Heck reaction with ethyl (E)- and (Z)-3-fluoropropenoate

Article abstract of DOI:10.1016/j.jfluchem.2016.07.009

The use of monofluoro alkene substrates in the Heck reaction is relatively unknown. The reaction between ethyl E-3-fluoropropenoate or ethyl Z-3-fluoropropenoate with iodobenzene and palladium acetate produces only ethyl 3-fluoropropenoate (Z-6). Some los

Full text of DOI:10.1016/j.jfluchem.2016.07.009

Journal of Fluorine Chemistry 189 (2016) 68–69
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Journal of Fluorine Chemistry
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Short Communication
Heck reaction with ethyl (E)- and (Z)-3-fluoropropenoate
Timothy B. Patrick*, Angela A. Blay
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:
Received 2 May 2016
Received in revised form 8 July 2016
Accepted 18 July 2016
The use of monofluoro alkene substrates in the Heck reaction is relatively unknown. The reaction
between ethyl E-3-fluoropropenoate or ethyl Z-3-fluoropropenoate with iodobenzene and palladium
acetate produces only ethyl 3-fluoropropenoate (Z-6). Some loss of fluorine occurs from the E isomer.
ã 2016 Elsevier B.V. All rights reserved.
Available online 19 July 2016
Keywords:
Heck reaction
Palladium coupling
Fluorocinnamates
1. Introduction
fluoropropenoates, 4 and 5. The results of this study provide a
unique result in that in each case only the Z-6 isomer is obtained.
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 conditions [3],
very little is known about the use of mono-fluorinated alkene
substrates. In 1991 Heitz and Knebelkamp reported that palladi-
um-catalyzed coupling of aryl iodides with 1,1-difluoroethene
showed coupling accompanied mostly by loss of a fluorine atom
Also the fluorinated compound is very reactive. Usually fluorinated
substrates are very unreactive in the Heck reaction [8].
ꢀ
Arylation of Z-4 proceeds readily at 90 to give substitution at
the 3-position and retention of the stereochemistry. A very small
amount of material found was thought to come from arylation at
the 2-position (less than 1%).
[4]. Ichikawa reported in 2006 several intramolecular cyclizations
of 1,1-diflluoroalkenes with palladium catalysis to also give
products with loss of a fluorine atom [5].
Arylation of E-5 proceeds regioselectively at the 3-position. The
alkene stereochemistry is inverted in the product which again is Z-
2. Results and discussion
6
without formation of the E isomer. Product 7 is formed with loss
Earlier we reported that the Heck reaction with 3-fluorobute-
none (1) occurred easily to give the Z- arylated ketone (3) without
loss of fluorine [6].
of a fluorine atom.
Control experiments showed that neither Z-4 nor E-5 were
interconverted during the procedure. The same results were
In 2011 we described the preparation of the fluoropropenoates
Z-4 and E-5, along with their behavior in 3 + 2 cycloaddition
reactions [7]. We now extend our Heck procedure to the E- and Z-3-
ꢀ
ꢀ
obtained at 50 C and 90 C. It is possible that the catalyst system
causes the isomerization. The commonly accepted mechanism for
the Heck reaction requires a syn elimination of HPdL from the
intermediates trans-A and/or -B shown below [8,9]. Only cis-B can
give the product observed (Z-6) for both cases, but trans-A, not - B
should be formed from Z-4. Thus the results of this Heck procedure
*
Corresponding author.
E-mail address: tpatric@siue.edu (T.B. Patrick).
http://dx.doi.org/10.1016/j.jfluchem.2016.07.009
022-1139/ã 2016 Elsevier B.V. All rights reserved.
0

T.B. Patrick, A.A. Blay / Journal of Fluorine Chemistry 189 (2016) 68–69
69
with fluorinated substrates E-5 and Z-4 are unique in that only Z-6
is observed and that the fluorinated substrate is very reactive.
over anhydrous Na
2
SO
4
. The residue formed after evaporation of
the ether was chromatographed on 200–425 mesh silica gel
eluting with a n-hexane/ethyl acetate mixture. Unreacted starting
material was obtained at higher temperatures.
3
.3. Analytical data for Heck reaction products
3
.3.1. Ethyl Z-3-fluoro-3-phenylpropenoate (Z-6). (from Z-4)
Eluted with 9:1 hexane:ethyl acetate as a yellow liquid. 48%
1
yield. H NMR (CDCl
3
, TMS)
3
d 1.24 (t, 3H, CH , JHH = 4 Hz), 4.10, 4.10
3
. Experimental procedure
(
(
q, 2H, CH
m, 5H, aromatic); C NMR
2
, JHH = 7 Hz), 6.25 (d, H, CH, JHH = 3 Hz, JHF = 15 Hz), 7.19
13
d
14.6 (s, CH
3
), 60.8 (s, CH
2
), 83.5 (CH, d,
O);
3.1. Preparations of ethyl Z-3-fluoropropenoate (Z-4) and E-3-
J = 5 Hz), 118.4 (CF, d, J = 5 Hz), 130.4-144.5 aromatic, 166.5 (C
¼
fluoropropenoate (E-5)
1
9
F NMR (CFCl
From E-5. Use of the E isomer in the procedure gave Z-6.
Ethyl cinnamate (7) was identified by comparison to an
3
)
d
ꢁ70.1.
The preparations of ethyl Z-3-fluoropropenoate (Z-4) and E-3-
fluoropropenoate (E-5) have been reported previously [7].
authentic sample prepared by the Heck procedure.
3.2. General procedure for the palladium (II)-catalyzed heck reaction
References
Iodobenzene (2), ester Z-4 or E-5, triethylamine, palladium (II)
acetate, triphenylphosphine, and dimethyl formamide were
weighed into a 10 ml round-bottomed vial in the ratio 1 mol:
[
[
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, Liebscher, Chem. Rev. 133 (2007) 133.
3
mol: 3 mol: 0.05 mol: 0.1 mol, respectively. The vial was equipped
4] W. Heitz, A. Knebelkamp, Makromol. Chem. Rapid Commun. 12 (1991) 69.
5] J. Ichikawa, K. Sakoda, J. Mihara, N. Ito, J. Fluorine Chem. 127 (2006) 489.
with a triangular magnetic spinning bar and sealed with a screw
ꢀ
cap. The reaction mixture was heated for 20 h at 90 C (oil bath
[6] T.B. Patrick, K. Gorrell, J. Rogers, J. Fluorine Chem. 128 (2007) 710.
[
[
[
7] T.B. Patrick, J. Neumann, A. Tatro, J. Fluorine Chem 132 (2011) 779.
8] H.A. Dieck, R.F. Heck, J. Am. Chem. Soc. 96 (1974) 1133.
9] C. Amatore, A. Jutland, Acc. Chem. Res. 33 (2000) 314.
temperature), allowed to cool and then extracted with diethyl
ether/water (30:70). The organic layer was washed with saturated
3
NaHCO , saturated NaCl, and several portions of water, and dried