Polonovski reaction

What is Polonovski reaction?

The transformation described as the Polonovski reaction involves the conversion of a tertiary amine oxide into an N,N-disubstituted acetamide and an aldehyde. This reaction was initially discovered by Polonovski in 1927. It is commonly carried out by treating the tertiary amine oxide with acetic anhydride or acetyl chloride, hence the name Polonovski reaction.

Polonovski reaction - general reaction scheme - Polonovski transformation - Polonovski demethylation - Polonovski rearrangement - Polonovski elimination
Polonovski reaction
  • R1, R2, R3 = alkyl, aryl
  • R = CH3, CF3

Due to the different reaction pathways that the resulting acetylated tertiary amine oxide can undergo, including the elimination of an α-hydrogen and the cleavage of one alkyl group on the nitrogen atom, various terms are used to refer to this reaction. These include Polonovski transformation, Polonovski demethylation, Polonovski rearrangement, and Polonovski elimination.

A modification of the Polonovski reaction was introduced by Potier in 1968, where trifluoroacetic anhydride is used instead of acetic anhydride or acetyl chloride. This modification, known as the Polonovski-Potier reaction, has proven to be valuable in alkaloid chemistry. It allows the reaction to stop at the iminium stage, which can then be trapped by the addition of cyanide to form an amino nitrile. The Polonovski-Potier reaction is also referred to as the Potier modification, Potier-Polonovski rearrangement, and Potier-Polonovski fragmentation.

The mechanism of elimination in the Polonovski reaction is believed to follow an E2 type mechanism, where the breaking of one of the carbon-nitrogen bonds requires activation by an adjacent electron-donating group and an anti-periplanar orientation to the N-O bond. However, cis-elimination has been observed for nupharidine-type alkaloids. It is worth noting that a similar transformation can also be catalyzed by an enzyme such as iron cytochrome P-450.