REAGENTS WITH CARBONMETAL BONDS ORGANOMETALLIC SYNTHESIS OF ALCOHOLS

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REAGENTS WITH CARBON-METAL BONDSORGANOMETALLIC
SYNTHESISOF ALCOHOLS

• Chapter 15

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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

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Problem Assignment

• In Text Problems
• 15-1 through 15-13
• End-of-Chapter Problems
• 1 through 3

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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.

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• Up to now, we really havent looked at methods of
  forming C-C bonds. Weve formed C-O bonds, C-Cl
  bonds, and C-Br bonds in many examples, but what
  about C-C bonds?

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Can anyone suggest a C-C bond formation reaction
that we have already encountered?
The Diels-Alder reaction!
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Lets 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.
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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.
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Generalized Method
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Formation of Organolithium Reagents
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Example

• Typical solvents
• diethyl ether
• tetrahydrofuran (THF)
• hydrocarbons (pentane, hexane, etc.)

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• 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-Nas or R-Ks.

Who knows why E2 dehydrohalogenation happens in
this reaction?
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Formation of Grignard Reagents
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Example

• Typical solvents
• Diethyl ether (b.p. 35 C)
• Tetrahydrofuran -- THF (b.p. 65 C)
• Dioxane (b.p. 101 C)

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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!
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Why might you need different solvents?
This reaction is too slow at 35 C.
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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.
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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
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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.
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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
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We can use the reaction of organometallic
reagents with sources of proton deliberately
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Do You Remember This?
Why does the nucleophile go to the CH2 group and
not the R-CH group?
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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

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Crude outline of a mechanism
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Examples
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Reasoning by analogy, you could do...
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Reaction with Carbonyl Compounds
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Crude outline of the mechanism of carbonyl
addition
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Outcome of the reaction of an organometallic with
carbonyl compounds
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Example
The product is a secondary alcohol
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Example 2
The product is a tertiary alcohol.
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From PLKE-Micro-3...
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Preparation of Alkanes
Wurtz Reaction
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Example of a Wurtz Reaction
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The reaction occurs in two steps
The second step is an SN2 reaction with the
organosodium compound acting as the nucleophile.
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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.

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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)

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

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• 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.

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Lithium Dialkylcuprates
a lithium dialkylcuprate
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Example
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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)

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Example
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This wouldnt work by a Wurtz synthesis...
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Also...

• In general, allylic halides are unreactive in
  organometallic reactions.
• Not here!

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This would be impossible by other methods
Stereospecific!
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Also...
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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!
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Alkynylorganometallic Compounds
Section 15.8 -- assigned as reading
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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)
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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.
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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

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Example
We are transferring the R group from Mg to
Cd. Mg E - 2.38 volts Cd E - 0.40
volts Organocadmium reagents are very useful (see
Chapter 17), but they cannot be made directly.
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Preparation of Tetraphenyltin
Na E -2.71 volts Sn E 0.01 volts
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Preparation of an Organosilane
How would you make TMS?
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Speculate
Na E - 2.71 volts Pb E - 0.13
volts Perhaps an organosodium reagent is formed
initially, and then the ethyl group is
transferred from the sodium to the lead.