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Disampaikan oleh : Dr. Sri Handayani 2013
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.
1 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
2 Mechanism of the Michael Reaction
The Stork Enamine Reaction
O O O a. N H CH2CH2CH O
b. CH2 CH CH
+ c. H /H2O
3 Mechanism of the Stork Enamine Reaction
Enolates react with carbonyls
4 The Aldol addition and its products
Mechanism of the Aldol reaction
5 The Aldol condensation makes α,β-unsaturated carbonyls
The Aldol intermediate is not always isolated
6 What’s the mechanism?
The mixed Aldol can be a mess
7 Mixed Aldol works if one has no α-hydrogens
Mixed aldol works if enolate is pre-formed
8 The Claisen condensation makes β-keto esters
Mechanism
9 The essential difference between Aldol and Claisen
leaving group
Why the Claisen only happens once: acidity of β-dicarbonyl
10 Mixed Claisen in which one component has no α-hydrogens
Mixed Claisen between ketone and ester
pKa ~ 20 pKa ~ 25
Why don’t we get Aldol with ester enolate nucleophile?
11 Mixed Claisen with formic or carbonate ester
Synthesis problem, from cyclohexanone
12 Solution
Synthesis problem, from cyclohexanone
13 Solution
The Dieckmann Condensation: an intramolecular Claisen condensation
14 Mechanism
15 Intramolecular Aldol can give two possible ring sizes
Intramolecular Aldol can give two possible ring sizes
16 Six-membered rings are preferred
17 The Robinson Annulation: Michael Addition, then intramolecular Aldol condensation
18 Retrosynthetic breakdown
Robinson retrosynthesis
19 Retrosynthetic breakdown
Robinson retrosynthesis
20