Chapter 14 Organometallic Compounds Copyright © The McGraw-Hill Companies, Inc. Permission required...

Chapter 14Chapter 14Organometallic CompoundsOrganometallic Compounds

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Metal is the parent Li

Cyclopropyllithium Vinylsodium

H2C CHNa

CH3CH2MgCH2CH3

Diethylmagnesium

CH3MgI

Methylmagnesiumiodide

Polarity of Bonds

R X+ –

R M– +

organometallics are a source of nucleophilic

carbon

Polarity of Bonds

CH3F CH3Li

(same for Ar—X)

It is an oxidation-reduction reaction:

carbon is reduced and metal is oxidized.

Organolithium Compounds

R X + 2Li R Li + LiX

normally prepared by reaction of alkyl halides with lithium

Examples

(CH3)3CCl + 2Li

diethylether

–10°C

(CH3)3CLi + LiCl

(75%) Br + 2Li

diethylether

35°C

Li + LiBr

(95-99%)

Electron Bookkeeping

R X + Li [R X] + Li+•–

R• + •• X–

•

Li•LiR••

Preparation of Organomagnesium Compounds:

Grignard Reagents

(same for Ar—X)

Grignard Reagents

R X + Mg RMgX

prepared by reaction of alkyl halides with magnesium

Diethyl ether is most often used solvent. Tetrahydrofuran is also used.

Examplesdiethylether

–10°C(96%)

Br + Mg

diethylether

35°C

MgBr

(95%)

Cl + Mg

MgCl

R X + Mg

Electron Bookkeeping

[R X] + Mg+•–

R• + •• X–

•• •

R••Mg+

Mg+•

•• X–

I > Br > Cl >> F

RX > ArX

Order of Reactivity

certain groups cannot be present in

the solvent

the halide from which the Grignard reagent

is prepared

the substance with which the Grignard reagent reacts

Forbidden Groups

Anything with an OH, SH, or NH group

Forbidden Groups

therefore:

- cannot use H2O, CH3OH, CH3CH2OH, etc. as solvents

- cannot prepare Grignard reagent from substances such as HOCH2CH2Br, etc.

Organolithium and Organomagnesium Compounds as Brønsted Bases

Brønsted basicity

R

M

H

OR'••

••

R H

OR'••

••••–

M+

– +

Grignard reagents (M = MgX) and organolithium reagents (M = Li) are strong bases.

Example

(100%)

+ H2O

+ LiOH

CH3CH2CH2CH2Li

CH3CH2CH2CH3

Example MgBr

(100%)

+ CH3OH + CH3OMgBr

Acetylenic Grignard Reagents

are prepared by an acid-base reaction

CH3CH2MgBr

+CH3CH3

stronger acid

weaker acid

HC CH

HC CMgBr

+

Synthesis of Alcohols Using Synthesis of Alcohols Using

Grignard ReagentsGrignard Reagents

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Grignard reagents act as nucleophilestoward the carbonyl group

R

MgX

C

O••

••

– +

–

MgX+

R C

O••

•• ••

diethylether

••

R C

OH••

H3O+

Two-step sequence gives an alcohol as the isolated product.

formaldehyde to give primary alcohols

aldehydes to give secondary alcohols

ketones to give tertiary alcohols

esters to give tertiary alcohols

Grignard reagents react with:

Grignard reagents react with formaldehyde

R

MgX

C

O

••

•• –MgX

+

– +R C

O••

•• ••

••

R C

OH••

H3O+

diethylether

Product is a primary alcohol.

H HH

H

H

H

Example

diethylether

Cl

Mg

MgCl

C O

H

H CH2OMgCl

H3O+

CH2OH

(64-69%)

Grignard reagents react with aldehydes

R

MgX

C

O

••

•• –

– +R C

O••

•• ••

••

R C

OH••

H3O+

diethylether

Product is a secondary alcohol.

H R'H

R'

H

R'

MgX+

Example

diethylether

Mg

C O

H3C

H

H3O+

(84%)

CH3(CH2)4CH2Br CH3(CH2)4CH2MgBr

CH3(CH2)4CH2CHCH3

OMgBr

CH3(CH2)4CH2CHCH3

OH

Grignard reagents react with ketones

R

MgX

C

O

••

•• –MgX+

– +R C

O••

•• ••

••

R C

OH••

H3O+

diethylether

Product is a tertiary alcohol.

R" R'R"

R'

R"

R'

Example

diethylether

Mg

H3O+

(62%)

CH3Cl CH3MgCl O CH3ClMgO CH3HO

Organolithium reagents react with Organolithium reagents react with aldehydes and ketones in the same aldehydes and ketones in the same

way that Grignard reagents do.way that Grignard reagents do.

Synthesis of AlcoholsUsing Organolithium Reagents

Example

(76%)

H2C CHLi +

CH

O

1. diethyl ether

2. H3O+ CH2CHCH

OH

Synthesis of Acetylenic Alcohols

Using Sodium Salts of Acetylenes

HC CH

NaNH2

NH3

HC CNa

HC CNa +1. NH3

2. H3O+

O HO C CH (65-75%)

CHCH3(CH2)3C + CH3CH2MgBr

CMgBrCH3(CH2)3C + CH3CH3

diethyl ether

1. H2C O2. H3O+

CCH2OHCH3(CH2)3C

(82%)

Using Acetylenic Grignard Reagents

14.9Retrosynthetic Analysis

Retrosynthetic analysis is the process by Retrosynthetic analysis is the process by which we plan a synthesis by reasoning which we plan a synthesis by reasoning backward from the desired product (the backward from the desired product (the "target molecule")."target molecule").

Retrosynthetic Analysis of Alcohols

C

OH

Step 1 Locate the carbon that bears the hydroxyl group.

Retrosynthetic Analysis of Alcohols

C

OH

Step 2 Disconnect one of the groups attached to this carbon.

Retrosynthetic Analysis of Alcohols

C

OH

Retrosynthetic Analysis of Alcohols

C

O

What remains is the combination of Grignard reagent and carbonyl compound that can be used to prepare the alcohol.

MgX

Example C

OH

CH3

CH2CH3

C CH2CH3

O

CH3MgX

There are two other possibilities.

Can you see them?

Synthesis

C

OH

CH3

CH2CH3

C CH2CH3

O

1.

2. H3O+

CH3BrMg, diethyl ether

CH3MgBr