南开大学-高等有机合成-陈悦Week-1-Thu.ppt

Chapter 1. Alkylation of Enolates and Other Carbon Nucleophiles Sept. 25, 2008 Endocyclic Enolate Trans is slightly more favorable 2. 1. Mechanism Endocyclic Enolate (Cont’d) 3. 4. 5. 6. Endocyclic Enolate (Prediction by molecular mechanics calculations) 7. 8. Alkylation of Ketone Enolates (Examples) Alkylation of Ketone Enolates (Examples) 5. 6. 7. 8. Alkylation of Ketone Enolates (Examples) Enolate Formation in Acyclic Systems and Their Stereochemistry 1. 9. 10. Enolate Formation in Acyclic Systems 2. Factors: 1. Cation chelation, 2. Allylic-strain, 3. dipolar repulsion Chelated Not Chelated Alpha, beta unsaturated ketone enolates 1. 2. 1.2.3. Alkylation of Aldehydes, Esters, Carboxylic Acids, Amides, and Nitriles . 1. 2. 3. or 1.2.3. Alkylation of Aldehydes, Esters, Carboxylic Acids, Amides, and Nitriles 1. 2. 3. Alkylation of alpha hydroxyl dialkyl malate esters, Alkylation of Esters, Carboxylic Acids, Amides, and Nitriles 1. 2. 3. Alkylation of Esters, Carboxylic Acids, Amides, and Nitriles (cont’d) Alkylation of Esters, Carboxylic Acids, Amides, and Nitriles (cont’d) 1.2.4. Generation and Alkylation of Dianions - alkylation of more basic carbon 1.2.4. Generation and Alkylation of Dianions (cont’d) 1.2.5. Intramolecular Alkylation of Enolates Less strained more strained 1.2.5. Intramolecular Alkylation of Enolates (cont’d) 1. 2. 3. 1.2.5. Intramolecular Alkylation of Enolates (cont’d) 1.2.5. Intramolecular Alkylation of Enolates (cont’d) 1.2.6. Control of Enantioselectivity in Alkylation Reactions Oxazolidinones N-acyl derivatives 1.2.6. Control of Enantioselectivity in Alkylation Reactions Other chiral auxiliary 1. 2. 3. 4. 1.2.6. Control of Enantioselectivity in Alkylation Reactions 1.2.6. Control of Enantioselectivity in Alkylation Reactions 1.2.6. Control of Enantioselectivity in Alkylation Reactions Why low dr? 1.2.6. Control of Enantioselectivity in Alkylation Reactions Why low dr? 1.2.6. Control of Enantioselectivity in Alkylation Rea