Ferrier rearrangement
Encyclopedia
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.
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) anomer
s of the 2-glycoside, with the double bond shifted to position 3,4.
, C-glycosides can be formed. With triethylsilane
(R'=H), the reaction yields a 2,3-unsaturated desoxy sugar.
as the heteroatom was described in 1984 for the synthesis of the antibiotic
substance streptazolin
.
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
that involves a nucleophilic substitution
Nucleophilic substitution
In organic and inorganic chemistry, nucleophilic substitution is a fundamental class of reactions in which an electron nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom or a group of atoms called the leaving group; the positive or partially positive...
reaction combined with an allylic shift in a glycal
Glycal
Glycal is a name for cyclic enol ether derivatives of sugars having a double bond between carbon atoms 1 and 2 of the ring. The term “glycal” should not be used for an unsaturated sugar that has a double bond in any position other than between carbon atoms 1 and 2.-History of Glycals:The first...
(a 2,3-unsaturated
Unsaturated compound
In organic chemistry, a saturated compound is a chemical compound that has of a chain of carbon atoms linked together by single bonds and has hydrogen atoms filling all of the other bonding orbitals of the carbon atoms. Alkanes are an example of saturated compounds...
glycoside
Glycoside
In chemistry, a glycoside is a molecule in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. These can be activated by enzyme...
). It was discovered by the carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
chemist Robert J. Ferrier.
Mechanism
In the first step, a delocalized allyloxocarbenium ion (2) is formed, typically with the aid of a Lewis acidLewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
like indium(III) chloride
Indium(III) chloride
Indium chloride is the chemical compound with the formula InCl3. This colorless salt finds some use in organic synthesis as a Lewis acid. It is also the most available soluble derivative of indium.-Synthesis and structure:...
or boron trifluoride
Boron trifluoride
Boron trifluoride is the chemical compound with the formula BF3. This pungent colourless toxic gas forms white fumes in moist air. It is a useful Lewis acid and a versatile building block for other boron compounds.-Structure and bonding:...
. This ion reacts in situ with an alcohol, yielding a mixture of the α (3) and β (4) anomer
Anomer
In carbohydrate chemistry, an anomer is a special type of epimer. It is one of two stereoisomers of a cyclic saccharide that differs only in its configuration at the hemiacetal or hemiketal carbon, also called the anomeric carbon. Anomerization is the process of conversion of one anomer to the other...
s of the 2-glycoside, with the double bond shifted to position 3,4.
Examples
| Lewis acid | Alcohol | Conditions | Results |
|---|---|---|---|
| InCl3 Indium(III) chloride Indium chloride is the chemical compound with the formula InCl3. This colorless salt finds some use in organic synthesis as a Lewis acid. It is also the most available soluble derivative of indium.-Synthesis and structure:... |
methanol Methanol Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol... |
in dichloromethane Dichloromethane Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents... |
α:β = 7:1 |
| dioxane | water Water Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a... |
heating | 75% yield |
| SnCl4 Tin(IV) chloride Tin chloride, also known as tin tetrachloride or stannic chloride is a chemical compound with the formula SnCl4.At room temperature it is a colourless liquid, which fumes on contact with air, giving a stinging odor... |
methanol | in dichloromethane, –78 °C, 10 min | 83% yield, α:β = 86:14 |
| BF3 Boron trifluoride Boron trifluoride is the chemical compound with the formula BF3. This pungent colourless toxic gas forms white fumes in moist air. It is a useful Lewis acid and a versatile building block for other boron compounds.-Structure and bonding:... ·O(C2H5)2 |
isopropanol | in dichloromethane, RT Room temperature -Comfort levels:The American Society of Heating, Refrigerating and Air-Conditioning Engineers has listings for suggested temperatures and air flow rates in different types of buildings and different environmental circumstances. For example, a single office in a building has an occupancy ratio per... , 24 hr |
95% yield |
| ZnCl2 Zinc chloride Zinc chloride is the name of chemical compound with the formula ZnCl2 and its hydrates. Zinc chlorides, of which nine crystalline forms are known, are colorless or white, and are highly soluble in water. ZnCl2 itself is hygroscopic and even deliquescent. Samples should therefore be protected from... |
ethanol Ethanol Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a... |
in toluene Toluene Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic... , RT, 30–60 min |
65–95% yield, α:β = 89:11 |
| BF3·O(C2H5)2 | benzyl alcohol Benzyl alcohol Benzyl alcohol is an organic compound with the formula C6H5CH2OH. The benzyl group is often abbreviated "Bn", thus benzyl alcohol is denoted as BnOH. Benzyl alcohol is a colorless liquid with a mild pleasant aromatic odor. It is a useful solvent due to its polarity, low toxicity, and low vapor... |
in dichloromethane, –20 °C to RT, 1 hr | 98% yield |
Forming of C-glycosides
By replacing the alcohol with a silaneSilane
Silane is a toxic, extremely flammable chemical compound with chemical formula SiH4. In 1857, the German chemists and Friedrich Woehler discovered silane among the products formed by the action of hydrochloric acid on aluminum silicide, which they had previously prepared...
, C-glycosides can be formed. With triethylsilane
Triethylsilane
Triethylsilane is a silane with the molecular formula C6H16Si. It is a trialkylsilicon hydride compound with a reactive Si-H bond. This colorless liquid is often used in organic synthesis, specifically for the hydrosilation of olefins to give alkyl silanes...
(R'=H), the reaction yields a 2,3-unsaturated desoxy sugar.
Nitrogen analogue
An analogous reaction with nitrogenNitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
as the heteroatom was described in 1984 for the synthesis of the antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
substance streptazolin
Streptazolin
Streptazolin is a antibiotic and antifungal substance isolated in 1981 from Streptomyces viridochromogenes.Because of its polymerisation tendency, it is not suitable for therapeutic use...
.