Organometallic ReagentsCarbon-Metal Bonds

R X+ –

R M– +

Nucleophilic carbon

Organometallic Reagents

same for Ar—X

is an oxidation-reduction reaction: carbon is reduced

Organolithium Reagents

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°CLi + LiBr

(95-99%)

Preparation of Organomagnesium 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.

Nobel Prize 1912

Born: 6 May 1871, Cherbourg, France

Died: 13 December 1935, Lyon, France

Affiliation at the time of the award: Nancy University, Nancy, France

Examplesdiethylether

–10°C(96%)

Br + Mg

diethylether

35°CMgBr

(95%)

Cl + Mg MgCl

Alkyl halides, vinyl halides, and aryl halides can all be used to form organolithium and organomagnesiumcompounds

However, these organometallic compounds cannot be prepared from compounds containing acidic groups (OH, NH2, NHR, SH, C=CH, CO2H)Cannot use H2O, CH3OH, CH3CH2OH, etc. as solventsCannot prepare from substances such as HOCH2CH2Br, etc.

Synthesis of Alcohols Grignard or Organolithium Reagents

Organolithium reagents react with carbonyls in the same

general way that Grignard reagents do.

• Direct formation of a Grignard reagent, involves an alkyl halide reacted with Mg metal.

Grignard Reagents

Indirect Grignard Reagents

Grignard Reagents can be prepared from other Grignard Reagents (trans-metallation)

Indirect Grignard Reagents

α-acetylenic Grignard Reagents are prepared by an acid-base Grignard reaction

CH3CH2MgBr

+CH3CH3

stronger acid

weaker acid

HC CH

HC CMgBr

+

Question• Select the best method to prepare

CH3CH2CºCMgI.• A) CH3CH2CºC-I + Mg (in diethyl

ether)• B) I-CH2CH2CºCH + Mg(OH)2 (in

diethyl ether)• C) CH3CH2CºCH + CH3MgI (in

diethyl ether)• D) CH3CH2CºCH + Mg (in diethyl

ether)

• A Grignard reagent, RMgX, is a very strong base and a good nucleophile; water/moisture MUST be avoided in its reaction.

Grignard Reactions

QuestionIf water can’t be used as a solvent, can other

protic solvents be used instead?

Yes (A) / No (B)

Example

MgBr

(100%)

+ CH3OH

+ CH3OMgBr

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

other aldehydes to give secondary alcohols

ketones to give tertiary alcohols

esters to give tertiary alcohols

Grignard reagents react with:

formaldehyde to give primary 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

ClMg

MgCl

C O

H

H

CH2OMgClH3O+

CH2OH

(64-69%)

formaldehyde to give primary alcohols

aldehydes to give secondary alcohols

Grignard reagents react with:

Question• The reaction between propanal and

ethylmagnesium chloride followed by H3O+ will produce

• A) B)

• C) D)

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

HH3O+

(84%)

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

CH3(CH2)4CH2CHCH3

OMgBr

CH3(CH2)4CH2CHCH3

OH

Question

• What is the product of the reaction of ethylmagnesium bromide (CH3CH2MgBr) with butanal (CH3CH2CH2CH=O) followed by dilute acid?

• A) 2-hexanol• B) 1-butanol• C) 3-hexanol• D) 3-pentanol

Example

(76%)

H2C CHLi + CH

O

1. diethyl ether2. H3O+

CH2CHCH

OH

formaldehyde to give primary alcohols

aldehydes to give secondary alcohols

ketones to give tertiary alcohols

Grignard reagents react with:

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'

Question

• What is the product of the reaction shown at the right?

• A) B)

• C) D)

Example

diethylether

Mg

H3O+

(62%)

CH3Cl CH3MgCl

O

CH3ClMgOCH3HO

Question

• Two alcohols, each having the molecular formula C11H22O, are formed in the reaction of methyl lithium with 3-(R)-tert-butylcyclohexanone. These two alcohols are

• A) constitutional isomers.• B) enantiomers in equal amounts.• C) enantiomers in unequal amounts.• D) diastereomers.

Preparation of Tertiary AlcoholsFrom Esters and Grignard Reagents

Grignard reagents react with esters

R

MgX

C

O••

•• –MgX+

– +R C

O••

•• ••

diethylether

OCH3••

•• OCH3••

••

R'R'

but species formed is unstable and dissociates under the reaction conditions to form a ketone

Grignard reagents react with esters

R

MgX

C

O••

•• –MgX+

– +R C

O••

•• ••

diethylether

OCH3••

•• OCH3••

••

R'R'

–CH3OMgX

C

O

R R'

••••

this ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol

Example

2 CH3MgBr + (CH3)2CHCOCH3

O

1. diethyl ether2. H3O+

(CH3)2CHCCH3

OH

CH3

(73%)

Two of the groups attached to the tertiary carbon come from the Grignard reagent

Question• Which one of the compounds below will be

produced when 2 moles of methylmagnesium bromide is added to 1 mole of methyl propanoate (CH3CH2CO2CH3) followed by acid?

• A) CH3CH2COCH3

• B) CH3CH2CO2-MgBr• C) (CH3)2C(OH)CH2CH3

• D) CH3CH2CH2CH3

• E) 3-methyl-2-butanol

1) xs CH3CH2CH2MgBr, Et2O

2) H3O+

A.

B.

C.

D.

O

O

O

O

OH

OH

OH

What is the product of the following reaction?

Question

Grignard Reactions

Question

• Which one of the compounds below will be produced when methylmagnesium bromide is added to propanoic acid (CH3CH2CO2H)?

• A) CH3CH2COCH3

• B) CH3CH2CO2-MgBr• C) CH3CH2CH(OH)CH3

• D) CH3CH2CH2CH3