1. Synthesis of Alcohols Reduction of Aldehydes and Ketones Common reducing agents and conditions: NaBH 4 ( sodium borohydride ) alcohol, ether, or H 2 O as solvent (1) LiAlH 4 (lithium aluminum hydride =LAH) (2) H 3 O + Raney Ni finely divided H 2 -bearing form of Ni also reduces C=C to alkane

2. Synthesis of Alcohols Reducing agent: a substance that causes another to be reduced. LAH NaBH 4 H 2 Mechanism of Hydride Reduction:

3. Synthesis of Alcohols Reduction of Aldehydes and Ketones 1 o (from aldehyde) or 2 o (from ketone) alcohol formed as product LiAlH 4 or NaBH 4 LiAlH 4 or NaBH 4

4. Reduction of Acids and Esters using LAH LAH can reduce not only aldehydes and ketones but also carboxylic acids and esters. Synthesis of Alcohols Notice: 2 step process

5. Synthesis of Alcohols Reduction of Acids and Esters using LAH Examples:

6. Synthesis of Alcohols NaBH 4 is a weaker reducing agent than LAH. NaBH 4 reduces only aldehydes and ketones. No reaction

7. Synthesis of Alcohols Example: Predict the major product formed in each of the following reactions:

8. Synthesis of Alcohols Example: Predict the major product formed in each of the following reactions:

9. Synthesis of Alcohols Example: Predict the product.

10. Synthesis of Alcohols Nucleophilic Addition of Organometallic Reagents Organometallic reagent: An organic compound that contains a covalent bond between a carbon atom and a metal atom Carbon is more electronegative than most metals C-M bond is polarized Carbon is nucleophilic

11. Synthesis of Alcohols Two common organometallic reagents for producing alcohols: Grignard Reagent Organomagnesium halide Organolithium compounds

12. Synthesis of Alcohols Preparation of Grignard Reagents Alkyl halide: 1 o, 2 o, or 3 o Vinyl, allyl, aryl halides Ether must be used as a solvent to stabilize the Grignard reagent

13. Synthesis of Alcohols Examples: Mg (s)/

14. Synthesis of Alcohols Preparation of Organolithiums Alkyl halide: 1 o, 2 o, 3 o halide Vinyl, allyl, aryl Solvent: ether, alkanes

15. Synthesis of Alcohols Examples: Phenyl lithium

16. Synthesis of Alcohols Grignard reagents and organolithiums are strong nucleophiles Behave like R - Attack electrophilic carbons Aldehydes, ketones Esters, acid chlorides Epoxides

17. Synthesis of Alcohols Attack of R - on an aldehyde or ketone produces an alkoxide ion which can be protonated to form an alcohol.

18. Synthesis of Alcohols Addition of RMgX or RLi to Formaldehyde: forms primary alcohol

19. Synthesis of Alcohols Addition of RMgX or RLi to Aldehydes forms secondary alcohol

20. Synthesis of Alcohols Addition of RMgX or RLi to Aldehydes:

21. Synthesis of Alcohols Addition of RMgX or RLi to Ketones forms tertiary alcohol

22. Synthesis of Alcohols Addition of RMgX or RLi to Esters forms tertiary alcohol with two identical R groups identical R groups come from the organometallic reagent

23. Synthesis of Alcohols The addition of RMgX or RLi to an ester occurs in two steps: R - displaces an alkoxide group, forming a ketone A second R - attacks the carbonyl, forming the alcohol (after protonation)

24. Synthesis of Alcohols Addition of RMgX or RLi to Acid Chlorides forms tertiary alcohol with two identical R groups identical R groups come from the organometallic reagent

25. Synthesis of Alcohols The addition of RMgX or RLi to an acid chloride occurs in two steps: R - displaces the chloride ion, forming a ketone A second R - attacks the carbonyl, forming the alcohol (after protonation)

26. Synthesis of Alcohols Examples:

27. Synthesis of Alcohols Addition of RMgX or RLi to Epoxides forms primary alcohol with two more carbons than the original alkyl halide

28. Synthesis of Alcohols Example: Predict the product of each reaction.

29. Synthesis of Alcohols Limitations/Side Reactions of RMgX and RLi RMgX and RLi are strong nucleophiles and strong bases React with acidic protons Incompatible with water, ROH, RSH, R-NH-R’, and RCO 2 H

30. Synthesis of Alcohols Limitations/Side Reactions of RMgX and RLi RMgX and RLi will react with any multiple bond that contains a strongly electronegative element. RMgX and RLi will react with C=O, S=O, C=N, N=O and C N present in the solvent, organometallic reagent, or substrate