Petasis-Ferrier Rearrangement

Petasis-Ferrier Rearrangement

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  • General Characteristics

The Lewis acid-promoted rearrangement of enol acetals to cyclic ethers, which involves an oxygen-to-carbon transposition, is known as the Petasis-Ferrier rearrangement. This reaction is generally referred to as the “Type II” Ferrier rearrangement.

Al(III), Hg(II), and Pd(II) reagents are often used for this reaction.

  • General References

・Ferrier, R. J. J. Chem. Soc. Perkin Trans. 1 1979, 1455. DOI: 10.1039/P19790001455
・Petasis, N. A.; Lu, S.-P. J. Am. Chem. Soc. 1995, 117, 6394. DOI: 10.1021/ja00128a044
・Petasis, N. A.; Lu, S.-P. Tetrahedron Lett. 1996, 37, 141. doi:10.1016/0040-4039(95)02114-0
・Ferrier, R. J.; Middleton, S. Chem. Rev. 1993, 93, 2779. DOI: 10.1021/cr00024a008

  • Reaction Mechanism

Note the difference between this reaction and the Type I Ferrier reaction, which is the allylic substitution of 1,2-glycals.


  • Examples

An application in the total synthesis of phorboxazole A.[1]




An interesting variant which effects one-carbon homologation.[2]


  • Experimental Procedure

  • Experimental Tips

The exo-olefin enol acetals are commonly prepared from β-hydroxycarboxylic acids and aldehydes, which form cyclic acetals, followed by olefination with the Petasis reagent.


  • References

[1] Smith, A. B., III; Minbiole, K. P.; Verhoest, P. R.; Schelhaas, M. J. Am. Chem. Soc. 2001, 123, 10942. DOI: 10.1021/ja011604l
[2] O’Neil, E.; Kingree, S. V.; Minbiole, K. P. C. Org. Lett. 2005, 7, 515. DOI: 10.1021/ol047426t

  • Related Reactions


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  • External Links

Petasis-Ferrier Rearrangement (PDF)