Chapter 18 I Acidity at the alpha C 18 1 1 Alpha hydrogens are acidic due to resonance stabilization A Aldehydes are more acidic than ketones 2 Formation of Enolates reactive Enolate will push Equilibrium A Weak moderate bases only partially promote Enolate formation B Stronger bases completely promote enolate formation 3 Enolates are ambident can attack from C and O II Keto Enol Equilibria 18 2 1 tautomerization rapid equilibrium btwn keto and enol forms A Keto form is thermodynamically favorable B Base catalyzed enol formation C Acid catalyzed 2 Equilibrium can lead to isomerization III Reactions of Enols 18 3 1 Halogenation alpha halogenation A Monohalogenation occurs under acidic conditions B Base mediated process produces polyhalogenated products 2b systems with no enolizable Hs ketones as nucleophiles iii Slow reagent addition 3 Intramolecular aldol reactions 18 7 5 and 6 membered rings are favored VI Properties of alpha beta unsaturated carbonyls 18 8 1 Enones are more stable than the saturated species bc of resonance suggests electrophile beta carbon A Non conjugated enones will walk into conjugation 2 Enones undergo typical reactions of alkenes and carbonyls 3 Conjugate additions 18 9 A Nucleophilic addition to an enone B Weak nucleophiles will add 1 4 thermodynamic control makes most stable species amines alcohols CN enolates alkoxides C Strong nucleophiles add 1 2 18 10 organolithiums RMgX add both kinetic control usually form unstable products hydrides add 1 2 with aldehydes D Organocuprates add R 1 4 E Double alkylation 4 The Michael Addition 18 11 Enolate addition to enones 1 4 forms 1 5 dicarbonyl compounds 5 The Robinson Annulation ring forming A Michael addition aldol condensation intramolecular Chapter 23 I Claisen condensations 23 1 ester enolate NAS A Deprotonation is required for rxn success 2 Retro reverse Claisen 3 Mixed Claisen only one zero enolizable Hs 4 Intramolecular Claisens Dieckmann 5 Mixed Claisens with ketones II Retrosynthesis analysis 1 Aldols give beta keto alcohols 2 Michael Addition give 1 5 dicarbonyls 3 Claisens give beta keto esters 1 3 dicarbonyls III Use of beta dicarbonyls in synthesis 23 3 1 Beta dicarbonyl anions are nucleophiles 2 Decarboxylation mechanism A Thermal loss of CO2 3 The acetoacetic ester synthesis synthesis of substituted ketones methyl ketones 4 The Malonic ester synthesis substituted COOHs 5 Michael additions 23 3 IV Acyl Anion Equivalents 23 4 1 Acyl anions cannot be made reverse polarization or unpolung 2 Dithianes cyclic thioacetals 2 Thioazolium salts aldehyde couplings
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