Ferrier rearrangement

Not to be confused with the Ferrier carbocyclization (also called 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.^[1][2]

A typical Ferrier rearrangement

Ferrier rearrangement
Named after	Robert J. Ferrier
Reaction type	Rearrangement reaction
Identifiers
RSC ontology ID	RXNO:0000229

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.^[3]

Examples

Lewis acid	Alcohol	Conditions	Results
InCl3	methanol	in dichloromethane	α:β = 7:1[4]
dioxane	water	heating	75% yield[5]
SnCl4	methanol	in dichloromethane, –78 °C, 10 min	83% yield, α:β = 86:14[6]
BF3·O(C2H5)2	isopropanol	in dichloromethane, RT, 24 hr	95% yield[7][8]
ZnCl2	ethanol	in toluene, RT, 30–60 min	65–95% yield, α:β = 89:11[9][10]
BF3·O(C2H5)2	benzyl alcohol	in dichloromethane, –20 °C to RT, 1 hr	98% yield[11]

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.^[3]

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.^[12]

Nitrogen analogue of the Ferrier rearrangement