4476
J. Dambacher et al. / Tetrahedron Letters 46 (2005) 4473–4477
Ph3PCHCO2Me (1.5 equiv)
Water, 20 °C, 1 h
CO2Me
CHO
n
31; n = 3; 80%, E/Z = 82/18
32; n = 4; 84%, E/Z = 81/19
33; n = 6; 86%, E/Z = 80/20
n
Ph3PCHCO2t-Bu (1.5 equiv)
CO2t-Bu
CHO
34; 77%, E/Z = >99/1
Water, 20 °C, 1 h
TBSO
TBSO
Ph3PCHCO2CH2CCl3 (1.5 equiv)
Water, 20 °C, 18 h
CHO
CO2CH2Cl3
35; 73%, E/Z = 85/15
1
Ph3PCHCO2Me (1.5 equiv)
Water, 20 °C, 1 h
CO2Me
CHO
Ph
Ph
E/Z = 85/15 36; 98%
Ph3PCHCO2t-Bu (1.0 equiv)
HO2C
HO2C
CHO
CO2t-Bu
37; 74%, E/Z = >99/1
Water, 20 °C, 30 min
Scheme 2. Wittig reactions in water applied to aliphatic aldehydes.
a-carbon of ethyl cinnamate.22 Thus, a very fast deute-
rium exchange occurs, which is in accordance with what
has been postulated by Bestmann using EtOD.23
2. (a) Maerckar, A. Org. React. 1965, 14, 270–490; (b)
Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–
927; (c) Kolodiazhnyi, O. I. Phosphorus Ylides, Chemistry
and Application in Organic Synthesis; Wiley-VCH: Wein-
heim, 1999.
3. Patil, V. J.; Ma¨vers, U. Tetrahedron Lett. 1996, 37, 1281–
1284.
4. Fodor, G.; To¨mo¨sko¨zi, I. Tetrahedron Lett. 1961, 579–
582.
5. (a) Nonnenmacher, A.; Mayer, R.; Plieninger, H.
Liebigs Ann. Chem. 1983, 2135–2140; (b) Isaacs, N. S.;
El-Din, G. N. Tetrahedron Lett. 1987, 28, 2191–
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Garagan, S.; Kayser, M. M. J. Org. Chem. 1994, 59, 1126–
Water has been illustrated as an efficient medium for the
Wittig reaction employing stabilized ylides and alde-
hydes. This work demonstrates that solubility of the re-
agents and substrates is not of a paramount nature, even
though pronounced hydrophobic entities are present.
Since water has its own distinctive place among possible
solvent systems, water should always be considered as a
possible medium in the improvement and development
of new organic reactions. Not only is water shown as
an extremely useful medium for the synthesis of car-
bon–carbon double bonds, but this letter also exempli-
fies advances toward the synthesis of alkenes using an
environmentally friendly approach. Further develop-
ment of the aqueous Wittig reaction is currently under
investigation in our laboratory.
´
1128; Benzoic acid: (c) Fliszar, S.; Hudson, R. F.;
Salvadori, G. Helv. Chim. Acta 1964, 47, 159–162; (d)
Ruchardt, C.; Panse, P.; Eichler, S. Chem. Ber. 1967, 100,
¨
1144–1164; (e) Corey, E. J.; Clark, D. A.; Goto, G.;
Marfat, A.; Mioskowski, C.; Samuelsson, B.; Hammar-
stro¨m, S. J. Am. Chem. Soc. 1980, 102, 1436–1439; (f)
Marriott, D. P.; Bantick, J. R. Tetrahedron Lett. 1981, 22,
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Vill, V.; Mataka, S.; Tashiro, M. J. Chem. Res., Synop.
1997, 248–249; Phase transfer catalyst: (h) Stafford, J. A.;
McMurry, J. E. Tetrahedron Lett. 1988, 29, 2531–2534;
Cyclodextrins: (i) Westman, G.; Wennerstro¨m, O.;
Raston, I. Tetrahedron 1993, 49, 483–488.
Acknowledgements
This work was funded by the San Diego Foundation
(Blasker) and the San Diego State University Founda-
tion. The authors also thank Dr. Frances Separovic,
Ms. Mariceli Puga, and Mr. Ian Ballard for crucial
assistance.
7. (a) Xu, C.; Chen, G.; Fu, C.; Huang, X. Synth. Commun.
1995, 25, 2229–2233; (b) Spinella, A.; Fortunati, T.;
Soriente, A. Synlett 1997, 93–94.
8. Matikainen, J. K.; Kaltia, S.; Hase, T. Synlett 1994, 817–
818.
Supplementary data
9. Silveira, C. C.; Perin, G.; Braga, A. L. J. Chem. Res.,
Synop. 1994, 492–493.
´
10. Boulaire, V. L.; Gree, R. Chem. Commun. 2000, 2195–
2196.
11. (a) Russel, M. G.; Warren, S. J. Chem. Soc., Perkin Trans.
1 2000, 505–513; For Wittig–Horner reaction in aqueous
media, see: (b) Villieras, J.; Rambaud, M. Synthesis 1983,
300–303; (c) Rambaud, M.; Vecchio, A.; Villieras, J.
Synth. Commun. 1984, 14, 833–841; (d) Villieras, J.;
Rambaud, M.; Graff, M. Tetrahedron Lett. 1985, 26, 53–
56; (e) Mouloungui, Z.; Delmas, M.; Gaset, A. J. Org.
Chem. 1989, 54, 3936–3941.
Experimental procedures and spectral data (1H NMR
and 13C NMR) for pertinent compounds (PDF).
Supplementary data associated with this article can be
References and notes
1. (a) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 580,
44–68; (b) Wittig, G.; Scho¨llkopf, U. Chem. Ber. 1954, 87,
1318–1330; (c) Wittig, G. Science 1980, 210, 600–604, and
references cited herein.
12. E/Z-Ratio = 87:13.
13. Kazmierczak, F.; Helquist, P. J. Org. Chem. 1989, 54,
3988–3992.