Carbanions | — C: – The conjugate bases of weak acids, strong bases, excellent nucleophiles.

1. Alpha-halogenation of ketones

Alpha-hydrogens: 1o > 2o > 3o

Mechanism for base promoted alpha-bromination of acetone: 1) 2) Rate = k [acetone] [base]

1) 2) 3) 4) “enol”

Carbanions. The conjugate bases of weak acids; strong bases, good nucleophiles. 1. enolate anions 2. organometallic compounds 3. ylides 4. cyanide 5. acetylides

Aldehydes and ketones: nucleophilic addition Esters and acid chlorides: nucleophilic acyl substitution Alkyl halides: SN2 Carbanions as the nucleophiles in the above reactions.

Carbanions as the nucleophiles in nucleophilic addition to aldehydes and ketones: a) aldol condensation “crossed” aldol condensation b) aldol related reactions (see problem 21.18 on page 811) c) addition of Grignard reagents d) Wittig reaction

Carbanions as the nucleophiles in nucleophilic addition to aldehydes and ketones: c) addition of Grignard reagents Grignard reagents are examples of organo metallic carbanions.

a) Aldol condensation. The reaction of an aldehyde or ketone with dilute base or acid to form a beta-hydroxycarbonyl product.

nucleophilic addition by enolate ion.

With dilute acid the final product is the α,β-unsaturated carbonyl compound!

NB: An aldehyde without alpha-hydrogens undergoes the Cannizzaro reaction with conc. base.

Crossed aldol condensation: If you react two aldehydes or ketones together in an aldol condensation, you will get four products. However, if one of the reactants doesn’t have any alpha hydrogens it can be condensed with another compound that does have alpha hydrogens to give only one organic product in a “crossed” aldol. NaOH

N.B. If the product of the aldol condensation under basic conditions is a “benzyl” alcohol, then it will spontaneously dehydrate to the α,β-unsaturated carbonyl.

A crossed aldol can also be done between an aldehyde and a ketone to yield one product. The enolate carbanion from the ketone adds to the more reactive aldehyde.

b) Aldol related reactions: (see problem 21 b) Aldol related reactions: (see problem 21.18 page 811 of your textbook).

Perkin condensation

Wittig reaction (synthesis of alkenes) 1975 Nobel Prize in Chemistry to Georg Wittig Ph = phenyl

nuclephilic addition by ylide carbanion, followed by loss of Ph3PO (triphenylphosphine oxide)

Carbanions as the nucleophiles in nucleophilic acyl substitution of esters and acid chlorides. a) Claisen condensation a reaction of esters that have alpha-hydrogens in basic solution to condense into beta-keto esters

Mechanism for the Claisen condensation:

Crossed Claisen condensation:

b) Coupling of lithium dialkyl cuprate with acid chloride

4. Carbanions as nucleophiles in SN2 reactions with R’X: a) Corey-House synthesis of alkanes R2CuLi + R’X  R-R’ b) metal acetylide synthesis of alkynes RCC-M+ + R’X  RCCR’ c) Malonate synthesis of carboxylic acids d) Acetoacetate synthesis of ketones 5. Michael Addition to α,β-unsaturated carbonyl compounds

Carbanions are the conjugate bases of weak acids and are therefore strong bases and excellent nucleophiles that can react with aldehydes/ketones (nucleophilic addition), esters/acid chlorides (nucleophilic acyl substitution), and alkyl halides (SN2), etc.

Reactions involving carbanions as nucleophiles: Alpha-halogenation of ketones Nucleophilic addition to aldehydes/ketones a) aldol and crossed aldol b) aldol related reactions c) Grignard synthesis of alcohols d) Wittig synthesis of alkenes Nucleophilic acyl substitution with esters and acid chlorides a) Claisen and crossed Claisen b) R2CuLi + RCOCl (next slide)

SN2 with alkyl halides a) Corey-House b) metal acetylide c) Malonate synthesis d) Acetoacetate synthesis 5. Michael Addition to α,β-unsaturated carbonyl compounds