A
1,2-Wittig rearrangement is a categorization of
chemical reactionsOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
in
Organic chemistryOrganic chemistry is a discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation of chemical compounds that contain carbon...
, and consists of a
1,2-rearrangementA 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...
of an
etherEther is a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
with an alkyllithium compound . The reaction is named for
Nobel PrizeThe Nobel Prize is a Sweden-based international monetary prize. The award was established by the 1895 will and estate of Swedish chemist and inventor Alfred Nobel. It was first awarded in Physics, Chemistry, Physiology or Medicine, Literature, and Peace in 1901...
winning chemist
Georg WittigGeorg Wittig was a German chemist who reported a method for synthesis of alkenes from aldehydes and ketones using compounds called phosphonium ylides in the Wittig reaction. He shared the Nobel Prize in Chemistry with Herbert C...
.
The intermediate product is an alkoxy lithium salt and the final product an
alcoholIn chemistry, an alcohol is any organic compound in which a hydroxyl group is bound to a carbon atom of an alkyl or substituted alkyl group. An important group of acohols is formed by the simple acyclic alcohols, the general formula for which is C
nH
2n+1OH...
. When R
2 is a good
leaving groupIn chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonate esters,...
and
electron withdrawingThe Polar effect or electronic effect in chemistry is the effect exerted by a substituent on modifying electrostatic forces operating on a nearby reaction center...
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...
such as a
cyanideA cyanide is any chemical compound that contains the cyano group , which consists of a carbon atom triple-bonded to a nitrogen atom. Inorganic cyanides are hydrogen cyanide salts in which cyanide is generally the anion CN
-. Organic compounds that have a -C≡N functional group bonded to...
(CN) group, this group is eliminated and the corresponding
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...
is formed.
The
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
centers on the formation of a free radical pair with lithium migrating from the carbon atom to the oxygen atom.
A
1,2-Wittig rearrangement is a categorization of
chemical reactionsOrganic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions and redox reactions. In organic synthesis, organic reactions are used...
in
Organic chemistryOrganic chemistry is a discipline within chemistry which involves the scientific study of the structure, properties, composition, reactions, and preparation of chemical compounds that contain carbon...
, and consists of a
1,2-rearrangementA 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...
of an
etherEther is a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
with an alkyllithium compound . The reaction is named for
Nobel PrizeThe Nobel Prize is a Sweden-based international monetary prize. The award was established by the 1895 will and estate of Swedish chemist and inventor Alfred Nobel. It was first awarded in Physics, Chemistry, Physiology or Medicine, Literature, and Peace in 1901...
winning chemist
Georg WittigGeorg Wittig was a German chemist who reported a method for synthesis of alkenes from aldehydes and ketones using compounds called phosphonium ylides in the Wittig reaction. He shared the Nobel Prize in Chemistry with Herbert C...
.
The intermediate product is an alkoxy lithium salt and the final product an
alcoholIn chemistry, an alcohol is any organic compound in which a hydroxyl group is bound to a carbon atom of an alkyl or substituted alkyl group. An important group of acohols is formed by the simple acyclic alcohols, the general formula for which is C
nH
2n+1OH...
. When R
2 is a good
leaving groupIn chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonate esters,...
and
electron withdrawingThe Polar effect or electronic effect in chemistry is the effect exerted by a substituent on modifying electrostatic forces operating on a nearby reaction center...
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...
such as a
cyanideA cyanide is any chemical compound that contains the cyano group , which consists of a carbon atom triple-bonded to a nitrogen atom. Inorganic cyanides are hydrogen cyanide salts in which cyanide is generally the anion CN
-. Organic compounds that have a -C≡N functional group bonded to...
(CN) group, this group is eliminated and the corresponding
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...
is formed.
Reaction mechanism
The
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
centers on the formation of a free radical pair with lithium migrating from the carbon atom to the oxygen atom. The R radical then recombines with the
ketylA ketyl group in organic chemistry is an anion radical with the general structure C-O. in which an oxygen radical is bonded directly to carbon. This radical is very unstable and appears in chemical reactions as a reactive intermediate...
.
The alkyl group migrates in the order of thermodynamical stability methyl < primary alkyl < secondary alkyl < tertiary alkyl in this is line with the radical mechanism. The radical-ketyl pair is short lived and due to a
solvent cage effectThe cage effect in chemistry describes how properties of a molecule are affected by its surroundings.* In a solvent a molecule is often more accurately described existing in a cage of solvent molecules, the so-called solvent cage....
some isomerizations take place with retention of configuration.
With certain allyl aryl ethers a competing reaction mechanism takes place . The reaction of
allyl phenyl ether 1 with
sec-butyllithium at -78°C gives the lithiated intermediate
2 which on heating to -25°C only shows the rearranged product
5 but not
4 after trapping the lithium alkoxide with
trimethylsilyl chlorideTrimethylsilyl chloride, also known as chlorotrimethylsilane is a silyl halide, with a variety of different uses in chemistry. It has the formula 3SiCl, and under standard conditions it is a colourless liquid, which is stable in the absence of water...
. This result rules out a radical-ketyl intermediate
3a in favor of the
Meisenheimer complexA Meisenheimer complex or Jackson-Meisenheimer complex in organic chemistry is a 1:1 reaction adduct between an arene carrying electron withdrawing groups and nucleophile...
3b. Additional evidence for this mechanism is provided by the finding that with a para tert-butyl substituent the reaction is retarded.
The reaction is a formal
dyotropic reactionA dyotropic Reaction in organic chemistry is a type of organic reaction and more specifically a pericyclic valence isomerization in which two sigma bonds simultaneously migrate intramolecularly...
.