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Review CHAPTER of 140B R i f Enols, Enols Enolates and the Aldol Condensation: , Unsaturated -Unsaturated Aldehydes and Ketones
Strong bases can remove hydrogens leading to anions called enolate ions or enolates enolates.
Enol formation leads to deuterium exchange exchange.
Enol formation leads to racemization racemization.
Cat. Cat.
Aldehydes and ketones react with halogens at their -carbons.
Further halogenation is slow because the electron-withdrawing halogen substituent makes enolization more difficult.
Singly halogenated product molecules are not attacked until all of the starting aldehyde or ketone has been used up.
Alkylation of Enolates - Side Reactions:
Regioisomeric Products: If the starting ketone is unsymmetrical, g g y , either -carbon may be alkylated. Multiple Alkylations: Even ketones may lose a second -hydrogen and become alkylated a second time. E2 elimination: Enolate ion is a fairly strong base. Condensation Reactions: Aldehyde alkylations usually fail because their enolate ions undergo a highly favorable condensation reaction (aldol condensation ...).
The ketone possesses a single -hydrogen and the primary allylic halide is an excellent SN2 substrate.
Aldehydes undergo base-catalyzed condensations (aldol condensation):
A single aldol product can be obtained from the reaction of two different aldehydes when one of them has no enolizable hydrogen atoms.
Intramolecular aldol condensation: reaction of an enolate ion I t l l ld l d ti ti f l t i and a carbonyl group within the same molecule.
Intermolecular reaction is minimized by running the reaction in a dilute solution. Formation of 5- or 6-membered rings is favorable.
The least strained ring is formed (5- or 6-membered).
Organometallic reagents may attack the ,-unsaturated carbonyl function in either 1,2- 1,4-fashion. or Organolithium reagents react almost exclusively by adding at the carbonyl carbon.
Enolate ions undergo conjugate additions to ,-unsaturated aldehydes and k ld h d d ketones in the Michael addition. h i h l ddi i
With some Michael acceptors, the products of the initial addition Mi h l t th d t f th i iti l dditi are capable of a second intramolecular aldol condensation, resulting in ring formation.
This sequence of Michael addition followed by intramolecular aldol condensation is called a Robinson annulation.
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Important Concepts H d Hydrogens next t a carbonyll group are acidic: t to b idi
Carbonyl group is electron-withdrawing Resulting enolate ion is resonance-stabilized resonance stabilized
both the carbon and the oxygen Haloalkanes prefer the carbon Protonation of the oxygen leads to enols
Electrophilic Attack on enolates can occur at
Enol-Keto Conversion Aldehydes and ketones y
are in equilibrium with their tautomeric enol forms. The equilibrium is catalyzed by acid or base.
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Important Concepts H l Halogenation of carbonyll compounds may b ti f b d be
acid- or base-catalyzed. Acid: attack at the double bond subsequent q renewed enolization is slowed down by the halogen Base: attack at the carbon subsequent renewed enolization is speeded up by the halogen
Aldol Condensation Nucleophilic, reversible
attack of an enolate at the carbonyl carbon of an aldehyde or ketone Michael Addition Attack of an enolate at the carbon of an ,-unsaturated carbonyl compound
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Important Concepts ,-Unsaturated Ald h d and Ketones U t t d Aldehydes d K t
Show normal chemistry at each individual double bond Conjugated system may react as a whole: Acid- d base-catalyzed 1 4 dditi A id and b t l d 1,4-additions Alkyllithiums normally attack the carbonyl function