Enolate anion

An enolate is the anion of the enol form of a carbonyl compound. Enolates generated by deprotonation of a CH -acidic hydrogen in α - position to the carbonyl. There can be two limiting structures formulate enolates are ambident anions thus. Enolates are good nucleophiles that react preferentially with soft electrophiles ( especially carbon electrophiles ) at the α - position.

Generation

Deprotonation of a carbonyl compound with a strong base. Incomplete deprotonation equilibrium already hydroxides or alcoholates enough (pKa of ketones is about 20, of esters 25 ). With stronger bases results in complete deprotonation. This most commonly lithium diisopropylamide ( LDA), as well as lithium hexamethyldisilazide ( LHMDS ), potassium hexamethyldisilazide ( KHMDS ) or lithium tetramethylpiperidide ( LTMP ) is used. However, the bases used must not be itself nucleophilicity, otherwise they will attack the carbonyl compound at the electrophilic carbonyl carbon and not deprotonate. Therefore, for example, lithium alkyls, such as butyllithium are not suitable.

Structure

Regioselectivity

In asymmetric ketones are often two regioisomers conceivable that arise in the deprotonation. Under thermodynamic control ( weak base, higher temperature) is preferably deprotonated at the place where the more highly substituted double bond is formed ( thermodynamic enolate, 2). Under kinetic control (strong bases such as LDA, low temperatures, typically -78 ° C) is preferred, however, the sterically more accessible proton away, there arises the lower substituted enolate double bond ( kinetic enolate, 1).

Stereoselectivity

The geometry of the double bond enolate (where R> is methyl ) is determined by the size of the substituents R '. There are two options for this: (O ) - ( Z)- enolates and (O ) - ( E)- enolates. The addition (O ) before the E / Z specification to clarify that only the relative configuration between the enolate oxygen and the Subsitutenten the enolate double bond is considered, which does not have to match the IUPAC nomenclature for double bonds. Large substituents R ' prefer (O) - (Z)- enolate, small substituent (O ) - ( E)- enolate. As a major tertiary alkyl substituents and - NR2 come into question. As a small substituents we group on primary alkyl substituents, and -OR and -SR.

In organic synthesis, chiral Auxilare for the stereoselective reaction among others use of enolates.

Reactions

Good nucleophiles as enolates may be reacted with a variety of electrophiles. Possible electrophiles include alkyl halides ( alkylation), the carboxylic acid chlorides ( acylation), carbonyl compounds ( aldol ), Michael acceptors, epoxides, vinyl and aryl halides. All of these electrophiles rely exclusively on the C atom of the enolates. An attack on the enolate oxygen is rare and occurs only by hard electrophiles ( HSAB principle ), such as silyl chlorides or sulfonic acid derivatives.