Decarboxylation of fluorosulfones for the preparation fluoroalkylidene precursors

Article abstract of DOI:10.1016/j.jfluchem.2011.03.005

The synthesis of fluorosulfones by alkylation of fluoroacetate derivatives is reported. Their decarboxylation reaction under Krapcho conditions is a convenient process to prepare fluorosulfones as reagents for fluoroalkene synthesis.

Full text of DOI:10.1016/j.jfluchem.2011.03.005

Journal of Fluorine Chemistry 134 (2012) 128–135
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Decarboxylation of fluorosulfones for the preparation fluoroalkylidene precursors
a,
b,**
*
Florent Larnaud a,b, Emmanuel Pfund a, Bruno Linclau
, Thierry Lequeux
a Laboratoire de Chimie Mole´culaire et Thioorganique, UMR CNRS 6507 & FR3038, ENSICAEN, Universite´ de Caen Basse-Normandie, 6 boulevard du Mare´chal Juin, 14050, Caen, France
b School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
A R T I C L E I N F O
A B S T R A C T
Article history:
The synthesis of fluorosulfones by alkylation of fluoroacetate derivatives is reported. Their
decarboxylation reaction under Krapcho conditions is a convenient process to prepare fluorosulfones
as reagents for fluoroalkene synthesis.
Received 27 January 2011
Received in revised form 3 March 2011
Accepted 4 March 2011
ß 2011 Elsevier B.V. All rights reserved.
Available online 15 March 2011
Keywords:
Fluorosulfones
Benzothiazole
Julia–Kocienski reaction
Krapcho
Decarboxylation
Presentation of the Caen’s group
use of HCFCs and CFCs as starting chemicals. To circumvent this
The fluorine group of the UMR CNRS 6507 at the ENSICAEN,
University of Caen, is managed by the Professor Thierry Lequeux
since 1996, and Dr Emmanuel Pfund since 2006. The works of the
group are focused on the synthesis of enzyme inhibitors and
peptide mimics. To design new medicinal drugs the main objective
is the development of new tools to allow short and rapid synthesis
of fluoroorganic compounds containing a fluoroalkenes bridge or a
difluorophosphonate unit. The two major topics are: (1) New
applications of the Julia–Kocienski fluoroolefination reaction and
(2) Rapid synthesis of difluoromethylphosphonates as phosphate
mimics.
limitation, the group developed a sustainable fluorosulfide, which
avoids the use of such reagents. This sulfide involves in the
synthesis of enzyme inhibitors allows an easy access to fluorinated
hydroxyphosphonates that are building blocks for the synthesis of
acyclic nucleosides.
1. Introduction
New generations of modified pheromones, herbicides and
medicines, which contain a fluoroolefin moiety present a better
bioactivity than the original non-fluorinated compounds [1]. In
this field, fluorinated peptide mimics represent an important class
and it has been established that the fluorinated carbon–carbon
double bond acts as a surrogate of an amide bond of a natural
peptide [2].
The synthesis of monofluoroalkenes has mainly been achieved
by elimination reactions on suitable substituted fluoroalkene
precursors [3], modification of fluorovinyl sulfones, gem-bromo-
fluoroalkenes, or fluoroalkenoates [4], as well as by methods that
directly form the C55C(F) bond. Wittig-type methods are often
(1) Julia–Kocienski Fluoroolefination: a convenient one-step
synthesis of fluoroethylidene derivatives.
Since many years, the group was focused on a straightforward
synthesis of fluoro-olefins, and we described a modification of the
Julia–Kocienski olefination to prepare, in only one step, fluoroalk-
ylidene derivatives from a fluoroalkylbenzothiazolylsulfone and
aldehydes or ketones. This method is general and was used to
introduce other functional groups, to prepare peptide isosteres in
few steps.
(2) Difluoromethylenephosphonate as mimics of phosphates.
The synthesis of difluoromethylphosphonates is becoming
difficult due to environmental protective laws restricting the
applied for the synthesis of terminal fluoroalkenes,
a-fluoro-a,b-
unsaturated esters, as well as 1-fluoro-1-arylmethylidene deriva-
tives. Recently, the Julia–Kocienski reaction has emerged as an
attractive one-step method for fluoroalkene synthesis (Scheme 1)
[5].
We, and others have described the Julia–Kocienski fluoroole-
fination of carbonyl compounds to prepare fluoroalkylidene
derivatives in one step, from fluoroalkylbenzothiazolyl- or N-
phenyltetrazolylsulfones and aldehydes or ketones (equation 1)
* Corresponding author. Tel.: +33 2 3145 2854; fax: +33 2 3145 2865.
** Corresponding author. Tel.: +44 23 8059 3816; fax: +44 23 8059 6805.
E-mail addresses: bruno.linclau@soton.ac.uk (B. Linclau),
thierry.lequeux@ensicaen.fr (T. Lequeux).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.03.005

F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
129
O
DBU, H2O
H
F
R'
O
S
O
S
N
S
8
N
S
F
O
cat., THF
F
O
R
+
1
R
R2
base,
O
Ar1
R1
(1)
R = alkyl, aryl, H, F or EWG
R
CO2Et
CO2Et
51-73%
S
R
R
F
F
O O
R2
F
9
7
R' = Ph, CH=CH2
R = Me, Et, H or F
Ph
N
F
Scheme 3. Decarbethoxylation of sulfonylester derivatives.
1
Ar1
R
H
base,
Ar2
R1
S
(2)
Ar2
O
NTs
In this paper, we report our recent progress for the synthesis of
alkylated fluorosulfones related to structure 1, in which an
extended reaction scope is demonstrated both for the alkylation
and decarboxylation reactions. In particular, alternative conditions
have been developed, that allowed the exclusive decarboxylation
of benzyl and allyl-substituted substrates and avoided the
formation of acrylate derivatives 9.
CF3
N
N
N
N
Ar1
=
N
Ph
S
N
F3C
Scheme 1. One-step synthesis of fluoroalkenes.
2. Results and discussion
[6]. This olefination has proven an efficient way for the synthesis of
-fluoro- -unsaturated esters, sulfones, nitriles, amides, and
aryls from corresponding fluorosulfones [5d]. Recently, Hu
introduced a modified method for monofluoroalkene synthesis
using fluorosulfoximines and nitrones (Eq. (2) [7].
The Julia–Kocienski reaction is efficient and represents the most
direct route to build non-conjugated fluoroalkylidene derivatives,
as exemplified by a recent one step synthesis of allylamines [8].
However, the main limitation of this reaction is the synthesis of the
starting reagents bearing an alkyl chain or a functionalized alkyl
chain. For that reason different approaches for their synthesis have
been reported in the literature (Scheme 2). These include the
synthesis of fluoroalkylsulfones 1 by fluorination of the corre-
a
a,b
The benzothiazolylsulfone 10 was synthesized according to the
literature procedure [11], by alkylation of the mercaptobenzothia-
zole with ethyl bromofluoroacetate followed by the oxidation of
the corresponding sulfide. We reported the alkylation of fluor-
osulfone 10, in the presence of DBU, with reactive halides such as
iodomethane, benzyl bromide and allyl iodide, in moderate to good
yields (Table 1, entries 1,7,10) [12a]. This work was extended to
other alkylhalides to afford sulfones 7a–j. The alkylation reaction
using primary alkyl iodides afforded the sulfones 7a–d in good
yield after 2–3 h under stirring at 20 8C (entries 1, 2, 4, 5). In order
to avoid using iodoalkanes as reagents, the reaction was also
investigated with bromoalkanes. However, reaction with ethyl
bromide did not reach completion under the same conditions (not
shown). Nevertheless, addition of a catalytic amount of Bu4NI led
to the alkylated sulfone in an equally good 79% yield (entry 3).
sponding sulfones or a-halo-sulfides 2 (Eq. (1)) [6,9], by alkylation
of the corresponding monofluorosulfone 3, prepared from CH2FCl
(Eq. (2)) [10], and by aza-Michael addition of amines onto
fluorovinylsulfones 6 (Eq. (4)) [8]. Interestingly, direct electrophilic
fluorination of benzothiazolyl sulfones was reported to be low
yielding [6b]. In a previous paper, we reported a complementary
With a b-substituted iodoalkane (entry 6) low yield was observed
even after 16 h under stirring at room temperature. Substituted
benzylbromide derivatives gave good yields (entries 8–9).
Interestingly, the reaction with allyl bromide was higher-yielding
compared to using allyl iodide (entries 10, 11). When substituted
allyl bromides were involved the alkylation reaction proceeded
smoothly and from 3- and 4-bromobutene a mixture of E/Z
butenylsulfones (entries 12, 13) was obtained following a SN2 and
approach, which consists of preparing fluoroalkylsulfones
1
(Ar = benzothiazole) by alkylation of a sulfonylester derivative 4,
followed a decarbethoxylation reaction (Eq. (3)) [11,12].
During this study, it was noticed that the yield of the
decarbethoxylation step, which required reflux conditions, de-
creased with increasing size of the alkyl chain [12]. In addition,
undesired sulfone elimination leading to fluoroacrylates 9 was
observed with allylic and benzylic substrates (Scheme 3). In this
process, the formation of the difluoromethylsulfone (R55F) and the
fluoromethylsulfone (R55H) were the most facile reactions and
occur already at 20 8C, probably due to the high inductive effect of
the fluoromethylene and the difluoromethylene groups.
’
SN2 pathway. Alkylation of 10 in the presence of Cs2CO3 was not
efficient and observed yields were lower and did not exceed 50%.
With an improved alkylation method in hand, the decarboxyl-
ation reaction was investigated next (Table 2). Decarboxylation of
fluorosulfones 7 mediated by DBU and a small amount of water
(Table 2, Method A) is thought to proceed by attack of hydroxide on
the ester function, to afford the tetrahedral intermediate 11
(Scheme 4). Subsequent elimination, either directly (as shown), or
via the corresponding ester saponification product, leads to
alkylsulfones 8 after in situ protonation (path a) [12,13]. This
X
Ar1
Ar1
S
+
(eq 1)
F
R
Br
S
S
R
2
(O)n
n = 0, 2
F
X = H or Cl, Br
R
OH
OEt
F
or F
F
F
R = H
Ar1
(a)
R
Ar1
(eq 2)
N
S
N
S
+
S
F
R
X
RX
SO2
SO2
11
O
O
O
X = Cl, Br
Ar1
3
DBU, H2O,
THF
S
O
R
8
R = COOEt
OEt
-CO2, EtOH
O
7
R = Me, Et, H or F
F
R
F
1
RX
Ar1
OEt
Ar1
(eq 3)
S
O
S
O
S
N
O
O
O
O O
H
F
R'
(b)
O
R'-NH2
F
5
4
Ar1
S
CO2Et
H
F
S
CO2Et
(eq 4)
O
O
9
R'
R' = Ph, CH=CH2
6
Scheme 2. Synthesis of fluoroalkylsulfone.
Scheme 4. Synthesis of the decarboxylated sulfone.

130
F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
Table 1
Alkylation of the benzothiazole derivative.
R
F
F
RX, DBU, THF
CO2Et
CO2Et
N
N
SO2
SO2
S
S
10
7a-j
.
Entry
RX (1.2 equiv.)
Conditions
Product
Yield (%)
1
2
3
4
5
6
MeI
1 h, r.t.
7a, R = Me
7b, R = Et
92a
79
79
84
72
41
EtI
2 h, r.t.
EtBr
Bu4NI (5 mol%), 4 h, r.t.
3 h, r.t.
n-BuI
7c, R = n-Bu
7d, R = C12H25
7e, R =
C12H25I (2 equiv.)
(2.5 equiv.)
3 h, r.t.
16 h, r.t.
7
8
9
2 h, r.t.
2 h, r.t.
2 h, r.t.
7f, R =
7g, R =
7h, R =
7i, R =
93a
77
67
10
11
X = I, 1 h, r.t.
63a
69
X = Br, 2 h, r.t.
12
2 h, r.t.
2 h, r.t.
7j, R =
7j, R =
88 (E/Z = 80/20)
60 (E/Z = 80/20)
13
(E/Z = 85/15)
a
See [12a].
decarboxylation method works well for the unsubstituted
substrate 10 (entry 1), but yields decrease rapidly with increasing
steric bulk of the substituent, with no conversion at all in case of a
butyl group (entries 2–4). Furthermore, in the case of allyl and
benzyl substituents, an alternative base-induced desulfonylation
starting sulfone was observed at 190 8C (oil bath). At 130 8C the
reagent and product appeared to be stable and the reaction
reached completion after 8 h under stirring. Under these condi-
tions, the corresponding fluoromethyl and ethyl sulfones 12 and 8a
were isolated in 54% and 81% yields, respectively (Table 2, entries 1
and 2). DMF as solvent was investigated but a complex mixture
was obtained. Experiments with sodium chloride or lithium
chloride led to the same yields, and the optimum amount of the
chloride source was determined to be 2 equivalents. Water is
necessary to the reaction: an experiment under strictly anhydrous
conditions led to a moderate yield (<50%), and the optimum
amount of water was established to be 10 equivalents (not shown).
From the unsubstituted substrate 10, Method A still provided the
best yield in the decarboxylation (entry 1) [12].
Substrates containing a larger alkyl chain, such as ethyl, butyl
and dodecyl, gave the corresponding decarboxylation products
8b–d, but a longer reaction time is required, and the yield erodes
slightly with the chain length (entries 3–5). Nevertheless,
reasonable yields were obtained, which represents a significant
improvement compared to Method A.
process was observed leading to the corresponding
a,b-unsatu-
rated esters 9 (entries 6, 9) [14]. Presumably, this elimination
process became competitive by the stabilization of the resulting
products through conjugation.
To avoid this competitive desulfonylation reaction, decar-
boxylation of sulfone
7 under neutral Krapcho conditions
(Scheme 5) appeared more attractive. In addition, as the
reaction proceeds by nucleophilic attack of the chloride ion
on the ester ethyl group, as opposed to the carbonyl group, this
method was expected to be less susceptible to steric hindrance
caused by bulky R-groups.
First, experiments were conducted to determine temperature
and reaction time to reach completion. Decomposition of the
R
Significantly, when benzyl and allyl substituents (entries 6–10)
were investigated, no competitive sulfone elimination to give the
acrylate derivatives 9 was observed, and the corresponding
decarboxylation products 8f–j were obtained in moderate to good
yields. Sulfones 8, 12 have already proven to be excellent reagents
for the synthesis of fluoroalkylidenes [6].
O
O
R
O
O
F
F
NaCl, H2O, DMSO
80 °C or 160 °C
N
N
S
SO2
8
SO2
S
7
Cl
Scheme 5. Decarbethoxylation reaction under Krapcho conditions.

F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
131
Table 2
Scope of the decarboxylation reaction.
R
F
F
CO2Et
N
Method A or B
R
N
S
SO2
SO2
S
12, 8a-j
10, 7a-j
.
Entry
R=
Method Aa
Method Bc
Product
Product
Yield (%)
Reaction time yield (%)
1
2
3
4
5
6
10, R = H
12, R = H
77b
52
33b
0
12, R = H
8 h
54
7a, R = Me
7b, R = Et
7c, R = n-Bu
7d, R = C12H25
7f, R =
8a, R = Me
8b, R = Et
8a, R = Me
8b, R =Et
8 h
81
16 h
71
8c, R = n-Bu
8c, R = n-Bu
8d, R = C12H25
8f, R =
16 h
65
16 h
53
9a, 68(Z/E = 98:2)b
16 h
62
7
8
9
7g, R =
7h, R =
7i, R =
8g, R =
8h, R =
8i, R =
16 h
40
16 h
70
9b, 27 (Z/E = 86:14)b
16 h
51
10
7j, R =
(Z/E = 20/80)
8j, R =
(Z/E =20/80)
8 h
58
a
Method A: DBU (1.7 equiv), H2O catalytic, AcOEt, 50–70 8C, 16 h.
Reported by [12a].
b
c
Method B: NaCl (2 equiv), H2O (10 equiv.), DMSO, 130 8C.
3. Conclusion
further purification. Flash column chromatography was realized
using silica gel 60 (40–63 m) (Merck). Thin layer chromatogra-
phy was performed using pre-coated TLC-sheets Alugram1 SIL G/
UV254 plates, on which the spots were visualized by UV-irradiation
and/or by KMnO4 solution. NMR spectra were recorded on a
m
In conclusion, we report a significantly improved procedure for
the synthesis of fluoroalkylsulfones, which are fluoroalkylidene
precursors. This work is based on the alkylation of the easily
available sulfonylester 10, followed by its decarboxylation under
Krapcho conditions to afford a variety of fluorosulfones in good
yield. In addition, under these neutral decarboxylation conditions
no competitive desulfonylation reaction was observed, which
greatly increases the scope of the method to prepare a variety of
heterocyclic fluorosulfones.
300 MHz or 400 MHz apparatus in deuterated solvent at 25 8C. 19
NMR spectral lines are with respect to the internal references
CFCl3. All chemical shifts are reported in parts per million (ppm)
F
d
and coupling constants are in hertz (Hz). High-resolution mass
data were recorded on a high-resolution mass spectrometer in the
EI or ESI mode.
4. Experimental
4.2. General procedure for the formation of alkylated sulfones 7a–j
4.1. General
To fluorosulfone 10, dissolved in dry THF (0.07 M), alkylhalide
(1.2 equiv.) and DBU (1.4 equiv.) were consecutively added
dropwise. The reaction mixture was stirred at 20 8C, then quenched
with saturated aqueous NH4Cl and extracted with CH2Cl2. The
combined organic layers were washed with brine and dried over
anhydrous MgSO4, filtered and concentrated under reduced
pressure. The residue was purified by column chromatography,
All commercially available reagents were obtained from Aldrich
and used as received. All glassware was dried overnight at 120 8C
and cooled to room temperature under a continuous nitrogen flow.
THF was dried using a solvent generator from ‘‘Innovative
Technologies Inc.’’. HPLC grade ethyl acetate was used without

132
F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
3
3
3
and all compounds were obtained as solids after dissolution in
CH2Cl2, followed by slow evaporation of the solvent.
2JHH 14.6 Hz, JHF 10.9 Hz, JHH 9.8 Hz, JHH 5.0 Hz), 1.59–1.50 (m,
2H), 1.31 (t, 3H, 3JHH 7.2 Hz, OCH2CH3), 1.25 (m, 18H), 0.88 (3H, t,
d
3JHH 6.8 Hz, (CH2)11CH3). 13C NMR (100 MHz, CDCl3) 162.8 (d, 2JCF
4.2.1. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluoropropanoate (7a)
[12a]
25.4 Hz, C55O), 160.9, 152.7, 137.9, 128.5, 127.8, 126.0, 122.2, 108.1
(d, 1JCF 235.2 Hz), 63.7 (OCH2CH3), 31.9, 30.6 (d, 2JCF 19.9 Hz), 29.6
(2 C), 29.5, 29.3, 29.08, 29.05, 22.65, 22.62, 22.61, 14.1
((CH2)11CH3), 13.9 (OCH2CH3). 19F NMR (376 MHz, CDCl3)
The general procedure was followed from 10 (1.50 g,
4.95 mmol), iodomethane (0.37 mL, 5.93 mmol, 1.2 equiv.), DBU
(1.03 mL, 6.92 mmol, 1.4 equiv.) and THF (75 mL). The reaction
mixture was stirred for 1 h. Column chromatography: pentane/
AcOEt, 90:10. Yield of 7a (mp 64–66 8C) as white crystals: 1.44 g,
3
3
d
À 156.7 (dd, 1F, JHF 38.1 Hz, JHF 10.9 Hz). MS (ESI+) m/z (%)
472.3 ((M+H)+, 100). HRMS (MS+) for C23H35FNO4S2 (M+H)+ calcd
472.1992, found 472.1971.
92%. 1H NMR (300 MHz, CDCl3)
d 8.28–8.26 (m, 1H), 8.04–8.02 (m,
1H), 7.69–7.61 (m, 2H), 4.41–4.30 (m, 2H, OCH2CH3), 2.17 (d, 3H,
4.2.5. Ethyl 2-(benzothiazol-2-ylsulfonyl)-2-fluoro-4-
3
3JHF 21.4 Hz), 1.28 (t, 3H, JHH 6.95 Hz, OCH2CH3). 13C NMR
methylpentanoate (7e)
(75 MHz, CDCl3)
d
163.2 (d, 2JCF 24.3 Hz, C55O), 160.3, 152.6, 137.9,
The general procedure was followed with 10 (500 mg,
1.65 mmol), 1-iodo-2-methylpropane (0.48 mL, 4.12 mmol,
2.5 equiv.), DBU (0.35 mL, 2.31 mmol, 1.4 equiv.) and THF
(25 mL). The reaction mixture was stirred for 16 h. Column
chromatography: pentane/AcOEt, 90:10. Yield of 7e (mp 76 8C) as
white crystals: 243 mg, 41%. IR (neat) 2963 (w), 1761 (s), 1459 (m),
128.6, 127.9, 125.9, 122.2, 105.5 (d, 1JCF 233.3 Hz), 63.9 (OCH2CH3),
2
17.8 (d, JCF 19.9 Hz), 13.8 (OCH2CH3). 19F NMR (282 MHz, CDCl3)
3
d
À 148.1 (q, 1F, JHF 21.4 Hz).
4.2.2. Ethyl 2-(benzothiazol-2-ylsulfonyl)-2-fluorobutanoate (7b)
[12a]
1347 (s), 1316 (m), 1227 (s), 1151 (s) cmÀ1
.
1H NMR (400 MHz,
The general procedure was followed from 10 (200 mg,
0.66 mmol), iodoethane (0.064 mL, 0.79 mmol, 1.2 equiv.), DBU
(0.14 mL, 0.92 mmol, 1.4 equiv.) and THF (10 mL). The reaction
mixture was stirred for 2 h. Column chromatography: pentane/
AcOEt, 90:10. Yield of 7b (mp 62–64 8C) as white crystals: 173 mg,
CDCl3) 8.29–8.27 (m, 1H), 8.06–8.03 (m, 1H), 7.69–7.62 (m, 2H),
d
3
2
4.44–4.31 (m, 2H, OCH2CH3), 2.63 (ddd, 1H, JHF 40.9 Hz, JHH
14.7 Hz, 3JHH 6.8 Hz, CH2CH(CH3)2), 2.39 (ddd, 1H, 2JHH 14.7 Hz, 3JHF
8.2 Hz, 3JHH 6.8 Hz, CH2CH(CH3)2), 1.88 (1 H, tqq, 3JHH 6.8 Hz, 3JHH
3
3
6.8 Hz, JHH 6.8 Hz, CH2CH(CH3)2), 1.31 (t, 3H, JHH 14.3 Hz,
79%. 1H NMR (300 MHz, CDCl3)
1H), 7.70–7.61 (m, 2H), 4.43–4.33 (m, 2H, OCH2CH3), 2.82–2.46 (m,
d
8.29–8.26 (m, 1H), 8.06–8.03 (m,
OCH2CH3), 1.00–0.97 (m, 6H, CH2CH(CH3)2). 13C NMR (100 MHz,
2
CDCl3)
d
163.0 (d, JCF 25.4 Hz, C55O), 160.7, 152.6, 137.9, 128.5,
3
3
1
2H, CH2CH3), 1.31 (t, 3H, JHH 7.1 Hz, OCH2CH3), 1.08 (t, 3H, JHH
127.8, 126.0, 122.2, 108.3 (d, JCF 237.6 Hz), 63.7 (OCH2CH3), 38.0
(d, 2JCF 19.1 Hz), 24.7, 23.0, 22.9 (d, 4JCF 2.2 Hz), 13.8 (OCH2CH3). 19
F
NMR (376 MHz, CDCl3)
MS (ESI+) (m/z) 360.1 ((M+H)+, 100%), 200.0 (66%), 182.0 (93%).
HRMS (MS+) for C15H19FNO4S2 (M+H)+ Calcd. 360.0740; Found.
360.0742.
7.4 Hz, CH2CH3). 13C NMR (75 MHz, CDCl3)
C55O), 160.9, 152.7, 137.9, 128.6, 127.9, 126.0, 122.3, 108.4 (d, 1JCF
235.8 Hz), 63.8 (OCH2CH3), 24.6 (d, JCF 19.9 Hz, CH2CH3), 13.9
(OCH2CH3), 7.0 (d, 3JCF 3.6 Hz, CH2CH3). 19F NMR
d
162.6 (d, JCF 25 Hz,
2
d
À155.3 (dd, 1F, 3JHF 40.9 Hz, 3JHF 8.2 Hz).
2
d
À 158.9 (dd, 3JHF
3
37.6 Hz, JHF 11.8 Hz).
4.2.3. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluorohexanoate (7c)
The general procedure was followed with 10 (150 mg,
0.49 mmol), iodobutane (0.068 mL, 0.59 mmol, 1.2 equiv.), DBU
(0.10 mL, 0.69 mmol, 1.4 equiv.) and THF (7.5 mL). The reaction
mixture was stirred for 3 h. Column chromatography: pentane/
AcOEt, 90:10. Yield of 7c (mp 106–108 8C) as white crystals:
178 mg, 84%. IR (neat) 2960 (w), 1765 (s), 1348 (s), 1211 (s), 1162
4.2.6. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluoro-3-
phenylpropanoate (7f) [12a]
The general procedure was followed with 10 (1.00 g, 3.3 mmol),
benzylbromide (0.47 mL, 3.96 mmol, 1.2 equiv.), DBU (0.68 mL,
4.62 mmol, 1.4 equiv.) and THF (50 mL). The reaction mixture was
stirred for 2 h. Column chromatography: pentane/AcOEt, 90:10.
Yield of 7f (mp 86–88 8C) as white crystals: 1.12 g, 86%. 1H NMR
(s) cmÀ1. 1H NMR (400 MHz, CDCl3)
d
8.27–8.25 (m, 1H), 8.048.02
(300 MHz, CDCl3) d 8.30–8.28 (m, 1H), 8.08–8.05 (m, 1H), 7.71–
(m, 1H), 7.687.60 (m, 2H), 4.424.31 (m, 2H, OCH2CH3), 2.742.57 (m,
1H, CH2CH2CH2CH3), 2.522.42 (m, 1H, CH2CH2CH2CH3), 1.661.47
(m, 2H, CH2CH2CH2CH3), 1.451.36 (m, 2H, CH2CH2CH2CH3), 1.30 (t,
7.63 (m, 2H), 7.23–7.28 (m, 5H), 4.28–4.17 (m, 2H, OCH2CH3), 3.90
(dd, 1H, 3JHF 38.7 Hz, 2JHH 14.6, CH2Ph), 3.82 (dd, 1H, 2JHH 14.6 Hz,
3JHF 12.9 Hz, CH2Ph), 1.16 (t, 3H, 3JHH 6.95 Hz, OCH2CH3). 13C NMR
d
2
3H, 3JHH 7 Hz, OCH2CH3), 0.92 (t, 3H, 3JHH 7 Hz, CH2CH2CH2CH3) 13
C
(75 MHz, CDCl3)
d
161.8 (C55O, JCF 25.4 Hz), 160.7, 152.7, 137.9,
NMR (100 MHz, CDCl3)
d
162.7 (d, 2JCF 25.3 Hz, C55O), 160.9, 152.6,
130.6, 130.3 (2 C),128.7 (2 C), 128.6, 128.1, 127.9, 126.0, 122.3,
1
1
2
137.9, 128.5, 127.8, 125.9, 122.2, 108.1 (d, JCF 235.2 Hz), 63.7
(OCH2CH3), 30.3 (d, 2JCF 19.4 Hz, CH2CH2CH2CH3), 24.7
(CH2CH2CH2CH3), 22.2 (CH2CH2CH2CH3), 13.8 (OCH2CH3), 13.6
(CH2CH2CH2CH3). 19F NMR (282 MHz, CDCl3)
38.7 Hz, 3JHF 12.9 Hz). MS (ESI+) m/z (%) 360.2 ((M+H)+, 100). HRMS
(MS+) for C15H18FNO4S2Na (M+Na)+ calcd 382.0553, found
382.0559.
107.2 (d, JCF 237.7 Hz), 63.6 (OCH2CH3), 36.7 (d, JCF 18.80 Hz),
13.7 (OCH2CH3). 19F NMR (282 MHz, CDCl3)
38.7 Hz, JHF 12.9 Hz).
d
À 155.0 (dd, 1F, 3JHF
3
d
À 157.0 (dd, 1F, 3JHF
4.2.7. Ethyl 2-(benzothiazol-2-ylsulfonyl)-3-(4-bromophenyl)-2-
fluoropropanoate (7g)
The general procedure was followed with 10 (200 mg,
0.66 mmol),
4-Bromobenzylbromide
(198 mg,
0.79 mmol,
4.2.4. Ethyl 2-(benzothiazol-2-ylsulfonyl)-2-fluorotetradecanoate
(7d)
1.2 equiv.), DBU (0.14 mL, 0.92 mmol, 1.4 equiv.) and THF
(10 mL). The reaction mixture was stirred for 2 h. Column
chromatography: pentane/AcOEt, 90:10. Yield of 7 g (mp 126–
128 8C) as white crystals: 240 mg, 77%. IR (neat) 2360 (s), 2341 (s),
1750 (m), 1354 (m), 1162 (m), 1012 (m) cmÀ1. 1H NMR (300 MHz,
The general procedure was followed with 10 (200 mg,
0.66 mmol), iodododecane (0.33 mL, 1.32 mmol, 2 equiv.), DBU
(0.14 mL, 0.92 mmol, 1.4 equiv.) and THF (10 mL). The reaction
mixture was stirred for 3 h. Column chromatography: pentane/
AcOEt, 95:5. Yield of 7d (mp 68–70 8C) as white crystals: 224 mg,
CDCl3)
d 8.30–8.27 (m, 1H), 8.08–8.03 (m, 1H), 7.72–7.63 (m, 2H),
7.43 (d, 2H, 3JHH 8.4 Hz), 7.12 (d, 2H, 3JHH 8.4 Hz), 4.29–4.18 (m, 2H,
72%. IR (neat) 2919 (m), 1750 (s), 1462 (m), 1356 (s), 1164 (s) cmÀ1
1H NMR (400 MHz, CDCl3)
8.29–8.26 (m, 1H), 8.05–8.03 (m, 1H),
.
OCH2CH3), 3.85 (dd, 1H, JHF 38.7 Hz, JHH 12.3 Hz, CH2Ph), 3.77
(dd, 1H, 3JHF 12.9 Hz, 2JHH 12.3 Hz, CH2Ph). 1.18 (t, 3H, 3JHH 7.0 Hz,
d
OCH2CH3). 13C NMR (75 MHz, CDCl3) 161.8 (d, 2JCF 24.9 Hz, C55O),
3
2
d
7.69–7.62 (m, 2H), 4.41–4.33 (m, 2H, OCH2CH3), 2.65 (dddd, 1H,
3JHF 38.1 Hz, 2JHH 14.6 Hz, 3JHH 11.5 Hz, 3JHH 4.8 Hz), 2.46 (1H, dddd,
160.5, 152.7, 137.9, 132.0, 131.9, 129.6, 128.7, 128.0, 126.0, 122.4,

F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
133
1
2
122.3, 106.8 (d, JCF 238.6 Hz), 63.8 (OCH2CH3), 36.1 (d, JCF
HRMS (MS+) for C15H17FNO4S2 (M+H)+ calcd. 358.0583, found
358.0594.
18.8 Hz, CH2Ph) 13.8 (OCH2CH3). 19F NMR (282 MHz, CDCl3)
d
À 155.4 (dd, 1F, 3JHF 38.7 Hz, 3JHF 12.9 Hz). MS (ESI+) m/z (%) 474
((M-81Br)+ (53)), 472 ((M-79Br)+, 52). HRMS (MS+) for
4.3. General procedure for the formation of decarboxylated sulfones
,
C
18H16FNO4S279Br (M+H)+ calcd, 471.9688 found. 471.9692.
13 and 8a–j
4.2.8. Ethyl 2-(benzothiazol-2-ylsulfonyl)-2-fluoro-3-o-
tolylpropanoate (7h)
The sulfone (10, 7a–j) was dissolved in DMSO (0.75 M), then
NaCl (2 equiv.) and H2O (10 equiv.) were added. The resulting
mixture was stirred for 8 h or 16 h at 130 8C. DMSO was removed
under high vacuum and the residue was dissolved in CH2Cl2. The
organic phase was washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by
column chromatography.
The general procedure was followed with 10 (400 mg,
1.30 mmol), 2-Methylbenzylbromide (0.21 mL, 1.58 mmol,
1.2 equiv.), DBU (0.28 mL, 1.84 mmol, 1.4 equiv.) and THF
(20 mL). The reaction mixture was stirred for 2 h. Column
chromatography: pentane/AcOEt, 90:10.Yield of 7 h (mp 112–
114 8C) as white crystals: 359 mg, 67%. IR (neat) 2360 (s), 2341 (s),
1747 (m), 1164 (m), 1353 (m), 1160 (s) cmÀ1
CDCl3) 8.31–8.27 (m, 1H), 8.07–8.04 (m, 1H), 7.71–7.62 (m, 2H),
7.18–7.08 (m, 4H), 4.34–4.19 (m, 2H, OCH2CH3), 4.12–3.96 (m, 2H,
CH2Ph), 2.30 (s, 3H, Ph-CH3), 1.17 (t, 3H, 3JHH 7.1 Hz, OCH2CH3). 13
.
1H NMR (300 MHz,
4.3.1. 2-(Fluoromethylsulfonyl)benzothiazole (12) [6a,12a]
d
The general procedure was followed with 10 (250 mg,
0.82 mmol), DMSO (1.1 mL), NaCl (96 mg, 1.64 mmol) and H2O
(0.15 mL, 8.2 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 12 (mp 144–
146 8C) as white crystals: 103 mg, 54%). 1H NMR (300 MHz, CDCl3)
C
NMR (75 MHz, CDCl3)
d
162.2 (d, 2JCF 24.9 Hz, C55O), 160.9, 152.7,
138.1, 137.8, 130.8, 130.3 (d, 4JCF 1.2 Hz), 129.3, 128.6, 128.1, 127.9,
1
126.1, 125.9, 122.3, 107.9 (d, JCF 239.4 Hz), 63.7 (OCH2CH3), 33.3
2
5
(d, JCF 19 Hz, CH2Ph), 19.7 (d, JCF = 3.3 Hz, Ph-CH3), 13.7
d 8.28–8.25 (m, 1H), 8.07–8.04 (m, 1H), 7.71–7.62 (m, 2H), 5.60 (d,
(OCH2CH3). 19F NMR (282 MHz, CDCl3)
d
À 155.1 (dd, 1F, JHF
2H, JHF 47.3 Hz). 13C NMR (75 MHz, CDCl3)
d
162.2, 152.7, 137.3,
3
2
33.3 Hz, 3JHF 15.0 Hz). MS (ESI+) m/z (%) 430.2 ((M+Na)+, 14), 408.2
((M+H)+, 5). HRMS (MS+) for C19H18FNO4S2Na (M+Na)+ calcd,
430.0553, found. 430.0554
128.5, 128.0, 125.8, 122.4, 90.6 (d, JCF 223.4 Hz). 19F NMR
(282 MHz, CDCl3)
1
2
d
À 211.1 (t, 1F, JHF 47.3 Hz).
4.3.2. 2-(2-Fluoroethylsulfonyl)benzothiazole (8a) [6,12a]
4.2.9. Ethyl 2-(2-benzothiazolylsulfonyl)-2-fluoro-4-pentenoate (7i)
[12a]
The general procedure was followed with 7a (250 mg,
0.79 mmol), DMSO (1.05 mL), NaCl (92 mg, 1.58 mmol) and H2O
(0.14 mL, 7.90 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8a (mp 76–
The general procedure was followed with 10 (800 mg,
2.64 mmol), allyl bromide (0.27 mL, 3.16 mmol, 1.2 equiv.), DBU
(0.55 mL, 3.69 mmol, 1.4 equiv.) and THF (40 mL). The reaction
mixture was stirred for 2 h. Column chromatography (Pentane/
AcOEt, 90:10. Yield of 7i (mp 84–86 8C) as white crystals: 340 mg,
78 8C) as a white crystals: 156 mg, 81%. 1H NMR (300 MHz, CDCl3)
d
8.29–8.26 (m, 1H), 8.06–8.03 (m, 1H), 7.70–7.60 (m, 2H), 5.84 (dq,
69%. 1H NMR (300 MHz,CDCl3)
d
8.30–8.27 (m, 1H), 8.07–8.04 (m,
1H, 2JHF 48.0 Hz, 3JHH 6.5 Hz, CH2F), 1.91 (dd, 3H, 3JHF 25.8 Hz, 3JHH
1H), 7.71–7.62 (m, 2H), 5.75–5.66 (m, 1H, CH2CH55CH2), 5.36–5.28
(m, 2H, CH2CH55CH2), 4.37 (q, 2H, 3JHH 7.3 Hz, OCH2CH3), 3.50–3.21
(m, 2H, CH2CH55CH2), 1.30 (t, 3H, 3JHH 7.3 Hz, OCH2CH3). 13C NMR
6.5 Hz, CH3). 13C NMR (75 MHz, CDCl3)
d 162.0, 152.8, 137.4, 128.4,
127.8, 125.8, 122.3, 99.4 (d, 1JCF 220 Hz), 13.0 (d, 2JCF 19.9 Hz, CH3).
2
3
19F NMR (282 MHz, CDCl3)
25.8 Hz).
d
À 171.8 (dq, 1F, JHF 48.0 Hz, JHF
(75 MHz, CDCl3)
128.6, 127.9, 126.7 (CH2CH55CH2), 126.0, 122.7 (CH2CH55CH2),
d
162.1 (d, 2JCF 25.4 Hz, C55O), 160.7, 152.7, 138.0,
1
2
122.3, 106.8 (d, JCF 236.6 Hz), 63.8 (OCH2CH3), 35.3 (d, JCF
18.8 Hz, (CH2CH55CH2)), 13.9 (OCH2CH3). 19F NMR (282 MHz,
4.3.3. 2-(1-Fluoropropylsulfonyl)benzothiazole (8b) [6,12a]
The general procedure was followed with 7b (157 mg,
0.47 mmol), DMSO (0.63 mL), NaCl (55.3 mg, 0.95 mmol) and
H2O (0.085 mL, 4.7 mmol). Column chromatography: pentane/
AcOEt, 90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8b (mp 100–
102 8C) as white crystals: 87.2 mg, 71%. 1H NMR (300 MHz, CDCl3)
3
3
CDCl3)
d
À 156.7 (dd, 1F, JHF 34.4 Hz, JHF 12.9 Hz).
4.2.10. Ethyl 2-(benzothiazol-2-ylsulfonyl)-2-fluorohex-4-enoate (7j)
The general procedure was followed with 10 (300 mg,
0.99 mmol), 3-Bromo-but-1-ene (0.12 mL, 1.19 mmol, 1.2 equiv.)
or crotylbromide (0.12 mL, 1.19 mmol, 1.2 equiv.), DBU (0.21 mL,
1.38 mmol, 1.4 equiv.) and THF (15 mL). The reaction mixture was
stirred for 2 h. Column chromatography: pentane/AcOEt, 90:10.
Yield of 7j as a mixture of (E)- and (Z)-alkenes in a ratio of 80/20 as
white crystals: m = 310 mg, 88%. IR (neat) 2920 (w), 1469 (m),
d
8.26–8.23 (m, 1H), 8.04–8.01 (m, 1H), 7.68–7.58 (m, 2H), 5.61
(ddd, 1H, 2JHF 49.4 Hz, 3JHH 9.3 Hz, 3JHH 3.6 Hz, CHF), 2.45–2.04 (m,
2H, CH2CH3), 1.21 (t, 3H, 3JHH 7.5 Hz, CH2CH3). 13C NMR (75 MHz,
CDCl3)
d 162.5, 152.7, 137.3, 128.3, 127.7, 125.6, 122.3, 103.1 (d,
2
3
1JCF 222.0 Hz), 20.8 (d, JCF 19.6 Hz, CH2CH3), 8.8 (d, JCF 3.9 Hz,
1339 (s), 1315 (m), 1216 (m), 1156 (s) cmÀ1
.
1H NMR (400 MHz,
CH2CH3). 19F NMR (282 MHz, CDCl3)
49.4 Hz, JHF 33.3 Hz, JHF 16.1 Hz).
d
À 179.4 (ddd, 1F, JHF
2
3
3
CDCl3) 8.29–8.27 (m, 1H), 8.06–8.03 (m, 1H), 7.69–7.62 (m, 2H),
d
5.83–5.70 (m, 1H, CH2CH55CHCH3), 5.35–5.27 (m, 1H,
CH2CH55CHCH3), 4.39–4.30 (m, 2H, OCH2CH3), 3.58–3.14 (m, 2H,
CH2CH55CHCH3), 1.68–1.67 (m, 3H, CH2CH55CHCH3), 1.30 (t, 3H,
4.3.4. 2-(2-Fluoropentanylsulfonyl)benzothiazole (8c)
The general procedure was followed with 7c (302 mg,
0.84 mmol), DMSO (1.12 mL), NaCl (98 mg, 1,68 mmol) and H2O
(0.15 mL, 8,40 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8c (mp 84–
86 8C) as white crystals: 157 mg, 65%. IR (neat) 2955 (w), 2359 (m),
3
2
OCH2CH3, JHH 7.3 Hz). 13C NMR (100 MHz, CDCl3)
d 161.9 (d, JCF
24.6 Hz), 160.5, 152.4, 137.6, 133.5 (CH2CH55CHCH3, E), 131.5
(CH2CH55CHCH3, Z), 128.3, 127.5, 125.7, 121.9, 118.6 (d, 3JCF 2.4 Hz,
1
CH2CH55CHCH3), 106.8 (d, JCF 236 Hz), 63.5 (OCH2CH3, Z), 63.4
2
(OCH2CH3, E), 34.0 (d, JCF 19 Hz, CH2CH55CHCH3), 17.8
(CH2CH55CHCH3, E), 13.6 (OCH2CH3, E), 13.5 (OCH2CH3, Z), 12.8
1468 (m), 1228 (s), 1160 (s) cmÀ1
. d
1H NMR (400 MHz, CDCl3)
(CH2CH55CHCH3, Z). 19F NMR (376 MHz, CDCl3)
d–156.4 (dd, 1F,
8.28–8.26 (m, 1H), 8.05–8.03 (m, 1H), 7.68–7.61 (m, 2H), 5.67 (ddd,
3JHF 36.8 Hz, 3JHF 9.5 Hz, Z),–156.5 (dd, 1F, 3JHF 36.8 Hz, 3JHF 10.9 Hz,
E). MS (ESI+) (m/z) 358.1 ((M+H)+, 34), 200.0 (31), 182.0 (100).
1H, JHF 51.8 Hz, JHH 10 Hz, JHH 3.5 Hz, CHF), 2.39–2.11 (m, 2H,
2
3
3
CH2CH2CH2CH3), 1.71–1.58 (m, 2H, CH2CH2CH2CH3), 1.49–1.40

134
F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
3
(m, 2H, CH2CH2CH2CH3), 0.96 (t, 3H, JHH 7 Hz, CH2CH2CH2CH3).
(MS+) for C15H12FNO2S2Br (M+H)+ calcd 399.9477, found
399.9483.
13C NMR (100 MHz, CDCl3)
d 162.6, 152.8, 137.4, 128.3, 127.8,
125.7, 122.3, 102.3 (d, JCF 221 Hz), 26.5 (d, JCF 18.5 Hz,
1
2
CH2CH2CH2CH3), 26.4 (CH2CH2CH2CH3), 22.0 (CH2CH2CH2CH3),
4.3.8. 2-(1-Fluoro-2-o-tolylethylsulfonyl)benzothiazole (8h)
13.6 (CH2CH2CH2CH3). 19F NMR (282 MHz, CDCl3)
d
À 178.1 (ddd,
The general procedure was followed with 7 h (178.5 mg,
0.439 mmol), DMSO (0.60 mL), NaCl (51.3 g, 0.88 mmol) and
H2O (0.08 mL, 4.4 mmol). Column chromatography: pentane/
AcOEt, 90:10. The product was obtained after dissolution in
CH2Cl2 followed by slow evaporation of the solvent. Yield of 8 h
(mp 120–122 8C) as white crystals: 102.3 mg, 70%. IR (neat) 2360
(s), 2341 (s), 1466 (m), 1343 (m), 1155 (s) cmÀ1. 1H NMR (300 MHz,
3
3
2JHF 51.8 Hz, JHF 34.0 Hz, JHF 17.2 Hz). MS (ESI+) m/z (%) 288.1
((M+H)+, 15). HRMS (MS+) for C12H15FNO2S2 (M+H)+ calcd
288.0523, found 288.0526.
4.3.5. 2-(1-Fluorotridecylsulfonyl)benzothiazole (8d)
The general procedure was followed with 7d (396 mg,
0.84 mmol), DMSO (1.12 mL), NaCl (98 mg, 1.68 mmol) and H2O
(0.15 mL, 8.4 mmol). Column chromatography: pentane/AcOEt,
95:5. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8d (mp
86 8C) as white crystals: 177 mg, 53%. IR (neat) 2917 (s), 2848 (w),
CDCl3)
d 8.28–8.26 (m, 1H), 8.07–8.04 (m, 1H), 7.71–7.61 (m, 2H),
2
3
3
7.26–7.15 (m, 4H), 5.80 (ddd, 1H, JHF 47.3 Hz, JHH 10.5 Hz, JHH
2.1 Hz, CHF), 3.69 (ddd, 1H, 3JHF 39.8 Hz, 2JHH 15.6 Hz, 3JHH 2.1 Hz,
CH2Ph), 3.44 (ddd, 1H, JHF 16.1 Hz, JHH 15.6 Hz, JHH 10.5 Hz,
CH2Ph), 2.39 (s, 3H, Ph-CH3). 13C NMR (75 MHz, CDCl3)
162.3,
3
2
3
d
1468 (m), 1351 (s), 1318 (w), 1160 (s) cmÀ1
.
1H NMR (400 MHz,
152.8, 137.4, 137.0, 131.4, 130.8, 130.3, 128.4, 127.9, 126.4, 125.8,
CDCl3)
d
8.30–8.27 (m, 1H), 8.06–8.04 (m, 1H), 7.70–7.62 (m, 2H),
122.3, 101.9 (d, 1JCF 224.7 Hz), 30.4 (d, 2JCF 19.6 Hz, CH2Ph), 19.5 (d,
5.66 (ddd, 1H, 2JHF 49.0 Hz, 3JHH 9.9 Hz, 3JHH 3.1 Hz, CHF), 2.37–2.09
5JCF 1.1 Hz, Ph-CH3). 19F NMR (282 MHz, CDCl3)
d
À 177.3 (ddd, 2JHF
3
(m, 2H), 1.73–1.52 (m, 2H), 1.45–1.22 (m, 18H), 0.89 (t, 3H, JHH
47.3 Hz, 3JHF 39.8 Hz, 3JHF 16.1 Hz). MS (ESI+) (m/z) 336.1 ((M+H)+,
6.8 Hz, (CH2)11CH3). 13C NMR (100 MHz, CDCl3)
d
162.6, 152.9,
14), 332.3 (17), 331.3 (77), 241.1 (20). HRMS (MS+) for
137.5, 128.3, 127.8, 125.8, 122.3, 102.3 (d, 1JCF 222.5 Hz), 31.9, 29.6,
C
16H14FNO2S2Na (M+Na)+ calcd. 358.0342, found. 358.0342.
2
3
29.5, 29.4, 29.3, 29.2, 28.9, 26.8 (d, JCF 19.2 Hz), 24.4 (d, JCF
2.2 Hz), 22.7, 14.1 ((CH2)11CH3). 19F NMR (376 MHz, CDCl3)
4.3.9. 2-(1-Fluorobut-3-enylsulfonyl)benzothiazole (8i)
2
3
3
d
À 177.8 (ddd, 1F, JHF 49.0 Hz, JHF 36.8 Hz, JHF 16.4 Hz). MS
The general procedure was followed with 7i (154 mg,
0.45 mmol), DMSO (0.60 mL), NaCl (53 mg, 0.90 mmol) and H2O
(0.08 mL, 4.45 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8i (mp 92–
94 8C) as white crystals: 62 mg, 51%. IR (neat) 2960 (w), 2360 (s),
(ESI+)(m/z) 400.3 ((M+H)+, 100), 200.0 (26), 182.0 (69). HRMS
(MS+) for C20H31FNO2S2 (M+H)+ calcd. 400.1780, found 400.1765.
4.3.6. 2-(2-Fluorophenylethylsulfonyl)benzothiazole (8f)
The general procedure was followed with 7f (200 mg,
0.5 mmol), DMSO (0.67 mL), NaCl (59.4 mg, 1 mmol) and H2O
(0.09 mL, 5 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8f (mp
106–108 8C) as white crystals: 99.7 mg, 62%. IR (neat) 2943 (w),
2342 (s), 1464 (m), 1337 (m), 1318 (m), 1154 (m) cmÀ1
(400 MHz, CDCl3) 8.27–8.25 (m, 1H), 8.05–8.03 (m, 1H), 7.68–
7.60 (m, 2H), 5.92–5.82 (m, 1H, CH2CH55CH2), 5.71 (ddd, 1H, JHF
.
1H NMR
d
2
3
3
47.3 Hz, JHH 9.54 Hz, JHH 3.5 Hz, CHF), 5.35–5.28 (m, 2H,
CH2CH55CH2), 3.15–2.86 (m, 2H, CH2CH55CH2). 13C NMR
(100 MHz, CDCl3)
1759 (w), 1340 (s), 1153 (s), 1077 (s) cmÀ1
CDCl3) 8.23–8.21 (m, 1H), 8.01–7.99 (m, 1H), 7.64–7.57 (m,
2H), 7.32–7.22 (m, 5H), 5.79 (ddd, 1H, 2JHF 47.3 Hz, JHH 10.5 Hz,
.
1H NMR (400 MHz,
d
162.2, 152.8, 137.4, 128.7 (d, JCF 1.9 Hz,
3
d
CH2CH55CH2), 128.4, 127.8, 125.7, 122.3, 120.9 (CH2CH55CH2),
3
1
2
101.2 (d, JCF 223.5 Hz), 31.5 (d, JCF 19.4 Hz, CH2CH55CH2). 19F
3
2
3
2
3
3JHH 2.5 Hz, CHF), 3.65 (ddd, 1H, JHF 38.7 Hz, JHH 14.9 Hz, JHH
NMR (282 MHz, CDCl3)
d
À 178.0 (ddd, 1F, JHF 47.3 Hz, JHF
3
2
3
3
2.5 Hz, CH2Ph), 3.42 (ddd, 1H, JHF 17.2 Hz, JHH 14.9 Hz, JHH
10.5 Hz, CH2Ph). 13C NMR (100 MHz, CDCl3)
162.2, 152.8,
137.4, 133.0, 129.5, 128.9, 128.4, 127.9, 127.8, 125.8, 122.3,
34.4 Hz, JHF 17.2 Hz). MS (ESI+) m/z (%) 272.1 ((M+H)+, 6). HRMS
(MS+) for C11H10FNO2S2Na (M+Na)+ calcd. 294.0029, found
294.0034.
d
1
2
102.2 (d, JCF 225.5 Hz), 33.2 (d, JCF 19.4 Hz, CH2Ph). 19F NMR
2
3
(282 MHz, CDCl3)
d
À 178.0 (ddd, 1F, JHF 47.3 Hz, JHF 38.7 Hz,
4.3.10. 2-(1-Fluoropent-3-enylsulfonyl)benzothiazole (8j)
3JHF 17.2 Hz). MS (ESI+) m/z (%) 344.0 ((M+Na)+, 100), 322.0
((M+H)+, 69). HRMS (MS+) for C15H12FNO2S2Na (M+Na)+ calcd
344.0186, found 344.0190.
The general procedure was followed with 7j (300 mg
0.84 mmol), DMSO (1.12 mL), NaCl (98 mg, 1.68 mmol) and H2O
(0.15 mL, 8.40 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8j as a
mixture of (E)- and (Z)-alkenes in a ratio of 80/20 as white crystals:
138 mg, 58%. IR (neat) 2989 (w), 1769 (s), 1460 (m), 1317 (m), 1347
(s), 1265 (m), 1217 (s), 1140 (m) cmÀ1. 1H NMR (400 MHz, CDCl3)
8.29–8.26 (m, 1H), 8.06–8.04 (m, 1H), 7.70–7.61 (m, 2H), 5.82–5.56
(m, 2H), 5.51–5.43 (m, 1H, CH2CH55CHCH3), 3.08–2.78 (m, 2H,
CH2CH55CHCH3), 1.72–1.69 (m, 3H, CH2CH55CHCH3). 13C NMR
4.3.7. 2-(2-(4-Bromophenyl)-1-fluoroethylsulfonyl) benzothiazole
(8g)
The general procedure was followed with 7g (151 mg,
0.32 mmol), DMSO (0.44 mL), NaCl (37 mg, 0.64 mmol) and H2O
(0.058 mL, 3.2 mmol). Column chromatography: pentane/AcOEt,
90:10. The product was obtained after dissolution in CH2Cl2
followed by slow evaporation of the solvent. Yield of 8g (mp 136–
138 8C) as white crystals: 50,4 mg, 40%. IR (neat) 2360 (s), 2341 (s),
d
(100 MHz, CDCl3)
d 162.4, 152.8, 137.4, 132.1 (CH2CH55CHCH3, E),
1466 (m), 1342 (s), 1155 (s), 1012 (m) cmÀ1
CDCl3)
.
1H NMR (300 MHz,
130.4 (CH2CH55CHCH3, Z), 128.4, 127.8, 125.8, 122.3, 121.1 (d, 3JCF
2.4 Hz, CH2CH55CHCH3, E), 120.1 (d, 3JCF 2.4 Hz, CH2CH55CHCH3, Z),
101.63 (d, 1JCF 223.3 Hz, E), 101.55 (d, 1JCF 224.1 Hz, Z), 30.5 (d, 2JCF
d
8.27–8.24 (m, 1H), 8.07–8.04 (m, 1H), 7.70–7.61 (m, 2H),
7.47 (d, 2H, 3JHH 8.4 Hz), 7.18 (d, 2H, 3JHH 8.4 Hz), 5.79 (ddd, 1H, 2JHF
48.4 Hz, 3JHH 10.2 Hz, 3JHH 2.4 Hz, CHF), 3.60 (ddd, 1H, 3JHF 38.7 Hz,
2
19.9 Hz, CH2CH55CHCH3, E), 25.0 (d, JCF 19.9 Hz, CH2CH55CHCH3,
Z), 18.0 (CH2CH55CHCH3, E), 13.0 (CH2CH55CHCH3, Z). 19F NMR
(376 MHz, CDCl3)
3JHF 16.4 Hz, Z), À177.7 (ddd, 1F, JHF 47.7 Hz, JHF 34.1 Hz, JHF
16.4 Hz, E). MS (ESI+) (m/z) 286.1 ((M+H)+, 95), 200.0 (14), 182.0
(100). HRMS (MS+) for C12H12FNO2S2 (M+H)+ calcd. 286.0372,
found 286.0367.
2JHH 14.9 Hz, 3JHH 2.3 Hz, CH2Ph), 3.39 (ddd, 1H, 3JHF 17.2 Hz, 2JHH
3
2
3
14.9 Hz, JHH 10.2 Hz, CH2Ph). 13C NMR (75 MHz, CDCl3)
d
162.0,
d
À 177.61 (ddd, 1F, JHF 47.7 Hz, JHF 34.1 Hz,
2 3 3
152.8, 137.4, 132.0, 131.9, 131.2, 128.5, 127.9, 125.8, 122.3, 121.9,
1
2
101.7 (d, JCF 224.7 Hz), 32.8 (d, JCF 19.4 Hz, CH2Ph). 19F NMR
2
3
3
(282 MHz, CDCl3)
17.2 Hz). MS (ESI+) (m/z) 400.0 ((M+H)+, 49), 182 (100). HRMS
d
À 177.2 (ddd, JHF 48.4, JHF 38.7 Hz, JHF

F. Larnaud et al. / Journal of Fluorine Chemistry 134 (2012) 128–135
135
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Acknowledgments
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This work was supported by the European programme
‘‘Innovative Synthesis, Culture, and Entrepreneurship in Chemis-
try’’ (ISCE-Chem). The European Community (INTERREG IVa, trans-
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