Nenitzescu synthesis

What is Nenitzescu synthesis?

The Nenitzescu synthesis, which was first reported in 1931, involves the direct formation of an α,β-unsaturated ketone by acylation of alkenes with acyl halides, facilitated by aluminum chloride AlCl3. This reaction is also referred to as the Nenitzescu acylation or the Nenitzescu reductive acylation.

Nenitzescu synthesis - general reaction scheme - Nenitzescu acylation - Nenitzescu reductive acylation
Nenitzescu synthesis
  • R1, R2 = H, alkyl
  • R3 = alkyl, aryl
Nenitzescu synthesis - general reaction scheme - Nenitzescu acylation - Nenitzescu reductive acylation
Nenitzescu synthesis
  • R1, R2 = H, alkyl
  • R3 = alkyl, aryl

In the presence of benzene or hexane, the formation of saturated ketones can occur due to intermolecular hydrogen transfer from the solvent. Cyclopropyl groups, due to their intrinsic strain, react similarly to olefinic functionalities and can be readily acylated as well.

However, the Nenitzescu synthesis is often complicated by the formation of β-halo ketones, β,γ-enones, or β-acyloxy ketones under various reaction conditions. This complication can be overcome by using vinyl mercuric chloride for acylation, which results in high stereochemistry purity.

References

Nenitzescu, C.D. and Ionescu, C.N. (1931), Durch Metall-halogenide katalysierte Reaktionen. I. Über die Einwirkung von Aluminiumchlorid auf Halogenverbindungen in Gegenwart von Cycloparaffinen. [Reactions catalyzed by metal halides. I. On the action of aluminum chloride on halogen compounds in the presence of cycloparaffins.] Justus Liebigs Ann. Chem., 491: 189-210. https://doi.org/10.1002/jlac.19314910112

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