Claisen rearrangement

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The Claisen rearrangement is a powerful carbon-carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a [3,3]-sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl.

The Claisen rearrangement
The Claisen rearrangement

Discovered in 1912, the Claisen rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement.[1][2][3]

Many reviews have been written.[4][5][6][7]

Mechanism

The Claisen rearrangement (and its variants) are exothermic (about 84 kJ/mol), concerted pericyclic reactions which according to the Woodward-Hoffmann rules show a suprafacial reaction pathway.

There are substantial solvent effects in the Claisen reactions. More polar solvents tend to accelerate the reaction to a greater extent. Hydrogen-bonding solvents gave the highest rate constants. For example, ethanol/water solvent mixtures give rate constants 10-fold higher than sulfolane.[1][2]

Trivalent organoaluminium reagents, such as trimethylaluminium, have been shown to accelerate this reaction.[8][9]

Variations

Aromatic Claisen rearrangement

The aromatic variation of the Claisen rearrangement is the [3,3]-sigmatropic rearrangement of an allyl phenyl ether to an intermediate which quickly tautomerizes to an ortho-substituted phenol.

The Claisen rearrangement
The Claisen rearrangement

Bellus-Claisen rearrangement

The Bellus-Claisen rearrangement is the reaction of allylic ethers, amines, and thioethers with ketenes to give γ,δ-unsaturated esters, amides, and thioesters.[10][11][12]

The Bellus-Claisen rearrangement
The Bellus-Claisen rearrangement

Eschenmoser-Claisen rearrangement

The Eschenmoser-Claisen rearrangement proceeds from an allylic alcohol to a γ,δ-unsaturated amide, and was developed by Albert Eschenmoser in 1964.[13][14]

The Eschenmoser-Claisen rearrangement
The Eschenmoser-Claisen rearrangement

Ireland-Claisen rearrangement

The Ireland-Claisen rearrangement is the reaction of an allylic acetate with strong base (such as Lithium diisopropylamide) to give a γ,δ-unsaturated carboxylic acid.[15][16][17]

The Ireland-Claisen rearrangement
The Ireland-Claisen rearrangement

Johnson-Claisen rearrangement

The Johnson-Claisen rearrangement is the reaction of an allylic alcohol with trimethyl orthoacetate to give a γ,δ-unsaturated ester.[18]

The Johnson-Claisen rearrangement
The Johnson-Claisen rearrangement

Hetero-Claisens

Aza-Claisen

An iminium can serve as one of the pi-bonded moieties in the rearrangement.[19]

An example of the Aza-Claisen rearrangement
An example of the Aza-Claisen rearrangement

Chromium Oxidation

Chromium can oxidize allylic alcohols to alpha-beta unsaturated ketones on the opposite side of the unsaturated bond from the alcohol. This is via a concerted hetero-claisen reaction, although there are mechanistic differences since the chromium atom has access to d- shell orbitals which allow the reaction under a less constrained set of geometries.[20][21]

File:ClaisenOx.png

Chen-Mapp Reaction

The Chen-Mapp reaction also known as the [3,3]-Phosphorimidate Rearrangement or Staudinger-Claisen Reaction installs a phosphite in the place of an alcohol and takes advantage of the Staudinger Ligation to convert this to an imine. The subsequent claisen is driven by the fact that a P=O double bond is more energetically favorable than a P=N double bond.[22]

The Mapp Reaction
The Mapp Reaction

Overman rearrangement

The Overman rearrangement (named after Larry Overman) is a Claisen rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides.[23][24][25][26]

The Overman rearrangement
The Overman rearrangement

Zwitterionic Claisen rearrangement

Unlike typical Claisen rearrangements which require heating, zwitterionic Claisen rearrangements take place at or below room temperature. The acyl ammonium ions are highly selective for Z-enolates under mild conditions.[27][28]

The zwitterionic Claisen rearrangement
The zwitterionic Claisen rearrangement

Claisen rearrangement in nature

The enzyme Chorismate mutase (EC 5.4.99.5) catalyzes the Claisen rearrangement of chorismate ion to prephenate ion, a key intermediate in the shikimic acid pathway (the biosynthetic pathway towards the synthesis of phenylalanine and tyrosine).[29]

Chorismate mutase catalyzes a Claisen rearrangement
Chorismate mutase catalyzes a Claisen rearrangement

References

  1. Claisen, L.; Ber. 1912, 45, 3157.
  2. Claisen, L.; Tietze, E.; Ber. 1925, 58, 275.
  3. Claisen, L.; Tietze, E.; Ber. 1926, 59, 2344.
  4. Hiersemann, M.; Nubbemeyer, U. (2007) The Claisen Rearrangement. Wiley-VCH. ISBN 3527308253
  5. Rhoads, S. J.; Raulins, N. R.; Org. React. 1975, 22, 1-252. (Review)
  6. Ziegler, F. E.; Chem. Rev. 1988, 88, 1423-1452. (Review)
  7. Wipf, P.; Comp. Org. Syn. 1991, 5, 827-873.
  8. Goering, H. L.; Jacobson, R. R.; J. Am. Chem. Soc. 1958, 80, 3277.
  9. White, W. N.; Wolfarth, E. F.; J. Org. Chem. 1970, 35, 2196.
  10. Malherbe, R.; Bellus, D.; Helv. Chim. Acta 1978, 61, 3096-3099.
  11. Malherbe, R.; Rist, G.; Bellus, D.; J. Org. Chem. 1983, 48, 860-869.
  12. Gonda, J.; Angew. Chem. Int. Ed. 2004, 43, 3516-3524.
  13. Wick, A. E.; Felix, D.; Steen, K.; Eschenmoser, A.; Helv. Chim. Acta 1964, 47, 2425-2429.
  14. Wick, A. E.; Felix, D.; Gschwend-Steen, K.; Eschenmoser, A.; Helv. Chim. Acta 1969, 52, 1030-1042.
  15. Ireland, R. E.; Mueller, R. H.; J. Am. Chem. Soc. 1972, 94, 5897-5898. (doi:10.1021/ja00771a062)
  16. Ireland, R. E.; Willard, A. K.; Tetrahedron Lett. 1975, 16, 3975-3978.
  17. Ireland, R. E.; Mueller, R. H.; Willard, A. K.; J. Am. Chem. Soc. 1976, 98, 2868-2877. (doi:10.1021/ja00426a033)
  18. Johnson, W. S. et al.; J. Am. Chem. Soc. 1970, 92, 741.
  19. Kurth, M. J.; Decker, O. H. W.; J. Org. Chem. 1985, 50, 5769-5775.
  20. Dauben, W. G.; Michno, D. M. J. Org. Chem., 1977, 42, 682.
  21. Organic Syntheses, Vol. 82, p.108 (2005). (Article)
  22. Chen, B. Mapp, A K. J. Am. Chem. Soc. 2005, 127, 6712. Abstract
  23. Overman, L. E. J. Am. Chem. Soc. 1974, 96, 597.
  24. Overman, L. E. J. Am. Chem. Soc. 1976, 98, 2901.
  25. Overman, L. E. Accts. Chem. Res. 1980, 13, 218-224.
  26. Organic Syntheses, Coll. Vol. 6, p.507; Vol. 58, p.4 (Article)
  27. Yu, C.-M.; Choi, H.-S.; Lee, J.; Jung, W.-H.; Kim, H.-J. J. Chem. Soc., Perkin Trans. 1 1996, 115-116.
  28. Nubbemeyer, U. J. Org. Chem. 1995, 60, 3773-3780.
  29. Ganem, B. Angew. Chem. Int. Ed. Engl. 1996, 35, 936-945.

See also

de:Claisen-Umlagerung it:Trasposizione di Claisen