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.
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 (open access publication) 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.
Nitrogen analogue An analogous reaction with nitrogen as the heteroatom was described in 1984 for the synthesis of the antibiotic substance streptazolin.
References