ORGANIC
LETTERS
2006
Vol. 8, No. 20
4457-4460
Exceptionally Mild, High-Yield Synthesis
of -Fluoro Acrylates
r
Barbara Zajc* and Shivani Kake
Department of Chemistry, The City College and The City UniVersity of New York,
138th Street at ConVent AVenue, New York, New York 10031
Received July 1, 2006
ABSTRACT
Novel achiral and chiral alkyl
benzothiazol-2-ylsulfonyl)acetates. DBU-mediated condensations of these fluorinated synthons with aldehydes proceed in a facile manner at
C or at room temperature giving high yields of -fluoro acrylates. Ketones are unreactive under these conditions. The presence of fluorine
renders the synthon substantially more reactive compared to the unfluorinated analogue. Reactivity of -(1,3-benzothiazol-2-ylsulfonyl)-
fluoroacetate and the Horner Wadsworth Emmons reagent (EtO)2P(O)CHFCOOEt has also been compared.
r-(1,3-benzothiazol-2-ylsulfonyl)-r-fluoroacetates can be readily synthesized by metalation−fluorination of (1,3-
0
°
r
r
r-
−
−
R-Fluoro-R,â-unsaturated esters are useful synthetic inter-
mediates1 and key precursors to various biologically relevant
molecules.2 Several syntheses have been developed for their
preparation, such as the Wittig and Horner-Wadsworth-
Emmons reactions,3 Peterson’s olefination,4 reactions of
carbonyl compounds with alkyl esters of tert-butyl-5a,b as well
as phenylsulfinyl5c fluoroacetates and with phenylselanyl
fluoroacetate,5d as well as other methods.6
synthesis of vinyl fluorides has not received much attention.8
Recently, we have developed an efficient synthetic method
for the preparation of fluorinated 1,3-benzothiazol-2-yl
benzyl sulfones (BT-sulfones).8a Upon condensation of these
fluorinated synthons with aldehydes and ketones, high yields
of regiospecifically fluorinated stilbene and styrene deriva-
tives were formed.8a Herein, we report a simple synthesis of
alkyl R-(1,3-benzothiazol-2-ylsulfonyl)-R-fluoroacetates as
reagents for the synthesis of R-fluoro acrylates and their
reactivity in the modified Julia olefination.
The one-pot Julia olefination7 is widely used for the
introduction of unsaturation; however, its use for the
At the onset, we decided to synthesize the tert-butyl ester
derivative because of its lower sensitivity toward hydrolysis.
tert-Butyl bromoacetate was allowed to react with the sodium
salt of 2-mercapto-1,3-benzothiazole, and the resulting sulfide
(1) (a) Fluorine-Containing Synthons; Soloshonok, V. A., Ed.; American
Chemical Society: Washington, DC, 2005. (b) Also see: Special Issue on
Fluorinated Synthons. J. Fluorine Chem. 2004, 125, 477-645.
(2) SelectiVe Fluorination in Organic and Bioorganic Chemistry; Welch,
J. T., Ed.; American Chemical Society: Washington, DC, 1991; pp 105-
133.
(3) For example, see: (a) Suzuki, Y.; Sato, M. Tetrahedron Lett. 2004,
45, 1679-1681. (b) Sano, S.; Saito, K.; Nagao, Y. Tetrahedron Lett. 2003,
44, 3987-3990. (c) Sano, S.; Teranishi, R.; Nagao, Y. Tetrahedron Lett.
2002, 43, 9183-9186. (d) Bargiggia, F.; Dos Santos, S.; Piva, O. Synthesis
2002, 427-437. (e) Sano, S.; Ando, T.; Yokoyama, K.; Nagao, Y. Synlett
1998, 777-779. (f) Thenappan, A.; Burton, D. J. J. Org. Chem. 1990, 55,
4639-4642. (g) Etemad-Moghadam, G.; Seyden-Penne, J. Bull. Soc. Chim.
Fr. 1985, 448-454.
(4) Lin, J.; Welch, J. T. Tetrahedron Lett. 1998, 39, 9613-9616.
(5) (a) Chevrie, D.; Lequeux, T.; Pommelet, J.-C. Tetrahedron 2002,
58, 4759-4767. (b) Chevrie, D.; Lequeux, T.; Pommelet, J.-C. Org. Lett.
1999, 1, 1539-1541. (c) Allmendinger, T. Tetrahedron 1991, 47, 4905-
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Chem. Lett. 2005, 34, 998-999.
(6) For example, see: (a) Xu, J.; Burton, D. J. J. Org. Chem. 2005, 70,
4346-4353. (b) Barma, D. K.; Kundu, A.; Zhang, H.; Mioskowski, C.;
Falck, J. R. J. Am. Chem. Soc. 2003, 125, 3218-3219. (c) Clemenceau,
D.; Cousseau, J. Tetrahedron Lett. 1993, 34, 6903-6906. (d) Shen, Y.;
Zhou, Y. J. Fluorine Chem. 1993, 61, 247-251. (e) Fuchigami, T.; Hayashi,
T.; Konno, A. Tetrahedron Lett. 1992, 33, 3161-3164. (f) Usuki, Y.;
Iwaoka, M.; Tomoda, S. J. Chem. Soc., Chem. Commun. 1992, 1148-
1150. (g) Ishihara, T.; Kuroboshi, M. Chem. Lett. 1987, 1145-1148. (h)
Kitazume, T.; Ishikawa, N. Chem. Lett. 1981, 1259-1260.
(7) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563-2585.
(8) (a) Ghosh, A. K.; Zajc, B. Org. Lett. 2006, 8, 1553-1556. (b) Chevrie,
D.; Lequeux, T.; Demoute, J. P.; Pazenok, S. Tetrahedron Lett. 2003, 44,
8127-8130.
10.1021/ol0616236 CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/02/2006