Organometallic Compounds

1. OrganometallicCompounds 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. 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. M g B r B r M g Butylmagnesium bromide (an alkyl Grignard reagent) B r M g M g B r Phenylmagnesium bromide (an aryl Grignard reagent) 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 + 1-Bromobutane ether + Bromobenzene

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

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!

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!

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

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

15. Grignard reagents react productively with: formaldehyde to give primary alcohols aldehydesto give secondary alcohols ketonesto give tertiary alcohols esters to give tertiary alcohols CO2to 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 • 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. 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!

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

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

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

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

34. Practice

35. Practice

36. The Same Chemistry is seen With Organolithium Reagents O + CH H2C CHLi 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?