WWU -- Chemistry REAGENTS WITH CARBON- METAL BONDS; ORGANOMETALLIC SYNTHESIS OF ALCOHOLS Chapter 15.
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Transcript of WWU -- Chemistry REAGENTS WITH CARBON- METAL BONDS; ORGANOMETALLIC SYNTHESIS OF ALCOHOLS Chapter 15.
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REAGENTS WITH CARBON-METAL BONDS;
ORGANOMETALLIC SYNTHESIS
OF 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 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?
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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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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.
C Br
R
HH
Nu: Nu C
R
H
H+ Br-
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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.
R
C
HH
+ C Br
R
HH
C C
RR
H HH H
+ Br-
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Generalized Method
R X + 2 M R M + MX
M = a metal
R X + M R M X
For a monovalent metal:
For a divalent metal:
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Formation of Organolithium Reagents
R X R Li+ +
R = 1°, 2°, 3°, aryl
X = I > Br > Cl
2 Li Li X
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Example:
2 Li + CH3 CH2 CH2 CH2 Brhexane
CH3 CH2 CH2 CH2 Li
+ LiBr
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-Na’s or R-K’s.
Who knows why E2 dehydrohalogenation happens in this reaction?
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Formation of Grignard Reagents
R X R Mg+ Mgether
X
R = 1°, 2°, 3°, aryl
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Example:
CH3 C CH3
CH3
Cl
+ Mgether
CH3 C CH3
CH3
MgCl
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.
R
Mg
X
CH3 CH2
O
CH2
CH3CH2
O
CH2CH3 CH3
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?
Br + Mgether
35 °CMgBr
Cl + Mg65 °C
MgClTHF
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:
2 R-MgX R2Mg + MgX2
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:
R MgX
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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.
R MgX R: MgX
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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
R MgX + R H + MgX+
R Li + R H + Li+
H+
H+
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We can use the reaction of organometallic reagents with sources of proton deliberately
CH3 CH2 CH CH3
Br
CH3 CH2 CH CH3
Mg
CH3 CH2 CH CH3
D
Mg
ether
Br
D2O
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Do You Remember This?
Why does the nucleophile go to the CH2 group and not the R-CH group?
Nu: CH CH2
O
R+ R CH CH2 Nu
OH
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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
CH2CH2
O
R MgX R CH2 CH2 O
R CH2 CH2 OH
+ether ..
:.. MgX
+_
H2O
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Crude outline of a mechanism
CH2 CH2
O
"R:-" + R CH2 CH2 O
H+
R CH2 CH2 OH
ether
(from RMgX)
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Examples:
CH3 MgI + CH2 CH2
O
ether H2OCH3 CH2 CH2 OH
60% yield
Li
CH2CH
O+
CH2 CH
OHether H2O
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Reasoning by analogy, you could do...
CH2
CH2 O
CH2
+ R MgXether
H2OR CH2 CH2 CH2 OH
Oxetane(trimethylene oxide)
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Reaction with Carbonyl Compounds
R MgX R C
R
R
O R C OH
R
R
O
CR R
+..
:.. MgX
+_ H2Oether
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Crude outline of the mechanism of carbonyl addition
"R:-"
(from R-MgX)
C O
R'
R
R C O
R
R'
H+
R
C
R'
OHR
R, R' = H, alkyl, or aryl
+
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Outcome of the reaction of an organometallic with carbonyl compounds
R M + C O
H
H
R C OH
H
Hformaldehyde primary alcohol
R M + C O
H
R
R C OH
R
Hsecondary alcohol
R M + C O
R'
R
R C OH
R
R'ketones tertiary alcohol
other aldehydes
(M = Li or MgX)
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Example
CH3 CH2 CH2 MgBr + CH3 CH2 C H
O
ether
H2O, H+
CH3 CH2 CH2 C
OH
H
CH2 CH3
Propylmagnesium bromide Propanal (Propionaldehyde)
3-Hexanol
The product is a secondary alcohol
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Example #2O
+ CH3 MgIether
H2O, H+
OHCH3
Cyclohexanone
Methylmagnesium iodide
1-Methylcyclohexanol
The product is a tertiary alcohol.
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From “PLKE-Micro-3”...
MgBr + C
O
1) ether
2) H2O, H+
C
OH
Phenylmagnesium bromide
Benzophenone
Triphenylmethanol
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Preparation of Alkanes
Wurtz Reaction
R X + 2 Na2 R R + 2 NaX
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Example of a Wurtz Reaction
2 CH3 CH2 CH2 Br + 2 Na CH3 CH2 CH2 CH2 CH2 CH3
+ 2 NaBr
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The reaction occurs in two steps:
1)
2)
CH3 CH2 CH2 Br 2 Na CH3 CH2 CH2 Na
+
CH3 CH2 CH2 Na
+
CH3 CH2 CH2 Br
CH3 CH2 CH2 CH2 CH2 CH3
Br
+ Br
+
Na
Na
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
R X R Li
R Li Cu
R
R
Li
2 + CuI0°C
etherLi
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Example
2 CH3 Li + CuI0 °C
etherCu
CH3
CH3
Li
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The dialkylcuprate is a very good alkylating agent.
R X + R2CuLi0 °C
ether
X = Cl, Br, I
R R + R Cu
+ Li X
•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
CH3
CH2CH2
CH2CH2
I+ (CH3)2CuLi
0 °Cether
CH3
CH2CH2
CH2CH2
CH3
+ CH3 Cu + Li I
98% yield
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This wouldn’t work by a Wurtz synthesis...
I
+ (CH3)2CuLi0 °C
ether
CH3
75% yield
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Also...
Br
+ (CH3)2CuLi0 °C
ether
CH3
•In general, allylic halides are unreactive in organometallic reactions.
•Not here!
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This would be impossible by other methods:
C C
H
C8H17
I
H
(E)-1-Iodo-1-decene
+ (C4H9)2CuLi0 °C
ether
C C
H
C8H17
C4H9
H
(E)-5-TetradeceneStereospecific!
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Also...
R C Cl
O
+ R2CuLi0 °C
etherR C R
O
+ R Cu
+ Li Cl
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Synthesis of Manicone
CH3
CH2CH
CHC
CCl
O
CH3 CH3
+ (C2H5)2CuLi
-78.5 °C ether
CH3
CH2CH
CHC
CCH2
CH3
O
CH3CH3
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
R M C CH R C C R
R H+ + M+
:
_
Section 15.8 -- assigned as reading
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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.
CH2 ICH3 +ether
CH3 CH2 ZnZn
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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...
4 CH3 CH2 Br + 4 Na-Pb
CH2 Pb CH2
CH2
CH2
CH3
CH3
CH3
CH3
sodium-lead alloy
Tetraethyllead
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
2 RMgX + CdCl2 R Cd R + 2 MgXCl
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
4 BrNa
toluene111 °C
4 Na
SnCl4
Snm.p. 229 °C
Na: E° = -2.71 volts
Sn: E° = +0.01 volts
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Preparation of an Organosilane
4 CH3 CH2 MgBrSiCl4
CH3 CH2 Si CH2 CH3
CH2
CH2
CH3
CH3
How would you make TMS?
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Speculate:
4 CH3 CH2 Br + 4 Na-Pb
CH2 Pb CH2
CH2
CH2
CH3
CH3
CH3
CH3
sodium-lead alloy
Tetraethyllead
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.