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;  61 5.1 & 5.2 OCFC-Chapter 5-1 Chapter 5-1

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

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

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

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

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

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

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