Edited with the trial version of Foxit Advanced PDF Editor To remove this notice, visit: www.foxitsoftware.com/shopping Disampaikan oleh : Dr. Sri Handayani 2013 α-Carbonyl Nucleophiles Michael and Stork reactions Aldol condensation Claisen condensation The Michael Reaction Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position. 1 The Michael Reaction Addition of any β-dicarbonyl compound to any α,β-unsaturated carbonyl compound, in the β position. Generic “Michael” addition “Michael” addition 2 Mechanism of the Michael Reaction The Stork Enamine Reaction O O O a. N H CH CH CH 2 2 O b. CH2 CH CH + c. H /H2O 3 Mechanism of the Stork Enamine Reaction Enolates react with carbonyls 4 The Aldol addition and its products Mechanism of the Aldol reaction 5 The Aldol condensation makes α,β-unsaturated carbonyls The Aldol intermediate is not always isolated 6 What’s the mechanism? The mixed Aldol can be a mess 7 Mixed Aldol works if one has no α-hydrogens Mixed aldol works if enolate is pre-formed 8 The Claisen condensation makes β-keto esters Mechanism 9 The essential difference between Aldol and Claisen leaving group Why the Claisen only happens once: acidity of β-dicarbonyl 10 Mixed Claisen in which one component has no α-hydrogens Mixed Claisen between ketone and ester pKa ~ 20 pKa ~ 25 Why don’t we get Aldol with ester enolate nucleophile? 11 Mixed Claisen with formic or carbonate ester Synthesis problem, from cyclohexanone 12 Solution Synthesis problem, from cyclohexanone 13 Solution The Dieckmann Condensation: an intramolecular Claisen condensation 14 Mechanism 15 Intramolecular Aldol can give two possible ring sizes Intramolecular Aldol can give two possible ring sizes 16 Six-membered rings are preferred 17 The Robinson Annulation: Michael Addition, then intramolecular Aldol condensation 18 Retrosynthetic breakdown Robinson retrosynthesis 19 Retrosynthetic breakdown Robinson retrosynthesis 20.