1. Organometallic Compounds
Chapter 15
Guest Lecturer: Prof. Jonathan L. Sessler

2. AWOL!

3. Organometallic Compounds
Organometallic compound: a compound that contains a carbon-metal bond
In this chapter, we focus on organometallic compounds of Mg, Li, and Cu
these classes illustrate the usefulness of organometallics in modern synthetic organic chemistry
they illustrate how the use of organometallics can bring about transformations that cannot be accomplished in any other way
several more recent reactions of organometallic compounds are discussed in Chapter 24

4. Organometallic Reagents
The Key Concepts:
Make a carbon negatively charged/polarlized so it is nucleophilic.
Reaction with electrophilic carbons can make carbon-carbon bonds.
This is a Big Deal!

5. Grignard Reagents Discovered by Victor Grignard in 1900
The First Organometallic Reagents…
Grignard Reagents
Discovered by Victor Grignard in 1900
Key factors are ethereal solvent and water-free conditions
Awarded Nobel Prize in 1912
Victor Grignard
Grignard, Victor , 1871–1935, French chemist. He shared the 1912 Nobel Prize in Chemistry for his work in organic synthesis based on his discovery (1900) of the Grignard Reagent. He taught at the Univ. of Nancy (1909–19) and at the Univ. of Lyons (from 1919 until the end of his career).

6. Grignard Reagents Grignard reagent: an organomagnesium compound
prepared by addition of an alkyl, aryl, or alkenyl (vinylic) halide to Mg metal in diethyl ether or THF
ether B r + M g M g B r
1-Bromobutane
Butylmagnesium bromide
(an alkyl Grignard reagent)
ether B r + M g M g B r
Bromobenzene
Phenylmagnesium
bromide
(an aryl Grignard reagent)

7. An Alternative to Grignard Reagents are Alkyl Lithiums
Both are prepared from alkyl, vinyl, and aryl halides under anhydrous conditions

8. Grignard and Organolithium Reagents
Given the difference in electronegativity between carbon and magnesium (lithium), the C-Mg (C-Li) bond is polar covalent, with C- and Mg+ ( Li+ )
Grignard and organolithium reagents behave like carbanions
Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge 23 23 23

9. Grignard and Organolithium Reagents
Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge
Carbanions are strong bases--they are easily quenched by even very weak acids (water, alcohols, amines, amides, carboxylic acids, even terminal alkynes). A limitation to utility! 23 23 23

10. Grignard and Organolithium Reagents
Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge
Carbanions are strong bases--they are easily quenched by even very weak acids (water, alcohols, amines, carboxylic acids, amides, even terminal alkynes). A limitation to utility! 23 23 23

11. Limitations
Can’t make Grignards with acidic or electro-philic functional groups present in the molecule:
R2NH pKa 38-40
Terminal Alkynes pKa 25
ROH pKa 16-18
Carbonyls & Nitros pKa 11-27

12. Grignard and Organolithium Reagents
Carbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge
Carbanions are also great nucleophiles. This is the reason for their great utility!

13. Key Point: Grignard and Organolithium Reagents
Great nucleophiles that add efficiently to electrophilic carbons, such as epoxides and carbonyl group of aldehydes, ketones and esters. However, their basicity can be a limitation!
Epoxides illustrate how many common organic functional groups contain electrophilic carbons 23 23 23

14. Grignard and Organolithium Reagents
Carbanions (nucleophiles) can react with electrophilic carbon centers in favorable cases. The net result is a carbon-carbon bond--a big deal!
Grignards and organolithium reagents react with many oxygen-containing electrophiles, but not with alkyl halides.
We’ll illustrate this with epoxides.
Recall, acidic protons will “kill” our reagents and/or won’t allow them to be generated in the first place 23 23 23

15. Grignard reagents react productively with:
formaldehyde to give primary alcohols
aldehydes to give secondary alcohols
ketones to give tertiary alcohols
esters to give tertiary alcohols
CO2 to give acids
epoxides to give primary alcohols
The one we are choosing for the sake of initial illustration

16. Epoxides: The Example We Want to Stress
New C-C bond d+ d-
Considered
Retrosyn-
thetically:
These is an extremely valuable reaction…
Worth celebrating!

17. Prof. Iverson Would Normally Play His Trumpet Here!
But, he is gone…

18. Another Kind of Celebration!
Cost of Attending USC (per year): $50,000
Gymnastics, Tumbling and Cheerleading Lessons: $20,000
Keeping Hair Just The Right Shade of Blond: $10,000
Cheering for the Wrong Team: Priceless!

19. Back to Work: A Related Example
Detailed Mechanism Highlighting Retention of Stereochemistry
New C-C bond
Key Points to Note:
Attack at least hindered carbon
Mechanism is SN2-like in initial step
Single enantiomeric product
Chiral center not affected by reaction
Relief of ring strain helps drive reaction
H3O+ breaks up initial salt

20. Two More Examples of Additions to Epoxides
New C-C bond
New C-C bond
Note: Stereochemistry at epoxide retained in product

21. Key point: Orientation Matters!

22. Gilman Reagents
Lithium diorganocopper reagents, known more commonly as Gilman reagents
prepared by treating an alkyl, aryl, or alkenyl lithium compound with Cu(I) iodide

23. Gilman Reagents Coupling with organohalogen compounds Example
form new carbon-carbon bonds by coupling with alkyl and alkenyl chlorides, bromides, and iodides. (Note that this doesn’t work with Grignard or organolithium reagents. THEY ARE TOO BASIC AND DO E2 ELIMINATIONS.)
Example
New C-C bond

24. Gilman Reagents
coupling with a vinylic halide is stereospecific; the configuration of the carbon-carbon double bond is retained
New C-C bond

25. Gilman Reagents
A variation on the preparation of a Gilman reagent is to use a Grignard reagent with a catalytic amount of a copper(I) salt

26. Gilman Reagents Reaction with epoxides
regioselective ring opening (attack at least hindered carbon)
New C-C bond

27. Interim Summary of Introduction to Organometallic Reagents…
Organolithium reagents and Grignard reagents are very basic but also great nucleophiles. They react with epoxides at the less hindered site to give a two-carbon chain extended alcohol. They do not couple with alkyl-, aryl-, or vinyl halides.
Gilman reagents react with epoxides as do organolithium reagents and Grignard reagents. However, they also add to alkyl-, aryl-, and vinyl halides to make new C-C bonds.

28. Feeling Lost?
Fortunately, Dr. Iverson will be back on Monday!

29. Back to Grignard Reagents…
Meanwhile….
Back to Grignard Reagents…
Addition of a Grignard reagent to formaldehyde followed by H3O+ gives a 1° alcohol
This sequence (mechanism) is general and important! 24 24 24

30. Grignard Reactions These are valuable and important reactions…
Please add to your card stock!

31. Grignard reagents react with esters
OCH3 •• R'
diethyl ether d+ R C
OCH3 •• d– R
MgX C + O O ••
• •
MgX
• • •• –
but species formed is unstable and dissociates under the reaction conditions to form a ketone 23

32. Grignard reagents react with esters
OCH3 •• R'
diethyl ether d+ R C
OCH3 •• d– R
MgX C + O O ••
• •
MgX
• • •• –
–CH3OMgX
this ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol C O R R'
• • •• 23

33. 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

34. Practice

35. Practice

36. O + H2C CHLi CH 1. diethyl ether 2. H3O+ CHCH CH2 (76%) OH
The Same Chemistry is seen With Organolithium Reagents O +
H2C
CHLi CH
1. diethyl ether
2. H3O+
CHCH
CH2
(76%) OH

37. Practice

38. Organometallics are one of the classic ways of activating CO2

39. End of Lecture. Any Questions?