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
weaker acid
+
HC
CMgBr
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
+
(100%)
CH3OMgBr
Grignard reagents act as nucleophiles
toward the carbonyl group
– R
+
C
diethyl
ether
R
C
• O • + MgX
• •• •–
MgX O ••
••
H3O+
two-step sequence
gives an alcohol as
the isolated product
R
C
•• 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
– R
H
+ H
C
H
diethyl
ether
R
C
•• O ••
•• –
MgX O ••
••
H
+
MgX
H3O+
product is a
primary alcohol
H
R
C
•• OH
••
H
Example
Mg
Cl
MgCl
diethyl
ether
H
C
O
H
CH2OH
(64-69%)
H3O+
CH2OMgCl
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
– R
H
+ R'
C
MgX O ••
••
H
diethyl
ether
R
C
R'
•• O •• + MgX
•• –
H3O+
product is a
secondary alcohol
H
R
C
•• OH
••
R'
Example
Mg
CH3(CH2)4CH2Br
diethyl
ether
CH3(CH2)4CH2MgBr
H3C
C
O
H
CH3(CH2)4CH2CHCH3
OH
(84%)
H3O+
CH3(CH2)4CH2CHCH3
OMgBr
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
OH
(76%)
CH2
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'
C
R"
diethyl
ether
R
C
•• O ••
•• –
MgX O ••
••
R'
+
H3O+
product is a
tertiary alcohol
MgX
R"
R
C
•• OH
••
R'
Question
• What is the product of the reaction shown at
the right?
•
A)
B)
•
C)
D)
Example
Mg
CH3Cl
HO
(62%)
CH3
diethyl
ether
H3O+
CH3MgCl
O
ClMgO
CH3
Question
• Two alcohols, each having the molecular
formula C11H22O, are formed in the reaction of
methyl lithium with 3-(R)-tertbutylcyclohexanone. 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
3
••
C
MgX O ••
••
R'
diethyl
ether
R
C
••
OCH3
••
• 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
3
••
C
R'
diethyl
ether
R
OCH3
••
• O • + MgX
• •• •–
MgX O ••
••
this ketone then
goes on to react with
a second mole of the
Grignard reagent to
give a tertiary alcohol
C
••
–CH3OMgX
R
R'
C
O ••
••
Example
O
2 CH3MgBr + (CH3)2CHCOCH3
1. diethyl ether
2. H3O+
OH
(CH3)2CHCCH3
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
Question
What is the product of the following reaction?
O
2) H3O+
O
A.
1) xs CH3CH2CH2MgBr, Et2O
O
C.
O
OH
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