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


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


Problem Assignment

• In Text Problems– 15-1 through 15-13

• End-of-Chapter Problems– 1 through 3


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.


• 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?


Can anyone suggest a C-C bond formation reaction that we have already encountered?

The Diels-Alder reaction!


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-


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-


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:


Formation of Organolithium Reagents

R X R Li+ +

R = 1°, 2°, 3°, aryl

X = I > Br > Cl

2 Li Li X


Example:

2 Li + CH3 CH2 CH2 CH2 Brhexane

CH3 CH2 CH2 CH2 Li

+ LiBr

Typical solvents:

•diethyl ether

•tetrahydrofuran (THF)

•hydrocarbons (pentane, hexane, etc.)


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?


Formation of Grignard Reagents

R X R Mg+ Mgether

X

R = 1°, 2°, 3°, aryl


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)


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!


Why might you need different solvents?

Br + Mgether

35 °CMgBr

Cl + Mg65 °C

MgClTHF

This reaction is too slow at 35 °C.


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.


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


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


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+


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


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


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


Crude outline of a mechanism

CH2 CH2

O

"R:-" + R CH2 CH2 O

H+

R CH2 CH2 OH

ether

(from RMgX)


Examples:

CH3 MgI + CH2 CH2

O

ether H2OCH3 CH2 CH2 OH

60% yield

Li

CH2CH

O+

CH2 CH

OHether H2O


Reasoning by analogy, you could do...

CH2

CH2 O

CH2

+ R MgXether

H2OR CH2 CH2 CH2 OH

Oxetane(trimethylene oxide)


Reaction with Carbonyl Compounds

R MgX R C

R

R

O R C OH

R

R

O

CR R

+..

:.. MgX

+_ H2Oether


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

+


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)


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


Example #2O

+ CH3 MgIether

H2O, H+

OHCH3

Cyclohexanone

Methylmagnesium iodide

1-Methylcyclohexanol

The product is a tertiary alcohol.


From “PLKE-Micro-3”...

MgBr + C

O

1) ether

2) H2O, H+

C

OH

Phenylmagnesium bromide

Benzophenone

Triphenylmethanol


Preparation of Alkanes

Wurtz Reaction

R X + 2 Na2 R R + 2 NaX


Example of a Wurtz Reaction

2 CH3 CH2 CH2 Br + 2 Na CH3 CH2 CH2 CH2 CH2 CH3

+ 2 NaBr


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.


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.


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)


• Can we do an alkylation of carbon?

• Can we do it better?

• Can we make odd-numbered alkanes?


• 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.


Lithium Dialkylcuprates

a lithium dialkylcuprate

R X R Li

R Li Cu

R

R

Li

2 + CuI0°C

etherLi


Example

2 CH3 Li + CuI0 °C

etherCu

CH3

CH3

Li


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)


Example

CH3

CH2CH2

CH2CH2

I+ (CH3)2CuLi

0 °Cether

CH3

CH2CH2

CH2CH2

CH3

+ CH3 Cu + Li I

98% yield


This wouldn’t work by a Wurtz synthesis...

I

+ (CH3)2CuLi0 °C

ether

CH3

75% yield


Also...

Br

+ (CH3)2CuLi0 °C

ether

CH3

•In general, allylic halides are unreactive in organometallic reactions.

•Not here!


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!


Also...

R C Cl

O

+ R2CuLi0 °C

etherR C R

O

+ R Cu

+ Li Cl


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!


Alkynylorganometallic Compounds

R M C CH R C C R

R H+ + M+

:

_

Section 15.8 -- assigned as reading


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


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.


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


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.


Preparation of Tetraphenyltin

4 BrNa

toluene111 °C

4 Na

SnCl4

Snm.p. 229 °C

Na: E° = -2.71 volts

Sn: E° = +0.01 volts


Preparation of an Organosilane

4 CH3 CH2 MgBrSiCl4

CH3 CH2 Si CH2 CH3

CH2

CH2

CH3

CH3

How would you make TMS?


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.

wwu -- chemistry reagents with carbon- metal bonds; organometallic synthesis of alcohols chapter 15

Documents

cc bonds

carboncarbon bonds

cc bond formation reaction

co bonds

cbr bonds

available reagents

organopotassium reagents

familiar reaction