1. Reduction of Aldehydes and Ketones 1 19.8 Reduction of Aldehydes and Ketones to Alcohols

2. Reduction with LiAlH 4 and NaBH 4 2 19.8 Reduction of Aldehydes and Ketones to Alcohols

3. Reduction with LiAlH 4 LiAlH 4 serves as a source of hydride ion (H: - ) LiAlH 4 is very basic and reacts violently with water; anhydrous solvents are required 3 19.8 Reduction of Aldehydes and Ketones to Alcohols

4. Reduction with LiAlH 4 Like other strong bases, LiAlH 4 is also a good nucleophile Additionally, the Li + ion is a built-in Lewis-acid 4 19.8 Reduction of Aldehydes and Ketones to Alcohols

5. Reduction with LiAlH 4 Each of the remaining hydrides become activated during the reaction 5 19.8 Reduction of Aldehydes and Ketones to Alcohols

6. Reduction with NaBH 4 Na + is a weaker Lewis acid than Li + requiring the use of protic solvents Hydrogen bonding then serves to activate the carbonyl group 6 19.8 Reduction of Aldehydes and Ketones to Alcohols

7. Reduction with LiAlH 4 and NaBH 4 Reactions by these and related reagents are referred to as hydride reductions These reactions are further examples of nucleophilic addition 7 19.8 Reduction of Aldehydes and Ketones to Alcohols

8. Selectivity with LiAlH 4 and NaBH 4 LiAlH 4 reduces all carbonyl groups NaBH 4 is less reactive – Reduces Aldehydes Ketones Esters (slowly) – Does not reduce Carboxylic acids Amides Nitro groups Alkyl halides Alkyl tosylates 8 19.8 Reduction of Aldehydes and Ketones to Alcohols

9. Problems Which reducing agent, LiAlH4 or NaBH4 is more appropriate for reduction of the following reagents? Draw the products. 9

10. Reduction by Catalytic Hydrogenation Hydride reagents are more commonly used However, catalytic hydrogenation is useful for selective reduction of alkenes 10 19.8 Reduction of Aldehydes and Ketones to Alcohols

11. Grignard Addition Grignard reagents with carbonyl groups is the most important application of the Grignard reagent in organic chemistry 11 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

12. Grignard Addition 12 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

13. Importance of the Grignard Addition This reaction results in C-C bond formation The synthetic possibilities are almost endless 13 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

14. Importance of the Grignard Addition 14 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

15. Grignard Addition R-MgX reacts as a nucleophile; this group is also strongly basic behaving like a carbanion The addition is irreversible due to this basicity 15 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

16. Problems Give the products for the following Grignard reactions: 16

17. Organolithium and Acetylide Reagents These reagents react with aldehydes and ketones analogous to Grignard reagents 17 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

18. Problems Give the products for the following rxns: 18

19. Reactions with Amines 19 Secondary Amine

20. 20 Reactions with Primary Amines

21. Dehydration is typically the rate- limiting step 21

22. Reactions with Secondary Amines 22

23. 23

24. Problems 1)Draw the products for the following reactions: 24

25. 2)Draw the mechanism for the formation of the imine in the previous question 25