1 α-Carbonyl Nucleophiles Michael and Stork reactions Aldol condensation Claisen 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 Edited with the trial version of Foxit Advanced PDF Editor To remove this notice, visit: www.foxitsoftware.com/shopping
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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
Edited with the trial version of Foxit Advanced PDF Editor
To remove this notice, visit:www.foxitsoftware.com/shopping
2
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
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