CH 19 - Enolate Anions and Enamines

enolates are formed by

deprotonation at the a-carbon of an aldehyde or ketone

• the resulting anion is stabilized through resonance

despite most of the negative charge in the enolate residing on the more electronegative oxygen atom, enolates typically function as

nucleophiles via reaction at the a-carbon

aldol reactions involved

nucleophilic addition of an enolate to the C=O group of an aldehyde or ketone (same or different compound)

• reaction is either acid or base-catalyzed

aldol reactions - dehydration = warming of the aldol reaction mixture is often sufficient to cause

elimination of water to make a,B-saturated carbonyl compound

crossed aldol reactions

reaction between enolate of one compound and C=O of a different compound

crossed aldol reaction generally only efficient when one compound has

no a-hydrogens and cannot provide enolate component

intramolecular aldol reactions

useful to form 5- and 5-membered rings

recognizing aldol reactions

• identify new C-C bond

• carbon with -OH group was the electrophile

• other C on new bond is the a-carbon of nucleophile

claisen condensation

nucleophilic acyl substitution reaction with ester enolate as the nucleophile

clauses condensation product

a B-ketoester

what is used as reagent in claisen condensation

alkoxide base often

crossed claisen condensations

• only useful is one ester has no a-hydroegns

• acceptor is used in excess

B-ketoester products are stable, but can

decarboxylate upon hydrolysis to B-ketoacid

product of claisen condensation followed by decarboxylation is substitution of -OR group with an alkyl group to make

a ketone

examines formed by reaction of

2 amine with aldehyde or ketone

most common amines are

pyrrolidine and morpholine

enamines works like

a premade enolate

enamines - alkylation

product is a ketone

enamines are less basic than enolates, so produces

less unwanted elimination

enamines - acylation works with

acid chlorides and anhydrides

• creates ketones

conjugate addition - Micheal reaction

addition of nucleophiles to B carbon of a,B-unsaturated carbonyl compounds

Micheal reaction - nucleophile acceptors (electrophiles) includes

aldehydes, ketones, esters, amides, nitriles, and nitro compound

micheal reaction - effective nucleophiles include

B-diketone, B-ketoester, B-ketonitrile, B-diester, enamine, amine

Micheal reaction - Gilman cooperates

will reliably react at B carbon

• eliminates alkene

LDA is used to irreversibly produce enolates of

aldehydes, ketones, and esters

with 1 eq of LDA, can make solutions containing

only one enolate in crossed aldol and crossed claisen reactions

enolates from LDA - with non symmetric ketones,

two enolates possibles (depending on conditions)

kinetic control

reaction goes at less hindered position with strong, hindered base like LDA

thermodynamic control -

enolate in presence of excess ketone can equilibrate to more slowly formed but more stable enolate