1. 18.11 Effects of Conjugation in  -Unsaturated Aldehydes and Ketones

2. Relative Stability aldehydes and ketones that contain a carbon- carbon double bond are more stable when the double bond is conjugated with the carbonyl group than when it is not compounds of this type are referred to as ,  unsaturated aldehydes and ketones

3. Relative Stability CH 3 CH O CHCH 2 CCH 3 (17%) K = 4.8 (83%) O CH 3 CH 2 CH CHCCH 3 

4. Acrolein H2CH2CH2CH2C CHCHO

5. Acrolein H2CH2CH2CH2C CHCHO

6. Acrolein H2CH2CH2CH2C CHCHO

7. Acrolein H2CH2CH2CH2C CHCHO

8. Resonance Description C O C C +–C O C C

9. Resonance Description C O C C +–C O C C +–C O C C

10.  -Unsaturated aldehydes and ketones are more polar than simple aldehydes and ketones.  -Unsaturated aldehydes and ketones contain two possible sites for nucleophiles to attack carbonyl carbon  -carbon Properties

11.  -Unsaturated aldehydes and ketones are more polar than simple aldehydes and ketones.  -Unsaturated aldehydes and ketones contain two possible sites for nucleophiles to attack carbonyl carbon  -carbon Properties C O C C 

12. Dipole Moments Butanal trans-2-Butenal  = 2.7 D  = 3.7 D O O –––– –––– ++++ ++++ ++++ greater separation of positive and negative charge

13. 18.12 Conjugate Addition to  -Unsaturated Carbonyl Compounds

14. 1,2-addition (direct addition) nucleophile attacks carbon of C=O 1,4-addition (conjugate addition) nucleophile attacks  -carbon Nucleophilic Addition to  -Unsaturated Aldehydes and Ketones

15. attack is faster at C=O attack at  -carbon gives the more stable product Kinetic versus Thermodynamic Control

16. HY+ C C CO1,2-addition C C C OHY formed faster major product under conditions of kinetic control (i.e. when addition is not readily reversible)

17. HY+ C C CO1,4-addition C C C OHY enol goes to keto form under reaction conditions

18. HY+ C C CO1,4-addition keto form is isolated product of 1,4-addition is more stable than 1,2-addition product C C COH Y

19. HY+ C C CO1,2-addition C C C OHY 1,4-addition C C COH Y C=O is stronger than C=C

20. observed with strongly basic nucleophiles Grignard reagents LiAlH 4 NaBH 4 Sodium acetylide strongly basic nucleophiles add irreversibly 1,2-Addition

21. ExampleO CH 3 CH CHCH + HC CMgBr 1. THF 2. H 3 O + OH CH 3 CH CHCHC CH (84%)

22. observed with weakly basic nucleophiles cyanide ion (CN – ) thiolate ions (RS – ) ammonia and amines azide ion (N 3 – ) weakly basic nucleophiles add reversibly 1,4-Addition

23. Example KCN ethanol, acetic acid (93-96%)O C 6 H 5 CH CHCC 6 H 5 O C 6 H 5 CHCH 2 CC 6 H 5 CN

24. Example KCN ethanol, acetic acid (93-96%)O C 6 H 5 CH CHCC 6 H 5 O C 6 H 5 CHCH 2 CC 6 H 5 CN via C 6 H 5 CH CC 6 H 5 CN – O CH C 6 H 5 CH CC 6 H 5 CN – O CH

25. Example O CH 3 C 6 H 5 CH 2 SH HO –, H 2 O (58%)O CH 3 SCH 2 C 6 H 5

26. Example via O CH 3 C 6 H 5 CH 2 SH HO –, H 2 O (58%) – O CH 3 SCH 2 C 6 H 5 O CH 3 SCH 2 C 6 H 5 CH 3 SCH 2 C 6 H 5 – O

27. 18.13 Addition of Carbanions to  -Unsaturated Carbonyl Compounds: The Michael Reaction

28. Stabilized carbanions, such as those derived from  -diketones undergo conjugate addition to ,  -unsaturated ketones. Michael Addition

29. Example (85%)O H2CH2CH2CH2C CHCCH 3 CH 3 OO O OO CH 2 CH 2 CCH 3 KOH, methanol +

30. The Michael reaction is a useful method for forming carbon-carbon bonds. It is also useful in that the product of the reaction can undergo an intramolecular aldol condensation to form a six-membered ring. One such application is called the Robinson annulation. Michael Addition

31. Example O CH 3 OO CH 2 CH 2 CCH 3 NaOH heat OHO CH 3 O not isolated; dehydrates under reaction conditions

32. Example (85%) O CH 3 OO CH 2 CH 2 CCH 3 NaOH heat OO CH 3 OHO O

33. 18.14 Conjugate Addition of Organocopper Reagents to  -Unsaturated Carbonyl Compounds

34. The main use of organocopper reagents is to form carbon-carbon bonds by conjugate addition to ,  -unsaturated ketones. Addition of Organocopper Reagents to  -Unsaturated Aldehydes and Ketones

35. ExampleO CH 3 (98%) + LiCu(CH 3 ) 2 O CH 3 1. diethyl ether 2. H 2 O

36. 18.15 Alkylation of Enolate Anions

37. Enolate ions are nucleophiles and react with alkyl halides. However, alkylation of simple enolates does not work well. Enolates derived from  -diketones can be alkylated efficiently. Enolate Ions in S N 2 Reactions

38. Example CH 3 CCH 2 CCH 3 OO+ CH 3 I K 2 CO 3 CH 3 CCHCCH 3 OO CH 3 (75-77%)