Synthesis of 2-trifluoromethoxyethyl trifluoromethoxyacetate and derived 2-trifluoromethoxyacrylates

Article abstract of DOI:10.1016/S0022-1139(02)00152-5

The synthesis of 2-trifluoromethoxyethyl trifluoromethoxyacetate 2 by oxidation of bis(2-trifluoromethoxyethyl)ether 1 followed by its anionic condensation with aldehydes, ketones and immonium salts under mild conditions, and further dehydration or deamination, enabled the preparation of 3-aryl and 3-alkyl-2-trifluoromethoxacrylates 8a-e as well as the parent 2-trifluoromethoxyacrylate 8f.

Full text of DOI:10.1016/S0022-1139(02)00152-5

Journal of Fluorine Chemistry 117 (2002) 161–166
Synthesis of 2-trifluoromethoxyethyl trifluoromethoxyacetate
and derived 2-trifluoromethoxyacrylates
Jean-Claude Blazejewski, Elsa Anselmi, Angelika Wernicke, Claude Wakselman*
´
SIRCOB, ESA CNRS 8086, Universite de Versailles, 45 Avenue des Etats-Unis, 78035 Versailles, France
Received 17 April 2002; received in revised form 27 May 2002; accepted 30 May 2002
Dedicated to Professor Lev M. Yagupolskii on the occasion of his 80th birthday.
Abstract
The synthesis of 2-trifluoromethoxyethyl trifluoromethoxyacetate 2 by oxidation of bis(2-trifluoromethoxyethyl)ether 1 followed by its
anionic condensation with aldehydes, ketones and immonium salts under mild conditions, and further dehydration or deamination, enabled
the preparation of 3-aryl and 3-alkyl-2-trifluoromethoxacrylates 8a–e as well as the parent 2-trifluoromethoxyacrylate 8f.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Trifluoromethoxy group; Ether oxidation; Acrylates; Ester condensation; Aldehydes; Ketones; Eschenmoser salt
1. Introduction
of trifluoromethoxyacetate esters and the study of their
transformation to 2-trifluoromethoxyacrylates derivatives.
These compounds may find potential use in the preparation
of polymers for example as core materials for optical
waveguides [13].
The trifluoromethoxy group, which has been referred to as
a super-halogen [1] or a pseudo-halogen [2], is perhaps the
least well understood fluorine substituent [3]. A renewed
interest seems to have arisen around this group, at least in the
aromatic series [4]. In a recent publication in this journal [5],
Rozen noted that: ‘‘Aromatic trifluoromethyl ethers are well
known and have many applications in the pharmaceutical
and agricultural domains [. . .]. Aliphatic trifluoromethyl
ethers, however, are rare and difficult to make’’. This is
mainly because there is no general direct method for the
introduction of the OCF3 group in aliphatic molecules [6].
Methyl trifluoromethoxy acetate for example has been pre-
pared [7] using the carbonyl fluoride/sulfur tetrafluoride
protocol ðROH ! ROCðOÞF ! ROCF3Þ [8]. Recent
advances in the fluorodesulfurization reaction [5,9–11]
enabled the preparation of some unfunctionalized aliphatic
trifluoromethyl ethers under mild conditions (action of DBH
and HF/pyridine to xanthates), avoiding the use of toxic
reagents. Our own work in this area has shown that func-
tional molecules bearing this group are now readily acces-
sible by this methodology [12]. As a continuation of our
efforts toward the elaboration of ready to use trifluoro-
methoxy bearing synthons, we address here the preparation
2. Results and discussion
2.1. Preparation of 2-trifluoromethoxyethyl
trifluoromethoxyacetate 2
We recently described the synthesis of bis(2-trifluoro-
methoxyethyl)ether 1 by action of DBH and HF/pyridine on
a diethylene glycol bisxanthate, as well as its functionaliza-
tion to 2-trifluoromethoxyethyl triflate [12]. We thought that
this readily obtained compound may also be useful for the
preparation of trifluoromethoxyacetate esters, provided that
a suitable reagent could be found for its oxidation a to the
central oxygen atom. Initial trials under Sharpless conditions
[14] were unsuccessful, the starting material 1 being recov-
ered unchanged after prolonged reaction time. Obviously a
stronger oxidising agent was needed to effect the conversion
to ester 2. The powerful reagent dimanganese heptoxide was
described as being able to oxidise smoothly simple aliphatic
ethers in satisfactory yields at low temperature (À45 8C)
[15]. In the case of ether 1, we had to run the reaction at room
temperature overnight to achieve complete conversion.
Under these conditions and thanks to the symmetrical nature
* Corresponding author. Tel.: þ33-1-39-25-44-11;
fax: þ33-1-39-25-44-52.
E-mail address: wakselma@aspirine.chimie.uvsq.fr (C. Wakselman).
0022-1139/02/$ – see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 1 5 2 - 5

162
J.-C. Blazejewski et al. / Journal of Fluorine Chemistry 117 (2002) 161–166
Scheme 1.
of ether 1, the ester 2 could be obtained in 47% yield in a
pure state after a simple filtration (Scheme 1).
70:30) retaining both trifluoromethoxy groups. No conden-
sation product was observed using monomeric formalde-
hyde [19] under such conditions.
2.2. Condensation of ester 2 with carbonyl compounds
2.3. Preparation of acrylates 8a–e by dehydration of
alcohols 6a–e
The chemistry of trifluoromethoxyacetates is poorly
known [7]. We initially supposed, by analogy with our work
on ethyl trifluoromethylthioacetate [16], that the Knoeve-
nagel condensation of ester 2 with carbonyl compounds
could be successful. Using the same conditions as before
[16], we did not however observe the condensation of 2 with
benzaldehyde (Scheme 2). Instead, we isolated the amino
compound 3 as the major product (38%), resulting from the
nucleophilic substitution of OCF3 by piperidine. Thus, the
behaviour of the trifluoromethoxy group in such reaction is
closer to that expected for a chlorine atom rather than a fluorine
atom or a trifluoromethylthio group. bis(Pentamethylene)urea
4 was also observed as a by product in this condensation. It
possibly originates from further reaction of piperidine with
carbonyl fluoride formed by decomposition of the trifluoro-
methoxide leaving group (CF3OÀ ! COF2 þ FÀ).
Alcohols 6a–e obtained in the previous condensation
proved unexpectedly stable towards dehydration conditions.
In a preliminary attempt, we tried to dehydrate the phenyl
derivative 6a using azeotropic distillation of benzene in the
presence of a trace of acid (PTSA). We did not observe
however the clean formation of the desired acrylate 8a.
Instead, we isolated the diphenyl derivative 7 (74%) as the
major product (Scheme 4).
Better results were obtained by holding a mixture of 6a,
powdered phosphorus pentoxide, and dry sand at 90 8C for
3 h, acrylate 8a being isolated in 45% yield. Unfortunately,
these dehydration conditions cannot be applied to alcohols
6b–e. A more general method was found using thionyl
chloride and pyridine as the dehydrating medium
(Scheme 5) [20].
Using conditions described earlier by our laboratory [17]
for the preparation of the lithium enolate of ethyl fluoroace-
tate, later modified by Welch [18] (HMDSLi, THF, HMPA),
we were however able to condense the anion of 2 with various
carbonyl compounds 5a–e (including a ketone 5e) in satis-
factory yields, provided that the temperature of the reaction
medium is maintained at À85 8C (Scheme 3).
Using this combination of reagents, substituted acrylates
8a–e were obtained in 20–95% yield with high Z-stereo-
3
selectivity (Table 1), as shown by the small JðC¼O;HÞ
coupling constants (2.2–4.4 Hz) between the carbonyl group
and the vinylic hydrogen atom [21]. The lower yield was
observed for the most sensitive substrate 8b (entry 2).
Using aldehydes 5a–d, alcohols 6a–d were thus obtained
as inseparable mixtures of two diastereoisomers (55:45 to
2.4. Preparation of the parent acrylate 8f
As stated before, the parent acrylate 8f (R1 ¼ H, R2 ¼ H)
could not be obtained by condensation of the anion of 2 with
formaldehyde. However, a related condensation could be
Scheme 2.
Scheme 4.
Scheme 3.
Scheme 5.

J.-C. Blazejewski et al. / Journal of Fluorine Chemistry 117 (2002) 161–166
163
Table 1
Trifluoromethoxyacrylates derivatives 8 prepared
4.1. Oxidation of bis(2-trifluoromethoxyethyl)ether 1 by
dimanganese heptoxide
c,d
Entry
Product Z/Ea
Yield (%)b
3JC¼O;H
(Hz)
dH;acrylic
(ppm)
A ca. 1 M solution of dimanganese heptoxide in CCl4
(25 ml) was added to a solution of the fluorinated ether 1
(3 g, 12.4 mmol) in 40 ml CCl4. The mixture was stirred
overnight, filtered over a pad of Celite1 and washed with
diethylether. The filtrate was evaporated under vacuum to
give 1.5 g (47%) of 2-trifluoromethoxyethyl trifluoromethox-
yacetate (2) as a colourless liquid. Boiling point (Siwoloboff)
154–156 8C. Found: C, 28.07; H, 2.40%. C6H6F6O4 requires:
C, 28.14; H, 2.36%. 1H NMR d (ppm): 4.16–4.21 and 4.42–
4.47 (2ꢀ 2H, 2ꢀ m, CH2CH2); 4.56 (2H, s, CF3OCH2C(O)).
19F NMR d (ppm): À61.7 and À62.1 (2ꢀ s, CF3). 13C NMR d
(ppm): 62.68 (C(O)OCH2); 62.7 (q, JCF ¼ 3:7 Hz,
CF3OCH2C(O)); 121.39 and 121.44 (2ꢀ q, JCF ¼ 257 and
255 Hz, CF3); 165.8 (C=O). IR (CCl4) 1764 cmÀ1. MS (EI)
m/z: 257 (Mþꢁ, 1); 129 (13); 113 (42); 99 (100%).
1
2
3
4
5
6
8a
8b
8c
8d
8e
8f
100/0
95/5
97/3
94/6
–
54
20
86
24
95
3
4.4
2.7
2.2
2.7
–
7.49
7.42
6.77
6.78
–
5.74, 6.23
–
ND
a Ratio determined by 19F NMR analysis of the crude mixture.
b Isolated yields of Z isomer.
c For the Z isomer.
d Coupling constants were determined with simultaneous selective
decoupling of the CH2O(CO) protons.
4.2. Preparation of the anion of 2-trifluoromethoxyethyl
trifluoromethoxyacetate 2
HMPA (0.34 ml, 2 mmol) followed by 2-trifluoromethox-
yethyl trifluoromethoxyacetetate 2 (0.5 g, 2 mmol) was
added to a solution of lithium bis(trimethylsilyl)amide
(prepared from a solution of 5.9 mmol of hexamethyldisi-
lazane in 20 ml THF and 5.9 mmol of methyllithium in
diethylether under argon) cooled to À85 8C.
Scheme 6.
achieved using the Eschenmoser salt 9 (Scheme 6) albeit in
low yield (Table 1, entry 6).
4.3. Condensation of 2-trifluoromethoxyethyl
trifluoromethoxyacetate 2 with carbonyl compounds
The intermediate amine 10 was not isolated. Upon qua-
ternisation (MeI) followed by mild basic treatment (NEt3),
we observed the smooth formation of acrylate 8f.
4.3.1. Attempted condensation of 2-trifluoromethoxyethyl
trifluoromethoxyacetate 2 with benzaldehyde in the
presence of piperidine
3. Conclusion
A solution of ester 2 (0.3 g, 1.2 mmol), benzaldehyde
(0.12 g, 1.13 mmol) and piperidine (0.24 ml, 2.4 mmol) in
acetonitrile (20 ml) was refluxed for 3 days. The solvent was
removed under reduced pressure and the residue was pur-
ified by column chromatography (silica gel; pentane/diethy-
lether solvent gradient). Earlier fractions contained
unreacted benzaldehyde followed by bis(pentamethyle-
ne)urea 4 identified by comparison of its spectral character-
istics with published data. Further fractions (diethylether)
were pooled and distilled (Kugelrohr, 150 8C, 10 mmHg) to
give (110 mg, 38%) of 2-trifluoromethoxyethyl piperidinoa-
We have shown that trifluoromethoxyethyl trifluoro-
methoxyacetate 2 could be prepared by oxidation of fluori-
nated glyme 1. Condensation of the anion of 2 with various
carbonyl compounds or derivatives, followed by dehydra-
tion, afforded substituted or unsubstituted trifluoromethox-
yacrylates 8a–f.
4. Experimental
1
NMR spectra were recorded otherwise stated as CDCl3
solutions, on a Bruker AC-300 spectrometer. Reported
coupling constants and chemicals shifts were based on a
first order analysis. Internal reference was the residual peak
of CHCl3 (7.27 ppm) for 1H NMR (300 MHz), central peak
of CDCl3 (77 ppm) for 13C NMR (75 MHz) spectra and
internal CFCl3 (0 ppm) for 19F NMR (282 MHz) spectra. IR
spectra were recorded as CCl4 solutions on an Impact 400D
Nicolet spectrophotometer. High resolution mass spectra
were performed with a Finnigan MAT 95S spectrometer.
cetate (3) as a colourless oil. H NMR d (ppm): 1.32–1.50
(2H, m, NCH2CH2CH2); 1.53–1.70 (4H, m, NCH2CH2);
2.42–2.54 (4H, m, NCH2); 3.16 (2H, s, NCH2CO); 4.11–
4.20 and 4.28–4.39 (4H, 2m, CF3OCH2CH2). 19F NMR d
(ppm): À61.6 (s, CF3). 13C NMR d (ppm): 23.7 (1C,
NCH2CH2CH2); 25.7 (2C, NCH2CH2); 54.2 (2C, NCH2);
59.9 and 61.3 (CH2C(O)OCH2); 64.9 (q, JCF ¼ 3:2 Hz,
CF3OCH2); 121.4 (q, JCF ¼ 255 Hz, CF3); 170.3 (C=O).
IR (CCl4) 1769 cmÀ1. MS (EI) m/z: 255 (Mþꢁ, 3); 98
(100%).

164
J.-C. Blazejewski et al. / Journal of Fluorine Chemistry 117 (2002) 161–166
4.3.2. Condensation of the anion of 2-trifluoromethoxyethyl
trifluoromethoxyacetate 2 with carbonyl compounds
CF3OCH2); 68.4 (CHOH); 77.0 (q, JCF ¼ 2:2 Hz, CF3OCH);
108.8 and 110.6 (3- and 4-furyl-C); 123.2 and 123.3 (2ꢀ q,
JCF ¼ 258 and 256 Hz, CF3); 143.1 (5-furyl-C); 150.2
(2-furyl-C); 166.4 (C=O). IR (CCl4) 3480; 1758 cmÀ1. MS
(EI) m/z: 352 (Mþꢁ, 15); 266 (17); 69 (100%).
The anion of 2-trifluoromethoxyethyl trifluoromethoxya-
cetate 2 was prepared as before (Section 4.2). After 5 min
stirring, the carbonyl compound 5 (2 mmol) was added
rapidly at À85 8C. The reaction was then held at À78 8C
for 30 min before the addition of a saturated ammonium
chloride solution (4 ml). The temperature was raised to
20 8C and the mixture was diluted with hexane (60 ml)
and water (20 ml). The organic layer was washed with
diluted hydrochloric acid (2 M) until acidic, then with water
2-Trifluoromethoxyethyl 3-hydroxy-2-trifluoromethoxy-
valerate 6c. A 50% yield, oily mixture (70/30) of diaster-
eoisomers. Found: C, 34.51; H, 3.91%. C9H12F6O5 requires:
1
C, 34.41; H, 3.85%. H NMR d (ppm): 1.03 and 1.04 (3H,
2ꢀ t, major isomer J ¼ 7:6 Hz and minor isomer
J ¼ 7:3 Hz, CH3); 1.51–1.74 (2H, m, CH2CHOH both iso-
mers); 2.15 and 2.30 (1H, 2ꢀ br s, OH minor and major
isomer); 3.88–4.01 (1H, m, CHOH both isomers); 4.16–4.23
(2H, m, CF3OCH2 both isomers); 4.36–4.57 (2H, m,
CF3OCH2CH2 both isomers); 4.59 and 4.61 (1H, 2ꢀ d, minor
isomer J ¼ 3:3 Hz and major isomer J ¼ 4:6 Hz, CF3OCH).
19F NMR d (ppm): À60.38 and À61.88 (2ꢀ s, CF3 major
˚
and dried (4 A molecular sieves). After the removal of the
solvents, the residue was eluted on a silica gel column (40/
60, diethylether/pentane) affording the condensation pro-
duct 6. Yields and part of the NMR data are shown in Table 1.
2-Trifluoromethoxyethyl 3-hydroxy-3-phenyl-2-trifluoro-
methoxypropionate 6a. A 36% yield, oily mixture (40/60) of
diastereoisomers. Found: C, 43.35; H, 3.39%. C13H12F6O5
isomer); À60.38 and À61.84 (2ꢀ s, CF3 minor isomer). 13
C
1
requires: C, 43.11; H, 3.34%. H NMR d (ppm): 2.61 and
NMR d (ppm): (major isomer) 9.5 (CH3); 25.2 (CH2CH3);
62.6 (C(O)OCH2); 64.5 (q, JCF ¼ 3:4 Hz, CF3OCH2); 72.9
(CHOH); 77.9 (q, JCF ¼ 2:8 Hz, CF3OCH); 123.1 and 123.1
(2ꢀ q, JCF ¼ 257 and 256 Hz, CF3); 167.0 (C=O); (minor
isomer) 9.5 (CH3); 25.8 (CH2CH3); 62.7 (C(O)OCH2); 64.5
(q, JCF ¼ 3:4 Hz, CF3OCH2); 73.0 (CHOH); 77.4 (q,
JCF ¼ 2:6 Hz, CF3OCH); 123.1 and 123.2 (2ꢀ q,
JCF ¼ 258 and 254 Hz, CF3); 167.3 (C=O). IR (CCl4)
3480; 1763 cmÀ1. MS (EI) m/z: 314 (Mþꢁ, 1); 256 (100%).
2-Trifluoromethoxyethyl 3-hydroxy-2-trifluoromethoxy-
nonanoate 6d. A 24% yield, oily mixture (55/45) of diaster-
eoisomers. Found: C, 42.48; H, 5.21%. C13H20F6O5
requires: C, 42.17; H, 5.45%. 1H NMR d (ppm): 0.85–
0.95 (3H, m, CH3 both isomers); 1.23–1.43 (8H, m, (CH2)4
both isomers); 1.50–1.70 (2H, m, CH2CHOH both isomers);
2.5 (1H, br s, OH both isomers); 3.98–4.10 (1H, m, CHOH
both isomers); 4.17–4.24 (2H, m, CF3OCH2 both isomers);
4.40–4.56 (2H, m, CF3OCH2CH2 both isomers); 4.57 and
4.61 (1H, 2ꢀ d, minor isomer J ¼ 3:3 Hz and major isomer
J ¼ 4:3 Hz, CF3OCH). 19F NMR d (ppm): À60.36 and
À61.88 (2ꢀ s, CF3 major isomer); À60.38 and À61.91
(2ꢀ s, CF3 minor isomer). 13C NMR d (ppm): (major
isomer) 13.9 (CH3); 22.5, 25.2, 28.9, 31.6, 32.7 ((CH2)5);
62.6 (C(O)OCH2); 64.5 (q, JCF ¼ 3:4 Hz, CF3OCH2); 71.7
(CHOH); 78.3 (q, JCF ¼ 2:3 Hz, CF3OCH); 123.1 and 123.1
(2ꢀ q, JCF ¼ 258 and 256 Hz, CF3); 167.3 (C=O); (minor
isomer) 13.9 (CH3); 22.5, 25.3, 28.9, 31.6, 32.0 ((CH2)5);
62.7 (C(O)OCH2); 64.51 (q, JCF ¼ 3:4 Hz, CF3OCH2); 71.6
(CHOH); 77.8 (q, JCF ¼ 2:3 Hz, CF3OCH); 123.1 and 123.1
(2ꢀ q, JCF ¼ 258 and 256 Hz, CF3); 167.9 (C=O). IR (CCl4)
3454; 1767 cmÀ1. MS (EI) m/z: 370 (Mþꢁ, 1); 256 (100%).
2-Trifluoromethoxyethyl 3-hydroxy-2-trifluoromethoxyi-
sovalerate 6e. A 31% yield, oil. Found: C, 34.15; H, 3.68%.
C9H12F6O5 requires: C, 34.41; H, 3.85%. 1H NMR d (ppm):
1.34 and 1.35 (2ꢀ 3H, 2ꢀ s, C(CH3)2); 2.45 (1H, br s, OH);
4.18–4.23 (2H, m, CF3OCH2); 4.40–4.55 (2H, m,
CF3OCH2CH2); 4.45 (1H, s, CF3OCH). 19F NMR d
(ppm): À60.60 and À61.95 (2ꢀ s, CF3). 13C NMR d
2.69 (1H, 2ꢀ br s, OH major and minor isomers); 3.90–4.15
(2H, m, CF3OCH2 both isomers); 4.20–4.43 (2H, m,
CF3OCH2CH2 both isomers); 4.73 and 4.79 (1H, 2ꢀ d,
minor isomer J ¼ 5:6 Hz and major isomer J ¼ 5:9 Hz,
CF3OCH); 5.1–5.2 (1H, br s, PhCH both isomers); 7.4–7.5
(5H, br s, ArH). 19F NMR d: À60.47 and À61.75 (2ꢀ s, CF3
major isomer); À60.5 and À61.73 (2ꢀ s, CF3 minor isomer).
13C NMR d (ppm): (major isomer) 62.7 (C(O)OCH2); 64.4 (q,
JCF ¼ 3:5 Hz, CF3OCH2); 73.5 (CHOH); 78.2 (q,
JCF ¼ 2:3 Hz, CF3OCH); 121.2 and 121.4 (2ꢀ q,
JCF ¼ 258 and 255 Hz, CF3); 126.5 (2C, ArC); 128.6 (2C,
ArC); 129.0 (ArC); 137.5 (quaternary ArC); 166.7 (C=O);
(minor isomer) 62.3 (q, JCF ¼ 3:5 Hz, CF3OCH2); 62.7
(C(O)OCH2); 73.8 (CHOH); 79.3 (q, JCF ¼ 2:3 Hz,
CF3OCH); 121.2 and 121.3 (2ꢀ q, JCF ¼ 258 and 255 Hz,
CF3); 126.5 (2C, ArC); 128.7 (2C, ArC); 129.1 (ArC); 136.7
(quaternary ArC); 166.6 (C=O). IR (CCl4) 3677; 1752 cmÀ1
.
MS (EI) m/z: 362 (Mþꢁ, 1); 345 (10); 107 (100%).
2-Trifluoromethoxyethyl 3-hydroxy-3-furyl-2-trifluoro-
methoxypropionate 6b. A 50% yield, oily mixture (66/34)
of diastereoisomers. Found: C, 37.77; H, 2.44%.
C11H10F6O6 requires: C, 37.51; H, 2.86%. 1H NMR d
(ppm): 2.70 and 2.78 (1H, 2ꢀ d, J ¼ 7:2 and 8.2 Hz, OH
major and minor isomers); 4.10–4.20 (2H, m, CF3OCH2
both isomers) 4.40–4.50 (2H, m, CF3OCH2CH2 both iso-
mers); 4.95 and 4.97 (1H, 2ꢀ d, minor isomer J ¼ 4:6 Hz
and major isomer J ¼ 5:9 Hz, CF3OCH); 5.10–5.20 (1H, m,
CHOH both isomers); 6.36–6.40 (1H, m, 4-furyl-H both
isomers); 6.41–6.50 (1H, m, 3-furyl-H both isomers); 7.43
(1H, br s, 5-furyl-H both isomers). 19F NMR d (ppm):
À60.64 and À61.85 (2ꢀ s, CF3 both isomers). 13C NMR
d (ppm): (major isomer) 63.1 (C(O)OCH2); 64.5 (q,
JCF ¼ 3:3 Hz, CF3OCH2); 67.8 (CHOH); 76.5 (q,
JCF ¼ 2:2 Hz, CF3OCH); 109.1 and 110.6 (3- and 4-furyl-
C); 123.2 and 123.3 (2ꢀ q, JCF ¼ 258 and 256 Hz, CF3);
143.2 (5-furyl-C); 150.3 (2-furyl-C); 166.5 (C=O); (minor
isomer) 62.9 (C(O)OCH2); 64.5 (q, JCF ¼ 3:8 Hz,

J.-C. Blazejewski et al. / Journal of Fluorine Chemistry 117 (2002) 161–166
165
(ppm): 25.1 and 25.3 (C(CH3)2); 62.5 (C(O)OCH2); 64.4 (q,
JCF ¼ 3:3 Hz, CF3OCH2); 71.3 (C(CH3)2); 80.9 (q,
JCF ¼ 2:2 Hz, CF3OCH); 123.1 and 123.1 (2ꢀ q,
JCF ¼ 260 and 257 Hz, CF3); 167.3 (C=O). IR (CCl4)
3677; 1767 cmÀ1. MS (EI) m/z: 315 (Mþꢁ þ 1, 55); 297
(52), 213 (63), 171 (92), 59 (100%).
JCF ¼ 3:8 Hz, CF3OCH2); 112.9 (4-furyl-C); 118.1 (=CH);
120.7 (3-furyl-C); 122.6 and 123.3 (2ꢀ q, JCF ¼260 and
255 Hz, CF3); 131.3 (q, JCF ¼ 2:2 Hz, =C–OCF3); 145.9 (5-
furyl-C); 147.0 (2-furyl-C); 161.8 (C=O). IR (CCl4) 1731;
1644 cmÀ1. MS (EI) m/z: 344 (Mþꢁ, 100%).
2-Trifluoromethoxyethyl 3-ethyl-2-trifluoromethoxya-
crylate (Z) 8c. Oil. Found: C, 36.08; H, 3.51%. C9H10F6O4
requires: C, 36.50; H, 3.40%. 1H NMR d (ppm): 1.11 (3H, t,
J ¼ 7:5 Hz, CH3); 2.37 (2H, quint., J ¼ 7:5 Hz, CH2CH=);
4.17–4.25 (2H, m, CF3OCH2); 4.42–4.48 (2H, m,
CF3OCH2CH2); 6.77 (1H, t, J ¼ 7:9 Hz, =CH). 19F NMR
d (ppm): À58.7 (s, =C–OCF3); À61.7 (s, CH2OCF3). 13C
4.3.3. Dehydration of alcohols 6a–e with p-toluenesulfonic
acid
A mixture of alcohol 6a (20 mg, 0.053 mmol) in benzene
(20 ml) containing p-toluenesulfonic acid was refluxed for
24 h in a Dean–Stark apparatus. The solvent was then
removed under reduced pressure and the residue purified
by TLC (SiO2, dichloromethane) affording diphenyl adduct
7 (17 mg, 74%) as an oil: 1H NMR d (ppm): 3.75–3.97 (2H,
m, CF3OCH2); 4.04–4.31 (2H, m, CF3OCH2CH2); 4.52 (1H,
d, JCF ¼ 8:6 Hz, CF3OCH or CHPh2); 5.24 (1H, d,
JCF ¼ 8:6 Hz, CHPh2 or CF3OCH); 7.24–7.37 (10H, m,
ArH). 19F NMR d (ppm): À60.5 and À61.7 (2ꢀ s, CF3).
13C NMR d (ppm): 53.4 (CHPh2); 62.5 (CH2OC(O)); 64.3
(q, JCF ¼ 3:4 Hz, CF3OCH2); 77.8 (q, JCF ¼ 2:5 Hz,
CF3OCH); 121.2 and 121.4 (2ꢀ q, JCF ¼ 258 and
255 Hz, CF3); 127.5 and 127.7 (2C, ArC); 128.3 and
128.5 (4C, ArC); 128.7 (4C, ArC); 137.8 and 138.0 (2C,
ArC). MS (EI) m/z: 422 (Mþꢁ, 1); 167 (100%).
NMR
d (ppm): 13.0 (CH3); 20.6 (=CHCH2); 62.2
(C(O)OCH2); 64.6 (q, JCF ¼ 3:5 Hz, CF3OCH2); 122.3 (q,
JCF ¼ 257 Hz, CF3); 123.2 (q, JCF ¼ 254 Hz, CF3); 135.6 (q,
JCF ¼ 2:2 Hz, =C–OCF3); 139.0 (=CH); 161.2 (C=O). IR
(CCl4) 1747; 1660 cmÀ1. MS (EI) m/z: 296 (Mþꢁ, 5); 113
(77); 84 (55); 69 (100%).
2-Trifluoromethoxyethyl 3-hexyl-2-trifluoromethoxya-
crylate (Z) 8d. Oil. Found: C, 44.62; H, 5.11%.
1
C13H18F6O4 requires: C, 44.32; H, 5.155%. H NMR d:
0.86-0.96 (3H, m, CH3); 1.25–1.55 (8H, m, (CH2)4); 2.35
(2H, dt, J ¼ 7:5 and 7.4 Hz, CH2CH=); 4.19-4.24 (2H, m,
CF3OCH2); 4.43–4.48 (2H, m, CF3OCH2CH2); 6.78 (1H, t,
J ¼ 7:7 Hz, =CH); 19F NMR d (ppm): À58.6 (s, =C–OCF3);
À61.8 (s, CH2OCF3). 13C NMR d (ppm): 13.9 (CH3); 22.5,
26.3, 27.9, 28.9, 31.4 ((CH2)5); 62.5 (C(O)OCH2); 64.7 (q,
JCF ¼ 3:4 Hz, CF3OCH2); 120.6 (q, JCF ¼ 259 Hz, CF3);
121.5 (q, JCF ¼ 255 Hz, CF3); 123.2 (=C–OCF3); 138.2
(=CH); 161.3 (C=O). IR (CCl4) 1737; 1650 cmÀ1. MS
(CI, NH3) m/z: 387 (Mþꢁ þ 2NH3, 25); 370 (100); 252 (6%).
2-Trifluoromethoxyethyl 3,3-dimethyl-2-trifluorometho-
xyacrylate 8e. Oil. Found: C, 36.07; H, 3.49%. C9H10-
F6O4 requires: C, 36.50; H, 3.40%. 1H NMR d (ppm):
1.99 and 2.21 (6H, 2s, CH3); 4.18–4.24 (2H, m, CF3OCH2);
4.41–4.47 (2H, m, CF3OCH2CH2). 19F NMR d (ppm):
À58.9 (s, =C–OCF3); À61.9 (s, CH2OCF3). 13C NMR d
(ppm): 20.3 and 21.0 (2CH3); 62.0 (C(O)OCH2); 64.7 (q,
JCF ¼ 3:5 Hz, CF3OCH2); 121.1 (q, JCF ¼ 258 Hz, CF3);
121.6 (q, JCF ¼ 255 Hz, CF3); 131.8 (q, JCF ¼ 2:0 Hz,
=C–OCF3); 136.30 (=C(CH3)2); 161.8 (C=O). IR (CCl4)
1721; 1655 cmÀ1. MS (CI, NH3) m/z: 331 (Mþꢁ þ 2NH3,
35); 314 (Mþꢁ þ NH3, 100); 296 (Mþꢁ, 3%).
4.3.4. Dehydration of alcohols 6a–e with thionyl chloride
Thionyl chloride (5 ml) was added dropwise to a stirred
solution of the alcohol 6 (0.25 mmol) in dry pyridine (8 ml)
cooled on an ice bath. The mixture was slowly raised to room
temperature and stirred for 18 h. The reaction was quenched
with ice and extracted with dichloromethane. The organic
phase was washed with water and dried (MgSO4). After
removal of the solvents, the remaining residue was purified
by column chromatography (silica gel; pentane/diethy-
lether: 90/10).
2-Trifluoromethoxyethyl 3-phenyl-2-trifluoromethoxya-
crylate (Z) 8a. Oil; HRMS Found: 344.0479. C13H10F6O4
1
requires: 344.0483. H NMR d (ppm): 4.24-4.29 (2H, m,
CF3OCH2); 4.49–4.55 (2H, m, CF3OCH2CH2); 7.40–7.47
(3H, m, ArH); 7.49 (1H, s, =CH); 7.69–7.78 (2H, m, ArH).
19F NMR d (ppm): À57.6 (s, =C–OCF3); À61.7 (s,
CH2OCF3). 13C NMR d (ppm): 62.8 (C(O)OCH2); 64.7
(q, JCF ¼ 3:4 Hz, CF3OCH2); 120.6 and 121.5 (2ꢀ q,
JCF ¼ 261 and 255 Hz, CF3); 128.8 (2C, ArC); 130.6 (qua-
ternary ArC); 130.9 (2C, ArC); 130.95 (ArC); 132.3 (=CH);
134.0 (q, JCF ¼ 1:9 Hz, =C¼¼OCF3); 162.0 (C=O). IR
(CCl4) 1739; 1650 cmÀ1. MS (EI) m/z: 344 (Mþꢁ, 100%).
2-Trifluoromethoxyethyl 3-furyl-2-trifluoromethoxyacry-
late (Z) 8b. Oil. HRMS Found: 335.0358. C11H8F6O5
4.4. Synthesis of 2-trifluoromethoxyethyl
2-trifluoromethoxyacrylate 8f
The anion of 2-trifluoromethoxyethyl trifluoromethoxya-
cetate 2 was prepared as before (Section 4.2) from 4 mmol of
ester. Solid Eschenmoser salt 9 (3.7 g, 20 mmol) was then
slowly added. The mixture was stirred for 2.5 h at À78 8C
before the addition of saturated ammonium chloride solution
(4 ml), neutralization with 1 M hydrochloric acid and
extraction with ethyl acetate. The organic phase was washed
with water and dried (MgSO4). After removal of the solvent,
the residue was eluted on a silica gel column (pentane/diethyl-
1
requires: 335.0354. H NMR d (ppm): 4.22–4.28 (2H, m,
CF3OCH2); 4.47–4.53 (2H, m, CF3OCH2CH2); 6.57 (1H,
dd, J ¼ 3:2 and 1.7 Hz, 4-furyl-H); 7.03 (1H, d, J ¼ 3:3 Hz,
3-furyl-H); 7.42 (1H, s, =CH); 7.61 (1H, d, J ¼ 1:7 Hz, 5-
furyl-H). 19F NMR d (ppm): À57.5 (s, =C-OCF3); À61.7 (s,
CH2OCF3). 13C NMR d (ppm): 62.8 (C(O)OCH2); 64.8 (q,

166
J.-C. Blazejewski et al. / Journal of Fluorine Chemistry 117 (2002) 161–166
[3] G.A. Olah, T. Yamamoto, T. Hashimoto, J.G. Shilh, N. Trivedi,
B.P. Singh, M. Piteau, J.A. Olah, J. Am. Chem. Soc. 109 (1987)
3708.
ether: 60/40). The fraction with Rf 0.45 (160 mg) was collected
and stirred for 12 h with methyl iodide (1 ml). Triethylamine
(5 ml) was then added and the mixture was stirred for addi-
tional 12 h. After concentration, the residue was purified by
TLC (SiO2, pentane/diethylether: 90/10) to give 30 mg
(0.11 mmol, 3%) of 2-trifluoromethoxyethyl 2-trifluoro-
methoxyacrylate 8f as an oil. HRMS Found: 269.0256.
[4] E. Castagnetti, M. Schlosser, Chem. Eur. J. 8 (2002) 799.
[5] I. Ben-David, D. Rechavi, E. Mishani, S. Rozen, J. Fluorine Chem.
97 (1999) 75.
[6] M.A. McClinton, D.A. McClinton, Tetrahedron 48 (1992) 6555.
[7] L.M. Yagupol’skii, A.N. Alekseenko, A.Ya. Il’chenko, Ukr. Khim.
Zh. 44 (1978) 1057.
1
C7H7F6O4 requires: 269.0249. H NMR d (ppm): 4.21–4.26
[8] P.E. Aldrich, W.A. Sheppard, J. Org. Chem. 29 (1964) 1717.
[9] J. Kollonitsch, S. Marburg, L.M. Perkins, J. Org. Chem. 41 (1976)
3107.
(2H, m, CF3OCH2); 4.46–4.51 (2H, m, CF3OCH2CH2); 5.74
(1H, dq, JHH ¼ 2:6, JHF ¼ 1:3 Hz, =CHa); 6.23 (1H, dq,
JHH ¼ 2:6, JHF ¼ 1:3 Hz, =CHb). 19F NMR d (ppm):
À59.5 (s, =C–OCF3); À61.7 (s, CH2OCF3). 13C NMR d
(ppm): 63.0 (C(O)OCH2); 64.5 (q, JCF ¼ 3:4 Hz, CF3OCH2);
121.9 (q, JCF ¼ 259 Hz, CF3); 123.2 (q, JCF ¼ 255 Hz, CF3);
114.7 (q, JCF ¼ 1:1 Hz, =CH2); 142.3 (q, JCF ¼ 1:7 Hz, =C–
[10] S.C. Sondej, J.A. Katzenellenbogen, J. Org. Chem. 51 (1986)
3508.
[11] K. Kanie, Y. Tanaka, K. Suzuki, M. Kuroboshi, T. Hiyama, Bull.
Chem. Soc. Jpn. 73 (2000) 471.
[12] J.-C. Blazejewski, E. Anselmi, C. Wakselman, J. Org. Chem. 66
(2001) 1061.
OCF3); 160.3 (C=O). IR (CCl4) 1751; 1639 cmÀ1
.
[13] J.-C. Blazejewski, J.W. Hofstraat, C. Lequesne, C. Wakselman, U.E.
Wiersum, J. Fluorine Chem. 97 (1999) 191.
[14] H.J. Carlsen, T. Katsuki, V.S. Martin, K.B. Sharpless, J. Org. Chem.
46 (1981) 3936.
¨
[15] M. Tromel, M. Russ, Angew. Chem. Int. 26 (1987) 1007.
Acknowledgements
[16] E. Anselmi, J.-C. Blazejewski, C. Wakselman, J. Fluorine Chem. 107
(2001) 315.
This work enters in the frame of the European TMR
programme ERB FMRX-CT970120, entitled ‘‘Fluorine As a
Unique Tool for Engineering Molecular Properties’’.
[17] H. Molines, M.H. Massoudi, D. Cantacuzene, C. Wakselman,
Synthesis (1983) 322.
[18] J.T. Welch, K. Seper, S. Eswarakrishnam, J. Sapartino, J. Org. Chem.
49 (1984) 4720.
[19] M. Schlosser, T. Jenny, Y. Guggisberg, Synlett (1990) 704.
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Batsanov, J.A.K. Howard, J. Chem. Soc., Perkin Trans. 1 (2000)
1639.
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