Chapter 18: Enols and EnolatesChapter 18: Enols and Enolates

Overview

Enols :

Enolates :

18.1 – The 18.1 – The Hydrogen and Its p Hydrogen and Its pKaKa

18.2 – The Aldol Condensation18.2 – 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 H18.2 – The Aldol Condensation (loss of H22O)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 Reactions18.3 – Mixed (Crossed) Aldol Reactions

all present in solution at same time

2 enolizable substrates leads to multiple products

18.3 – Mixed (Crossed) Aldol Reactions18.3 – Mixed (Crossed) Aldol Reactions

Usually use 1 non-enolizable substrate:

Elimination of H2O common when conjugation results, can also be induced by heating the reaction mixture

18.4 – Alkylation of Enolate Ions18.4 – Alkylation of Enolate Ions

• Greek staphyle meaning “a bunch of grapes” • Greek kokkos meaning “berry” • aureus = yellow

Staphylococcus aureus (MRSA, VRSA)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

O

OHO

O

OHO

NHAc

O

H3C

OAcNHAc

OO

CH3HO

NHAc

Type 5 Type 8

O

O

HO

O

AcOO

NHAc

O

H3CNHAc

O

OCH3HO

AcHN

HO

n n

Bacterial Capsular Polysaccharides – Bacterial Capsular Polysaccharides – serotypesserotypes

18.5 – Enolization and Enol Content18.5 – 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 Content18.5 – Enolization and Enol Content

18.5 – Base-Catalyzed Enolization18.5 – Base-Catalyzed Enolization

Enolate resonance forms – not tautomers

18.5 – Acid-Catalyzed Enolization18.5 – Acid-Catalyzed Enolization

Sequential proton transfers

18.6 – Stabilized Enols18.6 – Stabilized Enols

18.7 – 18.7 – -Halogenation of Aldehydes and Ketones-Halogenation of Aldehydes and Ketones

• The reaction overall is a substitution• The reaction is regiospecific – only -H is replaced

18.8 – Mechanism of 18.8 – Mechanism of -Halogenation of Aldehydes and Ketones-Halogenation of Aldehydes and Ketones

Very good cation generated (hetero-atom stabilized)

18.9, 18.10 – The Haloform Reaction and 18.9, 18.10 – The Haloform Reaction and -Deuteration-Deuteration

-Deuteration

Iodoform reaction

A methyl ketoneiodoform

18.11 – Conjugation in 18.11 – Conjugation in ,,-Unsaturated Systems-Unsaturated Systems

Carbonyl carbon and -carbon have positive character

AcroleinFigure 18.2

Pi system iscompletelydelocalized

18.12 – Conjugate Addition to 18.12 – Conjugate Addition to ,,-Unsaturated Systems-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 Reaction18.13 – 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 Sequence18.13 – Michael Addition – Robinson Annulation Sequence

Application:

18.14 – Conjugate Addition of Organocopper Reagents18.14 – Conjugate Addition of Organocopper Reagents