A convenient one-step synthesis of fluoroethylidene derivatives

Article abstract of DOI:10.1016/j.tetlet.2003.09.027

A convenient one-step synthesis of gem-monofluoroalkylolefins starting from aldehydes or ketones was developed. This method comprises the utilisation of 2-(1-fluoroethyl)sulfonyl-1,3-benzothiazole according to Julia's procedure and opens a new opportunity

Full text of DOI:10.1016/j.tetlet.2003.09.027

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8127–8130
A convenient one-step synthesis of fluoroethylidene derivatives
D. Chevrie,a T. Lequeux,a,* J. P. Demouteb and S. Pazenokb,*
aLaboratoire de Chimie Mole´culaire et Thioorganique, Universite´ de Caen-ENSICaen, UMR CNRS 6507,
6 Boulevard du Mare´chal Juin, 14050 Caen cedex, France
bBayer CropScience GmbH, Industriepark Hoechst, G 837, D-65926 Frankfurt am Main, Germany
Received 21 July 2003; revised 26 August 2003; accepted 4 September 2003
Dedicated to Professor D. Naumann University of Cologne on the occasion of his 60th birthday
Abstract—A convenient one-step synthesis of gem-monofluoroalkylolefins starting from aldehydes or ketones was developed. This
method comprises the utilisation of 2-(1-fluoroethyl)sulfonyl-1,3-benzothiazole according to Julia’s procedure and opens a new
opportunity for the synthesis of fluoroalkylidene derivatives.
© 2003 Elsevier Ltd. All rights reserved.
The introduction of fluorine atoms into organic
molecules is a very useful approach for the modification
of biological activity. Compounds containing a single
fluorine atom attached to a double bond are of great
interest due to their biological properties. Previously,
we have shown that replacement of one of the methyl
groups in esters of cis-chrysanthemic acid by one
fluorine atom increases the insecticidal activity (Fig. 1).1
nation, comprising for example the reaction of phenyl-
sulfonylfluoromethyllithium with a carbonyl compound
to form a-fluoro-b-hydroxyphenylsulfonyl derivatives.5
Further dehydration with CH3SO2Cl followed by
reductive desulfonylation leads to the olefins. The same
complex and multistep procedure has been used for
olefination with PhSOCHFCH3.6a Numerous efforts
have been made in order to develop alternative meth-
ods and to circumvent these drawbacks.5,6
The most common method for the synthesis of alkenes
containing an [(Alk)CF=] moiety is the reaction of an
aldehyde or ketone with fluorinated Horner–Wad-
worth–Emmons (HWE) reagents like Ph3PꢀCHF or
(EtO)2(O)PCHFCOOEt.2 A major limitation of this
approach is the difficulty in accessing the phosphorane
which requires a monofluorohalomethane or ethane,
such as CH2FI or AlkCHFBr which are either not
available commercially or are very expensive, or in the
case of the phosphonate, further modification of car-
boalkoxy group.3,4 Another method is the use of
fluoromethylsulfonylbenzene PhSO2CH2F for the olefi-
In 1993 Julia and co-workers7 described a one-step
olefination procedure as a convenient alternative to the
HWE reaction. According to this novel method ben-
zothiazole sulfones 2 react with aldehydes or ketones,
to afford alkenes (Scheme 1). Since the publication by
Julia, a number of synthetic applications of this reac-
tion have been reported in the literature.8
In the course of our search for an improved synthesis of
compound 1, which initially was prepared via bro-
mofluorination/reduction of 4,7,7-trimethyl-3-oxabicy-
clo-[4.1.0]-hept-4-en-2-one,9 we decided to prepare the
corresponding fluorine-containing analogues of the
Julia reagent and to explore their reactivity towards
aldehydes and ketones.
Figure 1.
* Corresponding authors. Tel.: +33-231452854; fax: +33-231452877;
e-mail: lequeux@ismra.fr
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.027

8128
D. Che6rie et al. / Tetrahedron Letters 44 (2003) 8127–8130
For the synthesis of a benzothiazole containing a 2-
fluoroethylsulfonyl group we investigated three differ-
ent synthetic pathways: the direct alkylation of
2-mercaptobenzothiazole with halofluoroalkane, the
electrophilic fluorination of 2-ethylsulfanyl or sulfonyl-
benzothiazole and the Halex reaction from 2-
chloroethylsulfanylbenzothiazole.
Scheme 4.
In the first approach the alkylation of 2-mercaptoben-
zothiazole with 1-bromo-1-fluoroethane was success-
fully performed under phase transfer catalyst
conditions,10 using an excess of the bromofluoroalkane
without solvent (Scheme 2). After 4 h at room tempera-
ture, the alkylation was complete and 2-(1-
fluoroethylthio)benzothiazole 3 was obtained i n 74%
yield.
perature or H2O2 in acetic acid. After 24 h, fluorosul-
fone 6 was obtained as a pale yellow crystalline product
in 75% overall yield which could be directly used in the
Julia reaction (Scheme 3).15 We noticed that the chlori-
nation of 4 proceeded with formation of a side product
(10%), which contained one additional chlorine atom
on the aromatic ring. As shown later, this did not affect
the reactivity of the final sulfone 6.
Due to the high cost of 1-bromo-1-fluoroethane and the
need to use it in large excess (10 equiv.), we tested the
direct fluorination of 2-ethylsulfanylbenzothiazole as an
alternative route. We found that the electrophilic fluori-
nation of 4 with F-TEDA (Selectfluor™) in the pres-
ence of triethylamine,11 afforded the expected sulfide 3
after overnight stirring at room temperature. However,
3 was isolated in low yield (30–35%) due to the compet-
itive formation of 2-ethylsulfinylbenzothiazole as by-
product. All attempts to introduce one fluorine atom by
treating the corresponding 2-ethylsulfonylbenzothiazole
with N-fluorobenzenesulfonimide12 led to a mixture of
various fluorinated products.
The olefination of carbonyl compounds with sulfone 6
was performed according to the Julia procedure in
THF solution in the presence of a strong base (Scheme
4). The results obtained are presented in Table 1.16
When NaHMDS was used as base at −78°C (method
A),16 the olefination of aldehydes 7a–g proceeded
smoothly and afforded the fluoroethylidene derivatives
8a–g in 48–88% yields. In this case the mixture was
stirred for 2 h at −78°C and slowly warmed to −10°C
over 30 min, before quenching. Surprisingly, it was
possible to use the cheaper tBuOK (method B)16
instead of NaHMDS and to perform olefination at
−15°C. Under these conditions we obtained the alkenes
in good yield, but with a low E/Z selectivity (2/3 to
1/1). All attempts to improve the E/Z ratio by using
other bases (KHMDS, LiHMDS) or by changing the
solvent (toluene) or the temperature were unsuccessful.
Ketones were found to be less reactive than aldehydes.
When non-enolizible ketones 7h or 7j were reacted with
sulfone 6 and tBuOK at −15°C, alkenes were isolated
in lower yields (5–15%) and no product was detected
from cyclic ketone 7i. However, by using NaHMDS at
−78°C (method A),16 the corresponding monofluoro-
olefins 8h–j were obtained in one step and isolated in
49–69% yields (Table 1).
Fortunately, the introduction of one fluorine atom
through a Halex reaction of the chlorosulfide 5 was
successful (Scheme 3). We found that 2-ethylsulfanyl-
benzothiazole 4 easily reacted with N-chlorosuccin-
imide to give 2-(1-chloroethylsulfanyl)benzothiazole 5.
The monochlorosulfide was found to be too unstable to
be purified via distillation or crystallisation, and was
used without any further purification. The fluorination
of the sulfide 5 was achieved using 3HF–NEt3 (Franz
reagent13) in the presence of ZnBr2 in CH3CN solu-
tion.14 The crude fluorosulfide 3 was then oxidised
using either mCPBA in dichloromethane at room tem-
In conclusion, we report a simple and convenient one-
step procedure for the preparation of fluoroalkylidene
derivatives from aldehydes and ketones. The method
allows the preparation of a variety of fluoroalkenes
bearing different functional groups. The process is also
easy to control and scale up.17
Scheme 2.
Acknowledgements
We are grateful to Professor S. Z. Zard (Ecole
Polytechnique, Palaiseau, France) for helpful discus-
sions.
Scheme 3.

D. Che6rie et al. / Tetrahedron Letters 44 (2003) 8127–8130
8129
Table 1. Olefination of aldehydes and ketones from fluorosulfone 6
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8130
D. Che6rie et al. / Tetrahedron Letters 44 (2003) 8127–8130
15. Experimental:
16. General procedure for the olefination of aldehydes or
ketones:
(a) 2-(1-Chloroethylsulfanyl)benzothiazole 5: A solution
of 2-(1-ethylsulfanyl)benzothiazole 4 (2 g, 10.24 mmol) in
30 ml CH2Cl2 was heated to 45°C and then N-chlorosuc-
cinimide (2.05 g, 15.36 mmol) was added in one portion.
The mixture was stirred for 2 h at 45°C and then cooled,
washed with water and dried over MgSO4. The solvent
was removed under reduced pressure to give the title
product as an oil (2.38 g) which was used for the fluorina-
tion without any purification. 1H NMR (250 MHz,
CDCl3): l 2.06 (d, 3JHH=6.7 Hz, 3H, CH3), 6.15 (q,
3JHH=6.7 Hz, 1H, CHCl), 7.38 (t, 3JHH=7.5 Hz, 1H,
Method A: To a THF solution of 2-(1-fluoroethylsul-
fonyl)benzothiazole 6 (1 equiv.) and the appropriate car-
bonyl compound (1.05 equiv.) a 1 M solution of sodium
bis(trimethlysilyl)amide (1.1 equiv.) in THF was added
slowly at −78°C. The mixture was stirred for 2 h at −78°C
and then allowed to warm up to room temperature and
then quenched with water. The aqueous layer was
extracted with ethyl acetate and dried over MgSO4. After
solvent evaporation the crude product was purified via
recrystallization or column chromatography.
Method B: To a cold THF solution (−17°C) of 2-(1-
fluoroethylsulfonyl)benzothiazole 6 (1 equiv.) and the
appropriate carbonyl compound (1.05 equiv.) a solution
of tBuOK (1.1 equiv.) in THF was slowly added. The
resulting solution was stirred for 30 min and then
quenched by addition of aqueous ammonium chloride
solution. The reaction was worked-up in a similar man-
ner to that described for method A.
3
3
CH), 7.49 (t, JHH=7.5 Hz, 1H, CH), 7.83 (d, JHH=7.5
3
Hz, 1H, CH), 8.00 (d, JHH=7.5 Hz, 1H, CH).
(b) 2-(1-Fluoroethylsulfanyl)benzothiazole 3: A mixture of
2-(1-chloroethylsulfanyl)benzothiazole
5 (1.96 g, 8.53
mmol), anhydrous zinc bromide (2.5 g, 11.1 mmol) and
triethylamine trihydrofluoride (5.56 mL, 34.12 mmol) in
acetonitrile (30 mL), was stirred at 70°C for 6 h. The
mixture was cooled, dissolved in ethyl acetate washed
with water and dried over MgSO4. The solvent was
removed in vacuum to give the crude title product which
was used without purification (91% purity). 1H NMR
(250 MHz, CDCl3): l 1.88 (dd, 3JHH=6.5 Hz, 3JHF=20.3
Hz, 3H, CH3), 6.71 (dq, 3JHH=6.5 Hz, 2JHF=53.8 Hz,
1H, CHF), 7.38 (t, 3JHH=7.5 Hz, 1H, CH), 7.48 (t,
Methyl
(1R-cis)-3-[(E/Z)-2-fluoro-1-propenyl]-2,2-di-
methylcyclopropane-1-carboxylate 8f: Following method
B, from a solution of methyl ester 7f (668 mg, 4.28
mmol), sulfone 6 (1 g, 4.08 mmol) in THF (10 mL) and
a solution of tBuOK (502 mg, 4.48 mmol) in THF (5
mL), a mixture of alkenes 8f (607 mg; 80%) (E/Z ratio:
45/55) was obtained after purification of the crude oil by
flash column chromatography (petroleum ether/ethyl ace-
3JHH=7.5 Hz, 1H, CH), 7.83 (d, JHH=7.5 Hz, 1H, CH),
3
7.99 (d, 3JHH=7.5 Hz, 1H, CH); 19F NMR (235 MHz,
CDCl3/CFCl3): l −142.45 (dq, 3JHF=20.3 Hz, JHF
=
2
1
tate: 95/5). H NMR (250 MHz, CDCl3): l 1.19–1.21 (m,
53.8 Hz, 1F, CHF).
(c) 2-(1-Fluoroethylsulfonyl)benzothiazole 6: Crude 2-(1-
fluoroethylsulfanyl)benzothiazole was dissolved in
12H, CH3 (E,Z)), 1.62–1.70 (m, 3H, H3,H1(E), H1(Z)),
3
1.91 (d, 3JHF=16.8 Hz, 3H, CH3 (Z)), 1.92 (d, JHF
=
3
17.3 Hz, 3H, CH3 (E)), 2.12 (t, 3JHH=9.3 Hz, 1H, H3
(Z)), 3.60 (s, 6H, CO2Me (Z,E)), 4.91 (dd, 3JHF=36.7
Hz, 3JHH=9.6 Hz, 1H, CH (Z)), 5.35 (dd, 3JHF=20.7
Hz, 3JHH=8.2 Hz, 1H, CH (E)); 19F NMR (235 MHz,
CDCl3/CFCl3): l −92.5 (dq, 3JHF=20.7 Hz, 3JHF=17.3
Hz, E isomer), −103.2 (dq, 3JHF=36.7 Hz, 3JHF=16.8
CH2Cl2 and m-chloroperbenzoic acid (2.5 equiv.) was
added to this solution. The mixture was stirred overnight
at room temperature, and then washed with 1 M sodium
hydroxide solution and dried over MgSO4. The solvent
was removed under reduced pressure and the crude
product was recrystallized from methanol to give the title
product 6 (1.55 g, 75%) (mp 75–78°C). 1H NMR (250
MHz, CDCl3): l 1.92 (dd, JHF=23.2 Hz, JHH=6.5 Hz,
3H, CH3), 5.84 (dq, 2JHF=47.9 Hz, 3JHH=6.5 Hz, 1H,
CHF), 7.50–7.65 (m, 2H), 8.05 (d, 3JHH=8.0 Hz, 1H),
8.27 (d, 3JHH=7.6 Hz, 1H); 13C NMR (62.9 MHz,
CDCl3): l 12.01 (d, 2JCF=20.2 Hz, CH3), 99.35 (d,
1JCF=219.9 Hz, CF), 122.27, 125.71, 127.79, 128.35
(CH), 137.40, 152.79, 162.00; 19F NMR (235 MHz,
Hz, Z isomer). 13C NMR (62.9 MHz, CDCl3): l 4.1 (d,
2
3
3
2JCF 32.6, CH3 (E)), 14.5, 14.6 (s, CH3), 17.9 (d, JCF
=
30.1 Hz, CH3 (Z)), 28.2, 28.3 (s, C1), 28.5, 28.6 (s, CH3),
29.5 (d, 3JCF=12.6 Hz, C3 (Z)), 30.4 (d, 3JCF=9.6 Hz, C3
(E)), 51.0, 51.1 (s, OCH3), 99.5 (d, 2JCF=11 Hz, CH (E)),
100.6 (d, 2JCF=28 Hz, CH (Z)), 158.2 (d, 1JCF=249.7,
CF), 171.1 (s, CO), 171.5 (s, CO); MS (EI, 70 eV): m/z
(%) 186 (22), 156 (89), 152 (7), 141 (33), 139 (100), 113
(15), 111 (45), 93 (6); HMRS (EI) calcd for C10H15FO2
(M+): 186.106. Found: 186.099.
3
2
CDCl3/CFCl3): l −172.0 (dq, JHF=23.2 Hz, JHF=47.9
Hz, 1F, CHF); MS (EI, 70 eV): m/z (%) 245 (7), 136 (52),
108 (100), 91 (19), 47 (18); HMRS (EI) calcd for
C9H8FNO2S2 (M+): 244.998. Found: 245.005.
17. Pazenok, S.; Demoute, J. P.; Zard, S.; Lequeux, T. Patent
WO 0,240,459, 2002; Chem. Abstr. 2002, 136, 386131.