Ferrier reaction

What is Ferrier reaction?

In 1962, Ferrier et al. first reported the acid-catalyzed or induced rearrangement of glycals with various nucleophiles or aglycons, using protic acids like sulfuric acid or Lewis acids such as SnBr4, EtAlCl2, and Pd(CH3CN)2Cl2, with BF3·Et2O being the most commonly used. Some neutral catalysts like iodonium dicollidinium perchlorate, DDQ, and montmorillonite K-10 have also been developed for substrates sensitive to acidic conditions.

Ferrier reaction - general reaction scheme
Ferrier reaction

R = Bn, Ac (see list acronyms)

Ferrier reaction - general reaction scheme
Ferrier reaction

R = Bn, Ac (see list acronyms)

InCl3 has been found to be a highly effective catalyst, but must be used with TMSCl to avoid needing a stoichiometric amount. Nucleophiles used include alcohols, thio-alcohols, amino acids, monosaccharides, and carbo-nucleophiles. This reaction predominantly produces α-anomers in good to excellent yield and is commonly known as the Ferrier rearrangement or Ferrier reaction, which is different from another type of rearrangement also developed by Ferrier et al. (Ferrier-II rearrangement).

While the mechanism of this reaction remains unclear, it is proposed to involve an allylic isomerization of the glycal to a 2,3-dideoxy sugar followed by a SN1-type reaction through a cyclic allylic oxocarbenium ion in quasi-axial orientation. This reaction also works for exo-rings and 1,2-cyclopropanated sugars.

References

Ferrier, R. J.; Overend, W. G. and Ryan, A. E., “712. The reaction between 3,4,6-tri-O-acetyl-D-glucal and p-nitrophenol” J. Chem. Soc., 1962, 3667-3670
DOI: 10.1039/JR9620003667

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