1. Organometallic Reagents Carbon-Metal Bonds

2. RX ++++ ––––RM –––– ++++ Nucleophilic carbon

3. Organometallic Reagents

4. same for Ar—X is an oxidation-reduction reaction: carbon is reduced Organolithium Reagents R X + 2Li R Li + LiX normally prepared by reaction of alkyl halides with lithium

5. Examples (CH 3 ) 3 CCl + 2Li diethyl ether –10°C (CH 3 ) 3 CLi + LiCl (75%) Br + 2Li diethyl ether 35°C Li + LiBr (95-99%)

6. Preparation of Organomagnesium Reagents

7. same for Ar—X “Grignard” Reagents R X + Mg RMgX prepared by reaction of alkyl halides with magnesium Diethyl ether is most often used solvent. Tetrahydrofuran is also used.

8. Nobel Prize 1912 Born: 6 May 1871, Cherbourg, France Died: 13 December 1935, Lyon, France Affiliation at the time of the award: Nancy University, Nancy, France

9. Examples diethyl ether –10°C (96%) Br + Mg diethyl ether 35°C MgBr (95%) Cl + Mg MgCl

10. Alkyl halides, vinyl halides, and aryl halides can all be used to form organolithium and organomagnesium compounds However, these organometallic compounds cannot be prepared from compounds containing acidic groups (OH, NH 2, NHR, SH, C=CH, CO 2 H) Cannot use H 2 O, CH 3 OH, CH 3 CH 2 OH, etc. as solvents Cannot prepare from substances such as HOCH 2 CH 2 Br, etc.

11. Synthesis of Alcohols Grignard or OrganolithiumReagents Synthesis of Alcohols Grignard or Organolithium Reagents Organolithium reagents react with carbonyls in the same general way that Grignard reagents do.

12. Direct formation of a Grignard reagent, involves an alkyl halide reacted with Mg metal. Grignard Reagents

13. Indirect Grignard Reagents Grignard Reagents can be prepared from other Grignard Reagents (trans-metallation)

14. Indirect Grignard Reagents α-acetylenic Grignard Reagents are prepared by an acid-base Grignard reaction CH 3 CH 2 MgBr + CH 3 CH 3 stronger acid weaker acid HCCH HC CMgBr +

15. Question Select the best method to prepare CH 3 CH 2 C  CMgI. A)CH 3 CH 2 C  C-I + Mg (in diethyl ether) B)I-CH 2 CH 2 C  CH + Mg(OH) 2 (in diethyl ether) C)CH 3 CH 2 C  CH + CH 3 MgI (in diethyl ether) D)CH 3 CH 2 C  CH + Mg (in diethyl ether)

16. A Grignard reagent, RMgX, is a very strong base and a good nucleophile; water/moisture MUST be avoided in its reaction. Grignard Reactions Question If water can’t be used as a solvent, can other protic solvents be used instead? Yes (A) / No (B)

17. Example MgBr (100%) + CH 3 OH + CH 3 OMgBr

18. Grignard reagents act as nucleophiles toward the carbonyl group RMgX C O –––– ++++ – MgX + R C O diethyl ether R C OH H3O+H3O+H3O+H3O+ two-step sequence gives an alcohol as the isolated product

19. formaldehyde to give primary alcohols other aldehydes to give secondary alcohols ketones to give tertiary alcohols esters to give tertiary alcohols Grignard reagents react with:

20. formaldehyde to give primary alcohols Grignard reagents react with:

21. Grignard reagents react with formaldehyde RMgX C O – MgX+ –––– ++++ R C O R C OH H3O+H3O+H3O+H3O+ diethyl ether product is a primary alcohol HHHH H H

22. Example diethyl ether Cl Mg MgCl C OHH CH 2 OMgCl H3O+H3O+H3O+H3O+ CH 2 OH (64-69%)

23. formaldehyde to give primary alcohols aldehydes to give secondary alcohols Grignard reagents react with:

24. Question The reaction between propanal and ethylmagnesium chloride followed by H 3 O + will produce A) B) C)D)

25. Grignard reagents react with aldehydes RMgX C O – –––– ++++ R C O R C OH H3O+H3O+H3O+H3O+ diethyl ether product is a secondary alcohol HR' H R' H R' MgX+

26. Example diethyl ether Mg C O H3CH3CH3CH3CH H3O+H3O+H3O+H3O+ (84%) CH 3 (CH 2 ) 4 CH 2 Br CH 3 (CH 2 ) 4 CH 2 MgBr CH 3 (CH 2 ) 4 CH 2 CHCH 3 OMgBr OH

27. Question What is the product of the reaction of ethylmagnesium bromide (CH 3 CH 2 MgBr) with butanal (CH 3 CH 2 CH 2 CH=O) followed by dilute acid? A)2-hexanol B)1-butanol C)3-hexanol D)3-pentanol

28. Example (76%) H2CH2CH2CH2CCHLi + CHCHCHCHO 1. diethyl ether 2. H 3 O + CH 2 CHCH OH

29. formaldehyde to give primary alcohols aldehydes to give secondary alcohols ketones to give tertiary alcohols Grignard reagents react with:

30. Grignard reagents react with ketones RMgX C O – MgX+ –––– ++++ R C O R C OH H3O+H3O+H3O+H3O+ diethyl ether product is a tertiary alcohol R"R' R" R' R" R'

31. Question What is the product of the reaction shown at the right? A)B) C)D)

32. Example diethyl ether Mg H3O+H3O+H3O+H3O+ (62%) CH 3 Cl CH 3 MgCl O CH 3 ClMgO HO

33. Question Two alcohols, each having the molecular formula C 11 H 22 O, are formed in the reaction of methyl lithium with 3-(R)-tert- butylcyclohexanone. These two alcohols are A)constitutional isomers. B)enantiomers in equal amounts. C)enantiomers in unequal amounts. D)diastereomers.

34. Preparation of Tertiary Alcohols From Esters and Grignard Reagents

35. Grignard reagents react with esters RMgX C O – MgX + –––– ++++ R C O diethyl ether OCH 3 R' R' but species formed is unstable and dissociates under the reaction conditions to form a ketone

36. Grignard reagents react with esters RMgX C O – MgX + –––– ++++ R C O diethyl ether OCH 3 R' R' –CH 3 OMgX C ORR' this ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol

37. Example 2 CH 3 MgBr + (CH 3 ) 2 CHCOCH 3 O 1. diethyl ether 2. H 3 O + (CH 3 ) 2 CHCCH 3 OH CH 3 (73%) Two of the groups attached to the tertiary carbon come from the Grignard reagent

38. Question Which one of the compounds below will be produced when 2 moles of methylmagnesium bromide is added to 1 mole of methyl propanoate (CH 3 CH 2 CO 2 CH 3 ) followed by acid? A)CH 3 CH 2 COCH 3 B)CH 3 CH 2 CO 2 -MgBr C)(CH 3 ) 2 C(OH)CH 2 CH 3 D)CH 3 CH 2 CH 2 CH 3 E) 3-methyl-2-butanol

39. What is the product of the following reaction? Question

40. Grignard Reactions

41. Question Which one of the compounds below will be produced when methylmagnesium bromide is added to propanoic acid (CH 3 CH 2 CO 2 H)? A)CH 3 CH 2 COCH 3 B)CH 3 CH 2 CO 2 -MgBr C)CH 3 CH 2 CH(OH)CH 3 D)CH 3 CH 2 CH 2 CH 3