Reactions at the α

Carbon of Carbonyl

Compounds

Formation of Regioselective Enolates

Synthesis of g-keto esters:

Enamines can also be used in Michael

additions:

NCN+

N

CN

EtOH

reflux

O

H2OCN

Summary of Enolate Chemistry

O

R

H

+ :B

Resonance-stabilized

enolate

O

R

O

RH:B +

.1Formation of an Enolate:

Racemization:

Ph

OR'

HR

Enantiomers

Ph

OH

R

R'OH

or H3O

Enol(achiral)

Ph

OR'

RH

OH

or H3O

Halogenation of Aldehydes & Ketones:

O

RR'

H

O

RR'

X

+ X2

acid

or base

Specific example: haloform reaction:

O

PhH

H

O

Ph

X

+ 3 X2

OH

H2O

X

X

O

Ph OCHX3 +

H

Halogenation of Carboxylic Acids: The HVZ Reaction:

O

OHR

O

OHR

X

1. X2, P

2. H2O

Direct Alkylation via Lithium Enolates:

Specific example:

O

H(R')

O

H(R')

LDA, THF

R

(formation of thekinetic enolate)

RR'' X

O

H(R')R

-78oC

R''

O O Li O

CH3ILDA, THF

-78oC

Direct Alkylation of Esters:

O

OEtR

O

OEtR

LDA

THF

R' BrO

OEtR

R'

Acetoacetic Ester Synthesis:

O

OEt

1. NaOEt

2. RBr

O O

OEt

O

RO

1. OH, heat

2. H3O+

3. heat, ( CO2)R

O

OEt

1. tBuOK

2. R'Br

O O

OEt

O

O

R

RR R'

R'

1. OH, heat

2. H3O+

3. heat, ( CO2)

Malonic Ester Synthesis:

O

OEt

1. NaOEt

2. RBrEtO

O O

OEtEtO

O

R

HO

O1. OH, heat

2. H3O+

3. heat, ( CO2)R

O

OEt

1. tBuOK

2. R'BrEtO

O O

OEtEtO

O

HO

O

R

RR R'

R'

1. OH, heat

2. H3O+

3. heat, ( CO2)

Stork Enamine Reaction:

1.

2. heat3. H2O

O

RR + R'2NH R

NR'2

R

R R

O

R''

R'' Br

Enamine