Chapter 18 provides knowledge of enols, enolates, enals, and enones. The main contents of this chapter include all of the following: Keto-enol equilibria, aldol condensation, intramolecular aldol, preparation,.and other contents. | Chapter 18: Enols, Enolates, Enals, and Enones α-Hydrogens in carbonyl compounds are acidic 12/13/2014 1 Deprotonation of a carbonyl compound: Stoichiometric deprotonation: KH, LDA Compare: propene ~40 Dominant form Enolates: “Oxaallyls” Acetone enolate Note: RLi and RMgX usually add to carbonyl Equilibrium deprotonation: NaOH, NaOR Reactivity: Ambident, attack on either O or C: Alkylation on C is dominant Kinetic protonation on O, followed by tautomerism Tautomerization Enolate formation can be regioselective Traces of acid (free amine, slight excess of ketone) give equilibration to more stable enolate Keto-Enol Equilibria H+ or –OH cat. K <<1 usually We often don’t need stoichiometric enolate formation: Acid or base forms enols or enolates in equilibrium concentrations, sufficient for many further transformations. H+ or –OH cat. Worse, because CH3 stabilizes keto form “Keto form” “Enol form” Mechanisms of enol to keto tautomerization (and the reverse): Acid-catalyzed Base-catalyzed | Chapter 18: Enols, Enolates, Enals, and Enones α-Hydrogens in carbonyl compounds are acidic 12/13/2014 1 Deprotonation of a carbonyl compound: Stoichiometric deprotonation: KH, LDA Compare: propene ~40 Dominant form Enolates: “Oxaallyls” Acetone enolate Note: RLi and RMgX usually add to carbonyl Equilibrium deprotonation: NaOH, NaOR Reactivity: Ambident, attack on either O or C: Alkylation on C is dominant Kinetic protonation on O, followed by tautomerism Tautomerization Enolate formation can be regioselective Traces of acid (free amine, slight excess of ketone) give equilibration to more stable enolate Keto-Enol Equilibria H+ or –OH cat. K <<1 usually We often don’t need stoichiometric enolate formation: Acid or base forms enols or enolates in equilibrium concentrations, sufficient for many further transformations. H+ or –OH cat. Worse, because CH3 stabilizes keto form “Keto form” “Enol form” Mechanisms of enol to keto tautomerization (and the reverse): Acid-catalyzed Base-catalyzed How is enolization detected ? Most easily by NMR: H-D exchange with D2O, D+, or D2O, -OD (α-H signals disappear). Other consequence of enolization: Loss of stereochemistry Cis More stable Trans Halogenation: uses catalytic H+ or HO- Acid-catalyzed: Base-catalyzed: + Cl2 HCl + HCl + Cl2 NaOH +NaCl Stops here! Perchlorination Mechanisms: Acid-catalyzed Ethenol is e-rich Like a Markovnikov alkene bromination, but open cation, not: Br substituent slows further halogenation Bromonium ion Both are octets Less basic Octet Octet, but strained Base-catalyzed Br substituent increases the acidity of the α-Hs: Speeds further halogenation. Like an SN2 reaction Alkylation Alkylation of enolates can be difficult to control 1. Enolate ion is a strong base: E2 problems • Alkylation best when using halomethanes, primary haloalkanes, or allylic halides 2. Aldehydes are attacked by enolates at carbonyl carbon “Aldol condensation” (later) • Better to use the less reactive (at carbonyl) ketones Ketones have
