New preparation of difluoroiodomethylsulfanylbenzenes and their radical addition to unsaturated compounds initiated by sodium dithionite

Article abstract of DOI:10.1016/j.tet.2007.12.018

Difluoroiodomethylsulfanylbenzene (3a) and 1-chloro-4-difluoroiodomethylsulfanylbenzene (3b) are novel and efficient difluoromethylating reagents via the reaction with unsaturated compounds, such as alkenes, ethynylbenzene, pent-4-en-1-ols, and pent-4-eno

Full text of DOI:10.1016/j.tet.2007.12.018

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2259e2269
www.elsevier.com/locate/tet
New preparation of difluoroiodomethylsulfanylbenzenes and their radical
addition to unsaturated compounds initiated by sodium dithionite
Xueyan Yang a, Xiang Fang a, Xianjin Yang a, Min Zhao a, Yizheng Han a,
Yongjia Shen a, Fanhong Wu a,b,
*
a Laboratory for Advanced Material and Institute of Fine Chemicals, East China University of Science and Technology,
130 Meilong Road, Shanghai 200237, PR China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, PR China
Received 17 August 2007; received in revised form 31 October 2007; accepted 4 December 2007
Available online 14 December 2007
Abstract
Difluoroiodomethylsulfanylbenzene (3a) and 1-chloro-4-difluoroiodomethylsulfanylbenzene (3b) are novel and efficient difluoromethylating
reagents via the reaction with unsaturated compounds, such as alkenes, ethynylbenzene, pent-4-en-1-ols, and pent-4-enoic acids initiated by
Na2S2O4, to afford the corresponding adducts, tetrahydrofuran derivatives, and g-butyrolactones containing difluoromethylene group in moder-
ate to good yields.
Ó 2007 Published by Elsevier Ltd.
Keywords: Difluoroiodomethylsulfanylbenzene; Difluoromethylene; g-Butyrolactone; Addition; Tetrahydrofuran derivatives
1. Introduction
formation of Grignard reagents.12 However, it is still highly
desirable to develop new effective, convenient, and general
preparation methods and new difluoromethylating reagents.
Polyfluoroalkyl iodides, which can react with various
unsaturated substrates via free radical addition, an efficient
method for the preparation of polyfluoroalkylated derivatives,
have better reactivity than the corresponding bromides.13 We
are convinced that, similar to polyfluoroalkyl iodides, function-
alized difluoromethyl iodides may proceed by free radical addi-
tion reaction under the appropriate conditions giving adducts
and the formed CeI bond could be further elaborated. This pro-
moted us to develop new functionalized difluoromethyl iodides.
In recent years, gem-difluoromethylated compounds with CF2
adjacent to sulfur atom have been attractive due to their syn-
thetic utilities.11,14 But limited examples were reported on the
introduction of CF2 bonding to sulfur atom, especially difluoro-
methylated sulfanyl group,11,12,15 into organic compounds.
Here, we wish to describe the new preparation of novel difluo-
romethylating reagents, difluoroiodomethylsulfanylbenzene
(3a) and 1-chloro-4-difluoroiodomethylsulfanylbenzene (3b),
The selective introduction of a gem-difluoromethylene
(CF2) moiety into organic compounds is of great importance
because this group is usually considered as an isopolar and
isosteric replacement for oxygen1 and some molecules con-
taining CF2 group are potential broad spectrum antibiotics,2
inhibitors of HIV-1 reverse transcriptase,3,4 and antitumor
agents.5 Introduction of CF2 group into organic molecules is
often realized through the conversion of a carbonyl into a di-
fluoromethylene group with (diethylamino)sulfur trifluoride
(DAST)6 or other reagents.7 Compounds with CF2 moiety,
such as XCF2COOEt and CF2X2 (X¼I, Br, Cl), are also
used to introduce CF2 group into organic compounds via rad-
ical,8 carbene,9 and ionic reactions.3,10 Recently, PhSCF2Br
has been demonstrated to be a versatile gem-difluoromethylat-
ing reagent via the radical reaction promoted by SmI211 or the
* Corresponding author.
E-mail address: wfh@ecust.edu.cn (F. Wu).
0040-4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.12.018

2260
X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
SCF2I
by halogen exchange and the study of their radical addition to
unsaturated compounds initiated by Na2S2O4. The reaction of
3a and 3b with alkenes and alkynes afforded the corresponding
adducts. The reaction of 3a and 3b with pent-4-en-1-ols and
pent-4-enoic acids followed by the intramolecular replacement
of CeI bond gave tetrahydrofuran derivatives and g-butyrolac-
tones containing phenylsulfanyl difluoromethyl moiety.
S
R1
Na2S2O4/NaHCO3
25 °C
R1
4a'-4f'
+
F
F
I
R
5aa'-5af'
5ba'-5bf'
R
3a, 3b
SCF2I
I
Na2S2O4/NaHCO3
25 °C
+
CF2S
R
2. Results and discussion
trans-
7a: R = H
7b: R = Cl
6
R
3a, 3b
2.1. Preparation of 3a and 3b
SCF2I
S
I
Difluoroiodomethylsulfanylbenzene (3a) and 1-chloro-4-
difluoroiodomethylsulfanylbenzene (3b) can be prepared by
nucleophilic reaction of benzenethiol (1a) and 4-chloro-benze-
nethiol (1b) with CF2I2 in very low yields as reported in the
literature.16 Herein, we developed a convenient and efficient
method to prepare 3a and 3b by halogen exchange reaction
of bromodifluoromethylsulfanylbenzene (2a) and 1-chloro-4-
bromodifluoromethylsulfanylbenzene (2b) in the presence of
sodium iodide (Scheme 1). While 2a and 2b were easily ob-
tained by the reaction of sodium phenylthiolate with dibromo-
difluoromethane,17 conversion of CF2Br to CF2I by halogen
exchange reaction was usually difficult to occur and there
were limited reports on such a transformation. Previous reports
showed that the reaction usually proceeded in acetone18 and
butanone.19 However, the reaction of 2 with NaI didn’t occur
when only acetone or butanone was used as the solvent. While
in DMF, 2 converted completely in several hours giving a com-
plicated mixture with less than 10% of 3 formed. When the
reaction of 2a with NaI was carried out in the mixture of
acetone and DMF (4.4:1 v/v) under reflux for a week, 3a
was obtained in 56% yield. For 2b, the reaction proceeded
in acetone and DMF (2.0e4.0:1 v/v) to afford 50% of 3b.
R
Na2S2O4/NaHCO3
25 °C
F
F
+
O
O
R
9a: R = H
9b: R = Cl
8
3a, 3b
Scheme 2.
adducts and 1e1.5 mol equiv of alkenes were used (Scheme
2). The detailed results are summarized in Table 1. For termi-
nal alkenes 4a0e4f0, the reaction gave the corresponding
adducts 5aa0e5af0 and 5ba0e5bf0 with CF2 group adding to
terminal carbon of the double bond in 50e70% yields (Table
1, entries 1e6 and 9e14). When cyclopentene 6 was used as
the substrate, the reaction gave only trans isomers 7a and 7b.
The NMR signal of the proton of CHI in 7a and 7b exhibited
a quartet at d 4.49 ppm (J¼5.2 Hz) and d 4.46 ppm (J¼5.1 Hz)
with coupling to adjacent RFCH and CH2, which resembled
closely to those of the polyfluoroalkyl analog characterized
previously.25,26 Free radical addition of 3 in a trans mode to
cyclopentene conformed to the pattern observed in reactions
of this type, since the cis adducts would be disfavored because
of steric interactions between RF and I groups.25,26 The reac-
tion of 3a and 3b with diallyl ether 8 gave tetrahydrofuran
SH
SCF2Br
SCF2I
Table 1
Addition of 3 to alkenes and ethynylbenzene
NaH
DMF
NaI
acetone/DMF
+ BrCF2Br
Entry
3
4
R1
Product
Yield (%)
R
R
R
1a: R = H;
1b: R = Cl
2a: R = H;
3a: R = H;
3b: R = Cl
1
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
3b
3b
4a0
4b0
4c0
4d0
4e0
4f0
6
(CH2)5CH3
(CH2)3CH3
CH2OH
5aa0
5ab0
5ac0
5ad0
5ae0
5af0
7a
75.1
78.3
77.2
70.5
80.0
55.6
69.2
66.7
73.8
71.8
75.3
63.8
67.9
65.9
69.6
75.2
2b: R = Cl
2
3
Scheme 1.
4
CH2CN
5
CH2OCOCH2CH3
CH2CH2Br
Cycloheptene
Diallyl ether
(CH2)5CH3
(CH2)3CH3
CH2OH
6
2.2. Reactions of 3a and 3b with alkenes and alkynes
7
8
8
9a
The addition of polyfluoroalkyl iodides to alkenes or
alkynes can be realized under conditions of photolysis,20 elec-
trolysis,21 thermal,22 and free radical initiators.23 Since
Na2S2O4 has been shown to be a good initiator and gave
high yields of adducts under mild conditions,23a it was chosen
in this study. This type of reaction typically took place at low
temperature (5e10 ꢀC), while the addition of 3a and 3b to
alkenes didn’t occur when the reaction temperature was lower
than 10 ꢀC. At higher temperature (20e30 ꢀC), the reaction
proceeded smoothly for 0.5e1 h affording the corresponding
9
4a0
4b0
4c0
4d0
4e0
4f0
6
5ba0
5bb0
5bc0
5bd0
5be0
5bf0
7b
10
11
12
13
14
15
16
CH2CN
CH2OCOCH2CH3
CH2CH2Br
Cycloheptene
Diallyl ether
8
9b
17
18
3a
3b
10
10
12a
12b
55.0
52.0
Ph
Ph

X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
2261
derivatives 9a and 9b, indicating a radical mechanism.8b The
Table 2
Reaction of 3 with pent-4-en-1-ols 13a0ed0
addition of 2a to 1-hexene was also investigated, giving a com-
plicated mixture with low conversion of 2a. This indicated that
3a has better reactivity than the corresponding bromides.
The addition reaction of 3 with ethynylbenzene 10 was car-
ried out under the similar conditions affording adducts 11 and
a trace of 12. After prolonged standing in air or during column
chromatography on silica gel 12 was obtained as the main
product (Scheme 3). For 3a, only E-12a was observed. For
3b, a mixture of E/Z isomers was obtained in 7.6:1 ratio based
on 1H NMR with E isomer as the main product. The NMR sig-
nal of alkenyl hydrogen of E-12b (d 7.14 ppm) appeared more
downfield than that of Z isomer (d 7.08 ppm).26 The major or
only E isomer may be derived from the vinyl radical 11ꢁ,
which was more stable than 11ꢁ0 for the lower steric hindrance
between RSCF2 (R¼Ph, C6H4Cl-p) (Fig. 1) and the electron
donor.27 In vinyl radicals 11ꢁ and 11ꢁ0, phenyl group was usu-
ally thought to favor the linear form in order to ensure a better
orbital overlap for resonance.27 It was reported that oxygen,
sulfur, or nitrogen atom adjacent to carbonefluorine bond
greatly increased the adduct’s reactivity toward nucleo-
philes.28 Therefore, compounds 11 with CF2 adjacent to sulfur
and double bond were readily hydrolyzed to give compounds
12 on prolonged standing in the air or during the column chro-
matographic purification on silica gel.
SCF2I
R1
R2
R1
R2
R
1.Na2S2O4/NaHCO3
OH
F
F
+
R2
S
2. DMF, heating1h
R2
O
R
14aa'-14ad'
14ba'-14bd'
13a': R1=Me, R2=H
3a, 3b
13b':R1=H, R2=H
13c': R1=H, R2=Me
13d':R1=Ph, R2=H
Entry
3
13
Temperature (ꢀC) Product Yield (%) Trans/cisa
1
2
3
4
5
6
7
8
a
3a 13a0 130
3a 13b0 130
14aa0
14ab0
14ac0
14ad0
14ba0
14bb0
14bc0
14bd0
52.1
54.3
60.0
65.2
66.1
66.4
65.0
56.0
1.51:1
d
d
3a 13c0
110
3a 13d0 130
3b 13a0 130
3b 13b0 130
2.73:1
1.44:1
d
d
2.70:1
3b 13c0
3b 13d0 130
110
Based on 1H NMR.
with alkenes to give the corresponding adducts, which were
converted to phenylsulfanyl difluoromethylated tetrahydrofu-
ran derivatives 14 by heating in DMF for 1 h. For 2-methyl-
pent-4-en-1-ol (13a0) and 2-phenyl-pent-4-en-1-ol (13d0),
a mixture of trans/cis isomers was obtained (Table 2, entries
1, 4, 5, and 8) with trans isomer as the major product. Signif-
icant chemical shift differences between the two protons at C-3
(for example, Dd¼1.10 ppm for cis-14aa0, 0.82 ppm for cis-
14ad0) indicated a cis isomer. Small differences (for example,
Dd¼0.0 ppm for trans-14aa0, 0.12 ppm for trans-14ad0) pointed
totrans configuration. The results wereconsistent withtheestab-
lished stereochemistry of 2,4-disubstituted tetrahydrofurans.30
The stereochemistry of 14aa0 and 14ad0 was further ascertained
by analysis of their 1He1H NOESY spectra. For 14aa0, the ap-
parent correlated peaks between H-2 (d¼4.33e4.28 ppm) and
the three protons on CH3 (d¼1.03 ppm) showed that CH3 group
and H-2 lied in cis position, which indicated a trans orientation
of H-2 and H-4. For 14ad0, the apparent correlated peaks be-
tween H-2 (d¼4.40e4.38 ppm) and H-4 (d¼3.58e3.43 ppm)
were observed in its cis isomer (Fig. 2).
SCF2I
I
S
Na2S2O4/NaHCO3
25 °C
+
F
F
R
R
3a, 3b
11a: R = H
11b: R = Cl
10
I
S
silica gel or air
O
R
12a: R = H
12b: R = Cl
Scheme 3.
2.3. Their reactions with pent-4-en-1-ols
2.4. Their reactions with pent-4-enoic acids
We have described that fluoroalkylation of pent-4-en-1-ols
initiated by Na2S2O4 gave adducts, which could be cyclized by
heating in DMF or acetonitrile giving fluorinated tetrahydrofu-
ran derivatives.29 The addition reaction of 3a and 3b to pent-4-
en-1-ols 13a0e13d0 was realized under the similar conditions
The reaction of 3 and pent-4-enoic acids 15a0e15f0 was
carried out in the presence of 1e1.2 equiv NaOH for 6e8 h
at 20e30 ꢀC yielding difluoromethylated g-butyrolactones
16 in 55e74% yields. The data are summarized in Table 3.
The results showed that for 2-substituted-pent-4-enoic acids
15c0e15f0, a mixture of cis/trans isomers was obtained.
H
.
H
S
NOE
NOE
.
S
F
F
F
F
H4
Ph
R
CH3
H4
11.
R
11.'
F H2
2
F
H
F
F
S
O
O
Ph
Ph
S
E-isomer
Z-isomer
cis-14ad'
trans-14aa'
1
Figure 1.
Figure 2. He1H NOESY of trans-14aa0 and cis-14ad0.

2262
X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
Table 3
Reaction of 3 with pent-4-enoic acids
I
R1
2
I
R1
2
R1
+
PhSCF2
syn-17
PhSCF2
R'
R'
R'
SCF2I
PhSCF2I
4
+
4
R2
R1
R1
R2
anti-17
R
13: R' = CH2OH
15: R' = COOH
Na2S2O4/NaHCO3
F
F
COOH
+
O
R2
NaOH, 25 °C, 6-8h
S
O
R2
trans-isomer
cis-isomer
R
15a': R1=H, R2=H; 15b':R1=H, R2=Me
15c': R1=Me, R2=H; 15d': R1=Bz, R2=H
15e': R1=Ph, R2=H
16aa'-16af'
16ba'-16bf'
Figure 4.
3a, 3b
15f': R1=p-MeOC6H4CONH, R2=H
Most of the products exhibited a typical AB pattern signal
19
in the 19F NMR spectrum.8d For example, F NMR of 5be0
Entry
3
15
Product
Trans/cisa
Yield (%)
exhibited two doublets of multiplets at ꢂ72.10 ppm and
ꢂ73.47 ppm. The lower field signal was a doublet of doublet
of doublets with J¼206.5, 16.9, 10.8 Hz. The higher field sig-
nal was also a doublet of doublet of doublets with J¼206.5,
16.0, 13.2 Hz.
1
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
15a0
15b0
15c0
15d0
15e0
15f0
15a0
15b0
15c0
15e0
15d0
15f0
16aa0
16ab0
16ac0
16ad0
16ae0
16af0
16ba0
16bb0
16bc0
16bd0
16be0
16bf0
d
d
74.0
70.0
66.2
72.1
57.0
55.3
64.8
64.2
63.9
71.0
59.2
58.3
2
3
1:1.02
1:1.30
2.33:1
1.28:1
d
4
5
6
7
3. Conclusion
8
d
9
1:1.07
1:1.28
2.11:1
1.09:1
In summary, a new method for the preparation of difluoro-
iodomethylsulfanylbenzene (3a) and 1-chloro-4-difluoro-
iodomethylsulfanylbenzene (3b) was developed from
bromodifluoromethylsulfanylbenzene (2a) and 1-chloro-4-bro-
modifluoromethylsulfanylbenzene (2b) through a halogen ex-
change process in the presence of NaI in a mixture of DMF/
acetone. The reaction of 3a and 3b with unsaturated com-
pounds, such as alkenes, alkynes, pent-4-en-1-ols, and pent-
4-enoic acids, initiated by Na2S2O4 afforded the corresponding
adducts, tetrahydrofuran derivatives, and g-butyrolactones
containing phenylsulfanyl difluoromethyl moiety, in moderate
to good yields.
10
11
12
a
Based on 1H NMR.
NOE
NOE
H
CH3
H
Ph
O
F
F
H
H
F
F
O
O
O
Ph
S
Ph S
trans-lactone
cis-lactone
Figure 3. 1He1H NOESY of trans-lactone and cis-lactone.
Analysis of the crude products by 1H NMR spectrum and
integration of signals attributed to the CHeO indicated that
the cis/trans ratio ranged from 1:1.02 to 2.33:1. For alkyl
group on C2, cis isomer was obtained as the main product (en-
tries 3, 4, 9, and 10). While for Ph or NH group on C2, trans
isomer dominated in the reaction. Similar to tetrahydrofuran
derivatives, the differences of the chemical shifts between
the two protons on C-4 in cis-16 were more significant than
those in trans isomer.31 The further confirmation of the stereo-
chemistry of the lactones was obtained by analysis of the
1He1H NOESY spectra of each isomer (Fig. 3).
4. Experimental
4.1. General information
Melting points are uncorrected. IR spectra were measured
on a Nicolet Magna IR-550 spectrometer. High-resolution
mass spectra were recorded on a Finnigan GCeMS-4021
spectrometer. NMR spectra were recorded in CDCl3 solution
at 20 ꢀC on a Bruker AC-500 spectrometer operating at
500 MHz (1H), 125.8 MHz (13C), and 470.5 MHz (19F).
Chemical shifts (d) are given in parts per million relative to
1
TMS for H and 13C, and relative to CFCl3 for 19F. Column
Similar to the addition reaction of polyfluoroalkyl iodides
to alkenes initiated by sodium dithionite,24 we proposed that
the mechanism of addition of 3 to olefins 4 may involve a sin-
gle electron transfer (SET) process for the anion radical. The
reaction of 3 with pent-4-en-1-ols 13 and pent-4-enoic acids
15 to give the corresponding tetrahydrofuran derivatives 14
and g-butyrolactones 16 may involve the addition of RFI to
double bond through a SET process and then followed by
intramolecular SN2 reaction.29,32 The syn- and anti-diastereo-
mer obtained in radical addition cyclized to give the corre-
sponding trans and cis isomers (Fig. 4).33 The weak steric
hinderance between the groups on C2 (R1 and R2) and the
groups on C4 (I and PhSCF2CH2) may affect the ratio of
syn/anti isomers.
chromatography was performed using silica gel H, particle
size 20e30 mm.
4.2. General procedure for the preparation of 3
The mixture of 2 (0.126 mol), NaI (57 g, 0.38 mol), and
acetone/DMF (100 mL) was stirred under reflux for a week.
After evaporation of acetone, the residue was cooled to room
temperature and water (60 mL) was added. The mixture was
extracted with ethyl ether (3ꢃ50 mL). The combined organic
layers were washed with saturated Na2SO3, brine, and water.
After drying and removal of solvent, the residue was purified
by fractional distillation to give a pale yellow oil 3a (56.0%

X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
2263
yield, bp 70e72 ꢀC/1 mmHg) and 3b (50.0% yield, bp 80e
4.3.4. 5,5-Difluoro-3-iodo-5-phenylsulfanyl-
pentanenitrile (5ad0)
Colorless oil. IR (film): 3061, 2252, 1580, 1364, 1328,
84 ꢀC/1 mmHg).
1
1237, 1213, 1150, 1061, 1025 cmꢂ1. H NMR: d 7.60e7.26
4.3. General procedure for the addition of 3 to olefins and
ethynylbenzene
(m, 5H, PhH), 4.45e4.41 (m, 1H, CHI), 3.23 (dd, 1H,
J1¼17.6 Hz, J2¼6.3 Hz, CH2CN), 3.15 (dd, 1H, J1¼17.6 Hz,
J2¼3.9 Hz, CH2CN), 2.97e2.91 (m, 2H, CF2CH2). 13C
NMR: d 136.9, 131.1, 130.0, 129.3 (t, J¼287.5 Hz), 126.0,
117.5, 48.6 (t, J¼24.2 Hz), 30.5, 10.1. 19F NMR: d ꢂ75.69
To the mixture of 3 (2 mmol), alkenes, or ethynylbenzene
(2e3 mmol), acetonitrile (6 mL), and water (2 mL) was added
the mixture of sodium dithionite (560 mg, 3.2 mmol) and
sodium bicarbonate (270 mg, 3.2 mmol) at 20e30 ꢀC in
20 min. After stirring for 0.5e1 h at the same temperature,
water (ca. 15 mL) was added and the mixture was extracted
with ethyl ether (3ꢃ15 mL). The combined organic layers
were washed with saturated brine and dried over anhydrous so-
dium sulfate. After evaporation of ethyl ether, the crude prod-
uct was purified by column chromatography eluting with PE
and EA to give the corresponding product.
(dt, 1F, JFeF¼210.3 Hz, JHeF¼13.4 Hz), ꢂ74.9 (dt, 1F, JFeF
¼
210.3 Hz, JHeF¼15.1 Hz). HRMS (EI), C11H10F2INS calcd:
352.9547; found: 352.9546.
4.3.5. Propionic acid 4,4-difluoro-2-iodo-4-phenylsulfanyl-
butyl ester (5ae0)
Colorless oil. IR (film): 3026, 1744, 1579, 1422, 1383, 1354,
1271, 1217, 1167, 1082, 1028 cmꢂ1. 1H NMR: d 7.61e7.38 (m,
5H, PhH), 4.47e4.42 (m, 1H, CHI), 4.35e4.27 (m, 2H, CH2O),
2.94e2.80 (m, 2H, CF2CH2), 2.37 (q, 2H, J¼7.6 Hz, CH2CO),
1.16 (t, 3H, J¼7.6 Hz, CH3). 13C NMR: d 174.2, 136.9, 130.8,
129.9, 129.3 (t, J¼280.1 Hz), 126.7, 68.9, 46.3 (t, J¼24.3 Hz),
4.3.1. (1,1-Difluoro-3-iodo-nonylsulfanyl)-benzene (5aa0)
Colorless oil. IR (film): 3062, 1575, 1215, 1190, 1155, 1111,
1048, 1026 cmꢂ1. 1H NMR: d 7.30e7.53 (m, 5H, PhH), 4.30e
4.25 (m, 1H, CHI), 2.93e2.82 (m, 1H, CF2CH2), 2.79e2.68 (m,
1H, CF2CH2), 1.72e1.67 (m, 2H), 1.45e1.39 (m, 1H), 1.33e
1.18 (stack, 7H), 0.82 (t, 3H, J¼7.7 Hz, CH3). 13C NMR:
d 136.9, 130.7, 129.8, 129.7 (t, J¼281.4 Hz), 127.5, 50.1 (t,
J¼23.5 Hz), 40.7, 32.3, 30.2, 28.9, 25.9, 23.2, 14.7. 19F
NMR: d ꢂ70.61 (ddd, 1F, JFeF¼206.6 Hz, J1HeF¼17.4 Hz,
28.1, 17.0, 9.7. 19F NMR (CDCl3) d ꢂ71.97 (ddd, 1F, JFeF
¼
208.5 Hz, J1HeF¼16.9 Hz, J2HeF¼11.3 Hz), ꢂ73.37 (dt, 1F,
JFeF¼208.5 Hz, JHeF¼14.4 Hz). HRMS (EI), C13H15F2IO2S
calcd: 399.9806; found: 399.9819.
4.3.6. (5-Bromo-1,1-difluoro-3-iodo-pentylsulfanyl)-
benzene (5af0)
Colorless oil. IR (film): 3059, 1475, 1439, 1246, 1200,
.
1160, 1054, 1028 cmꢂ1 1H NMR: d 7.62e7.38 (m, 5H,
J2HeF¼9.9 Hz), ꢂ73.36 (dt, 1F, JFeF¼206.6 Hz, J2HeF
¼
14.8 Hz). HRMS (EI), C15H21F2IS calcd: 398.0377; found:
398.0368.
PhH), 4.48e4.54 (m, 1H, CHI), 3.61e3.57 (m, 1H, CH2Br),
3.50e3.45 (m, 1H, CH2Br), 3.05e2.96 (m, 1H, CF2CH2),
2.82e2.79 (m, 1H, CF2CH2), 2.28e2.23 (m, 2H, CH2CH2Br).
13C NMR: d 137.0, 130.9, 129.9, 129.7 (t, J¼281.0 Hz), 126.7,
49.9 (t, J¼23.7 Hz), 42.6, 33.9, 22.7. 19F NMR: d ꢂ70.00
(ddd, 1F, JFeF¼208.4 Hz, J1HeF¼17.4 Hz, J2HeF¼9.4 Hz),
ꢂ73.09 (dt, 1F, JFeF¼208.4 Hz, JHeF¼15.3 Hz). HRMS
(EI), C11H12BrF2IS calcd: 419.8835; found: 419.8827.
4.3.2. (1,1-Difluoro-3-iodo-heptylsulfanyl)-benzene (5ab0)
Colorless oil. IR (film): 3062, 1575, 1230, 1209, 1155,
1116, 1048, 1026 cmꢂ1 1H NMR: d 7.61e7.37 (m, 5H,
.
PhH), 4.38e4.33 (m, 1H, CHI), 3.00e2.90 (m, 1H,
CF2CH2), 2.86e2.78 (m, 1H, CF2CH2), 1.80e1.76 (m, 2H),
1.51e1.46 (m, 1H), 1.43e1.33 (stack, 3H), 0.92 (t, 3H,
J¼7.2 Hz, CH3). 13C NMR: d 136.9, 130.7, 129.8, 129.7 (t,
J¼281.2 Hz), 127.0, 50.1 (t, J¼23.3 Hz), 40.4, 32.4, 25.8,
22.4, 14.6. 19F NMR: d ꢂ70.62 (ddd, 1F, JFeF¼206.6 Hz,
4.3.7. trans-[Difluoro-(2-iodo-cyclopentyl)-methylsulfanyl]-
benzene (7a)
J1HeF¼17.4 Hz, J2HeF¼9.9 Hz), ꢂ73.38 (dt, 1F, JFeF
¼
Colorless oil. IR (film): 3060, 1346, 1305, 1194, 1149, 1065,
1026 cmꢂ1. 1H NMR: d 7.62e7.36 (m, 5H, PhH), 4.49 (q, 1H,
J¼5.2 Hz, CHI), 3.13e3.11 (m, 1H, CF2CH), 2.18e2.12 (m,
2H), 2.05e1.97 (m, 1H), 1.91e1.85 (m, 2H), 1.78e1.62 (m,
1H). 13C NMR: d 137.0, 131.8 (t, J¼282.2 Hz), 130.5, 129.7,
127.0, 59.9 (t, J¼22.1 Hz), 41.8, 27.7, 26.1, 22.9. 19F NMR:
d ꢂ78.50 (dd, 1F, JFeF¼205.2 Hz, JHeF¼13.2 Hz), ꢂ80.32
(dd, 1F, JFeF¼205.2 Hz, JHeF¼14.8 Hz). HRMS (EI),
C12H13F2IS calcd: 353.9751; found: 353.9763.
206.6 Hz, JHeF¼15.1 Hz). HRMS (EI), C13H17F2IS calcd:
370.0064; found: 370.0069.
4.3.3. 4,4-Difluoro-2-iodo-4-phenylsulfanyl-
butan-1-ol (5ac0)
Colorless oil. IR (film): 3383 (br), 3060, 1581, 1366, 1264,
1206, 1153, 1068, 1028 cmꢂ1. 1H NMR: d 7.61e7.37 (m, 5H,
PhH), 4.48e4.44 (m, 1H, CHI), 3.81e3.62 (m, 2H, CH2O),
3.03e2.93 (m, 1H, CF2CH2), 2.87e2.77 (m, 1H, CF2CH2),
1.25 (t, 1H, J¼7.0 Hz, OH). 13C NMR: d 136.9, 130.8, 129.8,
129.5 (t, J¼292.1 Hz), 126.7, 68.4, 45.9 (t, J¼24.0 Hz), 27.1.
4.3.8. 3-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-4-iodomethyl-
tetrahydro-furan (9a)
Colorless oil. IR (film): 3059, 1580, 1311, 1240, 1214,
19F NMR: d ꢂ71.50 (ddd, 1F, JFeF¼207.5 Hz, J1HeF
¼
1
17.4 Hz, J2HeF¼9.9 Hz), ꢂ73.40 (dt, 1F, JFeF¼207.5 Hz,
JHeF¼15.3 Hz). HRMS (EI), C10H11F2IOS calcd: 343.9543;
found: 343.9543.
1167, 1115, 1051, 961, 914, 750, 691 cmꢂ1. H NMR: d (ma-
jor) 7.61e7.38 (m, 5H, PhH), 4.03 (t, 1H, J¼8.4 Hz), 3.99
(ddd, 1H, J1¼9.0 Hz, J2¼6.1 Hz, J3¼0.80 Hz), 3.75 (dd, 1H,

2264
X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
J1¼9.0 Hz, J2¼4.1 Hz), 3.61 (t, 1H, J¼8.4 Hz), 3.19 (ddd, 1H,
J1¼9.9 Hz, J2¼4.8 Hz, J3¼0.67 Hz), 3.02 (t, 1H, J¼9.9 Hz),
2.79e2.74 (m, 1H, CF2CH2), 2.72e2.65 (m, 1H, CF2CH2),
2.45e2.08 (stack, 2H, CHCH); d (minor) 7.61e7.38 (m, 5H,
PhH), 4.18 (t, 1H, J¼8.1 Hz), 3.98 (dd, 1H, J1¼9.3 Hz,
J2¼6.9 Hz), 3.58 (dd, 1H, J1¼9.3 Hz, J2¼5.9 Hz), 3.53 (t, 1H,
J1¼8.1 Hz), 3.29 (dd, 1H, J1¼9.8 Hz, J2¼4.9 Hz), 3.13 (t, 1H,
J¼9.8 Hz), 2.45e2.08 (stack, 4H, CF2CH2, CHCH). 13C NMR:
d (major) 136.9, 130.7, 129.9 (t, J¼276.8 Hz), 129.8, 127.1,
74.4, 72.4, 45.8, 38.7, 36.9 (t, J¼23.9 Hz), 4.4; d (minor) 136.9,
130.7, 129.9 (t, J¼276.8 Hz), 129.8, 127.1, 74.9, 74.6, 48.3, 42.2
(t, J¼22.2 Hz), 42.0, 7.9. 19F NMR: d (major) ꢂ72.00 (ddd, 1F,
JFeF¼206.1 Hz, J1HeF¼17.9 Hz, J2HeF¼10.4 Hz), ꢂ74.00 (ddd,
1F, JFeF¼206.1 Hz, J1HeF¼17.9 Hz, J2HeF¼14.1 Hz); d (minor)
2.87 (m, 1H, CF2CH2), 2.79e2.71 (m, 1H, CF2CH2), 1.99
(s, 1H, OH). 13C NMR: d 136.5, 135.9, 128.5, 127.5 (t,
J¼281.4 Hz), 123.4, 66.7, 44.2 (t, J¼23.8 Hz), 25.1. 19F
NMR: d ꢂ71.66 to ꢂ72.13 (m, 1F), ꢂ73.40 to ꢂ73.80 (m,
1F). HRMS (EI), C10H10ClF2IOS calcd: 377.9154; found:
377.9147.
4.3.13. 5-(4-Chloro-phenylsulfanyl)-5,5-difluoro-3-iodo-
pentanenitrile (5bd0)
Pale yellow oil. IR (film): 3086, 2253, 1605, 1572, 1262,
1
1237, 1212, 1148, 1093, 1061 cmꢂ1. H NMR: d 7.44e7.28
(m, 4H, PhH), 4.36e4.31 (m, 1H, CHI), 3.15 (dd, 1H,
J1¼17.6 Hz, J2¼6.3 Hz, CH2CN), 3.06 (dd, 1H, J1¼17.6 Hz,
J2¼4.3 Hz, CH2CN), 2.92e2.84 (m, 2H, CF2CH2). 13C NMR:
d 136.5, 136.1, 128.6, 127.3 (t, J¼281.4 Hz), 122.7, 115.9,
46.9 (t, J¼23.8 Hz), 28.9, 8.2. 19F NMR: d ꢂ71.60 (dt, 1F,
ꢂ71.44 (ddd, 1F, JFeF¼207.0 Hz, J1HeF¼18.3 Hz, J2HeF
¼
10.4 Hz), ꢂ74.23 (dt, 1F, JFeF¼207.0 Hz, JHeF¼16.2 Hz).
HRMS (EI), C13H15OF2IS calcd: 383.9856; found: 383.9856.
JFeF¼207.5 Hz, JHeF¼13.6 Hz), ꢂ74.92 (dt, 1F, JFeF¼
207.5 Hz, JHeF¼15.0 Hz). HRMS (EI), C11H9ClF2INS calcd:
4.3.9. 3-Iodo-3-phenyl-thioacrylic acid S-phenyl ester (12a)
White crystal with mp: 130e131 ꢀC. IR (KBr): 3051, 1689,
386.9157; found: 386.9157.
1
1577 cmꢂ1. H NMR: d 7.37e7.27 (m, 10H, PhH), 7.15 (s,
4.3.14. Propionic acid 4-(4-chloro-phenylsulfanyl)-4,4-
difluoro-2-iodo-butyl ester (5be0)
Pale yellow oil. IR (film): 1744, 1573, 1261, 1230, 1162,
.
1091, 1015 cmꢂ1 1H NMR: d 7.46e7.29 (m, 4H, PhH),
1H, ]CH). 13C NMR: d 185.8, 142.6, 137.9, 135.1, 130.3,
130.2, 129.9, 128.7, 128.6, 127.8, 117.3. MS (EI, m/z): 366
(Mþ, 0.2), 257 (100), 129 (12), 102 (36). Anal. Calcd for
C15H11IOS: C, 49.20; H, 3.03. Found: C, 49.36; H, 2.96.
4.36e4.33 (m, 1H, CHI), 4.28e4.20 (m, 2H, CH2O), 2.90e
2.69 (m, 2H, CF2CH2), 2.31 (q, 2H, J¼7.6 Hz, CH2CO), 1.09
(t, 3H, J¼7.6 Hz, CH3). 13C NMR: d 174.2, 138.2, 137.6,
130.2, 129.0 (t, J¼281.3 Hz), 125.0, 68.9, 46.4 (t, J¼24.0 Hz),
28.1, 16.7, 9.7. 19F NMR: d ꢂ72.10 (ddd, 1F, JFeF¼206.5 Hz,
4.3.10. 1-Chloro-4-(1,1-difluoro-3-iodo-nonylsulfanyl)-
benzene (5ba0)
Paleyellowoil.IR(film):1574,1476,1261, 1216,1156,1094,
1048, 1014 cmꢂ1. 1H NMR: d 7.45e7.26 (m, 4H, PhH), 4.28e
4.22 (m, 1H, CHI), 2.90e2.82 (m, 1H, CF2CH2), 2.79e2.70
(m, 1H, CF2CH2), 1.71e1.67 (m, 2H), 1.45e1.41 (m, 1H),
1.34e1.18 (stack, 7H), 0.81 (t, 3H, J¼6.9 Hz, CH3). 13C NMR:
d 136.4, 135.7, 128.3, 127.7 (t, J¼281.9 Hz), 123.6, 48.4 (t,
J¼23.0 Hz), 39.0, 30.6, 28.5, 27.2, 23.8, 21.5, 13.0. 19F NMR:
J1HeF¼16.9 Hz, J2HeF¼10.8 Hz), ꢂ73.47 (ddd, 1F, JFeF
¼
206.5 Hz, J1HeF¼16.0 Hz, J2HeF¼13.2 Hz). HRMS (EI),
C13H14ClF2IO2S calcd: 433.9416; found: 433.9415.
4.3.15. 1-(5-Bromo-1,1-difluoro-3-iodo-pentylsulfanyl)-4-
chloro-benzene (5bf0)
d ꢂ70.48 (ddd, 1F, JFeF¼207.5 Hz, J1HeF¼17.9 Hz, J2HeF
¼
Pale yellow oil. IR (film): 1573, 1288, 1247, 1200, 1161,
1094, 1054, 1033, 1012 cmꢂ1. 1H NMR: d 7.46e7.28 (m, 4H,
PhH), 4.44e4.38 (m, 1H, CHI), 3.53e3.49 (m, 1H, CH2Br),
3.42e3.37 (m, 1H, CH2Br), 2.98e2.88 (m, 1H, CF2CH2),
2.81e2.71 (m, 1H, CF2CH2), 2.20e2.15 (m, 2H, CH2CH2Br).
13C NMR: d 138.0, 137.4, 130.0, 129.2 (t, J¼281.8 Hz),
124.8, 49.7 (t, J¼23.4 Hz), 42.4, 33.8, 22.2. 19F NMR:
9.9 Hz), ꢂ73.27 (dt, 1F, JFeF¼207.5 Hz, JHeF¼14.8 Hz).
HRMS (EI), C15H20ClF2IS calcd: 431.9987; found: 431.9987.
4.3.11. 1-Chloro-4-(1,1-difluoro-3-iodo-heptylsulfanyl)-
benzene (5bb0)
Pale yellow oil. IR (film): 1573, 1262, 1230, 1158, 1113, 1095,
1041, 1013 cmꢂ1. 1H NMR: d 7.46e7.28 (m, 4H, PhH), 4.27e
4.24 (m, 1H, CHI), 2.90e2.84 (m, 1H, CF2CH2), 2.77e2.72 (m,
1H, CF2CH2), 1.72e1.68 (m, 2H), 1.49e1.41 (m, 1H), 1.29e
1.24 (stack, 3H), 0.85 (t, 3H, J¼7.0 Hz). 13C NMR: d 138.2,
137.4, 130.1, 129.4 (t, J¼281.8 Hz), 125.2, 50.1 (t, J¼23.0 Hz),
d ꢂ69.86 (ddd, 1F, JFeF¼206.1 Hz, J1HeF¼16.9 Hz, J2HeF
¼
9.9 Hz), ꢂ72.85 (dt, 1F, JFeF¼206.1 Hz, JHeF¼15.3 Hz).
HRMS (EI), C11H11BrClF2IS calcd: 453.8446; found:
453.8451.
40.4, 32.3, 25.4, 22.3, 14.6. 19F NMR: d ꢂ70.53 (ddd, 1F, JFeF
¼
4.3.16. trans-1-Chloro-4-[difluoro-(2-iodo-cyclopentyl)-
methylsulfanyl]-benzene (7b)
Pale yellow oil. IR (film): 1571, 1475, 1256, 1195, 1176,
.
1148, 1093, 1064, 1043 cmꢂ1 1H NMR: d 7.56e7.34 (m,
204.7 Hz, J1HeF¼17.9 Hz, J2HeF¼9.9 Hz), ꢂ73.33 (ddd, 1F,
JFeF¼204.7 Hz, J1HeF¼16.0 Hz, J2HeF¼14.6 Hz). HRMS (EI),
C13H16ClF2IS calcd: 403.9674; found: 403.9646.
4H, PhH), 4.46 (q, 1H, J¼5.1 Hz, CHI), 3.17e3.07 (m, 1H,
CF2CH), 2.18e2.12 (m, 2H), 2.01e1.97 (m, 1H), 1.90e1.77
(m, 2H), 1.78e1.71 (m, 1H). 13C NMR: d 138.3, 137.2,
131.6 (t, J¼282.5 Hz), 130.0, 125.4, 59.9 (t, J¼21.9 Hz),
4.3.12. 4-(4-Chlorophenylthio)-4,4-difluoro-2-
iodobutan-1-ol (5bc0)
Pale yellow oil. IR (film): 3325 (br), 1570, 1207, 1166,
.
4.39e4.35 (m, 1H, CHI), 3.74e3.61 (m, 2H, CH2O), 2.95e
1092, 1020 cmꢂ1
1H NMR: d 7.46e7.29 (m, 4H, PhH),
41.8, 27.8, 26.1, 22.5. 19F NMR: d ꢂ78.82 (dd, 1F, JFeF
¼
204.7 Hz, JHeF¼14.1 Hz), ꢂ79.93 (dd, 1F, JFeF¼204.7 Hz,

X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
2265
JHeF¼14.6 Hz). HRMS (EI), C12H12ClF2IS calcd: 387.9361;
5H, PhH), 4.33e4.28 (m, 1H, CHO), 3.99 (dd, 1H,
J1¼8.4 Hz, J2¼6.9 Hz, CH2O), 3.30 (dd, 1H, J1¼8.4 Hz,
J2¼6.6 Hz, CH2O), 2.58e2.42 (m, 1H, CF2CH2), 2.38e2.19
(stack, 2H, CF2CH2, CHCH3), 1.81e1.70 (m, 2H,
CH2CHCH3), 1.03 (d, 3H, J¼6.8 Hz, CH3); d (cis) 7.62e
7.34 (m, 5H, PhH), 4.23e4.19 (m, 1H, CHO), 3.90 (t, 1H,
J¼8.0 Hz, CH2O), 3.36 (t, 1H, J¼8.0 Hz, CH2O), 2.58e2.42
(m, 1H, CF2CH2), 2.38e2.19 (stack, 3H, CF2CH2, CHCH3,
CH2CHCH3), 1.21e1.15 (m, 1H, CH2CHCH3), 1.04 (d, 3H,
J¼6.4 Hz, CH3). 13C NMR: d (trans) 136.8, 130.4, 129.6,
129.3 (t, J¼278.8 Hz), 127.6, 75.5, 75.1, 45.3 (t,
J¼22.5 Hz), 40.8, 33.6, 18.6; d (cis) 136.8, 130.4, 129.6,
129.3 (t, J¼278.8 Hz), 127.6, 75.3, 74.0, 45.5 (t,
J¼22.7 Hz), 42.1, 34.9, 18.1. 19F NMR: d (trans) ꢂ71.08
(ddd, 1F, JFeF¼207.0 Hz, J1HeF¼15.1 Hz, J2HeF¼12.2 Hz),
ꢂ72.86 (dt, 1F, JFeF¼207.0 Hz, JHeF¼16.0 Hz); d (cis)
found: 387.9361.
4.3.17. 3-[(4-Chloro-phenylsulfanyl)-difluoro-methyl]-4-
iodomethyl-tetrahydro-furan (9b)
Paleyellow oil. IR(film):1573, 1476, 1260, 1241, 1215, 1168,
1093, 1014 cmꢂ1. 1HNMR:d(major)7.43e7.25(m, 4H),3.91(t,
1H, J¼8.0 Hz), 3.87 (dd, 1H, J1¼8.9 Hz, J2¼6.3 Hz), 3.63
(dd, 1H, J1¼8.9 Hz, J2¼4.3 Hz), 3.51 (t, 1H, J¼8.0 Hz), 3.08
(dd, 1H, J1¼9.7 Hz, J2¼4.9 Hz), 2.92 (t, 1H, J¼9.7 Hz), 2.67e
2.62 (m, 1H, CF2CH2), 2.60e2.53 (m, 1H, CF2CH2), 2.30e
2.01 (stack, 2H, CHCH); d (minor) 7.43e7.25 (m, 4H, PhH),
4.06 (t, 1H, J¼7.8 Hz), 3.83 (dd, 1H, J1¼9.0 Hz, J2¼7.3 Hz),
3.47 (dd, 1H, J1¼9.0 Hz, J2¼6.0 Hz), 3.41 (t, 1H, J¼7.8 Hz),
3.19 (dd, 1H, J1¼9.1 Hz, J2¼4.0 Hz), 3.03 (t, 1H, J¼9.1 Hz),
2.32e2.01 (stack, 4H, CF2CH2, CHCH). 13C NMR: d (major)
137.9, 137.1, 129.9, 129.5 (t, J¼279.9 Hz), 125.2, 74.0, 72.0,
45.6, 38.4, 36.6 (t, J¼23.5 Hz), 4.3; d (minor) 137.9, 137.0,
129.9, 129.4 (t, J¼279.9 Hz), 125.3, 74.5, 74.3, 48.0, 41.9 (t,
J¼23.2 Hz), 41.8, 7.9. 19F NMR: d (major) ꢂ71.62 (ddd, 1F,
JFeF¼203.7 Hz, J1HeF¼17.9 Hz, J2HeF¼10.4 Hz), ꢂ73.67 (dt,
1F, JFeF¼203.7 Hz, JHeF¼15.8 Hz); d (minor) ꢂ71.3 (ddd, 1F,
JFeF¼204.7 Hz, J1HeF¼18.3 Hz, J2HeF¼9.9 Hz), ꢂ73.75 (dt,
ꢂ70.93 (ddd, 1F, JFeF¼207.0 Hz, J1HeF¼15.1 Hz, J2HeF
12.7 Hz), ꢂ72.94 (dt, 1F, JFeF¼207.0 Hz, JHeF
¼
¼
16.5 Hz). HRMS (EI), C13H16F2OS calcd: 258.0890; found:
258.0887.
4.4.2. 2-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-tetrahydro-
furan (14ab0)
Colorless oil. IR (film): 3060, 1581, 1440, 1240, 1168,
.
1126, 1083, 1025 cmꢂ1 1H NMR: d 7.62e7.34 (m, 5H,
1F,
JFeF¼204.7 Hz,
JHeF¼16.2 Hz).
HRMS
(EI),
C13H14ClF2IOS calcd: 417.9467; found: 417.9467.
PhH), 4.19e4.11 (m, 1H, CHO), 3.90e3.85 (m, 1H, CH2O),
3.79e3.74 (m, 1H, CH2O), 2.55e2.45 (m, 1H, CF2CH2),
2.33e2.22 (m, 1H, CF2CH2), 2.16e2.10 (m, 1H), 1.94e1.83
(m, 2H), 1.60e1.52 (m, 1H). 13C NMR: d 136.3, 129.8,
129.3, 128.7 (t, J¼278.7 Hz), 127.0, 74.0, 67.8, 44.5 (t,
4.3.18. 3-(4-Chloro-phenyl)-3-iodo-thioacrylic acid
S-phenyl ester (12b)
White crystal with mp: 103e104 ꢀC. E/Z¼7.6:1. IR (KBr):
1
3050, 1691, 1570, 1092 cmꢂ1. H NMR: d (Z) 7.42e7.22 (m,
9H, PhH), 7.08 (s, 1H, ]CH); d (E) 7.42e7.22 (m, 9H, PhH),
7.14 (s, 1H, ]CH). 13C NMR: d (Z) 186.0, 143.9, 136.8,
136.4, 131.5, 131.2, 130.2, 129.7, 129.2, 126.1, 114.0; d (E)
185.1, 142.5, 137.5, 136.7, 136.3, 130.4, 130.1, 128.7,
128.5, 126.2, 118.1. MS (EI, m/z): 400 (Mþ, 0.1), 257 (100),
102 (41). Anal. Calcd for C15H10ClIOS: C, 44.97; H, 2.52.
Found: C, 45.39; H, 2.36.
J¼22.7 Hz), 36.4, 25.6. 19F NMR: d ꢂ71.16 (ddd, 2F, JFeF
¼
207.0 Hz, J1HeF¼15.5 Hz, J2HeF¼12.7 Hz), ꢂ72.93 (dt, 2F,
JFeF¼207.0 Hz, JHeF¼16.2 Hz). HRMS (EI), C12H14F2OS
calcd: 244.0733; found: 244.0724.
4.4.3. 2-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-3,3-dimethyl-
tetrahydro-furan (14ac0)
Colorless oil. IR (film): 3023, 1583, 1473, 1261, 1176,
.
1051, 1021 cmꢂ1 1H NMR: d 7.64e7.35 (m, 5H, PhH),
4.4. General procedure for the reaction of 3 with pent-4-
en-1-ols 13
3.95e3.86 (stack, 2H, CH2O, CHO), 3.71 (dd, 1H,
J1¼8.3 Hz, J2¼2.9 Hz, CH2O), 2.29e2.15 (m, 2H, CF2CH2),
1.84e1.78 (m, 1H, CH2C), 1.75e1.70 (m, 1H, CH2C), 1.04
(s, 3H, CH3), 0.88 (s, 3H, CH3). 13C NMR: d 136.9, 130.3,
130.1 (t, J¼279.2 Hz), 129.6, 127.7, 82.2, 66.5, 41.6, 41.3,
40.4 (t, J¼23.3 Hz), 25.3, 22.0. 19F NMR: d ꢂ70.64 (dt, 1F,
The addition of 3 (2 mmol) to pent-4-en-1-ols 13 (2 mmol)
was carried out under the same conditions as alkenes. After
usual work-up, the crude adduct was dissolved in DMF
(4 mL), the mixture was heated in 130 ꢀC oil bath for 1 h,
and then cooled to room temperature. The mixture was treated
with 10% Na2SO3 (10 mL) and then extracted with ethyl ether
(3ꢃ10 mL). The combined organic layers were washed with
saturated brine and water, and then dried over anhydrous so-
dium sulfate. After removal of ethyl ether, the residue was pu-
rified by column chromatography eluting with PE and EA to
give the corresponding tetrahydrofuran derivatives.
JFeF¼205.1 Hz, JHeF¼15.3 Hz), ꢂ71.67 (dt, 1F, JFeF
¼
205.1 Hz, JHeF¼14.5 Hz). HRMS (EI), C14H18F2OS calcd:
272.1046; found: 272.1028.
4.4.4. 2-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-4-phenyl-
tetrahydro-furan (14ad0)
Colorless oil. IR (film): 3061, 1603, 1494, 1253, 1223,
1
1170, 1081, 1026 cmꢂ1. H NMR: d (trans): 7.64e7.25 (m,
4.4.1. 2-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-4-methyl-
tetrahydro-furan (14aa0)
Colorless oil. IR (film): 3060, 1612, 1582, 1441, 1169,
10H, PhH), 4.53e4.48 (m, 1H, CHO), 4.26 (dd, 1H,
J1¼8.5 Hz, J2¼7.4 Hz, CH2O), 3.75 (t, 1H, J¼8.5 Hz,
CH2O), 3.58e3.43 (m, 1H, CHPh), 2.68e2.52 (m, 1H,
CF2CH2), 2.45e2.31 (m, 1H, CF2CH2), 2.30e2.22 (m, 1H,
1
1136, 1101, 1025 cmꢂ1. H NMR: d (trans) 7.62e7.34 (m,

2266
X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
CH2CHPh), 2.17e2.11 (m, 1H, CH2CHPh); d (cis) 7.64e7.25
(m, 10H, PhH), 4.40e4.38 (m, 1H, CHO), 4.19 (t, 1H,
J¼8.2 Hz, CH2O), 3.85 (t, 1H, J¼8.2 Hz, CH2O), 3.58e3.43
(m, 1H, CHPh), 2.68e2.52 (stack, 2H, CF2CH2, CH2CHPh),
2.45e2.31 (m, 1H, CF2CH2), 1.79e1.77 (m, 1H, CH2CHPh).
13C NMR: d (trans) 142.8, 137.0, 130.6, 129.8, 129.4, 129.3 (t,
J¼278.4 Hz), 128.0, 127.6, 127.1, 75.4, 74.8, 45.6 (t,
J¼22.7 Hz), 45.1, 41.0; d (cis) 142.5, 137.0, 130.6, 129.8,
129.4, 129.3 (t, J¼278.4 Hz), 127.9, 127.6, 127.4, 75.6,
74.9, 46.1, 45.3 (t, J¼22.3 Hz), 42.2. 19F NMR: d (trans)
ꢂ70.97 (dt, 1F, JFeF¼207.5 Hz, JHeF¼15.5 Hz), ꢂ72.63 (dt,
1F, JFeF¼207.5 Hz, JHeF¼16.0 Hz); d (cis) ꢂ70.80 (dt, 1F,
3.96e3.86 (stack, 2H, CHO, CH2O), 3.69 (dd, 1H,
J1¼7.9 Hz, J2¼3.1 Hz, CH2O), 2.29e2.18 (m, 2H, CF2CH2),
1.85e1.79 (m, 1H, CH2C), 1.76e1.71 (m, 1H, CH2C), 1.05
(s, 3H, CH3), 0.89 (s, 3H, CH3). 13C NMR: d 138.2, 137.0,
129.9, 129.8 (t, J¼262.0 Hz), 126.1, 81.6, 66.6, 41.7, 41.3,
40.4 (t, J¼23.1 Hz), 25.3, 22.0. 19F NMR: d ꢂ70.99 to
ꢂ71.06 (m, 2F). HRMS (EI), C14H17ClF2OS calcd:
306.0657; found: 306.0657.
4.4.8. 2-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-4-
phenyl-tetrahydro-furan (14bd0)
Colorless oil. IR (film): 3086, 1568, 1386, 1251, 1163, 1094,
.
1043, 1001 cmꢂ1 1H NMR: d (trans) 7.58e7.24 (m, 9H,
JFeF¼207.5 Hz, JHeF¼13.2 Hz), ꢂ72.87 (dt, 1F, JFeF
¼
207.5 Hz, JHeF¼15.4 Hz). HRMS (EI), C18H18F2OS calcd:
PhH), 4.52e4.47 (m, 1H, CHO), 4.26 (dd, 1H, J1¼8.5 Hz,
J2¼7.6 Hz, CH2O), 3.76 (t, 1H, J¼8.5 Hz, CH2O), 3.52e3.43
(m, 1H, CHPh), 2.68e2.54 (m, 1H, CF2CH2), 2.48e2.30 (m,
1H, CF2CH2), 2.29e2.23 (m, 1H, CH2CHPh), 2.16e2.10 (m,
1H, CH2CHPh); d (cis) 7.58e7.24 (m, 9H, PhH), 4.42e4.10
(m, 1H, CHO), 4.19 (t, 1H, J¼8.3 Hz, CH2O), 3.83 (t, 1H,
J¼8.3 Hz, CH2O), 3.52e3.43 (m, 1H, CHPh), 2.68e2.54
(stack, 2H, CF2CH2, CH2CHPh), 2.48e2.30 (m, 1H,
CF2CH2), 1.78e1.72 (m, 1H, CH2CHPh). 13C NMR: d (trans)
142.0, 137.5, 136.5, 129.3, 128.7, 128.4 (t, J¼279.4 Hz),
127.2, 126.6, 125.2, 74.6, 74.0, 44.8 (t, J¼22.4 Hz), 44.3,
40.3; d (cis) 141.6, 137.5, 136.5, 129.3, 128.6, 128.4 (t,
J¼279.4 Hz), 127.1, 126.7, 125.2, 74.8, 74.2, 45.3, 44.5 (t,
320.1046; found: 320.1046.
4.4.5. 2-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-4-
methyl-tetrahydro-furan (14ba0)
Colorless oil. IR (film): 3065, 1574, 1477, 1259, 1230, 1171,
1137, 1095, 1015 cmꢂ1. 1H NMR: d (trans) 7.55e7.34 (m, 4H,
PhH), 4.34e4.26 (m, 1H, CHO), 4.01 (dd, 1H, J1¼8.3 Hz,
J2¼6.7 Hz, CH2O), 3.32 (dd, 1H, J1¼8.3 Hz, J2¼6.9 Hz,
CH2O), 2.58e2.42 (m, 1H, CF2CH2), 2.39e2.18 (stack, 2H,
CF2CH2, CHCH3), 1.85e1.74 (stack, 2H, CH2CHCH3), 1.04
(d, 3H, J¼6.8 Hz, CH3); d (cis) 7.55e7.34 (m, 4H, PhH),
4.24e4.15 (m, 1H, CHO), 3.93 (t, 1H, J¼7.8 Hz, CH2O), 3.37
(t, 1H, J¼7.8 Hz, CH2O), 2.58e2.42 (m, 1H, CF2CH2), 2.39e
2.18 (m, 3H, CF2CH2, CHCH3, CH2CHCH3), 1.21e1.18 (m,
1H, CH2CHCH3), 1.05 (d, 3H, J¼6.5 Hz, CH3). 13C NMR:
d (trans) 138.1, 137.1, 129.9, 129.1 (t, J¼279.2 Hz), 126.0,
75.7, 73.9, 45.4 (t, J¼22.4 Hz), 40.8, 33.7, 18.6; d (cis) 138.1,
137.1, 129.9, 129.1 (t, J¼279.2 Hz), 126.0, 75.3, 75.2, 45.5 (t,
J¼22.4 Hz), 42.1, 35.0, 18.1. 19F NMR: d (trans) ꢂ70.65 (dt,
J¼22.4 Hz), 41.4. 19F NMR: d (trans) ꢂ70.64 (dt, 1F, JFeF
¼
206.5 Hz, JHeF¼14.1 Hz), ꢂ72.54 (dt, 1F, JFeF¼206.5 Hz,
JHeF¼16.0 Hz); d (cis) ꢂ70.72 (dt, 1F, JFeF¼206.1 Hz, JHeF
¼
14.1 Hz), ꢂ72.67 (dt, 1F, JFeF¼206.1 Hz, JHeF¼16.0 Hz).
HRMS (EI), C18H17ClF2OS calcd: 354.0657; found: 354.0657.
4.5. General procedure for the reaction of 3 with pent-4-
enoic acids 15
1F, JFeF¼205.6 Hz, JHeF¼13.6 Hz), ꢂ72.70 (dt, 1F, JFeF
¼
¼
205.6 Hz, JHeF¼16.5 Hz); d (cis) ꢂ70.73 (dt, 1F, JFeF
205.6 Hz, JHeF¼13.9 Hz), ꢂ72.78 (dt, 1F, JFeF¼205.6 Hz,
JHeF¼16.2 Hz). HRMS (EI), C13H15ClF2OS calcd: 292.0500;
found: 292.0500.
Pent-4-enoic acid 15 (2 mmol) was dissolved in a solution
of NaOH (80 mg, 2 mmol) in water (2 mL). Acetonitrile
(6 mL) and 3 (2 mmol) were then added while stirring. So-
dium dithionite (560 mg, 3.2 mmol) and sodium bicarbonate
(270 mg, 3.2 mmol) were added to the solution at 25 ꢀC in
20 min. After stirring for 6e8 h at this temperature, water
(ca. 15 mL) was added. The mixture was extracted with ethyl
ether (3ꢃ15 mL). The combined organic layers were washed
with saturated brine and dried over anhydrous sodium sulfate.
After evaporation of ethyl ether, the crude product was puri-
fied by column chromatography eluting with PE and EA to
give the corresponding lactones.
4.4.6. 2-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-
tetrahydro-furan (14bb0)
IR (film): 3063, 1574, 1477, 1258, 1171, 1093, 1016 cmꢂ1
.
1H NMR: d 7.55e7.26 (m, 4H, PhH), 4.18e4.12 (m, 1H,
CHO), 3.91e3.86 (m, 1H, CH2O), 3.98e3.76 (m, 1H, CH2O),
2.51e2.43 (m, 1H, CF2CH2), 2.32e2.27 (m, 1H, CF2CH2),
2.17e2.12 (m, 1H), 2.00e1.85 (m, 2H), 1.60e1.53 (m, 1H).
13C NMR: d 138.2, 137.1, 129.9, 129.2 (t, J¼279.2 Hz),
126.0, 74.5, 68.6, 45.1 (t, J¼22.9 Hz), 32.8, 26.2. 19F NMR
(CDCl3) d ꢂ70.69 (ddd, 1F, JFeF¼205.6 Hz, J1HeF¼15.1 Hz,
4.5.1. 5-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-dihydro-
furan-2-one (16aa0)
J2HeF¼12.2 Hz), ꢂ72.69 (dt, 1F, JFeF¼205.6 Hz, JHeF
¼
16.2 Hz). HRMS (EI), C12H13ClF2OS calcd: 278.0344; found:
278.0344.
Colorless oil. IR (film): 3062, 1780, 1603, 1250, 1219, 1187,
1154, 1073, 1023 cmꢂ1. 1H NMR: d 7.62e7.34 (m, 5H, PhH),
4.84e4.78 (m, 1H, CHO), 2.73e2.63 (m, 1H, CF2CH2),
2.59e2.36 (stack, 4H, CF2CH2, CH2CO, CH2CH2CO), 2.01e
1.93 (m, 1H, CH2CH2CO). 13C NMR: d 176.8, 136.9, 130.8,
129.9, 128.5 (t, J¼278.8 Hz), 126.8, 75.7, 44.5 (t, J¼23.8 Hz),
29.3, 29.1. 19F NMR: d ꢂ71.45 (ddd, 1F, JFeF¼210.8 Hz,
4.4.7. 2-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-
3,3-dimethyl-tetrahydro-furan (14bc0)
Colorless oil. IR (film): 3066, 1574, 1259, 1177, 1093,
.
1050, 1015 cmꢂ1 1H NMR: d 7.56e7.34 (m, 4H, PhH),

X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
2267
J1HeF¼16.9 Hz, J2HeF¼10.8 Hz), ꢂ73.56 (dt, 1F, JFeF¼
210.8 Hz, JHeF¼15.8 Hz). HRMS (EI), C12H12O2F2S calcd:
258.0526; found: 258.0527.
4.5.5. 5-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-3-phenyl-
dihydro-furan-2-one (16ae0)
White powder with mp: 78e80 ꢀC. IR (KBr): 3085, 3062,
1767, 1603, 1362, 1274, 1252, 1159, 1091, 1064, 1039 cmꢂ1
.
4.5.2. 5-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-4,4-dimethyl-
dihydro-furan-2-one (16ab0)
1H NMR: d (cis) 7.63e7.26 (m, 10H, PhH), 4.87e4.81 (m,
1H, CHO), 3.93e3.87 (m, 1H, CHPh), 2.95e2.91 (m, 1H,
CH2CHCO), 2.88e2.68 (m, 1H, CF2CH2), 2.56e2.45 (m, 1H,
CF2CH2), 2.24e2.20 (m, 1H, CH2CHCO); d (trans) 7.63e
7.26 (m, 10H, PhH), 4.99e4.94 (m, 1H, CHO), 3.93e3.87 (m,
1H, CHPh), 2.88e2.68 (stack, 2H, CF2CH2, CH2CHCO),
2.56e2.45 (stack, 2H, CF2CH2, CH2CHCO). 13C NMR:
d (cis) 176.4, 136.9, 136.5, 130.8, 129.9, 129.7, 129.5 (t,
J¼274.6 Hz), 128.7, 128.1, 126.3, 73.5, 47.3, 44.5 (t,
J¼23.7 Hz), 39.1; d (trans) 176.8, 136.9, 137.0, 130.8, 129.9,
129.7, 129.5 (t, J¼274.6 Hz), 128.4, 128.1, 126.8, 74.0, 45.7,
44.4 (t, J¼23.64 Hz), 37.2. 19F NMR: d ꢂ71.13 to ꢂ71.64 (m,
1F), ꢂ73.38 to ꢂ73.89 (m, 1F). HRMS (EI), C18H16F2O2S
calcd: 334.0839; found: 334.0833.
Colorless oil. IR (film): 3062, 1784, 1580, 1396, 1377, 1311,
1288, 1255, 1232, 1199, 1172, 1152 cmꢂ1. 1H NMR: d 7.63e
7.39 (m, 5H, PhH), 4.35 (d, 1H, J¼8.4 Hz, CHO), 2.45 (d, 1H,
J¼16.8 Hz, CH2C), 2.51e2.50 (m, 2H, CF2CH2), 2.31 (d, 1H,
J¼16.8 Hz, CH2C), 1.16 (s, 3H, CH3), 0.99 (s, 3H, CH3). 13C
NMR: d 175.8, 136.9, 130.7, 129.8, 129.0 (t, J¼279.5 Hz),
126.9, 82.8, 44.9, 40.3, 39.1 (t, J¼24.6 Hz), 24.8, 21.8. 19F
NMR: d ꢂ72.02 (dt, 1F, JFeF¼208.9 Hz, JHeF¼14.6 Hz),
ꢂ72.61 (dt, 1F, JFeF¼208.9 Hz, JHeF¼13.9 Hz). HRMS (EI),
C14H16F2O2S calcd: 286.0839; found: 286.0840.
4.5.3. 5-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-3-methyl-
dihydro-furan-2-one (16ac0)
Colorless oil. IR (film): 2833, 1760, 1580, 1368, 1210, 1179,
1160, 1115, 1072, 1044 cmꢂ1. 1H NMR: d (cis) 7.32e7.55 (m,
5H, PhH), 4.65e4.58 (m, 1H, CHO), 2.70e2.50 (stack, 3H,
CF2CH2, CHCO, CH2CHCO), 2.38e2.25 (m, 1H, CF2CH2),
1.60e1.52 (m, 1H, CH2CHCO), 1.21 (d, 3H, J¼6.8 Hz, CH3);
d (trans) 7.32e7.55 (m, 5H, PhH), 4.84e4.77 (m, 1H, CHO),
2.70e2.50 (stack, 2H, CF2CH2, CHCO), 2.38e2.25 (m, 1H,
CF2CH2), 2.25e2.17 (m, 1H, CH2CHCO), 2.09e2.05 (m, 1H,
CH2CHCO), 1.24 (d, 3H, J¼7.4 Hz, CH3). 13C NMR: d (cis)
179.1, 136.9, 130.8, 129.9, 128.5 (t, J¼278.8 Hz), 126.9, 73.5,
44.7 (t, J¼24.6 Hz), 38.5, 36.5, 15.5; d (trans) 179.6, 136.9,
130.8, 129.9, 128.5 (t, J¼278.8 Hz), 126.9, 73.5, 44.4 (t,
J¼23.4 Hz), 36.1, 34.3, 16.3. 19F NMR: d ꢂ71.37 (ddd, 1F,
JFeF¼210.8 Hz, J1HeF¼16.0 Hz, J2HeF¼10.8 Hz), ꢂ73.73
(dt, 1F, JFeF¼210.8 Hz, JHeF¼15.5 Hz). HRMS (EI),
C13H14F2O2S calcd: 272.0683; found: 272.0689.
4.5.6. N-[5-(2,2-Difluoro-2-phenylsulfanyl-ethyl)-2-oxo-
tetrahydro-furan-3-yl]-4-methoxy-benzamide (16af0)
White powder with mp: 152e153 ꢀC. IR (KBr, cmꢂ1): 3417,
3058, 1774, 1661, 1607, 1373, 1311, 1254, 1185, 1099, 1062,
1
1038 cmꢂ1. H NMR: d (cis) 7.75e7.38 (m, 7H, PhH), 7.02
(br, 1H, NH), 6.87e6.84 (m, 2H, PhH), 4.71e4.78 (stack, 2H,
CHO, CHNH), 3.81 (s, 3H, OCH3), 3.10e3.00 (m, 1H,
CH2CHCO), 2.79e2.71 (m, 1H, CF2CH2), 2.49e2.35 (m, 1H,
CF2CH2), 2.12e1.02 (m, 1H, CH2CHCO); d (trans) 7.75e
7.38 (m, 7H, PhH), 7.16 (br, 1H, NH), 6.87e6.84 (m, 2H,
PhH), 5.10e5.08 (m, 1H, CHNH), 4.70e4.65 (m, 1H, CHO),
3.81 (s, 3H, OCH3), 2.69e2.50 (stack, 2H, CF2CH2,
CH2CHCO), 2.49e2.35 (stack, 2H, CF2CH2, CH2CHCO). 13
C
NMR: d (cis) 175.5, 167.8, 137.0, 130.8, 130.0, 129.8, 129.7,
128.3 (t, J¼276.8 Hz), 126.7, 125.7, 114.5, 73.5, 56.0, 51.0,
44.4 (t, J¼23.8 Hz), 37.0; d (trans) 175.9, 163.3, 137.0, 130.8,
130.0, 129.8, 129.7, 128.4 (t, J¼276.8 Hz), 126.7, 125.6,
114.5, 74.1, 56.0, 49.3, 44.4 (t, J¼23.8 Hz), 35.1. 19F NMR:
d ꢂ71.69 to ꢂ72.23 (m, 1F), ꢂ72.90 to ꢂ73.46 (m, 1F).
HRMS (EI), C20H19F2NO4S calcd: 407.1003; found: 407.1007.
4.5.4. 3-Benzyl-5-(2,2-difluoro-2-phenylsulfanyl-ethyl)-
dihydro-furan-2-one (16ad0)
Colorless oil. IR (film): 3060, 1769, 1600, 1363, 1280, 1244,
1
1216, 1183, 1150, 1093, 1070, 1054, 1024 cmꢂ1. H NMR:
d (cis) 7.59e7.17 (m, 10H, PhH), 4.68e4.60 (m, 1H, CHO),
3.29 (dd, 1H, J1¼14.0 Hz, J2¼4.2 Hz, PhCH2), 2.93e2.91 (m,
1H, CHBn), 2.73 (dd, 1H, J1¼14.0 Hz, J2¼9.5 Hz, PhCH2),
2.59e2.53 (m, 1H, CF2CH2), 2.48e2.43 (m, 1H, CH2CHCO),
2.36e2.29 (m, 1H, CF2CH2), 1.71e1.64 (m, 1H, CH2CHCO);
d (trans) 7.59e7.17 (m, 10H, PhH), 4.62e4.59 (m, 1H, CHO),
3.16 (dd, 1H, J1¼13.7 Hz, J2¼4.6 Hz, PhCH2), 2.96e2.90 (m,
1H, CHBn), 2.83 (dd, 1H, J1¼13.7 Hz, J2¼9.1 Hz, PhCH2),
2.59e2.53 (m, 1H, CF2CH2), 2.36e2.29 (m, 1H, CF2CH2),
2.28e2.21 (m, 1H, CH2CHCO), 2.11e2.05(m, 1H, CH2CHCO).
13C NMR: d (cis) 177.5, 138.7, 136.6, 130.6, 129.6, 129.2, 129.1,
128.2 (t, J¼278.1 Hz), 127.3, 126.6, 73.6, 44.3 (t, J¼23.8 Hz),
42.8, 36.7, 36.4; d (trans) 178.4, 138.5, 136.9, 130.8, 129.9,
129.6, 129.4, 128.4 (t, J¼275.6 Hz), 127.6, 127.3, 73.6, 44.4 (t,
J¼23.8 Hz), 41.4, 34.8, 33.6. 19F NMR: d ꢂ71.31 to ꢂ71.91
(m, 1F), ꢂ73.52 to ꢂ74.11 (m, 1F). HRMS (EI), C19H18F2O2S
calcd: 348.0996; found: 348.0956.
4.5.7. 5-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-
dihydro-furan-2-one (16ba0)
Colorless oil. IR (film): 3087, 1780, 1251, 1218, 1185, 1154,
1093, 1075, 1013 cmꢂ1. 1H NMR: d 7.46e7.40 (m, 4H, PhH),
4.74e4.68 (m, 1H, CHO), 2.64e2.53 (m, 1H, CF2CH2),
2.48e2.30 (stack, 4H, CF2CH2, CH2CO, CH2CH2CO), 1.94e
1.85 (m, 1H, CH2CH2CO). 13C NMR: d 176.7, 138.1, 137.4,
130.1, 128.2 (t, J¼279.4 Hz), 125.1, 44.5 (t, J¼23.5 Hz), 75.6,
29.3, 29.0. 19F NMR: d ꢂ73.72 (ddd, 1F, JFeF¼209.4 Hz,
J1HeF¼16.5 Hz, J2HeF¼11.3 Hz), ꢂ71.50 (dt, 1F, JFeF
¼
209.4 Hz, JHeF¼15.1 Hz). HRMS (EI), C12H11ClF2O2S calcd:
292.0136; found: 292.0136.
4.5.8. 2-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-
3,3-dimethyl-tetrahydro-furan (16bb0)
Colorless oil. IR (film): 3065, 1780, 1573, 1287, 1260, 1232,
1198, 1152, 1094, 1069, 1013 cmꢂ1. 1H NMR: d 7.44e7.23 (m,

2268
X. Yang et al. / Tetrahedron 64 (2008) 2259e2269
4H, PhH), 4.31 (dd, 1H, J1¼8.6 Hz, J2¼2.3 Hz, CHO), 2.31 (d,
1H, J¼16.8 Hz, CH2C), 2.18 (d, 1H, J¼16.8 Hz, CH2C), 2.35e
3.88 (m, 1H, CHPh), 2.92e2.90 (m, 1H, CH2CHCO), 2.77e
2.71 (m, 1H, CF2CH2), 2.55e2.44 (m, 1H, CF2CH2), 2.18e
2.15 (m, 1H, CH2CHCO); d (trans) 7.55e7.26 (m, 9H, PhH),
4.98e4.93 (m, 1H, CHO), 3.93e3.88 (m, 1H, CHPh), 2.70e
2.62 (stack, 4H, CF2CH2, CH2CHCO). 13C NMR: d (cis)
176.5, 138.2, 137.6, 136.4, 130.2, 129.6, 128.7, 128.5, 128.2
(t, J¼279.4 Hz), 125.0, 73.3, 47.3, 44.5 (t, J¼23.6 Hz), 39.1;
d (trans) 176.8, 138.2, 137.6, 136.9, 130.2, 129.8, 128.5, 128.2
(t, J¼279.4 Hz), 128.1, 125.0, 73.8, 45.8, 44.6 (t, J¼23.6 Hz),
2.17 (m, 2H, CF2CH2), 1.03 (s, 3H, CH3), 0.87 (s, 3H, CH3). 13
C
NMR: d 174.1, 136.5, 135.6, 128.4, 127.2 (t, J¼280.0 Hz),
123.7, 80.9, 43.0, 37.4 (t, J¼24.2 Hz), 38.6, 23.0, 20.0. 19F
NMR:
d
C14H15ClF2O2S calcd: 320.0449; found: 320.0450.
ꢂ72.32 to ꢂ72.21 (m, 2F). HRMS (EI),
4.5.9. 5-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-ethyl]-3-
methyl-dihydro-furan-2-one (16bc0)
Colorless oil. IR (film): 3086, 1780, 1573, 1261, 1165,
37.3. 19F NMR: d (cis) ꢂ71.39 (ddd, 1F, JFeF¼209.4 Hz, J1HeF
¼
16.0 Hz, J2HeF¼10.8 Hz), ꢂ73.75 (dt, 1F, JFeF¼209.4 Hz,
JHeF¼15.5 Hz); d (trans) ꢂ71.39 (ddd, 1F, JFeF¼209.4 Hz,
1
1094, 1073, 1040, 1015 cmꢂ1. H NMR: d (cis) 7.47e7.28
(m, 4H, PhH), 4.61e4.56 (m, 1H, CHO), 2.67e2.52 (stack,
3H, CF2CH2, CHCH3, CH2CHCO), 2.34e2.31 (m, 1H,
CF2CH2), 1.58e1.51 (m, 1H, CH2CHCO), 1.20 (d, 3H,
J¼6.7 Hz, CH3); d (trans) 7.47e7.28 (m, 4H, PhH), 4.80e
4.75 (m, 1H, CHO), 2.67e2.52 (stack, 2H, CF2CH2,
CHCH3), 2.34e2.31 (m, 1H, CF2CH2), 2.19e2.15 (m, 1H,
CH2CHCO), 2.09e2.04 (m, 1H, CH2CHCO), 1.22 (d, 3H,
J¼7.35 Hz, CH3). 13C NMR: d (cis) 179.0, 138.2, 137.2,
130.1, 128.2 (t, J¼279.5 Hz), 125.1, 73.3, 44.6 (t,
J¼23.7 Hz), 38.4, 36.1, 15.4; d (trans) 179.6, 138.2, 137.5,
130.1, 128.3 (t, J¼279.5 Hz), 125.1, 73.3, 44.4 (t,
J¼23.4 Hz), 36.4, 34.3, 16.3. 19F NMR: d ꢂ73.19 to ꢂ71.71
(m, 1F), ꢂ71.44 (ddd, 1F, JFeF¼209.4 Hz, J1HeF¼16.5 Hz,
J2HeF¼14.5 Hz). HRMS (EI), C13H13ClF2O2S calcd:
306.0293; found: 306.0293.
J1HeF¼16.0 Hz, J2HeF¼10.8 Hz), ꢂ73.77 (dt, 1F, JFeF¼
209.4 Hz, JHeF¼12.2 Hz). HRMS (EI), C18H15ClF2O2S
calcd: 368.0449; found: 368.0448.
4.5.12. N-{5-[2-(4-Chloro-phenylsulfanyl)-2,2-difluoro-
ethyl]-2-oxo-tetrahydro-furan-3-yl}-4-methoxy-benzamide
(16bf0)
White solid with mp: 179e181 ꢀC. IR (KBr): 3415, 1774,
1659, 1607, 1575, 1260, 1181, 1094, 1064, 1039, 1016 cmꢂ1
.
1H NMR: d (cis) 7.69e6.83 (m, 8H, PhH), 6.63 (d, 1H,
J¼5.2 Hz, NH), 4.79e4.75 (m, 1H, CHNH), 4.73e4.68 (m,
1H, CHO), 3.78 (s, 3H, OCH3), 3.09e3.03 (m, 1H, CH2CHCO),
2.65e2.54 (m, 1H, CF2CH2), 2.47e2.38 (m, 1H, CF2CH2),
2.20e1.93 (m, 1H, CH2CHCO); d (trans) 7.69e6.83 (m, 8H,
PhH), 6.69 (d, 1H, J¼5.0 Hz, NH), 5.05e5.03 (m, 1H,
CHNH), 4.61e4.56 (m, 1H, CHO), 3.78 (s, 3H, OCH3),
2.65e2.54 (stack, 2H, CF2CH2, CH2CHCO), 2.47e2.38 (stack,
2H, CF2CH2, CH2CHCO). 13C NMR: d (cis) 174.8, 165.6,
161.9, 137.7, 135.7, 129.6, 129.1, 127.3 (t, J¼278.3 Hz),
125.5, 124.7, 113.7, 71.3, 55.4, 49.1, 43.3 (t, J¼23.1 Hz),
33.9; d (trans) 179.5, 165.5, 161.9, 137.6, 135.6, 129.5, 129.2,
127.3 (t, J¼278.3 Hz), 125.4, 124.7, 113.7, 72.5, 55.4, 47.9,
43.4 (t, J¼23.4 Hz), 33.2. 19F NMR: d (cis) ꢂ71.95 (ddd, 1F,
JFeF¼209.4 Hz, J1HeF¼15.5 Hz, J2HeF¼11.8 Hz), ꢂ73.29 to
ꢂ73.80 (m, 1F); d (trans) ꢂ71.79 (ddd, 1F, JFeF¼209.4 Hz,
J1HeF¼15.1 Hz, J2HeF¼11.8 Hz), ꢂ73.29 to ꢂ73.80 (m, 1F).
HRMS (EI), C20H18ClF2NO4S calcd: 441.0613; found:
441.0612.
4.5.10. 3-Benzyl-5-[2-(4-chloro-phenylsulfanyl)-2,2-
difluoro-ethyl]-dihydro-furan-2-one (16bd0)
Colorless oil. IR (film): 3085, 3061, 1780, 1260, 1167, 1092,
1014 cmꢂ1. 1H NMR: d (cis) 7.38e7.05 (m, 9H, PhH), 4.47e
4.44 (m, 1H, CHO), 3.14 (dd, 1H, J1¼14.0 Hz, J2¼4.1 Hz,
CH2Ph), 2.82e2.78 (m, 1H, CHBn), 2.61 (dd, 1H,
J1¼14.0 Hz, J2¼9.5 Hz, CH2Ph), 2.47e2.44 (m, 1H,
CF2CH2), 2.32e2.25 (m, 1H, CH2CHCO), 2.21e2.08 (m, 1H,
CF2CH2), 1.57e1.50 (m, 1H, CH2CHCO); d (trans) 7.38e
7.05 (m, 9H, PhH), 4.53e4.48 (m, 1H, CHO), 3.02 (dd, 1H,
J1¼13.7 Hz, J2¼4.1 Hz, CH2Ph), 2.82e2.78 (m, 1H, CHBn),
2.70 (dd, 1H, J1¼13.7 Hz, J2¼9.5 Hz, CH2Ph), 2.47e2.44 (m,
1H, CF2CH2), 2.21e2.08 (stack, 3H, CF2CH2, CH2CHCO).
13C NMR: d (cis) 176.1, 137.2, 136.5, 135.7, 128.4, 127.9,
127.7, 126.6 (t, J¼279.2 Hz), 125.7, 123.5, 72.0, 42.8 (t,
J¼23.7 Hz), 41.3, 34.8, 34.0; d (trans) 176.7, 136.8, 136.5,
135.7, 128.4, 130.0, 127.8, 126.7 (t, J¼279.2 Hz), 125.9,
123.5, 71.9, 42.7 (t, J¼23.4 Hz), 39.6, 35.2, 31.9. 19F NMR:
d (cis) ꢂ71.24 (ddd, 1F, JFeF¼209.4 Hz, J1HeF¼15.5 Hz,
J2HeF¼11.3 Hz), ꢂ73.24 to ꢂ73.75 (m, 1F); d (trans) ꢂ71.37
(ddd, 1F, JFeF¼209.4 Hz, J1HeF¼15.5 Hz, J2HeF¼11.3 Hz),
ꢂ73.24 to ꢂ73.75 (m, 1F). HRMS (EI), C19H17ClF2O2S calcd:
382.0606; found: 382.0606.
Acknowledgements
We thank the National Natural Science Foundation of
China (Grant No. 20672034) for financial support.
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