Chapter 13 Reactions at the α-Carbon of Carbonyl Compounds Paula Yurkanis Bruice University of California, Santa Barbara

Contents of Chapter 13 Acidity of Alpha Hydrogens Keto-enol Tautomers Alkylation of Enolate Ions Aldol Condensation No Claisen, Malonic/Acetoacetic Ester, or Decarboxylation No Bioloogical Reactions Chapter 13

Acidity of a Hydrogens In the presence of a strong base, a proton a to a carbonyl group can be removed to form an enolate ion stabilized by electron delocalization: Chapter 13

Alkylation of Enolate Ions Enolate ions are alkylated (bonds made to carbon) at the alpha carbon: Chapter 13

Product Analysis Polarize the alpha carbon negative and an alpha hydrogen positive and swap partners with the positive and negative fragments of the alkylating reagent Chapter 13

Acidity of a Hydrogens This is Base-Catalyzed Enolization Reprotonation of the enolate ion can give an enol: This is Base-Catalyzed Enolization Chapter 13

Keto–Enol Tautomerism Under ordinary conditions, all aldehydes and ketones are in equilibrium with the corresponding enol forms. Interconversion of these isomers is catalyzed by acids or bases. For most simple aldehydes and ketones, the equilibrium lies on the side of the keto form because the carbon–oxygen double bond is stronger than a carbon–carbon double bond. Chapter 13

Acid-Catalyzed Enolization Chapter 13

Sample Problem Draw two enol forms for the following compound: Chapter 13

The Aldol Reaction The most important reaction of an enolate anion derived from an aldehyde or ketone is nucleophilic addition to the carbonyl group of another carbonyl-containing compound. Chapter 13

Mechanism of the Aldol Addition Step 1 – Deprotonation: Chapter 13

Mechanism of the Aldol Addition Step 2 – Nucleophilic Addition of Enolate Ion: Chapter 13

Mechanism of the Aldol Addition Step 3 – Reaction of alkoxide anion with solvent (protonation): Chapter 13

Dehydration of Aldol Products b-Hydroxyaldehydes and b-hydroxyketones are very easily dehydrated to give a,b-unsaturated aldehydes or ketones. Chapter 13

Aldol Reaction Product Analysis To figure out dehydration product of aldol reaction place carbonyl O of one molecule under 2 alpha H’s of the other molecule Erase the H’s and the O Extend the carbonyl double bond from the carbonyl C of the lower molecule to the alpha carbon of the upper molecule Chapter 13

Aldol Reaction Product Analysis Chapter 13

Retrosynthetic Analysis Draw structural formulas for the two carbonyl-containing compounds that react to give cinnamaldehyde: Chapter 13