Diels-Alder reactions (and other cycloadditions) are accelerated in water due to a combination of enforced hydrophobic interactions and hydrogen bonding, their relative contributions depending on the nature of the diene and dienophile. Subsequent work has shown that a large variety of other organic reactions show comparable favorable characteristics in aqueous media.
Lewis-acid catalysis of Diels-Alder reactions involving bidentate dienophiles in water is possible; also if the beneficial effect of water on the catalyzed reaction is reduced relative to pure water. There are no additional effects on endo-exo selectivity. As expected, catalysis by Cu2+ ions is much more efficient than specific-acid catalysis.15 Using a-amino acids as chiral ligands, Lewis-acid enan-tioselectivity is enhanced in water compared to organic solvents. Micelles, in the absence of Lewis acids, are poor catalysts, but combining Lewis-acid catalysis and micellar catalysis leads to a rate accelaration that is enzyme-like.14
In many cases, synthetic organic chemistry in aqueous media1,2 offers important advantages for clean, green chemistry. Industrial applications have been realized and further developments are envisaged. For a long time, solubility constraints were seen as a major disadvantage, but now that recent work by Sharpless et al.16 has shown that several types of bimolecular organic reactions involving reactants insoluble in the aqueous phase are remarkably accelerated when performed in aqueous suspensions with efficient stirring ("on water reactions"), the situation has changed dramatically. The exact mechanism of these heterogeneous aqueous reactions is not yet known, but this work might well be a major breakthrough in aqueous synthetic chemistry.
The advantages of aqueous reaction media include:
• No pollution of the environment
• Synthetic efficiency and often easy work-up
• Simple chemical processes, including easy heat control
• Good solvent for mechanistic studies
• Unique molecular association via hydrophobic interactions
• Good solvent for fast (catalytic), (stereo)selective transformations
In physical organic chemistry, future detailed kinetic studies and sophisticated molecular dynamics computer simulations17 will lead to a still more thorough understanding of the exact role of the aqueous reaction medium in organic transformations. Particularly the effects of hydrophobic interactions are of great interest.18 Since water is essential for life processes, these studies will bring organic chemistry and biochemistry closer together.
1. Grieco, P. A. Organic Synthesis in Water, Blackie, London, 1998.
2. Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueuos Media, John Wiley & Sons, New York, 1997.
3. Blokzijl, W.; Blandamer, M. J.; Engberts, J. B. F. N. J. Am. Chem. Soc. 1991, 113, 4241-4246.
4. Otto, S.; Blokzijl, W.; Engberts, J. B. F. N. J. Org. Chem, 1994, 59, 5372-5376.
5. Wijnen, J. W.; Engberts, J. B. F. N. J. Org. Chem., 1997, 62, 2039-2044.
6. Van der Wel, G. K.; Wijnen J. W.; Engberts, J. B. F. N. J. Org. Chem, 1996, 61, 9001 -9005.
7. Breslow, R.; Rideout, D. C. J. Am. Chem. Soc., 1980, 102, 7816-7817.
8. Blokzijl, W.; Ph.D. Dissertation, University of Groningen, The Netherlands, 1991.
9. Blokzijl, W.; Engberts, J. B. F. N. J. Am. Chem. Soc., 1992, 114, 5440-5442.
10. Engberts, J. B. F. N. Pure Appl. Chem., 1995, 67, 823-828.
11. Otto, S.; Bertoncin, F.; Engberts, J. B. F. N. J. Am. Chem. Soc, 1996, 118, 7702-7707.
12. Otto, S.; Engberts, J. B. F. N. J. Am. Chem. Soc, 1999, 121, 6798-6806.
13. Otto, S.; Bocaletti, G.; Engberts, J. B. F. N. J. Am. Chem. Soc., 1998, 120, 42384239.
14. Otto, S.; Engberts, J. B. F. N.; Kwak, J. C. T. J. Am. Chem. Soc., 1998, 120, 9517952.
15. Mubofu, E. B.; Engberts, J. B. F. N. J. Phys. Org. Chem., 2004, 17, 180-186.
16. Narayan, S.; Muldoon, J.; Finn, M. G.; et al. Angew. Chem. Int. Ed., 2005, 44, 32753279.
17. For two examples, see, (a) Chandrasekhar, J.; Shariffskul, S.; Jorgensen, W. L. J. Phys. Chem. B, 2002, 106, 8078-8085; (b) Rispens, T.; Lensink, M. F.; Berendsen, H. J. C.; Engberts, J. B. F. N. J. Phys. Chem. B, 2004, 108, 5483-5488.
18. Otto, S.; Engberts, J. B. F. N. Org. Biomol. Chem., 2003, 1, 2809-2820.
Was this article helpful?