ORGANIC
LETTERS
2009
Vol. 11, No. 20
4728-4731
Synthesis of 2-Fluoro-3-phenylthio-1,3-
butadiene and 2-Trifluoromethyl-3-phenylthio-
1,3-butadiene and Their Reactivities
toward Various Dienophiles
Kamaldeep Paul, Ji Hye Hwang, Ji Hoon Choi, and In Howa Jeong*
Department of Chemistry and Medical Chemistry, Yonsei UniVersity, Wonju 220-710, Korea
Received August 11, 2009
ABSTRACT
A general approach for the synthesis of novel 2-fluoro-3-phenylthio-1,3-butadiene (8) and 2-trifluoromethyl-3-phenylthio-1,3-butadiene (9) from
monobromoalkene and dibromoalkenes has been developed. Subsequent Diels-Alder reactions of these dienes with symmetrical and
unsymmetrical dienophiles in the presence of Lewis acids gave a variety of fluorinated six-membered carbocycles in moderate to high yields.
The Diels-Alder reaction has proven to be an exceptionally
powerful method for carbon-carbon bond formation in organic
synthesis.1 Modification of diene and dienophile components
led to a significant extension of synthetic utility of the
Diels-Alder reaction. The introduction of heterosubstituents
has a significant influence on the reactivity, regioselectivity, and
stereochemistry of the diene and also adds versatility in further
reactions of the cycloadducts.2 Consequently, these dienes are
becoming well established as useful intermediates in organic
synthesis. The comprehensive review by Boger and Weinreb
elaborates the various examples of [4+2]-cycloadditions with
heteroatom containing dienes and dienophiles.3 In the past
several decades, much effort has been devoted to introduce the
fluorine or trifluoromethyl functionality into organic molecules
because of the dramatic effects of functionality on their structure
stability, reactivity, and biological activity of the resulting
compounds.4 Fluorine-containing molecules have many ap-
plications in various fields such as pharmaceutical, agricultural
chemistry, and material science.5 Consequently, a wide variety
of methods have hitherto been developed for the preparation
of these fluorine-incorporated compounds,6 but only scarce
examples are known for fluorinated dienes.7 Especially, there
(3) Boger, D. L.; Weinreb, S. M. Hetero Diels-Alder Methodology in
Organic Synthesis; Academic Press: San Diego, CA, 1987.
(4) (a) Welch, J. T. Tetrahedron 1987, 43, 3123. (b) Welch, J. T.;
Eswarakrishnam, S. Fluorine in Bioorganic Chemistry; Wiley: New York,
1991. (c) Resnati, G. Tetrahedron 1993, 49, 9385. (d) Organofluorine
Componds in Medicinal Chemistry and Biomedical Applications; Filler, R.,
Kobayashi, Y., Yagupolski, L. M., Eds.; Elsevier Science Publishers B.V.:
Amsterdam, The Netherlands, 1993. (e) Organofluorine Chemistry, Prin-
ciples and Chemical Applications; Banks, R. E., Smart, B. E., Tatlow, J. C.,
Eds.; Plenum Press: New York, 1994. (f) InVentory of Industrial Fluoro-
biochemicals; Becker, A., Ed.; Eyrolles: Pairs, France, 1996. (g) Smart,
B. E. Chem. ReV. 1996, 96, 1555. (h) Resnatic, G.; Soloshnok, V. A.
Tetrahedron 1996, 52, 1. (i) Hudlicky, M.; Pavlath, A. E., Eds. Chemistry
of Organic Fluorine Compounds; American Chemical Society: Washington,
DC, 1996; p 187.
(1) Oppolzer, W. Intermolecular Diels-Alder Reactions. In Compre-
hensiVe Organic Synthesis; Pergamon Press: New York, 1991; Vol. 5, p 315.
(2) (a) Petrzilka, M.; Grayson, J. I. Synthesis 1981, 753. (b) Bridges,
A. J.; Fischer, J. W. Tetrahedron Lett. 1983, 24, 447. (c) Bridges, A. J.;
Fischer, J. W. J. Chem. Soc., Chem. Commun. 1982, 665. (d) Trost, B. M.;
Vladuchick, W. C.; Bridges, A. J. J. Am. Chem. Soc. 1980, 102, 3548. (e)
McDonald, E.; Suksamrarn, A.; Wylie, R. D. J. Chem. Soc., Perkin Trans.
1 1979, 1893. (f) Clennan, E. L.; Nagraba, K. J. Org. Chem. 1987, 52,
294. (g) Jeganathan, S.; Okamura, W. H. Tetrahedron Lett. 1982, 23, 4763.
(h) Garratt, P. J.; Tsotinis, A. Tetrahedron Lett. 1986, 27, 2761. (i) Pollok,
T.; Schmidbaur, H. Tetrahedron Lett. 1987, 28, 1085.
(5) (a) SelectiVe Fluorination in Organic and Bioorganic Chemistry;
ACS Symp. Ser. No. 456; Welch, J. T., Ed.; American Chemical Society:
Washington, DC, 1991. (b) Biomedical Frontiers of Fluorine Chemistry;
ACS Symp. Ser. No. 639; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.;
American Chemical Society: Washington, DC, 1996.
10.1021/ol901867q CCC: $40.75
Published on Web 09/24/2009
2009 American Chemical Society