1. Oxidation-Reduction & Organometallic
Chapter 12
Alcohols from
Carbonyl Compounds
Oxidation-Reduction & Organometallic
Compounds

2. Structure of the Carbonyl Group
Carbonyl compounds
Aldehyde
Ketone
Carboxylic acid
Ester
Amide

3. Structure
Carbonyl carbon: sp2 hybridized
Planar structure

4. Polarization and resonance structure

5. 1A. Reactions of Carbonyl Compounds with Nucleophiles
One of the most important reactions of carbonyl compounds is nucleophilic addition to the carbonyl group

6. Two important nucleophiles:
Hydride ions (from NaBH4 and LiAlH4)
Carbanions (from RLi and RMgX)
Another important reactions:

7. Overall order lowest oxidation state of carbon highest oxidation

8. Alcohols by Reduction of Carbonyl Compounds
(1o alcohol)

9. 3A. Lithium Aluminum Hydride
LiAlH4 (LAH)
Not only nucleophilic, but also very basic
React violently with H2O or acidic protons (e.g. ROH)
Usually reactions run in ethereal solvents (e.g. Et2O, THF)
Reduces all carbonyl groups

10. Examples

11. 3B. Sodium Borohydride
NaBH4
less reactive and less basic than LiAlH4
can use protic solvent (e.g. ROH)
reduces only more reactive carbonyl groups (i.e. aldehydes and ketones) but not reactive towards esters or carboxylic acids

12. Examples

13. 3C. Overall Summary of LiAlH4 and NaBH4 Reactivity
reduced by LiAlH4
reduced by NaBH4
ease of reduction

14. Organometallic Compounds
Compounds that contain carbon-metal bonds are called organometallic compounds

15. Preparation of Organolithium & Organomagnesium Compounds
6A. Organolithium Compounds
Preparation of organolithium compounds
Order of reactivity of RX
RI > RBr > RCl

16. Example

17. 6B. Grignard Reagents
Preparation of organomagnesium compounds (Grignard reagents)
Order of reactivity of RX
RI > RBr > RCl

18. 7B. Reactions of Grignard Reagents with Epoxides (Oxiranes)
Grignard reagents react as nucleophiles with epoxides (oxiranes), providing convenient synthesis of alcohols

19. Via SN2 reaction

20. Also work for substituted epoxides

21. 7C. Reactions of Grignard Reagents with Carbonyl Compounds

22. Mechanism

23. Alcohols from Grignard Reagents

24. R, R’ = H (formaldehyde)
1o alcohol

25. R = alkyl, R’ = H (higher aldehydes)
2o alcohol

26. R, R’ = alkyl (ketone)
3o alcohol

27. Reaction with esters
3o alcohol

28. Mechanism

29. Examples

30. Examples

31. Examples

32. Examples

33. 8A. How to Plan a Grignard Synthesis
Synthesis of

34. Method 1
Retrosynthetic analysis
Synthesis

35. Method 2
Retrosynthetic analysis
Synthesis

36. Method 3
Retrosynthetic analysis
Synthesis

37. 8B. Restrictions on the Use of Grignard Reagents
Grignard reagents are useful nucleophiles but they are also very strong bases
It is not possible to prepare a Grignard reagent from a compound that contains any hydrogen more acidic than the hydrogen atoms of an alkane or alkene

38. A Grignard reagent cannot be prepared from a compound containing an –OH group, an –NH– group, an –SH group, a –CO2H group, or an –SO3H group
Since Grignard reagents are powerful nucleophiles, we cannot prepare a Grignard reagent from any organic halide that contains a carbonyl, epoxy, nitro, or cyano (–CN) group

39. Grignard reagents cannot be prepared in the presence of the following groups because they will react with them:

40. 8C. The Use of Lithium Reagents
Organolithium reagents have the advantage of being somewhat more reactive than Grignard reagents although they are more difficult to prepare and handle

41. 8D. The Use of Sodium Alkynides
Preparation of sodium alkynides
Reaction via ketones (or aldehydes)

42. Protecting Groups

43. Retrosynthetic analysis
However

44. Need to “protect” the –OH group first