Reduction of Aldehydes and Ketones

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

2. Reduction with LiAlH4 and NaBH4 19.8 Reduction of Aldehydes and Ketones to Alcohols

3. Reduction with LiAlH4 • LiAlH4 serves as a source of hydride ion (H:-) • LiAlH4 is very basic and reacts violently with water; anhydrous solvents are required 19.8 Reduction of Aldehydes and Ketones to Alcohols

4. Reduction with LiAlH4 • Like other strong bases, LiAlH4 is also a good nucleophile • Additionally, the Li+ ion is a built-in Lewis-acid 19.8 Reduction of Aldehydes and Ketones to Alcohols

5. Reduction with LiAlH4 • Each of the remaining hydrides become activated during the reaction 19.8 Reduction of Aldehydes and Ketones to Alcohols

6. Reduction with NaBH4 • Na+ is a weaker Lewis acid than Li+ requiring the use of protic solvents • Hydrogen bonding then serves to activate the carbonyl group 19.8 Reduction of Aldehydes and Ketones to Alcohols

7. Reduction with LiAlH4 and NaBH4 • Reactions by these and related reagents are referred to as hydride reductions • These reactions are further examples of nucleophilic addition 19.8 Reduction of Aldehydes and Ketones to Alcohols

8. Selectivity with LiAlH4 and NaBH4 • LiAlH4 reduces all carbonyl groups • NaBH4 is less reactive • Reduces • Aldehydes • Ketones • Esters (slowly) • Does not reduce • Carboxylic acids • Amides • Nitro groups • Alkyl halides • Alkyl tosylates 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.

10. Reduction by Catalytic Hydrogenation • Hydride reagents are more commonly used • However, catalytic hydrogenation is useful for selective reduction of alkenes 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 19.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

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

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

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

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

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

19. Reactions with Amines Secondary Amine

20. Reactions with Primary Amines

21. Dehydration is typically the rate-limiting step

22. Reactions with Secondary Amines

24. Problems • Draw the products for the following reactions:

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