Chapter 18: Enols and Enolates Overview Enols : Enolates :

18.1 – The  Hydrogen and Its pKa

18.2 – The Aldol Condensation When appropriate base is used, both aldehyde and enolate present in solution, this leads to the aldol reaction

18.2 – The Aldol Condensation (loss of H 2 O) When the reaction is run at low temperature the aldol product may be isolated; at elevated temperature the elimination occurs

18.3 – Mixed (Crossed) Aldol Reactions all present in solution at same time 2 enolizable substrates leads to multiple products

18.3 – Mixed (Crossed) Aldol Reactions Usually use 1 non-enolizable substrate: Elimination of H 2 O common when conjugation results, can also be induced by heating the reaction mixture

18.4 – Alkylation of Enolate Ions

Greek staphyle meaning “a bunch of grapes” Greek kokkos meaning “berry” aureus = yellow Staphylococcus aureus (MRSA, VRSA)

Gram-positive, cluster-forming coccus Cause food poisoning, endocarditis, osteomyelitis Can cause septiceamia, infections on implants Becoming increasingly resistant to antibiotics MRSA strains appeared in 1961 VRSA first reported in the USA in 2002

Microcapsule (carbohydrate) – defends against phagocytosis

Bacterial Capsular Polysaccharides – serotypes

18.5 – Enolization and Enol Content Tautomers – two structures that differ by placement of an atom or a group The enol form is usually in low concentration since the C=O is more stable Tautomerism is acid-catalyzed and base-catalyzed

18.5 – Enolization and Enol Content

18.5 – Base-Catalyzed Enolization Enolate resonance forms – not tautomers

18.5 – Acid-Catalyzed Enolization Sequential proton transfers

18.6 – Stabilized Enols

18.7 –  -Halogenation of Aldehydes and Ketones The reaction overall is a substitution The reaction is regiospecific – only  -H is replaced

18.8 – Mechanism of  -Halogenation of Aldehydes and Ketones Very good cation generated (hetero-atom stabilized)

18.9, – The Haloform Reaction and  -Deuteration  -Deuteration Iodoform reaction A methyl ketone iodoform

18.11 – Conjugation in ,  -Unsaturated Systems Carbonyl carbon and  -carbon have positive character Acrolein Figure 18.2 Pi system is completely delocalized

18.12 – Conjugate Addition to ,  -Unsaturated Systems More reactive nucleophiles (e.g. RMgX) attack the most +ve C i.e. the carbonyl carbon. These reactions are usually irreversible. Softer nucleophiles undergo reversible addition and lead to the more stable (thermodynamically favoured) 1,4-addition product.

18.13 – The Michael Reaction H alpha to two C=O will be more acidic than next to one C=O, deprotonation leads to a soft nucleophile that adds 1,4-

18.13 – Michael Addition – Robinson Annulation Sequence Application:

18.14 – Conjugate Addition of Organocopper Reagents