Evaluation of Zard trifluoromethylketone synthesis for the preparation of potential bifunctional fluorinated synthons

Article abstract of DOI:10.1016/j.jfluchem.2007.05.002

In the quest for potential bifunctional fluorinated synthons, we examined the behavior of chlorodifluoroacetic and hexafluoroglutaric anhydride in their reaction with acid chlorides in the presence of pyridine under the conditions of Zard trifluoromethylketone synthesis. Chlorodifluoroacetic anhydride led easily to the expected chlorodifluoromethyl ketones in the case of relatively non-encumbered primary acid chlorides. In the case of hexafluoroglutaric anhydride we observed the unexpected formation of α substituted hexafluorocyclohexane-1,3-dione derivatives among with the corresponding fluorinated 3-chloro-cyclohexenones.

Full text of DOI:10.1016/j.jfluchem.2007.05.002

Journal of Fluorine Chemistry 128 (2007) 1235–1240
www.elsevier.com/locate/fluor
Evaluation of Zard trifluoromethylketone synthesis for the
preparation of potential bifunctional fluorinated synthons
Patrick Diter, Emmanuel Magnier,
*
Jean-Claude Blazejewski
´
Institut Lavoisier de Versailles, UMR CNRS 8180, Universite de Versailles, St Quentin en Yvelines,
45 avenue des Etats-Unis, 78035 Versailles Cedex, France
Received 28 March 2007; received in revised form 4 May 2007; accepted 7 May 2007
Available online 22 May 2007
This article is dedicated to Professor Kenji Uneyama in honor of his 2007 ACS Award for creative work in Fluorine Chemistry.
Abstract
In the quest for potential bifunctional fluorinated synthons, we examined the behavior of chlorodifluoroacetic and hexafluoroglutaric anhydride
in their reaction with acid chlorides in the presence of pyridine under the conditions of Zard trifluoromethylketone synthesis. Chlorodifluoroacetic
anhydride led easily to the expected chlorodifluoromethyl ketones in the case of relatively non-encumbered primary acid chlorides. In the case of
hexafluoroglutaric anhydride we observed the unexpected formation of a substituted hexafluorocyclohexane-1,3-dione derivatives among with the
corresponding fluorinated 3-chloro-cyclohexenones.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Chlorodifluoroacetic anhydride; Hexafluoroglutaric anhydride; Chlorodifluoromethyl ketones; Hexafluorocyclohexane-1,3-diones; 3-Chloro-hexa-
fluorocyclohexenones
1. Introduction
compounds obtained by the telomerization of tetrafluoroethy-
lene, either with diiodine (a,v-diiodoperfluoroalkanes) [3] or
with methanol (1H, 1H, vH-perfluorinated alcohols) [4].
Attention was also given to the desymmetrization of a,v-
perfluorinated diacids or their derivatives [5].
Fluorinated bifunctional synthons of the type X-(CF2)n-Y
are very useful intermediates in widely different areas like
biochemistry, catalysis or material science. Their interest is
dependent on their chain length. Thus, the first terms of this
series (n = 1) have gained great importance for the introduction
of the difluoromethylene unit into bioactive molecules as an
isostere of the ethereal oxygen atom [1]. With the development
of fluorous chemistry, there is a growing demand from non-
fluorine specialized laboratories, for ready to use long chains
compounds (typically n = 3–8), bearing fluorinated synthons
[2]. In this area, after an extensive exploitation of simple
perfluoroalkylated chains, the demand seems now to shift
towards more elaborated synthons, and more specifically to
easily functionalizable (in the sense of common organic
chemistry) unsymmetrical ones. Fluorinated materials to
achieve this goal may be derived from perfluoroalkyl
Some years ago, Zard and co-workers described a very
convenient synthesis of trifluoromethyl ketones by the reaction
of nucleophilic ketene species, generated from acid chlorides,
with trifluoroacetic anhydride [6]. This methodology enjoyed a
great success for the trifluoromethylation of various acidic
substrates [7]. To our knowledge, this reaction has seldom been
used for the introduction of fluorinated groups differing from
trifluoromethyl [8].
In this context, we examined the behavior of two readily and
commercially available fluorinated anhydrides in this reaction.
On one hand, chlorodifluoroacetic anhydride was expected to
lead to chlorodifluoroketones as potential difluoromethylene
synthons. On the other hand, hexafluoroglutaric anhydride was
thought to be a convenient precursor for the preparation of
unsymmetrical bifunctional hexafluorinated chains, amenable
to further chemical elaborations. We present here our results
concerning these two fluorinated anhydrides.
* Corresponding author. Fax: +33 1 39 25 44 52.
E-mail address: jcblaz@chimie.uvsq.fr (J.-C. Blazejewski).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.05.002

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P. Diter et al. / Journal of Fluorine Chemistry 128 (2007) 1235–1240
Table 1
Table 2
The reaction of chlorodifluoroacetic anhydride 1 with acid chlorides in the
presence of pyridine
The reaction of hexafluoroglutaryl anhydride 4 with acid chlorides
Entry
R in 5
Ratio 8:9
Isolated yield (%)
entry
R
Yielda (%) of 4
1
2
3
a PhCH2CH2
b CH3(CH2)7
c CH3(CH2)9
0:100
84
30–55
79
1
2
3
4
5
6
4a
PhCH2CH2CH2
b
CH3(CH2)n
80
60–79
<5
0
50:50–20:80
50:50–0:100
4b–c
4d
4e
4f
4g
CH3CHPhCH2
Cyclohexyl
PhCH2
0c
preparation of primary and relatively unhindered chlorodi-
fluoromethyl ketones. As pointed out very recently by Percy,
the synthesis of this kind of aliphatic chlorodifluoromethyl
ketones by the organometallic route is by no means a trivial
task, stressing thus the interest of the present study [10].
Menthylch2
0
a
Isolated yields.
b
c
n = 8, 14.
Reaction performed at 20, 0 or À30 8C.
2.1.1. Reactions of hexafluoroglutaric anhydride
Based on the mechanism proposed for the formation of
trifluoromethyl ketones [6a], we initially thought that the
reaction of a hexafluoroglutaric anhydride 6 with acid chlorides
under the conditions of Zard’s reaction could lead to an open
chain dissymmetric fluorinated acid 7 (Scheme 2).
Scheme 1.
2. Results and discussion
Unexpectedly, instead of acid 7, we observed either the
exclusive formation of 9a with 4-phenylpropanoic acid
chloride, or the formation of the symmetrical fluorinated b-
diketones 8b–c accompanied by the 3-chlorocyclohexenones
9b–c when we used a long alkyl chain acid chloride as the
chosen starting material (Table 2).
2.1. Reactions of chlorodifluoroacetic anhydride
We are aware of only one report suggesting the use of
chlorodifluoroacetic anhydride 1 for the synthesis of a
chlorodifluoromethyl ketone in the arachidonic acid series
[8a]. However, the scope of this reaction was not fully explored.
In our hands, under the conditions described by Zard [6a], the
reaction of chlorodifluoroacetic anhydride with simple primary
aliphatic acids 2 (Table 1, entries 1 and 2) was straightforward
and gave easy access to a-chlorodifluoromethyl ketones 4 in
satisfactory isolated yields (Scheme 1). As was observed with
trifluoroacetic anhydride, no reaction occurs with secondary
aliphatic acids (Table 1, entry 4). Moreover, branching at the b-
carbon of the acid function was deleterious to the outcome of
the reaction (Table 1, entries 3, 5 and 6) [6a,b].
Due to the similar polarities of 8 and 9, we were not able to
completely separate the two compounds by chromatography;
only a small amount of pure chloroketone 9b could be isolated
by this technique. The formation of a precipitate in the reaction
mixture in these particular cases explains perhaps the difference
in reactivity observed between 5a and 5b–c. We did not obtain
significant modification of the proportion of the two
compounds in different solvents (dichloromethane, toluene)
but it was possible to reduce the proportion of 8b from 50% to
20% with a long reaction time (6–36 h for 9b) and to complete
conversion in 72 h (9c). However, the mixture of diketones 8b–
c with chloroketones 9b–c, could be easily totally converted to
chloroketones 9b–c by oxalyl chloride [11] giving some
evidence for the prior formation of 8 over 9 in the reaction
medium.
In a reappraisal of Zard’s method, a Boehringer group
recently showed that the reaction of trifluoroacetic anhydride
with secondary acids was possible, provided that the reaction
was run in toluene [9]. We also tried this modified protocol with
chlorodifluoroacetic anhydride. In the present case, we
observed considerable darkening of the reaction medium with
apparent decomposition of the anhydride before any useful
reaction occurs with the intermediate ketene. It seems thus that,
to date, this methodology could be applied only for the
2.1.2. Structure determination
The determination of the structures assigned to compounds 8
and 9, relied on the micro analytical analysis results as well as
their mass spectrometric analysis, which confirm the presence
Scheme 2.

P. Diter et al. / Journal of Fluorine Chemistry 128 (2007) 1235–1240
1237
Fig. 2. NMR numbering for compound 8b.
Fig. 1. NMR numbering for compounds 9a and 9b.
of a chlorine atom for 9. All the structures proposed were also
consistent with the observed spectral data.
of the ethylenic carbons C3 at 143 ppm are vicinal to a
difluoromethylene which (as shown by the presence of 2JCF and
3JCF) suggests a cyclic structure like in 9 (Fig. 1). The first
ethylenic signal at 141 ppm appears as a triplet with only one
coupling constant 3JC2F (3 Hz). This ethylenic carbon C2 three
bonds away from the fluorine atoms is thus located between C1
and C3. The signal of one of the two methylene groups shows a
very low coupling constant with the fluorine atoms (< 1 Hz)
which can be tentatively attributed to a 4JCF and then to the C7
methylene carbon. For the other compound 9b, we obtained
similar data for the new cycle formed with three signals for the
three difluoromethylene groups and the disappearance of the
proton of one methylene on the C2 carbon atom.
2.1.2.1. Structure of the chloroenones 9. For the molecule 9a,
we observed three signals in the 19F NMR spectrum, one for
each CF2, which suggests a non symmetrical structure as
expected for 7 but the presence of a chlorine atom revealed by
the mass spectrometry invalidates this structure. The 1H NMR
spectra showed the signals for the phenyl group and only two
triplets for two methylene groups. The third methylene group
present in the starting materials had thus disappeared. The
analysis of the 13C NMR spectra gave more information; the
presence of a phenyl group and only two methylene groups was
confirmed. Moreover, we observed one carbonyl signal at
178 ppm and two ethylenic carbons at 141 and 143 ppm. The
loss of these signals in DEPT, as well as the 2D NMR HETCOR
experiments demonstrated the absence of proton linked to these
two carbon atoms. The same coupling pattern was found for the
carbonyl and the second ethylenic signal: triplet of triplets for a
2JCF (27 Hz) and a 3JCF (3 Hz). The carbonyl atom C1 and one
2.1.2.2. Structure of the diketone 8b. With a long alkyl chain
in place of the 3-phenylpropyl group for the substrate 5, we
observe as well as 9b the formation of another compound 8b. In
this case, a symmetrical structure is suggested by the presence
of only two signals in the 19F NMR spectrum for the three
difluoromethylene groups at 121 and 134 ppm. In the 1H NMR
Scheme 3.

1238
P. Diter et al. / Journal of Fluorine Chemistry 128 (2007) 1235–1240
spectrum we obtain the characteristic system for a long carbon
chain with an additional triplet signal at 2.8 ppm integrating for
only one proton and a multiplet for a methylene group at
2.4 ppm when compared to the 1H NMR spectrum of 9b.
Connected with the mass spectral data, these results were
compatible with the symmetrical diketone 8a (Fig. 2). This
compound was not isolated, but analyzed within the mixture
with the chloroketone.
4. Experimental
4.1. General
Each reaction was carried out under an argon atmosphere in
a freshly distilled solvent, unless otherwise noted. Dichlor-
omethane was distilled from calcium hydride. Pyridine was
distilled and stored under argon. Reactions were monitored by
thin-layer chromatography on silica gel 60 F254, or by 19F NMR
spectroscopy. Unless otherwise noted, yields refer to materials
purified by column chromatography or distillation under
reduced pressure.
2.1.3. Mechanism of the reaction
Based on current knowledge [6], the formation of the
diketone 9 during this reaction may be tentatively explained
by initial nucleophilic attack of the betaine species 10
(resulting from ketene formation induced by pyridine from
the acid chloride 5), on hexafluoroglutaric anhydride 6. We
initially expected that the reaction would stop at the stage of
the carboxylate intermediate 11 so formed (Scheme 3). The
following steps of this reaction are far from trivial. The
observed transformation of 11 to a cyclohexanedione
skeleton may be foreseen by further activation of the
carboxylate group in 11 to 12 in the form of a mixed
anhydride by reaction with either an excess of anhydride 6 or
acid chloride 5 [12]. Ensuing intramolecular cyclisation
occurring via the enol form of the remaining carbonyl group
in 12 should lead to intermediate 13. The addition of a
nucleophilic species (such as chloride, carboxylate, etc.) on
the carbonyl pyridinium function may lead to the inter-
mediate 14 which can either evolve back to 13 or lead to 15.
Once enolate 15 is obtained, the introduction of the chlorine
atom can be explained by a mechanism similar to the
chlorination of b-diketones described by Heathcock et al.
[11]: formation of an enol-ester 16 from the enolate with 5 or
6 which is displaced by a chloride ion to afford 9. The low
solubility of one of the intermediates 13 or 15 in the reaction
medium as it was observed experimentally with the
formation of a precipitate, should stop this last reaction
and explain the presence of 8 after hydrolysis for some of our
substrates.
NMR spectra were recorded on a Bruker AC-300 spectro-
meter. Reported coupling constants and chemicals shifts were
based on a first order analysis. Internal reference was the
1
residual peak of CHCl3 (7.27 ppm) for H (300 MHz), central
peak of CDCl3 (77 ppm) for 13C (75 MHz) spectra and internal
CFCl3 (0 ppm) for 19F (282 MHz) NMR spectra. Melting points
were determined on a Mettler FP61 melting point apparatus. IR
spectra were recorded on a Nicolet Impact 400D. Low-
resolution mass spectra were recorded on a HP MS 5989B
spectrometer. Elemental analyses were carried out at ICSN
(Gif-sur-Yvette). Silica gel from Merck (Kieselgel 60 ACC,
35–70 or 70–200 mesh) was used for column chromatography.
4.2. General procedure
4.2.1. General procedure for the synthesis of
chlorodifluoroketone
To a solution of acid (1.15 mmol) in anhydrous dichlor-
omethane was added oxalyl chloride (0.15 mL, 1.37 mmol) and
the reaction mixture was stirred at room temperature for 2 h.
Then solvent and an excess of oxalyl chloride were removed off
under reduced pressure. The remaining oil was diluted in
anhydrous dichloromethane (20 mL) with chlorodifluoroanhy-
dride (1 mL, 5.7 mmol) and cooled at 0 8C. Pyridine was slowly
added (0.6 mL, 6.8 mmol), the cooling bath was removed and
the reaction was monitored by 19F NMR. After 1–4 h, a solution
of hydrochloric acid 1 M was cautiously added and the reaction
mixture was extracted successively with dichloromethane
(3 Â 20 mL), the organic phase was washed with brine, dried
over MgSO4, filtered and concentrated in vacuo. The crude oil
was purified by silica gel chromatography, (pentane to pentane/
ether: 9/1 depending on the substrate).
Use of the conditions described by Reeves et al. (reflux of
toluene with acid as starting materials) [9] to avoid the
presence of chloride ions in the reaction mixture did not give
the expected result. The direct transformation of the acid 5
into the b-diketone 8 was not observed. The anhydride 6
showed a total lack of reactivity under these particular
conditions.
4.2.2. General procedure for the synthesis of
chlorohexafluorocyclohex-2-enone
3. Conclusions
To a solution of acid (2.5 mmol) in anhydrous dichlor-
omethane was added oxalyl chloride (0.25 mL, 2.9 mmol) and
the reaction mixture was stirred at room temperature for 2 h.
Then solvent and excess of oxalyl chloride were removed under
vacuum. The remaining oil was diluted in dry dichloromethane
(20 mL) and cooled at 0 8C with hexafluorochloroanhydride
(1 mL, 7.44 mmol). Pyridine was slowly added (1.2 mL,
13.6 mmol), the cooling bath was removed and the reaction
was monitored by 19F NMR. A solution of hydrochloric acid
1 M was cautiously added and the reaction mixture was
We have shown that the synthesis of relatively unhindered
chlorodifluoromethyl ketones using the reaction of chlorodi-
fluoroacetic anhydride with acid chlorides in the presence of
pyridine is a viable alternative to the organometallic pathway.
Under these reaction conditions hexafluoroglutaric anhydride
leads to the unexpected formation of hexafluorocyclohexane-1,
3-dione and or fluorinated 3-chloro-cyclohex-2-enones. The
chemistry of these new compounds is currently under
investigation [15].

P. Diter et al. / Journal of Fluorine Chemistry 128 (2007) 1235–1240
1239
2
F = 260.0 Hz, JC–F = 26.0 Hz); 126.8 (C12); 128.5–128.7
extracted with dichloromethane (3 Â 20 mL), washed by a
solution of sodium chloride. The organic layer was dried over
MgSO4, filtered and concentrated in vacuo. The crude residue
was purified by silica gel chromatography, (pentane/ether: 9/1).
When the substrate is an alkyl acid, the extracted reaction
mixture was mixed with oxalyl chloride (0.5 mL, 5.8 mmol, 2
equiv) at 40 8C for 2 h and the cooled reaction mixture was
hydrolyzed, extracted and purified with the usual work up.
3
(C10, C11); 138.8 (C9); 141.2 (t, C2, JC–F = 3.0 Hz);143.0
(tt, C3, 2JC–F = 27.0 Hz, 3JC–F = 3.0 Hz); 178.0 (t t, C1 = O, 2JC–
3
F = 27.0 Hz, JC–F = 3.0 Hz); IR (film, ymax, cmÀ1): 3436
(nCHsp2); 2934 (nCHsp3); 1721 (nCO); MS (IE) m/z (%): 91 (100);
342 (M+, 7); MS (GC/CI CH4) m/z (%): 91(16); 307
(MH+ÀHCl, 100); 325 (MH+ÀH2O, 99); 343 (MH+, 51);
Anal.: calc. for C14H9OF6Cl (342.66): C, 49.1; H, 2.65; found:
C, 49.1; H, 2.7.
4.3. Analytical description
4.3.5. 3-chloro-4,4,5,5,6,6-hexafluoro-2-octylcyclohex-2-
enone (9b)
4.3.1. 1-Chloro-1,1-difluoro-5-phenylpentan-2-one
(4a)[13]
Colorless oil; 19F NMR d (ppm): À111.6 (m, 2F, C4);
À126.8 (m, 2F, C6); À133.8 (m, 2F, C5); 1H RMN d (ppm): 0.86
(t, 3H); 1.25 (m, 12H); 2.43 (t, 2H C7); 13C RMN d (ppm): 14.0;
1
Colorless oil; 19F NMR d (ppm): À68.7 (s, ÀCF2Cl); H
3
(ppm): 1.9 (quint., 2H,–CH2–CH2–CH2, JH–
RMN
d
3
4
H = 6.9 Hz); 2.6 (t, 2H, –CH2–CH2–CH2, JH–H = 7.9 Hz);
2.7 (t, 2H, –CH2–CH2–CH2, 3JH–H = 7.5 Hz); 7.2 (m, 5H, Ph.);
13C RMN d (ppm): 24.4 (C4); 34.3–34.6 (C3, C5); 119.8 (t,–
22.6; 26.8 (t, C7, JCF < 1 Hz); 27.6; 29.0; 29.1; 29.3; 31.8;
1
105.3 (ttt, C5, JC–F = 261.0 Hz; JC–F = 27.0 Hz, JC–
2
3
1
F = 2.0 Hz,); 108.4; 108.5 (ttq, C4, C6, JC–F = 261.0 Hz;
CF2Cl, 1JCF = 306.0 Hz); 126.3 (C9); 128.5–128.6 (4C, C7, C8);
2JC–F = 25.5 Hz, 3JC–F = 2.0 Hz); 142.0 (C3, tt 2JC–
2
3
F = 27.0 Hz JC–F = 2.0 Hz); 142.5 (C2 t, JC–F = 5.0 Hz);
3
140.7 (C6); 191.8 (t, C2, JC–F = 29.0 Hz); IR (film, ymax
,
cmÀ1): 3091 (nCHsp2); 2934; 2858; 1757 (nCO); 1444; 1152 (nC–
C); 1065; 912; 686; MS (GC/CI CH4) m/z (%): 273/275
(M+ + C2H5, 5); 233/235 (MH+, 5); 215/217 (MH+ÀH2O, 100);
147 (M+ÀCF2Cl, 5); 104 (6); 91(4); Anal.: calc. for
C11H11OF2Cl (232.65): C, 56.8; H, 4.8; found: C, 57.2; H, 5.1.
178.3 (CO, tt, 2JC–F = 24.0 Hz, 3JC–F = 3.0 Hz); IR (film, ymax
,
cmÀ1): 3050 (nCHsp2); 2929 (nCHsp3); 2863; 1726 (nCO); 1178;
691; MS (GC/CI CH4) m/z (%): 173 (30); 315 (MH+-HCl, 20);
351/353 (MH+, 100); 379/381 (M + C2H5 , 20).
+
4.3.6. 3-chloro-4,4,5,5,6,6-hexafluoro-decanylcyclohex-2-
enone (9c)
4.3.2. 1-chloro-1,1-difluoro-undecan-2-one (4b)
Colorless oil; 19F NMR d (ppm): À68.8 (s, 2F); 1H RMN d
(ppm): 0.89 (t, 3H, CH3); 1.27 (s, 12H, 6CH2); 1.65 (m, 2H, H
for Cb); 2.75 (t, 2H, H for Ca); 13C RMN d (ppm): 14. (C11);
22.6; 28.7; 29.1; 29.2; 29.6; 31.7 (C5–C10); 22.8 (C4); 35.12
Colorless oil; 19F NMR d (ppm): À111.7 (m, 2F, CF2 C4);
1
À126.8 (m, 2F, CF2 C6); À133.9 (m, 2F, CF2 C5); H RMN d
(ppm): 0.87 (t, 3H); 1.25 (m, 16H); 2.63 (t, 2H C7); 13C RMN d
4
(ppm): 14.1; 22.7; 26.8 (t, C7, JCF < 1 Hz); 27.6; 29.1; 29.2;
1
2
(C3); 119.9 (t, C1, JC–F = 306.0 Hz); 192 (t, C2 = O, JC–
F = 29.5 Hz); IR (film, ymax, cmÀ1): 2929 (nCHsp3); 2847; 1787
(nCO); 1178 (nC–C); MS (GC/CI CH4) m/z (%): 155
(M+ÀCF2Cl, 50); 185–187 (M+ÀC4H7, 35); 199 (M+ÀC3H6,
29); 221–223 (MH+ÀHF, 15); 241 (MH+, 100); 243 (MH+, 30);
269 (M+ÀC2H5, 13); Anal.: calc. for C11H19OF2Cl (240.71): C,
54.9; H, 7.95; found: C, 54.3; H, 7.6.
1
29.3 (2C); 31.5; 31.8; 105.3 (ttt, C5, JC–F = 261.0 Hz; JC–
2
3
F = 27.0 Hz, JC–F = 2.0 Hz); 108.4–108.5 (ttq, C4, C6, JC–
1
2
F = 261.0 Hz; JC–F = 25.5 Hz, JC–F = 2.0 Hz); 142.0 (C3, tt
3
3
3
2JC–F = 27.0 Hz JC–F = 2.0 Hz); 142.5 (C2 t, JC–F = 5.0 Hz);
2
178.2 (CO, tt, JC–F = 24 Hz, JC–F = 3.0 Hz); IR (film, ymax
3
,
cmÀ1): 2960; 2852; 1726; 1593; 1450; 1219; 1147; 860; 574.
MS (GC/CI CH4) m/z (%): 83(100); 343 (MH+ÀHCl, 40); 379/
381 (MH+, 100); 407/409 (M + C2H5 , 10); Anal.: calc. for
+
4.3.3. 1-Chloro-1,1-difluoro-heptadecan-2-one (4c)[14]
Colorless oil; 19F NMR d (ppm): À68.8 (s, 2F); 1H RMN d
(ppm): 0.89 (t, 3H, CH3); 1.27 (m, 24H, 12CH2); 1.69 (m, 2H, H
for Cb); 2.75 (t, 2H, H for Ca); 13C RMN (ppm): 14.1; 22.7;
22.9: 28.7; 29.2; 29.3; 29.5; 29.6; 29.65; 29.7; 31.9; 35.1; 119.8
(t, C1, 1JC–F = 306.0 Hz); 191.9 (t, C2 = O, 2JC–F = 29.0 Hz); IR
(film, ymax, cmÀ1): 2934; 2847; 1762; 1465; 1142; 901; 717;
MS (GC/CI CH4) m/z (%): 239 (M+ÀCF2Cl, 20); 325/327
C16H21OF6Cl (378.78): C, 50.7; H, 5.6; found: C, 50.7; H, 5.9.
Acknowledgements
The authors would like to thank Marie Tintin and Aurore de
Brondeau for their helpful experimental participation and
Sophie Clift for improvement of the English manuscript.
(MH+, 100); 353/355 (M + C2H5 , 5); Anal.: calc. for
+
References
C17H31OF2Cl (324.88): C, 62.85; H, 9.6; found: C, 62.7; H, 9.6.
[1] K. Mikami, Y. Itoh, M. Yamanaka, Chem. Rev. 104 (2004) 1–16.
´
[2] J.A. Gladysz, P. Curran, I.T. Horvath, Handbook of Fluorous Chemistry,
4.3.4. 3-Chloro-4,4,5,5,6,6-hexafluoro-2-(2-phenyl)ethyl-
cyclohex-2-enone (9a)
Wiley–VCH Verlag GmbH & Co. KgaA, Weinheim, Germany, 2004.
[3] (a) K. Baum, A.A. Malik, J. Org. Chem. 59 (1994) 6804–6807;
´
(b) A. Manseri, B. Ameduri, B. Boutevin, M. Kotora, M. Hajek, G.
Colorless oil; 19F NMR d (ppm): À111.7 (m, 2F, C4);
À126.6 (m, 2F, C6); À133.8 (m, 2F, C5); 1H RMN d (ppm): 2.76
(t, 2H, J = 7.9 Hz); 2.96 (t, 2H, J = 7.9 Hz); 7.1–7.3 (m, 5H);
13C RMN d (ppm): 29.6 (C7); 32.7 (C8); 105.5; 108.3 (t, C4, C6,
Caporiccio, J. Fluorine Chem. 73 (1995) 151–158;
´ ´ ´
(c) P. Barthelemy, B. Ameduri, E. Chabaud, J.-L. Popot, B. Pucci, Org.
Lett. 1 (1999) 1689–1692;
2
1
1JC–F = 260.0 Hz, JC–F = 26.0 Hz); 108.4 (qt, C5, JC–
(d) A. Polidori, M. Presset, F. Lebaupain, B. Ameduri, J.-Luc. Popot,

1240
P. Diter et al. / Journal of Fluorine Chemistry 128 (2007) 1235–1240
´
C. Breyton, B. Pucci Bioorg, Med. Chem. Lett. 16 (2006) 5827–
5831.
[8] (a) I.P. Street, H.-K. Lin, F. Laliberte, F. Ghomashchi, Z. Wang, H.
Perrier, N.M. Tremblay, Z. Huang, P.K. Weech, M.H. Gelb, Biochemistry
32 (1993) 5935–5940;
[4] (a) C. Wakselman, T. Nguyen, J. Org. Chem. 42 (1977) 565–566;
(b) T. Nguyen, M. Rubinstein, C. Wakselman, Synth. Commun. 13 (1983)
81–86;
(b) C. Aubert, J.-F. Rontani, Rapid Commun. Mass Spectrom. 14 (2000)
960–966;
´ ´ ´ ´
(c) Z. Szlavik, G. Tarkanyi, Z. Skribanek, E. Vass, J. Rabai, Org. Lett. 3
(d) C.M. Ticep, L.M. Bryman, Tetrahedron 57 (2001) 2689–2700;
(e) B. Jose, Y. Oniki, T. Kato, N. Nishino, Y. Sumida, M. Yoshida, Bioorg.
Med. Chem. Lett. 14 (2004) 5343–5346.
(2001) 2365–2366.
[5] (a) P. Mougenot, P. Mertens, M. Nguyen, R. Touillaux, J. Marchand-
Brynaert, J. Org. Chem. 61 (1996) 408–412;
[9] J.T. Reeves, F. Gallou, J.J. Song, Z. Tan, H. Lee, N.K. Yee, C.H.
Senanayake, Tetrahedron Lett. 48 (2007) 189–192.
[10] J.A.L. Miles, L. Mitchell, J.M. Percy, K. Singh, E. Uneyama, J. Org.
Chem. 72 (2007) 1575–1587.
(b) S. Pensec, F.-G. Tournilhac, Chem. Commun. (1997) 441–442;
´
´ ´
(c) Z. Szlavik, A. Csampai, M.P. Krafft, J.G. Riess, J. Rabai, Tetrahedron
Lett. 38 (1997) 8757–8760;
(d) S. Pensec, F.-G. Tournilhac, P. Bassoul, C. Durliat, J. Phys. Chem. B
[11] R.D. Clark, C.H. Heathcock, J. Org. Chem. 41 (1976) 636–643.
[12] We used about 3–6 equivalents of anhydride and pyridine for one of acid
chloride.
102 (1998) 52–60.
[6] (a) J. Boivin, L. El Kaim, S.Z. Zard, Tetrahedron Lett. 33 (1992) 1285–
´ ´ ´
[13] J.-P. Begue, D. Bonnet-Delpon, D. Mesureur, G. Nee, S.-W. Wu, J. Org.
1288;
(b) J. Boivin, L. El Kaim, S.Z. Zard, Tetrahedron 51 (1995) 2573–
Chem. 57 (1992) 3807–3814.
2584;
[14] K.M. Neder, S.A. French, S.P.F. Miller, Tetrahedron 50 (1994) 9847–
(c) J. Boivin, L. El Kaim, S.Z. Zard, Tetrahedron 51 (1995) 2585–
2592.
9864.
[15] We warmly thank a referee for improvement of the manuscript and his
suggestions.
[7] S.Z. Zard, Org. Biomol. Chem. 5 (2007) 205–213.