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Nucleophilic reactions involving enolate anions (2)
Aldehydes, Ketons and other carbonyl compounds having H on α-C -> in equilibrium (in solution) -> Keto-Enol tautomerization
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Nucleophilic reactions involving enolate anions
Acylation of enolate anions -> Claisen reaction (condensation)
2 mol ester - (base) -> β-ketoester
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Nucleophilic reactions involving enolate anions
Acylation of enolate anions -> Claisen reaction (condensation)
OEt- -> is strong base rather than good leaving groupe
reaction will run further -> anolate anion produced ->
acid required to regenerate β-ketoester
H+ /acid
If on α-C just one H -> no reaction under this condition
-> no α-H left to produce anolate anion resonance structure
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Nucleophilic reactions involving enolate anions
Acylation of enolate anions -> Claisen reaction (condensation)
Claisen and aldol in nature -> Cholesterol biosynthesis
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Nucleophilic reactions involving enolate anions
Intramolecular Claisen reaction -> Dieckman reaction
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Nucleophilic reactions involving enolate anions
Mixed Claisen reaction
Better synthesis approach !!!
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Nucleophilic reactions involving enolate anions
Aldol - Claisen reaction -> prediction of product
Aldol -> Keton is electrophile
Claisen -> Ester is electrophile
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Nucleophilic reactions involving enolate anions
Aldol - Claisen reaction -> prediction of product
Aldol + Claisen reaction are in equilibria
-> disturbing the equilibria -> product formation
1. Dehydration in aldol (slide 14)
2. Ionization in Claisen (slide 27)
-> Ionization determinant -> Claisen reaction occurs
Product from Claisen gives the more acidic product
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Nucleophilic reactions involving enolate anions
Reverse Claisen reaction
Driving force for Claisen reaction -> formation of enolate anion of the β-ketoester product (ionization)
If they cannot be formed -> reverse reaction controls equilibrium
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Nucleophilic reactions involving enolate anions
Decarboxylation reactions
β-ketoesters + acid catalysed -> β-ketoacid -> loss of carbon dioxide -> decarboxylated
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Nucleophilic reactions involving enolate anions
Decarboxylation reactions
β-ketoesters + acid catalysed -> β-ketoacid -> loss of carbon dioxide -> decarboxylated
β-ketoesters are intermediates to obtain substituted ketons
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Nucleophilic reactions involving enolate anions
Decarboxylation reactions
β-ketoesters + acid catalysed -> β-ketoacid -> loss of carbon dioxide -> decarboxylated
β-ketoesters are intermediates to obtain substituted ketons
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Nucleophilic reactions involving enolate anions
Nucleophilic addition to conjugated systems
1,2 addition versus 1,4 addititon:
-> Nu good leaving group -> 1,2 addition is reversible -> 1,4 product (thermodynamic control)
-> Nu bad leaving group -> 1,2 addition irreversible -> 1,2 product (kinetic control)
-> stereochemistry also important -> large Nu –> 1,4 addition preferred
Except -> Grignard + LiAlH4 hydration -> 1,2 addition
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Nucleophilic reactions involving enolate anions
Nucleophilic addition to conjugated systems
Grignard
LiAlH4 Hydration
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Nucleophilic reactions involving enolate anions
Nucleophilic addition to conjugated systems – Michael reactions
Enolate anion as nucleophile
Production of Steroid hormones (Testosterone male sex hormone)
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Nucleophilic reactions involving enolate anions
Nucleophilic addition to conjugated systems – Michael reactions
Michael acceptors can be carcinogenic
Michael acceptors can also be utilized by the human body