Organometallic Reagents

Carbon-Metal Bonds
+ – – +
R X R M

Nucleophilic carbon
Organometallic Reagents
 Organolithium Reagents

normally prepared by reaction of alkyl halides

with lithium

R X + 2Li R Li + LiX

same for Ar—X

is an oxidation-reduction reaction: carbon

is reduced
 Examples
diethyl
ether
(CH3)3CCl + 2Li (CH3)3CLi + LiCl
–10°C
(75%)

diethyl
ether
Br + 2Li Li + LiBr
35°C
(95-99%)
Preparation of Organomagnesium
Reagents
 “Grignard” Reagents

prepared by reaction of alkyl halides

with magnesium

R X + Mg RMgX

same for Ar—X

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
Examples
diethyl
ether
Cl + Mg MgCl
–10°C
(96%)

diethyl
ether
Br + Mg MgBr
35°C
(95%)
 Alkyl halides, vinyl halides, and aryl
halides can all be used to form
organolithium and organomagnesium
compounds
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 solvents
Cannot 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.
 Grignard Reagents
• Direct formation of a Grignard reagent, involves
an alkyl halide reacted with Mg metal.
 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 + HC CH
stronger acid

CH3CH3 + HC CMgBr
weaker acid
 Question
• Select the best method to prepare
CH3CH2CCMgI.
• A) CH3CH2CC-I + Mg (in diethyl
ether)
• B) I-CH2CH2CCH + Mg(OH)2 (in
diethyl ether)
• C) CH3CH2CCH + CH3MgI (in
diethyl ether)
• D) CH3CH2CCH + Mg (in diethyl
ether)
 Grignard Reactions
• A Grignard reagent, RMgX, is a very strong base
and a good nucleophile; water/moisture MUST be
avoided in its reaction.

Question
If water can’t be used as a solvent, can other
protic solvents be used instead?

Yes (A) / No (B)

Example

MgBr + CH3OH

+ CH3OMgBr

(100%)
 Grignard reagents act as nucleophiles
toward the carbonyl group

+ diethyl
– R R C
C ether

MgX O •• • O • + MgX
• •• •–
••
H3O+

two-step sequence
R C
gives an alcohol as
the isolated product •• OH
••
 Grignard reagents react with:

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 formaldehyde

H
H + H diethyl
– R R C H
C ether
•O•
+
MgX O •• • •• •– MgX
••

H3O+ H

product is a R C H
primary alcohol
•• OH
••
Example

Mg
Cl MgCl
diethyl
ether
H
C O
H

H3O+
CH2OH CH2OMgCl

(64-69%)
 Grignard reagents react with:

formaldehyde to give primary alcohols

aldehydes to give secondary alcohols

 Question
• The reaction between propanal and
ethylmagnesium chloride followed by
H3O+ will produce

• A) B)

• C) D)
 Grignard reagents react with aldehydes

H
H + R' diethyl
– R R C R'
C ether

MgX O •• • O • + MgX
• •• •–
••

H3O+ H

product is a R C R'
secondary alcohol
•• OH
••
 Example

Mg
CH3(CH2)4CH2Br CH3(CH2)4CH2MgBr
diethyl
ether H3C

C O
H
H3O+
CH3(CH2)4CH2CHCH3 CH3(CH2)4CH2CHCH3

OH OMgBr
(84%)
 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
O

H2 C CHLi + CH

1. diethyl ether
2. H3O+

CHCH CH2

OH
(76%)
 Grignard reagents react with:

formaldehyde to give primary alcohols

aldehydes to give secondary alcohols

ketones to give tertiary alcohols
 Grignard reagents react with ketones

R"
R" + R' diethyl
– R R C R'
C ether
•O• +
MgX O •• • •• •– MgX
••

H3O+ R"

product is a R C R'
tertiary alcohol
•• OH
••
 Question
• What is the product of the reaction shown at
the right?

• A) B)

• C) D)
 Example

Mg
CH3Cl CH3MgCl
diethyl
ether O

HO CH3 ClMgO CH3

H3O+

(62%)
 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 Alcohols
From Esters and Grignard Reagents
 Grignard reagents react with esters

•• R'
R' + OCH diethyl
– R ••
3 ••
C ether R C OCH3
••
MgX O •• • O • + MgX
• •• •–
••

but species formed is

unstable and dissociates
under the reaction
conditions to form a ketone
 Grignard reagents react with esters

•• R'
R' + OCH diethyl
– R ••
3 ••
C ether R C OCH3
••
MgX O •• • O • + MgX
• •• •–
••

–CH3OMgX
this ketone then
goes on to react with R R'
a second mole of the C
Grignard reagent to
give a tertiary alcohol O ••
••
 Example
O

2 CH3MgBr + (CH3)2CHCOCH3

1. diethyl ether
2. H3O+

Two of the groups

OH attached to the
tertiary carbon
(CH3)2CHCCH3
come from the
CH3 Grignard reagent
(73%)
 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
 Question
What is the product of the following reaction?
1) xs CH3CH2CH2MgBr, Et2O
O

O 2) H3O+

A. O
C.
OH O

B. D.
OH OH
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