4.3: Ketone Enolates
- Page ID
- 22904
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Kinetic vs. Thermodynamic Enolate
Enolate Regiochemistry must also be considered...
If we consider the energetics of the reaction, we can selectively produce one enolate.
Carbon vs. Oxygen Nucleophilicity
Ketones can be alkylated by very reactive electrophiles:
Enolates can act as nucleophiles at either the carbon or oxygen termini. The oxygen center acts as a hard nucleophiles while the carbon center acts as a soft nucleophile.
O alkylation can be favored by several methods
Stereochemistry
Cyclohexanones
β-vetivone
The Stork synthesis of β-vetivone provides an elegant use of this selectivity.
SAMP/RAMP
For unreactive enolates, the hydrazone can be formed and deprotonated with n-BuLi. This provides a metallo-enamine which is very reactive. Metallo-enamines will even react with poor electrophiles.
This alkylation can be rendered enantioselective by use of SAMP or RAMP