Nucleophilic reactions involving enolate anions (2)

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

2. Acylation of enolate anions -> Claisen reaction (condensation) Nucleophilic reactions involving enolate anions 2 mol ester - (base) -> β-ketoester

3. 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 Nucleophilic reactions involving enolate anions H+ /acid If on α-C just one H -> no reaction under this condition -> no α-H left to produce anolate anion resonance structure

4. Acylation of enolate anions -> Claisen reaction (condensation) Claisen and aldol in nature -> Cholesterol biosynthesis Nucleophilic reactions involving enolate anions

5. Intramolecular Claisen reaction -> Dieckman reaction Nucleophilic reactions involving enolate anions

6. Mixed Claisen reaction Nucleophilic reactions involving enolate anions

7. Mixed Claisen reaction Nucleophilic reactions involving enolate anions Better synthesis approach !!!

8. Aldol - Claisen reaction -> prediction of product Aldol -> Keton is electrophile Claisen -> Ester is electrophile Nucleophilic reactions involving enolate anions

9. Aldol - Claisen reaction -> prediction of product • Aldol + Claisen reaction are in equilibria • -> disturbing the equilibria -> product formation • Dehydration in aldol (slide 14) • Ionization in Claisen (slide 27) • -> Ionization determinant -> Claisen reaction occurs • Product from Claisen gives the more acidic product Nucleophilic reactions involving enolate anions

10. 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 Nucleophilic reactions involving enolate anions

11. Decarboxylation reactions β-ketoesters + acid catalysed -> β-ketoacid -> loss of carbon dioxide -> decarboxylated Nucleophilic reactions involving enolate anions

12. Decarboxylation reactions β-ketoesters + acid catalysed -> β-ketoacid -> loss of carbon dioxide -> decarboxylated Nucleophilic reactions involving enolate anions β-ketoesters are intermediates to obtain substituted ketons

13. Decarboxylation reactions β-ketoesters + acid catalysed -> β-ketoacid -> loss of carbon dioxide -> decarboxylated β-ketoesters are intermediates to obtain substituted ketons Nucleophilic reactions involving enolate anions

14. Nucleophilic addition to conjugated systems Nucleophilic reactions involving enolate anions

15. Nucleophilic addition to conjugated systems Nucleophilic reactions involving enolate anions

16. Nucleophilic addition to conjugated systems Nucleophilic reactions involving enolate anions 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

17. Nucleophilic addition to conjugated systems Nucleophilic reactions involving enolate anions Grignard LiAlH4 Hydration

18. Nucleophilic addition to conjugated systems – Michael reactions Enolate anion as nucleophile Nucleophilic reactions involving enolate anions Production of Steroid hormones (Testosterone male sex hormone)

19. Nucleophilic addition to conjugated systems – Michael reactions Michael acceptors can be carcinogenic Nucleophilic reactions involving enolate anions Michael acceptors can also be utilized by the human body

20. Nucleophilic addition to conjugated systems – Michael reactions Michael acceptors can also be utilized by the human body Nucleophilic reactions involving enolate anions Interacts with proteins -> cell damage