11 Enols, Enolates, and Carbon–Carbon Bond Formation

The α-Carbon and Carbonyl Reactivity

The α-carbon is the carbon directly next to a carbonyl carbon; the next carbon along the chain is the β-carbon. An α-hydrogen is attached to the α-carbon. For example, in propanone, $\mathrm{CH_3-C(=O)-CH_3}$, each methyl carbon is an α-carbon.

An α-hydrogen is more acidic than an ordinary alkane hydrogen because removing it produces a conjugate base stabilized by the neighboring carbonyl. The approximate $pK_a$ of a propanone α-hydrogen is $19$, compared with about $60$ for an alkane hydrogen. This difference helps explain why carbonyl compounds can react at their α-carbons.

Enols and Keto–Enol Tautomerism

An enol has a carbon–carbon double bond with an alcohol group attached directly to one of the alkene carbons, represented as $\mathrm{C=C-OH}$. In keto–enol tautomerism, a carbonyl compound and its enol interconvert as a hydrogen and a double bond change position. They are constitutional isomers, not resonance forms.

For propanone, the relationship can be represented as:

Most simple aldehydes and ketones exist mainly in the keto form at equilibrium. Enol content can be greater when the enol receives additional stabilization, for example from conjugation or intramolecular hydrogen bonding.

Enolization can be catalyzed by either acid or base. Under acid catalysis, the carbonyl oxygen is protonated before an α-hydrogen is removed to form the enol. Under base catalysis, a base removes the α-hydrogen to form an enolate; protonation at oxygen then gives the enol.

Enolate Formation and Resonance

A base removes an α-hydrogen to form an enolate ion. The ion is represented by resonance contributors that place the negative charge on either carbon or oxygen:

These contributors are not separate molecules; they depict one ion with delocalized charge. The carbon-centered contributor helps explain why an enolate can form carbon–carbon bonds, while the oxygen-centered contributor reflects the ion’s stabilization.

A strong base such as lithium diisopropylamide (LDA) can convert a carbonyl compound substantially into its enolate. Weaker bases often establish an equilibrium with only a small fraction present as enolate. If a compound has nonequivalent α-carbons, it may form different enolates; the base, solvent, temperature, and reaction time can affect which predominates.

Enolate Alkylation

Enols and enolates can act as nucleophiles at the α-carbon. When an enolate reacts with an electrophile, a new bond can replace an α-hydrogen, giving an α-substituted carbonyl compound.

In enolate alkylation, the enolate carbon attacks an alkyl halide and displaces its leaving group through an $S_\mathrm{N}2$ mechanism. For example:

This reaction is most suitable for methyl or primary alkyl halides, which allow the required backside attack. Tertiary alkyl halides generally do not undergo this substitution effectively because elimination competes strongly.

The Aldol Reaction

The aldol reaction joins two aldehyde or ketone molecules. One partner forms an enolate and acts as the donor; the other retains its carbonyl group and acts as the electrophile. The initial product is a β-hydroxy aldehyde or β-hydroxy ketone, collectively called a β-hydroxy carbonyl compound. At least one reaction partner must have an α-hydrogen to form the enol or enolate donor.

In a base-catalyzed aldol reaction:

1. A base removes an α-hydrogen from the donor carbonyl, forming an enolate.

2. The enolate’s α-carbon attacks the electrophile’s carbonyl carbon. The carbonyl π electrons move to oxygen, producing an alkoxide and a new carbon–carbon bond.

3. The alkoxide is protonated to give the β-hydroxy carbonyl product and regenerate the base.

For ethanal, the overall addition is:

The product is 3-hydroxybutanal. Its hydroxyl group is at the β-carbon relative to the remaining aldehyde carbonyl. The initial formation of this β-hydroxy carbonyl is called aldol addition.

Aldol Condensation and Product Features

Under conditions that promote dehydration, often heating, the β-hydroxy carbonyl product can lose water. This step changes an aldol addition into an aldol condensation and forms a conjugated carbonyl compound. For the ethanal product:

The product, but-2-enal, has a carbon–carbon double bond between its α- and β-carbons, conjugated with the carbonyl. The alkene may have $E$ or $Z$ geometry; the more stable product is often favored, but the outcome depends on the reaction and its conditions.

Aldol addition can also create a stereogenic center at the carbon bearing the hydroxyl group. In an achiral environment, if both enantiomeric pathways are equally accessible, formation of that center commonly gives a racemic mixture. Some reactions instead show stereoselectivity depending on the substrate and conditions.

Choosing Aldol Partners

When the same carbonyl compound serves as both donor and electrophile, a self-aldol reaction may occur. A crossed-aldol reaction uses two different carbonyl compounds. If both partners can form enolates, several products may result, so choosing which partner forms the enolate is important.

To favor one crossed-aldol product, chemists commonly select partners so that one forms the enolate selectively while the other acts mainly as the electrophile. A carbonyl compound with no α-hydrogen cannot form an enolate and may serve as the electrophilic partner, although selectivity still depends on the conditions.

An intramolecular aldol reaction is also possible when a single molecule contains two carbonyl groups. An enolate at one site can attack the other carbonyl, often closing a ring.

Takeaway: Identify which partner forms the enolate and which acts as the electrophile; this distinction is central to predicting aldol products.