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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
a.
N
H
b.
CH2
O
CH2CH2CH
O
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