Enols and Enolates Lecture Notes
Definitions
- Alpha carbons: Carbons directly attached to the carbonyl carbon.
- Beta, Gamma, Delta carbons: Carbons further away, sequentially, from the carbonyl carbon.
- Enols and Enolates: Formed at the alpha carbons.
Reactivity
- Enols and enolates form only from alpha carbons with hydrogens.
- Ketones often have two alpha carbons.
- If alpha carbon lacks hydrogens, it cannot form enols or enolates.
Structure
- Enol: Alcohol directly attached to a C=C double bond.
- Enolate: Formed from ketone or aldehyde with a strong base, having a negative charge shared between O and alpha carbon.
- Tautomers: Constitutional isomers differing by proton placement and double bond position.
Mechanism
- Acid-Catalyzed: Protonation of ketone oxygen, attack on electrophiles.
- Base-Catalyzed: Base deprotonates, forming an enolate with resonance stabilization.
Stability and Exceptions
- Keto forms are generally more stable, but exceptions include:
- 1,3-diketones: Enol form stable due to intramolecular hydrogen bonding and conjugation.
- Phenols: Favor enol form due to aromaticity.
Formation and Reactions
- Enolate Formation: Strong base converts aldehyde/ketone to enolate.
- Enolates as Nucleophiles: React with electrophiles to form products, e.g., alpha-halogenation.
Acidity and Base Selection
- Alpha hydrogens are more acidic due to resonance-stabilized enolates.
- Choice of base affects full or partial conversion to enolate:
- Weak bases (e.g., sodium ethoxide): Partial conversion.
- Strong bases (e.g., LDA, sodium hydride): Full conversion.
Example Mechanisms
- Tautomerization: Switching between keto and enol forms under acidic or basic conditions.
- Aldol Reaction: Enolate attacks aldehyde/ketone forming beta-hydroxy ketone or aldehyde.
- Condensation: Heating promotes conversion to alpha-beta unsaturated aldehyde/ketone.
Crossed Aldol Reactions
- Successful when one reactant is a good electrophile without alpha hydrogens.
- Control is achieved using LDA or specific reaction conditions.
Intramolecular Aldol Reactions
- Suitable for forming five- or six-membered rings with good yields.
This lecture provided a comprehensive overview of enols and enolates, their formation, reactivity, and applications in organic reactions, with special emphasis on the mechanisms and conditions affecting their stability and transformation. Always consider the acidity of alpha hydrogens and the resonance stability of resulting structures when predicting outcomes of reactions involving enols and enolates.