Aldehydes and Ketones II. Oxidation and Reduction: Synthesis

1. Aldehydes and Ketones II. Oxidation and Reduction: Synthesis Chapter 17 WWU -- Chemistry

2. Assignment for Chapter 17 • Sections 17.0 through 17.2 • Section 17.3 -- SKIP • Sections 17.4 through 17.12 • Section 17.13 through 17.15 -- SKIP • Sections 17.16 through 17.20 • Problems WWU -- Chemistry

3. Problem Assignment • In-Text Problems • 17-1 through 17-11 • 17-15 through 17-18 • End-of-Chapter Problems • 1 through 4 (all parts) WWU -- Chemistry

4. Reduction of a Carbonyl Group to an Alcohol WWU -- Chemistry

5. What If We Had the World’s Simplest Nucleophile? WWU -- Chemistry

6. If we could make this work, we would have means of reducing the carbonyl group. • Go back and re-read the Special Topics box at the beginning of Chapter 14. WWU -- Chemistry

7. Lithium Aluminum Hydride Lithium aluminum hydride, LiAlH4, is a very powerful hydride donor, and thus it is an excellent reducing agent. WWU -- Chemistry

8. Outline WWU -- Chemistry

9. Lithium Aluminum HydrideReduction of Aldehydesand Ketones These reactions typically go in very high yield. WWU -- Chemistry

10. Learn it this way: WWU -- Chemistry

11. Aluminum is required to coordinate with the oxygen of the carbonyl group. For example, in the absence of aluminum (using sodium hydride, NaH as the reducing agent), there is no reduction. WWU -- Chemistry

12. You Must Be Careful! LiOH + Al(OH) + 4 H2 LiAlH + 4 H O 4 2 3 WWU -- Chemistry

13. A similar, but less reactive, reducing agent is sodium borohydride, NaBH4. WWU -- Chemistry

14. Sodium Borohydride Reduction of Aldehydes and Ketones WWU -- Chemistry

15. Example In general, the reduction should proceed equally easily from either side, yielding two mirror-image products. WWU -- Chemistry

16. Sodium Borohydride Reduction of Camphor (endo) (exo) In this case, approach by borohydride from the upper side is sterically hindered by the bridge methyl group. The result is a predominance of exo alcohol. WWU -- Chemistry

17. Sodium Borohydride Reduction of Norcamphor • Here, it is the underside of the molecule that is more sterically hindered, so the favored alcohol is the endo alcohol. • Similar results are obtained with lithium aluminum hydride. WWU -- Chemistry

18. Another example: WWU -- Chemistry

19. Contrast these two reactions Note that sodium borohydride is more selective. WWU -- Chemistry

20. Catalytic Hydrogenation ofAldehydes and Ketones WWU -- Chemistry

21. Reduction of a Carbonyl Group to a Methylene Group WWU -- Chemistry

22. We are trying to accomplish... WWU -- Chemistry

23. Clemmensen Reduction Zn(Hg) is a zinc amalgam WWU -- Chemistry

24. The mechanism of the Clemmensen reduction involves the formation of some sort of zinc-ketone complex. • This reaction is a good method for the reduction of acid-stable carbonyl compounds (Note that the reaction takes place in the presence of concentrated HCl). WWU -- Chemistry

25. Example of a Clemmensen Reduction Notice that the reduction does not affect the carboxyl group WWU -- Chemistry

26. Wolff-Kishner Reduction WWU -- Chemistry

27. The mechanism involves the formation of a hydrazine adduct, which loses water to form a hydrazone. • The hydrazone then rearranges to lose a molecule of nitrogen gas, leaving behind a carbanion. • The carbanion picks up a proton from the solvent to form the product. WWU -- Chemistry

28. This will never show up on any of my exams! WWU -- Chemistry

29. The Wolff-Kishner reduction is useful for the reduction of carbonyl compounds that are stable in strong base. (Note that the reaction takes place in the presence of concentrated KOH or other base) WWU -- Chemistry

30. Example WWU -- Chemistry

31. Desulfurization WWU -- Chemistry

32. Advantages: High yields Mild and nearly neutral reaction conditions • Disadvantages: Stinky! Raney Nickel is tricky to prepare WWU -- Chemistry

33. Example of a Raney Nickel Desulfurization WWU -- Chemistry

34. WWU -- Chemistry