A novel method for the synthesis of aromatic E-β-chlorovinylketones

Article abstract of DOI:10.1016/S0040-4039(00)00702-4

The reaction of aromatic acetylenic ketones with aqueous HCl promoted by catalytic FeSO₄ gave a E,Zmixture of β-chlorovinylketones which isomerized almost exclusively to the E-β-isomer upon heating. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00702-4

Tetrahedron Letters 41 (2000) 4709±4711
A novel method for the synthesis of aromatic
E-b-chlorovinylketones
Jose Juan Conde,a,* Michael Martuccia and Mark Olsenb
aDepartment of Synthetic Chemistry, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road,
PO Box 1539, King of Prussia, PA 19406, USA
bAnalytical Sciences, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, PO Box 1539, King of Prussia,
PA 19406, USA
Received 31 March 2000; revised 14 April 2000; accepted 17 April 2000
Abstract
The reaction of aromatic acetylenic ketones with aqueous HCl promoted by catalytic FeSO4 gave a
E,Zmixture of b-chlorovinylketones which isomerized almost exclusively to the E-b-isomer upon heating
# 2000 Elsevier Science Ltd. All rights reserved.
b-Chlorovinylketones have proved to be versatile and valuable materials in organic synthesis.1
The synthesis of b-chlorovinylketones has been performed under a diversity of conditions2
although a mixture of E and Z isomers is often obtained. Recent methods have used LiCl for the
preparation of such compounds but the yields were poor and the selectivity low.2d Gaseous HCl
is also known to a€ord E or Z-chlorovinylketones depending on the reaction temperature.2e
We report herein a novel and cost e€ective method for the preparation of aromatic b-chloro-
vinylketones from terminal acetylenic ketones that were readily prepared from the corresponding
acid chlorides.3 Thus the reaction of aromatic acetylenic ketones (Eq. (1)) with aqueous HCl in
the presence of a catalytic amount of FeSO4 in acetic acid as solvent a€orded the corresponding
mixture of E,Z-chlorovinylketones which was easily converted by heating the reaction mixture for
several hours, exclusively to the E-isomer 3 (Table 1). We have observed that prior to heating, the
Z-isomer 2 was the major product formed along with a small amount of 3 which is the thermo-
dynamically more stable compound.2e
ꢀ1†
* Corresponding author.
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00702-4

4710
Table 1
Preparation of E,b-chlorovinylketones 3a±g
A variety of acetylenic ketones were submitted to these reaction conditions and the results are
summarized in Table 1. While aromatic ketones gave satisfactory results, substrates with aliphatic R
groups showed little or no formation of the desired product. When R=Cl-(CH2)4 (entry 3g), the
reaction proceeded at 80ꢁC for 24 h to yield a mixture of isomers which did not undergo isomerization.
When the substates depicted in Table 1 were treated with aqueous HCl (1N) in AcOH in the
absence of FeSO4 no reaction took place which suggests that Fe(II) coordinates with the carbonyl
group and/or the triple bond activating the alkyno ketones. On the other hand, equimolecular or
excess amount of Fe(II) increased the rate of the reaction.
Typical preparation of ꢀ-E-chlorovinylketones: to a stirring solution of acetylenic ketone (Table 1)
in acetic acid was added 1.1 equivalents of aqueous HCl (1N) at room temperature followed by 0.1
equiv. of FeSO4. The reaction mixture was then heated (see conditions; Table 1) for several hours.
When completed, water was added followed by EtOAc at ambient temperature. The organic layer
was separated and washed with H2O. After drying over MgSO4, the solution was concentrated
under vacuum to give a residue which was puri®ed by ¯ash chromatography (EtOAc:hexane, 1:10).4
In conclusion, we have described an ecient and cost e€ective method for the synthesis of
aromatic b-chlorovinylketones from the acetylenic precursors.
Acknowledgements
We thank Dr. Andrew Allen for 400 MHz 1H NMR measurements.
References
1. (a) Pohland, A.; Benson, W. Chem. Rev. 1966, 66, 161. (b) Corey, E. J.; Beames, B. J. Am. Chem. Soc. 1972, 94,
7210. (c) Bhalero, T.; Devalla, S. Synth. Commun. 1993, 23, 2213.

4711
2. (a) Taniguchi, M.; Kobayashi, S.; Nakagawa, M.; Hino, T. Tetrahedron Lett. 1986, 27, 4763. (b) Fujisawa, T.;
Tanaka, A.; Ukaji, Y. Chem. Lett. 1989, 1255. (c) Price, C.; Pappalardo, J. J. Am. Chem. Soc. 1950, 2613. (d) Ma,
S.; Lu, X.; Li, Z. J. Org. Chem. 1992, 57, 709. (e) Calalchi, B.; Landini, D.; Montanari, F. J. Chem. Soc. C 1969,
1204.
3. Karpf, M.; Huguet, J.; Dreiding, A. Helv. Chim. Acta 1982, 65, 13.
4. All compounds were characterized by spectroscopic and analytical methods.