2F, s), À112.8 (1F, ddd, JF–F = 258.5 Hz, JF–
H = 30.6 Hz, JF–H = 7.1 Hz), À114.3 (1F, ddd, JF–F = 258.5 Hz,
À86.8 (3F, s), À116.7 (1F, ddd, JF–F = 267.9 Hz, JF–H
=
28.2 Hz, JF–H = 9.4 Hz), À118.3 (1F, ddd, JF–F = 267.9 Hz, JF–
H = 28.2 Hz, JF–H = 9.4 Hz); trans À86.7 (3F, s), À116.9 (1F,
ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz), À118.4
(1F, ddd, JF–F = 267.9 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz). EI-
MS (m/z) 322 (M+, 59), 91 (100). HRMS cacld for C15H15O2F5:
322.0992, found: 322.0992.
3.1.14. 2-Benzyl-5-(2,2,3,3-tetrafluoro-3-chloropropyl)-d-
valerolactone (3bc)
J
F–H = 28.2 Hz, JF–H = 9.4 Hz). EI-MS (m/z) 276 (M+, 2), 250
(29), 248 (100). HRMS cacld for C10H13O2F4Cl: 276.0540,
found: 276.0540.
White solid; m.p. 50–53 8C. IR (cmÀ1, KBr) 2958, 1720 (d-
lactone), 1094, 937, 741, 700. H NMR (CDCl3, 500 MHz) d
1
7.34–7.28 (2.5H, m), 7.25–7.18 (2.5H, m), 4.73–4.66 (0.5H,
m), 4.65–4.57 (0.5H, m), 3.40 (0.5H, dd, J = 13.7 Hz,
J = 4.1 Hz), 3.33 (0.5H, dd, J = 13.9 Hz, J = 4.4 Hz), 2.86–
2.76 (1H, m), 2.72–2.55 (1H + 1H, m), 2.40–2.22 (1H, m),
2.10–1.95 (1H + 0.5H, m), 1.92–1.85 (0.5H, m), 1.78–1.68
3.1.11. 2-Ethyl-5-(2,2,3,3,4,4,5,5-octafluoro-5-
chloropentyl)-d-valerolactone (3cb)
White solid; m.p. 59–60 8C. IR (cmÀ1, KBr) 2953, 1731 (d-
lactone), 1186, 1128, 795, 695. 1H NMR (CDCl3, 500 MHz) d

X. Fang et al. / Journal of Fluorine Chemistry 129 (2008) 280–285
285
(0.5H, m), 1.68–1.52 (0.5H + 1H, m). 13C NMR (CDCl3,
125.8 MHz) d cis 171.7, 138.4, 129.2, 128.6, 126.7, 116.1–
111.6 (2C, m), 74.7, 42.5, 37.6, 37.1 (t, J = 21.4 Hz), 29.6, 24.8;
trans 173.7, 138.6, 129.1, 128.6, 126.7, 123.5–120 (2C, m),
71.2, 39.9, 36.7, 36.3 (t, J = 21.5 Hz), 27.2, 22.4. 19F NMR
(CDCl3, 470 MHz) d cis À72.7 (2F, s), À112.6 (1F, ddd, JF–
F = 258.5 Hz, JF–H = 28.2 Hz, JF–H = 4.7 Hz), À114.2 (1F, ddd,
171.7, 138.4, 129.2, 128.6, 126.7, 102.3–97.9 (6C, m), 74.4,
42.5, 37.6, 37.4 (t, J = 21.2 Hz), 29.6, 24.9; trans 173.6, 138.6,
129.1, 128.6, 126.7, 117.6–113.2 (6C, m), 70.8, 39.9, 36.7, 36.6
(t, J = 21.3 Hz), 27.3, 22.3. 19F NMR (CDCl3, 470 MHz) d
À81.7 (3F, t, J = 9.6 Hz), À112.5 to À114.6 (2F, m), À122.7
(2F, s), À123.8 (2F, s), À124.5 (2F, s), 127.1 (2F, q, J = 9.4 Hz).
EI-MS (m/z) 522 (M+, 69), 91 (100). HRMS cacld for
C19H15O2F13: 522.0864, found: 522.0864.
J
F–F = 258.5 Hz, JF–H = 28.2 Hz, JF–H = 9.4 Hz); trans À72.7
(2F, s), À112.9 (1F, ddd, JF–F = 258.5 Hz, JF–H = 28.2 Hz, JF–
H = 9.4 Hz), À114.3 (1F, ddd, JF–F = 258.5 Hz, JF–H = 28.2 Hz,
J
F–H = 9.4 Hz). EI-MS (m/z) 340 (M + 2+, 31), 338 (M+, 100),
Acknowledgement
91 (78). HRMS cacld for C15H15O2F4Cl: 338.0697, found:
338.0697.
This research work was supported by the National Natural
Science Foundation of China (Grant no. 20672034).
3.1.15. 2-Benzyl-5-(2,2,3,3,4,4,5,5-octafluoro-5-
chloropentyl)-d-valerolactone (3cc)
White solid; m.p. 61–64 8C. IR (cmÀ1, KBr) 2945, 1725 (d-
lactone), 1130, 742, 698. 1H NMR (CDCl3, 500 MHz) d 7.33–
7.29 (2.5H, m), 7.25–7.18 (2.5H, m), 4.75–4.68 (0.5H, m),
4.67–4.61 (0.5H, m), 3.40 (0.5H, dd, J = 13.7 Hz, J = 4.1 Hz),
3.34 (0.5H, dd, J = 13.9 Hz, J = 4.4 Hz), 2.86–2.76 (1H, m),
2.72–2.53 (1H + 1H, m), 2.40–2.20 (1H, m), 2.10–1.95
(1H + 0.5H, m), 1.92–1.84 (0.5H, m), 1.79–1.53
(0.5H + 0.5H + 1H, m). 13C NMR (CDCl3, 125.8 MHz) d cis
172.4, 139.1, 129.9, 129.3, 127.4, 114.9–109.8 (4C, m), 75.1,
43.2, 38.2, 38.1 (t, J = 20.9 Hz), 30.3, 25.5; trans 174.3, 139.3,
129.8, 129.3, 127.4, 125.1–120.0 (4C, m), 71.6, 40.6, 37.4, 37.2
(t, J = 21.1 Hz), 27.9, 23.0. 19F NMR (CDCl3, 470 MHz) d
À69.0 (2F, t, J = 12.7 Hz), À112.5 to À114.7 (2F, m), À120.7
(2F, s), À123.9 (2F, s). EI-MS (m/z) 440 (M + 2+, 12), 438 (M+,
38), 91 (100). HRMS cacld for C17H15O2F8Cl: 438.0633,
found: 438.0633.
References
[1] F. Bennett, D.W. Knight, G. Fenton, J. Chem. Soc. Perkin Trans. 1 (1991)
133–140.
[2] N. Acton, R.J. Roth, J. Org. Chem. 57 (1992) 3610–3614.
[3] C. Wang, G.A. Russell, J. Org. Chem. 64 (1999) 2066–2069.
[4] (a) I. Ojima, J.R. McCarthy, J.T. Welch, ACS Symposium Series 639
American Chemical Society, Washington, DC, 1996;
(b) T. Itoh, K. Kudo, K. Yokota, N. Tanaka, S. Hayase, M. Renou, Eur. J.
Org. Chem. (2004) 406–412.
[5] N.O. Brace, J. Org. Chem. 29 (1964) 1247–1249.
[6] (a) X.W. Zou, F.H. Wu, Y.J. Shen, S. Xu, W.Y. Huang, Tetrahedron 59
(2003) 2555–2560;
(b) F.H. Wu, X.Y. Yang, Z.H. Wang, W.Y. Huang, J. Fluorine Chem. 128
(2007) 84–86;
(c) S.J. Mao, X. Fang, L. Ba, F.H. Wu, J. Fluorine Chem. 128 (2007) 5–
11;
(d) X.Y. Yang, Y.P. Zhu, X. Fang, X.J. Yang, F.H. Wu, Y.J. Shen, J.
Fluorine Chem. 128 (2007) 174–178;
(e) X.Y. Yang, Z.H. Wang, X. Fang, X.J. Yang, F.H. Wu, Y.J. Shen,
Synthesis 12 (2007) 1768–1778.
3.1.16. 2-Benzyl-5-(2,2,3,3,4,4,5,5,6,6,7,7,7-
[7] (a) N.O. Brace, J. Fluorine Chem. 108 (2001) 147–175;
(b) N.O. Brace, Paper 0.20 Presented at the Fourth International Sympo-
sium Organic Free Radicals Sponsored by the Royal Society of Chemistry,
July 10, University of St. Andrews, Scotland, 1984.
[8] (a) Q.Y. Chen, Z.Y. Yang, J. Fluorine Chem. 28 (1985) 399–411;
(c) Z.Y. Yang, D.J. Burton, J. Fluorine Chem. 45 (1989) 435–439.
[9] (a) N.O. Brace, J. Org. Chem. 27 (1962) 4491–4498;
(b) N.O. Brace, J. Org. Chem. 36 (1971) 1904–1909.
[10] W.M. Qiu, D.J. Burton, J. Org. Chem. 58 (1993) 419–423.
[11] R.T. Conley, Infrared Spectroscopy, Second ed., Allyn and Bacon, Inc.,
Boston, 1966, pp. 143–150/167–173.
tridecafluoroheptyl)-d-valerolactone (3dc)
White solid; m.p. 75–77 8C. IR (cmÀ1, KBr) 1720 (d-
lactone), 1192, 1144, 701. 1H NMR (CDCl3, 500 MHz) d 7.34–
7.29 (2.5H, m), 7.25–7.18 (2.5H, m), 4.75–4.68 (0.5H, m),
4.67–4.60 (0.5H, m), 3.40 (0.5H, dd, J = 13.7 Hz, J = 4.1 Hz),
3.34 (0.5H, dd, J = 13.9 Hz, J = 4.4 Hz), 2.87–2.77 (1H, m),
2.72–2.53 (1H + 1H, m), 2.40–2.22 (1H, m), 2.10–1.96
(1H + 0.5H, m), 1.92–1.85 (0.5H, m), 1.80–1.54
(0.5H + 0.5H + 1H, m). 13C NMR (CDCl3, 125.8 MHz) d cis