20.27 : エステルの還元カップリングによるα-ヒドロキシケトン: アシロイン縮合の概要

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.