Organometallic Reagents Carbon-Metal Bonds

1. Organometallic ReagentsCarbon-Metal Bonds

2. R X R M Nucleophilic carbon + – – +

3. Organometallic Reagents

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

5. Examples diethylether (CH3)3CCl + 2Li (CH3)3CLi + LiCl –10°C (75%) diethylether Br + 2Li Li + LiBr 35°C (95-99%)

6. Preparation of Organomagnesium Reagents

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

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

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, NH2, NHR, SH, C=CH, CO2H) Cannot use H2O, CH3OH, CH3CH2OH, etc. as solvents Cannot prepare from substances such as HOCH2CH2Br, etc.

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

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

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

14. HC CH stronger acid HC CMgBr weaker acid Indirect Grignard Reagents α-acetylenic Grignard Reagents are prepared by an acid-base Grignard reaction + CH3CH2MgBr + CH3CH3

15. Question • Select the best method to prepare CH3CH2CºCMgI. • A) CH3CH2CºC-I + Mg (in diethyl ether) • B) I-CH2CH2CºCH + Mg(OH)2 (in diethyl ether) • C) CH3CH2CºCH + CH3MgI (in diethyl ether) • D) CH3CH2CºCH + Mg (in diethyl ether)

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

17. Example + CH3OH MgBr + CH3OMgBr (100%)

18. diethylether R C R + MgX O MgX •• •• •• – H3O+ R C OH •• •• Grignard reagents act as nucleophilestoward the carbonyl group + – two-step sequence gives an alcohol as the isolated product C O •• ••

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

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

21. H H H diethylether H R C R + MgX O MgX •• •• •• H R H C OH •• •• Grignard reagents react with formaldehyde product is a primary alcohol + – C O •• – •• H3O+

22. Cl MgCl H O C H CH2OH CH2OMgCl Example Mg diethylether H3O+ (64-69%)

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

24. Question • The reaction between propanal and ethylmagnesium chloride followed by H3O+ will produce • A) B) • C) D)

25. diethylether R C R + O MgX MgX •• •• •• R C OH •• •• Grignard reagents react with aldehydes H product is a secondary alcohol H R' + – R' C O •• – •• H3O+ H R'

26. H3C O C H CH3(CH2)4CH2CHCH3 CH3(CH2)4CH2CHCH3 OH OMgBr Example Mg CH3(CH2)4CH2Br CH3(CH2)4CH2MgBr diethylether H3O+ (84%)

27. Question • What is the product of the reaction of ethylmagnesium bromide (CH3CH2MgBr) with butanal (CH3CH2CH2CH=O) followed by dilute acid? • A) 2-hexanol • B) 1-butanol • C) 3-hexanol • D) 3-pentanol

28. O CH H2C CHLi CHCH CH2 OH Example + 1. diethyl ether 2. H3O+ (76%)

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

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

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

32. CH3 CH3 HO ClMgO Example Mg CH3Cl CH3MgCl diethylether O H3O+ (62%)

33. Question • Two alcohols, each having the molecular formula C11H22O, 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 AlcoholsFrom Esters and Grignard Reagents

35. •• diethylether OCH3 •• •• OCH3 R C R •• O MgX •• •• •• Grignard reagents react with esters R' R' + – but species formed is unstable and dissociates under the reaction conditions to form a ketone C + MgX O •• – ••

36. •• diethylether OCH3 •• •• OCH3 R C R •• O MgX •• •• •• R R' C O Grignard reagents react with esters R' R' + – this ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol C + MgX O •• – •• –CH3OMgX •• ••

37. O (CH3)2CHCOCH3 Example + 2 CH3MgBr Two of the groups attached to the tertiary carbon come from the Grignard reagent 1. diethyl ether 2. H3O+ OH (CH3)2CHCCH3 CH3 (73%)

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 (CH3CH2CO2CH3) followed by acid? • A) CH3CH2COCH3 • B) CH3CH2CO2-MgBr • C) (CH3)2C(OH)CH2CH3 • D) CH3CH2CH2CH3 • E) 3-methyl-2-butanol

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

40. Grignard Reactions

41. Question • Which one of the compounds below will be produced when methylmagnesium bromide is added to propanoic acid (CH3CH2CO2H)? • A) CH3CH2COCH3 • B) CH3CH2CO2-MgBr • C) CH3CH2CH(OH)CH3 • D) CH3CH2CH2CH3