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The Seyferth–Gilbert homologation is a
Recently a safer and more scalable approach has been developed for the synthesis of alkynes from aldehydes. This protocol takes advantage of a stable sulfonyl azide, rather than tosyl azide, for the ''in situ'' generation of the Ohira−Bestmann reagent.
chemical reaction
A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and break ...
of an aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used as ...
ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...
1 (or aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...
) with dimethyl (diazomethyl)phosphonate 2 and potassium tert-butoxide
Potassium ''tert''-butoxide is the chemical compound with the formula K+(CH3)3CO−. This colourless solid is a strong base (pKa of conjugate acid around 17), which is useful in organic synthesis. It exists as a tetrameric cubane-type cluster. ...
to give substituted alkyne
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Acetylene
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Propyne
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1-Butyne
In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and no ...
s 3. Dimethyl (diazomethyl)phosphonate 2 is often called the Seyferth–Gilbert reagent.
This reaction is called a '' homologation'' because the product has exactly one additional carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes ...
more than the starting material.
Reaction mechanism
Deprotonation of the Seyferth–Gilbert reagent A gives an anion B, which reacts with the ketone to form theoxaphosphetane
An oxaphosphetane is a molecule containing a four-membered ring with one phosphorus, one oxygen and two carbon atoms. In a 1,2-oxaphosphetane phosphorus is bonded directly to oxygen, whereas a 1,3-oxaphosphetane has the phosphorus and oxygen atom ...
D. Elimination of dimethylphosphate E gives the vinyl
Vinyl may refer to:
Chemistry
* Polyvinyl chloride (PVC), a particular vinyl polymer
* Vinyl cation, a type of carbocation
* Vinyl group, a broad class of organic molecules in chemistry
* Vinyl polymer, a group of polymers derived from viny ...
diazo-intermediate Fa and Fb. The generation of nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at seve ...
gas gives a vinyl
Vinyl may refer to:
Chemistry
* Polyvinyl chloride (PVC), a particular vinyl polymer
* Vinyl cation, a type of carbocation
* Vinyl group, a broad class of organic molecules in chemistry
* Vinyl polymer, a group of polymers derived from viny ...
carbene G, which via a 1,2-migration forms the desired alkyne H.
Bestmann modification
The dimethyl (diazomethyl)phosphonate carbanion can be generated ''in situ'' from dimethyl-1-diazo-2-oxopropylphosphonate (also called the Ohira-Bestmann reagent) by reaction with methanol andpotassium carbonate
Potassium carbonate is the inorganic compound with the formula K2 CO3. It is a white salt, which is soluble in water. It is deliquescent, often appearing as a damp or wet solid. Potassium carbonate is mainly used in the production of soap and gl ...
as the base by cleavage of the acetyl group
In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl ...
as methyl acetate
Methyl acetate, also known as MeOAc, acetic acid methyl ester or methyl ethanoate, is a carboxylate ester with the formula CH3COOCH3. It is a flammable liquid with a characteristically pleasant smell reminiscent of some glues and nail polish remo ...
. Reaction of Bestmann's reagent with aldehydes gives terminal alkynes often in very high yield and fewer steps than the Corey–Fuchs reaction.
The use of the milder potassium carbonate makes this procedure much more compatible with a wide variety of functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the res ...
s.
Improved ''in situ'' generation of the Ohira-Bestmann reagent
Recently a safer and more scalable approach has been developed for the synthesis of alkynes from aldehydes. This protocol takes advantage of a stable sulfonyl azide, rather than tosyl azide, for the ''in situ'' generation of the Ohira−Bestmann reagent.
Other modifications
Another modification for less reactive aldehydes is made by replacement of potassium carbonate withcaesium carbonate
Caesium carbonate or cesium carbonate is a white crystalline solid compound. Caesium carbonate has a high solubility in polar solvents such as water, alcohol and DMF. Its solubility is higher in organic solvents compared to other carbonates like ...
in MeOH and results in a drastic yield increase.
See also
* Corey–Fuchs reaction * Horner–Wadsworth–Emmons reaction *Wittig reaction
The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide called a Wittig reagent. Wittig reactions are most commonly used to convert aldehydes and ketones to alkenes. Most ...
References
{{DEFAULTSORT:Seyferth-Gilbert homologation Carbon-carbon bond forming reactions Rearrangement reactions Name reactions