Reactions at the α Carbon of Carbonyl Compounds PDF

Reactions at the α Carbon of Carbonyl Compounds Regioselective Formation of Enolates Synthesis of g-keto esters: ❖  Enamines can also be used in Michael ❖ additions: N EtOH N + CN...

Reactions at the α Carbon of Carbonyl Compounds Regioselective Formation of Enolates Synthesis of g-keto esters: ❖  Enamines can also be used in Michael ❖ additions: N EtOH N + CN reflux CN O CN H2O  Summary of Enolate Chemistry Formation of an Enolate:.1 O O + :B R R H Resonance- stabilized enolate O H:B + R Racemization: R' O R' OH R' O OH OH R H H Ph or H3O R Ph or H3O R Ph Enol (achiral) Enantiomers Halogenation of Aldehydes & Ketones: O O R' acid R' R + X2 R or base H X Specific example: haloform reaction: ❖ O O H OH X Ph + 3 X2 Ph H H2O X H X O CHX3 + Ph O Halogenation of Carboxylic Acids: The HVZ Reaction: O O 1. X2, P R R OH OH 2. H2O X Direct Alkylation via Lithium Enolates: O O O LDA, THF R'' X R o R R H(R') -78 C H(R') H(R') (formation of the R'' kinetic enolate) Specific example: ❖ O O Li O LDA, THF CH3I -78oC Direct Alkylation of Esters: O O LDA R R OEt THF OEt O R' Br R OEt R' Acetoacetic Ester Synthesis: O O O O 1. NaOEt OEt 2. RBr OEt 1. OH−, heat R O 2. H3O+ R 3. heat, (− CO2) O O O O 1. tBuOK OEt 2. R'Br OEt R R' R O 1. OH−, heat R 2. H3O+ 3. heat, (− CO2) R' Malonic Ester Synthesis: O O O O 1. NaOEt EtO OEt 2. RBr EtO OEt 1. OH−, heat R O 2. H3O+ R HO 3. heat, (− CO2) O O O O 1. tBuOK EtO OEt 2. R'Br EtO OEt R R' R O 1. OH−, heat R HO 2. H3O+ 3. heat, (− CO2) R' Stork Enamine Reaction: O NR'2 R R + R' NH R 2 R Enamine O 1. R'' Br R R 2. heat 3. H2O R''