The
Seyferth-Gilbert homologation is a the
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
of an
arylIn the context of organic molecules, aryl refers to any functional group or substituent derived from a simple aromatic ring, may it be phenyl, thiophene, indolyl, etc . "Aryl" is used for the sake of abbreviation or generalization....
ketoneIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
1 (or
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
) with dimethyl (diazomethyl)phosphonate
2 and
potassium tert-butoxidePotassium tert-butoxide is the chemical compound with the formula
3COK. This colourless solid is a strong base useful in organic synthesis. It exists as a tetrameric cubane-like cluster...
to give substituted
alkyneAlkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC...
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
carbonCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
more than the starting material.
Deprotonation of the Seyferth-Gilbert reagent
A give an anion
B which reacts with the ketone to form the oxaphosphatane
D.
The
Seyferth-Gilbert homologation is a the
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
of an
arylIn the context of organic molecules, aryl refers to any functional group or substituent derived from a simple aromatic ring, may it be phenyl, thiophene, indolyl, etc . "Aryl" is used for the sake of abbreviation or generalization....
ketoneIn organic chemistry, a ketone is a type of compound that features a carbonyl group bonded to two other carbon atoms, i.e., R3CCO-CR3 where R can be a variety of atoms and groups of atoms...
1 (or
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
) with dimethyl (diazomethyl)phosphonate
2 and
potassium tert-butoxidePotassium tert-butoxide is the chemical compound with the formula
3COK. This colourless solid is a strong base useful in organic synthesis. It exists as a tetrameric cubane-like cluster...
to give substituted
alkyneAlkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC...
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
carbonCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
more than the starting material.
Reaction mechanism
Deprotonation of the Seyferth-Gilbert reagent
A give an anion
B which reacts with the ketone to form the oxaphosphatane
D. Elimination of dimethylphosphate
E gives the
vinylA vinyl compound is any organic compound that contains a vinyl group , −CH=CH2. These are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...
diazoDiazo refers to a type of organic compound that has two linked nitrogen compounds. The general formula is R
2C=N
2. The simplest example of a diazo compound is diazomethane. The electronic structure of diazo compounds involves a positive charge on the central nitrogen and...
-intermediate
Fa and
Fb. The generation of
nitrogenNitrogen is a chemical element that has the symbol N and atomic number 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless and mostly inert diatomic gas at standard conditions, constituting 78% by volume of Earth's atmosphere.Many industrially important...
gas gives a
vinylA vinyl compound is any organic compound that contains a vinyl group , −CH=CH2. These are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...
carbeneIn chemistry, a carbene is a organic molecule containing a carbon atom with six valence electrons and having the general formula RR'C:. Carbenes are classified into two varieties, singlets and triplets. Most carbenes are very short lived, although persistent carbenes are known.The prototypical...
G which via a
1,2-migrationA 1,2-rearrangement or 1,2-migration or 1,2-shift or Whitmore 1,2-shift is an organic reaction where a substituent moves from one atom to another atom in a chemical compound. In a 1,2 shift the movement involves two adjacent atoms but moves over larger distances are possible...
forms the desired alkyne
H.
Bestmann modification
Dimethyl (diazomethyl)phosphonate can be generated
in situIn situ is a Latin phrase meaning in the place. It is used in many different contexts.-Aerospace:In the aerospace industry, equipment on board aircraft must be tested in situ, or in place, to confirm everything functions properly as a system. Individually, each piece may work but interference from...
from dimethyl-1-diazo-2-oxopropylphosphonate (also called
Bestmann's reagent) by reaction with
methanolMethanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with formula CH3OH . It is toxic: drinking 10 ml will cause blindness, and as little as 100 ml will cause death...
and
potassium carbonatePotassium carbonate is a white salt, soluble in water , which forms a strongly alkaline solution. It can be made as the product of potassium hydroxide's absorbent reaction with carbon dioxide. It is deliquescent, often appearing a damp or wet solid...
. Reaction of Bestmann's reagent with aldehydes gives terminal alkynes often in very high yield.
The use of the milder potassium carbonate makes this procedure much more compatible with a wide variety of
functional groupIn organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part...
s.
See also
- Corey-Fuchs reaction
The Corey-Fuchs reaction, also known as the Ramirez-Corey-Fuchs reaction, is a series of chemical reactions designed to transform an aldehyde into an alkyne. The formation of the 1,1-dibromoolefins via phosphine-dibromomethylenes was originally discovered by Desai and McKelvie...
- Horner-Wadsworth-Emmons reaction
The Horner-Wadsworth-Emmons reaction is the chemical reaction of stabilized phosphonate carbanions with aldehydes to produce predominantly E-alkenes....
- Wittig reaction
The Wittig Reaction is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide to give an alkene and triphenylphosphine oxide....