Enones undergo many kinds of reactions. They are electrophilic at both the carbonyl carbon as well as the β-carbon. Depending on conditions, either site is attacked by nucleophiles. Additions to the alkene are called conjugate additions. One type of conjugate addition is the Michael addition, which is used in the conversion of mesityl oxide into isophorone. The alkene portion of enones are often good dienophiles in Diels–Alder reactions. They are activated even further by Lewis acids, which bind to the carbonyl oxygen. Enones are readily reduced. They can undergo reduction of the carbonyl or the alkene selectively, or reduction of both functional groups. Enones undergo the Nazarov cyclization reaction and in the Rauhut–Currier reaction. Sterically unhindered enones such as methyl vinyl ketone are prone to polymerization. Enones are good ligands for low-valent metal complexes, examples being Fe3 and trisdipalladium.
Related compounds
Enone is not to be confused with ketene. An enamine is a cousin of an enone, with the carbonyl replaced by an amine group.
Regiospecific formation is the controlled enolate formation by the specific deprotonation at one of the α-carbons of the ketone starting molecule. This provides one of the best understood synthetic strategies to introduce chemical complexity in natural product and total syntheses. A prominent example of its use is in the total synthesis of progesterone illustrated in Figure "Regiospecific enolate formation in the total synthesis of progesterone". When ketones are treated with base, enolates can be formed by deprotonation at either α-carbon. The selectivity is determined by both the steric and electronic effects on the α-carbons as well as the precise base used. Enolate formation will be thermodynamically favoured at the most acidic proton which depends on the electronic stabilization of the resulting anion. However, the selectivity can be reversed by sterically hindering the thermodynamic product and therefore kinetically favouring deprotonation at the other α-carbon centre. Traditional methods for regioselective enolate formation use either electronic activating groups or steric blocking groups. Enone can also serve as a precursor for regiospecific formation of enolate, here the enone is a “masked functionality” for the enolate. This process is first described by Gilbert Stork who is best known for his contributions to the study of selective enolate formation methods in organic synthesis. The Stork method also uses enone as a “masked functionality” of enolate. Reacting enone with lithium metal generates the enolate at the α-carbon of the enone. The enolate product can either be trapped or alkylated. By using “masked functionality”, it is possible to produce enolates that are not accessible by traditional methods. The “masked functionality” approach to regiospecific enolate formation has been widely used in total synthesis of natural products. For example, in the total synthesis of the steroid hormone progesterone, Stork and co-workers used the “masked functionality” to stereospecifically construct one of the quaternary carbons in the molecule.
