ORGANIC
LETTERS
1999
Vol. 1, No. 10
1539-1541
Thia-Wittig-like Reactions as a New
Route for the Stereoselective Synthesis
of (Z)-Fluoroalkenoates
David Chevrie, Thierry Lequeux,* and Jean-Claude Pommelet*
Laboratoire de Chimie Mole´culaire et Thio-organique, UMR CNRS 6507,
UniVersite´ de Caen-ISMRA, 6 BouleVard du Mare´chal Juin,
14050 Caen Cedex, France
Received July 21, 1999
ABSTRACT
Stereoselective syntheses of (Z)-fluoroalkenoates 3a−g have been developed in three steps from the readily available fluorosulfide 5 and
aldehydes. This preparation, involving a Durst reaction, was highly stereoselective and led to fluoroalkenes in 50−60% overall yields, without
purification of intermediates.
It is well-established that the replacement of hydrogen atoms
of organic molecules by fluorine atoms strongly modifies
their chemical, physical, and biological properties. Several
applications reported the enhancement of the half-life of
drugs due to the high stability of the carbon-fluorine bond
or the synthesis of suicide inhibitors induced by the elimina-
tion of fluorine atom during the metabolization process.1
Toward this goal, the fluorovinylic moiety has been intro-
duced in various bioactive compounds such as sex phero-
mones, ribonucleotides, or retinal analogues.2
on concerted elimination of â-mesyloxy sulfoxides afforded
(E)-fluoroalkenes with moderate selectivity.4 Concerning the
preparation of the Z isomer, the most elegant and direct
approach consisted of alkylating the ethyl phenylsulfinyl
fluoroacetate to produce exclusively (Z)-fluoropropenoates
by a stereoselective elimination of sulfenic acid.5 On the other
hand, a phenylselenenyl fluoride equivalent has been used
to produce (Z)-fluoroalkenoates from diazoesters.6 Few
methods have reported the selective synthesis of (Z)-
fluoroalkenoates from aldehydes. The most efficient are the
zinc-copper chloride promoted reaction of methyl difluo-
roacetate with carbonyl compounds,7 the Peterson olefination
involving aldehydes and R-fluoro-R-silyl acetate as a starting
building block,8 and the transformation of fluorinated sym-
The widely used strategy to build (E)-fluoroalkenoates
from aldehydes is the Horner-Wadsworth-Emmons reac-
tion (HWE), involving the commercially available triethyl
2-fluoro-2-phosphonoacetate.3 Alternative approaches based
(1) Welch, J. T. Tetrahedron 1987, 43, 3123-3197.
(2) Camps, F.; Coll, J.; Fabrias, G.; Guerrero, A. Tetrahedron 1984, 40,
2871-2878. McCarthy, J. R.; Matthews, D. P.; Stemerick, D. M.; Huber,
E. W.; Bey, P.; Lippert, B. J.; Snyder, R. D.; Sunkara, P. S. J. Am. Chem.
Soc. 1991, 113, 7339-7440. Francesh, A.; Alvarez, R.; Lopez, S.; de Lera,
A. R. J. Org. Chem. 1997, 62, 310-319.
(3) Burton, D. J.; Yang, Z. Y.; Qui, W. Chem. ReV. 1996, 96, 1641-
1715. Sano, S.; Ando, T.; Yokoyama, K.; Nagao, Y. Synlett 1998, 777-
779.
(4) Satoh, T.; Itoh, N.; Onda, K.; Kitoh, Y.; Yamakawa, K. Tetrahedron
Lett. 1992, 33, 1483-1484.
(5) Allmendinger, T. Tetrahedron 1991, 47, 4905-4914.
(6) Usuki, Y.; Iwaoka, M.; Tomoda, S. J. Chem. Soc., Chem. Commun.
1992, 1148-1150.
(7) Ishihara, T.; Kuroboshi, M. Chem. Lett. 1987, 1145-1148.
(8) Welch, J. T.; Lin, J. Tetrahedron Lett. 1998, 39, 9613-9616.
(9) Ishihara, T.; Shintani, A.; Yamanaka, H. Tetrahedron Lett. 1998, 39,
4865-4868.
10.1021/ol990178u CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/17/1999