1. Chapter 14 Organometallic Compounds

2. 14.1 Organometallic Nomenclature7

3. Methylmagnesium iodide
Metal Is the “Parent” Li
Cyclopropyllithium
Vinylsodium
H2C
CHNa
CH3CH2MgCH2CH3
Diethylmagnesium
CH3MgI
Methylmagnesium iodide 8

4. 14.2 Carbon-Metal Bonds in Organometallic Compounds

5. Organometallics are a source of nucleophilic carbon.
Polarity of Bonds + – – + R X R M
Organometallics are a source of nucleophilic carbon. 4

6. Polarity of Bonds
CH3F
CH3Li 4

7. 14.3 Preparation of Organolithium Compounds9

8. Organolithium Compounds
Normally prepared by reaction of alkyl halides with lithium. R
X + 2Li R
Li + LiX
same for Ar—X
An oxidation-reduction reaction: carbon is reduced. 10

9. Examples diethyl ether (CH3)3CCl + 2Li (CH3)3CLi + LiCl –30°C (75%)Br
+ 2Li Li
+ LiBr
35°C
(95-99%) 11

10. Electron Bookkeeping R X + Li [R X] + Li+ R• + X– Li• R Li • • – • •14

11. 14.4 Preparation of Organomagnesium Compounds: Grignard Reagents15

12. Prepared by reaction of alkyl halides with magnesium.
Grignard Reagents
Prepared by reaction of alkyl halides with magnesium. R
X + Mg
RMgX
same for Ar—X
Diethyl ether is most often used solvent. Tetrahydrofuran is also used. 10

13. Examples diethyl ether Cl MgCl + Mg –10°C (96%) diethyl ether Br + Mg
MgBr
35°C
(95%) 11

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

15. I > Br > Cl >> F
Order of Reactivity
I > Br > Cl >> F
RX > ArX 18

16. 14.5 Organolithium and Organomagnesium Compounds as Brønsted Bases22

17. Certain groups cannot be present in: the solvent,
Forbidden Groups
Certain groups cannot be present in:
the solvent,
the halide from which the Grignard reagent is prepared,
or the substance with which the Grignard reagent reacts. 19

18. Anything with an OH, SH, or NH group.
Forbidden Groups
Anything with an OH, SH, or NH group.
Therefore, cannot use H2O, CH3OH, CH3CH2OH, etc. as solvents.
Cannot prepare Grignard reagent from substances such as HOCH2CH2Br, etc. 20

19. Brønsted basicity – R H OR' – M + + R M H OR'••
• • – M + + R M H
OR'
• • ••
Grignard reagents (M = MgX) and organolithium reagents (M = Li) are strong bases. 23

20. Example
Note: We are concerned here with relative strength or weakness of reactants and products as acids or bases (e.g., H2O is not considered a “strong acid” normally).
CH3CH2CH2CH2Li
+ H2O
Stronger base
Stronger acid
CH3CH2CH2CH3 +
LiOH
(100%)
Weaker acid
Weaker base 11

21. Example MgBr + CH3OH Stronger base Stronger acid + CH3OMgBr (100%)
Weaker acid
Weaker base 11

22. Approximate Acidities
Compound pKa
(CH3)3CH 71
CH3CH3 62 CH
Ethylene 45
Benzene 43
Ammonia 36
Acetylene 26
Water 16
Hydrocarbons are very weak acids.
Their conjugate bases are very strong bases.
Grignard reagents and organolithium reagents are strong bases. 25

23. Acetylenic Grignard Reagents
Prepared by an acid-base reaction.
CH3CH2MgBr + HC CH
Stronger acid
Weaker acid
Stronger base
CH3CH3 + HC
CMgBr
Weaker base 26

24. 14.6 Synthesis of Alcohols Using Grignard Reagents

25. Grignard Reagents Act as Nucleophiles Toward the Carbonyl Group
diethyl ether –
MgX + R C O ••
• • + – R
MgX C O
• • •• •• R C OH
• •
H3O+
Two-step sequence gives an alcohol as the isolated product. 23

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. 3

27. Grignard reagents react with:
Formaldehyde to give primary alcohols. 3

28. Grignard Reagents React with Formaldehyde
diethyl ether + R C – R
MgX C
MgX + O O ••
• •
• • •• –
H3O+ •• R C OH
• •
Product is a primary alcohol. 23

29. Example Mg Cl
MgCl
diethyl ether C O H
H3O+
CH2OH
CH2OMgCl
(64-69%) 5

30. Grignard reagents react with:
Formaldehyde to give primary alcohols.
Aldehydes to give secondary alcohols. 3

31. Grignard Reagents React with Aldehydes
diethyl ether + R C – R
MgX R' C
MgX + O O ••
• •
• • •• –
H3O+ H
Product is a secondary alcohol. •• R C OH
• • R' 23

32. Example Mg CH3(CH2)4CH2Br CH3(CH2)4CH2MgBr diethyl ether C O H3C H
H3O+
CH3(CH2)4CH2CHCH3 OH
CH3(CH2)4CH2CHCH3
OMgBr
(84%) 5

33. Grignard reagents react with:
Formaldehyde to give primary alcohols.
Aldehydes to give secondary alcohols.
Ketones to give tertiary alcohols. 3

34. Grignard Reagents React with Ketones
diethyl ether + R C – R
MgX R' C
MgX + O O ••
• •
• • •• –
H3O+
R" •• R C OH
• •
Product is a tertiary alcohol. R' 23

35. Example Mg
CH3Cl
CH3MgCl
diethyl ether O
CH3 HO
CH3
ClMgO
H3O+
(62%) 5

36. 14.7 Synthesis of Alcohols Using Organolithium Reagents
Organolithium reagents react with aldehydes and ketones in the same way that Grignard reagents do. 10

37. Example CH O +
H2C
CHLi
1. diethyl ether
2. H3O+
CH2
CHCH OH
(76%) 5

38. 14.8 Synthesis of Acetylenic Alcohols12

39. Using Sodium Salts of Acetylenes
NaNH2 HC CH HC
CNa
NH3 HC
CNa +
1. NH3
2. H3O+ O HO C CH
(65-75%) 13

40. Using Acetylenic Organolithium Reagents
Note: Not shown here is that the OH on oestrone has to be protected (e.g., temporarily converted to an ether) prior to the reaction and then deprotected.

41. Using Acetylenic Grignard ReagentsCH
CH3(CH2)3C +
CH3CH2MgBr
diethyl ether
CMgBr
CH3(CH2)3C +
CH3CH3
1. H2C O
2. H3O+
CCH2OH
CH3(CH2)3C
(82%) 13

42. 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").
E. J. Corey 14

43. Retrosynthetic Analysis of Alcohols
Step 1. Locate the carbon that bears the hydroxyl group. 15

44. Retrosynthetic Analysis of Alcohols
Step 2. Disconnect one of the groups attached to this carbon. 15

45. Retrosynthetic Analysis of Alcohols15

46. Retrosynthetic Analysis of Alcohols
MgX C O
What remains is the combination of Grignard reagent and carbonyl compound that can be used to prepare the alcohol. 15

47. There are two other possibilities.
Example C OH
CH3
CH2CH3
There are two other possibilities.
CH3MgX C
CH2CH3 O 20

48. Synthesis Mg, diethyl ether CH3Br CH3MgBr C CH2CH3 O 1. 2. H3O+ C OH21

49. 14.10 Preparation of Tertiary Alcohols from Esters and Grignard Reagents24

50. Grignard Reagents React with Esters
OCH3 •• R'
diethyl ether + R C
OCH3 •• – R
MgX C + O O ••
• •
MgX
• • •• –
But species formed is unstable and dissociates under the reaction conditions to form a ketone. 23

51. Grignard Reagents React with Esters
OCH3 •• R'
diethyl ether + R C
OCH3 •• – R
MgX C + O O ••
• •
MgX
• • •• –
This ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol.
– CH3OMgX C O R R'
• • •• 23

52. Example O + 2 CH3MgBr (CH3)2CHCOCH3 1. diethyl ether 2. H3O+
Two of the groups attached to the tertiary carbon come from the Grignard reagent. OH
(CH3)2CHCCH3
CH3
(73%) 26

53. 14.11 Alkane Synthesis Using Organocopper Reagents

54. Lithium Dialkylcuprates
Lithium dialkylcuprates are useful synthetic reagents.
They are prepared from alkyllithiums and a copper(I) halide.
2RLi CuX
R2CuLi LiX
[customary solvents are diethyl ether and tetrahydrofuran (THF)] 2

55. The alkyllithium first reacts with the copper(I) halide.
How?
The alkyllithium first reacts with the copper(I) halide. R Li R Cu
Li+ I– Cu I
Then a second molecule of the alkyllithium reacts with the alkylcopper species formed in the first step.
Li+ – R Li Cu 3

56. Lithium Diorganocuprates Are Used to Form C—C Bonds
R2CuLi +
R'X R R'
RCu
LiX
Ar2CuLi +
R'X Ar R' +
ArCu +
LiX 4

57. Example: Lithium Dimethylcuprate
(CH3)2CuLi +
CH3(CH2)8CH2I
diethyl ether
CH3(CH2)8CH2CH3
(90%)
Primary alkyl halides work best (secondary and tertiary alkyl halides undergo elimination). 6

58. Example: Lithium Diphenylcuprate
(C6H5)2CuLi +
CH3(CH2)6CH2I
diethyl ether
CH3(CH2)6CH2C6H5
(99%) 7

59. Vinylic Halides Can Be Used+
(CH3CH2CH2CH2)2CuLi Br
diethyl ether
CH2CH2CH2CH3
(80%) 8

60. Aryl Halides Can Be Used+
(CH3CH2CH2CH2)2CuLi I
diethyl ether
CH2CH2CH2CH3
(75%) 8

61. 14.12 An Organozinc Reagent for Cyclopropane Synthesis

62. Iodomethylzinc Iodide
Formed by reaction of diiodomethane with zinc that has been coated with copper (called zinc-copper couple). Cu
CH2I Zn
ICH2ZnI
Reacts with alkenes to form cyclopropanes.
Reaction with alkenes is called the Simmons-Smith reaction. 6

63. Example
CH2CH3
CH2CH3
CH2I2, Zn/Cu
H2C C
diethyl ether
CH3
CH3
(79%) 6

64. Stereospecific syn-Addition
CH3CH2
CH2CH3 H
CH2I2, Zn/Cu
diethyl ether
CH3CH2
CH2CH3 H 6

65. Stereospecific syn-Addition
CH3CH2 H C H
CH2CH3
diethyl ether
CH2I2, Zn/Cu
CH3CH2
CH2CH3 H 6

66. 14.13 Carbenes and Carbenoids

67. Carbenes are very reactive; normally cannot be isolated and stored.
A species that contains a divalent carbon (carbon with two bonds and six electrons). C •• Br
Dibromocarbene
Carbenes are very reactive; normally cannot be isolated and stored.
Carbenes are intermediates in certain reactions.
Carbenoids are carbenes complexed to metals; an example is iodomethylzinc iodide (14.2). 6

68. Generation of Dibromocarbene
OC(CH3)3 – •• • C + Br H Br H +
OC(CH3)3 •• C Br – • 7

69. Generation of Dibromocarbene•• C – + Br Br Br C Br – • 7

70. Carbenes React with Alkenes to Yield Cyclopropanes
KOC(CH3)3 Br
+ CHBr3
(CH3)3COH Br
CBr2 is a highly reactive (short-lived) intermediate.
(75%) 7

71. Example of Why the Synthesis of Cyclopropanes Is Important
Chrysanthemum cinerariaefolium (Dalmatian chrysanthemum)
Pyrethrin
(natural insecticide)

72. Example of Why the Synthesis of Cyclopropanes Is Important
Cypermetrin is an insecticide that is highly effective against a wide range of crop-damaging insects. It is also active against mosquitoes.