Properties of ,-Unsaturated Aldehydes and Ketones

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Conjugated unsaturated aldehydes and ketones are more stable than their unconjugated isomers.

Enones, or ,-unsaturated carbonyl groups, are stabilized by resonance.

As a result, acids or bases catalyze a rearrangement of ,-unsaturated carbonyl compounds to their conjugated --isomers.

,-Unsaturated aldehydes and ketones undergo the reactions typical of their component functional groups.

The conjugated carbonyl group of ,-unsaturated aldehydes and ketones can undergo reactions involving the entire functional system by:

Acid-catalyzed mechanisms

Radical mechanisms

Nucleophilic addition mechanisms

Conjugate Additions to ,-Unsaturated Aldehydes and Ketones

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The entire conjugated system takes part in 1,4-additions.

Addition reactions involving only one of the two bonds are called 1,2-additions.

Several reagents add to the conjugated system in a 1,4-manner. This is called conjugate addition.

The nucleophilic part of the reagent attaches to the -carbon and the electrophilic part (proton) attaches to the carbonyl oxygen.

When A is H, the initial product is an enol, which then tautomerizes to its keto form.

The end result then appears to be a 1,2-addition.

Oxygen and nitrogen nucleophiles undergo conjugate additions.Conjugate additions of water, alcohols, amines and similar nucleophiles undergo 1,4 additions:

These reactions are generally faster and result in higher yields when a base is used as the catalyst.

These processes are readily reversed at elevated temperatures.

1,4-products (carbonyl compounds) usually form rather than 1,2-products (hydrates, hemiacetals and hemiaminals) because they are more stable.

Exceptions include amine derivatives for which 1,2-addition results in an insoluble product (hydroxylamine, semicarbazide or the hydrazines).

Hydrogen cyanide also undergoes conjugate addition.A conjugated aldehyde or ketone may react with cyanide in the presence of acid.

The reaction proceeds through a 1,4-addition pathway. • Protonation of the oxygen• Nucleophilic attack• Enol-keto tautomerization

1,2- and 1,4-Additions of Organometallic Reagents

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Organometallic reagents may attack the ,-unsaturated carbonyl function in either 1,2- or 1,4-fashion.

Organolithium reagents react almost exclusively by attacking the carbonyl carbon.

Grignard reagents with ,-unsaturated aldehydes and ketones may give 1,2-addition, 1,4-addition or both, depending upon the particular substrates and conditions.

Organocuprates are much more specific, undergoing primarily 1,4-addition reactions.

The first isolable intermediate in a copper-mediated 1,4-addition reaction is an enolate ion. This is trapped by the alkylating species.

Conjugate Additions of Enolate Ions: Michael Addition and Robinson Annulation

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Enolate ions undergo conjugate additions to ,-unsaturated aldehydes and ketones in a reaction called the Michael addition.

With some Michael acceptors, the products of the initial addition are capable of a second intramolecular aldol condensation reaction, resulting in ring formation.

This sequence of Michael addition followed by intramolecular aldol condensation is called a Robinson annulation.