1. Chapter 14 Organometallic Compounds Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. Metal is the parent Li CyclopropyllithiumVinylsodium H2CH2C CHNa CH 3 CH 2 MgCH 2 CH 3 Diethylmagnesium CH 3 MgI Methylmagnesium iodide

3. Polarity of Bonds RX ++ –– RM –– ++ organometallics are a source of nucleophilic carbon

4. Polarity of Bonds CH 3 FCH 3 Li

5. (same for Ar—X) It is an oxidation-reduction reaction: carbon is reduced and metal is oxidized. Organolithium Compounds RX + 2LiRLi + LiX normally prepared by reaction of alkyl halides with lithium

6. 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%)

7. Electron Bookkeeping RX + Li [RX]X] + Li + – R + X–X– Li R

8. Preparation of Organomagnesium Compounds: Grignard Reagents

9. (same for Ar—X) Grignard Reagents RX + MgRMgX prepared by reaction of alkyl halides with magnesium Diethyl ether is most often used solvent. Tetrahydrofuran is also used.

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

11. RX + Mg Electron Bookkeeping [RX]X] + Mg + – R + X–X– R Mg + X–X–

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

13. 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 Forbidden Groups

14. Anything with an OH, SH, or NH group Forbidden Groups therefore: - cannot use H 2 O, CH 3 OH, CH 3 CH 2 OH, etc. as solvents - cannot prepare Grignard reagent from substances such as HOCH 2 CH 2 Br, etc.

15. Organolithium and Organomagnesium Compounds as Brønsted Bases

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

17. Example (100%) + H 2 O + LiOH CH 3 CH 2 CH 2 CH 2 Li CH 3 CH 2 CH 2 CH 3

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

20. Acetylenic Grignard Reagents are prepared by an acid-base reaction CH 3 CH 2 MgBr + CH 3 stronger acid weaker acid HC CH HC CMgBr +

21. Synthesis of Alcohols Using Grignard Reagents Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

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

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

24. Grignard reagents react with formaldehyde R MgX C O – MgX + –– ++ R C O R C OH H3O+H3O+ diethyl ether Product is a primary alcohol. HH H H H H

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

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

27. Example diethyl ether Mg C O H3CH3C H H3O+H3O+ (84%) CH 3 (CH 2 ) 4 CH 2 BrCH 3 (CH 2 ) 4 CH 2 MgBr CH 3 (CH 2 ) 4 CH 2 CHCH 3 OMgBr CH 3 (CH 2 ) 4 CH 2 CHCH 3 OH

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

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

30. Organolithium reagents react with aldehydes and ketones in the same way that Grignard reagents do. Synthesis of Alcohols Using Organolithium Reagents

31. Example (76%) H2CH2C CHLi + CHCH O 1. diethyl ether 2. H 3 O + CH 2 CHCH OH

32. Synthesis of Acetylenic Alcohols

33. Using Sodium Salts of Acetylenes HCCH NaNH 2 NH 3 HCCNa HCCNa + 1. NH 3 2. H 3 O + O HO C CH (65-75%)

34. CH CH 3 (CH 2 ) 3 C + CH 3 CH 2 MgBr CMgBr CH 3 (CH 2 ) 3 C + CH 3 diethyl ether 1. H 2 C O 2. H 3 O + CCH 2 OH CH 3 (CH 2 ) 3 C (82%) Using Acetylenic Grignard Reagents

35. 14.9 Retrosynthetic Analysis Retrosynthetic analysis is the process by which we plan a synthesis by reasoning backward from the desired product (the "target molecule").

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

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

38. Retrosynthetic Analysis of Alcohols C OH

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

40. Example C OH CH 3 CH 2 CH 3 C O CH 3 MgX There are two other possibilities. Can you see them?

41. Synthesis C OH CH 3 CH 2 CH 3 C O 1. 2. H 3 O + CH 3 Br Mg, diethyl ether CH 3 MgBr