Scope and limitations of the Julia-Kocienski reaction with fluorinated sulfonylesters

Article abstract of DOI:10.1016/j.tet.2009.03.041

The study of the Julia-Kocienski reaction between fluorinated arylsulfone and ketones is described. The corresponding fluoroalkenes were isolated in moderate to good yields from β- and δ-substituted cyclic ketones. From acyclic ketones and α-substituted c

Full text of DOI:10.1016/j.tet.2009.03.041

Tetrahedron 65 (2009) 3967–3973
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Scope and limitations of the Julia–Kocienski reaction with
fluorinated sulfonylesters
*
`
Charlene Calata, Jean-Marie Catel, Emmanuel Pfund, Thierry Lequeux
Laboratoire de Chimie Mole´culaire et Thioorganique, UMR CNRS 6507, FR 3038, Universite´ de Caen Basse-Normandie, ENSICAEN,
6 Bd du Mare´chal Juin, 14050 Caen Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The study of the Julia–Kocienski reaction between fluorinated arylsulfone and ketones is described. The
Received 28 January 2009
Received in revised form 11 March 2009
Accepted 16 March 2009
corresponding fluoroalkenes were isolated in moderate to good yields from
b- and d-substituted cyclic
ketones. From acyclic ketones and -substituted cyclic ketones a decarbethoxylation reaction of the
a
sulfonylesters occurred. This decarbethoxylation reaction opened a new route for the preparation of
a variety of fluoroalkylsulfones as potential building blocks for the preparation of fluoroalkenes.
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 26 March 2009
Keywords:
Julia–Kocienski reaction
Fluoroalkenes
Fluorinated alkylsulfones
Decarbethoxylation
1. Introduction
2. Results and discussion
It is well established that the fluorovinylic moiety plays an
important role in the field of medicinal chemistry. It has been in-
troduced onto nucleotides, carbohydrates, vitamins, prostaglan-
dins, steroids, and peptides to improve their physiological
stabilities or their biological activities.1 Among the numerous
methods for the preparation of fluoroolefins,2 the HWE and
Peterson reactions are the most common. However, these ap-
proaches are mostly efficient with reagents bearing electron-
withdrawing groups. Thus, access to fluoroolefins containing an
alkyl or functionalized alkyl chain still remains challenging and
usually requires several steps.3 Since the past decade, our labora-
tory is devoted to the development of new fluoroolefination
reagents and, in 2002 we reported the first one-step synthesis of
fluoroalkylidenes via the modified Julia reaction.4 This approach
has been adopted as a good alternative to the Wittig-type reactions.
We previously showed the modified Julia reaction could be
applied to the stereoselective synthesis of fluoroalkenoates from
ethyl benzothiazolylfluorosulfonyl acetate 1, aldehydes and DBU in
the presence or absence of MgBr2 (Scheme 1, path a or b).6a
The modified Julia reaction success depends on the nature of
the aromatic ring of the starting sulfone and in this field, others p-
deficient systems such as 1-phenyltetrazolyl-, bis-trifluoromethyl-
phenyl-, and 2-pyrimidyl-sulfones were reported as good substrates
for the preparation of alkenes.10 To identify the most efficient aro-
matic moiety for the Julia–Kocienski reaction involving ketones,
fluorosulfones 3 and 5 were prepared. These latter were obtained by
the alkylation of 2-mercaptopyrimidine and 1-phenyltetrazole with
ethyl bromofluoroacetate. Corresponding thioethers 2 and 4 were
F
By this way gem-fluoroaryl alkenes,5
a a-fluoro-
-fluoroacrylates,6
a
-unsaturated amides,7 nitriles,8 and sulfones9 have been pre-
CO2Et
R
a
,b
F
H
pared in good yields. However, this new fluoroolefination reaction
has mainly been studied with aldehydes and only few examples
using ketones were reported. In this paper, the scope and limita-
tions of the modified Julia reaction between heteroaryl-
fluorosulfones and ketones are reported.
CO2Et
N
S
SO2
F
1
b
H
CO2Et
R
R = Alkyl, aryl
Scheme 1. Stereoselective synthesis of fluoroalkenoates.
* Corresponding author. Tel.: þ33 231452854; fax: þ33 231452865.
E-mail address: thierry.lequeux@ensicaen.fr (T. Lequeux).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.041

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C. Calata et al. / Tetrahedron 65 (2009) 3967–3973
Table 1
F
N
Julia–Kocoenski reaction with sulfone 1 and ketones
SH
SH
S
CO2Et
N
F
N
N
a, b
c
SO2
Entry
1
Ketone
Product
Yield %
57a
N
N
CO2Et
F
2
3
O
CO2Et
Ph
N
Ph
N
Ph
N
F
F
7
CO2Et
CO2Et
d
a, b
N
N
N
N
N
N
S
SO2
F
O
2
3
40a
60a
N
N
N
4
5
CO2Et
8
Scheme 2. Two-steps preparation of fluorosulfones 3, 5. (a) tBuOK, THF, 30 min
at ꢁ17 ꢀC. (b) BrCHFCO2Et, THF, ꢁ17 ꢀC to rt, 2 h, 81–82%. (c) (NH4)6Mo7O24$4H2O,
H2O2, EtOH, 16 h at rt, 84%. (d) NaIO4, RuCl3 catalytic, MeCN, H2O, 16 h at rt, 35%.
CO2Et
H
H
H
O
F
isolated in 81% and 82% yields, respectively. Oxidation of 2 into
sulfones was realized in the presence of H2O2/Mo(VI), while 4 re-
quired stronger oxidant such as NaIO4/Ru(III) (Scheme 2). Alterna-
tive synthesis of tetrazolylsulfones can be realized by direct
electrophilic or electrolytic fluorination of 1-phenyltetrazolyl-sul-
fone and sulfide or by alkylation of the corresponding thiol.5,6b,11
The reactivity of sulfones 1, 3, and 5 was then evaluated in
a model fluoroolefination reaction of 4-tert-butylcyclo-hexanone
(Scheme 3). The reaction was realized from 1, applying the exper-
imental conditions used for aldehydes,6a and it was found that the
reaction was slower. It required at least 6 h at room temperature to
reach completion instead of the 2 h needed from aldehydes. Indeed,
in the presence of DBU, the corresponding fluoroalkene 6 was
formed in moderate to good yield from sulfones 1, 3, and 5. Sulfones
containing the pyrimidine and 1-phenyltetrazole displayed the
same reactivity while benzothiazolylfluorosulfone 1 gave the best
results.
H
9
CO2Et
F
O
4
60a
10
CO2Et
F
O
5
6
70a
10b
11
CO2Et
F
O
12
F
N
SO2
7
94c
S
O
13
a
The Julia–Kocienski olefination using ethyl benzothiazolyl-
sulfonyl acetate 1 was extended to other ketones. The Barbier-type
conditions were applied by following this scheme. DBU (1.4 equiv)
was added to a mixture of fluorosulfone 1 (1 equiv) and ketones
(1.2 equiv) in THF. Reactions were performed at room temperature
for 6 h. Results are summarized in Table 1. From non-functionalized
cyclic ketones such as cyclohexanone and cyclopentanone, corre-
sponding fluoroalkenes 7 and 8 were obtained in moderate yields
(Table 1, entries 1 and 2). Introduction of alkyl groups at the
Isolated yield.
Volatile compound.
Conversion deducted by 19F NMR.
b
c
base instead of DBU. However, this modification had no influence
on the Julia–Kocienski reaction efficiency, and only traces of al-
kenes were detected. Attempts to optimize the fluoroolefination of
t
bulky ketones by changing the base (NaHMDS, BuOK, 1,1,3,3-tet-
ramethylguanidine), the temperature, the order of addition of the
reagents, the concentration or by introducing additives such as
phase transfer agent (TBAB) or polar solvent (HMPA) already
employed in the modified Julia reaction, were unsuccessful.10e
This competitive decarbethoxylation reaction has already been
mentioned by Najera during the olefination of aldehydes with bis-
trifluoromethylated arylsulfones.12 This reaction observed from
fluorosulfone 1 appeared attractive to prepare new halogeno- and
alkyl-substituted fluoro-sulfones through the alkylation or halo-
genation of 1. These reagents should be useful for the synthesis of
fluoroalkylidenes or mono- and gem-difluoroalkenes. First, we
concentrated our efforts on the optimization of the decarbethoxy-
lation reaction of ethyl benzothiazolylsulfonyl acetate 1. An over-
night treatment of 1 with DBU in THF at room temperature afforded
sulfone 13 in 30% yield. When ethyl acetate was used instead of THF,
sulfone 13 was obtained in 47% yield. Increase of the reaction time
did not improve the yield and we noticed the formation of non-
identified products. These could be issued from the intermediate
benzothiazolylfluoromethyl carbanion (BTSO2CHFꢁ). The reaction
was realized in presence of a catalytic amount of water (1%) to trap
this anion. In this case, 13 was isolated in 77% yield and the reaction
was easily scaled up to 2 g scale. Furthermore, similar results were
observed either in THF or ethyl acetate (Scheme 4).
b
-position of cyclic ketones did not affect the reaction efficiency.
Indeed, from cis/trans 2-decalone, 3-methylcyclohexanone, and 3-
methylcyclopentanone, fluorinated -unsaturated esters 9–11
a,b
were isolated as a mixture of stereoisomers in 60–70% yield (Table
1, entries 3–5).
Attempts to increase the selectivity by changing the base
t
(NaHMDS, BuOK, 1,1,3,3-tetramethylguanidine) and the reaction
temperature were unsuccessful. However, from linear ketones,
such as 2-pentanone, traces of alkenes were formed, while from
acetone, fluoroacrylate 12 was obtained after 12 h at 20 ꢀC. In spite
of a complete conversion of sulfone 1, fluoroalkene 12 was isolated
in low yield due to its high volatility (Table 1, entry 6). In contrast,
from
was observed even after 24 h under stirring at 20 ꢀC or under
reflux. The cyclic -substituted ketones such as -tetralone, 2-
a-sterically hindered cyclic ketones, no olefination reaction
a
a
methylcyclohexanone, and 2,6-dimethylcyclohexanone led to fluo-
rosulfone 13 exclusively (Table 1, entry 7). The amount of sulfone 13
was limited to 10% when 1,1,3,3-tetramethylguanidine was used as
F
F
CO2Et
a
CO2Et
Ar
SO2
1: Ar = 2-Benzothiazolyl
The decarbethoxylation reaction was explored from haloge-
nated and alkylated fluorosulfones to prepare useful fluorinated
modified Julia reagents. Alkylation reactions of sulfone 1 followed
by a decarbethoxylation were then studied. Alkylation reactions
were conducted from 1 under the Barbier-type conditions. DBU
6
3: Ar = 2-Pyrimidinyl
5: Ar = 2-(1-phenyltetrazolyl)
Scheme 3. Reactivity of sulfones 1, 3, and 5 in the Julia–Kocienski reaction. (a) 4-tert-
Butylcyclohexanone, DBU, THF, 6 h at rt, 82% from 1, 46% from 3, 47% from 5.

C. Calata et al. / Tetrahedron 65 (2009) 3967–3973
3969
Table 3
F
Decarbethoxylation reactions of sulfones 14–18
CO2Et
F
N
S
N
S
a
SO2
SO2
Entry
1
Starting sulfone
Product
Yield %
51
13
1
F
N
S
14
SO2
F
O
19
OEt
Nu
N
S
SO2
F
N
S
I
2
3
15
16
33
SO2
20
Scheme 4. Synthesis of the decarbethoxylated sulfone 13. (a) DBU, H2O catalytic,
AcOEt or THF, 16 h at rt, 77%.
F
EtO2C
21
Z:E = 86:14a
2713
(1.4 equiv) was added to a mixture of fluorosulfone 1 (1 equiv) and
alkyl halide (1.4 equiv) in THF. Reactions were realized at room
temperature over 1 h (Table 2 entries 1–4). From good alkylating
reagent, such as methyl iodide, sulfone 14 was obtained in 92%
yield. The reaction also worked with primary non-activated re-
agent. From ethyl iodide, 15 was isolated in 67% yield (Table 2,
entries 1 and 2). However no alkylation was observed from the
corresponding bromoalkane. In contrast, from activated bro-
moalkanes, such as benzyl bromide, corresponding sulfone 17 was
isolated in excellent yield (93%). The alkylation reaction with allyl
iodide afforded sulfone 16 in 63% yield (Table 2, entries 3 and 4).
Introduction of a second fluorine atom was realized by using NFSI.
However, the expected difluorosulfone 18 was accompanied with
a by-product identified as the corresponding decarbethoxylated
sulfone 23 by 19F NMR analysis of the crude mixture. These sulfones
were formed in a 2:3 ratio. The fluorination reaction of 1 was in-
stantaneous and even by quenching the mixture after 5 min under
stirring, sulfone 23 was still present in 20%. Additional experiments
with 1,1,3,3-tetramethylguanidine prevented this decarbethoxy-
lation and afforded ethyl benzothiazolylsulfonyl-difluoroacetate 18
in 70% yield without trace of 23 (Table 2, entry 5).
F
Ph
EtO2C
4
5
17
18
686
22
Z:E = 98:2a
F
F
N
63
SO2
23
a Determined by measurement of the 3JHF coupling constants.
S
decarbethoxylation (Table 3, entries 1–5). Sulfones 14 and 15 were
treated overnight with DBU in THF in the presence of a catalytic
amount of water. However, corresponding decarbethoxylated sul-
fones 19 and 20 were formed in less than 20% yield. Complete
conversion of 14 and 15 was observed after 48 h under stirring at
50 ꢀC. In these cases, 19 and 20 were isolated by flash chromato-
graphy in non-optimized 51% and 33% yields, respectively (Table 3,
entries 1 and 2). This new approach combining alkylation and
decarbethoxylation reactions of sulfone esters opened an alterna-
tive access to alkylated fluorosulfones, known as precursors of
fluoroalkylidenes.4 However, this method showed some limits
since no trace of decarbethoxylated sulfones was detected from
sulfones 16 and 17. In these two cases, instead of the expected
sulfones, fluoroalkenes 21 and 22 were isolated in 68 and 27% yield
with a good Z selectivity (Table 3, entries 3 and 4). In contrast, from
difluorinated ester 18 the decarbethoxylation was instantaneous at
room temperature and difluoromethyl-benzothiazolylsulfone 23
was isolated in good yield (Table 3, entry 5).
The competitive desulfonylation reaction leading to fluoro-
alkenes 21 and 22, observed from sulfones 16 and 17, was due to the
lability of the benzylic or allylic hydrogen atoms.14 In addition, this
desulfonylation reaction was easier and exclusive when the
alkylation of 1 was attempted with ethyl bromoacetate (Scheme 5).
The corresponding known fluorofumaric ester 2415 was obtained
exclusively and isolated in 31% yield (Z/E¼87:13).
Having in hands a-substituted fluorinated sulfone esters 14–18,
the previous experimental conditions were applied to study their
Table 2
Alkylation or fluorination reactions of sulfone 1
Entry
1
Electrophile
substituted sulfone
Yield %
92
F
CO2Et
N
S
CH3I
SO2
14
F
CO2Et
CO2Et
N
S
2
3
C2H5I
67
63
SO2
15
F
N
S
H2C]CHCH2I
SO2
16
Ph
F
CO2Et
N
S
4
5
PhCH2Br
93
70
SO2
17
O
O
-ArSO2H
N
S
F
CO2Et
a
S
1
F
CO2Et
H
EtO2C
F
F
CO2Et
N
S
NFSI
H
EtO2C
24
SO2
18
Scheme 5. Desulfonation reaction. (a) DBU, BrCH2CO2Et (1.1 equiv), THF, 20 ꢀC,1 h, 31%.

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C. Calata et al. / Tetrahedron 65 (2009) 3967–3973
This decarbethoxylation reaction of fluorosulfones seems to be
The crude product was purified by flash silica gel chromatography
sensitive to the steric hindrance, the electrophilic character of the
ester and the nature of the leaving group. From non-substituted
sulfone ester 1, the decarbethoxylation is efficient at room tem-
perature, while from the corresponding alkylated sulfones longer
reaction time and elevated temperature are required. Finally, the
decarbethoxylation reaction was most efficient from difluorinated
sulfone ester 18 in which the electrophilic character of the ester
function is exalted by the introduction of a second fluorine atom.
This experimental observation supports the evidence of the for-
mation of the intermediate I suspected in the decarbethoxylation
process.
to afford sulfides 2 and 4.
4.2.1. Ethyl 2-fluoro-2-(2-pyrimidinylthio)acetate (2)
General procedure was followed with 2-mercaptopyrimidine
(0.500 g, 2.67 mmol), ethyl bromofluoroacetate (0.31 mL,
t
2.43 mmol), BuOK (0.350 g, 3.16 mmol). The purification by flash
chromatography (pentane/AcOEt, 8:2) afforded 2 (0.442 g, 81%) as
a
colorless oil. 1H NMR (250.13 MHz, CDCl3)
d
1.33 (t, 3H,
3JHH¼7.2 Hz), 4.33 (q, 2H, JHH¼7.1 Hz), 7.09 (d, 1H, JFH¼50.6 Hz),
3
1
7.12 (t, 1H, JHH¼4.9 Hz), 8.60 (d, 2H, JHH¼4.9 Hz); 19F NMR
3
3
1
(235.35 MHz, CDCl3)
d
ꢁ165.60 (d, 1F, JFH¼51.7 Hz); 13C NMR
(62.90 MHz, CDCl3)
d
13.9, 62.7, 91.0 (d, 1JCF¼229.5 Hz), 118.2, 157.8,
2
3. Conclusion
165.9 (d, JCF¼27.0 Hz), 167.6, 177.6; MS (EI) m/z 217.1 (MþH, 30),
197.0 (100), 169.0 (5), 113.0 (6); HRMS (EIþ) m/z calcd for [MþH]þ
C8H10FN2O2S: 217.0447; found: 217.0435.
In summary, we reported the limits and the scope of the Julia–
Kocienski reaction from ethyl benzothiazolylfluorosulfonyl acetate
1 and ketones. The corresponding fluoroalkenes were obtained in
4.2.2. Ethyl 2-fluoro-2-(1-phenyl-5-tetrazolylthio)acetate (4)
General procedure was followed with 2-mercaptophenyl-tet-
razole (0.500 g, 2.80 mmol), ethyl bromofluoroacetate (0.31 mL,
moderate to good yields from
b- and d-substituted cyclic ketones
but without any selectivity. In contrast, from acyclic ketones and
a
-
t
substituted cyclic ketones, the modified Julia olefination reaction
led to the decarbethoxylated sulfone 13 as the main reaction
product in spite of several changes of reaction conditions. In ad-
dition, an efficient synthesis of sulfone 13 has also been developed
starting from sulfone 1 via a decarbethoxylation reaction per-
formed with DBU in THF or ethyl acetate in the presence of a cata-
lytic amount of water. Finally, this new approach can be used to
prepare new fluorinated alkylsulfones. We showed that sulfone 1
was easily alkylated and in some cases, the resulting sulfone could
be decarbethoxylated to produce fluorosulfones that are important
building blocks in the synthesis of fluoroalkenes.4 The study of their
reactivity in the modified Julia olefination reaction is under
progress.
2.55 mmol), BuOK (0.370 g, 3.31 mmol). The purification by chro-
matography (pentane/AcOEt, 8:2) afforded 46b (0.647 g, 82%) as
a white solid (mp¼47–49 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d 1.34 (t,
3
3
3H, JHH¼7.2 Hz), 4.34 (q, 2H, JHH¼7.1 Hz), 6.96 (d, 1H,
1JFH¼50.5 Hz), 7.51–7.61 (m, 5H); 19F NMR (235.35 MHz, CDCl3)
d
ꢁ161.27 (d, 1F, 1JFH¼49.4 Hz); 13C NMR (62.90 MHz, CDCl3)
d 14.3,
63.9, 92.2 (d, 1JCF¼241.0 Hz), 124.6, 130.4, 131.2, 133.3, 150.2, 164.4
2
(d, JCF¼26.0 Hz); MS (EI) m/z 283.1 (MþH, 68), 240.1 (100), 161.0
(71), 150.0 (54), 118 (17); HRMS (EIþ) m/z calcd for [MþH]þ
C11H12FN4O2S: 283.0665; found: 283.0658.
4.3. Preparation of sulfones 3 and 5
4.3.1. Ethyl 2-fluoro-2-(2-pyrimidinylsulfonyl)acetate (3)
4. Experimental section
4.1. General
In a 25 mL round bottom flask under N2 were placed
(NH4)6Mo7O24$4H2O (0.383 g, 0.31 mmol) and H2O2 (4.94 mL,
47.40 mmol, 30%). After cooling to 0 ꢀC, a solution of sulfide 2
(0.342 g, 1.58 mmol) in EtOH (2.7 mL) was added dropwise. The
mixture was stirred for 16 h at room temperature and quenched
with H2SO4 (3 mL, 10%). EtOH was removed by evaporation and
a NaCl (1 g, 17.10 mmol) was added. The resulting mixture was
extracted with CH2Cl2/Et2O (1:1, 3ꢂ20 mL). Combined organic
layers were washed with brine (3 mL), dried over MgSO4, filtered,
and evaporated under reduced pressure. Purification of the crude
mixture by flash silica gel chromatography (CH2Cl2) afforded 3
All commercially available reagents were bought from Aldrich
and used as received. For anhydrous conditions the glassware was
put in the oven at 120 ꢀC the day before and cooled to room tem-
perature under a continuous nitrogen flow. THF was dried at
a solvent generator from ‘Innovative Technologies Inc.’, which uses
an activated alumina column to remove water. HPLC grade ethyl
acetate was used without further purification. Flash column chro-
matography was realized on silica gel 60 (40–63
mm) from Merck
(0.330 g, 84%) as a colorless oil. 1H NMR (250.13 MHz, CDCl3)
d 1.24
3
3
with air pressure and was detected by thin layer chromatography,
on which the spots were visualized by UV-irradiation and/or
KMnO4 solution. NMR spectra were recorded on a 250 MHz or
400 MHz apparatus in deuterated solvent at 25 ꢀC. 19F NMR spectral
lines are with respect to the internal references CFCl3. All chemical
(t, 3H, JHH¼7.2 Hz), 4.31 (q, 2H, JHH¼7.0 Hz), 6.28 (d, 1H,
1JFH¼47.1 Hz), 7.64 (t, 1H, JHH¼4.9 Hz), 8.94 (d, 2H, JHH¼4.9 Hz);
3
3
19F NMR (235.35 MHz, CDCl3)
d
ꢁ185.13 (d, 1F, JFH¼46.9 Hz); 13C
1
NMR (62.90 MHz, CDCl3)
d
14.2, 64.1, 94.8 (d, 1JCF¼232.7 Hz), 125.2,
2
159.4, 161.5 (d, JCF¼39.6 Hz), 163.8, 207.4; MS (EI) m/z 271.0
(MþNaþ, 100), 249.0 (MþHþ, 23), 197.0 (100), 169.0 (5), 113.0 (6);
HRMS (EIþ) m/z calcd for [MþH]þ C8H10FN2O4S: 249.0345; found:
249.0339.
shifts are reported in
d parts per million (ppm) and coupling con-
stants are in hertz (Hz). High-resolution mass data were recorded
on a high-resolution mass spectrometer in the EI or ESI mode.
4.2. General procedure for the preparation of sulfides 2 and 4
4.3.2. Ethyl 2-fluoro-2-(1-phenyl-5-tetrazolylsulfonyl)acetate (5)
In a 25 mL round bottom flask were placed sulfide 4 (0.200 g,
0.71 mmol), MeCN (1.2 mL), and H2O (2.4 mL). NaIO4 (0.641 g,
2.99 mmol) and RuCl3$3H2O (2.400 mg, 0.015 mmol) were in-
troduced and the resulting mixture was stirred overnight, then
hydrolyzed with H2O (2.4 mL), and extracted with Et2O (2ꢂ2.4 mL).
Combined organic layers were washed with a saturated NaHCO3
solution (2ꢂ2 mL) and brine (2ꢂ2 mL), dried over MgSO4, filtered,
and concentrated under reduced pressure. The crude product was
purified by flash silica gel column chromatography (CH2Cl2/pentane,
8:2) to afford 56b (0.076 g, 35%) as a white solid (mp¼85–88 ꢀC).
In a 50 mL round bottom flask under N2 were placed 2-mer-
captoaryl (1.1 equiv) and dry THF (4 mL). The solution was cooled to
t
ꢁ17 ꢀC and a solution of BuOK (1.3 equiv) in dry THF (3 mL) was
slowly added. After 30 min stirring at ꢁ17 ꢀC, ethyl bromo-
fluoroacetate (1.0 equiv) was introduced dropwise. The resulting
mixture was stirred at room temperature for 2 h, then quenched
with a saturated NH4Cl solution (10 mL) and extracted with
CH2Cl2/Et2O (1:1, 2ꢂ30 mL). Combined organic layers were washed
with brine (5 mL), dried over MgSO4, filtered, and concentrated.

C. Calata et al. / Tetrahedron 65 (2009) 3967–3973
3971
1H NMR (250.13 MHz, CDCl3)
d
1.35 (t, 3H, 3JHH¼7.1 Hz), 4.40 (q, 2H,
3H, 3JHH¼7.0 Hz), 1.33–1.50 (m, 1H), 1.51–1.54 (m, 2H), 1.71–1.85 (m,
4H), 2.78–2.81 (m,1H), 3.38–3.68 (m,1H), 4.24 (q, 2H, 3JHH¼7.0 Hz);
3JHH¼7.2 Hz), 6.15 (d, 1H, 1JFH¼44.0 Hz), 7.60–7.64 (m, 5H); 19F NMR
1
(235.35 MHz, CDCl3)
d
ꢁ180.01 (d, 1F, JFH¼47.1 Hz); 13C NMR
19F NMR (235.35 MHz, CDCl3)
d
ꢁ131.29 (m,1F), ꢁ131.88 (m,1F); 13
C
(62.90 MHz, CDCl3)
d
13.8, 64.5, 97.1 (d, 1JCF¼238.0 Hz), 125.6, 129.6,
NMR (62.90 MHz, CDCl3) d 14.1, 22.1–26.4 (m), 27.0–28.1 (m), 32.3–
2
131.8, 132.5, 151.1, 158.9 (d, JCF¼23.0 Hz), 177.7; MS (EI) m/z 337.0
(MþNaþ, 100), 315.1 (MþHþ, 35), 176.0 (13), 117.1 (38); HRMS (EIþ)
m/z calcd for [MþH]þ C11H12FN4O4S: 315.0563; found: 315.0564.
33.4 (m), 34.3–35.6 (m), 60.8, 67.0, 135.7–135.9 (m), 141.0 (d,
2
1JCF¼246.0 Hz), 161.6 (d, JCF¼36.0 Hz); MS (EI) m/z 201.1 (MþHþ,
100), 173.1 (70), 153.1 (20), 130.2 (8); HRMS (EIþ) m/z calcd for
[MþH]þ C11H18FO2: 201.1291; found: 201.1287.
4.4. General procedure for the preparation of fluoro-
alkenes 7–11
4.4.5. Ethyl 2-fluoro-2-(3-methylcyclopentylidene)acetate (11)
General procedure was followed with 3-methylcyclopentanone
(0.085 mL, 0.79 mmol). The purification by flash chromatography
(pentane/AcOEt, 98:2) afforded 11 as a mixture of two stereoiso-
mers (1/1, 0.085 g, 70%) as a colorless oil. 1H NMR (250.13 MHz,
In a 25 mL round bottom flask were placed sulfone 1 (0.200 g,
0.65 mmol, 1.0 equiv), ketone (0.79 mmol, 1.2 equiv), and dry THF
(10 mL). DBU (0.17 mL, 1.12 mmol, 1.7 equiv) was added dropwise
and the solution was stirred during 6 h at room temperature. The
mixture was quenched with a saturated NH4Cl solution (5 mL) and
brine (2 mL), and then extracted with CH2Cl2 (2ꢂ30 mL). Combined
organic layers were washed with brine (5 mL), dried over MgSO4,
filtered, and evaporated under reduced pressure. The crude product
was purified by flash silica gel chromatography to afford corre-
sponding fluoroalkenes 7–11.
3
3
CDCl3)
d
0.88–0.91 (d, 3H, JHH¼6.3 Hz), 1.29 (t, 3H, JHH¼7.1 Hz),
1.36–1.88 (m, 6H), 2.78–2.83 (m, 1H), 3.31–3.37 (m, 1H), 4.23 (q, 2H,
3JHH¼7.1 Hz); 19F NMR (235.35 MHz, CDCl3)
d
ꢁ130.84 (m, 1F),
ꢁ131.32 (m, 1F), ꢁ126.90, ꢁ126.91 (m, 1F); 13C NMR (62.90 MHz,
CDCl3)
d 14.1, 22.0, 25.9–26.4 (m), 27.0–27.3 (m), 33.4, 33.4, 33.7,
34.3–35.6 (m), 60.8, 135.7–135.8 (m), 141.0 (d, 1JCF¼246.0 Hz), 161.5
2
(d, JCF¼36.0 Hz); MS (EI) m/z 186.1 (100), 158.1 (70), 143.0 (52);
HRMS (EIþ) m/z calcd for [M]þ C10H15FO2: 186.1055; found:
4.4.1. Ethyl 2-cyclohexylidene-2-fluoroacetate (7)
186.1050.
General procedure was followed with cyclohexanone (0.08 mL,
0.72 mmol). The purification by flash chromatography (pentane/
4.5. Preparation of sulfone 13
AcOEt, 98:2) afforded 7 (0.070 g, 57%) as a colorless oil. 1H NMR
3
(250.13 MHz, CDCl3)
d
1.26 (t, 3H, JHH¼7.1 Hz), 1.52–1.62 (m, 6H),
In a 250 mL round bottom flask were placed sulfone 1 (2 g,
6.59 mmol) and AcOEt (100 mL). DBU (1.30 mL, 9.23 mmol) and
H2O (0.4 mL) were added and the solution was stirred during 16 h
at room temperature. The mixture was hydrolyzed with saturated
NH4Cl solution (20 mL). The organic layer was separated and the
aqueous layer was extracted with CH2Cl2 (2ꢂ50 mL). Combined
organic layers were washed with brine (30 mL), dried over MgSO4,
filtered, and evaporated under reduced pressure. The crude product
was purified by flash silica gel chromatography (pentane/AcOEt,
9:1) to afford 13 (1.182 g, 77%) as a white solid (mp¼144–147 ꢀC). 1H
2.25–2.27 (m, 2H), 2.63–2.65 (m, 2H), 4.21 (q, 2H, 3JHH¼7.1 Hz); 19
F
NMR (235.35 MHz, CDCl3)
d
3
ꢁ131.39 (s, 1F); 13C NMR (62.90 MHz,
CDCl3)
d
14.1, 27.0 (d, JCF¼1.4 Hz), 27.4, 27.5, 27.4, 27.8 (d,
3JCF¼2.3 Hz), 60.8, 136.3 (d, JCF¼12.0 Hz), 140.9 (d, 1JCF¼245.0 Hz),
161.6 (d, 2JCF¼35.0 Hz); MS (EI) m/z 186.1 (M, 68), 158.0 (100), 157.1
(35); HRMS (EIþ) m/z calcd for [M]þ C10H15FO2: 186.1056; found:
186.1054.
2
4.4.2. Ethyl 2-cyclopentylidene-2-fluoroacetate (8)
General procedure was followed with cyclopentanone (0.07 mL,
0.79 mmol). The purification by flash chromatography (pentane/
NMR (250.13 MHz, CDCl3)
d
5.58 (d, 2H, 1JFH¼46.76 Hz), 7.64–7.69
(m, 2H), 8.04–8.07 (m, 1H), 8.25–8.29 (m, 1H); 19F NMR
AcOEt, 98:2) afforded 8 (0.045 g, 40 %) as a colorless oil. 1H NMR
(235.35 MHz, CDCl3)
(62.90 MHz, CDCl3)
d
ꢁ210.87 (t, 1F, JFH¼46.83 Hz); 13C NMR
1
3
1
(250.13 MHz, CDCl3)
d
1.26 (t, 3H, JHH¼7.1 Hz), 1.56–1.74 (m, 4H),
d
91.0 (d, JCF¼223.27 Hz), 122.7, 126.1, 128.3,
2.43–2.48 (m, 2H), 2.60–2.66 (m, 2H), 4.20 (q, 2H, 3JHH¼7.1 Hz); 19
F
128.9, 137.7, 153.1, 162.6, 178.2; MS (EI) m/z 231.9 (MþHþ, 100),
258.0 (10); HRMS (EIþ) m/z calcd for [MþH]þ C8H7FNO2S2:
231.9902; found: 231.9911.
NMR (235.35 MHz, CDCl3)
d
ꢁ126.27 (m, 1F); 13C NMR (62.90 MHz,
CDCl3)
d
14.6, 25.9, 27.3, 30.8 (d, 3JCF¼2.9 Hz), 31.3 (d, 3JCF¼1.2 Hz),
2
1
61.2, 141.6 (d, JCF¼15.0 Hz), 141.8 (d, JCF¼244.0 Hz), 161.6 (d,
2JCF¼34.0 Hz); MS (EI) m/z 172.1 (M, 36), 144.1 (100); HRMS (EIþ)
m/z calcd for [M]þ C9H13FO2: 172.0899; found: 172.0898.
4.6. General procedure for the preparation of fluoro-
sulfones 14–17
4.4.3. Ethyl 2-fluoro-2-(2-decalinylidene) acetate (9)
In a 50 mL round bottom flask under N2 were placed sulfone 1
(1.0 equiv), halide (1.2–1.4 equiv), and THF (10 mL). DBU (1.4 equiv)
was added dropwise and the solution was stirred 1 h at room
temperature. The reaction mixture was quenched with a saturated
NH4Cl solution (3 mL) and then extracted with CH2Cl2 (2ꢂ20 mL).
Combined organic layers were washed with brine (10 mL), dried
over MgSO4, filtered, and evaporated under reduced pressure. The
crude product was purified by flash silica gel chromatography to
afford corresponding fluorinated sulfones 14–17.
General procedure was followed with 2-decalone (0.12 mL,
0.79 mmol). The purification by flash chromatography (pentane/
AcOEt, 98:2) afforded 9 under a mixture of four stereoisomers (1/
0.8/0.9/0.9, 0.094 g, 60%) as a colorless oil. 1H NMR (250.13 MHz,
CDCl3)
d 0.99–1.79 (m, 15H), 1.96–3.62 (m, 4H), 4.00–4.35 (m, 2H);
19F NMR (235.35 MHz, CDCl3)
d
ꢁ129.90 (s, 1F), ꢁ131.15 (s, 1F),
ꢁ131.46 (s, 1F), ꢁ131.57 (s, 1F); 13C NMR (62.90 MHz, CDCl3)
d 14.1,
20.9, 22.5 (m), 24.4–29.2 (m), 31.5, 33.1 (m), 33.9 (m), 34.6 (m), 37.7
(m), 42.8, 44.0 (m), 60.3 (m), 135.3 (m), 139.7 (m), 143.4 (m), 161.8
(m), 171.0; MS (EI) m/z 240.2 (M, 41), 195.1 (52), 117.0 (100); HRMS
(EIþ) m/z calcd for [M]þ C14H21FO2: 240.1525; found: 240.1533.
4.6.1. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluoropropanoate (14)
General procedure was followed with sulfone 1 (0.200 g,
0.66 mmol), CH3I (0.05 mL, 0.79 mmol), and DBU (0.14 mL,
0.92 mmol). The purification by flash chromatography (pentane/
AcOEt, 98:2) afforded 14 (0.193 g, 92%) as a white solid (mp¼65–
4.4.4. Ethyl 2-fluoro-2-(3-methylcyclohexylidene)acetate (10)
General procedure was followed with 3-methylcyclohexanone
(0.097 mL, 0.79 mmol). The purification by flash chromatography
(pentane/AcOEt, 98:2) afforded 10 under a mixture of two stereo-
66 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d
1.28 (t, 3H, 3JHH¼7.1 Hz), 2.16
3
(d, 3H, JHH¼21.3 Hz), 4.31–4.36 (m, 2H), 7.62–7.67 (m, 2H), 8.02–
isomers (1/1, 0.070 g, 60%) as a colorless oil. 1H NMR (250.13 MHz,
8.05 (m, 1H), 8.25–8.29 (m, 1H); 19F NMR (235.35 MHz, CDCl3)
3
CDCl3)
d
0.94, 0.96 (d, 3H, JHH¼2.0 Hz), 1.00–1.23 (m, 1H), 1.32 (t,
d
ꢁ147.89 (q, 1F, 3JFH¼21.1 Hz); 13C NMR (62.90 MHz, CDCl3)
d 13.8,

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C. Calata et al. / Tetrahedron 65 (2009) 3967–3973
2
1
17.8 (d, JCF¼20.7 Hz), 63.9, 96.7 (d, JCF¼234.9 Hz), 122.2, 126.0,
127.8, 128.6, 137.9, 152.6, 160.2 (d, 2JCF¼23.3 Hz); MS (EI) m/z 318.0
(MþHþ, 47), 200.0 (50), 182.0 (100); HRMS (EIþ) m/z calcd for
[MþH]þ C12H13FNO4S2: 318.0270; found: 318.0272.
3H, 3JHH¼7.1 Hz), 4.40 (q, 2H, 3JHH¼7.1 Hz), 7.23–7.65 (m, 2H), 7.98–
8.02 (m, 1H), 8.26–8.29 (m, 1H); 19F NMR (235.35 MHz, CDCl3)
d
ꢁ105.82 (s, 1F); 13C NMR (62.90 MHz, CDCl3)
d 14.1, 65.6, 113.8 (t,
1JCF¼301.4 Hz), 122.3, 126.4, 128.2, 129.2, 138.3, 152.8, 157.5 (d,
2JCF¼31.5 Hz); MS (EI) m/z 322.0 (MþHþ, 77), 294.0 (100), 200.0
(62), 182.0 (49), 135.0 (8); HRMS (EIþ) m/z calcd for [MþH]þ
C11H10F2NO4S2: 322.0019; found: 322.0013.
4.6.2. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluorobutanoate (15)
General procedure was followed with sulfone 1 (0.200 g,
0.66 mmol), iodoethane (0.063 mL, 0.79 mmol), and DBU (0.14 mL,
0.92 mmol). The purification by flash chromatography (CH2Cl2/
pentane, 95:5) afforded 15 (0.146 g, 67%) as a white solid (mp¼62–
4.8. General procedure for the formation of decarboxylated
sulfones 19, 20 and esters 21, 22
63 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d
1.07 (t, 3H, 3JHH¼8.0 Hz), 1.30
3
(t, 3H, JHH¼8.0 Hz), 2.53–2.72 (m, 2H), 4.34–4.40 (m, 2H), 7.63–
In a 50 mL round bottom flask were placed sulfone 14–17
(1 equiv) and AcOEt (10 mL). DBU (1.7 equiv) and H2O (catalytic
amount) were introduced and the solution was stirred for 6–48 h at
50 ꢀC or 70 ꢀC according to the substrate. The reaction mixture was
hydrolyzed with a saturated NH4Cl solution (3 mL) and extracted
with CH2Cl2 (2ꢂ30 mL). Combined organic layers were washed
with brine (10 mL), dried over MgSO4, filtered, and evaporated
under reduced pressure. The crude product was purified by flash
silica gel chromatography to afford compounds 19–22.
7.68 (m, 2H), 8.02–8.05 (m, 1H), 8.26–8.28 (m, 1H); 19F NMR
(235.35 MHz, CDCl3)
d
ꢁ158.68 (dd,1F, 3JFH¼36.7 Hz, 3JFH¼36.7 Hz);
13C NMR (62.90 MHz, CDCl3)
d
6.9, 7.0, 13.9, 24.6 (d, JCF¼19.9 Hz),
2
63.8, 108.4 (d, 1JCF¼235.5 Hz), 122.2, 126.0, 127.8, 128.6, 137.9, 152.7,
160.9, 162.6 (d, 2JCF¼24.97 Hz); MS (EI) m/z 332.0 (MþHþ, 83),199.9
(67), 181.9 (100); HRMS (EIþ) m/z calcd for [MþH]þ C13H15FNO4S2:
332.0427; found: 332.0436.
4.6.3. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluoro-4-
pentenoate (16)
4.8.1. 2-(2-Fluoroethylsulfonyl)benzothiazole (19)
General procedure was followed with sulfone 1 (0.250 g,
0.82 mmol), allyl iodide (0.083 mL, 0.91 mmol), and DBU (0.18 mL,
1.23 mmol). The purification by flash chromatography (pentane/
General procedure was followed with sulfone 14 (0.184 g,
0.63 mmol), DBU (0.16 mL,1.07 mmol), and H2O (four drops) during
16 h at 50 ꢀC. The purification by flash chromatography (CH2Cl2/
AcOEt, 95:5) afforded 16 (0.177 g, 63%) as a white solid (mp¼86–
pentane, 9:1) afforded 19 (0.073 g, 51%) as a white solid (mp¼75–
3
3
87 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d
1.20 (t, 3H, JHH¼8.0 Hz),
78 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d
1.82 (dd, 3H, JHH¼6.4 Hz,
3
3
1
3.18–3.35 (m, 2H), 4.28 (q, 2H, JHH¼8.0 Hz), 5.20–5.27 (m, 2H),
3JHF¼23.6 Hz), 5.75 (dq, 1H, JHH¼6.5 Hz, JFH¼41.4 Hz), 7.52–7.62
5.59–5.64 (m, 1H), 7.55–7.61 (m, 2H), 7.96–7.98 (m, 1H), 8.19–8.21
(m, 2H), 8.17–8.19 (m, 1H), 8.20–8.21 (m, 1H); 19F NMR
(m, 1H); 19F NMR (235.35 MHz, CDCl3)
d
ꢁ156.38 (dd, 1F,
(235.35 MHz, CDCl3)
d
ꢁ171.55 (dq, 1F, 3JFH¼23.0 Hz, 1JFH¼48.5 Hz);
3
2
3JFH¼36.7 Hz, JFH¼36.6 Hz); 13C NMR (62.90 MHz, CDCl3)
d
13.9,
13C NMR (62.90 MHz, CDCl3)
d
13.0 (d, JCF¼20.1 Hz), 99.4 (d,
2
1
35.3 (d, JCF¼19.2 Hz), 63.8, 106.8 (d, JCF¼236.8 Hz), 122.2, 122.7,
126.0, 126.7, 126.8, 127.9, 128.6, 137.9, 152.7, 160.7, 162.1 (d,
2JCF¼24.92 Hz); MS (EI) m/z 344.0 (MþHþ, 59), 199.9 (40), 181.9
(100); HRMS (EIþ) m/z calcd for [MþH]þ C14H15FNO4S2: 344.0427;
found: 344.0429.
1JCF¼219.5 Hz), 122.3, 125.7, 127.8, 128.4, 137.4, 152.8, 162.0; MS (EI)
m/z 246.0 (MþHþ, 62), 200.0 (36), 182.0 (100); HRMS (EIþ) m/z
calcd for [MþH]þ C9H9FNO2S2: 246.0059; found: 246.0047.
4.8.2. 2-(2-Fluoropropylsulfonyl)benzothiazole (20)
General procedure was followed with sulfone 15 (0.180 g,
0.54 mmol), DBU (0.14 mL, 0.92 mmol), and H2O (four drops) dur-
ing 48 h at 70 ꢀC. The purification by flash chromatography (pen-
tane/AcOEt, 95:5) afforded 20 (0.044 g, 33%) as a white solid
4.6.4. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluoro-3-
phenylpropanoate (17)
General procedure was followed with sulfone
1 (0.170 g,
0.56 mmol), benzyl bromide (0.093 mL, 0.79 mmol), and DBU
(0.12 mL, 0.78 mol). The purification by flash chromatography
(pentane/AcOEt, 95:5) afforded 17 (0.205 g, 93%) as a yellow oil. 1H
(mp¼100–101 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d 1.16 (t, 3H,
3
3JHH¼7.5 Hz), 2.06–2.34 (m, 2H), 5.53 (ddd, 1H, JHH¼3.5 Hz,
1
3JHH¼9.3 Hz, JHF¼48.4 Hz), 7.53–7.61 (m, 2H), 7.95–7.97 (m, 1H),
NMR (250.13 MHz, CDCl3)
d
1.03 (t, 3H, 3JHH¼8.0 Hz), 3.67–3.98 (m,
8.18–8.20 (m, 1H); 19F NMR (235.35 MHz, CDCl3)
d
ꢁ179.14 (ddd, 1F,
3
1
2H), 4.06–4.16 (m, 2H), 7.11–7.20 (m, 5H), 7.49–7.57 (m, 2H), 7.91–
3JFH¼16.3 Hz, JFH¼33.8 Hz, JFH¼48.6 Hz); 13C NMR (62.90 MHz,
3
2
7.93 (m, 1H), 8.13–8.17 (m, 1H); 19F NMR (235.35 MHz, CDCl3)
CDCl3)
d
8.8 (d, JCF¼3.7 Hz), 20.8 (d, JCF¼19.6 Hz), 103.2 (d,
3
3
d
ꢁ154.85 (dd, 1F, JFH¼38.6 Hz, JFH¼38.5 Hz); 13C NMR
1JCF¼222.1 Hz), 122.3, 125.8, 127.9, 128.3, 137.4, 152.8, 162.6; MS (EI)
m/z 260.0 (MþHþ, 57), 200.0 (31), 182.0 (100); HRMS (EIþ) m/z
calcd for [MþH]þ C10H11FNO2S2: 260.0215; found: 260.0228.
2
(62.90 MHz, CDCl3)
d
14.1, 36.7 (d, JCF¼18.8 Hz), 63.7, 107.2 (d,
1JCF¼238.3 Hz), 122.3, 125.9, 128.0, 128.1, 128.7, 128.9, 130.3, 130.6,
2
131.1, 137.9, 152.7, 160.7, 161.9 (d, JCF¼24.8 Hz), 171.1; MS (EI) m/z
394.1 (MþHþ, 73), 200.0 (22), 182.0 (100); HRMS (EIþ) m/z calcd for
[MþH]þ C18H17FNO4S2: 394.0583; found: 394.0598.
4.8.3. Ethyl 2-fluoro-2,4-pentadienoate (21)
General procedure was followed with sulfone 16 (0.140 g,
0.41 mmol), DBU (0.10 mL, 0.69 mmol), and H2O (six drops) during
48 h at 70 ꢀC. The purification by flash chromatography (pentane/
AcOEt, 95:5) afforded 21 under a mixture of two isomers (Z/
E¼86:14, 0.016 g, 27%) as a yellow oil. 1H NMR (250.13 MHz, CDCl3)
4.7. Preparation of difluorosulfone 18
In a 25 mL round bottom flask under N2 were placed sulfone 1
(0.200 g, 0.66 mmol), NFSI (0.250 g, 0.79 mmol), and THF (10 mL).
1,1,3,3-Tetramethylguanidine (0.10 mL, 0.79 mmol) was added
dropwise and the solution was stirred 5 min at room temperature.
The reaction mixture was quenched with a saturated NH4Cl solu-
tion (3 mL) and then extracted with CH2Cl2 (2ꢂ20 mL). Combined
organic layers were washed with NaHCO3 (5 mL), brine (10 mL),
dried over MgSO4, filtered, and evaporated under reduced pressure.
The crude product was purified by flash silica gel chromatography
(pentane/AcOEt, 9:1) to afford difluorosulfone 18 (0.147 mg, 70%) as
d
1.21–1.31 (m, 6H), 4.20–4.27 (m, 4H), 5.34–5.38 (m, 2H), 5.41–5.53
(m, 2H), 6.31–6.66 (m, 4H); 19F NMR (235.35 MHz, CDCl3)
d
ꢁ127.56
(d, 1F, JFH¼28.9 Hz, Z), ꢁ122.62 (d, 1F, JFH¼19.3 Hz, E); 13C NMR
3
3
(62.90 MHz, CDCl3)
d 14.1, 29.7, 36.5, 61.7, 116.4, 127.5, 127.7, 128.6,
129.2, 129.3, 130.1, 146.0 (d, 1JCF¼268.0 Hz), 162.3 (d, 2JCF¼34.3 Hz).
4.8.4. Ethyl 2-fluoro-3-phenylacrylate (22)
General procedure was followed with sulfone 17 (0.180 g,
0.45 mmol), DBU (0.11 mL, 0.76 mmol), and H2O (six drops) during
48 h at 70 ꢀC. The purification by flash chromatography (pentane/
a white solid (mp¼73–75 ꢀC). 1H NMR (250.13 MHz, CDCl3)
d 1.29 (t,

C. Calata et al. / Tetrahedron 65 (2009) 3967–3973
3973
Dauben, W. G.; Kohler, B.; Roesle, A. J. Org. Chem. 1985, 50, 2007; (g) Grieco, P. A.;
Takigawa, T.; Vedananda, T. R. J. Org. Chem. 1985, 50, 3111; (h) Mc Donald, I. A.;
Lacoste, J. M.; Bey, P.; Wagner, J.; Zreika, M.; Palfreyman, M. G. J. Am. Chem. Soc.
1984, 106, 3354; (i) Bartlett, P. A.; Otake, A. J. Org. Chem. 1995, 60, 3107; (j) Welch,
J. T.; Lin, J. Tetrahedron 1996, 52, 291; (k) Allmendiger, T.; Felder, E.; Hungerbuhler,
E. Tetrahedron Lett. 1990, 31, 7301; (l) Waelchli, R.; Gamse, R.; Bauer, W.; Meigel,
H.; Lier, E.; Feyen, J. H. M. Bioorg. Med. Chem. Lett.1996, 6,1151; (m) Mc Comsey, D.
F.; Hawkins, J. M.; Andrade-Gorden, P.; Addo, M. F.; Oksenberg, D.; Maryanoff, B. E.
Bioorg. Med. Chem. Lett. 1999, 9, 1423.
2. (a) Burton, D. J.; Yang, Z. Y.; Qiu, W. Chem. Rev. 1996, 96, 1641; (b) Van Steenis, J.
H.; Van Der Gen, A. J. Chem. Soc., Perkin Trans. 1 2002, 2117; (c) Sano, S.; Ter-
anishi, R.; Nagao, Y. Tetrahedron Lett. 2002, 43, 9183; (d) Sano, S.; Saito, K.;
Nagao, Y. Tetrahedron Lett. 2003, 44, 3987; (e) Asakura, N.; Usuki, Y.; Lio, H.
J. Fluorine Chem. 2003, 124, 81; (f) Suzuki, Y.; Sato, M. Tetrahedron Lett. 2004, 45,
1679; (g) Yoshida, M.; Komata, A.; Hara, S. Tetrahedron 2006, 62, 8636; (h)
Narumi, T.; Tomita, K.; Inokuchi, E.; Kobayashi, K.; Oishi, S.; Ohno, H.; Fujii, N.
Tetrahedron 2008, 64, 4332.
AcOEt, 95:5) afforded 21 under a mixture of two isomers (Z/E¼98:2,
0.060 g, 68%) as a yellow oil. 1H NMR (250.13 MHz, CDCl3)
1.29 (t,
d
3
3
3H, JHH¼7.2 Hz), 4.26 (q, 2H, JHH¼7.2 Hz), 6.83 (d, 1H,
3JHF¼35.2 Hz), 7.25–7.33 (m, 3H), 7.54–7.56 (m, 2H); 19F NMR
3
(235.35 MHz, CDCl3)
d
ꢁ125.29 (d, 1F, JFH¼35.2 Hz, Z), ꢁ117.17 (d,
1F, 3JFH¼21.9 Hz, E); 13C NMR (62.90 MHz, CDCl3)
d 13.0, 60.9, 116.4,
127.5, 127.7, 128.6, 128.7, 129.2, 129.3, 130.1, 130.2, 146.0 (d,
1JCF¼268.0 Hz), 162.3 (d, JCF¼34.3 Hz); MS (EI) m/z 194.0 (MþHþ,
2
100), 165.0 (37), 149.0 (34), 129 (17), 121 (17), 101 (33), 75 (18), 50
(11); HRMS (EIþ) m/z calcd for [MþH]þ C11H12FO2: 195.0821; found:
195.0819.
4.9. Preparation of difluorosulfone 23
3. (a) Hata, H.; Kobayashi, T.; Amii, H.; Uneyama, K.; Welch, J. T. Tetrahedron Lett.
2002, 43, 6099; (b) Asakura, N.; Usuki, Y.; Iio, H.; Tanaka, T. J. Fluorine Chem.
2006, 127, 800; (c) Yoshimatsu, M.; Murase, Y.; Itoh, A.; Tanabe, G.; Muroaka, O.
Chem. Lett. 2005, 34, 998; (d) Wong, A.; Welch, C. J.; Kuethe, J. T.; Vasquez, E.;
Shaimi, M.; Henderson, D.; Davies, I. W.; Hughes, D. L. Org. Biomol. Chem. 2004,
2, 168; (e) Okada, M.; Nakamra, Y.; Saito, A.; Sato, A.; Horikawa, H.; Taguchi, T.
Tetrahedron Lett. 2002, 42, 5845; (f) Xu, J.; Burton, D. J. Org. Lett. 2002, 4, 831; (g)
Chen, C.; Wilcoxen, K.; Huang, C. Q.; Strack, N.; Mc Carthy, J. R. J. Fluorine Chem.
2000, 101, 285; (h) Chen, C.; Wilcoxen, K.; Kyung-il, K.; Mc Carthy, J. R. Tetra-
hedron Lett. 1997, 38, 7677; (i) Petasis, N. A.; Yudin, A. K.; Zavialov, I. A.; Prakash,
G. K.; Olah, G. A. Synlett 1997, 606; (j) Kawasaki, T.; Ichige, T.; Kitazume, T. J. Org.
Chem. 1998, 63, 7525; (k) Baati, R.; Gouverneur, V.; Miokowski, C. J. Org. Chem.
2000, 65, 1235; (l) Dutheuil, G.; Lei, X.; Pannecoucke, X.; Quirion, J. C. J. Org.
Chem. 2005, 70, 1911; (m) Lei, X.; Dutheuil, G.; Pannecoucke, X.; Quirion, J. C.
Org. Lett. 2004, 6, 2101; (n) Allmendiger, T. Tetrahedron 1991, 47, 4905; (o)
Wang, Y.; Xu, J.; Burton, D. J. Org. Chem. 2006, 71, 7780.
In a 100 mL round bottom flask were placed sulfone 18
(0.616 mg, 1.92 mmol) and AcOEt (30 mL). DBU (0.40 mL,
2.68 mmol) and H2O (15 drops) were added and the solution was
stirred 16 h at room temperature. The reaction mixture was
quenched with a saturated NH4Cl solution (10 mL) and extracted
with CH2Cl2 (2ꢂ30 mL). Combined organic layers were washed
with brine (10 mL), dried over MgSO4, filtered, and evaporated
under reduced pressure. The crude product was purified by flash
silica gel chromatography (pentane/AcOEt, 9:1) to afford 23
(0.304 g, 63%) as
(250.13 MHz, CDCl3)
a
d
white solid (mp¼133–135 ꢀC). 1H NMR
6.51 (t, 1H, 1JHF¼52.8 Hz), 7.59–7.66 (m, 2H),
8.00–8.02 (m, 1H), 8.25–8.27 (m, 1H); 19F NMR (235.35 MHz, CDCl3)
4. (a) Chevrie, D.; Lequeux, T.; Pazenok, S.; Demoute, J. P. Tetrahedron Lett. 2003,
44, 8127; (b) Pazenok, S.; Demoute, J. P.; Zard, S.; Lequeux, T. PCT Int. Appl. WO
0240459 A1, 2002; Chem. Abstr. 2002, 136, 386131.
5. (a) Ghosh, A. K.; Zajc, B. Org. Lett. 2006, 8, 1553; (b) Zhang, W.; Zhu, L.; Hu, J.
Tetrahedron 2007, 63, 10569.
d
ꢁ121.36 (d, 1F, 1JFH¼53.4 Hz); 13C NMR (62.90 MHz, CDCl3)
d 113.4
(t, 1JCF¼288.1 Hz), 121.3, 125.2, 127.2, 128.0, 136.8, 151.9, 157.7; MS
(EI) m/z 250.0 (MþHþ, 63), 200.0 (50), 182.0 (100); HRMS (EIþ) m/z
calcd for [MþH]þ C8H6F2NO2S2: 249.9808; found: 249.9796.
6. (a) Pfund, E.; Lebargy, C.; Rouden, J.; Lequeux, T. J. Org. Chem. 2007, 72, 7871; (b)
Zajc, B.; Kake, S. Org. Lett. 2006, 8, 4457.
7. Alonso, D. A.; Fuensanta, M.; Gomez-Bengoa, E.; Najera, C. Eur. J. Org. Chem.
2008, 2915.
8. Del Solar, M.; Ghosh, A. K.; Zajc, B. J. Org. Chem. 2008, 73, 8206.
9. He, M.; Ghosh, A. K.; Zajc, B. Synlett 2008, 999.
10. (a) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett 1998, 26; (b)
Kocienski, P. J.; Bell, A.; Blakemore, P. R. Synlett 2000, 365; (c) Baudin, J. B.;
Hareau, G.; Julia, S. A.; Lorne, R.; Ruel, O. Bull. Soc. Chim. Fr. 1993, 856; (d) Wnuk,
S. F.; Rios, J. M.; Khan, J.; Hsu, Y. L. J. Org. Chem. 2000, 65, 4169; (e) Blackemore,
P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563; (f) Gueyrard, D.; Haddoub, R.;
Salem, A.; Bacar, N. S.; Goekjian, P. G. Synlett 2005, 520.
Acknowledgements
This work has been performed within the Interregional Organic
Chemistry Network (CRUNCh network). The CNRS and the ‘Re´gion
Basse-Normandie’ are gratefully thanked for their financial
supports.
11. Zagipa, B.; Nagura, H.; Fuchigami, T. J. Fluorine Chem. 2007, 128, 1168.
12. Alonso, D. A.; Fuensanta, M.; Gomez-Bengoa, E.; Najera, C. Adv. Synth. Catal.
2008, 350, 1823.
13. Johnson, W. H.; Wang, S. C.; Stanley, T. M.; Czerwinski, R. M.; Almrud, J. J.;
Poelarends, G. J.; Murzin, A. G.; Whitman, C. P. Biochemistry 2004, 43, 10490.
14. (a) Najera, C.; Yus, M. Tetrahedron 1999, 55, 10547; (b) Prakash, G. K.; Chacko, S.;
Vaghoo, H.; Shao, N.; Gurung, L.; Mathew, T.; Olah, G. A. Org. Lett. 2009, 11, 1127.
15. Gorgues, A.; Ste´phan, D.; Cousseau, J. J. Chem. Soc., Chem. Commun. 1989, 1493.
References and notes
1. (a) Welch, J. T. Tetrahedron 1987, 43, 3123; (b) Choi, Y.; Lee, K.; Hong, J. H.; Schinazi,
R. F.; Chu, C. K. Tetrahedron Lett. 1998, 39, 4437; (c) Gerfen, G. J.; Van der Donk,
W. A.; Yu, G.; Mc Carthy, J. R.; Jarvi, E. T.; Matthews, D. P.; Farrar, C.; Griffin, R. G.;
Stubbe, J. J. Am. Chem. Soc.1998,120, 3823; (d) Pawson, B. A.; Chan, K. K.; Denoble,
J.; Han, R. J. L.; Piermattie, V.; Specian, A. C.; Srisethnil, S. J. Med. Chem. 1979, 22,
1059; (e) Chan, K. K.; Specian, A. C.; Pawson, B. A. J. Med. Chem. 1981, 24, 101; (f)