1 Nucleophilic reactions involving enolate anions (2) Aldehydes, Ketons and other carbonyl compounds having H on α-C -> in equilibrium (in solution) ->

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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

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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

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Nucleophilic reactions involving enolate anions

Nucleophilic addition to conjugated systems

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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

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Nucleophilic reactions involving enolate anions

Nucleophilic addition to conjugated systems – Michael reactionsMichael acceptors can also be utilized by the human body

Interacts with proteins -> cell damage