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α-Carbonyl Nucleophiles

Michael and Stork reactionsAldol condensationClaisen condensation

The Michael Reaction

Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position.

Disampaikan oleh : Dr. Sri Handayani 2013

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The Michael Reaction

Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position.

Generic “Michael” addition

“Michael” addition

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Mechanism of the Michael Reaction

The Stork Enamine Reaction

O OCH2CH2CH

Oa. b. c. H+/H2O

N H

CH2 CH CH

O

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Mechanism of the Stork Enamine Reaction

Enolates react with carbonyls

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The Aldol addition and its products

Mechanism of the Aldolreaction

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The Aldol condensation makes α,β-unsaturated carbonyls

The Aldol intermediate is not always isolated

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What’s the mechanism?

The mixed Aldol can be a mess

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Mixed Aldol works if one has no α-hydrogens

Mixed aldol works if enolate is pre-formed

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The Claisen condensation makes β-keto esters

Mechanism

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The essential difference between Aldol and Claisen

leaving group

Why the Claisen only happens once: acidity of β-dicarbonyl

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Mixed Claisen in which one component has no α-hydrogens

Mixed Claisenbetween ketone and ester

Why don’t we get Aldol with ester enolatenucleophile?

pKa ~ 20 pKa ~ 25

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Mixed Claisen with formic or carbonate ester

Synthesis problem, from cyclohexanone

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Solution

Synthesis problem, from cyclohexanone

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Solution

The Dieckmann Condensation: an intramolecular Claisen condensation

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Mechanism

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Intramolecular Aldol can give two possible ring sizes

Intramolecular Aldol can give two possible ring sizes

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Six-membered rings are preferred

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The Robinson Annulation: Michael Addition, then intramolecular Aldol condensation

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Retrosynthetic breakdown

Robinson retrosynthesis

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Retrosynthetic breakdown

Robinson retrosynthesis