Ferrier rearrangement

Not to be confused with the Ferrier carbocyclization or Ferrier II reaction, a reaction discovered by the same chemist.

The Ferrier rearrangement is an organic reaction that involves a nucleophilic substitution reaction combined with an allylic shift in a glycal (a 2,3-unsaturated glycoside). It was discovered by the carbohydrate chemist Robert J. Ferrier.

A typical Ferrier rearrangement

Mechanism

In the first step, a delocalized allyloxocarbenium ion (2) is formed, typically with the aid of a Lewis acid like indium(III) chloride or boron trifluoride. This ion reacts in situ with an alcohol, yielding a mixture of the α (3) and β (4) anomers of the 2-glycoside, with the double bond shifted to position 3,4.

Examples

Lewis acid	Alcohol	Conditions	Results
InCl3	methanol	in dichloromethane	α:β = 7:1
dioxane	water	heating	75% yield
SnCl4	methanol	in dichloromethane, –78 °C, 10 min	83% yield, α:β = 86:14
BF3·O(C2H5)2	isopropanol	in dichloromethane, RT, 24 hr	95% yield
ZnCl2	ethanol	in toluene, RT, 30–60 min	65–95% yield, α:β = 89:11
BF3·O(C2H5)2	benzyl alcohol	in dichloromethane, –20 °C to RT, 1 hr	98% yield

Modifications

Forming of C-glycosides

By replacing the alcohol with a silane, C-glycosides can be formed. With triethylsilane (R'=H), the reaction yields a 2,3-unsaturated deoxy sugar.

Forming of a C-glycoside via Ferrier rearrangement

Nitrogen analogue

An analogous reaction with nitrogen as the heteroatom was described in 1984 for the synthesis of the antibiotic substance streptazolin.

Nitrogen analogue of the Ferrier rearrangement