Chapter 18: Carbonyl Compounds III

Transcription

1 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* Alkylation and Acylation of the α-carbon Using an Enamine Intermediate Alkylation of the β-carbon: the Michael eaction* The Aldol eaction Form β-ydroxyaldehydes or β-ydroxyketones* Dehydration of Aldol Addition Products: Formation of α,β-unsaturated Aldehydes and Ketones* The Mixed Aldol eaction The Claisen Condensation Forms a β-keto Ester* The Mixed Claisen Condensation Intramolecular Condensation and Addition eactions* xocarboxylic Acids Can Be Decarboxylated* The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acids The Acetoacetic Ester Synthesis: A Way to Synthesize Methyl Ketones Designing a Synthesis VII: Making New Carbon-Carbon Bonds eactions at the α-carbon in Biological Systems # * Sections that will be focused # Sections that will be skipped ecommended additional problems , ,

2 Class Note 18.1 The Acidity of an α-ydrogens* A. pka of α-hydrogen of carbonyl derivatives ' ' ' ' α N ' ' ' B. esonance effect 2

3 18.2 Keto-Enol Tautomers* ' ' A. Mechanism in acidic condition B. Mechanism in basic condition 3

4 18.3 Enolization and 18.4 ow Enols and Enolate Ions eact* A. Analysis of enols and enolates 4

5 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

6 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 CX 3 6

7 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

8 18.7 α-alogenated Carbonyl Compounds Are Useful in Synthesis* A. Analysis of α-halogenated carbonyl Compounds B. Examples 8

9 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

10 B. Examples (i) C 3 1) LDA, TF 2) C 3 I (ii) CN 1) LDA, TF 2) C 3 C 2 I 10

11 C. Potential problem in alkylation of the α-carbon of carbonyl compounds C 3 1) LDA, TF 2) C 3 I 11

12 18.10 Alkylation and Acylation of the α-carbon Using an Enamine Intermediate N + N catalytic pyrrolidine enamine A. Examples 1) catalytic + N 2) C 3 Br 3) 2, + 12

13 18.11 Alkylation of the β-carbon: the Michael eaction* A. Michael reaction 3 C C 3 + C 3 C 3-13

14 B. Examples (i) + 3 C C 3 base (?) (ii) C 2 C C CN base (?) 14

15 C. Stork enamine reaction N + C 3 Cl 2 15

16 18.12 The Aldol eaction Form β-ydroxyaldehydes or β-ydroxyketones* base A. Mechanism 16

17 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 18.14 The Mixed Aldol eaction A. Potential problem in aldol reaction (i) Et - Na + Et (ii) + Me - Na + Me 18

19 B. Solution (i) + Me - Na + Me 19

20 18.15 The Claisen Condensation Forms a β-keto Ester* and The Mixed Claisen Condensation ' base ' + ' A. Mechanism 20

21 B. Examples (i) base (?) C 2 C 3 (ii) base (?) C 3 + C 2 C 3 21

22 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

23 B. Intramolecular aldol reaction (i) 3 C C 3 Me - Na + Me (ii) 3 C C 3 Et - Na + Et 23

24 (iii) 3 C Et - Et Na + (iv) obinson annulation + C 3 base +, heat

25 xocarboxylic Acids Can Be Decarboxylated* A. Easier in acidic condition: mechanism B. Examples of compounds containing 3-oxocarboxylic acid 25

26 18.19 The Malonic Ester Synthesis: A Way to Synthesize a Carboxylic Acids and The Acetoacetic Ester Synthesis: A Way to Synthesize Methyl Ketones? 3 C 2 C C 2 C 3 26

27 A. Examples: 27

28 18.21 Designing a Synthesis VII: Making New Carbon-Carbon Bonds synthesis of C 2 from 3 C C 3 28