Heck reaction with 3-fluoro-3-buten-2-one

Article abstract of DOI:10.1016/j.jfluchem.2008.02.006

3-Fluoro-3-buten-2-one (2) is readily prepared from 1-fluoro-1-chloro-2-methoxy-2-methylcyclopropane (1) in 82% yield by heating the cyclopropane in aqueous quinoline solution. Ketone 2 reacts with aryl iodides (3) in a Heck reaction catalyzed by Pd(OAc)₂ to give Z-3-fluorobenzalacetones (4) in 36-86% yield.

Full text of DOI:10.1016/j.jfluchem.2008.02.006

Journal of Fluorine Chemistry 129 (2008) 983–985
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Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Heck reaction with 3-fluoro-3-buten-2-one
*
Timothy B. Patrick , Titus Y. Agboka, Keith Gorrell
Department of Chemistry, Southern Illinois University, Edwardsville, IL 62026 USA
A R T I C L E I N F O
A B S T R A C T
Article history:
3-Fluoro-3-buten-2-one (2) is readily prepared from 1-fluoro-1-chloro-2-methoxy-2-methylcyclopro-
pane (1) in 82% yield by heating the cyclopropane in aqueous quinoline solution. Ketone 2 reacts with aryl
iodides (3) in a Heck reaction catalyzed by Pd(OAc)2 to give Z-3-fluorobenzalacetones (4) in 36–86% yield.
ß 2008 Elsevier B.V. All rights reserved.
Received 30 January 2008
Received in revised form 20 February 2008
Accepted 25 February 2008
Available online 4 March 2008
Keywords:
Heck reaction
Fluorovinyl ketone
Palladium coupling
Fluorobenzalacetone
1. Introduction
Our interest in new fluorinated intermediates for use in
synthetic chemistry led us to develop a Heck procedure with, 3-
The Heck reaction holds a prominent position among the
palladium-catalyzed carbon–carbon bond forming reactions [1,2].
Although a vast amount of information is available for the Heck
reactions with regard to substrates and reaction condition [3], very
little is known about the use of fluorinated alkene substrates. In
1991, Heitz and Knebelkamp reported that palladium-catalyzed
coupling of aryl iodides with 1,1-difluoroethene showed coupling
accompanied mostly by loss of a fluorine atom [4]. Ichikawa et al.
reported in 2006 several intramolecular cyclizations of 1,1-
diflluoroalkenes with palladium catalysis to also gave products
with loss of a fluorine atom [5].
fluoro-3-buten-2-one (2), a fluorinated analog of methyl vinyl
ketone. Ketone 2 was previously prepared by Schlosser and co-
workers [7] in 50% yield by heating 1 in water. We improved the
preparation of the 2 from the cyclopropane 1, by heating 1 in a
solution of quinoline and water to produce 2 in 82%. The ketone
distils from the reaction in 82% yield and high purity. If water is not
added to the solution 2-fluoro-3-methoxy-1,3-butadiene is formed
in 85% yield [8].
2. Results and discussion
In 2003, Cacchi et al. reported that coupling reactions of methyl
vinyl ketone with aryl iodides gave good yields of the Heck product
accompanied by small amounts of a conjugate addition product [6].
When the ketone 2 is subjected to palladium-catalyzed Heck
coupling with several aryl iodides (3), new Z-3-fluorobenzalace-
tones (4) are obtained in high yields with the Z-configuration as
determined from NMR coupling constants, J = 36–39 Hz. No
evidence is found for the presence of conjugate addition products
or E isomers.
* Corresponding author. Tel.: +1 618 650 3582; fax: +1 618 650 3556.
E-mail address: tpatric@siue.edu (T.B. Patrick).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.02.006

984
T.B. Patrick et al. / Journal of Fluorine Chemistry 129 (2008) 983–985
Table 1
Heck reaction products from 2
ArI (3)
% 4
86
dF, J (Hz)
ArI (3)
% 4
73
dF, J (Hz)
À123.9 (33.9)
À126.8 (36.7)
51
78
À124.4 (35.4)
À123.8 (36.7)
82
75
À125.6 (37.7)
À123.7 (33.6)
62
À125.2 (36.6)
44
36
À124.0 (36.4)
59(s), 70(d)
À124.0 (36.7), À123.0 (36.3)
À124.2 (36.3)
Single (s) addition and double (d). Each compound is contaminated with about 1% of the other compound.
Our reactions used Pd(OAc)2 in DMF solution with triphenyl-
phosphine as the ligand and triethylamine as the base. The results
are presented in Table 1.
3. Experimental procedure
3.1. Preparation of 3-fluoro-3-buten-2-one (2)
A mixture of 1-chloro-1-fluoro-2-methoxy-2-methylcylopro-
pane (4 g, 0.029 mol), water (6.32 g), quinoline (6.32 g) and
hydroquinone (4–5 crystals) was heated in an oil bath (80 8C)
for 6 h. The reaction mixture was allowed to cool to room
temperature and then distilled under reduced pressure. The
receivers were cooled in dry ice-acetone. 3-Fluoro-3-buten-2-
one (2) was obtained as a clear colorless liquid (2.07 g, 82%). Three
crystals of hydroquinone were added to the distilled 3-fluorobut-
3-en-2-one and stored in the refrigerator until used in Heck
reaction. H NMR (CDCl3, TMS) d 2.4 (d, J = 1.5 Hz, 3H, CH3), d 5.30
(m, 2H, vinyl; 19F NMR (CFCl3) d À116.2 (m)
The trans relationship between the aryl and acyl groups
observed in the Heck reaction with methyl vinyl ketone is still
observed in the configuration of 4. The required syn elimination [9]
in the intermediate A below to give Z-4 must show little steric
interaction between the aryl group and the fluorine atom.
3.2. General procedure for the palladium (II)-catalyzed Heck reaction
Aryl halide (3), 3-fluoro-3-buten-2-one (2), triethylamine,
palladium (II) acetate, triphenylphosphine, and dimethyl forma-
mide (5 ml) were weighed into a 10 ml round-bottomed vial in the
ratio 1:3:3:0.05:0.1 mol, respectively. The vial was equipped with
a triangular magnetic spinning bar and sealed with a screw cap.
The reaction mixture was heated for 20 h at 90 8C (oil bath
temperature), allowed to cool and then extracted with diethyl
ether/water (30:70). The organic layer was washed with saturated
NaHCO3, saturated NaCl and several portions of 15% hydrochloric
acid solution, and dried over anhydrous Na2SO4. The residue
In conclusion, we have shown that 3-fluoro-3-buten-2-one (2)
can be readily prepared and reacted smoothly in Heck reactions
with aryl iodides to give Z-3-fluorobenzalacetones (4) in good yield
with Z stereoselectivity. Neither conjugate addition nor fluoride
elimination was observed. This is possibly the first reported Heck
reaction of a simple fluorinated alkene.

T.B. Patrick et al. / Journal of Fluorine Chemistry 129 (2008) 983–985
985
J = 36.7), 7.4–8.0 (m 9H, arom); 13C NMR (CDCl3, TMS) d 25 (s,
CH3), d 115 (s, CH), 130–143 (m, arom), 153.0 (d, CF, J = 288 Hz),
192 (d, C O). Anal. calcd for C16H13FO: C, 79.98, H, 5.45, F, 7.91.
Found, C, 80.11, H, 5.56, F, 8.00.
formed after evaporation of the ether was chromatographed on
200–425 mesh silica gel eluting with a n-hexane/ethyl acetate
mixture.
(Z)-4-(3-Trifluoromethylphenyl)-3-fluoro-3-buten-2-one (4g):
1H NMR (CDCl3, TMS) d 2.2 (s, 3H, CH3), 6.8 (d, 1H, J = 35.4 Hz),
7.2–7.6 (m, 4H, arom); 13C NMR (CDCl3, TMS) d 26 (s, CH3), 119
(s, CH), 127–141 (m, arom and CF3), 154 (d, CF, J = 294.3 Hz),
193 (d, C O); 19F NMR (CDCL3, CFCl3) d À64.0 (CF3). Anal. calcd
for C11H8F4O: C, 56.90, H, 3.47, F 32.73. Found, C, 56.86, H, 3.35,
F, 32.88.
(Z)-4-(1-H-indol-5-yl)-3-fluoro-3-buten-2-one (4h): mp 57–
59; 1H NMR (CDCl3, TMS) d 2.4 (s, 3H, CH3), d 6.6 (m), 7.0 (d, CH,
J = 36.7 Hz), d 7.4–8.0 (m, 5H, arom), 8.4 (br, H–N); 13C NMR
(CDCl3, TMS) d 26 (s, CH3), 120 (CH), 104, 112, 118, 125, 128,
137 (arom), d 153 (d, CF, J = 256.4 Hz), d 192.68 (d, C O). Anal.
calcd for C12H10FNO: C, 70.93, H, 4.96, F, 9.35. Found, C, 70.66,
H, 5.12, F, 9.55.
3.3. Analytical data for Heck reaction products, 4
F NMR data are given in Table 1 (CFCl3).
(Z)-4-Phenyl-3-fluoro-3-buen-2-one (4a): 1H NMR (CDCl3,
TMS) d 2.4 (s, 3H, CH3), 6.8 (d, 1H, J = 33.9 Hz), 7.5 (m, 5H,
arom); 13C NMR (CDCl3, TMS) d 25 (s, CH3), 115 (s, CH), 128–
132 (m, arom), 154 (d, CF, J = 301.8 Hz), 192.4 (d, C O). Anal.
calcd for C10H9FO: C, 73.16, H, 5.53, F, 11.57. Found, C, 73.00, H,
5.67, F, 11.34.
(Z)-4-(2-Methoxyphenyl)-3-fluoro-3-buten-2-one (4b): 1H
NMR (CDCl3, TMS) d 2.4 (s, 3H, CH3), 3.9 (s, 3H, OCH3), 7.0
(d, 1, CH, J = 37.7 Hz)), 7.4–7.9 (m, 4H, arom); 13C NMR (CDCl3,
TMS) d 25 (s, CH3), 56 (s, O-CH3), 120 (s, CH), 125–130 (arom),
154.0 (d, CF, J = 301 Hz), 192 (d,
11H11FO2: C, 68.03, H, 5.71, F, 9.87. Found, C, 68.12, H, 5.45,
F, 9.79.
(Z)-4-(4-Methylphenyl)-3-fluoro-3-buten-2-one (4c): 1H NMR
(CDCl3, TMS) d 2.2 (s, 3H, CH3), 2.5 (s, 3H, Ph-CH3), 6.8 (d, 1H,
J = 33.6 Hz), 7.2–7.7 (m, 5H, arom); 13C NMR (CDCl3, TMS) d 21
(s, CH3), 26 (s, CH3), 116 (s, CH), 127–141 (m, arom), 154 (d, CF,
J = 294.3 Hz), 193 (d, C O). Anal. calcd for C11H11FO: C, 74.14,
H, 6.22, F, 10.66. Found, C, 74.15, H, 6.35, F, 10.39.
(Z)-4-(4-Chlorophenyl)-3-fluoro-3-buten-2-one (4d): 1H NMR
(CDCl3, TMS) d 2.2 (s, 3H, CH3), 6.8 (d, 1H, J = 36.6 Hz), 7.2–7.6
(m, 4H, arom); 13C NMR (CDCl3, TMS) d 26 (s, CH3), 116 (s, CH),
127–141 (m, arom), 154 (d, CF, J = 294.3 Hz), 193 (d, C O).
Anal. calcd for C10H8ClFO: C, 60.47, H, 4.06, F, 4.57. Found, C,
60.55, H, 4.24, F, 4.50.
C
O). Anal. calcd for
(Z)-3-Fluoro-4-(1-naphthyl)-3-fluoro-3-buten-one (4i): mp
66–67, 1H NMR (CDCl3, TMS) d 2.3 (s, 3H, CH3), 6.8 (d, 1H,
J = 36.4)), 7.2–7.6 (m, 7H, arom); 13C NMR (CDCl3, TMS) d 25 (s,
CH3), 119.6 (s, CH), 125–133 (m, arom), 153.0 (d, CF,
J = 290 Hz), 194 (d, C O). Anal. calcd for C14H11FO: C, 78.49,
H, 5.18, F, 8.87. Found, C, 78.19, H, 5.37, F, 9.04.
C
(Z)-3-Fluoro-4-(9-phenanthryl)-3-fluoro-3-buten-one
(4j):
mp 79–82, 1H NMR (CDCl3, TMS) d 2.3 (s, 3H, CH3), 6.76 (d,
1H, J = 36.3 Hz), 7.4–7.8 (m, 9H, arom); 13C NMR (CDCl3, TMS) d
25 (s, CH3), 120 (s, CH), 122–138 (m, arom), 153.0 (d, CF,
J = 299 Hz), 192 (d, C O). Anal. calcd for C18H13FO: C, 81.80, H,
4.96, F, 7.19. Found, C, 81.83, H, 4.77, F, 7.32.
Acknowledgment
(Z)-4-(4-Iodophenyl)-3-fluoro-3-but-2-one (4es): 1H NMR
(CDCl3, TMS) d 2.4 (s, 3H, CH3), 6.8 (d, CH, J = 36.7 Hz), 7.4–
7.6 (m, 4H, arom); 13C NMR (CDCl3, TMS) d 26 (s, CH3), 116 (s,
CH), 127–141 (m, arom), 154 (d, CF, J = 305.4 Hz) 193 (d, C O).
Anal. calcd for C10H8FIO: C, 41.41, H, 2.78, F, 6.55. Found, C,
41.70, H, 2.58, F, 6.56.
This research was funded by the National Science Foundation
RUI program.
References
(Z,Z)-1,4-bis(3-fluoro-3-buten-2-one)benzene (4ed): 1H NMR
(CDCl3, TMS) d 2.5 (s, 6H, 2CH3), 6.8 (d, 2H, J = 36.3 Hz), 7.8–7.6
(m, 4H, arom); 13C NMR (CDCl3, TMS) d 26 (s, 2CH3), d 115 (s,
CH), 128–132 (m, arom), 154 (d, CF, J = 271.7 Hz), 193 (d, C O).
Anal. calcd for C14H12F2O2: C, 67.20, H, 4.83, F, 15.18. Found, C,
67.02, H, 4.77, F, 15.33.
[1] A. de Meijere, F.E. Meyer, Angew. Chem. Int. Ed. Engl. 33 (1994) 2379.
[2] R.F. Heck, in: B.M. Trost (Ed.), Comprehensive Organic Synthesis, vol. 4, Pergamon,
New York, 1991.
[3] L. Yin, J. Liebscher, Chem. Rev. 133 (2007) 133.
[4] W. Heitz, A. Knebelkamp, Makromolekulare Chemie, Rapid Commun. 12 (1991) 69.
[5] J. Ichikawa, K. Sakoda, J. Mihara, N. Ito, J. Fluorine Chem. 127 (2006) 489.
[6] S. Cacchi, G. Farizi, H. Goggiamani, Arkovoc xiii (2003) 58.
[7] Y. Bessiere, D.N.H. Savary, M. Schlosser, Helv. Chim. Acta 173 (1977) 1739.
[8] T.B. Patrick, K. Gorrell, J. Rogers, J. Fluorine Chem. 128 (2007) 710.
[9] H.A. Dieck, R.F. Heck, J. Am. Chem. Soc. 96 (1974) 1133.
(Z)-3-Fluoro-4-(2-biphenyl)-3-fluoro-3-buten-one (4f): mp
44–47, 1H NMR (CDCl3, TMS) d 2.3 (s, 3H, CH3), 6.8 (d, 1H,