Name: acyloin condensation: ester coupling pathway
Uploaded: 2023-04-30T11:23:12.000Z
Duration: 1 min 19 s
Channel: JoVE

Besides pinacol and McMurry reactions, acyloin condensation is another reductive coupling reaction that involves esters.
In this reaction, esters react in the presence of a metal source of electrons in an aprotic solvent to form an &#945;-hydroxy ketone, also termed acyloin.
The reaction proceeds through the formation of ketyls, which undergo radical dimerization to form an unstable tetrahedral intermediate and then further collapse, giving a 1,2-diketone.
Since a 1,2-diketone is comparatively more reactive than a ketone towards electrophiles and reducing agents, transferring two electrons readily reduces the 1,2-diketone to an enediolate.
Finally, acidification of enediolate gives an &#945;-hydroxy ketone with a good yield. However, the reactivity of nucleophilic enediolate often leads to the formation of byproducts.
To prevent unwanted side reactions, trimethylsilyl chloride is added to silylate the enediolate, giving a bis-silyl ether, which is further hydrolyzed with aqueous acid to yield an &#945;-hydroxy ketone as the final product.

α-hydroxyketonen via reductieve koppeling van esters: overzicht van acyloïnecondensatie

&alpha;-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview

De pinacol- en McMurry-reacties omvatten de reductieve koppeling van ketonen of aldehyden. Op soortgelijke wijze levert de bimoleculaire reductieve koppeling van twee estermoleculen in aanwezigheid van natriummetaal in een aprotisch oplosmiddel een α-hydroxyketonproduct op. Het α-hydroxyketon wordt ook wel acyloïne genoemd, dus de reactie wordt 'acyloïnecondensatie' genoemd.


 <img alt="Figure1" src="/files/ftp_upload/12908/12908_PT_Figure_1.svg" style="text-align: center; height: 65px;" />


 Bij de acyloïnecondensatiereactie worden esters omgezet in ketylen, die radicaaldimerisatie ondergaan om een onstabiel tetraëdrisch tussenproduct te vormen. Verder stort dit tussenproduct in elkaar waardoor een 1,2-diketontussenproduct ontstaat. De 1,2-diketonen zijn relatief reactiever dan ketonen ten opzichte van elektrofielen en reductiemiddelen vanwege de lagere π*-energie. Daarnaast worden twee elektronen achtereenvolgens overgebracht naar het 1,2-diketon om een enediolaat te vormen. Ten slotte wordt het enediolaattussenproduct geblust met zuur, waardoor een α-hydroxyketon met een goede opbrengst wordt verkregen.


 Vaak worden naast het hoofdproduct enkele bijproducten verkregen vanwege de reactiviteit van nucleofiel enediolaat. Om de nevenreacties te overwinnen en de opbrengst aan acyloïne te verbeteren, wordt trimethylsilylchloride gebruikt om het enediolaat te silyleren. Dit resulteert in een bis-silylether, verder gehydrolyseerd met waterig zuur om α-hydroxyketonen te geven.

α-Hydroxyketonen via reductieve koppeling van esters: overzicht van acyloïnecondensatie

The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester ...

hydroxy-ketones-via-reductive-coupling-esters-acyloin-condensation

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Organic Chemistry

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Onderdeel 1

Radical Chemistry

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KEY TERMS AND CONCEPTS

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acyloin condensation: ester coupling pathway

Acyloin condensation is a reaction that joins two ester molecules to form an alpha-hydroxy ketone. The product is also called an acyloin. In this reaction, sodium metal is used in an aprotic solvent, which supports the reductive coupling step.

The reaction is related to the pinacol and McMurry reactions, which also involve reductive coupling of ketones or aldehydes. Here, the ester first becomes a ketyl. These ketyl species undergo radical dimerization and form an unstable tetrahedral intermediate. That intermediate then collapses to give a 1,2-diketone intermediate.

The 1,2-diketone is more reactive than a ketone toward electrophiles and reducing agents because it has lower pi-star energy. Two electrons then transfer in sequence to form an enediolate. The enediolate is finally quenched with acid to produce the alpha-hydroxy ketone. This reaction can give a good yield, but side products may also form because the enediolate is nucleophilic.

Trimethylsilyl chloride can be used to reduce those side reactions and improve the acyloin yield. It silylates the enediolate to form a bis-silyl ether. Aqueous acid then hydrolyzes this intermediate to give the alpha-hydroxy ketone.

Acyloin Condensation: Ester Coupling Pathway

acyloin-condensation-ester-coupling-pathway

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Allylic Chlorination by Radical Chain Reaction

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radical substitution: allylic bromination

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Peroxide Effect in HBr Addition to Alkenes

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Hydrogen Bromide Addition to Alkenes by Radicals

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HBr Selectivity in Alkene Addition Thermodynamics

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Pinacol Coupling and Solvent Effects

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Titanium-Coupled Alkenes from Carbonyls

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&alpha;-hydroxy ketones via reductive coupling of esters: acyloin condensation overview

Acyloin condensation is a reaction that joins two ester molecules to form an alpha-hydroxy ketone. The product is also called an acyloin. In this reaction, sodium metal is used in an aprotic solvent, which supports the reductive coupling step. The reaction is related to the pinacol and McMurry reactions, which also involve reductive coupling of ketones or aldehydes. Here, the ester first becomes a ketyl. These ketyl species undergo radical dimerization and form an unstable tetrahedral...

key terms and concepts

Learn how acyloin condensation couples two esters with sodium metal to form alpha-hydroxy ketones, including ketyls, enediolates, and yield improvement.

Acyloin Condensation: Ester Coupling Pathway | JoVE K12

organic chemistry

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Acyloin Condensation: Ester Coupling Pathway

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