Question

Specific enolates of unsymmetrical ketones can be obtained by reduction of an alpha, beta-unsaturated ketone (enone) with lithium-(0) in liquefied ammonia. Alkylation of the derived enolate gives an alpha-alkyl derivative of the corresponding saturated ketone, which is not the same as that obtained by a base-mediated enolization/alkylation of the saturated ketone itself.

Provide an explanation for the turnover in the regiochemical course of the alkylation reactions.

Answer 1

Enone reduction by dissolved metal (Li/NH₃);

metal The dissolving metal reduction (Li/NH₃) of enones by lithium metal in liquid ammonia is C=C bond of the enone is reduced, with the C=O bond remaining unaffected. Alcohol is required as a proton source and, in total, two electrons and two protons are added in a stepwise manner, giving net addition of a molecule of hydrogen to the double bond.

Sodium metal gives a single electron which forms a radical anion that is protonated by the alcohol to form a radical. A second electron transfer forms an anion that can undergo tautomerization to an enolate.

The enolate is stable to further reduction and protonation during the work-up will give a ketone. But reaction with an alkyl halide is more useful, because of the enolate forms only where the double bond of the enone was, regioselective alkylation becomes possible.

In the above two reactions, one side of ketone only alkylation reaction happened. Another side of the ketone not affected by alkylation. Thus Specific enolates of unsymmetrical ketones can be obtained by reduction of an alpha, beta-unsaturated ketone (enone) with lithium-(0) in liquefied ammonia.

Simple ketone on alkylation gives two different product;

From the above reaction, we can confirm that simple ketone gives different regiometric products. The regioisomers are formed based on the which base we are used for making enolates.

The bulky base gives a less substituted product

The small base gives a more substituted product.