Preparation of 4-trifluoroethylidene-1,3-dioxolane derivatives via new stable (trifluoromethyl)ethynylation reagent

Article abstract of DOI:10.1016/S0040-4039(03)01779-9

Perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolane derivatives 2a-q were prepared in excellent yields from the reaction of new stable (trifluoromethyl)ethynylation reagent 1a with 1.3 equiv. of TBAF at -15°C for 10 min, followed by treatment with 2 equiv. of phenyl perfluoroalkylated ketone derivatives at room temperature. The reaction of 1a with 1.3 equiv. of TBAF, followed by treatment with 1 equiv. of aldehyde or ketone at -15°C for 10 min and then with trifluoroacetophenone (1 equiv.) at room temperature afforded perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolane derivatives 2t-u in moderate yields.

Full text of DOI:10.1016/S0040-4039(03)01779-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7213–7216
Preparation of 4-trifluoroethylidene-1,3-dioxolane derivatives via
new stable (trifluoromethyl)ethynylation reagent
a,
a
b
In Howa Jeong, * Sung Lan Jeon and Bum Tae Kim
a
Department of Chemistry, Yonsei University, Wonju, South Korea
b
Korea Research Institute of Chemical Technology, Daejeon, South Korea
Received 18 June 2003; revised 18 July 2003; accepted 18 July 2003
Abstract—Perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolane derivatives 2a–q were prepared in excellent yields from the
reaction of new stable (trifluoromethyl)ethynylation reagent 1a with 1.3 equiv. of TBAF at −15°C for 10 min, followed by
treatment with 2 equiv. of phenyl perfluoroalkylated ketone derivatives at room temperature. The reaction of 1a with 1.3 equiv.
of TBAF, followed by treatment with 1 equiv. of aldehyde or ketone at −15°C for 10 min and then with trifluoroacetophenone
(
©
1 equiv.) at room temperature afforded perfluoroalkylated 4-trifluoroethylidene-1,3-dioxolane derivatives 2t–u in moderate yields.
2003 Elsevier Ltd. All rights reserved.
In recent years, considerable effort has been paid to the
synthesis of fluorinated 1,3-dioxolane compounds
because of their application to material science. For
example, 4-trifluoroethylidene-1,3-dioxolane derivatives
their importance in material science, methodology for
the preparation of fluorinated dioxolane derivatives has
been quite limited. Generally, 4- or 5-fluorinated 1,3-
dioxolanes were prepared from the fluorination of 4- or
5-chlorinated 1,3-dioxolane which can be prepared via
1
exhibited nonlinear optical properties and 2,2-bis(trifl-
4
uoromethyl)-4,5-dichloro-4,5-difluoro-1,3-dioxolane is a
precursor to 2,2-bis(trifluoromethyl)-4,5-difluoro-1,3-
chlorination of 1,3-dioxolane. Radical addition reac-
tion of 1,3-dioxolane with perfluoro-1-alkenes in the
presence of BPO also afforded 4-fluoroalkylated 1,3-
2
dioxole which is a monomer for a new Teflon-AF
5
fluorocopolymer showing outstanding thermal and
chemical stability. Fluorinated dioxolane exocyclic
olefins are also a quite useful intermediate to give
corresponding epoxides which are useful as lubricants,
dioxolane in excellent yields. 2,2-Bis(trifluoromethyl)-
4-methylidene as an exocyclic olefin was synthesized via
dehydrobromination of 2,2-bis(trifluoromethyl)-4-bro-
momethyl-1,3-dioxolane prepared from the reaction of
3
3
curing materials, adhesives and coatings. In spite of
epibromohydrin with hexafluoroacetone. Ishihara
Scheme 1.
Keywords: (trifluoromethyl)ethynylation reagent; perfluoroalkylated 1,3-dioxolane derivatives.
*
Corresponding author. Fax: 82-33-760-2182; e-mail: jeongih@dragon.yonsei.ac.kr
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01779-9

7
214
I. H. Jeong et al. / Tetrahedron Letters 44 (2003) 7213–7216
reported that 2,5-disubstituted 4-trifluoroethylidene-
,3-dioxolanes as trifluoromethylated exocyclic olefin
can be prepared from the reaction of trifluoropropyne
ture for 1 h, afforded 2a (1:1 diasteromer ratio) in 99%
yield, while 1b and 1c provided 2a under the same
reaction conditions in 90% and 85% yields, respectively.
When the reaction of 1a with TBAF was performed at
−35°C for 10 min, followed by reaction with 2,2,2-trifl-
uoroacetophenone at room temperature for 1 h, 2a was
obtained in lower yield (80%). As was mentioned in
previous paper, intermediate A (Scheme 2) generated
from the reaction of 1a with TBAF was suggested to
have an equilibrium with N-methoxy-N-methylbenza-
mide and tetrabutylammonium trifluoropropynyl anion
which acts as a (trifluoromethyl)ethynylation reagent to
react with 2,2,2-trifluoroacetophenone. N-Methoxy-N-
methylbenzamide which is a key reagent to synthesize 1
and relatively expensive was always recovered in quan-
titative yield at the end of reaction. We also carried out
the direct reaction of 2,2,2-trifluoroacetophenone (2
equiv.) with trifluoropropynyl lithium generated from
the reaction of 2-bromotrifluoropropene with LDA at
−78°C or from the reaction of trifluoropropyne with
n-BuLi at −78°C, but desired product 2a was obtained
in only 35% yield. Tetrabutylammonium, the counter
cation of trifluoropropynyl anion, plays an important
role to afford 2a.
1
with enol silyl ether generated from aldehyde in the
6
presence of tetrabutylammoniun fluoride. Similarly,
the reaction of 2-bromotrifluoropropene with ketones
having a-hydrogen from carbonyl group in the presence
of sodium methoxide also afforded 2,2,5,5-tetra-
substituted 4-trifluoroethylidene-1,3-dioxolanes in high
10
1
yields. Although the reaction mechanisms of these two
reactions are not clear, it seems likely that generation of
enolate as an intermediate is a key step to proceed
those reactions. Therefore, aldehydes or ketones having
a-hydrogen from carbonyl group must be used to give
4-trifluoroethylidene-1,3-dioxolanes in these reactions.
To overcome this limitation and introduce perfluoro-
alkyl group on the ring, we wish to describe a novel and
efficient method for the synthesis of 4-trifluoroethyli-
dene-1,3-dioxolane derivatives via new stable (trifl-
7,8
uoromethyl)ethynylation reagent.
New stable (trifluoromethyl)ethynylation reagents 1a–c
were easily prepared in 70–94% yields from the reaction
of Weinreb amides with trifluoropropynyl lithium gen-
erated from the reaction of 2-bromotrifluoropropene
The reactions of 1a with 2,2,2-trifluoroacetophenone or
pentafluoroethyl phenyl ketone derivatives having pro-
ton, chloro, fluoro, methoxy, trifluoromethyl, vinyl and
phenoxy group on the benzene rings afforded 2a–o in
9
with LDA at −78°C, followed by quenching with
trimethylsilyl chloride (Scheme 1). The use of trifluoro-
propynyl lithium generated from the reaction of trifl-
uoropropyne with n-BuLi provided (trifluoromethyl)-
9
7–99% yields. However, the longer reaction time was
1
0
ethynylation reagent 1a in only 80% yield. This result
is different from Tipping’s work in which treatment of
an ethereal solution of the Weinreb amide with an
ethereal solution of trifluoropropynyl lithium resulted
required in reaction of 1a with ketone derivatives hav-
ing chloro, fluoro, 2-methoxy and trifluoromethyl on
the benzene ring. Trifluoromethylated ketones having
heterocyclic moieties such as a thiophene and a furan
also reacted with tetrabutylammonium trifluoropropy-
nyl anion to give the corresponding dioxolanes 2p and
1
1
in tar formation.
We examined the potential of 1a–c as (trifl-
uoromethyl)ethynylation reagent via the reaction of
2
q in 98–99% yields. When 1a was reacted with TBAF,
followed by reaction with 1,1,1-trifluoroacetone under
the same reaction condition, however, several products
which could not be identified were obtained. The treat-
ment of tetrabutylammonium trifluoropropynyl anion
with 2 equiv. aldehyde such as butanal or cyclohexan-
carbaldehyde resulted in the formation of the corre-
sponding 4-trifluoroethylidene-1,3-dioxolane derivatives
2r and 2s in 72–74% yields, while the reaction with 2
1
a–c with tetrabutylammonium fluoride (TBAF), fol-
lowed by reaction with 2,2,2-trifluoroacetophenone at
several reaction temperature to give 4-trifluoroethyli-
dene-1,3-dioxolane derivative 2a. It was found that the
reaction of 1a (1.3 equiv.) with TBAF (1.3 equiv.) in
ether at −15°C for 10 min, followed by reaction with
2,2,2-trifluoroacetophenone (2 equiv.) at room tempera-
Scheme 2.

I. H. Jeong et al. / Tetrahedron Letters 44 (2003) 7213–7216
7215
equiv. of ketones did not provide any desired products.
The experimental results of these reactions are summa-
rized in Table 1. When tetrabutylammonium trifluoro-
propynyl anion was treated with 1 equiv. of aldehyde or
ketone, followed by treatment with 1 equiv. of trifl-
uoroacetophenone, the corresponding 4-trifluoroethyli-
dene-1,3-dioxolane derivatives 2t and 2u were obtained
in 72% and 82% yields, respectively (Scheme 3).
was added and then allowed to stir for another 1 h. The
reaction mixture was extracted with ether twice. The
ether solution was dried over anhydrous MgSO and
4
chromatographed on SiO column. Elution with a mix-
2
ture of hexane and ethyl acetate (9:1) provided 0.219 g
of 2a (E:Z=1:1) in 99% yield. 2a (one isomer): mp
1
64–65°C: H NMR (CDCl ) l 7.70–7.66 (m, 4H), 7.52–
3
1
9
7.48 (m, 6H), 5.40 (q, J=7.1 Hz, 1H); F NMR
CDCl , internal standard CFCl ) l −58.64 (d, J=7.1
(
3
3
A typical reaction procedure for the preparation of 2a
is as follows. A 25 mL two-neck round bottom flask
equipped with a magnetic stirrer bar, a septum and
reflux condenser connected to an argon source was
charged with 1a (0.430 g, 1.3 mmol) and ether (5 mL)
and then cooled to −15°C. Tetrabutylammonium
fluoride (1.3 mmol, 1.0 M solution in THF) was slowly
added into flask and then the mixture was stirred for 10
min. After the reaction mixture was warmed to room
temperature, trifluoroacetophenone (0.212 g, 2.0 mmol)
Hz, 3F), −77.17 (s, 3F), −82.51 (s, 3F); MS, m/z
(relative intensity) 442 (M , 1), 373 (32), 199 (13), 171
+
(10), 151 (29), 105 (100), 77 (12); IR (KBr) 3136, 3078,
2937, 1709, 1500, 1454, 1279, 1207, 1132, 1063, 731, 698
−
1
cm . Anal. calcd for C H F O : C, 51.60; H, 2.51.
19
11
9
2
1
Found: C, 51.44; H, 2.47%. 2a (other isomer): oil: H
NMR (CDCl ) l 7.52–7.17 (m, 10H), 5.43 (q, J=7.1
Hz, 1H); F NMR (CDCl , internal standard CFCl ) l
3
19
3
3
−58.53 (d, J=7.1 Hz, 3F), −76.84 (s, 3F), −83.18 (s,
+
3F); MS, m/z (relative intensity) 442 (M , 8), 373 (44),
Table 1. Preparation of 4-trifluoroethylidene-1,3-dioxolane derivatives 2
Compound 2
R1
R2
t (h)
Yield (%)a,b
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
C H
4-F-C H
4-Cl-C H
4-CH O-C H
2-CH O-C H
4-CF -C H
3-CF -C H
1
2
2
1
3
5
5
1
1
1
1
12
2
1
1
1
1
1
99
98
97
99
99
98
98
97
99
99
99
97
98
97
98
98
99
72
74
6
5
6
4
6
4
3
6
4
4
3
6
3
6
4
4
3
6
4-CH ꢀCH-C H
2
6
4
4-C H O-C H
6
5
6
4
C F
C H
2
5
5
5
5
5
5
6
5
C F
4-CH O-C H
4-CF -C H
4
4-Cl-C H
2
3
6
4
C F
2
3
6
C F
2
6 4
C F
4-CH ꢀCH-C H
4
2
2
6
C F
2
4-C H O-C H
6
5
6
4
CF3
CF3
2-Thienyl
2-Furyl
H
C H
3
7
s
Cy
H
2
a
Isolated yield.
b
All products were obtained as a 1:1 diastereomer mixture.
Scheme 3.

7
216
I. H. Jeong et al. / Tetrahedron Letters 44 (2003) 7213–7216
1
3
1
5
99 (93), 171 (70), 151 (100), 105 (20), 77 (66); IR (KBr)
5. Cirkva, V.; Paleta, O. J. Fluorine Chem. 1999, 94, 141–
136, 3078, 2937, 1709, 1500, 1454, 1279, 1207, 1132,
156.
−
1
063, 731, 698 cm . Anal. calcd for C H F O : C,
6. Ishihara, T.; Yamasaki, Y.; Ando, T. Tetrahedron Lett.
1985, 26, 79–82.
1
9
11
9
2
1.60; H, 2.51. Found: C, 51.48; H, 2.49%.
7
8
9
. (a) Nokami, J.; Yoshizane, K.; Matsuura, H.; Sumida, S.
J. Am. Chem. Soc. 1998, 120, 6609–6610; (b) Ooi, T.;
Miura, T.; Maruoka, K. J. Am. Chem. Soc. 1998, 120,
Acknowledgements
1
0790–10791.
. (a) Billard, T.; Bruns, S.; Langlois, B. R. Org. Lett. 2000,
, 2101–2103; (b) Billard, T.; Langlois, B. R.; Blond, G.
This work was supported by grant No. R05-2003-000-
0308-0 from the Basic Research Program of the Korea
Science and Engineering Foundation.
2
1
Tetrahedron Lett. 2000, 41, 8777–8780; (c) Motherwell,
W. B.; Storey, L. J. Synlett 2002, 646–648.
. (a) Yamanaka, H.; Araki, T.; Kawabara, M.; Fukunishi,
K.; Nomura, M. Nippon Kagaku Kaishi 1986, 1321–1328;
References
(
b) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org.
Chem. 1995, 60, 6046–6056; (c) Mizutani, K.; Yamazaki,
T.; Kitazume, T. J. Chem. Soc., Chem. Commun. 1995,
1
2
3
4
. Watanabe, A.; Kono, H.; Suzuki, Y.; Sugiyama, Y.;
Mitamura, S. JP Pat. 2-226125, 1990.
. Resnick, P. R. US Pat. 3,865,845, 1975; US Pat.
51–52; (d) Katritzky, A. R.; Qi, M.; Wells, A. P. J.
Fluorine Chem. 1996, 80, 145–147.
3
,978,030, 1976.
1
0. Jeong, I. H.; Jeon, S. L.; Min, Y. K.; Kim, B. T.
Tetrahedron Lett. 2002, 43, 7171–7174.
1. Sibous, L.; Tipping, A. E. J. Fluorine Chem. 1993, 62,
39–49.
. Hung, M.-H.; Rozen, S.; Feiring, A. E.; Resnick, P. R. J.
Org. Chem. 1993, 58, 972–973.
. Hung, M.-H.; Resnick, P. R. J. Am. Chem. Soc. 1990,
1
1
12, 9671–9672.