Chapter 18: Carbonyl Compounds III Learning bjectives: 1. Write the mechanism for keto-enol tautomerization and explain the consequence of such tautomerizarion in the optical chiral of compound. 2. emember the approximate pka value for the α-hydrogen of a carbonyl group. 3. Provide appropriate bases for the formation of enolate and use such enolate for halogenation and alkylation. 4. Be able to write the general electron-pushing (arrow-pushing) mechanisms of Aldol reaction, Michael reaction, Claisen condensation, and Dieckmann condensation. 5. Be able to write the general electron-pushing (arrow-pushing) mechanisms for decarboxylation of 3-oxocarboxylic acids 6. Be able to employ the above-mentioned reaction for the formation of new carbon-carbon bond Sections: 18.1 The Acidity of an α-ydrogens* 18.2 Keto-Enol Tautomers* 18.3 Enolization 18.4 ow Enols and Enolate Ions eact* 18.5 alogenation of the α-carbon of Aldehydes and Ketones* 18.6 alogenation of the α-carbon of Carboxylic Acids: The ell-volhard-zelinski (VZ) eaction 18.7 α-alogenated Carbonyl Compounds Are Useful in Synthesis* 18.8 Using LDA to Form an Enolate* 18.9 Alkylation of the α-carbon of Carbonyl Compounds* 18.10 Alkylation and Acylation of the α-carbon Using an Enamine Intermediate 18.11 Alkylation of the β-carbon: the Michael eaction* 18.12 The Aldol eaction Form β-ydroxyaldehydes or β-ydroxyketones* 18.13 Dehydration of Aldol Addition Products: Formation of α,β-unsaturated Aldehydes and Ketones* 18.14 The Mixed Aldol eaction 18.15 The Claisen Condensation Forms a β-keto Ester* 18.16 The Mixed Claisen Condensation 18.17 Intramolecular Condensation and Addition eactions* 18.18 3-xocarboxylic Acids Can Be Decarboxylated* 18.19 The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acids 18.20 The Acetoacetic Ester Synthesis: A Way to Synthesize Methyl Ketones 18.21 Designing a Synthesis VII: Making New Carbon-Carbon Bonds 18.22 eactions at the α-carbon in Biological Systems # * Sections that will be focused # Sections that will be skipped ecommended additional problems 18.48 18.58, 18.60 18.70, 18.72 18.85 1
Class Note 18.1 The Acidity of an α-ydrogens* A. pka of α-hydrogen of carbonyl derivatives ' ' ' ' α N ' ' ' B. esonance effect 2
18.2 Keto-Enol Tautomers* ' ' A. Mechanism in acidic condition B. Mechanism in basic condition 3
18.3 Enolization and 18.4 ow Enols and Enolate Ions eact* A. Analysis of enols and enolates 4
18.5 alogenation of the α-carbon of Aldehydes and Ketones* A. Acid-catalyzed halogenation C 3 X 2 (Cl 2, Br 2, I 2 ) 3 + C 2 X 5
B. Base-promoted halogenation X 2 (Cl 2, Br 2, I 2 ) (excess) - C 2 CX 2 C. aloform reaction X 2 (Cl 2, Br 2, I 2 ) (excess) C - 3 + CX 3 6
18.6 alogenation of the α-carbon of Carboxylic Acids: The ell-volhard-zelinski (VZ) eaction 1) PBr 3, Br 2 2) 2 Br 7
18.7 α-alogenated Carbonyl Compounds Are Useful in Synthesis* A. Analysis of α-halogenated carbonyl Compounds B. Examples 8
18.8 Using LDA to Form an Enolate* N lithium diisopropylamide (LDA) 18.9 Alkylation of the α-carbon of Carbonyl Compounds* A. Analysis of the reaction 9
B. Examples (i) C 3 1) LDA, TF 2) C 3 I (ii) CN 1) LDA, TF 2) C 3 C 2 I 10
C. Potential problem in alkylation of the α-carbon of carbonyl compounds C 3 1) LDA, TF 2) C 3 I 11
18.10 Alkylation and Acylation of the α-carbon Using an Enamine Intermediate N + N catalytic + + 2 pyrrolidine enamine A. Examples 1) catalytic + N 2) C 3 Br 3) 2, + 12
18.11 Alkylation of the β-carbon: the Michael eaction* A. Michael reaction 3 C C 3 + C 3 C 3-13
B. Examples (i) + 3 C C 3 base (?) (ii) C 2 C 3 + 3 C CN base (?) 14
C. Stork enamine reaction N + C 3 Cl 2 15
18.12 The Aldol eaction Form β-ydroxyaldehydes or β-ydroxyketones* base A. Mechanism 16
18.13 Dehydration of Aldol Addition Products: Formation of α,β-unsaturated Aldehydes and Ketones* A. Aldol condensation B. Examples (i) + Me - Me (ii) Et - Na + Et 17
18.14 The Mixed Aldol eaction A. Potential problem in aldol reaction (i) Et - Na + Et (ii) + Me - Na + Me 18
B. Solution (i) + Me - Na + Me 19
18.15 The Claisen Condensation Forms a β-keto Ester* and 18.16 The Mixed Claisen Condensation ' base ' + ' A. Mechanism 20
B. Examples (i) base (?) C 2 C 3 (ii) base (?) C 3 + C 2 C 3 21
18.17 Intramolecular Condensation and Addition eactions* A. Intramolecular Claisen reaction (Dieckmann condensation) (i) 3 C C 3 Me - Na + Me (ii) 3 C 2 C C 2 C 3 Et - Et Na + 22
B. Intramolecular aldol reaction (i) 3 C C 3 Me - Na + Me (ii) 3 C C 3 Et - Na + Et 23
(iii) 3 C Et - Et Na + (iv) obinson annulation + C 3 base +, heat + 2 24
18.18 3-xocarboxylic Acids Can Be Decarboxylated* A. Easier in acidic condition: mechanism B. Examples of compounds containing 3-oxocarboxylic acid 25
18.19 The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acids and 18.20 The Acetoacetic Ester Synthesis: A Way to Synthesize Methyl Ketones? 3 C 2 C C 2 C 3 26
A. Examples: 27
18.21 Designing a Synthesis VII: Making New Carbon-Carbon Bonds synthesis of C 2 from 3 C C 3 28