1. Dr. Wolf's CHM 201 & 202 14-1 Chapter 14 Organometallic Compounds

2. Dr. Wolf's CHM 201 & 202 14-2 Organometallic Nomenclature

3. Dr. Wolf's CHM 201 & 202 14-3 Metal is the parent Li Cyclopropyllithium Vinylsodium H2CH2CH2CH2C CHNa CH 3 CH 2 MgCH 2 CH 3 Diethylmagnesium CH 3 MgI Methylmagnesium iodide

4. Dr. Wolf's CHM 201 & 202 14-4 Carbon-Metal Bonds in Organometallic Compounds

5. Dr. Wolf's CHM 201 & 202 14-5 F4.0H2.1 O3.5Cu1.9 N3.0Zn1.6 C2.5Al1.5 H2.1 Mg1.2 Li1.0 Na0.9 K0.8 Electronegativities

6. Dr. Wolf's CHM 201 & 202 14-6 Polarity of Bonds RX ++++ ––––RM –––– ++++ organometallics are a source of nucleophilic carbon

7. Dr. Wolf's CHM 201 & 202 14-7 Polarity of Bonds CH 3 F CH 3 Li

8. Dr. Wolf's CHM 201 & 202 14-8 Preparation of Organolithium Compounds

9. Dr. Wolf's CHM 201 & 202 14-9 same for Ar—X An oxidation-reduction reaction: carbon is reduced Organolithium Compounds R X + 2Li R Li + LiX normally prepared by reaction of alkyl halides with lithium

10. Dr. Wolf's CHM 201 & 202 14-10 ExamplesExamples (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%)

11. Dr. Wolf's CHM 201 & 202 14-11 Electron Bookkeeping R X + Li [RX] + Li + – R + X–X–X–X– Li Li RLi

12. Dr. Wolf's CHM 201 & 202 14-12 Preparation of Organomagnesium Compounds: Grignard Reagents

13. Dr. Wolf's CHM 201 & 202 14-13 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.

14. Dr. Wolf's CHM 201 & 202 14-14 ExamplesExamples diethyl ether –10°C (96%) Br + Mg diethyl ether 35°C MgBr (95%) Cl + Mg MgCl

15. Dr. Wolf's CHM 201 & 202 14-15R X + Mg Electron Bookkeeping [RX] + Mg + – R + X–X–X–X– R Mg + X–X–X–X–

16. Dr. Wolf's CHM 201 & 202 14-16 I > Br > Cl >> F RX > ArX Order of Reactivity

17. Dr. Wolf's CHM 201 & 202 14-17 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

18. Dr. Wolf's CHM 201 & 202 14-18 Anything with an OH, SH, or NH group i.e. an acidic hydrogen 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.

19. Dr. Wolf's CHM 201 & 202 14-19 Organolithium and Organomagnesium Compounds as Brønsted Bases

20. Dr. Wolf's CHM 201 & 202 14-20 Brønsted basicity RMHOR' RH OR' –M + –––– ++++ Grignard reagents (M = MgX) and organolithium reagents (M = Li) are strong bases.

21. Dr. Wolf's CHM 201 & 202 14-21 ExampleExample (100%) + H 2 O + LiOH CH 3 CH 2 CH 2 CH 2 Li CH 3 CH 2 CH 2 CH 3 water is a stronger acid than butane

22. Dr. Wolf's CHM 201 & 202 14-22 ExampleExample MgBr (100%) + CH 3 OH + CH 3 OMgBr methanol is a stronger acid than benzene

23. Dr. Wolf's CHM 201 & 202 14-23 Table 14.2 Approximate Acidities of Hydrocarbons HydrocarbonpKa (CH 3 ) 3 CH71 CH 3 CH 3 62 CH 4 60 Ethylene45 Benzene43 Ammonia36 Acetylene26 Water16 Hydrocarbons are very weak acids. Their conjugate bases are very strong bases. Grignard reagents and organolithium reagents are strong bases.

24. Dr. Wolf's CHM 201 & 202 14-24 Acetylenic Grignard Reagents are prepared by an acid-base reaction CH 3 CH 2 MgBr + CH 3 CH 3 stronger acid weaker acid HCCH HC CMgBr +

25. Dr. Wolf's CHM 201 & 202 14-25 Synthesis of Alcohols Using Grignard Reagents

26. Dr. Wolf's CHM 201 & 202 14-26 Grignard reagents act as nucleophiles toward the carbonyl group RMgX C O – MgX + –––– ++++ R C O R C OH H3O+H3O+H3O+H3O+ diethyl ether two-step sequence gives an alcohol as the isolated product

27. Dr. Wolf's CHM 201 & 202 14-27 formaldehyde to give primary alcohols aldehydes to give secondary alcohols ketones to give tertiary alcohols esters to give tertiary alcohols Grignard reagents react with:

28. Dr. Wolf's CHM 201 & 202 14-28 formaldehyde to give primary alcohols Grignard reagents react with:

29. Dr. Wolf's CHM 201 & 202 14-29 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 HH H H H H

30. Dr. Wolf's CHM 201 & 202 14-30 ExampleExample diethyl ether Cl Mg MgCl C OHH CH 2 OMgCl H3O+H3O+H3O+H3O+ CH 2 OH (64-69%)

31. Dr. Wolf's CHM 201 & 202 14-31 formaldehyde to give primary alcohols aldehydes to give secondary alcohols Grignard reagents react with:

32. Dr. Wolf's CHM 201 & 202 14-32 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+

33. Dr. Wolf's CHM 201 & 202 14-33 ExampleExample 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

34. Dr. Wolf's CHM 201 & 202 14-34 formaldehyde to give primary alcohols aldehydes to give secondary alcohols ketones to give tertiary alcohols Grignard reagents react with:

35. Dr. Wolf's CHM 201 & 202 14-35 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'

36. Dr. Wolf's CHM 201 & 202 14-36 ExampleExample diethyl ether Mg H3O+H3O+H3O+H3O+ (62%) CH 3 Cl CH 3 MgCl O CH 3 ClMgO HO

37. Dr. Wolf's CHM 201 & 202 14-37 Organolithium reagents react with aldehydes and ketones in the same way that Grignard reagents do. Synthesis of Alcohols Using Organolithium Reagents

38. Dr. Wolf's CHM 201 & 202 14-38 ExampleExample (76%) H2CH2CH2CH2CCHLi + CHCHCHCHO 1. diethyl ether 2. H 3 O + CH 2 CHCH OH

39. Dr. Wolf's CHM 201 & 202 14-39 Synthesis of Acetylenic Alcohols

40. Dr. Wolf's CHM 201 & 202 14-40 Using Sodium Salts of Acetylenes HCCH NaNH 2 NH 3 HC CNa HC + 1. NH 3 2. H 3 O + O HOC CHCHCHCH (65-75%)

41. Dr. Wolf's CHM 201 & 202 14-41 CH CH 3 (CH 2 ) 3 C + CH 3 CH 2 MgBr CMgBr CH 3 (CH 2 ) 3 C + CH 3 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

42. Dr. Wolf's CHM 201 & 202 14-42 Retrosynthetic Analysis Retrosynthetic analysis is the process by which we plan a synthesis by reasoning backward from the desired product (the "target molecule").

43. Dr. Wolf's CHM 201 & 202 14-43 Retrosynthetic Analysis of Alcohols C OH Step 1 Locate the carbon that bears the hydroxyl group.

44. Dr. Wolf's CHM 201 & 202 14-44 Retrosynthetic Analysis of Alcohols C OH Step 2 Disconnect one of the groups attached to this carbon.

45. Dr. Wolf's CHM 201 & 202 14-45 Retrosynthetic Analysis of Alcohols COH

46. Dr. Wolf's CHM 201 & 202 14-46 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

47. Dr. Wolf's CHM 201 & 202 14-47 ExampleExample C OH CH 3 CH 2 CH 3 C O CH 3 MgX There are two other possibilities. Can you see them?

48. Dr. Wolf's CHM 201 & 202 14-48 SynthesisSynthesis C OH CH 3 CH 2 CH 3 C O1. 2. H 3 O + CH 3 Br Mg, diethyl ether CH 3 MgBr

49. Dr. Wolf's CHM 201 & 202 14-49 Preparation of Tertiary Alcohols From Esters and Grignard Reagents (also in Chapter 19)

50. Dr. Wolf's CHM 201 & 202 14-50 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

51. Dr. Wolf's CHM 201 & 202 14-51 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

52. Dr. Wolf's CHM 201 & 202 14-52 ExampleExample 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

53. Dr. Wolf's CHM 201 & 202 14-53 Alkane Synthesis Using Organocopper Reagents

54. Dr. Wolf's CHM 201 & 202 14-54 Lithium dialkylcuprates are useful synthetic reagents. They are prepared from alkyllithiums and a copper(I) halide. 2RLi + CuX R 2 CuLi + LiX [customary solvents are diethyl ether and tetrahydrofuran (THF)] Lithium Dialkylcuprates

55. Dr. Wolf's CHM 201 & 202 14-55 the alkyllithium first reacts with the copper(I) halide How?How?RLi CuI Li + RCu I–I–I–I–

56. Dr. Wolf's CHM 201 & 202 14-56 the alkyllithium first reacts with the copper(I) halide then a second molecule of the alkyllithium reacts with the alkylcopper species formed in the first step Li + – How?How?RLi CuI RCu I–I–I–I–RLi RCu RCu R

57. Dr. Wolf's CHM 201 & 202 14-57 R 2 CuLi + R'X RR'+ RCu + LiX Ar 2 CuLi + R'X ArR' + ArCu + LiX Lithium diorganocuprates are used to form C—C bonds

58. Dr. Wolf's CHM 201 & 202 14-58 primary alkyl halides work best (secondary and tertiary alkyl halides undergo elimination) diethyl ether (CH 3 ) 2 CuLi + CH 3 (CH 2 ) 8 CH 2 I CH 3 (CH 2 ) 8 CH 2 CH 3 (90%) Example: Lithium dimethylcuprate

59. Dr. Wolf's CHM 201 & 202 14-59 Example: Lithium diphenylcuprate diethyl ether (C 6 H 5 ) 2 CuLi + CH 3 (CH 2 ) 6 CH 2 I CH 3 (CH 2 ) 6 CH 2 C 6 H 5 (99%)

60. Dr. Wolf's CHM 201 & 202 14-60 (CH 3 CH 2 CH 2 CH 2 ) 2 CuLi Vinylic halides can be used + diethyl ether Br CH 2 CH 2 CH 2 CH 3 (80%)

61. Dr. Wolf's CHM 201 & 202 14-61 (CH 3 CH 2 CH 2 CH 2 ) 2 CuLi Aryl halides can be used + diethyl ether I CH 2 CH 2 CH 2 CH 3 (75%)

62. Dr. Wolf's CHM 201 & 202 14-62 An Organozinc Reagent for Cyclopropane Synthesis

63. Dr. Wolf's CHM 201 & 202 14-63 Iodomethylzinc iodide reacts with alkenes to form cyclopropanes reaction with alkenes is called the Simmons-Smith reaction CH 2 I 2 + Zn ICH 2 ZnI Cu formed by reaction of diiodomethane with zinc that has been coated with copper (called zinc-copper couple)

64. Dr. Wolf's CHM 201 & 202 14-64 diethyl ether ExampleExample H2CH2CH2CH2C C CH 2 CH 3 CH 3 CH 2 I 2, Zn/Cu CH 2 CH 3 CH 3 (79%) I CH 2 ZnI via

65. Dr. Wolf's CHM 201 & 202 14-65 Stereospecific syn-addition diethyl ether CH 2 I 2, Zn/Cu C C CH 3 CH 2 CH 2 CH 3 HH CH 3 CH 2 CH 2 CH 3 HH

66. Dr. Wolf's CHM 201 & 202 14-66 Stereospecific syn-addition diethyl ether CH 2 I 2, Zn/Cu C C CH 3 CH 2 CH 2 CH 3 H H CH 3 CH 2 CH 2 CH 3 H H

67. Dr. Wolf's CHM 201 & 202 14-67 Carbenes and Carbenoids

68. Dr. Wolf's CHM 201 & 202 14-68 CarbeneCarbene name to give to species that contains a divalent carbon (carbon with two bonds and six electrons) CBrBr Dibromocarbene (same chemistry with dichlorocarbenes) Carbenes are very reactive; normally cannot be isolated and stored. Are intermediates in certain reactions.

69. Dr. Wolf's CHM 201 & 202 14-69 Generation of Dibromocarbene C Br Br Br H + OC(CH 3 ) 3 – H+ C Br BrBr–

70. Dr. Wolf's CHM 201 & 202 14-70 Generation of Dibromocarbene + C Br BrBr– C BrBr Br–

71. Dr. Wolf's CHM 201 & 202 14-71 Carbenes react with alkenes to give cyclopropanes + CHBr 3 Br Br (75%) CBr 2 is an intermediate stereospecific syn addition KOC(CH 3 ) 3 (CH 3 ) 3 COH

72. End of Chapter 14