WWU -- Chemistry REAGENTS WITH CARBON- METAL BONDS; ORGANOMETALLIC SYNTHESIS OF ALCOHOLS Chapter 15

WWU -- Chemistry Assignment DO: Sections 15.0 through 15.7 READ: Sections 15.8 and SKIP: Section 15.9 DO: Section DO: Problems

WWU -- Chemistry Problem Assignment In Text Problems –15-1 through End-of-Chapter Problems –1 through 3

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

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

WWU -- Chemistry 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 Generalized Method

WWU -- Chemistry Formation of Organolithium Reagents

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

WWU -- Chemistry 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 Formation of Grignard Reagents

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

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

WWU -- Chemistry 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 were R-MgX, which is what we shall do in this course.

WWU -- Chemistry Owing to the electronegativity difference between the metal and carbon, the carbon- metal bond has a great deal of partial ionic character. The bonds are polar covalent in nature. This means that we can write:

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

WWU -- Chemistry Do You Remember This? Why does the nucleophile go to the CH 2 group and not the R-CH group?

WWU -- Chemistry 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 Crude outline of a mechanism

WWU -- Chemistry Examples:

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

WWU -- Chemistry Reaction with Carbonyl Compounds

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

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

WWU -- Chemistry Example The product is a secondary alcohol

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

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

WWU -- Chemistry Preparation of Alkanes Wurtz Reaction

WWU -- Chemistry Example of a Wurtz Reaction

WWU -- Chemistry The reaction occurs in two steps: The second step is an S N 2 reaction with the organosodium compound acting as the nucleophile.

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

WWU -- Chemistry 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 Lithium Dialkylcuprates a lithium dialkylcuprate

WWU -- Chemistry Example

WWU -- Chemistry 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 Example

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

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

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

WWU -- Chemistry Also...

WWU -- Chemistry 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 Alkynylorganometallic Compounds Section assigned as reading

WWU -- Chemistry Other Organometallic Reagents Organozinc reagents are used in synthesis owing to their greater selectivity (see J. Vyvyan) 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.

WWU -- Chemistry If the reaction of alkyl halide with metal is too slow, one can make a metal alloy with sodium or potassium. For example, lead, by itself is too unreactive. But we can do... Tetraethyllead (TEL) used to be used in gasoline as an anti- knock agent.

WWU -- Chemistry Reactions with Metal Salts We can transfer an R group from one metal to another. Generally this works when we transfer an alkyl group from a more active to a less active metal (from a negative E° to a positive E°) This reaction is energetically favorable -- exothermic We need to consider reduction potentials

WWU -- Chemistry Example We are transferring the R group from Mg to Cd. Mg:E° = volts Cd:E° = volts Organocadmium reagents are very useful (see Chapter 17), but they cannot be made directly.

WWU -- Chemistry Preparation of Tetraphenyltin Na:E° = volts Sn:E° = volts

WWU -- Chemistry Preparation of an Organosilane How would you make TMS?

WWU -- Chemistry Speculate: Na:E° = volts Pb:E° = volts Perhaps an organosodium reagent is formed initially, and then the ethyl group is transferred from the sodium to the lead.