REAGENTS WITH CARBON-METAL BONDS; ORGANOMETALLIC SYNTHESIS OF ALCOHOLS

1. REAGENTS WITH CARBON-METAL BONDS;ORGANOMETALLIC SYNTHESISOF ALCOHOLS Chapter 15 WWU -- Chemistry

2. Assignment • DO: Sections 15.0 through 15.7 • READ: Sections 15.8 and 15.10 • SKIP: Section 15.9 • DO: Section 15.11 • DO: Problems WWU -- Chemistry

3. Problem Assignment • In Text Problems • 15-1 through 15-13 • End-of-Chapter Problems • 1 through 3 WWU -- Chemistry

4. Reagents with Carbon-Metal Bonds • How do we make large molecules when most of our available reagents are relatively simple in structure? • How do we “dock” two large molecular fragments together? • What we need are methods of forming carbon-carbon bonds. WWU -- Chemistry

5. Up to now, we really haven’t looked at methods of forming C-C bonds. We’ve formed C-O bonds, C-Cl bonds, and C-Br bonds in many examples, but what about C-C bonds? WWU -- Chemistry

6. Can anyone suggest a C-C bond formation reaction that we have already encountered? The Diels-Alder reaction! WWU -- Chemistry

7. Let’s go back to a very familiar reaction, nucleophilic substitution: Now, if our nucleophilic atom werecarbon, we would have a method that we could adapt and develop. WWU -- Chemistry

8. Consider: Here is the theme of this chapter. It introduces a new class of reagents that are capable of acting as carbon nucleophiles, opening the door to our being able to combine small molecular fragments and build large molecules from them. WWU -- Chemistry

9. Generalized Method WWU -- Chemistry

10. Formation of Organolithium Reagents WWU -- Chemistry

11. Example: • Typical solvents: • diethyl ether • tetrahydrofuran (THF) • hydrocarbons (pentane, hexane, etc.) WWU -- Chemistry

12. Some important points to consider: • organosodium and organopotassium reagents are difficult to form -- this method is best for organolithium reagents. • E2 dehydrohalogenation is an important side reaction, especially if the alkyl halide is secondary or tertiary. This problem is particularly serious with R-Na’s or R-K’s. Who knows why E2 dehydrohalogenation happens in this reaction? WWU -- Chemistry

13. Formation of Grignard Reagents WWU -- Chemistry

14. Example: • Typical solvents: • Diethyl ether (b.p. 35 °C) • Tetrahydrofuran -- THF (b.p. 65 °C) • Dioxane (b.p. 101 °C) WWU -- Chemistry

15. An ether is required to form a stable Grignard complex. Formation of this complex is exothermic; the reaction is sufficiently exothermic to boil the solution without having to add external heat! WWU -- Chemistry

16. Why might you need different solvents? This reaction is too slow at 35 °C. WWU -- Chemistry

17. The complete structure of the Grignard reagent is quite complex. It is probably an equilibrium mixture of the type: While this may be more correct, it is easier to treat the Grignard reagent as if it wereR-MgX, which is what we shall do in this course. WWU -- Chemistry

18. Owing to the electronegativity difference between the metal and carbon, the carbon-metal bond has a great deal ofpartial ionic character.The bonds arepolar covalentin nature. This means that we can write: WWU -- Chemistry

19. In fact, we can treat the Grignard (or any organometallic) reagent according to: Thus, the organometallic reagent acts as a source of “R:-”, which is the conjugate base of an alkane. We therefore expect the organometallic reagents to be very basic and strongly nucleophilic. WWU -- Chemistry

20. If the organometallic reagents are basic, then we should see them react readily with acids. Any source of H+ will bring about this reaction: acids, carboxylic acids, water, alcohols, amines, even atmospheric moisture WWU -- Chemistry

21. We can use the reaction of organometallic reagents with sources of proton deliberately WWU -- Chemistry

22. Do You Remember This? Why does the nucleophile go to the CH2 group and not the R-CH group? WWU -- Chemistry

23. Reaction with Epoxides • Notice that: • whatever the length of the carbon chain in R, the product has added two carbons • the product is a terminal alcohol WWU -- Chemistry

24. Crude outline of a mechanism WWU -- Chemistry

25. Examples: WWU -- Chemistry

26. Reasoning by analogy, you could do... WWU -- Chemistry

27. Reaction with Carbonyl Compounds WWU -- Chemistry

28. Crude outline of the mechanism of carbonyl addition WWU -- Chemistry

29. Outcome of the reaction of an organometallic with carbonyl compounds WWU -- Chemistry

30. Example The product is a secondary alcohol WWU -- Chemistry

31. Example #2 The product is a tertiary alcohol. WWU -- Chemistry

32. From “PLKE-Micro-3”... WWU -- Chemistry

33. Preparation of Alkanes Wurtz Reaction WWU -- Chemistry

34. Example of a Wurtz Reaction WWU -- Chemistry

35. The reaction occurs in two steps: The second step is an SN2 reaction with the organosodium compound acting as the nucleophile. WWU -- Chemistry

36. Characteristics of the Wurtz Reaction: • Characteristically poor yields • “Worst Reaction” • Works only with primary alkyl halides • With secondary and tertiary alkyl halides, all you get is alkene. • Why? • Only even-numbered alkanes can be prepared -- both halves have to be the same. WWU -- Chemistry

37. The Wurtz Reaction is an example of an Alkylation Reaction • Alkylation: a reaction to attach an alkyl group to some other atom. • Other alkylations we have encountered include: • Williamson ether synthesis (alkylation of oxygen) • Wurtz reaction (alkylation of carbon) • Alkylation of amines (nitrogen) • S-AdM (biological methylation) WWU -- Chemistry

38. Can we do an alkylation of carbon? • Can we do it better? • Can we make odd-numbered alkanes? WWU -- Chemistry

39. Obviously, the answer to the previous questions is “yes”! • A new type of organometallic reagent, a lithium dialkylcuprate, affords us the possibility of alkylating carbon in good yield • We also have a route to the synthesis of an odd numbered alkane -- the two halves being joined do not have to be the same. WWU -- Chemistry

40. Lithium Dialkylcuprates a lithium dialkylcuprate WWU -- Chemistry

41. Example WWU -- Chemistry

42. The dialkylcuprate is a very good alkylating agent. • This reaction is known as the Corey-House synthesis. • Note that the two alkyl groups do not have to be identical! -- (unlike the Wurtz reaction) WWU -- Chemistry

43. Example WWU -- Chemistry

44. This wouldn’t work by a Wurtz synthesis... WWU -- Chemistry

45. Also... • In general, allylic halides are unreactive in organometallic reactions. • Not here! WWU -- Chemistry

46. This would be impossible by other methods: Stereospecific! WWU -- Chemistry

47. Also... WWU -- Chemistry

48. Synthesis of Manicone Manicone is a pheromone secreted by certain male ants as they swarm. It causes female ants of the same species to swarm at the same time the males do. This facilitates mating! WWU -- Chemistry

49. Alkynylorganometallic Compounds Section 15.8 -- assigned as reading WWU -- Chemistry

50. Other Organometallic Reagents We can also make R-Zn, R-Sb, R-As, R-Be, R-Ca, R-Hg, R-Sn, … reagents. We choose other metals for different degrees of reactivity and for greater selectivity. Organozinc reagents are used in synthesis owing to their greater selectivity (see J. Vyvyan) WWU -- Chemistry