1. Carbonyl Compounds III
Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 19
Carbonyl Compounds III
Reactions at the
a-Carbon
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall

2. The a-Hydrogen Is Acidic
the anion is stabilized
by resonance
A carbon acid is a compound with a relatively acidic
hydrogen bonded to an sp3-hybridized carbon

4. Esters Are Less Acidic Than
Aldehydes and Ketones
The electrons are not as readily delocalized

5. In these compounds, the electrons left behind from
deprotonation can be delocalized onto a more
electronegative atom

6. The acidity of the a-hydrogens is attributed to
charge stabilization by resonance

7. Keto–Enol Tautomerism

8. The enol tautomer can be stabilized by intramolecular
hydrogen bonding
In phenol, the enol tautomer is aromatic

11. An Enol Is a Better Nucleophile
Than an Alkene
Carbonyl compounds that form enol undergo substitution
reactions at the a-carbon: an a-substitution reaction

12. a-Substitution Reaction
An Acid-Catalyzed
a-Substitution Reaction

13. a-Substitution Reaction
A Base-Catalyzed
a-Substitution Reaction

14. An Enolate Is an Ambident Nucleophile
Reaction at the C or O site depends on the electrophile
and on the reaction condition
Protonation occurs preferentially on the O site
Otherwise, the C site is likely the nucleophile

15. Acid-Catalyzed Halogenation
Under acidic conditions, one a-hydrogen is substituted for a bromine

16. Base-Promoted Halogenation
Under basic conditions, all the a-hydrogens are
substituted for bromines

17. Conversion of a Methyl Ketone to a Carboxylic Acid

18. Halogenation of the a-Carbon of Carboxylic Acids

19. When the a-carbon is halogenated, it becomes
electrophilic
An E2 elimination will occur if a bulky base is used

20. Using LDA to Form an Enolate

21. Alkylation of the a-Carbon of
Carbonyl Compounds

22. Two different products can be formed if the ketone is not
symmetrical

23. The less substituted a-carbon can be alkylated if …
+Li
Bu-

24. Enamine Reacts with Electrophiles

25. The alkylation step is an SN2 reaction

26. Direct alkylation of a carbonyl compound yields several
products
In contrast, alkylation of an aldehyde or a ketone using
an enamine intermediate yields the monoalkylated
product

27. Aldehydes and ketones can be acylated via an enamine
intermediate

28. The Michael Addition

30. Mechanism of the Michael Reaction

31. The Stork Enamine Reaction
Enamines are used in place of enolates in Michael
reactions

32. One molecule of a carbonyl compound acts as a
nucleophile and the other carbonyl compound acts as an
electrophile

34. Ketones are less susceptible than aldehydes to attack by nucleophiles

35. An aldol addition product loses water to form an aldol
condensation product

37. The Mixed Aldol Addition

38. One product will be formed if one of the carbonyl
compounds does not have any a-hydrogen

39. Primarily one product can be formed by using LDA to
deprotonate one of the carbonyl compounds

40. Condensation of Two Ester Molecules

42. The reaction can be driven to completion by removal of a proton from the b-keto ester
The Claisen condensation requires an ester with two
a-hydrogens and an equivalent amount of base

43. The Mixed Claisen Condensation

44. Because of the difference in the acidities of the
a-hydrogens in the two carbonyl compounds, primarily
one product is obtained

46. Intramolecular Aldol Additions

48. The Robinson Annulation

49. Decarboxylation of
3-Oxocarboxylic Acids

50. Acid catalyzes the intramolecular transfer of the proton

51. A malonic ester synthesis forms a carboxylic acid with two more carbon atoms than the alkyl halide

53. Preparation of Carboxylic Acids with Two Substituents Bonded to the
a-Carbon

54. Synthesis of Methyl Ketone by Acetoacetic Ester Synthesis

56. Designing a Synthesis to Make New Carbon–Carbon Bonds

57. Preparation of the Ester

58. A Biological Aldol Condensation

59. A Biological Claisen Condensation