20.27:
α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
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 α-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 α-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 α-hydroxy ketone as the final product.
20.27:
α-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 α-hydroxy ketone product. The α-hydroxy ketone is also called acyloin, so the reaction is referred to as ‘acyloin condensation.’
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 π* 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 α-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 α-hydroxy ketones.