1. Chapter 14Organometallic Compounds

2. 14.1Organometallic Nomenclature

3. Li H2C CHNa Cyclopropyllithium Vinylsodium CH3CH2MgCH2CH3 CH3MgI Diethylmagnesium Methylmagnesiumiodide Metal is the parent

4. 14.2Carbon-Metal BondsinOrganometallic Compounds

5. R X R M Polarity of Bonds organometallics are a source of nucleophilic carbon + – – +

6. Polarity of Bonds CH3F CH3Li

7. 14.3Preparation of Organolithium Compounds

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

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

10. [R X] R X + Li Li• • • + R• R Li X– • • Electron Bookkeeping + Li+ •– •

11. 14.4Preparation of Organomagnesium Compounds: Grignard Reagents

12. 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

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

14. [R X] R X + Mg • Mg+ • • • + R• R Mg+ X– X– • • • Electron Bookkeeping • • + Mg+ •– •

15. Order of Reactivity I > Br > Cl >> F RX > ArX

16. Forbidden Groups certain groups cannot be present in the solvent the halide from which the Grignard reagent is prepared the substance with which the Grignard reagent reacts

17. Forbidden Groups therefore cannot use H2O, CH3OH, CH3CH2OH, etc. as solvents cannot prepare Grignard reagent from substances such as HOCH2CH2Br, etc. Anything with an OH, SH, or NH group

18. 14.5Organolithium and Organomagnesium Compounds as Brønsted Bases

19. R H R H – •• + M M OR' OR' •• •• Brønsted basicity Grignard reagents (M = MgX) and organolithium reagents (M = Li) are strong bases. + – •• ••

20. Example + H2O CH3CH2CH2CH2Li CH3CH2CH2CH3 + LiOH (100%)

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

22. Table 14.1Approximate Acidities Hydrocarbons are very weak acids. Their conjugate bases are very strong bases. Grignard reagents and organolithium reagents are strong bases. Compound pKa (CH3)3CH 71 CH3CH3 62 CH4 60 Ethylene 45 Benzene 43 Ammonia 36 Acetylene 26 Water 16

23. HC CH stronger acid HC CMgBr weaker acid Acetylenic Grignard Reagents are prepared by an acid-base reaction + CH3CH2MgBr + CH3CH3

24. 14.6Synthesis of Alcohols Using Grignard Reagents

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

40. 14.7Synthesis of AlcoholsUsing Organolithium Reagents Organolithium reagents react with aldehydes and ketones in the same way that Grignard reagents do.

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

42. 14.8Synthesis of Acetylenic Alcohols

43. HC CH HC CNa O C CH HO 1. NH3 + HC CNa 2. H3O+ (65-75%) Using Sodium Salts of Acetylenes NaNH2 NH3

44. CH3(CH2)3C CH CH3(CH2)3C CMgBr 1. H2C O 2. H3O+ CH3(CH2)3C CCH2OH (82%) Using Acetylenic Grignard Reagents + CH3CH2MgBr diethyl ether + CH3CH3

45. 14.9Retrosynthetic Analysis Retrosynthetic analysis is the process by which we plan a synthesis by reasoning backward from the desired product (the "target molecule").

46. C OH Retrosynthetic Analysis of Alcohols Step 1 Locate the carbon that bears the hydroxyl group.

47. C OH Retrosynthetic Analysis of Alcohols Step 2 Disconnect one of the groups attached to this carbon.

48. C Retrosynthetic Analysis of Alcohols OH

49. MgX C O Retrosynthetic Analysis of Alcohols What remains is the combination of Grignard reagent and carbonyl compound that can be used to prepare the alcohol.

50. CH3 CH2CH3 C OH O C CH2CH3 Example There are two other possibilities. Can you see them? CH3MgX