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.

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

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

The pinacol and McMurry reactions involve the reductive coupling of ketones or aldehydes. Similarly, the bimolecular reductive coupling of two ester molecules in the presence of sodium metal in an aprotic solvent yields an &#945;-hydroxy ketone product. The &#945;-hydroxy ketone is also called acyloin, so the reaction is referred to as &#8216;acyloin condensation.&#8217;
<img alt="Organic synthesis; Claisen condensation mechanism; chemical reaction diagram with reactants and products." src="/files/ftp_upload/12908/12908_PT_Figure_1.svg" style="text-align: center; height: 65px;" data-altupdatedat="1761830439000" data-alt="Figure1" />
In the acyloin condensation reaction, esters are converted to ketyls, which undergo radical dimerization to form an unstable tetrahedral intermediate. Further, this intermediate collapses to give a 1,2-diketone intermediate. The 1,2-diketones are comparatively more reactive than ketones towards electrophiles and reducing agents because of lower &#960;* energy. Consequently, two electrons sequentially transfer to the 1,2-diketone to form an enediolate. Lastly, the enediolate intermediate is quenched with acid to yield an &#945;-hydroxy ketone with a good yield.
Often some by-products are obtained alongside the major product because of the reactivity of nucleophilic enediolate. To overcome the side reactions and improve the yield of an acyloin, trimethylsilyl chloride is used to silylate the enediolate. This results in a bis-silyl ether, further hydrolyzed with aqueous acid to give &#945;-hydroxy ketones.

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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JoVE Core

Organic Chemistry

Unit 1

Radical Chemistry

KEY TERMS AND CONCEPTS

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

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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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