1. Chapter 5. C-C Bonds with Stabilized Carbanions
Organic Chemistry of Fine Chemicals
Spring 2006
Chapter 5. C-C Bonds with Stabilized Carbanions
Stabilization by two -M groups or
stronger acids: active methylene group,  61 top
deprotonation with weak bases: alkoxides & amines;  & 5.2
OCFC-Chapter 5-1
Chapter 5-1

2. Stabilized Carbanions with Two -M (I)
Organic Chemistry of Fine Chemicals
Spring 2006
Stabilized Carbanions with Two -M (I)
alkylation:  61 bottom & 62 top
anion formation followed by addition of electrophiles
dialkylation
the same alkyl groups: ‘one-pot’ reaction,  62 middle
different alkyl groups: stepwise,  62 bottom
importance of the (steric/electronic) nature of the alkyl groups
dianions:  63 bottom
OCFC-Chapter 5-1
Chapter 5-1

3. Competing Reactions of Enolates
Organic Chemistry of Fine Chemicals
Spring 2006
Competing Reactions of Enolates
Ambident nucleophiles
C- vs. O-alkylation: soft vs hard
E+ (halide)  cation (Na+)
solvent (alcohol)  steric hindrance
OCFC-Chapter 5-1
Chapter 5-1

4. Stabilized Carbanions with Two -M (II)
Organic Chemistry of Fine Chemicals
Spring 2006
Stabilized Carbanions with Two -M (II)
Decarboxylation of alkylated products:  64 bottom
 64 bottommost & 65 top, middle
malonates: synthetic equivalent of - CH2CO2H
acetoacetates: synthetic equivalent of - CH2COCH3
a side reaction with basic hydrolysis:  66 top
OCFC-Chapter 5-1
Chapter 5-1

5. Stabilized Carbanions with Two -M (III)
Organic Chemistry of Fine Chemicals
Spring 2006
Stabilized Carbanions with Two -M (III)
Acylation:  66 bottom & 67 top; 5.8, 5.8a & 5.8b
no alcohols used:
reaction with acyl halides
equilibrium between the enolate & product (5.8a):
2 eq. of base
Mg(OEt)2: ether-soluble & 2 eq. of base,  67 middle
acidic hydrolysis to give R-COCH3,  67 bottom & 68 top
monodecarboxylation: b-ketoesters/acids;  68 middle
deacylation with basic hydrolysis: b-ketoesters;  68 bottom
OCFC-Chapter 5-1
Chapter 5-1

6. Stabilized Carbanions with Two -M (IV)
Organic Chemistry of Fine Chemicals
Spring 2006
Stabilized Carbanions with Two -M (IV)
Condensation reactions:  69 top (5.12)
a catalytic amount of the base  equilibrium reaction: - H2O
weaker base  stabilized carbanion & electrophilic carbonyls
Knoevenagel condensation:  69 bottom & 70
no self-condensations: mechanism;  70 middle
ammonium salt catalyst: imminium ion intermediate,  70 bottom
Doebner condensation:  71 top (a variation of Knoevenagel)
E-alkenes
OCFC-Chapter 5-1
Chapter 5-1

7. Condensation Reactions: Mechanism [Ch. 18]
Organic Chemistry of Fine Chemicals
Spring 2006
Condensation Reactions: Mechanism [Ch. 18]
OCFC-Chapter 5-1
Chapter 5-1

8. Stabilized Carbanions with Two -M (V)
Organic Chemistry of Fine Chemicals
Spring 2006
Stabilized Carbanions with Two -M (V)
The Michael reaction:  71 bottommost
Knoevenagel followed by conjugate addition:  72 top
catalytic base:  72 middle (5.15) &  72 middle reactions
Michael reaction vs Knoevenagel condensation
a,b-unsaturated aldehyde:  72 bottom
addition at the end of the conjugated system:  73 top
OCFC-Chapter 5-1
Chapter 5-1